Single Arm, Open Label Phase 1b/2 Study of SGN-LIV1A in Combination With Pembrolizumab for First-Line Treatment of Patients With Unresectable Locally-Advanced or Metastatic Triple-Negative Breast Cancer
Phase: PHASE1
Conditions: Triple Negative Breast Neoplasms
Sponsor: Seagen Inc.

 
T his d oc u me nt c o ntai ns i nf or mati o n pr o prietar y t o Sea ge n I nc.  T he i nf or mati o n is bei n g pr o vi de d t o y o u f or t he 
p ur p ose of c o n d ucti n g a cli nic al trial f or Sea ge n I nc.  Y o u ma y discl ose t he c o nte nts of t his d oc u me nt t o st u d y 
pers o n nel u n der y o ur s u per visi o n a n d t o y o ur I nstit uti o nal R e vie w B oar d (I R B) or Et hics C o m mittee ( E C) f or t he 
sa me p ur p ose. Y o u ma y n ot discl ose t he c o nte nts of t his d oc u me nt t o a n y ot her part y, u nl ess g o ver n me nt re g ulati o ns 
or la ws re q uire s uc h discl os ur e, wit h o ut pri or writte n per missi o n fr o m Sea ge n I nc.  A n y s u p ple me ntal i nf or mati o n 
t hat ma y be a d de d t o t his d oc u me nt is pr o prietar y t o Sea ge n I nc.  a n d s h o ul d be ha n dle d usi n g t he discl os ure 
pr oce d ure  descri be d a b o ve.  
 
Pr ot oc ol N u m ber:  
S G N L V A -0 0 2  
Versi o n:  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
Pr ot oc ol Title:  
Si n gle Ar m, O p e n La bel P hase 1 b/ 2 St u d y of S G N -LI V 1 A i n 
C o m bi nati o n wit h Pe m br oliz u ma b f or First -Li n e Treat me nt of 
Patie nts wit h U nresecta bl e L o call y -A d va nce d or Metastatic 
Tri ple -Ne gati ve Breast C a ncer  
I n vesti g ati o n al Dr u g: 
La di rat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A ) 
P h ase:  
1 b/ 2  
I N D N u m ber: 
1 1 7 5 3 2  
E u dr a C T N u m ber:  
2 0 1 7 -0 0 2 2 8 9 -3 5  
S p o ns or:  
Sea ge n I nc.  
2 1 8 2 3 3 0t h Dri ve S E  
B ot hell, W A 9 8 0 2 1, U S A  
Me dic al M o nit or:  
, M D, P h D 
Sea ge n I nc.  
Tel: 
 
E -mail: 
  
St u d y Direct or  
, P har mD  
Sea ge n I nc.  
Tel: 
 
E -mail: 
  
S A E E m ail or  F a x:  
See e mail or fa x n u m ber s pecifie d o n t he S A E re p ort f or m.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)
P P D
P P D
P P D
P P D
P P D
P P D

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2  of 1 5 2  
P R O T O C O L S Y N O P SI S   
Pr ot oc ol N u m ber   
S G N L V A -0 0 2  
Versi o n   
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
P h ase   
1 b/ 2  
Pr o d uct N a me   
La di rat uz u ma b Ve d oti n ( L V; S G N-LI V 1 A)  
S p o ns or   
Sea ge n I nc.  
2 1 8 2 3 3 0t h Dri ve S E  
B ot hell, W A 9 8 0 2 1, U S A  
 
Pr ot oc ol Tit le  
Si n gle Ar m, O pe n La b el P has e 1 b/ 2 St u d y of S G N -LI V 1 A i n C o m bi nati o n wit h P e m br oliz u ma b f or First -Li ne 
Treat me nt of P atie nts wit h U nresecta ble L ocall y -A d va nce d or Metastatic Tri p le-Ne gati ve Breast Ca ncer  
 St u d y O bjecti ves   
Pri m ary   
E val uate t he safet y a n d t olera bilit y of t he c o m bi nat i o n of la dirat uz u ma b ve d oti n ( L V; S G N -LI V 1 A ) a n d 
pe m br oliz u ma b i n patie nts wit h l ocall y -a d va nce d or metastatic tri ple -ne gati ve breast ca ncer ( L A/ M T N B C)  
I de ntif y t he rec o m me n de d d ose a n d sc he d ule of L V  i n c o m bi nati o n wit h pe m br oliz u ma b i n patie nts wit h L A/ M 
T N B C  
E val uate t he c o nfir me d o bj ecti ve res p o nse rate ( O R R) as me as ure d b y Res p o nse E val uati o n Criteria i n S oli d 
T u m ors ( R E CI S T) v 1. 1  of t he c o m bi nati o n of L V  a n d pe m br oliz u ma b i n patie nts wit h L A/ M T N B C  
Sec o n d ary   
E val uate d urati o n of res p o nse ( D O R), disease c o ntr ol rate ( D C R), a n d pr o gressi o n -free s ur vi val ( P F S) as meas ure d 
b y R E CI S T v 1. 1  
E val uate o verall s ur vi val ( O S)  
E x pl or at ory   
E val uate O R R, D O R, D C R, a n d P F S as meas ure d b y I m m u ne Res p o nse E val uati o n Criteria i n S oli d T u m ors 
(i R E CI S T) 
Assess p har mac o ki netics ( P K) a n d  i nci de nce of a ntit hera pe utic a nti b o dies ( A T As) of L V  
E val uate pr o gra m me d deat h li ga n d 1 ( P D -L 1) a n d LI V -1 e x pressi o n -res p o nse relati o ns hi ps 
Assess e x pl orat or y bi o mar kers (e. g., i n t he t u m or i m m u ne micr oe n vir o n me nt or peri p her y) of st u d y treat me nt -
me diate d  p har mac o d y na mic effects  
St u d y P o p ul ati o n   
Eli gi ble patie nts are at least 1 8 years of a ge wit h u nresecta ble L A/ M, hist ol o gicall y d oc u me nte d T N B C (estr o ge n 
rece pt or [ E R]/ pr o gester o ne rece pt or [ P R]/ h u ma n e pi der mal gr o wt h fact or rece pt or 2 [ H E R 2]-ne gati ve) w h o ha ve 
n ot pre vi o usl y recei ve d c yt ot o xic t hera p y f or treat me nt of u nresecta ble L A/ M breast ca ncer ( B C).  P arts A –  C d o 
n ot  re q uire preselecti o n base d o n P D-L 1 stat us ; h o we ver, for P art D o nl y, eli gi ble patie nts  m ust ha ve a P D -L 1 
c o m bi ne d p ositi ve sc ore ( C P S)  < 1 0 . A mi ni m u m of 6  m o nt hs m ust ha ve ela pse d after a n y pri or treat me nts gi ve n 
wit h c urati ve i nte nt. T h o u g h t u m or e x pressi o n of LI V -1 is n ot re q uire d f or e nr oll me nt, fres h t u m or t iss ue is re q uire d 
acr oss all parts of t he st u d y  i n patie nts wit h accessi ble t u m ors f or e x pl orat or y bi o mar ker a nal ysis, i ncl u di n g 
e val uati o n of LI V -1 e x pressi o n. I n patie nts wit h i naccessi bl e t u m ors or ot her safet y c o ncer ns, arc hi val tiss ue ma y be 
s u b mitte d if it was c ollecte d after c o m pleti o n of t he patie nt’s m ost rece nt c yt ot o xic t hera p y. If neit her is a vaila ble, 
please disc uss wit h me dical m o nit or. I n P art D o nl y , P D -L 1 C P S < 1 0 stat us will be  deter mi ne d  l ocall y at t he 
i n vesti gati ve site b y a P D -L 1  i m m u n o hist oc he mistr y (I H C) assa y usi n g t he 2 2 C 3 cl o ne . P atie nts m ust ha ve at least 1 
t u m or lesi o n ≥1 0 m m i n t he l o n gest dia meter or l y m p h n o de of  ≥1 5  m m i n t he s h ort a xis as meas ure d b y 
R E CI S T  v  1. 1. A n Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) perf or ma nce stat us  of 0 or 1 a n d a de q uate re nal, 
he p atic, a n d he mat ol o gical f u ncti o n are re q uire d at baseli ne. P atie nts m ust n ot ha ve recei ve d pri or i m m u n o -
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3  of 1 5 2  
o nc ol o g y t hera p y, i ncl u di n g c hec k p oi nt i n hi bit ors ( C PIs), a n d ca n ha ve n o hist or y of ot her seri o us mali g na nc y 
wit hi n t he past 3 years. Pre -e xisti n g ne ur o pat h y ≥ Gra de 2 is n ot per mitte d.  
N u m ber of Pl a n ne d P atie nts   
A p pr o xi matel y 1 8 9 – 2 1 1  patie nts are e x pecte d t o be e nr olle d, i ncl u di n g a p pr o xi matel y 1 2 – 2 4 patie nts e nr olle d i n 
P art A ( L V  d ose de -escalati o n), a p pr o xi matel y 7 3 patie nts i n P art B (e x pa nsi o n), a p pr o xi matel y 6 4  patie nts i n P art C 
(L V  wee kl y [ q 1 w k] d osi n g) , a n d a p pr o xi matel y 4 0  patie nts i n P art D  ( L V Da y 1, Da y 8 i n 2 1 -da y c ycle d osi n g) . I n 
P art B, a p pr o xi matel y 4 8 patie nts will be e nr olle d at t he ma xi m u m a d mi nistere d d ose ( M A D) of L V  2. 5  m g/ k g a n d 
a p pr o xi matel y 2 5 patie nts will be e nr olle d at t he l o wer d ose of 2. 0  m g/ k g L V  i n c o m bi nati o n wit h pe m br oliz u ma b. 
I n P art C, a p pr o xi matel y 6 4 p atie nts, i ncl u di n g a p pr o xi matel y 6 0 patie nts i n t he e x pa nsi o n c o h ort , will be e nr olle d 
a n d will recei ve L V  1. 0 or 1. 2 5  m g/ k g o n Da y 1, Da y 8, a n d Da y 1 5 i n e ver y 2 1 -da y c ycle, i n c o m bi nati o n wit h 
pe m br oliz u ma b a d mi nistere d o n Da y 1 of e ver y c ycle.  I n P art D, a p pr o xi matel y 4 0 patie nts  will be e nr olle d a n d will 
recei ve L V 1. 5 m g/ k g o n Da y 1 a n d Da y 8  (off  Da y 1 5) i n e ver y 2 1-da y c ycle, n ot t o e xce e d 2 0 0 m g per i nf usi o n, i n 
c o m bi nati o n wit h pe m br oliz u ma b a d mi nistere d o n Da y 1 of e ver y c ycle.  
St u d y Desi g n   
T his is a si n gle -ar m, o pe n -la b el, m ultice nter trial desi g ne d t o assess t he safet y a n d efficac y of L V  i n c o m bi nati o n 
wit h pe m br oliz u ma b f or t he treat me nt of L A/ M T N B C. P atie nts wil l be e nr olle d i nt o P art A, P art B, P art C , a n d 
P art  D se q ue ntiall y. P atie nts will e nr oll i n P art B C o h ort 1 a n d P art B C o h ort 2 se q ue ntiall y.  
I n P art A, patie nts will recei ve a d ose of L V  2. 5  m g/ k g as a n i ntra ve n o us (I V) i nf usi o n o ver a p pr o xi matel y 
3 0  mi n u tes f oll o we d b y pe m br oliz u ma b 2 0 0  m g I V o ver a p pr o xi matel y 3 0 mi n utes o n Da y 1 of eac h 2 1 -da y c ycle . 
I n c o ns ultati o n wit h t he s p o ns or, eli gi ble patie nts alrea d y o n treat me nt pri or t o A me n d me nt 2, ma y ha ve t heir 
ma xi m u m wei g ht ca p per i nf usi o n  i ncrease d t o 1 0 0 k g or re mai n at 8 0  k g , if t he y are recei vi n g be nefit (c o m plete 
res p o nse [ C R], partial res p o ns e [ P R], or sta ble disease [ S D]). P atie nts recei vi n g > 2 0 0 m g L V  per i nf usi o n  are 
re q uire d t o be a d mi nistere d pr o p h ylactic gra n ul oc yte-c ol o n y sti m u lati n g fact or ( G-C S F). D osi n g ma y be de -
escalate d base d u p o n t he fre q ue nc y of d ose - li miti n g- t o xiciti es ( D L Ts) i n C ycle 1.  
P art B i ncl u des 2 e x pa nsi o n c o h orts. P art B C o h ort 1 will re cei ve t he M A D of L V  2. 5  m g/ k g. P art B C o h ort 2 will 
recei ve t he d ose of L V  2. 0  m g/ k g. P atie nts will e nr oll se q ue ntiall y i nt o C o h ort 1 f oll o we d b y C o h ort 2.  P atie nts 
recei vi n g > 2 0 0 m g L V  per i nf usi o n are re q uire d t o be a d mi nistere d 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).  
I n P art C, patie nts will recei ve L V  1. 0 or 1. 2 5  m g/ k g o n Da y 1, Da y 8, a n d Da y 1 5 i n e ver y 2 1 -da y c ycle , n ot t o 
e xcee d 2 0 0  m g per i nf usi o n , i n c o m bi nati o n wit h pe m br oliz u ma b a d mi nistere d o n Da y 1 of e ver y c ycle . P art  C will 
ha ve d ose escalati o n a n d e x pa nsi o n c o h orts. D ose escalati o n i n P art C will be c o n d ucte d usi n g t he m o difie d t o xicit y 
pr o ba bilit y i nter val ( m T PI) met h o d (Ji 2 0 1 0). At least 2  patie nts will be e nr olle d i n eac h d ose escalati o n  c o h ort.  T he 
safet y m o nit ori n g c o m mittee (S M C ) will e val u ate t he safet y of eac h d ose -le vel c o h ort a n d ma ke d ose 
escalati o n/ de -escalati o n rec o m me n dati o ns usi n g t he m T PI decisi o n r ules. O nl y 1 d ose -es calati o n c o h ort will be o pe n 
at a ti me.  
T he d ose -e x pa nsi o n c o h orts i n P art C will assess t he efficac y, safet y, a n d t olera bilit y i n a lar ger n u m ber of patie nts. 
D ose -e x pa nsi o n c o h orts ma y be o pe ne d at a n y d ose le vel t hat has cleare d D L T e val uati o n. D L T e val uati o n will o nl y 
i ncl u de data fr o m t he d ose-esc alati o n c o h orts ; h o we ver, t he t otalit y of data fr o m all patie nts at eac h d ose le vel will 
be use d t o deter mi ne t he rec o m me n de d q 1 w k L V  d ose.  
I n P art D, patie nts will recei ve L V 1. 5 m g/ k g a d mi nistere d  o n Da y 1  a n d Da y 8  (off  Da y 1 5 ) of  e ver y 2 1 -da y c ycle, 
n ot t o e xcee d 2 0 0 m g per i nf usi o n, i n c o m bi nati o n wit h pe m br oliz u ma b a d mi nistere d o n D a y 1 of e ver y c ycle. 
O n g oi n g, real -ti me, c o nti n u o us re vie w of patie nt safet y a n d seri o us a d verse e ve nts (S A Es ) will be c o n d ucte d b y t he 
s p o ns or’s Dr ug Safet y De p art me nt. A d diti o nall y, t he i n de pe n de nt safet y m o nit ori n g c o m mittee (I S M C) will e ns ure 
peri o dic safet y data re vie w t hr o u g h o ut t he st u d y.  
U n der A me n d me nt 2 a n d later, d osi n g f or patie nts i n P arts A a n d B is base d o n patie nt act ual b o d y wei g ht, e xce pt 
f or patie nts wei g hi n g > 1 0 0 k g, w here d osi n g will be base d o n a 1 0 0 k g ma xi m u m wei g ht per i nf usi o n . F or patie nts 
i n P arts C  a n d D, L V  d osi n g is base d o n t he patie nt’s act ual b o d y wei g ht b ut t here will be n o wei g ht ca p per 
i nf usi o n. A n i n di vi d ual’s d ose  ma y be m o difie d base d u p o n treat me nt -relate d a d verse e ve nts ( A Es). I n all patie nts, 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4  of 1 5 2  
pe m br oliz u ma b 2 0 0  m g will be a d mi nistere d b y I V i nf usi o n a p pr o xi matel y 6 0 – 9 0 mi n utes after a d mi nistrati o n of 
L V . 
Res p o nses will be assesse d b y  c o m p ute d t o m o gra p h y  (C T ) sca n a n d/ or ma g netic res o na nc e i ma gi n g ( M RI) sca n 
e ver y 6 wee ks ( ± 3  da ys) f or t he first 1 2 m o nt hs after t he first d ose of L V  a n d pe m br oliz u ma b a n d e ver y 1 2 wee ks 
( ± 7 da ys) t hereafter t hr o u g h t he e n d of t he safet y f oll o w-u p p eri o d . N o a d diti o nal sca ns or r es p o nse assess me nts are 
re q uire d after t he safet y f oll o w-u p peri o d , h o we ver ad diti o nal sca n s or res p o nse assess me nts ma y be perf or me d as 
part of t he patie nt’s sta n dar d of care  at a n y ti me. O bj ecti ve r es p o nses will be c o nfir me d at least 4  wee ks after first 
d oc u me ntati o n of res p o nse. R E CI S T  v 1. 1 will be use d t o sc ore res p o nses f or t he pri mar y a n d sec o n dar y e n d p oi nts, 
a n d i R E CI S T will be use d f or e x pl orat or y e n d p oi nts. I n vesti gat ors will ma ke treat me nt decisi o ns base d o n site 
assess me nts of sca ns usi n g i R E CI S T . 
P atie nts will c o nti n ue t o recei ve st u d y treat me nt u ntil diseas e pr o gressi o n, u nacce pta ble t o xicit y, i n vesti gat or 
decisi o n, c o nse nt wit h dra wal, or st u d y ter mi nati o n b y t he s p o ns or. P e m br oliz u ma b ma y be a d mi nistere d f or a 
ma xi m u m of 3 5 c ycles (a p pr o xi mately 2 years) . If L V  or pe m br oliz u ma b is disc o nti n ue d, patie nts ma y c o nti n ue t o 
recei ve t he ot her dr u g wit h me dical m o nit or a p pr o val. P atie nts w h o disc o nti n ue st u d y treat me nt i n t he a bse nce of 
disease pr o gressi o n will be f oll o we d e ver y 6 wee ks f or res p o nse as sess me nts, p h ysical e xa mi nati o ns, a n d s ur vi val 
u ntil wit h dra wal of c o nse nt, i nitiati o n of a ne w a ntica ncer t hera p y, deat h, or st u d y cl os ure, w hic he ver occ urs first. 
After 1 year o n st u d y, t he fre q ue nc y of f oll o w -u p visits will be re d uce d t o e ver y 1 2  wee ks.  All patie nts, i ncl u di n g 
t h ose wit h pr o gressi ve disease ( P D), will be f oll o we d f or s ur vi val u ntil t he e n d of t he safet y f oll o w-u p peri o d, deat h , 
or st u d y cl os ure, w hic he ver oc c urs first.  
After disease pr o gressi o n or i nitiati o n of a ne w a ntica ncer tre at me nt , s ur vi val f oll o w-u p will be c o n d ucte d e ver y 
1 2  wee ks ( ± 2  wee k s) starti n g fr o m t he last ra di o gra p hic sca n de m o nstrati n g disease pr o gressi o n or fr o m i nitiati o n of 
t he ne w a ntica ncer treat me nt. S ur vi val f oll o w-u p will c o nti n ue  u ntil t he e n d of t he safet y f oll o w-u p peri o d, deat h , or 
st u d y cl os ure, w hic he ver c o mes first. F oll o w -u p ma y be c o n d ucte d wit h cli nic visits or tele p h o ne calls. N o f urt her 
res p o nse assess me nts are re q uire d.O n a peri o dic basis, a n S M C will m o nit or t he safet y of patie nts partici pati n g i n 
the trial. T he S M C will be res p o nsi ble f or e val uati n g t he res ults of safet y a nal yses a n d will ma ke rec o m me n dati o ns 
t o t he s p o ns or. A n o n g oi n g, re al-ti me re vie w of patie nt safet y a n d ( S A Es) will als o be c o n d ucte d b y t he s p o ns or’s 
Dr u g Safet y De p art me nt. I n a d diti o n, a n I S M C c o m p ose d of p h ysicia ns w h o are n ot i n v ol ve d i n t his st u d y, as well 
as sp o ns or re prese ntati ves,  will p eri o dicall y re vie w c u m ulati ve safet y data a n d pr o vi de rec o m me n dati o ns t o t he 
s p o ns or. C o nti n u o us m o nit ori n g of t he be nefit -ris k pr ofile will be c o n d ucte d a n d c o nti n uati o n of e nr oll me nt t o t he 
c o h ort ma y be altere d de p e n di n g o n t he be nefit -ris k pr ofile.  
Test Pr o d uct, D ose, a n d M o de of A d mi nistr ati o n   
P arts A a n d B: L V  (e ver y 3 wee ks [ q 3 w k ]); 2. 0 or 2. 5  m g/ k g; a p pr o xi matel y 3 0 -mi n ute I V i nf usi o n o n Da y 1 of 
e ver y 2 1 -da y c ycle.  
P art C: L V  ( q 1 w k); 1. 0 or  1. 2 5  m g/ k g; a p pr o xi matel y 3 0 -mi n ute I V i nf usi o n o n Da y 1, Da y  8, a n d Da y 1 5 of e ver y 
2 1 -da y c ycle.  T he ma xi m u m d ose w ill b e 2 0 0 m g per i nf usi o n.  
Pri or t o A me n d me nt 2, t he wei g ht ca p is 8 0  k g. F or patie nts i n P arts A a n d B treate d u n der A me n d me nt 2 a n d later, 
t he ma xi m u m wei g ht ca p per i nf usi o n will b e i ncrease d fr o m 8 0  k g t o 1 0 0  k g. P atie nts w h o recei ve > 2 0 0  m g L V  per 
i nf usi o n i n P arts A a n d  B  are als o re q uire d t o be a d mi nister e d pr o p h ylactic G -C S F.  
P art D: L V 1. 5  m g/ k g; a p pr o xi matel y 3 0 -mi n ute I V i nf usi o n o n Da y 1 a n d Da y 8 ( off  Da y 1 5)  of e ver y 2 1 -da y 
c ycle. T he ma xi m u m d ose will b e 2 0 0  m g per i nf usi o n . 
P e m br oliz u ma b: 2 0 0  m g; 3 0 -mi n ute I V i nf usi o n e ver y 2 1 da ys gi ve n a p pr o xi matel y 6 0 – 9 0  mi n utes after L V . 
D ur ati o n of Tre at me nt   
P atie nts ma y c o nti n ue o n treat me nt u ntil disease pr o gressi o n as deter mi ne d b y i R E CI S T, u nacce pta ble t o xicit y, 
i n vesti gat or decisi o n, c o nse nt wit h dra wal or st u d y ter mi nati o n b y t he s p o ns or. P e m br oliz u ma b ma y be a d mi nistere d 
f or a ma xi m u m of 3 5 c ycles (a p pr o xi matel y 2 years) . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5  of 1 5 2  
Effic ac y Assess me nts   
A ntit u m or acti vit y will be ass esse d b y ra di o gra p hic t u m or i ma gi n g at pr ot oc ol -s pecifie d ti me p oi nts. Res p o nse 
assess me nt f or pri mar y a n d sec o n dar y efficac y e n d p oi nts will be e val uate d usi n g R E CI S T v 1. 1.  E x pl orat or y 
efficac y e n d p oi nts will be e val uate d usi n g i R E CI S T.   
P h ar m ac o ki netic a n d I m m u n o ge nicit y Assess me nts   
P atie nt ser u m a n d plas ma sa m ples will  be o btai ne d f or L V  P K a n d A T A  e val uati o n at pr ot oc ol  s pecifie d ti me p oi nts. 
C o nce ntrati o ns of a nti b o d y-dr u g c o nj u gate ( A D C ) L V  a n d m o n o met h yl a uristati n E ( M M A E) will be meas ure d i n 
plas ma a n d A T A i n ser u m.  
Starti n g wit h A me n d me nt 1 1, P K a n d i m m u n o ge nicit y assess me nts will n ot be c o n d ucte d  after C ycle 1 . 
Bi o m ar ker Assess me nts   
T u m or sa m ples a n d bl o o d will be c ollecte d at pr ot oc ol -s pecifie d ti me p oi nts. Bi o mar ker a nal ysis will n ot be utilize d 
f or patie nt selecti o n (wit h t he e xce pti o n o f P D -L 1 f or P art D patie nts ). Bi o mar ker assess me nts i n t u m or tiss ue ma y 
i ncl u de, b ut are n ot li mite d t o: meas ure me nt of LI V 1  a n d P D -L 1 pr otei ns, ge ne e x pressi o n, disease s u bt y pe, t u m or 
i m m u ne micr oe n vir o n me nt, a n d m utati o nal l oa d. Assess me nts i n bl o o d ma y i ncl u de b ut are n ot li mite d t o: c yt o ki ne 
or ot her pr otei n meas ure me nts, a b u n da nce a n d p he n ot y pes of i m m u ne cell s u bsets, a n d circ ulati n g n ucleic aci ds. 
Met h o ds of a nal ysis ma y i ncl u de I H C, m ulti ple x i m m u ne hist ofl u oresce nce ( mI H F), m utati o n a n d ge ne e x pressi o n 
pr ofili n g b y Ne xt Ge nerati o n Se q ue nci n g, fl o w c yt o metr y, E LI S A, a n d T cell rece pt or beta ( T C R β) i m m u n o S E Q 
a nal ysis.  
Starti n g wit h A me n d me nt 1 1, bi o mar ker assess me nts will n ot be c o n d ucte d  after C ycle 1 . 
S afet y Assess me nt s  
Safet y assess me nts will i ncl u d e t he s ur veilla nce a n d rec or di n g of A Es, p h ysical e xa mi nati o n fi n di n gs, vital si g ns, 
electr ocar di o gra ms ( E C Gs), c o nc o mita nt me dicati o ns, a n d la b orat or y tests.  
St atistic al M et h o ds   
Safet y a n d efficac y e n d p oi nts will b e s u m marize d wit h descri pti ve statistics.  
T he safet y a nal ysis set will i ncl u de patie nts treate d wit h a n y a m o u nt o f L V  or pe m br oliz u ma b. T his is als o referre d 
t o as t he all treate d patie nts set f or s o me efficac y a nal yses. T he D L T-e val ua ble ( D E) a nal ysis set i ncl u des all 
patie nts i n t he safet y a nal ysis set w h o eit her ( 1) e x perie nce a D L T or ( 2) recei ve at least 7 5 % of i nte n de d L V  a n d 
pe m br oliz u ma b d oses a n d are f oll o we d f or t he f ull D L T e val uati o n peri o d ( C ycle 1). T he D E patie nt set will be t he 
pri mar y p o p ulati o n f or P art A, a n d will b e use d f or t he deter mi nati o n of t he M A D  f or P art B. T he all treate d a nal ysis 
set i ncl u des all e nr olle d patie nts w h o recei ve a n y a m o u nt of L V or pe m br oliz u ma b  a n d will be t he pri mar y set f or 
efficac y a nal ysis. T he efficac y -e val ua ble ( E E) set i ncl u des all patie nts i n t he all treate d a nal ysis set w h o ha ve b ot h a 
baseli ne a n d at least 1 e v al ua ble p ost -baseli ne disease assess me nt acc or di n g t o t he R E CI S T v 1. 1 a n d i R E CI S T 
criteria, or per i n vesti gat or deter mi nati o n of cli nical disease pr o gressi o n.  
E xact 9 5 % c o nfi de nce i nter vals ( CIs) f or O R R a n d D C R will be pr o vi de d. D O R, P F S, a n d O S will be a nal yze d 
usi n g t he Ka pla n -Meier met h o d. T he pri mar y a nal yses of efficac y e n d p oi nts  will be perf or me d f or all treate d 
patie nts a nal ysis set. All safet y a nal yses will be base d o n t he safet y a nal ysis set.  
A p pr o xi matel y 6 0 patie nts t ot al are e x pecte d t o be e nr o lle d at t he M A D ass u mi n g t hat P art A will e nr oll 1 2 patie nts 
at t he M A D a n d P art B C o h ort 1 will e nr oll a p pr o xi matel y 4 8 patie nts, at t he M A D. Base d o n t he S G N L V A -0 0 1 
P hase 1 st u d y, it is esti mate d t hat a b o ut 7 0 % of patie nts are LI V -1 -p ositi ve. T h us, a p pr o xi matel y 4 2  LI V -1 -p ositi ve 
patie nts i n t otal will be e nr olle d at t he M A D. Ass u mi n g t he o bser ve d O R R is bet wee n 5 0 % a n d 7 0 %, t he wi dt hs of 
2 -si de d 9 5 % CIs are s u m mari ze d bel o w. 
C o nfir me d O R R  
E x pecte d wi dt h of 9 5 % CI o n 
LI V -1 -p ositi ve patie nts ( N = 4 2)  
E x pecte d wi dt h of 9 5 % CI o n all 
patie nts at t he M A D ( N = 6 0)  
5 0 %  
± 1 6 %  
± 1 3 %  
6 0 %  
± 1 6 %  
± 1 3 %  
7 0 %  
± 1 5 %  
± 1 2 %  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6  of 1 5 2  
P art B C o h ort 2 will e nr oll a p pr o xi matel y 2 5  patie nts at 2. 0  m g/ k g. Wit h t he patie nts i n P art A e nr olle d at 
2. 0  m g/ k g, a p pr o xi matel y 3 0 patie nts i n t otal will be e nr olle d at 2. 0  m g/ k g. Ass u mi n g t he o bser ve d O R R is bet wee n 
5 0 -7 0 %, t he wi dt hs of 2 -si de d 9 5 % CI s are s u m marize d as b el o w. 
C o nfir me d O R R  
E x pecte d wi dt h of 9 5 % CI o n all patie nts at 2. 0 m g/ k g  
( N = 3 0) 
5 0 %  
± 1 8 %  
6 0 %  
± 1 8 %  
7 0 %  
± 1 6 %  
 
P art C will e nr oll a p pr o xi matel y 6 4 patie nts i n t otal a n d 6 2 patie nts at selecte d d ose le vel (ass u mi n g 2 patie nts i n 
eac h d ose escalati o n c o h ort  of 1. 0 a n d 1. 2 5  m g/ k g , a n d 6 0  patie nts i n t he e x pa nsi o n c o h ort  at 1. 2 5  m g/ k g ). 
Ass u mi n g t he  o bser ve d O R R is bet wee n  5 0 % – 7 0 %, t he ta ble bel o w s u m marize s t he 2-si d e d 9 5 % e xact CI s a m o n g 
t he 6 2  patie nts  at t he selecte d d ose le vel  of 1. 2 5  m g/ k g  ( 2 i n d ose escalati o n a n d 6 0 i n d ose e x pa nsi o n c o h ort). 
 
N u m ber of c o nfir me d 
O bj ecti ve Res p o nses  
C o nfir me d O R R  ( %) 
9 5 % e xact CI ( N = 6 2)  
3 1  
5 0 %  
3 7 %, 6 3 %  
3 7  
6 0 %  
4 6 %, 7 2 %  
4 3  
6 9 %  
5 6 %, 8 0 %  
 
A p pr o xi matel y 4 0 patie nts will b e e nr olle d i n P art D . O n g oi n g, real-ti me, c o nti n u o us re vie w of patie nt safet y a n d 
S A Es will be c o n d ucte d b y t he s p o ns or’s Dr u g Safet y De p art me nt. A d diti o nall y, t he I S M C will e ns ure  peri o dic 
safet y data re vie w t hr o u g h o ut t he st u d y. 
Prese nte d i n t he ta ble bel o w are t he 2 -si de d 9 5 % e xact CIs a m o n g 4 0 patie nts at 1. 5  m g/ k g ass u mi n g t he o bser ve d 
O R R is bet wee n 5 0 % a n d 7 0 %.  
 
N u m ber of c o nfir me d 
O bj ecti ve  Res p o nses  
C o nfir me d O R R  ( %) 
9 5 % e xact CI  
( N =4 0)  
2 0  
5 0 %  
3 4 %, 6 6 %  
2 4  
6 0 %  
4 3 %, 7 5 %  
2 8  
7 0 %  
5 3 %, 8 3 %  
 
T his sa m ple size of 4 0 patie nts w o ul d a d diti o nall y pr o vi de t he f oll o wi n g pr o ba bilities of o bser vi n g at least 1 patie nt 
ha vi n g a n A E, as s u m marize d bel o w.  
Tr ue A E I nci de nce Rate  
Pr o ba bilit y of O bser vi n g at Le ast O ne   
P atie nt Ha vi n g a n A E  
( N =4 0)  
5 %  
8 7 %  
1 0 %  
9 9 %  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7  of 1 5 2  
T A B L E  O F C O N T E N T S  
P R O T O C O L S Y N O P SI S  .............................................................................................................................................. 2  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S  .............................................................................. 1 1  
1  
I N T R O D U C TI O N ................................................................................................................................ 1 4  
1. 1  Breast Ca ncer  ............................................................................................................................................. 1 4  
1. 2  Tri ple -Ne gati ve Breast Ca ncer  .................................................................................................................. 1 5  
1. 3  LI V -1  ......................................................................................................................................................... 1 5  
1. 4  La dirat uz u ma b Ve d oti n  ............................................................................................................................. 1 6  
1. 4. 1  Mec ha nis m of Acti o n of L V  ........................................................................................................ 1 6  
1. 4. 2  Precli nical E x perie nce wit h L V  ................................................................................................... 1 6  
1. 4. 3  Cli nical E x perie nce wit h L V  ....................................................................................................... 1 6  
1. 5  P e m br oliz u ma b B ac k gr o u n d  ...................................................................................................................... 1 7  
1. 5. 1  P har mace utical a n d T hera pe utic Bac k gr o u n d  ............................................................................. 1 7  
1. 5. 2  Pre -cli nical a n d Cli nical Trials  .................................................................................................... 1 8  
1. 6  Rati o nale f or St u d y  .................................................................................................................................... 1 8  
2  
O BJ E C TI V E S A N D E N D P O I N T S ...................................................................................................... 2 0  
3  
I N V E S TI G A TI O N A L P L A N ............................................................................................................... 2 1  
3. 1  S u m mar y of St u d y Desi g n  ......................................................................................................................... 2 1  
3. 1. 1  P art A: D ose De -escalati o n .......................................................................................................... 2 2  
3. 1. 2  P art B: E x pa nsi o n  ........................................................................................................................ 2 4  
3. 1. 3  P art C: W ee kl y L V d osi n g  .......................................................................................................... 2 4  
3. 1. 4  P art D: Da y 1 a n d Da y 8 e ver y 2 1 -da ys L V d osi n g  .................................................................... 2 6  
3. 1. 5  D ose -Li miti n g T o xicit y  ............................................................................................................... 2 7  
3. 2  Disc ussi o n a n d Rati o nale f or St u d y D esi g n  ............................................................................................... 2 9  
3. 2. 1  Met h o d of Assi g ni n g P atie nts t o Treat me nt Gr o u ps  ................................................................... 3 0  
3. 2. 2  Rati o nale f or Selecti o n of q 3 w k D oses  ....................................................................................... 3 1  
3. 2. 3  L V  3 1  
3. 2. 4  P e m br oliz u ma b  ............................................................................................................................ 3 6  
3. 2. 5  Bl i n di n g ....................................................................................................................................... 3 7  
4  
S T U D Y P O P U L A TI O N  ....................................................................................................................... 3 8  
4. 1  I ncl usi o n Criteria ....................................................................................................................................... 3 8  
4. 2  E xcl usi o n Criteria  ...................................................................................................................................... 4 0  
4. 3  C hil d beari n g P ote ntial  ............................................................................................................................... 4 1  
4. 4  Re m o val of P atie nts fr o m T hera p y or Assess me nt  .................................................................................... 4 2  
4. 4. 1  Disc o nti n uati o n of St u d y Treat me nt  ............................................................................................ 4 2  
4. 4. 2  P atie nt Wit h dra wal fr o m St u d y  ................................................................................................... 4 2  
5  
T R E A T M E N T S  .................................................................................................................................... 4 3  
5. 1  Treat me nts A d mi nistere d  ........................................................................................................................... 4 3  
5. 2  I n vesti gati o nal St u d y Dr u g: L V ................................................................................................................. 4 3  
5. 2. 1  Descri pti o n  .................................................................................................................................. 4 3  
5. 2. 2  Met h o d of Pr oc ure me nt  ............................................................................................................... 4 3  
5. 2. 3  D ose a n d A d mi nistrati o n  ............................................................................................................. 4 3  
5. 2. 4  O ver d ose  ...................................................................................................................................... 4 5  
5. 2. 5  D ose M o dificati o ns  ..................................................................................................................... 4 5  
5. 2. 6  St ora ge a n d Ha n dli n g  .................................................................................................................. 5 1  
5. 2. 7  P ac ka gi n g a n d La b eli n g  .............................................................................................................. 5 1  
5. 2. 8  Pre p arati o n ................................................................................................................................... 5 1  
5. 3  P e m br oliz u ma b  .......................................................................................................................................... 5 1  
5. 3. 1  Descri pti o n  .................................................................................................................................. 5 1  
5. 3. 2  Met h o d of Pr oc ure me nt  ............................................................................................................... 5 2  
5. 3. 3  D ose a n d A d mi nistrati o n  ............................................................................................................. 5 2  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8  of 1 5 2  
5. 3. 4  O ver d ose  ...................................................................................................................................... 5 2  
5. 3. 5  D ose M o d ificati o ns ..................................................................................................................... 5 2  
5. 3. 6  St ora ge a n d Ha n dli n g  .................................................................................................................. 5 8  
5. 3. 7  P ac ka gi n g a n d La b eli n g  .............................................................................................................. 5 8  
5. 3. 8  Pre p arati o n ................................................................................................................................... 5 8  
5. 4  Re q uire d Pre me dicati o n a n d P ost me dicati o n  ............................................................................................ 5 9  
5. 5  C o nc o mita nt T hera p y  ................................................................................................................................ 5 9  
5. 5. 1  Re q uire d C o nc o mita nt T hera p y ................................................................................................... 5 9  
5. 5. 2  All o we d C o nc o mita nt T hera p y  ................................................................................................... 5 9  
5. 5. 3  Pr o hi bite d C o nc o mita nt T hera p y  ................................................................................................. 6 0  
5. 6  Ma na ge me nt of A d verse Reacti o ns  ........................................................................................................... 6 1  
5. 6. 1  Ma na ge me nt of I nf usi o n Reacti o ns  ............................................................................................. 6 1  
5. 6. 2  S u p p orti ve Care G ui deli nes f or P e m br oliz u ma b  ......................................................................... 6 2  
5. 7  Ma na ge me nt of H y per gl yce mi a  ................................................................................................................. 6 2  
5. 8  Treat me nt C o m plia nce  ............................................................................................................................... 6 3  
6  
S T U D Y A C TI VI TI E S  .......................................................................................................................... 6 4  
6. 1  Sc he d ule of E ve nts  .................................................................................................................................... 6 4  
6. 2  P a rts A a n d B ( q 3 w k L V d osi n g) ............................................................................................................... 6 4  
6. 2. 1  Scree ni n g Visit ( Da ys – 2 8 t o 1)  .................................................................................................. 6 4  
6. 2. 2  B aseli ne Visit ( Da ys – 7 t o 1)  ....................................................................................................... 6 4  
6. 2. 3  Treat me nt P eri o d ( Da y 1 t o Da y 2 1)  ........................................................................................... 6 5  
6. 3  P arts C ( q 1 w k L V d osi n g) a n d D ( Da ys 1 a n d 8 L V d osi n g)  .................................................................... 6 6  
6. 3. 1  Scree ni n g Visit ( Da y – 2 8 t o 1)  .................................................................................................... 6 6  
6. 3. 2  B aseli ne Visit ( Da y – 7 t o 1)  ........................................................................................................ 6 7  
6. 3. 3  Treat me nt P eri o d ( Da y 1 t o 2 1 of eac h c ycle)  ............................................................................. 6 7  
6. 4  Res p o nse Assess me nts  ............................................................................................................................... 6 9  
6. 5  E n d of Treat me nt Visit ( 3 0 t o 3 7 da ys after last d ose of st u d y dr u g)  ........................................................ 6 9  
6. 6  F oll o w -u p  ................................................................................................................................................... 6 9  
6. 7  E n d of St u d y/ E n d of F oll o w -u p  ................................................................................................................. 7 0  
7  
S T U D Y A S S E S S M E N T S  .................................................................................................................... 7 1  
7. 1  Scree ni n g/ Baseli ne Assess me nts  ............................................................................................................... 7 1  
7. 1. 1  Electr ocar di o gra m  ....................................................................................................................... 7 1  
7. 2  Res p o nse/ Efficac y Assess me nts  ................................................................................................................ 7 1  
7. 3  P har mac o ki netic a n d I m m u n o ge nicit y Assess me nts  ................................................................................. 7 2  
7. 4  Bi o mar ker St u dies  ..................................................................................................................................... 7 3  
7. 4. 1  Bi o mar kers i n S oli d T u m or Tiss ue  .............................................................................................. 7 3  
7. 4. 2  Bi o mar kers i n Bl o o d .................................................................................................................... 7 4  
7. 4. 3  Bi os peci me n Re p osit or y  .............................................................................................................. 7 5  
7. 5  Safet y Assess me nts  .................................................................................................................................... 7 5  
7. 5. 1  A d verse E ve nts  ............................................................................................................................ 7 5  
7. 5. 2  Vital Si g ns  ................................................................................................................................... 8 1  
7. 5. 3  Cli n ical La b orat or y T ests ............................................................................................................ 8 2  
7. 5. 4  P h ysical E xa mi nati o n  .................................................................................................................. 8 3  
7. 5. 5  Pre g na nc y T esti n g  ....................................................................................................................... 8 3  
7. 6  A p pr o priate ness of Meas ure me nts  ............................................................................................................. 8 3  
8  
D A T A Q U A LI T Y C O N T R O L  A N D Q U A LI T Y A S S U R A N C E  ........................................................ 8 4  
8. 1  Site Trai ni n g a n d M o nit ori n g Pr oce d ures  .................................................................................................. 8 4  
8. 2  Data Ma na ge me nt Pr oce d ures  ................................................................................................................... 8 4  
8. 3  Access t o S o urce Data  ............................................................................................................................... 8 5  
8. 4  Acc urac y a n d Relia bilit y of D ata  ............................................................................................................... 8 5  
8. 5  Q ualit y Ass ura nce Pr oce d ures  ................................................................................................................... 8 5  
8. 6  Data Ha n dli n g a n d Rec or d Kee pi n g  .......................................................................................................... 8 5  
8. 6. 1  Data Ha n dli n g  .............................................................................................................................. 8 5  
8. 6. 2  I n vesti gat or Rec or d Rete nti o n ..................................................................................................... 8 5  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9  of 1 5 2  
9  
D A T A A N A L Y SI S M E T H O D S  .......................................................................................................... 8 7  
9. 1  Deter mi nati o n of Sa m ple Size  ................................................................................................................... 8 7  
9. 1. 1  P art A  ........................................................................................................................................... 8 7  
9. 1. 2  P art B  ........................................................................................................................................... 8 7  
9. 1. 3  P art C  ........................................................................................................................................... 8 8  
9. 1. 4  P art D  ........................................................................................................................................... 8 8  
9. 2  St u d y E n d p oi nt Defi niti o ns  ....................................................................................................................... 8 9  
9. 2. 1  O bj ecti ve Res p o nse Rate  ............................................................................................................. 8 9  
9. 2. 2  D urati o n of Res p o nse  .................................................................................................................. 8 9  
9. 2. 3  Disease C o ntr ol Rate  ................................................................................................................... 9 0  
9. 2. 4  Pr o gressi o n -Free S ur vi val  ........................................................................................................... 9 0  
9. 2. 5  O verall S ur vi val  .......................................................................................................................... 9 0  
9. 3  St atistical a n d A nal ytical Pla ns  .................................................................................................................. 9 1  
9. 3. 1  Ge neral C o nsi derati o ns  ............................................................................................................... 9 1  
9. 3. 2  Ti mi n g of A nal ys es  ..................................................................................................................... 9 2  
9. 3. 3  P atie nt Dis p ositi o n  ...................................................................................................................... 9 2  
9. 3. 4  P atie nt C haracteristics  ................................................................................................................. 9 2  
9. 3. 5  Treat me nt C o m plia nce  ................................................................................................................ 9 2  
9. 3. 6  Efficac y A nal yses  ........................................................................................................................ 9 3  
9. 3. 7  P har mac o ki netic a n d I m m u n o ge nicit y A nal yses  ......................................................................... 9 3  
9. 3. 8  Bi o mar ker A nal yses  .................................................................................................................... 9 3  
9. 3. 9  Safet y A nal yses  ........................................................................................................................... 9 3  
9. 3. 1 0  I nteri m A nal yses .......................................................................................................................... 9 4  
1 0  
I N F O R M E D C O N S E N T, E THI C A L R E VI E W, A N D R E G U L A T O R Y 
C O N SI D E R A TI O N S  ............................................................................................................................ 9 6  
1 0. 1  
I nf or me d C o nse nt ................................................................................................................................. 9 6  
1 0. 2  
E t hical Re vie w ...................................................................................................................................... 9 6  
1 0. 3  
Re g ulat or y C o nsi derati o ns  .................................................................................................................... 9 6  
1 0. 3. 1  I n vesti gat or I nf or mati o n .............................................................................................................. 9 7  
1 0. 3. 2  Pr ot oc ol A me n d me nts a n d St u d y T er mi nati o n  ............................................................................ 9 7  
1 0. 4  
St u d y D oc u me ntati o n, Pri vac y, a n d Rec or ds Rete nti o n  ....................................................................... 9 7  
1 0. 5  
Cli nical Trial A gree me nt  ...................................................................................................................... 9 7  
1 1  
R E F E R E N C E S  ..................................................................................................................................... 9 8  
A P P E N DI X  A:  
S C H E D U L E O F E V E N T S ( Q 3 W K L V D O SI N G; P A R T S A A N D B)  ................................... 1 0 4  
A P P E N DI X  B:  
P K A N D A T A S A M P LI N G TI M E P OI N T S ( Q 3 W K L V  D O SI N G; P A R T S A A N D  
B)  
1 0 7  
A P P E N DI X  C:  
S C H E D U L E O F E V E N T S ( P A R T S C A N D D)  ....................................................................... 1 0 8  
A P P E N DI X  D:  
P K A N D A T A S A M P LI N G TI M E P OI N T S ( P A R T S  C  A N D D)  ........................................... 1 1 0  
A P P E N DI X  E:  
BI O M A R K E R S A M P LI N G T I M E P OI N T S ............................................................................ 1 1 1  
A P P E N DI X  F:  
P E R F O R M A N C E S T A T U S S C A L E S C O N V E R SI O N  ........................................................... 1 1 2  
A P P E N DI X  G:  
G UI D A N C E O N C O N T R A C E P TI O N  ..................................................................................... 1 1 3  
A P P E N DI X  H:  
P -G P A N D C Y P 3 A I N D U C E R S/I N HI BI T O R S  ....................................................................... 1 1 4  
A P P E N DI X  I: 
N E W Y O R K H E A R T A S S O C I A TI O N C L A S SI FI C A TI ON  ................................................... 1 1 5  
A P P E N DI X  J: 
R E CI S T C RI T E RI A S U M M A R Y ( V E R SI O N 1. 1)  .................................................................. 1 1 6  
A P P E N DI X  K:  
I R E CI S T: G UI D E LI N E S F O R R E S P O N S E C RI T E RI A F O R U S E I N T RI A L S 
T E S TI N G I M M U N O T H E R A P E U TI C S  ............................................................................................ 1 1 7  
A P P E N DI X  L:  
M Y E L OI D G R O W T H F A C T O R S U P P O R T R E C O M M E N D A TI O N S  .................................. 1 1 9  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0  of 1 5 2  
A P P E N DI X  M:  
M O DI FI E D T O XI CI T Y P R O B A BI LI T Y I N T E R V A L D E SI G N SI M U L A TI O N 
R E P O R T  ............................................................................................................................................. 1 2 1  
A P P E N DI X  N:  
N A TI O N A L KI D N E Y F O U N D A TI O N, E S TI M A T E D G F R C A L C U L A TI O N  ..................... 1 2 7  
A P P E N DI X  O: I N V E S TI G A T O R SI G N A T U R E P A G E  ......................................................................................... 1 2 8  
A P P E N DI X  P: D O C U M E N T  HI S T O R Y  ................................................................................................................. 1 2 9  
 
LI S T O F I N -T E X T T A B L E S   
T a ble  1:  
Pla n ne d d ose le vels f or P art C ( q 1 w k L V d osi n g)  ................................................................................ 2 6  
T a ble  2:  
m T PI decisi o n matri x  ........................................................................................................................... 2 6  
T a ble  3:  
Re q uire d d ose m o dificati o ns f or L V -ass ociate d t o xicities ( P arts A a n d B)  .......................................... 4 7  
T a ble  4:  
Q 1 w k L V d ose re d ucti o ns f or P art C  .................................................................................................... 4 8  
T a ble 5:  
L V d ose re d ucti o ns f or P art D  .............................................................................................................. 4 9  
T a ble  6:  
D ose m o dificati o ns f or L V tre at me nt -relate d a d verse e ve nts ( P arts C a n d D) ..................................... 5 0  
T a ble  7:  
D ose m o dificati o n a n d t o xicit y ma na ge me nt g ui deli nes f or i m m u ne -relate d A Es ass ociate d 
wit h pe m br oliz u ma b  ............................................................................................................................. 5 4  
T a ble  8:  
P e m br oliz u ma b i nf usi o n reacti o n d ose m o dificati o n a n d treat me nt g ui deli nes  .................................... 5 7  
T a ble  9:  
2 -si de d 9 5 % e xact c o nfi de nce i nter vals f or P art C ............................................................................... 8 8  
T a ble  1 0:  
2 -si de d 9 5 % e xact c o nfi de nce i nter vals f or P art D ............................................................................... 8 9  
T a ble  1 1:  
Bi o mar ker sa m pli n g ti me p oi nts –  P arts A a n d B *  ............................................................................. 1 1 1  
T a ble  1 2:  
Bi o mar ker sa m pli n g ti me p oi nts –  P arts C a n d D *  ............................................................................. 1 1 1  
T a ble  1 3:  
Decisi o n r ules f or S G N L V A -0 0 2 –  P art C, b y m T PI f or eac h d ose le vel wit h tar get M T D = 
2 5 %  ..................................................................................................................................................... 1 2 2  
 
LI S T O F I N -T E X T FI G U R E S   
Fi g ure  1:  
S G N L V A -0 0 2 st u d y sc he ma ( P arts A a n d B)  ...................................................................................... 2 1  
Fi g ure  2:  
S G N L V A -0 0 2 st u d y sc he ma ( P arts C a n d D)  ...................................................................................... 2 2  
Fi g ure 3:  
P erce nt c ha n ge i n s u m of t u m or dia meters f or efficac y -e val ua ble patie nts wit h sec o n d -li ne 
m T N B C treate d wit h a starti n g d ose of 1. 2 5 m g/ k g q 1 w k  ................................................................... 3 3  
Fi g ure 4:  
P erce nt c ha n ge i n s u m of t u m or dia meters b y breast ca ncer s u bt y pe a n d d ose  .................................... 3 5  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1  of 1 5 2  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S   
A D C  
a nti b o d y-dr u g c o nj u gate  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferase  
a P T T  
acti vate d partial t hr o m b o plasti n ti me  
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  
A T A  
a ntit hera p e utic a nti b o dies  
BI C R  
bli n de d i n de p e n de nt ce ntral re vie w  
β -h C G  
beta h u ma n c h ori o nic g o na d otr o pi n  
B C  
breast ca ncer  
C E A  
carci n oe m br y o nic a nti ge n  
C B C  
c o m plete bl o o d c o u nt  
C B R  
cli nical be nefit rate  
cf D N A 
cell-free D N A 
CI  
c o nfi de nce i nter val  
C N S  
ce ntral ner v o us s yste m  
C PI  
c hec k p oi nt i n hi bit or  
C R  
c o m plete res p o nse  
C R F  
case re p ort f or m  
C T  
c o m p ute d t o m o gra p h y  
C T L A -4  
c yt ot o xic T -l y m p h oc yte-ass ociate d pr otei n 4  
C Y P 3 A  
c yt oc hr o me P 4 5 0 3 A  
C Y P 3 A 4  
c yt oc hr o me P 4 5 0 3 A 4  
D C R  
disease c o ntr ol rate  
D E  
D L T -e val ua ble  
D L T  
d ose -li miti n g t o xicit y 
D O R  
d urati o n of res p o nse  
E C G  
electr ocar di o gra m  
E CI  
e ve nts of cli nical i nterest  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
E D C  
electr o nic data ca pt ure  
E E  
efficac y-e val ua ble  
E O T  
e n d of treat me nt  
E R  
estr o ge n rece pt or  
F F P E  
f or mali n fi xe d paraffi n e m be d de d 
G -C S F  
gra n ul oc yte -c ol o n y sti m ulati n g fact or  
G F R  
gl o mer ular filtrati o n rate  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2  of 1 5 2  
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 b A 1c  
he m o gl o bi n A 1c  
H B V  
he p atitis B vir us  
H E R 2  
h u ma n e pi der mal gr o wt h fact or rece pt or 2  
H L  
H o d g ki n l y m p h o ma  
I B 
I n vesti gat or’s Br oc h ure 
I C D 
i m m u n o ge nic cell deat h 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n  
i C P D 
c o nfir me d pr o gressi ve disease  
I E C 
I n de p e n de nt Et hics C o m mitte e 
I H C 
i m m u n o hist oc he mistr y 
I N D 
i n vesti gati o nal ne w dr u g 
I N R 
i nter nati o nal n or malize d rati o 
ir A E 
i m m u ne-relate d a d verse e ve nts 
I R B 
I nstit uti o nal Re vie w B oar d 
i R E CI S T 
I m m u ne Res p o nse E val uati o n Criteria i n S oli d T u m ors 
I R R 
i nf usi o n-relate d reacti o n 
I S M C 
i n de p e n de nt safet y m o nit ori n g c o m mittee 
i U P D 
u nc o nfir me d pr o gressi ve disease  
I V 
i ntra ve n o us 
L A/ M  
l ocall y-a d va nce d or metastatic  
L A R  
le gall y a ut h orize d re prese ntati ve 
L V  
la dirat uz u ma b ve d oti n; S G N-LI V 1 A  
m A b  
m o n ocl o nal a nti b o d y  
M A D  
ma xi m u m a d mi nistere d d ose  
m B C  
metastatic breast ca ncer  
m T N B C  
metastatic tri ple -ne gati ve breast ca ncer  
m T PI  
m o difie d t o xicit y pr o ba bilit y i nter val  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
mI H F  
m ulti ple x i m m u ne hist ofl u oresce nce  
M M A E  
m o n o met h yl a uristati n E  
M RI  
ma g netic res o na nce i ma gi n g  
M T D  
ma xi m u m t olerate d d ose  
N CI C T C A E  
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  
O R R  
o bj ecti ve res p o nse rate  
O S  
o verall s ur vi val  
P B P K  
p h ysi ol o gicall y -base d P K  
P C R  
p ol y merase c hai n reacti o n  
P D  
pr o gressi ve disease  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3  of 1 5 2  
P D -1  
pr o gra m me d deat h 1  
P D -L 1  
pr o gra m me d deat h li ga n d 1  
P D -L 2  
pr o gra m me d deat h li ga n d 2  
P F S  
pr o gressi o n -free s ur vi val 
P -g p  
P -gl yc o pr otei n  
P K  
p har mac o ki netic  
P P o S  
B a yesia n pre dicti ve pr o ba bilit y of s uccess  
P R  
partial res p o nse  
P R  
pr o gester o ne rece pt or  
P T  
pr ot hr o m bi n ti me  
P T T  
partial t hr o m b o plasti n ti me  
q 1 w k  
e ver y 1 wee k / wee kl y 
q 2 w k  
e ver y 2  wee ks  
q 3 w k  
e ver y 3 wee ks  
R E CI S T  
Res p o nse E val uati o n Criteria i n S oli d T u m ors  
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S D  
sta ble disease 
S M C  
safet y m o nit ori n g c o m mittee 
S U S A Rs  
s us pecte d u ne x pecte d seri o us a d verse reacti o ns  
T C R β  
T cell rece pt or beta  
TI L  
t u m or-i nfiltrati n g l y m p h oc yte 
T N  
tri ple-ne gati ve  
T N B C  
tri ple-ne gati ve breast ca ncer  
T S H  
t h yr oi d sti m ulati n g h or m o ne 
T T P  
ti me t o pr o gressi o n 
U L N  
u p per li mit of n or mal  
U P M  
u nit pr o ba bilit y mass  
U S  
U nite d States  
U S P  
U nite d States P har mac o peia  
W B C  
w hite bl o o d cell  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4  of 1 5 2  
1.  
I N T R O D U C TI O N  
1. 1.  
Br e a st C a n c er   
A part fr o m ca ncers of t h e s ki n, breast c a ncer ( B C) is t he m ost c o m m o n mali g na nc y i n w o m e n i n 
t he U S. Des pite rece nt a d va nces i n treat me nt, it is sec o n d o nl y t o l u n g ca ncer as a ca use of 
ca ncer deat h i n w o me n. I n 2 0 1 7, it was esti mate d t hat t here w o ul d be 2 5 2, 7 1 0 ne w cas es of 
i n vasi ve B C i n w o me n i n t he U S, a n d a p pr o xi matel y 4 0, 6 1 0 deat hs (A merica n Ca ncer S ociet y 
( A C S) 2 0 1 7). F or t h e vast maj orit y of patie nts, t he eti ol o g y is u n k n o w n. W hile t he disease ca n 
arise fr o m eit her t he l o b ular or d uctal e pit heli u m, 8 5 % – 9 0 % o f i n vasi ve carci n o mas are d uctal i n 
ori gi n (D u p o nt 1 9 8 5 ). B C is a heter o ge ne o us disease a n d tr eat me nt is base d o n a n u m ber of 
pr o g n ostic a n d pre dicti ve fact ors t hat i ncl u de t u m or hist ol o g y, h or m o ne  rece pt or c o nte nt a n d 
h u ma n e pi der mal gr o wt h fact or rece pt or 2 ( H E R 2) stat us, as well as a xillar y n o dal i n v ol ve me nt, 
detecta ble met astatic dise ase, patie nt a ge, a n d me n o pa usal stat us. Treat me nt varies fr o m l ocal 
c o ntr ol wit h s ur ger y a n d/ or ra diati o n t hera p y t o s yste mic disease re q uiri n g c yt ot o xic 
c he m ot hera p y, e n d ocri ne t hera p y, bi ol o gi c a ge nts, or a c o m bi nati o n of t hes e. M ost ne w 
dia g n oses of B C are ma d e at a n earl y sta ge; h o w e ver, a p pr o xi matel y 1/ 3 of t hese patie nts will 
e ve nt uall y de vel o p r ec urre nt or me tastatic diseas e (O' S ha u g h ness y 2 0 0 5 ). L ocalize d disease is 
c ura ble, wit h a 5 -year relati ve s ur vi val of 9 8 % t hat decreases t o 8 4 % i n t h ose w h ose diseas e has 
s prea d t o t he re gi o nal l y m p h n o des. T he pr o g n osis is p o or i n t h ose wit h metastatic breast ca n cer 
( m B C), wit h a 5-year rel ati ve s ur vi val of less t ha n 2 4 % (H o wla der 2 0 1 3 ). He nce, t h e c urre nt 
t hera pies f or metastatic disease dela y dise ase pr o gressi o n, b ut are n ot c urati ve.  
Metastatic B C re mai ns a n i nc ura ble ill ness f or t he maj orit y of patie nts. O nl y a s elect f e w wit h 
hi g hl y c he m ose nsiti ve t u m ors will ac hie ve a c o m plete res p o nse ( C R) wit h c o m bi nati o n 
c he m ot hera p y re gi me ns (Gree n b er g 1 9 9 6 ). He nce f or t he re m ai ni n g p atie nts, treat me nt is 
palliati ve a n d is i nitiate d i n a n atte m pt t o dela y dis ease pr o gressi o n, alle viat e disease s y m pt o ms, 
i m pr o ve or mai ntai n q ualit y of life, a n d p ote ntiall y pr ol o n g s ur vi v al (O' S ha u g h ness y 2 0 0 5 ). 
W o me n wit h metastatic disease are i nitiall y stratifie d acc or di n g t o t u m or h or m o ne rece pt or stat us 
a n d H E R 2 a m plificati o n. A variet y of treat me nt o pti o ns are a vaila bl e, i ncl u di n g e n d o cri ne 
t hera p y s uc h as ta m o xife n, ar o matase i n hi bit ors, f ul vestra nt f or w o me n wit h h or m o ne rece pt or-
p ositi ve disease, or c yt ot o xic c he m ot hera p y a d mi nistere d as m o n ot hera p y or i n c o m bi nati o n wit h 
ot her c yt ot o xic dr u gs or bi ol o gics (e. g., tr ast uz u ma b f or H E R 2 -p ositi ve t u m ors). C urre nt 
g ui deli nes rec o m me n d s yste mic c he m ot hera p y f or w o me n wit h h or m o ne -rece pt or ne gative 
disease t hat is n ot l ocalize d t o b o ne or s oft tiss ue a n d is ass ociate d wit h s y m pt o matic visceral 
disease or f or w o me n wit h h or m o ne rece pt or -p ositi ve disease t hat has d e m o nstrate d resista nce t o 
e n d ocri ne t hera p y (C arls o n 2 0 1 1 ). 
Resista nce t o c he m ot hera p y acc o u nts f or grea ter t h a n 9 0 % of t he tr eat me nt f ail ures i n patie nts 
wit h metastatic ca ncer (L o n gle y 2 0 0 5 ; Ri vera 2 0 1 0 ). As a res ult, treat me nt o pti o ns are li mite d 
f or patie nts wit h m B C w h o ha ve ha d pri or e x p os ure t o c he m ot hera p y. O nce patie nts pr o gress t o 
re q uiri n g c he m ot hera p y i n t he metastatic setti n g, 2 5 %– 4 5 % of t he m ac hie ve a n o bjecti ve 
res p o nse wit h first li ne si n gle-a ge nt c h e m ot hera p y f or metastatic disease a n d ha ve a ti me t o 
pr o gressi o n ( T T P) of 5 – 8 m o nt hs (B urstei n 2 0 1 1 ). Wit h sec o n d li ne c he m ot hera p y i n t he 
metastatic setti n g, t he o bj ec ti ve res p o ns e rat e ( O R R) di mi nis hes t o 1 5 %– 3 0 % wit h a T T P of 2 – 5 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 5  of 1 5 2  
m o nt hs, a n d f oll o wi n g t hir d li ne t hera p y, t he O R R is 0 % – 2 0 % wit h a T T P of 1 – 4  m o nt hs. 
He nce, f or w o me n wit h m B C w h o re q uir e c he m ot hera p y, t he cli nical be nefits are mar gi n al, a n d 
n o ne are c ura ti ve. 
1. 2.  
Tri pl e -N e g ati v e Br e a st C a n c er   
Tri ple -ne gati ve breast ca ncer ( T N B C) acc o u nts f or a p pr o xi matel y 1 0 % – 2 0 % of B Cs. T hes e 
t u m ors lac k estr o ge n, pr o gester o ne, a n d H E R 2 rece pt ors an d are ass o ciate d wit h p o orer 
pr o g n osis c o m p are d t o ot her t y p es of B C. T N B C has a hi g h pr oliferati ve rat e a n d a 
heter o ge n e o us ge ne e x pressi o n pr ofile. Patie nts wit h metastatic tri ple -ne gati ve breast c a ncer 
( m T N B C) ha ve a me di a n o verall s ur vi val ( O S) of less t ha n 1 year (R o dler 2 0 1 0 ; de n Br o k 2 0 1 7 ). 
T he lac k of h or m o ne a n d H E R 2 rece pt ors li mits treat me nt o pti o ns i n T N B C t o c urre ntl y 
a vaila ble c h e m ot hera p y i n b ot h t he l ocal a n d metastatic setti n gs. C o nsi derati o ns f or treati n g 
l ocall y-a d va n ce d or m etastatic ( L A/ M) disease i n cl u de pre vi o us c he m ot hera p y e x p os ure, 
perf or ma n ce stat us, c o m or bi d c o n diti o ns, t u m or c haract eristics, patie nt  prefere n ce, a n d q ualit y of 
life c o ncer ns. Se q ue ntial si n gle-a ge nt s yste mic c h e m ot hera pies ass ociate d wit h mi ni mal t o xicit y 
are preferre d. C o m m o nl y use d si n gle a ge nts i ncl u de ta xa nes a n d a nt hr ac ycli nes. Sta n dar d 
cli nical practice is t o c o nti n ue first li ne c he m ot hera p y u ntil pr o gressi o n. T he c h oice of 
c he m ot hera p y f or m B C is n ot well defi ne d. T here are n o p u blis he d e vi d e nce -base d cli nical 
g ui deli nes wit h e x plicit rec o m me n dati o ns a b o ut w hat s yste mic treat me nt is m ore a p pr o pri ate f or 
t hese patie nts wit h a d va n ce d T N B C. I n rece nt P hase 2 a n d 3 T N B C trials o n first li ne si n gle -
a ge nt c he m ot hera pies, i n cl u di n g ta x a nes, plati n u ms, a n d a nt hrac ycli nes, t he O R R was 
a p pr o xi matel y 2 9 % – 4 0 % a n d t he me dia n pr o gressi o n -free s ur vi val ( P F S) was 3– 6 m o nt hs 
(Hel wic k 2 0 1 5 ; Is a k off 2 0 1 5; R u g o 2 0 1 5 ). C o m bi nati o n t hera pies of tr a diti o nal 
c he m ot hera p e utic a ge nts (e. g., ge mcita bi ne  +  car b o plati n) are als o use d. Rece nt a nal yses s h o w 
c o m bi nati o n t hera pies c o nfer little t o n o s ur vi val be nefits a n d ha v e a hi g her t o xicit y pr ofile w he n 
c o m pare d t o t he s e q ue nti al si n gle-a ge nt c he m ot hera p y (Carls o n 2 0 1 1 ; Dear 2 0 1 3 ). 
Gi ve n t he c urre nt la n dsca pe, t here is a n o b vi o us a n d ur ge nt nee d f or n o vel t hera pies i n t he first 
li ne L A/ M setti n g t hat ca n pr o vi de cli nical a n d s ur vi val be nefit. 
1. 3.  
LI V -1   
LI V -1 is a me m ber of t he s ol ute carrier fa mil y 3 9, a n d is a m ultis pa n tra ns me m bra ne pr otei n 
wit h p utati ve zi nc tra ns p orter a n d met all o pr otei nase acti vit y (Ta yl or 2 0 0 3 ). It was first i de ntifie d 
as a n estr o ge n i n d uce d ge ne i n t he B C cell li ne Z R -7 5 -1 (Ma n ni n g 1 9 8 8 ). S u bse q ue ntl y, n or mal 
tiss ue e x pressi o n has bee n de m o nstrate d i n h or m o nall y-re g ulate d tiss ues wit h t he hi g hest 
e x pressi o n i n breast a n d pr ostate sa m ples (S uss ma n 2 0 1 4 ). 
LI V -1 e x pressi o n has bee n li n ke d wit h mali g na nt pr o gressi o n t o metastasis a n d is ass ociate d 
wit h l y m p h n o d e i n v ol ve me nt i n B C (Ma n ni n g 1 9 9 4 ). It is e x presse d i n al m ost all m B C t u m ors, 
wit h m o derate -t o-hi g h e x pressi o n i n 8 6 % of H R +/ H E R 2 -, 7 4 % of H E R 2 +, a n d 7 1 % of T N B Cs 
(F orer o 2 0 1 6 ). LI V -1 h as bee n dete cte d i n a n u m b er of ca ncer t y pes i ncl u di n g breast, pr ostate, 
mela n o ma, o varia n, cer vical, uteri ne, a n d pa ncreatic ca ncer (M a n ni n g 1 9 8 8 ; Ma n ni n g 1 9 9 4 ; 
Dress ma n 2 0 0 1 ; T ozl u 2 0 0 6 ; U n n o 2 0 0 9 ; S uss ma n 2 0 1 4 ). I n a n i m m u n o hist oc he mistr y (I H C) 
a nal ysis c o n d ucte d b y Sea ge n I nc. , t h e hi g h est pre vale nce a n d le vel of e x pressi o n is see n i n 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 6  of 1 5 2  
breast d uctal carci n o ma ( 9 3 % of rela ps e d p ost -treat me nt patie nt sa m ples), pr ostate 
a de n ocarci n o ma ( 7 2 % of rela pse d p ost -tr eat me nt, castrati o n-resista nt patie nt sa m ples) a n d 
m ela n o ma ( 8 2 % of pri mar y mela n o ma bi o psies) (S uss ma n 2 0 1 4 ). 
1. 4.  
L a dir at u z u m a b V e d oti n   
La dirat uz u ma b ve d oti n ( L V; S G N -LI V 1 A ) is a n a nti b o d y-dr u g c o nj u gate ( A D C) directe d 
a gai nst t he LI V -1 a nti ge n a n d  is bei n g d e vel o pe d t o treat patie nts wit h LI V-1 -p ositi ve 
mali g na n cies, s uc h as B C. T he a nti b o d y b ac k b o n e of L V , h LI V 2 2, is a h u ma nize d I g G 1 
m o n ocl o nal a nti b o d y ( m A b) t hat is c he micall y c o nj u gate d t o a s y nt h etic a n al o g ( m o n o met h yl 
a uristati n E [ M M A E]) of t he nat urall y occ urri n g t u b uli n -disr u pti n g dr u g, d olastati n 1 0. T he 
pr otease -clea v a ble vali ne -citr ulli ne malei mi d oca pr o yl li n ker c o v ale ntl y attac hes M M A E t o 
h LI V 2 2. A n a v era ge of 4 M M A E m olec ules is prese nt o n eac h a nti b o d y m olec ule.  
1. 4. 1.  
M e c h a ni s m of A cti o n of L V   
S u bse q ue nt t o bi n di n g t o cell -s urface LI V-1, L V  is i nter nalize d a n d traffi c k e d t hr o u g h t he 
e n d oc ytic pat h w a y t o reac h t he l ys os o mes. Pr ote ol ytic de gra dati o n of t h e dr u g li n ker  i n 
l ys os o mes rel eases M M A E, w hic h bec o mes a vail a ble f or t u b uli n bi n di n g. I nteracti o n bet wee n 
M M A E a n d t u b uli n disr u pts t he cell ular micr ot u b ule net w or k, arrests cells at t he G 2/ M p hase of 
t he cell c ycle, pre v e nts c ell di visi o n, a n d e ve nt uall y lea ds t o cell ular a p o pt osis. A ntit u m or 
acti vit y a n d i m m u n os pecificit y of L V  h a ve b ee n d e m o nstrate d i n vitr o a n d i n vi v o wit h m o dels 
re pres e nti n g LI V-1 -e x pressi n g breast, pr ostate, a n d cer vical ca n cer.  
1. 4. 2.  
Pr e cli ni c al E x p eri e n c e wit h L V   
T he t o xicit y of L V  f oll o wi n g i ntra v e n o us (I V) a d mi nistrati o n has bee n e val uate d i n rats (si n gle- 
a n d re peat -d ose st u dies) a n d m o n ke ys (si n gle -d os e st u d y o nl y). T h e d ose -li miti n g t o xicit y ( D L T) 
was b o ne marr o w s u p pr essi o n, wit h c o nc o mita nt re d ucti o ns i n he mat ol o g y e n d p oi nts 
( pre d o mi na ntl y a ne mia a n d ne utr o pe nia). D ose-d e pe n de nt t o xicities i ncl u de d li ver, s mall 
i ntesti ne, ma m mar y gla n ds, t h y m us, ki d ne y, s plee n, o var y, mese nteric l y m p h n o de, s ki n, a n d 
rect u m. 
Si milar h e mat o p oietic cell de pleti o n a n d tar get or ga ns of t o xicit y h a ve bee n o bser ve d f or M M A E 
(t he c yt ot o xic c o m p o ne nt of L V ) a d mi nistere d at m olar e q ui vale nts of A D C hi g hest n o n-se v erel y 
t o xic d ose le vels. A n a d diti o nal M M A E-relate d t o xicit y, n ot o bser ve d t o date i n t he L V  st u dies, 
is de ge n erati o n of s per m atic e pit heli u m i n t he male re pr o d ucti ve tract. Treat me nt wit h M M A E 
d uri n g pre g na n c y i n rats als o le d t o e m br y o -fetal de vel o p me nt t o xicit y c h aracterize d b y 
si g nifica nt i ncreas es i n t otal res or pti o ns, p ost i m pla ntati o n l oss, earl y deli ver y, a n d l oss of via ble 
fet uses. 
A c o m plete s u m mar y of t he n o ncli nical data rele va nt t o t he i n vesti gati o nal pr o d uct a n d its st u d y 
i n h u ma n s u bjects is pr o vi de d i n t he L V  I n vesti gat or’s Br oc h ure (I B). 
1. 4. 3.  
Cli ni c al E x p eri e n c e wit h L V   
T he safet y a n d efficac y of L V  is bei n g e val uat e d i n a n o n g oi n g p h ase 1 d os e-escalati o n st u d y i n 
patie nts wit h hea vil y pretreate d, u nresecta ble L A/ M T N B C ( Pr ot oc ol S G N L V A -0 0 1). I n t h e 
5 3  patie nts treate d t o dat e wit h m o n ot hera p y L V , i ncl u di n g 3 5 patie nts wit h tri ple-ne gati ve ( T N ) 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 7  of 1 5 2  
disease, t he ma xi m u m t olerate d d os e ( M T D) was n ot e xcee de d aft er es calati n g t o 2. 8  m g/ k g 
e ver y 3 w ee ks ( q 3 w k). N o D L Ts i n C ycle 1 were o bser ve d i n t he 1 9  D L T -eval ua ble ( D E) 
patie nts. L V  was ge n erall y w ell t olerate d, a n d t h e m ost c o m m o n a d verse e v e nts ( A Es) of a n y 
gra de i ncl u de d fati g ue, n a usea, al o p ecia, decrease d a p petite, c o nsti pati o n, peri p heral ne ur o pat h y, 
a n d ne utr o pe nia. Of t he 3 0 patie nts wit h LI V -1 p osit i ve T N disease e v al ua ble f or res p o ns e 
treate d at d os es fr o m 1. 5– 2. 8  m g/ k g, 1 1  ( 3 7 %) ac hie ve d a n o bjecti ve parti al res p o nse ( P R) ( n o 
c o m plete re missi o ns) i ncl u di n g 6  ( 2 0 %) t hat were c o nfir me d P R (as prese nte d b y F orer o A, et al 
at S A B C S 2 0 1 6). Diseas e c o ntr ol rat e ( D C R) was 6 7 % ( 1 1  P R, 9 sta ble disease [ S D]) a n d 
cli nical be nefit r ate ( C B R = O R + S D ≥2 4  wee ks) was 4 7 % ( 1 4  p atie nts). Gi ve n t he acti vit y 
o bser ve d wit h L V  i n pati e nts wit h hea vil y pretreat e d L A/ M T N B C, t here is reas o n t o s u p p ort t he 
h y p ot hesis t hat L V  will h a ve si g nifica nt si n gle -a ge nt acti vit y i n patie nts wit h pre vi o usl y 
u ntreate d L A/ M T N B C.   
See t he L V  I B f or c o m plete cli nical safet y i nf or m ati o n. 
1. 5.  
P e m br oli z u m a b B a c k gr o u n d   
Pe m br oliz u ma b is a p ote nt h u ma nize d i m m u n o gl o b uli n G 4 (I g G 4) m A b wit h hi g h s pecificit y of 
bi n di n g t o t he pr o gra m me d cell deat h 1 ( P D -1) rece pt or, t h us i n hi biti n g its i nteracti o n wit h 
pr o gra m me d cell deat h li ga n d 1 ( P D -L 1) a n d pr o gra m me d cell deat h li ga n d 2  ( P D-L 2). Base d o n 
precli nical i n vitr o data, pe m br oliz u ma b has hi g h affi nit y a n d p ote nt rece pt or bl oc ki n g acti vit y 
f or P D-1. Pe m br oliz u ma b has a n acce pta bl e precli nical safet y pr ofile a n d is i n cli nical 
de vel o p me nt as a n I V i m m u n ot hera p y f or a d va nce d mali g na n cies. Ke ytr u d a ®  ( pe m br oliz u ma b) 
is i n dicate d f or t he tr eat me nt of patie nts acr oss a n u m ber of i n dicati o ns. F or m ore details o n 
s pecific i n dicati o ns r efer t o t he I n v esti gat or’s Br oc h ure.  
Refer t o t he I B/a p pr o ve d la beli n g f or detaile d bac k gr o u n d i nf or mat i o n o n M K-3 4 7 5.  
1. 5. 1.  
P h ar m a c e uti c al a n d T h er a p e uti c B a c k gr o u n d   
T he i m p orta nce of i ntact i m m u ne s ur veilla nce f u ncti o n i n c o ntr olli n g o ut gr o wt h of ne o plastic 
tra nsf or mati o ns has bee n k no w n f or deca des (Disis 2 0 1 0 ). Acc u m ulati n g e vi de nce s h o ws a 
c orrel ati o n bet wee n t u m or -i nfiltrati n g l y m p h oc ytes i n ca ncer tiss ue a n d fa v ora ble pr o g n osis i n 
vari o us mali g n a ncies. I n partic ular, t he prese n ce of C D 8 + T -cells a n d t he rati o of C D 8 + effect or 
T cells/ F o x P 3 + re g ul at or y T cell s c orrelates wit h i m pr o ve d pr o g n osis a n d l o n g-ter m s ur vi val i n 
s oli d mali g na ncies, s uc h as o varia n, c ol orect al, a n d pa ncreatic ca ncer; he pat ocell ular carci n o ma; 
mali g na nt mela n o ma; a n d re nal c ell carci n o ma. T u m or -i nfiltrati n g l y m p h o c yt es ca n b e e x pa n de d 
e x  vi v o a n d rei nf use d, i n d uci n g d ura ble o bjecti ve t u m or res p o nses i n ca n cers s uc h as mela n o ma 
(D u dle y 2 0 0 5 ; H u n der 2 0 0 8 ). 
T he P D -1 rece pt or -li ga n d i nteracti o n is a maj or p at h wa y hijac k e d b y t u m ors t o s u p press i m m u ne 
c o ntr ol. T he n or mal f u n cti o n of P D -1, e x presse d o n t he cell s urface of acti v ate d T  cells u n der 
healt h y c o n diti o ns, is t o d o w n -m o d ulate u n wa nte d or e x cessi ve i m m u ne re s p o nses, i ncl u di n g 
a ut oi m m u ne reacti o ns. P D -1 (e n c o de d b y t he ge n e P dc d 1 ) is a n I g s u perfa mil y m e m ber relate d 
t o C D 2 8 a n d c yt ot o xic T-l y m p h oc yte-ass oci ate d pr otei n 4 ( C T L A -4) t hat has bee n s h o w n t o 
ne gati vel y re g ulat e a nti ge n rece pt or si g nali n g u p o n e n ga ge me nt of its li ga n ds ( P D -L 1 a n d/ or 
P D -L 2) (O kaza ki 2 0 0 1 ; Gree n wal d 2 0 0 5 ). 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 8  of 1 5 2  
T he str uct ure of m uri ne P D -1 has bee n res ol ve d (Z ha n g 2 0 0 4 ). P D-1 a n d its fa mil y me m bers are 
t y pe I tra ns me m br a ne gl yc o pr otei ns c o ntai ni n g a n I g-Varia ble -t y pe d o m ai n res p onsi ble f or 
li ga n d bi n di n g a n d a c yt o plas mic tail res p o nsi ble f or t he bi n di n g of si g nali n g m olec ul es. T he 
c yt o plas mic tail of P D -1 c o ntai ns 2  t yr osi ne-base d si g nali n g m otifs, a n i m m u n orece pt or 
t yr osi ne-base d i n hi biti o n m otif, a n d a n i m m u n orece pt or t yr osi ne -bas e d s witc h m otif. F oll o wi n g 
T cell sti m ulati o n, P D -1 recr uits t he t yr osi ne p h os p hatases, S H P -1 a n d S H P -2, t o t he 
i m m u n orece pt or t yr osi ne-base d s witc h m otif wit hi n its c yt o plas mic tail, lea di n g t o t he 
de p h os p h or yl ati o n of effect or m olec ules, s u c h as C D 3 z eta, pr otei n ki nase C -t heta, a n d 
zeta-c hai n-ass ociate d pr otei n ki nase, w hic h are i n v ol ve d i n t he C D 3 T cell si g nali n g cas ca d e 
(O kaza ki 2 0 0 1 ; C he m nitz 2 0 0 4 ; S he p par d 2 0 0 4 ; Rile y 2 0 0 9 ). T he m ec ha nis m b y w hic h P D-1 
d o w n -m o d ulates T cell res p o nses is si milar t o, b ut disti nct fr o m t hat of C T L A -4, beca use b ot h 
m olec ules re g ulat e a n o v erla p pi n g set of si g nali n g pr otei ns (Parr y 2 0 0 5 ; Fra ncisc o 2 0 1 0 ). As a 
c o nse q ue nce, t he P D -1/ P D -L 1 pat h wa y is a n attracti ve tar get f or t hera p e utic i nter ve nti o n i n 
u nresect a ble L A/ M T N B C.  
1. 5. 2.  
Pr e -cli ni c al a n d Cli ni c al Tri al s   
T her a p e utic st u dies i n m o use m o dels ha ve s h o w n t hat a d mi nistrati o n of a nti b o dies bl oc ki n g 
P D -1/ P D -L 1 i nteracti o n e n ha nces i nfiltrati o n of t u m or -s pecific C D 8 + T cells a n d ulti matel y 
lea ds t o t u m or rejecti o n, eit her as a m o n ot hera p y or i n c o m bi nati o n wit h ot her treat me nt 
m o dalities (Str o me 2 0 0 3 ; Bla n k 2 0 0 4 ; Hira n o 2 0 0 5 ; C urra n 2 0 1 0 ; Pil o n -T h o mas 2 0 1 0 ; We ber 
2 0 1 0 ; S pra n ger 2 0 1 4 ). A nti-m o use P D -1 or a nti -m o use P D -L 1 a nti b o dies ha ve de m o nstrat e d 
a ntit u m or res p o nses i n m o dels of s q ua m o us cell carci n o ma, pa n creatic carci n o ma, mela n o ma, 
ac ute m yel oi d le u ke mia, a n d c ol orectal carci n o ma (Str o me 2 0 0 3 ; Z ha n g 2 0 0 4 ; N o mi 2 0 0 7 ; 
C urra n 2 0 1 0 ; Pil o n -T h o mas 2 0 1 0 ). I n s uc h st u di es, t u m or i nfiltrati o n b y C D 8 + T cells a n d 
i ncreas e d I F N-γ, gra nz y me B a n d p erf ori n e x pressi o n were o bser ve d, i n dicati n g t hat t he 
mec ha nis m u n derl yi n g t h e a ntit u m or acti vit y of P D -1 c hec k p oi nt i n hi biti o n i n v ol ve d l ocal 
i nfiltrati o n a n d acti vati o n of effect or T cell f u ncti o n i n  vi v o (C urra n 2 0 1 0 ). E x peri me nts ha ve 
c o nfir me d t he i n vi v o efficac y of a nti -m o use P D -1 a nti b o d y as a m o n ot hera p y, as well as i n 
c o m bi nati o n wit h c he m ot hera p y, i n s y n ge n eic m o use t u m or m o dels (see t h e I B).  
J ustificati o n f or t he pla n ne d d ose of pe m br oliz u ma b f or t his st u d y is detail e d i n Secti o n  3. 2. 3. 1 . 
1. 6.  
R ati o n al e f or St u d y   
F or patie nts wit h m B C, t here are n o c urati ve o pti o ns. W hile s yste mic treat me nts ai m t o pr ol o n g 
s ur vi val, c o ntr ol disease pr o gressi o n, alle viate s y m pt o ms, a n d e n ha nce p atie nt q ualit y o f life, t he 
5 -year s ur vi val rates f or patie nts wit h dista nt -sta ge disease re mai n l o w at 2 4 % (H o wla der 2 0 1 3 ). 
E vi de nc e of a nti -t u m or acti vit y has bee n o bser ve d wit h L V  m o n ot hera p y i n patie nts wit h hea vil y 
pretreate d T N B C, a n d it is t heref ore warra nt e d t o e x pl ore c o m bi ni n g t his tar get e d a ge nt wit h 
ot her treat me nts, s uc h as c hec k p oi nt i n hi bit ors ( C PIs).  
Alt h o u g h C PIs re pre se nt a si g nifica nt a d va n ce me nt i n t he treat me nt of ca n cer, patie nts wit h 
L A/ M T N B C c o nti n ue t o ha ve a v er y p o or pr o g n osis a n d c o m bi ni n g C PIs wit h a n o vel t hera p y, 
s uc h as L V , ma y b e be neficial. A nti-P D( L) 1 a ge nts i n c o m bi nati o n wit h c he m ot hera p y ha v e 
bee n s h o w n t o be effic aci o us i n m T N B C (Sc h mi d 2 0 1 8 ). L V  a n d pe m br oliz u ma b act t hr o u g h 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 9  of 1 5 2  
disti nct a n d c o m ple me ntar y mec h a nis ms of act i o n. L V , a directl y c yt ot o xic a ge nt, ma y i n d uce 
i m m u n o ge nic cell deat h (I C D). B y a d mi nistrati n g L V  i n c o m bi nati o n wit h pe m br oliz u ma b, it is 
h y p ot hesize d t hat LI V -e x pressi n g t u m or cells kille d b y L V  will p ote ntiall y acti vate t he i n nate 
i m m u ne s yste m t o i nitiate a ntit u m or i m m u ne res p o nse. At t he sa me ti me , t he C PI 
pe m br oliz u ma b u nleas hes t he a ntit u m or acti vit y of T  l y m p h oc yt es b y t ar geti n g t he T cell 
i n hi biti o n pat h wa y. T here are c urre ntl y n o d ata a v aila ble f or t his c o m bi nati o n i n B C; h o we ver, 
bre nt u xi ma b ve d oti n, a n ot her A D C wit h t he sa me M M A E dr u g li n ker, has bee n st u die d i n 
c o m bi nati o n wit h t he C PI ni v ol u ma b f or treat me nt of H o d g ki n l y m p h o ma ( H L). Preli mi nar y 
data s u g gest t hat bre nt u xi ma b ve d oti n, a C D 3 0 -directe d A D C, i ncreases t u m or i m m u n o ge nicit y 
b y i n d uc ti o n of I C D, a nti ge n prese nt ati o n, a n d t u m or i m m u ne i nfiltrati o n (Gar dai 2 0 1 5 ). 
Preli mi nar y cli nical data f or bre nt u xi ma b ve d oti n i n c o m bi nati o n wit h ni v ol u ma b i n 
rela pse d/r efract or y H L d e m o nstrate i ncrease d a ntit u m or acti vit y a b o v e w hat w o ul d be e x pecte d 
wit h t he a d diti ve effects of eac h a ge nt, alt h o u g h t he n u m ber of patie nts treate d is s mall ( n = 1 2) 
(Diefe n b ac h 2 0 1 7 ). 
It is h yp ot hesize d t hat c o m bi ni n g L V  wit h pe m br oliz u ma b  will res ult i n i m pr o ve d res p o nse rates 
a n d ma y be s y ner gistic, wit h t he p ote ntial t o pr ol o n g P F S a n d O S i n patie nts wit h L A/ M B C. 
M ore o ver, b ot h a ge nts are well t olerate d, ha ve fe w o verla p pi n g Gra de 3 – 5 t o xic ities, a n d ca n be 
i nf use d i n t he o ut patie nt setti n g. T his st u d y will e val uate t he safet y a n d a ntit u m or acti vit y of L V  
i n c o m bi nati o n wit h pe m br oliz u ma b i n a p o p ulati o n of patie nts f or w h o m sta n dar d t hera p y is 
u nsatisfact or y . 
A c o m plete s u m mar y of t he cli ni cal a n d n o ncli nical data rel e va nt t o L V  a n d pe m br oliz u ma b a n d 
t heir st u d y i n h u ma n s u bj ects is pr o vi de d i n eac h pr o d uct’s I B. T he s p o ns or ac k n o wle d ges t hat 
n o precli nical dat a t o c haracterize t he a ntit u m or acti vit y a n d t o xicit y of t h e L V  a n d 
pe m br oliz u ma b c o m bi nati o n ha ve bee n ge nerate d.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 0  of 1 5 2  
2.  
O B J E C TI V E S A N D E N D P O I N T S  
Pri m ar y S afet y O bjecti ves  
C orres p o n di n g E n d p oi nt  
E val uate t he safet y a n d t olera bilit y of t he 
c o m bi nati o n of L V  a n d pe m br oliz u ma b i n patie nts 
wit h L A/ M T N B C  
I de ntif y t he rec o m me n de d d ose a n d sc he d ule of L V  
i n c o m bi nati o n wit h pe m br oli z u ma b i n patie nts 
wit h L A/ M T N B C  
T y pe , i nci de nce, se verit y, seri o us ness, a n d 
relate d ness of A Es 
La b orat or y a b n or malities  
I nci de nce of D L T  
Pri m ar y Effic ac y O bjecti ve  
C orres p o n di n g E n d p oi nt  
E val uate t he c o nfir me d O R R of t he c o m bi nati o n of 
L V  a n d pe m br oliz u ma b i n patie nts wit h L A/ M 
T N B C  
C o nfir me d O R R as deter mi ne d b y t he i n vesti gat or 
acc or di n g t o 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  
Sec o n d ar y Effic ac y O bjecti ves  
C orres p o n di n g E n d p oi nts  
E val uate t he D O R, D C R, P F S, a n d O S  
D O R as deter mi ne d b y R E CI S T v 1. 1  
D C R as deter mi ne d b y R E CI S T  v 1. 1.  
P F S as deter mi ne d b y R E CI S T v 1. 1  
O S  
E x pl or at or y Effic ac y O bjecti ves  
C orres p o n di n g E n d p oi nts  
E val uate t he O R R, D O R, D C R, a n d P F S acc or di n g 
t o i R E CI S T 
O R R as deter mi ne d b y i R E CI S T  
D O R as deter mi ne d b y i R E CI S T  
D C R as deter mi ne d b y i R E CI S T  
P F S as deter mi ne d b y i R E CI S T  
P h ar m ac o ki netic a n d I m m u n o ge nicit y O bjecti ves  
C orres p o n di n g E n d p oi nts  
Assess p har mac o ki netics ( P K) a n d  i nci de nce of 
a ntit hera p e utic a nti b o dies ( A T As) of L V  
Selecte d P K para meters f or L V , a n d M M A E 
I nci de nce of A T As t o L V  
Bi o m ar kers O bjecti ves  
C orres p o n di n g E n d p oi nts  
E val uate t he P D -L 1 a n d LI V -1 e x pressi o n -res p o nse 
relati o ns hi p 
Assess e x pl orat or y bi o mar kers (e. g., i n t he t u m or 
i m m u ne micr oe n vir o n me nt or peri p her y) of st u d y 
treat me nt-me diate d p har mac o d y na mic effects  
P D -L 1 a n d LI V -1 e x pressi o n -res p o nse relati o ns hi p 
f oll o wi n g treat me nt wit h L V  a n d pe m br oliz u ma b  
Relati o ns hi p bet wee n bi o mar kers i n bl o o d a n d t u m or 
tiss ue t o efficac y, safet y, or ot her bi o mar ker 
e n d p oi nts f oll o wi n g treat me nt wit h 
L V / pe m br oliz u ma b (see Secti o n 7. 4 ) 
R E CI S T = Res p o nse E val u ati o n Criteria i n S oli d T u m ors; i R E CI S T =I m m u ne Res p o nse E val u ati o n Criteria i n S oli d T u m ors.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 1  of 1 5 2  
3.  
I N V E S TI G A TI O N A L P L A N  
3. 1.  
S u m m ar y of St u d y D e si g n   
T he st u d y c o nsists of Parts A, B , C, a n d D . Parts A a n d B are d e picte d sc h e maticall y i n Fi g ure  1 . 
T he st u d y assess me nt sc he d ule will be t he sa me f or Parts A a n d B, wit h e xce pti o ns t o C ycle  1 
Da y 3 a n d Da y 5 (see A p pe n di x  B ). Parts C  a n d D  are de pi cte d i n Fi g ure  2 . T he st u d y 
assess me nt sc he d ule will be t he sa me f or Parts C a n d D, wit h  t he e x ce pti o n of Da y 1 5 d osi n g 
o nl y rel e va nt t o Part C  (s ee A p pe n di x  C ). 
Fi g ur e  1 : 
S G N L V A -0 0 2 st u d y s c h e m a ( P art s A a n d B)  
 
a 
Res p o nse assess me nts t o be perf or me d e ver y 6 wee ks ( ± 3 da ys) f or t h e first 1 2 m o nt hs a n d e ver y 1 2 we e ks ( ± 7  da ys) 
t h ereafter, re gar dless of d ose dela ys. F oll o wi n g e n d of st u d y treat me nt, n o a d diti o nal sca ns or res p o nse assess me nts are 
re q uire d after t he safet y f oll o w-u p peri o d, h o we ver a d diti o nal sca ns or res p o nse assess me nts ma y be perf or me d as p art of 
t h e patie nt’s sta n dar d of care at a n y ti me . F or first o bjecti ve res p o nse ( C R or P R), a sca n will be perf or me d at least 4 wee ks 
after first d oc u me ntati o n of res p o nse.   
b  
P atie nts w h o disc o nti n ue st u d y treat me nt i n t h e a bse nce of disease pr o gressi o n will c o nti n ue t o be e val u ate d f or re s p o nse 
e ver y 6 wee ks u ntil c o m pleti o n of  t h e safet y f oll o w-u p peri o d ( 3 0 da ys p ost treat me nt f or L V  a n d 9 0 da ys p ost treat me nt f or 
p e m br oliz u ma b ). T he i n vesti gat or will be e x pecte d t o m o nit or f or a n d re p ort a n y S A Es a n d pre g na ncies, as d etaile d i n 
Secti o n  7. 5. 1. 2  a n d Secti o n  7. 5. 1. 4  f or patie nt s w h o are still recei vi n g treat me nt or  i n t he safet y f oll o w-u p peri o d. See  
Secti o n  0  f or details . 
c 
Ne wl y  o btai ne d c ore or e xcisi o nal t u m or bi o ps y. F or patie nts wit h i naccessi ble t u m ors or ot her safet y c o ncer ns, arc hi val 
tiss ue ma y be s u b mitte d. If neit her a de q uate fres h n or arc hi ve d tiss ue is a vaila ble, please c o ntact t he me dical m o nit or. See 
Secti o n 7. 4. 1  f or details.  
d  
Bi o ps y o btai ne d o n C ycle 1 Da y 5 ( wi n d o w Da ys 4 – 7) f or patie nts i n P art A wit h accessi ble t u m ors or at C ycle 1 Da y  1 5 
( wi n d o w Da ys 1 5– 2 1) f or patie nts i n P art B wit h accessi ble t u m ors. 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 2  of 1 5 2  
Fi g ur e  2 : 
S G N L V A -0 0 2 st u d y s c h e m a ( P art s  C  a n d D ) 
 
a 
Res p o nse assess me nts t o be perf or me d e ver y 6 wee ks ( ± 3 da ys) f or t h e first 1 2 m o nt hs a n d e ver y 1 2 we e ks ( ± 7  da ys) 
t h ereafter, re gar dless of d ose dela ys. F or first o bjecti ve res p o nse ( C R or P R), a sca n will be perf or me d at least 4 wee ks after 
first d oc u me ntati o n of res p o nse. F oll o wi n g e n d of st u d y treat me nt, n o a d diti o nal sca ns or res p o nse assess me nts are re q uire d 
after t he safet y f oll o w -u p peri o d, h o we ver a d diti o nal sca ns or res p o nse assess me nts ma y be perf or me d as p art of t h e 
patie nt’s sta n dar d of care at a n y ti me.  
b  
P atie nts w h o disc o nti n ue st u d y treat me nt i n t h e a bse nce of disease pr o gressi o n will c o nti n ue t o be e val u ate d f or res p o nse 
e ver y 6 wee ks u ntil c o m pleti o n of t h e safet y f oll o w -u p peri o d ( 3 0 da ys p ost treat me nt f or L V a n d 9 0 da ys p ost treat me nt f or 
pe m br oliz u ma b). T he i n vesti gat or will be e x pecte d t o m o nit or f or a n d re p ort a n y S A Es a n d pre g na ncies, as d etaile d i n 
Secti o n  7. 5. 1. 2  a n d Secti o n  7. 5. 1. 4  f or patie nts w h o are still recei vi n g treat me nt or i n t he safet y f oll o w-u p peri o d. See 
Secti o n  0  f or details. 
c 
Arc hi v al or ne wl y o btai ne d c ore or e xcisi o nal t u m or bi o ps y. If neit her arc hi ve d tiss ue n or a de q uate fres h is a vaila ble, pleas e 
c o ntact t h e me dical m o nit or . See Secti o n 7. 4. 1  f or details. 
 
Patie nts will be e val uate d f or res p o ns e assess me nts e ver y 6 wee ks ( ± 3 da ys) f or t he first 
1 2  m o nt hs, a n d e ver y 1 2 wee ks ( ± 7 d a ys) t hereaft er, re gar dless of d os e del a ys, t hereafter t hr o u g h 
t he e n d of t he safet y f oll o w-u p peri o d. N o a d diti o nal sca ns or res p o nse ass ess me nts are re q uire d 
after t he s afet y f oll o w -u p peri o d. A d diti o nal sca ns or res p o nse assess me nts ma y b e perf or me d as 
part of t he patie nt’s sta n d ar d of care  at a n y ti me. Patie nts w h o ac hie ve S D or better will be 
eli gi ble t o c o nti n ue recei vi n g st u d y treat me nt u ntil disease pr o gressi o n, u nacce pta ble t o xicit y, 
i n vesti gat or d ecisi o n, c o nse nt wit h dra wal, or st u d y ter mi nati o n b y t he s p o ns or. I ntra patie nt d ose 
escalati o n or d e -es calati o n t o a d ose le vel s h o w n t o be safe m a y be per mitte d wit h s p o ns or 
a p pr o val i n t he e v e nt t hat a patie nt t olerates st u d y treat me nt.  
Pe m br oliz u ma b a d mi nistrati o n will be ca p pe d at 3 5 c ycles (a p pr o xi matel y 2 years) . 
Disease pr o gressi o n f or deter mi ni n g eli gi bilit y of treat me nt c o nti n uati o n will be base d o n 
i m m u ne Res p o nse E val uati o n Criteria f or S oli d T u m ors (i R E CI S T). 
3. 1. 1.  
P art A: D o s e D e -e s c al ati o n   
T his part of t he st u d y is d esi g ne d t o e val uate t h e safet y of L V  a d mi nistere d i n c o m bi nati o n wit h 
pe m br oliz u ma b, a n d t o i de ntif y t he m a xi m u m a d mi nistere d d ose ( M A D) f or Part B. Patie nts will 
recei v e L V  2. 5  m g/ k g I V ( ma xi m u m wei g ht ca p p er i nf usi o n at 8 0 k g) as a 3 0-mi n ute i nf usi o n 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 3  of 1 5 2  
f oll o we d b y pe m br oliz u ma b 2 0 0  m g I V as a 3 0 -mi n ute i nf usi o n o n Da y  1 q 3 w k . Patie nts treate d 
u n der A me n d me nt 2 a n d later will recei ve L V  2. 5  m g/ k g (ca p pe d at 1 0 0  k g). I n c o ns ultati o n wit h 
t he s p o ns or, eli gi ble p atie nts alrea d y o n tr eat me nt pri or t o A me n d me nt 2, ma y h a ve t heir 
ma xi m u m wei g ht ca p per i nf usi o n  i ncrease d t o 1 0 0 k g or re mai n at 8 0  k g, if t he y are recei vi n g 
be nefit ( C R, P R, or S D). Patie nts recei vi n g > 2 0 0  m g L V  p er i nf usi o n  are re q uire d t o be 
a d mi nistere d  pr o p h ylacti c gra n ul oc yte -c ol o n y sti m ulati n g fact or ( G -C S F). Pe m br oliz u ma b will 
be a d mi nistere d a p pr o xi matel y 6 0  t o 9 0  mi n utes after i nf usi o n of L V  is c o m plete. D L Ts will be 
assesse d i n t he first treat me nt cycle, t hr o u g h C ycl e  2 Da y 1.  
Bl o o d sa m ples f or P K  a n d i m m u n o ge nicit y a nal ysis ma y  be c ollecte d t o s u p p ort t he st u d y 
e n d p oi nts. P har mac o d y n a mic a n d e x pl orat or y bi o mar ker st u dies will als o be c o n d ucte d o n 
patie nt bl o o d sa m ples a n d t u m or tiss ue o btai ne d t hr o u g h o ut t he tri al, i ncl u di n g sa m ples o btai ne d 
t o deter mi ne eli gi bilit y.  As of pr ot oc ol A me n d me nt 1 1, n o P K, i m m u n o ge nicit y, P D, or 
bi o mar ker sa m ples will b e o btai ne d aft er C ycle 1.  
Part A of t his st u d y will e nr oll a p pr o xi matel y 1 2 – 2 4 patie nts. T he d ose de -escalati o n pla n f or L V  
i n t his part of t he st u d y re q uires de-escalati o n i n t he e ve nt t hat t he D L T rat e is ≥1/ 3 of patie nts 
gi ve n t he c urre nt d ose. T his pla n is as f oll o ws:  
I nitiall y, 6 patie nts will be gi v e n t he starti n g d ose of 2. 5 m g/ k g (ca p pe d at 8 0  k g pri or t o 
A me n d me nt 2 or 1 0 0 k g u n der A me n d me nt 2 a n d later). E nr oll me nt will pr ocee d as f oll o ws:  
a. If < 2 of 6 p atie nts e x perie nce D L T at 2. 5 m g/ k g, 6 m ore patie nts will be e nr olle d at t he 
sa me d ose le vel of 2. 5 m g/ k g.  
i. If < 4 of t h ese 1 2 patie nts e x perie nce D L Ts, Part B will be i nitiate d at 2. 5 m g/ k g.  
ii. If ≥4 of 1 2 patie nts e x perie nce D L Ts, t he d os e will be de -es calate d t o 2. 0  m g/ k g a n d 
t he st u d y will pr ocee d as descri be d f or d ose d e-es calati o n bel o w.  
b.  If ≥2 of 6 patie nts e x peri e nce D L T at 2. 5 m g/ k g, t he d ose le vel will be l o were d t o 
2. 0  m g/ k g (ca p pe d at 8 0 k g p ri or t o A m e n d me nt 2 or 1 0 0 k g u n d er A me n d me nt 2 a n d 
later) a n d 6 p atie nts will be e nr olle d at t his d ose le vel.  
i. If < 2 of 6 p atie nts gi v e n 2. 0 m g/ k g e x perie nce D L Ts, 6 m ore patie nts will be 
e nr olle d at 2. 0  m g/ k g.  
•  
If < 4 of t h ese 1 2 patie nts e x perie nce D L Ts. Part B will i nitiate at 2. 0 m g/ k g.  
•  
If ≥4 of 1 2 patie nts e x perie nce D L Ts, t he d os e of L V  will be f urt her d e -es calate d 
as deter mi ne d b y t he s p o ns or i n c o ns ultati o n wit h t he safet y m o nit ori n g 
c o m mittee ( S M C).  
ii. If ≥2 of 6 patie nts gi ve n 2. 0  m g/ k g e x perie nce D L Ts, t he d ose of L V  will b e f urt her 
de -escalate d as deter mi n e d b y t h e s p o ns or i n c o ns ultati o n wit h t he S M C.  
A n S M C c o nsisti n g of t he me dical m o nit or, t he st u d y statisticia n, a dr u g s afet y re prese ntati ve, 
a n d st u d y i n vesti gat or(s) will m o nit or patie nt safet y t hr o u g h o ut t he trial. I n Part A, t he safet y of 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 4  of 1 5 2  
c o m bi nati o n treat me nt will be e val uate d b y t he S M C pri or t o e x pa nsi o n of e nr oll me nt i n Part B. 
After 6 patie nts ha v e bee n f oll o we d t hr o u g h t he e n d of t he D L T peri o d,  or at t he p oi nt t hat 2 or 
m ore patie nts e x perie nce a D L T, w hic he ver c o mes first, t he S M C will re vie w all a vaila ble data 
a n d ma ke a rec o m me n d ati o n f or o ne of t he f oll o wi n g:  
1.  T o e x pl ore Part A f urt her a n d treat u p t o 6 a d diti o nal patie nts at t he sa me d ose le vel 
pre vi o usl y teste d, or wit h a n y m o dificati o ns t hat ma y i n cl u de, b ut are n ot li mite d t o:  
a. D ose de -escalati o n of L V  t o 2. 0 m g/ k g  
b.  E val uati o n of a n i nter me diate or l o wer d ose le vel of L V  
c. D ose re -escalati o n bac k t o L V  2. 5  m g/ k g (ca p pe d at 1 0 0 k g) if 2. 0  m g/ k g  is pr o ve n t o be 
safe 
2.  T o cl ose t he st u d y t o a d diti o nal e nr oll me nt  
I n a d diti o n t o t he S M C, a n i n de pe n de nt safet y m o nit ori n g c o m mittee (I S M C) c o m p ose d of 
p h ysicia ns w h o are n ot i n v ol ve d , as well as sp o ns or re prese ntati ves,  i n t his st u d y will 
peri o dicall y re v ie w c u m ulati ve safet y data a n d pr o vi de rec o m me n d ati o ns t o t he s p o ns or. 
3. 1. 2.  
P art B: E x p a n si o n   
Part B is desi g ne d t o f urt her e val u ate t he safet y a n d a ntit u m or acti vit y of t h e c o m bi nati o n of L V  
a n d pe m br oliz u ma b a n d t o ma xi mize t he be nefit -ris k pr ofile. T his part of t h e st u d y will be 
c o n d ucte d i n 2 c o h orts. P atie nts will e nr oll se q ue ntiall y i nt o C o h ort 1 f oll o we d b y C o h ort  2. 
Part  B C o h ort 1 will recei ve t he M A D of L V  2. 5  m g/ k g, (ca p pe d at 1 0 0 k g) i n c o m bi nati o n wit h 
pe m br oliz u ma b. Part B C o h ort 2 will recei ve a d os e of L V  2. 0  m g/ k g (ca p p e d at 1 0 0 k g), i n 
c o m bi nati o n wit h pe m br oliz u ma b (see Secti o n  3. 2. 3. 1  f or rati o nale of Part B C o h ort 2). Patie nts 
recei vi n g > 2 0 0 m g L V  p er i nf usi o n are re q uir e d t o be a d mi nistere d 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).  
Patie nts will recei ve L V  a n d pe m br oliz u ma b q 3 w k . Pe m br oliz u ma b, 2 0 0 m g I V will be gi ve n 
per t he U S pres cri bi n g i nf or mati o n o n t he sa me da y as L V , a p pr o xi matel y 6 0-9 0  mi n utes 
f oll o wi n g L V  i nf usi o n. 
A p pr o xi matel y 7 3 p atie nts will be e nr olle d i n Part B of t he st u d y (a p pr o xi matel y 4 8 i n C o h ort  1 
a n d a p pr o x i matel y 2 5 i n C o h ort 2). 
T he S M C a n d I S M C will c o nti n ue t o m o nit or t he safet y of L V  a n d pe m br oliz u ma b. T he S M C 
will meet re g ularl y d uri n g Part A b ut c o n ve ne as nee de d i n Part B. T he I S M C will meet 
peri o dicall y.  
3. 1. 3.  
P art C: W e e kl y L V  d o si n g   
Part C will test wee kl y ( q 1 w k) d osi n g of L V  a d mi nistere d o n Da y 1, Da y 8, a n d Da y 1 5 of e ver y 
2 1 -da y c ycl e  n ot t o e x cee d 2 0 0  m g per i nf usi o n  i n c o m bi nati o n wit h pe m br oliz u ma b 
a d mi nistere d o n Da y 1 o f e ver y c ycle. 
Part C will c o nsist of  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 5  of 1 5 2  
1.  D ose escalati o n c o h orts  
2.  E x pa nsi o n c o h orts  
U p t o a p pr o xi matel y 6 4 patie nts ma y b e e nr olle d i n Part C. T he t otalit y of data fr o m all patie nts 
i n d ose escalati o n a n d e x pa nsi o n c o h orts will be use d t o deter mi ne t he rec o m me n de d q 1 w k L V  
d ose i n c o m bi nati o n wit h pe m br oliz u ma b.  
D ose escalati o n will be gi n at d ose le vel 0. T he fi rst 2 patie nts e nr olle d at eac h d ose le vel will be 
e val uate d f or D L Ts. If L V  d ose le vel 0 clears D L T e val uati o n, s u bse q ue nt patie nts ma y b e 
e nr olle d at d ose le v el 1 or i n t he d ose le vel 0 e x pa nsi o n c o h orts. See  Ta ble  2  f or d ose le vels a n d 
Secti o n 3. 2. 1  f or details o n assi g ni n g patie nts t o treat me nt gr o u ps.  
3. 1. 3. 1.  
P art C : D o s e E s c al ati o n C o h ort  
T he starti n g d os e of L V  will be d ose le vel 0 at 1. 0  m g/ k g o n Da y 1, Da y 8, a n d Da y  1 5. Pla n ne d 
d ose le vels are s h o w n i n Ta ble  1 . Pe m br oliz u ma b will be a d mi nistere d o n Da y 1 a p pr o xi matel y 
6 0  t o 9 0 mi n utes after i nf usi o n of L V  is c o m plet e. 
O nl y 1 d ose escal ati o n c o h ort will be o pe n at a ti me . D L T e val u ati o n will o nl y i nc l u de data fr o m 
d ose -escalati o n c o h orts a n d will be assesse d acc or di n g t o t he D L T criteria i n Secti o n  3. 1. 5 . Ot her 
d ose le vels ma y be e val u ate d base d o n t he t otalit y of t he safet y d ata a n d/ or rec o m me n dati o ns 
fr o m t he S M C. 
T he S M C will m o nit or safet y d uri n g d ose es calati o n i n Part C a n d ma y rec o m me n d e x pa nsi o n of 
a n y c o h ort t o f urt her e v al uate t he safet y at a gi ve n d ose or e nr oll me nt of a d diti o nal c o h ort s t o 
i n vesti gate i nter me diate or a d diti o nal d ose le vels of L V . T he S M C will c o nti n ue t o re vie w 
c u m ulati ve safet y d ata i n or der t o i de ntif y safet y c o ncer ns t hat ma y e mer ge d ue t o c u m ulati ve 
e x p os ure, after t he D L T wi n d o w, or at a l o w fre q ue nc y. I n a d diti o n,  t he S M C will assess A E 
data fr o m patie nts i n d os e -e x pa nsi o n c o h orts t o i de ntif y s afet y si g nals. F or m ore details, see 
Secti o n 7. 5. 1 . 
D ose escalati o n will be g ui de d b y t he m o difie d t o xicit y pr o ba bilit y i nter val ( m T PI) m et h o d (Ji 
2 0 1 0 ). T he m T PI met h o d is a m o del-base d d ose -es calati o n desi g n t hat uses a Ba yesia n statistical 
fra me w or k a n d a beta-bi n o mial hierarc hic m o d el (see A p pe n di x  M  f or m ore details a n d 
sce nari os). Usi n g a tar get D L T rate of 2 5 % wit h a 5 % mar gi n, t he d osi n g-d ecisi o n r ules are:  
1.  Escalate if c urre nt D L T r ate is m ost li kel y < 2 0 %  
2.  C o nti n ue if c urre nt D L T rate is m ost li kel y bet w ee n 2 0 % a n d 3 0 %  
3.  De -es calate if c urre nt D L T rate is m ost li kel y > 3 0 %  
 
Eac h d ose c o h ort will start wit h 2 patie nts. T he S M C will e val uate t he safet y of eac h d ose -le vel 
c o h ort a n d ma ke d o s e es calati o n/ de-es calati o n r ec o m me n dati o ns usi n g t he decisi o n matri x i n 
Ta ble  2 . Escal ati o n t o t he ne xt d ose le vel will occ ur if 0 of 2 e val u a ble patie nts e nc o u nter a D L T. 
If 1 of 2 e v al ua ble patie nts e nc o u nter a D L T, a n a d diti o nal 4 patie nts will be accr ue d (t otal of 
6  D L T -e val u a ble patie nts). If 2 of 2 e val ua ble p atie nts at a d ose le vel e nc o u nter a D L T, f urt her 
e val uati o n of t hat d ose le vel ma y b e  all o we d if rec o m me n de d b y t h e S M C. Escalati o n t o t he ne xt 
d ose le vel will occ ur if ≤1 of 6 e val ua ble p atie nts e nc o u nter a D L T (s ee T a ble  2 , c ol u m n 5). T he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 6  of 1 5 2  
M T D will be esti mate d base d o n data fr o m all pati e nts acr oss all e v al uate d d ose le vels 
(A p pe n di x  M ). If n o d oses are s afe, d os e escalati o n will st o p, a n d n o M T D will be declare d.  
T he s p o ns or (i n c o ns ultati o n wit h t he S M C) ma y, f or safet y reas o ns, o v erri de t he m o del’s 
all ocati o n of a patie nt t o a partic ular d ose le vel.  
T a bl e  1 : 
Pl a n n e d d o s e l e v el s f or P art C ( q 1 w k L V  d o si n g)  
D ose Le vel  
W ee kl y L V  D ose ( m g/ k g/ w k)  
Ma xi m u m L V  d ose i n a 3 -wee k c ycle ( m g/ k g/c ycle)  
0  
1. 0 0  
3. 0 0  
1  
1. 2 5  
3. 7 5  
T he ma xi m u m d ose will be 2 0 0  m g per i nf usi o n at all d ose le vels.  
 
T a bl e  2 : 
m T PI d e ci si o n m atri x  
 
N u m ber of D L T -E val ua ble P atie nts Treate d at C urre nt D ose  
N u m ber of Patie nts wit h D L Ts  
 
2  
3  
4  
5  
6  
7  
8  
9  
0  
E  
E  
E  
E  
E  
E  
E  
E  
1  
S  
S  
S  
S  
E  
E  
E  
E  
2  
D a 
D  
D  
S  
S  
S  
S  
S  
3  
 
D U  
D U  
D U  
D  
S  
S  
S  
4  
 
 
D U  
D U  
D U  
D U  
D U  
D  
5  
 
 
 
D U  
D U  
D U  
D U  
D U  
6  
 
 
 
 
D U  
D U  
D U  
D U  
7  
 
 
 
 
 
D U  
D U  
D U  
8  
 
 
 
 
 
 
D U  
D U  
9  
 
 
 
 
 
 
 
D U  
E = Escalate t o t h e ne xt hi g her d ose, S = Sta y at t h e c urre nt d ose, D = De -escal ate t o t h e ne xt l o wer d ose, D U = C urre nt d ose is 
u nacce pta bl y t o xic . 
a 
D ose will be de -escalate d if t h e first 2 D L T -e val u a ble p atie nts i n a d ose le vel e x perie nce a D L T. F urt h er e val u ati o n of t h at 
d ose le vel ma y be all o we d if rec o m me n de d b y t h e S M C.  
3. 1. 3. 2.  
P art C: E x p a n si o n C o h ort   
E x pa nsi o n c o h orts ma y b e o pe ne d at a n y d ose le vel t hat has cleare d D L T e val uati o n. U p t o 
a p pr o xi matel y 6 0 patie nts will be e nr olle d i n e x pa nsi o n c o h orts.  
T he t otalit y of data fr o m all patie nts i n d ose escalati o n a n d e x pa nsi o n will be use d t o deter mi ne 
t he rec o m me n d e d q 1 w k L V  d os e. After t he q 1 w k d ose has bee n d eter mi ne d, a d diti o n al patie nts 
ma y b e e nr olle d at t he rec o m me n de d d ose.  
3. 1. 4.  
P art D: D a y  1 a n d D a y 8  e v er y 2 1 -d a y s L V d o s i n g  
 Part D will assess L V 1. 5 m g/ k g a d mi nistere d o n Da y 1 a n d Da y 8 ( off  Da y 1 5) of e ver y 2 1 -da y 
c ycle, n ot t o e x cee d 2 0 0 m g per i nf usi o n , i n c o m bi nati o n wit h pe m br oliz u ma b a d mi nistere d o n 
Da y 1 of e v er y c ycle. A p pr o xi matel y 4 0 p atie nts  wit h  P D -L 1 C P S < 1 0  will  be e nr olle d i n Part  D. 
O n g oi n g, real -ti me, c o nti n u o us re vie w of patie nt safet y a n d S A Es will be c o n d ucte d b y t he 
s p o ns or’s Dr u g Safet y D e part me nt. A d diti o nall y, t he I S M C will e ns ure p eri o dic safet y data 
re vie w t hr o u g h o ut t he st u d y. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 7  of 1 5 2  
3. 1. 5.  
D o s e -Li miti n g T o xi cit y   
D L Ts are o nl y assesse d d uri n g Part A a n d d ose escalati o n c o h orts i n Part C of t he st u d y.  
T he D L T -e val uati o n peri o d is t he first treat me nt c ycl e i n Part A a n d Part C d ose escal ati o n. 
Patie nts w h o e x perie nce a D L T i n C ycl e 1 s h o ul d n ot recei ve f urt h er treat m e nt wit h L V  a n d 
pe m br oliz u ma b, u nless cli nical be nefit is de m o nstrate d wit h a de q u atel y ma na ge d t o xicit y. 
S u bse q ue nt d oses will be defi ne d b y t he me dical m o nit or i n disc ussi o n wit h t he site i n vesti gat or, 
i n t he c o nte xt of t he t y pe of A E o bser ve d. 
T he I Bs f or L V  a n d pe m br oliz u ma b i n di vi d uall y descri be A Es c o m m o nl y o bser ve d relati ve t o 
eit her a ge nt, as well as less c o m m o n seri o us fi n di n gs. T he res pecti ve I Bs s h o ul d be refere n ce d 
w he n attri b uti n g ca usalit y; h o we v er, t he fi nal decisi o n re gar di n g ca usali t y is at t he discreti o n of 
t he i n vesti gat or. 
If a n y patie nt e nr olle d i n Part A or Part C d ose escalati o n disc o nti n ues t he st u d y wit h o ut D L T 
d uri n g t he D L T peri o d, a n ot her patie nt ma y be e nr olle d at t he sa me d ose le vel f or D L T 
e val uati o n. H o we v er, t he ori gi nal patie nt will be i ncl u de d i n t he safet y a nal ysis.  
N o D L T e val u ati o n will be c o n d ucte d i n Part D, b eca use n o D L T was o bser ve d wit h L V 
1. 5  m g/ k g wee kl y d osi n g i n S G N L V A -0 0 1 (see Secti o n 3. 2. 3. 4 ). F urt her m ore, p har m ac o ki netic 
e x p os ure of L V gi ve n 1. 5  m g/ k g o n Da ys 1 a n d 8 e ver y 3 wee ks will n ot s ur pass L V gi ve n 
1. 5  m g/ k g wee kl y.  
3. 1. 5. 1.  
D o s e -Li miti n g T o xi cit y i n P art A   
A D L T i n Part A is defi n e d as 1 of t he f oll o wi n g t hat is c o nsi dere d relate d t o L V  or t he 
c o m bi nati o n, a n d ca n n ot be attri b ute d t o pe m br oliz u ma b al o ne:  
● 
A n y cli nicall y si g nifica nt, n o n -he mat ol o gi c A E ≥ Gra de 3 acc or di n g t o t he Nati o nal 
Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteri a f or A d verse E ve nts ( N CI C T C A E), 
Versi o n  4. 0 3 (e x ce pti o ns n ote d i n list bel o w)  
● 
≥ Gra de 3 fe brile n e utr o p e nia  
● 
Gra de 4 t hr o m b o c yt o p e nia or Gra d e 3 t hr o m b oc yt o pe nia ass ociat e d wit h cli nicall y 
si g nifica nt blee di n g t hat re q uires me dical i nter ve nti o n 
● 
Gra de 4 a ne mia u nrelate d t o u n derl yi n g dise ase  
● 
Disc o nti n uati o n d uri n g C ycl e 1 d ue t o treat me nt -relate d t o xicit y 
● 
Pr ol o n ge d d ela y ( > 2 wee ks) i n i nitiati n g C ycle 2 d ue t o treat me nt -relate d t o xicit y 
● 
Gra de 5 e ve nt ( d eat h)  
 
T he f oll o wi n g e ve nts will n ot be c o nsi dere d a D L T:  
● 
Gra de 3 fati g ue t hat i m pr o ves t o ≤ Gra de 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
● 
Gra de 3 t u m or pai n t hat i m pr o ves t o ≤ Gra de 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 8  of 1 5 2  
● 
L V  i nf usi o n: Gra de 3 i nf usi o n-relate d reacti o ns (I R Rs) t hat res ol ve wit hi n 1 da y wit h or 
wit h o ut me dical assess me nt  
● 
≥ Gra de 3 n o n -he mat ol o gic al la b orat or y a b n or malities t hat res ol ve t o ≤ Gra de  1 wit hi n 
7  da ys wit h or wit h o ut o pti mal me dical ma na ge m e nt 
● 
Is olat e d Gra d e 3 or 4 ele ctr ol yte i m bal a nces/a b n or malities a n d Gra d e 3 ele vati o ns i n 
bl o o d gl uc ose n ot ass o ciate d wit h cli nical se q uel ae t hat are c orrecte d wit h 
s u p ple me ntati o n/a p pr o priate ma na ge me nt wit hi n 3 da ys 
● 
Gra de 3 ras h t hat i m pr o v es t o ≤ Gra de 2 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
● 
Gra de 3 n a usea t h at i m pr o ves t o ≤ Gra de 1 wit hi n 3  da ys wit h or wit h o ut me dical 
assess me nt  
● 
Gra de 3 diarr hea t hat i m pr o ves t o ≤ Gra d e 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
● 
Gra de 3 v o miti n g t h at  i m pr o ves t o ≤ Gra d e 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
 
T he f oll o wi n g e ve nt will n ot  be c o nsi dere d  D L T e val ua ble:  
● 
Pe m br oliz u ma b i nf usi o n: ≥ Gra de 3 I R Rs –  t hese patie nts m ust be disc o nti n ue d fr o m 
pe m br oliz u ma b (see Secti o ns 5. 3. 5 , 9. 3. 1. 7 ), a n d are n ot e val ua bl e f or D L Ts. 
3. 1. 5. 2.  
D o s e -Li miti n g T o xi cit y i n P art C   
A D L T i n Part C is defi ne d as 1 of t he f oll o wi n g t hat is c o nsi dere d relate d t o L V  or t he 
c o m bi nati o n, a n d ca n n ot be attri b ute d t o pe m br oliz u ma b al o ne:  
● 
A n y cli nicall y si g nifica nt, n o n -he mat ol o gi c A E ≥ Gra de 3 acc or di n g t o t he N CI  C T C A E, 
Versi o n 4. 0 3 (e x ce pti o ns n ote d i n list bel o w)  
● 
≥ Gra de 3 fe brile n e utr o p e nia  
● 
Gra de 4 t hr o m b o c yt o p e nia or Gra d e 3 t hr o m b oc yt o pe nia ass ociat e d wit h cli nicall y 
si g nifica nt ble e di n g t hat re q uires me dical i nter ve nti o n  
● 
Gra de 4 a ne mia u nrelate d t o u n derl yi n g dise ase  
● 
Disc o nti n uati o n d uri n g C ycl e 1 d ue t o treat me nt -relate d t o xicit y 
● 
I n a bilit y t o recei ve all 3 d oses of L V  ( Da ys 1, 8, a n d 1 5) d ue t o patie nt n ot meeti n g 
d osi n g criteri a (see Secti o n 5. 2. 3. 5 ) 
● 
Pr ol o n ge d d ela y ( > 2 wee ks) i n i nitiati n g C ycle 2 d ue t o treat me nt -relate d t o xicit y 
● 
Gra de 5 e ve nt ( d eat h)  
 
T he f oll o wi n g e ve nts will n ot be c o nsi dere d a D L T:  
● 
Gra de 3 fati g ue t hat i m pr o ves t o ≤ Gra de 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
● 
Gra de 3 t u m or pai n t hat i m pr o ves t o ≤ Gra de 1 wit hi n 3 da ys wit h or wit h o ut me dical 
assess me nt  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 2 9  of 1 5 2  
● 
L V  i nf usi o n: Gra de 3 I R Rs t hat res ol ve wit hi n 1 da y wit h or wit h o ut me dical assess me nt  
● 
≥ Gra de 3 n o n -h e mat ol o gic al la b orat or y a b n or malities t hat res ol ve t o ≤ Gra de  1 wit hi n 
7  da ys wit h or wit h o ut o pti mal me dical ma na ge m e nt  
● 
Is olat e d Gra d e 3 or 4 ele ctr ol yte i m bal a nces/a b n or malities a n d Gra d e 3 ele vati o ns i n 
bl o o d gl uc ose n ot ass o ciate d wit h cli nical se q uel a e t hat are c orrecte d wit h 
s u p ple me ntati o n/a p pr o priate ma na ge me nt wit hi n 3 da ys 
● 
Gra de 3 ras h t hat i m pr o v es t o ≤ Gra de 2 wit hi n 3 da ys wit h or wit h o ut me dical treat me nt  
● 
Gra de 3 n a usea, di arr h ea or v o miti n g t hat i m pr o ves t o ≤ Gra de 1 wit hi n 3  d a ys wit h or 
wit h o ut me dical treat me nt  
 
T he f oll o wi n g e ve nt will n ot be c o nsi dere d D L T e val ua ble:  
● 
Pe m br oliz u ma b i nf usi o n: ≥ Gra de 3 I R Rs –  t hese patie nts m ust be disc o nti n ue d fr o m 
pe m br oliz u ma b (see Secti o ns 5. 6. 1. 2 , 5. 6. 1. 3 ) a n d are n ot e val ua ble f or D L Ts.  
 
Patie nts w h o d o n ot c o m plete t he 2 1 -da y D L T e v al uati o n p eri o d f or reas o ns ot her t ha n D L T will 
n ot be c o nsi dere d f or d os e -escalati o n decisi o ns a n d/ or deter mi nati o n of t he M T D. Patie nts w h o 
are c o nsi d ere d n o n -e val u a ble f or d ose -escalati o n decisi o ns a n d/ or M T D a n d will be re place d at 
t he sa me d ose le v el. 
3. 2.  
Di s c u s si o n a n d R ati o n al e f or St u d y D e si g n   
T he F D A’s “ G ui d a nce o n Cli nical Trial E n d p oi nts f or t he A p pr o val of Ca ncer Dr u gs a n d 
Bi ol o gics ” ( Ma y 2 0 0 7) was c o nsi dere d pri or t o t he selecti o n of pri mar y a n d sec o n dar y e n d p oi nts 
f or t his st u d y. T he e n d p oi nts of t his st u d y are a p pr o priate f or e val uati n g the safet y of L V  
treat me nt i n c o m bi nati o n wit h pe m br oliz u ma b f or patie nts wit h L A/ M T N B C. Sta n dar dize d 
R E CI S T v 1. 1 criteri a (Eise n ha uer 2 0 0 9 ) (A p pe n di x  J), a n d i R E CI S T g ui deli nes (Se y m o ur 2 0 1 7 ) 
(A p pe n di x  K ) w he n a p plica ble, will be e m pl o ye d b y i n vesti gat ors t o e val uate res p o nses a n d 
deter mi ne s u bse q ue nt treat me nt. I n t his patie nt p o p ulati o n, w here t he maj orit y of t he p atie nts 
w h o res p o n d t o t he a n tit u m or t hera p y ac hie ve P R, O R R, as a direct meas ure of a ntit u m or 
acti vit y, is t he m ost a p pr o priate e n d p oi nt t o assess treat me nt be nefit. T he pri mar y e n d p oi nt of 
O R R as assesse d b y R E CI S T v 1. 1 all o ws a direct c o m paris o n of t his st u d y wit h re p orte d 
i m m u n ot hera p y tri als t hat ha ve als o use d R E CI S T v 1. 1, as well as wit h c he m ot hera p y trials.  
I m m u n ot hera pe utic a ge nts s uc h as pe m br oliz u ma b ma y pr o d uce a ntit u m or effects b y 
p ote ntiati n g e n d o ge n o us ca ncer -s pecific i m m u ne res p o nses. T he res p o nse patter ns see n wit h 
s uch a n a p pr oac h ma y e xte n d be y o n d t he t y pical ti me c o urse of res p o nses s ee n wit h c yt ot o xic 
a ge nts a n d ca n ma nifest a cli nical res p o ns e after a n i nitial i ncrease i n t u m or b ur de n or e ve n t he 
a p peara nce of ne w lesi o ns. Sta n dar d R E CI S T criteria ma y t heref ore n ot  pr o vi de a n acc urat e 
res p o nse ass ess me nt of i m m u n ot hera pe utic a ge nts. T heref ore, i n a d diti o n t o R E CI S T, t his st u d y 
will e m pl o y i m m u ne -m o difie d R E CI S T (i R E CI S T) f or t u m or ass ess me nts t o acc o u nt f or t h e 
a p peara nce of p ossi ble n e w lesi o ns a n d all o w ra di o gra p h ic pr o gressi o n t o be c o nfir me d at a 
s u bse q ue nt assess me nt. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 0  of 1 5 2  
T o f urt her assess t he si g nifica nce of O R R i n t his st u d y, t he d ura bilit y of res p o nse will be 
e val uate d as a sec o n dar y e n d p oi nt.  
T he D L T e v al uati o n i n Part A of t he st u d y will pr o vi de a n o p p ort u nit y t o assess safet y a n d 
t olera bilit y of t he c o m bi nati o n treat me nt, t he c o m p o ne nts of w hic h ha v e pre vi o usl y bee n 
assesse d f or s afet y i n ot h er setti n gs a n d will als o pr o vi de a n o p p ort u nit y t o deter mi ne t he M A D 
f or Part B of t he st u d y. T he starti n g d os e f or L V  in Part A is 2. 5  m g/ k g q 3 w k (ca p p e d at 8 0  k g 
pri or t o A me n d me nt 2 or 1 0 0 k g u n der A me n d me nt 2 a n d later). If t his d ose le vel is n ot 
t olerate d, a ste p-d o w n  d ose le vel at 2. 0  m g/ k g q 3 w k is i ncl u de d i n t he st u d y desi g n a n d ma y be 
teste d. T he d ose e x pa nsi o n part ( Part B) will pr o vi de a d diti o nal safet y data f or c o m bi ni n g q 3 w k 
L V  wit h pe m br oliz u ma b. Pe m br oliz u ma b will be a d mi nistere d at t he sta n d ar d d ose. A n S M C 
a n d I S M C will m o nit or safet y, a n d t he s afet y e n d p oi nts are a p pr o priate f or e val uati n g t he safet y 
of t he  c o m bi nati o n re gi m e ns.  
Part C will e val uate t he s afet y a n d efficac y of L V  w he n a d mi nistere d i n m ore fre q ue nt, l o wer 
d oses t ha n t h ose teste d i n Parts A a n d B. D ose fi n di n g i n Part C will use t he m T PI met h o d (s ee 
Secti o n s 3. 1. 3. 1  a n d 3. 2. 3. 3 ). 
Part D will e val uate t he s afet y a n d efficac y of L V 1. 5  m g/ k g w he n a d mi nistere d o n Da ys 1 a n d  8 
(off D a y 1 5 ) of e ver y 2 1 -da y  c ycle i n c o m bi nati o n wit h pe m br oliz u ma b a d mi nistere d o n Da y 1 
of e ver y c ycle .  
T o better u n derst a n d relati o ns hi ps bet wee n pre -tr eat me nt B C’s bi ol o gi cal c haract eristics a n d 
patie nt o utc o me, a fres hl y o btai ne d pretr eat me nt t u m or bi o ps y ( or arc hi val tiss ue c ollecte d aft er 
t he m ost rece nt c yt ot o xic t hera p y) will be use d f or bi o mar ker assess me nts. Bi o mar ker 
assess me nts will n ot be use d f or patie nt sel ecti o n ( wit h t he e x ce pti o n of P D-L 1 f or Part  D 
patie nts)  beca use it is c urre ntl y u n k n o w n if bi o mar ker e x pressi o n will i m pact o utc o me.  
3. 2. 1.  
M et h o d of A s si g ni n g P ati e nt s t o Tr e at m e nt Gr o u p s   
F oll o wi n g i nf or me d c o ns e nt a n d scree ni n g assess me nts, patie nts will be e nr olle d i nt o Part  A, 
Part B, a n d Part C se q ue ntiall y. Patie nts will e nr oll i n Part B C o h ort 1 a n d Part B C o h ort  2 
se q ue ntiall y. I n t his o pe n -la bel, si n gl e-ar m st u d y, e nr oll me nt a n d treat me nt i n Part  A will be 
c o m plete d bef ore e nr oll me nt be gi ns i n Part B . T he safet y a n d t olera bilit y of t he c o m bi nati o n 
treat me nt will be e val u ate d, a n d a M A D will be deter mi ne d b y a n S M C pri or t o e x pa nsi o n of 
e nr oll me nt t o e val uate tr eat me nt effect i n Part B. O pe ni n g of a n d e nr oll me nt i n Part B will be 
deter mi ne d b y t he s p o ns or.  
I n Part C, if a d ose-escal ati o n c o h ort a n d a n e x pa n de d l o wer -d os e c o h ort are c o nc urre ntl y o pe n 
f or e nr oll me nt, patie nts will be prefere ntiall y e nr olle d t o t he d ose-escalati o n c o h ort. M ulti ple 
e x pa nsi o n c o h orts ma y b e o pe ne d c o nc urre ntl y ; c o h ort assi g n me nt will be deter mi ne d b y t he 
s p o ns or. T he c o h ort assi g n me nts a n d decisi o ns will be d oc u me nte d i n t he cli nical trial master 
file. 
I n Part D, e nr oll me nt will be c o nti n u o us  wit h o ut pa use.  N o D L T e val uati o n will be c o n d ucte d i n 
P art D, beca us e n o D L T was o bser v e d wit h L V 1. 5  m g/ k g wee kl y d osi n g i n S G N L V A -0 0 1 (see 
S ecti o n 3. 2. 3. 4 ). F urt her m ore, p har mac o ki netic e x p os ure of L V gi ve n 1. 5  m g/ k g o n Da ys 1 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 1  of 1 5 2  
a n d 8 e ver y 3 wee ks will n ot s ur pass L V gi ve n 1. 5  m g/ k g wee kl y . O n g oi n g, real -ti me, 
c o nti n u o us re vie w of patie nt safet y a n d S A Es will be c o n d ucte d b y t h e s p o ns or’s Dr u g Safet y 
De part me nt. A d diti o nall y, t he I S M C will e ns ure peri o dic safet y d ata re vie w t hr o u g h o ut t he 
st u d y.  
3. 2. 2.  
R ati o n al e f or S el e cti o n of q 3 w k D o s e s   
Alt h o u g h pe m br oliz u ma b a n d L V  ha d n ot bee n c o m bi ne d pri or t o t his st u d y, t he M M A E p a yl oa d 
(as part of t h e dr u g bre nt u xi ma b ve d oti n) ha d bee n teste d wit h t he P D-1 i n hi bit or ni v ol u ma b i n 
patie nts wit h H L i n a P hase 1/ 2 trial (Herrera 2 0 1 6 ). Of 4 2 patie nts e nr olle d, fati g u e was t he 
m ost c o m m o n A E occ urri n g  i n 4 0 % of p atie nts, f oll o we d b y n a usea, I R R, pr urit us, a n d ras h. 
P ote ntial i m m u ne -relate d a d verse e ve nts (ir A Es) i ncl u de d I R R ( 3 6 %), ras h ( 2 9 %), diarr hea 
( 2 6 %), tra ns a mi nase el e v ati o n ( 1 0 %), a n d h y p ot h yr oi dis m ( 5 %). All of t hes e were Gra de 1 a n d 2 
e x ce pt f or 1 tra nsa mi nas e ele vati o n e v e nt of Gra d e 3/ 4. T here were n o d os e re d ucti o ns or 
disc o nti n uati o ns d ue t o A Es.  
As t he c o m bi nati o n of bre nt u xi ma b ve d oti n a n d ni v ol u ma b has de m o nstrate d a ma na gea ble 
safet y pr ofile, t h e starti n g d oses of pe m br oliz u ma b a n d L V  will be at t he f ull rec o m me n de d d ose 
of eac h m olec ule. B ot h L V  a n d pe m br oliz u ma b are well t olerate d wit h fe w o verla p pi n g 
Gra de  3 – 5 t o xicities. H o we ver, beca us e of t he p ot e ntial f or o verl a p pi n g h e patic a n d 
gastr oi ntesti nal t o xicities f or pe m br oliz u ma b a n d L V , s p ecial ca uti o n will be ta ke n b y 
perf or mi n g a pla n n e d safet y e val uati o n aft er t he first 6  patie nts ha ve bee n f oll o we d t hr o u g h t he 
e n d of t he D L T p eri o d i n Part A, or at t he p oi nt t hat 2 or m ore patie nts e x perie nce a D L T, 
w hic he ver c o mes first. T he S M C w ill re vie w all a vaila ble data a n d m a ke rec o m me n dati o ns 
i ncl u di n g d ose de-escalati o n if i n dicate d.  
3. 2. 3.  
L V   
Pri or t o A me n d me nt 2, L V  will be a d mi nistere d at 2. 5  m g/ k g o n Da y  1 of eac h 2 1 -da y c ycle i n 
t his pr o p ose d p hase 1 b/ 2 st u d y. D osi n g is base d o n patie nt act ual b o d y wei g ht, e xce pt f or 
patie nts wei g hi n g > 8 0  k g, w here d osi n g will be base d o n a n 8 0 k g ma xi m u m wei g ht. F or 
patie nts i n Parts A a n d B treate d u n der A me n d me nt 2 a n d later, t he ma xi m u m wei g ht ca p per 
i nf usi o n will be i ncrease d fr o m 8 0 k g t o 1 0 0 k g. Patie nts w h o recei v e > 2 0 0  m g L V  p er i nf usi o n  
i n Parts A a n d B are als o re q uire d t o be a d mi nistere d pr o p h ylactic G -C S F. T his d ose a n d 
re gi me n has de m o nstr ate d a n acce pta ble s afet y pr ofile a n d e nc o ura gi n g cli nical acti vit y i n t he 
p hase 1 st u d y ( S G N L V A -0 0 1).  
I n S G N L V A-0 0 1, L V  m o n ot hera p y w as a d mi nistere d o n Da y 1 of eac h 2 1 -da y c ycl e. T he st u d y 
e val uate d escalati n g d ose le vels of 0. 5, 1. 0, 1. 5, 2. 0, 2. 5, a n d 2. 8  m g/ k g. A n  M T D was n ot 
reach e d i n t he d ose -escalati o n part of st u d y, a n d n o D L Ts were o bser ve d at a n y of t he d ose 
escalati o n le vels. Treat m e nt -e mer ge nt A Es re p ort e d i n ≥3 0 % of patie nts w ere fati g u e, na usea, 
al o pecia, d ecrease d a p petite, c o nsti pati o n, a n d peri p heral ne ur o pat h y.  
I n ci de nce of ne utr o p e nia ( Gra d e ≥3), i ncl u di n g fe brile ne utr o pe nia, i n crease d wit h i ncreasi n g 
d ose le vels.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 2  of 1 5 2  
A n e val uati o n of safet y e ve nts at 2. 0  m g/ k g ( N = 1 9) a n d 2. 5  m g/ k g wit h d oses ≤2 0 0  m g ( N = 1 8) 
re veal e d n o fe brile ne utr o pe nic e ve nts or n e utr o p e nia-ass oci ate d ( S A Es), n o Gra de 5 e ve nts, a n d 
a si milar rate of d os e disc o nti n uati o ns/re d ucti o ns i n eac h c o h ort. Ne utr o p e nia was m ore c o m m o n 
at L V  2. 5  m g/ k g; a m o n g t he 1 1  patie nts w h o e x perie nce d S A Es, 5 p atie nts ha d ne utr o pe nia. 
Fe brile n e utr o pe nia o cc urre d at 2. 5  m g/ k g wit h d oses > 2 0 0  m g i n 2  of 1 1 patie nts. N o ot her 
treat me nt-relate d deat hs occ urre d o n st u d y. D ose mo dificati o ns d ue t o A Es were m or e c o m m o n 
at 2. 5 m g/ k g wit h d oses > 2 0 0  m g.  
O bjecti ve res p o ns es wit h m o n ot hera p y were o nl y see n i n m T N B C patie nts. I m pr o v e d a ntit u m or 
acti vit y w as o bser ve d wit h i ncreasi n g d ose le vels of L V  i n hea vil y pretreat e d m T N B C patie nts. 
P Rs ha ve bee n o bser ve d i n 1 4 of 4 2 e val ua ble p atie nts treate d at d ose le vels of 1. 5 t o 2. 8  m g/ k g. 
C o nfir me d P R, D C R, a n d me dia n D O R were hi g her i n t he 2. 5  m g/ k g ( ≤2 0 0  m g) d ose l e vel 
c o m pare d t o t he 2. 0  m g/ k g d ose l e vel.  
I n s u m mar y, t he pr o p ose d d ose re gime n of 2. 5  m g/ k g, o n Da y 1 of eac h 2 1 -da y c ycle, is 
a ntici pate d t o pr o vi de a fa v ora ble b ala nce of acti vit y a n d safet y o bser ve d i n t he p hase 1 trial 
S G N L V A -0 0 1. T o dat e, o bjecti ve res p o nses wit h m o n ot hera p y were see n i n m T N B C patie nts. 
I m pr o v e d a ntit u m or acti vit y was o bser ve d wit h i ncreasi n g d ose le vels of L V  i n hea vil y 
pretreate d m T N B C patie nts. P Rs ha ve bee n o bser ve d i n 1 4 of 4 2  e val ua bl e patie nts treate d at 
d ose le vels of 1. 5  m g/ k g t o 2. 8  m g/ k g. C o nfir m e d P R, D C R, a n d me dia n D O R were hi g her i n t he 
2. 5  m g/ k g d ose le vel c o m pare d t o t he 2. 0  m g/ k g d ose le vel. U p date d data s u g geste d t h at t he 
O R R mi g ht be hi g h er f or patie nts recei vi n g > 2 0 0  m g per c ycle t h a n t h ose recei vi n g ≤2 0 0  m g p er 
c ycle (M o di 2 0 1 7 ) ( Data o n File). T h us, i ncreasi n g t he ma xi m u m wei g ht ca p per i nf usi o n  t o 
1 0 0  k g, b ut r e q uiri n g gr o wt h fact or s u p p ort f or patie nts w h o will recei ve 2 0 0 t o 2 5 0  m g per 
i nf usi o n, s h o ul d pr o vi de a fa v ora ble bal a nce of safet y a n d acti vit y f or p atie nts recei vi n g L V . 
3. 2. 3. 1.  
R ati o n al e f or P art B C o h ort 2 L V  2. 0 m g/ k g i n C o m bi n ati o n wit h 
P e m br oli z u m a b   
L V  2. 5  m g/ k g a n d 2. 0  m g/ k g i n c o m bi nati o n wit h pe m br oliz u ma b ha ve b ot h bee n teste d i n 
Part  A, d ose -fi n di n g p has e. Preli mi nar y data s h o we d t hat t he re gi me n at b ot h L V  d os e le vels w as 
t olera ble wit h ma na gea bl e A Es . L V  2. 5  m g/ k g, t he M A D, was f urt her e val uate d i n Part  B 
C o h ort  1 e x pa nsi o n. Preli mi nar y effic ac y a nal ysis of L V  i n c o m bi nati o n wit h pe mbr oliz u ma b 
de m o nstrate t hat t he c o m bi nati o n has c o m para bl e pr o misi n g acti vit y at t he t w o i n vesti gate d L V  
d oses. C o nti n u o us m o nit ori n g b y t he I S M C s u g geste d t hat L V  2. 0  m g/ k g ma y h a ve better 
t olera bilit y, al beit i n a s mall sa m ple size. W hile b ot h L V  d oses a re t olera ble a n d ha ve s h o w n a 
ma na gea bl e t o xicit y pr ofile, o p p ort u nities re mai n t o e ns ure t he be n efits of t hera p y are 
ma xi mize d. A me n d me nt 4 ai ms t o better assess t olera bilit y a n d i m pr o ve t he ris k -be nefit pr ofile 
of L V  i n c o m bi nati o n wit h pe m br oliz u ma b t hro u g h t he a d diti o n of a n e x pa nsi o n c o h ort at t he 
l o wer L V  2. 0  m g/ k g d os e.  
3. 2. 3. 2.  
R ati o n al e f or S el e cti o n of q 1 w k L V  D o s e s i n C o m bi n ati o n wit h 
P e m br oli z u m a b   
M ulti ple li nes of e vi de nce s u p p ort t hat q 1 w k d osi n g ma y res ult i n i m pr o ve d efficac y a n d s afet y 
of L V . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 3  of 1 5 2  
I n Parts A a n d B of t his st u d y, as of 2 Dec 2 0 1 9, a t otal of 8 8 patie nts ha d recei ve d L V  at d oses 
of 2. 0  m g/ k g or 2. 5  m g/ k g a d mi nistere d q 3 w k i n c o m bi nati o n wit h pe m br oliz u ma b. T he 
c o m bi nati o n has bee n s h o w n t o be acti ve wit h a t olera ble safet y pr ofile. T he c o nfir me d o verall 
res p o nse rate was 4 0 % a m o n gst t he efficac y e val ua ble patie nts (Data o n File ). N o ne w safet y 
si g nal was o bs er ve d wit h t he c o m bi nati o n. Gastr oi ntesti nal A Es were p re d o mi na nt c o m pare d t o 
ot her A Es. M ost A Es were l o w t o m o derat e gra d e i n se verit y wit h na usea, fati g u e, a n d 
al o pecia b ei n g t he m ost c o m m o n A Es. T he m ost c o m m o n se vere A Es ( Gra de 3 or 4) was 
ne utr o pe nia occ urri n g i n 1 3 % of patie nts.  
T he starti n g d os e of L V  i n Part C is 1. 0 m g/ k g/ w k i n c o m bi nati o n wit h pe m br oliz u ma b. T his L V  
d ose res ults i n a P K area-u n der -t he-c ur ve ( A U C) e x p os ure si milar t o L V  of 2. 5  m g/ k g q 3 w k. At 
t hese si milar P K e x p os ures, it is n ot a ntici pate d t hat t here will be a d etri me nt i n t he cli nic al 
effic ac y or s afet y pr ofile.  
T his is f urt her s u p p orte d b y o bser vati o ns i n St u d y S G N L V A -0 0 1 i n w hic h L V  m o n ot hera p y 
q 1 w k d oses of 1. 0  a n d 1. 2 5  m g/ k g/ w k were safel y deli vere d wit h o ut D L Ts. T u m or size 
re d ucti o ns i n breast ca ncer patie nts were o bser ve d at t he l o west d ose le vel e val uate d 
( 1. 0 m g/ k g/ w k). T h e m ost rece nt pr eli mi nar y a nal ys es of d ose e x pa nsi o n c o h ort i n st u d y 
S G N L V A -0 0 1 ( 6 -J a n-2 0 2 1  data s na ps h ot, Sea ge n I n c., data o n file) de m o nstrate d t hat m ost 
effic ac y-e val ua ble p atie nts wit h sec o n d -li ne m T N B C recei vi n g L V 1. 2 5 m g/ k g q 1 w k  ha d 
re d ucti o ns i n t u m or size (Fi g ure 3 ), d e m o nstrati n g t hat L V a d mi nistere d q 1 w k  has cli nical 
acti vit y a gai nst m T N B C.  
Fi g ur e 3 : 
P er c e nt c h a n g e i n s u m of t u m or di a m et er s f or effi c a c y-e v al u a bl e p ati e nt s wit h 
s e c o n d -li n e m T N B C tr e at e d wit h a st arti n g d o s e of 1. 2 5 m g/ k g q 1 w k  
 
S o urce: 6 -Ja n-2 0 2 1  data s na ps h ot, Sea ge n I nc., data o n file  
 
At t he ti me of t he data s n a ps h ot, safet y data were  a vaila ble f or 5 2  patie nts w h o ha d recei ve d L V 
at 1. 2 5 m g/ k g q 1 w k . A Es o bser ve d at a greater t ha n 3 0 % i nci de nce (a n y gra de) i n patie nts 
recei vi n g L V 1. 2 5 m g/ k g q 1 w k  i ncl u de d fati g ue ( 5 6 %), na usea ( 5 4 %), peri p heral se ns or y 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 4  of 1 5 2  
ne ur o pat h y ( 4 4 %), decrease d a p petite ( 4 2 %) , a n d c o nsti pati o n ( 3 3 %). M ost e ve nts were l o w 
gra de . C o m mo n Gra d e 3 or hi g her A Es were n e utr o pe nia ( 1 7 %), fati g ue ( 1 4 %), 
h y per gl ycae mia  ( 1 1. 5 %), a n d h y p o p h os p h atae mia ( 1 1. 5 %) . T his A E pr ofile s u g gests t hat L V 
1. 2 5  m g/ k g q 1 w k  is t olera ble a n d ma n a gea ble.  
I n t he i nitial 1 7 s u bjects treate d wit h L V q 1 w + pe m br oliz u ma b i n st u d y S G N L V A-0 0 2 ( data 
s na ps h ot 7-Dec -2 0 2 0), t h ere w as n o e mer ge nce of ne w safet y si g n als c o m pare d t o 
L V  q 3 w  +  pe m br oliz u ma b.  
P K m o deli n g data d eri ve d fr o m o ver 2 0 0 p atie nts pre vi o usl y tr eat e d wit h L V  s u g gest 
i m pr o ve me nts i n t he safet y pr ofile of L V  q 1 w k d osi n g ma y be d u e i n part t o t he re d uce d C ma x  
c o m pare d t o q 3 w k d osi n g ( Data o n File). I n a d diti o n, L V  q 1 w k d osi n g is a ntici pate d t o res ult i n 
hi g her C tr o u g h c o nce ntrati o n le vels (t he l o west c o n ce ntrati o n reac h e d b y a dr u g b ef ore t he ne xt 
d ose is a d mi nistere d), w hic h are c orrelate d wit h i m pr o ve d effi cac y.  
Ot her A D Cs ha v e bee n s h o w n t o ha ve i m pr o ve d s afet y, acti vit y, or b ot h w he n a d mi nistere d at 
differe nt d os es  a n d m ore fre q ue nt r e gi me ns t ha n t h ose ori gi n all y teste d. F or e x a m ple, 
trast uz u ma b e mta nsi ne ( T-D M 1), has i m pr o ve d efficac y wit h si milar safet y pr ofiles w he n d ose d 
q 1 w k c o m pare d t o q 3 w k (Beera m 2 0 1 2 ; T h uss -Patie nce 2 0 1 7 ). 
3. 2. 3. 3.  
R ati o n al e f or m T PI M et h o d ol o g y i n P art C   
T he m T PI d os e escalati o n met h o d, w hic h has bee n use d f or d ose fi n di n g i n ot her o nc ol o g y trials 
(Ya p 2 0 1 1 ; Ji 2 0 1 3; Garri d o -La g u na 2 0 1 9 ), was c h ose n f or t his st u d y b eca use of t he p ote ntial 
a d va nta ges it has o v er t h e tra diti o nal “ 3 + 3 ” a p pr oac h f or d os e fi n di n g. I n a d diti o n t o pr o vi di n g 
t he a bilit y t o esti mate t he M T D m ore acc uratel y (Ji 2 0 1 3; A na nt ha kris h na n 2 0 1 7 ) (A p pe n di x  M ), 
t he m T PI a p pr oac h e n ha nces patie nt safet y i n se v eral wa ys. First, t he m T PI met h o d us es 
i nf or mati o n fr o m all treat e d patie nts rat her t ha n o nl y usi n g data fr o m t he d ose le vel u n der 
i n vesti gati o n. Sec o n d, fe wer patie nts are tr eate d a b o ve t he M T D w he n c o m pare d t o t he 
tra diti o nal “ 3 + 3” a p pr oac h (Ji 2 0 1 3; A na nt ha kris h na n 2 0 1 7 ). T hir d, b y all o wi n g fle xi ble c o h ort 
siz es, t he m ost a p pr o priate patie nts ca n b e e x p ose d t o st u d y dr u g d uri n g d os e escal ati o n, 
pr o vi di n g hi g her p o wer t o i de ntif y safe a n d effecti ve d oses (Ji 2 0 1 3). 
3. 2. 3. 4.  
R at i o n al e f or S el e cti o n of L V D o si n g o n D a y s 1 a n d 8 ( off D a y 1 5) i n 
E v er y 2 1 -d a y C y cl e i n C o m bi n ati o n wit h P e m br oli z u m a b  i n Fir st -Li n e  
m T N B C  Wit h P D -L 1 C P S < 1 0  P ati e nt s  i n P art D  
St u d y S G N L V A -0 0 1 Part E e val uates w ee kl y L V m o n ot hera p y i n patie nts wit h m T N B C or 
H R +/ H E R 2 - disease. Wee kl y L V m o n ot hera p y of 1. 0 m g/ k g. 1. 2 5 m g/ k g a n d 1. 5 m g/ k g were 
gi ve n o n Da y 1, Da y 8, a n d Da y 1 5 i n e ver y 2 1 -da y c ycle . U p t o a p pr o xi matel y 8 2 patie nts 
( 4 2 H R +/ H E R 2 - a n d 4 0 m T N B C) were pla n ne d f or e nr oll me nt. D uri n g d ose escal ati o n, d oses of 
L V ra n gi n g fr o m 1. 0 m g/ k g u p t o 1. 5 m g/ k g were safel y deli vere d wit h o ut D L Ts.  
Preli mi nar y effic ac y d ata fr o m St u d y S G N L V A -0 0 1 is s h o w n i n  
Fi g ure 4  b el o w w hic h de m o nstrates t he best perce nta ge c ha n ge i n t he s u m of t u m or dia meters 
fr o m baseli ne ( data c ut 0 6-J a n-2 0 2 1). W hile o nl y o ne T N B C p atie nt was d ose d wit h L V 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 5  of 1 5 2  
1. 5  m g/ k g q 1 w k, preli mi nar y data i n patie nts wit h H E R 2 -/ H R + m B C s h o w e d d ose-res p o nse 
c orrel ati o n wit h i ncreasi n g d ose of L V q 1 w k.  
Fi g ur e 4 : 
P er c e nt c h a n g e i n s u m of t u m or di a m et er s b y br e a st c a n c er s u bt y p e a n d d o s e  
 
S o urce: Sea ge n, data  o n file ( data c ut 0 6 -J a n-2 0 2 1)  
E ve n t h o u g h b etter effic ac y h a d bee n o bser ve d wit h 1. 5 m g/ k g, preli mi nar y res ults le d t o 
1. 2 5  m g/ k g bei n g c h ose n f or f urt her e x pa nsi o n i n St u d y S G N L V A -0 0 1 b eca use of t he hi g her 
fre q ue n c y of ne utr o pe nia e x perie nce d at 1. 5 m g/k g. M ost of t he cli nicall y si g nifica nt n e utr o pe nia 
occ urre d aft er 3 wee kl y d oses at t he 1. 5 m g/ k g d os e le vel. T hes e o bser vati o ns s u g geste d t h at an  
L V d osi n g h oli da y ma y b e nee d e d t o miti gate ne utr o pe nia.  
P har mac o ki netic a n al ysis of relati ve d osi n g i nte nsi t y ( R DI) wit h L V 1. 2 5 m g/ k g q 1 w k i n 
m o n ot hera p y als o s h o we d t hat d ose i nte nsit y start e d t o decrease at C ycl e 2, wit h d osi n g re d u ce d 
t o 2 d oses i n e ver y 2 1-d a y c ycle o ver ti me ( Sea ge n data o n file). T his s u p p orts t hat a dr u g 
h oli da y c o ul d b e be nefici al f or l o n g-ter m treat me nt. I m ple me nti n g a dr u g h oli da y ma y miti gate 
t o xicities, re d uce t he n ee d f or d ose m o dificati o n, a n d t heref ore i m pr o ve efficac y. T his is f urt h er 
s u p p orte d b y P K si m ulati o n w hic h de m o nstrate d t hat gi vi n g L V 1. 5 m g/ k g o n Da ys 1 a n d 8 
e ver y 2 1  da ys res ulte d i n si milar dr u g e x p os ures as t hat of 1. 2 5 m g/ k g q 1 w k d osi n g 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 6  of 1 5 2  
( Da ys 1,  8,  a n d 1 5). He n ce, a d mi nistrati o n of L V 1. 5 m g/ k g o n Da ys 1 a n d 8 e ver y 2 1 da ys m a y 
res ult i n i m pr o ve d effic ac y a n d safet y of L V. 
Part  D will o nl y e nr oll patie nts wit h P D -L 1 C P S < 1 0. Pe m br oliz u ma b + c he m ot hera p y has 
recei v e d re g ul at or y a p pr o val i n t he 1 L a d va nce d T N B C P D -L 1 hi g h ( C P S ≥1 0) s u b p o p ulati o n 
base d o n a n o v erall s ur vi val be nefit  (S c h mi d 2 0 1 8 ; C ortes 2 0 2 0 ). Si milar be nefit was n ot 
o bser ve d i n patie nts wit h P D -L 1 C P S < 1 0, w here t he sta n dar d of care re mai ns c he m ot hera p y a n d 
t he o utc o mes are p o or (res p o nse rates ~ 4 0 % a n d m e dia n P F S a b o ut 5. 5 m o nt hs). T h us, t hese 
patie nts  re pres e nt a p o p ulati o n t hat c o nti n ues t o ha ve hi g h u n met me dical nee d. T his o n g oi n g 
S G N L V A -0 0 2 st u d y has de m o nstrate d t hat L V  + pe m br oliz u ma b  n ot o nl y is acti ve a gai nst 
m T N B C b ut als o ca n h a v e a ma na gea ble s afet y pr ofile s u g gesti n g t hat L V  + pe m br oliz u ma b  
ma y pr o vi d e a n o pti o n f or t hese patie nts.  
3. 2. 4.  
P e m br oli z u m a b   
T he pla n ne d d ose of pe m br oliz u ma b f or t his st u d y is 2 0 0  m g q 3 w k. Base d o n t he t otalit y of data 
ge n erat e d i n t he Ke ytr u d a de vel o p me nt pr o gra m, 2 0 0  m g q 3 w k is t he a p pr o priate d ose of 
pe m br oliz u ma b f or a d ults acr oss all i n dicati o ns a n d re gar dl ess of t u m or t y p e. As o utli ne d bel o w, 
t his d ose is j ustifie d b y 
● 
Cli nical data fr o m 8 ra n d o mize d st u dies de m o nstrati n g flat d os e - a n d e x p os ure-efficac y 
relati o ns hi ps fr o m 2 m g/ k g q 3 w k t o 1 0  m g/ k g e ver y 2 wee ks ( q 2 w k),  
● 
Cli nical data s h o wi n g me a ni n gf ul i m pr o ve me nt i n be nefit -ris k i ncl u di n g o v erall s ur vi val 
at 2 0 0 m g q 3 w k acr oss m ulti ple i n dicati o ns, a n d  
● 
P har mac ol o g y data s h o wi n g f ull tar g et sat urati o n i n b ot h s yste mic cir c ulati o n (i nferre d 
fr o m P K data) a n d t u m or (i nferre d fr o m p h ysi ol o gicall y-b ase d P K [ P B P K] a nal ysis) at 
2 0 0  m g q 3 w k.  
A m o n g t he 8 ra n d o mize d d ose -c o m paris o n st u dies, a t otal of 2 2 6 2 partici pa nts were e nr olle d 
wit h mela n o ma a n d n o n -s mall cell l u n g ca ncer, c o veri n g differe nt diseas e setti n gs (treat me nt 
naï ve, pre vi o usl y treate d, P D -L 1 e nric h e d, a n d all -c o mers) a n d differe nt treat me nt setti n gs 
( m o n ot hera p y a n d i n c o m bi nati o n wit h c he m ot hera p y). Fi ve st u dies c o m p are d 2 m g/ k g  q 3 w k  
vers us 1 0  m g/ k g q 2 w k  ( K N 0 0 1 C o h ort B 2, K N 0 0 1 C o h ort D, K N 0 0 2, K N 0 1 0, a n d K N 0 2 1), a n d 
3 st u dies c o m pare d 1 0  m g/ k g q 3 w k vers us 1 0  m g/ k g q 2 w k  ( K N 0 0 1 C o h ort B 3, K N 0 0 1 C o h ort 
F 2 a n d K N 0 0 6). All of t h ese st u dies de m o nstrate d flat d ose - a n d e x p os ure-res p o nse relati o ns hi ps 
acr oss t he d oses st u die d re prese nti n g a n a p pr o xi mate 5 - t o 7. 5-f ol d differe n ce i n e x p os ure. T he 
2  m g/ k g ( or 2 0 0  m g fi x e d -d ose) q 3 w k pr o vi d e d si milar res p o nses t o t he hi g hest d oses st u die d. 
S u bse q ue ntl y, flat d ose - a n d e x p os ure-res p o ns e relatio ns hi ps were als o o bs er ve d i n ot her t u m or 
t y pes i ncl u di n g hea d a n d nec k ca ncer, bla d der ca n cer, gastri c ca n cer, a n d cl assical H L, 
c o nfir mi n g 2 0 0  m g q 3 w k as t he a p pr o priate d ose i n de pe n de nt of t he t u m or t y pe. T h ese fi n di n gs 
are c o nsiste nt wit h t he m ec ha nis m  of acti o n of pe m br oliz u ma b, w hic h acts b y i nteracti o n wit h 
i m m u ne cells, a n d n ot via direct bi n di n g t o ca n cer cells. 
A d diti o nall y, p har mac ol o g y dat a cle arl y s h o w tar get sat urati o n at 2 0 0  m g q 3 w k. First, P K data 
i n K N 0 0 1 e val uati n g tar get-me diate d dr u g dis p ositi o n c o ncl usi vel y d e m o nstrate d sat ur ati o n of 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 7  of 1 5 2  
P D -1 i n s yste mic cir c ulati o n at d oses m uc h l o wer t ha n 2 0 0  m g q 3 w k. Sec o n d, a P B P K a nal ysis 
was c o n d ucte d t o pre dict t u m or P D -1 sat urati o n o ver a wi de ra n ge of t u m or pe netrati o n a n d 
P D -1 e x pressi o n. T his e val uati o n c o ncl u de d t hat p e m br oliz u ma b at 2 0 0  m g q 3 w k ac hie ves f ull 
P D -1 sat urati o n i n b ot h bl o o d a n d t u m or.  
Fi nall y, p o p ul ati o n P K a nal ysis of pe m br oliz u ma b, w hic h c haracterize d t he i nfl ue nce of b o d y 
wei g ht a n d ot her partici p a nt c o variat es o n e x p os ure, has s h o w n t hat t he fi x e d -d osi n g pr o vi d es 
si milar c o ntr ol of P K varia bilit y as wei g ht-b ase d d osi n g, wit h c o nsi dera ble o verla p i n t he 
distri b uti o n of e x p os ures fr o m t he 2 0 0  m g q 3 w k fi x e d d ose a n d 2  m g/ k g q 3 w k d ose. S u p p orte d 
b y t hese P K c haracteristics a n d  gi ve n t hat fi x e d-d ose has a d va nt a ges of re d uce d d osi n g 
c o m ple xit y a n d re d uce d p ote ntial of d osi n g err ors, t he 2 0 0  m g q 3 w k fi x e d -d ose was selecte d f or 
e val uati o n acr oss all pe m br oliz u ma b pr ot oc ols.  
3. 2. 5.  
Bli n di n g   
T his is a n o pe n -la bel st u d y. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 8  of 1 5 2  
4.  
S T U D Y P O P U L A TI O N   
Patie nts m ust meet all of t he e nr oll me nt criteri a t o be eli gi ble f or t his st u d y. Eli gi bilit y criteria 
ma y n ot be wai ve d b y t h e i n vesti gat or a n d are s u bject t o re vie w i n t he e ve nt of a g o o d cli nical 
practice a u dit a n d/ or healt h re g ul at or y a ut h orit y i ns pecti o n.  
4. 1.  
I n cl u si o n Crit eri a  
1.  Metastati c or l ocall y-a d v a nce d, hist ol o gi call y d oc u me nte d T N B C (a bse nce of H E R 2, 
estr o ge n rece pt or [ E R], a n d pr o gester o n e rece pt or [ P R] e x pressi o n).  
a. H E R 2 ne gati vit y is defi n e d as eit her of t he f oll o wi n g b y l ocal la b orat or y assess me nt 
(W olff 2 0 1 4 ): 
i. I n sit u h y bri dizati o n no n -a m plifie d (rati o of H E R 2 t o C E P 1 7 < 2. 0 or si n gle pr o be 
a vera ge H E R 2 ge n e c o p y n u m ber < 4 si g nals/cell), or  
ii. I H C 0 or I H C 1 +. If m or e t ha n o ne test res ult is a vaila ble a n d n ot all res ults meet t he 
i ncl usi o n criteri o n defi niti o n, all res ults s h o ul d be disc usse d wit h t he me dical m o nit or 
t o esta blis h eli gi bilit y of t he patie nt. 
b.  E R a n d P R ne gati vit y are defi ne d as p er c urre nt A merica n S ociet y of Cli nical 
O nc ol o g y/ C olle ge of A m erica n Pat h ol o gists  ( A S C O/ C A P) g ui deli nes via I H C a nal ysis. 
c. Part D o nl y: T u m or tiss u e P D -L 1 C P S < 1 0 as deter mi ne d b y a P D -L 1 I H C assa y usi n g 
t he 2 2 C 3 cl o ne. 
2.  Ha ve n ot pre vi o usl y recei ve d c yt ot o xic t hera p y f or t he treat me nt of u nresecta ble L A/ M B C. 
Treat me nt wit h a ge nts ot her t ha n h or m o nall y -dir ecte d/e n d ocri n e t hera pi es will be c o u nte d as 
re gi me ns. 
3.  F or patie nts pr e vi o usl y tr eate d wit h c urati ve i nte nt, at least 6 m o nt hs m ust ha ve ela ps e d 
bet wee n t he c o m pleti o n of s uc h treat me nt (e. g., d ate of pri mar y breast t u m or s ur ger y or date 
of last a dj u va nt c yt ot o xic t hera p y a d mi nistrati o n, w hic he ver occ ur re d last) a n d first 
d oc u me nte d l ocal or dist a nt disease rec urre nce.  
4.  Meas ura ble  dis ease as defi ne d i n R E CI S T v 1. 1: at least 1 t u m or lesi o n ≥1 0  m m i n t he l o n gest 
dia meter, or a l y m p h n o d e ≥1 5  m m i n s h ort a xis meas ure m e nt. Tar get lesi o ns sit uate d i n a 
pre vi o usl y irra diate d area are c o nsi d ere d meas ura ble o nl y if t he y h a ve s h o w n u ne q ui v o cal 
pr o gressi o n base d o n R E CI S T v 1. 1 aft er ra diati o n t hera p y. Patie nts wit h b o ne -o nl y 
metastatic lesi o ns will be e x cl u de d.  
5.  Patie nts ≥1 8 years of a ge.  
6.  A n Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) Perf or ma nce Stat us sc ore of 0 or 1.  
7.  A ble t o pr o vi de a de q u ate  tiss ue o btai ne d rece ntl y fr o m a t u m or lesi o n f or bi o mar ker a n al ysis. 
C ore nee dle or e x cisi o nal bi o ps y is preferre d. If neit her is p ossi ble, disc uss wit h s p o ns or 
w het her bi o ps y o btai ne d via alter nati ve met h o ds ma y b e a p pr o priate.  
a. N ote: Patie nts f or w h o m rece nt/fres h sa m ples ca n n ot be o btai ne d (e. g., i naccessi ble 
t u m or or patie nt safet y c o ncer ns) ma y s u b mit a n arc hi ve d s p eci me n i n place of t he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 3 9  of 1 5 2  
rece nt/fres h tiss ue if it w as c ollecte d after c o m pleti o n of t he patie nt’s m ost rece nt 
c yt ot o xic t hera p y. If neit he r is a vaila ble, pl ease disc uss wit h me dical m o nit or. 
8.  T he f oll o wi n g b aseli ne la b orat or y data:  
● 
a bs ol ute ne utr o p hil c o u nt ≥1, 5 0 0/ µ L  
● 
platelet c o u nt ≥1 0 0, 0 0 0/ μ L  
● 
he m o gl o bi n ≥8. 0 g/ d L  
● 
ser u m bilir u bi n ≤1. 5 x u p per li mit of n or mal ( U L N) or ≤3 x U L N f or patie nts wit h 
Gil bert’s disease  
● 
ser u m creati ni ne ≤1. 5 x U L N O R gl o mer ular filtrati o n rate ( G F R) ≥6 0 m L/ mi n/ 1. 7 3  m 2 
f or patie nt wit h creati ni ne le vels > 1. 5 x i nstit uti o nal U L N. G F R calc ulati o n is f o u n d i n 
A p pe n di x  N . 
● 
Ala ni ne a mi n otra nsf eras e ( A L T) a n d as partate a mi n otra nsferas e ( A S T) ≤1. 5 x  U L N or 
≤3 x U L N if li ver metastases are prese nt  
● 
I nter nati o nal n or malize d rati o (I N R) or pr ot hr o m bi n ti me ( P T) ≤1. 5 x U L N u nless s u bject 
is recei vi n g a ntic o a g ula nt t hera p y as l o n g as P T or partial t hr o m b o plasti n ti me ( P T T) is 
wit hi n t hera pe utic ra n ge of i nte n de d use of a ntic o a g ul a nts  
● 
Acti vate d partial t hr o m b o plasti n ti me (a P T T) ≤1. 5 x U L N u nless s u bject is recei vi n g 
a ntic oa g ula nt t hera p y as l o n g as P T or P T T is wit hi n t hera pe utic ra n ge of i nte n de d use of 
a ntic oa g ula nts  
9.  F or patie nts of c hil d beari n g p ote ntial as d efi ne d i n Secti o n 4. 3 , t he f oll o wi n g sti p ulati o ns 
a p pl y:  
a. M ust ha ve a ne gati ve ser u m or uri ne pre g n a nc y test ( mi ni m u m se nsiti vit y 2 5  mI U/ m L or 
e q ui vale nt u nits of beta h u ma n c h ori o nic g o na d otr o pi n [ β -h C G]) res ult wit hi n 3  da ys 
pri or t o t he first d ose of L V / pe m br oliz u ma b. Patie nts wit h false p ositi ve res ults a n d 
d oc u me nte d verificati o n t hat t he patie nt is n ot pre g na nt are eli gi ble f or partici pati o n.  
b.  M ust a gree n ot t o tr y t o b ec o me pre g na nt fr o m t he ti me of e nr oll me nt u ntil at least 
6  m o nt hs after t he fi nal d ose of st u d y dr u g. If heter ose x uall y acti ve, m ust c o nsiste ntl y us e 
2 hi g hl y effecti ve m et h o ds of birt h c o ntr ol (as defi ne d i n A p pe n di x  G ) d uri n g t his ti me 
peri o d.  
c. M ust a gree n ot t o breastf ee d or d o nat e o va, starti n g at ti me of i nf or me d c o nse nt a n d 
c o nti n ui n g t hr o u g h 6  m o nt hs after t he fi n al d ose of st u d y dr u g a d mi nistrati o n.  
1 0.  Male patie nts u n der t he f oll o wi n g c o n diti o ns:  
a. M ust a gree n ot t o d o nate s per m starti n g at ti me of i nf or me d c o ns e nt a n d c o nti n ui n g 
t hr o u g h o ut t he st u d y peri o d a n d f or at least 6 m o nt hs after t he fi nal st u d y dr u g 
a d mi nistrati o n.  
b.  If heter os e x uall y acti ve wit h n o n-pre g na nt, pr e g n a nt, or breastfee di n g p art ner, m ust 
c o nsiste ntl y use 2 hi g hl y effecti ve met h o ds of birt h c o ntr ol (as defi ne d i n A p pe n di x  G ) 
starti n g at ti me of i nf or me d c o nse nt a n d c o nti n ui n g t hr o u g h o ut t he st u d y a n d f or at least 
6  m o nt hs after t he fi nal d ose of st u d y dr u g a d mi nistrati o n. 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 0  of 1 5 2  
1 1.  Patie nt m ust pr o vi de writte n i nf or me d c o nse nt if t he y are a ble t o. If a patie nt is u na ble t o 
pr o vi de writte n i nf or me d c o nse nt, t he n writte n i nf or me d c o nse nt ca n be pr o vi de d b y a le gall y 
a ut h orize d re pres e ntati ve ( L A R) i n acc or da n ce wit h l ocal le gal re q uire me nts.  
4. 2.  
E x cl u si o n Crit eri a   
1 2.  Pri or treat me nt wit h L V . 
1 3.  Pri or i m m u n o -o nc ol o g y t hera p y (e. g., t hera pies affecti n g t h e P D -L 1, P D -L 2, C T L A -4, or 
C D 1 3 7 pat h wa y s, or a n y ot her a nti b o d y or dr u g s p ecificall y tar geti n g T cell c osti m ulati o n or 
c hec k p oi nt pat h w a ys).  
1 4.  Pre -e xisti n g ne ur o pat h y of Gra d e ≥2.  
1 5.  Hist or y of a n ot her mali g na nc y wit hi n 3  years pri or t o scree ni n g, wit h t he e x ce pti o n of t h ose 
wit h a ne gli gi ble ris k of metastasis or deat h ( e. g., a p pr o xi mate 5 -year O S of ≥9 0 %), s uc h as 
a de q uatel y tr eate d carci n o ma i n sit u of t he cer vi x, n o n -mela n o ma s ki n carci n o ma, l ocalize d 
pr ostate ca n cer, d uctal carci n o ma i n sit u, or Sta ge I uteri ne ca ncer.  
1 6.  Hist or y of carci n o mat o us me ni n gitis or acti ve ce ntral ner v o us s yste m ( C N S) metastases. 
Patie nts are eli gi ble if C N S metastases are a de q u atel y tr eate d a n d patie nts ha ve 
ne ur ol o gi call y ret ur n e d t o baseli ne (e x ce pt f or resi d ual si g ns or s y m pt o ms relate d t o t he C N S 
treat me nt) f or at least 4 wee ks pri or t o e nr oll me nt. I n a d diti o n, patie nts m ust be c o m pletel y 
off c ortic oster oi ds.  
1 7.  Hist or y of l e pt o me ni n geal carci n o mat osis.  
1 8.  Acti ve i nfecti o n re q uiri n g s yste mic treat me nt ≤7 da ys b ef ore d ose of st u d y dr u g. R o uti ne 
a nti micr o bial pr o p h yl a xis is per mitte d.  
1 9.  K n o w n t o be p ositi ve f or he patitis B b y s urface a nti ge n e x pressi o n, acti ve h e patitis  C 
i nfecti o n ( p ositi ve b y p ol y m erase c hai n reacti o n [ P C R] or o n a nti viral t hera p y f or he p atitis C 
wit hi n t he last 6 m o nt hs), or a k n o w n hist or y of bei n g ser o p osi ti ve f or HI V. Patie nts w h o 
ha ve bee n treat e d f or h e p atitis C i nfecti o n are per mitte d if t he y ha v e d oc u me nte d s ustai ne d 
vir ol o gic res p o nse of 1 2 wee ks.  
2 0.  D oc u me nte d hist or y of a cere bral vas c ular e ve nt (str o ke or tra nsie nt isc h e mic attac k), 
u nsta ble a n gi na, m y ocar dial i nfarcti o n, or car diac s y m pt o ms c o nsiste nt wit h c o n gesti ve heart 
fail ure, Class III-I V, b y Ne w Y or k Heart Ass ociati o n criteria wit hi n 6 m o nt hs pri or t o st u d y 
e nr oll me nt ( See A p p e n di x  I). 
2 1.  O n g oi n g, cli nic all y si g nifica nt t o xicit y ( Gra d e 2 or hi g her) ass o ciate d wit h pri or treat me nt 
i ncl u di n g s yste mic t hera p y, ra di ot hera p y, or s ur ger y. 
2 2.  Has recei ve d pri or ra di ot hera p y wit hi n 2 wee ks of start of st u d y tr eat me nt. A patie nt is als o 
e x cl u de d if ra di ot hera p y occ urre d m ore t ha n 2 wee ks pri or t o start of st u d y treat me nt b ut t he 
patie nt has n ot rec o v ere d fr o m ra diati o n -relate d t o xicities, re q uires c ortic oster oi ds, or has ha d 
ra diati o n p ne u m o nitis. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 1  of 1 5 2  
2 3.  Acti ve a ut oi m m u ne disease t hat has re q uir e d s yste mic treat me nt i n past 2 years (i.e.,  wit h use 
of disease m o dif yi n g a ge nts, c ortic oster oi ds, or i m m u n os u p pressi ve dr u gs). Re place me nt 
t hera p y (e. g., t h yr o xi ne, i ns uli n, or p h ysi ol o gi c c ortic oster oi d re place me nt t hera p y f or 
a dre nal or pit uitar y i ns ufficie nc y, et c.) is n ot c o nsi dere d a f or m of s yste mic treat me nt.  
2 4.  Hist or y of i nterstitial l u n g diseas e.  
2 5.  C urre nt p ne u m o nitis, or hist or y of ( n o n -i nfecti o us, i ncl u di ng ra di ati o n i n d uce d) p ne u m o nitis 
t hat re q uire d ster oi ds. 
2 6.  Has a dia g n osis of i m m u n o deficie nc y or is recei vi n g c hr o nic s yste mic ster oi d t hera p y (i n 
d oses e x cee di n g 1 0  m g d ail y of pre d nis o ne e q ui v ale nt) or a n y ot her f or m of 
i m m u n os u p pressi ve t hera p y wit hi n 7 da ys pri or t o t he first d ose of st u d y treat me nt. T he us e 
of c ortic oster oi ds f or p h ysi ol o gical r e place m e nt ma y b e a p pr o ve d after c o ns ultati o n wit h t he 
s p o ns or. 
2 7.  Patie nts w h o are breastfee di n g, pre g na nt, or pl a n ni n g t o bec o m e pre g n a nt fr o m ti me of 
i nf or me d c onse nt u ntil 6 m o nt hs after fi nal d ose of st u d y dr u g a d mi nistrati o n.  
2 8.  K n o w n h y p erse nsiti vit y t o a n y e x ci pie nt c o ntai ne d i n t he dr u g f or m ulati o n of L V  or 
pe m br oliz u ma b.  
2 9.  Has recei ve d tra nsf usi o n of bl o o d pr o d ucts (i ncl u di n g platelets or re d bl o o d cells) or 
a d mi nistrati o n of c ol o n y sti m ulati n g fact ors (i n cl u di n 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], or rec o m bi na nt er yt hr o p oieti n ) wit hi n 4 wee ks pri or t o 
st u d y Da y 1.  
3 0.  Ot her seri o us u n derl yi n g me dical c o n diti o n t hat, i n t he o pi ni o n of t h e i n vesti gat or, w o ul d 
i m pair t he a bilit y t o recei ve or t olerat e t he pla n ne d treat me nt a n d f oll o w-u p; a n y ps yc hiatric 
or s u bsta nce a b use dis or ders t hat w o ul d i nterfere wit h t he partici pa nt’s a bilit y t o c o o perate 
wit h t he re q uire me nts of t he trial.  
3 1.  Has recei ve d a li ve vacci ne wit hi n 3 0 da ys of pla n ne d start of st u d y t hera p y.  
a. N ote: seas o nal i nfl ue nza vacci nes f or i njecti o n are ge n erall y i nacti vate d fl u vacci nes a n d 
are all o w e d; h o we ver i ntra nasal i nfl ue nza v acci n es (e. g., Fl u -Mist) are li ve atte n uate d 
vacci nes  a n d are n ot all o we d.  
3 2.  Has n ot rec o v ere d (e. g., t o ≤ Gra de 1 or t o baseli n e) fr o m A Es d u e t o a pre vi o usl y 
a d mi nistere d t hera p y.  
3 3.  Has ha d a n all o ge nic tiss ue/s oli d or ga n tr a ns pla nt.  
4. 3.  
C hil d b e ari n g P ot e nti al   
A patie nt of c hil d beari n g p ote ntial is defi ne d as a n y o ne b or n fe m ale w h o has e x perie nce d 
me narc h e a n d has n ot u n der g o ne s ur gi cal steriliz ati o n (e. g., h ysterect o m y, bilateral 
sal pi n gect o m y, bilateral o o p h orect o m y) or c o m plete d me n o pause. M e n o pa use is defi ne d 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 2  of 1 5 2  
cli nicall y as 1 2  m o nt hs of a me n orr hea i n a w o ma n o ver a ge 4 5 i n t he a bse n ce of ot her bi ol o gical, 
p h ysi ol o gical, or p h ar mac ol o gic al ca us es.  
4. 4.  
R e m o v al of P ati e nt s fr o m T h er a p y or A s s e s s m e nt  
Sea ge n or t heir d esi g n ee m ust be n otifie d if a patie nt is wit h dra w n fr o m st u d y treat me nt or fr o m 
t he st u d y. T he reas o n(s) f or wit h dra wal m ust be d o c u me nte d i n t he patie nt’s me dical rec or ds 
an d / or cas e re p ort f or m ( C R F).  
4. 4. 1.  
Di s c o nti n u ati o n of St u d y Tr e at m e nt   
A patie nt’s st u d y tr eat me nt ma y be disc o nti n ue d f or a n y of t he f oll o wi n g reas o ns:  
● 
Pr o gressi ve disease ( P D)  
● 
A E  
● 
Pre g n a nc y  
● 
I n v esti gat or decisi o n 
● 
Patie nt decisi o n, n o n -A E  
● 
St u d y t er mi nati o n b y s p o ns or  
● 
Ot her, n o n -A E  
 
Patie nts w h o disc o nti n ue fr o m st u d y tr eat me nt will re mai n o n st u d y f or f oll o w -u p u nless t he y 
wit h dra w c o nse nt.  
Disc o nti n uati o n of pe m br oliz u ma b ma y be c o nsi d ere d f or patie nts  w h o ha v e att ai ne d a 
c o nfir me d C R t hat has bee n treate d f or at least 8 c ycl es ( 2 4 wee ks) a n d h a d at least 2  treat me nts 
wit h pe m br oliz u ma b be y o n d t he date w he n t h e i nitial C R was declare d.  
Patie nts w h o disc o nti n ue pe m br oliz u ma b ma y c o nti n ue t o recei ve L V  wit h me dical m o nit or 
a p pr o val (see Secti o n 5. 2. 5 ). Si milarl y, patie nts t hat disc o nti n ue L V  ma y c o nti n ue t o recei ve 
pe m br oliz u ma b wit h me dical m o nit or a p pr o val ( s ee Secti o n 5. 3. 5 ). 
4. 4. 2.  
P ati e nt Wit h dr a w al fr o m St u d y   
A n y p atie nt ma y be disc o nti n ue d fr o m t he st u d y f or a n y of t he f oll o wi n g reas o ns:  
● 
Patie nt wit h dra wal of c o nse nt  
● 
St u d y t er mi nati o n b y s p o ns or  
● 
C o m pleti o n  of pr ot oc ol s pecifie d safet y f oll o w-u p  (see Secti o n  ●) 
● 
L ost t o f oll o w -u p  
● 
Deat h  
● 
Ot her  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 3  of 1 5 2  
5.  
T R E A T M E N T S   
5. 1.  
Tr e at m e nt s A d mi ni st er e d   
All patie nts will recei ve L V , t he i n v esti gati o nal a ge nt u n d er st u d y i n t his pr ot oc ol, i n 
c o m bi nati o n wit h pe m br oliz u ma b. L V  will be a d mi nistere d first, f oll o we d b y pe m br oliz u ma b 
a p pr o xi matel y 6 0 – 9 0 mi n utes after i nf usi o n of L V  is c o m plete. 
5. 2.  
I n v e sti g atio n al St u d y Dr u g: L V   
L V  is a n A D C c o nsisti n g of t he a nti-LI V 1 A m A b h LI V 2 2 c o nj u gate d t o M M A E, a s y nt hetic 
a nal o g of t he nat urall y occ urri n g t u b uli n -bi n di n g a ge nt, d olastati n 1 0.  
D etaile d i nf or mati o n des cri bi n g t he pre p arati o n, a d mi nistrati o n, a n d st ora ge of L V  is l ocate d i n 
t he L V  P h ar mac y I nstr ucti o ns.  
5. 2. 1.  
D e s cri pti o n   
L V  is a st erile, pres er vati ve-free, w hite t o off-w hit e l y o p hilize d ca ke or p o w der f or rec o nstit uti o n 
f or I V a d mi nistrati o n. L V  is s u p plie d b y Sea ge n  i n si n gle-us e glass vials. Eac h dr u g pr o d uct vial 
c o ntai ns L V  f or I njecti o n, tre hal ose, histi di ne, a n d p ol ys or bat e 8 0. Dr u g pr o d uct vials are la bele d 
wit h a n o mi nal c o nte nt of 4 0  m g/ vial. Eac h vial c o ntai ns 4 5  m g of L V . E n o u g h o verfill is 
i ncl u de d t o all o w f or 4 0 m g of L V  t o b e wit h dra w n f or use. 
W he n rec o nstit ute d wit h 8. 8 m L Water f or I njecti o n ( W FI), U nite d States P har mac o peia ( U S P), 
t he c o nce ntr ati o n of rec o nstit ute d L V  pr o d uct is 5  m g/ m L. T he rec o nstit ute d dr u g pr o d uct is a 
clear t o sli g htl y o p alesce nt, c ol orless t o li g ht yell o w s ol uti o n wit h n o visi ble partic ul ate m atter. 
T he p H is a p pr o xi matel y 6. 0. T he rec o nstit ute d s ol uti o n is s u bse q ue ntl y dil ute d i n sterile 
0. 9 %  S o di u m C hl ori de f or I njecti o n, U S P, f or I V a d mi nistrati o n.  
5. 2. 2.  
M et h o d of Pr o c ur e m e nt   
L V  will be pr o vi de d b y t he s p o ns or.  
5. 2. 3.  
D o s e a n d A d mi ni str ati o n   
5. 2. 3. 1.  
All P art s   
I n t he a bse n ce of IR Rs, t he i nf usi o n rate f or all patie nts s h o ul d be calc ulate d i n or der t o ac hi e ve a 
3 0 -mi n ute i nf usi o n peri o d. H o we ver, gi ve n t he varia bilit y of i nf usi o n p u m ps fr o m site t o site, a 
wi n d o w bet wee n – 5 mi n utes a n d + 1 0  mi n utes is per mitte d (i.e., i nf usi o n ti me is 
3 0  mi n utes -5  mi n/ + 1 0 mi n).  
L V m ust n ot be a d mi nistere d as a n I V p us h or b ol us. L V s h o ul d n ot be mi x e d wit h ot her 
me dicati o ns.  
Wei g ht -base d d osi n g of L V is bas e d o n t he patie nt’s act ual b o d y wei g ht. D oses m ust be a dj uste d 
f or patie nts w h o e x perie n ce a ≥1 0 % c ha n ge i n wei g ht fr o m b aseli ne. Patie nt wei g ht m ust be 
meas ure d d uri n g all rele v a nt assess me nt wi n d o ws as descri be d i n t he s c he d ule of e ve nts 
(A p pe n di x  A ). If wei g ht is assesse d per i nstit uti o nal sta n dar d of care at a ti me p oi nt n ot re q uire d 
per pr ot oc ol (e. g., Da y 8 or Da y 1 5) a n d t here is a ≥1 0 % c ha n ge i n w ei g ht fr o m baseli ne, L V 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 4  of 1 5 2  
d ose m ust be a dj uste d acc or di n gl y. Ot her d ose a dj ust me nts f or c ha n ges i n b o d y wei g ht are 
per mitte d per i nstit uti o nal sta n dar d.  
5. 2. 3. 2.  
P art s A a n d B   
Pri or t o A me n d me nt 2, L V  at a d ose of 2. 5  m g/ k g (ca p pe d at 8 0 k g  per i nf usi o n ) will be 
a d mi nistere d o n Da y 1 o f e ver y 2 1-d a y c ycl e b y I V i nf usi o n gi ve n o ver a p pr o xi matel y 
3 0  mi n utes. F or patie nts treate d u n d er A me n d m e nt  2 a n d later, t he ma xi m u m wei g ht ca p per 
i nf usi o n will be i ncrease d fr o m 8 0 k g t o 1 0 0 k g. A n y p atie nt recei vi n g > 2 0 0  m g L V  p er i nf usi o n  
( wei g ht > 8 0 k g) is re q uir e d t o recei ve pr o p h ylactic G -C S F. F or patie nts wei g hi n g ≥1 0 0  k g, 
d osi n g will be base d o n 1 0 0 k g. I n c o ns ultati o n wit h t he s p o ns or, eli gi ble p atie nts alrea d y o n 
treat me nt pri or t o A me n d me nt 2, ma y h a ve t heir m a xi m u m wei g ht ca p per i nf usi o n  i ncreas e d t o 
1 0 0  k g or re mai n at 8 0 k g if t he y are recei vi n g b e nefit ( C R, P R, or S D).  
Pri or t o A me n d me nt 2, f or patie nts wei g hi n g greater t ha n 8 0 k g, d ose calc ulati o ns will be base d 
o n 8 0 k g (i n cl u di n g d ose re d ucti o ns). F or p atie nts tre ate d u n der A me n d me nt  2  a n d l ater, t he 
m a xi m u m w ei g ht c a p per i nf usi o n will be i ncre ase d fr o m 8 0  k g t o 1 0 0  k g, t heref ore, t he 
m a xi m u m d ose will be 2 5 0  m g per i nf usi o n w he n d osi n g at 2. 5 m g/ k g a n d 2 0 0  m g per 
i nf usi o n w he n d osi n g at 2. 0  m g/ k g.  F or patie nts w h o recei ve > 2 0 0  m g L V  p er i nf usi o n, 
pr o p h yla ctic G -C S F a d mi nistrati o n is re q uire d a n d will be gi ve n t o patie nts o n t he da y after 
st u d y treat me nt is gi ve n, wit h a visit wi n d o w of Da y 2– 4. R o u n di n g is per missi ble wit hi n o ne 
milli gra m of n o mi nal d ose.  
5. 2. 3. 3.  
P art C   
L V  will be gi ve n o n Da y 1, Da y 8, a n d Da y 1 5 i n e ver y 3 -wee k c ycle.  
At least 7 da ys m ust ela pse bet wee n a d mi nistrati o ns of L V . T here will be n o wei g ht ca p per 
i nf usi o n. T he ma x i m u m d ose will be 2 0 0 m g per i nf usi o n.  
5. 2. 3. 4.  
P art D   
L V  will be gi ve n  at a d os e of 1. 5 m g/ k g  b y I V i nf usi o n o ver a p pr o xi matel y 3 0  mi n utes  o n Da y  1  
a n d Da y 8 i n e v er y 2 1 -d a y  c ycle. L V wi ll N O T  be a d mi nistere d o n Da y 1 5 f or patie nts e nr olle d 
i n Part D.  
At least 7 da ys m ust ela pse bet wee n a d mi nistrati o ns of L V. T he ma xi m u m d ose will be 2 0 0  m g  
per i nf usi o n.  
5. 2. 3. 5.  
L V  D o si n g Crit eri a   
D ose m o dificati o n g ui deli nes f or L V  are det aile d i n Ta ble  3  a n d T a ble  6 . T he f oll o wi n g 
la b orat or y criteria m ust b e met o n Da y 1 of eac h c ycl e pri or t o L V  a d mi nistrati o n:  
● 
Ne utr o p hil c o u nt ≥1 0 0 0 / µ L ( ≤ Gra de 2) 
● 
A S T  ≤ Gra de 2  
● 
A L T  ≤ Gra d e 2  
● 
T otal bilir u bi n ≤ Gra de 2  
● 
Bl o o d gl uc ose ≤2 5 0  m g/ d L or ≤1 3. 9  m m ol/ L  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 5  of 1 5 2  
If t hese criteria are n ot m et o n t he da y of d osi n g, h ol d t he L V  d os e u ntil criteria are met. I n 
a d diti o n, h ol d L V  d osi n g f or patie nts wit h ≥ Gra d e 2 peri p heral ne ur o p at h y.  A d diti o nal 
i nf or mati o n o n L V  d os e m o dificati o ns  ca n be f o u n d i n Ta ble  3  a n d Ta bl e  6 . Please see T a ble  7  
f or i nf or mati o n o n pe m br oliz u ma b d osi n g. 
I n Part C, ne utr o p hil c o u nt m ust als o be ≥1 0 0 0 / µ L ( ≤ Gra d e 2) pri or t o L V  a d mi nistrati o n o n 
Da ys  8 a n d 1 5 of eac h c ycle.  
I n Part D, ne utr o p hil c o u nt m ust als o be ≥1 0 0 0/ µ L ( ≤ Gra d e 2) pri or t o L V a d mi nistrati o n o n 
Da y  8 of eac h c ycle.  
5. 2. 4.  
O v er d o s e   
I n t he e ve nt of a n o ver d ose > 1 0 % of L V , t he site s h o ul d n otif y t he s p o ns or as s o o n as t he y are 
a ware of t he o v er d ose. T he patie nt s h o ul d be cl os el y m o nit ore d f or a d v erse reacti o ns, 
partic ularl y ne utr o p e nia. S u p p orti ve care p er i nstit uti o nal sta n dar ds s h o ul d be a d mi nistere d. 
A d here n ce t o c urre n t cli nical practice g ui deli nes f or t he use of w hite bl o o d cell ( W B C) gr o wt h 
fact ors (s ee A p p e n di x  L ) is str o n gl y rec o m me n de d f or t he ma na ge me nt of n e utr o pe nia a n d 
fe brile ne utr o p e nia (Cra wf or d 2 0 1 0 ; S mit h 2 0 1 5 ). 
5. 2. 5.  
D o s e M o difi c ati o n s   
Patie nts w h o e x perie nce D L T i n C ycle 1 (t he D L T e val uati o n peri o d) s h o ul d n ot recei ve f urt her 
treat me nt wit h L V  a n d p e m br oliz u ma b u nless cli nical be nefit is o bser ve d,  a n d t he A E(s) is 
a de q uatel y ma n a ge d wit h se verit y i m pr o vi n g t o Gra de 1 or l o wer. S u bse q ue nt d oses will be 
defi ne d b y t he me dic al m o nit or i n disc ussi o n wit h t he  site i n vesti gat or i n t h e c o nte xt of t he t y pe 
of A E(s) o bser ve d.  
I n t he e ve nt a p atie nt is u na ble t o t olerate t heir d os e le vel, a d diti o nal treat me nt c ycles ( C ycl e 2 or 
later) ma y b e a d mi nistere d at a l o wer d ose le vel. C o ns ultati o n wit h t he me dical m o nit or is 
str o n gl y e n c o ura ge d. 
Patie nts w h o disc o nti n ue pe m br oliz u ma b d ue t o a pe m br oliz u ma b -relate d A E ma y c o nti n ue L V . 
Si milarl y, p atie nts w h o disc o nti n ue L V  f or a L V -relate d A E ma y c o nti n ue pe m br oliz u ma b. 
5. 2. 5. 1.  
P art s A a n d B   
If a patie nt h as a cli nicall y si g nifica nt, u nr es ol ve d A E o n Da y 1 of a n y c ycl e, t he start of t he 
c ycle ma y b e dela ye d f or u p t o 1 4 da ys. D ela ys of > 1 4 da ys m ust be a p pr o ve d b y t h e me dical 
m o n it or. 
D ose m o dificati o ns f or L V  treat me nt ass oci ate d t o xicit y are des cri be d i n Ta ble  3 . A n y d e viati o ns 
fr o m t hese m o dificati o ns s h o ul d be disc usse d wit h t he me dical m o nit or. 
Pri or t o A me n d me nt 2, t he ma xi m u m d oses after m o dificati o n are:  
● 
1 6 0  m g f or p atie nts re d u ce d t o 2. 0  m g/ k g  
● 
1 2 0  m g f or p atie nts re d u ce d t o 1. 5  m g/ k g  
 
F or patie nts treate d u n der A me n d me nt 2 a n d later, t he ma xi m u m d oses after m o dificati o n are:  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
La dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 4 6  of 1 5 2  
● 
2 0 0  m g f or p atie nts re d u ce d t o 2. 0  m g/ k g  
● 
1 5 0  m g f or p atie nts re d u ce d t o 1. 5  m g/ k g  
● 
1 2 5  m g f or p atie nts re d u ce d t o 1. 2 5  m g/ k g  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 0 ; 2 4 -Ma y -2 0 2 2  
La dirat uz u ma b Ve d oti n ( L V; S G N -L I V 1 A) 
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 7  of 1 5 2  
T a bl e  3 : 
R e q uir e d d o s e m o difi c ati o n s f or L V -a s s o ci at e d t o xi citi e s ( P art s A a n d B)  
T o xicit y  
Gra d e 1  
Gra de 2  
Gra de 3  
Gra d e 4  
P eri p heral ne ur o pat h y a 
C o nti n ue at 
sa me d ose 
le vel 
Wit h h ol d u ntil t o xicit y 
res olves t o ≤ Gra de 1; 
t he n res u me treat me nt at 
t he ne xt l o wer d ose le vel 
Wit h h ol d u ntil t o xicit y res ol ves t o 
≤ Gra de 1, t he n res u me treat me nt at 
t he ne xt l o wer d ose le vel 
Disc o nti n ue treat me nt  
H y per gl yce mia  
H ol d f or gl uc ose > 2 5 0  m g/ d L or > 1 3. 9 m m ol/ L. T esti n g  ma y be re peate d o n t he sa me da y of d osi n g. D ose ma y be deli vere d o n t he 
sa me da y o nce ele vate d bl o o d gl uc ose has i m pr o ve d t o ≤2 5 0  m g/ d L or ≤1 3. 9  m m ol/ L a n d patie nt is cli nicall y a n d meta b olicall y 
sta ble.  
N o n -he mat ol o gic a 
(e xce pt p eri p heral 
ne ur o pat h y a n d 
ele vate d bl o o d gl uc ose)  
C o nti n ue at 
sa me d ose 
le vel 
C o nti n ue at sa me d ose 
le vel 
Wit h h ol d d ose u ntil t o xicit y is 
≤ Gra de  2 or has ret ur ne d t o 
baseli ne, t he n res u me treat me nt at 
sa me d ose le vel b 
Wit h h ol d d ose u ntil t o xicit y is ≤ Gra d e  2 or has 
ret ur ne d t o baseli ne, t he n re d uce d ose t o t he ne xt 
l o wer d ose le vel a n d res u me tr eat me nt, or 
disc o nti n ue at t he discreti o n of t he i n vesti gat or b, c 
He mat ol o gic a 
C o nti n ue at 
sa me d ose 
le vel 
C o nti n ue at sa me d ose 
le vel 
Wit h h ol d u ntil t o xicit y res ol ves t o 
≤ Gra de  2 or baseli ne. d, e F or 
ne utr o pe ni a, str o n gl y c o nsi d er 
W B C Gr o wt h F act or s u p p o rt,  
t he n res u me treat me nt at t he s a me 
d ose le vel. Pr o p h yl actic W B C 
Gr o wt h F act or s u p p ort s h o ul d be 
str o n gl y c o nsi dere d f or 
s u bse q ue nt c ycles. ( See 
A p pe n di x  L ) 
Wit h h ol d u ntil t o xicit y res ol ves t o ≤ Gra d e  2 or 
baseli ne. d, e F or ne utr o pe ni a, str o n gl y c o nsi der 
W B C Gr o wt h F act or s u p p o rt,  t he n res u me 
treat me nt at t he sa me d ose le vel. Pr o p h yl actic 
W B C Gr o wt h F act or s u p p o rt is re q uire d f or 
all s u bse q ue nt c y cles.  If Gra d e 4 ne utr o pe nia 
rec urs des pite W B C Gr o wt h F act or s u p p ort, 
c o nsi der d ose re d ucti o n t o 2. 0  m g/ k g or 
disc o nti n uati o n  ( See A p pe n di x  L ) 
Fe brile ne utr o pe nia a 
 
 
W B C Gr o wt h Fact or s u p p ort is re q uire d f or treat me nt of fe brile ne utr o pe nia.  Wit h h ol d 
u ntil fe brile ne utr o pe ni a res ol ves a n d ne utr o p hil c o u nt r et ur ns t o ≤ Gr a de  2 or 
b aseli ne t he n res u me tre at me nt at t he s a me d ose le vel. Pr o p h ylactic W B C Gr o wt h 
Fact or s u p p ort is re q uire d f or all s u bse q ue nt c ycles.  If fe bril e ne utr o pe ni a rec urs 
des pite W B C Gr o wt h f act or s u p p ort, c o nsi der d ose re d ucti o n t o 2. 0  m g/ k g or 
disc o nti n u ati o n  ( See A p pe n di x  L ) 
N ote: Pri or t o A me n d me nt 2, f or patie nts wei g hi n g > 8 0  k g, d osi n g will be base d o n 8 0  k g. F or patie nts treate d u n der A me n d me nt 2 a n d later, t he ma xi m u m wei g ht ca p per 
i nf usi o n will be i n crease d fr o m 8 0  k g t o 1 0 0  k g. P atie nts w h o recei ve > 2 0 0  m g L V  per i nf usi o n  are als o re q uire d t o be a d mi nistere d pr o p h ylac tic G-C S F.  
a 
O nl y 2 d ose re d ucti o ns are all o we d. A d diti o nal t o xicities s h o ul d be ma na ge d wit h d ose dela ys . 
b  
P atie nts w h o de vel o p Gra de  3 or 4 electr ol yte la b orat or y a b n or malities ma y c o nti n ue st u d y treat me nt wit h o ut i nterr u pti o n if a ma na ge me nt pla n c o nsiste n t wit h i nstit uti o nal 
practice a n d re g ular m o nit ori n g are p ut i n place . 
c 
Treat me nt s h o ul d be disc o nti n ue d f or patie nts w h o e x perie nce Gra de  4 I R Rs . 
d  
S u p p ort wit h bl o o d pr o d uct tra nsf usi o ns all o we d per i nstit uti o nal sta n dar d of care . 
e 
P atie nts w h o de vel o p Gra de  3 or 4 l y m p h o pe nia ma y c o nti n ue st u d y tre at me nt wit h o ut i nterr u pti o n .
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 0 ; 2 4 -Ma y -2 0 2 2  
La dirat uz u ma b Ve d oti n ( L V; S G N -L I V 1 A) Sea ge n I nc. - C o nfi de ntial  
P a ge 4 8  of 1 5 2  
5. 2. 5. 2.  
P art C ( q 1 w k L V  d o si n g)   
D ose m o dificati o n g ui deli nes f or L V  f or selecte d A Es are d etaile d i n Ta ble  6 . 
If a patie nt h as an  A E or la b criteri o n  t hat pre ve nts d osi n g o n Da y 1 of a n y c ycle, t he start of t he 
c ycle ma y b e dela ye d f or u p t o 1 4 da ys. D ela ys of > 1 4 da ys m ust be a p pr o ve d b y t h e me dical  
m o nit or.  
I n t he e ve nt of a n A E or l a b criterio n  t hat pre ve nts d osi n g of L V  d uri n g t h e c ycle (e. g. , Da y  8 or 
1 5 , Secti o n  5. 2. 3. 5 ), t he L V  d os e f or t h e wee k s h o ul d be wit h hel d  u p t o 4 da ys . L V  ma y be 
res u me d w he n t h e d osi n g criteria are met.  
If a d ose(s) of L V  is wit h hel d, t he c orres p o n di n g visit ma y b e s ki p pe d a n d res u me at t he 
f oll o wi n g w ee k (e. g., if t he Da y 8  d ose is s ki p pe d, visits will res u me o n D a y 1 5 ; if Da y 1 5 d ose 
is s ki p pe d, visits will res u me on  Da y 1 of t he f oll o wi n g c ycle).  
D ose re d u cti o n of L V  ma y be c o nsi dere d i n t he e v e nt of rec urre nt A E des pite wit h hel d d oses. 
D ose re -escalati o n f oll o wi n g d ose re d ucti o n is n ot all o we d. D ose le vels f or L V  d ose re d ucti o ns 
i n Part C are s h o w n i n Ta ble  4 . 
T a bl e  4 : 
Q 1 w k L V  d o s e r e d u cti o n s  f or P art C 
Starti n g d ose  
First d ose re d ucti o n  
( m g/ k g/ w k) 
Sec o n d d ose re d ucti o n 
( m g/ k g/ w k) 
D ose le vel 0 ( 1. 0 m g/ k g/ w k)  
0. 7 5  
0. 5  
D ose le vel 1 ( 1. 2 5 m g/ k g/ w k)  
1. 0  
0. 7 5  
 
F or n o ncli nical e ve nts re q uiri n g alterati o n i n d osi n g sc h e d ule (e. g., h oli da ys, sc h e d uli n g 
c o nflicts), a + 2 -da y d osi n g wi n d o w is all o we d. If m ore t ha n a + 2 -da y  wi n d o w is nee de d, t he 
me dical m o nit or  m ust be c o ns ulte d . T he me dical m o nit or m ust a p pr o ve s ki p pe d d ose (s) f or 
n o ncli nical e ve nts. At least 7 da ys m ust ela pse b et wee n a d mi nistrati o ns of L V . 
5. 2. 5. 3.  
P art D ( D a y 1 a n d D a y 8 L V d o si n g)   
D ose m o dificati o n g ui deli nes f or L V f or selecte d A Es are d etaile d i n Ta ble  6 . 
If a patie nt h as a n A E or la b criteri o n t hat pre ve nts d osi n g o n Da y 1 of a n y c ycle, t he start of t he 
c ycle ma y b e dela ye d f or  u p t o 2 1  da ys. D ela ys of > 2 1  da ys m ust be a p pr o ve d b y t h e me dical 
m o nit or.  
I n t he e ve nt of a n A E or l a b criteri o n t hat pre ve nts d osi n g of L V  o n Da y 8 d uri n g t he c ycle ( e. g., 
Secti o n  5. 2. 3. 5 ), t he L V d ose f or t he wee k ma y  b e wit h hel d u p t o 4  da ys. L V ma y be res u me d 
w he n t he d osi n g criteri a are met. If a d ose of L V is wit h hel d f or m ore t ha n 4  da ys, t h e 
c orres p o n di n g visit ma y be s k i p pe d a n d d osi n g res u med  at t he f oll o wi n g visit  (e g, if t he Da y 8 
d ose is s ki p pe d, visits will res u me o n Da y 1 of t he f oll o wi n g c ycl e).  
D ose re d u cti o n of L V ma y be c o nsi dere d i n t he e v e nt of rec urre nt A E des pite wit h hel d d oses. 
D ose re -escalati o n f oll o wi n g  d ose re d ucti o n is n ot all o we d. D ose le vels f or L V d ose re d ucti o ns 
i n Part D  are s h o w n i n  T a ble 5 . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc ol  
A me n d me nt 1 0 ; 2 4 -Ma y -2 0 2 2  
La dirat uz u ma b Ve d oti n ( L V; S G N -L I V 1 A) Sea ge n I nc. - C o nfi de ntial  
P a ge 4 9  of 1 5 2  
T a bl e 5 : 
L V d o s e r e d u cti o n s f or P art D  
Starti n g d ose  
First d ose re d ucti o n  
Sec o n d d ose re d ucti o n a 
1. 5 m g/ k g  
1. 2 5  m g/ k g  
1. 0 0  m g/ k g b 
f 
If patie nts h a ve m ore t h a n 2 d ose re d ucti o ns ( wit h me dical m o nit or a p pr oval), d ose will be t he ne xt a p pr o priate re d uce d 
d ose le vel deter mi n e d b y disc ussi o n bet wee n i n vesti gat or a n d me dical m o nit or.  
g  
T he d ose ma y be re d uce d t o 0. 7 5  m g/ k g/ wee k f oll o wi n g a p pr o val fr o m t h e me dical m o nit or.  
 
F or n o ncli nical e ve nts re q uiri n g alterati o n i n d osi n g sc h e d ule (e. g., h oli da ys, sc h e d uli n g 
c o nflicts), a +4 -da y d osi n g wi n d o w is all o we d. If m ore t ha n a + 4 -da y wi n d o w is nee de d, t he 
me dical m o nit or m ust be c o ns ulte d. T he me dical m o nit or m ust a p pr o ve s ki p pe d d ose(s) f or 
n o ncli nical e ve nts.  At least 7 da ys m ust ela pse b et wee n a d mi nistrati o ns of L V.   
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 5 0  of 1 5 2  
T a bl e  6 : 
D o s e m o difi c ati o n s f or L V  tr e at m e nt-r el at e d a d v er s e e v e nt s ( P arts  C  a n d D ) 
T o xicit y  
Gra d e 1  
Gra d e 2  
Gra de 3  
Gra de 4  
P eri p heral 
ne ur o pat h y a 
C o nti n ue at 
sa me d ose 
le vel 
Wit h h ol d u ntil 
t o xicit y res ol ves t o 
≤ Gra d e 1; treat me nt 
ma y res u me at t he 
ne xt l o wer d ose le vel 
(see T a ble  4  f or P art 
C or T a ble 5  f or P art 
D ) 
Wit h h ol d u ntil t o xicit y res ol ves t o 
≤ Gra de 1, t he n res u me treat me nt at t he 
ne xt l o wer d ose le vel (see T a ble  4  f or 
P art C or T a ble 5  f or P art D) 
Disc o nti n ue treat me nt  
H y per gl yce mia  
H ol d f or bl o o d gl uc ose > 2 5 0  m g/ d L or > 1 3. 9  m m ol/ L. Res u me treat me nt o nce ele vate d bl o o d gl uc ose has i m pr o ve d t o ≤2 5 0  m g/ d L or 
≤1 3. 9  m m ol/ L a n d s u bj ect is cli nicall y a n d meta b olicall y sta ble (see Secti o n 5. 7  f or details). 
N o n -he mat ol o gic a 
(e xce pt p eri p heral 
ne ur o pat h y a n d 
ele vate d bl o o d 
gl uc ose)  
C o nti n ue at 
sa me d ose 
le vel 
C o nti n ue at sa me 
d ose le vel  
Wit h h ol d d ose u ntil t o xicit y is ≤ Gra de  2 
or has ret ur ne d t o baseli ne, t he n res u me 
treat me nt at sa me d ose le velb 
Wit h h ol d d ose u ntil t o xicit y is ≤ Gra d e  2 or has ret ur ne d 
t o baseli ne, t he n re d uce d ose t o t he ne xt l o wer d ose le vel 
(see T a ble  4  f or P art C or T a ble 5  f or P art D) a n d res u me 
treat me nt, or disc o nti n ue at t he discreti o n of t he 
i n vesti gat orb, c 
He mat ol o gic a  
C o nti n ue at 
sa me d ose 
le vel 
C o nti n ue at sa me 
d ose le vel  
Wit h h ol d u ntil t o xicit y res ol ves t o 
≤ Gra de 2 or baseli ne d, e, t he n res u me 
treat me nt at t he sa me d ose le vel. If t he 
d ose is hel d > 4 8  h o urs, t he d ose ma y be 
o mit te d a n d d osi n g ma y res u me o n t he  
ne xt sc he d ule d d osi n g da y.  Se e 
Secti o ns  5. 5. 2  a n d 5. 5. 2. 1  o n all o we d 
c o nc o mita nt t hera p y a n d m yel oi d gr o wt h 
fact ors. 
Wit h h ol d u ntil t o xicit y res ol ves t o ≤ Gra d e 2 or baseli ne
d, e, 
t he n re d uce d ose t o t he ne xt l o wer d ose le vel (see T a ble  4  
f or P art C or T a ble 5  f or P art D) if treat me nt is res u med b, c. 
If t he d ose is hel d > 4 8 h o urs, t he d ose ma y be o mitte d a n d 
d osi n g ma y res u me o n t he ne xt sc he d ule d d osi n g da y. If 
Gra de 4 ne utr o pe nia rec urs, re d uce d ose t o t he ne xt l o wer 
d ose le vel (see T a ble  4  f or P art C or T a ble 5  f or P art D) if 
treat me nt is res u me d, or disc o nti n ue at t he discreti o n of 
t he i n vesti gat or. See Secti o ns 5. 5. 2  a n d 5. 5. 2. 1  o n all o we d 
c o nc o mita nt t hera p y a n d m yel oi d gr o wt h fact ors.  
Fe brile ne utr o pe nia a 
N ot 
a p plica ble 
N ot a p plica ble  
Wit h h ol d u ntil fe brile ne utr o pe nia res ol ves a n d ne utr o p hil c o u nt ret ur ns t o ≤ Gra d e 2 or baseli ne a n d 
t he n res u me treat me nt at t he ne xt l o wer d ose le vel (see T a ble  4  f or P art C or T a ble 5  f or Part D). If t he 
d ose is hel d > 4 8 h o urs, t he d ose ma y be o mitte d a n d d osi n g ma y res u me o n t he ne xt sc he d ule d d osi n g 
da y. If fe brile ne utr o pe nia rec urs, re d uce d ose t o t he ne xt l o wer d ose le vel (see T a ble  4  f or P art C or 
T a ble 5  f or P art D) if treat me nt is res u me d, or disc o nti n ue at t he discreti o n of t he i n vesti gat or. See 
Secti o ns  5. 5. 2  a n d 5. 5. 2. 1  o n all o we d c o nc o mita nt t hera p y a n d m yel oi d gr o wt h fact ors.  
T he ma xi m u m d ose will be 2 0 0  m g per i nf usi o n f or  patie nts e nr olle d i n P art s C  a n d D. 
a 
O nl y 2 d ose re d ucti o ns are all o we d wit h o ut pri or me dical m o nit or a p pr o val. A d diti o nal t o xicities s h o ul d be ma na ge d wit h d ose dela ys. Me dical m o nit or a p pr o val is n ee de d 
f or f urt h er d ose re d ucti o n. 
b  
P atie nts w h o de vel o p Gr a de 3 or 4 electr ol yte la b orat or y a b n or malities ma y c o nti n ue st u d y treat me nt wit h o ut i nterr u pti o n if a ma na ge me nt pla n c o nsiste nt  wit h i nstit uti o nal 
practice a n d re g ular m o nit ori n g are p ut i n place.  
c 
Treat me nt s h o ul d be disc o nti n ue d f or patie nts w h o e x perie nce Gra de  4 i nf usi o n -relate d reacti o ns. 
d  
S u p p ort wit h bl o o d pr o d uct tra nsf usi o ns all o we d per i nstit uti o nal sta n dar d of care.  
e 
P atie nts w h o de vel o p Gra de  3 or 4 l y m p h o pe nia ma y c o nti n ue st u d y tre at me nt wit h o ut i nterr u pti o n.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 1  of 1 5 2  
5. 2. 6.  
St or a g e a n d H a n dli n g   
Si n gle -u se vials c o nt ai ni n g L V  m ust be st or e d u n der refri gerati o n at 2 – 8° C i n a n a p pr o priate 
sec ure d area accessi ble o nl y t o t he p har m acist, i n vesti gat or, or a d ul y desi g nate d pers o n.  
C he mical a n d p h ysical st a bilit y of t he rec o nstit ute d dr u g pr o d uct has b ee n de m o n strate d f or 
2 4  h o urs at 2 – 8° C a n d at r o o m te m perat ur e. H o we ver, L V  dr u g pr o d uct d oes n ot c o ntai n 
preser vati ves; t heref ore, fr o m a micr o bi ol o gical st a n d p oi nt, o pe ne d a n d rec o nstit ute d vials 
s h o ul d be use d i m me diatel y. If n ot use d i m me diat el y, t he i n-us e st ora ge s h o ul d n ot be l o n ger 
t ha n 2 4 h o urs u n der refri gerati o n at 2 – 8 ° C. T he pre pare d d osi n g s ol uti o n (rec o nstit ute d dr u g 
pr o d uct s ol uti o n a n d sali ne dil uti o n i n a n I V ba g or p ol y pr o p yl e ne s yri n ge) s h o ul d be 
a d mi nistere d wit hi n 8 h o urs after e x p osi n g t o a m bie nt te m perat ure a n d li g ht c o n diti o n.  
It is rec o m me n de d t hat t h e dr ug pr o d uct vials a n d s ol uti o ns be pr otecte d fr o m direct s u nli g ht 
u ntil t he ti me of use.  
D o n ot s ha ke rec o nstit ute d L V . 
A n y p artiall y us e d vials or pre pare d d osi n g s ol uti o ns s h o ul d be discar de d b y t he site acc or di n g t o 
i nstit uti o nal dr u g dis p osal pr oce d ures. U n use d vials ma y o nl y be disc ar de d b y t he site after 
a ut h orizati o n b y t he s p o ns or.  
5. 2. 7.  
P a c k a gi n g a n d L a b eli n g   
L V  is s u p plie d i n glass vi als. T he dr u g pr o d u ct vials are la bel e d as L V , t he c o m p o u n d c o de. 
Refer t o t he P har m ac y I nstr ucti o ns f or a sa m ple la bel of L V . 
5. 2. 8.  
Pr e p ar ati o n   
Rec o m me n de d safet y me as ures f or ha n dli n g a n d pre parati o n i ncl u de mas ks, pr otecti ve c l ot hi n g, 
gl o ves, a n d vertical la mi nar airfl o w s afet y ca bi nets.  
Bef ore a d mi nistrati o n, L V  m ust be rec o nstit ute d a n d dil ute d. Dil ute d s ol uti o ns of L V  are sta ble 
at a c o nce ntrati o n ra n ge of 0. 3  m g/ m L t o 2. 5  m g/ m L. T he f or m ulati o n c o ntai ns n o preser vati ve 
a n d is i nte n de d f or si n gle use o nl y; i nf usi o n s ol uti o ns s h o ul d be pre pare d a n d tra nsferre d usi n g 
ase ptic tec h ni q ue i n a bi osafet y h o o d.  
Mi xi n g of l ot/ batc h n u m bers is n ot all o we d f or pre parati o n of a si n gl e d ose; h o we ver, use of a 
differe nt l ot/ batc h n u m ber is  all o we d f or s u bse q ue nt d oses d uri n g tr eat me nt c ycles.  
Detaile d dr u g pre parati o n i nstr ucti o ns are pr o vi de d i n t he P har mac y I nstr u cti o ns.  
5. 3.  
P e m br oli z u m a b   
Patie nts will recei ve pe m br oliz u ma b 2 0 0  m g i n c o m bi nati o n wit h L V . 
5. 3. 1.  
D e s cri pti o n   
Pe m br oliz u ma b will be s u p plie d as a 1 0 0  m g/ 4 m L ( 2 5  m g/ m L) s ol uti o n i n a si n gle -use vial.  
Pe m br oliz u ma b f or i njecti o n is a ste rile, preser vati ve-free, cl ear t o sli g htl y o palesce nt, c ol orless 
t o sli g htl y yell o w s ol uti o n t hat re q uires dil uti o n f or I V i nf usi o n. Eac h vial c o ntai ns 1 0 0 m g of 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 2  of 1 5 2  
pe m br oliz u ma b i n 4 m L of s ol uti o n. Eac h 1 m L of s ol uti o n c o ntai ns 2 5  m g of pe m br oliz u ma b 
a n d is f or m ulate d i n L-histi di ne, p ol ys or bate, s u cr ose, a n d W FI U S P.  
5. 3. 2.  
M et h o d of Pr o c ur e m e nt   
Pe m br oliz u ma b will be pr o vi de d t o all st u d y sites b y t he s p o ns or. I n c o u ntries o utsi de t he U S, 
pe m br oliz u ma b will als o be rela b ele d b y t he s p o ns or, t o meet c o u ntr y -s p ecific re g ulat or y 
re q uire me nts. 
5. 3. 3.  
D o s e a n d A d mi ni str ati o n   
N O T E: St u d y treat me nt s h o ul d be gi n as cl ose as p ossi ble t o t he date o n w hic h t he patie nt is 
e nr olle d.  
St u d y treat me nt of p e m br oliz u ma b will be a d mi nistere d o n Da y 1 of eac h 2 1 -da y c ycl e, aft er all 
pr oce d ures a n d ass ess me nts ha ve bee n c o m plete d as detaile d i n Secti o n 6  a n d A p pe n di x  A , 
A p pe n di x  B , a n d A p pe n di x  C . 
Pe m br oliz u ma b will be a d mi nistere d as a d ose of 2 0 0  m g usi n g a 3 0 -mi n ut e I V i nf usi o n gi ve n 
a p pr o xi matel y 6 0 – 9 0 mi n utes after a d mi nistrati o n of L V . Sites s h o ul d ma ke e ver y eff ort t o tar get 
i nf usi o n ti mi n g t o be as cl ose t o 3 0 mi n utes as p ossi ble. H o we ver, gi v e n t he varia bilit y of 
i nf usi o n p u m ps fr o m site t o site, a wi n d o w bet wee n – 5 mi n utes a n d + 1 0  mi n utes is per mitte d 
(i.e., i nf usi o n ti me is 3 0 mi n utes – 5 mi n/ + 1 0 mi n).  
T he p har mac y ma n ual c o ntai ns s pecific i nstr ucti o ns f or  t he pre p arati o n of t he pe m br oliz u ma b 
i nf usi o n a n d a d mi nistrati o n of i nf usi o n s ol uti o n. 
5. 3. 4.  
O v er d o s e   
F or t his trial, a n o ver d ose will be defi ne d as ≥1 0 0 0  m g ( 5 ti mes t he d ose) of pe m br oliz u ma b. N o 
s pecific i nf or m ati o n is a vaila ble o n t he treat me nt of o ver d ose of pe m br oliz u ma b. I n t h e e ve nt of 
a n o ver d ose, t h e site s h o ul d n otif y t he s p o ns or as s o o n as t he y are a ware of t he o ver d ose. T h e 
patie nt s h o ul d be o bser ve d cl osel y f or si g ns of t o xicit y. A p pr o priate s u p p orti ve treat me nt s h o ul d 
be pr o vi de d if cli nic all y i n dicate d.  
5. 3. 5.  
D o s e M o difi c ati o n s   
5. 3. 5. 1.  
D o s e M o difi c ati o n a n d T o xi cit y M a n a g e m e nt f or I m m u n e -R el at e d A E s 
A s s o ci at e d wit h P e m br oli z u m a b   
A Es ass ociate d wit h pe m br oliz u ma b e x p os ure ma y re pres e nt a n i m m u n ol o gic eti ol o g y. T hes e 
i m m u ne-relate d A Es (ir A Es) ma y occ ur s h ortl y aft er t he first d ose or se veral m o nt hs after t he 
last d ose of pe m br oliz u ma b treat me nt a n d m a y affect m ore t ha n o ne b o d y s yste m 
si m ulta ne o usl y. T heref ore, earl y rec o g niti o n a n d i nitiati o n of treat me nt is critical t o re d uce 
c o m plicati o ns. Base d o n e xisti n g cli nical st u d y data, m ost ir A Es were re versi ble a n d c o ul d be 
ma na ge d wit h i nterr u pti o ns of pe m br oliz u ma b, a d mi nistrati o n of c ortic oster oi ds a n d/ or ot her 
s u p p orti ve care. F or s us pecte d ir A Es, e ns ure a de q uate e val u ati o n t o c o nfir m eti ol o g y or e x cl u de 
ot her ca us es. A d diti o nal pr oce d ures or tests s uc h as br o nc h osc o p y, e n d osc o p y, s ki n bi o ps y m a y 
be i ncl u de d as part of t he e val uati o n . Base d o n t he se verit y of ir A Es, wit h h ol d or per ma ne ntl y 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 3  of 1 5 2  
disc o nti n ue pe m br oliz u ma b a n d a d mi nister c ortic oster oi ds. D ose m o dificati o n a n d t o xicit y 
ma na ge me nt g ui deli nes f or ir A Es ass ociat e d wit h pe m br oliz u ma b are pr o vi de d i n Ta ble  7 . 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 5 4  of 1 5 2  
T a bl e  7 : 
D o s e m o difi c ati o n a n d t o xi cit y m a n a g e m e nt g ui d eli n e s f or i m m u n e -r el at e d A E s a s s o ci at e d wit h p e m br oli z u m a b 
Ge neral i nstr ucti o ns:  
1.  Se vere a n d life -t hreate ni n g ir A Es s h o ul d be treate d wit h I V c ortic oster oi ds f oll o we d b y oral ster oi ds. Ot her i m m u n os u p pressi ve treat me nt 
s h o ul d be gi n if t he ir A Es are n ot c o ntr olle d b y c ortic oster oi ds.  
2.  P e m br oliz u ma b m ust b e per ma ne ntl y disc o nti n ue d if t he  ir A E d oes n ot res ol ve or t he c ortic oster oi d d ose is n ot ≤1 0 m g/ da y wit hi n 1 2 wee ks of 
t he last pe m br oliz u ma b treat me nt.  
3.  T he c ortic oster oi d ta per s h o ul d be gi n w he n t he ir A E is ≤ Gra de 1 a n d c o nti n ue at least 4 wee ks.  
4.  If pe m br oliz u ma b has bee n wit h hel d, pem br oliz u ma b ma y res u me after t he ir A E decrease d t o ≤ Gra d e  1 after c ortic oster oi d ta per.  
 
I m m u ne-rel ate d 
A Es  
T o xicit y gr a de or 
c o n diti o ns 
( C T C A E v 4. 0) 
Acti o n wit h  
pe m br oliz u m a b  
ir A E m a n a ge me nt wit h 
c ortic oster oi d a n d/ or ot her 
t her a pies  
M o nit or i n g a n d f oll o w -u p  
P ne u m o nitis  
Gra d e 2  
Wit h h ol d  
A d mi nister c ortic oster oi ds 
(i nitial d ose of 1– 2  m g/ k g 
pre d nis o ne or e q ui vale nt) 
f oll o we d b y ta per 
A d d pr o p h ylactic a nti bi otics 
f or o p p ort u nistic i nfecti o ns 
M o nit or patie nts f or si g ns a n d s y m pt o ms of p ne u m o niti s 
E val uate patie nts wit h s us pect e d p ne u m o nitis wit h 
ra di o gra p hic i ma gi n g a n d i niti ate c ortic oster oi d 
treat me nt 
Gra d e 3 or 4, or 
rec urre nt Gra d e 2 
P er ma ne ntl y 
disc o nti n ue  
Diarr hea/ C olitis  
Gra d e 2 or 3  
Wit h h ol d  
A d mi nister c ortic oster oi ds 
(i nitial d ose of 1 – 2  m g/ k g 
pre d nis o ne or e q ui vale nt) 
f oll o we d b y ta per 
M o nit or patie nts f or si g ns a n d s y m pt o ms of e nter oc olitis 
(i.e., diarr hea, a b d o mi nal pai n, bl o o d or m uc us i n st o ol 
wit h or wit h o ut fe ver) a n d of b o wel perf orati o n 
(i.e., perit o neal si g ns a n d ile us).  
P atie nts wit h ≥ Gra d e 2 diarr hea s us pecti n g c olitis 
s h o ul d c o nsi der GI c o ns ultati o n a n d perf or mi n g 
e n d osc o p y t o r ule o ut c olitis.  
P atie nts wit h diarr hea/c olitis s h o ul d be a d vise d t o dri n k 
li beral q ua ntities of clear fl ui ds. If s ufficie nt oral fl ui d 
i nta ke is n ot feasi ble, fl ui d a n d electr ol ytes s h o ul d be 
s u bstit ute d via I V i nf usi o n. 
Rec urre nt Gra d e 3 
or Gra d e 4  
P er ma ne ntl y 
disc o nti n ue  
A S T/ A L T 
ele vati o n or 
I ncrease d 
bilir u bi n  
Gra d e 2  
Wit h h ol d  
A d mi nister c ortic oster oi ds 
(i nitial d ose of 0. 5– 1  m g/ k g 
pre d nis o ne or e q ui vale nt) 
f oll o we d b y ta per 
M o nit or wit h li ver f u ncti o n tests (c o nsi der wee kl y or 
m ore fre q ue ntl y u ntil li ver e nz y me val ue ret ur ne d t o 
baseli ne or is sta ble)  
Gra d e 3 or 4  
P er ma ne ntl y 
disc o nti n ue  
A d mi nister c ortic oster oi ds 
(i nitial d ose of 1 – 2  m g/ k g 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 5 5  of 1 5 2  
I m m u ne-rel ate d 
A Es  
T o xicit y gr a de or 
c o n diti o ns 
( C T C A E v 4. 0) 
Acti o n wit h  
pe m br oliz u m a b  
ir A E m a n a ge me nt wit h 
c ortic oster oi d a n d/ or ot her 
t her a pies  
M o nit or i n g a n d f oll o w -u p  
pre d nis o ne or e q ui vale nt) 
f oll o we d b y ta per 
T y pe 1 dia betes 
mellit us ( T 1 D M) 
or 
H y per gl yce mia  
Ne w o nset T 1 D M 
or  
Gra d e 3 or 4 
h y per gl yce mia 
ass ociate d wit h 
e vi de nce of β -cell 
fail ure 
Wit h h ol d
a 
I nitiate i ns uli n re place me nt 
t hera p y f or patie nts  wit h 
T 1 D M  
A d mi nister a nti -
h y per gl yce mic i n patie nts  
wit h h y per gl yce mia  
M o nit or patie nts  f or h y per gl yce mia or ot her si g ns a n d 
s y m pt o ms of dia betes. 
H y p o p h ysitis  
Gra d e 2  
Wit h h ol d  
A d mi nister c ortic oster oi ds 
a n d i nitiate h or m o nal 
re place me nts as cli nicall y 
i n dicate d.  
M o nit or f or si g ns a n d s y m pt o ms of h y p o p h ysitis 
(i ncl u di n g h y p o pit uitaris m a n d a dre nal i ns ufficie nc y) 
Gra d e 3 or 4  
Wit h h ol d or 
per ma ne ntl y 
disc o nti n ue a  
H y pert h yr oi dis m  Gra d e 2  
C o nti n ue  
Treat wit h n o n -selecti ve 
beta -bl oc kers (e. g., 
pr o pra n ol ol) or t hi o na mi des 
as a p pr o priate  
M o nit or f or si g ns a n d s y m pt o ms of t h yr oi d dis or ders.  
Gra d e 3 or 4  
Wit h h ol d or  
per ma ne ntl y 
disc o nti n ue a 
H y p ot h yr oi dis m  
Gra d e 2 – 4  
C o nti n ue  
I nitiate t h yr oi d re place me nt 
h or m o nes (e. g., 
le v ot h yr o xi ne or 
li ot h yr o ni ne) per sta n dar d of 
care  
M o nit or f or si g ns a n d s y m pt o ms of t h yr oi d dis or ders.  
Ne p hritis  a n d 
re nal d ysf u ncti o n  
Gra d e 2  
Wit h h ol d  
A d mi nister c ortic oster oi ds 
( pre d nis o ne 1 – 2  m g/ k g or 
e q ui vale nt) f oll o we d b y 
ta per. 
M o nit or c ha n ges of re nal f u ncti o n  
Gra d e 3 or 4  
P er ma ne ntl y 
disc o nti n ue  
M y ocar ditis  
Gra d e 1  
Wit h h ol d  
Base d o n se verit y of A E, 
a d mi nister c ortic oster oi ds  
E ns ure a de q uate e val uati o n t o c o nfir m eti ol o g y a n d/ or 
e xcl u de ot her ca uses  
Gra d e 2, 3 , or 4  
P er ma ne ntl y 
disc o nti n ue  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 5 6  of 1 5 2  
I m m u ne-rel ate d 
A Es  
T o xicit y gr a de or 
c o n diti o ns 
( C T C A E v 4. 0) 
Acti o n wit h  
pe m br oliz u m a b  
ir A E m a n a ge me nt wit h 
c ortic oster oi d a n d/ or ot her 
t her a pies  
M o nit or i n g a n d f oll o w -u p  
All ot her irA Es  
P ersiste nt Gra d e 2  
Wit h h ol d  
Base d o n se verit y of A E, 
a d mi nister c ortic oster oi ds  
E ns ure a de q uate e val uati o n t o c o nfir m eti ol o g y or 
e xcl u de ot her ca uses  
Gra d e 3  
Wit h h ol d or 
disc o nti n ue b 
Gra d e 4 or 
rec urre nt Gra d e 3 
P er ma ne ntl y 
disc o nti n ue  
GI = gastr oi ntesti nal; T 1 D M = T y pe 1 dia betes mellit us . 
N O T E: F or patie nts wit h Gra de 3 or 4 i m m u ne -relate d e n d ocri n o pat h y w here wit h h ol di n g of pe m br oliz u ma b is re q uire d, pe m br oliz u ma b ma y be res u me d w he n A E 
res ol ves t o ≤ Gra de 2 a n d is c o ntr olle d wit h h or m o nal re place me nt t h era p y or ac hie ve d meta b olic c o ntr ol (i n case of T 1 D M).  
a 
T he  decisi o n t o wit h h ol d or per ma ne ntl y disc o nti n ue pe m br oliz u ma b is at t h e discreti o n of t h e i n vesti gat or or treati n g p h ysicia n. If c o ntr ol ac hie ve d or ≤ Gra de  2, 
pe m br oliz u ma b ma y be res u me d.  
b  
E ve nts t hat re q uire disc o nti n uati o n i n cl u de, b ut are n ot li mite d t o G uillai n -Barre S y n dr o me, e nce p halitis, m yelitis, Dr u g Ras h wit h E osi n o p hilia a n d S yste mic 
S y m pt o m ( D R E S S ), Ste ve ns-J o h ns o n S y n dr o me ( SJ S), T o xic E pi der mal Necr ol ysis ( T E N), a n d ot her cli nicall y i m p orta nt ir A Es (e. g., vasc ulitis a n d scler osi n g 
c h ola n gitis). 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 7  of 1 5 2  
5. 3. 5. 2.  
D o s e M o difi c ati o n a n d T o xi cit y M a n a g e m e nt of I nf u si o n R e a cti o n s 
R el at e d t o P e m br oli z u m a b   
Pe m br oliz u ma b ma y ca use se vere or life -t hreat e ni n g i nf usi o n-reacti o ns i ncl u di n g se v ere 
h y perse nsiti vit y or a na p h yl a xis. Si g ns a n d s y m pt o ms us uall y de vel o p d uri n g or s h ortl y after dr u g 
i nf usi o n a n d ge nerall y res ol ve c o m pletel y wit hi n 2 4 h o urs of c o m pleti o n of i nf usi o n. D ose 
m o dificati o n a n d t o xicit y ma na ge me nt g ui deli nes o n pe m br oliz u ma b ass ociate d i nf usi o n reacti o n 
are pr o vi d e d i n Ta ble  8 . 
T a bl e  8 : 
P e m br oli z u m a b i nf u si o n r e a cti o n d o s e m o difi c ati o n a n d tr e at m e nt g ui d eli n e s  
N CI C T C A E Gr a de  
Tre at me nt  
Pre me dic ati o n at  
S u bse q ue nt D osi n g  
Gra d e 1  
Mil d reacti o n; i nf usi o n 
i nterr u pti o n n ot i n dicate d; 
i nter ve nti o n n ot i n dicate d 
I ncrease m o nit ori n g of vital si g ns as me dicall y 
i n dicate d u ntil t he patie nt is dee me d me dicall y 
sta ble i n t he o pi ni o n of t he i n vesti gat or. 
N o ne  
Gra d e 2  
Re q uires t hera p y or 
i nf usi o n i nterr u pti o n b ut 
res p o n ds pr o m ptl y t o 
s y m pt o matic treat me nt 
(e. g., a nti hista mi nes, 
N S AI Ds, narc otics, I V 
fl ui ds); pr o p h ylactic 
me dicati o ns i n dicate d f or 
≤2 4 hrs.  
St o p I nf usi o n.  
A d diti o nal a p pr o priate me dical t hera p y ma y 
i ncl u de b ut is n ot li mite d t o:  
I V fl ui ds 
A nti hista mi n es  
N S AI Ds  
Ac eta mi n o p he n  
Narc otics  
I ncrease m o nit ori n g of vital si g ns as me dicall y 
i n dicate d u ntil t he patie nt is dee me d me dicall y 
sta ble i n t he o pi ni o n of t he i n vesti gat or. 
If s y m pt o ms res ol ve wit hi n 1 h o ur of st o p pi n g 
dr u g i nf usi o n, t he i nf usi o n ma y be restarte d at 
5 0 % of t he ori gi nal i nf usi o n rate (e. g., fr o m 
1 0 0  m L/ hr t o 5 0 m L/ hr). Ot her wise,  d osi n g will 
be hel d u ntil s y m pt o ms res ol ve a n d t he patie nt 
s h o ul d be pre me dicate d f or t he ne xt sc he d ule d 
d ose.  
P atie nt s w h o de vel o p Gr a de 2 t o xicit y des pite 
a de q u ate pre me dic ati o n s h o ul d be 
per m a ne ntl y disc o nti n ue d fr o m f urt her st u d y 
dr u g tre at me nt.  
P atie nt ma y be pre me dicate d 
1. 5 h ( ± 3 0 mi n utes) pri or t o 
i nf usi o n of pe m br oliz u ma b 
wit h:  
Di p he n h y dra mi ne 5 0  m g p o 
( or e q ui vale nt d ose of 
a nti hista mi ne).  
Aceta mi n o p he n 5 0 0 – 1 0 0 0  m g 
p o ( or e q ui vale nt d ose of 
a nal gesic).  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 8  of 1 5 2  
N CI C T C A E Gr a de  
Tre at me nt  
Pre me dic ati o n at  
S u bse q ue nt D osi n g  
Gra d es 3 or 4  
Gra d e 3:  
Pr ol o n ge d (i.e., n ot ra pi dl y 
res p o nsi ve t o s y m pt o matic 
me dicati o n a n d/ or brief 
i nterr u pti o n of i nf usi o n); 
rec urre nce of s y m pt o ms 
f oll o wi n g i nitial 
i m pr o ve me nt; 
h os pitalizati o n i n dicate d 
f or ot her cli nical se q uelae 
(e. g., re nal i m pair me nt, 
p ul m o nar y i nfiltrates)  
Gra d e 4:  
Life -t hreate ni n g; press or 
or ve ntilat or y s u p p ort 
i n dicate d 
St o p I nf usi o n.  
A d diti o nal a p pr o priate me dical t hera p y ma y 
i ncl u de b ut is n ot li mite d t o:  
E pi n e p hri ne * *  
I V fl ui ds 
A nti hista mi n es  
N S AI Ds  
Ac eta mi n o p he n  
Narc otics  
O x y ge n  
Press ors  
C ortic oster oi ds  
I ncrease m o nit ori n g of vital si g ns as me dicall y 
i n dicate d u ntil t he patie nt is dee me d me dicall y 
sta ble i n t he o pi ni o n of t he i n vesti gat or. 
H os pitalizati o n ma y be i n dicat e d.  
* *I n cases of a na p h yla xis, e pi ne p hri ne s h o ul d be 
use d i m me diatel y.  
P atie nt is per ma ne ntl y disc o nti n ue d fr o m f urt her 
st u d y dr u g treat me nt. 
N o s u bse q ue nt d osi n g  
A p pr o priate res uscitati o n e q ui p me nt s h o ul d be a vaila ble at t he be dsi de a n d a p h ysicia n rea dil y a vail a ble d uri n g t h e peri o d of 
dr u g a d mi nistrati o n.  
F or f urt h er i nf or mati o n, please refer t o t h e C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts v 4. 0 ( C T C A E) at 
htt p://cte p.ca ncer. g o v  
5. 3. 5. 3.  
Ot h er All o w e d D o s e I nt e rr u pti o n f or P e m br oli z u m a b  
Pe m br oliz u ma b ma y b e i nterr u pte d f or sit uati o ns ot her t ha n treat me nt -relat e d A Es s uc h as 
me dical/s ur gical e v e nts or l o gistical r eas o ns n ot relate d t o s t u d y t hera p y. Patie nts s h o ul d be 
place d bac k o n st u d y t h era p y wit hi n 3 wee ks of t h e sc he d ule d i nterr u pti o n, u nless ot her wise 
disc usse d wit h t he s p o ns or. T he reas o n f or i nterr u pti o n s h o ul d be d oc u me nte d i n t he patie nt's 
st u d y rec or d. 
Patie nts w h o disc o nti n u e L V  d u e t o a n L V -relat e d A E ma y c o nti n ue pe m br oliz u ma b wit h 
a p pr o val of t he m e dical m o nit or if t here is e vi de n ce of cli nical be nefit. T h e ma xi m u m all o we d 
n u m ber of pe m br oliz u ma b c ycles is 3 5 (a p pr o xi matel y 2 years) . 
5. 3. 6.  
St or a g e a n d H a n dli n g   
Pe m br oliz u ma b s h o ul d be st ore d a n d h a n dle d per t he p har mac y m a n ual.  
5. 3. 7.  
P a c k a gi n g a n d L a b eli n g   
Pe m br oliz u ma b is c o m merciall y a v aila ble i n t he U S.  
5. 3. 8.  
Pr e p ar ati o n   
Pe m br oliz u ma b s h o ul d be pre pare d p er t he p har m ac y ma n ual.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 5 9  of 1 5 2  
5. 4.  
R e q uir e d Pr e m e di c ati o n a n d P o st m e di c ati o n   
Patie nts w h o e x perie nce a Gra d e 1 or Gra de 2 I R R ma y recei v e s u bse q ue nt i nf usi o ns wit h 
pre me dicati o n as d escri b e d i n Secti o n 5. 6. 1 . Pri or t o t he first d ose of L V , r o uti ne pre me dicati o n 
s h o ul d n ot be a d mi nistere d f or t he pre ve nti o n of I R Rs. 
5. 5.  
C o n c o mit a nt T h er a p y   
All c o nc o mita nt me dicati o ns, bl o o d pr o d ucts, a n d ra di ot hera p y a d mi nistere d will be rec or de d 
fr o m Da y 1 ( pre d ose) t hr o u g h t he s afet y re p orti n g peri o d. A n y c o n c o mita nt me dicati o n gi v e n f or 
a st u d y pr ot o c ol -rel ate d A E s h o ul d be rec or de d fr o m t he ti me of i nf or me d c o nse nt. 
5. 5. 1.  
R e q uir e d C o n c o mit a nt T h er a p y   
Patie nts i n Parts A a n d B: Starti n g wit h A me n d me nt 2, it is ma n dat or y t hat patie nts i n Parts  A 
a n d B w h o are a d mi nistere d > 2 0 0  m g L V  p er i nf usi o n  recei ve pr o p h yl actic G -C S F treat me nt 
starti n g wit h t heir first c ycle of t hera p y at a > 2 0 0 m g L V  d ose. It is als o str o n gl y rec o m me n de d 
t hat t hese patie nts c o nti n ue t o recei ve pr o p h ylactic G-C S F at s u bse q u e nt c ycl es re gar dless of t he 
L V  d os e, if it is dee me d t o be  nee d e d per i n vesti gat ors' cli nical j u d ge me nt. T heref ore, p atie nts 
recei vi n g > 2 0 0 m g L V  m ust n ot ha ve c o ntrai n dicati o ns t o m yel oi d gr o wt h fact ors a n d m ust be 
willi n g t o recei ve t he m. A d diti o nall y, patie nts i n Parts A a n d B w h o e x perie nce Gra de  4 
ne utr o pe ni a or fe brile n e utr o pe nia of a n y gra de i n a n y c ycle, m ust recei v e m yel oi d gr o wt h 
fact ors i n all s u bse q ue nt c ycles. M yel oi d gr o wt h f act or s u p p ort is als o re q uire d f or tr eat me nt of 
fe brile ne utr o p e nia i n P arts A a n d B. As p er A S C O g ui deli nes, pr o p h yl acti c gr owt h fact ors 
s h o ul d start 1-3  da ys after L V  a d mi nistrati o n. M yel oi d gr o wt h fact ors (i ncl u di n g pe gfil grasti m) 
s h o ul d n ot be gi ve n wit hi n 2 4 h o urs pri or t o t he d ose of L V . If pe gfil grasti m is use d, a o ne-ti me 
d ose is rec o m me n de d. If dail y gr o wt h fact or s u p p or t is use d, treat f or at least 5-7  da ys or u ntil 
t he a bs ol ute ne utr o p hil c o u nt is > 1 0 0 0/ m m3 (≤ Gra de 2).  
5. 5. 2.  
All o w e d C o n c o mit a nt T h er a p y   
Patie nts ma y recei v e all s u p p orti ve treat me nts  acc or di n g t o t he i nstit uti o nal sta n dar d.  
All c o nc o mita nt me dicati o ns a n d bl o o d pr o d ucts a d mi nistere d will be c ollecte d fr o m Da y  1 
( pre d ose) t hr o u g h t he safet y re p orti n g peri o d. A n y c o nc o mita nt me dicati o n gi ve n f or a st u d y 
pr ot oc ol -relat e d A E s h o ul d be recor de d fr o m t he ti me of i nf or me d c o ns e nt. C o nc o mita nt 
me dicati o ns a d mi nistere d after 3 0 da ys after t he l ast d ose of st u d y treat me nt s h o ul d be rec or de d 
f or S A Es a n d e v e nts of cli nical i nterest ( E CIs) as defi ne d i n Secti o n 7. 5. 1. 6 . 
T he use of a nti bi otics, w he n a p plica ble, is all o we d.  
W B C gr o wt h f act or s u p p ort, i ncl u di n g pri mar y or sec o n dar y pr o p h yla xis a n d treat me nt, is 
str o n gl y e n c o ura ge d per t he A S C O 2 0 1 5 U p date (S mit h 2 0 1 5 ) (see A p pe n di x  L ), wit h t he 
e x ce pti o n of pri mar y pr o p h yla xis ( C ycle 1 us e) i n patie nts e nr olle d i n t he d ose escal ati o n parts 
( wit h t he e x ce pti o n of patie nts w h o recei v e > 2 0 0 m g L V  p er i nf usi o n). Tra nsf usi o ns  of bl o o d 
pr o d ucts ma y be a d mi nistere d acc or di n g t o t he i nstit uti o nal sta n dar d . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 0  of 1 5 2  
Patie nts s h o ul d be u p -t o-date o n a n y rec o m me n de d vacci nati o ns pri or t o st u d y e ntr y. Seas o nal 
i nacti vate d ( kille d) i nfl ue nza vacci ne is all o we d. A d diti o nal vacci nati o n d uri n g t h e c o urse of t he 
st u d y treat me nt m ust be disc usse d pri or t o a d mi nistrati o n wit h t he me dical m o nit or.  
If t he patie nt is ta ki n g c hr o nic s u p pressi ve or pr o p h ylactic a nti-i nfecti ves (a nti viral, a ntif u n gal, 
or a nti bacterial), d oc u me ntati o n of i n vesti gati o ns t o e ns ure t he a bse nce of acti ve i nfecti o n m ust 
be c o m plete d pri or t o e nr oll me nt. T he patie nt s h o ul d c o nti n ue s u p pressi ve or pr o p h yl actic a nti -
i nfecti ves f or t h e d urati o n of st u d y partici pati o n. 
Patie nts w h o are recei vi n g P -gl yc o pr ot ei n ( P -g p) or str o n g c yt oc hr o me P 4 5 0 3 A ( C Y P 3 A) 
i n hi bit ors c o nc o mita ntl y wit h L V  s h o ul d be cl osel y m o nit ore d f or a d verse reacti o ns. Base d u p o n 
e val uati o n of t he a nti -C D 3 0 M M A E A D C bre nt u xi ma b ve d oti n ( A dcetris) ( A D C E T RI S ®  
Prescri bi n g I nf or m ati o n,  Sea ge n , J u ne 2 0 2 3 ), c o nc o mita nt use of P-g p i n hi bit ors or str o n g 
c yt o c hr o me P 4 5 0 3 A 4 ( C Y P 3 A 4) i n hi bit ors has t he p ote ntial t o i ncreas e t he e x p os ure t o M M A E 
(t he c yt ot o xic c o m p o ne nt of L V  a n d bre nt u xi ma b ve d oti n). C o nc o mita nt use of P -g p i n d ucers or 
str o n g C Y P 3 A 4 i n d ucers c o ul d decrease e x p os ure t o M M A E. See A p pe n di x  H  f or a list of P-g p 
a n d C Y P 3 A i n d ucers a n d i n hi bit ors.  
Palliati ve ra di ot hera p y (e. g., treat me nt f or sta bl e s y m pt o matic metastasis) is per mitte d w hile o n 
st u d y treat me nt u p o n a p pr o val b y t h e me dical m o nit or pr o vi de d it d oes n ot i nterfere wit h 
assess me nt of t u m or res p o nse per R E CI S T v 1. 1, p ut t he patie nt at ris k f or i ncreas e d or w orse ne d 
A Es, a n d is n ot bei n g us e d t o treat P D. Palliati ve ra di ot hera p y s h o ul d be gi ve n n o s o o ner t ha n 
2  wee ks bef ore or 2 wee ks after treat me nt wit h L V  a n d pe m br oliz u ma b.  
5. 5. 2. 1.  
M y el oi d Gr o wt h F a ct or s   
M yel oi d gr o wt h fact ors  (i ncl u di n g pe gfil grasti m) s h o ul d n ot be gi ve n wit hi n 2 4 h o urs pri or t o 
a n y d os e o f L V . I n Parts C  a n d D, m yel oi d gr o wt h fact or use is all o we d per A S C O g ui deli nes. 
H o we ver, f or patie nts e nr olle d i n Part C  a n d D, l o n g-acti n g m yel oi d gr o wt h fact ors (s u c h as 
pe gfil grasti m) ma y n ot b e a p pr o pri ate beca use L V  is gi ve n eit her wee kl y  or o n Da ys 1 a n d  8 
e ver y 2 1  da ys . L o n g-acti n g m yel oi d gr o wt h f act ors s h o ul d o nl y b e gi ve n w he n t here is s ufficie nt 
ti me f or t he gr o wt h f act ors t o ha ve cleare d a n d f or gr o wt h sti m ulat or y acti vit y t o ha ve ceas e d. 
5. 5. 3.  
Pr o hi bit e d C o n c o mit a nt T h er a p y   
Patie nts are pr o hi bite d fr o m recei vi n g t he f oll o wi n g t hera pies d uri n g t he s cree ni n g a n d treat me nt 
p hase of t his trial:  
● 
A nti ne o plastic s yste mic c he m ot hera p y or bi ol o gi cal t hera p y  
● 
I m m u n ot hera p y n ot s pecifie d i n t his pr ot oc ol  
● 
C he m ot hera p y n ot s pecifie d i n t his pr ot oc ol  
● 
I n v esti gati o nal a ge nts ot her t ha n pe m br oliz u ma b a n d L V  
● 
Ra diati o n t hera p y wit h t he f oll o wi n g e x ce pti o ns:  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 1  of 1 5 2  
○ 
Ra diati o n t hera p y t o a s y m pt o matic, n o n -tar get s olitar y lesi o n ma y b e c o nsi dere d o n 
a n e x ce pti o nal case -b y -case basis aft er c o ns ultati o n wit h s p o ns or. T he patie nt m ust 
ha ve cle ar meas ura ble disease o utsi de t he ra diate d fiel d.  
○ 
Palliati ve ra diati o n t hera p y ma y b e all o we d u n d er t he criteria o utli ne d i n 
Secti o n  5. 5. 2 . 
● 
Li ve v acci n es wit hi n 3 0 da ys pri or t o t he first d os e of st u d y treat me nt a n d w hile 
partici pati n g i n t he tri al. E x a m ples of li ve vacci nes i ncl u de, b ut are n ot li mite d  t o, t he 
f oll o wi n g: measles, m u m ps, r u bella, c hic ke n p o x, yell o w fe ver, ra bies, Bacill us 
Cal mette -G ueri n, a n d t y p h oi d ( oral) vacci ne. Seas o nal i nfl ue nza vacci n es f or i njecti o n 
are ge n erall y kille d vir us vacci nes a n d are all o we d. H o we ver, i ntra nas al i nfl ue n za 
vacci nes (e. g., Fl u - Mist
® ) are li ve atte n u ate d vacci nes, a n d are n ot all o we d. 
● 
S yste mic gl uc oc ortic oi ds f or a n y p ur p os e ot her t h a n t o m o d ulate s y m pt o ms fr o m a n 
e ve nt of cli nical i nterest of s us pecte d i m m u n ol o gi c eti ol o g y. T h e use of p h ysi ol o gic 
d oses o f c ortic oster oi ds ma y b e a p pr o ve d aft er c o ns ultati o n wit h t he s p o ns or. 
○ 
N ote: I n h ale d ster oi ds are all o we d f or ma na ge me nt of ast h ma.  
Patie nts w h o, i n t he assess me nt b y t he i n vesti gat or, re q uire t he us e of a n y of t he af ore me nti o ne d 
treat me nts f or cli nical mana ge me nt s h o ul d be re m o ve d fr o m t he trial. Patie nts ma y recei ve ot her 
me dicati o ns t hat t he i n vesti gat or dee ms t o be me dicall y n ecess ar y.  
Patie nts i n Part C d ose escalati o n c o h orts s h o ul d n ot recei ve pr o p h ylactic G -C S F i n C ycle  1.  
T he E x cl usi o n Criteria descri be ot her me dicati o ns t hat are pr o hi bite d i n t his trial.  
T here are n o pr o hi bite d t hera pies d uri n g t he p ost -treat me nt f oll o w-u p p h ase.  
5. 6.  
M a n a g e m e nt of A d v er s e R e a cti o n s   
5. 6. 1.  
M a n a g e m e nt of I nf u si o n R e a cti o n s   
5. 6. 1. 1.  
L V   
I R Rs ma y occ ur d uri n g t he i nf usi o n of st u d y tr eat me nt. T he i nf usi o n s h o uld be a d mi nistere d at a 
site pr o perl y e q ui p pe d a n d staffe d t o ma na ge a n a p h yla xis s h o ul d it occ ur. R o uti ne pre me dicati o n 
s h o ul d n ot be a d mi nistere d f or t he pre ve nti o n of I R Rs pri or t o t he first d ose of L V . 
All s u p p orti ve meas ures c o nsiste nt wit h o pti mal pati e nt care s h o ul d be gi ve n t hr o u g h o ut t he 
st u d y acc or di n g t o i nstit uti o nal sta n dar ds. S u p p orti ve meas ures ma y i n cl u de e xte n di n g t he 
i nf usi o n ti me a n d/ or a d mi nisteri n g me dicati o ns f or I R Rs. 
Patie nts w h o ha ve e x peri e nce d a Gra d e 1 or Gra d e 2 I R R wit h L V  s h o ul d be pre me dicate d f or 
s u bse q ue nt i nf usi o ns. 
Patie nts w h o e x perie nce a Gra d e 3 I R R ma y p ote ntiall y recei ve a d diti o nal treat me nt wit h L V  at 
t he discreti o n of t he i n vesti gat or after disc ussi o n wit h t he s p o ns or’s me dical m o nit or. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 2  of 1 5 2  
Pre me dicati o n ma y i ncl u de aceta mi n o p he n, a n a nti hista mi ne, a n d a c ortic oster oi d a d mi nistere d 
3 0 – 6 0 mi n utes pri or t o eac h i nf usi o n or acc or di n g t o i nstit uti o nal sta n dar ds.  
If a na p h yl a xis or a Gra de 4 I R R occ urs, L V  a d mi nistrati o n s h o ul d be i m me diatel y a n d 
per ma ne ntl y disc o nti n ue d.  
5. 6. 1. 2.  
P e m br o li z u m a b  
Please refer t o t he rec o m me n dati o ns i n Ta ble  8 . 
5. 6. 1. 3.  
I nf u si o n R el at e d R e a cti o n of U n c ert ai n C a u s e   
If a patie nt e x perie nces a n I R R aft er recei vi n g b ot h st u d y treat me nts a n d a si n gle ca use of t he 
I R R ca n n ot be deter mi ne d, b ot h sets of g ui deli nes f or I R Rs m ust be f oll o we d. 
5. 6. 2.  
S u p p orti v e C ar e G ui d eli n e s f or P e m br oli z u m a b   
Patie nts s h o ul d recei ve a p pr o priate s u p p orti ve care meas ures as dee me d necessar y b y t he treati n g 
i n vesti gat or. S u g geste d s u p p orti ve care meas ures f or t he ma na ge me nt of A Es wit h p ote ntial 
i m m u n ol o gic eti ol o g y are o utli ne d al o n g wit h t he d ose m o dificati o n g ui d eli nes i n Secti o n 5. 3. 5 , 
Ta ble  7 . W here ap pr o pri ate, t hese g ui deli nes i ncl u de t he use of oral or I V treat me nt wit h 
c ortic oster oi ds, as w ell as a d diti o nal a nti -i nfla m mat or y a ge nts if s y m pt o ms d o n ot i m pr o ve wit h 
a d mi nistrati o n of c ortic oster oi ds. N ote t hat se veral c o urses of ster oi d ta p eri n g ma y b e necessar y 
as s y m pt o ms ma y w ors e n w he n t he ster oi d d ose is decrease d. F or eac h dis or der, atte m pts s h o ul d 
be ma de t o r ule o ut ot her ca uses s uc h as metastati c disease or bacterial or viral i nfecti o n, w hic h 
mi g ht re q uir e a d diti o nal s u p p orti ve care. T he tr eat me nt g ui deli nes are i nte n de d t o be a p plie d 
w he n t he I n vesti gat or d et er mi nes t he e v e nts t o be relate d t o pe m br oliz u ma b.  
N ote: If aft er t he e val uati o n of t he e ve nt, it is deter mi ne d n ot t o be relate d t o pe m br oliz u ma b, t he 
i n vesti gat or d o es n ot nee d t o f oll o w t he treat me nt g ui da nce. Refer t o Secti o n 5. 3. 5  f or g ui deli nes 
re gar di n g d os e m o dificati o n a n d s u p p orti ve care. 
It ma y b e necessar y t o p erf or m c o n diti o nal pr oce d ures s uc h as br o nc h osc o p y, e n d os c o p y, or s ki n 
p h ot o gra p h y as part of e v al uati o n of t he e ve nt.  
5. 7.  
M a n a g e m e nt of H y p er gl y c e mi a   
I n v esti gat ors s h o ul d m o nit or bl o o d gl uc ose le vels a n d are a d vise d t o perf or m a d diti o nal 
assess me nts if a n y s y m pt o ms of h y per gl yce mia are o bser ve d, i n cl u di n g a t h or o u g h e val uati o n 
f or i nfecti o n. I n a d diti o n, if ster oi ds are us e d t o treat a n y ot her c o n diti o n, bl o o d gl uc os e le vels 
ma y re q uire a d diti o nal m o nit ori n g. If ele vate d bl o o d gl uc os e le vels are o bs er ve d, patie nts s h o ul d 
be treate d acc or di n g t o l ocal sta n dar d of care a n d referral t o e n d ocri n ol o g y ma y b e c o nsi dere d.  
Patie nts, es peciall y t h ose wit h a hist or y of or o n g oi n g dia bet es mellit us or h y p e r gl yce mia, s h o ul d 
be a d vise d t o i m me diatel y n otif y t heir p h ysicia n if t heir gl uc os e le vels be c o me diffic ult t o 
c o ntr ol or if t he y e x perie nce s y m pt o ms s u g gesti ve of h y p er gl yce mia s uc h as fre q ue nt uri n ati o n, 
i ncreas e d t hirst, bl urre d visi o n, fati g ue, a n d head ac he.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 3  of 1 5 2  
Patie nts w h o e nter t he st u d y wit h ele v ate d he m o gl o bi n A 1c ( H b A 1c) ( ≥6. 5 %) or fasti n g gl uc os e 
( ≥1 2 6 m g/ d L or ≥7. 0 m m ol/ L) at scree ni n g s h o ul d recei ve gl u c ose ma na ge me nt pri or t o or 
wit hi n 1  wee k of starti n g st u d y treat me nt.  
I n Part A a n d B, bl o o d gluc ose s h o ul d be c h ec ke d pri or t o eac h d osi n g a n d d ose s h o ul d be 
wit h hel d f or bl o o d gl u c ose > 2 5 0  m g/ d L or > 1 3. 9  m m ol/ L, testi n g ma y be re peate d o n t h e sa me 
da y of d osi n g. L V  d ose ma y b e deli vere d o n t he sa me da y o nce t he patie nt’s bl o o d gl uc ose h as 
i m pr o ve d t o ≤2 5 0 m g/ d L or ≤1 3. 9  m m ol/ L a n d t h e patie nt is cli nicall y a n d meta b olicall y sta bl e.  
I n Part C, bl o o d gl uc ose ma y b e c hec ke d o n Da y 8 a n d Da y 1 5 b y fi n gerstic k as i n dicate d, 
partic ularl y i n patie nts at ris k f or h y per gl yce mia. Da y 8 a n d 1 5 d osi n g wit h L V  s h o ul d be 
wit h hel d f or bl o o d gl u c ose > 2 5 0  m g/ d L or > 1 3. 9  m m ol/ L. T esti n g ma y b e re peat e d o n t he da y of 
d osi n g. L V  d ose m a y be deli vere d o n t he s a me da y o nce t he patie nt’s bl o o d gl uc ose has 
i m pr o ve d t o ≤2 5 0 m g/ d L or ≤1 3. 9  m m ol/ L a n d t h e patie nt is cli nicall y a n d meta b olicall y sta bl e.  
I n Part D, bl o o d gl u c ose ma y b e c hec ke d o n Da y 8 b y fi n gerstic k as i n dicate d, partic ularl y i n 
patie nts at ris k f or h y per gl yce mia. Da y 8 d osi n g wit h L V s h o ul d be wit h h el d f or bl o o d gl uc ose 
> 2 5 0  m g/ d L or > 1 3. 9  m m ol/ L. Testi n g m a y be re peate d o n t he d a y of d osi n g. L V d os e ma y be 
deli vere d o n t he s a me da y o nce t he patie nt’s bl o o d gl uc ose has i m pr o ve d t o ≤2 5 0  m g/ d L or 
≤1 3. 9  m m ol/ L a n d t he patie nt is cli nicall y a n d met a b olicall y sta bl e . 
5. 8.  
Tr e at m e nt C o m pli a n c e   
St u d y dr u g a d mi nistrati o n will be perf or me d b y st u d y site staff a n d d oc u m e nte d i n s o urce 
d oc u me nts . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 4  of 1 5 2  
6.  
S T U D Y A C TI VI TI E S   
6. 1.  
S c h e d ul e of  E v e nt s   
A Es a n d c o nc o mita nt me dicati o ns will be rec or de d fr o m Da y 1 ( pre d ose) t hr o u g h t h e safet y 
re p orti n g peri o d (s ee Secti o n 7. 5. 1. 3 ). A n y st u d y pr ot oc ol-relat e d A E ( defi ne d i n 
Secti o n  7. 5. 1. 1 ), as well as a n y c o nc o mita nt me di cati o ns gi ve n f or tr eat me nt of t he A E, s h o ul d 
be rec or de d fr o m t he ti me of i nf or me d c o nse nt. Sc he d ules of e ve nts are pr o vi de d i n A p pe n di x  A , 
A p pe n di x  B , A p pe n di x  C , A p pe n di x  D , a n d A p pe n di x  E . 
St u d y acti vities are liste d b y visit i n t his secti o n a n d descri pti o ns of all st u d y ass ess me nts are 
prese nte d i n Secti o n 7 . 
6. 2.  
P art s A a n d B ( q 3 w k L V  d o si n g)   
6. 2. 1.  
S cr e e ni n g Vi sit ( D a y s – 2 8 t o 1)   
● 
I nf or me d c o ns e nt 
● 
St u d y eli gi bilit y p er i ncl usi o n/e xcl usi o n criteria  
● 
Me dical hist or y ( See Secti o n 7. 1 ) 
● 
Brai n C T or ma g n etic res o na nce i ma gi n g ( M RI)  
● 
C ollecti o n of arc hi ve d t u m or s peci me n, if a v aila ble  
● 
Bi o ps y, fres hl y o btai ne d, s u b mitte d f or ce ntral assess me nt (see A p pe n di x  E ) 
● 
Electr ocar di o gra m ( E C G) (see Secti o n 7. 1. 1 ) 
● 
Ser ol o g y f or he p atitis B s urface a nti ge n a n d a nti he patitis B c ore a nti b o d y ( detaile d i n 
Secti o n 7. 5. 3 ) 
● 
P C R f or he patitis C vir us ( detaile d i n Secti o n 7. 5. 3 ) 
● 
H b A 1c a n d fasti n g bl o o d gl uc ose ( detaile d i n Secti o n 7. 5. 3 ) 
○ 
If H b A 1c or fasti n g gl uc ose is ele vate d wit h c o nfir mati o n u p o n re peat testi n g ( H b A 1c 
≥6. 5 %, fasti n g gl u c ose ≥1 2 6  m g/ d L, or ≥7. 0  m m ol/ L), t he p atie nt s h o ul d recei ve 
gl uc ose m a na ge m e nt bef ore C ycle 1 Da y 1 or wit hi n t he first wee k of C ycl e 1  
● 
P T/ P T T/a P T T/I N R ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C T of c hest, a b d o me n, a n d pel vis (a n d nec k if cli nicall y i n dicat e d) ( M RI ma y als o be 
acce pta ble; see Secti o n 7. 1 ) T h yr oi d f u ncti o n tests ( detaile d i n S ecti o n 7. 5. 3 ) 
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 2. 2.  
B a s eli n e Vi sit ( D a y s – 7 t o 1)   
● 
Hei g ht a n d wei g ht (see Secti o n 7. 1 ) 
● 
Vital  si g ns (see Secti o n 7. 5. 2 ) 
● 
P h ysical e x a mi nati o n (see Secti o n 7. 5. 4 ) 
● 
E C O G Perf or ma n ce stat us (see A p pe n di x  F ) 
● 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C o m plete bl o o d c o u nt ( C B C) wit h differe ntial ( det aile d i n Secti o n 7. 5. 3 ) 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 5  of 1 5 2  
● 
Pre g n a nc y test f or patie nts of c hil d beari n g p ote nti al –  perf or m e d wit hi n 3 da ys pri or t o 
C ycle 1 Da y 1 ( perf or me d l ocall y)  
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 2. 3.  
Tr e at m e nt P eri o d ( D a y 1 t o D a y  2 1)   
6. 2. 3. 1.  
D a y 1   
F or C ycle 1, if b aseli ne visit acti vities occ ur wit hi n 1 da y pri or t o Da y 1, t h e f oll o wi n g 
assess me nts d o n ot nee d t o be re peate d. F or C ycle 2 a n d be y o n d, t hese assess me nts ha ve a 
wi n d o w of -2 da ys:  
● 
P h ysical e x a mi nati o n (see Secti o n 7. 5. 4 ) 
● 
Wei g ht  
● 
E C O G perf or ma nce stat us (see A p pe n di x  F ) 
● 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) t o be e v al u ate d pri or t o i nf usi o n. 
H ol d d ose if bl o o d gl uc ose le vel is > 2 5 0  m g/ d L.  
● 
C B C wit h differe ntial ( d etaile d i n Secti o n 7. 5. 3 ) t o be e v al u ate d pri or t o i nf usi o n. 
● 
Pre g n a nc y test (f or patie nts of c hil d beari n g p ote ntial; perf or me d l ocall y; d oes n ot nee d t o 
be re peate d if p erf or m e d wit hi n 3 da ys of Da y 1)  
● 
T h yr oi d f u ncti o n tests ( d etaile d i n Secti o n 7. 5. 3 ; t o i ncl u de T S H, T 3 or free T 3, a n d 
free T 4). Da y 1 of eac h o d d -n u m bere d c ycle o nl y (i.e. C ycl es 1, 3, 5, 7, etc.)  
 
T he f oll o wi n g pr oce d ures m ust be perf or me d o n D a y 1 of e ver y c ycle:  
● 
Vital si g ns ( wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, wit hi n 6 0 mi n utes pri or t o 
pe m br oliz u ma b i nf usi o n, wit hi n 2 h o urs of e n di n g eac h i nf usi o n, a n d d uri n g i nf usi o n/s as 
cli nicall y i n dicat e d  (See Secti o n  7. 5. 2 ) 
● 
Pre d ose bl o o d sa m ples f or bi o mar kers ( C ycl e 1  o nl y ). See ti me p oi nts i n A p pe n di x  E . 
● 
Pre d ose bl o o d sa m ples f or P K ( C ycl e 1  o nl y ). See ti me p oi nts i n A p pe n di x  B . 
● 
P ost d ose bl o o d sa m ples f or P K ( C ycle 1  o nl y ). See ti me p oi nts i n A p pe n di x  B . 
● 
Pre d ose bl o o d sa m ples f or A T A ( C ycle 1  o nl y ). See ti me p oi nts i n A p pe n di x  B . 
● 
L V  i nf usi o n (if d osi n g criteria i n Secti o n 5. 2. 3. 5  are met)  
● 
Pe m br oliz u ma b i nf usi o n  
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 2. 3. 2.  
D a y 3 ( P art B C y cl e 1 r e q uir e d f or p ati e nt s i n U S sit e s, o pti o n al f or 
p ati e nt s o ut si d e U S sit e s; wi n d o w: D a y s 3 – 4)   
● 
Bl o o d sa m ples f or P K  
6. 2. 3. 3.  
D a y 5 ( P art A C y cl e 1 o nl y; wi n d o w: D a y s 4 – 7)   
● 
Fres h t u m or bi o ps y  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 6  of 1 5 2  
● 
Bl o o d sa m ples f or P K   
● 
Bl o o d sa m ples f or bi o mar kers   
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 2. 3. 4.  
D a y 8 ( C y cl e s 1 -2 o nl y; ± 2 d a y s)   
● 
C B C wit h differe ntial ( d etaile d i n Secti o n 7. 5. 3 ) 
● 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
● 
C ycle 1 o nl y:  
○ 
Bl o o d sa m ples f or P K  
6. 2. 3. 5.  
D a y 1 5 ( C y cl e 1 o nl y; ± 2 d a y s)   
● 
Fres h t u m or bi o ps y o nl y f or patie nts e nr olle d i n P art B ( wi n d o w: Da ys 1 5 – 2 1)  
● 
Bl o o d sa m ples f or P K  
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 3.  
P art s  C ( q 1 w k L V  d o si n g)  a n d D ( D a y s 1  a n d 8 L V d o si n g)   
6. 3. 1.  
S cr e e ni n g Vi sit ( D a y – 2 8 t o 1)   
● 
I nf or me d c o ns e nt 
● 
St u d y eli gi bilit y p er i ncl usi o n/e xcl usi o n criteria  
● 
Me dical hist or y ( See Secti o n 7. 1 ) 
● 
Brai n C T or M RI  
● 
Bi o ps y, arc hi val or fres hl y o btai ne d, s u b mitte d f or t he f oll o wi n g: 
○ 
C e ntral assess me nt  of e x pl orat or y bi o mar ker assess me nts  (see A p pe n di x  E ) 
○ 
Part D o nl y: L ocal la b orat or y det er mi nati o n of P D -L 1 C P S < 1 0 b y a P D -L 1 I H C 
assa y usi n g t h e 2 2 C 3 cl o ne  (see Secti o n  7. 1 ) 
● 
E C G (see Secti o n 7. 1. 1 ) 
● 
Ser ol o g y f or he p atitis B s urface a nti ge n a n d a nti he patitis B c ore a nti b o d y ( detaile d i n 
Secti o n 7. 5. 3 ) 
● 
P C R f or he patitis C vir us ( detaile d i n Secti o n 7. 5. 3 ) 
● 
H b A 1c a n d fasti n g bl o o d gl uc ose ( detaile d i n Secti o n 7. 5. 3 ) 
○ 
If H b A 1c or fasti n g gluc ose is ele vate d wit h c o nfir mati o n u p o n re peat testi n g ( H b A 1c 
≥6. 5 %, fasti n g gl u c ose ≥1 2 6  m g/ d L, or ≥7. 0 m m ol/ L), t he p atie nt s h o ul d recei ve 
gl uc ose m a na ge m e nt bef ore C ycle 1 Da y 1 or wit hi n t he first wee k of C ycl e 1  
● 
P T/ P T T/a P T T/I N R ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C T of c hest, a b d o me n, a n d pel vis (a n d nec k if cli nicall y i n dicat e d) ( M RI ma y als o be 
acce pta ble; see Secti o n 7. 1 ) 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 7  of 1 5 2  
● 
T h yr oi d f u ncti o n tests ( d etaile d i n S ecti o n 7. 5. 3 ) 
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 3. 2.  
B a s eli n e Vi sit ( D a y – 7 t o 1)   
● 
Hei g ht a n d wei g ht (see Secti o n 7. 1 ) 
● 
Vital si g ns (see Secti o n  7. 5. 2 ) 
● 
P h ysical e x a mi nati o n (see Secti o n 7. 5. 4 ) 
● 
E C O G Perf or ma n ce stat us (see A p pe n di x  F ) 
● 
Ser u m c he mistr y  p a nel ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C B C wit h differe ntial ( d etaile d i n Secti o n 7. 5. 3 ) 
● 
Pre g n a nc y test f or patie nts of c hil d beari n g p ote nti al –  perf or m e d wit hi n 3 da ys pri or t o 
C ycle  1 Da y 1 ( perf or me d l ocall y)  
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 3. 3.  
Tr e at m e nt P eri o d ( D a y 1 t o 2 1 of e a c h c y cl e)   
6. 3. 3. 1.  
D a y 1   
T he f oll o wi n g assess me nts ha ve a wi n d o w of -2 d a ys.  If bas eli ne visit acti vities occ ur wit hi n 
2  da y s pri or t o Da y 1, t he assess me nts d o n ot nee d t o be re peate d.  
● 
Pre -d ose  
○ 
P h ysical e x a m  
○ 
Wei g ht  
○ 
E C O G perf or ma nce stat us (see  A p pe n di x  F ) 
○ 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) t o be e val uate d pri or t o i nf usi o n. 
H ol d d ose if bl o o d gl uc ose le vel is > 2 5 0  m g/ d L.  
○ 
C B C wit h differe ntial ( d etaile d i n Secti o n 7. 5. 3 ) t o be e val uat e d pri or t o i nf usi o n. 
○ 
Pre g n a nc y test (f or patie nts of c hil d beari n g p ote ntial; perf or me d l ocall y; d oes n ot 
nee d t o be re peat e d if perf or me d wit hi n 3 da ys of Da y 1)  
○ 
T h yr oi d f u ncti o n tests ( d eta ile d i n Secti o n 7. 5. 3 ; t o i ncl u de T S H, T 3 or free T 3, a n d 
free T 4). Da y 1 of eac h o d d -n u m bere d c ycle o nl y (i.e. C ycl es 1, 3, 5, 7, etc.)  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 8  of 1 5 2  
T he f oll o wi n g pr oce d ures m ust be perf or me d o n D a y 1:  
● 
Vital si g ns ( wit hi n 6 0  mi n utes pri or t o L V  i nf usi o n, wit hi n 6 0 mi n utes pri or t o 
pe m br oliz u ma b i nf usi o n, wit hi n 2  h o urs of e n di n g eac h i nf usi o n, a n d d uri n g i nf usi o n/s as 
cli nicall y i n dicat e d  (See Secti o n  7. 5. 2 ) 
● 
Pre d ose bl o o d sa m ples f or bi o mar kers ( C ycl e 1 o nl y ). See ti me p oi nts i n  A p pe n di x  D .  
● 
Pre d ose bl o o d sa m ples f or P K ( C ycl e 1  o nl y ). See ti me p oi nts i n A p pe n di x  D . 
● 
P ost d ose bl o o d sa m ples f or P K ( C ycle 1  o nl y ). See ti me p oi nts i n A p pe n di x  D .  
● 
Pre d ose bl o o d sa m ples f or A T A ( C ycle  1  o nl y ). See ti me p oi nts i n A p pe n di x  D .  
● 
L V  i nf usi o n (if d osi n g criteria i n Secti o n 5. 2. 3. 5  are met)  
● 
Pe m br oliz u ma b i nf usi o n  
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
6. 3. 3. 2.  
D a y 3 ( C y cl e 1 o nl y; r e q uir e d f or p ati e nt s i n U S sit e s, o pti o n al f or 
p ati e nt s o ut si d e U S sit e s; wi n d o w: D a y s 3 – 4)   
● 
Bl o o d sa m ples f or P K  
6. 3. 3. 3.  
D a y 8   
● 
Pre -d ose  
○ 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) t o be e v alu ate d pri or t o i nf usi o n  
( C ycl es 1 a n d 2 o nl y). 
○ 
C B C wit h differe ntial ( -2 -da y wi n d o w; detaile d i n Secti o n 7. 5. 3 ) t o be e v al u ate d 
pri or t o i nf usi o n.  
○ 
B l o o d sa m ples f or P K assess me nt ( C ycl e 1 o nl y; s ee A p pe n di x  D ) 
● 
Vital si g ns ( wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, wit hi n 2 h o urs of e n di n g of i nf usi o n, 
a n d d uri n g i nf usi o n as cli nicall y i n dicat e d. See Secti o n 7. 5. 2 ) 
● 
L V  i nf usi o n 
● 
P ost -d ose  
○ 
C ycle 1 o nl y : bl o o d sa m ples f or P K assess me nt (A p pe n di x  D ) 
6. 3. 3. 4.  
D a y 1 5   
P art C  
● 
Pre -d ose  
○ 
Ser u m c h e mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) t o be e v al u ate d pri or t o i nf usi o n 
( C ycl es 1 a n d 2 o nl y). 
○ 
C B C wit h differe ntial ( -2 -da y wi n d o w; detaile d i n Secti o n 7. 5. 3 ) t o be e v al u ate d 
pri or t o i nf usi o n.  
○ 
Bl o o d sa m ples f or P K assess me nt ( C ycl e 1 o nl y; s ee  A p pe n di x  D )  
● 
Vital si g ns ( wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, wit hi n 2 h o urs of e n di n g of i nf usi o n, 
a n d d uri n g i nf usi o n as cli nicall y i n dicat e d. See Secti o n 7. 5. 2 )  
● 
L V  i nf usi o n (if d osi n g criteria i n Secti o n 5. 2. 3. 5  are met)  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 6 9  of 1 5 2  
● 
P ost -d ose  
○ 
C ycle 1 o nl y: bl o o d sa m ples f or P K assess me nt ( A p pe n di x  D ) 
P art D  
● 
C B C wit h differe ntial ( -2 -da y wi n d o w; detaile d i n Secti o n 7. 5. 3  ( C ycl es 1 a n d 2 o nl y). 
6. 4.  
R e s p o n s e A s s e s s m e nt s   
Ti me p oi nts f or ra di o gra p hic e x a ms s h o ul d be cale n dar bas e d a n d d o n ot d e pe n d o n c ycl e visits 
(see Secti o n 7. 2 ). I m a gi n g s h o ul d be c o n d ucte d o n t he f oll o wi n g sc h e d ule u ntil disease 
pr o gressi o n, u nacce pta bl e t o xicit y, start of a ne w ca ncer t hera p y, c o nse n t wit h dra wal, 
i n vesti gat or d ecisi o n, st u d y ter mi nati o n b y t he s p o ns or, or deat h, w hi c he ver c o mes first: 
E ver y 6 wee ks ( ± 3 da ys) f or 1 2 m o nt hs after t he first d ose of L V  a n d p e m br oliz u ma b  
E ver y 1 2 wee ks ( ± 7 da ys) t hereafter  
N o a d diti o nal sca ns or res p o nse a ssess me nts are re q uire d after t he s afet y f oll o w-u p peri o d, 
h o we ver a d diti o nal sca ns or res p o nse assess me nts ma y b e perf or me d as p art of t he patie nt’s 
sta n dar d of care at a n y ti me. 
6. 5.  
E n d of Tr e at m e nt Vi sit ( 3 0 t o 3 7 d a y s aft er l a st d o s e of st u d y dr u g)   
E n d of treat me nt ( E O T) visits s h o ul d occ ur 3 0 t o 3 7 da ys after t h e last d ose of st u d y dr u g u nless 
dela ye d d ue t o a n A E. N ote: T he ti me t o E O T visit ma y be l o n ger t ha n 3 7 da ys, b ut i n n o  case 
s h o ul d it be < 3 0 da ys. H o we ver, E O T e val u ati o ns m ust be perf or me d b ef ore i nitiati o n of a ne w 
t hera p y. If E O T e v al uati o ns are c o m plet e d bef ore 3 0 da ys after t h e last st u d y treat me nt, t he 
patie nt will be c o ntacte d 3 0 t o 3 7 da ys f oll o wi n g t he last treat me nt t o assess f or A Es.  
● 
E C O G Perf or ma n ce stat us (see  A p pe n di x  F ) 
● 
P h ysical e x a mi nati o n (see Secti o n 7. 5. 4 ) 
● 
Pre g n a nc y test (f or patie nts of c hil d beari n g  p ote ntial; perf or me d l ocall y)  
● 
Ser u m c he mistr y p a nel ( detaile d i n Secti o n 7. 5. 3 ) 
● 
C B C wit h differe ntial ( d etaile d i n Secti o n 7. 5. 3 ) 
● 
H b A 1c ( perf or m e d l ocall y)  
● 
C T of c hest, a b d o me n, a n d pel vis (a n d nec k if cli nicall y i n dicat e d) ( M RI ma y als o be 
acce pta ble; see Secti o n 7. 1 ) ( n ot re q uir e d if c o n d u cte d wit hi n 4 wee ks pri or t o E O T) 
● 
C ollecti o n of c o nc o mita nt me dicati o n i nf or mati o n  
● 
C ollecti o n of A Es  
 
If patie nts are disc o nti n ui n g treat me nt d ue t o P D, a n d a bi o ps y was d o ne as sta n dar d of care at 
disease pr o gressi o n, a t u m or sa m ple is re q ueste d, if a vaila ble.  
6. 6.  
F oll o w -u p   
Patie nts w h o disc o nti n ue st u d y treat me nt i n t he a bse nce of disease pr o gressi o n will re mai n o n 
t he st u d y f or f oll o w-u p u ntil wit h dra wal of c o nse nt, i nitiati o n of a ne w a ntica ncer t hera p y, deat h, 
or st u d y cl os ur e, w hic h e ver occ urs first.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 0  of 1 5 2  
T he first f oll o w -u p visit will occ ur 6 wee ks ( ± 1 wee k) fr o m t he m ost rece nt  pri or ra di o gra p hi c 
res p o nse e v al uati o n. S u bse q ue nt f oll o w-u p visits will be sc he d ule d f or 6  wee ks ( ± 1 wee k) fr o m 
t he pre vi o us f oll o w-u p visit.  After 1 year o n st u d y, t he fre q u e nc y of f oll o w -u p visits will be 
re d uce d t o e ver y 1 2 wee ks ( ±1  wee k).  
T he f oll o w i n g assess me nts will be c o n d ucte d at f oll o w-u p visits  u ntil pr o gressi o n or i nitiati o n of 
a ne w a ntica ncer treat me nt  t hr o u g h t he e n d of t he safet y f oll o w-u p p eri o d : 
● 
P h ysical e x a mi nati o n (see Secti o n 7. 5. 4 ) 
● 
C T of c hest, a b d o me n, a n d pel vis (a n d nec k if cli nicall y i n dicat e d) ( M RI ma y als o be 
acce pta ble; see Secti o n 7. 1 ); after a year of f oll o w-u p, re d uce fre q ue n c y t o i nstit uti o n’s 
sta n dar d of care u ntil pr o gressi o n or i nitiati o n of a ne w a ntica n cer t h era p y.  
● 
C o nc o mita nt me dicati o n i nf or mati o n a n d A Es t o b e c o llecte d if s eri o us a n d c o nsi dere d t o 
be st u d y tr eat me nt -relate d. 
S afet y F oll o w -U p  
Patie nts disc o nti n ui n g treat me nt will be f oll o we d f or t he pr ot oc ol re q uire d s afet y f oll o w -u p 
peri o d , u nless  a d diti o nal safet y c o n cer ns warra nt f urt her f oll o w-u p : 
•  3 0 da ys p ost  tr eat me nt f or L V  a n d  
•  9 0 da ys p ost tr eat me nt f or p e m br oliz u ma b.  
N o a d diti o nal f oll o w -u p is re q uire d after t he s afet y f oll o w -u p peri o d.  
After diseas e pr o gressi o n or i nitiati o n of a ne w a ntica ncer treat me nt, s ur vi val f oll o w -u p will be 
c o n d ucte d, e v er y 1 2 w ee ks ( ± 2 wee ks) starti n g fr o m t he last ra di o gra p hic sca n de m o nstrati n g 
disease pr o gressi o n or fr o m i nitiati o n of t he ne w a ntica ncer treat me nt u ntil c o m pleti o n of t he 
safet y f oll o w-u p p eri o d, deat h, or st u d y cl os ure, w hic he ver c o mes first. F oll o w -u p ma y b e 
c o n d ucte d wit h cli nic visits or tele p h o ne calls. N o f urt her res p o nse ass ess me nts will be 
c o n d ucte d.  
6. 7.  
E n d of St u d y/ E n d of F oll o w -u p   
T he date t he p atie nt met criteria f or st u d y dis c o nti n uati o n a n d t he reas o n f or st u d y 
disc o nti n uati o n will be rec or de d.  
T he st u d y will be cl ose d w he n n o patie nts re m ai n i n f oll o w -u p.  
F or patie nts  still recei vi n g treat me nt or  i n t he safet y f oll o w-u p p eri o d, t he i n vesti gat or will be 
e x pecte d t o m o nit or f or a n d re p ort a n y S A Es a n d pre g na nci es, as detaile d i n Secti o n  7. 5. 1. 2  a n d 
Secti o n  7. 5. 1. 4  f or eac h patie nt . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 1  of 1 5 2  
7.  
S T U D Y A S S E S S M E N T S   
7. 1.  
S cr e e ni n g/ B a s eli n e A s s e s s m e nt s   
O nl y patie nts w h o meet all i ncl usi o n a n d e x cl usi o n criteria s pecifie d i n Secti o n 4  will be e nr olle d 
i n t his st u d y. 
● 
Patie nt me dical hist or y i ncl u des a t h or o u g h re vie w of si g nifi ca nt past me dical hist or y, 
c urre nt c o n diti o ns, a n y tr eat me nt f or pri or mali g n a ncies a n d res p o nse t o pri or treat me nt, 
a n d a n y c o n c o mita nt me dicati o ns.  
● 
P h ysical e x a mi nati o ns s h o ul d i ncl u de assess me nts of t he f oll o wi n g b o d y p arts/s yste ms: 
a b d o me n, e xtre mities, hea d, heart, l u n gs, nec k, a n d ne ur ol o gical. F or a d ult patie nts o nl y, 
meas ure me nts of h ei g ht o btai ne d wit hi n t he pri or 1 2 m o nt hs ma y be utilize d.  
● 
Vita l si g ns will i ncl u de meas ure me nts of res pirat or y rate, p ulse rate, a n d s yst olic a n d 
diast olic bl o o d press ure w hile t he patie nt is i n a seate d p ositi o n, p ulse o xi metr y, a n d 
te m perat ur e. 
Cli nical la b orat or y tests i ncl u di n g P T/ P T T/a P T T/I N R, H b A 1c, ser ol o g y f o r he patitis B, P C R f or 
he patitis C, pre g n a nc y test (eit her uri ne or s er u m, f or patie nts of c hil d beari n g p ote ntial), a n d 
t h yr oi d f u n cti o n tests (t o i ncl u de T S H, T 3 or free T 3, a n d free T 4) are re q uire d f or all patie nts at 
scree ni n g. Cli nical la b orat or y t ests are f urt her d et aile d i n Secti o n 7. 5. 3 . 
A brai n sca n ( C T wit h c o ntrast/ M RI  sca n) f or baseli ne t u m or i ma gi n g s h o ul d be perf or me d t o 
assess disease at baseli ne.  
F or patie nts e nr olle d i n Part D, a vaila bl e a n d a d e q uate arc hi val or fres h bas eli ne t u m or bi o ps y 
tiss ue is re q uire d (see Secti o n 7. 4. 1  f or details). T he me dical m o nit or s h o ul d be c o ntact e d t o 
c o nsi der alter nati ves i n t he e ve nt a t u m or s a m ple is n ot a vaila ble. T u m or tiss ue P D -L 1 C P S < 1 0 
will be deter mi ne d b y a P D -L 1 I H C assa y usi n g t he 2 2 C 3 cl o ne . 
7. 1. 1.  
El e ctr o c ar di o gr a m   
E C Gs are t o be o btai n e d per i nstit uti o nal sta n dar d at ti me p oi nts defi ne d i n Secti o n 6 , 
A p pe n di x  A , a n d A p pe n di x  C . 
7. 2.  
R e s p o n s e/ Effi c a c y A s s e s s m e nt s   
Treat me nt r es p o nse will be assesse d b y ra di o gra p hic t u m or e val uati o n e ver y 6 wee ks ( ± 3  da ys) 
f or 1 2 m o nt hs after t he first d ose of L V  a n d p e m br oliz u ma b a n d e ver y 1 2  wee ks ( ± 7  d a ys) 
t hereafter a n d s h o ul d b e calc ulate d fr o m C ycle 1 Da y 1 d uri n g treat me nt. Ti me p oi nts f or 
ra di o gra p hic e x a mi nati o ns s h o ul d be cale n dar bas e d a n d d o n ot de pe n d o n c ycle visits. T he 
sc he d ule of res p o nse assess me nts s h o ul d n ot be a dj uste d f or d ose dela ys, d ose i nterr u pti o ns, or 
ot her reas o ns f or c h a n ges i n t he ti mi n g of a patie nt’s st u d y acti vities.  N o a d diti o nal sca ns or 
res p o nse ass ess me nts are re q uire d after t h e safet y f oll o w-u p peri o d, h o we v er a d diti o nal sca ns or 
res p o nse ass ess me nts ma y be p erf or me d as p art of t he patie nt’s sta n dar d of care at a n y ti me.  
S piral C T sca ns of c hest, a b d o me n, a n d pel vis m ust be o btai ne d; a C T of t he nec k m ust als o be 
o btai ne d if d oc u me nte d or s us pecte d i n v ol ve me nt i n t his re gi o n. A dia g n ostic q ualit y C T is 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 2  of 1 5 2  
re q uire d u nless medi call y c o ntr ai n dicate d. F or patie nts u na ble t o t olerate c o ntrast -e n ha n ce d C T 
assess me nts, M RI i ma gi n g is acce pta bl e. P atie nts m ust be e v al u ate d wit h s a me i m a gi n g 
m o d alit y t hr o u g h o ut t he st u d y f or effic ac y assess me nts.  If a n y ot h er ra di o gra p hi c or diseas e 
assess me nt e x a mi nati o n is c o n d ucte d per sta n dar d of care, t he ass ess me nt i nf or mati o n will be 
c ollecte d i n t he C R F.  
T he deter mi nati o n of a ntit u m or acti vit y will be bas e d o n o bjecti ve res p o nse assess me nts ma de 
acc or di n g t o R E CI S T Versi o n 1. 1 (f or pri mar y a n d  sec o n dar y e n d p oi nts) a n d i R E CI S T (f or 
e x pl orat or y e n d p oi nts). Treat me nt de cisi o ns b y t he i n vesti gat or will be base d o n i R E CI S T.  
Beca use of t h e p ossi bilit y of a n i nitial i ncreas e i n t u m or b ur de n ca us e d b y i m m u ne cell 
i nfiltrati o n i n t he setti n g of a T cell res p o nse (t er me d pse u d o pr o gressi o n) wit h pe m br oliz u ma b 
treat me nt, ra di o gra p hic pr o gressi o n per R E CI S T v 1. 1 ma y n ot be i n dicati ve of tr ue diseas e 
pr o gressi o n. T he i R E CI S T all o w f or c o nti n ue d tr eat me nt be y o n d a p pare nt pr o gressi o n of diseas e 
i n or der t o c o nfir m r es p o nse. I n patie nts w h o ha v e i nitial e vi de nce of ra di ol o gical P D per 
R E CI S T v 1. 1, it is at t he discreti o n of t he treati n g p h ysicia n w het her t o c o nti n ue a patie nt o n 
st u d y treat me nt u ntil re peat i ma gi n g is o btai ne d. T his cli nical j u d g me nt decisi o n s h o ul d be base d 
o n t he patie nt’s o verall cli nical c o n diti o n, i ncl u di n g perf or ma n ce stat us, cli nical s y m pt o ms, a n d 
la b orat or y dat a. Patie nts ma y recei ve st u d y treat m e nt w hile waiti n g f or c o nfir mati o n of P D if 
t he y are cli nicall y sta bl e as defi ne d b y t he f oll o wi n g criteria: 
● 
A bse nce of si g ns a n d s y m pt o ms i n dicati n g diseas e pr o gressi o n  
● 
N o decli ne i n E C O G perf or ma nce stat us  
● 
A bse nce of ra pi d pr o gressi o n of disease  
● 
A bse nce of pr o gressi ve t u m or at critical a nat o mical sites (e. g., c or d c o m pr essi o n) 
re q uiri n g ur ge nt alter nati ve me dical i nter v e nti o n  
 
W he n feasi ble, patie nts s h o ul d n ot disc o nti n ue treat me nt  u ntil  pr o gressi o n is c o nfir me d. T his 
all o wa nce t o c o nti n ue treat me nt des pite i nitial ra di ol o gic pr o gressi o n ta kes i nt o acc o u nt t he 
o bser vati o n t hat s o me patie nts ca n ha ve a tra nsie nt t u m or flare i n t he first f e w m o nt hs after t he 
start of i m m u n ot hera p y, b ut wit h s u bse q ue nt disease res p o ns e. Patie nts t hat are dee me d cli nicall y 
u nsta ble are n ot r e q uire d t o ha ve re p eat i ma gi n g f or c o nfir mati o n of P D.  
Patie nts’ cli nical data m ust be a vaila ble f or C R F s o urce verificati o n. C o pies of t u m or i ma ges 
m ust be ma de a vaila ble f or re vie w b y t h e s p o ns or ( or its desi g n ee), u p o n re q uest.  
7. 3.  
P h ar m a c o ki n eti c a n d I m m u n o g e ni cit y A s s e s s m e nt s   
Bl o o d sa m ples f or P K a n d A T A assess me nt f or Parts A a n d B will be c ollecte d at ti me p oi nts 
descri be d i n A p p e n di x  B . P K a n d A T A sa m pli n g ti me p oi nts f or Part s C  a n d D are d escri be d i n  
A p pe n di x  D . Starti n g wit h a me n d me nt 1 1, P K a n d i m m u n o ge nicit y assess me nts will n ot be 
c o n d ucte d after C ycle 1.  
Se nsiti ve, q ualifie d E LI S A or L C/ M S M S assa ys, as a p pr o priat e, will be us e d t o meas ure 
c o nce ntr ati o ns of A D C ( L V ), t otal a nti b o d y, a n d M M A E i n plas ma a n d A T A i n ser u m. P K 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 3  of 1 5 2  
pa ra meters will be esti mate d f or A D C, t otal a nti b o d y, a n d M M A E. Relate d a nal yt es of L V ma y 
als o be meas ur e d usi n g a p pr o priate ass a ys.  
7. 4.  
Bi o m ar k er St u di e s   
T u m or sa m ples a n d bl o o d f or e x pl orat or y bi o mar kers a nal yses m a y  be c oll ecte d at pr ot o c ol -
s pecifie d ti me p oi nts (see A p pe n di x  E ). Bi o mar ker assess me nts will not be use d f or patie nt 
selecti o n. Starti n g wit h A me n d me nt 1 1, bi o mar ker assess me nts will n ot be c o n d ucte d  after 
C ycle  1.  
Met h o ds of a nal ysis ma y i ncl u de I H C, m ulti ple x i m m u ne hist ofl u oresce nce ( mI H F), m utati o n 
a n d ge ne e x pressi o n pr ofili n g b y Ne xt Ge nerati o n Se q ue nci n g, fl o w c yt o metr y, E LI S A, a n d 
T  cell rece pt or bet a ( T C R β) i m m u n o S E Q a nal ysis.  
7. 4. 1.  
Bi o m ar k er s i n S oli d T u m or Ti s s u e   
T o better u n derst a n d relati o ns hi ps bet wee n pre -tr eat me nt bi ol o gical c haract eristics of t he t u m or 
a n d B C patie nt o utc o mes, a fres hl y o btai ne d pretr eat me nt t u m or bi o ps y is r e q uire d f or p atie nts i n 
Parts A a n d B wit h accessi ble t u m ors (f or i nstr ucti o ns see La b orat or y Ma n u al).  
F or patie nts i n Parts A a n d B wit h i n accessi ble t u m ors or ot her safet y c o ncer ns, arc hi val tiss ue 
ma y b e s u b mitte d if it was c ollecte d after c o m pleti o n of t he patie nt’s m ost r ece nt c yt ot o xic 
t hera p y.  
F or patie nts i n Part s C  a n d D, arc hi val tiss ue c ollecte d after c o m pleti o n of t he patie nts m ost 
rece nt c yt ot o xic t hera p y s h o ul d be s u b mitte d. If arc hi val tiss ue is n ot a vaila ble, a fres hl y 
o btai ne d pretr eat me nt t u m or bi o ps y wit h accessi ble t u m ors ca n be use d (f or i nstr ucti o ns see 
La b orat or y M a n ual). If n eit her fres h n or a d e q uate arc hi ve d tiss ue is a v aila ble, please disc uss t his 
re q uire me nt wit h t he me dical m o nit or. 
F or fres hl y o btai ne d t u m or bi o psies, c ore n ee dle or e x cisi o nal bi o ps y is pr eferre d. If neit her is 
p ossi ble, disc uss wit h me dical m o nit or w het her bi o ps y o btai ne d via alter nati ve met h o ds  ma y be 
a p pr o priate.  
F or arc hi val tiss ue, f or m ali n fi x e d paraffi n e m b e d de d ( F F P E) bl oc ks are re q ueste d. If n o bl oc k is 
a vaila ble, sli des ma y be s u b mitte d wit h me dical m o nit or a p pr o val . 
St u dies of C PIs i n p atie nts wit h se veral differe nt s oli d ca ncers ha ve s h o w n a p ositi ve ass ociati o n 
of pretreat me nt t u m or -i nfiltrati n g l y m p h o c yt es ( TI Ls) as well as P D-L 1 e x pressi o n wit h 
i m pr o ve d o utc o mes (R ose n ber g 2 0 1 6 ; Sc h mi d 2 0 1 7 ). I n t ur n, TI Ls a n d P D -L 1 e x pressi o n are 
ele vate d f oll o wi n g m o n ot hera p y wit h M M A E -li n ke d A D Cs acc or di n g t o precli nical dat a (Ca o 
2 0 1 7 ). T his s u g gests t hat a c o m bi nati o n of L V  a n d C PI treat me nt c o ul d be s y ner gistic. I n 
a d diti o n, efficac y of C PIs is de pe n de nt o n m utati o nal l oa d of t u m ors, w hile a c o m bi nati o n of 
C PIs wit h L V  ma y be i n de pe n de nt of m utati o nal l oa d, a n d t h us be efficaci o us i n a lar ger patie nt 
p o p ulati o n t ha n C PI m o n ot hera p y.  
T o c haracteriz e a n d c orrelate pre dicti ve a n d pr o g n ostic pre -treat me nt bi o mar kers a n d treat me nt-
ass ociate d c h a n ges i n t he t u m or i m m u ne micr oe n vir o n me nt wit h patie nt o utc o me, a n o n -
treat me nt bi o ps y is r e q uire d bet wee n Da ys 4 t o 7 of C ycl e 1 f or p atie nts wit h accessi ble t u m ors 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 4  of 1 5 2  
i n Part A of t he st u d y. F or patie nts wit h accessi ble t u m ors i n Part B, a n o n-treat me nt bi o ps y is 
re q uire d b et wee n Da ys 1 5 a n d 2 1 of C ycle 1. T w o c ores s h o ul d be o btai ne d. C ore nee dle or 
e x cisi o nal bi o ps y is pr eferre d. If neit he r is p ossi ble, disc uss wit h s p o ns or w het her bi o ps y 
o btai ne d via alter nati ve met h o ds ma y be a p pr o pri ate. T he o n -tr eat me nt bi o ps y s h o ul d be 
o btai ne d fr o m t he sa me l esi o n as t he pre -treat me nt ( or arc hi v al) bi o ps y, if p ossi ble. F urt her 
i nstr ucti o ns o n bi o ps y collecti o n are f o u n d i n t he La b orat or y M a n ual.  
N o o n -treat me nt bi o psies are re q uire d f or patie nts i n Parts C  or D . 
T o c haracteriz e a n d u n d ersta n d treat me nt r esista nce, a n a d diti o nal o pti o nal fres h bi o ps y is 
re q ueste d at E O T f or patie nts i n Parts A a n d B with accessi ble resi d ual t u m or, a gai n fr o m t he 
sa me lesi o n as pre vi o us bi o psies if p ossi ble. A fres h bi o ps y at E O T is n ot re q ueste d f or patie nts 
i n Parts C  or D . 
I n U S patie nts o nl y, if a t u m or tiss ue sa m ple is o btai ne d as part of sta n dar d of care at a n y ti me 
p oi nt d uri n g t he st u d y, wit h t he patie nt’s c o nse nt, eit her a part of t hat sa m ple or a n a d diti o nal 
sa m ple o btai ne d d uri n g t he sa me pr o ce d ure ma y b e o btai ne d t o s u b mit t o t he s p o ns or.  
E x pl orat or y b i o mar ker assess me nts i n fres hl y o btai ne d ( or arc hi val) pre- a n d o n -treat me nt t u m or 
tiss ue ma y i ncl u de, b ut n ot be li mite d t o: 
● 
E x pressi o n of LI V 1  a n d P D-L 1 pr otei ns  
● 
Ge ne e x pressi o n a n al ysis (e. g., differe nt LI V 1  is of or ms, P D-L 1)  
● 
Mar kers of disease s u bt y pe (e. g., T C G A s u bt y pes)  
● 
M utati o nal l oa d  
● 
Mar kers of t he t u m or i m m u ne micr oe n vir o n me nt (e. g., C D 8, F O X P 3, C D 6 8)  
7. 4. 2.  
Bi o m ar k er s i n Bl o o d   
Effects of L V  a n d p e m br oliz u ma b treat me nt of B C patie nts a n d s uccessf ul t hera p y ma y als o lea d 
t o c ha n ges i n li qui d bi o mar kers, e. g., b y c h a n ges i n t he acti vati o n state of p eri p heral i m m u ne 
cells, s ol u ble c yt o ki n es, cell -free D N A (cf D N A), T C R β cell pellet, a n d/ or e x os o mes. T o 
u n dersta n d d y na mic c ha n ges of t hese s ol u ble bi o m ar kers a n d t heir relati o ns hi p t o efficac y a n d 
safet y, bl o o d sa m ples ma y be  c ollecte d at vari o us ti me p oi nts d uri n g t he st u d y. Bi o mar ker 
assess me nts i n bl o o d sa m ples ma y i ncl u de, b ut ma y n ot be li mite d t o:  
● 
A b u n da nce a n d p he n ot y p e of i m m u ne cell s u bsets  
● 
A b u n da nce a n d treat me nt -relate d c ha n ges of c yt oki nes (s uc h as I F N g, C X C L 9, C X C L 1 0) 
or ot her pr otei ns (s u c h as t u m or mar kers C A 1 5 -3, C A 2 7 -2 9, or carci n oe m br y o nic a nti ge n 
[ C E A]) 
● 
A b u n da nce of cir c ulati n g n ucleic aci ds (e. g., cf D N A) or e x os o mes as mar kers of t u m or 
res p o nse or t hera p y resista nce 
● 
Cl o nalit y of T C R β b y i m m u n o S E Q a nal ysis  
 
Refer t o t he La b orat or y Ma n ual f or i nf or mati o n o n c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt 
of sa m ple.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 5  of 1 5 2  
7. 4. 3.  
Bi o s p e ci m e n R e p o sit or y   
F or patie nts i n t he U S w h o pr o vi de a d diti o nal c o nse nt, re mai ni n g de -i de ntifie d u n use d bl o o d 
a n d/ or tiss ue ma y  b e retai ne d b y t he s p o ns or a n d use d f or f ut ure res earc h, i ncl u di n g b ut n ot 
li mite d t o t he e val uati o n of tar gets f or n o vel t hera pe utic a ge nts, t he bi ol o g y of A D C sensiti vit y 
a n d resista nce mec h a nis ms, a n d t he i de ntificati o n of bi o mar kers of A D Cs. Bl o o d a n d tiss ue 
sa m ples d o nate d f or f ut ure res earc h will be a n o n y mize d a n d retai ne d f or a peri o d of u p t o 
2 5  years. If a d diti o nal c o nse nt is n ot pr o vi de d, a n y re mai ni n g bi o l o gical sa m ples will be 
destr o ye d f oll o wi n g st u d y c o m pleti o n. Patie nts ma y wit h dra w per missi o n f or t he rete nti o n of 
sa m ples at a n y ti me. 
Bi os peci me n re p osit or y s a m ple c ollecti o n o nl y a p plies t o cli nical sites wit hi n t he U S.  
7. 5.  
S af et y A s s e s s m e nt s   
T he assess me nt of s afet y d uri n g t he c o urse of t his st u d y will c o nsist of t he s ur veilla nce a n d 
rec or di n g of A Es i ncl u di n g S A Es, r ec or di n g of c o nc o mita nt me dicati o n, a n d meas ure me nts of 
pr ot oc o l-s pecifi e d p h ysi cal e x a mi nati o n fi n di n gs a n d la b orat or y tests.  
Safet y will be m o nit ore d o ver t he c o urse of t he st u d y b y a n S M C as des cri b e d i n Secti o n  9. 3. 9. 6 . 
I n a d diti o n t o t he S M C, a n I S M C c o m p ose d of p h ysicia ns w h o are n ot i n v ol ve d i n t his st u d y, as 
well as sp o ns or re prese nt ati ves,  will peri o dicall y re vie w c u m ulati ve safet y data a n d pr o vi de 
rec o m me n dati o ns t o t he s p o ns or. 
7. 5. 1.  
A d v er s e E v e nt s   
7. 5. 1. 1.  
D efi niti o n s   
A d verse E ve nt   
Acc or d i n g t o t he I nt er nati o nal C o u ncil f or Har m o nisati o n (I C H) E 2 A g ui d eli ne Defi niti o ns a n d 
Sta n dar ds f or E x pe dite d Re p orti n g, a n d 2 1 C F R 3 1 2. 3 2, i n vesti gati o nal ne w dr u g (I N D) Safet y 
Re p orti n g, a n A E is a n y u nt o war d me dical o cc urre nce i n a patie nt or cli nical i n vesti gati o nal 
s u bject a d mi nistere d a m e dici nal pr o d uct a n d w hic h d oes n ot necessaril y h a ve a ca usal 
relati o ns hi p wit h t his treat me nt. 
T he f oll o wi n g i nf or mati o n s h o ul d be c o nsi dere d w he n deter mi ni n g w het her or n ot t o rec or d a 
test res ult, me dical c o n diti on, or ot her i nci de nt o n t he A d verse E ve nts a n d Pre -e xisti n g 
C o n diti o ns C R F:  
● 
All st u d y pr ot oc ol -relate d A Es t hat occ ur after t h e c o nse nt f or m is si g ne d b ut bef ore 
treat me nt all ocati o n m ust be re p ort e d b y t he i n vesti gat or. 
● 
All me dical c o n diti o ns prese nt or o n g oi n g pre d os e o n st u d y Da y 1 s h o ul d b e rec or de d.  
● 
All A Es (re gar dless of relati o ns hi p t o st u d y dr u g) s h o ul d be rec or de d fr o m st u d y Da y  1 
t hr o u g h t he e n d of t he safet y re p orti n g peri o d (see Secti o n 6 ). C o m plicati o ns t hat occ ur i n 
ass ociati o n wit h a n y pr oce d ure (e. g., bi o ps y) s h o ul d be rec or de d as A Es w h et her or n ot 
t he pr oce d ure w as pr ot oc ol ma n date d. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 6  of 1 5 2  
● 
C ha n ges i n me di cal c o n diti o ns a n d A Es, i ncl u di n g c ha n ges i n se v erit y, fre q ue nc y, or 
c haracter, d uri n g t h e safet y re p orti n g p eri o d s h o ul d be rec or de d.  
● 
I n ge neral, a n a b n or mal la b orat or y v al ue s h o ul d n ot be rec or de d as a n A E u nless it is 
ass ociate d wit h cli nical si g ns or s y m pt o ms, re q uir es a n i nter ve nti o n, re s ults i n a S A E, or 
res ults i n st u d y ter mi nati o n or i nterr u pti o n/ disc o nti n uati o n of st u d y treat me nt. W he n 
rec or di n g a n A E res ulti n g fr o m a la b orat or y a b n or malit y, t he res ulti n g me dical c o n diti o n 
rat her t ha n t h e a b n or malit y itself s h o ul d be rec or de d (e. g., rec or d “a n e mia” rat her t ha n 
“l o w he m o gl o bi n”).  
Seri o us A d verse E ve nts   
A n A E s h o ul d be classifi e d as a n S A E if it meets o ne of t he f oll o wi n g criteria:  
Fatal:  
A E res ulte d i n deat h  
Life t hreate ni n g:  
T he A Es place d t he patie nt at i m me diate ris k of deat h. T his classificati o n d oes n ot 
a p pl y t o a n A E t hat h y p ot hetic all y mi g ht ca use deat h if it were m ore se vere.  
H os pitalizati o n:  
T he A E res ulte d i n h os pitalizati o n or pr ol o n ge d a n e xisti n g  i n patie nt h os pitalizati o n. 
H os pitalizati o ns f or electi ve me dical or s ur gical pr oce d ures or treat me nts pla n ne d 
bef ore t he si g ni n g of i nf or me d c o nse nt i n t he st u d y or r o uti ne c hec k -u ps are n ot S A Es 
b y t his criteri o n. A d missi o n t o a palliati ve u nit or h os pic e care facilit y is n ot 
c o nsi dere d t o be a h os pitalizati o n. H os pitalizati o ns or pr ol o n ge d h os pitalizati o ns f or 
sc he d ule d t hera p y of t he u n derl yi n g ca ncer or st u d y tar get disease nee d n ot be 
ca pt ure d as S A Es.  
Disa bli n g/ 
i nca pacitati n g: 
A n A E t hat res ulte d i n a persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n 
of t he patie nt’s a bilit y t o c o n d uct n or mal life f u ncti o ns.  
C o n ge nital a n o mal y or 
birt h defect:  
A n a d verse o utc o me i n a c hil d or fet us of a patie nt e x p ose d t o t he m olec ule or st u d y 
treat me nt re gi me n bef ore c o nce pti o n or d uri n g pre g na nc y. 
Me dicall y si g nifica nt:  
T he A E di d n ot meet a n y of t he a b o ve criteria b ut  c o ul d ha ve j e o par dize d t he patie nt 
a n d mi g ht ha ve re q uire d me di cal or s ur gical i nter ve nti o n t o pre ve nt o ne of t he 
o utc o mes liste d a b o ve or i n v ol ves s us pecte d tra ns missi o n via a me dici nal pr o d uct of 
a n i nfecti o us a ge nt. P ote ntial dr u g -i n d uce d li ver i nj ur y ( DI LI) als o is c o nsi dere d a 
me dicall y si g nifica nt e ve nt. (see Secti o n 7. 5. 1. 2  f or t he defi niti o n of p ote ntial DI LI.) 
A d verse E ve nt Se verit y   
A E se verit y s h o ul d be gra de d usi n g t he N CI C T C A E, versi o n 4. 0 3. T hes e criteria are pr o vi de d i n 
t he st u d y ma n ual. 
A E se verit y a n d s eri o us n ess are assesse d i n de pe n de ntl y. ‘ Se verit y’ c h aract erizes t he i nte nsit y of 
a n A E. ‘ Seri o us’ is a re g ulat or y d efi niti o n a n d ser ves as a g ui de t o t he s p o ns or f or defi ni n g 
re g ulat or y re p orti n g o bli gati o ns (s ee defi niti o n f or S A Es, a b o ve). 
Rel ati o ns hi p of t he A d verse E ve nt t o St u d y Tre at me nt   
T he relati o ns hi p of eac h A E t o eac h st u d y treat me nt ( L V , p e m br oliz u ma b) s h o ul d be e val uate d 
b y t he i n vesti gat or usi n g t he f oll o wi n g criteria:  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 7  of 1 5 2  
Relate d:  
T here is e vi de nce t o s u g gest a ca usal relati o ns hi p bet wee n t he dr u g a n d t he A E, s uc h 
as:  
A si n gle occ urre nce of a n e ve nt t hat is u nc o m m o n a n d k n o w n t o be str o n gl y 
ass ociate d wit h dr u g e x p os ure (e. g., a n gi oe de ma, he patic i nj ur y, Ste ve ns -J o h ns o n 
S y n dr o me)  
O ne or m ore occ urre nces of a n e ve nt t hat is n ot c o m m o nl y ass ociate d wit h dr u g 
e x p os ure, b ut is ot her wise u nc o m m o n i n t he p o p ulati o n e x p ose d t o t he dr u g (e. g., 
te n d o n r u pt ure) 
U nrelate d:  
A n ot her ca use of t he A E is m ore pla usi ble (e. g., d ue t o u n d erl yi n g disease or occ urs 
c o m m o nl y i n t he st u d y p o p ulati o n), or a te m p oral se q ue nce ca n n ot be esta blis he d wit h 
t he o nset of t he A E a n d a d mi nistrati o n of t he st u d y treat me nt, or a ca usal relati o ns hi p 
is c o nsi dere d bi ol o gicall y i m pla usi ble 
7. 5. 1. 2.  
Pr o c e d ur e s f or Eli citi n g a n d R e c or di n g A d v er s e E v e nt s   
I n v esti gat or a n d st u d y pers o n nel will re p ort all A Es a n d S A Es w het her elicite d d uri n g p atie nt 
q uesti o ni n g, disc o vere d d uri n g p h ysic al e xa mi nati o n, la b orat or y testi n g a n d/ or ot her mea ns b y 
rec or di n g t he m o n t he C R F a n d/ or S A E f or m, as a p pr o priate. 
Eliciti n g A d verse E ve nts   
A n o pe n -e n d e d or n o n -directe d met h o d of q uesti o ni n g s h o ul d be use d at eac h st u d y visit t o elicit 
t he re p orti n g of A Es. 
Rec or di n g A d verse E ve nts   
T he f oll o wi n g i nf or mati o n s h o ul d be rec or de d o n t he A d verse E ve nts a n d Pre -e xisti n g 
C o n diti o ns C R F:  
● 
Descri pti o n i ncl u di n g o nset a n d res ol uti o n dates  
● 
W het her it met S A E criteria  
● 
Se verit y  
● 
Relati o ns hi p t o st u d y tr eat me nt or ot her ca usalit y  
● 
O utc o me  
Di a g n osis vs Si g ns or S y m p t o ms  
I n ge neral, t he use of a u nif yi n g dia g n osis is preferre d t o t he listi n g o ut of i n di vi d ual s y m pt o ms. 
Gr o u pi n g of s y m pt o ms i nt o a dia g n osis s h o ul d o nl y be d o n e if eac h c o m p o ne nt  si g n a n d/ or 
s y m pt o m is a me dicall y c o nfir me d c o m p o ne nt of a dia g n osis as e vi de nce d b y sta n dar d me dical 
te xt b o o ks. If a n y as p ect of a si g n or s y m pt o m d oes n ot fit i nt o a classic patter n of t he dia g n osis, 
re p ort t he i n di vi d ual s y m pt o m as a se parate A E. 
I m p ort a nt e x ce pti o ns f or t his st u d y are a d verse reacti o ns ass ociate d wit h t he i nf usi o n of st u d y 
dr u g. F or I R Rs, r ec or d t h e N CI C T C A E ter m of ‘i nf usi o n relate d reacti o n’ wit h a n o verall le vel 
of se verit y ( per N CI C T C A E). I n a d diti o n, rec or d eac h si g n or s y m pt o m  of t he reacti o n as a n 
i n di vi d ual A E. If m ulti ple si g ns or s y m pt o ms occ ur wit h a gi ve n i nf usi o n-relate d e v e nt, eac h 
si g n or s y m pt o m s h o ul d be rec or de d se p aratel y wit h its le vel of se verit y.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 8  of 1 5 2  
Rec or di n g Seri o us A d verse E ve nts   
F or S A Es, rec or d t he e ve nt(s) o n b ot h t he C R F a n d a n S A E f or m.  
T he f oll o wi n g s h o ul d be c o nsi dere d w he n rec or di n g S A Es:  
● 
Deat h is a n o utc o me of a n e ve nt. T he e v e nt t hat res ulte d i n t he deat h s h o ul d be rec or de d 
a n d re p ort e d o n b ot h a n S A E f or m a n d C R F. 
● 
F or h os pitalizati o ns, s ur gical, or dia g n ostic pr oce d ures, t he ill ness lea di n g t o t he s ur gi cal 
or dia g n ostic pr oce d ure s h o ul d be rec or de d as t he S A E, n ot t he pr oce d ure itself. T he 
pr oce d ure s h o ul d be ca pt ure d i n t he nar rati ve as p art of t he acti o n ta ke n i n res p o nse t o t he 
ill ness. 
Pr o g ressi o n of t he U n derl yi n g M ali g n a nc y   
Si nce pr o gressi o n of u n d erl yi n g mali g na n c y is bei n g ass esse d as a n efficac y varia ble, it s h o ul d 
n ot be re p orte d as a n A E or S A E.  T he ter ms “ Disease Pr o gressi o n”, “ Pr o gressi o n of Disease”, or 
“ Mali g n a nt Disease Pr o gressi o n” a n d ot her si milar ter ms s h o ul d n ot be use d t o descri be a n A E 
or S A E. H o we ver, cli nic al s y m pt o ms of pr o gressi o n ma y b e re p orte d as A Es or S A Es if t he 
s y m pt o m ca n n ot be d eter mi ne d as e x cl usi vel y d ue t o pr o gressi o n of t he u n derl yi n g mali g na n c y 
or d oes n ot fit t he e x pecte d patter n of pr o gressi o n f or t he diseas e u n der st u d y. I n a d diti o n, 
c o m plicati o ns fr o m pr o gressi o n  of t he u n derl yi n g mali g na n c y s h o ul d be re p orte d as A Es or 
S A Es.  
Pre g n a nc y   
It is t he res p o nsi bilit y of i n vesti gat ors or t h eir desi g nees t o re p ort a n y pre g n a nc y or lactati o n 
(s p o nta ne o usl y re p orte d t o t he m) t hat occ urs i n a p atie nt ( or part n er of a male patie nt) d uri n g t he 
trial. If a patie nt b ec o mes pre g na nt w hile o n st u d y, t he site will c o ntact t he patie nt at least 
m o nt hl y a n d d oc u me nt t he patie nt’s stat us u ntil t he pre g na n c y has b ee n c o m plete d or ter mi nate d.  
Pre g n a ncies a n d lactati o ns t hat occ ur after t he c o nse nt f or m is si g ne d b ut b ef ore tr eat me nt 
all ocati o n m ust be re p ort e d b y t h e i n vesti gat or if t he y ca use t h e patie nt  t o b e e x cl u de d fr o m t he 
trial. 
N otificati o n t o Dr u g Sa fet y: C o m plete a Pre g n a nc y Re p ort F or m f or all pre g na n cies a n d 
lactati o ns t hat occ ur fr o m t he ti me of treat me nt all ocati o n u ntil t he c o m pleti o n of t he safet y 
f oll o w-u p peri o d or 3 0 d a ys f oll o wi n g t he l ast d ose of st u d y dr u g(s) if t h e p atie nt  i nitiates ne w 
a ntica ncer t hera p y, w hic he ver is earlier. I n cl u de a n y pre g na nci es t hat occ ur i n t he part ner of a 
male st u d y patie nt. O nl y re p ort pre g n a ncies t h at occ ur i n a mal e patie nt’s p art ner if t he esti mate d 
date of c o n ce pti o n is after t he male patie nt’s first st u d y dr u g d ose. E mail or fa x t o t he s p o ns or’s 
Dr u g Safet y D e part me nt wit hi n 4 8 h o urs of bec o mi n g a ware of a pre g na n c y. All pre g na n cies 
will be m o nit ore d f or t he f ull d urati o n; all peri natal a n d ne o natal o utc o mes s h o ul d be re p orte d. 
I nfa nts s h o ul d be f oll o we d f or a mi ni m u m of 8 wee ks. 
C ollecti o n of data o n t he C R F: All pre g n a ncies (as descri be d a b o ve) t hat o cc ur wit hi n 3 0  da ys of 
t he last d ose of st u d y dr u g(s) will als o be rec or de d o n t he A d verse E ve nts a n d Pre-E xisti n g 
C o n diti o ns C R F.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 7 9  of 1 5 2  
Pre g n a nc y o utc o mes of s p o nt a ne o us a b orti o n, misse d a b orti o n, be ni g n h y d ati dif or m m ole, 
bli g hte d o v u m, fetal d eat h, i ntra uteri ne deat h, miscarri a ge, a n d still birt h m ust be re p orte d as 
S A Es.  C o n ge nital a n o malies or birt h defects, as defi ne d b y t h e ‘seri o us’ crit eri o n a b o ve (see 
defi ni ti o ns Secti o n 7. 5. 1. 1 ) s h o ul d be re p ort e d as S A Es. S uc h e ve nts m ust be re p ort e d wit hi n 
2 4  h o urs t o t he s p o ns or eit her b y electr o nic me dia or pa per.  El ectr o nic re p orti n g pr oce d ures ca n 
be f o u n d i n t he ele ctr o nic data ca pt ur e ( E D C) data e ntr y g ui d eli nes. Pa per re p orti n g pr oce d ures 
ca n be f o u n d i n t he I n vesti gat or Tri al File Bi n der ( or e q ui vale nt).  
P ote nti al Dr u g -I n d uce d Li ver I nj ur y  
T he o bser vati o n of t h e critical i m p orta nce of altere d li ver f u ncti o n has b ee n referre d t o 
i nf or mall y as H y’s La w (Re u be n 2 0 0 4 ). H y’s La w ca n be use d t o esti mate se verit y a n d t he 
li keli h o o d t hat a st u d y dr u g ma y ca use a n i ncrease d i nci de nce of se vere he p at ot o xicit y. 
T he a bse n ce of he pat ot o xicit y i n cli nical trials pr o vi des a li mite d pre dicti ve val ue f or p ote ntial 
he pat ot o xicit y i n t he cli nical setti n g(s) bei n g st u die d. H o we v er, fi n di n g 1 H y’s La w case i n 
cli nical trials is o mi n o us; fi n di n g 2 cases is hi g hl y pre dicti ve of a p ote ntial f or se vere DI LI.  
Defi niti o n   
Briefl y, p ote ntial H y’s La w c as es i ncl u de t he f oll o wi n g 3 c o m p o n e nts:  
3 4.  A mi n otra nsferase ( A L T a n d/ or A S T) ele vati o n > 3 x U L N,  
A N D  
3 5.  T otal bilir u bi n > 2 x U L N, wit h o ut i nitial fi n di n gs of c h olestasis (i.e., el e vate d ser u m al kali ne 
p h os p hatase),  
A N D  
3 6.  N o ot her i m me diatel y a p pare nt p ossi ble ca us es of a mi n otra nsferase el e vati o n a n d 
h y per bilir u bi ne mia, i ncl u di n g, b ut n ot li mite d t o, viral he patitis, pre -e xisti n g c hr o nic or ac ute 
li ver disease, or t h e a d mi nistrati o n of ot her dr u g(s) k n o w n t o be he p at ot o xic. 
Re p orti n g Re q uire me nts   
A n y p ote ntial H y’s La w case s h o ul d be h a n dle d as a s us pecte d u ne x pecte d seri o us a d verse 
reacti o n ( S U S A R) ass o ciate d wit h t he use of t he dr u g a n d re p orte d pr o m ptl y t o t he s p o ns or. 
Re p orti n g s h o ul d  i ncl u de all a vaila ble i nf or mati o n a n d s h o ul d i nitiate cl ose f oll o w-u p u ntil 
c o m plete res ol uti o n of t h e pr o ble m a n d c o m pleti o n of all atte m pts t o o btai n s u p ple me ntar y data.  
F oll o w -u p f or A b n or m al L a b or at or y Res ults S u g gesti n g P ote nti al DI LI   
I n ge neral, a n i ncreas e of ser u m A L T or A S T t o > 3 x U L N s h o ul d be f oll o we d b y re p eat testi n g 
wit hi n 4 8 t o 7 2 h o urs of ser u m A L T, A S T, al kali ne p h os p hatase, a n d t otal bilir u bi n, t o c o nfir m 
t he a b n or malities a n d t o deter mi ne w het h er t he y are w ors e ni n g. 
A p pr o priate me di cal assess me nt s h o ul d be i nitiate d t o i n vesti gate p ote ntial c o nf o u n di n g fact ors 
a n d alter nati ve ca uses of he pat ot o xicit y. D uri n g t his i n vesti gati o n, c o nsi der h ol di n g st u d y dr u g.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 0  of 1 5 2  
7. 5. 1. 3.  
R e p orti n g P eri o d s f or A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s   
T he safet y re p orti n g peri o d f or A Es is fr o m st u d y Da y 1 ( pre d ose) t hr o u g h t he E O T visit or 
3 0  da ys after t h e last st u d y treat me nt, w hic he v er is later. T he re p orti n g peri o d f or S A Es is fr o m 
st u d y Da y 1 ( pre d os e) t hr o u g h t he E O T visit or 9 0 da ys after t h e last st u d y treat me nt, w hic he ver 
is later. E ve nts will be rec or de d at eac h e x a mi nati o n o n t he A d verse E ve nt C R Fs/ w or k s heets. 
H o we ver, all st u d y pr ot oc ol -relat e d A Es are t o be rec or de d fr o m t he ti me of i nf or me d c o ns e nt. 
All S A Es t hat occ ur aft er t he safet y re p orti n g peri o d a n d are c o nsi dere d st u d y treat me nt -relate d 
i n t he o pi ni o n of t he i n vesti gat or s h o ul d als o be re p orted t o t he s p o ns or.  T h e i n vesti gat or will 
ma ke e ver y atte m pt t o f oll o w all patie nts wit h n o n -seri o us A Es f or o ut c o me. 
T he re p orti n g ti mefra me f or A Es meeti n g a n y s eri o us criteria is descri be d i n Secti o n  7. 5. 1. 4 . 
S A Es will be f oll o we d u ntil si g nifica nt c ha n ges ret ur n t o baseli ne, t he e ve nt sta bilizes 
(rec o v eri n g/res ol vi n g) or is n o l o n ger c o nsi dere d cli nicall y si g nifica nt b y t he i n vesti gat or, or t he 
pati e nt dies or wit h dra ws c o nse nt. All n o n -seri o us A Es will be f oll o we d t hr o u g h t he s afet y 
re p orti n g peri o d. Cert ai n n o n-seri o us A Es of i nterest ma y b e f oll o we d u ntil res ol uti o n, ret ur n t o 
baseli ne, or st u d y cl os ure, w hic he ver c o mes first. I n partic ular t hes e i ncl u de A Es of peri p heral 
ne ur o pat h y i n all patie nts.  
7. 5. 1. 4.  
S eri o u s A d v er s e E v e nt s R e q uir e I m m e di at e R e p orti n g   
Wit hi n 2 4 h o urs of o bser vi n g or lear ni n g of a n S A E, i n vesti gat ors are t o re p ort t he e ve nt t o t he 
s p o ns or, re gar dless of t he relati o ns hi p of t he e ve nt t o t he st u d y treat me nt re gi me n.  
F or i nitial S A E re p orts, a vaila ble cas e details are t o be rec or de d o n a n S A E f or m. At a mi ni m u m, 
t he f oll o wi n g s h o ul d be i ncl u de d: 
● 
Patie nt n u m ber  
● 
Date of e v e nt o nset  
● 
Descri pti o n of t he e v e nt  
● 
St u d y treat me nt, if k n o w n  
 
T he c o m plete d S A E f or m a n d S A E Fa x C o ver S heet are t o be e maile d or fa x e d t o t he s p o ns or’s 
Dr u g Safet y D e part me nt wit hi n 2 4 h o urs (see e mail or fa x n u m ber s pecifie d o n t he S A E re p ort 
for m).  
Rele va nt f oll o w -u p i nf or mati o n is t o be s u b mitte d t o t he s p o ns or as s o o n as it bec o mes a vaila ble.  
7. 5. 1. 5.  
S p o n s or S af et y R e p orti n g t o R e g ul at or y A ut h oriti e s   
I n v esti gat ors are re q uire d t o re p ort all S A Es, i ncl u di n g a ntici pat e d S A Es, t o t he s p o ns or (see 
Secti o n  7. 5. 1. 4 ). 
T he s p o ns or will re p ort all S A Es , i ncl u di n g S U S A Rs, t o reg ulat or y a ut h orities as re q uir e d per 
l ocal le gislati o n or re g ulat or y re p orti n g re q uir e me nts. 
I n t he U S, e n d p oi nts t hat assess disease-relat e d m ortalit y or maj or m or bi dit y, as well as ot her 
S A Es t hat are n ot st u d y e n d p oi nts b ut are k n o w n c o nse q ue nces of t he  u n derl yi n g disease or 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 1  of 1 5 2  
c o n diti o n t hat are a ntici p ate d t o occ ur i n t he st u d y p o p ulati o n, s h o ul d n ot be re p ort e d t o t he F o o d 
a n d Dr u g A d mi nistrati o n ( F D A) as i n di vi d ual I N D safet y re p orts per t h e fi nal r ule a me n di n g t he 
I N D safet y re p orti n g re q uire me nts u n der 2 1 C F R 3 1 2. 3 2 a n d t he F D A’s g ui da nce Safet y 
Assess me nt f or I N D Safet y Re p orti n g G ui da n ce f or I n d ustr y ( draft g ui da nce Dece m ber 2 0 1 5).  
I n t his st u d y, t he S A Es t hat d o n ot re q uire i n di vi d u al I N D safet y re p orts be s u b mitte d t o t he F D A 
are pr o gressi o n of t he  u n derl yi n g ca ncer. T h ese a ntici pate d S A Es will be re vie we d p eri o dicall y 
b y a n S M C a n d  Sea ge n  Dr u g Safet y D e part me nt. If u p o n re vie w, a n S A E is occ urri n g at a hi g h er 
rate t ha n t hat w hic h w o ul d be e x pecte d f or t h e st u d y p o p ulati o n, t he n a n I N D safet y re p ort f or 
t he S A E will be s u b mitte d t o t he F D A. 
7. 5. 1. 6.  
E v e nt s of Cli ni c al I nt er e st   
Selecte d n o n -seri o us a n d seri o us A Es are als o k n o w n as E ve nts of Cli nical I nterest ( E CIs) a n d 
m ust be re p or te d t o t he s p o ns or. 
F or t he ti me peri o d be gi n ni n g w he n t h e c o nse nt f or m is si g ne d u ntil treat me nt all ocati o n, a n y 
E CI, or f oll o w -u p t o a n E CI, w hic h o cc urs i n a n y patie nt, m ust be re p orte d wit hi n 2 4 h o urs t o t he 
s p o ns or if it ca uses t he p atie nt t o be e x cl ude d fr o m t he trial, or is t he res ult of a pr ot oc ol -
s pecifie d i nter ve nti o n, i ncl u di n g b ut n ot li mite d t o was h o ut or disc o nti n uati o n of us ual t hera p y, 
diet, or a pr oce d ure.  
F or t he ti me peri o d be gi n ni n g at treat me nt all ocati o n t hr o u g h 3 0 d a ys f oll o wi n g t he l ast st u d y 
dr u g d os e, a n y E CI, or f oll o w -u p t o a n E CI, w het h er or n ot rel ate d t o t he s p o ns or’s pr o d uct, m ust 
be re p ort e d wit hi n 2 4 h o urs t o t he s p o ns or, eit her b y el ectr o nic me di a or pa per. Electr o ni c 
re p orti n g pr oce d ures ca n be f o u n d i n t he E D C data e ntr y g ui d eli nes.  
E CIs f or t his trial i ncl u de:  
1.  A n o ver d ose of eit her st u d y pr o d u ct, as defi ne d i n Secti o ns 5. 2. 4  a n d 5. 3. 4 , a n d is n ot 
ass ociate d wit h cli nical s y m pt o ms or a b n or mal la b orat or y res u lts. 
2.  A n ele vate d A S T or A L T la b val ue t hat is ≥3 x U L N, a n d a n el e vate d t otal bilir u bi n la b val ue 
t hat is ≥2 x U L N a n d, at t he sa me ti me, a n al k ali ne p h os p hatase la b val u e t hat is < 2 x U L N, as 
deter mi ne d b y wa y of pr ot oc ol -s pecifie d la b orat or y testi n g, or u nsc he d ule d la b orat or y 
testi n g. * 
* N ote: T hese criteria are base d u p o n a v aila ble re g ulat or y g ui da nce d o c u me nts. T he p ur p ose of 
t he criteria is t o s pecif y a t hres h ol d of a b n or mal h e patic tests t hat ma y re q uire a n a d diti o nal 
e val uati o n f or a n u n derl yi n g eti ol o g y. T he trial sit e g ui d a nce f or ass ess me nt a n d f oll o w -u p of 
t hese criteri a ca n b e f o u n d i n t he I n v esti gat or Trial File Bi n der ( or e q ui vale nt). 
7. 5. 2.  
Vit al Si g n s   
Vital si g ns i ncl u de me as ure me nts of res pirat or y rate, p ulse rat e, a n d s yst olic a n d diast olic bl o o d 
press ure w hile t h e patie nt is i n a seate d p ositi o n, p ulse o xi metr y, a n d te m perat ure.  
Vital si g ns s h o ul d be me as ure d wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, wit hi n 6 0 mi n utes pri or 
t o pe m br oliz u ma b i nf usi o n ( Da y 1 o nl y), wit hi n 2 h o urs of e n di n g eac h i nf usi o n, a n d d uri n g 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 2  of 1 5 2  
i nf usi o n/s as cli nicall y i n dicate d. I n a d diti o n, vital si g ns s h o ul d be meas ure d at ot her s pecifi e d 
ti me p oi nts as o utli ne d i n t he sc he d ule of acti vities (see A p pe n di x  A  a n d A p pe n di x  C ). 
7. 5. 3.  
Cli ni c al L a b or at or y T e st s   
F or Part A a n d Part B C o h ort 1, sa m ples will be dra w n f or ce ntral a n d l ocal la bs. L o cal 
la b orat or y testi n g will i ncl u de bl o o d gl u c ose a n d ot her i nstit uti o nal sta n dar d tests f or e val uati n g 
safet y a n d ma ki n g cli nical decisi o ns. T he f oll o wi n g la b orat or y ass ess me nts will be perf or me d b y 
a ce ntr al la b orat or y d uri n g t he c o urse of t he st u d y (sc he d ul e i n A p pe n di x  A  a n d A p pe n di x  C ): 
● 
T he ser u m c h e mistr y p a n e l is t o i ncl u de t he f oll o wi n g tests: al b u mi n, al kali ne 
p h os p hatase, A L T, A S T, bl o o d urea nitr o ge n, calci u m, creati ni ne, c hl ori de, bl o o d 
gl uc ose, p h os p h or us, p otassi u m, s o di u m, t otal bilir u bi n, a m ylas e, li pase, a n d uric aci d.  
● 
T he C B C wit h differe ntial is t o  i ncl u de t he f oll o wi n g tests: W B C c o u nt wit h fi ve-part 
differe ntial ( ne utr o p hils, l y m p h oc ytes, m o n oc ytes, e osi n o p hils, a n d bas o p hils), R B C 
c o u nt, a bs ol ute ne utr o p hil c o u nt, platelet c o u nt, he m o gl o bi n, a n d he mat o crit.  
● 
T u m or mar kers (if alr ea d y bei n g p erf or m e d per t h e site’s sta n dar d of care) s uc h as C E A, 
C A 1 5 -3, a n d C A 2 7 -2 9  
F or Part A a n d Part B C o h ort 1, t he f oll o wi n g la b orat or y assess me nts will b e perf or me d o nl y b y 
l ocal la b orat ories at sc he d ule d ti me p oi nts d uri n g t he c o urse of t h e st u d y (see A p pe n di x  A ): 
● 
H b A 1c: if H b A 1 c is ele v ate d d uri n g scree ni n g, a re peat H b A 1c m ust be o btai ne d  
● 
Fasti n g bl o o d gl uc os e is o nl y re q uire d at scree ni n g ( ot her sc he d ule d tests d o n ot re q uire 
t he patie nt t o fast). If fasti n g bl o o d gl uc ose is ele v ate d d uri n g scree ni n g, a re peat f asti n g 
bl o o d gl uc ose m ust be o btai ne d.  
● 
C oa g ulati o n para meters: P T, P T T, a P T T, a n d I N R  
● 
He patitis B vir us ( H B V) ser ol o g y: H Bs A g a n d H Bc A b; H B V D N A test f or patie nts wit h 
a ne gati ve H Bs A g test a n d a p ositi ve t otal H Bc A b.  
● 
He patitis C viral l oa d b y P C R.  
● 
T h yr oi d f u ncti o n tests, i ncl u di n g T S H, T 3 or free T 3, a n d free T 4.  
● 
F or patie nts of c hil d beari n g p ote ntial, a s er u m or uri ne β -h C G pre g n a nc y test wit h 
se nsiti vit y of at least 2 5  mI U/ m L.  
F or Part B C o h ort 2 a n d Part s C  a n d D, all la b orat or y assess me nts will be perf or me d l o call y a n d 
res ults are t o be s u b mitte d t o t he ce ntral la b orat or y ( wit h t he e x ce pti o n of pre g na nc y t esti n g, 
w hic h d oes n ot nee d t o b e s u b mitte d t o t he ce ntral la b orat or y).  
Refer t o t he La b orat or y Ma n ual f or i nf or mati o n o n c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt 
of sa m ples.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 3  of 1 5 2  
7. 5. 4.  
P h y si c al E x a mi n ati o n   
P h ysical e x a mi nati o ns s h o ul d i ncl u de assess me nts of t he f oll o wi n g b o d y p arts/s yste ms: 
a b d o me n, e xtre mities, hea d, heart, l u n gs, nec k, a n d ne ur ol o gical. F or a d ult patie nts o nl y, 
meas ure me nts of h ei g ht o btai ne d wit hi n t he pri or 1 2 m o nt hs ma y be utilize d.  
7. 5. 5.  
Pr e g n a n c y T e sti n g   
F or w o me n of c hil d beari n g p ote ntial, a s er u m or uri ne β -h C G pre g n a nc y test wit h se nsiti vit y of 
at least 2 5  mI U/ m L will be perf or me d at bas eli ne, wit hi n 3  da ys pri or t o eac h Da y 1 st u d y dr u g 
d ose  at eac h c ycl e, a n d at t he E O T visit . A ne gati ve pre g na n c y res ult is re q uire d bef ore t he 
patie nt ma y recei ve st u d y dr u g. Pre g na nc y t ests ma y als o be re p eate d as re q ueste d per 
I nstit uti o nal Re vie w B oar d (I R B)/ I n de p e n de nt Et hics C o m mittee (I E C) or if re q uire d b y l ocal 
re g ulati o ns. 
7. 6.  
A p pr o pri at e n e s s of M e a s ur e m e nt s   
T he safet y me as ures t h at will be use d i n t his trial are c o nsi dere d sta n dar d pr oce d ures f or 
e val uati n g t he p ote ntial  a d verse effects of st u d y me dicati o ns.  
I m m u n o ge nicit y is c o m m o nl y assesse d f or bi ol o gics; t heref ore, sta n dar d tests ma y  b e perf or me d 
t o detect t he p ossi ble prese nce of s p ecific a nti b o dies t o L V . P K assess me nts are als o c o m m o n i n 
cli nical st u dies t o hel p c h aract erize d ose -e x p os ure-res p o nse relati o ns hi ps. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 4  of 1 5 2  
8.  
D A T A Q U A LI T Y C O N T R O L  A N D Q U A LI T Y A S S U R A N C E   
8. 1.  
Sit e Tr ai ni n g a n d M o nit ori n g Pr o c e d ur e s   
A st u d y ma n u al wit h i nstr ucti o ns f or st u d y c o m plia nce a n d C R F c o m pleti o n will be pr o vi de d. 
Pri or t o t he e nr oll me nt of patie nts at t he site,  Sea ge n  or its desi g n ate d cli nical a n d  me dical 
pers o n nel will re vie w t h e f oll o wi n g ite ms wit h t he i n vesti gat or a n d cli nic staff:  
● 
T he pr ot oc ol, st u d y o bj ecti ves, eli gi bilit y re q uire m e nts, st u d y pr oce d ures, re gistrati o n 
a n d wit h dra w al pr ocess es  
● 
C urre nt I B/ p ac ka ge i nsert  
● 
Rec or di n g a n d re p orti n g A Es a n d S A Es  
● 
E nr oll me nt g oals a n d st u d y ti meli nes  
● 
T he C R F c o m pleti o n pr o cess a n d s o urce d oc u m e ntati o n re q uire me nts  
● 
M o nit ori n g re q uir e me nts  
● 
I R B/I E C re vie w a n d a p pr o val pr ocess 
● 
I nf or me d c o ns e nt pr ocess 
● 
G o o d Cli nical Practice g ui deli nes a n d relat e d re g ulat or y d o c u me ntati o n re q uire me nts  
● 
Ke y st u d y t ea m r oles a n d res p o nsi bilities  
● 
I n v esti gati o nal pr o d uct st ora ge, acc o u nta bilit y, la beli n g, dis pe nsi n g, a n d rec or d kee pi n g 
● 
Patie nt c o di n g  
● 
St u d y s a m ples/s peci me n c ollecti o n, ha n dli n g, a n d s hi p pi n g  
● 
Pr ot oc ol c o m plia nce  
● 
Cli n ical st u d y rec or d kee pi n g, d oc u me nt rete nti o n, a n d a d mi nistrati ve re q uire me nts 
 
M o nit ori n g visits will occ ur peri o dicall y, wit h fre q ue nc y de p e n de nt o n t he rate of e nr oll me nt a n d 
w or kl oa d at e ac h site. D uri n g m o nit ori n g visits, t he  Sea ge n  re prese ntati ve will re vie w re g ul at or y 
d oc u me ntati o n, C R Fs, s o urce d oc u m e ntati o n, a n d i n vesti gati o nal pr o d u ct st ora ge, pre parati o n, 
a n d acc o u nta bilit y. T he C R Fs will be re vie we d f or c o m plete ness, a d here n ce t o t he pr o vi de d 
g ui deli nes, a n d acc urac y c o m pare d t o t he s o urce d oc u m e nts. T he i n vesti gat ors m ust e ns ure t hat 
t he m o nit or is all o we d t o i ns pect all s o urce d o c u me nts perti ne nt t o st u d y patie nts a n d  m ust 
c o o perat e wit h t he m o nit or t o e ns ure t hat a n y pr o ble ms n ote d i n t he c o urse of t he trial are 
res ol ve d. T he i n vesti gat or m ust mai ntai n a c o m pre he nsi ve a n d ce ntralize d fili n g s yste m of all 
st u d y-relate d d oc u m e ntati o n t hat is s uita ble f or i ns pecti o n b y Sea ge n  or its desi g nat e d m o nit ors 
a n d b y q u alit y ass ura nce a u dit ors, or re prese ntati v es of re g ulat or y a ut h orities.  
8. 2.  
D at a M a n a g e m e nt  Pr o c e d ur e s   
Sea ge n  will pr o vi de C R F C o m pleti o n G ui deli nes f or electr o ni c C R F (e C R F) data e ntr y. St u d y 
s pecific dat a ma na ge m e nt pr oce d ures will be mai ntai ne d i n t he data ma na ge me n t pla n. Q ueries 
res ulti n g fr o m e dit c hec ks a n d/ or data verificati o n pr oce d ures will be p oste d electr o nicall y i n t he 
e C R F. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 5  of 1 5 2  
8. 3.  
A c c e s s t o S o ur c e D at a   
T he i n vesti gat or will per mit t he s p o ns or’s re pres e ntati ves t o m o nit or t he st u d y as fre q u e ntl y as 
t he s p o ns or dee ms ne cessar y t o deter mi ne t hat pr ot oc ol a d here n ce a n d dat a rec or di n g are 
satisfact or y. A p pr o priate meas ures t o pr otect patie nt c o nfi de ntialit y are t o b e e m pl o ye d d uri n g 
m o nit ori n g. T he C R Fs a n d relate d s o urce d oc u m e nts will be re vie we d i n d etail b y t he m o nit or at 
eac h site visit. Ori gi nal s o urce d oc u m e nts or certifie d c o pies are nee de d f or re vie w. T his re vie w 
i ncl u des i ns pecti o n of data ac q uire d as a re q uire m e nt f or partici p ati o n i n t his st u d y a n d ot her 
me dical rec or ds as r e q uir e d t o c o nfir m t hat t he i nf or mati o n c o ntai ne d i n t he C R Fs, s uc h as 
disease assess me nts, A Es, a n d c o nc o mita nt me dicati o ns, is c o m plete a n d c orrect. Ot h er st u d y 
rec or ds, s u c h as c orres p o n de nce wit h t he s p o ns or a n d t he I R B/I E C a n d scree ni n g a n d dr u g 
acc o u nta bilit y l o gs will als o be i ns pecte d. All s o urce data a n d st u d y rec or ds m ust als o be 
a vaila ble f or i ns pecti o n b y re pres e ntati ves of re g ul at or y a ut h orities or a u dits b y s p o ns or a u dit ors.  
8. 4.  
A c c ur a c y a n d R eli a bilit y of D at a   
Ste ps t o be ta ke n t o ass ure t he acc urac y a n d relia bilit y of data i ncl u d e:  
● 
T he selecti o n of q u alifie d i n vesti gat ors a n d a p pr o priate st u d y ce nters.  
● 
Re vie w of pr ot oc ol pr oce d ures wit h t he i n vesti gat ors a n d ass ociat e d pers o n nel pri or t o 
t he st u d y. 
● 
Peri o dic m o nit ori n g visits b y t he desi g n ate d m o nit or(s).  
● 
C R Fs will be re vie we d f or acc urac y a n d c o m plet e ness b y t he desi g nate d m o nit or(s) 
d uri n g m o nit ori n g visits t o t he st u d y c e nters. A n y discre pa n cies will be res ol ve d wit h t he 
i n vesti gat or or d esi g nees as a p pr o priat e. 
8. 5.  
Q u alit y A s s ur a n c e Pr o c e d ur e s   
T he Researc h a n d De vel o p me nt Q ualit y ( R D Q) gr o u p or its  desi g n ee ma y c o n d uct a u dits at t he 
cli nical site or ot her st u d y-relate d facilities a n d or ga nizati o ns. A u dit re p orts will be retai ne d b y 
t he R D Q gr o u p of Sea ge n  as part of t he writte n rec or d.  
8. 6.  
D at a H a n dli n g a n d R e c or d K e e pi n g   
8. 6. 1.  
D at a H a n dli n g   
It is t he i n vesti gat or’s res p o nsi bilit y t o e ns ure t he acc urac y, c o m plete ness, l e gi bilit y, a n d 
ti meli ness of t he data re p orte d t o t he s p o ns or i n t he C R Fs a n d i n all re q uir e d re p orts. Dat a 
re p orte d o n t he C R F t h at is deri ve d fr o m s o urce d o c u me nts s h o ul d be c o nsiste nt wit h t he s o urce 
d oc u me nts or t he discre p a ncies s h o ul d be e x plai ne d.  
A n y c ha n ge or c orrecti o n t o a C R F will be mai ntai ne d i n a n a u dit trail wit hi n t he E D C s yste m. 
Data c h a n ges ma y o nl y b e ma de b y t h ose i n di vi d uals s o a ut h orize d. T he i n vesti gat or s h o ul d 
retai n rec or ds of t he c ha n ges a n d c orrecti o ns, writte n a n d/ or electr o nic. 
8. 6. 2.  
I n v e sti g at or R e c or d R et e nti o n  
T he i n vesti gat or s hall ret ai n st u d y dr u g dis p ositi o n rec or ds a n d all s o urce d oc u me ntati o n (s uc h 
as ori gi n al E C G traci n gs, la b orat or y re p orts, i n patie nt or office patie nt rec or ds) f or t h e ma xi m u m 
peri o d re q uir e d b y t he c o u ntr y a n d i nstit uti o n i n w hic h t he st u d y will be c o n d ucte d, or f or t he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 6  of 1 5 2  
peri o d s pecifie d b y Se a ge n , w hic he v er is l o n ger. T he i n vesti gat or m ust c o ntact Sea ge n  pri or t o 
destr o yi n g a n y rec or ds ass ociate d wit h t he st u d y. If t h e i n vesti gat or wit h dra ws fr o m t he st u d y 
( d ue t o rel oc ati o n, retire me nt, etc.), t he rec or ds s hall be tra nsferre d t o a m ut uall y a gree d u p o n 
desi g nee, s uc h as a n ot her i n vesti gat or or I R B/I E C. N otice of s uc h tr a nsfer will be pr o vi de d i n 
writi n g t o  Sea ge n . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 7  of 1 5 2  
9.  
D A T A  A N A L Y SI S M E T H O D S   
9. 1.  
D et er mi n ati o n of S a m pl e Si z e   
A p pr o xi matel y 1 8 9 -2 1 1 patie nts will be e nr olle d i n t his st u d y, of w hic h a p pr o xi matel y 
1 2 -2 4  patie nts will be e nr olle d i n Part A, a p pr o xi matel y 7 3 p atie nts will be e nr olle d i n Part  B 
(a p pr o xi matel y 4 8 i n C o h ort 1 a n d a p pr o xi matel y 2 5 i n C o h ort 2), a p pr o xi matel y 6 4  p atie nts will 
be e nr olle d i n Part C , a n d a ppr o xi matel y 4 0 patie nts will be e nr olle d i n Part D . 
9. 1. 1.  
P art A   
Part A will start wit h 6 patie nts at 2. 5  m g/ k g, ca p pe d at 8 0 k g pri or t o A m e n d me nt 2 or 1 0 0  k g 
u n der A me n d me nt 2 a n d la ter. If 2 or m ore patie nts e x perie nce a D L T, t he d ose le vel will be 
de -escalate d t o 2. 0  m g/ k g, ca p pe d at 8 0 k g pri or t o A me n d me nt 2 or 1 0 0  k g f or patie nts treate d 
u n der A me n d me nt 2 a n d later. If t here are < 2  patie nts e x perie nci n g D L Ts, t he d ose le vel will be 
e x pa n de d t o a t otal of 1 2 patie nts. If 4 or m ore p atie nts e x perie nce a D L T a m o n g t he 1 2  patie nts, 
t he d ose le vel will be de-escalate d t o 2. 0  m g/ k g, as descri be d a b o ve. If < 4 patie nts e x perie nce a 
D L T a m o n g t he 1 2  patie nts, Part B C o h ort 1 of t he st u d y m a y b e i nitiate d at 2. 5  m g/ k g, ca p pe d 
as descri be d a b o ve.  
If t he d ose le v el is re d uce d t o 2. 0 m g/ k g, t his d ose le vel will i nitiall y e nr oll 6 patie nts a n d t he 
sa me d ose de-escalati o n al g orit h m will be use d. If f urt her de -escalati o n is nee de d, t he d os e le vel 
will be deter mi ne d b y t he s p o ns or i n c o ns ultati o n wit h t he S M C.  
If t he tr ue i nci d e nce rate of D L T is 1 0 %, t he pr o ba bilit y of de-escalati o n t o 2. 0  m g/ k g is 1 2 %. 
T he pr o ba bilit y of de -escalati o n i ncreas es t o 9 6 % if t he tr ue i nci de n ce rate of D L T is 5 0 %.  
9. 1. 2.  
P art  B   
O nce t he M A D has bee n i de ntifie d i n Part A, p atie nts will be e nr olle d i n Part  B C o h ort 1 at t he 
M A D. A p pr o xi matel y 4 2 LI V -1 -p ositi ve patie nts i n t otal will be e nr olle d at t he M A D. Base d o n 
t he S G N L V A-0 0 1 p has e 1 st u d y, it is esti mate d t hat a b o ut 7 0 % of patie nts are LI V -1 -p ositi ve. 
A p pr o xi matel y 6 0 p atie nts are e x pecte d t o be e nr olle d at t he M A D, ass u mi n g t hat Part A will 
e nr oll 1 2 patie nts at t he M A D a n d a p pr o xi matel y 4 8 patie n ts are e x pecte d t o be e nr olle d i n 
Part  B C o h ort 1 at t he M A D. Ass u mi n g t he o bs er ve d O R R is bet wee n 5 0 % a n d 7 0 %, t he wi dt hs 
of 2 -si de d 9 5 % c o nfi de n ce i nter vals ( CIs) are s u m marize d as bel o w.  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 8  of 1 5 2  
 
Part B C o h ort 2 will e nr oll a p pr o xi matel y 2 5 p atie nts at 2. 0  m g/ k g. Wit h t he patie nts i n Part  A 
e nr olle d at 2. 0  m g/ k g, a p pr o xi matel y 3 0 p atie nts i n t otal will be e nr olle d at 2. 0  m g/ k g. Ass u mi n g 
t he o bser ve d O R R is bet wee n 5 0 % t o 7 0 %, t h e wi dt hs of 2-si de d 9 5 % CIs are s u m marize d as 
bel o w.  
C o nfir me d O R R  
E x pecte d wi dt h of 9 5 % CI o n all patie nts at 2. 0 m g/ k g  
( N = 3 0) 
5 0 %  
± 1 8 %  
6 0 %  
± 1 8 %  
7 0 %  
± 1 6 %  
9. 1. 3.  
P art C   
I n Part C, it is esti mate d t hat a p pr o xi matel y 4 t o 1 2 patie nts (ass u mi n g e val uati o n of 2 d ose 
le vels) will be treat e d i n d ose escal ati o n. O perati n g c h aracteristics of t he d ose escal ati o n desi g n, 
i ncl u di n g t he a v era ge n u m ber of patie nts all ocate d t o eac h d ose acr oss a v ariet y of t o xicit y 
sce nari os, are prese nte d i n t he si m ulati o n re p ort (A p pe n di x  M ). 
U p t o a p pr o xi matel y 6 4 patie nts ma y b e e nr olle d acr oss t he d ose escalati o n a n d e x pa nsi o n 
c o h orts i n Part  C  (ass u mi n g 2 patie nts i n eac h of t he d ose escalati o n c o h ort of  1. 0 a n d 
1. 2 5  m g/ k g,  a n d 6 0  patie nts i n t he e x pa nsi o n c o h ort  at t he selecte d d ose le vel  of 1. 2 5  m g/ k g ). 
Ta ble  9  s u m marizes t he 2-si de d 9 5 % e x act CI s a m o n g 6 2  patie nts at 1. 2 5 m g/ k g  ( 2 i n d ose 
escalati o n a n d 6 0 i n d ose e x pa nsi o n c o h ort)  ass u mi n g t he o bser ve d O R R is bet wee n 5 0 % a n d 
7 0 %.   
T a bl e  9 : 
2 -si d e d 9 5 % e x a ct c o nfi d e n c e i nt er v al s  f or P art C 
N u m ber of c o nfir me d 
O bj ecti ve Res p o nses  
C o nfir me d O R R ( %) 
9 5 % e xact CI  ( N =6 2 ) 
3 1  
5 0 %  
3 7 %, 6 3 %  
3 7  
6 0 %  
4 6 %, 7 2 %  
4 3  
6 9 %  
5 6 %, 8 0 %  
9. 1. 4.  
P art D   
A p pr o xi matel y 4 0 p atie nts will be e nr olle d i n Part D. O n g oi n g, real -ti me, c o nti n u o us re vie w of 
patie nt safet y a n d S A Es will be c o n d ucte d b y t he s p o ns or’s Dr u g Safet y De part me nt.  
A d diti o nall y, t he I S M C will e ns ure peri o dic s afet y dat a re vie w t hr o u g h o ut t he st u d y.  
Prese nte d i n t he ta ble b el o w are t he 2 -si de d 9 5 % e x act CIs a m o n g 4 0 patie nts at 1. 5  m g/ k g 
ass u mi n g t he o bser ve d O R R is bet wee n 5 0 % a n d 7 0 %.   
C o nfir me d O R R  
E x pecte d wi dt h of 9 5 % CI o n 
LI V -1 -p ositi ve patie nt s ( N = 4 2) 
E x pecte d wi dt h of 9 5 % CI o n all patie nts 
at t he M A D  ( N = 6 0) 
5 0 %  
± 1 6 %  
± 1 3 %  
6 0 %  
± 1 6 %  
± 1 3 %  
7 0 %  
± 1 5 %  
± 1 2 %  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 8 9  of 1 5 2  
T a bl e  1 0 : 
2 -si d e d 9 5 % e x a ct c o nfi d e n c e i nt er v al s f or P art D  
N u m ber of c o nfir me d 
O bj ecti ve Res p o nses  
C o nfir me d O R R( %)  
9 5 % e xact CI  
( N =4 0)  
2 0  
5 0 %  
3 4 %, 6 6 %  
2 4  
6 0 %  
4 3 %, 7 5 %  
2 8  
7 0 %  
5 3 %, 8 3 %  
 
T his sa m ple siz e of 4 0 patie nts w o ul d a d diti o nall y pr o vi de t he f oll o wi n g  pr o ba bilities of 
o bser vi n g at least 1 patie nt ha vi n g a n A E, as s u m marize d bel o w.   
Tr ue A E I nci de nce Rate  
Pr o ba bilit y of O bser vi n g at Le ast O ne   
P atie nt Ha vi n g a n A E  
( N =4 0)  
5 %  
8 7 %  
1 0 %  
9 9 %  
 
9. 2.  
St u d y E n d p oi nt D efi niti o n s   
St u d y e n d p oi nts are pres e nte d i n Secti o n 2 . Efficac y e n d p oi nt defi niti o ns are pres e nte d i n t his 
secti o n. 
9. 2. 1.  
O bj e cti v e R e s p o n s e R at e   
T he ke y efficac y e n d p oi nt of t his st u d y is c o nfir m e d O R R, defi ne d as t he pr o p orti o n of patie nts 
wit h c o nfir me d C R or P R, as deter mi ne d b y t he i n vesti gat or acc or di n g t o R E CI S T v 1. 1. Patie nts 
w h o d o n ot ha ve at least 2 (i nitial res p o nse a n d c o nfir mati o n sca n ) p ost-b aseli ne res p o nse 
assess me nts, as descri be d i n Secti o n 7. 2  of t he pr ot oc ol, will be c o u nte d as n o n -res p o n ders. 
E x pl orat or y a nal ysis of o bjec ti ve res p o nse will be base d o n i R E CI S T. 
9. 2. 2.  
D ur ati o n of R e s p o n s e   
D O R is defi ne d as t he ti me fr o m start of t he first d oc u me ntati o n of o bjecti ve res p o nse ( C R or P R 
t hat is s u bse q ue ntl y c o nfir me d), t o t he first d oc u m e ntati o n of disease pr o gressi o n ( per 
R E CI S T  v 1. 1 or per i n vesti gat or cl ai m of cli nical pr o gressi o n), or t o deat h d ue t o a n y ca us e, 
w hic he ver c o mes first.  
D O R data will be ce ns ore d as descri be d bel o w:  
● 
Patie nts w h o d o n ot ha ve P D a n d are still o n st u d y at t he ti me of a n a n al ysis will be 
ce ns ore d at t he date of t he last disease ass ess me nt d oc u me nti n g a bse nce of P D.  
● 
Patie nts w h o ha ve starte d a ne w a ntit u m or treat me nt pri or t o d oc u me ntati o n of P D will be 
ce ns ore d at t he date of t he  last disease ass ess me nt pri or t o t he start of a n e w t hera p y. 
N ote: Palliati ve ra di ot hera p y o n a n o n -tar get lesi o n t hat is n ot pr o gressi n g will n ot be 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 0  of 1 5 2  
c o nsi dere d a s u bse q ue nt a ntica ncer t hera p y; h o we ver, ra di ot hera p y o n a n y tar get lesi o n 
will be c o nsi dere d  s u bse q ue nt a ntica ncer t hera p y. 
● 
Patie nts w h o are re m o ve d fr o m t he st u d y pri or t o d oc u me ntati o n of P D will be ce ns ore d 
at t he date of t he l ast disease assess me nt d o c u me nti n g t he a bs e nce of P D.  
D O R will o nl y be calc ulate d f or patie nts a c hie vi n g a c o nfir me d C R or P R.  
A nal ysis of D O R will als o be perf or me d bas e d o n i R E CI S T g ui deli nes, wit h i D O R defi ne d as 
t he ti me fr o m first d oc u me ntati o n of o bjecti ve res p o nse (t hat is s u bse q ue ntl y c o nfir m e d) per 
i n vesti gat or t o t he first d oc u me ntati o n of o bjecti v e disease pr o gressi o n (t h at is s u bse q ue ntl y 
c o nfir me d), or t o deat h d ue t o a n y ca us e, w hic he v er c o mes first. Disease pr o gressi o n is 
c o nsi dere d t o be c o nfir m e d wit h o ut t he c o nfir mati o n sca n if patie nt has cli nical pr o gressi o n or 
bec o mes cli nicall y u nsta ble.  
9. 2. 3.  
Di s e a s e C o ntr ol R at e   
T he D C R is defi ne d as t h e pr o p orti o n of patie nts wit h C R, P R, or S D acc or di n g t o R E CI S T  v 1. 1. 
Patie nts w h o d o n ot ha ve p ost -baseli ne res p o ns e assess me nts as descri be d i n Secti o n  7. 2  of t he 
pr ot oc ol will be c o u nte d as n o n -res p o n d ers. 
A nal ysis of D C R will als o be perf or me d bas e d o n i R E CI S T g ui deli nes, wit h i D C R defi ne d as 
i C R + i P R + i S D. 
9. 2. 4.  
Pr o gr e s si o n -Fr e e S ur vi v al   
P F S is defi ne d as t he ti me fr o m start of st u d y treat me nt t o first d oc u me ntati o n of o bjecti ve 
pr o gressi o n of diseas e ( P D per R E CI S T  v 1. 1 or per i n vesti gat or clai m of cli nical pr o gressi o n), or 
t o 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 are e nr olle d b ut fail t o recei ve 
st u d y treat me nt, t he e nr oll me nt date will be use d as t he starti n g p oi nt i n t he calc ulati o n of P F S.  
T he sa me ce ns ori n g r ules o utli ne d i n Secti o n 9. 2. 2  f or D O R will be a p plie d t o P F S. Patie nts 
lac ki n g a n e v al uati o n of t u m or res p o nse after t heir first d ose will ha ve t heir e ve nt ti me ce ns ore d 
at Da y 1.  
A nal ysis of P F S will als o be perf or me d bas e d o n i R E CI S T g ui deli nes, wit h i P F S defi ne d as t he 
ti me fr o m start of st u d y treat me nt t o t he first d oc u me ntati o n of o bjecti ve disease pr o gressi o n 
(t hat is s ubse q ue ntl y c o nfir me d). T he d ate of pr o gressi o n is t he first date at w hic h pr o gressi o n 
criteria are met (i. e., t he date of u nc o nfir me d pr o gressi ve diseas e [i U P D]), pr o vi de d t hat 
c o nfir me d pr o gressi ve disease (i C P D) is esta blis h e d at t he ne xt assess me nt. Dis ease pr o gressi o n 
is c o nsi dere d t o be c o nfir me d wit h o ut t he c o nfir m ati o n sca n if patie nt has cli nical pr o gressi o n or 
bec o mes cli nicall y u nsta ble.  
9. 2. 5.  
O v er all S ur vi v al   
O S is defi ne d as  t he ti me fr o m start of st u d y treat me nt t o date of deat h d u e t o a n y ca use. I n t he 
a bse nce of deat h, s ur vi val ti me will be ce ns ore d at t he last date t he patie nt is k n o w n t o be ali ve. 
F or patie nts w h o e nr oll b ut fail t o recei ve st u d y tr eat me nt, t he e nr oll me n t d ates will be use d as 
t he starti n g p oi nts i n t he calc ulati o n of O S. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 1  of 1 5 2  
9. 3.  
St ati sti c al a n d A n al yti c al Pl a n s   
T he statistical a n d a nal ytical pla ns prese nt e d bel o w s u m marize t he m ore c o m plete pla ns t o be 
detaile d i n t he statistical a nal ysis pla n ( S A P). A c ha n ge t o t he data a nal ysis met h o ds descri be d i n 
t he pr ot oc ol will re q uire a pr ot oc ol a me n d me nt o nl y if it alters site c o n d u ct (e. g., a d di n g bas eli ne 
assess me nts t o defi ne a s u b gr o u p). T h e S A P will be fi nalize d pri or t o data base l oc k. A n y 
c ha n ges t o t he met h o ds d escri be d i n t he fi n al S A P will be descri be d a n d j ustifie d i n t he cli nical 
st u d y re p ort. 
9. 3. 1.  
G e n er al C o n si d er ati o n s   
I n ge neral, descri pti ve statistics will be prese nte d t hat i ncl u de t he n u m ber of o bser vati o ns, mea n, 
me dia n, sta n dar d de viati o n, mi ni m u m a n d ma xi m u m f or c o nti n u o us varia bles, a n d t he n u m ber 
a n d perce nta ges ( of n o n -missi n g) per cate g or y f or cate g ori cal varia bl es.  
T he 2 -si de d 9 5 % e x act CI usi n g Cl o p per-Pears o n met h o d (Cl o p per 1 9 3 4 ) will be calc ulate d f or 
t he res p o nse rates w h ere a p plica ble (e. g., O R R).  
F or ti me -t o-e v e nt e n d p oi nts, t he me dia n s ur vi val ti me will be esti mate d usi n g t he Ka pla n -M eier 
met h o d; t he ass ociate d 9 5 % CI will be calc ulat e d base d o n t he c o m ple me nt ar y l o g -l o g 
tra nsf or mati o n (C ollett 1 9 9 4 ). 
9. 3. 1. 1.  
R a n d o mi z ati o n a n d Bli n di n g   
T his is a si n gle ar m, o p e n -la bel st u d y. Bli n di n g will n ot be perf or me d. 
9. 3. 1. 2.  
A dj u st m e nt s f or C o v ari at e s   
A dj u st me nts f or c o variat es are n ot pla n n e d. 
9. 3. 1. 3.  
H a n dli n g of Dr o p o ut s a n d Mi s si n g D at a   
Missi n g data will n ot be i m p ute d, wit h t he e x ce pti o n of A E dates w hile cal c ulati n g d urati o n of 
e ve nts a n d treat me nt -e m er ge nt stat us; details will be pr o vi de d i n t he S A P. F or ti me -relate d 
e n d p oi nts, e. g., P F S, patie nts w h o ha ve n o s pecifi e d e ve nt will be ce ns ore d at t he ti me of t he last 
vali d assess me nt of t he e n d p oi nt(s).  
9. 3. 1. 4.  
M ulti c e nt er St u di e s   
T here are m ulti ple ce nt ers i n t his st u d y; h o we v er, it is n ot a ntici pate d t hat a n y ce nter will accr ue 
e n o u g h p atie nts t o warra nt a n a nal ysis b y ce nter.  
9. 3. 1. 5.  
M ulti pl e C o m p ari s o n s a n d M ulti pli cit y   
N o m ulti ple c o m paris o ns are pla n n e d a n d n o al p h a a dj ust me nt is nee de d.  
9. 3. 1. 6.  
D at a Tr a n sf or m ati o n s a n d D eri v ati o n s   
T i me varia bles bas e d o n 2 dates (e. g., start date a n d e n d date) will be calc ul ate d as (e n d date –  
start date + 1 [i n da ys]) u nless ot her wise s pecifie d i n t he pla n ne d a nal ysis s ecti o n.  
Baseli ne v al ues use d i n all statistical a nal yses will be t he m ost rece nt n o n -missi n g meas ure m e nt 
pri or t o t he first d ose of L V  u nless ot h er wise s pecifie d i n t he a nal ysis pla n.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 2  of 1 5 2  
9. 3. 1. 7.  
A n al y si s S et s   
T he all treate d a nal ysis s et i ncl u des all patie nts w h o recei v e a n y a m o u nt of L V or 
pe m br oliz u ma b . T he all treate d a nal ysis set will be use d as t he pri mar y dat aset f or efficac y 
a nal ysis.  
T he safet y a nal ysis set i ncl u des all patie nts w h o recei ve a n y a m o u nt of L V  or pe m br oliz u ma b. 
T he safet y a nal ysis set will be use d f or all safet y a n d P K a nal ys es. T his is als o calle d t he all 
treate d patie nts set f or efficac y a n al ys es. 
T he effi cac y -e v al ua ble ( E E) a nal ysis set i ncl u des all patie nts i n t he all treat e d a nal ysis set w h o 
ha d b ot h a baseli ne a n d at least o ne p ost -baseli ne disease assess me nt acc or di n g t o t he R E CI S T 
v 1. 1 a n d i R E CI S T criteria w he n a p plica ble, or w h o ha d cli nical diseas e pr o gressi o n per 
i n vesti gat or. 
T he D L T -e val ua ble ( D E) a nal ysis s et i ncl u des all treate d p atie nts i n Part A w h o eit her 
( 1) e x perie nce d a D L T or ( 2) recei ve d at least 7 5 % of i nte n de d L V  a n d p e m br oliz u ma b d oses 
a n d were f oll o we d f or t h e f ull D L T e val u ati o n peri o d. Patie nts will be re place d f or D L T 
e val uati o n if, f or reas o ns ot her t ha n D L T, t he y are i neli gi ble f or D L T e v al uati o n (e. g., 
pe m br oliz u ma b I R R Gra de ≥3, recei pt of pr o hi bite d c o nc o mita nt me dicati o n, t he y d o n ot meet 
eli gi bilit y criteria), or t he y d o n ot c o m plete t h e D L T e val uati o n peri o d.  
9. 3. 1. 8.  
E x a mi n ati o n of S u b gr o u p s   
As e x pl orat or y a nal yses, s u b gr o u p a nal yses ma y b e c o n d ucte d f or selecte d e n d p oi nts. S u b gr o u ps 
ma y i ncl u d e, b ut are n ot li mite d t o, t he f oll o wi n g:  
● 
A ge  
● 
Metastatic sites  
● 
LI V 1  e x pressi o n  
● 
Disease s u bt y pe  
9. 3. 2.  
Ti mi n g  of A n al y s e s   
T he pri mar y a n al ysis will be c o n d ucte d w h e n all treate d patie nts ha ve co m e off  st u d y. 
S u bse q ue nt c ut off dates ma y b e defi ne d a n d c orres p o n di n g data base l oc ks ma y o cc ur t o all o w 
f or m ore precise esti mates of ti me-t o-e ve nt e n d p oi nts.  
9. 3. 3.  
P ati e nt Di s p o siti o n   
A n acc o u nti n g of st u d y p atie nts b y dis p ositi o n will be ta b ulate d a n d t he n u m ber of patie nts  i n 
eac h a nal ysis set will be s u m marize d. Patie nts w h o disc o nti n ue st u d y treat me nt a n d patie nts w h o 
wit h dra w fr o m t he st u d y will be s u m marize d wit h reas o n f or disc o nti n uati o n or wit h dra wal.  
9. 3. 4.  
P ati e nt C h ar a ct eri sti c s   
De m o gra p hics a n d ot her baseli ne c haracteristics will be s u m marize d.  
9. 3. 5.  
Tr e at m e nt C o m pli a n c e   
T he d ose a d mi nistere d at eac h c ycle f or eac h treat me nt a ge nt will be assess e d a n d d ose i nte nsit y 
will be s u m mariz e d.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 3  of 1 5 2  
9. 3. 6.  
Effi c a c y A n al y s e s   
T he pri mar y a n al ysis of efficac y e n d p oi nts will be base d o n t he all treate d a nal ysis set . 
A d diti o nal a nal ysis of efficac y e n d p oi nts will  be p erf or me d usi n g t he E E a n al ysis set  as 
a p pr o priate. 
9. 3. 6. 1.  
Pri m ar y Effi c a c y A n al y s e s   
T he pri mar y effic ac y e n d p oi nt is t he c o nfir me d O R R per i n vesti gat or assess me nt. T he O R R is 
defi ne d as t he pr o p orti o n of patie nts wit h c o nfir m e d C R or P R acc or di n g t o R E CI S T  v 1. 1. 
Patie nts w h o d o n ot ha ve at least 2 p ost -baseli ne res p o nse assess me nts (i nitial res p o nse a n d 
c o nfir mati o n sca n) will be c o u nt e d as n o n -res p o n d ers. T he o bser ve d O R R a n d its c orres p o n di n g 
e x act 2 -si de d 9 5 % CI will be s u m marize d usi n g t he Cl o p per-Pears o n met h o d (Cl o p p er 1 9 3 4). 
9. 3. 6. 2.  
S e c o n d ar y Effi c a c y A n al y s e s   
T he D C R per R E CI S T v 1. 1 will be s u m marize d, a n d its e x act 2 -si de d 9 5 % CI usi n g t he Cl o p per-
Pears o n met h o d (Cl o p per 1 9 3 4 ) will be calc ulat e d.  
D O R, P F S per R E CI S T v 1. 1, a n d O S will be esti mate d usi n g Ka pla n -Mei er met h o d ol o g y, a n d 
Ka pla n -Mei er pl ots will be pr o vi de d. Me dia ns a n d 9 5 % CIs ma y b e calc ul ate d, as a p pr o priate.  
9. 3. 6. 3.  
A d diti o n al Effi c a c y A n al y s e s   
T he O R R a n d D C R per i R E CI S T will be s u m marize d, a n d t heir e x act 2 -si de d 9 5 % CIs usi n g t h e 
Cl o p per -Pears o n met h o d (Cl o p per 1 9 3 4 ) will be calc ulate d.  
D O R a n d P F S per i R E CI S T will be esti mate d usi n g Ka pla n -Mei er met h o d ol o g y, a n d Ka pla n -
Meier pl ots will be pr o vi de d. Me dia ns a n d 9 5 % CIs ma y b e calc ulate d, as a p pr o priate.  
9. 3. 7.  
P h ar m a c o ki n eti c a n d I m m u n o g e ni cit y A n al y s e s   
T otal A nti b o d y dr u g -c o nj u gate ( L V ) a n d u nc o nj u gat e d dr u g ( M M A E) c o n ce ntrati o ns will be 
s u m marize d wit h descri pti ve statistics at eac h P K sa m pli n g ti me p oi nt usi n g t he safet y a n al ysis 
set. Selecte d P K para met ers f or A D C (L V ) a n d M M A E will be esti mate d. Data ma y be 
c o m bi ned wit h P K data fr o m ot her cli nical trials wit h L V  f or p o p ulati o n P K a nal yses. 
T he i nci de nce of A T A will be s u m marize d usi n g t he safet y a nal ysis set.  
9. 3. 8.  
Bi o m ar k er A n al y s e s   
Relati o ns hi ps of bi o mar ker para meters (e. g., bas eli ne val ues, a bs ol ute a n d relati ve c ha n ges fr o m 
baseli ne) t o efficac y, safet y, a n d P K para meters will be e x pl ore d. Relati o ns hi ps a n d ass ociate d 
data t hat are deter mi ne d t o be of i nterest will be s u m marize d.  
9. 3. 9.  
S af et y A n al y s e s   
T he safet y a nal ysis set will be use d t o s u m marize all safet y e n d p oi nts.  
9. 3. 9. 1.  
E xt e nt of E x p o s ur e   
D urati o n of treat me nt, n u m ber of c ycl es, t otal d ose, a n d d ose i nte nsit y will be s u m marize d. D ose 
m o dificati o ns will als o be s u m mariz e d.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 4  of 1 5 2  
9. 3. 9. 2.  
A d v er s e E v e nt s   
A n o ver vie w of A Es will pr o vi de a ta b ulati o n of t he i nci de nce of all A Es, treat me nt -e mer ge nt 
A Es, treat me nt -relate d A Es, Gra de 3 a n d hi g her A Es, S A Es, treat me nt-rel ate d S A Es, deat hs, a n d 
A Es lea di n g t o st u d y tr eat me nt disc o nti n uati o n. A Es will be defi ne d as tr eat me nt e mer ge nt if 
t he y are n e wl y occ urri n g or w orse n f oll o wi n g st u d y treat me nt. 
A Es will be liste d a n d s u m mariz e d b y Me dical Di cti o nar y f or Re g ul at or y Acti vities ( Me d D R A), 
preferre d t er m, se verit y, a n d relati o ns hi p t o st u d y dr u g. I n t he e v e nt of m ulti ple occ urre nces of 
t he sa me A E wit h t he sa me preferre d ter m i n 1 patie nt, t he A E will be c o u nte d o nce as t he 
occ urre nce. T he i nci de n ce of A Es will be ta b ulate d b y preferre d t er m a n d treat me nt gr o u p. A Es 
lea di n g t o pr e mat ure disc o nti n uati o n of st u d y dr u g will be s u m marize d a n d liste d i n t he sa me 
ma n ner.  
9. 3. 9. 3.  
D e at h s a n d S eri o u s A d v er s e E v e nt s   
S A Es will be liste d a n d s u m mariz e d i n t he sa me ma n ner as all A Es. E ve nts wit h a fatal o utc o me 
will be liste d.  
9. 3. 9. 4.  
Cli ni c al L a b or at or y R e s ult s   
La b orat or y v al ues (e. g., c he mistr y, he m at ol o g y, a n d p ul m o nar y f u ncti o n tests) ma y b e pres e nte d 
gra p hicall y b y visit. S u m mar y st atistics ma y b e ta b ulate d as a p pr o pr iate b y sc he d ule d visit. 
La b orat or y v al ues will be liste d wit h gra de per N CI C T C A E v 4. 0 3 a n d fla g ge d w he n val u es are 
o utsi de t he n or mal refere nce ra n ge.  
9. 3. 9. 5.  
Ot h er S af et y A n al y s e s   
Vit al  Si g ns   
Vital si g ns (res pirat or y rate, p ulse rat e, s yst olic a n d diast olic bl o o d press ure w hile t he patie nt is 
i n a seate d p ositi o n, p ulse o xi metr y, a n d te m perat ure) will be liste d for eac h vital si g n b y 
sc he d ule d visit. S u m mar y statistics a n d c h a n ge fr o m baseli ne a n d/ or pre d ose t o p ost d ose ma y b e 
ta b ulate d w here a p pr o pri ate. 
E C O G St at us   
E C O G stat us will be s u m marize d f or Baseli ne/ Da y 1 a n d E O T. S hifts fr o m baseli ne t o t he best 
a n d w orst p ost baseli ne sc ore ma y be ta b ul ate d.  
E C G   
E C G stat us ( n or mal, a b n or mal cli nicall y si g nifica nt, or a b n or mal n ot cli nicall y si g nifica nt) m a y 
be s u m mariz e d f or eac h s c he d ule d E C G a n d  s hifts fr o m baseli ne ma y b e ta b ulate d. 
9. 3. 9. 6.  
I nt eri m A n al y s e s  
N o f or mal i nteri m a nal ys es are pl a n ne d. A n S M C will peri o dicall y m o nit or t he trial f or safet y. 
T he S M C will re vie w e x pe dite d S A Es as t he y are recei v e d. F urt her det ails will be pr o vi de d i n 
t he S M C C harter. I n a d diti o n t o t he S M C, a n I S M C c o m p ose d of p h ysi cia ns w h o are n ot 
i n v ol ve d i n t his st u d y, as well as sp o ns or re prese nt ati ves,  will peri o dicall y re vie w c u m ulati ve 
safet y data a n d pr o vi de rec o m me n dati o ns t o t he s p o ns or. F urt her details will be pr o vi de d i n t he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 5  of 1 5 2  
I S M C C harter. I nteri m d ata fr o m t he st u d y ma y b e prese nt e d at scie ntific meeti n gs s uc h as t he 
a n n ual meeti n g of t he A S C O.  
C o nti n u o us m o nit ori n g of t he be nefit -ris k pr ofile will be c o n d ucte d a n d c o nti n uati o n of 
e nr oll me nt t o t he c o h ort ma y b e altere d de pe n di n g o n t he be nefit -ris k pr ofile. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 6  of 1 5 2  
1 0.  
I N F O R M E D C O N S E N T, E THI C A L R E VI E W, A N D R E G U L A T O R Y 
C O N SI D E R A TI O N S   
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 N ote f or G ui da nce o n G o o d Cli nical 
Practice (I C H Har m o nise d Tri partite G ui deli ne E 6 [ R 2]; F D A C F R [ 2 1 C F R § 5 0, 5 6, 3 1 2]), 
De clarati o n of Helsi n ki ( Brazil, 2 0 1 5), a n d all a p plica ble re g ulat or y re q uir e me nts.  
1 0. 1.  
I nf or m e d C o n s e nt  
T he i n vesti gat or is res p o nsi ble f or pres e nti n g t he ris ks a n d be nefits of st u d y partici pati o n t o t he 
patie nt i n si m ple ter ms usi n g t he I R B/I E C a p pr o v e d i nf or me d c o ns e nt d oc u me nt a n d f or 
e ns uri n g p atie nts are re -c o nse nte d w he n t he i nf or me d c o nse nt d oc u me nt is u p date d d uri n g t he 
st u d y, if re q uire d. T he i n vesti gat or will e ns ure t hat writte n i nf or me d c o nse nt is o btai ne d fr o m 
eac h p atie nt if t he y are a ble, or fr o m a L A R, if a p plica ble t o t his st u d y, b y o btai ni n g t he 
si g nat ur e a n d dat e o n t he i nf or me d c o nse nt d oc u m e nt pri or t o t he perf or ma nce of pr ot o c ol 
e val uati o ns or pr oce d ures.  
If i nf or med c o nse nt is o btai ne d fr o m a L A R re prese ntati ve f or a p atie nt w h o is u na ble t o pr o vi de 
i nf or me d c o nse nt at st u d y e ntr y (if a p plica ble), b ut t he patie nt is later a ble t o pr o vi de i nf or me d 
c o nse nt, t he i n vesti gat or m ust o btai n writte n i nf or me d c o nse nt fr o m t h e p atie nt.  
1 0. 2.  
Et hi c al R e vi e w   
T he i n vesti gat or will pr o vi de t he s p o ns or or its desi g nee wit h d oc u me ntati o n of t he I R B/I E C 
a p pr o val of t he pr ot oc ol a n d t he i nf or me d c o nse nt d oc u me nt b ef ore t he st u d y ma y b e gi n at t he 
i n vesti gati ve site(s). T he na me a n d a d dress of t he re vie wi n g et hics c o m mittee are pr o vi de d i n t he 
i n vesti gat or file. 
T he i n vesti gat or will s u p pl y t he f oll o wi n g t o t he i n vesti gati ve site’s I R B/I E C:  
● 
Pr ot oc ol a n d a me n d me nts  
● 
I nf or me d c o ns e nt d oc u m e nt a n d u p dates 
● 
Cli nical I B a n d u p dat es  
● 
Rele va nt c urri c ula vitae, if re q uire d  
● 
Re q uire d safet y a n d S A E re p orts  
● 
A n y a d diti o nal s u b missi o ns re q uire d b y t he site’s I R B/I E C  
 
T he i n vesti gat or m ust pr o vi de t he f oll o wi n g d o c u me ntati o n t o t he s p o ns or or its desi g nee:  
● 
T he I R B/I E C peri o dic (e. g., q uarterl y, a n n u al) re -a p pr o val of t he pr ot oc ol.  
● 
T he I R B/I E C a p pr o vals of a n y a me n d me nts t o t h e pr ot oc ol or re visi o ns t o t he i nf or me d 
c o nse nt d oc u me nt.  
● 
T he I R B/I E C r ecei pt of safet y a n d S A E re p orts, as a p pr o priate.  
1 0. 3.  
R e g ul at or y C o n si d er ati o n s   
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 et hical pri nci ples state d i n t he 
a p plica ble g ui deli nes o n g o o d cli nic al practi ce, a n d all a p plica ble l ocal a n d/ or re gi o nal la ws, 
r ules, a n d re g ulati o ns. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 7  of 1 5 2  
1 0. 3. 1.  
I n v e sti g at or I nf or m ati o n  
T he c o ntact i nf or mati o n a n d q ualificati o ns of t he pri nci pal i n vesti gat or a n d s u bi n vesti gat ors a n d 
na me a n d a d dress of t he researc h facilities are i n cl u de d i n t he i n vesti gat or file.  
1 0. 3. 2.  
Pr ot o c ol A m e n d m e nt s a n d St u d y T er mi n ati o n   
A n y i n vesti gat or -i nitiate d c ha n ges t o t he pr ot o c ol ( wit h t he e x ce pti o n of c ha n ges t o eli mi nate a n 
i m me diate hazar d t o a st u d y patie nt) m ust be a p pr o ve d b y t h e s p o ns or pri or t o see ki n g a p pr o val 
fr o m t he I R B/I E C, a n d pri or t o i m ple me nti n g. T h e i n vesti gat or is res p o nsi ble f or e nr olli n g 
pati e nts w h o ha ve met pr ot oc ol eli gi bilit y criteria. Pr ot oc ol de viati o ns m ust be re p ort e d t o t he 
s p o ns or a n d t he l ocal I R B/I E C i n acc or da n ce wit h I R B/I E C p olicies.  
T he s p o ns or ma y ter mi nate t he st u d y at a n y ti me. T he I R B/I E C m ust be a d vise d i n writi n g of 
st u d y c o m pleti o n or earl y ter mi nati o n.  
1 0. 4.  
St u d y D o c u m e nt ati o n, Pri v a c y, a n d R e c or d s R et e nti o n   
T o pr otect t he safet y of partici pa nts i n t he st u d y a n d t o e ns ure acc urate, c o m plete, a n d relia ble 
data, t he i n vesti gat or will kee p rec or ds of l a b orat or y tests, cli nical n otes, a n d patie nt me dical 
rec or ds i n t he p atie nt files as ori gi n al s o urce d o c u me nts f or t he st u d y. If re q ueste d, t he 
i n vesti gat or will pr o vi de t he s p o ns or, its lice nsees a n d colla b orat ors, a p plica ble re g ulat or y 
a ge ncies, a n d a p plica bl e I R B/I E C wit h direct access t o ori gi nal s o urce d oc u me nts or certifie d 
c o pies. 
Rec or ds c o ntai ni n g patie nt me dical i nf or mati o n m ust be ha n dle d i n acc or da nce wit h l ocal a n d 
nati o nal la ws, r ules, a n d re g ulati o ns a n d c o nsiste nt wit h t he ter ms of t he patie nt a ut h orizati o n 
c o ntai ne d i n t he i nf or me d c o nse nt d oc u me nt f or t he st u d y (t h e A ut h orizati o n). Care s h o ul d be 
ta ke n t o e ns ure t h at s uc h rec or ds are n ot s h are d wit h a n y p ers o n or f or a n y p ur p ose n ot 
c o nte m plate d b y t he A ut h orizati o n. F urt her m ore, C R Fs a n d ot her d oc u me nts t o be tra nsferre d t o 
t he s p o ns or s h o ul d be c o m plete d i n strict acc or da nce wit h t he i nstr ucti o ns pr o vi de d b y t he 
s p o ns or, i ncl u di n g t he i nstr ucti o ns re gar di n g t he c o di n g of patie nt i de ntit ies. 
I n c o m plia nce wit h l ocal a n d/ or re gi o nal re g ulati o ns, t his trial ma y be re gistere d a n d tri al res ults 
ma y b e p oste d o n p u blic re gistries, s uc h as Cli nical Trials. g o v.  
1 0. 5.  
Cli ni c al Tri al A gr e e m e nt   
Pa y me nts b y t he s p o ns or t o i n vesti gat ors a n d i nstit uti o ns c o n d ucti n g t he trial, re q uire me nts f or 
i n vesti gat ors’ i ns ur a nce, t he p u blicati o n p olic y f or cli nical trial data, a n d ot her re q uir e me nts are 
s pecifie d i n t he cli nical trial a gree m e nt. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 8  of 1 5 2  
1 1.  
R E F E R E N C E S   
A merica n Ca n cer S oci et y H o w c o m m o n is breast ca ncer? 2 0 1 7. 
htt ps:// w w w.ca ncer. or g/c a ncer/ breast -ca n cer/a b o ut/ h o w -c o m m o n-is-breast -ca ncer. ht ml  
Access e d: Ma y 2 2, 2 0 1 7.  
 
A na nt ha kris h na n R, Gree n S, C ha n g M, et al. S yste matic c o m paris o n of t h e statistical o perati n g 
c haracteristics of v ari o us p hase I o nc ol o g y d esi g ns. C o nte m p Cli n Trials C o m m u n. 
2 0 1 7; 5: 3 4 -4 8.  
 
Beera m M, Kr o p I E, B urris H A, et al. A p has e 1 st u d y of wee kl y d o si n g of trast uz u ma b 
e mta nsi ne ( T -D M 1) i n patie nts wit h a d va nce d h u ma n e pi der mal gr o wt h fact or 2 -p ositi ve 
breast c a ncer. Ca ncer. 2 0 1 2; 1 1 8( 2 3): 5 7 3 3 -4 0.  
 
Bla n k C, Br o w n I, Peters o n A C, et al. P D -L 1/ B 7 H -1 i n hi bits t he effect or p h ase of t u m or 
rejecti o n b y T cell rece pt or ( T C R) tra ns ge nic C D 8 + T cells. Ca ncer Res. 
2 0 0 4; 6 4( 3): 1 1 4 0 -5.  
 
B urstei n HJ. I ntr o d u cti o n: C urre nt a n d f ut ure a p pr oac hes t o c h e m ot hera p y i n patie nts wit h 
resista nt breast c a ncer. S e mi n O nc ol. 2 0 1 1; 3 8 S u p pl 2: S 1-2.  
 
Ca o A T, La w C L, G ar dai SJ, Heis er R A. Bre nt u xi ma b ve d oti n -dri ve n i m m u n o ge ni c cell deat h 
e n ha nces a ntit u m or i m m u ne res p o nses, a n d is p ote ntiate d b y P D 1 i n hi biti o n i n vi v o. 
Ca ncer Res. 2 0 1 7; 7 7( 1 3 s u p pl): A bstract 5 5 8 8.  
 
Carls o n R W, Allre d D C, A n ders o n B O, et al. I n v asi ve breast c a ncer. J N atl C o m pr Ca nc Net w. 
2 0 1 1; 9( 2): 1 3 6 -2 2 2.  
 
C he m nitz J M, Parr y R V, Nic h ols K E, J u ne C H, Rile y J L. S H P -1 a n d S H P -2 ass ociate wit h 
i m m u n orece pt or t yr osi ne-base d s witc h m otif of pr o gra m me d deat h 1 u p o n pri mar y 
h u ma n T cell sti m ulati o n, b ut o nl y rece pt or li gati o n  pre ve nts T cell acti vati o n. J 
I m m u n ol. 2 0 0 4; 1 7 3( 2): 9 4 5-5 4.  
 
Cl o p per CJ, Pears o n E S. T he use of c o nfi de nce or fi d ucial li mits ill ustrate d i n t he case of t h e 
bi n o mial. Bi o metri ka. 1 9 3 4; 2 6( 4): 4 0 4 -1 3.  
 
C ollett D. I nter v al -ce ns ore d s ur vi val data. M o d elli n g s ur vi val dat a i n me dical res earc h. L o n d o n, 
C ha p ma n & H all. 1 9 9 4: 2 3 7 -5 1.  
 
C ortes J, Dieras V, L ore n ze n S, et al. Efficac y a n d safet y of trast uz u ma b e mta nsi ne pl us 
ca pecita bi ne vs trast uz u ma b e mta nsi ne al o ne i n p atie nts wit h pre vi o usl y tr eate d E R B B 2 
( H E R 2)-p ositi ve metastatic breast c a ncer: a p hase 1 a n d ra n d o mize d p hase 2 trial. J A M A 
O nc ol. 2 0 2 0; 6( 8): 1 2 0 3 -9.  
 
Cra wf or d J, Caserta C, R oila F. He mat o p oietic gr o wt h fact ors: E S M O Cli nical Practice 
G ui deli nes f or t he a p plicati o ns. A n n O nc ol. 2 0 1 0; 2 1 S u p pl 5: v 2 4 8 -5 1.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 9 9  of 1 5 2  
C urra n M A, M o ntal v o W, Ya gita H, Allis o n J P. P D -1 a n d C T L A -4 c o m bi nati o n bl oc ka de 
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2 0 1 3( 1 2): C D 0 0 8 7 9 2.  
 
de n Br o k W D, S peers C H, G o n dara L, et al. S ur vi val wit h metastatic breast ca ncer base d o n 
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5 6.  
 
Diefe n bac h C S, C o n n ors J M, Frie d ber g J W, et al. H o d g ki n l y m p h o ma: c urre nt stat us a n d cli nical 
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Dress ma n M A, Walz T M, La v e da n C, et al. Ge nes t hat c o -cl uster wit h estr o ge n rece pt or al p h a i n 
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D u dle y M E, W u n derlic h  J R, Ya n g J C, et al. A d o pti ve cell tra nsfer t hera p y f oll o wi n g n o n-
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D u p o nt W D, Pa ge D L. Ris k fact ors f or bre ast ca n cer i n w o me n wit h pr oliferati ve breast diseas e. 
N E n gl J Me d. 1 9 8 5; 3 1 2( 3): 1 4 6 -5 1.  
 
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 o urs: 
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S u p pl): A bstract P 3 -1 4 -0 5.  
 
Fra n cisc o L M, Sa ge P T, S har pe A H. T h e P D -1 pat h wa y i n t olera nce a n d a ut oi m m u nit y. 
I m m u n ol Re v. 2 0 1 0; 2 3 6: 2 1 9-4 2.  
 
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2 0 1 5; 7 5( 1 5 S u p pl): A bstract 2 4 6 9.  
 
Garri d o -La g u na I, Kr o p I, B urris H A, 3r d, et al. First -i n-h u ma n,  p hase I st u d y of P F -0 6 6 4 7 2 6 3, 
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O nc ol. 1 9 9 6; 1 4( 8): 2 1 9 7 -2 0 5.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 0  of 1 5 2  
Gree n wal d RJ, Free ma n GJ, S har pe A H. T he B 7 fa mil y re visite d. A n n u Re v I m m u n ol. 
2 0 0 5; 2 3: 5 1 5 -4 8.  
 
Hel wic k C. T N T trial s u p p orts plati n u ms i n B R C A -m ut ate d breast ca n cer. T he A S C O P ost. 
htt p:// w w w.asc o p ost.c o m/iss ues/fe br uar y -2 5 -2 0 1 5/t nt -trial-s u p p orts-plati n u ms -i n-brca -
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Hira n o F, Ka ne k o K, Ta m ura H, et al. Bl oc ka d e of B 7 -H 1 a n d P D -1 b y m o n ocl o nal a nti b o dies 
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H o wla der N, N o o ne A M, Kra pc h o M, G ars hell J, Ne y m a n N, Alte kr use S F, K osar y C L, Y u M, 
R u hl J, Tatal o vic h Z, C h o H, Mari ott o A, Le wis D R, C he n H S, Fe uer EJ, Cr o ni n K A 
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M D ba se d o n N o ve m b er 2 0 1 2 S E E R data s u b missi o n, p oste d t o t he S E E R we b site, 
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L o n gle y D B, J o h nst o n P G. M olec ular mec ha nis ms of dr u g resista nce. J Pat h ol. 2 0 0 5; 2 0 5( 2): 2 7 5 -
9 2.  
 
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a 4. 4 k b m R N A i n t he Z R -7 5 -1 h u ma n breast ca n cer cell li ne. M ol Cell E n d ocri n ol. 
1 9 8 8; 5 9( 3): 2 0 5 -1 2.  
 
Ma n ni n g D L, R o b erts o n J F, Ellis I O, et al. Oestr o ge n -re g ul ate d ge n es i n breast ca n cer: 
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M o di S, P usztai L, F orer o A, et al. P hase 1 st u d y of t he a nti b o d y -dr u g c o nj u gat e S G N -LI V 1 A i n 
patie nts wit h hea vil y pretreate d tri ple -ne gati ve m etastatic breast c a ncer. Pr ocee di n gs of 
t he 2 0 1 7 Sa n A nt o ni o Breast Ca ncer S y m p osi u m. 2 0 1 7: A bstract P D 3 -1 4.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 1  of 1 5 2  
N o mi T, S h o M, A ka h ori T, et al. Cli nical si g nifica nce a n d t hera p e utic p ote ntial of t he 
pr o gra m me d deat h -1 li ga n d/ pr o gra m me d deat h -1 pat h wa y i n h u ma n pa n creatic ca ncer. 
Cli n Ca ncer Res. 2 0 0 7 ; 1 3( 7): 2 1 5 1-7.  
 
O' S ha u g h n ess y J. E xte n di n g s ur vi val wit h c h e m ot hera p y i n metastatic breast ca ncer. O nc ol o gist. 
2 0 0 5; 1 0 S u p pl 3: 2 0 -9.  
 
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rece pt or-me diate d si g n ali n g b y r ecr uiti n g src h o m ol o g y 2 -d o mai n -c o ntai ni n g t yr osi ne 
p h os p hatase 2 t o p h os p h ot yr osi ne. Pr oc Natl Aca d Sci U S A. 2 0 0 1; 9 8( 2 4): 1 3 8 6 6 -7 1.  
 
Parr y R V, C he m nitz J M, Fra u wirt h K A, et al. C T L A -4 a n d P D -1 rece pt ors i n hi bit T -cell 
acti vati o n b y disti nct me c ha nis ms. M ol  Cell Bi ol. 2 0 0 5; 2 5( 2 1): 9 5 4 3 -5 3.  
 
Pil o n -T h o mas S, Mac ka y A, V o hra N, M ule JJ. Bl oc ka de of pr o gra m me d d eat h li ga n d 1 
e n ha nces t he t hera pe utic effic ac y of c o m bi nati o n i m m u n ot hera p y a gai nst m ela n o ma. J 
I m m u n ol. 2 0 1 0; 1 8 4( 7): 3 4 4 2-9.  
 
Re u be n A. H y's la w. He p at ol o g y. 2 0 0 4; 3 9( 2): 5 7 4 -8.  
 
Rile y J L. P D -1 si g nali n g i n pri mar y T cells. I m m u n ol Re v. 2 0 0 9; 2 2 9( 1): 1 1 4 -2 5.  
 
Ri vera E. Ma na ge me nt of metastatic breast ca n cer: m o n ot hera p y o pti o ns f or patie nts resista nt t o 
a nt hrac ycli n es a n d ta x a n es. A m J Cli n O nc ol. 2 0 1 0; 3 3( 2): 1 7 6 -8 5.  
 
R o dler E, K or de L, Gral o w J. C urre nt treat me nt o pti o ns i n tri ple ne gati ve breast ca n cer. Breast 
Dis. 2 0 1 0; 3 2( 1 -2): 9 9 -1 2 2.  
 
R ose n ber g J E, H off ma n -Ce nsits J, P o wles T, et al. Atez oliz u ma b i n patie nts wit h l ocall y 
a d va nce d a n d metastatic ur ot helial ca rci n o ma w h o ha ve pr o gresse d f oll o wi n g treat me nt 
wit h plati n u m -base d c he m ot hera p y: a si n gle -ar m, m ultice ntre, p hase 2 trial. La n cet. 
2 0 1 6; 3 8 7( 1 0 0 3 1): 1 9 0 9 -2 0.  
 
R u g o H S, Barr y W T, M ore n o -As pitia A, et al. Ra n d o mize d p hase III trial of paclita xel o nce per 
wee k  c o m p are d wit h na n o particle al b u mi n -b o u n d na b -paclita xel o nce p er wee k or 
i x a be pil o ne wit h be vaciz u ma b as first-li ne c h e m ot hera p y f or l ocall y rec urre nt or 
metastatic breast ca ncer: C A L G B 4 0 5 0 2/ N C C T G N 0 6 3 H ( Allia nce). J Cli n O nc ol. 
2 0 1 5; 3 3( 2 1): 2 3 6 1 -9.  
 
Sc h m i d P, A da ms S, R u g o H S, et al. Atez oliz u ma b a n d na b-paclita xel i n a d va nce d tri ple -
ne gati ve breast ca n cer. N E n gl J Me d. 2 0 1 8; 3 7 9( 2 2): 2 1 0 8 -2 1.  
 
Sc h mi d P, Cr uz C, Braite h F S, et al. Atez oliz u ma b i n metastatic T N B C ( m T N B C): l o n g -ter m 
cli nical o utc o mes a n d bi o mar ker a nal yses. Ca ncer Res. 2 0 1 7; 7 7( S u p pl 1 3): A bstract 2 9 8 6.  
 
Se y m o ur L, B o gaerts J, Perr o ne A, et al. i R E CI S T: g ui deli nes f or res p o ns e criteria f or us e i n 
trials testi n g i m m u n ot hera pe utics. La n cet O nc ol. 2 0 1 7; 1 8( 3):e 1 4 3 -5 2.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 2  of 1 5 2  
S he p par d K A, Fitz LJ, Lee J M, et al. P D -1 i n hi bits T -cell rece pt or i n d uce d p h os p h or ylati o n of 
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2 0 0 4; 5 7 4( 1 -3): 3 7 -4 1.  
 
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 merica n S ociet y of Cli nical O nc ol o g y Cli nical Practice G ui deli ne U p dat e. J Cli n O nc ol. 
2 0 1 5; 3 3( 2 8): 3 1 9 9 -2 1 2.  
 
S pra n ger S, K o blis h H K, H ort o n B, et al. Mec ha nis m of t u m or rejecti o n wit h d o u blets of C T L A -
4, P D -1/ P D -L 1, or I D O bl oc ka de i n v ol ves rest ore d I L -2 pr o d ucti o n a n d pr oliferati o n of 
C D 8( +) T cells directl y wit hi n t he t u m or micr oe n vir o n me nt. J I m m u n ot her Ca ncer. 
2 0 1 4; 2: 3.  
 
Str o me S E, D o n g H, Ta m ura H, et al. B 7 -H 1 bl o c ka de a u g me nts a d o pti ve T -cell i m m u n ot hera p y 
f or s q ua m o us cell carci n o ma. Ca ncer Res. 2 0 0 3; 6 3( 1 9): 6 5 0 1 -5.  
 
S uss ma n D, S mit h L M, A n ders o n M E, et al. S G N -LI V 1 A: a n o vel a nti b o d y -dr u g c o nj u gate 
tar geti n g LI V-1 f or t he treat me nt of metastatic breast ca ncer. M ol Ca ncer T her. 
2 0 1 4; 1 3( 1 2): 2 9 9 1 -3 0 0 0.  
 
Ta yl or K M, M or ga n H E, J o h ns o n A, Ha dle y LJ, Nic h ols o n RI. Str uct ur e -f u ncti o n a nal ysis of 
LI V -1, t he breast c a ncer -ass ociate d pr otei n t hat b el o n gs t o a ne w s u bfa mil y of zi nc 
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T h uss -Patie nce P C, S ha h M A, O hts u A, et al. Trast uz u ma b e mta nsi ne vers us ta xa ne use f or 
pre vi o usl y tr eate d H E R 2 -p ositi ve l ocall y a d va nce d or metastatic gastric or gastr o -
oes o p ha geal j u ncti o n a d e n ocarci n o ma ( G A T S B Y): a n i nter nati o nal ra n d o mise d, o pe n -
la bel, a da pti ve, p h ase 2/ 3 st u d y. La n cet O nc ol. 2 0 1 7; 1 8( 5): 6 4 0-5 3.  
 
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rece pt or al p ha i n breast t u m or bi o ps y s peci me ns, usi n g a lar ge-s cale real-ti me re verse 
tra nscri pti o n-P C R a p pr oac h. E n d ocr Relat Ca ncer. 2 0 0 6; 1 3( 4): 1 1 0 9 -2 0.  
 
U n n o J, Sat o h K, Hir ota M, et al. LI V -1 e n ha nces t he a g gressi ve p h e n ot y p e t hr o u g h t he 
i n d ucti o n of e pit helial t o mese nc h y mal tra nsiti o n i n h u ma n pa ncreatic carci n o ma cells. 
I nt J O nc ol. 2 0 0 9; 3 5( 4): 8 1 3-2 1.  
 
We ber J. I m m u ne c hec k p oi nt pr otei ns: a ne w t hera pe utic para di g m f or ca n cer --precli nical 
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fact or rece pt or 2 testi n g i n breast c a ncer: A merica n S ociet y of Cli nical O n c ol o g y/ C olle ge 
of A meric a n Pat h ol o gists cli nical practice g ui deli n e u p date. Arc h Pat h ol La b Me d. 
2 0 1 4; 1 3 8( 2): 2 4 1 -5 6.  
 
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2 2 0 6 i n patie nts wit h a d va nce d s oli d t u m ors. J Cli n O nc ol. 2 0 1 1; 2 9( 3 5): 4 6 8 8 -9 5.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 3  of 1 5 2  
Z ha n g X, Sc h wartz J C, G u o X, et al. Str uct ural a n d f u ncti o nal a nal ysis of t he c osti m ulat or y 
rece pt or pr o gra m me d deat h-1. I m m u nit y. 2 0 0 4; 2 0( 3): 3 3 7 -4 7.  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 4  of 1 5 2  
A P P E N DI X  A:  
S C H E D U L E O F E V E N T S ( Q 3 W K L V  D O SI N G; P A R T S A A N D  B)   
Visit Wi n d o w  
Baseli ne/ Scree ni n g  E nr oll me nt  
2 1 -da y C ycle  
E O T  
F oll o w -u p  
D 1  
D 5  
D 8  
D 1 5  
D – 2 8 t o 
1  
D – 7 t o 
1  
D – 7 t o 1  
See f o ot n otes f or 
wi n d o w  
D 4 – 7  
± 2 d  
± 2 d  
3 0 – 3 7 da ys 
p ost last 
d ose  
E ver y 6 wee ks ±  1 
wee k B (u nless 
ot her wise state d)  
Baseli ne a n d Safet y 
Assess me nts  
Inf or me d c o nse nt 
X  
 
Eli gi bilit y d oc u me ntati o n s u b mitte d t o  
s p o ns or pri or t o st u d y start 
 
 
 
 
 
 
Incl usi o n/e xcl usi o n 
X  
 
 
 
 
 
 
 
Me dical hist or y  
X  
  
 
 
 
 
 
 
P h ysical E xa m  
 
X  
X A, R  
 
 
 
X  
X  
Hei g ht ( baseli ne o nl y) a n d Wei g ht  
 
X  
X A, R  
 
 
 
 
 
Vital si g ns C  
 
X  
X  
 
 
 
 
 
Brai n C T or M RI  
X  
 
 
 
 
 
 
 
Initiate c ollecti o n of arc hi ve d t u m or 
s peci me n  
(if a vaila ble)O  
X  
 
 
 
 
 
 
 
Fres hl y o btai ne d bi o ps y D, O (see als o 
Ap pe n di x  E ) 
X  
 
 
X E  
 
X E  
X F  
 
E C G  
X  
 
 
 
 
 
 
 
Pre g na nc y test ( perf or me d l ocall y)  
( patie nts of c hil d beari n g p ote ntial o nl y) 
 
X G  
X G  
 
 
 
X  
 
E C O G perf or ma nce stat us 
 
X  
X A, R  
 
 
 
X  
 
He patitis B a n d C scree ni n g S  
X  
 
 
 
 
 
 
 
C B C wit h differe ntial O  
 
X  
X A, R  
 
X Q  
 
X  
 
P T/ P T T/a P T T/I N R  
X  
 
 
 
 
 
 
 
H b A1c I,S 
X  
 
 
 
 
 
X  
 
Fasti n g bl o o d gl uc ose H ,S 
X  
 
 
 
 
 
 
 
Ser u m c he mistr y pa nel O ,S 
 
X  
X A, I,R  
 
X Q  
 
X  
 
T h yr oi d f u ncti o n  testsJ,S 
X  
 
 
O n Da y 1 R  of eac h o d d -n u m bere d c ycle while o n treat me nt  
(e. g., Da y 1 of C ycles 1, 3, 5, 7, etc) 
 
 
C o nc o mita nt me dicati o ns & A Es  
C ollect a n y relate d t o  
st u d y pr ot oc ol pr oce d ures t hat 
res ult i n e xcl usi o n fr o m t he trial 
or st u d y ter mi nati o n  
C ollect fr o m Da y 1 ( pre d ose) t hr o u g h 3 0 da ys ( A Es) or 9 0 da ys ( S A Es) p ost last 
d ose or t hr o u g h E O T visit, whic he ver is laterB ,K  
X B, K  
Treat me nt  
L V  
 
 
 
X M  
 
 
 
 
 
Pe m br oliz u ma b  
 
 
 
X  
 
 
 
 
 
P K/ A T A  
Sa m ples f or P K  
 
 
 
C ycle 1 O nl y: See P K/ A T A/ Bi o mar ker Ta bles ( Ap pe n di x  B  a n d Ap pe n di x  E ) 
 
Sa m ples f or A T A  
 
 
 
 
Bl o o d sa m ple f or bi o mar ker a nal ysis  
 
 
 
 
Res p o nse 
Assess me nts N  
C T or M RI of c hest, a b d o me n, pel vis 
(a n d nec k if cli nicall y i n dicate d) 
X  
 
 
Assess me nts t o be perf or me d e ver y 6 wee ks ( ± 3 da ys) f or t he first 
1 2  m o nt hs a n d e ver y 1 2 wee ks ( ± 7 da ys) t hereafter, re gar dless of 
d ose dela ys (see Secti o n 7. 2 ) 
X P 
X L  
S u bse q ue nt a ntica ncer t hera p y stat us 
( ma y be c o n d ucte d wit h i n-cli nic visit or 
via p h o ne calls)  
 
 
 
 
 
 
 
 
X  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 5  of 1 5 2  
S ur vi val stat us ( ma y be c o n d ucte d wit h 
i n-cli nic visit or via p h o ne calls) 
 
 
 
 
 
 
 
 
X  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 6  of 1 5 2  
A  
F or C ycle 1 o nl y, if baseli ne visit acti vities occ ur wit hi n 1 da y pri or t o Da y 1, t hese assess me nts d o n ot nee d t o be re peate d.  
B  
F or patie nts wh o disc o nti n ue st u d y treat me nt  i n t he a bse nce of disease pr o gressi o n, perf or m e ver y 6 wee ks  (± 1 wee k)  u ntil pr o gressi o n or i nitiati o n of a ne w a ntica n cer t hera p y. After 1 year o n st u d y, re d uce 
fre q ue nc y t o e ver y 1 2  wee ks ( ± 1  wee k) . All patie nts, i ncl u di n g t h ose wit h pr o gressi ve disease, will be f oll o we d f or s ur vi val u ntil c o m pleti o n of t he safet y f oll o w-u p peri o d, deat h or st u d y cl os ure, whic he ver 
occ ur s first e ver y 1 2 wee ks ( ± 1 wee k) u nless ot her wise state d . 
C  
Vital si g ns i ncl u de res pirat or y rate, p ulse rate, a n d s yst olic a n d diast olic bl o o d press ure while patie nt is i n a seate d p osi ti o n, p ulse o xi metr y, a n d te m perat ure. O btai n wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, 
wit hi n 6 0 mi n utes pri or t o pe m br oliz u ma b i nf usi o n, a n d wit hi n 2 h o urs of e n di n g eac h i nf usi o n, a n d d uri n g i nf usi o n/s as cli ni call y i n dicate d. 
D  
Patie nts wit h accessi ble t u m ors o nl y. C ore nee dle or e xcisi o nal bi o ps y is preferre d. If neit her is p ossi ble, disc uss wit h s p o ns or whet her bi o ps y o btai ne d via alter nati ve met h o ds ma y be a p pr o priate.  
E  
Bi o ps y c ollecte d d uri n g C ycle 1 o nl y. Patie nts i n Part A wit h accessi ble t u m ors are re q uire d t o ha ve a bi o ps y bet wee n Da ys 4 a n d 7. Patie nts i n Part B wit h accessi ble t u m ors are re q uire d t o ha ve a bi o ps y 
bet wee n Da ys 1 5 a n d 2 1.  
F  
An a d diti o nal o pti o nal bi o ps y is re q ueste d ( wit h se parate c o nse nt) at E O T f or patie nts wit h accessi ble resi d ual t u m or fr o m t h e sa me lesi o n as pre vi o us bi o psies, if p ossi ble. In a d diti o n , i n U S patie nts o nl y, if a 
t u m or tiss ue sa m ple is o btai ne d as part of sta n dar d of care at a n y ti me p oi nt d uri n g t he st u d y, wit h t he patie nt’s c o nse nt, eit her a part of t hat sa m ple or a n a d diti o nal sa m ple o btai ne d d uri n g t he sa me pr oce d ure is 
re q ueste d t o be s u b mitte d t o t he s p o ns or.  Bi o mar ker assess me nts will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol A me n d me nt 1 1.  
G  
Pre g na nc y test m ust be perf or me d wit hi n 3 da ys pri or t o eac h st u d y dr u g d ose.  
H  
If H b A1c or fasti n g bl o o d gl uc ose is ele vate d d uri n g scree nin g, a re peat H b A1c or fasti n g bl o o d gl uc ose m ust be o btai ne d.  
I 
Bl o o d gl uc ose sa m ple s h o ul d be o btai ne d bef ore a d mi nistrati o n of st u d y dr u gs or a n y gl uc ose -c o ntai ni n g fl ui d. H ol d d ose if bl o o d gl uc ose le vel is > 2 5 0 m g/ d L or > 1 3. 9 m m ol/ L, testi n g ma y be re pea te d o n 
sa me da y of d osi n g. If H b A1c or fasti n g gl uc ose are ele vate d ( H b A1c ≥6. 5 %, fasti n g gl uc ose ≥1 2 6 m g/ d L or ≥7. 0 m m ol/ L) u p o n re peat testi n g, patie nt s h o ul d recei ve gl uc ose ma na ge me nt pri or t o or wit hi n 
o ne wee k of starti n g st u d y treat me nt.  
J 
T h yr oi d f u n cti o n tests i ncl u de T S H, T 3 or free T 3, a n d free T 4.  
K  
T o be c ollecte d if seri o us a n d c o nsi dere d t o be st u d y treat me nt -relate d. 
L  
F or patie nts wh o disc o nti n ue st u d y treat me nt, perf or m e ver y 6 wee ks  (± 1 wee k)  d uri n g t he first year, t he n re d uce fre q ue nc y per i nstit uti o n’s sta n dar d of care u ntil pr o gressi o n or i nitiati o n of a ne w a nti ca ncer 
t hera p y u nless ot her wise state d . 
M  
F or patie nts recei vi n g > 2 0 0  m g L V  per i nf usi o n  ( wei g ht > 8 0 k g), pr o p h ylactic G-C S F a d mi nis trati o n is re q uire d a n d will be gi ve n t o patie nts o n t he da y after st u d y treat me nt is gi ve n, wit h a visit wi n d o w of 
Da y  2 -4. If pe gfil grasti m is use d, a o ne -ti me d ose is rec o m me n de d. If dail y gr o wt h fact or s u p p ort is use d, treat f or at least 5-7 da ys or u n til t he a bs ol ute ne utr o p hil c o u nt is > 1 0 0 0/ m m3 ( ≤ Gra de 2). H ol d d ose if 
d osi n g criteria o utli ne d  i n Secti o n 5. 2. 3. 5  are n ot met. 
N  
Ti mi n g of res p o nse assess me nts s h o ul d be calc ulate d fr o m C ycle 1 Da y 1.  
O  
Refer t o t he la b orat or y ma n ual f or i nf or mati o n o n c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt of sa m ple.  
P  
N ot re q uire d if c o n d ucte d wit hi n 4 wee ks pri or t o E O T.  
Q  
C ycle s 1 -2 o nl y  
R  
F or C ycle 2 a n d be y o n d, ma y be perf or me d u p t o 2 da ys pri or t o Da y 1.  
S  
F or Part A a n d Part B C o h ort 1, la b orat or y assess me nts are t o be perf or me d l ocall y a n d ce ntrall y. F or Part B C o h ort  2, la b orat or y assess me nts are t o be perf or me d l ocall y a n d res ults are t o be s u b mitte d t o t he 
ce ntral la b orat or y ( wit h t he e xce pti o n of pre g na nc y testi n g); detaile d i n Secti o n 7. 5. 3 . 
T  
F oll o w -u p will occ ur e ver y 6 wee ks ( ± 1 wee ks) 3 0 da ys p ost last treat me nt f or patie nts o n L V o nl y a n d 9 0 da ys f or t h ose o n pe m br oli z u ma b. 
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 7  of 1 5 2  
A P P E N DI X  B:  
P K A N D A T A S A M P LI N G TI M E P OI N T S ( Q 3 W K L V  D O SI N G; P A R T S A A N D  B)   
C ycle C  
St u d y 
Da y  
Ti me  
Wi n d o w  
Relati ve Ti me  
L V P K  
P e m br oliz u ma b P K  
L V A T A  
P e m br oliz u ma b 
A T A  
C ycle 1  
Da y 1  
Pre d ose of 
L V  
Wit hi n 8 hrs
 
S T A R T of L V i nf usi o n  
X  
X  
X  
X  
E n d of L V 
i nf usi o n 
Wit hi n 3 0  mi n  
E N D of L V i nf usi o n  
X  
 
 
 
E n d of 
pe m br oliz u m
a b i nf usi o n  
Wit hi n 3 0  mi n  
E N D of 
pe m br oliz u ma b 
i nf usi o n 
 
X  
 
 
Da y 3 B  
4 8 hrs  
Da y 3 -4  
S T A R T of L V i nf usi o n  
X  
X  
 
 
Da y 5 A  
9 6 hrs  
Da y 4 – 7  
S T A R T of L V i nf usi o n  
X  
X  
 
 
Da y 8  
1 6 8 hrs  
± 4 8 hrs  
S T A R T of L V i nf usi o n  
X  
X  
 
 
Da y 1 5  
3 3 6 hrs  
± 4 8 hrs  
S T A R T of L V i nf usi o n  
X  
X  
 
 
C ycles 2 a n d 4  
Da y 1  
Pre d ose of 
L V  
Wit hi n 8 hrs  
S T A R T of L V i nf usi o n  
X  
X  
X  
X  
E n d of L V 
i nf usi o n 
Wit hi n 3 0 mi n  
E N D of L V i nf usi o n  
X  
 
 
 
E n d of 
pe m br oliz u m
a b i nf usi o n  
Wit hi n  3 0 mi n  
E N D of 
pe m br oliz u ma b 
i nf usi o n 
 
X  
 
 
C ycles 3, 5, a n d 
e ver y 5 c ycles 
t hereafter (e. g., 
C ycles 1 0, 1 5)  
Da y 1  
Pre d ose of 
L V i nf usi o n  
Wit hi n 8 hrs  
S T A R T of L V i nf usi o n  
X  
X  
X  
X  
E O T  
X  
X  
X  
X  
A  
Da y 5 assess me nts t o be perf or me d f or patie nts i n Part A o nl y.  
B  
Da y 3 assess me nts ( Part B C ycle 1 o nl y) r e q uire d f or U S patie nts, o pti o nal f or E X -U S patie nts. Re q uires se parate i nf or me d c o nse nt f or E X -U S patie nts.  
C  
Bi o mar ker assess me nts will o nl y be c ollecte d d uri n g C ycle 1  as of pr ot oc ol A me n d me nt 1 1 . 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 8  of 1 5 2  
A P P E N DI X  C:  
S C H E D U L E O F E V E N T S ( P A R T S  C  A N D D )  
Visit Wi n d o w  
Baseli ne/ Scree ni n g  
E nr oll me nt  
2 1 -da y C ycle  
E O T  
F oll o w -u p  
D 1  
D 8  
D 1 5  
D – 2 8 t o 1  
D – 7 t o 1  
D – 7 t o 1 
See f o ot n otes f or 
wi n d o w  
See f o ot n otes f or 
wi n d o w  
See f o ot n otes f or 
wi n d o w  
3 0 – 3 7 da ys p ost 
last d ose 
E ver y 6 wee ks  
± 1 wee k B ,V  
Baseli ne a n d 
Safet y 
Assess me nts  
I nf or me d c o nse nt 
X  
 
Eli gi bilit y d oc u me ntati o n s u b mitte d t o  
s p o ns or pri or t o st u d y start 
 
 
 
 
 
I ncl usi o n/e xcl usi o n 
X  
 
 
 
 
 
 
Me dical hist or y  
X  
  
 
 
 
 
 
P h ysical E xa m  
 
X  
X A, Q  
 
 
X  
X  
Hei g ht ( baseli ne o nl y) a n d Wei g ht  
 
X  
X A, Q  
 
 
 
 
Vital si g ns C  
 
X  
X  
X  
X U  
 
 
Brai n C T or M RI  
X  
 
 
 
 
 
 
I nitiate c ollecti o n of arc hi ve d t u m or 
s peci me n  
(if a vaila ble) N ,V  
X  
 
 
 
 
 
 
Fres hl y o btai ne d bi o ps y D, M , T (see als o 
Ap pe n di x  E ) 
X  
 
 
 
 
 
 
E C G  
X  
 
 
 
 
 
 
Pre g na nc y test ( perf or me d l ocall y)  
( patie nts of c hil d beari n g p ote ntial o nl y) 
 
X E  
X E  
 
 
X  
 
E C O G perf or ma nce stat us  
 
X  
X A, P 
 
 
X  
 
He patitis B a n d C scree ni n gQ  
X  
 
 
 
 
 
 
C B C wit h differe ntial M ,Q  
 
X  
X A, Q  
X  
X U  
X  
 
P T/ P T T/a P T T/ I N RQ  
X  
 
 
 
 
 
 
H b A1c G ,Q  
X  
 
 
 
 
X  
 
Fasti n g bl o o d gl uc ose F ,Q  
X  
 
 
 
 
 
 
Ser u m c he mistr y pa nel M ,Q  
 
X  
X A ,G ,Q  
X G, R  
X G ,R ,S  
X  
 
T h yr oi d f u ncti o n testsH ,Q   
X  
 
 
O n Da y 1 S of eac h o d d -n u m bere d c ycle while o n treat me nt  
(e. g., Da y 1 of C ycles 1, 3, 5, 7, etc) 
 
 
 
C o nc o mita nt me dicati o ns & A Es  
C ollect a n y relate d t o  
st u d y pr ot oc ol pr oce d ures t hat res ult i n 
e xcl usi o n fr o m t he trial or st u d y 
ter mi nati o n 
C ollect fr o m Da y 1 ( pre d ose) t hr o u g h 3 0 da ys (A Es ) or 9 0 da ys ( S A Es) p ost last d ose or 
t hr o u g h E O T visit, whic he ver is laterB ,I 
X I,J 
Treat me nt K  
L V K O ,P 
 
 
 
X  
X  
X S 
 
 
Pe m br oliz u ma b  
 
 
 
X  
 
 
 
 
P K/ A T A  
Sa m ples f or P K  
 
 
 
C ycle 1 O nl y: See P K/ A T A/ Bi o mar ker Ta bles  (Ap pe n di x  D  a n d Ap pe n di x  E ) 
 
Sa m ples f or A T A  
 
 
 
 
Bl o o d  sa m ple f or bi o mar ker a nal ysis 
 
 
 
 
Res p o nse 
Assess me nts L  
C T or M RI of c hest, a b d o me n, pel vis (a n d 
nec k if cli nicall y i n dicate d) S  
X  
 
 
Assess me nts t o be perf or me d e ver y 6 wee ks ( ± 3 da ys) f or t he first 
1 2  m o nt hs a n d e ver y 1 2 wee ks ( ± 7 da ys) t hereafter, re gar dless of d ose 
dela ys (see Secti o n 7. 2 ) 
X N  
X J 
S u bse q ue nt a ntica ncer t hera p y stat us ( ma y 
be c o n d ucte d wit h i n -cli nic visit or via 
p h o ne calls)  
 
 
 
 
 
 
 
X  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0 9  of 1 5 2  
S ur vi val stat us  ( ma y be c o n d ucte d wit h i n-
cli nic visit or via p h o ne calls) 
 
 
 
 
 
 
 
X  
A  
F or C ycle 1 o nl y, if baseli ne visit acti vities occ ur wit hi n 2  da y s pri or t o Da y 1, t hese assess me nts d o n ot nee d t o be re peate d.  
B  
F or patie nts wh o disc o nti n ue st u d y treat me nt  i n t he a bse nce of disease pr o gressi o n, perf or m e ver y 6 wee ks  (± 1 wee k)  u ntil pr o gressi o n or i nitiati o n of a ne w a ntica ncer t hera p y.  After 1 year o n st u d y, re d uce 
fre q ue nc y t o e ver y 1 2 wee ks ( ± 1  wee ks).  All patie nts , i ncl u di n g t h ose wit h pr o gressi ve disease, will be f oll o we d f or s ur vi val u ntil c o m pleti o n of t he safet y f oll o w-u p peri o d,  deat h , or st u d y cl os ure, w hic he ver 
occ urs first  u nless state d ot her wise.   
C  
Vital si g ns i ncl u de res pirat or y rate, p ulse rate, a n d s yst olic a n d diast olic bl o o d press ure while patie nt is i n a seate d p osi ti o n, p ulse o xi metr y, a n d te m perat ure. O btai n wit hi n 6 0 mi n utes pri or t o L V  i nf usi o n, 
wit hi n 6 0 mi n utes pri or t o pe m br oliz u m a b i nf usi o n ( Da y 1 o nl y), a n d wit hi n 2 h o urs of e n di n g eac h i nf usi o n, a n d d uri n g i nf usi o n/s as cli nicall y i n dicate d.  
D  
If arc hi ve d t u m or s peci me n is n ot c ollecte d a n d f or patie nts wit h accessi ble t u m ors o nl y. C ore nee dle or e xcisi o nal bi o ps y is preferre d. If  neit her is p ossi ble, disc uss wit h s p o ns or whet her bi o ps y o btai ne d via 
alter nati ve met h o ds ma y be a p pr o priate.  
E  
Pre g na nc y test m ust be perf or me d wit hi n 3 da ys pri or t o eac h Da y 1 st u d y dr u g d ose. 
F  
If H b A1c or fasti n g bl o o d gl uc ose is ele vate d d uri n g scree nin g, a re peat H b A1c or fasti n g bl o o d gl uc ose m ust be o btai ne d.  
G  
Bl o o d gl uc ose sa m ple s h o ul d be o btai ne d bef ore a d mi nistrati o n of st u d y dr u gs or a n y gl uc ose -c o ntai ni n g fl ui d. H ol d d ose if bl o o d gl uc ose le vel is > 2 5 0 m g/ d L or > 1 3. 9 m m ol/ L, testi n g ma y be re pea te d o n 
sa me da y of d osi n g. If H b A1c or fasti n g gl uc ose are ele vate d ( H b A1c ≥6. 5 %, fasti n g gl uc ose ≥1 2 6 m g/ d L or ≥7. 0 m m ol/ L) u p o n re peat testi n g, patie nt s h o ul d recei ve gl uc ose ma na ge me nt pri or t o or wit hi n 
o ne wee k of starti n g st u d y treat me nt.  
H  
T h yr oi d f u n cti o n tests i ncl u de T S H, T 3 or free T 3, a n d free T 4.  
I 
T o be c ollecte d if seri o us a n d c o nsi dere d t o be st u d y treat me nt -relate d. 
J 
F or patie nts wh o disc o nti n ue st u d y treat me nt i n t he a bse nce of disease pr o gressi o n, perf or m e ver y 6 wee ks ( ± 1 wee k) d uri n g t he fir st year, t he n re d uce fre q ue nc y per i nstit uti o n’s sta n dar d of care u ntil 
pr o gressi o n or i nitiati o n of a ne w a ntica ncer t hera p y  u nless ot her wise state d.  
K  
T he ma xi m u m d ose is 2 0 0  m g per i nf usi o n.  
L  
Ti mi n g of res p o nse assess me nts s h o ul d be calc ulate d fr o m C ycle 1  Da y 1.  
M  
Refer t o t he la b orat or y ma n ual f or i nf or mati o n o n c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt of sa m ple.  
N  
N ot re q uire d if c o n d ucte d wit hi n 4 wee ks pri or t o E O T.  
O  
At least 7 da ys m ust ela pse bet wee n a d mi nistrati o ns of L V . H ol d d ose if d osi n g criteri a o utli ne i n Secti o n 5. 2. 3. 5  are n ot met. 
P  
F or C ycle 2 a n d be y o n d, ma y be perf or me d u p t o 2 da ys pri or t o Da y 1.  
Q  
La b orat or y assess me nts are t o be perf or me d l ocall y a n d res ults are t o be s u b mitte d t o t he ce ntral la b orat or y ( wit h t he e xce pti o n of pre g na nc y testi n g); detaile d i n Secti o n 7. 5. 3 . 
R  
C ycles 1 a n d 2 o nl y.  
S  
Part C o nl y.  
T  
I n Part D o nl y, arc hi val or fres hl y o btai ne d t u m or tiss ue will be use d t o deter mi ne eli gi bilit y base d o n P D -L 1 C P S < 1 0 stat us as deter mi ne d l ocall y b y a P D -L1 I H C assa y usi n g t he 2 2 C 3 cl o ne.  
U  
C ycles 1 a n d 2 o nl y f or Part D a n d e ver y c ycle f or Part C.  
V  
F oll o w -u p will occ ur e ver y 6 wee ks ( ± 1 wee ks) 3 0 da ys p ost last treat me nt f or patie nts o n L V o nl y a n d 9 0 da ys f or t h ose o n pe m br oliz u ma b.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 0  of 1 5 2  
A P P E N DI X  D : 
P K A N D A T A S A M P LI N G TI M E P OI N T S ( P A R T S  C  A N D D )  
C ycle  
St u d y 
Da y  
Ti me C  
Wi n d o w  
Relati ve Ti me  
L V P K  
P e m br oliz u ma b 
P K  
L V A T A  
P e m br oliz u ma b 
A T A  
C ycle 1  
Da y 1  
Pre d ose of L V  
Wit hi n 
8  hrs  
S T A R T of L V 
i nf usi o n 
X  
X  
X  
X  
E n d of L V 
i nf usi o n 
Wit hi n 
3 0  mi n  
E N D of L V 
i nf usi o n 
X  
 
 
 
E n d of 
pe m br oliz u ma b 
i nf usi o n 
Wit hi n 
3 0  mi n  
E N D of 
pe m br oliz u ma b 
i nf usi o n 
 
X  
 
 
Da y 
3 A  
4 8 hrs  
Da y 3 -4  
S T A R T of Da y  1 
L V i nf usi o n  
X  
 
 
 
Da y 8  
Pre -d ose of L V  
Wit hi n 
8  hrs  
S T A R T of L V 
i nf usi o n 
X  
 
 
 
E n d of L V 
i nf usi o n 
Wit hi n 
3 0  mi n  
E N D of L V 
i nf usi o n 
X  
 
 
 
Da y 
1 5 B   
Pre -d ose of L V  
Wit hi n 
8  hrs  
S T A R T of L V  
i nf usi o n 
X  
 
 
 
E n d of L V 
i nf usi o n 
Wit hi n 
3 0  mi n  
E N D of L V 
i nf usi o n 
X  
 
 
 
C ycles 2 a n d 4  
Da y 1  
Pre d ose of L V  
Wit hi n 
8  hrs  
S T A R T of L V 
i nf usi o n 
X  
X  
X  
X  
E n d of L V 
i nf usi o n 
Wit hi n 
3 0  mi n  
E N D of L V 
i nf usi o n 
X  
 
 
 
C ycles 3, 5, 
a n d e ver y 
5  c ycles 
t hereafter (e. g., 
C ycles 1 0, 1 5)  
Da y 1  
Pre d ose of L V 
i nf usi o n 
Wit hi n 
8  hrs  
S T A R T of L V 
i nf usi o n 
X  
X  
X  
X  
E O T  
X  
X  
X  
X  
A  
Da y 3 assess me nts re q uire d f or U S patie nts, o pti o nal f or E X -U S patie nts. Re q uires se parate i nf or me d c o nse nt f or E X -U S patie nts  
B  
Part C o nl y.  
C  
Bi o mar ker assess me nts will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol A me n d me nt 1 1.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)  
 Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 1  of 1 5 2  
A P P E N DI X  E : 
BI O M A R K E R S A M P LI N G T I M E P OI N T S  
T a bl e  1 1 : 
Bi o m ar k er s a m pli n g ti m e p oi nt s –  P art s A a n d B*  
C ycle  
St u d y Da y  
Ti me C  
Wi n d o w  
Relati ve Ti me  
C yt o ki nes  
cf D N A 
E x os o mes  
I m m u ne 
s u bsets 
T C R β Cell 
P ellet  
Fres h 
Bi o ps y  
 
 
N/ A  
 
 
 
 
 
 
 
 
Scree ni n g  Da y – 2 8 t o – 1  
N/ A  
N/ A  
N/ A  
 
 
 
 
 
X  
C ycle 1  
Da y 1  
Pre d ose  
Wit hi n 8 hr  
S T A R T of 
i nf usi o n 
X  
X  
X  
X  
X  
 
Da y 5  
–  
Da y 4 – 7  
S T A R T of 
i nf usi o n 
 
 
 
 
 
X A  
Da y 1 5  
3 3 6 h  
± 2 4 hr  
S T A R T of 
i nf usi o n 
 
 
 
 
 
X A  
C ycles 
2,  3  
Da y 1  
Pre d ose  
Wit hi n 8 hr  
S T A R T of 
i nf usi o n 
X  
X  
X  
X  
X  
 
E O T  
X  
X  
X  
X  
X  
X B  
*If a d diti o nal tests, i ncl u di n g b ut n ot li mite d t o t u m or mar ker assess me nts, are perf or me d as p art of sta n dar d of care, please s u b mit t h ose res ults. 
A  
Patie nts i n Part A wit h accessi ble t u m ors are re q uire d t o ha ve a bi o ps y bet wee n Da ys 4 a n d 7 of C ycle 1. Patie nts i n Part B w it h accessi ble t u m ors are re q uired t o ha ve a bi o ps y bet wee n Da ys 1 5 a n d 2 1 of 
C ycle 1.  
B  
O pti o nal bi o ps y; re q uires se parate i nf or me d c o nse nt.  
C  
Bi o mar ker assess me nts will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol a me n d me nt 1 1.  
 
T a bl e  1 2 : 
Bi o m ar k er s a m pli n g ti m e p oi nt s –  P art s  C  a n d D * 
C ycle B  
St u d y Da y  
Ti me  
Wi n d o w  
Relati ve Ti me  
C yt o ki nes  
cf D N A 
T C R β Cell P ellet  Fres h Bi o ps y  
 
 
N/ A  
 
 
 
 
 
 
Scree ni n g  
Da y – 2 8 t o – 1  
N/ A  
N/ A  
N/ A  
 
 
 
X A  
C ycle 1, 2, a n d 
4  
Da y 1  
Pre d ose  
Wit hi n 8 hr  
S T A R T of 
i nf usi o n 
X  
X  
X  
 
E O T  
X  
X  
X  
 
*If a d diti o nal tests, i ncl u di n g b ut n ot li mite d t o t u m or mar ker assess me nts, are perf or me d as p art of sta n dar d of care, please s u b mit t h ose res ults.  
A  
Fres h t u m or bi o ps y re q uire d if arc hi val tiss ue is n ot a vaila ble.  
B  
Bi o mar ker assess me nts will o nl y be c ollect e d d uri n g C ycle 1 as of pr ot oc ol a me n d me nt 1 1.  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 2  of 1 5 2  
A P P E N DI X  F : 
P E R F O R M A N C E S T A T U S S C A L E S C O N V E R SI O N   
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)
C O P Y RI G H T E D M A T E RI A L

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 3  of 1 5 2  
A P P E N DI X  G : 
G UI D A N C E O N C O N T R A C E P TI O N   
F or t he p ur p os es of t his g ui da nce, c o m plete a bsti ne nce, if c o nsiste nt wit h t he s u bject’s preferre d 
lifest yle, is a n acce pta ble f or m of c o ntr ace pti o n. C om plete a bsti ne nce is defi ne d as a bsti ne nce 
starti n g fr o m t he ti me of i nf or me d c o nse nt a n d c o nti n ui n g t hr o u g h o ut t he st u d y a n d u ntil t he e n d 
of t he safet y f oll o w-u p p eri o d.  
Acce pt a ble met h o ds f or hi g hl y effecti ve birt h c o ntr ol ( pre ve nti n g c o nce pti o n)   
S u bjects w h o are of c hil d be ari n g p ote nti al a or w h ose p art ners are of c hil d be ari n g p ote nti al a a n d w h o 
are se x u all y acti ve i n a w a y t h at c o ul d le a d t o pre g n a nc y m a y c h o ose a n y T W O o f t he f oll o wi n g 
met h o ds:  
I ntra uteri ne de vice wit h fail ure rate < 1 % 
T u bal li gati o n  
Vasect o m y (at least 9 0 da ys fr o m t he date of s ur ger y wit h a se me n a nal ysis d oc u me nti n g a z o os per mia)  
B arrier met h o d/s ( male or fe male c o n d o m wit h or wit h o ut s p er mici de, cer vical ca p wit h or wit h o ut 
s per mici de, dia p hra g m wit h or wit h o ut s per mici de)  
a 
A pers o n of c hil d beari n g p ote ntial is d efi n e d as a n y o ne b or n fe mal e w h o has e x perie nce d me narc he a n d w h o has n ot 
u n der g o ne s ur gical sterilizati o n (e. g., h ysterect o m y, bilateral  sal pi n gect o m y, bilateral o o p h orect o m y) or has n ot 
c o m plete d me n o pa use. Me n o pa use is d efi n e d cli nicall y as 1 2 m o nt hs of a me n orr hea i n a pers o n b or n fe male o ver 
a ge 4 5 i n t he a bse nce of ot her bi ol o gical, p h ysi ol o gical, or p har ma c ol o gical ca uses.  
 
Acce pt a bl e met h o ds f or pre ve nti n g sec o n d ar y e x p os ure t o se mi n al fl ui d   
S u bjects b or n m ale a n d w h o are se x u all y acti ve wit h a pre g n a nt or bre astfee di n g pers o n, m ust use t he 
c o ntr ace pti v es i n O pti o n 1 or 2:  
O pti o n 1: Male c o n d o m ( wit h or wit h o ut s per mici de) a n d cer vical ca p  
O pti o n 2: Male c o n d o m ( wit h or wit h o ut s per mici de) a n d dia p hra g m  
 
U n acce pt a ble met h o ds of c o ntr ace pti o n   
P eri o dic a bsti ne nce  
N o met h o d  
Wit h dra wal  
R h yt h m  
S per mici de o nl y  
Pr o gesti n -o nl y pills  
C o nc o mita nt use of fe male a n d male c o n d o ms  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 4  of 1 5 2  
A P P E N DI X  H : 
P -G P A N D C Y P 3 A I N D U C E R S/I N HI BI T O R S   
N O T E: A d diti o nal P -g p i n d ucers/i n hi bit ors or str o n g C Y P 3 A i n d ucers/i n hi bit ors ma y bec o me 
a vaila ble w hile t he cli nical trial is o n g oi n g. T he f oll o wi n g state me nts w o ul d a p pl y t o t h ose 
me dicati o ns i n a d diti o n t o t h ose liste d i n t he ta ble bel o w.  
Patie nts w h o are recei vi n g P -g p or str o n g C Y P 3 A i n hi bit ors c o nc o mita ntl y wit h L V  s h o ul d be 
cl osel y m o nit ore d f or a d verse reacti o ns. Base d u p o n e val uati o n of t he a nti -C D 3 0 M M A E A D C 
bre nt u xi ma b ve d oti n ( A dcetris) ( A D C E T RI S Pres cri bi n g I nf or mati o n, Sea ge n , J u ne 2 0 2 3 ), 
c o nc o mita nt use of P -g p i n hi bit ors or str o n g C Y P 3 A 4 i n hi bit ors has t he p ote ntial t o i ncrease t he 
e x p os ure t o M M A E (t he c yt ot o xic c o m p o ne nt of L V  a n d bre nt u xi ma b ve d oti n). C o nc o mita nt use 
of P -g p i n d uc ers or str o n g C Y P 3 A 4 i n d ucers c o ul d decrease e x p os ure t o M M A E.  
P -g p I n hi bit ors  
Str o n g C Y P 3 A I n hi bit ors  
a mi o dar o ne  
b oce pre vir  
car ve dil ol  
clarit hr o m yci n  
clarit hr o m yci n  
c o bicistat  
dr o ne d ar o ne  
c o ni va pta n  
itrac o naz ole  
da n o pre vir a n d rit o na vir 
la pati ni b 
diltiaze m  
l o pi na vir a n d rit o na vir 
el vite gra vir a n d rit o na vir  
pr o pafe n o ne  
gra pefr uit j uice  
q ui ni di ne  
i delalisi b 
rit o na vir 
i n di na vir a n d rit o na vir 
ra n olazi ne 
itrac o naz ole 
sa q ui na vir a n d rit o na vir 
ket oc o naz ole  
tela pre vir 
l o pi na vir a n d rit o na vir  
ti pra na vir a n d rit o na vir 
nefaz o d o ne  
vera p a mil  
nelfi na vir  
 
parita pre vir a n d rit o na vir a n d ( o m bitas vir a n d/ or dasa b u vir)  
 
p osac o naz ole  
 
rit o na vir 
 
sa q ui na vir a n d rit o na vir 
 
tela pre vir 
 
ti pra na vir a n d rit o na vir 
 
tr olea n d o m yci n 
 
v oric o naz ole  
P -g p I n d ucers/ Str o n g C Y P 3 A I n d ucers  
 
a vasi mi be 
 
car ba maze pi ne  
 
p he n yt oi n  
 
rifa m pi n 
 
St J o h n’s w ort  
 
ti pra na vir a n d rit o na vir * 
 
* P -g p i n d ucer o nl y.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 5  of 1 5 2  
A P P E N DI X  I: 
N E W Y O R K H E A R T A S S O C I A TI O N C L A S SI FI C A TI ON   
A F u ncti o n al a n d T her a pe utic Cl assific ati o n f or Pres cri pti o n of P h ysic al Acti vit y f or 
C ar di ac P atie nts   
O n -li ne s o urce: htt p:// w w w. heart. or g/ H E A R T O R G/ C o n diti o ns/ Heart Fail ure/ A b o ut Heart Fail ure/ Classes -of -H eart -
Fail ure _ U C M _ 3 0 6 3 2 8 _ Article.js p  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)
C O P Y RI G H T E D M A T E RI A L

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 6  of 1 5 2  
A P P E N DI X  J : 
R E CI S T C RI T E RI A S U M M A R Y ( V E R SI O N 1. 1)   
R e s p o n s e E v al u ati o n Crit eri a i n S oli d T u m or s  
T er m 
Defi niti o n  
C o m plete res p o nse ( C R)  
Disa p peara nce of all tar get lesi o ns. A n y pat h ol o gical l y m p h n o des 
m ust ha ve re d ucti o n i n s h ort a xis t o < 1 0  m m.  
P artial res p o nse ( P R)  
A ≥3 0 % decrease i n t he s u m of dia meters of tar get lesi o ns, t a ki n g as 
refere nce t he baseli ne s u m dia meters. 
Pr o gressi ve disease ( P D)  
At least a 2 0 % i ncrease i n t he s u m of dia meters of tar get lesi o ns, 
ta ki n g as refere nce 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 an a bs ol ute 
i ncrease of at least 0. 5 c m. T he a p peara nce of o ne or m ore ne w 
lesi o ns is als o c o nsi dere d pr o gressi o n.  
Sta ble disease ( S D)  
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 ualif y f or P D, ta ki n g as refere nce t he s mallest s u m dia meters 
w hile o n st u d y.  
Meas ura ble lesi o n  
M ust be acc uratel y meas ure d i n at least o ne di me nsi o n (l o n gest 
dia meter i n t he pla ne of meas ure me nt is t o be rec or de d) wit h a 
mi ni m u m size of 1 0  m m b y C T sca n ( C T slice t hic k ness n o greater 
t ha n 5 m m).  
F r o m R E CI S T V ersi o n 1. 1 (Eise n ha uer 2 0 0 9 ) 
 
A res p o nse ( C R or P R) will be c o nsi dere d c o nfir me d if t he f oll o wi n g dise ase assess me nt (at least 
4  wee ks after t he i nitial r es p o nse) still s h o ws res p o nse ( C R or P R). I n cases w here t he i nitial 
res p o nse is f oll o we d b y S D, it will be c o nsi dere d as c o nfir me d if t h e S D is later f oll o we d b y P R 
or C R. F or e x a m ple, if a patie nt ha d P R i n wee k 8, S D i n wee k 1 2, a n d P R i n wee k 1 6, t his P R 
will be c o nsi dere d as c o nfir me d.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 7  of 1 5 2  
A P P E N DI X  K : 
I R E CI S T: G UI D E LI N E S F O R R E S P O N S E C RI T E RI A 
F O R U S E I N T RI A L S T E S TI N G I M M U N O T H E R A P E U TI C S   
Res p o nse will als o be ass esse d usi n g i R E CI S T g ui deli nes (Se y m o ur 2 0 1 7 ). I m m u n ot hera pe utics 
ma y res ult i n i nfiltrati o n of i m m u ne cells lea di n g t o tra nsie nt i ncrease i n t he siz e i n mali g na nt 
lesi o ns, or u n detecta ble l esi o ns bec o mi n g d etect a ble. T he criteria are i de ntical t o t h ose of 
R E CI S T Versi o n 1. 1 i n ma n y res pects b ut ha ve b ee n a d a pte d t o acc o u nt f or i nsta nces w h ere a n 
i ncreas e i n t u m or b ur de n, or t he a p peara n ce of ne w lesi o ns, d oes n ot reflect tr ue t u m or 
pr o gressi o n.  
Ke y differe nces are des cri be d bel o w. All res p o nses defi ne d usi n g i R E CI S T g ui deli nes are 
desi g nat e d wit h a prefi x; i R E CI S T ti me -p oi nt a n d best res p o nses will be rec or de d se paratel y.  
C o nfir mi n g Dise ase Pr o gressi o n   
U nli k e R E CI S T Versi o n 1. 1, t he i R E CI S T g ui d eli nes re q uire t h e c o nfir m ati o n of pr o gressi o n 
a n d use t he ter ms i U P D ( u nc o nfir me d pr o gressi o n) a n d i C P D (c o nfir me d pr o gressi o n). 
C o nfir mat or y s ca ns s h o ul d be perf or m e d at least 4 wee ks, b ut n o l o n ger t ha n 8 wee ks afte r 
i U P D. 
F or i C P D t o be c o nfir me d, f urt her i ncreas e i n t u m or b ur de n, c o m p are d t o t he last assess me nt, 
m ust be see n as e vi de n ce d b y 1 or m or e of t he f oll o wi n g:  
● 
C o nti n ue d i ncrease i n t u m or b ur de n (fr o m i U P D) w here R E CI S T Versi o n 1. 1 defi niti o ns 
of pr o gressi o n  ha d b ee n met (fr o m na dir) i n tar get, n o n -tar get diseas e or ne w lesi o ns 
○ 
Pr o gressi o n i n tar get disease w ors e ns wit h a n i ncrease of at least 5  m m i n t he a bs ol ute 
val ue of t he s u m  
○ 
C o nti n ue d u ne q ui v ocal pr o gressi o n i n n o n -tar get disease wit h a n i ncreas e i n t u mor 
b ur de n  
○ 
I n crease i n size of pre vi o usl y i de ntifie d ne w lesi o n(s) (a n i ncreas e of at least 5 m m i n 
t he a bs ol ute val ue of t h e s u m of t h ose c o nsi dere d t o be tar get ne w lesi o ns) or 
a d diti o nal ne w lesi o ns.  
● 
R E CI S T Versi o n 1. 1 criteria are met i n lesi o n t y p es (t ar get or n o n -tar get or ne w lesi o ns) 
w here pr o gressi o n w as n ot pre vi o usl y i de ntifie d, i ncl u di n g t he a p peara nce of a d diti o nal 
ne w lesi o ns.  
 
If i U P D is n ot c o nfir me d at t he ne xt assess me nt, t he n t he a p pr o priate res p o nse will be assi g n e d 
(i U P D if t he criteri a are still met, b ut n o w orse ni n g, or i S D, i P R, or i C R if t h ose criteria are met 
c o m pare d t o bas eli ne).  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 8  of 1 5 2  
Ne w Lesi o ns   
Ne w lesi o ns s h o ul d be assesse d a n d meas ure d as t he y a p pear usi n g R E CI S T Versi o n 1. 1 criteria 
( ma xi m u m of 5 lesi o ns, n o m ore t ha n 2 per site, at least 1 0 m m i n l o n g a xis ( or 1 5  m m i n s h ort 
a xis f or n o dal lesi o ns), a n d rec or de d as N e w Lesi o ns -Tar get ( N L T) a n d Ne w Lesi o n -N o n -Tar get 
( N L N T) t o all o w clear differe ntiati o n fr o m baseli n e tar get a n d n o n -tar get lesi o ns. 
Ne w lesi o ns ma y eit her meet t he criteri a of N L T or N L N T t o dri ve i U P D ( or i C P D). H o we ver, 
t he meas ure m e nts of tar get lesi o ns s h o ul d N O T be i ncl u de d i n t he s u m of meas ures of ori gi nal 
tar get lesi o ns i de ntifie d at baseli ne. Rat her, t hes e meas ure me nts will be c ollecte d se paratel y i n 
t he s o urce d o c u me nts. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1 9  of 1 5 2  
A P P E N DI X  L :  M Y E L OI D G R O W T H F A C T O R S U P P O R T 
R E C O M M E N D A TI O N S   
F or patie nts i n Parts A a n d B : Pri m ar y Pr o p h yl a xis  wit h gra n ul oc yt e -c ol o n y sti m ulati n g fact or 
(G -C S F) starti n g wit h t h e first c ycle of L V  a n d c o nti n ui n g t hr o u g h s u bs e q u e nt c ycles is 
rec o m me n de d f or patie nts w h o ha ve a p pr o xi matel y 2 0 % or hi g h er ris k of fe brile ne utr o p e nia. 
Starti n g wit h A me n d me nt 2  f or patie nts i n Parts A a n d B, G -C S F is re q uire d f or patie nts 
wei g hi n g > 8 0 k g at baseli ne, sta rti n g wit h t heir first c ycl e of t hera p y a n d at eac h s u bse q ue nt 
c ycle. T heref ore, p atie nts wei g hi n g > 8 0 k g m ust n ot ha ve c o ntrai n dicati o ns t o m yel oi d gr o wt h 
fact ors a n d m ust be willi n g t o recei ve t h e m. 
F or patie nts i n Part  C : Pri mar y pr o p h yl actic G-C S F is n ot per mitte d i n t he D L T e val uati o n 
peri o d d uri n g d ose es calati o n.  
F or patie nts i n Part D: Pri mar y pr o p h yl actic G -C S F ma y n ot be a p pr o priate beca use L V is gi ve n 
eit her wee kl y or o n Da ys 1 a n d 8 e ver y 2 1 da ys.  
Patie nts i n Parts A  a n d B w h o e x perie nce Gra d e 4  ne utr o pe nia or fe brile n e utr o pe nia of a n y 
gra de i n a n y c ycle, m ust recei v e m yel oi d gr o wt h fact ors i n all s u bse q ue nt c ycl es. M yel oi d 
gr o wt h fact or s u p p ort is als o re q uire d f or treat me nt of fe brile ne utr o pe nia  i n Parts A a n d B. 
Str o n gl y c o nsi der pri mar y pr o p h yl a xis w he n all o we d per pr ot oc ol base d o n patie nt, disease, a n d 
treat me nt ris k fact ors, i ncl u di n g t he f oll o wi n g: 
A ge ≥6 5 years  
A d va nce d disease  
Pre vi o us c he m ot hera p y or ra diati o n t hera p y  
Pre -e xisti n g ne utr o pe nia or b o ne marr o w i n v ol ve me nt wit h t u m or  
I nfecti o n 
O pe n w o u n ds or rece nt s ur ger y  
P o or perf or ma nce stat us or p o or n utriti o nal stat us  
P o or re nal f u ncti o n  
Li ver d ysf u ncti o n, m ost n ota bl y ele vate d bilir u bi n  
Car di o vasc ular disease  
M ulti ple c o m or bi d c o n diti o ns  
 
Sec o n d ar y pr o p h yl a xis  wit h G -C S F is rec o m me n de d f or patie nts i n Parts C  a n d D w h o 
e x perie nce a n e utr o pe nic c o m plicati o n wit h pre vi o us c ycl e of t hera p y (f or w hic h pri mar y 
pr o p h yla xis was n ot recei ve d), w he n d ose re d u cti o n or dela y ma y c o m pr o mise treat me nt 
o utc o me wit h L V . 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 0  of 1 5 2  
Tre at me nt wit h G -C S F  is str o n gl y rec o m me n de d f or patie nts i n Part C wit h fe ver a n d 
ne utr o pe nia w h o are at hi g h ris k f or i nfecti o n -ass o ciate d c o m plicati o ns or w h o ha ve pr o g n ostic 
fact ors t hat are pre dicti ve of p o or cli nical o utc o mes. Hi g h-ris k feat ur es i ncl u de: 
Se psis s y n dr o me ( h y p ote nsi o n a n d m ulti -or ga n d ysf u ncti o n)  
A ge > 6 5 years  
Pr of o u n d ne utr o pe nia (a bs ol ut e ne utr o p hil c o u nt < 0. 1 x 1 0 9/ L) 
U nc o ntr olle d pri mar y disease  
P ne u m o nia  
I n vasi 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 m e of fe ver  
Pri or e pis o de of fe brile ne utr o pe nia  
 
Refer t o t he Pres cri bi n g I nf or mati o n f or t he a p plica ble G -C S F t o deter mi ne t he a p pr o priat e 
a d mi nistrati o n wi n d o w f or use wit h L V . 
T he c h oice of G -C S F is as deter mi ne d b y i n vesti gat or.  
Refere n ce: (Cra wf or d 2 0 1 0 ; S mit h 2 0 1 5 ) 
 
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St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 1  of 1 5 2  
A P P E N DI X  M : M O DI FI E D T O XI CI T Y P R O B A BI LI T Y I N T E R V A L  
D E SI G N SI M U L A TI O N R E P O R T   
I ntr o d ucti o n  
Part C of t his st u d y e val u ates wee kl y ( q 1 w k) L V  d osi n g ( Da y 1, Da y 8, a n d Da y 1 5 of e v er y 
3 -wee k c ycle). T he pri m ar y o bjecti ve of Part C is t o e val uate t he safet y, t olera bilit y, a n d i de ntif y 
the rec o m me n d e d d ose of L V . T o xicit y is meas ure d b y d os e-li miti n g t o xicities ( D L Ts) o bser ve d 
wit hi n t he first c ycl e. D ose escal ati o n i n Part  C will be c o n d ucte d acc or di n g t o a m o difie d 
t o xicit y pr o ba bilit y i nter val met h o d ( m T PI). 
D O S E E S C A L A TI O N   
O ver vie w   
T here will be 2 sel ecte d d ose le vels f or L V  i n Part C. I nter me di ate d oses of L V  ma y als o be 
e val uate d d uri n g t he e x ec uti o n p hase at t he discreti o n of t he s p o ns or u p o n rec o m me n dati o n b y 
t he Safet y M o nit ori n g C o m mittee ( S M C). 
T he starti n g d os e le vel of L V  is 1. 0 m g/ k g. D ose escalati o n is c o n d ucte d acc or di n g t o a n m T PI 
met h o d a n d acc or d i n g t o a set of r ules g o v er ni n g e ntr y i nt o t he st u d y a n d assi g n me nt of d ose 
le vel. Decisi o ns are des cri be d i n Secti o n 3 . 1. 3 of t he st u d y pr ot o c ol a n d det aile d i n t his 
a p pe n di x. T he y are b ase d o n t he p osteri or distri b uti o n of t he D L T rat e a n d d eri ve d i n de pe n d e ntl y 
f or eac h d ose le v el. T he trial is cl osel y m o nit ore d f or safet y a n d f or i d e ntificati o n of t he M T D. If 
t he S M C rec o m me n ds e x pl orati o n of a n i nter me di ate d ose le vel, a n a d diti o nal d ose le vel ma y be 
a d de d.  
M o difie d T o xicit y Pr o b a bilit y I nter v al Met h o d   
D ose escalati o n is c o n d ucte d usi n g t he m o difi e d t o xicit y pr o ba bilit y i nt er val met h o d. T he 
i m ple me ntati o n pr o gra ms are a v aila ble at: htt ps:// u desi g n.lai yac o ns ulti n g. c o m/ . 
F or eac h d ose l e vel, i, t he pr o ba bilit y of a D L T o n d ose i is de n ote d b y pi. T he tar get t o xicit y 
pr o ba bil it y i n t his st u d y is defi ne d as 2 5 %, wit h a 5 % mar gi n. T he e q ui v ale nce i nter val is 
[ 2 0 %, 3 0 %], w hic h c o ntai ns t he d oses cl ose t o t he tr ue tar get D L T rate t h at p h ysicia ns w o ul d 
dee m acce pta ble f or tr eati n g f ut ure patie nts. T he e q ui vale nce i nter val partiti o n s t he u nit i nter val 
( 0, 1) i nt o 3 s u bi nter vals: ( 0, 2 0 %), [ 2 0 %, 3 0 %], a n d ( 3 0 %, 1). D oses i n t hese 3 i nter vals 
c orres p o n d t o:  
1.  U n der d osi n g: pi < 2 0 %  
2.  Pr o per d osi n g: 2 0 % ≤ pi ≤3 0 %  
3.  O ver d osi n g: pi > 3 0 %  
 
I n eac h d os e le vel, t he pri or distri b uti o n of D L T pr o ba bilit y, pi, is ass u me d t o be n o n -i nf or mati ve 
Beta( 1, 1). Aft er eac h patie nt is treate d a n d assesse d f or D L T, t he p osteri or distri b uti o n of pi is 
u p date d t o Bet a( 1 + xi, 1 + ni –  xi), w here xi a n d ni de n ote t he n u m ber of D L Ts a n d t h e n u m ber 
of D L T -e v alua ble p atie nts at d ose le vel i, res p ecti vel y. T h e d ose -escal ati o n decisi o n is base d o n 
t he u nit pr o ba bilit y mass ( U P M) o n t he p osteri or distri b uti o n of pi. F or a gi ve n i nter val [ a, b], t he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 2  of 1 5 2  
U P M is defi ne d as t he rati o of t he pr o ba bilit y of t h e i nter val t o t he le n gt h of t he i nter val, w here 
f or a n y D L T pr o ba bilit y pi a n d  
0 ≤ a < b ≤ 1,  
U P M(a, b) = Pr(a < pi < b) / ( b –  a)  
After t he t o xicit y o utc o m es are o bs er ve d, t h e U P M o n ( 0, 2 0 %), [ 2 0 %, 3 0 %], a n d ( 3 0 %, 1) at t he 
c urre nt d ose is calc ulat e d, a n d t he d osi n g d ecisi o n r ules are:  
1.  Escalate ( E), if ( 0, 2 0 %) has t he lar gest U P M  
2.  Sta y at t he c urre nt d ose ( S), if [ 2 0 %, 3 0 %] has t he lar gest U P M  
3.  De -es calate ( D), if ( 3 0 %, 1) has t he lar gest U P M  
 
I n a d diti o n, t he t o xicit y of a d ose is defi n e d as bei n g u nacce pta ble if t here is m ore t ha n a 9 5 % 
pr o ba bilit y t hat t he D L T rate is hi g h er t ha n 2 5 %,  
T o xicit y at d ose i is u nacce pta ble: Pr( pi > 2 5 %) > 9 5 %  
If d ose le vel i is deter mi ne d t o be u nacce pta ble, t h e ne xt patie nts are treate d at d ose le vel i –  1 
a n d d oses i a n d hi g her are e x cl u d e d fr o m t he trial. If i = 1, t he trial is ter mi n ate d, a n d it is 
c o ncl u de d t hat n o d ose le vel is safe, if t here are n o l o wer d ose le vels of i nterest t o e x pl ore. T he 
decisi o n r ules f or eac h d ose le vel are pr o vi de d i n Ta ble  1 3 . 
T a bl e  1 3 : 
D e ci si o n r ul e s f or S G N L V A -0 0 2 –  P art C, b y m T PI f or e a c h d o s e l e v el wit h t ar g et 
M T D = 2 5 %  
 
N u m ber of D L T -E val ua ble P atie nts Treate d at C urre nt D ose  
N u m b er of T o xicities  
 
2  
3  
4  
5  
6  
7  
8  
9  
0  
E  
E  
E  
E  
E  
E  
E  
E  
1  
S  
S  
S  
S  
E  
E  
E  
E  
2  
D a 
D  
D  
S  
S  
S  
S  
S  
3  
 
D U  
D U  
D U  
D  
S  
S  
S  
4  
 
 
D U  
D U  
D U  
D U  
D U  
D  
5  
 
 
 
D U  
D U  
D U  
D U  
D U  
6  
 
 
 
 
D U  
D U  
D U  
D U  
7  
 
 
 
 
 
D U  
D U  
D U  
8  
 
 
 
 
 
 
D U  
D U  
9  
 
 
 
 
 
 
 
D U  
E = Escalate t o t h e ne xt hi g her d ose, S = Sta y at t h e c urre nt d ose, D = De -escal ate t o t h e ne xt l o wer d ose, D U = C urre nt d ose is 
u nacce pta bl y t o xic  
a 
D ose will be de -escalate d if t h e first 2 D L T -e val u a ble p atie nts i n a d ose le vel e x perie nce D L T. F urt her e val u ati o n of t h at 
d ose le vel ma y b e all o we d if rec o m me n de d b y t h e S M C.  
 
At t he e n d of t he trial w h e n t he t o xicit y o utc o mes of all t he e nr olle d D L T -e val ua ble patie nts are 
o bser ve d, a d os e will be selecte d as t h e esti mate d M T D. T he esti mati o n is se parat e d fr o m t he 
desi g n f or d ose fi n di n g. T h e M T D is selecte d b y perf or mi n g a n is ot o nic re gressi o n t hat b orr o ws 
stre n gt h acr oss d oses. Let p̂i be t he p osteri or mea n of D L T rat e. T he p o ole d a djace nt vi olat ors 
al g orit h m ( P A V A) is a p plie d o n p̂i s o t hat t he res ulti n g tra nsf or m e d val ues p̂i * i ncrease wit h t he 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 3  of 1 5 2  
d ose le vels. T hat is, p̂i * ≤ p̂i + 1 * f or all i. T he rec o m me n de d M T D is t he hi g hest d ose wit h a 
t o xicit y pr o ba bilit y p̂i * less t ha n or e q ual t o t he tar get D L T rate 2 5 %, i.e., 
Esti mate d M T D = ma x {i: p̂i *≤2 5 % }  
D ose -Esc al ati o n R ules   
1.  D ose escalati o n be gi ns wit h patie nt e nr oll me nt t o d ose le vel of 1. 0  m g/ k g. At least 
2  D L T -e val u a ble patie nts per d ose le vel are re q uir e d t o escalat e at a n y d os e le vel. O nce all 
patie nts i n t he pre vi o us c o h ort ha ve c o m plete d D L T e val uati o n, patie nts ca n be e nr olle d t o 
t he ne xt d ose-le vel c o h ort. S u bse q ue nt e nr oll me nt a n d d ose selecti o n occ urs via t he 
f oll o wi n g r ules: 
2.  If a d ose le v el i is u nacce pta ble, de-es calate t o t he l o wer d ose le vel a n d ne v er trea t f ut ure 
patie nts at le vel i. If i = 1, st o p t he trial a n d c o ncl u de n o d ose is safe.  
I nteri m M o nit ori n g  
T he d ose escalati o n will be cl osel y m o nit ore d f or safet y a n d f or i de ntifica ti o n of t he M T D. If n o 
d oses are s afe, d os e escal ati o n f or t hat p o p ulati o n will st o p, a n d n o M T D will be declare d.  
S afet y M o nit ori n g   
If n o d oses are safe, d ose escalati o n will sto p, a n d n o M T D will be declare d. F or mall y, if  
Pr( pi > 2 5 %) > 9 5 % f or all i  
I de ntific ati o n of t he M T D  
After eac h d ose -le vel c o h ort, t he esti mati o n of M T D will be perf or me d. If t he m o del’s ne xt 
rec o m me n de d d os e is t he sa me or bel o w t he M T D, t he d ose escalati o n ma y be st o p pe d a n d M T D 
ca n be d eclare d. Alter n ati vel y, if t he m o del’s ne xt rec o m me n de d d os e is a b o ve t he esti mate d 
M T D le vel, a n d patie nts ha ve alr ea d y bee n treate d at t he hi g h er d ose le vel, a n d t he o bser ve d 
D L T rate at t he rec o m me n de d hi g h er d ose le vel e xcee ds t he tar get D L T rate of 2 5 %, t he d ose 
escalati o n ma y als o b e st o p pe d a n d M T D ca n be d eclare d.  
Si m ul ati o n St u dies   
T o e val uate t he o p erati n g c haracteristics of t he d os e -escalati o n desi g n, si m ulati o n st u dies were 
perf or me d f or t he f oll o wi n g sce nari os.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 4  of 1 5 2  
 
 
T he pl ots ill ustrate t he tr ue D L T rat e at eac h d ose le vel. F or Part C si m ulati o n, d ose le vel 1  is 
1. 0  m g/ k g a n d d ose le v el 2  is 1. 2 5 m g/ k g. F or e x a m ple, Sce nari o 1 ass u me t hat M T D is 
1. 2 5  m g/ k g, Sce nari o 2 ass u me t hat M T D is 1. 0  m g/ k g, a n d Sce nari o 3 ass u me t hat n o selecte d 
d ose is safe.  
I n eac h s ce n ari o, t he d os e-escalati o n a n d M T D -esti mati o n pr o cess is re place d wit h 
1 0 0 0  re plicati o ns. T he pr o ba bilit y of selecti n g a n M T D, a vera ge n u m ber of D L T a n d t he a v era ge 
n u m ber of patie nts treate d, at eac h d os e le vel is pr o vi de d.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 5  of 1 5 2  
 
 
Sce nari o 1:  
M T D is 1. 2 5 m g/ k g  
P ossi ble M T D D ose Le vel  
N o d ose  
is safe 
1. 0 m g/ k g  
1. 2 5 m g/ k g  
P ( Select t he Tr ue M T D) = 0. 5 3  
A vera ge D L T rate = 0. 1 9  
A vera ge n u m ber of patie nts 
a b o ve M T D = N A 
Tr ue D L T rate  
 
0. 1 2  
0. 2 2  
Mea n n u m ber of 
patie nts at d ose le vel  
 
4. 2 0  
5. 2 7  
Mea n n u m ber of D L Ts 
at d ose le vel 
 
0. 5 2  
1. 1 9  
Pr ( C h ose n M T D)  
0. 1 0  
0. 3 7  
0. 5 3  
Pr = pr o ba bilit y  
 
 
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 6  of 1 5 2  
Sce nari o 1:  
M T D is 1. 0 m g/ k g  
P ossi ble M T D D ose Le vel  
N o d ose  
is safe 
1. 0 m g/ k g  
1. 2 5 m g/ k g  
P ( Select t he Tr ue M T D) = 0. 4 9  
A vera ge D L T rate = 0. 3 4  
A vera ge n u m ber of patie nts 
a b o ve M T D = 3. 9 
Tr ue D L T rate  
 
0. 2 2  
0. 4 0  
Mea n n u m ber of 
patie nts at d ose le vel  
 
5. 5 0  
3. 8 9  
Mea n n u m ber of D L Ts 
at d ose le vel 
 
1. 2 3  
1. 5 7  
Pr ( C h ose n M T D)  
0. 3 5  
0. 4 9  
0. 1 6  
 
 
 
Sce nari o 1:  
M T D is 1. 0 m g/ k g  
P ossi ble M T D D ose Le vel  
N o d ose  
is safe 
1. 0 m g/ k g  
1. 2 5 m g/ k g  
P ( Select t he Tr ue M T D) = N A  
A vera ge D L T rate = 0. 4 7  
A vera ge n u m ber of patie nts 
a b o ve M T D = N A 
Tr ue D L T rate  
 
0. 3 5  
0. 4  
Mea n n u m ber of 
patie nts at d ose le vel  
 
4. 8 7  
2. 4 8  
Mea n n u m ber of D L Ts 
at d ose le vel 
 
1. 7 5  
0. 9 6  
Pr ( C h ose n M T D)  
0. 6 2  
0. 2 5  
0. 1 3  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 7  of 1 5 2  
A P P E N DI X  N : 
N A TI O N A L KI D N E Y F O U N D A TI O N, E S TI M A T E D G F R 
C A L C U L A TI O N   
T he f oll o wi n g calc ul ati o n is use d t o deter mi ne G F R.  
G F R ( m L/ mi n/ 1. 7 3 m 2) = 1 7 5 × ( Scr)-1. 1 5 4 × ( A ge) -0. 2 0 3 × ( 0. 7 4 2 if fe male) × ( 1. 2 1 2 if A frica n 
A merica n)  
● 
Scr is ser u m creati ni ne  
● 
κ is 0. 7 f or fe m ales a n d 0. 9 f or males  
● 
α is – 0. 3 2 9 f or fe m ales a n d – 0. 4 1 1 f or males  
● 
mi n i n dicates t he mi ni m u m of Scr/ κ or 1  
● 
ma x i n dicates t he ma xi m u m of Scr/ κ or 1  
Fr o m: Le ve y A, Ste ve ns L, Sc h mi d C, Z h a n g Y, Castr o A, Fel d ma n H, K use k J, E g gers P, V a n Le nte F, Gree ne T, C ores h J, 
C K D -E PI ( C hr o nic Ki d ne y Disease E pi d e mi ol o g y C olla b orati o n) ( 2 0 0 9). A ne w e q uati o n t o esti mat e G F R. A n n I nter n Me d 
1 5 0( 9): 6 0 4 -6 1 2.  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 8  of 1 5 2  
A P P E N DI X  O : I N V E S TI G A T O R SI G N AT U R E P A G E   
 
I n vesti g at or St ate me nt a n d Si g n at ure  
 
I h a ve rea d t he attac he d pr ot oc ol e ntitle d Si n gle Ar m, O pe n La b el P hase 1 b/ 2 St u d y of 
S G N -LI V 1 A i n C o m bi nati o n wit h Pe m br oliz u ma b f or First -Li n e Treat me nt of Patie nts wit h 
U nresecta ble L ocall y -A d va nce d or M etastatic Tri ple -Ne gati ve Breast Ca n cer  
I u n d ersta n d a n d a gree t o t he pr o visi o ns of t he pr ot oc ol, a n d I acce pt t he res p o nsi bilities liste d 
a b o ve i n m y r ole as pri n ci pal i n vesti gat or f or t he st u d y.  
 
 
 
I n vesti gat or Si g nat ure 
 
Date  
 
 
 
 
 
 
 
 
 
I n vesti gat or Na me, Pri nte d 
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2 9  of 1 5 2  
A P P E N DI X  P : D O C U M E N T HI S T O R Y  
Versi o n  
Date  
Ori gi nal  
1 4 -Se p -2 0 1 7  
A me n d me nt 1  
2 9 -Ma y -2 0 1 8  
A me n d me nt 2  
1 4 -A u g -2 0 1 8  
A me n d me nt 3  
0 7 -Fe b -2 0 1 9  
A me n d me nt 4  
1 4 -J u n-2 0 1 9  
A me n d me nt 5  
2 8 -Fe b -2 0 2 0  
A me n d me nt 6  
2 4 -J ul-2 0 2 0  
A me n d me nt 7  
1 2 -Oct -2 0 2 0  
A me n d me nt 8  
0 5 -Mar -2 0 2 1  
A me n d me nt 9  
0 9 -N o v -2 0 2 1  
A me n d me nt 1 0  
2 4 -Ma y -2 0 2 2  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 0  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 1   
Secti o n(s)  
C ha n ge  
Rati o nale  
Title p a ge  
C ha n ge of me dical m o nit or c o ntact i nf o  
U p date t o st u d y pers o n nel  
Pr ot oc ol S y n o psis, 
Fi g ure  1, 3. 2, 4. 1, 
7. 4. 1, A p pe n di x A  
S pecifie d t hat p atie nts wit h i naccessi ble t u m ors 
ma y s u b mit arc hi val t u m or sa m ples d uri n g 
scree ni n g if c ollecte d after c o m pleti o n of pri or 
t hera pies. 
Clarificati o n  
Pr ot oc ol S y n o psis, 
Fi g ure  1, 3, 7. 2, 
A p pe n di x A  
I ma gi n g visit sc he d ule c ha n ge d fr o m a cli nic-
visit -base d sc he d ule t o a cale n dar -base d 
sc he d ule 
Kee ps i ma gi n g sc he d ule m ore 
c o nsiste nt i n t he e ve nt of patie nt d ose 
dela ys.  
Pr ot oc ol S y n o psis, 
A p pe n di x A  
S pecifie d t hat p atie nts w h o disc o nti n ue 
treat me nt will be f oll o we d u ntil pr o gressi o n or 
start of a ne w ca ncer t hera p y 
Clarificati o n  
Pr ot oc ol S y n o psis, 
3. 1. 1, 3. 1. 2, 9. 3. 1 0  
A d diti o n of a n I S M C t o re vie w c u m ulati ve 
safet y data 
A d diti o nal meas ure t o e ns ure patie nt 
safet y 
Pr ot oc ol S y n o psis, 
4. 1  
C h a n ge d re q uire me nt f or 1 2 m o nt hs t o ha ve 
ela pse d bet wee n pri or treat me nt wit h c urati ve 
i nte nt a n d disease rec urre nce. T his peri o d is 
n o w 6 m o nt hs.  
Ne w data i n dicate t hat a 6 m o nt h 
peri o d is m ore ali g ne d wit h ot her rece nt 
a n d o n g oi n g cli nical trials i n t his 
p o p ulati o n.  
Pr ot oc ol S y n o psis, 
7. 4, A p pe n di x C  
Re place me nt of “ A da pti ve T C R” wit h 
“cl o nalit y of T C R β” t o t he bi o mar ker 
assess me nts list a n d a d diti o n of T C R β 
i m m u n o S E Q a nal ysis t o met h o ds of a nal ysis 
list 
Clarificati o n  
Pr ot oc ol S y n o psis, 
3. 1. 1  
Re w or de d e x pla nati o n of t otal patie nt n u m bers 
a n d e x pecte d n u m bers t o be e nr olle d at t he 
rec o m me n de d d ose 
Clarificati o n  
List of 
A b bre viati o ns a n d 
Defi niti o ns of 
T er ms  
A d diti o n of I S M C  
U p date d t o i ncl u de a ne w ter m use d i n 
t he d oc u me nt 
1. 6  
Se nte nce was a d de d re gar di n g t he s p o ns or’s 
ac k n o wle d ge me nt t hat n o precli nical data ha ve 
bee n ge nerate d t o c haracterize a ntit u m or 
acti vit y wit h L V  a n d pe m br oli z u ma b 
c o m bi nati o n t hera p y.  
Clarificati o n  
Fi g ure  1, 6. 3, 7. 4. 1, 
A p pe n di x A, 
A p pe n di x C  
Ti mi n g of o n -treat me nt bi o ps y c ha n ge d fr o m 
C 1 D 5 f or all patie nts t o C 1 D 5 f or patie nts i n 
P art A a n d C 1 D 1 5 f or patie nts i n P art B.  
Rece nt data fr o m ot her st u dies s u p p ort 
a nal ysis of bi o mar kers o ver a wi der 
ra n ge of ti me. 
3. 1. 3, 5. 2. 5  
C ha n ge d “treat me nt wit h L V  or 
pe m br oliz u ma b ” t o “treat me nt wit h L V  a n d 
pe m br oliz u ma b ”  
C orrecti o n  
3. 1. 3  
A d de d t he p hrase “e xce pti o ns n ote d bel o w” t o 
t he first criteria f or D L T 
Clarificati o n  
3. 2  
A d de d “i n a d diti o n t o R E CI S T ” t o e x pla nati o n 
of i R E CI S T res p o nse criteria  
Clarificati o n  
4. 1  
S pecifie d u nits f or e G F R as m L/ mi n/ 1. 7 3 m 2 
C orrecti o n  
5. 2. 3  
A d de d a wi n d o w of all o wa ble ti me f or L V  
i nf usi o n t o occ ur 
Pr o vi des f urt her g ui da nce t o sites a n d 
s u p p orts c o nsiste nt i nf usi o n ti mes 
acr oss t he st u d y  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 1  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
5. 2. 5  
C ha n ge d “ dela ys of > 1 4 da ys m ust be 
disc usse d wit h me dical m o nit or” t o “ dela ys of 
> 1 4 da ys m ust b e a p pr o ve d b y me dical 
m o nit or”  
S u p p orts c o nsiste nc y i n d osi n g acr oss 
t he st u d y 
T a ble  1  
L V  d ose m o dificati o n c ha n ges t o ele vate d 
bl o o d gl uc ose a n d ne utr o pe nia  
E n ha nce me nt of patie nt safet y base d o n 
u p date d u n dersta n di n g of dr u g effects; 
clarificati o n re gar di n g ne utr o pe nia  
T a ble  2  
P e m br oliz u ma b d ose m o dificati o n c ha n ges t o 
m y ocar ditis, ne p hritis, ot her i m m u ne -relate d 
A e s 
E n ha nce me nt of patie nt safet y base d o n 
u p date d u n dersta n di n g of dr u g effects  
5. 5. 2, 5. 5. 3  
A d de d criteria t o per mit c o nc o mita nt 
ra di ot hera p y 
Fee d bac k fr o m i n vesti gat ors t o better 
ali g n wit h sta n dar ds of care  
5. 7  
Ne w secti o n a d de d o n ma na ge me nt of 
h y per gl yce mia  
E n ha nce me nt of patie nt safet y base d o n 
u p date d u n dersta n di n g of dr u g ef fects 
6, 7. 5. 3,  
A p pe n di x A  
S pecifie d w hic h la b orat or y tests are t o be 
perf or me d ce ntrall y a n d/ or l ocall y  
Clarificati o n  
6. 2, A p pe n di x A  
S pecifie d criteria f or re peat testi n g of H b A 1c 
or referral f or gl uc ose ma na ge me nt  
E n ha nce me nt of patie nt safet y base d  o n 
u p date d u n dersta n di n g of dr u g effects  
6. 3  
S pecifie d w hic h assess me nts m ust be 
perf or me d pre d ose  
Clarificati o n  
6. 6, 7. 5. 5,  
A p pe n di x A  
Pre g na nc y test a d de d at 2 4 we e ks after E O T  
C o m plia nce wit h healt h a ut h orit y 
re g ulati o ns 
6. 7  
St u d y cl os ure criteria a d de d  
Clarificati o n  
7. 4. 1, 7. 4. 3  
S pecifie d t hat o nl y U S patie nts will be as ke d t o 
c o nse nt t o s u b missi o n of left o ver tiss ue fr o m 
u nsc he d ule d bi o psies a n d f or s peci me n 
i ncl usi o n i n t he bi os peci me n r e p osit or y. Als o 
s pecifie d t hat p atie nts ma y wit h dra w 
per mis si o n f or rete nti o n of sa m ples at a n y ti me 
Clarificati o n  
7. 5. 2, A p pe n di x A  
A d de d a meas ure me nt of vital si g ns wit hi n 
2  h o urs after eac h i nf usi o n  
E n ha nce me nt of patie nt safet y  
7. 5. 3  
List of cli nical la b orat or y tests u p date d t o 
i ncl u de G G T a n d bl o o d gl uc ose  
Clarificati o n  
A p pe n di x  E  
H or m o nal birt h c o ntr ol met h o ds re m o ve d fr o m 
list of “ Acce pta ble met h o ds” a n d a d de d t o 
“ u nacce pta ble met h o ds” list  
H or m o nal c o ntrace pti o n is 
c o ntra -i n dicate d i n B C patie nts 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 2  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 2   
Secti o n(s)  
C ha n ge  
Rati o nale  
Pr ot oc ol S y n o psis, 
3. 1. 1, 3. 2. 2, 5. 2. 3, 
5. 2. 5, 9. 1  
C ha n ge d t he ma xi m u m d ose per c ycle f or 
patie nts d ose d at 2. 5 m g/ k g fr o m 2 0 0 m g t o 
2 5 0  m g. I n a d diti o n, t he ma xi m u m wei g ht ca p 
was c ha n ge d fr o m 8 0 k g t o 1 0 0 k g  
T he ma xi m u m d ose all o wa ble was 
c ha n ge d t o i ncrease efficac y i n patie nts 
w h o wei g h > 8 0 k g  
Pr ot oc ol S y n o psis, 
3. 1. 1, 3. 2. 2, 5. 2. 3, 
5. 5. 1, T a ble 1, 
A p pe n di x A  
A d de d la n g ua ge t o i n dicate t hat pr o p h ylactic 
G -C S F is n o w ma n dat or y f or patie nts w h o 
wei g h > 8 0 k g a n d will be gi ve n t o patie nts o n 
t he da y after st u d y treat me nt is gi ve n, wit h a 
visit wi n d o w of Da y 2 -4  
T he i ncrease i n t he d ose ca p t o 2 5 0 m g 
L V , b ut re q uiri n g gr o wt h fact ors 
s u p p ort f or patie nts w h o will r ecei ve 
> 2 0 0 m g L V  per c ycle, s h o ul d pr o vi de 
a fa v ora ble bala nce of acti vit y a n d 
safet y f or patie nts recei vi n g L V  
List of 
A b bre viati o ns a n d 
Defi niti o ns of 
T er ms  
A d de d “ m T N B C”  
U p date d t o i ncl u de a ne w ter m use d i n 
t he d oc u me nt 
Fi g ure 1, 4. 1, 7. 4. 1, 
A p pe n di x A  
Re m o ve d t he bi o ps y re q uire me nt of a n 1 8 
ga u ge nee dle a n d a d de d la n g ua ge relate d t o 
bi o ps y met h o ds “ C ore nee dle or e xcisi o nal 
bi o ps y is preferre d. If neit her is p ossi ble, 
disc uss wit h s p o ns or w het her bi o ps y o btai ne d 
via alter nati ve met h o ds ma y be  a p pr o priate.”  
Clarificati o n  
3. 1. 1  
U p date d st u d y desi g n t o i ncl u de d ose 
re-escalati o n la n g ua ge: “ D ose re -escalati o n 
bac k t o L V  2. 5 m g/ k g ( ma xi m u m d ose of 2 5 0 
m g) if 2. 0 m g/ k g is pr o ve n t o be safe.”  
T o all o w f or re -c halle n ge of L V  2. 5 
m g/ k g d osi n g  
3. 1. 3  
U p date d D L T criteria t o s pecif y t hat Gra de 3 
diarr hea a n d v o miti n g are n ot c o nsi dere d D L Ts 
if t he y res ol ve t o Gra de 1 wit hi n 3 da ys. 
U p date d defi niti o n of D L T. A d de d t he 
la n g ua ge “ wit h or wit h o ut me dical assess me nt” 
t o t he f oll o wi n g e ve nts n ot t o be c o nsi dere d at 
D L T: fati g ue, t u m or pai n, ras h, na usea, a n d 
v o miti n g.  
Clarificati o n a n d ali g n me nt wit h ot her 
pe m br oliz u ma b c o m bi nati o n st u dies  
4. 1, 1 0. 1  
A d de d t hat patie nt or patie nt’s L A R ca n 
pr o vi de writte n i nf or me d c o ns e nt i n acc or da nce 
wit h l ocal le gal re q uire me nts 
Ali g n me nt wit h t he I C Fs  
4. 2  
C ha n ge d C N S metastases e xcl usi o n criteria t o 
o nl y e xcl u de patie nts wit h car ci n o mat o us 
me ni n gitis or acti ve C N S met astases, wit h t he 
e xce pti o n of patie nts w h ose C N S metastases 
are a d e q uatel y treate d a n d w h o ha ve 
ne u r ol o gicall y ret ur ne d t o baseli ne f or at least 4 
wee ks pri or t o e nr oll me nt  
T o re d uce e xcl usi o n t o e nr oll me nt  
4. 2  
A d de d E xcl usi o n Criteria 1 1 a n d 2 2 relate d t o 
pri or ra di ot hera p y a n d all o ge nic tiss ue/s oli d 
or ga n tra ns pla nt, res pecti vel y  
Ali g n me nt wit h ot her  pe m br oliz u ma b 
c o m bi nati o n st u dies  
5. 5. 2, A p pe n di x F  
C ha n ge d “ C Y P 3 A 4” t o “ C Y P 3 A” i n t he list of 
P -g p a n d C Y P 3 A i n d ucers a n d i n hi bit ors  
Ali g n me nt wit h ot her st u dies wit hi n t he 
pr o gra m  
6. 3. 1, A p pe n di x A  
Clarifie d pr oce d ures perf or me d o n Da y 1  
Clarificati o n  
6. 3. 1, 6. 3. 3, 6. 3. 4, 
6. 3. 5  
A d de d t he assess me nts “ C olle cti o n of 
c o nc o mita nt me dicati o n i nf or mati o n” a n d 
“ C ollecti o n of A e s” t o Da ys 5, 8, a n d 1 5 
T o ali g n wit h t he S O E  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 3  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
3. 1, 6. 3. 3, A p pe n di x 
B, A p pe n di x C  
Re m o ve d Da y 5 visit fr o m P art B  
T o ti mel y ali g n bi o ps y a n d P K/ P D 
c ollecti o n f or c orrelati o n a nal ysis  
6. 4, 6. 5, A p pe n di x 
A  
A d de d ne w secti o n f or Res p o nse Assess me nts 
a n d ne w f o ot n ote t o t he S O E stati n g t hat 
res p o nse assess me nts are “ N ot re q uire d if 
c o n d ucte d wit hi n 4 wee ks pri or t o E O T ”  
T o de -c o u ple res p o nse assess me nts 
fr o m sta n dar d visit da ys as t hese 
assess me nts n o l o n ger relate t o visit 
c ycles  
7. 4. 2, 7. 5. 3  
A d de d t u m or mar kers C E A, C A 1 5 -3, a n d 
C A 2 7 -2 9 (if alrea d y bei n g perf or me d per t he 
site’s sta n dar d of care) t o bi o mar ker 
assess me nts  
T o detect p oss i ble pse u d o pr o gressi o n 
9. 3. 6. 2, 9. 3. 6. 3  
U p date d sec o n dar y a n d a d diti o nal a nal yses i n 
t he d oc u me nt b o d y 
T o ali g n wit h t he pr ot oc ol s y n o psis  
A p pe n di x A  
A d de d criteria f or a re peat assess me nt t o be 
o btai ne d if fasti n g bl o o d gl uc ose is ele vate d 
d uri n g scree ni n g a n d a d de d f o ot n otes f or 
ti mi n g of res p o nse assess me nts a n d refere nce 
t o t he la b ma n ual f or i nf or mati o n o n sa m ple 
c ollecti o n  
Clarificati o n  
A p pe n di x C  
A d de d f o ot n ote “If a d diti o nal tests, i ncl u di n g 
b ut n ot li mite d t o t u m or mar ker assess me nts, 
are perf or me d as part of sta n dar d of care, 
please s u b mit t h ose res ults.”  
Clarificati o n  
A p pe n di x F  
U p date d list of P -g p a n d C Y P 3 A i n hi bit ors  
T o c o m pl y wit h t he u p date d 2 0 1 6 F D A 
ta ble f or P-g p a n d str o n g C Y P 3 A 
i n hi bit ors 
A p pe n di x G  
U p date d Ne w Y or k Heart Ass ociati o n 
classificati o n la n g ua ge t o ali g n wit h o nli ne 
s o urce 
Clarificati o n  
A p pe n di x K  
C ha n ge d calc ulati o n use d t o deter mi ne G F R  
Clarificati o n  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 4  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 3   
Secti o n(s)  
C ha n ge  
Rati o nale  
Pr ot oc ol S y n o psis 
Fi g ure 1 f o ot n ote, 
3. 1, 6. 4, 7. 2, 
A p pe n di x A  
C ha n ge d ra di o gra p hic e xa m t o be e ver y 6 
wee ks f or 1 2 m o nt hs  
T he ra di o gra p hic e xa m peri o d was 
s h orte ne d bet wee n 6-1 2 m o nt hs t o 
m ore acc uratel y meas ure P F S  
Pr ot oc ol S y n o psis, 
Fi g ure 1 f o ot n ote, 
3. 1, 6. 4, 7. 2, 
A p pe n di x A  
I ncrease d ra di o gra p hic e xa m wi n d o w after 1 2 
m o nt hs fr o m ± 3 da ys t o ± 7 da ys  
T o pr o vi de m ore fle xi bilit y t o patie nts  
Pr ot oc ol S y n o psis 
Fi g ure 1 f o ot n ote  
C o nfir me d o bj ecti ve res p o nses t o be at least 4 
wee ks after d oc u me nte d res p o nse  
Si m plif y re q uire me nt  
Pr ot oc ol S y n o psis, 
3. 1, 5. 3. 5. 3  
U p date d pe m br oliz u ma b ma xi m u m d ose t o 
i ncl u de 3 5 c ycles or 2 4 m o nt hs, w hic he ver 
occ urs first  
U p date d t o reflect c urre nt prescri bi n g 
rec o m me n dati o ns of pe m br oliz u ma b  
3. 1  
St u d y sc he d ule will be t he sa me f or P arts A 
a n d B e xce pt f or C ycle 1 Da y 3 a n d Da y 5  
U p date d t o reflect ne w P K 
re q uire me nts 
3. 1  
Re m o ve d se nte nce a b o ut LI V -1 p ositi ve patie nt 
defi niti o ns  
P atie nts are n ot scree ne d f or LI V -1  
3. 1. 3  
A d de d G ra d e 4 t o Aes n ot c o nsi dere d a D L T 
f or ras h, na usea, diarr hea, a n d v o miti n g 
T o e n ha nce patie nt safet y  
4. 1  
F or patie nts w h o d o n ot ha ve tiss ue sa m ple 
a vaila ble, disc uss wit h me dical m o nit or.  
T o re d uce e xcl usi o n t o e nr oll me nt  
4. 2  
E dite d la n g ua ge re gar di n g  e xcl usi o n f or 
ra diati o n t hera p y wit hi n 2 wee ks 
Clarificati o n  
5. 2. 5  
All o w d ose dela ys f or a cli nic all y -si g nifica nt, 
u nres ol ve d A E o n Da y 1 of a n y c ycle, rat her 
t ha n o nl y C ycle 2 a n d be y o n d. 
Clarificati o n  
5. 7, 6. 2, A p pe n di x 
A  
P atie nts wit h h y per gl yce mia s h o ul d be gi n 
gl uc ose ma na ge me nt bef ore st arti n g st u d y or 
wit hi n o ne wee k of starti n g tre at me nt. P atie nts 
are n ot re q uire d t o ha ve a referral.  
S G N -L V A 1 A ma y ca use or w orse n 
h y per gl yce mia, t heref ore treat me nt f or 
h y per gl yce mia s h o ul d be gi n pri or t o or 
wit hi n o ne wee k of starti n g st u d y 
treat me nt 
6. 2, A p pe n di x A  
C oa g ulati o n pa nel perf or me d d uri n g scree ni n g 
i nstea d of baseli ne visit 
M o ve d t o scree ni n g t o all o w site t o 
assess patie nt eli gi bilit y  
6. 2, 7. 1, A p pe n di x 
A  
Re m o ve d b o ne sca n re q uire me nt  
T o a v oi d s u bj ecti n g patie nts t o p ossi bl y 
e xtra ne o us testi n g  
6. 3  
Re m o ve d “ of eac h c ycle” after C ycle 1 hea di n g  
Clarificati o n  
6. 3. 1, A p pe n di x A  
A d de d pr oce d ures ca n be perf or me d u p t o 2 
da ys pri or Da y 1 i n C ycle 2 a n d be y o n d; A d de d 
wi n d o ws t o f o ot n otes f or Da y 1 ac ti vities i n 
A p pe n di x A t o matc h te xt i n 6. 3. 1  
Ali g n me nt t o pre vi o us pr ot oc ol 
( A me n d me nt 1); Clarificati o n 
6. 3. 1, A p pe n di x A  
H b A 1c n ot re q uire d o n Da y 1  
Re q uire me nt met at scree ni n g  
6. 3. 1, 6. 5, A p pe n di x 
A  
C oa g ulati o n pa nel n ot re q uire d o n Da y 1 or 
E O T  
Re q uire me nt met at scree ni n g  
6. 3. 1, A p pe n di x C  
C ha n ge d pre d ose bl o o d sa m pl es f or bi o mar kers 
re q uire d f or C ycles 1, 2, a n d 3 o nl y 
Li mit sa m ples t o w hat ca n reas o na bl y 
be a nal yze d.  
6. 3. 1, A p pe n di x B  
C ha n ge d pre d ose bl o o d sa m pl es f or P K a n d 
A T A re q uire d f or  C ycles 1, 2, 3, 4, 5, a n d 
e ver y 5 c ycles t hereafter  
A d de d t o better assess P K a n d A T A 
(i m m u n o ge nicit y) 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 5  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
6. 3. 1, A p pe n di x B  
C ha n ge d p ost d ose bl o o d sa m ples f or P K 
re q uire d f or C ycles 1, 2, a n d 4 
C ollecti o ns i n C ycles 6 a n d 8 are n o 
l o n ger re q uire d. 
6. 3. 2, A p pe n di x B  
Da y 3 a d de d f or P art B C ycle 1. Re q uire d f or 
U S p atie nts, o pti o nal f or e x -U S patie nts. Bl o o d 
sa m ples f or P K 
A d de d t o ca pt ure M M A E ma xi m u m 
c o nce ntrati o n  
6. 3. 3, 6. 3. 4, 6. 3. 5  
Re m o ve d bl o o d sa m ples f or bi o mar kers o n 
Da ys 5, 8, a n d 1 5  
Li mit sa m ples t o w hat ca n reas o na bl y 
be a nal yze d.  
6. 3. 4, 6. 3. 5, 
A p pe n di x A  
Safet y la bs ( C B C a n d ser u m c he mistr y) o nl y 
re q uire d i n C ycles 1-4  
T o a v oi d s u bj ecti n g patie nts t o p ossi bl y 
e xtra ne o us testi n g  
6. 5, A p pe n di x A  
Re m o ve E O T E C G re q uire me nt  
T o a v oi d s u bj ecti n g patie nts t o p ossi bl y 
e xtra ne o us testi n g  
7. 5. 1. 1  
All A es m ust b e re p orte d after c o nse nt f or m is 
si g ne d 
C ha n ge d t o matc h A E re p orti n g 
la n g ua ge t hr o u g h o ut d oc u me nt 
7. 5. 1. 2  
C ha n ge d A E re p orti n g  
T o e ns ure t hat re p orte d A es d o n ot 
arise e xcl usi vel y fr o m diseas e 
pr o gressi o n  
9. 3. 1. 7  
D E a nal ysis defi ne d  
Clarificati o n  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 6  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 4   
Secti o n(s)  
C ha n ge  
Rati o nale  
Pr ot oc ol S y n o psis, 
Fi g ure 1:
 
S G N L V A -0 0 2 
st u d y sc he ma, 7. 4. 1  
A d diti o nal la n g ua ge a d de d t o tiss ue bi o ps y 
re q uire me nt. 
Clarificati o n  
Pr ot oc ol S y n o psis, 
3. 1. 2, 3. 2, 3. 2. 1, 
7. 5. 3, 9. 1, 9. 3. 1 0  
A d diti o n of P art B C o h ort 2 wit h c o nti n u o us 
m o nit ori n g f or ris k -be nefit pr ofile. Refer t o 
P art B C o h ort 1 as “ M A D” i nstea d  of 
“rec o m me n de d d ose.”  
T o assess t he o pti mal d ose of L V  i n 
c o m bi nati o n wit h pe m br oliz u ma b  
Pr ot oc ol S y n o psis, 
3. 1. 1, 3. 2, 3. 2. 2. 1, 
5. 2. 3, T a ble 5:
 
Re q uire d d ose 
m o dificati o ns f or 
L V -ass ociate d 
t o xicities, 5. 5. 1, 9. 1 
Re m o ve d refere nces t o ma xi m u m L V  d ose i n 
m g a n d re place d wit h wei g ht ca p (e xce pt i n  
S ecti o n 5. 2. 3 a n d if refere nci n g G -C S F 
treat me nt). 
Clarificati o n  
Pr ot oc ol S y n o psis  
A d de d “ u ntil deat h or st u d y cl os ure, w hic he ver 
occ urs first” t o le n gt h t hat pati e nts will be 
f oll o we d. 
Clarificati o n  
Pr ot oc ol S y n o psis, 
3. 1. 1, 3. 2, 3. 2. 2. 1, 
5. 2. 3, 5. 2. 5, T a ble 5:
 
Re q uire d d ose 
m o dificati o ns f or 
L V -ass ociate d 
t o xicities, 9. 1 
A d de d “a n d later” after secti o ns q ualif yi n g 
c ha n ges wit h A me n d me nt 2  
U p date la n g ua ge t o reflect a d diti o nal 
a me n d me nts.  
Pr ot oc ol S y n o psis, 
9. 3. 6. 1, 9. 3. 6. 3  
C ha n ge d pri mar y a nal yses of LI V -1 p ositi ve 
patie nts t o e x pl orat or y a nal ysis  
Pri mar y a nal ysis is base d o n all -c o mers  
List of 
A b bre viati o ns a n d 
Defi niti o ns of 
T er ms  
U p date d a b bre viati o ns ta ble  
U p date d ta ble t o matc h c urre nt pr ot oc ol  
1. 5, 1. 5. 1, 3. 2. 2. 2, 
3. 2. 2. 3  
U p date d pe m br oliz u ma b bac k gr o u n d  
U p dates ma de per Merc k re q uire me nts  
1. 6  
A d diti o n of A nti -P D( L) 1 la n g ua ge i n rati o nale 
f or st u d y 
U p date d t o fit c urre nt treat me nt 
la n dsca pe 
3. 2. 2. 1  
Clarifie d la n g ua ge ar o u n d ne utr o pe nia S A E  
Cl arificati o n  
4. 1  
Re m o ve d la n g ua ge fr o m i ncl usi o n criteria 4: 
“ meas ura ble disease per c o m p ute d t o m o gra p h y 
( C T) sca n as defi ne d b y R E CI S T v 1. 1 … ” 
Clarificati o n per R E CI S T v 1. 1  
5. 2. 5  
A d de d t hir d d ose re d ucti o n of 1. 2 5 m g/ k g  
All o w 2 d ose re d ucti o ns f or patie nts 
t hat start at 2. 0 m g/ k g 
T a ble 5:  Re q uire d 
d ose m o dificati o ns 
f or L V -ass ociate d 
t o xicities, 5. 7, 6. 2, 
A p pe n di x A  
A d de d ma na ge me nt of h y per gl yce mia la n g ua ge  Clarificati o n  
6. 2, 6. 2. 2, 6. 2. 3. 1, 
6. 2. 3. 4, 6. 2. 3. 5, 6. 5, 
7. 5. 3, A p pe n di x A  
A d d use of ce ntral la b orat or y f or P art B C o h ort 
2  
T o all o w res ults t o be a nal yze d b y t he 
ce ntral la b orat or y  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 7  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
Pr ot oc ol S y n o psis, 
Fi g ure 1:
 
S G N L V A -0 0 2 
st u d y sc he ma, 7. 4. 1  
A d diti o nal la n g ua ge a d de d t o tiss ue bi o ps y 
re q uire me nt. 
Clarificati o n  
6. 2. 3. 4, 6. 2. 3. 5, 
A p pe n di x A  
Re m o ve all D 1 5 safet y dra ws ( P K a n d bi o ps y 
re mai n) a n d c ha n ge D 8 dra ws t o C ycle 1-2 
o nl y  
Re d uce bl o o d dra w b ur de n f or patie nts  
7 . 2, A p pe n di x A 
A d diti o n of BI C R f or P art B C o h ort 2  
All o w f or o pti o n of i n de pe n de nt re vie w 
of sca ns  
7. 4. 1  
A d de d 2 5 sli de F F P E re q uire me nt  
Pr o vi de a de q uate tiss ue f or bi o mar ker 
data  
7. 4. 1, 7. 4. 2  
Re m o ve d “ce ntral” bef ore “la b orat or y ma n ual”  
Clarificati o n  
7. 5. 1. 1  
Clarif y t hat o nl y st u d y pr ot oc ol -related  A Es are 
re p orte d after i nf or me d c o nse nt bef ore 
treat me nt i nitiati o n  
Clarificati o n  
7. 5. 1. 2  
C ha n ge d la n g ua ge re gar di n g i n vesti gati n g 
p ote ntial ca uses of he pat ot o xi cit y t o “c o nsi der 
h ol di n g st u d y dr u g”  
U p da te t o sta n dar dize d la n g ua ge 
7. 5. 3  
Re m o ve d L D S a n d G G T fr o m list of c he mistr y 
pa nel (tests pre vi o usl y re m o ve d fr o m pr ot oc ol)  
C orrecti o n  
A p pe n di x B  
C ha n ge d A p pe n di x B c ycle c ol u m n t o reflect 
sc he d ule i n te xt 
C orrecti o n  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 8  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 5   
Secti o n(s)  
C ha n ge  
Rati o nale  
S y n o psis, 2, 3. 1, 
3. 1. 3, 3. 1. 4. 2, 3. 2, 
3. 2. 1, 3. 2. 3. 2, 
3. 2. 3. 3, 5. 2. 3, 5. 2. 5, 
5. 2. 3. 2, 5. 2. 5. 2, 
5. 5. 1, 5. 5. 2. 1, 5. 5. 3, 
5. 7, 6. 3, 6. 5, 7. 4. 1, 
7. 5. 2, 7. 5. 3, 9. 1, 
9. 1. 3, A p pe n di x C, 
A p pe n di x D, 
A p pe n di x E, 
A p pe n di x M  
A d de d a wee kl y L V  d osi n g sc he d ule ( P art C). 
Affecte d secti o ns i ncl u de  
- 
O bj ecti ves a n d e n d p oi nts  
- 
St u d y desi g n  
- 
D ose -li miti n g t o xicit y 
- 
Rati o nale f or st u d y desi g n  
- 
Met h o d of assi g ni n g patie nts t o 
treat me nt gr o u ps 
- 
Rati o nale f or selecti o n of d oses  
- 
L V  d ose a n d a d mi nistrati o n  
- 
L V  d ose m o dificati o ns  
- 
Re q uire d c o nc o mita nt t hera p y  
- 
Pr o hi bite d c o nc o mita nt t hera p y  
- 
Ma na ge me nt of h y per gl yce mi a  
- 
St u d y acti vities  
- 
Bi o mar kers i n s oli d t u m or tiss ue  
- 
Deter mi nati o n of sa m ple size  
- 
P K, A T A, a n d bi o mar ker sa m pli n g 
ti me p oi nts f or P art C 
- 
m T PI i nter val desi g n si m ulati o n re p ort  
T o e val uate wee kl y L V  d osi n g i n 
c o m bi nati o n wit h pe m br oliz u ma b  
S y n o psis, 3. 1, 6. 6, 
A p pe n di x A  
C ha n ge d fre q ue nc y of f oll o w -u p visits fr o m 
e ver y 1 2 wee ks t o e ver y 6 we e ks f or t he first 
year o n st u d y u ntil disease pr o gressi o n or 
i nitiati o n of a ne w t hera p y. After 1 year o n 
st u d y, t he fre q ue nc y of f oll o w-u p visits will be 
re d uce d t o e ver y 1 2 wee ks. 
T o i m pr o ve efficac y m o nit ori n g  
3. 1  
I ntrapatie nt d ose escalati o n or de -escalati o n t o 
a d ose le vel s h o w n t o be safe ma y be per mitte d 
wit h s p o ns or a p pr o val i n t he e ve nt t hat a 
patie nt t olerates st u d y treat me nt.  
T o all o w o pti mal d osi n g f or patie nts 
w h o t olerate st u d y treat me nt  
3. 1. 1, 3. 2. 3. 1, 
A p pe n di x A  
Clarifie d t hat t he ma xi m u m wei g ht ca p a n d 
d ose ca p are per i nf usi o n, n ot per c ycle.  
Clarificati o n  
5. 2. 3. 3, 6. 2. 3, 6. 3. 3, 
A p pe n di x A  
A d de d L V  d osi n g criteria  
T o s pecif y mi ni m u m criteria t o be met 
pri or t o L V  d osi n g  
5. 2. 5  
U p date d d ose m o dificati o ns:  
 
P atie nts w h o e x perie nce D L T i n C ycle 1 (t he 
D L T e val uati o n peri o d) s h o ul d n ot recei ve 
f urt her treat me nt wit h L V  a n d pe m br oliz u ma b 
u nless cli nical be nefit is de m o nstrate d wit h  
o bser ve d a n d t he A E(s) is  a de q uatel y ma na ge d 
t o xicit y wit h se verit y i m pr o vi n g t o  Gra de 1 or 
l o wer. S u bse q ue nt d oses will be defi ne d b y t he 
me dical m o nit or i n disc ussi o n wit h t he site 
i n vesti gat or i n t he c o nte xt of t he t y pe of A E(s) 
o bser ve d.  
I n t he e ve nt a patie nt is u na ble t o t olerate t heir 
d ose le vel, a d diti o nal treat me nt c ycles ( C y cle 2 
or later) ma y be a d mi nistere d at a l o wer d ose 
Clarificati o n a n d t o ali g n wit h c urre nt 
L V  d ose m o dificati o n 
rec o m me n dati o ns 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3 9  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
le vel. C o ns ultati o n wit h t he me dical m o nit or is 
str o n gl y e nc o ura ge d. 
6. 2. 1, 7. 1  
Re m o ve d ser ol o g y f or he patitis C a n d s pecifie d  
t hat P C R f or he p atitis C viral l oa d s h o ul d be 
perf or me d at scree ni n g  
T o ali g n wit h e xcl usi o n criteri a  
6. 2. 1, 6. 3. 1, 7. 1, 
7. 5. 3, A p pe n di x A, 
A p pe n di x C  
A d de d acti vate d partial t hr o m b o plasti n ti me 
(a P T T) t o scree ni n g assess me nts 
T o ali g n wit h i ncl usi o n cri teri a 
A p pe n di x G  
U p date d g ui da nce o n c o ntrace pti o n  
T o ali g n wit h E ur o pea n g ui da nce  
T hr o u g h o ut pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns  
C orrecti o n a n d clarificati o n  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 0  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 6   
Secti o n(s)  
C ha n ge  
Rati o nale  
S y n o psis , T a ble  1 , 
3. 1. 3 , 5. 2. 3. 2 , 
T a ble  5 , 
A p pe n di x  C  
Re vise d la n g ua ge t o state t hat t he ma xi m u m 
d ose of L V  i n P art C  is 2 0 0 m g per i nf usi o n.  
T o ali g n wit h c urre nt g ui deli nes f or 
L V . 
S y n o psis , 3. 1. 2 , 
3. 2. 3 , 5. 2. 3. 1 , 5. 5. 1 , 
5. 5. 2 , 5. 5. 2. 1 , 
A p pe n di x  C , 
A p pe n di x  L  
A d de d la n g ua ge clarif yi n g t hat pr o p h ylactic 
G -C S F t hera p y is o nl y re q uire d f or P arts A a n d 
B.   
C orrecti o n a n d clarificati o n  a n d t o 
ali g n wit h c urre nt g ui deli nes f or L V . 
S y n o psis , 3. 1 , 
5. 3. 5. 3  
U p date d pe m br oliz u ma b ma xi m u m d ose t o 
i ncl u de 3 5 c ycles (a p pr o xi mat el y 2 years). 
U p date d t o reflect c urre nt prescri bi n g 
rec o m me n dati o ns of pe m br oliz u ma b. 
S y n o psis , 6. 6  
A d de d te xt t o state t he f oll o w-u p visits will 
als o be disc o nti n ue d f or patie nts w h o i nitiate a 
ne w a ntica ncer treat me nt f or c o nsiste nc y wit h 
t he rest of t he pr ot oc ol. 
C orrecti o n a n d clarificati o n.  
S y n o psis , 3. 2. 3  
A d de d la n g ua ge clarif yi n g t hat t he wei g ht ca p 
a p plies t o  P arts A a n d B o nl y.  
C orrecti o n a n d clarificati o n.  
5. 2. 3. 3  
A d de d la n g ua ge t o c orrect t o L V  d osi n g 
criteria a n d t o refer t o d ose m o dificati o ns 
ta bles: 
T otal bilir u bi n ≤ Gra de 1 2  
A d diti o nal i nf or mati o n o n L V  d ose 
m o dificati o ns ca n be f o u n d i n T a ble 3 a n d 
T a ble  5. Please see T a ble 6 f or i nf or mati o n o n 
pe m br oliz u ma b d osi n g.  
C orrecti o n a n d clarificati o n . 
5. 2. 5. 2  
C orrecte d t he d ose wit h h ol di n g e xa m ple.  
C orrecti o n.  
T a ble  5  
Re vise d la n g ua ge t o c orrect i nc o nsiste n cies a n d 
clarif y d ose m o dificati o ns.  
C orrecti o n a n d clarificati o n.  
T a ble  6  
Re vise d la n g ua ge f or pe m br oliz u ma b d ose 
m o dificati o n s. 
U p date d t o reflect c urre nt prescri bi n g 
rec o m me n dati o ns of pe m br oliz u ma b. 
5. 5. 1 , 5. 5. 2  
Re m o ve d te xt fr o m Secti o n 5. 5. 1  t hat was 
d u plicate d i n S ecti o n 5. 5. 2. M o ve d te xt 
“ A d diti o nal vacci nati o n d uri n g t he c o urse of 
t he st u d y treat me nt m ust be disc usse d pri or t o 
a d mi nistrati o n wit h t he me dic al m o nit or” to 
Secti o n 5. 5. 2.  
C orrecti o n a n d clarificati o n.  
6. 3. 3 , 7. 3  
C orrecte d a p p e n di x li n ks f or P K a n d A T A 
sa m ples. 
C orrecti o n.  
6. 3. 3. 3 , 6. 3. 3. 4 , 
A p pe n di x  C  
A d de d ser u m c he mistr y pa nel c ollecti o n t o Da y 
8 a n d Da y 1 5 d uri n g C ycles 1 a n d 2 i n t he 
wee kl y d osi n g sc he d ule.  
T o ali g n wit h c urre nt g ui deli nes f or 
L V . 
7. 2  
A d de d te xt stati n g t hat i ma ges fr o m P art C will 
be c ollecte d b y a BI C R.  
C orrecti o n.  
7. 5. 1. 2  
Re m o ve d “ or are t he res ult of a pr ot oc ol -
s pecifie d i nter ve nti o n, s uc h as a pr oce d ure” 
fr o m t he pre g na nc y secti o n. 
C orrecti o n.  
7. 5. 5 , A p pe n di x  C  
Re vise d te xt t o clarif y t hat pre g na nc y  tests 
m u st b e perf or me d wit hi n 3 da ys pri or t o eac h 
Da y 1 st u d y dr u g d ose at eac h c ycle.  
C orrecti o n a n d clarificati o n.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 1  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
A p pe n di x  G  
A d de d te xt clarif yi n g t hat c o ntrace pti o n s h o ul d 
be use d u ntil at least 6 m o nt hs after t he fi nal 
d ose.  
C orrecti o n.  
A p pe n di x  L  
Re vise d a p pe n di x te xt t o ali g n wit h ot her 
Seattle Ge netics pr ot oc ols t hat use L V . 
C orrecti o n a n d clarificati o n a n d t o 
ali g n wit h c urre nt g ui deli nes f or L V . 
T hr o u g h o ut pr ot oc ol  
Mi n or c ha n ges t o c orrect i nc o nsiste ncies, 
c orrect a n d a d d cr oss -refere nc es, fi x 
t y p o gra p hical err ors, a n d clarificati o ns. 
C orrecti o n a n d clarificati o n.  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 2  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 7   
Secti o n(s)  
C ha n ge  
Rati o nale  
List of 
A b bre viati o ns a n d 
Defi niti o ns of 
T er ms  
A d diti o n of S U S A Rs  
U p date d t o i ncl u de a ne w ter m use d i n 
t he d oc u me nt 
T a ble 3  
Re vise d t he d ose m o dificati o ns ta ble  
C orrecti o ns a n d clarificati o ns  
T a ble 5  
Re vise d t he q 1 w k d ose m o difi cati o n s ta ble 
C orrecti o n s a n d clarificati o ns  
5. 5. 2  
A d de d te xt: 
W B C gr o wt h fact or s u p p ort, i ncl u di n g pri mar y 
or sec o n dar y pr o p h yla xis a n d treat me nt, is 
str o n gl y e nc o ura ge d per t he A S C O 2 0 1 5 
U p date  ( S mit h 2 0 1 5) (see A p pe n di x L ), wit h 
t he e xce pti o n of pri mar y pr o p h yla xis ( C ycle 1 
use) i n patie nts e nr olle d d uri n g  i n t he d ose 
escalati o n i n P art C parts ( wit h t he e xce pti o n of 
patie nts w h o recei ve > 2 0 0 S G N -L V 1 A m g per 
i nf usi o n). 
C orrecti o n.  
7. 5. 1. 5  
U p date d t he s p o ns or safet y re p orti n g secti o n t o 
ali g n wit h c urre nt pr ot oc ol te m plate la n g ua ge 
o n re p orti n g S A Es:  
 
I n vesti gat ors are re q uire d t o re p ort all S A Es, 
i ncl u di n g a ntici pate d S A Es, t o t he s p o ns or (see 
Secti o n 7. 5. 1. 4 ). 
 
T he s p o ns or will re p ort all S A Es , i ncl u di n g 
S U S A Rs,  t o re g ulat or y a ut h orities as re q uire d 
per l ocal  le gislati o n or re g ulat or y re p orti n g 
re q uire me nts. 
T o ali g n wit h re g ulat or y g ui da nce  
T hr o u g h o ut pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns  
C orrecti o n a n d clarificati o n  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 3  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 8   
Secti o n(s)  
C ha n ge  
Rati o nale  
S y n o psis, 3. 1. 3, 9. 1, 
9. 1. 3  
A d de d 4 0 patie nts t o P art C  
E nlar ge data b ase t o b etter defi ne a n d 
i nf or m L V + P e m br oliz u ma b safet y 
a n d efficac y  
T a ble 7  
U p date d pe m br oliz u ma b d ose m o dificati o ns 
ta ble. 
T o ali g n wit h u p date d g ui deli nes.  
T hr o u g h o ut pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns  
C orrecti o n a n d clarificati o n  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 4  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 9   
 
Secti o n(s)  
C ha n ge  
Rati o nale  
S y n o psis, 3. 2 , 3. 2. 4 , 
3. 3 , 3. 3. 1 , 3. 3. 3. 4 , , 
5. 3. 3. 4 , 5. 3. 3. 5 , 
5. 3. 5. 3 , 5. 6. 2. 1 , 5. 8 , 
6. 4 , 6. 4. 1 , 6. 4. 3. 4 , 
6. 6 , 7. 2 , 7. 3 , 7. 4 , 
7. 5. 1 , 7. 6. 3 , 9. 2 , 
9. 2. 4 , Fi g ure  2 , 
T a ble  6 , 
A p pe n di x  C , 
A p pe n di x  D , 
A p pe n di x  E  
A d de d a ne w sc he d ule of 1. 5 m g/ k g L V d osi n g 
o n Da ys 1 a n d 8 e ver y 2 1 da ys ( P art D).  
Affecte d secti o ns i ncl u de  
- 
St u d y desi g n  
- 
Rati o nale f or st u d y desi g n  
- 
Met h o d of assi g ni n g patie nts t o 
treat me nt gr o u ps 
- 
Rati o nale f or selecti o n of d oses  
- 
L V d ose a n d a d mi nistrati o n  
- 
L V d osi n g criteria  
- 
L V d ose m o dificati o ns  
- 
All o we d c o nc o mita nt t hera p y  
- 
Ma na ge me nt of h y per gl yce mi a  
- 
St u d y acti vities  
- 
St u d y assess me nts  
- 
Bli n de d i n de pe n de nt ce ntral re vie w 
( BI C R) of i ma gi n g 
- 
Bi o mar ker sa m pli n g i n s oli d t u m or 
tiss ue 
- 
Cli nical la b orat or y tests  
- 
Deter mi nati o n of sa m ple size  
T o e val uate 1. 5 m g/ k g L V d osi n g o n 
Da ys 1 a n d 8 ( off Da y 1 5) i n 
c o m bi nati o n wit h pe m br oliz u ma b.  
S y n o psis, 4. 2 , 7. 2 , 
A p pe n di x  C   
A d de d eli gi bilit y criteri o n f or P art D patie nts 
wit h m T N B C i n t he L A/ M B C setti n g  w h o  als o 
ha ve P D -L 1 C P S < 1 0  t o t he i ncl usi o n criteria 
a n d t hat P D -L 1 stat us will be deter mi ne d 
l ocall y at t he i n vesti gati ve site usi n g t he P D-L 1 
I H C 2 2 C 3 p har m D x F D A-a p pr o ve d test.  
T o assess t he safet y a n d acti vit y of 1. 5 
m g/ k g L V d osi n g o n Da ys 1 a n d 8 ( off 
Da y 1 5) i n c o m bi nati o n w it h 
pe m br oliz u ma b i n patie nts wit h 
m T N B C i n t he L A/ M B C setti n g  w h o 
ha ve P D -L 1 C P S < 1 0 . 
S y n o psis, 6. 4. 1 , 7. 2 , 
7. 5. 1 , A p pe n di x  C  
Clarifie d t hat arc hi val or fres h t u m or tiss ue is 
re q uire d acr oss all parts of t he st u d y f or ce ntral 
assess me nt of e x pl orat or y bi o mar ker a nal yses 
as well as f or l ocal assess me nt of P D -L 1 f or 
eli gi bilit y of P art D patie nts.  
T o e ns ure a p pr o priate t u m or tiss ue is 
a vaila ble f or assess me nt of eli gi bilit y 
f or P art D patie nts a n d f or assess me nt 
of e x pl orat or y bi o mar ker a nal yses.  
S y n o psis, 9. 2 , 9. 2. 4  
A d de d 4 0 patie nts t o st u d y i n P art D a n d als o, 
c ha n ge d o verall e nr oll me nt fr o m 1 4 9 -1 6 1 
patie nts t o 1 8 9 -2 1 1.  
T o e ns ure s ufficie nt patie nts are 
e val uate d t o deter mi ne t he safet y a n d 
acti vit y of 1. 5 m g/ k g L V d osi n g o n 
Da ys 1 a n d 8 ( off Da y 1 5) i n 
c o m bi nati o n wit h pe m br oliz u ma b i n 
patie nts wit h m T N B C i n t he L A/ M B C 
setti n g w h o ha ve P D-L 1 C P S < 1 0.  
S y n o psis,   
3. 2. 1 , 7. 6 , 9. 4. 1 0  
A d de d t hat t he I S M C i ncl u de d sp o ns or 
re prese ntati ves. 
Clarificati o n.  
6. 4. 3. 4  
A d de d t hat o nl y C B C will be d o ne f or P art D 
o n Da y 1 5 C ycles 1 a n d 2.  
T o e val uate patie nt he mat ol o g y pa nel 
o n Da y 1 5 f oll o wi n g recei vi n g L V o n 
Da ys 1 a n d 8.  
S y n o psis,  
9. 4. 1. 7 , 9. 4. 6 ,  
9. 4. 6. 1  
Re m o ve d t he I T T a nal ysis set a n d ma de t he all 
treate d a nal ysis set t he pri mar y set f or efficac y 
a nal ysis. 
T o ali g n wit h a rece nt a me n d me nt t o 
t he Statistical A nal ysis Pla n. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 5  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
S y n o psis ,  
9. 4. 6 , 9. 4. 6. 2 , 
9. 4. 6. 3  
C ha n ge d t he la n g ua ge ‘sec o n d ar y efficac y 
a nal yses’ as ‘a d diti o nal a nal ys es of efficac y 
e n d p oi nts’ a n d re m o ve d t he I T T a n d all treate d 
patie nts a na l ysis sets f or t h ose a nal yses t o 
clarif y t hat t he E E a nal ysis set w o ul d be use d 
f or t hese a d diti o nal a nal yses as a p pr o priate. 
T o ali g n wit h a rece nt a me n d me nt t o 
t he Statistical A nal ysis Pla n. 
3. 2. 5 , 3. 3. 1  
A d de d rati o nale  f or n o D L T e val uati o n of t he 
P art D re gi me n  
T o pr o vi de a scie ntific e x pla nati o n as 
t o w h y a D L T e val uati o n of t he P art D 
re gi me n is n ot nee de d. 
3. 3. 3. 4  
A d de d rati o nale f or t he patie nt p o p ulati o n f or 
P art D patie nts wit h m T N B C i n t he L A/ M B C 
setti n g w h o als o ha ve P D-L 1 C P S < 1 0  
T o  pr o vi de scie ntific rati o nale  
5. 3. 3. 1  
Create d a secti o n f or ‘All P arts ’ u n der Secti o n 
5. 2. 3 D ose a n d A d mi nistrati o n a n d m o ve d 
la n g ua ge fr o m u n der ‘P arts A a n d B ’ t hat is 
a p plica ble t o all parts  of t he st u d y  t o t he ne w 
secti o n, i ncl u di n g la n g ua ge re gar di n g i nf usi o n 
rates a n d  wei g ht -base d d osi n g.  
C orrecti o n.  
7. 4  
A d diti o n of meas ure me nts of c o nce ntrati o ns of 
t otal a nti b o d y i n plas ma a n d als o t hat relate d 
a nal ytes of L V ma y be meas ur e d usi n g 
a p pr o priate assa ys  
T o pr o vi de a d diti o nal data o n L V i n 
plas ma.  
7 . 5. 1 
C ha n ge d t hat if n o bl oc k is a vaila ble, t hat 2 5 
sli des ma y be s u b mitte d o nl y wit h me dical 
m o nit or a p pr o val.  
Beca use arc hi val tiss ue bl oc k is 
preferre d if fres h bi o ps y is n ot a n 
o pti o n f or eli gi bilit y of P art D, 
t heref ore, all ot her alter nati ves m ust b e 
a p pr o ve d b y t he me dical m o nit or.  
9. 4. 2  
C ha n ge d t he la n g ua ge of ‘ disc o nti n ue d fr o m’ 
t o ‘ca me off’ st u d y. 
T o be i ncl usi ve of patie nts w h o were 
l ost t o f oll o w-u p.  
S y n o psis, 9. 4. 1 0  
F or P art B C o h ort 2,  c o nti n u o us m o nit ori n g of 
t he be nefit-ris k pr ofile will be c o n d ucte d a n d 
c o nti n uati o n of e nr oll me nt t o t he c o h ort ma y be 
altere d de p e n di n g o n t he be nefit -ris k pr ofile 
C o nti n u o us m o nit ori n g of t he  
be nefit -ris k pr ofile a p plies t o all parts 
of t he st u d y.  
A p pe n di x  M  
U p date d t he li n k f or t he i m ple me ntati o n 
pr o gra ms f or t he m o difie d t o xicit y pr o ba bilit y 
i nter val met h o d 
C orrecti o n.  
T hr o u g h o ut pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns  
C orrecti o n a n d clarificati o n.  
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 6  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 1 0   
Secti o n(s)  
C ha n ge  
Rati o nale  
Title p a ge  
U p date d me dical m o nit or c o nt act i nf or mati o n  
P ers o n nel c ha n ge . 
Pr ot oc ol S y n o psis   
4. 1 , 6. 3. 1 , 7. 1 , 
A p pe n di x  C : 
F o ot n ote V  
Re m o ve d  t he re q uire me nt t o use t he P D -L 1 
I H C P har m D x F D A -a p pr o ve d assa y t o 
deter mi ne P D -L 1 C P S < 1 0 i n P art D. 
I n vesti gati ve sites ca n n o w det er mi ne P D -L 1 
C P S < 1 0 b y a P D -L 1 I H C assa y usi n g t he 
2 2 C 3 cl o ne . 
After i m ple me ntati o n of t he P D-L 1 
I H C P har m D x F D A-a p pr o ve d assa y 
re q uire me nt, it was f o u n d t hat t he 
maj orit y of U S a n d R est of W orl d  
i n vesti gati ve sites di d n ot ha ve access 
t o t his assa y. Sites were u na bl e t o 
e nr oll patie nts o n P art D. T he s p o ns or 
s u bse q ue ntl y d eter mi ne d t hat  usi n g a 
P D -L 1 I H C assa y wit h t he 2 2 C 3 cl o ne 
was s ufficie nt t o deter mi ne C P S < 1 0 
stat us f or e nr oll me n t. 
A p pe n di x  G  
Re m o ve d t he f oll o wi n g te xt fr o m A p pe n di x G.  
 
H or m o nal met h o ds of c o ntrace pti o n (e xcl u di n g 
pr o gesti n -o nl y pills; met h o d m ust be ass ociate d 
wit h i n hi biti o n of o v ulati o n), u nless 
c o ntrai n dicate d  
Clarificati o n i n res p o nse t o  a re q uest 
f or i nf or mati o n fr o m t he Re p u blic of 
K orea Mi nistr y of F o o d a n d Dr u g  
Safet y.  
H or m o nal c o ntrace pti o n is 
c o ntrai n dicate d i n breast ca nc er 
patie nts . T he s p o ns or a gree d t o re m o ve  
h or m o nal c o ntrace pti o n a ge nts fr o m 
A p pe n di x G f or clarit y.  
T hr o u g h o ut pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns  
C orrecti o n a n d clarificati o n.  
 
 
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 7  of 1 5 2  
S u m m ar y of C h a n g e s i n A m e n d m e nt 1 1  
Secti o n(s)  
C ha n ge  
Rati o nale  
Title P a ge  
U p date d me dical m o nit or  i nf or mati o n.  
P ers o n nel c ha n ge  
T hr o u g h o ut 
Pr ot oc ol  
Mi n or c orrecti o ns a n d clarific ati o ns.  
“Seattle Ge netics ” c ha n ge d t o “ Sea ge n I nc.”  
C orrecti o n a n d clarificati o n  
Pr ot oc ol S y n o psis  
T he f oll o wi n g te xt was a d de d:  
Res p o nses will be assesse d b y C T sca n a n d/ or ma g netic 
res o na nce i ma gi n g ( M RI) sca n e ver y 6 wee ks ( ± 3 da ys) 
f or t he first 1 2 m o nt hs after t he first d ose of L V a n d 
pe m br oliz u ma b a n d e ver y 1 2 wee ks ( ± 7 da ys) t hereafter 
t hr o u g h t he e n d of t he safet y f oll o w-u p peri o d. N o 
a d diti o nal sca ns or res p o nse assess me nts are re q uire d 
after t he safet y f oll o w -u p peri o d, h o we ver a d diti o nal 
sca ns or res p o nse assess me nts ma y be perf or me d as part 
of t he patie nt’s sta n dar d of care at a n y ti me.  
A ll patie nts, i ncl u di n g t h ose wit h pr o gressi ve disease, 
will b e f oll o we d f or s ur vi val u ntil t he e n d of t he safet y 
f oll o w-u p peri o d, deat h, or st u d y cl os ure, w hic he ver 
occ urs first.”  
After disease pr o gressi o n or i nitiati o n of a ne w a ntica ncer 
treat me nt, s ur vi val f oll o w-u p will be c o n d ucte d e ver y 1 2 
wee ks ( ± 2 wee ks) starti n g fr o m t he last ra di o gra p hic sca n 
de m o nstrati n g disea se pr o gressi o n or fr o m i nitiati o n of 
t he ne w a ntica ncer treat me nt. S ur vi val f oll o w-u p will 
c o nti n ue u ntil t he e n d of t he s afet y f oll o w -u p peri o d, 
deat h, or st u d y cl os ure, w hic he ver c o mes first. F oll o w -u p 
ma y be c o n d ucte d wit h cli nic visits or tele p h o ne cal ls. N o 
f urt her res p o nse assess me nts are re q uire d. 
Defi ne d  “ will” wit h “ ma y” i n t he f oll o wi n g se nte nce:  
P atie nt ser u m a n d plas ma sa m ples will be o btai ne d f or 
L V P K a n d A T A e val uati o n at pr ot oc ol s pecifie d ti me 
p oi nts. C o nce ntrati o ns of a nti b o d y -dr u g c o nj u gate ( A D C) 
L V a n d m o n o met h yl a uristati n E ( M M A E) will be 
meas ure d i n plas ma a n d A T A i n ser u m.  
Starti n g wit h A me n d me nt 1 1, P K a n d i m m u n o ge nicit y 
assess me nts will n ot be c o n d ucte d after C ycle 1.  
Starti n g wit h A me n d me nt 1 1, bi o mar ker assess me nts will 
n ot  be c o n d ucte d after C ycle 1.  
T o all o w fle xi bilit y i n data 
c ollecti o n of e x pl orat or y 
o bj ecti ves t o re d uce trial 
b ur de n.  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 8  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
Secti o n 3. 1  
T he f oll o wi n g te xt was a d de d:  
Fi g ure 1 f o ot n ote a a n d Fi g ure 2 f o ot n ote a : 
F oll o wi n g e n d of st u d y treat me nt, n o a d diti o nal s ca ns or 
res p o nse assess me nts are re q uire d after t he safet y 
f oll o w-u p peri o d, h o we ver a d diti o nal sca ns or res p o nse 
assess me nts ma y be perf or me d as part of t he patie nt’s 
sta n dar d of care at a n y ti me. 
Fi g ure 1 f o ot n ote b  a n d Fi g ure 2 f o ot n ote b : 
P atie nts w h o disc o nti n ue st u d y treat me nt i n t he a bse nce 
of disease pr o gressi o n will c o nti n ue t o be e val uate d f or 
res p o nse e ver y 6 wee ks u ntil c o m pleti o n of t he safet y 
f oll o w-u p peri o d ( 3 0 da ys p ost treat me nt f or L V a n d 
9 0  da ys p ost treat me nt f or pe m br oliz u ma b). T he 
i n vesti gat or will be e x pecte d t o m o nit or f or a n d re p ort 
a n y S A Es a n d pre g na ncies, as detaile d i n Secti o n 
7. 5. 1. 2  a n d Secti o n 7. 5. 1. 4 f or patie nts w h o are still 
recei vi n g treat me nt or i n t he s afet y f oll o w-u p peri o d. See 
Secti o n 6. 7 f or details.  
P atie nts will b e e val uate d f or res p o nse assess me nts e ver y 
6 wee ks ( ± 3 da ys) f or t he first 1 2 m o nt hs, a n d e ver y 1 2 
wee ks ( ± 7 da ys) t hereafter, re gar dless of d ose dela ys, 
t hereafter t hr o u g h t he e n d of t he safet y f oll o w-u p peri o d. 
N o a d diti o nal sca ns or res p o ns e assess me nts  are re q uire d 
after t he safet y f oll o w -u p peri o d. A d diti o nal sca ns or 
res p o nse assess me nts ma y be perf or me d as part of t he 
patie nt’s sta n dar d of care at a n y ti me.  
Clarificati o n  a n d U p date  
Secti o n 3. 1. 1  
Re place d “ will” wit h “ ma y” i n t he f oll o wi n g te xt:  
Bl o o d sa m ples f or P K a n d i m m u n o ge nicit y a nal ysis ma y 
be c ollecte d t o s u p p ort t he st u d y e n d p oi nts.  
T he f oll o wi n g te xt was a d de d:  
As of pr ot oc ol A me n d me nt 1 1, n o P K, i m m u n o ge nicit y, 
P D, or bi o mar ker sa m ples will be o btai ne d after C ycle 1.  
Re visi o n a n d U p date  
Secti o n 4. 4  
T he f oll o wi n g te xt  “S eattle Ge netics or t heir desi g nee 
m ust b e n otifie d if a patie nt is wit h dra w n fr o m st u d y 
treat me nt or fr o m t he st u d y. T he reas o n(s) f or wit h dra wal 
m ust b e d oc u me nte d i n t he patie nt’s me dical rec or ds a n d 
case re p ort f or m ( C R F)” was u p date d  t o “S ea ge n or t heir 
desi g nee m ust b e n otifie d if a patie nt is wit h dra w n fr o m 
st u d y treat me nt or fr o m t he st u d y. T he reas o n(s) f or 
wit h dra wal m ust b e d oc u me nt e d i n t he patie nt’s me dical 
rec or ds a n d/ or case re p ort f or m ( C R F).” 
Clarificati o n a n d U p date  
Secti o n 4. 4. 1  
T he f oll o wi n g w or d “s u bj ects” was re place d wit h 
“ patie nts” i n t he f oll o wi n g te xt: 
Disc o nti n uati o n of pe m br oliz u ma b ma y be c o nsi dere d f or 
patie nts w h o ha ve attai ne d a c o nfir me d C R t hat has bee n 
treate d f or at least 8 c ycles ( 2 4 wee ks) a n d ha d at least 2 
treat me nts wit h pe m br oliz u ma b be y o n d t he date w he n t he 
i nitial C R was declare d. 
Re visi o n  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4 9  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
Secti o n 4. 4. 2  
T he f oll o wi n g te xt was a d de d:  
C o m pleti o n of pr ot oc ol s pecifie d safet y f oll o w -u p 
( Secti o n 6. 6) 
U p date  
Secti o n 5. 5. 2 , 
A p pe n di x  H  
T he prescri bi n g i nf or mati o n was u p date d:  
B ase d u p o n e val uati o n of t he a nti -C D 3 0 M M A E A D C 
bre nt u xi ma b ve d oti n ( A dcetris) ( A D C E T RI S ® 
Prescri bi n g I nf or mati o n, Sea ge n, J u ne 2 0 2 3), 
c o nc o mita nt use of P -g p i n hi bit ors or str o n g c yt oc hr o me 
P 4 5 0 3 A 4 ( C Y P 3 A 4) i n h i bit ors has t he p ote ntial t o 
i ncrease t he e x p os ure t o M M A E (t he c yt ot o xic 
c o m p o ne nt of L V a n d bre nt u xi ma b ve d oti n).  
U p date  
Secti o n 5. 8  
T he f oll o wi n g te xt “a n d t he C R F ” was re m o ve d fr o m t he 
f oll o wi n g se nte nce: 
S t u d y dr u g a d mi nistrati o n will be perf or me d b y st u d y site 
staff a n d d oc u me nte d i n s o urce d oc u me nts a n d t he C R F . 
Clarificati o n  
Secti o n 6. 2. 3 , 
Secti o n 6. 3. 3  
All of t he C ycles were re m o ve d e xce pt f or C ycle 1.  
Clarificati o n  
Secti o n 6. 4  
T he f oll o wi n g te xt was a d de d: N o a d diti o nal sca ns or 
res p o nse assess me nts are re q uire d after t he safet y 
f oll o w-u p peri o d, h o we ver a d diti o nal sca ns or res p o nse 
assess me nts ma y be perf or me d as part of t he patie nt’s 
sta n dar d of care at a n y ti me. 
Pr o vi de m ore fle xi bilit y t o 
st u d y sites f or t he treat me nt 
a n d ma na ge me nt of  patie nts 
i n t he st u d y. 
Secti o n 6. 6  
T he f oll o wi n g te xt was a d de d:  
T he f oll o wi n g assess me nts will be c o n d ucte d at 
f oll o w-u p visits u ntil pr o gressi o n or i nitiati o n of a ne w 
a ntica ncer treat me nt t hr o u g h t he e n d of t he safet y 
f oll o w-u p peri o d . 
P atie nts disc o nti n ui n g treat me nt will be f oll o we d f or t he 
pr ot oc ol re q uire d safet y f oll o w -u p peri o d, u nless 
a d diti o nal safet y c o ncer ns warra nt f urt her f oll o w u p:  
• 
3 0 da ys p ost treat me nt f or L V a n d  
• 
9 0 da ys p ost treat me nt f or pe m br oliz u ma b.  
N o a d diti o nal f oll o w-u p is re q uire d after t he safet y 
f oll o w-u p peri o d.  
After disease pr o gressi o n or i nitiati o n of a ne w a ntica ncer 
treat me nt, s ur vi val f oll o w u p will be c o n d ucte d, e ver y 
1 2  wee ks ( ± 2 wee ks) starti n g fr o m t he last ra di o gra p hic 
sca n de m o nstrati n g disease pr o gressi o n or fr o m i nitiati o n 
of t he ne w a ntica ncer treat me nt u ntil c o m pleti o n of t he 
safet y f oll o w-u p peri o d, deat h, or st u d y cl os ure, 
w hic he ver c o mes first. F oll o w -u p ma y be c o n d ucte d wit h 
cli nic visits or tele p h o ne calls. N o f urt her res p o nse 
assess me nts  will be c o n d ucte d.  
Pr o vi de m ore fle xi bilit y t o 
st u d y sites f or t he treat me nt 
a n d ma na ge me nt of patie nts 
i n t he st u d y. 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 5 0  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
Secti o n 6. 7  
T he f oll o wi n g te xt was a d de d: 
F or patie nts still recei vi n g treat me nt or i n t he safet y 
f oll o w-u p peri o d, t he i n vesti gat or wi ll be e x pecte d t o 
m o nit or f or a n d re p ort a n y S A Es a n d pre g na ncies, as 
detaile d i n Secti o n 7. 5. 1. 2 a n d Secti o n 7. 5. 1. 4 f or eac h 
patie nt.  
Pr o vi de m ore fle xi bilit y t o 
st u d y sites f or t he treat me nt 
a n d ma na ge me nt of patie nts  
i n t he st u d y. 
Secti o n 7. 2  
T he f oll o wi n g te xt was a d de d: 
N o a d diti o nal sca ns or res p o ns e assess me nts are re q uire d 
after t he safet y f oll o w -u p peri o d, h o we ver a d diti o nal 
sca ns or res p o nse assess me nts ma y be perf or me d as part 
of t he patie nt’s sta n dar d of care at a n y ti me.  
Delete d “ I n a d diti o n, i ma ges fr o m P art B C o h ort 2 a n d 
P arts C a n d D will be c ollecte d b y a bli n de d i n de pe n de nt 
ce ntral re vie w ( BI C R) facilit y f or p ossi ble f ut ure 
a nal ysis. ”  
A d de d “ patie nts s h o ul d n ot disc o nti n ue treat me nt” t o t he 
f oll o wi n g te xt: 
W he n feasi ble, patie nts s h o ul d n ot disc o nti n ue treat me nt 
u ntil pr o gressi o n is c o nfir me d.  
U p date  
Secti o n 7. 3  
T he f oll o wi n g te xt was a d de d:  
Starti n g wit h a me n d me nt 1 1, P K a n d i m m u n o ge nicit y 
assess me nts will n ot be c o n d ucte d after C ycle 1.  
U p date  
Secti o n 7. 4  
Re place d “ will” wit h “ ma y” i n t he f oll o wi n g te xt: 
T u m or sa m ples a n d bl o o d f or e x pl orat or y bi o mar kers 
a nal yses ma y be c ollecte d at pr ot oc ol -s pecifie d ti me 
p oi nts (see A p pe n di x E).  
T he f oll o wi n g te xt was a d de d:  
Starti n g wit h a me n d me nt 1 1, bi o mar ker assess me n ts will 
n ot b e c o n d ucte d after C ycle 1.  
U p date  
Secti o n 7. 4. 2  
Re place d “are c ollecte d ” wit h “ ma y be c ollecte d ”  i n t he 
f oll o wi n g te xt:  
T o u n dersta n d d y na mic c ha n ges of t hese s ol u ble 
bi o mar kers a n d t heir relati o ns hi p t o efficac y a n d safet y, 
bl o o d sa m ples ma y be c ollecte d at vari o us ti me p oi nts 
d uri n g t he st u d y.  
Clarificati o n  
Secti o n 7. 4. 3  
Re place d  “ will b e retai ne d” wit h “ ma y be retai ne d”  i n t he 
f oll o wi n g te xt: 
F or patie nts i n t he U S w h o pr o vi de a d diti o nal c o nse nt, 
re mai ni n g de-i de ntifie d u n use d bl o o d a n d/ or tiss ue ma y 
be retai ne d b y t he s p o ns or a n d use d f or f ut ure researc h, 
i ncl u di n g b ut n ot li mite d t o t he e val uati o n of tar gets f or 
n o vel t hera p e utic a ge nts, t he bi ol o g y of A D C se nsiti vit y 
a n d resista nce mec ha nis ms, a n d t he i de ntificati o n of 
bi o mar kers o f A D Cs. 
Clarificati o n  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 5 1  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
Secti o n  7. 5. 1. 2  
A d de d “ t he c o m pleti o n of t he safet y f oll o w-u p peri o d ” t o 
t he f oll o wi n g te xt b el o w: 
N otificati o n t o Dr u g Safet y: C o m plete a Pre g na nc y 
Re p ort F or m f or all pre g na nci es a n d lactati o ns t hat occ ur 
fr o m t he ti me of treat me nt all ocati o n u ntil t he c o m pleti o n 
of t he safet y f oll o w -u p peri o d or 3 0 da ys f oll o wi n g t he 
last d ose of st u d y dr u g(s) if t he patie nt i nitiates ne w 
a ntica ncer t hera p y, w hic he ver is earlier.  
Re visi o n  
Secti o n 7. 5. 5  
Re m o ve d  t he f oll o wi n g te xt “a n d 2 4 wee ks afte r E O T 
( ± 1 wee k)” fr o m t he f oll o wi n g te xt:  
F or w o me n of c hil d beari n g p ote ntial, a ser u m or uri ne 
β -h C G pre g na nc y test wit h se nsiti vit y of at least 
2 5  mI U/ m L will be perf or me d at baseli ne, wit hi n 3 da ys 
pri or t o eac h Da y 1 st u d y dr u g d ose at eac h c ycle, a n d at 
t he E O T visit. 
Clarificati o n  
Secti o n 7. 6  
Re place d “ will b e perf or me d” wit h “ ma y be perf or me d”  
i n t he f oll o wi n g te xt: 
I m m u n o ge nicit y is c o m m o nl y assesse d f or bi ol o gics; 
t heref ore, sta n dar d tests ma y b e perf or me d t o detect t he 
p ossi ble prese nce of s pecific a nti b o dies t o L V. 
Clarificati o n  
Secti o n 9. 3. 2  
T he  f oll o wi n g te xt "the pri mar y a nal ysis will be 
c o n d ucte d w he n all treate d patie nts ha ve bee n f oll o we d 
f or at least 6 m o nt hs or ca me off st u d y, w hic he ver c o mes 
first” was u p date d t o “ the pri mar y a nal ysis will be 
c o n d ucte d w he n all treate d patie nts ha ve c o me off st u d y. ”  
U p date  
A p pe n di x A  
C o ncer ni n g f o ot n ote B , a d de d “c o m pleti o n of t he safet y 
f oll o w-u p peri o d ” a n d  “ u nless ot her wise state d”.  
C o ncer ni n g f o ot n ote F, a d de d “ Bi o mar ker assess me nts 
will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol 
a me n d me nt 1 1 ”. 
C o ncer ni n g f o ot n ote L , a d de d “ u nless ot her wise state d”. 
C o ncer ni n g f o ot n ote  T,  a d de d  "foll o w -u p will occ ur 
e ver y 6 wee ks ( ± 1 wee ks) 3 0 da ys p ost last treat me nt f or 
patie nts o n L V o nl y a n d 9 0 da ys f or t h ose o n 
pe m br oliz u ma b. ”  
Delete d f o ot n ote U , "f or P art B C o h ort 2, res p o nse 
assess me nts will be c ollecte d b y BI C R f or p ossi ble f ut ure 
a nal ysis”.  
U p date  
A p pe n di x B  
C o ncer ni n g f o ot n ote C , a d de d “Bi o mar ker assess me nts 
will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol 
a me n d me nt 1 1. ” 
U p date  
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)

 
St u d y S G N L V A -0 0 2  
Cli nical Pr ot oc o l 
A me n d me nt 1 1; 1 9 -Oct -2 0 2 3  
L a dirat uz u ma b Ve d oti n ( L V; S G N -LI V 1 A)   Sea ge n I nc. - C o nfi de ntial  
P a ge 1 5 2  of 1 5 2  
Secti o n(s)  
C ha n ge  
Rati o nale  
A p pe n di x C  
C o ncer ni n g r o w P K/ A T A , a d de d C ycle 1 o nl y t o “ See 
P K/ A T A/ Bi o mar ker T a bles ( A p pe n di x D a n d A p pe n di x 
E) ” as prese nte d i n A p pe n di x C.  
C o ncer ni n g f o ot n ote B, a d de d “ c o m pleti o n of t he safet y 
f oll o w-u p peri o d” a n d “ u nless ot her wise state d”.  
Delete d f o ot n ote F, “ p re g na nc y test t o be perf or me d 
2 4  wee ks ( ± 1 wee k) after E O T ”. 
Delete d f o ot n ote S, "res p o nse assess me nts will be 
c ollecte d b y BI C R f or p ossi ble f ut ure a nal ysis. ”  
A d de d f o ot n ote V, a d de d “f oll o w -u p will  occ ur e ver y 
6  wee ks ( ± 1 wee ks) 3 0 da ys p ost last treat me nt f or 
patie nts o n L V o nl y a n d 9 0 da ys f or t h ose o n 
pe m br oliz u ma b ”. 
U p date  
A p pe n di x D  
C o ncer ni n g f o ot n ote C, a d de d “ Bi o mar ker assess me nts 
will o nl y be c ollecte d d uri n g C ycle 1 as of pr ot oc ol 
a me n d me nt 1 1.”  
U p date  
A p pe n di x E  
C o ncer ni n g T a ble 1 1 f o ot n ote C a n d T a ble 1 2 f o ot n ote B , 
a d de d “ Bi o mar ker assess me nts will o nl y be c ollecte d 
d uri n g C ycle 1 as of pr ot oc ol a me n d me nt 1 1.”  
U p date  
A p pe n di x G  
Delete d t he f oll o wi n g te xt , “s yste mic e x p os ure (at least 
6  m o nt hs after t he fi nal d ose of st u d y dr u g; see 
Secti o n  4. 1).  t he safet y f oll o w-u p peri o d ” a n d a d de d “t he 
safet y f oll o w-u p peri o d.  
U p date  
A p pe n di x K  
Re place d “i n t he C R F” wit h “i n t he s o urce d oc u me nts”.  
Re visi o n  
 
0 9 0 1 7 7 e 1 a 1 3 6 3 7f 1\ A p pr o v e d\ A p pr o v e d O n: 1 3- N o v- 2 0 2 3 2 3: 4 0 ( G M T)