Clinical trial NCT05113966
Conditions: Triple Negative Breast Cancer
Keywords: TNBC Trodelvy Myelosuppression
Sponsor: G1 Therapeutics, Inc.
Start date: 2021-12-08; Completion date: 2024-06-13
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This was a Phase 2, multicenter, open-label, single-arm study evaluating the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in participants with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) who received at least 2 prior treatments, at least 1 in the metastatic setting.

Detailed description:
The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of the first dose of study treatment and was completed at the Safety Follow-up Visit. Trilaciclib and sacituzumab govitecan-hziy were administered intravenously (IV) in 21-day cycles. Study drug administration continued until progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the study, whichever occurred first. The first Survival Follow-up assessment occurred approximately 3 months after the Safety Follow-Up Visit and continued every 3 months until the end of the study (or death).

Arms: arm 1: Participants received trilaciclib + sacituzumab govitecan-hziy on days 1 \& 8 of a 21 day cycle. Trilaciclib is administered first, followed by sacituzumab govitecan-hziy. Administer diluted trilaciclib solution as a 30-minute IV infusion to be completed within 4 hours prior to the start of sacituzumab govitecan-hziy.
Interventions: intervention 1: Trilaciclib intervention 2: Sacituzumab Govitecan-hziy
Intervention descriptions: intervention 1: Single-use, sterile powder to be reconstituted and further diluted with 250 milliliters (mL) of normal saline (sodium chloride solution 0.9%) or dextrose 5% in water (D5W) intervention 2: 10 milligram per kilogram (mg/kg) reconstituted to a concentration of 1.1 mg/mL to 3.4 mg/mL in normal saline

Protocol documents:
Prot_000.pdf: 
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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   
 
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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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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 


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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. 


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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 


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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 


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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  


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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 


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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 
prese nce of li ver m etastasis. 


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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 
sta n dar d of care treat me nt b y t heir healt hcare pr o vi der o utsi de of t his st u d y. 


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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. 


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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. 


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1 6.  
R E F E R E N C E S 
Aa pr o M S, B o hli us J, Ca mer o n D A, et al. 2 0 1 0 u p date of E O R T C g ui deli nes f or t he use of 
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 
[ p u blis he d c orrecti o n a p p ears i n P L o S O ne. 2 0 1 4; 9( 1 0):e 1 1 0 6 0 6]. P L o S O ne. 
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-
Ne gati ve Breast Ca ncer. N E n gl J Me d. 2 0 2 1; 3 8 4( 1 6): 1 5 2 9- 4 1. 
Bar di a A, Ma yer I A, Va h dat L T, et al. Sacit uz u ma b G o viteca n- hzi y i n Refract or y Metastatic 
Tri ple- Ne gati ve Breast C a ncer. N E n gl J Me d. 2 0 1 9; 3 8 0( 8): 7 4 1- 5 1. 
Barr os o- S o usa R, T ola ne y S M. Cli nical De vel o p me nt of Ne w A nti b o d y- Dr u g C o nj u gat es i n 
Breast Ca ncer: T o I nfi nit y a n d Be y o n d. Bi o Dr u gs. 2 0 2 1; 3 5( 2): 1 5 9- 7 4. 
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 
i m m u n ot hera p y. Tra nsl O nc. 2 0 2 0; 1 3 : 1 0 0 7 3 8. 
Bisi J E, S orre nti n o J A, R o berts PJ, et al. Pr ecli nical c haracterizati o n of G 1 T 2 8: A n o vel 
C D K 4/ 6 i n hi bit or f or re d ucti o n of c he m ot hera p y-i n d uce d m yel os u p pressi o n. M ol Ca ncer 
T her. 2 0 1 6; 1 5: 7 8 3 – 9 3. 
B o de y G P, B uc kle y M, S at he Y S, Freireic h EJ. Q ua ntitati ve relati o ns hi ps bet wee n 
circ ulati n g le u k oc ytes a n d i nfecti o n i n p atie nts wit h ac ute le u k e mia. A n n I nter n Me d. 
1 9 6 6; 6 4( 2): 3 2 8- 4 0. 
B o hli us J, B o hl ke K, Castelli R, et al. Ma na ge me nt of Ca ncer- Ass ociate d A ne mia Wit h 
Er yt hr o p oiesis- Sti m ulati n g A ge nts: A S C O/ A S H Cli nical Practice G ui deli ne U p date. 2 0 1 9; 
3 7. 
B o nelli M, La M o nica S, F u mar ola C, et al. M ulti ple effects of C D K 4/ 6 i n hi biti o n i n ca ncer: 
Fr o m cell c ycle arrest t o i m m u n o m o d ulati o n. Bi oc he m P har mac ol. 2 0 1 9; 1 7 0: 1 1 3 6 7 6. 
B orc h er di n g N, K ol b R, G ullic ksr u d J, et al. Kee pi n g t u m ors i n c hec k: A me c ha nistic re vie w 
of cli nical res p o ns e a n d resista nce t o i m m u ne c hec k p oi nt bl oc ka de i n ca ncer. J M ol Bi ol. 
2 0 1 8; 4 3 0: 2 0 1 4- 2 9. 
Br o o k me yer R, Cr o wle y J. A c o nfi de nce i nter val f or t he me dia n s ur vi val ti me. Bi o metrics. 
1 9 8 2; 2 9- 4 1. 
Ca g gia n o V, Weiss R V, Ric kert T S, et al. I nci de nce, c ost, a n d m ort alit y of ne utr o pe nia 
h os pitaliz ati o n ass ociate d wit h c he m ot hera p y . Ca ncer. 2 0 0 5; 1 0 3( 9): 1 9 1 6- 2 4. 
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 
g ui deli nes f or a d va n ce d breast ca ncer ( A B C 5). A n n O nc ol. 2 0 2 0; 3 1( 1 2): 1 6 2 3- 4 9. 


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Cars o n J L, G u yatt G, He d dle N M, et al. Cli nical Practice G ui deli nes Fr o m t he A A B B: Re d 
Bl o o d Cell Tra nsf usi o n T hres h ol ds  a n d St ora ge. J A M A. 2 0 1 6; 3 1 6( 1 9): 2 0 2 5- 3 5. 
Car vajal- H a us d orf D, Alta n M, Velc heti V, et al. E x pressi o n a n d cli nical si g nifica n ce of P D-
L 1, B 7- H 3, B 7- H 4 a n d TI Ls i n h u ma n s mall cell l u n g Ca ncer ( S C L C). J I m m u n ot her Ca ncer. 
2 0 1 9 Mar 8; 7( 1): 6 5. 
C hai k o vs k y A C, Sa ge J. Be y o n d t he cell c ycl e: e n ha nci n g t he i m m u ne s ur veilla nce of t u m ors 
via C D K 4/ 6 i n hi biti o n. M ol Ca ncer Res. 2 0 1 8; 1 6: 1 4 5 4- 5 7. 
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 
t u m ors: re vise d R E CI S T g ui deli ne ( v ersi o n 1. 1). E ur J Ca ncer. 2 0 0 9; 4 5: 2 2 8- 4 7. 
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. 
F o ul kes W D, S mit h I E, Reis- Fil h o J S. Tri ple- ne gati ve breast ca ncer. N E n gl J Me d. 2 0 1 0 
N o v 1 1; 3 6 3( 2 0): 1 9 3 8- 4 8. 
Gi de T N, Wil m ott J S, Sc ol yer R A, et al. Pri mar y a n d ac q uir e d resista nce t o i m m u ne 
c hec k p oi nt i n hi bit ors i n metastatic mela n o ma. Cli n Ca ncer Res. 2 0 1 8; 2 4( 6). 
G oel S, De Crist o MJ, Watt A C, et al. C D K 4/ 6 i n hi biti o n tri g gers a nti-t u m or i m m u nit y. 
Nat ure 2 0 1 7; 5 4 8( 7 6 6 8): 4 7 1- 5. 
G usti netti G, Mi k uls ka M. Bl o o dstrea m i nfecti o ns  i n ne utr o pe nic ca ncer patie nts: A practical 
u p date. Vir ule nce. 2 0 1 6; 7( 3): 2 8 0- 9 7. 
Ha h ne n E, Ha u ke J, E n gel C, et al. Ger mli ne M ut ati o ns i n Tri ple- Ne gati ve Breast 
Ca ncer. Breast Care ( Bas el). 2 0 1 7; 1 2( 1): 1 5- 9. 
Hart L L, Ferrar ott o R, A n dric Z G, et al. M yel o preser vati o n wit h Trilacicli b i n Patie nts 
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-
Bli n d, Place b o- C o ntr olle d P hase II St u d y. A d v T h er. 2 0 2 1; 3 8( 1): 3 5 0- 6 5.  


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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 
ste m cells fr o m c he m ot h era p y-i n d u ce d e x ha usti o n. Sci Tra nsl Me d. 2 0 1 7a; 9. 
He Y, R oze b o o m L, Ri var d CJ, et al. M H C class II e x pressi o n i n l u n g ca ncer. L u n g C a ncer. 
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 
s ki n ste m cells. Cell. 2 0 0 8; 1 3 2( 2): 2 9 9- 3 1 0. 
J e n ki ns R W, Bar bie D A, Fla hert y K T. Mec h a nis ms of resista nce t o i m m u ne c hec k p oi nt 
i n hi bit ors. Brit J Ca ncer. 2 0 1 8; 1 1 8: 9- 1 6. 
Kassa m F, E nri g ht K, De nt R, et al. S ur vi val o utc o mes f or patie nts wit h metastatic tri ple-
ne gati ve breast ca n cer: i m plicati o ns f or cli nical practice a n d trial desi g n. Cli n Breast Ca ncer. 
2 0 0 9; 9( 1): 2 9- 3 3.  
Ka uf ma n R M, Dj ul be g o vic B D, Ger ns hei mer T, et al. Platelet Tra nsf usi o n: A Cli nical 
Practice G ui deli ne Fr o m t he A A B B. A n n I nter n Me d. 2 0 1 5; 1 6 2: 2 0 5- 1 3.  
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. 
K ozar K, Cie mer yc h M A, Re bel VI, et al. M o us e de vel o p me nt a n d cell pr oliferati o n i n t he 
a bse nce of D- c ycli ns. Cell. 2 0 0 4; 1 1 8( 4): 4 7 7 – 9 1. 
K u derer N M, Dal e D C, Cra wf or d J, et al. M ortalit y, m or bi dit y, a n d c ost ass ociate d wit h 
fe brile ne utr o p e nia i n a d ult ca ncer patie nts. Ca ncer. 2 0 0 6; 1 0 6( 1 0): 2 2 5 8- 6 6. 
Lai A Y, S orre nti n o J A, Str u m J C, et al. Tra nsie nt e x p os ure t o trilacicli b, a C D K 4/ 6 i n hi bit or, 
m o d ulates ge n e e x pressi o n i n t u m or i m m u ne i nfiltrates a n d pr o m otes a pr o-i nfla m mat or y 
t u m or micr oe n vir o n me nt. A merica n Ass o ciati o n f or Ca ncer R esearc h A n n ual Meeti n g 2 0 1 8; 
C hica g o, I L; A pril 1 4 – 1 8, 2 0 1 8 (a bstr 1 7 5 2). 
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Lai A Y, S orre nti n o J A, Dra g ne v K H, et al. C D K 4 / 6 i n hi biti o n e n ha nces a ntit u m or efficac y 
of c he m ot hera p y a n d i m m u ne c hec k p oi nt i n hi bit or c o m bi nati o ns i n precli nical m o dels a n d 
e n ha nces T-cell acti vati o n i n patie nts wit h S C L C recei vi n g c h e m ot hera p y. J I m m u n ot her 
Ca ncer. 2 0 2 0; 8. 
Le h m a n n B D, J o va n ocic B, C he n X, et al. Refi ne me nt of tri ple- ne gati ve breast c a ncer 
m olec ular s u bt y pes: i m plicati o ns f or ne oa dj u v a nt c he m ot hera p y s electi o n. P L o S O ne. 
2 0 1 6; 1 1e 0 1 5 7 3 6 8. 
Li Y, Kli p pel Z, S hi h X, et al. Relati o ns hi p bet wee n se verit y a n d d urati o n of c he m ot hera p y-
i n d uce d ne utr o pe ni a a n d ris k of i nfecti o n a m o n g p atie nts wit h n o n m yel oi d mali g na n cies. 
S u p p ort Care Ca ncer. 2 0 1 6; 2 4( 1 0): 4 3 7 7- 8 3. 
Li u Z, Li M, Jia n g Z, Wa n g X. A C o m pr e he nsi ve I m m u n ol o gic P ortrait of Tri ple- Ne gati ve 
Breast Ca ncer. Tra nsl ati o nal O nc ol o g y. 2 0 1 8; 1 1: 3 1 1- 2 9. 
Mal u m bres M, S otill o R, Sa nta maria D, et al. Ma m malia n cells c ycle wit h o ut t he D-t y p e 
c ycli n- de pe n d e nt ki nases C d k 4 a n d C d k 6. Cell. 2 0 0 4; 1 1 8( 4): 4 9 3- 5 0 4. 
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 i n O nc ol o g y 
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. 


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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 
He mat o p oietic Gr o wt h Fact ors. Versi o n 3. 2 0 2 1. N C C N, F ort Was hi n gt o n, P A. 
O ke n M M, Creec h R H, T or me y D C, et al. T o xicit y a n d res p o nse criteria of t he Easter n 
C o o perati ve O nc ol o g y Gr o u p. A m J Cli n O nc ol. 1 9 8 2; 5( 6): 6 4 9- 5 5. 
O ’ S ha u g h ness y J, Wri g ht G S, T h u m mala A R, et al. Trilacicli b i m pr o ves o verall s ur vi val 
w he n gi ve n wit h ge mcita bi ne/car b o plati n i n patie nts wit h metastatic tri ple- ne gati ve breast 
ca ncer: Fi nal a nal ysis of a ra n d o mize d P hase 2 tri al.  Sa n A nt o ni o Breast Ca ncer S y m p osi u m 
2 0 2 0; Sa n A nt o ni o, T X; Dece m b er 8- 1 1, 2 0 2 0. 
Pa dilla G, R o p ka M E. Q ualit y of life a n d c h e m ot hera p y-i n d u ce d ne utr o p e nia. Ca ncer N urs. 
2 0 0 5; 2 8( 3): 1 6 7- 7 1. 
Prat A, Bia n c hi G, T h o mas M, et al. Researc h- b as e d P A M 5 0 s u bt y pe pre di ct or i de ntifies 
hi g her res p o nses a n d i m pr o ve d s ur vi val o utc o mes i n H E R 2- p ositi ve breast ca ncer i n t he 
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 
p 1 6I n k 4 a L oss i n C ycli n- De pe n de nt Ki n ase 4/ 6 – De pe n de nt T u m ors a n d Tiss ues. Ca ncer R es 
2 0 0 7; 6 7: 4 7 3 2- 4 1. 
R u g o H S, T ola ne y S M, L oir at D, et al. I m pact of U G T 1 A 1 stat us o n t he safet y pr ofile of 
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 
 
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 8 
 
 
  
 
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.  


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 9 
 
 
  
 
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 
 
 


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 
 
9 0 
 
 
  
 
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. 


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 
 
9 1 
 
 
  
 
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.  
 


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 
 
9 2 
 
 
  
 
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. 


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 
 
9 3 
 
 
  
 
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. 


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 
 
1 0 0 
 
 
  
 
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. 
 
 

SAP_001.pdf: 
1
 
 
STATISTICAL ANALYSIS PLAN 
Protocol Title: 
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   
Protocol Version 
2.0 
Protocol Number: 
G1T28-213 
Compound: 
Trilaciclib for Injection, 300 mg/vial 
Study Phase: 
Phase 2 
Sponsor: 
G1 Therapeutics, Inc. 
Legal Registered Address: 
700 Park Offices Dr. Suite 200 
PO Box 110341  
Research Triangle Park, NC 27709 
Regulatory Agency Identifier 
Numbers: 
IND: 145091  
EudraCT: 2019-003826-25 
Statistical Analysis Plan 
Version: 
V 2.0 
Approval Date: 
04 Jun 2024 
 
 


Statistical Analysis Plan for Protocol G1T28-213 
Version   2.0
G1 Therapeutics 
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SAP SIGNATURE PAGE 
I have read and understand the contents of this Statistical Analysis Plan, Version 2.0 for 
Study G1T28-213, and I agree with all the statistical approaches, variable derivations, and data 
presentation detailed as described in this document. 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
  
  
 
 
 
 
 
 
 
Date 
  
  
 
Date 



PPD
PPD
PPD
PPD


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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................1 
SAP SIGNATURE PAGE ...............................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ......................................................................................................10 
1.1. 
Study Design ...............................................................................................................10 
1.2. 
Study Objectives .........................................................................................................11 
1.3. 
Sample Size Consideration .........................................................................................13 
2. 
THE NUMBER OF PLANNED ANALYSES ...........................................................15 
2.1. 
Final Planned Analysis - Analyses for Progression Free Survival, Tumor 
Response Endpoints, Myelosuppression Endpoints, and Overall Survival ................15 
3. 
ANALYSIS POPULATIONS ....................................................................................16 
3.1. 
The Full Analysis Set..................................................................................................16 
3.2. 
The Response Evaluable Population ..........................................................................16 
3.3. 
The safety population .................................................................................................16 
4. 
GENERAL CONSIDERATIONS FOR DATA SUMMARY AND 
DISPLAY ...................................................................................................................17 
4.1. 
Treatment Group Descriptions and Display in Table, Listings and Figures ..............17 
4.2. 
Data Summary and Precision......................................................................................17 
4.3. 
Definitions for Analysis Related Timepoint and Time Interval .................................18 
4.4. 
Study Day ...................................................................................................................19 
4.5. 
General Principles of Missing Data Handling ............................................................19 
5. 
DISPOSITION AND BASELINE CHARACTERISTICS ........................................20 
5.1. 
Patient Disposition ......................................................................................................20 
5.2. 
Demographics and Baseline Disease Characteristics .................................................21 
5.3. 
Medical/Surgical History and Ongoing Conditions ...................................................21 
5.4. 
Prior and Concomitant Medications ...........................................................................21 
5.5. 
Summary of Protocol Deviations................................................................................22 
5.5.1. 
Definitions and Process for Identifying Protocol Deviations .....................................22 
5.5.2. 
Summary of Protocol Deviations................................................................................23 
6. 
CLASSIFICATION OF PRIOR, CONCOMITANT, AND SUBSEQUENT 
ANTICANCER THERAPIES ....................................................................................24 
6.1. 
Prior Anticancer Therapies .........................................................................................24 


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6.2. 
Concomitant Anticancer Therapies ............................................................................24 
6.3. 
Subsequent Systemic Anticancer Therapies ...............................................................24 
7. 
STUDY DRUG EXPOSURE, DOSE INTENSITY AND MODIFICATION ...........26 
7.1. 
Duration of Study Drug Exposure ..............................................................................26 
7.2. 
Cumulative Dose and Dose Intensity .........................................................................26 
7.3. 
Study Drug Modifications ..........................................................................................28 
7.4. 
Duration of Total Follow-up .......................................................................................29 
8. 
EFFICACY ANALYSIS ............................................................................................30 
8.1. 
Definitions of Efficacy Endpoints ..............................................................................30 
8.1.1. 
Primary Efficacy Endpoints – Progression Free Survival ..........................................30 
8.1.2. 
Secondary Efficacy Endpoint – Anti-tumor Efficacy Endpoints ...............................31 
8.1.3. 
Secondary Efficacy Endpoint – Analysis for Overall Survival ..................................32 
8.1.4. 
Secondary Efficacy Endpoint – Myeloprotection Efficacy Endpoints .......................33 
8.1.4.1. 
Neutrophil-Related Endpoints ....................................................................................33 
8.1.4.2. 
RBC-Related Endpoints ..............................................................................................34 
8.1.4.3. 
Dose Modifications .....................................................................................................34 
8.2. 
Statistical Analysis Methods.......................................................................................35 
8.2.1. 
General Considerations for Efficacy Analysis ...........................................................35 
8.2.2. 
Analysis for Progression Free Survival (PFS) and Overall Survival .........................35 
8.2.3. 
Analysis for Secondary Endpoints - Anti-tumor Efficacy Endpoints ........................35 
8.2.4. 
Analysis for Secondary Endpoints - Myeloprotection Endpoints ..............................36 
8.2.4.1. 
Analysis for Binary Myelosuppression Endpoints .....................................................36 
8.2.4.2. 
Analysis for Counting Myelosuppression Endpoints .................................................36 
8.3. 
Handling of Missing Data ...........................................................................................36 
9. 
SAFETY ANALYSIS ................................................................................................37 
9.1. 
General Consideration of Safety Analysis ..................................................................37 
9.2. 
Adverse Events ...........................................................................................................37 
9.2.1. 
Definition and Classification of Adverse Events ........................................................37 
9.2.2. 
Imputation Rules for Missing Start or Stop Date for Adverse Events .......................38 
9.2.3. 
Analysis for Adverse Events ......................................................................................39 
9.3. 
Clinical Laboratory Data ............................................................................................40 
9.3.1. 
Laboratory Parameters ................................................................................................40 


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9.3.2. 
Analysis for Laboratory Parameters ...........................................................................41 
9.4. 
Vital Signs ..................................................................................................................42 
9.4.1. 
Vital Sign Parameters .................................................................................................42 
9.4.2. 
Analysis for Vital Signs ..............................................................................................43 
9.5. 
12-lead Electrocardiograms ........................................................................................43 
9.5.1. 
Electrocardiograms Parameters ..................................................................................43 
9.5.2. 
Analysis for Electrocardiograms Parameters ..............................................................44 
10. 
CHANGES FROM THE PROTOCOL ......................................................................45 
11. 
REFERENCES ...........................................................................................................46 
12. 
APPENDICES ............................................................................................................47 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................48 
APPENDIX 2. CUSTOMIZED MEDDRA QUERIES FOR TRILACICLIB AESIS ...............50 
 


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LIST OF TABLES 
Table 1 
Primary and Secondary Objectives and Endpoints .....................................................12 
Table 2 
Statistical Power .........................................................................................................14 
Table 3 
Definitions for Timepoints, Timepoint Related Assessments and Time 
Intervals ......................................................................................................................18 
Table 4 
Dose Administration Parameters for Study G1T28-213 ............................................27 
Table 5 
Protocol Permitted Dose Reduction by Study Drug ...................................................28 
Table 6 
PFS Calculation and Censoring Rules ........................................................................31 
Table 7 
Myeloprotection Endpoints ........................................................................................33 
Table 8 
Hematologic Preferred Terms to be Collapsed ...........................................................37 
Table 9 
Laboratory Categories and Parameters .......................................................................40 
Table 10 
Criteria for Potentially Clinically Significant Vital Signs ..........................................43 
Table 11 
Criteria for Potentially Clinically Significant ECG Findings .....................................44 
Table 12 
Schedule of Assessments ............................................................................................48 
 
 
LIST OF FIGURES 
Figure 1 
G1T28-213 Study Design Diagram ............................................................................11 
 
 
 


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LIST OF ABBREVIATIONS  
Abbreviation  
 Term 
aCSR 
Abbreviated clinical study report 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALC 
Absolute lymphocyte count 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
BMI 
Body mass index 
BOR 
Best overall response 
BRCA 
Breast cancer gene 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CBR 
Clinical benefit rate 
CDK 
Cyclin dependent kinase 
CI 
Confidence interval 
CR 
Complete response 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
Diastolic blood pressure 
DOR 
Duration of response 
EDC 
Electronic data capture 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EOT 
End of treament 


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Abbreviation  
 Term 
ESA 
Erythropoiesis-stimulating agent 
ETV 
End of Treatment Visit 
FAS 
Full analysis set 
G-CSF 
Granulocyte colony stimulating factor 
Hgb 
Hemoglobin 
HR 
Hazard ratio 
ID 
Identification 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NE 
Not evaluable 
ORR 
Objective response rate 
OS 
Overall survival 
PCS 
Potentially clinically significant 
PD 
Progressive disease 
PFS 
Progression free survival 
pMMR/MSS 
Proficient mismatch repair/microsatellite stable 
PR 
Partial response 
PT 
Preferred term 
RBC 
Red blood cell 
RE 
Response evaluable 
RECIST 
Response Evaluable Criteria in Solid Tumors 
SACT 
Subsequent anticancer treatment 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SD 
Stable disease 
SE 
Standard error 
SG 
Sacituzumab govitecan-hziy 
SI 
Standard international 
SN 
Severe neutropenia 


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Abbreviation  
 Term 
SOC 
System organ class 
SPSD 
Statistical Programming Supportive Documents 
TLF 
Tables, listings, and figures 
TNBC 
Triple-negative breast cancer  
TOC 
Table of contents 
WHO-DD 
World Health Organization Drug Dictionary 
 
 


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1. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) provides detailed statistical methods, variable definitions 
and derivations, and data handling that will be applied to analyze the clinical trial data collected 
during study G1T28-213, “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” based on the protocol Version 2.0 (dated 15 
November, 2021). 
 
Statistical Programming Supportive Documents (SPSD) will be developed based on the SAP to 
serve as companion documents of the SAP to guide programming realization of the SAP. SPSD 
contain three separate documents: 
1. The table of contents (TOC) for planned analyses (in Excel Spreadsheet). 
2. The reporting conventions (in Word). 
3. The shells or specificities for tables, listings, and figures (TLFs) generation (in Word).  
 
Statistical software SAS® (SAS Institute Inc., Cary, NC) Version 9.4 or later will be used to 
perform data analyses following the plan as laid out in this SAP.  
If there are differences between statistical analysis approaches described in the SAP and those in 
the protocol, the methods and approaches in the SAP will supersede those in the protocol. 
Changes and additions to the last signed off version of the SAP will be documented with 
corresponding rationale in the clinical study report (CSR). 
1.1. 
Study Design 
This is a Phase 2, multicenter, open-label, single arm study evaluating the safety and efficacy of 
trilaciclib administered prior to sacituzumab govitecan-hziy in patients with unresectable, locally 
advanced or metastatic triple-negative breast cancer (TNBC) who received at least 2 prior 
treatments, at least 1 in the metastatic setting.  
Approximately 45 patients were planned to be enrolled per Protocol Version 2.0. The sponsor 
decided to close enrollment to this study on February 14, 2023 in order to reallocate resources to 
other ongoing trilaciclib clinical trials. The final total number of patients enrolled in this study is 
30. 
Trilaciclib and sacituzumab govitecan-hziy will be administered intravenously (IV) in 21-day 
cycles as indicated below: 
 
Trilaciclib: 
Trilaciclib 240 mg/m2 administered as a 30-minute IV infusion completed within 4 hours prior 
to the start of sacituzumab govitecan-hziy on Day 1 and Day 8 of each 21-day treatment cycle.  
 
Sacituzumab govitecan-hziy: 
Sacituzumab govitecan-hziy 10 mg/kg administered IV on Day 1 and Day 8 of each 21-day 
treatment cycle. The first infusion is administered over 3 hours and patients are observed during 
the infusion and for at least 30 minutes following the initial dose for signs or symptoms of 
infusion-related reactions. Subsequent infusions may be administered over 1 to 2 hours if prior 


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infusions were tolerated, and patients should be observed during the infusion and for at least 30 
minutes after infusion.  
 
The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-
up Phase (Figure 1). The Treatment Phase begins on the day of enrollment and completes at the 
End of Treatment Visit. Survival Follow-up assessments should occur every 3 months after the 
End of Treatment Visit. 
Figure 1 
G1T28-213 Study Design Diagram 
 
 
DC=discontinued; PD=progressive disease; PI=Principal Investigator; WD=withdraw 
 
Patients enrolled in the study will be eligible to receive treatment until disease progression, 
unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the trial, 
whichever comes first. Treatment cycles will occur consecutively without interruption, except 
when necessary, to manage toxicities or for administrative reasons. There should be no more 
than a 3-week delay from the next scheduled dose of sacituzumab govitecan-hziy. A dosing 
delay >3 weeks from the next scheduled dose may be permitted on a case-by-case basis with the 
approval of the Investigator and Medical Monitor.  
 
Criteria which patients must meet in order to receive study drug on Day 1 and on Day 8 during 
treatment are provided in Section 9.2 of the study protocol.  
An End of Treatment Visit will occur approximately 14 days following a patient’s last dose of 
study treatment. The first Safety Follow-up visit (which may be a phone call) will occur 30 days 
after the last dose of study treatment. Patients will be followed for survival approximately every 
3 months after the End of Treatment Visit. Survival Follow-up Visits may be done via telephone, 
email, or clinic visit. Unless otherwise decided by the Sponsor, the study will continue until 
approximately 70% of patients enrolled in the study have died. 
 
1.2. 
Study Objectives  
Primary: 
To evaluate the anti-tumor efficacy of trilaciclib when administered prior to sacituzumab 
govitecan-hziy as measured by progression free survival (PFS).  


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Secondary:  
To evaluate the anti-tumor efficacy of trilaciclib administered prior to sacituzumab govitecan-
hziy as measured by the objective response rate (ORR), duration of objective response (DOR), 
clinical benefit rate (CBR), and overall survival (OS); evaluate the myeloprotective effects of 
trilaciclib; and assess the safety and tolerability of trilaciclib administered prior to sacituzumab 
govitecan-hziy.  
Specifically, the primary and secondary objectives and their associated endpoints are described 
in Table 1.  
Table 1 
Primary and Secondary Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objective  
 
To evaluate the anti-tumor activity of 
trilaciclib when administered prior to 
sacituzumab govitecan-hziy  
 
x PFS defined as time from the date of first 
dose of study drug to radiographic disease 
progression using RECIST v1.1 or death due 
to any cause, whichever occurs first; for 
patients without disease progression or death, 
PFS will be calculated per censoring rules.  
 
Secondary Objective: Efficacy  
 
To evaluate the anti-tumor activity of 
trilaciclib when administered prior to 
sacituzumab govitecan-hziy  
 
 
x ORR defined as the percentage of patients 
with BOR of confirmed CR or confirmed PR 
per RECIST v1.1  
x CBR defined as the percentage of patients 
with a BOR of confirmed CR, confirmed PR, 
or SD lasting 24 weeks or longer since the 
first date of study drug administration per 
RECIST v1.1 
x DOR defined as duration of objective 
response 
x OS defined as time from the date of first 
dose of study drug to death due to any cause 
for those who died; or time to last contact 
known as alive for those who survived in the 
study (censored cases)  
 
Secondary Objective: Myeloprotective effects of trilaciclib  
 
• To evaluate the myeloprotective 
effects of trilaciclib when administered 
prior to sacituzumab govitecan-hziy  
 
 
x Occurrence of SN (during Cycles 1/2 and 
overall study)  
x Occurrence of febrile neutropenia  
x Occurrence of G-CSF administration 


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Objectives 
Endpoints 
x Occurrence of Grade 3/4 decrease of 
hemoglobin 
x Occurrence and number of RBC transfusions 
on/after Week 5 
x Occurrence of ESA administration 
x Occurrence of Grade 3/4 decrease of 
platelets 
x Occurrence and number of platelet 
transfusions 
x Occurrence of serious infections  
x Use of IV antibiotics  
Secondary objectives: Safety 
 
To evaluate the safety and tolerability of 
trilaciclib when administered prior to 
sacituzumab govitecan-hziy  
 
x Occurrence and severity of AEs by NCI 
CTCAE v5.0  
x Trilaciclib AESIs  
x Changes in laboratory parameters 
(hematology and chemistry), vital signs and 
ECG parameters 
x Grade 3 or 4 abnormalities in chemistry 
laboratory parameters 
x Trilaciclib infusion interruptions 
x Sacituzumab govitecan-hziy infusion 
interruptions 
x Sacituzumab govitecan-hziy dose reduction 
and cycle delay  
AESI=adverse event of special interest; CBR=clinical benefit rate; CR=complete response; CTCAE=Common 
Terminology Criteria for Adverse Events; ECG=electrocardiogram; ESA= erythropoiesis-stimulating agent;G-CSF= 
granulocyte colony stimulating factor; IV=intravenous; NCI=National Cancer Institute; ORR=objective response 
rate; OS=overall survival; PFS=progression free survival; RBC=red blood cell; RECIST=Response Evaluable 
Criteria in Solid Tumors; SD=stable disease; SN=severe neutropenia; 
Other objectives and endpoints of the study can be found in Section 5 of the protocol.  
1.3. 
Sample Size Consideration  
The initial sample size was calculated to support the primary objective of the study, that is, to 
evaluate trilaciclib’s effect on PFS when administered prior to sacituzumab govitecan-hziy in 
patients with locally advanced or metastatic TNBC who received at least 2 prior treatments with 
at least 1 in the metastatic setting.  
This single-arm study was initially planned to enroll 45 patients during the 10-month accrual 
period with an approximate 30-month total study duration. With 45 patients and 14 months of 
follow-up after the last patient is dosed, Table 2 presents the required number of PFS events and 
statistical powers to detect hazard ratios (HRs) of 0.7 and 0. 8 at a 2-sided significance of 0.2 for 
a median PFS of the historical control group of 5.6 months, which was defined for patients 
without brain metastases treated with sacituzumab govitecan-hziy in the Phase 3 ASCENT trial 
(Bardia, 2021). The calculation is based on a one-sample log-rank test (Wu, 2015) with the 


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assumption that the survival time distributions for both study treatment and historic control 
group follow the Weibull distribution with a shape parameter of 1.00 (i.e., exponential 
distribution). PASS 2019, v19.0.8 was used for the power and sample size calculation. 
 
Table 2 
Statistical Power 
Hazard 
Ratio  
Median PFS for 
trilaciclib + sacituzumab 
govitecan-hziy (Months)  
Expected number of 
events in the study  
Statistical Power  
0.70  
8.0  
36  
80%  
0.80  
7.0  
38  
54%  
 
On February 14, 2023, the sponsor decided to close enrollment to this study in order to reallocate 
resources to other ongoing trilaciclib clinical trials. The final sample size is 30. 


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2. 
THE NUMBER OF PLANNED ANALYSES 
 
2.1. 
Final Planned Analysis - Analyses for Progression Free Survival, 
Tumor Response Endpoints, Myelosuppression Endpoints, and 
Overall Survival 
The final planned analysis will be conducted when approximately 70% of patients have died 
(i.e., 21 deaths). Study database will be locked to support the final OS analysis. The following 
specified analyses will be performed: 
x Analysis of progression free survival.  
x Analysis of tumor response endpoints (ORR, CBR, and DOR).  
x Analysis of myelosuppression endpoints.  
x Analysis of overall survival. 
x Analysis of safety data.  
The final planned analysis will be used to support the abbreviated clinical study report (aCSR). 
 


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3. 
ANALYSIS POPULATIONS 
3.1. 
The Full Analysis Set 
The full analysis set (FAS) includes all enrolled patients who received at least one dose of study 
drug. Unless otherwise specified, the FAS is the primary analysis set for all efficacy analyses. 
3.2. 
The Response Evaluable Population 
The Response Evaluable (RE) population includes all patients who are in the FAS, have 
measurable (target) tumor lesion(s) at baseline tumor assessment per RECIST v1.1, and have 
either of the following:  
1. At least one post-baseline tumor assessment. 
2. Discontinued treatment because of clinical progression prior to the first post-baseline 
tumor scan. 
3. Died due to disease progression prior to the first post-baseline tumor scan.  
The RE population will be the primary population for efficacy endpoints evaluating tumor 
responses. 
3.3. 
The safety population 
The safety population includes all enrolled patients who received at least one dose of study drug. 
All safety analyses will be evaluated using the safety population. 


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4. 
GENERAL CONSIDERATIONS FOR DATA SUMMARY AND 
DISPLAY 
4.1. 
Treatment Group Descriptions and Display in Table, Listings and 
Figures 
This is a single-arm study in which all patients are treated with Trilaciclib + Sacituzumab 
govitecan-hziy. For TLFs that will be generated following SAP execution, the term overall will 
be used to describe all patients in the populations defined in Section 3.    
4.2. 
Data Summary and Precision 
General Principles of Data Summary 
Data will be summarized for the respective analysis populations described in Section 3 in table 
format. All summary tables will only include an overall column for patients. In general, 
continuous variables will be summarized descriptively, i.e., the following summary statistics will 
be presented:  
x Number of patients with non-missing data (indicated by n) 
x Mean and standard deviation 
x Median 
x Q1 (first quartile) and Q3 (third quartile) 
x Minimum and maximum values.  
Categorical variables will be summarized categorically, i.e., number (n) and percentage of 
patients in each category will be presented. 
General Principle of Data Listings 
All collected data and derived variables will be included in patient data listings. An indicator will 
be provided for any imputed data element (e.g., imputed adverse event [AE] onset date). 
Columns in listings will be ordered by study site, patient ID, visit, and assessment or event date, 
if applicable, and then data elements. 
General Principles of Precision for Summary Statistics and Calculated Statistical 
Quantities 
The precision of summary statistics for continuous variables, including mean, median, Q1, Q3 
minimum, and maximum, will be consistent with the precision of the variable as collected unless 
the collected data are integers. When the collected data are integers (whole numbers), the 
summary statistics of mean, median, Q1 and Q3 will be presented in the format with an 
additional digit after the decimal point. Calculated quantities of variability (e.g., standard 
deviation, standard error [SE]) will be presented with one more decimal place than the precision 
of the variable that is collected. The boundaries of a confidence interval (CI) will keep the same 
precision as the point estimate. The estimated adjusted relative risk will be reported with two 
decimal places. 
For percentages, the total digits will be 3. That is, when the percentage has 2 digits prior to the 


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decimal point, there will only be 1 decimal place (e.g., 30.5%); while for a percentage that has 
only 1 digit prior to the decimal point, 2 digits places will be presented after the decimal point 
(e.g., 0.16%). 
Rounding will take place after all calculation steps are completed prior to result display. 
4.3. 
Definitions for Analysis Related Timepoint and Time Interval 
Timepoint and time intervals related to efficacy and safety data collected during the treatment 
period will be summarized. For each specific category of data, the time interval by which the 
data will be analyzed or summarized will be specified in the respective section in which the data 
analysis plan is described.  
To clarify data inclusion for each time interval of interest and baseline or end values for each 
given time interval, Table 3 presents definitions for timepoints, timepoint related assessments, 
and time intervals involved in statistical data analysis or summary. 
Table 3 
Definitions for Timepoints, Timepoint Related Assessments and Time 
Intervals 
Term 
Definition 
Start of study (date) 
Date of first dose of any study drug  
Study baseline 
(assessment) 
The last non-missing value prior to or on the date of the first dose of 
any study drug at the time that is before the time of the first study 
drug administration. If the event occurs on the same day as date of 
first dose of study drug but does not have the exact time captured, 
the event is assumed to have occurred prior to the first dose of study 
drug. 
Day 1 of Cycle X 
(date) 
The date when the first dose of any study drug for cycle X is 
administered. Day 1 of Cycle 1 (C1D1) is the same as the start of 
study.    
End of a cycle (date) 
It is defined as Day 1 of the subsequent cycle if the cycle is not the 
last cycle. For the last cycle, it is defined as the date of the End of 
Treatment Visit (ETV). If the ETV does not occur for a patient, End 
of the last cycle will be defined as 14 days post the last dose of any 
study drug.  
Duration of a cycle 
(days) 
Total number of days from Day 1 of the cycle  to End of the cycle. 
That is, End of the cycle – Day 1 of the cycle + 1. 
Duration of study drug 
exposure (weeks)  
The total number of weeks from Day 1 of Cycle 1 to the End of the 
last cycle in the study. That is, (End of the last cycle –Day 1 of Cycle 
1 + 1) / 7. 
Duration of total  
follow-up (months) 
The total number of months from Day 1 of Cycle 1 to either the date 
of death or last contact date in the study known alive, inclusive. That 
is, duration of total follow-up=(date of death or date of last contact 
date known alive – Day 1 of Cycle 1 + 1) /30.4375. 


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4.4. 
Study Day 
Study Day will be calculated for an event date or an assessment date relative to date of first dose 
of any study drug to provide additional information for interpretation of the event occurrence. 
Study Day is calculated as:  
x The start date of the event (visit date, onset date of an event, assessment date etc.) – date of 
first dose of any study drug + 1, if the event occurred on or after the date of first dose of any 
study drug. The day of first dose of any study drug will be Study Day 1. 
x 7KHVWDUWGDWHRIWKHHYHQWYLVLWGDWHRQVHWGDWHRIDQHYHQWDVVHVVPHQWGDWHHWFídate of 
first dose of any study drug, if the event occurred prior to the date of first dose of any study 
drug. The day before the date of first dose of any study drug will be Study Day -1.  
4.5. 
General Principles of Missing Data Handling 
In general, the observed data are used for analyses or data summaries. That is, no missing 
imputation will be performed. However, imputation of missing onset or stop dates for AE and 
concomitant medication will be adapted to determine the status of each AE and the 
prior/concomitant/subsequent status of each non-study treatment medication. Please refer to 
Section 9.2.2 for the rules of imputation of missing AE onset or stop date and Section 5.4 for the 
rules of imputation of missing concomitant onset or stop dates. 
For demographic and baseline characteristics, continuous variables will be summarized based on 
non-missing observations with the number of patients with non-missing data indicated. For a 
categorical variable with missing data, a category of “Missing” will be included as a separate 
category for the summary. That is, the number and percentage of patients in each category of the 
variable (including “Missing”) will be summarized and reported with the number of patients in 
the FAS population as the denominator for the percentage calculation.  
For primary and secondary efficacy endpoints, handling of missing data is described in Section 
8.3.  
 
 


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5. 
DISPOSITION AND BASELINE CHARACTERISTICS 
5.1. 
Patient Disposition  
A summary of patient disposition will be generated using all accumulated data as of the database 
lock date.  
Patient disposition summary will include the following 4 major sections:  
1. Disposition of all screened patients who signed informed consent  
2. Study drug disposition for patients in the safety population 
3. Study disposition for patients in the FAS 
4. Deaths among patients in the FAS 
The specific details for each section are described below.  
1. Disposition of all screened patients  
The total number of screened patients who signed informed consent will be presented as two 
mutually exclusive groups: those who were screen failures and those who were enrolled. For 
those in the FAS, patients who received at least one dose of any study drug and those who did 
not are further presented. Unless otherwise stated, the number of patients in the FAS will be the 
denominator for calculating percentages of patients in each of these categories.  
2. Study drug disposition 
The disposition for each study drug (trilaciclib and sacituzumab govitecan-hziy) will be 
summarized for those who have discontinued the study drug. For patients who have discontinued 
the study drug, the primary reasons for study drug discontinuation will be presented with the 
percentage of patients in each reason being calculated based on the number of patients who 
discontinued the study drug.  
3. Entered Survival Follow-up 
The number and percentage of patients who entered survival follow-up during the study will be 
summarized. The number of patients in the FAS will be the denominator for the percentage 
calculation. 
4. Study disposition  
The number and percentage of patients who discontinued from the study will be summarized. 
The number of patients in the FAS will be the denominator for the percentage calculation. The 
primary reason for study discontinuation will also be summarized, and the number of patients 
who discontinued the study will be the denominator for the percentage calculation for each 
reason of discontinuation. 
5. Death 
The number and percentage of patients who died during the study will be summarized overall for 
the FAS along with the primary reason of death (Progressive Disease, Adverse Event, Other). 
The number of patients in the FAS will be the denominator for calculating percentages of death, 


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and the number of patients who died will be the denominator for calculating the percentage of 
patients within each reason for death. 
A summary of enrollment status of all screened patients will also be presented by site. 
Study drug and study disposition information will be provided in data listings for all enrolled 
patients.  
5.2. 
Demographics and Baseline Disease Characteristics 
Demographics and baseline disease characteristics will be summarized  for the final analysis. 
Demographics including age at screening visit, age group (18-65, > 65), sex at birth, child-
bearing potential, ethnicity, and race will be summarized for all enrolled patients. In addition, 
BMI, BSA and Eastern Cooperative Oncology Group (ECOG) score will be summarized. 
Further, baseline disease characteristics such as stage at screening and at diagnosis, 
histopathological grade and type at diagnosis, BRCA mutation, TNBC status, and PD-L1 status 
will be summarized for the FAS. 
Data listing for demographics and baseline disease characteristics will be provided for the FAS.  
5.3. 
Medical/Surgical History and Ongoing Conditions 
Medical history, surgical history, and ongoing conditions at the Screening Visit will be 
summarized for the final analysis. 
Non-breast cancer related medical history and ongoing medical conditions as collected at 
baseline will be coded using Medical Dictionary for Regulatory Activities (MedDRA) version 
26.1 or later, and then summarized. Medical history and ongoing conditions will be presented by 
system organ class (SOC) and preferred term (PT) with SOC and PT all sorted in descending 
frequency based on the overall column. A patient will only be counted once within a particular 
SOC (PT) even if the patient has multiple conditions/diseases in the same SOC (PT). 
In addition, a data listing for medical history and ongoing medical conditions collected at the 
Screening Visit will be provided for the FAS. Furthermore, a data listing for prior surgerical 
procedures and radiotherapies will be generated for the FAS. 
5.4. 
Prior and Concomitant Medications  
Concomitant, non-cancer medications will be summarized for the FAS population. Prior 
medications will be presented in a data listing.  
Concomitant medications are those protocol-permitted medications that were given during the 
time interval from the first dose of any study drug to the end of the last cycle. Medications 
collected through electronic case report forms (eCRFs) will be coded to Anatomical Therapeutic 
Classification (ATC) and PT, where applicable, using the most recent World Health 
Organization Drug Dictionary (WHO-DD) version WHODrug-Global-B3 202309.   
Concomitant medications will be summarized by ATC and PT and presented in a descending 
order of frequency for ATC and PT within an ATC based on the overall group. If a patient took 
multiple medications within the same ATC, the patient will only be counted once for that ATC. 


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Similar logic applies to PT summaries. The number and percentage of patients receiving any 
concomitant medications will be summarized overall.  
Handling of Missing Start and/or End Date for Medications Entered into EDC 
Medications with incomplete start and/or end dates will be imputed according to the 
specifications described below. Those with incomplete start and/or end dates will be assumed to 
be concomitant if it cannot be shown that the medication was not taken outside of the treatment 
period.  
For completely missing or partially missing start dates: 
x If the start date has month and year but day is missing, the first dose date of any study 
drug will be used if the month and year is the same as the first dose date of any study 
drug, otherwise, the first day of the month will be used. 
x If the start date has year, but day and month are missing, then the first dose date of 
any study drug will be used if the year is the same as the first dose date of any study 
drug, otherwise January 1st will be used. 
x If the start date is completely missing, then it will be imputed as the first dose date of 
any study drug. 
After the imputation, the imputed start date will be compared with corresponding stop date, if 
available. If the imputed start date is later than the stop date, the start date will be imputed with 
the stop date instead. 
For completely missing or partially missing stop dates for concomitant medications that are not 
ongoing at the time of data cutoff: 
x If the stop date has month and year but day is missing, the last day of the month will 
be used. 
x If the stop date has year, but day and month are missing, December 31st will be used.  
x If the stop date is completely missing, the last dose date of any study drug will be 
used.  
After the imputation, the imputed stop date will be compared against the death date for patients 
who died. If the date is later than the death date, the date of death will be used to impute the stop 
date instead. 
Prior and concomitant medications will be listed with an indicator for prior or concomitant.  
5.5. 
Summary of Protocol Deviations  
5.5.1. 
Definitions and Process for Identifying Protocol Deviations  
Protocol deviation refers to situations where a patient’s eligibility for study entry or a specific 
data collection deviate from the entry criteria or study procedure as specified in the protocol. 
Protocol deviation cases at the patient level with specific data elements of concern need to be 
summarized and reported in the CSR. Protocol deviations will be categorized as major or minor. 
Major protocol deviations are those that could affect the integrity of the data or adversely affect 


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patients’ safety. Criteria that define major or minor protocol deviations will be specified, 
documented, and signed off on prior to study database lock. Specifically, a protocol deviation 
specifications document that describes the criteria defining major and minor protocol deviations, 
the categories of major protocol deviations, and the list of patients who had at least one protocol 
deviation case with the classification of major or minor will be created and signed off prior to 
study database lock.  
5.5.2. 
Summary of Protocol Deviations   
A protocol deviation summary will be generated for the final analysis. 
The number and percentage of patients in the FAS population with protocol deviations will be 
tabulated for each of the following categories.  
x Patients with at least one protocol deviation (major or minor)  
x Patients with at least one major protocol deviation  
x Patients with at least one protocol deviation in each of the major deviation categories  
Protocol deviations will be listed with details and flags indicating major or minor for the FAS 
population. 


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6. 
CLASSIFICATION OF PRIOR, CONCOMITANT, AND 
SUBSEQUENT ANTICANCER THERAPIES 
Prior therapies refer to those anticancer treatments that patients received prior to the first dose 
date of any study drug, including radiotherapies, surgical procedures, and systemic anticancer 
therapies.  
Concomitant therapies refer to those treatments, other than study drugs, that could be utilized 
concurrently with study drug(s) as specified in the protocol. That is, the therapies that were given 
in the time interval from the first dose of any study drug to the end of the last cycle 
Subsequent therapies refer to anticancer treatments received following investigational study drug 
discontinuation while the patient was still in the study (i.e., in the Survival Follow-up period).   
The rules of imputation of missing onset or stop dates for medications described in Section 5.4 
are, in general, applicable for missing onset or stop dates imputation for anticancer therapies in 
any format (radiotherapies, surgical procedures, or systemic anticancer therapies). 
6.1. 
Prior Anticancer Therapies 
Summaries of prior anticancer therapieswill be generated for the final analysis based on the FAS 
population. Prior therapies in the adjuvant context will be excluded from the analysis in this 
section. 
The number and percentage of patients with any prior anticancer therapies will be summarized 
for the FAS population. The number and percentage of patients with any prior radiotherapies, 
any prior surgical procedures that were related to breast cancer, and any prior systemic 
anticancer therapies will also be summarized. Prior systemic anticancer therapies will then be 
further summarized based on ATC and PT and presented in a descending order of frequency for 
ATC and PT withing an ATC based on the overall group.  
Data listings will be produced for all prior anticancer therapies, including detailed information 
related to prior systemic anticancer therapies such as setting, regimen, start/stop dates, and 
detailed information related to prior surgical procedures and radiotherapies for the FAS 
population. 
6.2. 
Concomitant Anticancer Therapies 
Summaries for concomitant anticancer therapies will be generated for the FAS population at the 
final analysis.  
The number and percentage of patients receiving any concomitant anticancer surgical procedures 
or radiotherapies that were related to disease under study will be summarized..  
Detailed information for concomitant surgical procedures and radiotherapies will be included in 
the data listing for the FAS population. 
6.3. 
Subsequent Systemic Anticancer Therapies 
Subsequent anticancer treatments (SACT) will be summarized for the FAS population at the 
final  analysis. 


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The number and percentage of patients receiving at least one SACT in any modality (systemic 
anticancer therapies, surgical procedure, or radiotherapy) as well as for each of the modalities 
will be summarized.  
In addition, for the subsequent systemic anticancer therapies, the total number of lines of therapy 
will be summarized both descriptively and categorically. The number of patients who had at least 
one dose of any systemic anticancer therapies will be the denominatorfor percentage calculation..  
Furthermore, the number and percentage of patients with any subsequent systemic anticancer 
therapies will be summarized based on ATC and PT and presented in a descending order of 
frequency for ATC and PT within an ATC.The best overall response to each subsequent line of 
therapy and disease progression status as collected will be presented in data listings.   
Handling of Missing Start Date for SACT 
SACTs with incomplete start dates will be imputed for the purpose of censoring ORR, CBR, 
DOR, and PFS, due to start of SACTs. The rules of imputations are described below. 
For completely missing or partially missing start dates:  
 
x If the start date has month and year but day is missing, the date of discontinuation of last 
study drug will be used if the month and year is the same as the date of discontinuation of 
last study drug, otherwise, the first day of the month will be used.  
 
x If the start date has year, but day and month are missing, then the date of discontinuation 
of last study drug will be used if the year is the same as the date of discontinuation of last 
study drug, otherwise January 1st will be used.  
 
x If the start date is completely missing, then it will be imputed as the date of 
discontinuation of last study drug.  
 
Corresponding data listings will be provided for the FAS population. 
 
 


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7. 
STUDY DRUG EXPOSURE, DOSE INTENSITY AND 
MODIFICATION  
Analyses described in this section will be based on the safety population unless otherwise 
specified. 
7.1. 
Duration of Study Drug Exposure  
Duration of study drug exposure (weeks) is defined as the duration from Day 1 of Cycle 1 to the 
End of cycle for the last cycle. That is, duration of drug exposure (weeks) = (End of cycle for the 
last cycle in the study – Day 1 of Cycle 1 + 1)/7, where the definitions for End of cycle for the 
last cycle and Day 1 of Cycle 1 are provided in Table 3. 
The duration of study drug exposure will be summarized at the final analysis. The total number 
of cycles that a patient received will be summarized as a continuous variable, as well as a 
categorical variable. That is, descriptive summary statistics will be provided for the total number 
of cycles that patients received, and the number and percentage of patients that received exactly 
0, 1, 2…, to the maximum number of cycles will also be summarized.  
Corresponding data listings will be provided.  
7.2. 
Cumulative Dose and Dose Intensity 
Dose administration parameters will be summarized at the final analysis.  
The definitions for cumulative delivered dose, delivered dose intensity, relative cumulative dose, 
and relative dose intensity at the patient level, along with other parameters involved in the 
calculation of these variables are presented in Table 4. All collected dose information will be 
used in the calculation.  
The calculated cumulative delivered dose, delivered dose intensity, relative cumulative dose, and 
relative dose intensity will be summarized as continuous variables.  
All variables described in Table 4 will be included in the data listing except for the study drug 
administration schedule. 


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Table 4 
Dose Administration Parameters for Study G1T28-213 
Parameter 
Meaning  
Trilaciclib  
Sacituzumab govitecan-hziy  
Study drug 
administration schedule   
Drug dose and schedule 
per protocol 
240 mg/m2 IV on Day 1 and Day 8 
of a 21-day cycle 
10 mg/kg IV administered on Day 1 and 
Day 8 of each 21-day cycle.  
Cumulative delivered 
dose [Unit] 
Sum of doses over the 
duration of the study drug 
administration  
Sum of doses over the duration of 
trilaciclib administration [mg/m2]* 
Sum of doses over the duration of 
sacituzumab govitecan-hziy 
administration [mg/kg] 
Delivered Dose  
Intensity [Unit] 
Cumulative dose 
administered per week  
Cumulative dose (mg/m2) / duration 
of study drug exposure in weeks 
[(mg/m2/week)] 
Cumulative dose (mg/kg) / duration of 
study drug exposure in weeks 
[(mg/kg/week)] 
Relative cumulative 
dose (%) 
Cumulative delivered dose 
over cumulative 
prescribed dose   
 [Cumulative delivered dose (mg/m2) 
/ (240 × 2 × number of cycles) 
(mg/m2)]*100 
 [Cumulative delivered dose (mg/kg) / (10 
× 2 × number of cycles) (mg/kg)]*100 
Relative dose intensity 
(%) 
Delivered dose intensity 
over prescribed dose 
intensity  
[Delivered dose 
intensity/(480/3)]*100 
[Delivered dose intensity/20/3]*100 
* Actual doses administered were collected in unit of mg on the eCRF. For calculation of cumulative delivered dose and delivered dose intensity, the actual dose 
administered at any visit will be derived as actual dose (mg) divided by BSA (m2) from the same visit. If BSA value from a visit is missing, it will be imputed 
as BSA from the previous visit. If BSA value from C1D1 is missing, it will be imputed as BSA from Screening Visit. If BSA from Screening Visit and C1D1 
are both missing, BSA value at C1D1 will be imputed as 1.7 m2.  
IV = intravenous. BSA = body surface area. C1D1 = Cycle 1 Day 1. 


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7.3. 
Study Drug Modifications 
Study drug modifications will be summarized at the final analysis.  
There are three types of study drug modification: dose reduction, cycle delay, and infusion 
interruption. The number of protocol-permitted dose reductions for each study drug are 
summarized in Table 5.  
Table 5 
Protocol Permitted Dose Reduction by Study Drug 
Study Drug 
Number of Dose Reductions Allowed 
Trilaciclib/placebo 
0 
Sacituzumab govitecan-hziy 
2 
Study drug modifications will be summarized in each of the following categories: chemotherapy 
dose reduction, treatment cycle delay, and infusion interruption. The number and percentage of 
patients who had any chemotherapy dose reduction, any cycle delay, cycle delay due to 
hematological toxicity, or any infusion interruption will be summarized.  
In addition, more detailed summaries outlined below will be provided. 
Dose reduction for Sacituzumab govitecan-hziy. For Sacituzumab govitecan-hziy, the number 
and percentage of patients who had at least one dose reduction will be summarized. In addition, 
the number and percentage of patients will be summarized in the following mutually exclusive 
categories: “Not Applicable (cycle 1 treatment only)”, 0, 1, or 2 reductions for the drug. The 
primary reason for dose reduction will be summarized. 
Cycle delay. Information regarding whether a cycle was delayed was collected in the eCRF for 
each cycle. The number of cycles that have been delayed will be summarized as a continuous 
variable. In addition, the number and percentage of patients in each of the following mutually 
exclusive categories will be summarized: “Not Applicable (cycle 1 treatment only)”, 0, 1, 2, …, 
maximum number of delays.  
The reasons for cycle delay collected in eCRF are as follows:  
x 
Low neutrophil count  
x 
Low platelet count  
x 
Both low neutrophil count and low platelet count  
x 
Other hematologic toxicity  
x 
Non-hematologic toxicity  
x 
Other  
Patients with reasons entered in the “Other” category will be further classified based on medical 
review of comments collected on the eCRFs into finer categories as appropriate. 
Infusion interruption. Infusion interruption was captured in the eCRF for each study drug with 
the reasons. Any infusion interruption is defined as infusion interruption of any study drug. 
The number of any and trilaciclib infusion interruptions will be summarized descriptively and 
categorically.  
Corresponding data listings will be provided for dose modifications.  


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7.4. 
Duration of Total Follow-up 
Duration of total follow-up will be summarized for the final analysis.  
Duration of total follow-up (months) refers to the time interval that a patient participated in this 
clinical study starting from date of C1D1. It will be calculated based on the definition provided 
below.     
Duration of total follow-up (months) = (date of death or date of last contact date known as alive 
– date of C1D1 + 1) /30.4375. 
The summary statistics for this variable will be included in the summary table for the OS 
analysis, and the patient level data will be included in the data listing described in Section 8.2.2. 
 


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8. 
EFFICACY ANALYSIS 
All efficacy analyses will be performed for the FAS population, unless specified otherwise. 
The primary efficacy endpoint for this study is the treatment effects on PFS. PFS and other 
efficacy endpoints related to tumor response (ORR, CBR, and DOR) and myeloprotection 
efficacy will also be evaluated based on data collected during the treatment period (see Section 
2.1). 
The treatment effect on OS will be evaluated when the number of events specified in Section 2.1 
are observed for OS. The clinical database will be locked for this analysis. At the time of the 
final planned analysis, all other efficacy analyses outlined for the study will also be conducted.   
8.1. 
 Definitions of Efficacy Endpoints 
8.1.1. 
Primary Efficacy Endpoints – Progression Free Survival 
Progressive disease (PD) and tumor response status are programmatically determined according 
to RECIST v1.1 based on the radiographic tumor assessment data recorded on the eCRF by the 
Investigator for target lesions, the investigator assessment of non-target lesions, and the status of 
new lesions. For a patient, the status of PD will be determined using all radiographic tumor scan 
data assessed prior to or on the date of the data cutoff to conduct the analysis for PFS. In the 
situation where PD and withdrawal of consent or PD and initiation of subsequent anticancer 
therapy occurred on the same day for a patient, the PD status will be assumed for that patient. 
Radiographic PD and death due to any cause during the study are referred to as PFS events.  
PFS is defined as the time (months) from date of C1D1 to the date of the first documented 
disease progression, or death in the absence of PD for those who had a PFS event, and the time 
from date of C1D1 to the censoring date for those who did not have a PFS event. Specifically, 
PFS is calculated as (date of PFS event or censoring – date of C1D1+ 1)/ 30.4375. The analysis 
for PFS will be based on the FAS. 
Details for PFS calculation and censoring rules can be found in Table 6.  


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Table 6 
PFS Calculation and Censoring Rules 
Situation 
Date of Event or Censoring 
Outcome 
Disease progression per 
RECIST Version 1.1 
Date of the first documented 
progression 
PFS event 
Death without a PD 
Date of death 
PFS event 
Incomplete or no baseline 
tumor assessments 
Date of C1D1 
Censored 
No progression 
Date of the last adequate 
radiological tumor assessment 
with no documented disease 
progression 
Censored 
Treatment discontinuation for 
reasons other than disease 
progression 
Date of the last adequate 
radiological tumor assessment 
with no documented progression 
Censored 
Subsequent anticancer 
treatment started prior to 
documented disease 
progression 
Date of last adequate radiologic 
assessment prior to or the date 
of initiation of subsequent 
anticancer treatment 
Censored 
8.1.2. 
Secondary Efficacy Endpoint – Anti-tumor Efficacy Endpoints  
The secondary anti-tumor endpoints include the following, which will be calculated and reported 
at the final analysis:  
x Best overall response (BOR) 
x Objective response rate (ORR) 
x Clinical benefit rate (CBR) 
x Duration of confirmed objective response (DOR) 
The analysis of these endpoints will be based on the RE population. Tumor scan data collected 
during the study will be the basis to classify tumor response status for patients in the RE 
population.  
At each tumor assessment visit, an overall timepoint response by RECIST v1.1 will be 
determined programmatically using the measurements recorded on the eCRF by the Investigator 
for target lesions, the Investigator assessment of non-target lesions, and records of new lesions.  


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If a patient has all or some of the following records prior to the final database lock, the earliest 
date of those will be used to determine the inclusion of tumor scan data for response status 
derivation: (i) radiographic disease progression; (ii) withdrawal of consent to obtain scans; (iii) 
death; (iv) lost to follow-up; or (v) initiation of subsequent anticancer therapy.  
Best Overall Response  
BOR categorizes a patient’s tumor response status into one of following mutually exclusive 
categories per RECIST v1.1: Complete Response (CR), Partial Response (PR), Stable Disease 
(SD), Progressive Disease (PD), and Not Evaluable (NE). The minimum duration of stable 
disease must be 5 weeks starting from the date of Cycle 1 Day 1 (the protocol scheduled tumor 
assessments is every 6 weeks for the first 36 weeks following Cycle 1 Day 1 (±7 days) and every 
9 weeks thereafter (±7 days)).  
Objective Response Rate 
Achieving an objective response for a patient is defined as having a CR or PR as the BOR. 
Objective response rate is defined as the proportion of the patients who achieved objective 
response on the RE population.  
Confirmed Objective Response Rate 
Confirmed CR or PR will be derived based on the principle described in RECIST v1.1. In the 
derivation, the minimum interval for confirmation of CR or PR is 4 weeks, and the minimum 
duration of treatment is 5 weeks (the protocol scheduled tumor assessments is every 6 weeks for 
the first 36 weeks following Cycle 1 Day 1 (±7 days) and every 9 weeks thereafter (±7 days)). 
Confirmed ORR (confirmed CR or PR) is defined as the proportion of the patients who achieved 
confirmed objective response. 
Clinical Benefit Rate 
Clinical benefit rate is defined as the proportion of patients with BOR of confirmed CR, 
confirmed PR, or SD lasting 24 weeks or longer, based on the RE population.  
Duration of Confirmed Objective Response  
DOR is calculated for patients who achieved confirmed CR or PR as the BOR status. It is 
defined as the time (months) from the date when the objective response of CR or PR was first 
documented to the date that radiographic progressive disease is documented, or death, whichever 
comes first. That is, DOR = (Date of documented disease progression or death – date of first 
documented CR or PR + 1)/30.4375.  
Censored DOR follows the same rules as the censoring rules for PFS (see Table 6).  
8.1.3. 
Secondary Efficacy Endpoint – Analysis for Overall Survival 
Overall survival is defined as the time (months) from the date of C1D1 to the date of death for 
patients who died in the study due to any cause or the time to the last contact date known to be 
alive for those patients who survived as of the final database lock for the final analysis (censored 
cases). OS will not be censored even if a patient receives subsequent anticancer treatments. 
The analysis for OS will be based on the FAS. 


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8.1.4. 
Secondary Efficacy Endpoint – Myeloprotection Efficacy Endpoints 
Secondary myeloprotection endpoints that are defined to assess trilaciclib’s effect on multiple 
lineage protection during the treatment period are described in Table 7 by lineage (i.e., 
neutrophils, and red blood cells [RBCs]). Endpoints that evaluate trilaciclib’s impact on study 
drug delivery during the treatment period are also described in Table 7.  
Unless otherwise specified, all endpoints described in Table 7 are derived based on data 
collected through scheduled and unscheduled visits during the treatment period. 
Table 7 
Myeloprotection Endpoints 
 
Lineage  
Endpoint 
Type of 
Variable 
Neutrophils 
Occurrence of severe neutropenia (during cycles 1/2 and overall 
study) 
Binary 
Occurrence of febrile neutropenia 
Binary 
Occurrence of G-CSF administration 
Binary 
RBCs 
Occurrence of Grade 3 or 4 decreased hemoglobin  
Binary 
Dose Modifications 
Occurrence of SG dose reduction 
Binary 
Number of SG dose reductions (event rate per 100 cycles) 
Counting 
Occurrence of cycle delay due to hematologic toxicity  
Binary 
Number of cycle delays due to hematologic toxicity (event rate 
per 100 cycles) 
Counting 
G-CSF=granulocyte colony stimulating factor; RBC=red blood cell, SG= sacituzumab govitecan-hziy.. 
8.1.4.1. 
Neutrophil-Related Endpoints 
Occurrence of Severe Neutropenia (during Cycles 1/2 and overall study) 
Occurrence of Severe Neutropenia (Grade 4 neutropenia) for a patient is defined as having as 
least one ANC value < 0.5 × 109/L among all ANC measurements regardless of scheduled or 
unscheduled visits. Occurrence of Severe Neutropenia is a binary random variable (Yes or No).  
Occurrence of Febrile Neutropenia 
FN is an AE as reported by the Investigator and captured in the eCRF. A PT term of FEBRILE 
NEUTROPENIA is used to identify a FN event. The occurrence of FN for a patient is defined as 
having at least one FN event and is a binary random variable (Yes or No). 
Occurrence and Number of Granulocyte Colony Stimulating Factor (G-CSF) Administrations 
Administration of G-CSF is collected throughout treatment period. Cycles where G-CSF was 
administered will be identified by comparing the start and stop dates of each administration of G-
CSF to cycle interval. If any of the time intervals in which G-CSF was administered overlapped 
with any dates between the start of a cycle and the end of the cycle, that cycle will be considered 
as having a G-CSF administration. Data handling conventions for missing start and stop dates are 
described in Section 5.4. 


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The occurrence of G-CSF administration for a patient is defined as having at least one cycle in 
which G-CSF was administrated for the patient. It is a binary random variable (Yes or No).  
The number of cycles with G-CSF administrations for a patient is the total number cycles where 
the patient received at least one dose of G-CSF. For patients who did not have any G-CSF use 
and those who were enrolled but did not receive any study treatment, the value of 0 will be 
assigned.  
8.1.4.2. 
RBC-Related Endpoints 
Occurrence of Grade 3 or 4 Decreased Hemoglobin  
Occurrence of Grade 3 or 4 decreased hemoglobin (Hgb) for a patient is defined as having at 
least one Hgb value that was < 8.0 g/dL among all scheduled or unscheduled assessments. It is a 
binary random variable (Yes or No).  
8.1.4.3. 
Dose Modifications 
Occurrence and Number of SG Dose Reduction  
The occurrence of a dose reduction for a patient is defined as having at least one dose reduction 
of SG in a cycle. Occurrence of SG dose reduction is a binary random variable (Yes or No). 
Number of SG dose reductions for a patient is defined as the total counts of SG dose reductions. 
In addition, SG that was permanently discontinued due to toxicity will be also counted as a dose 
reduction event. The value of 0 will be assigned to those patients who did not have any SG dose 
reductions. Number of SG dose reductions is a counting random variable and the summary 
statistics for this variable is event rate per 100 cycles. 
Occurrence and Number of Cycle Delays Due to Hematologic Toxicity 
Occurrence of cycle delays and the associated reason is collected in detail in the eCRF with the 
following mutually exclusive categories: Low neutrophil count, Low platelet count, Both low 
neutrophil count and low platelet count, Other hematologic toxicity, Non-hematologic toxicity, 
or Other. A cycle that was marked as delayed with the reason of Low neutrophil count, Low 
platelet count, Both low neutrophil count and low platelet count, or Other hematologic toxicity is 
considered a delay due to hematologic toxicity.  
Occurrence of cycle delays due to hematologic toxicity for a patient is defined as having at least 
one cycle delay due to hematologic toxicity and is a binary random variable (Yes or No). The 
number of cycle delays due to hematologic toxicity for a patient is defined as the total number of 
cycles that were delayed due to such reason for the patient during the treatment period. For 
patients who did not have any cycle delays due to hematologic toxicity, the value of 0 will be 
assigned. Number of cycle delays due to toxicity is a counting random variable and the summary 
statistics for this variable is event rate per 100 cycles. 
The analysis of myeloprotection endpoints will be based on the FAS population. 


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8.2. 
 Statistical Analysis Methods  
8.2.1. 
General Considerations for Efficacy Analysis 
Unless otherwise specified, the analyses of the treatment effect on PFS, OS and myeloprotection 
endpoints will be based on the FAS population.  Tumor response analyses including ORR, CBR 
and DOR will be based on the RE population.  
8.2.2. 
Analysis for Progression Free Survival (PFS) and Overall Survival 
For PFS, the number and percentage of patients with a PFS event (radiographic disease 
progression or died due to any cause) or censored will be summarized along with the reasons for 
censoring. Furthermore, the number and percentage of patients with disease progression or who 
died due to any cause will be summarized with the number of PFS events as the denominator for 
percentage calculation. For OS, the number and percentage of patients who died or are censored 
will be summarized. In addition, duration of total follow-up will also be summarized. 
Kaplan-Meier plots will be generated and the median, 25% and 75% percentile of PFS and OS 
will be estimated using the Kaplan-Meier method with their corresponding 95% confidence 
interval calculated based on the method by Brookmeyer and Crowley (1982). Additionally, 
Kaplan-Meier estimates will be provided for the survival probability along with their 95% 
confidence intervals (Kalbfleisch, 1980) at selected landmarks of 12, 18, and 24 months for PFS 
and OS. 
Data listings will be generated for PFS and OS, respectively. Tumor scan data will be included in 
the PFS data listing, while the duration of total follow-up will be included in the OS data listing. 
For each listing, detailed information supporting the calculation of PFS (or OS) along with the 
censoring indicator, and reasons for censoring will also be included. 
8.2.3. 
Analysis for Secondary Endpoints - Anti-tumor Efficacy Endpoints 
The analysis for BOR, CBR, and ORR (see variable definitions in Section 8.1.2) will be based on 
the RE population.  
Tumor response status classified by BOR will be tabulated with the number and percentage of 
patients in each category of CR, PR, SD, PD or NE, where the percentages are calculated based 
on the number of patients in the RE population. 
ORR along with its exact 95% two-sided CI using the Clopper-Pearson method will be 
computed.  
Confirmed ORR and CBR will be summarized and analyzed using the same methods as are used for 
the ORR. 
For patients who achieved CR or PR as BOR status, DOR will be analyzed. The Kaplan-Meier 
method will be used to estimate the median, 25% and 75% percentile of DOR, along with its 
95% CI calculated using the method by Brookmeyer and Crowley (1982).  
Data listings will include tumor scan data, Investigator determined timepoint responses and 
BOR, and programmatically derived tumor response status, and confirmed tumor response status. 


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8.2.4. 
Analysis for Secondary Endpoints - Myeloprotection Endpoints 
Statistical analysis methods for myelosuppression endpoints derived based on data collected 
during the treatment are described in this section. No corresponding data listings will be 
provided.  
8.2.4.1. 
Analysis for Binary Myelosuppression Endpoints 
For each binary myelosuppression endpoint as specified in Table 7 (Section 8.1.4), the number 
and percentage of patients with at least one occurrence during the treatment period will be 
summarized.  
8.2.4.2. 
Analysis for Counting Myelosuppression Endpoints 
For the counting myelosuppression endpoints as specified in Table 7 (Section 8.1.4), the total 
number of the events, and raw event rate per 100 units (weeks or cycles) will be summarized.   
8.3. 
Handling of Missing Data 
In general, the observed data will be used for analyses or data summary. That is, no missing data 
imputation will be performed.  
Missing data impact on time-to-event endpoints, including primary endpoint PFS, is in general 
managed by derivation rules (Section 8.1).  
 


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9. 
SAFETY ANALYSIS 
9.1. 
General Consideration of Safety Analysis 
Safety data summaries will be based on the safety population as defined in Section 3.3 of this 
SAP.  
Safety data collected during treatment will be summarized at the final analysis.  
Safety and tolerability will be assessed by AEs, laboratory tests, vital signs and ECG. Safety data 
will be summarized using descriptive statistics for all patients when appropriate. All safety data 
collected through scheduled and non-scheduled visits during the treatment period will be 
included in the safety data analyses. The treatment period for a patient is defined as the time 
interval from date of C1D1 to the date of End of Treatment (EOT) visit. If the EOT visit does not 
occur for the patient, then 14 days post the last dose in the last cycle will be used as the end date 
of treatment. Missing safety data will generally not be imputed, unless otherwise specified.  
Baseline assessment is, in general, defined as the last non-missing observation prior to receiving 
the first dose of any study drug.  
9.2. 
Adverse Events  
9.2.1. 
Definition and Classification of Adverse Events 
AEs are defined as those AEs occurring on or worsening in severity after the first dose of any 
study drug (i.e., the conventional treatment-emergent AEs). Only AEs as described above are 
collected in the study database. All AEs are reported since the first dose of any study drug until 
end of safety follow-up (30 days after the last dose of study drug). SAEs thought to be related to 
a study specific procedure are also collected between the time the patient signs the informed 
consent and the first dose of any study drug.  
AEs will be coded from verbatim text to PT and grouped by primary SOC according to 
MedDRA version 26.1 or later. The severity (toxicity grades 1-5) of AEs will be graded 
according to the NCI CTCAE version 5.0 by the Investigator.  
Hematologic Adverse Events 
AEs related to hematologic toxicity will be collapsed based on the PTs from MedDRA 
version 26.1 or later and will be summarized separately (see Section 9.2.3). Table 8 outlines 
those PTs that will be collapsed.  
Table 8 
Hematologic Preferred Terms to be Collapsed 
Term presented in the Output  
Preferred Term 
Neutropenia 
Neutropenia 
 
Neutrophil count decreased 
Anemia 
Anemia 
Anaemia 
Red blood cell count decreased 


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Term presented in the Output  
Preferred Term 
Hemoglobin decreased 
Thrombocytopenia 
Thrombocytopenia 
 
Platelet count decreased 
Lymphocytopenia 
Lymphocytopenia 
 
Lymphopenia 
 
Lymphocyte count decreased 
Leukopenia 
Leukopenia 
 
White blood cell count decreased 
Trilaciclib Adverse Events of Special Interest 
AEs of special interest (AESI) for trilaciclib have been identified, reflecting either the findings in 
the AEs from the previous studies of trilaciclib or class effects for CDK 4/6 inhibitors. AESI for 
trilaciclib will be identified by searching MedDRA PTs based on the Customized MedDRA 
Queries as detailed in Appendix 2.  
Specifically, trilaciclib AESI include the following 5 categories: 
x Injection site reaction/Phlebitis/Thrombophlebitis 
x Acute drug hypersensitivity reaction 
x Hepatotoxicity 
x Interstitial lung disease /Pneumonitis 
x Embolic and thrombotic events, venous 
9.2.2. 
Imputation Rules for Missing Start or Stop Date for Adverse Events 
 
AEs with start/stop dates that are partially or completely missing that are not ongoing at the time 
of data cutoff will be imputed according to the specifications below in order to classify AEs. 
For completely missing or partially missing AE start date: 
x If the start date has month and year but day is missing, the first dose date of any study 
drug will be used if the month and year is the same as the first dose date, otherwise, 
the first day of the month will be used. 
x If the start date has year, but day and month are missing, then the first dose date of 
any study drug will be used if the year is the same as the first dose date, otherwise 
January 1st will be used. 
x If the start date is completely missing, then it will be imputed as the first dose date of 
any study drug. 


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After the imputation, the imputed start date will be compared with AE stop date, if available. If 
the imputed start date is later than the stop date, the start date will be imputed with the stop date 
instead. 
For completely missing or partially missing AE stop dates: 
x If the stop date has month and year but day is missing, the last day of the month will 
be used. 
x If the stop date has year, but day and month are missing, December 31st will be used.  
x If the stop date is completely missing, the date of EOT visit will be used; if EOT visit 
does not exist, then the last dose date + 14 days will be used. 
After the imputation, the imputed AE stop date will be compared against the death date for 
patients who died. If the date is later than the death date, the date of death will be used to impute 
the stop date instead. 
Every attempt will be made to obtain complete information for AEs regarding severity 
(i.e., CTCAE Grade) and relationship to drug. However, in the rare case of missing data, the 
following conservative approach will be taken for summary purpose. The non-imputed raw data 
will be presented in AE listings. 
x Missing AE grade will be classified as “Grade 3”  
x Missing AE relationship will be classified as “Related”  
9.2.3. 
Analysis for Adverse Events 
AEs will be summarized by number and percentage of patients having at least one occurrence at 
the PT and SOC level overall. Patients with more than one occurrence of the same SOC (PT) will 
be counted only once within the SOC (PT) categorization. In general, the percentage of patients 
with an event will be calculated using the number of patients in the safety population as the 
denominator.  
AEs will also be summarized by CTCAE grade and relationship to study drug (to any study 
drugs and to each individual study drug). Should a patient experience more than one occurrence 
of the same SOC (PT), the patient’s worst occurrence (highest grade or highest related causality) 
will be used for the analysis and reporting.  
In AE summaries, the SOC and PT within a SOC will be presented in descending order based on 
the incidence from all patients. If the incidence for two or more PTs is equal, these PTs will be 
presented in an alphabetical order.  
An overall AE summary table will be generated to present general information related to AEs 
including the following categories: number and percentage of patients with any AE, Serious 
AEs, AEs with CTCAE Grade 3 or 4, AEs leading to discontinuation of any study drug, AEs 
leading to death, AEs related to study drug (to any study drug, to trilaciclib/placebo, and to each 
other study drug), and AESI for trilaciclib/placebo.  
In addition, the following summary tables will be generated, and they will be, in general, 
presented by SOC and PT unless otherwise specified.   


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1. AEs by decreasing frequency of PT 
2. AEs by SOC, PT, and CTCAE Grade 
3. AEs with CTCAE Grade 3 or 4 by SOC and PT 
4. AEs leading to discontinuation of any study drug  
5. AEs leading to death 
6. AEs related to any and each study drug  
7. Hematological AEs by collapsed PT and CTCAE grade  
8. Serious AEs 
9. Serious AEs related to any and each study drug  
10. AESI for trilaciclib 
In the above, hematological AEs will be reported as they are with the exception of item 7 
(Hematological AEs by collapsed PT and CTCAE grade), for which the collapsed terms as 
specified in Table 8 (Section 9.2.1) will be reported.  
Corresponding AE listings will be provided to clearly indicate, at the patient level, the AE and 
SAE occurrence, start/stop date, relative study days to onset or stop, grade and causality for each 
AE. AESI for trilaciclib/placebo will also be listed with a similar level of detail.  
9.3. 
Clinical Laboratory Data 
9.3.1. 
Laboratory Parameters 
Blood and urine samples for the determination of clinical chemistry, hematology, and urinalysis 
laboratory variables described in Table 9 will be measured according to Schedule of 
Assessments in Appendix 1. 
Table 9 
Laboratory Categories and Parameters 
Lab Category 
Lab Parameters 
Chemistry 
albumin, alkaline phosphatase (ALP), total bilirubin, calcium, chloride, creatinine, 
glucose, inorganic phosphorus, potassium, total protein, alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), sodium, 
blood urea nitrogen (BUN) 
Hematology 
hemoglobin, white blood cell (WBC), platelet counts, absolute neutrophil count 
(ANC), absolute lymphocyte count (ALC) 
Urinalysis 
semiquantitative dipstick: specific gravity, pH, evaluation of glucose, protein, 
bilirubin, ketones, leukocytes, and hemoglobin microscopic examination, including 
red blood cell (RBC), white blood cell (WBC), and casts will be performed, if 
necessary 
Lab = laboratory.  


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For hematology parameters, if absolute counts are not provided, those values will be derived 
from the differential counts by multiplying differential value with leukocyte value from the same 
sample. The normal ranges will be left missing in those cases.  
Clinical chemistry and hematology assessments will be graded according to NCI CTCAE 
criteria, Version 5.0 or later. The determination of CTCAE grade for each measurement will be 
based on the collected laboratory values and will not involve clinical judgement. For laboratory 
parameters that CTCAE toxicity grade are not available, they will not be included in the analyses 
in which toxicity grades are reported. Instead, these parameter results will be classified and 
reported by the low/normal/high based on the laboratory normal reference ranges.  
Abnormal Hepatic Laboratory Values 
Abnormal hepatic laboratory values are defined in the following categories including any 
occurrence among all on-treatment, post-baseline assessments including scheduled and 
unscheduled values.  
x Hy’s Law:  
o Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 
3x the upper limit of normal (ULN), alkaline phosphatase (ALP) < 2xULN, and 
WRWDOELOLUXELQ[8/1 
o Preexisting baseline ALT, AST, OR total bilirubin values above the upper limit of 
normal, and the patient subsequently presents with:  
- 
$67RU$/7WLPHVWKHEDVHOLQHYDOXHVDQGî8/1RUî8/1
(whichever is smaller)  
- 
concurrent with total bilirubin  times the baseline value OR î8/1
(whichever is smaller) 
x $67!DQG[8/1!DQG[8/1!DQG[8/1!DQG[
ULN, and > 20x ULN; AST > 5x ULN for more than 5 weeks. 
x $/7!DQG[8/1!DQG[8/1!DQG[8/1!DQG[
ULN, and > 20x ULN; ALT > 5x ULN for more than 5 weeks. 
x 7RWDOELOLUXELQ![8/1DQG[8/1[8/1 
 
9.3.2. 
Analysis for Laboratory Parameters  
Laboratory data from all central and local laboratories will be included in analyses. Different 
laboratories are likely using slightly different normal reference ranges, which should not affect 
the planned analysis since they are all categorical and reported based on CTCAE toxicity grade 
or relationship to the normal ranges. The default convention for reporting of laboratory units will 
be standard international (SI) units. If a lab value is reported using an inequality symbol e.g., less 
than (<) a certain value, or greater than (>) a certain value, the given numeric value will be used 
in the summary. Data will be presented in listings with their inequality symbol.  
For each parameter in the clinical chemistry and hematology laboratory group, respectively, 
CTCAE toxicity grading is used to classify patients into a toxicity grade from 1 to 5 (where 


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applicable) for each timepoint assessment. The number and percentage of patients with highest 
grade during the treatment period will be summarized for each grade from 1 to 4 and Grade 3-4, 
along with such summary for the value collected at baseline.   
For the laboratory parameters that cannot be classified by CTCAE grade, the number and 
percentage of patients in the categories of treatment-emergent low or treatment-emergent high 
based on the normal reference range associated with the parameter will be summarized.  
The number and percentage of patients in each category of abnormal hepatic laboratory values 
will be summarized. 
Laboratory parameters will be listed by the group of chemistry, hematology, and urinalysis. In 
the data listing, flags that indicate the corresponding CTCAE grades and the classifications 
relative to the laboratory reference ranges will be included. In addition, a separate listing will be 
prepared for patients who met Hy’s law, if any. 
9.4. 
Vital Signs  
9.4.1. 
Vital Sign Parameters 
Vital signs including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), 
weight, height, and body temperature will be measured according to Schedule of Assessments in 
Appendix 1.  
Baseline vital signs refers to the most recent measurements taken prior to the first dose (pre-dose 
C1D1). Post-baseline assessments refer to the measurements taken after the first dose of any 
study drug and during treatment period. Change from baseline to the highest/lowest value across 
all post-baseline measurements for each vital sign parameter will be calculated. Patients with a 
non-missing baseline and at least one non-missing measurement post-first dose for a given 
parameter will be included in the calculation.  
Patients are classified with respect to the criteria of potentially clinically significant (PCS) 
findings of vital signs, which are defined by the highest/lowest value among post-baseline 
assessments and/or the change from baseline to the highest/lowest observed value. Details of 
PCS criteria for vital signs can be found in Table 10.  


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Table 10 
Criteria for Potentially Clinically Significant Vital Signs 
 Parameter   
Direction  
Highest/Lowest Observed 
Value   
Change from Baseline to the 
Highest/Lowest Observed Value 
 SBP   
High 
 
 PP+J 
 ,QFUHDVHPP+J 
    
Low 
 
 PP+J 
 'HFUHDVHPP+J 
 DBP   
High 
 
 PP+J 
 ,QFUHDVHPP+J 
    
Low 
 
 PP+J 
 'HFUHDVHPP+J 
 Heart Rate 
High 
 
 ESP 
 ,QFUHDVHESP 
    
Low 
 
  ESP 
 'HFUHDVHESP 
 Weight   
High 
 
--   
 ,QFUHDVH 
 
Low 
 
 -- 
 'HFUHDVH 
bpm=beats per minute; DBP=diastolic blood pressure; SBP=systolic blood pressure 
9.4.2. 
Analysis for Vital Signs   
Number and percentage of patients who meet any PCS criteria for each vital sign parameter as 
well as for each criterion will be summarized.  
All observed vital sign values, change from baseline at each post-first dose assessment, and PCS 
flag will be listed. 
9.5. 
12-lead Electrocardiograms 
9.5.1. 
Electrocardiograms Parameters 
The standard 12-lead Electrocardiogram (ECG) will collect heart rate, PR interval, QRS interval, 
RR interval, and QT interval at the frequency according to Schedule of Assessments in 
Appendix 1. Investigator’s clinical interpretation of 12-lead ECG results by normal or abnormal 
will also be collected. 
Since either QTcF or QTcB could be collected by different study sites, QTcF (using Fridericia's 
method) will be calculated from the QT and RR (converted from collected ms to sec) intervals 
based on the formula:  
QTcF = Uncorrected QT/ (RR Interval)^1/3, if QT and/or RR are missing, the QTcF will be left 
as missing.  
Change from baseline to the highest/lowest value across all post-baseline measurements for 
QTcF will be calculated. Patients who had a non-missing baseline and at least one non-missing 
measurement post-first dose will be included in the calculation.  
The potentially clinically significant ECG findings are defined by the highest/lowest value across 
all post-baseline assessments while during the treatment period for all parameters except for 
QTcF, for which both observed values and change scores are used to define the PCS findings 
(Table 11). For QTcF, a total of 5 different criteria are defined; some criteria are mutually 
exclusive and some cumulative (denoted by Criterion Index in Table 11). 


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Table 11 
Criteria for Potentially Clinically Significant ECG Findings 
ECG Parameter  
Direction or 
Criterion Index 
Highest/Lowest 
Observed Value   
Change from Baseline to 
the Highest/Lowest 
Observed Value 
RR Interval   
High 
> 1200 ms   
-- 
 
Low 
< 500 ms   
-- 
PR Interval   
High 
PV  
-- 
QRS Interval   
High 
PV  
-- 
    
Low 
PV  
-- 
QT Interval   
High 
PV  
-- 
    
Low 
PV  
-- 
QTcF  
Index 1  
(mutually exclusive) 
PVHF 
-- 
 
 
DQGPVHF 
-- 
 
 
DQGPVHF 
-- 
 
 
PVHF 
-- 
 
Index 2  
PVHF 
-- 
 
Index 3 
PVHF 
-- 
 
Index 4  
(mutually exclusive) 
-- 
,QFUHDVH60  
 
 
-- 
,QFUHDVHDQGPV 
 
Index 5 
-- 
,QFUHDVH30 ms 
9.5.2. 
Analysis for Electrocardiograms Parameters 
For each ECG parameter in Table 11, the number and percentage of patients who met each 
potentially clinically significant criterion will be summarized.  
Investigator’s clinical interpretation of the 12-lead ECG results (normal or abnormal) will be 
tabulated to present shift from baseline to the worst case post-dose during the treatment period. 
Similarly, a shift table from baseline to the last post-baseline assessment during the treatment 
period will be generated.  
All ECG parameters as collected along with corrected values of QTcF will be included in the 
data listing. In the listing, the flag of meeting a PCS criterion and the flag indicating 
investigator’s determined abnormality are also included.  
 


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10. 
CHANGES FROM THE PROTOCOL 
 
x Approximately 45 patients were planned to be enrolled per Protocol Version 2.0. The 
sponsor decided to close enrollment to this study on February 14, 2023 in order to 
reallocate resources to other ongoing trilaciclib clinical trials. The final total number of 
patients enrolled in this study is 30. 
x The protocol has defined two planned analyses. The first planned analysis, analyses for 
progression free survival, tumor response endpoints, and myeloproctection endpoints, 
were to be conducted when approximately 80% of the patients have radiographically 
determined disease progression or have died.  The final planned analysis is to be 
conducted when approximately 70% of patients have died. The first planned analysis was 
not officially conducted as planned and was combined with the the final planned analysis 
(see Section 2.1).  
x The following secondary objectives, intended to evaluate the myeloprotective effects of 
Trilaciclib when administered prior to SG, were not conducted as part of the final 
analysis as they were not deemed critical for the aCSR: 
o Occurrence and number of RBC transfusions on/after Week 5 
o Occurrence of ESA administration 
o Occurrence of Grade 3/4 decrease of platelets 
o Occurrence and number of platelet transfusions 
o Occurrence of serious infections 
o Use of IV antibiotics 
x The protocol mentions the collection of ECOG performance status information.  The 
summary and listing of these data was deemed non-critical and will not be included for 
the aCSR.  
x The change from baseline summaries for laboratory assessment will not be included for 
the aCSR.  
 


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11. 
REFERENCES  
Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative 
Breast Cancer. N Engl J Med. 2021;384(16):1529-41.  
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics. 
1982;29-41. 
Kalbfleisch JD, Prentice RL. The Statistical Analysis of Failure Time Data. New York: John 
Wiley & Sons. 1980. 
Wu, Jianrong. Sample size calculation for the one-sample log-rank test. Pharmaceutical 
Statistics. 2015;Volume 14:26-33. 


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12. 
APPENDICES  


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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
Table 12 
Schedule of Assessments 
Assessment 
Screening  
Treatment Phase (1 cycle = 21 days) 
Follow-Up 
Phase 
See Protocol 
Section for 
Additional 
Details 
Every Cycle  
End of 
Treatment Visit 
Safety 
Follow-up   
Survival  
Follow-Up  
30 days 
prior to 
enrollment 
Day 1 
Day 8 
14 days after last 
dose of study 
treatment (±7d) 
30 days 
after last 
dose (+7d) 
Every 3 
months 
post-Safety 
Follow-up 
Informed Consent 
X 
 
 
 
 
 
Section 13.3  
Enrollment 
 
X 
[Cycle 1 (-7d)] 
 
 
 
 
Section 11.1.2  
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
Section 7  
Demographics 
X 
 
 
 
 
 
Section 11.1.3  
Medical History and Surgical History 
X 
 
 
 
 
 
Section 11.1.4  
Concomitant Medications 
X 
X 
 
 
Section 11.1.4  
Complete Physical Examination (include 
weight and height) 
X 
 
 
 
 
 
Section 11.3.2  
Symptom-directed Physical 
Examination (with weight only) 
 
X 
 
 
 
 
Section 11.3.2  
Vital Signs 
X 
X 
 
X 
 
 
Section 11.3.1  
ECOG Performance Status 
X 
X 
 
X 
 
 
Section 11.3.3  
Adverse Event Reporting 
 
X 
X 
 
Section 11.3.6  
Laboratory Assessments and Procedures 
Hematology 
X 
X 
X 
X 
 
 
Section 11.3.5  


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Assessment 
Screening  
Treatment Phase (1 cycle = 21 days) 
Follow-Up 
Phase 
See Protocol 
Section for 
Additional 
Details 
Every Cycle  
End of 
Treatment Visit 
Safety 
Follow-up   
Survival  
Follow-Up  
30 days 
prior to 
enrollment 
Day 1 
Day 8 
14 days after last 
dose of study 
treatment (±7d) 
30 days 
after last 
dose (+7d) 
Every 3 
months 
post-Safety 
Follow-up 
Chemistry 
X 
X a 
 
X 
 
 
Section 11.3.5  
Pregnancy Test (WOCBP only) 
X 
X 
 
X 
 
 
Section 11.3.5  
12-lead Electrocardiogram (in triplicate) 
X 
X 
[Cycle 1] 
X 
[Cycle 1] 
 
 
 
Section 11.3.4  
Study Treatment 
Trilaciclib 
 
X 
X 
 
 
 
Section 9.1  
Sacituzumab govitecan-hziy 
 
X 
X 
 
 
 
Section 9.1  
Disease Assessment 
Tumor Assessments (CT/MRI) 
X 
X b 
 
 
Section 11.2.1  
Survival Follow Up and Subsequent 
Anti-Cancer Treatments 
 
 
 
 
 
X 
Section 11.7  
CR=complete response; CT=computed tomography; d=day; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; 
FDG=[18F]-fluorodeoxyglucose; MRI=magnetic resonance imaging; NaF=sodium fluoride; PET=positron emission tomography; MRI=magnetic resonance 
imaging; Q6=every six; Q9=every 9; WOCBP=women of childbearing potential 
a Chemistry samples will be collected every cycle during Cycles 1-4 and every other cycle (Cycle 6, Cycle 8, etc.) if results are stable, per Investigator 
discretion. 
b CT/MRI of chest/abdomen/pelvis Q6 weeks (± 7d) through Week 36 relative to Cycle 1 Day 1 and Q9 weeks (± 7d) thereafter relative to Cycle 1 Day 1 until 
documented disease progression or subsequent anticancer therapy. Brain scan (MRI preferred) during screening is not required and should be performed per 
Investigator discretion based on clinical signs and symptoms. Additional brain MRI should be conducted if there are new clinical signs and symptoms 
suggestive of brain metastases. Bone metastases identified at baseline via a bone scan or PET (such as FDG-PET, NaF-PET, or other locally available PET 
options) to be followed at scheduled visits using localized CT or MRI as clinically indicated. If bone metastases cannot be seen on CT or MRI scans, bone 
scans or PET should be repeated, using the same diagnostic procedure bone metastases were at baseline, when CR is identified in target disease or when 
progression in bone is suspected. 


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APPENDIX 2. CUSTOMIZED MedDRA QUERIES FOR TRILACICLIB 
AESIs 
AESI Categories 
Preferred Terms 
Injection Site 
Reaction/ 
Phlebitis/ 
Thrombophlebitis 
 
Administration site phlebitis 
Periphlebitis 
Application site phlebitis 
Phlebitis 
Catheter site phlebitis 
Phlebitis deep 
Chemical phlebitis 
Phlebitis infective 
Infusion site phlebitis 
Septic phlebitis 
Infusion site thrombosis 
Thrombophlebitis 
Injection site phlebitis 
Thrombophlebitis septic 
Injection site thrombosis 
Thrombophlebitis superficial 
  
Vascular access site thrombosis 
Administration related reaction 
Infusion site erythema 
Administration site dermatitis 
Infusion site hypersensitivity 
Administration site 
hypersensitivity 
Infusion site pain 
Administration site pain 
Infusion site rash 
Administration site rash 
Infusion site reaction 
Administration site recall 
reaction 
Infusion site recall reaction 
Administration site urticaria 
Infusion site urticaria 
Administration site vasculitis 
Infusion site vasculitis 
Application site dermatitis 
Injection related reaction 
Application site hypersensitivity 
Injection site dermatitis 
Application site pain 
Injection site erythema 
Application site rash 
Injection site hypersensitivity 
Application site recall reaction 
Injection site pain 
Application site urticaria 
Injection site rash 
Application site vasculitis 
Injection site reaction 
Catheter site dermatitis 
Injection site recall reaction 
Catheter site hypersensitivity 
Injection site urticaria 
Catheter site pain 
Injection site vasculitis 
Catheter site rash 
Installation site urticaria 
Catheter site urticaria 
instillation site hypersensitivity 
Catheter site vasculitis 
instillation site pain 
Immediate post-injection reaction instillation site rash 
Infusion-related reaction 
Skin reaction 
Infusion site dermatitis 
Vessel puncture site rash 
  
Vessel puncture site vesicles 


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AESI Categories 
Preferred Terms 
Acute drug 
hypersensitivity 
reaction  
Allergic bronchitis 
Laryngitis allergic 
Allergic cough 
Laryngospasm 
Allergic eosinophilia 
Laryngotracheal oedema 
Allergic oedema 
Lip edema 
Allergic pharyngitis 
Lip swelling mast cell degranulation present 
Allergic reaction to excipient 
Mouth swelling 
Allergic respiratory disease 
oedema mouth 
Allergic respiratory symptom 
Oropharyngeal oedema 
Anaphylactic reaction 
Oropharyngeal spasm 
Anaphylactic shock 
Oropharyngeal swelling 
Anaphylactic transfusion reaction Palatal oedema 
Anaphylactoid reaction 
Palatal swelling 
Anaphylactoid shock 
Periorbital oedema 
Anaphylaxis treatment 
Periorbital swelling 
angioedema 
Pharyngeal oedema 
Bronchospasm 
Pharyngeal swelling 
Circulatory collapse 
Pruritus allergic 
Circumoral oedema 
Reaction to excipient 
Circumoral swelling 
Shock 
Distributive shock 
Shock symptom 
Documented hypersensitivity to 
administered product 
Swelling face 
Drug hypersensitivity 
Swelling of eyelid 
Drug reaction with eosinophilia 
and systemic symptoms 
Swollen tongue 
Epiglottic oedema 
Therapeutic product cross-reactivity 
Eye oedema 
Tongue oedema 
Eye swelling 
Tracheal oedema 
Eyelid oedema 
Type I hypersensitivity 
Face oedema 
Urticaria 
Hypersensitivity 
Urticaria contact 
Immune-mediated adverse 
reaction 
Urticaria popular 
Infusion related hypersensitivity 
reaction 
Urticarial dermatitis 
Laryngeal oedema 
Urticarial vasculitis 


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AESI Categories 
Preferred Terms 
Hepatotoxicity  
Acute hepatic failure 
Hepatitis acute 
Acute on chronic liver failure 
Hepatitis cholestatic 
Acute yellow liver atrophy 
Hepatitis chronic active 
Allergic hepatitis 
Hepatitis chronic persistent 
Autoimmune hepatitis 
Hepatitis fulminant 
Cholestatic liver injury 
Hepatitis toxic 
Chronic hepatic failure 
Hepatocellular foamy cell syndrome 
Chronic hepatitis 
Hepatocellular injury 
Coma hepatic 
Hepatotoxicity 
Drug-Induced Liver Injury 
Immune-mediated hepatitis 
Hepatic failure 
Liver disorder 
Hepatic infiltration eosinophilia 
Liver injury 
Hepatic necrosis 
Mixed liver injury 
Hepatic steato-fibrosis 
Non-alcoholic steatohepatitis 
Hepatic steatosis 
Steatohepatitis 
Hepatitis 
Subacute hepatic failure 
Interstitial Lung 
Disease (ILD) 
/Pneumonitis 
Acute interstitial pneumonitis 
Idiopathic interstitial pneumonia 
Acute lung injury 
Idiopathic pneumonia syndrome 
Acute respiratory distress 
syndrome 
Idiopathic pulmonary fibrosis 
Alveolar lung disease 
Immune-mediated pneumonitis 
Alveolitis 
Interstitial lung disease 
Alveolitis necrotizing 
Necrotizing bronchiolitis 
Autoimmune lung disease 
Obliterative bronchiolitis 
Diffuse alveolar damage 
Pneumonitis 
Eosinophilic pneumonia 
Pneumonitis chemical 
Eosinophilic pneumonia acute 
Progressive massive fibrosis  
Eosinophilic pneumonia chronic 
Pulmonary fibrosis 
Granulomatous pneumonitis 
Hypersensitivity pneumonitis 
Pulmonary toxicity 
  
Restrictive pulmonary disease 


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AESI Categories 
Preferred Terms 
Embolic and 
thrombotic 
events, venous  
Axillary vein thrombosis 
Pulmonary thrombosis 
Brachiocephalic vein occlusion 
Pulmonary vein occlusion 
Brachiocephalic vein thrombosis 
Pulmonary veno-occlusive disease 
Deep vein thrombosis 
Pulmonary venous thrombosis 
Embolism venous 
Subclavian vein occlusion 
Iliac vein occlusion 
Subclavian vein thrombosis 
Obstructive shock 
Superior vena cava occlusion 
Pelvic venous thrombosis 
Thrombosis 
Peripheral vein occlusion 
Vena cava embolism 
Peripheral vein thrombus 
extension 
Vena cava thrombosis 
Phlebectomy 
Venous occlusion 
Pulmonary embolism 
Venous thrombosis 
Pulmonary microemboli 
Venous thrombosis limb