A Dual-cohort, Open-label, Phase 2 Study of Brentuximab Vedotin and CHP (A+CHP) in the Frontline Treatment of Subjects With Peripheral T-cell Lymphoma (PTCL) With Less Than 10% CD30 Expression
Phase: PHASE2
Conditions: Peripheral T-cell Lymphoma
Sponsor: Seagen, a wholly owned subsidiary of Pfizer

 
 
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 nless g o ver n me nt 
re g ulati o ns or la ws re q uire s uc h discl os ure, wit h o ut pri or writte n per missi o n fr om Sea ge n. 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 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 3 5 -0 3 2  
Versi o n:  
A me n d me nt 3 ; 1 0  Marc h 2 0 2 1  
Pr ot oc ol Title:  
A d ual -c o h ort, o p e n -la bel, p hase 2 st u d y of bre nt u xi ma b ve d oti n 
a n d C H P ( A + C H P) i n t he fr o ntli ne treat me nt of s u bjects wit h 
peri p heral T -cell l y m p h o ma ( P T C L) wit h less t ha n 1 0 % C D 3 0 
e x pressi o n  
I n vesti g ati o n al Dr u g: 
Bre nt u xi ma b ve d oti n  
I n dic ati o n: 
Peri p heral T -cell l y m p h o ma  
P h ase:  
2  
I N D N u m ber: 
7 1 6 3 4  
E u dr a C T N u m ber:  
2 0 2 0 -0 0 2 3 3 6 -7 4  
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: 
 
S A E F a x:  
4 2 5. 5 2 7. 4 3 0 8 ( or fa x n u m ber s pecifie d o n s p o ns or’s S A E re p ort 
f or m) 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)
P P D
P P D
P P D

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2  of 6 4  
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 3 5 -0 3 2  
Versi o n  
A me n d me nt 3  
P h ase  
2  
Pr o d uct N a me  
Bre nt u xi ma b ve d oti n  
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 Title  
A d ual -c o h ort, o pe n -la bel, p hase 2 st u d y of bre nt u xi ma b ve d oti n a n d C H P ( A + C H P) i n t he fr o ntli ne treat me nt 
of s u bj ects wit h peri p heral T -cell l y m p h o ma ( P T C L) wit h less t ha n 1 0 % C D 3 0 e x pressi o n  
St u d y O bjecti ves  
Pri mar y:  
● T o e val uate  t he o bj ecti ve res p o nse rate ( O R R) per bli n de d i n de pe n de nt ce ntral re vie w ( BI C R) usi n g t he 
Re vise d Res p o nse Criteria f or Mali g na nt L y m p h o ma ( C hes o n 2 0 0 7)  
Sec o n dar y:  
● T o e val uate t he c o m plete res p o nse ( C R) f oll o wi n g c o m pleti o n of st u d y treat me nt ( C hes o n 2 0 0 7)  
● T o e val uate pr o gressi o n -free s ur vi val ( P F S) ( C hes o n 2 0 0 7) 
● T o e val uate o verall s ur vi val ( O S)  
● T o e val uate d urati o n of res p o nse ( D O R) ( C hes o n 2 0 0 7)  
● T o e val uate O R R per BI C R usi n g m o difie d L u ga n o criteria ( C hes o n 2 0 1 4)  
● T o  e val uate safet y a n d t olera bilit y  
St u d y P o p ul ati o n  
Ke y i ncl usi o n criteria i ncl u de s u bj ects a ge d 1 8 years a n d ol der wit h ne wl y dia g n ose d P T C L, e xcl u di n g s yste mic 
a na plastic lar ge cell l y m p h o ma (s A L C L), per t he Re vise d E ur o pea n -A merica n L y m p h o ma W orl d Healt h 
Or ga nizati o n ( W H O) 2 0 1 6 classificati o n; P T C L hist ol o g y; C D 3 0  e x pressi o n < 1 0 % b y l ocal assess me nt; a n d 
fl u or o de o x y gl uc ose ( F D G)-a vi d disease b y P E T a n d meas ur a ble disease of at least 1. 5 c m b y C T, as assesse d 
b y t he site ra di ol o gist.  
N u m ber of Pl a n ne d S u bjects  
U p t o a p pr o xi matel y 8 0 s u bj ects will be e nr olle d i n t h is st u d y. A p pr o xi matel y 4 0 s u bj ects wit h p ositi ve C D 3 0 
e x pressi o n ( ≥1 % t o < 1 0 %) a n d u p t o a p pr o xi matel y 4 0  s u bj ects wit h ne gati ve C D 3 0 e x pr essi o n ( < 1 %) b y l ocal 
assess me nt (ce ntral c o nfir mati o n) will b e e nr olle d.  
St u d y Desi g n  
T his is a d ual -c o h ort, o pe n -lab el, m ultice nter, p hase 2 cli nical trial desi g ne d t o e val uate t he efficac y a n d safet y 
of A + C H P i n s u bj ects wit h n o n -s A L C L P T C L a n d t u m or C D 3 0 e x pressi o n < 1 0 %. E nr oll me nt will be base d o n 
C D 3 0 e x pressi o n per l ocal la b assess me nt. A n arc hi ve d t u m or bi o ps y s peci me n will be s u b mitte d t o a ce ntral 
pat h ol o g y la b f or c o nfir mati o n of C D 3 0 e x pressi o n. O nl y s u bj ects wit h C D 3 0 e x pressi o n < 1 0 % per ce ntral 
c o nfir mati o n will be a nal yze d f or t he pri mar y a n d sec o n dar y e n d p oi nts. S u bj ects will recei ve 2 1 -da y c ycles of 
A + C H P f or a tar get of 6 -8 c ycles.  
Test Pr o d uct, D ose, a n d M o de of A d mi nistr ati o n  
S u bj ects will recei ve 6 -8 c ycles of A + C H P i n 2 1 -da y c ycles as f oll o ws: bre nt u xi ma b ve d oti n 1. 8  m g/ k g, 
c ycl o p h os p ha mi de 7 5 0 m g/ m 2, a n d d o x or u bici n 5 0 m g/ m 2, a d mi nistere d I V o n Da y 1 of ea c h c ycle, a n d 
pre d nis o ne 1 0 0 m g dail y a d mi nistere d orall y o n Da ys 1 −5 ( ± 1 da y wi n d o w) of eac h c ycle.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b v e d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3  of 6 4  
D ur ati o n of Tre at me nt  
St u d y treat me nt c o nsists of 6 -8 c ycles of A + C H P. T he ma xi m u m t otal d urati o n of t hera p y is 8  c ycles, or 
a p pr o xi matel y 6 m o nt hs . 
Effic ac y Assess me nts  
L y m p h o ma res p o nse a n d pr o gressi o n will be assesse d b y BI C R usi n g Re vise d Res p o nse Criteria f or Mali g na nt 
L y m p h o ma a n d m o difie d L u ga n o criteria. Ra di o gra p hic dise ase e val uati o ns, i ncl u di n g C T sca ns of nec k, c hest, 
a b d o me n a n d pel vis, will be assesse d at baseli ne, after C ycl e 4 of treat me nt, after t he c o m pleti o n of st u d y 
treat me nt, at 9, 1 2, 1 5, 1 8, 2 1 a n d 2 4 m o nt hs after i nitiati o n of st u d y treat me nt, a n d e ver y 6 m o nt hs t hereafter 
u ntil disease pr o gressi o n, s u bj ect d eat h, or a nal ysis o f t he pri mar y e n d p oi nt, w hic he ver c o mes first. A C T sca n 
will als o be perf or me d at t he ti me of s us pecte d cli nical pr o gressi o n. A P E T sca n is re q uire d at baseli ne, after 
C ycle 4, a n d after t he c o m pleti o n of st u d y treat me nt. S u bse q ue nt resta ge assess me nts ( C T sca ns o nl y) will be 
perf or me d acc or di n g t o t he cal e n dar, relati ve t o t he first d ose of st u d y treat me nt, t o e ns ure t hat t u m or 
pr o gressi o n is u nif or ml y assesse d bet wee n t he treat me nt ar ms.  
S afet y Assess me nts  
Safet y assess me nts will c o nsist of t he s ur veilla nce a n d rec or di n g of a d verse e ve nts ( A Es) i ncl u di n g seri o us 
a d verse e ve nts ( S A Es), rec or di n g of c o nc o mita nt me dicati o n, a n d meas ure me nts of p h ysic al e xa mi nati o n 
fi n di n gs a n d la b orat or y tests. 
St atistic al M et h o ds  
Efficac y a n d safet y e n d p oi nts will b e s u m marize d wit h descri pti ve statistics b y c o h ort, wit h t he C D 3 0 ne gati ve 
c o h ort a n d t he C D 3 0 p ositi ve c o h ort c o nsisti n g of s u bj ects wit h C D 3 0 e x pressi o n le vel < 1 % a n d ≥1 % t o 
< 1 0 %  per ce ntral testi n g, res pecti vel y. T he s u m mar y of o verall ( C D 3 0 ne gati ve a n d p ositi ve c o h ort c o m bi ne d) 
ma y be prese nte d as a p pr o priate. Descri pti ve statistics ( 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) will be use d t o descri be c o nti n u o us varia bles. Fr e q ue ncies a n d perce nta ges will be use d w he n 
prese nti n g cate g orical v aria bles (e g, O R R). Ti me -t o-e ve nt e n d p oi nts, s uc h as P F S, will be esti mate d usi n g 
Ka pla n -Meier met h o d ol o g y a n d Ka pla n -Meier pl ots will be prese nte d. Me dia ns f or ti me -t o-e ve nt a nal yses (e g, 
me dia n P F S), will be prese nte d a n d t w o -si de d 9 5 % c o nfi de nce i nter vals ( CIs) will be calc ulate d usi n g t he l o g-
l o g tra nsf or mati o n met h o d. 
S a m ple size deter mi n ati o n  
Cli nical data fr o m t his st u d y will b e prese nte d i n a descri pti ve ma n ner t o de m o nstrate c o nsiste nc y wit h 
n o n -a na plastic lar ge cell l y m p h o ma ( A L C L ) s u bj ects recei vi n g A+ C H P e nr olle d i n E C H E L O N -2 st u d y. T he 
st u d y is desi g ne d t o esti mate t he O R R at a reas o na ble le vel of precisi o n. U p t o a p pr o xi matel y 8 0 n o n -s A L C L 
P T C L will be e nr olle d i n t his st u d y, wit h u p t o a p pr o xi matel y 4 0 s u bj ects i n t he C D 3 0 ne gati ve ( < 1 %) c o h or t 
a n d a p pr o xi matel y 4 0 s u bj ects i n t he C D 3 0 p ositi ve ( 1 % t o < 1 0 %) c o h ort. I n t he C D 3 0 p ositi ve ( 1 % t o < 1 0 %) 
c o h ort wit h 4 0 s u bj ects, if 2 8  res p o nses are o bser ve d, t he esti mate d O R R w o ul d be 7 0 %, a n d t he ass ociate d 
2 -si de d 9 5 % CI usi n g t he Cl o p per-P ears o n m et h o d w o ul d be ( 5 3. 5 %, 8 3. 4 %).  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4  of 6 4  
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  ......................................................................... 7  
1  
I N T R O D U C TI O N ........................................................................................................................................... 9  
1. 1  
C D 3 0 -P ositi ve P eri p heral T -C ell L y m p h o mas  ..................................................................................... 9  
1. 2  
Cli nical E x perie nce wit h Bre nt u xi ma b Ve d oti n  ................................................................................. 1 1  
1. 3  
O verall Ris k a n d B e nefit Assess me nt  ................................................................................................. 1 1  
1. 4  
Rati o nale f or C urre nt Trial  ................................................................................................................. 1 2  
2  
O BJ E C TI V E S  ............................................................................................................................................... 1 2  
2. 1  
Pri mar y O bj ecti ve  ............................................................................................................................... 1 2  
2. 2  
Sec o n dar y O bj ecti ves  ......................................................................................................................... 1 3  
2. 3  
E n d p oi nts  ............................................................................................................................................ 1 3  
2. 3. 1  
Pri mar y E n d p oi nt  ................................................................................................................. 1 3  
2. 3. 2  
Sec o n dar y E n d p oi nts  ............................................................................................................ 1 3  
2. 3. 3  
A d diti o nal E n d p oi nts  ............................................................................................................ 1 3  
3  
I N V ES TI G A TI O N A L P L A N  ....................................................................................................................... 1 4  
3. 1  
S u m mar y of St u d y Desi g n  .................................................................................................................. 1 4  
3. 2  
Disc ussi o n a n d Rati o nale f or St u d y Desi g n ........................................................................................ 1 4  
3. 2. 1  
Met h o d of Assi g ni n g S u bj ects t o Treat me nt Gr o u ps  ........................................................... 1 5  
3. 2. 2  
Rati o nale f or Selecti o n of D os es  .......................................................................................... 1 5  
3. 2. 3  
Bli n di n g  ................................................................................................................................ 1 5  
4  
S T U D Y P O P U L A TI O N ................................................................................................................................ 1 5  
4. 1  
I ncl usi o n Criteria ................................................................................................................................ 1 5  
4. 2  
E xcl us i o n Criteria ............................................................................................................................... 1 7  
4. 3  
Re m o val of S u bj ects Fr o m T hera p y or Assess me nt  ........................................................................... 1 8  
4. 3. 1  
Disc o nti n uati o n of St u d y Treat me nt  .................................................................................... 1 8  
4. 3. 2  
S u bj ect Wit h dra wal Fr o m St u d y  .......................................................................................... 1 9  
5  
T R E A T M E N T S  ............................................................................................................................................ 1 9  
5. 1  
Treat me nts A d mi nistere d .................................................................................................................... 1 9  
5. 2  
I nvesti gati o nal St u d y Dr u g  ................................................................................................................. 1 9  
5. 2. 1  
Descri pti o n  ........................................................................................................................... 2 0  
5. 2. 2  
Met h o d of Pr oc ure me nt  ........................................................................................................ 2 0  
5. 2. 3  
D ose a n d A d mi nistrati o n  ...................................................................................................... 2 0  
5. 2. 4  
Re q uire d Pre me dicati o n a n d P ost me dicati o n  ....................................................................... 2 0  
5. 2. 5  
Ma na ge me nt of I nf usi o n Reacti o ns  ...................................................................................... 2 0  
5. 2. 6  
Ma na ge me nt of S us pecte d P M L  .......................................................................................... 2 1  
5. 2. 7  
St ora ge a n d Ha n dli n g  ........................................................................................................... 2 1  
5. 2. 8  
P ac ka gi n g a n d La b eli n g  ....................................................................................................... 2 1  
5. 2. 9  
Pre p arati o n  ........................................................................................................................... 2 1  
5. 3  
C ycl o p h os p ha mi de, D o x or u bi ci n, a n d Pre d nis o ne  ............................................................................. 2 2  
5. 3. 1  
Descri pti o n  ........................................................................................................................... 2 2  
5. 3. 2  
Met h o d of Pr oc ure me nt  ........................................................................................................ 2 2  
5. 3. 3  
D ose a n d A d mi nistrati o n  ...................................................................................................... 2 2  
5. 3. 4  
Re q uire d Pre me dicati o n a n d P ost me dicati o n  ....................................................................... 2 2  
5. 3. 5  
P ac ka gi n g a n d La b eli n g  ....................................................................................................... 2 3  
5. 3. 6  
Pre p arati o n  ........................................................................................................................... 2 3  
5. 3. 7  
St ora ge a n d Ha n dli n g  ........................................................................................................... 2 3  
5. 4  
D o se M o dificati o ns............................................................................................................................. 2 3  
5. 5  
C o nc o mita nt T hera p y  ......................................................................................................................... 2 4  
5. 5. 1  
Re q uire d C o nc o mita nt T hera p y f or HI V -P ositi ve S u bj ects  ................................................. 2 4  
5. 5. 2  
All o we d C o nc o mita nt T hera p y  ............................................................................................ 2 5  
5. 5. 3  
Pr o hi bite d C o nc o mita nt T hera p y  ......................................................................................... 2 5  
5. 6  
Treat me nt C o m plia nce  ....................................................................................................................... 2 6  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5  of 6 4  
6  
S T U D Y A C TI VI TI E S  ................................................................................................................................... 2 6  
6. 1  
Sc he d ule o f E ve nts ............................................................................................................................. 2 6  
6. 2  
Scree ni n g Visit ( Da y -2 8 t o Da y 1)  .................................................................................................... 2 6  
6. 2. 1  
B aseli ne Visit ( Da y -7 t o Da y 1)  .......................................................................................... 2 6  
6. 3  
Treat me nt P eri o d ( 2 1 -da y c ycl es)  ....................................................................................................... 2 7  
6. 3. 1  
E ver y C ycle: Da y 1  .............................................................................................................. 2 7  
6. 3. 2  
C ycle 4 O nl y: Da y 1 5 -2 1 ...................................................................................................... 2 7  
6. 3. 3  
Last Pla n ne d C ycle of Treat me nt: Da y 1 5 -2 1  ...................................................................... 2 7  
6. 4  
E n d -of -Treat me nt Visit ( 3 0 -3 7 da ys  after last d ose of st u d y dr u g)  .................................................... 2 8  
6. 5  
F oll o w -u p  ........................................................................................................................................... 2 8  
6. 6  
E n d of St u d y/ E n d of F oll o w -u p  .......................................................................................................... 2 8  
7  
S T U D Y A S S E S S M E N T S  ............................................................................................................................. 2 9  
7. 1  
Scree ni n g/ Baseli ne Assess me nts  ........................................................................................................ 2 9  
7. 1. 1  
Hist ol o gic S u bt y pe a n d C haracterizati o n of T u m or Tiss ue  .................................................. 2 9  
7. 2  
Res p o nse/ Efficac y Assess me nts b y t he I n vesti gat or  .......................................................................... 3 0  
7. 2. 1  
Bi os peci me n Sa m ples f or F ut ure Researc h  .......................................................................... 3 1  
7. 3  
Safet y Assess me nts ............................................................................................................................. 3 1  
7. 3. 1  
A d verse E ve nts  ..................................................................................................................... 3 1  
7. 3. 2  
Vital Si g ns  ............................................................................................................................ 3 6  
7. 3. 3  
Cli nical La b orat or y T ests  ..................................................................................................... 3 7  
7. 3. 4  
E C O G P erf or ma nce Stat us  ................................................................................................... 3 7  
7. 3. 5  
A d diti o nal M o nit ori n g f or HI V -P ositi ve a n d He p atitis -C -P ositi ve S u bj ects  ....................... 3 7  
7. 4  
A p pr o priate ness of Meas ure me nts ...................................................................................................... 3 7  
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  ................................................................ 3 8  
8. 1  
Site Trai ni n g a n d M o nit ori n g Pr oce d ures  ........................................................................................... 3 8  
8. 2  
Data Ma na ge me nt Pr oce d ures  ............................................................................................................ 3 8  
8. 3  
Access t o S o urce Data  ........................................................................................................................ 3 9  
8. 4  
Acc urac y a n d Relia bilit y of D ata ........................................................................................................ 3 9  
8. 5  
Q ualit y Ass ura nce Pr oce d ures  ............................................................................................................ 3 9  
8. 6  
Data Ha n dli n g a n d Rec or d Kee pi n g  ................................................................................................... 3 9  
8. 6. 1  
Data Ha n dli n g  ...................................................................................................................... 3 9  
8. 6. 2  
I n vesti gat or Rec or d Rete nti o n .............................................................................................. 4 0  
9  
D A T A A N A L Y SI S M E T H O D S  ................................................................................................................... 4 0  
9. 1  
Deter mi nati o n of Sa m ple Size  ............................................................................................................ 4 0  
9. 2  
St u d y E n d p oi nt Defi niti o ns  ................................................................................................................ 4 0  
9. 2. 1  
Pri mar y E n d p oi nt: O bj ecti ve Res p o nse Rate ( C hes o n 2 0 0 7)  ............................................... 4 0  
9. 2. 2  
Sec o n dar y Efficac y E n d p oi nts  ............................................................................................. 4 1  
9. 2. 3  
A d diti o nal E n d p oi nts  ............................................................................................................ 4 2  
9. 3  
Statistical a n d A nal ytical Pla ns  .......................................................................................................... 4 2  
9. 3. 1  
Ge neral C o nsi derati o ns  ........................................................................................................ 4 2  
9. 3. 2  
S u bj ect Dis p ositi o n  .............................................................................................................. 4 4  
9. 3. 3  
S u bj ect C haracteristics  ......................................................................................................... 4 4  
9. 3. 4  
Treat me nt C o m plia nce  ......................................................................................................... 4 4  
9. 3. 5  
Efficac y A nal yses  ................................................................................................................. 4 4  
9. 3. 6  
Safet y A nal yses  .................................................................................................................... 4 5  
9. 3. 7  
I nterim A nal ysis  ................................................................................................................... 4 5  
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  ................. 4 6  
1 0. 1  I nf or me d C o nse nt ............................................................................................................................... 4 6  
1 0. 2  Et hical  Re vie w  .................................................................................................................................... 4 6  
1 0. 3  Re g ulat or y C o nsi derati o ns .................................................................................................................. 4 7  
1 0 . 3. 1 
I n vesti gat or I nf or mati o n ....................................................................................................... 4 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  .................................................................... 4 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  ...................................................................... 4 7  
1 0. 5  Cli nical Trial A gree me nt  .................................................................................................................... 4 8  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6  of 6 4  
1 1  R E F E R E N C E S  .............................................................................................................................................. 4 9  
A P P E N DI X  A: S T U D Y S C H E D U L E  ................................................................................................................. 5 3  
A P P E N D I X B: E C O G P E R F O R M A N C E S T A T U S  ........................................................................................... 5 5  
A P P E N DI X  C: G UI D A N C E  O N C O N T R A C E P TI O N  ....................................................................................... 5 6  
A P P E N DI X  D: I N V E S TI G A T O R SI G N A T U R E P A G E  .................................................................................... 5 8  
A P P E N DI X  E: D O C U M E N T  HI S T O R Y  ............................................................................................................ 5 9  
 
LI S T O F I N -T E X T T A B L E S  
T a ble 1:  
St u d y treat me nt  .............................................................................................................................. 1 9  
T a ble 2:  
Rec o m me n de d d ose m o dificati o ns f or treat me nt -ass ociate d ne ur o pat h y  ...................................... 2 3  
T a ble 3:  
Rec o m me n de d d ose m o dificati o ns f or s u bj ects wit h re nal i m pair me nt  ........................................ 2 3  
T a ble  4:  
Res p o nse rates a n d ass ociate d 9 5 % c o nfi de nce i nter vals  .............................................................. 4 0  
 
LI S T O F I N -T E X T FI G U R E S  
Fi g ure 1:  
St u d y desi g n  .................................................................................................................................. 1 4  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 7  of 6 4  
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 + C H P  
bre nt u xi ma b ve d oti n, c ycl o p h os p ha mi de, d o x or u bici n, a n d pre d nis o ne  
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  
AI T L  
a n gi oi m m u n o blastic T -cell l y m p h o ma  
A L C L  
a na plastic lar ge cell l y m p h o ma  
A L T  
ala ni ne a mi n otra nsferase  
A N C  
a bs ol ute ne utr o p hil c o u nt  
A S T  
as partate a mi n otra nsferase  
A T A  
a ntit hera p e utic a nti b o dies  
A T L L  
a d ult T -cell le u ke mia/l y m p h o ma  
A U C  
area u n der t he c o nce ntrati o n -ti me c ur ve 
β -h C G  
beta h u ma n c h ori o nic g o na d otr o p hi n  
BI C R  
bli n de d i n de p e n de nt ce ntral re vie w  
B S A  
b o d y s urface area  
C B C  
c o m plete bl o o d c o u nt  
C e oi 
c o nce ntrati o n at t he e n d of i nf usi o n  
C F R  
C o de of Fe deral Re g ulati o ns  
C H O E P  
et o p osi de t o C H O P  
C H O P  
c ycl o p h os p ha mi de, d o x or u bici n, vi ncristi ne, a n d pre d nis o ne  
C H O P -2 1  
c ycl o p h os p ha mi de, d o x or u bici n, vi ncristi ne, a n d pre d nis o ne a d mi nistere d e ver y 2 1 da ys  
C H P  
c ycl o p h os p ha mi de, d o x or u bici n, a n d pre d nis o ne  
C ma x  
ma xi m u m c o nce ntrati o n  
C N S  
ce ntral ner v o us s yste m  
C R  
c o m plete res p o nse  
Cr C l 
creati ni ne cleara nce  
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 tr o u g h 
tr o u g h c o nce ntrati o n 
D O R  
d urati o n of res p o nse  
E C G  
electr ocar di o gra m  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
e G F R  
esti mate d gl o mer ular filtrati o n rate  
E M A  
E ur o pea n Me dici nes A ge nc y  
E O T  
e n d of treat me nt  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F D G  
fl u or o de o x y gl uc ose 
F S H  
f ollicle sti m ulati n g h or m o ne 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 8  of 6 4  
G C P  
G o o d Cli nical Practice  
H A A R T  
Hi g hl y Acti ve A ntiretr o viral T hera p y  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H R  
hazar d rati o  
H T L V -1  
h u ma n T -cell le u ke mia vir us -1  
I V 
I ntra ve n o us 
I D M C 
I n de p e n de nt Data M o nit ori n g C o m mittee 
I PI 
I nter nati o nal Pr o g n ostic I n de x 
I E C 
I n de p e n de nt Et hics C o m mitte e 
I N D 
i n vesti gati o nal ne w dr u g 
I R B 
I nstit uti o nal Re vie w B oar d 
M D R D  
M o dificati o n of Diet i n Re nal Disease  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
M F  
m yc osis f u n g oi des  
M M A E  
m o n o met h yl a uristati n E  
M T D  
ma xi m u m t olerate d d ose  
M U G A  
m ulti -gate d ac q uisiti o n  
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  
N H L  
n o n -H o d g ki n l y m p h o ma  
N K  
nat ural killer  
O R R  
o bj ecti ve res p o nse rate  
O S  
o verall s ur vi val  
P C R  
p ol y merase c hai n reacti o n  
P D  
pr o gressi ve disease  
P E T  
p ositr o n e missi o n t o m o gra p h y  
P F S  
pr o gressi o n -free s ur vi val 
P K  
p har mac o ki netics  
P M L  
pr o gressi ve m ultif ocal le u k oe nce p hal o pat h y  
P R  
partial res p o nse  
P T C L  
peri p heral T -cell l y m p h o ma  
S A E  
seri o us a d verse e ve nt 
s A L C L 
s yste mic a na plastic lar ge cell l y m p h o ma 
S A P  
statistical a nal ysis pla n  
S C T  
ste m cell tra ns pla nt 
T ma x  
ti me at w hic h t he ma xi m u m c o nce ntrati o n occ urs 
U L N  
u p per li mit of n or mal  
U S P  
U nite d States P har mac o peia  
W H O  
W orl d Healt h Or ga nizati o n  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 9  of 6 4  
1  
I N T R O D U C TI O N 
Bre nt u xi ma b ve d oti n is a C D 3 0 -directe d A D C c o nsisti n g of 3 c o m p o ne nts: 1) t he c hi meric 
I g G 1 a nti b o d y c A C 1 0, s pecific f or h u ma n C D 3 0, 2) t he micr ot u b ule-disr u pti n g a ge nt 
m o n o met h yl a uristati n E [ M M A E ], a n d 3) a pr otease-cl ea va bl e li n ker t hat c o vale ntl y 
attac hes M M A E t o c A C 1 0. Tar gete d deli ver y of M M A E t o C D 3 0 -e x pressi n g t u m or cells is 
t he pri mar y mec h a nis m of acti o n of bre nt u xi ma b ve d oti n (S ut herla n d 2 0 0 6 ). Bi n di n g of 
M M A E t o t u b uli n disr u pts t he micr ot u b ule net w or k wit hi n t he cell, s u bse q ue ntl y i n d uci n g 
cell c ycle arrest a n d a p o pt otic deat h of t he cell. Ot her n o ncli nical st u dies s u g gest a d diti o nal 
c o ntri b ut or y m ec ha nis ms of acti o n, i ncl u di n g a nti b o d y -d e pe n de nt cell ular p ha g o c yt osis; 
b ysta n der effects o n near b y cells i n t he t u m or micr oe n vir o n me nt d ue t o release d M M A E; a n d 
i m m u n o ge nic cell deat h (I C D) d ue t o e n d o plas mic retic ul u m stress w hic h dri ves e x p os ure of 
im m u ne acti vati n g m olec ules t hat ca n pr o m ote a T -cell res p o ns e (Ofl az o gl u 2 0 0 7 ; Li F 2 0 1 4 ; 
M uller 2 0 1 4 ; Ki m 2 0 1 5 ; Ca o  A 2 0 1 6 ; Gar dai 2 0 1 6 ). 
T he p hase 3 E C H E L O N -2 trial ( N C T 0 1 7 7 7 1 5 2) d e m o nstrate d t hat t he c o m bi nati o n of 
bre nt u xi ma b ve d oti n wit h c ycl o p h os p ha mi de, d o x or u bici n,  a n d pre d nis o ne ( A + C H P) was 
s u peri or t o c ycl o p h os p ha mi de, d o x or u bici n, vi ncristi ne, a n d pre d nis o ne ( C H O P) f or t he 
fr o ntli ne treat me nt of s u bjects wit h s yste mic a n a pl astic lar ge cell l y m p h o m a (s A L C L) or 
ot her C D 3 0 -e x pressi n g p eri p heral T -cell l y m p h o ma ( P T C L ) (H or witz 2 0 1 9 ) a n d s u p p orte d 
t he 2 0 1 8 F D A a p pr o val f or t his use. T his st u d y is bei n g c o n d ucte d as part of a p ost-
mar keti n g c o m mit me nt t o F D A t o assess t he effi cac y a n d safet y of A + C H P as fr o ntli ne 
treat me nt of s u bjects wit h n o n-s A L C L P T C L a n d C D 3 0 e x pressi o n less t ha n 1 0 %, w hic h 
was t he c ut off use d t o defi ne C D 3 0 p ositi vit y i n t he E C H E L O N -2 tri al.  
1. 1  C D 3 0 -P o siti v e P eri p h er al T -C ell L y m p h o m a s  
P T C L is a heter o ge ne o us gr o u p of rare l y m p h o pr oliferati ve dis or ders t hat ori gi nate fr o m 
cl o nal pr oliferati o n of mat ure, p ost -t h y mi c T l y m p h oc yt es ( T cells) (Wi n ber g 1 9 9 3 ). T h e 
2 0 0 8 W orl d Healt h Or ga niz ati o n ( W H O) classificati o n rec o g nize d 1 4 disti nct s u bt y pes of 
P T C L, wit h differe ntiati o n base d o n hist ol o g y a n d sites of i n v ol ve me nt (Bellei 2 0 1 2 ; 
Zi nz a ni  2 0 1 6 ). O verall, P T C L re pres e nts a p pr o xi matel y 1 0 % t o 1 5 % of n o n-H o d g ki n 
l y m p h o ma ( N H L) cases w orl d wi de, wit h t he greatest pre vale nce i n Asia n p o p ulati o ns d ue t o 
s u bt y pes ass o ciate d wit h viral i nfecti o n (A n ders o n 1 9 9 8 ; V ose 2 0 0 8 ; Bellei 2 0 1 2 ). Bas e d o n 
S E E R data, a p pr o xi matel y 4, 0 0 0 ne w cas es of P T C L were dia g n os e d i n t he U nite d States i n 
2 0 1 6 (Teras 2 0 1 6 ). 
P T C L ge nerall y occ urs i n ol der i n di vi d uals, wit h a me dia n a ge at dia g n osis i n t he si xt h or 
se ve nt h deca de. P u blis he d cli nical st u dies a n d retr os pecti ve re vi e ws s h o w a hi g her i n ci de nce 
of P T C L i n males t ha n fe males a n d i n Africa n A m erica n v ers us Ca ucasia n racial gr o u ps 
(V ose 2 0 0 8 ; Elli n 2 0 1 4 ; Teras 2 0 1 6 ). 
Hist oricall y, C H O P gi ve n f or 6 t o 8 c ycles was c o nsi dere d t o be t he sta n d ar d of care f or t h e 
maj orit y of P T C L s u bt y p es (V ose 2 0 0 8 ; Elli n 2 0 1 4 ; Ar mita ge 2 0 1 7 ; N C C N 2 0 1 8 ). 
C o m paris o n of n o n -ra n d o mize d cli nical trials d oes n ot s u p p ort a differe nce i n acti vit y 
bet wee n 6 or 8 c ycles of C H O P a n d b ot h a p pr oac hes were c o m m o nl y us e d i n cli nica l 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 0  of 6 4  
practice (C oiffier 2 0 0 2 ; Sc h mitz 2 0 1 0 ). G ui deli nes rec o m me n d a d mi nistrati o n of 6 c ycles of 
C H O P f or s u bjects wit h Sta ge I -II dise ase a n d I nt er nati o nal Pr o g n ostic I n d e x (I PI) sc ore of 
0 -2, 6 t o 8 c ycles of C H O P f or s u bjects wit h Sta ge I -II disease a n d a n I PI s c ore of 3-5, a n d 
6  t o 8 c ycl es f or all s u bjects wit h Sta ge III-I V dise ase (Sc h mitz 2 0 1 0 ; N C C N 2 0 1 8 ). Real 
w orl d data fr o m t he I nter nati o nal Peri p heral T -Cell a n d Nat ural Killer/ T -Cell L y m p h o m a 
St u d y a n d t he S we dis h L y m p h o ma Re gistr y i n dicate t hat m ore t ha n 8 5 % of P T C L s u bjects 
were tr eate d wit h a n a nt hrac ycli ne -base d m ulti -a ge nt c he m ot hera p y re gi me n, of w hic h 
C H O P was t he m ost c o m m o nl y use d (V os e 2 0 0 8 ; Elli n 2 0 1 4 ). 
C H O P has re mai ne d t he m ost c o m m o nl y us e d fr o ntli ne re gi me n f or pre vi o usl y -u ntr eate d 
s u bjects wit h P T C L f or d eca d es (Sa va ge 2 0 0 8a ; V ose 2 0 0 8 ; Elli n 2 0 1 4 ; Fe deric o 2 0 1 5 b ), 
a n d eff orts t o i m pr o ve u p o n it ha ve bee n disa p p oi nti n g. Alt h o u g h fe w ra n d o mize d trials ha ve 
bee n c o n d u cte d i n s u bjects wit h P T C L, res ults fr o m 2 s mall pr os pecti ve st u dies s h o we d t hat 
m ore a g gressi ve c he m ot h era p y re gi me ns c o nsisti n g of VI P + A B V D (et o p osi de, if os fa mi de, 
a n d cis plati n + d o x or u bici n, ble o m yci n, vi n blasti ne, a n d dacar bazi ne) or G E M -P 
( ge mcita bi ne, met h yl pre d nis ol o ne, a n d cis plati n) offere d n o mea ni n gf ul a d va nta ge o ver 
C H O P (Si m o n 2 0 1 0 ; Glees o n 2 0 1 8 ). T h o u g h a p ost-h oc a nal ysis of p o ole d data fr o m P T C L 
s u bjects treate d o n m ulti ple p hase 2 a n d 3 st u dies s u g geste d t h at t he a d diti o n of et o p osi de t o 
C H O P ( C H O E P) res ulte d i n i m pr o ve d 3 -year E F S (ti me t o sta n dar d  pr o gressi o n -free s ur vi val 
[ P F S] or u n pla n ne d t hera p y) i n y o u n ger (a ge ≤ 6 0 years) s u bjects, t his m ore a g gressi ve 
re gi me n pr o d uce d a d d e d t o xicit y wit h o ut a n i m pr o ve me nt i n O S (Sc h mitz 2 0 1 0 ). F urt her 
i nte nsificati o n of t he C H O E P re gi me n ( Me ga-C H O E P) i n y o u n ger s u bjects act uall y res ulte d 
in w orse o utc o mes (Sc h mitz 2 0 1 0 ). Si milarl y, retr os pecti ve a n al ysis of P T C L s u bjects 
treate d wit h i nte nsi ve c h e m ot hera p y re gi me ns (s u c h as h y per-C H O P a n d h y p er -C V A D) als o 
s u g geste d t h at t hese s u bj ects e x perie nce d w orse o utco mes t ha n t h ose treat e d wit h C H O P 
(Escal o n 2 0 0 5 ). 
N o n -s A L C L P T C Ls are a g gressi ve ne o plas ms wit h p o or pr o g n osis des pite treat me nt  wit h 
c o n ve nti o nal c he m ot hera p y. C o m plete res p o nse ( C R) rates wit h C H O P i n t hese a g gressi ve 
l y m p h o mas ra n ge fr o m a p pr o xi matel y 4 0 % t o 6 0 % wit h o bjecti ve res p o ns e rates ( O R Rs) of 
a p pr o xi matel y 7 5 % (M erca dal 2 0 0 8 ; Si m o n 2 0 1 0 ; Dear de n 2 0 1 1 ; Glees o n 2 0 1 8 ). Esti mates 
of l o n g -t er m o utc o me i n t he P T C L p o p ulati o n i ncl u de a me dia n P F S of 1 2 t o 1 8 m o nt hs a n d 
a me dia n O S of less t ha n 4  years (Sa v a ge 2 0 0 8 b ; V ose 2 0 0 8 ; Elli n 2 0 1 4 ). T he l o w rate of C R 
a n d 5-year O S rat es of < 5 0 % u n dersc ore t he hi g h u n met nee d i n t his s u bject p o p ulati o n.  
T he hi g h rate of s u bs e q u e nt disease pr o gressi o n a m o n g s u bjects r es p o n di n g t o fr o ntli ne 
t hera p y has le d t o t he us e of c o ns oli dati ve treat me nt wit h a ut ol o g o us ste m cell tra ns pla nt 
( A S C T) as a me a ns of i m pr o vi n g l o n g-ter m o utc o mes. W hile s o me si n gle-ar m st u dies ha ve 
s h o w n pr o misi ng res ults wit h t he use of c o ns oli dati ve A S C T, n o ra n d o mize d st u dies ha ve 
bee n c o n d u cte d (Rei mer 2 0 0 9 ; d' A m ore 2 0 1 2 ). P ost-treat me nt c o ns oli dati o n wit h A S C T has 
ne vert heless b ec o me p art of t he sta n dar d treat me nt pla n at ma n y ce nt ers, partic ularl y f or 
s u bjects wit h P T C L s u bt y p es ot her t ha n a n a plastic l y m p h o ma ki nas e + s A L C L 
(M os k o witz  2 0 1 4 ; Ar mita ge 2 0 1 7 ). G ui d eli nes s u p p ort o bser vati o n, a cli ni cal trial, or t he use 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 1  of 6 4  
of A S C T as acce pta ble o pti o ns f or s u bjects w h o ac hie ve a C R f oll o wi n g fr o ntli ne t hera p y 
(Dear de n 2 0 1 1 ; N C C N 2 0 1 8 ). 
E val uati o n of C D 3 0 e x pressi o n i n t he i nitial dia g n ostic w or k u p f or P T C L is rec o m me n de d: 
C D 3 0 is u ni versall y e x presse d a n d is pat h o g n o m o nic i n s A L C L. A m o n g n o n -s A L C L 
s u bt y pes, C D 3 0 e x pressi o n is m ore varia ble (Sa batti ni 2 0 1 3 ; B ossar d 2 0 1 4 ; Fe deric o 2 0 1 5a ; 
Hsi 2 0 1 7 ). E nr oll me nt criteria f or E C H E L O N -2 re q uire d C D 3 0 e x pressi o n of ≥1 0 % as 
deter mi ne d b y sta n dar d i m m u n o hist oc he mistr y (I H C). T he P T C L s u bt y pes e nr olle d i n 
E C H E L O N -2 w ere c o nsi dere d t o ha ve a mea ni n gf ul pre vale nce of C D 3 0 e x pressi o n a n d 
were ge nerall y tr eate d wit h C H O P as fr o ntli ne t hera p y.  
1. 2  Cli ni c al E x p eri e n c e wit h Br e nt u xi m a b V e d oti n  
I n E C H E L O N-2, tr eat me nt wit h A + C H P res ulte d i n statisticall y si g nifica nt a n d cli nicall y 
mea ni n gf ul i m pr o ve me nts i n t he pri mar y e n d p oi nt of P F S per bli n de d i n de pe n de nt ce ntr al 
re vie w ( BI C R), wit h a 2 9 % re d ucti o n i n t he ris k of a P F S e ve nt vers us C H O P (stratifie d 
H R = 0. 7 1 [ 9 5 % CI: 0. 5 4, 0. 9 3], P = 0. 0 1 1); t he me dia n P F S wit h A + C H P was 4 8. 2 m o nt hs 
vers us 2 0. 8 m o nt hs wit h C H O P. T he A + C H P ar m als o de m o nstrate d a statisticall y 
si g nifica nt s ur vi v al be nefit (H R = 0. 6 6 [ 9 5 % CI 0. 4 6, 0. 9 5], P = 0. 0 2 4 4). Wit h a me dia n 
f oll o w-u p of 4 2 m o nt hs, t he me dia n O S was n ot reac h e d f or eit her ar m. T he 7 5t h perce ntile 
of O S was n ot reac he d wit h A + C H P c o m pare d t o 1 7. 5 m o nt hs wit h C H O P. T he A + C H P 
re gi me n was w ell-t olerat e d a n d ha d a ma na gea ble safet y pr ofile t h at was c o m para ble wit h 
t hat of C H O P (H or witz 2 0 1 9 ). T he F D A a p pr o ve d A + C H P f or pre vi o usl y u ntreate d s A L C L 
or ot her C D 3 0 -e x pressi n g P T C Ls i n N o v e m ber 2 0 1 8 base d o n t his st u d y.  
A c o m plete s u m mar y of t he cli nical a n d n o ncli nical data rel e va nt t o bre nt u xi ma b ve d oti n 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 I n v esti gat or’s Br oc h ure. 
1. 3  O v er all Ri s k a n d B e n efit A s s e s s m e nt  
Bre nt u xi ma b ve d oti n is a p pr o ve d i n si x i n dicati o ns as m o n ot h era p y or i n c o m bi nati o n wit h 
c he m ot hera p y. Data fr o m pri or st u dies s u p p ort t he c o m bi nati o n of bre nt u xi ma b ve d oti n wit h 
c he m ot hera p y re gi me ns i n b ot h classic H o d g ki n l y m p h o ma  a n d N H L. I n E C H E L O N -2, i n 
t he setti n g of pre vi o usl y u ntreate d P T C L e x pressi n g C D 3 0  o n  > 1 0 %  of cells , t he 
c o m bi nati o n of A + C H P was s u peri or t o C H O P as fr o ntli ne t hera p y a n d le d t o t he a p pr o val of 
t his re gi me n b y t he F D A (f or C D 3 0 e x pressi n g P T C L) a n d t h e E ur o pea n C o m missi o n  (f or 
s A L C L). 
T here are m ulti ple reas o ns t o e x pect  t hat A + C H P will ha ve effi cac y i n P T C L wit h < 1 0 % 
C D 3 0 e x pressi o n. I n E C H E L O N-2 , C D 3 0 le v els were n ot pre dicti ve of  t h e li keli h o o d or 
d urati o n of res p o ns e  ( D O R) t o A + C H P i n patie nts  wit h n o n -A L C L P T C L  d o w n t o t he 1 0 % 
c ut off e nr olle d i n t he trial  (A d va ni 2 0 1 9 ). Bre nt u xi ma b ve d oti n m o n ot hera p y has als o bee n 
s h o wn  t o ha ve acti vit y i n P T C L a n d ot her l y m p h o mas wit h l o w ( < 1 0 %) or  ne gati ve C D 3 0 
e x pressi o n (J a ga dees h 2 0 1 9). T he lac k of c orrelati o n bet wee n C D 3 0 e x pressi o n a n d res p o nse 
t o bre nt u xi ma b ve d oti n is li kel y m ultifact orial, wit h t u m or heter o ge neit y a n d bi o ps y 
sa m pli n g err or pla yi n g a si g nifica nt r ol e. I n a d diti o n, C D 3 0 e x pressi o n ma y  be d y n a mic wit h 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d ot i n 
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 2  of 6 4  
i ntrat u m oral le vels var yi n g o ver ti me. B re nt u xi ma b ve d oti n is als o hi g hl y p ote nt a n d  ma y 
ha ve  a si g nifica nt treat m e nt effect at C D 3 0 e x pressi o n le vels bel o w t he c ut off detecta ble b y 
I H C. F urt her m ore, t he acti vit y of c ycl o p h os p ha mi de, d o x or u bici n, a n d pre d nis o ne ( C H P ) 
c he m ot hera p y i n P T C L is n ot de pe n de nt o n C D 3 0 e x pressi o n . It is t heref ore reas o n a ble t o 
e x pect t hat A + C H P will de m o nstrate efficac y i n s u bjects wit h P T C L a n d C D 3 0 
e x pressi o n  < 1 0 %. Si nce C D 3 0 is u ni versall y hi g hl y  e x presse d i n s A L C L  a n d s A L C L was 
o ver -re pres e nte d i n E C H E L O N-2 , t his st u d y will be li mite d t o P T C L s u bt y pes ot her t ha n 
s A L C L. 
I n t his S G N 3 5-0 3 2 st u d y of  s u bjects wit h P T C L wit h l o w le vels of C D 3 0 e x pressi o n, it is n ot 
a ntici pate d t hat t he safet y pr ofile of t he A + C H P r e gi me n will differ fr o m t hat see n i n 
E C H E L O N -2 . I n p atie nts wit h P T C L wit h l o wer l e vels of C D 3 0 e x pressi o n i n t he t u m or, it is 
n ot e x pecte d t hat A + C H P will res ult i n ne w or m ore se vere safet y fi n di n gs. T he C H P 
c he m ot hera p y c o m p o ne nts d o n ot tar get C D 3 0, a n d t h us t he si de effect pr ofiles of t hese 
a ge nts s h o ul d n ot be affecte d b y t he a m o u nt of C D 3 0 e x pressi o n i n t he t u m or bi o ps y. 
F urt her m ore, t h ere are n o data t hat s u g gest t he safet y pr ofile of bre nt u xi ma b ve d oti n is 
relate d t o t he a m o u nt of C D 3 0 e x pressi o n. 
Base d o n t h e t otalit y of t he o bser ve d s afet y a n d acti vit y data i n o n g oi n g cli nical st u dies of 
bre nt u xi ma b ve d oti n, t he be nefits a p pear t o o u t wei g h t he ris ks f or t he patie nt p o p ulati o ns 
u n der st u d y.  
1. 4  R ati o n al e f or C urr e nt Tri al  
I n E C H E L O N-2, A + C H P s h o we d efficac y acr oss a ra n ge of C D 3 0 e x pressi o n le vels, e ve n at 
t he l o west all o we d le vel of 1 0 % per l o cal assess m e nt. I n or der t o s u p p ort t he i n dicati o n of 
C D 3 0 -e x pressi n g P T C L, t he s p o ns or s u b mitte d data fr o m a n a d diti o nal 3 4 4 s u bjects wit h 
C D 3 0 -e x pressi n g P T C L a n d ot her lar ge -cell l y m p h o mas w h o ha d bee n treate d i n st u dies wit h 
bre nt u xi ma b ve d oti n as a si n gle a ge nt or i n c o m bi nati o n  wit h c he m ot hera p y, i n b ot h fr o ntli ne 
a n d rela ps e d/refract or y setti n gs. A m o n g t hese 3 4 4 s u bjects, 1 8 4 ha d t u m ors wit h C D 3 0 
e x pressi o n < 1 0 %, i ncl u di n g 8 3/ 1 8 4 wit h u n detecta ble C D 3 0 b y I H C ( C D 3 0 = 0). Acti vit y 
wit h bre nt u xi ma b ve d oti n was o bser v e d at all le v el s of C D 3 0 e x pressi o n, i ncl u di n g i n t u m ors 
wit h u n detecta ble C D 3 0 le vels (A d va ni 2 0 1 9 ; H or witz  2 0 1 9 ). 
Beca use bre nt u xi ma b ve d oti n has acti vit y i n l y m p h o mas wit h l o w C D 3 0 e x pressi o n, a n d 
beca use t h e acti vit y of C H P c he m ot hera p y i n P T C L is n ot de pe n de nt o n C D 3 0 e x pressi o n, it 
is reas o na ble t o e x pect t h at A + C H P will de m o nstrate efficac y i n s u bjects wit h P T C L a n d 
C D 3 0 e x pressi o n < 1 0 %. Si nce C D 3 0 is u ni versall y e x presse d a n d is pat h o g n o m o nic i n 
s A L C L, t his st u d y will b e li mite d t o P T C L s u bt y p es ot her t ha n s A L C L.  
2  
O B J E C TI V E S  
2. 1  Pri m ar y O bj e cti v e  
● 
T o e val uate t he O R R per bli n de d i n de pe n de nt ce ntral re vie w ( BI C R) usi n g Re vise d 
Res p o nse Criteria f or M ali g na nt L y m p h o ma criteria (C hes o n 2 0 0 7 ) 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 3  of 6 4  
2. 2  S e c o n d ar y O bj e cti v e s  
● T o e val uate t he c o m plete res p o nse ( C R) rate f oll o wi n g c o m pleti o n of st u d y treat me nt 
(C hes o n 2 0 0 7 ) 
● T o e val uate t he pr o gressi o n -free s ur vi val P F S (C h es o n 2 0 0 7 ) 
● T o e val uate o v erall s ur vi val ( O S)  
● T o e val uate D O R (C hes o n 2 0 0 7 ) 
● T o e val uate O R R per BI C R, usi n g m o difie d L u ga n o criteria (C h es o n 2 0 1 4 ) 
● T o e val uate t he s afet y a n d t olera bilit y  
2. 3  E n d p oi nt s  
2. 3. 1  Pri m ar y E n d p oi nt  
● O R R per BI C R f oll o wi n g t he c o m pleti o n of st u d y treat me nt usi n g Re vis e d Res p o nse 
Criteria f or Mali g na nt L y m p h o ma criteria (C h es o n 2 0 0 7 ) 
2. 3. 2  S e c o n d ar y E n d p oi nt s  
● C o m plete res p o nse rat e p er BI C R (C h es o n 2 0 0 7 ) 
● P F S per BI C R (C hes o n 2 0 0 7 ) 
● O S  
● D O R per BI C R  (C hes o n 2 0 0 7 ) 
● O R R per BI C R, usi n g m o difie d L u ga n o criteria (C hes o n 2 0 1 4 ) 
● T y pe, i n ci de nce, se verit y, seri o us ness, a n d relate d ness of a d verse e v e nts  
● La b orat or y a b n o r malities 
2. 3. 3  A d diti o n al E n d p oi nt s  
● O R R, C R rate, D O R, a n d P F S as assesse d b y t he I n vesti gat or usi n g C hes o n 2 0 0 7 
criteria  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 4  of 6 4  
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 his is a d ual -c o h ort, o pe n -la bel, m ultice nter, p has e 2 cli nical trial desi g ne d t o e val uate t he 
effic ac y a n d s afet y of A + C H P i n s u bjects wit h n o n -s A L C L P T C L a n d C D 3 0 
e x pressi o n  < 1 0 %. A n arc hi ve d t u m or bi o ps y s peci me n will be s u b mitte d t o a ce ntr al 
pat h ol o g y la b f or c o nfir mati o n of C D 3 0 e x pressi o n. E nr oll me nt will be base d o n C D 3 0 
e x pressi o n per l ocal la b assess me nt. O nl y s u bjects wit h C D 3 0 e x pressi o n < 1 0 % per ce ntral 
c o nfir mati o n will be a nal yz e d f or t h e pri mar y a n d sec o n dar y e n d p oi nts. S u bjects will recei ve 
2 1 -da y c ycl es of A + C H P f or a tar get of 6 -8 c ycles. A tar get of 6 -8 c ycles of st u d y tr eat me nt 
will be a d mi nistere d, per i n vesti gat or d ecisi o n, bas e d o n s u bject -s pecific c h aract eristics, 
i ncl u di n g sta ge of diseas e a n d I PI ris k sc ore. 
U p t o a p pr o xi matel y 8 0  s u bjects will be e nr olle d i n t his st u d y; a p pr o xi matel y 4 0 s u bjects will 
be e nr olle d i nt o t h e C D 3 0  p ositi ve c o h ort a n d u p t o a p pr o xi matel y 4 0  s u bjects will be 
e nr olle d i nt o t he C D 3 0 ne gati ve c o h ort. A st u d y s c he ma is pr o vi de d i n Fi g ure 1 . See 
A p pe n di x  A  f or a sc he d ule of e val uati o ns. 
Fi g ur e 1 : 
St u d y d e si g n  
 
 
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 E C H E L O N -2 trial de m o nstrate d a statisticall y si g nifica nt differe nce i n O R R bet wee n t he 
2 ar ms ( 8 3 % i n t he A -C H P ar m vs. 7 2 % i n t he C H O P ar m; p -val ue = 0. 0 0 3). T his si g nifica nt 
i m pr o ve me nt i n O R R is c o nsiste nt wit h t he statisticall y si g nifica nt a n d cli nicall y mea ni n gf ul 
i m pr o ve me nt i n b ot h P F S ( H R = 0. 7 1, p -val ue = 0. 0 1 1) a n d O S ( H R = 0. 6 6, p -val ue = 0. 0 0 3).  
Base d o n t h e E C H E L O N -2 res ults, Sea ge n b elie ves t hat O R R is a s uita ble pri mar y e n d p oi nt  
t o de m o nstrate cli nical b e nefit i n t his d ual -c o h ort, si n gle-ar m trial. T his is c o nsiste nt  wit h t he 
rec o m me n dati o n o utli ne d i n F D A (F D A 2 0 1 8 ) a n d E M A g ui da nce ( E M A 2 0 1 7) f or si n gle -
ar m trials. Pr o gressi o n -free s ur vi val will be a n al yz e d as a sec o n dar y e n d p oi nt f or s u p p orti ve 
e vi de nce. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 5  of 6 4  
Cli nical data fr o m t his st u d y will be prese nte d i n a descri pti ve ma n ner t o d e m o nstrate 
c o nsiste nc y wit h n o n -a na plastic lar ge cell l y m p h o ma ( A L C L ) s u bjects r ecei vi n g A-C H P 
e nr olle d i n E C H E L O N -2 st u d y. T he s a m ple siz e of 4 0 s u bjects i n t he ≥1 % t o < 1 0 % c o h ort 
was c h ose n t o all o w a de q uate precisi o n of esti mates of res p o ns e rates. Bas e d o n t he 
E C H E L O N -2 st u d y, if 2 8 res p o nses are o bser ve d, t he esti mate d O R R w o ul d be 7 0 %, a n d t he 
ass ociate d 2-si de d 9 5 % CI usi n g t he Cl o p per-Pears o n met h o d w o ul d be ( 5 3. 5 %, 8 3. 4 %).  
L y m p h o ma res p o nse a n d pr o gressi o n will be defi n e d usi n g t he s a me criteria t hat was use d i n 
t he E C H E L O N-2 st u d y (C hes o n 2 0 0 7 ). M o difie d L u ga n o criteri a will be a p plie d i n 
e val uati n g O R R as a sec o n dar y e n d p oi nt.  
3. 2. 1  M et h o d of A s si g ni n g S u bj e ct s t o Tr e at m e nt Gr o u p s  
T his is a si n gle ar m st u d y. S u bjects will be assi g n e d t o 1 of 2 c o h orts bas e d o n C D 3 0 
e x pressi o n; u p t o a p pr o xi matel y 4 0  s u bjects will be e nr olle d i n t he ne gati ve C D 3 0 
e x pressi o n  ( < 1 %) c o h ort a n d a p pr o xi matel y 4 0 s u bjects will be e nr olle d i n t he p ositi ve C D 3 0 
e x pressi o n ( ≥1 % t o < 1 0 %) c o h ort.  
3. 2. 2  R ati o n al e f or S el e cti o n of D o s e s  
I n a p hase 1 d os e -es calati o n st u d y of bre nt u xi ma b ve d oti n ( St u d y S G N 0 3 5 -0 0 1), t he M T D 
was defi ne d as 1. 8  m g/ k g I V a d mi nistere d e v er y 3  wee ks. T his d ose a n d s c h e d ule was f urt her 
e val uate d i n t w o pi v otal p hase 2 st u dies ( St u dies S G 0 3 5 -0 0 0 3 a n d S G 0 3 5 -0 0 0 4) i n s u bjects 
wit h C D 3 0 -p ositi ve he mat ol o gic mali g na n cies.  
I n t he p h ase 1 ( St u d y S G N 3 5-0 1 1) st u d y of bre nt u xi ma b ve d oti n i n c o m bi nati o n wit h C H P, 
t he M T D was defi ne d as 1. 8 m g/ k g I V a d mi nistere d c o nc o mita ntl y wit h C H P e ver y 3 wee ks. 
T he p hase 3 st u d y ( E C H E L O N -2; S G N 3 5 -0 1 4) c o nfir me d t hat t his d ose was well t olerate d i n 
c o m bi nati o n wit h C H P.  
3. 2. 3  Bli n di n g  
T his is a n o pe n -la bel st u d y. 
4  
S T U D Y P O P U L A TI O N  
Eli gi bilit y criteria ma y n ot be wai ve d b y t he 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 G o o d Cli nical Practice ( G C P) or Healt h Re g ulat or y A ut h orit y ( H R A) i ns pecti o n. 
A n y q u esti o ns re gar di n g a s u bject’s eli gi bilit y s h o ul d be disc usse d wit h t he s p o ns or’s st u d y 
ma na ge me nt gr o u p pri or t o e nr oll me nt.  
S u bjects m ust meet A L L  of t he f oll o wi n g i n cl usi o n criteria t o be eli gi ble f or t his st u d y:  
4. 1  I n cl u si o n Crit eri a 
1.  A ge 1 8 years or ol der.  
2.  Ne wl y dia g n ose d P T C L, e x cl u di n g s A L C L, p er t h e Re vise d E ur o pea n -A m erica n 
L y m p h o ma W orl d Healt h Or ga nizati o n ( W H O) 2 0 1 6 classificati o n.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 6  of 6 4  
3.  T he f oll o wi n g n o n -s A L C L P T C L s u bt y p es are eli gi ble: 
a. P T C L –  n ot ot her wise s p ecifie d ( P T C L -N O S)  
b.  A n gi oi m m u n o blastic T -cell l y m p h o m a ( AI T L)  
c. A d ult T -cell le u ke mia/l y m p h o ma ( A T L L; ac ut e a n d l y m p h o ma t y pes o nl y, m ust be 
p ositi ve f or h u ma n T cell le u ke mia vir us 1)  
d.  E nter o pat h y -ass o ciate d T -cell l y m p h o ma ( E A T L)  
e. He pat os ple nic T -cell l y m p h o ma  
f. M o n o m or p hic e pit heli otr o pic i ntesti nal T -cell l y m p h o ma ( M EI T C L)  
g.  I n d ole nt T-cell l y m p h o pr oliferati ve dis or der ( T -L P D) of t he gastr oi ntesti nal ( GI) tract  
h.  F ollic ular T -cell l y m p h o ma  
i. N o dal P T C L  wit h T -f olli c ular hel per ( T F H) p h e n ot y pe 
4.  C D 3 0 e x pressi o n < 1 0 % b y l oc al assess me nt  i n t u m or c o ntai ni n g l y m p h n o de or ot her 
e xtra n o dal s oft tiss ue bi o ps y ( See Secti o n 7. 1. 1 ) 
5.  Fl u or o de o x y gl uc os e ( F D G) -a vi d diseas e b y P E T a n d meas ura ble disease of at least 
1. 5  c m b y C T, as assesse d b y t he site ra di ol o gist. 
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 less t ha n or e q ual 
t o 2 (see A p pe n di x  B ). 
7.  T he f oll o wi n g re q uir e d b aseli ne la b orat or y data: 
● 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 s u bjects wit h Gil bert’s 
disease or d oc u me nte d h e patic i n v ol ve me nt wit h l y m p h o ma  
● ala ni ne a mi n otra nsf eras e ( A L T) a n d as part ate a mi n otra nsferase ( A S T) ≤3 X U L N or 
≤5 X  U L N f or s u bjects wit h d oc u me nt he patic i n v ol ve me nt wit h l y m p h o ma  
● ser u m creati ni ne ≤2 X U L N 
● esti mate d gl o mer ular filtr ati o n rate ( eG F R) > 4 5  m L/ mi n/ 1. 7 3 m 2 usi n g t he 
M o dificati o n of Diet i n Re nal Diseas e ( M D R D) st u d y e q u ati o n  pr o vi de d bel o w . 
eG F R ( m L/ mi n/ 1. 7 3 m2) = 1 7 5 x ( Scr)-1. 1 5 4 x ( A ge) -0. 2 0 3 x ( 0. 7 4 2 if fe male) x ( 1. 2 1 2 if 
Africa n A merica n)  
C o n versi o n t o creati ni ne cleara nce ( Cr C l) ( m L/ mi n) fr o m e G F R usi n g t h e M osteller 
b o d y s urface area ( B S A ) e q uati o n a n d di vi di n g b y 1. 7 3 t o deter mi ne d osi n g h ol ds.   
B S A ( m 2) = ( Hei g ht [ c m] x Wei g ht [ k g] / 3 6 0 0)1/ 2 
Cr C l ( m L/ mi n) = (e G F R [ m L/ mi n/ 1. 7 3 m2] x B S A [ m2])/ 1. 7 3 
● a bs ol ute ne utr o p hil c o u nt ( A N C) ≥1 0 0 0/ µ L ( u nl ess d oc u me nte d b o ne marr o w 
i n v ol ve me nt wit h l y m p h o ma) 
● platelet c o u nt ≥5 0, 0 0 0/ µ L ( u nl ess d oc u me nte d  b o ne marr o w i n v ol ve m e nt wit h 
l y m p h o ma) 
8.  T he f oll o wi n g re q uir e me nts f or s u bjects w h o are h u ma n i m m u n o deficie nc y vir us 
( HI V)-p ositi ve:  
● C D 4 + T -cell c o u nts ≥3 5 0 cell/ μ L wit hi n 2 8 da ys of Da y 1  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 7  of 6 4  
● N o ac q uire d i m m u ne d eficie nc y s y n dr o me -d efi ni n g o p p ort u nistic i nfecti o n wit hi n t he 
past 1 2 m o nt hs  
● O n esta blis he d hi g hl y acti ve a ntiretr o viral t hera p y f or at least 4 w ee ks wit h a n HI V 
viral l oa d less t ha n 4 0 0 c o pies/ m L wit hi n 2 8 da ys of Da y 1  
9.  Fe males of c hil d beari n g p ote ntial m ust ha ve a ne gati ve ser u m beta h u m a n c h or i o nic 
g o na d otr o p hi n ( β -h C G) pre g na nc y t est res ult wit hi n 7 da ys pri or t o t he first d ose of st u d y 
treat me nt a n d m ust a gree t o use a n effecti ve c o ntr ace pti o n met h o d d uri n g t he st u d y a n d 
f or at least 1 2  m o nt hs aft er t he last d ose of c ycl o p h os p ha mi de or 6 m o nt hs after t he l ast 
d ose of ot her st u d y treat me nt, w hic he ver is lat er (see A p pe n di x  C ). Fe males of n o n-
c hil d beari n g p ote ntial are t h ose w h o are p ost me n o pa usal greater t ha n 1 year or w h o ha v e 
ha d a bilateral t u bal li gati o n or h ysterect o m y.  
1 0.  Males w h o ha ve p art ners of c hil d beari n g p ote ntial m ust a gree t o use a n effecti ve 
c o ntrace pti ve met h o d d uri n g t he st u d y a n d f or 1 2  m o nt hs after t he last d ose of 
c ycl o p h os p ha mi de  or 6 m o nt hs after t he last d ose of ot her st u d y treat me nt, w hic he ver is 
later (see A p pe n di x  C ). 
1 1.  S u bjects or t heir le gall y a ut h orize d re prese nt ati ve m ust pr o vi de writte n i nf or me d c o nse nt.  
If i nf or me d c o nse nt is o btai ne d fr o m a le gall y a ut h orize d re pres e ntati ve f or a s u bject 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, b ut t he s u bject is later a ble t o 
pr o vi de i nf or me d c o ns e 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 he 
s u bject. 
4. 2  E x cl u si o n Crit eri a  
1.  C urre nt dia g n osis of a n y of t he f oll o wi n g:  
a. s A L C L 
b.  Pri mar y c uta ne o us T -cell l y m p h o pr oliferati ve dis or ders a n d l y m p h o mas  
c. M yc osis f u n g oi des ( M F), i ncl u di n g tra nsf or me d M F  
2.  Hist or y of a n ot her pr i mar y i n vasi v e ca n cer, he mat ol o gic mali g na n c y, or m yel o d ys plastic 
s y n dr o me t h at has n ot bee n i n re missi o n f or at least 3 years. E xce pti o ns are mali g na n cies 
wit h a ne gli gi ble ris k of metastasis or deat h ( e g, 5 -year O S ≥9 0 %), s uc h as 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 n cer.  
3.  Hist or y of pr o gressi ve m ultif ocal le u k oe nce p hal o pat h y ( P M L).  
4.  Cere bral/ me ni n geal disease relate d t o t he u n d erl yi n g mali g na n c y.  
5.  Pri or treat m e nt wit h bre nt u xi ma b ve d oti n  or d o x or u bici n . 
6.  Baseli ne p eri p heral ne ur o pat h y Gra de  2 ( per t h e N CI C T C A E, Versi o n 4. 0 3) or 
s u bjects wit h t he de m yeli nati n g f or m of C harc ot-Marie -T o ot h s y n dr o me.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 8  of 6 4  
7.  Left ve ntric ular eje cti o n fracti o n less t ha n 4 5 % or s y m pt o matic  car diac dis ease (i n cl u di n g 
s y m pt o matic ve ntric ular d ysf u ncti o n, s y m pt o matic c or o nar y art er y diseas e, a n d 
s y m pt o matic arr h yt h mias), or m y o car di al i nfarcti o n wit hi n t he past 6 m o nt hs, or pre vi o us 
treat me nt wit h c o m plete c u m ulati ve d ose of > 3 0 0 m g/ m2 of d o x o r u bici n. 
8.  A n y u n c o ntr olle d Gra de 3 or hi g h er ( p er t he Nati o nal Ca ncer I nstit ute’s C o m m o n 
Ter mi n ol o g y Criteri a f or A d verse E v e nts, N CI C T C A E Versi o n 4. 0 3) viral, bacterial, or 
f u n gal i nfecti o n wit hi n 2 wee ks pri or t o t he first 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. 
9.  C urre nt t hera p y wit h ot her s yste mic a nti -ne o pl astic or i n vesti gati o nal a ge nts. 
Partici pati o n i n ot her cli nical trials f or a n y c o n diti o n is n ot all o we d . Partici pati o n i n 
o bser vati o nal st u dies is per mitte d . 
1 0.  Fe males w h o ar e pre g n a nt or breastf ee di n g.  
1 1.  S u bjects wit h a 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 a n y of t he dr u g 
f or m ulati o ns of st u d y tr eat me nts. 
1 2.  S u bjects wit h k n o w n uri nar y o utfl o w o bstr ucti o n.  
1 3.  A n y ot her c o n diti o n t hat i n t he o pi ni o n of t he i n vesti gat or  w o ul d i m pact p atie nt safet y or 
a bilit y t o partici pate i n t h e trial.  
1 4.  C o ntrai n dicati o ns t o a n y of t he st u d y dr u gs.  
1 5.  Has recei ve d a li ve vacci ne wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g a n d m ust 
n ot recei ve a li ve vacci ne wit hi n 9 0 da ys after t he l ast d ose of st u d y dr u g (see 
Secti o n  5. 5. 3 ). Vacci nes ot her t ha n li ve vacci nes are per mitte d.  
4. 3  R e m o v al of S u bj e ct 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 s u bject 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 h e reas o n(s) f or wit h dr a wal m ust be d oc u me nte d i n t he s u bject’s me dical 
rec or ds a n d cas e re p ort f or m ( C R F). If a s u bject disc o nti n ues st u d y treat me nt, e ver y atte m pt 
s h o ul d be ma de t o f oll o w t he s u bject u ntil pr o gressi o n, deat h, or a d mi nistrati ve st u d y cl os ure. 
Fi nal assess me nts will be perf or me d b ef ore a n y ot her t hera pe utic i nter ve nti o n if p ossi ble. 
A d diti o nall y, a n y s u bse q ue nt treat me nts s h o ul d be d oc u me n te d o n t he s u bj ect’s me dical 
rec or ds a n d C R F. 
4. 3. 1  Di s c o nti n u ati o n of St u d y Tr e at m e nt  
T he st u d y tr eat me nt will be disc o nti n ue d i n case of pre g na n c y . 
A s u bject’s treat me nt wit h st u d y dr u g ma y b e disc o nti n ue d f or a n y of t he f oll o wi n g reas o ns:  
● C o m plete d treat me nt  
● Pr o gressi ve disease  
● A d verse e ve nt  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 1 9  of 6 4  
● I n v esti gat or decisi o n 
● S u bject 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  
S u bjects 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 ntil 
wit h dra wal fr o m t he st u d y (reas o ns f or st u d y disc o nti n uati o n liste d i n Secti o n 4. 3. 2 ). 
4. 3. 2  S u bj e ct Wit h dr a w al Fr o m St u d y  
A n y s u bject 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 rea s o ns: 
● S u bject 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  
● L ost t o f oll o w -u p  
● Deat h  
● Ot her  
I n case of pre g n a nc y, st u d y treat me nt m ust be ter mi nate d, a n d t he s u bject m ust be wit h dra w n 
fr o m t he cli nical trial. 
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  
T he st u d y tr eat me nts t o b e a d mi nistere d are des cri be d i n Ta ble 1 . 
T a bl e 1 : 
St u d y tr e at m e nt  
St u d y Treat me nt i n Eac h 2 1 -D a y C ycle  
Bre nt u xi ma b ve d oti n 1. 8 m g/ k g I V o n Da y 1 a 
C ycl o p h os p ha mi de 7 5 0  m g/ m 2 I V o n Da y 1  
D o x or u bici n 5 0 m g/ m 2 I V o n Da y 1 
Pre d nis o ne 1 0 0 m g p o dail y o n Da ys 1 -5 ( ± 1 da y wi n d o w)  
a 
A d mi nistere d o ver a p pr o xi matel y 3 0 mi n utes wit hi n 1 h o ur of c o m pleti n g treat me nt wit h ot h er a ge nts a d mi nistere d via 
I V 
5. 2  I n v e sti g ati o n al St u d y Dr u g 
Bre nt u xi ma b ve d oti n, t he i n vesti gati o nal a ge nt u n der st u d y i n t his pr ot oc ol, is a n A D C 
c o nsisti n g of t he a nti b o d y c A C 1 0, s pecific f or h u ma n C D 3 0; t he micr ot u b ule -disr u pti n g 
a ge nt M M A E; a n d a pr otease -clea v a ble li n ker t hat c o vale ntl y attac h es M M A E t o c A C 1 0. 
All  s u bjects i n t he st u d y will be a d mi nistere d bre nt u xi ma b ve d oti n. 
Detaile 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 bre nt u xi ma b 
ve d oti n is l ocate d i n t he P har mac y I nstr u cti o ns.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 0  of 6 4  
5. 2. 1  D e s cri pti o n  
Bre nt u xi ma b ve d oti n is a sterile, preser vati ve -free, w hite t o off-w hite l y o p hilize d ca ke or 
p o w der s u p plie d b y Sea ge n  i n si n gle-us e vials f or rec o nstit uti o n f or I V a d mi nistrati o n. Eac h 
vial of t he pr o d uct c o nt ai ns b re nt u xi ma b ve d oti n, tre hal ose, s o di u m citrat e, a n d 
p ol ys or bat e  8 0. See t he P har mac y I nstr ucti o ns f or f urt her i nf or m ati o n.  
5. 2. 2  M et h o d of Pr o c ur e m e nt  
Bre nt u xi ma b ve d oti n 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  
Bre nt u xi ma b ve d oti n will be a d mi nistere d o n Da y  1 of e ver y 2 1 -da y c ycle b y I V i nf usi o n 
gi ve n o v er a p pr o xi matel y 3 0  mi n utes (see Ta ble 1 ) a n d wit hi n 1 ho ur of c o m pleti n g 
treat me nt wit h ot her a ge nts a d mi nistere d via I V. I n t he a bse nce of i nf usi o n-relate d reacti o ns, 
t he i nf usi o n rate f or all s u bjects s h o ul d be calc ul ate d i n or der t o ac hie ve a 3 0-mi n ute i nf usi o n 
peri o d. Bre nt u xi ma b ve d oti n m ust n ot be a d mi ni stere d as a n I V p us h or b ol us. Bre nt u xi ma b 
ve d oti n s h o ul d n ot be mi x e d wit h ot her me dicati o ns.  
D osi n g is base d o n s u bject wei g ht acc or di n g t o t he i nstit uti o nal sta n dar d; h o we ver, d oses will 
be a dj uste d f or s u bjects w h o e x perie nce a ≥1 0 % c ha n ge i n w ei g ht fr o m baseli ne. A n 
e x ce pti o n t o wei g ht -bas e d d osi n g is ma de f or s u bjects wei g hi n g greater t ha n 1 0 0 k g; d oses 
will be base d o n 1 0 0 k g f or t hese i n di vi d uals. R o u n di n g is per missi ble wit hi n 5 % of t he 
n o mi nal d ose.  
D ose m o dificati o ns of t h e bre nt u xi ma b ve d oti n ar e descri b e d i n Secti o n 5. 4 . 
5. 2. 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  
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 v e nti o n of i nf usi o n-relate d 
reacti o ns pri or t o t he first d ose of st u d y tr eat me nt. H o we ver, s u bjects w h o e x perie nce a n 
i nf usi o n-relate d reacti o n ma y recei ve s u bse q ue nt i nf usi o ns of st u d y treat me nt wit h 
pre me dicati o n as d escri b e d i n Secti o n  5. 2. 5 . S u bjects w h o e x perie nce a Gra de 3 or Gra de  4 
i nf usi o n-relate d reacti o n ma y p ote ntiall y c o nti n ue t o recei ve a d diti o nal treat me nt wit h 
bre nt u xi ma b ve d oti n 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 u bjects s h o ul d be i n di vi d uall y e v al uate d t o ass ess t he nee d f or t u m or l ysis pr o p h yla xis pri or 
t o t he first d ose of bre nt u xi ma b ve d oti n. S u bjects s h o ul d recei ve pr o p h yl a xis as a p pr o priate 
per t he i n stit uti o nal sta n dar ds. 
5. 2. 5  M a n a g e m e nt of I nf u si o n R e a cti o n s  
I nf usi o n-relat e d reacti o ns 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 ul d 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 n a ge a na p h yl a xis s h o ul d 
it occ ur. All s u p porti ve meas ures c o nsiste nt wit h o pti mal s u bject 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 ncl 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 nf usi o n -relate d reacti o ns. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 1  of 6 4  
S u b jects will be m o nit ore d f or a p eri o d of 2 h o urs p ost-i nf usi o n of bre nt u xi ma b ve d oti n. 
S u bjects w h o ha ve e x perie nce d a n i nf usi o n -relat e d reacti o n s h o ul d be pre me dicate d f or 
s u bse q ue nt i nf usi o ns. 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 occ urs, st u d y treat me nt 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. 2. 6  M a n a g e m e nt of S u s p e ct e d P M L  
Si g ns a n d s y m pt o ms of pr o gressi ve m ultif ocal le u k oe nce p h al o pat h y ( P M L) ma y i n cl u de 
altere d me ntal stat us, m ot or deficits s uc h as he mi p aresis or at a xia, vis ual dist ur ba nces, or 
hi g her c ortical d ysf u ncti o n s uc h as d ys p hasia or a g n osia. See t he I n vesti gat or’s Br oc h ure f or  
f urt her det ails. 
If P M L is s us pecte d, h ol d f urt her d osi n g a n d u n d erta ke a dia g n ostic w or k-u p i ncl u di n g ( b ut 
n ot li mite d t o):  
● Ne ur ol o gic e x a mi nati o ns, as warra nte d  
● Brai n r a di ol o gi c feat ures b y ma g n etic res o n a nce i ma gi n g ( M RI)  
● P C R a nal ysis: J o h n C u n ni n g ha m vir us (J C V) D N A detecta bl e i n cere br os pi nal fl ui d  
If P M L is c o nfir me d, bre nt u xi ma b ve d oti n s h o ul d be per ma n e ntl y disc o nti n ue d. 
5. 2. 7  St or a g e a n d H a n dli n g  
Refri gerati o n s h o ul d be set at 2 t o 8° C f or st ora ge of vials a n d s ol uti o ns c o ntai ni n g 
bre nt u xi ma b ve d oti n. T he c o ntr olle d l ocati o n m ust be accessi ble o nl y t o t h e p har macist, t he 
i n vesti gat or, or a d ul y desi g nate d pers o n. Bre nt u xi ma b ve d oti n d oes n ot c o ntai n 
preser vati ves; t heref ore, o pe ne d a n d rec o nstit ute d vials of bre nt u xi ma b ve d oti n s h o ul d be 
use d as s o o n as p ossi ble. If n ot use d i m me diatel y, t he i n -use st ora ge s h o ul d n ot be l o n ger 
t ha n 2 4 h o urs. It is rec o m me n de d t hat bre nt u xi ma b ve d oti n 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. Rec o nstit ute d vials a n d s ol uti o ns m ust n ot be 
s ha ke n. Dr u g acc o u nt a bilit y i nstr ucti o ns are pr o vi de d i n t he P har mac y Bi n der.  
5. 2. 8  P a c k a gi n g a n d L a b eli n g  
Dr u g pr o d uct vials ma y b e la bele d as bre nt u xi ma b ve d oti n, t he U nite d States a d o pte d na me 
( U S A N) a n d t he I nter n ati o nal N o n pr o prietar y Na me (I N N), or as S G N‑3 5, t he c o m p o u n d 
c o de; t he 2 na mes ca n be use d i nterc ha n gea bl y.  
5. 2. 9  Pr e p ar ati o n  
Bre nt u xi ma b ve d oti n vials are pr o vi de d via si n gl e -use c o ntai ners. A n y parti all y use d vials or 
dil ute d d osi n g s ol uti o ns s h o ul d be discar de d usi n g a p pr o priate i nstit uti o nal dr u g dis p osal 
pr oce d ures.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 2  of 6 4  
Bre nt u xi ma b ve d oti n s h o ul d be rec o nstit ute d wit h t he a p pr o priat e a m o u nt of Sterile Water 
f or I njecti o n, U nite d Stat es P har mac o p eia ( U S P), or e q ui vale nt sta n dar d (s ee P har mac y 
I nstr u cti o ns f or details). T he vial s h o ul d be ge ntl y s wirle d u ntil t he c o nte nts are c o m plet el y 
diss ol ve d. T he vial m ust n ot be s ha ke n. T he rec o nstit ute d dr u g pr o d uct s h o ul d be i ns pecte d 
vis uall y f or a n y partic ul ate matter a n d disc ol or ati o n.  
T he re q uir e d v ol u me of rec o nstit ute d dr u g pr o d uct s h o ul d be dil ute d i nt o a n i nf usi o n ba g. 
T he ba g s h o ul d be ge ntl y i n verte d t o mi x t he s ol uti o n. T he ba g m ust n ot be s ha ke n. Pri or t o 
a d mi nistrati o n, t he rec o nstit ute d a n d dil ute d dr u g pr o d uct s h o ul d be i ns pecte d vis uall y f or 
a n y p artic ulate m atter a n d disc ol orati o n.  
Detaile d dr u g pr e 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  C y cl o p h o s p h a mi d e, D o x or u bi ci n, a n d Pr e d ni s o n e  
5. 3. 1  D e s cri pti o n  
All s u bjects i n t he st u d y will be a d mi nistere d t he C H P  c o m p o ne nts of t he C H O P re gi me n.  
C ycl o p h os p ha mi de is a nitr o ge n m ustar d al k yl a ti n g a ge nt. D o x or u bici n is a c yt ot o xic 
a nt hrac ycli n e a nti bi otic. Pre d nis o ne is a c ortic oster oi d.  Refer t o t he S u m mar y of Pr o d uct 
C haracteristics of C H P  f or f urt her d etails o n eac h st u d y dr u g a n d ass ociate d safet y ris ks. 
5. 3. 2  M et h o d of Pr o c ur e m e nt  
C H P  are c o m mer ciall y a vaila ble a n d a p pr o ve d b y t he U nite d States F D A a n d ot her 
re g ulat or y a ge ncies f or use i n treati n g s u bjects wit h m ulti ple t y p es of ca ncer. 
I n t he U nite d States, C H P  will be s u p plie d b y t he st u d y site a n d will be bille d t o s u bjects 
a n d/ or t heir t hir d -part y p a yer (i ns ur a nce, a healt hcare pr o vi d er, or a p plica bl e g o v er n me nt 
pr o gra m).  
I n re gi o ns o utsi de of t he U nite d States, C H P  will be s u p plie d t o st u d y sites b y t he s p o n s or. 
5. 3. 3  D o s e a n d A d mi ni str ati o n  
Refer t o Ta bl e 1  f or s pecific d oses. A d mi nistrati o n of st u d y tr eat me nt s h o ul d be acc or di n g t o 
t he i nstit uti o nal sta n dar d. D osi n g s h o ul d be bas e d o n t he s u bject’s baseli ne ( pre d ose, C ycl e  1 
Da y  1) hei g ht a n d wei g ht or per i nstit uti o nal sta n dar ds at t he site.  
D ose m o dificati o n g ui deli nes f or c ycl o p h os p h a mi de, d o x or u bici n, or pre d nis o ne are 
descri be d i n Secti o n 5. 4 . 
5. 3. 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  
T here are n o pr ot oc ol -re q uire d pre- or p ost me dicati o ns f or C H P . R o uti ne a nti-e metic 
pr o p h yla xis s h o ul d be a d mi nistere d per i nstit uti o nal sta n dar ds.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 3  of 6 4  
5. 3. 5  P a c k a gi n g a n d L a b eli n g  
I n t he U nite d States, s u p plies of C H P  are c o m merciall y a vaila ble. O utsi de of t he U nite d 
States, s u p plies will be la bele d t o meet c o u ntr y -s p ecific re g ulat or y re q uire me nts. 
5. 3. 6  Pr e p ar ati o n  
C H P  s h o ul d be pre pare d per i nstit uti o nal g ui deli nes. 
5. 3. 7  St or a g e a n d H a n dli n g  
C H P  s h o ul d be st ore d a n d ha n dle d per i nstit uti o nal g ui deli nes. 
5. 4  D o s e M o difi c ati o n s  
Ta ble 2  descri bes t he rec o m me n de d d ose m o dificati o ns f or bre nt u xi ma b ve d oti n treat me nt -
ass ociate d ne ur o pat h y.  
D oses re d u ce d f or treat m e nt -relat e d ne ur o pat h y s h o ul d n ot be re-es calate d wit h o ut disc ussi o n 
wit h t he s p o ns or.  
T a bl e 2 : 
R e c o m m e n d e d d o s e m o difi c ati o n s f or tr e at m e nt -a s s o ci at e d n e ur o p at h y  
Gra d e of  
Treat me nt -
Ass ociate d 
Ne ur o pat h y  
Rec o m me n de d D ose M o dificati o n  
Se ns or y Ne ur o pat h y  
M ot or Ne ur o pat h y  
1  
C o nti n ue st u d y treat me nt at sa me d ose 
le vel. 
C o nti n ue st u d y treat me nt at sa me  d ose 
le vel. 
2  
C o nti n ue st u d y treat me nt at t he sa me 
d ose le vel.  
Re d uce d ose le vels of bre nt u xi ma b 
ve d oti n t o 1. 2 m g/ k g u p t o a ma xi m u m 
of 1 2 0  m g e ver y 3 wee ks.  
3  
Re d uce d ose le vels of bre nt u xi ma b 
ve d oti n t o 1. 2 m g/ k g u p t o a ma xi m u m 
of 1 2 0  m g e ver y 3 wee ks  
Disc o nti n ue treat me nt wit h br e nt u xi ma b 
ve d oti n.  
4  
Disc o nti n ue treat me nt wit h br e nt u xi ma b 
ve d oti n.  
Disc o nti n ue treat me nt wit h br e nt u xi ma b 
ve d oti n.  
 
Ta ble 3  descri bes t he rec o m me n de d d ose m o dificati o ns f or bre nt u xi ma b ve d oti n  f or s u bjects 
wit h re nal i m pair me nt.  
T a bl e 3 : 
R e c o m m e n d e d d o s e m o difi c ati o n s f or s u bj e ct s wit h r e n al  i m p air m e nt 
I m pair me nt 
De gree of I m pair me nt  
Rec o m me n de d D ose  M o dificati o n  
Re nal  
N or mal  ( Cr Cl ≥8 0  m L/ mi n )a 
Mil d ( Cr C l > 5 0 -8 0  m L/ mi n) a  
M o derate ( Cr C l > 3 0 -5 0  m L/ mi n) a  
N o d osa ge a dj ust me nt is re q uire d f or n or mal, 
mil d, or m o derate re nal i m pair me nt . 
Se vere ( Cr Cl < 3 0 m L/ mi n) a 
A v oi d t he use of bre n t u xi ma b ve d oti n i n 
s u bj ects wit h se vere re nal i m p air me nt. 
a. 
e G F R > 4 5 m L/ mi n/ 1. 7 3 m 2 usi n g t h e M D R D st u d y e q uati o n  pr o vi d e d bel o w . 
e G F R ( m L/ mi n/ 1. 7 3 m 2) = 1 7 5 x ( Scr)-1. 1 5 4 x ( A ge) -0. 2 0 3 x ( 0. 7 4 2 if fe male) x ( 1. 2 1 2 if Afric a n A merica n ) 
C o n versi o n t o  Cr C l ( m L/ mi n) fr o m e G F R usi n g t h e M osteller B S A e q uati o n  a n d di vi di n g b y 1. 7 3  t o deter mi n e d osi n g 
h ol ds.  
B S A ( m 2) = ( Hei g ht [c m] x Wei g ht [k g ] / 3 6 0 0)1/ 2 
Cr C l ( m L/ mi n) = (e G F R [m L/ mi n/ 1. 7 3 m 2] x B S A  [ m2])/1. 7 3  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 4  of 6 4  
D ose m o dificati o ns f or bre nt u xi ma b ve d oti n ot her t ha n ne ur o pat h y  a n d re n al i m pair me nt  
s h o ul d be at t he discreti o n of t he i n vesti gat or; d ose re d ucti o ns of bre nt u xi ma b ve d oti n bel o w 
1. 2  m g/ k g are n ot per mitte d. Pr ol o n ge d d ose h ol ds of bre n t u xi ma b ve d oti n ( greater t ha n 
2 1  da ys) s h o ul d be disc usse d wit h t he Me dical M o nit or.  
D ose m o dificati o ns of c ycl o p h os p ha mi de, d o x or u bici n, or pre d nis o ne are all o we d per 
i nstit uti o nal sta n dar d of care or per t he p ac ka ge i nsert at t he discreti o n of t he i n vesti gat or. 
Per mitte d d ose m o dificati o ns i ncl u de disc o nti n uati o n of a treat me nt c o m p o ne nt.  
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 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 d verse e ve nt 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 f or HI V -P o siti v e S u bj e ct s  
HI V -p ositi ve s u bjects m ust be ma na ge d i n c o nj u n cti o n wit h a n HI V s pecialist. T he f oll o wi n g 
meas ures are re q uire d.  
5. 5. 1. 1  Hi g hl y A cti v e A ntir etr o vir al T h er a p y  
Hi g hl y Acti ve A ntiretr o viral T hera p y ( H A A R T) is a re q uir e me nt f or t he d urati o n of t he 
st u d y. Partici pa nts m ust be o n sta ble H A A R T t hera p y f or at least 7 da ys b ef ore C ycl e 1 
Da y  1. T he s p ecific a ge nts are at t he discreti o n of t he I n v esti gat or a n d us e of a ge nts c urre ntl y 
a vaila ble o n a n e x pa n de d access basis is all o we d. Use of e x peri me ntal a ntiretr o viral a ge nts or 
t h ose c o ntai ni n g zi d o v u di ne (i ncl u di n g C o m bi vir®  a n d Trizi vir ® ), rit o na vir (incl u di n g 
Kaletra ® ), C o bicistat ( Stri bil d® ), or a n ot her p ote nt C Y P 3 i n hi bit or are pr o hi bite d. 
Partici pa nts ta ki n g zi d o v u di ne - or rit o na vir -b ase d H A A R T m ust c ha n ge t o a differe nt 
re gi me n at least 7 d a ys pri or t o t hera p y i nitiati o n (see Secti o n 5. 5. 3 ). C ha n ges t o H A A R T 
t hera p y ma y be m a de if me dicall y n ecess ar y w hil e o n st u d y tr eat me nt (t o xicit y, fail ure of 
re gi me n, etc.). 
5. 5. 1. 2  P n e u m o c y sti s Pr o p h yl a xi s  
Tri met h o pri m s ulfa met h o x az ole ( Bactri m) m ust be gi v e n at t he o nset of t h era p y f or 
P ne u m oc ystis a n d T o x o plas m osis pr o p h yla xis, acc or di n g t o c urre nt NI H G ui deli nes f or t he 
Pre ve nti o n of O p p ort u nistic I nfecti o ns i n HI V -I nfecte d A d ults a n d A d oles ce nts. 
Alter nati vel y, da ps o ne ( 5 0 m g P O t wice d ail y), at o va q u o ne, or aer os olize d pe nta mi di ne ma y 
be s u bstit ute d f or P ne u m oc ystis pr o p h yla xis i n partici pa nts aller gic t o s ulf o na mi des. 
P ne u m oc ystis pr o p h yla xis s h o ul d be c o nti n ue d o nce t hera p y has bee n disc o nti n ue d.  
5. 5. 1. 3  M y c o b a ct eri u m a vi u m c o m pl e x ( M A C) Pr o p h yl a xi s  
Azit hr o m yci n 1, 2 0 0 m g P O o nce wee kl y m ust be i nitiate d f or pr o p h yl a xis if t he C D 4 c o u nt 
falls bel o w 5 0 cells/ µ L or is e x pecte d t o dr o p bel o w 5 0 cells/ µ L w hile o n c he m ot hera p y. 
Pr o p h yla xis ma y be disc o nti n ue d o nce t he C D 4 c o u nt is dee me d relia bl y a b o ve 5 0 cells/ µ L 
b y t he treati n g i n vesti gat or.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 5  of 6 4  
D ue t o t he gl yc o pr otei n P i n hi biti o n pr o perties of azit hr o m yci n, t his ma y i ncreas e t he dr u g 
e x p os ure a n d c o ntri b ute t o i ncreas e d t o xicit y. Caref ul m o nit ori n g f or bre nt u xi ma b ve d oti n -
relate d t o xicities s h o ul d be i nstit ute d i n s u bjects recei vi n g Azit hr o m yci n. 
Base d o n t h e P K of azit hr o m yci n a n d bre nt u xi ma b ve d oti n, t he st u d y tea m rec o m me n ds 
gi vi n g t he azit hr o m yci n o n Da ys 5, 1 2, a n d 1 9 of eac h c ycle.  
5. 5. 1. 4  Eff e ct of Ot h er Dr u g s o n Br e nt u xi m a b V e d oti n  
C Y P 3 A 4 I n hi bit ors/I n d u cers: M M A E is pri maril y meta b olize d b y C Y P 3 A 4. 
C o -a d mi nistrati o n of bre nt u xi ma b wit h str o n g C Y P 3 A 4 i n hi bit ors ma y i n crease e x p os ure t o 
M M A E. S u bjects w h o are recei vi n g str o n g C Y P 3 A 4 i n hi bit ors c o nc o mita ntl y wit h 
bre nt u xi ma b ve d o ti n s h o ul d be cl osel y m o nit or e d f or a d verse reacti o ns. A d diti o nall y, 
c o-a d mi nistrati o n of bre nt u xi ma b ve d oti n wit h p ote nt C Y P 3 A 4 i n d ucers m a y re d uce 
e x p os ure t o M M A E.  
P -gl yc o pr ot ei n ( P -g p) I n hi bit ors: C o -a d mi nistrati o n of bre nt u xi ma b ve d oti n wit h P -g p 
i n hibit ors ma y i ncrease e x p os ure t o M M A E. S u bjects w h o are recei vi n g P -g p i n hi bit ors 
c o nc o mita ntl y wit h br e nt u xi ma b ve d oti n s h o ul d be cl osel y m o nit ore d f or a d verse reacti o ns.  
5. 5. 2  All o w e d C o n c o mit a nt T h er a p y  
R o uti ne pre me dicati o n f or i nf usi o n -relate d reacti o ns s h o ul d n ot be a d mi nistere d pri or t o t he 
first d ose of bre nt u xi ma b ve d oti n. H o we ver, s u bjects w h o e x perie nce a n i nf usi o n-relate d 
reacti o n ma y recei ve s u bse q ue nt treat me nt wit h pre me dicati o n as des cri be d i n Secti o n 5. 2. 5 . 
R o uti ne i nfecti o us pr o p h yl a xis f or P ne u m oc ystis jir o veci p ne u m o nia ( P C P) s h o ul d be 
c o nsi dere d f or all s u bjects.  
T he use of tra nsf usi o ns, platelet a n d/ or c ol o n y -sti m ulati n g fact ors per i nstit uti o nal practice is 
per mitte d. I ntrat he cal pr o p h yla ctic treat me nt f or cere bral/ me ni n geal diseas e is per mitte d at 
t he discreti o n of t he i n vesti gat or. 
T he use of c ol o n y -sti m ulati n g fact ors a n d/ or c he m ot hera p y f or st e m-cell c ollecti o n t o e na ble 
a f ut ure a ut ol o g o us S C T is per mitte d per i nstit uti o nal sta n dar ds. C he m o m o bilizati o n of ste m 
cells is o nl y per mitte d after e n d of tr eat me nt ( E O T ) pr oce d ures are c o m plet e d.  
C o ns oli dati ve S C T or ra di ot hera p y ma y be gi ve n at t he i n vesti gat or’s discreti o n after E O T 
pr oce d u res are c o m plete d. At least 6 c ycles of st u d y treat me nt s h o ul d be gi ve n pri or t o 
i nitiati n g p ost treat me nt c o ns oli dati ve S C T or ra di ot hera p y. 
5. 5. 3  Pr o hi bit e d C o n c o mit a nt T h er a p y  
S u bjects m ust n ot recei ve a li ve vacci ne wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g 
a n d m ust n ot recei ve a li ve vacci ne wit hi n 9 0 da ys after t he last d ose of st u d y dr u g. E x a m ples 
of li ve vacci n es 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, 
varicella/z oster (c hi c ke n p o x), yell o w fe v er, ra bies, Bacill us Cal mette – G uéri n, a n d t y p h oi d 
vacci ne. Se as o nal i nfl ue n za vacci nes 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 n asal i nfl ue nza vacci nes (e g, Fl u Mist ® ) are li ve atte n uate d vacci nes 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 6  of 6 4  
a n d are n ot all o we d. Vacci nes ot her t ha n li ve vacci nes are p er mitte d. S u bjects ma y n ot 
recei v e ot her i n vesti gati o nal dr u gs, i m m u n os u p pressi ve me dicati o ns, ra di ot hera p y, or 
s yste mic a nti-n e o plastic t hera p y fr o m Da y 1 t hr o u g h E O T. I n a d diti o n, ot her pr o hi bite d 
c o nc o mita nt t hera pies s h o ul d be e x cl u de d i n acc or da nce wit h t he a p pr o ve d prescri bi n g 
i nf or mati o n f or eac h a ge nt. E x ce pti o ns are n ote d i n Secti o n 5. 5. 2 . 
5. 6  Tr e at m e nt C o m pli a n c e  
St u d y d r u g a d mi nistrati o n is 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 a n d t he C R F.  
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 d verse e ve nts a n d c o nc o mita nt me dicati o ns 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. An y st u d y pr ot oc ol -rel ate d a d verse e v e nt 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 as well as a n y c o nc o mita nt me dicati o ns gi ve n f or 
treat me nt of t he a d vers e e ve nt. A sc he d ule of e v e nts is pr o vi de d i n A p pe n di x  A . 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 assess me nts are 
prese nte d i n Secti o n 7 . 
6. 2  S cr e e ni n g Vi sit ( D a y -2 8 t o D a y 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  
● C D 3 0/ hist ol o gical c o nfir mati o n –  s u b missi o n of t u m or c o ntai ni n g l y m p h n o de or ot her 
e xtra n o dal s oft tiss ue bi o ps y wit hi n 3 0  da ys of e nr oll me nt f or ce ntral pat h ol o g y 
c o nfir mati o n of hist ol o g y, C D 3 0 e x pressi o n (see  Secti o n  7. 1. 1 ) 
● H u ma n T -cell le u ke mia vir us -1 ( H T L V -1) stat us (see Secti o n 7. 1 ) 
● C D 4 c o u nt f or HI V p ositi ve s u bjects o nl y (see Secti o ns 5. 5. 1  a n d 7. 3. 5 ) 
(s u b mit res ults t o ce ntral la b orat or y) 
● HI V viral l oa d f or HI V p ositi ve s u bjects o nl y (see Secti o ns 5. 5. 1  a n d 7. 3. 5 ) 
(s u b mit res ults t o ce ntral la b orat or y) 
● He m o gl o bi n ( H g b) A 1c (see Secti o n  7. 3. 3 ) 
● C T of c hest, nec k, a b d o me n, pel vis (see Secti o n 7. 2 ) 
● P E T sca n (see Secti o n 7. 2 ) 
● B o ne marr o w bi o ps y ( ma y be o bt ai ne d wit hi n 6 0 da ys of t he first d ose of st u d y 
treat me nt; see Secti o n 7. 2 ) 
● Ec h ocar di o gra m or m ulti -gate d ac q uisiti o n ( M U G A) sca n ( ma y be o btai ne d u p t o 
1  m o nt h  pri or t o t he first d ose of st u d y tr eat me nt)  
6. 2. 1  B a s eli n e Vi sit ( D a y -7 t o D a y 1)  
● Hei g ht a n d wei g ht  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 7  of 6 4  
● Electr ocar di o gra m  ( E C G) 
● Pre g n a nc y test f or fe mal es of c hil d beari n g p ot e ntial (see Secti o n  7. 3. 3 ) 
● E C O G perf or ma nce stat us (see Secti o n  7. 3. 4 ) 
● Ser u m c he mistr y p a nel  (s ee Secti o n 7. 3. 3 ) 
● C B C wit h differe ntial (s ee Secti o n  7. 3. 3 ) 
● eG F R usi n g t he M D R D e q uati o n (see Secti o n 7. 3. 3 ) 
6. 3  Tr e at m e nt P eri o d ( 2 1 -d a y c y cl e s)  
6. 3. 1  E v er y C y cl e: D a y 1  
● Vital si g ns (see Secti o n 7. 3. 2 ) 
● Pre g n a nc y test f or fe mal es of c hil d beari n g p ot e ntial  (see Secti o n 7. 3. 3 ) 
● L y m p h o ma ass ess me nt (see Secti o n 7. 2 ; c o n d ucte d wit hi n 4 8 h o urs pri or t o st u d y 
treatme nt i n C ycl e 1)  
● E C O G perf or ma nce stat us ( n ot re q uire d i n C ycle 1)  
● Ser u m c he mistr y  
● C B C wit h differe ntial  
● St u d y treat me nt; a d mi nistere d after all ass ess me nts ha ve bee n c o n d ucte d  
○ 
S u bjects will be m o nit ore d f or a p eri o d of 2 h o urs p ost -i nf usi o n of bre nt u xi ma b 
ve d oti n.  
● HI V p ositi ve s u bjects o nl y : C D 4 c o u nt a n d HI V viral l oa d at C ycle 2 a n d e v er y 4 
c ycles t hereaft er  
● eG F R  
6. 3. 2  C y cl e 4 O nl y: D a y 1 5 -2 1  
● C T of c hest, nec k, a b d o me n, pel vis  
● P E T sca n  
● B o ne marr o w bi o ps y t o c o nfir m res p o nse (if p ositi ve at baseli ne)  
6. 3. 3  L a st Pl a n n e d C y cl e of Tr e at m e nt: D a y 1 5 -2 1  
T he f oll o wi n g assess me nts m ust be o btai ne d f or s u bjects w h o c o m plete t he last pla n ne d 
c ycle of tr eat me nt. S u bje cts w h o disc o nti n ue treat me nt pri or t o t he pla n ne d last c ycl e of 
treat me nt s h o ul d ha ve a n E O T visit, as descri be d i n Secti o n 6. 4 . 
● L y m p h o ma ass ess me nt  
● C T of c hest, nec k, a b d o me n, pel vis  
● P E T sca n  
● B o ne marr o w bi o ps y t o c o nfir m res p o nse (if p ositi ve at basel i ne a n d n ot f o u n d t o be 
ne gati ve at a pri or rest a ge, see Secti o n 7. 2 ) 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 8  of 6 4  
6. 4  E n d -of -Tr e at m e nt Vi sit ( 3 0 -3 7 d a y s  aft er l a st d o s e of st u d y dr u g)  
If E O T e v al uati o ns are c o m plete d bef ore 3 0 da ys after t he l ast st u d y treat me nt, t he s u bject 
will be c o ntacte d b y p h o ne 3 0 -3 7 da ys f oll o wi n g t he last treat me nt t o assess f or a d verse 
e ve nts.  
E O T assess me nts will be perf or me d b ef ore a n y ot her t hera pe utic i nter ve nti o n, if p ossi ble.  
● Pre g n a nc y test f or fe mal es of c hil d beari n g p ot e ntial  
● E C O G perf or ma nce stat us  
● Ser u m c he mistr y  
● C B C wit h differe ntial  
● HI V p ositi ve s u bjects o nl y: C D 4 c o u nt  a n d HI V viral l oa d  
● eG F R  
T he f oll o wi n g res p o nse assess me nts are re q uire d if t he y were n ot c o n d uct e d at last c ycle of 
treat me nt: 
● L y m p h o ma ass ess me nt  
● C T of c hest, nec k, a b d o me n, pel vis  
● P E T sca n  
● B o ne marr o w bi o ps y t o c o nfir m res p o nse (if p ositi ve at baseli ne a n d n ot f o u n d t o be 
ne gati ve at a pri or rest a ge)  
6. 5  F oll o w -u p  
S u bjects w h o ha ve n ot yet e x perie nce d diseas e pr o gressi o n per i n vesti gat or assess me nt 
( base d o n t he Re vise d Res p o nse Criteria f or Mali g na nt L y m p h o ma) (C hes o n 2 0 0 7 ), t he 
f oll o wi n g ass ess me nts m ust be o btai ne d at 9, 1 2, 1 5, 1 8, 2 1, a n d 2 4 m o nt hs ( ± 1 wee k) after 
t he first d ose of st u d y treat me nt, a n d e ver y 6 m o nt hs t hereaft er ( ± 1  wee k) u ntil pr o gressi o n 
per i n vesti gat or, deat h, or a nal ysis of t he pri mar y e n d p oi nt, w hic he ver c o m es first.  
● C T of c hest, nec k, a b d o me n, pel v is 
● L y m p h o ma ass ess me nt  
T he f oll o wi n g assess me nts are re q uire d d uri n g f oll o w u p at t he ti me p oi nts descri be d. 
M o nt hs are rel ati ve t o t he first d ose of st u d y treat me nt. Assess me nts are t o be c o n d ucte d u ntil 
deat h or st u d y cl os ure u nless ot her wise s pecifie d. Assess me nts occ urri n g after 2 4 m o nt hs 
fr o m first d ose ma y be c o n d ucte d via a p h o n e call. 
● S ur vi val stat us a n d s u bse q ue nt a ntica ncer t hera pies recei v e d –  e ver y 
6  m o nt hs  ( ± 1 wee k u p t o M o nt h 3 0, ± 1  m o nt h after M o nt h 3 0) starti n g at M o nt h  1 2 
a n d after disease pr o gressi o n  
6. 6  E n d of St u d y/ E n d of F oll o w -u p  
T he st u d y will be cl ose d 2 years after e nr oll me nt of t he last s u bject, or w h e n n o s u bjects 
re mai n i n l o n g-ter m f oll o w-u p, w hic he v er occ urs first. A d diti o nall y, t h e s p o ns or ma y 
ter mi nate t he st u d y at a n y ti me. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 2 9  of 6 4  
T he d ate t he s u bject 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 c ollecte d.  
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 s u bjects 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.  
S u bject 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 nc o mita nt me dicati o ns.  
Car diac f u ncti o n will be deter mi ne d b y perf or mi n g eit her a n ec h ocar di o gra m or M U G A sca n 
( ma y b e o btai ne d u p t o 1 m o nt h  pri or t o t he first d ose of st u d y tr eat me nt).  
H T L V -1  stat us m ust be o btai ne d b y l o cal la b orat or y assess me nt t o i nf or m t he dia g n osis.  
7. 1. 1  Hi st ol o gi c S u bt y p e a n d C h ar a ct eri z ati o n of T u m or Ti s s u e  
Hist ol o gic s u bt y p e m ust be deter mi ne d b y l ocal p at h ol o g y ass ess me nt t o e na ble e nr oll me nt. 
Tiss ue sa m ples will be se nt t o t he ce ntral pat h ol o g y la b orat or y wit hi n 3 0  da ys of e nr oll me nt 
f or c o nfir m ati o n of C D 3 0 e x pressi o n. T u m or bl oc ks are preferre d if a vaila ble. S u bjects wit h 
ne gati ve C D 3 0 e x pressi o n ( < 1 %) a n d p ositi ve C D 3 0 e x pressi o n ( 1 % t o < 1 0 %) b y l ocal 
testi n g are eli gi ble f or e nr oll me nt.  
C D 3 0 e x pressi o n is t o be assesse d b y i m m u n o hist oc he mistr y usi n g tiss ue fr o m t he dia g n ostic 
bi o ps y. T he 3  f oll o wi n g criteria m ust be met t o declare C D 3 0 p ositi vit y: 
a. C D 3 0 detecte d i n ≥1 % of ne o plastic cells (i n cases w here e n u merati o n of ne o plastic 
cells is n ot p ossi ble, t otal l y m p h oc ytes ma y b e use d).  
b.  C D 3 0 stai ni n g at a n y i nte nsit y.  
c. Me m bra n o us, c yt o plas mi c, a n d/ or g ol gi patter n of e x pressi o n of t he C D 3 0 a nti ge n.  
S u b missi o n of t he t u m or tiss ue sa m ples fr o m a dia g n ostic bi o ps y wit hi n 3 0  da ys of e nr oll me nt 
is re q uire d f or ce ntr al c o nfir mati o n of C D 3 0 e x pressi o n a n d disease s u bt y pe. T he dia g n ostic 
s peci me n m ust be fr o m a mali g na nt l y m p h n o de or e xtra n o dal tiss ue o btai ne d b y c ore or 
e x cisi o nal/i ncisi o nal bi o ps y, a n d s h o ul d be fr o m t he sa me  s peci me n use d f or l ocal C D 3 0 
e x pressi o n testi n g. C uta ne o us b o ne, b o ne marr o w sa m ples , fi ne nee dl e as pirates, a n d 
c yt ol o g y sa m ples are u n acce pta bl e.  
A d diti o nal bi o mar ker ass ess me nts i n t u m or tiss ue ma y i ncl u d e, c haract erizati o n of t he t u m or 
micr oe n vir o n me n t, t u m or s u bt y pi n g, pr ofili n g of s o matic m utati o ns or alterati o ns i n ge n es or 
R N A c o m m o nl y altere d i n ca ncer, a n d dr u g effects. Assa ys ma y i n cl u de, b ut n ot li mite d t o, 
i m m u n o hist oc he mistr y a n d ne xt ge nerati o n se q ue nci n g of R N A a n d D N A. 
Details a n d s hi p pi n g  i nstr ucti o ns are pr o vi de d i n t he Researc h S peci me n La b orat or y Ma n ual. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 0  of 6 4  
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 b y t h e I n v e sti g at or  
L y m p h o ma ass ess me nts are t o be perf or me d at t h e ti me p oi nts o utli ne d i n Secti o n 6  a n d 
A p pe n di x  A . A n a de q uat e f oc use d l y m p h o ma assess me nt c o nsists of: 
● S u bject me dical hist or y, i ncl u di n g a t h or o u g h re vi e w of:  
○ 
T he s u bject’s c urre nt si g ns a n d s y m pt o ms, i ncl u di n g B s y m pt o ms (fe ver, ni g ht 
s weats, or w ei g ht l oss > 1 0 %) 
○ 
C o nc o mita nt me dicati o ns  
● P h ysical e x a mi nati o n, i ncl u di n g e v al uati o n of s ki n, hea d, e yes, ears, n ose, t hr oat, 
l y m p h n o des, heart, l u n gs, a b d o me n, bac k, e xtre mities, a n d ne ur ol o g y 
Ra di o gra p hic assess me nts ( C T of c hest, ne c k, a b d o me n, a n d pel vis) will be perf or me d at 
pr ot oc ol -s pecifi e d ti me p oi nts or if disease pr o gressi o n is s us pecte d. Assess me nt of 
l y m p h o ma pr o gressi o n b y t he i n vesti gat or will be ma de acc or di n g t o t he Re vise d Res p o nse 
Criteria f or Mali g na nt L y m p h o ma (C hes o n 2 0 0 7 ). Treat me nt decisi o ns b y t he i n vesti gat or 
will be base d o n t hese assess me nts. C T a n d P E T sca ns are re q uire d per pr ot oc ol as direct e d 
i n Secti o n 6  a n d A p pe n di x  A . A c o m bi ne d C T/ P E T ma y b e o btai ne d t o satisf y t he 
re q uire me nts f or C T a n d P E T sca n ni n g w he n b ot h are re q uire d p er pr ot oc ol, as l o n g as t he 
C T sca n is of dia g n ostic q ualit y. C T a n d/ or P E T s ca ns ma y als o be o bt ai ne d t hr o u g h o ut t he 
st u d y if cli nicall y i n dicat e d; if sca ns are perf or me d at n o n -pr ot oc ol s pecifie d ti me p oi nts, 
res ults will be c ollecte d i n t he s u bject’s C R F a n d i ma ges will be s u b mitte d f or ce ntr al re vi e w. 
A b o ne marr o w bi o ps y is re q uire d at baseli ne. I nf or mati o n fr o m a n assess me nt perf or me d 
wit hi n 6 0  da ys of t he first d ose of s t u d y tr eat me nt, as part of cli nical care, ma y b e use d t o 
satisf y t he b aseli ne b o ne marr o w bi o ps y re q uire m e nt. P ost baseli ne bi o psies are re q uire d t o 
c o nfir m res p o ns e if b o ne marr o w is p ositi ve at bas eli ne; t his c o nfir mati o n is t o be o btai ne d 
wit hi n 4 wee ks of d oc u m e ntati o n of res p o nse b y ra di o gra p hic ass ess me nt. Re peat b o ne 
marr o w bi o psies are n ot r e q uire d o nce b o ne marr o w is f o u n d t o be ne gati ve.  
If c uta ne o us lesi o ns are t he s ole site of pr o gressi ve disease, a bi o ps y m ust be o btai ne d t o 
hist ol o gicall y c o nfi r m pr o gressi o n. 
All s u bjects’ cli nical data a n d t u m or i ma ges m ust be a vaila ble f or C R F s o urce verificati o n. 
C o pies of all i ma gi n g st u dies m ust be ma de a vaila ble f or re vi e w b y t he s p o ns or ( or its 
desi g nee) a n d t he t hir d p art y i ma gi n g c ore l a b orat or y. Refer t o t he St u d y Ma n ual f or det ails 
(i nstr ucti o ns o n c ollecti n g a n d s u b mitti n g t u m or i ma gi n g st u dies f or t hir d-part y i ma gi n g c ore 
la b orat or y re vie w). 
T he sec o n d ar y deter mi nati o n of a ntit u m or efficac y will be O R R acc or di n g t o t he L u ga n o 
Classificati o n Re vise d S ta gi n g S yste m f or n o d al n o n-H o d g ki n a n d H o d g ki n l y m p h o mas 
(C hes o n 2 0 1 4 ) m o difie d t o ta ke i nt o acc o u nt C T res p o nse  i n t he e ve nt of a P E T P R 
( m o difie d L u ga n o criteri a). 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 1  of 6 4  
7. 2. 1  Bi o s p e ci m e n S a m pl e s f or F ut ur e R e s e ar c h  
I n t he U nite d States, re m ai ni n g de-i de ntifie d u n us e d tiss ue will be retai ne d b y Seage n  a n d 
use d f or f ut ure res earc h f or s u bjects w h o pr o vi de a d diti o nal c o nse nt. T he pla n ne d f ut ure 
researc h i ncl u des, b ut is n ot li mite d t o, t he e val uati o n of tar gets f or n o vel A D Cs, 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 o i de ntif y pre dicti ve p har mac o d y n a mic 
bi o mar kers of A D Cs. Tiss ue sa m ples d o nate d f or f ut ure  researc h will be ret ai ne d f or a peri o d 
of 2 5 years.  
F or s u bjects treate d o utsi de of t he U nite d States, or if a d diti o nal c o nse nt is n ot gra nt e d, a n y 
tiss ue sa m ples re mai ni n g after all st u d y testi n g is c o m plete d will be destr o ye d f oll o wi n g 
st u d y cl os ur e. 
7. 3  S a f 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 d verse e v e nts ( A Es) i ncl u di n g s eri o us a d verse e ve nts ( S A Es), rec 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 ol -s pecifie d p h ysic al e x a mi nati o n 
fi n di n gs a n d la b orat or y t ests. 
7. 3. 1  A d v er s e E v e nt s  
7. 3. 1. 1  D efi niti o n s  
A d verse E ve nt  
Acc or di n g t o t he I nt er nati o nal C o nfere nce o n Har m o nizati o n (I C H) E 2 A g ui deli 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 D Safet y 
Re p orti n g, a n a d vers e e v e nt is a n y u nt o w ar d me di cal occ urre n ce i n a s u bject or cli nical 
i n vesti gati o nal s u bject a d mi nistere d a me 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 u l 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 o n, 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 case re p ort f or m ( C R F):  
● Fr o m t he ti me of i nf or m e d c o nse nt t hr o u g h t he da y pri or t o st u d y Da y 1,  o nl y st u d y 
pr ot oc ol -relat e d a d verse e ve nts s h o ul d be rec or de d. 
● 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 d verse e ve nts (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 ( d uri n g a n d p ost d ose) t hr o u g h t h e e n d of t he safet y re p orti n g peri o d 
(see Secti o n  7. 3. 1. 3 ). 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 b e rec or de d as A Es w h et her or n ot t he pr oce d ure was pr ot o c ol 
ma n date d.  
● C ha n ges i n me di cal c o n diti o ns a n d a d verse e v e nts, i ncl u di n g c h a n ges i n se verit y, 
fre q ue n c y, or c h aracter, d uri n g t he s afet y re p orti n g peri o d s h o ul d be rec or de d. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 2  of 6 4  
● 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 d verse e ve nt 
u nless it is ass ociate d wit h cli nical si g ns or s y m pt o ms, re q uires a n i nter ve nti o n, 
res ults i n a seri o us a d verse e ve nt, 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 tr eat me nt. W he n rec or di n g a n a d v erse e ve nt 
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 he a b n or malit y itself s h o ul d be rec or de d (e g, rec or d “a ne 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 d vers e e ve n t s h o ul d be classifie d as a seri o us a d verse e ve nt ( S A E) if it meets o ne of t he 
f oll o wi n g criteria: 
Fatal:  
A d verse e ve nt res ulte d i n deat h  
Lif e t hreat e ni n g:  
T he a d verse e v e nts place d t he s u bject 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 d verse e v e nt t hat 
h y p ot hetic all y mi g ht ca use deat h if it were m ore s e vere.  
H os pitalizati o n:  
T he A E re q uire d 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 b efore 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 seri o us a d verse e ve nts b y t his 
criteri o n. A d missi o n t o a palliati ve u nit or h os pice 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 pita lizati o ns f or sc he d ule d t hera p y of t h e u n derl yi n g ca n cer or 
st u d y tar get disease n ee d n ot be ca pt ure d as S A Es. 
Disa bli n g/ 
i nca pacitati n g: 
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 s u bject’s a bilit y t o c o n d uct n or m al life f u ncti o ns.  
C o n ge nital 
a n o mal y or birt h 
defect:  
A n a d vers e o utc o me i n a c hil d or fet us of a s u bject e x p ose d t o t he 
m olec ule or st u d y treat m e 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 d verse e v e nt di d n ot meet a n y  of t he a b o v e criteria, b ut c o ul d 
ha ve je o par dize d t he s u bject a n d mi g ht ha ve re q uir e d me dical or 
s ur gic al i nter ve nti o n t o pre ve nt o ne of t he o utc o m es 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. 
 
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 Nati o nal Ca ncer I nstit ute’s C o m m o n Ter mi n ol o g y 
Criteria f or A d v erse E v e nts ( N CI C T C A E), Versi o n 4. 0 3. T hese 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 ul at or y defi 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 Seri o us A d verse E ve nts). 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 3  of 6 4  
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 d verse e ve nt t o eac h st u d y treat me nt [ bre nt u xi ma b ve d oti n or a n y 
c o m p o ne nt of C H P] s h o ul d be e val uate d b y t h e i n vesti gat or usi n g t he f oll o wi n g criteria:  
Relate d:  
T here is e vi de n ce t o s u g gest a ca us al relati o ns hi p bet wee n t he dr u g 
a n d t he a d verse e v e nt, s uc h as:  
● 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 oci ate d wit h 
dr u g e x p os ure (e g, a n gi o e de ma, he p atic i nj ur y, Ste ve ns -J o h ns o n 
S y n dr o me)  
● a n e ve nt t hat is n ot c o m m o nl y ass ociat e 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 us e of t he a d v erse e v e nt is m ore pla usi ble (e g, d ue t o 
u n derl yi n g dise ase 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 n ce ca n n ot be esta blis he d wit h t he o nset of t he a d verse 
e ve nt a n d a d mi nistrati o n of t he st u d y tr eat 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. 3. 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 
s u bject q uesti o ni n g, disc o vere d d uri n g p h ysic al e x a 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 seri o us 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 pt 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 b e d o ne 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 dic al 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, r e p ort t he i n di vi d ual s y m pt o m as a se parate a d v erse e ve nt.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 4  of 6 4  
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 t he 
bre nt u xi ma b ve d oti n. F or i nf usi o n -relate d reacti o ns, d o n ot use t he N CI C T C A E ter ms of 
‘c yt o ki n e rel ease s y n dr o me,’ ‘ac ute i nf usi o n reacti o n,’ or ‘aller gi c or h y perse nsiti vit y 
reacti o n.’ I nstea d, rec or d eac h si g n or s y m pt o m as a n i n di vi d ual a d verse e v e nt. 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-rel ate d e ve nt, eac h si g n or s y m pt o m s ho ul d 
be rec or de d se p aratel y wit h its le vel of se verit y.  
Rec or di n g Seri o us A d verse E ve nts  
F or S A Es, rec or d t he pri mar y e ve nt o n b ot h t he C R F a n d a n S A E f or m; e v e nts occ urri n g 
sec o n dar y t o t he pri mar y e ve nt s h o ul d be descri be d o n t he S A E f or m i n t he narrati ve 
descri pti o n of t he case.  
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 orte 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 gic al or dia g n ostic pr o ce d ure s h o ul d b e 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 n arrati ve as part 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 C a ncer  
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 t er ms “ Disease Pr o gressi o n”, “ Pr o gressi o n of 
Disease”, or “ Mali g na nt disease pr o gressi o n” a n d o t 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 nical s y m pt o ms of pr o gressi o n ma y be re p ort e d as A Es 
or S A Es if t he s y m pt o m ca n n ot be det er mi ne d as e x cl usi vel y d u e 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 disease 
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  
N otificati o n t o Dr u g Safet y: Base d o n t he esti mate d date of c o n ce pti o n, c o m pl ete a 
Pre g n a nc y Re p ort F or m f or all pre g na n cies t hat occ ur fr o m t he ti me of i nf or me d c o nse nt t o 
t he e n d of t he pr ot o c ol-d efi ne d c o ntr ace pti o n peri o d, i ncl u di n g a n y pre g na ncies t hat occ ur i n 
t he part ner of a male st u d y s u bject. Fa x t he f or m t o t he s p o ns or’s Dr u g Safet y De part me nt 
wit hi n 2 4  h o urs of bec o mi n g a w are of t he pre g n a nc y. All pre g na n cies t hat occ ur d uri n g t his 
ti me peri o d 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: Bas e d o n t he esti mate d date of c o nce pti o n, all pre g n a nci es t hat occ ur 
fr o m ti me of i nf or me d c o nse nt t o wit hi n 3 0 da ys of last st u d y dr u g d os e, i ncl u di n g 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 s u bj ect, will als o be rec or de d o n t he 
A d verse E v e nts a n d Pre -E xisti n g C o n diti o ns C R F. A b orti o n, w het her acci d e ntal, t hera p e utic, 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 5  of 6 4  
or s p o nta ne o us, s h o ul d be re p ort e d as a n S A E. C o n ge nital a n o malies or birt h defects, as 
defi ne d b y t he ‘s eri o us’ criteri o n a b o ve (s ee d efi niti o ns Secti o n 7. 3. 1. 1 ) s h o ul d be re p orte d as 
S A Es.  
P ote nti al Dr u g -I n d uce d Li ver I nj ur y 
H y’s La w ca n be us e 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 ncreas e 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 dr u g -i n d uce d li ver i nj ur y ( DI LI) i n t he cli nical setti n g(s) b ei n g st udie d. H o we ver, 
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 cas es is hi g hl y pre di cti 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 cas es i ncl u de t he f oll o wi n g 3 c o m p o n e nts:  
1.  A mi n otra nsferase ( A L T a n d/ or A S T) el e v ati o n > 3 x U L N  
A N D  
2.  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 (ie, el e vate d ser u m 
al kali ne p h os p hatase),  
A N D  
3.  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 l i mite d t o, viral he patitis, pre-e xisti n g c hr o nic 
or ac ute li ver disease, or t he a d mi nistrati o n of ot her dr u g(s) k n o w n t o be h e pat ot o xic.  
Re p orti n g Re q uire m e nts  
A n y p ote nti al H y’s L a w c ase s h o ul d be h a n dle d as a seri o us a d verse e v e nt ( S A E) a n d 
re p orte d pr o mptl 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 ory Res ults S u g g esti 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 w e d b y re peat 
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 her t he y are w orse 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 
wit h h ol di n g st u d y dr u g.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 6  of 6 4  
7. 3. 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 all A Es a n d S 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 he last st u d y tr eat me nt ( bre nt u xi ma b ve d oti n or a n y c o m p o ne nt of 
C H P), w hic he ver is later. H o we ver, all st u d y pr ot oc ol -relat e d A Es are t o be c ollecte d fr o m 
t he ti me of i nf or me d c o nse nt. All S A Es t hat occ ur after t he s afet 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 ort e d 
t o t he s p o ns or. 
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 s u bject 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 gh t he 
safet y re p orti n g p eri o d. Certai n n o n-seri o us A Es of i nterest ma y be 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 ur e. 
7. 3. 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 r e p ort t he e ve nt t o 
t he s p o ns or ( or desi g nee), re gar dl ess 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:  
● S u bject 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 fa x e d t o t he s p o ns or’s Dr u g 
Safet y De part me nt at ( 4 2 5) 5 2 7-4 3 0 8  wit hi n 2 4 h o urs.  
Rele va nt f oll o w -u p i nf or ma ti 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. 3. 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 uir e d t o re p ort all S A Es t o t he s p o ns or (see Secti o n 7. 3. 1. 4 ). T he s p o ns or 
will re p ort all S A Es, i ncl u di n g s us pect e d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs) t o 
re g ulat or y a ut h orities as re q uire d p er l ocal le gislati o n or re g ulat or y re p orti n g re q uire me nts. 
7. 3. 2  Vit al Si g n s  
Vital si g ns meas ur es are t o i ncl u de heart rate, bl o o d press ure, a n d te m perat ure. Vital si g ns 
will be meas ure d a n d rec or de d pri or t o t he start of st u d y dr u g a d mi nistrati o n at eac h c ycle as 
s pecifie d i n Secti o n 6  a n d A p pe n di x  A . 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 7  of 6 4  
7. 3. 3  Cli ni c al L a b or at or y T e st s  
T he f oll o wi n g l a b orat or y assess me nts will be perf or me d b y t h e l ocal la b t o e val uate  safet y at 
sc he d ule d ti me p oi nts (see A p pe n di x  A ) d uri n g t h e c o urse of t he st u d y a n d t he res ults ( n o 
bl o o d) will be se nt t o t he ce ntral la b:  
● T he ser u m c h e mis tr y p a n el 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, lactate 
de h y dr o ge nas e, p h os p h or us, p otassi u m, s o di u m, t otal bilir u bi n, uric aci d, a n d 
gl uc ose.  
● T he C B C wit h differe nti al is t o i ncl u de t he f oll o wi n g tests: w hite bl o o d cell c o u nt 
wit h fi ve -part differe ntial ( ne utr o p hils, l y m p h oc yt es, m o n oc yt es, e osi n o p hils, a n d 
bas o p hils), re d bl o o d cell c o u nt, platelet c o u nt, a n d he m o gl o bi n/ he mat ocrit.  
● H g b A 1 c will be o btai ne d at baseli n e.  
● A ser u m or uri ne β -h C G pre g na nc y t est f or fe males of c hil d beari n g p ote ntial  
● eG F R > 4 5  m L/ mi n/ 1. 7 3 m 2 usi n g t he M D R D st u d y e q u ati o n  pr o vi de d bel o w . 
eG F R ( m L/ mi n/ 1. 7 3 m 2) = 1 7 5 x ( Scr)-1. 1 5 4 x ( A ge) -0. 2 0 3 x ( 0. 7 4 2 if fe male) x ( 1. 2 1 2 if 
Africa n A merica n ) 
C o n versi o n t o Cr C l ( m L/ mi n) fr o m e G F R usi n g t h e M osteller B S A e q uati o n a n d 
di vi di n g b y 1. 7 3 t o d eter mi ne d osi n g h ol ds.   
B S A ( m 2) = ( Hei g ht [ c m] x Wei g ht [ k g] / 3 6 0 0)1/ 2 
Cr C l ( m L/ mi n) = (e G F R [ m L/ mi n/ 1. 7 3 m2] x B S A [ m2])/ 1. 7 3 
7. 3. 4  E C O G P erf or m a n c e St at u s  
E C O G perf or ma nce stat us (see A p pe n di x  B ) will be e val uat e d at pr ot oc ol-s pecifie d ti me 
p oi nts.  
7. 3. 5  A d diti o n al M o nit ori n g f or HI V -P o siti v e a n d H e p atiti s -C -P o siti v e S u bj e ct s  
HI V -p ositi ve s u bjects m ust be c o -ma na ge d wit h a n HI V s peci alist; m o nit ori n g of C D 4 
c o u nts a n d HI V viral l oa d will be d o ne at scree ni n g, C ycle 2 a n d e ver y 4 c ycl es t hereafter, at 
E O T, a n d s h o ul d be perf or me d acc or di n g t o i nstit uti o nal sta n dar d of  care. Carriers of c hr o nic 
he patitis C s h o ul d be cl osel y m o nit ore d f or cli nical a n d la b orat or y si g ns of acti ve i nfecti o n 
d uri n g st u d y treat me nt.  
7. 4  A p pr o pri at e n e s s of M e a s ur e m e nt s  
I nter nati o nall y acce pte d criteria f or t he e v al uati o n of l y m p h o ma will be e m pl o ye d t o ass ess 
t u m or lesi o n siz e a n d e xte nt of disease i n t he d eter mi nati o n of P F S a n d res p o nse rate i n t his 
st u d y (C hes o n 2 0 0 7 ; C hes o n 2 0 1 4 ). T he sc he d ul e f or t u m or i ma gi n g is c o nsiste nt wit h 
ge n eral o n c ol o gi cal pr actice a n d a p pr o priatel y b ala nces me as ure me nt of t u m or c o ntr ol wit h  
t he e x pe nse a n d s u bject i nc o n ve nie nce ass oci ate d wit h C T a n d P E T sca n ni n g. 
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.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 8  of 6 4  
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 ual 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 s u bjects at t he site, Sea ge n  or its desi g nate d cli nical a n d me dical 
pers o n nel wil l re vie w t he 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 n vesti gat or’s Br oc h ure/ pac ka ge i ns ert  
● 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 nstit uti o nal Re vie w B oar d/I n d e pe n d e nt Et hics C o m mittee (I R B/I E C) re vie w a n d 
a p pr o val pr o cess  
● I nf or me d c o ns e nt pr ocess 
● G C P 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  
● S u bject c o di n g a n d ra n d o mizati o n (if a p plica ble)  
● St u d y s a m p les/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 nical 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 oad at eac h site. D uri n g m o nit ori n g visits, t he Sea ge n  re pres e ntati ve will re vie w 
re g ulat or y d oc u m e 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 n al pr o d uct st ora ge, 
pre parati o n, a n d acc o u nt a bilit y. T he C R Fs will be re vie we d f or c o m plet e 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 o c u me 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 oc u m e nts perti ne nt t o st u d y 
s u bjects, a n d m ust c o o perate wit h t he m o nit or t o e ns ure t hat a n y pr o ble ms 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 h e nsi ve a n d 
ce ntralize d fili n g s yste m of all st u d y -relate d d o c u me 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 nate d m o nit ors a n d b y q ualit y ass ura nce a u dit ors, F D A re prese nt ati ves, or 
re pres e ntati ves of ot her re g ul at or y a ge n cies. 
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 e C R F data e ntr y. St u d y s pecific dat a 
ma na ge me nt pr o ce d ures will be mai ntai ne d i n t he data ma na ge me nt pla n. Q ueries res ulti n g 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 3 9  of 6 4  
fr o m e dit c hec ks a n d/ or d ata verifi cati o n pr oce d ures will be p oste d electr o nicall y i n the 
e C R F. 
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 n ecessar y t o deter mi ne t hat pr ot oc ol a d here nce a n d d ata rec or di n g are 
satisfact or y. A p pr o priate meas ures t o protect s u bject 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 me nts will be re vie we d i n detail b y t he 
m o nit or at eac h site visit. Ori gi nal s o urce d o c u me nts or certifie d c o pies are nee de d f or 
re vie w. T his r e 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 pati o n i n 
t his st u d y a n d ot her me di cal rec or ds as re q uire d t o c o nfir m i nf or mati o n c o ntai ne d i n t he 
C R Fs, s uc h as past hist or y, sec o n dar y di a g n oses, disease assess me nt rec or ds, a d verse e ve nts, 
a n d c onc o mita nt me dicati o ns. Ot her st u d y rec or ds, s uc h as c orres p o n de n ce 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 nt a bilit y l o gs will als o be i ns pecte d. All 
s o urce dat a 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 prese ntati ve s of t he 
F D A or ot h er re g ulat or y a ge ncies.  
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 o ce 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 ce nters. A n y dis cre pa n cies will be res ol ve d wit h 
t he i n vesti gat or or desi g n ees as a p pr o priate. 
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 gr o u p or its desi g nee m a 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 ons. A u dit re p orts will be retai ne d 
b y t he Cli nical Q ualit y Ass ura nce 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 m e nts or t he discre pa n cies 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 electr o nic d ata ca pt ure s yste m.  
T he i n vesti gat or s h o ul d r etai 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.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
B re nt u xi ma b ve d oti n 
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 0  of 6 4  
Data ha n dli n g pr oce d ures f or t his trial ha ve bee n desi g ne d t o p er mit data c ha n ges s o t hat t he y 
are d oc u m e nte d b y a n a u dit trail. Data c ha 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.  
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, c o pies of C R Fs ( or electr o ni c 
files), a n d all s o urce d oc u me ntati o n (s uc h as ori gi nal E C G traci n gs, la b orat or y re p orts, 
i n patie nt or office p atie nt rec or ds) f or t he m a xi m u m peri o d re q uire d b y t h e 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 u cte d, or f or t he peri o d s p ecifie d b y Sea ge n , 
w hic he ver 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 he i n vesti gat or wit h dra ws fr o m t he st u d y ( d ue t o rel ocati 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 tra nsfer will be pr o vi de d i n writi n g t o 
Sea ge n . 
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  
Cli nical data fr o m t his st u d y will be prese nte d i n a descri pti ve ma n ner t o d e m o nstrate 
c o nsiste nc y wit h n o n -A L C L s u bjects r ecei vi n g A -C H P e nr olle d i n E C H E L O N -2 st u d y. T he 
st u d y is desi g ne d t o esti mate t he O R R at a reas o na ble le vel of precisi o n. U p t o a p pr o xi matel y 
8 0 n o n -s A L C L P T C L s u bjects will be e nr olle d i n t his st u d y, wit h u p t o a p pr o xi matel y 
4 0  s u bjects i n t he C D 3 0 ne gati ve ( < 1 %) c o h ort a n d a p pr o xi matel y 4 0 s u bjects i n t he C D 3 0 
p ositi ve ( 1 % t o < 1 0 %) c o h ort. I n t h e C D 3 0 p ositi ve ( 1 % t o < 1 0 %) c o h ort wit h 4 0 s u bjects, if 
2 8 res p o nses are o bser ve d, t he esti mate d O R R w o ul d be 7 0 %,  a n d t he ass o ciate d 2 -si de d 
9 5 % CI usi n g t he Cl o p per -Pears o n met h o d w o ul d be ( 5 3. 5 %, 8 3. 4 %). A d diti o nal p ossi ble 
res p o nse rates a n d t he ass ociate d 9 5 % c o nfi de nce i nter vals are s h o w n i n Ta ble  4 . 
T a bl e  4 : 
R e s p o n s e rat e s a n d a s s o ci at e d 9 5 % c o nfi d e n c e int er v al s  
N  
O bser ve d  Res p o nses  
Res p o nse  Rate  
2 -si de d 9 5 % CI usi n g t he Cl o p per-P ears o n met h o d  
4 0  
3 0  
7 5 %  
( 58. 8 %, 8 7. 3 %)  
4 0  
2 8  
7 0 %  
( 5 3. 5 %, 8 3. 4 %) 
4 0  
2 4  
6 0 %  
( 4 3. 3 %, 7 5. 1 %) 
4 0  
2 0  
5 0 %  
( 3 3. 8 %, 6 6. 2 %) 
9. 2  St u d y E n d p oi nt D efi niti o n s  
9. 2. 1  Pri m ar y E n d p oi nt: O bj e cti v e R e s p o n s e R at e ( C h e s o n 2 0 0 7)  
T he pri mar y e n d p oi nt of t his st u d y is O R R per BI C R (C hes o n 2 0 0 7 ). O R R is defi ne d as t he 
pr o p orti o n of s u bjects wit h C R or P R f oll o wi n g t he c o m pleti o n of st u d y tr eat me nt (at E O T) 
acc or di n g t o t he Re vise d Res p o nse Criteria f or Mali g na nt L y m p h o ma (C hes o n 2 0 0 7 ). 
S u bjects w h ose disease res p o nse ca n n ot b e assess e d will be sc ore d as n o n -res p o n ders f or 
calc ulati n g t he O R R . 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 1  of 6 4  
9. 2. 2  S e c o n d ar y Effi c a c y E n d p oi nt s  
9. 2. 2. 1  O bj e cti v e R e s p o n s e R at e ( m o difi e d L u g a n o crit eri a [ C h e s o n 2 0 1 4])  
O R R is defi ne d as t he pr o p orti o n of s u bjects wit h C R or P R f oll o wi n g t he c o m pleti o n of 
st u d y treat me nt (at E O T) acc or di n g t o t he m o difie d L u ga n o criteri a (C hes o n 2 0 1 4 ). S u bjects 
w h ose disease res p o nse ca n n ot be assesse d will be sc ore d as n o n -res p o n d ers f or calc ul ati n g 
t he O R R. O R R usi n g m o difie d L u ga n o criteria (C hes o n 2 0 1 4 ) will be assesse d b y BI C R 
o nl y.  
9. 2. 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 t he first d oc u me ntati o n of o bjecti ve t u m or res p o nse ( C R or 
P R) t o t he first d oc u me ntati o n of t u m or pr o gressi o n ( per C hes o n 2 0 0 7 ) or deat h, w hic he v er 
c o mes first. S u bjects wit h o ut pr o gressi o n or deat h will be ce ns ore d; d e tails will be pr o vi de d 
i n t he statistical a nal ysis pla n ( S A P). D O R  will o nl y be calc ulate d f or t he s u bset of s u bjects 
ac hie vi n g a C R or P R. D O R as a sec o n d ar y e n d p oi nt will be assesse d b y BI C R.  
9. 2. 2. 3  C o m pl et e R e s p o n s e R at e  
C o m plete res p o nse ( C R) rate is defi ne d  as t he pr o p orti o n of s u bjects wit h C R f oll o wi n g t he 
c o m pleti o n of st u d y treat me nt (at E O T) usi n g Re vise d Res p o nse Criteria f or Mali g n a nt 
L y m p h o ma criteria (C hes o n 2 0 0 7 ). S u bjects w h ose disease res p o nse ca n n ot be assesse d will 
be sc ore d as n o n -res p o n d ers f or calc ulati n g t he C R rate. T he C R rate as a s ec o n dar y e n d p oi nt 
will be assesse d b y BI C R.  
9. 2. 2. 4  P F S  
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 
t u m or pr o gressi o n usi n g Re vise d Res p o nse Criteri a f or Mali g na nt L y m p h o ma criteria 
(C hes o n 2 0 0 7 ) or t o deat h d ue t o a n y ca us e, w hic he ver c o m es first. P F S d ata will be 
ce ns ore d o n t h e date  of t he last ra di ol o gical ass ess me nt of meas ure d l esi o ns d oc u me nti n g 
a bse nce of P D f or s u bjects w h o d o n ot ha ve o bjecti ve t u m or pr o gressi o n a n d are stil l o n 
st u d y at t he ti me of a n a n al ysis, are gi ve n a ntit u m or treat me nt ot her t h a n t he st u d y tr eat me nt 
or ste m cell tra ns pla nt (i n cl u des d o n or l y m p h o c yte i nf usi o n), or are re m o ve d fr o m st u d y 
pri or t o d oc u me ntati o n of o bjecti ve t u m or pr o gressi o n. S u bjects lac k i n g a n e val 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 1 da y. P F S as a 
sec o n dar y e n d p oi nt will be assesse d b y BI C R. 
9. 2. 2. 5  O v er all S ur vi v al  
O verall s ur vi val ( O S) is defi ne d as t he ti me fr o m first d ose t o deat h d ue t o a n y  ca use. 
S pecificall y,  
 
O S = Date of d eat h –  D ate of first d ose + 1  
F or a s u bject w h o is n ot k n o w n t o ha ve die d b y t h e e n d of st u d y f oll o w -u p, o bser vati o n of 
O S is ce ns ore d o n t he d ate t he s u bject was l ast k n o w n t o be ali ve (ie, d ate of last c o ntact). 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 2  of 6 4  
S u bje cts lac ki n g d ata be y o n d t he da y of first d ose will ha ve t heir s ur vi val ti me ce ns ore d o n 
t he date of first d ose (ie, O S d urati o n of 1 da y). 
9. 2. 3  A d diti o n al E n d p oi nt s  
9. 2. 3. 1  O R R, C R r at e, D O R, a n d P F S p er I n v e sti g at or  
O R R, C R rate, D O R a n d P F S per i n vesti gat or (C h es o n 2 0 0 7 ) will b e assess e d as a d diti o nal 
effic ac y e n d p oi nts.  
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 d s 
descri be d i n t he pr ot o c ol will re q uire a pr ot o c ol a me n d me nt o nl y if it alters a pri nci pal 
feat ur e of t he pr ot o c ol. T he S A P will be fi nalize d bef ore t h e data base l oc k f or t he st u d y. 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  
U nless ot her wise s pecifie d, ta b ular s u m maries will be prese nt e d se paratel y b y c o h ort, C D 3 0 
ne gati ve ( < 1 %) a n d C D 3 0 p ositi ve ( ≥1 % a n d < 1 0 %) per ce ntr al c o nfir mati o n, a n d ma y be 
prese nte d f or t he t otal. 
Si milar s u m maries f or selecte d e n d p oi nts will be pr o vi de d base d o n C D 3 0 e x pressi o n b y 
l ocal e val uati o n. F or s u bj ects wit h ce ntr al C D 3 0 ≥1 0 % a n d l ocal C D 3 0 < 1 0 %, if a n y, t heir 
data will be liste d, b ut ma y n ot b e s u m marize d if t he n u m ber of s uc h s u bjects is n ot 
s ufficie ntl y l ar ge. 
Descri pti ve c o m p aris o n  of res ults fr o m t he t w o c o h orts ( C D 3 0  < 1 % a n d C D 3 0  ≥1 % t o 
< 1 0 %) i n t his st u d y wit h hist orical data i n n o n -A L C L s u bjects i n E C H E L O N -2 st u d y will be  
perf or me d s e paratel y t o de m o nstrate c o nsiste nc y.  
De scri pti ve statistics ( 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) will be 
use d t o descri be c o nti n u o us varia bles. Fre q u e ncies a n d perce nta ges will be use d w he n 
prese nti n g cat e g orical v aria bles (e g, O R R). Ti me -t o-e ve nt e n d p oi nts, s uc h as P F S, wil l be 
esti mate d usi n g K a pla n -Meier met h o d ol o g y a n d Ka pla n -Mei er pl ots will be prese nt e d. 
Me dia ns f or ti me -t o-e ve nt a nal ys es (e g, me di a n P F S), will be deter mi ne d a n d t w o -si de d 9 5 % 
c o nfi de nce i nter vals ( CIs) will be calc ulat e d usi n g t he l o g -l o g tr a nsf or mati o n met h o d.  
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 n o pe n -la bel, si n gle ar m trial. N o ra n d o mizati o n or bli n di n g will be utilize d. 
9. 3. 1. 2  A dj u st m e nt s f or C o v ari at e s  
A dj ust me nts f or c o variat es are n ot pla n n e d.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 3  of 6 4  
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  
Wit h t he e x ce pti o n of t he sce nari os c o v ere d i n t his secti o n, missi n g data will n ot be i m p ute d. 
A E dates will be i m p ute d f or t he p ur p ose of calc ulati n g d urati o n of e ve nts a n d treat me nt -
e mer ge nt stat us.  
S u bjects wit h missi n g val ues of a vari a ble ot her t h a n res p o nse e n d p oi nts (e g,  O R R a n d C R 
rate) a n d ti me-t o-e ve nt e n d p oi nts (e g, O S a n d P F S) will be e x cl u de d fr o m t he a nal ysis of t hat 
e n d p oi nt. S u bjects w h ose disease res p o ns e ca n n ot be assesse d will be s c ore d as 
n o n -res p o n ders f or calc ul ati n g O R R a n d C R rate. Ce ns ori n g r ul es will be a p plie d t o t he 
esti mati o n of t he distri b uti o n of t he ti me -t o-e ve nt e n d p oi nts, details will be pr o vi de d i n t he 
S A P.  
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 ver it is n ot a ntici pate d t hat a n y ce nter will 
accr ue e n o u g h s u bjects t o w arra nt a n a n al 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 he date of pr o gressi o n will be t he earliest of all ra di ol o gic s ca n d ates f or t h e gi ve n disease 
assess me nt. N o ot her data tra nsf or m ati o n is pla n ne d f or t he pri mar y or sec o n dar y efficac y 
e n d p oi nts.  
9. 3. 1. 7  A n al y si s S et s  
F ull A nal ysis Set: T he F ull A nal ysis Set will i ncl u de all s u bjects w h o recei ve a n y a m o u nt of 
bre nt u xi ma b ve d oti n or a n y c o m p o n e nt of C H P.  
I nte nt t o treat (I T T) Set: T he I T T set will i ncl u de all e nr olle d s u bjects, r e gar dless of w het her 
s u bjects recei ve a n y a m o u nt of bre nt u xi ma b ve d oti n or a n y c o m p o ne nt of C H P after t he 
c o m pleti o n of e nr oll me nt.  
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 ora t 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. 
Detaile d met h o d ol o g y will be pr o vi de d i n t he S A P.  
9. 3. 1. 9  Ti mi n g of A n al y s e s  
T he data bas e c ut off date f or t he pri mar y a nal ysis will be c o n d ucte d w h e n all treate d patie nts 
i n t he C D 3 0 p ositi ve ( ≥1 % a n d < 1 0 %) c o h ort h a v e bee n f oll o w e d f or at least 6 m o nt hs, 
disc o nti n ue d fr o m st u d y, or ha d 3 0 da ys safet y f oll o w -u p after P D, w hic he v er c o mes first.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 4  of 6 4  
9. 3. 2  S u bj e ct Di s p o siti o n  
A n acc o u nti n g of st u d y s u bjects b y dis p ositi o n will be ta b ulate d b y c o h ort. S u bj ects w h o 
disc o nti n ue st u d y treat me nt a n d s u bjects w h o wit h dra w fr o m t he st u d y will be s u m marize d 
b y c o h ort a n d reas o n f or disc o nti n uati o n or wit h dra wal a n d liste d.  
9. 3. 3  S u bj e ct C h ar a ct eri sti c s  
De m o gra p hics, ot her bas eli ne c haracteristics, a n d c o nc o mita nt me dica ti o ns will be 
s u m marize d b y c o h ort a n d liste d. 
9. 3. 4  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 will be ass ess e d a n d d ose i nte nsit y will be s u m marize d. 
Details will be pr o vi de d i n t he S A P.  
9. 3. 5  Effi c a c y A n al y s e s  
T he F ull A nal ysis Set will be use d f or all efficac y a nal ys es. Se nsiti vit y a nal ysis usi n g all 
e nr olle d s u bjects will be c o n d ucte d if a p pr o priate.  
9. 3. 5. 1  Pri m ar y Effi c a c y A n al y s e s  
T he pri mar y e n d p oi nt f or t he st u d y is O R R per BI C R (C hes o n 2 0 0 7 ), a n d it will be 
s u m marize d b y c o h ort. A n e x act t w o-si de d 9 5 % c o nfi de nce i nter val 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. T he pri mar y a n al ysis o n t he pri mar y 
e n d p oi nt will be c o n d u ct e d base d o n t he F ull A nal ysis Set.  
I n t he e ve nt t hat t here are s u bjects w h o are e nr olle d b ut n ot treate d, a se nsiti vit y a nal ysis will 
be perf or me d bas e d o n I T T set, w here t he s u bjects w h o are e nr olle d b ut n ot treate d are 
c o u nte d “ n o n -res p o n ders ” i n t he O R R calc ulati o n.  
9. 3. 5. 2  S e c o n d ar y Effi c a c y A n al y s e s  
O R R per BI C R b y m o difie d L u ga n o criteria (C hes o n 2 0 1 4 ) a n d C R rate p er BI C R 
(C hes o n  2 0 0 7 ) will be s u m marize d b y c o h ort. T heir e x act t w o -si ded 9 5 % c o nfi de nce 
i nter vals usi n g t he Cl o p p er-Pears o n met h o d (Cl o p per 1 9 3 4 ) will be calc ulat e d.  
Ti me -t o-e ve nt se c o n dar y e n d p oi nts i ncl u di n g D O R, P F S per BI C R (C hes o n 2 0 0 7 ) a n d O S 
will be esti mate d usi n g K a pla n -Meier met h o d ol o g y a n d Ka pla n -M eier pl ots will be 
prese nte d. Me dia ns f or ti me -t o-e ve nt a nal yses ( m e dia n D O R, P F S a n d O S), will be prese nte d 
a n d t w o-si de d 9 5 % c o nfi de nce i nter vals ( CIs) will be calc ul ate d usi n g t h e l o g-l o g 
tra nsf or mati o n met h o d. Details o n t he ce ns ori n g al g orit h m will be pr o vi de d i n t he S A P. 
9. 3. 5. 3  A d diti o n al Effi c a c y A n al y s e s  
O R R, C R rate, D O R, a n d P F S per i n vesti gat or (C h es o n 2 0 0 7 ) will be a nal yze d usi n g t he 
c orres p o n di n g met h o ds s pecifie d i n Sect i o ns 9. 3. 5. 1  a n d 9. 3. 5. 2 . 
Details will be pr o vi de d i n t he S A P.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 5  of 6 4  
9. 3. 6  S af et y A n al y s e s  
T he F ull A nal ysis Set will be use d f or all safet y a n al yses.  
9. 3. 6. 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 b y 
c o h ort. D ose m o dificati o ns will als o be s u m mari ze d. 
Details will be pr o vi de d i n t he S A P.  
9. 3. 6. 2  A d v er s e E v e nt s  
A d verse e ve nts will be d efi ne d as tr eat me nt e mer ge nt if t he y are ne wl y occ urri n g or w orse n 
f oll o wi n g treat me nt wit h bre nt u xi ma b ve d oti n, c ycl o p h os p ha mi de, d o x or u bici n, or 
pre d nis o ne. T he i nci d e nce of  all A Es, treat me nt -e mer ge nt A Es, a n d tr eat m e nt -relat e d A Es 
will be ta b ulate d b y c o h ort. A Es will be classifie d b y s yste m or ga n class a n d preferre d t er m 
usi n g t he Me dic al Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A).  
A Es will be liste d a n d s u m mariz e d b y M e 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 h e e ve nt of m ulti ple occ urre n ces of t he sa me A E wit h t he sa me preferre d ter m 
i n o ne s u bject, t he A E will be c o u nte d o nce as t he occ urre nce (if a p plica ble, at t he hi g h est 
se verit y gra d e). The i n ci de nce of A Es will be ta b ulate d b y preferre d ter m a n d c o h ort. 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 or wit h dra wal fr o m t he st u d y will be 
s u m marize d a n d liste d i n t he sa me ma n ner. I n a d diti o n, se verit y gra de a n d res ol uti o n of eac h 
A E will be pr o vi de d i n d ata listi n g.  
9. 3. 6. 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  
Seri o us a d verse e ve nts will be liste d a n d s u m marize d i n t he sa me ma n ner as all A Es. 
A d verse e ve nts wit h a fatal o utc o me will be liste d.  
9. 3. 6. 4  Cli ni c al L a b or at or y R e s ult s  
S u m mar y statistics f or a ct ual val ues a n d f or c ha n ge fr o m baseli ne will be ta b ulate d as 
a p pr o priate f or la b orat or y res ults b y c o h ort a n d sc he d ule d visit. S u bjects wit h la b orat or y 
val ues o utsi de of t he n or mal refere nce ra n ge at a n y p ost baseli ne assess me nt will be liste d.  
9. 3. 7  I nt eri m A nal y si s  
N o f or mal i nteri m a nal ys es are pl a n ne d.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 6  of 6 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  
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]), 
Declarati o n of Helsi n ki ( Brazil 2 0 1 3), a n d all a p plica ble re g ul at or y re q uire 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 s u bject i n si m ple ter ms usi n g t he I R B/I E C a p pr o ve d i nf or me d c o nse nt d oc u me nt a n d f or 
e ns uri n g s u bj ects 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 h e 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 s u bject, or le gall y a ut h orize d re pres e nt ati ve, if a p plica ble, 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 me d c o nse nt is o btai ne d fr o m a le gall y a ut h orize d re pres entati ve f or a s u bject w h o is 
u na ble t o pr o vi de i nf or m e d c o nse nt at st u d y e ntr y, b ut t he s u bject is later a ble t o pr o vi de 
i nf or me d c o nse nt, t he i n v esti gat or m ust o btai n writte n i nf or me d c o nse nt fr o m t he s u bject. 
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 bef 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 v esti 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 n vesti gat or’s Br oc h ure a n d u p dates  
● 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 m e 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.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 7  of 6 4  
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 p les state d i n 
t he a p plica ble g ui deli nes o n g o o d cli nical practice, a n d all a p plica ble fe deral, state, a n d l ocal 
la ws, r ules, a n d re g ulati o ns. 
All data rec or de d i n t he C R F f or s u bjects partici pati n g i n t his st u d y will be tra nscri be d fr o m 
me dical rec or ds or ot her s o urce d oc u m e nts.  
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 ncl 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  
Pr ot oc ol a me n d me nts will be s u b mitte d t o t he I R B/I E C pri or t o i m ple me nti n g. T he 
i n vesti gat or is r es p o nsi ble f or e nr olli n g s u bjects 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 nce 
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. T h e cli nical trial will n ot be ter mi nate d earl y d u e t o 
e vi de nce of efficac y.  
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  
G o ver n me nt a ge nc y re g ulati o ns a n d directi ves re q uire t hat all st u d y d o c u me ntati o n 
pertai ni n g t o t he c o n d uct of a cli nical trial m ust be retai ne d b y t he i n vesti gat or u ntil n otifie d 
b y t he s p o ns or i n writi n g t h at rete nti o n is n o l o n ger necess ar y.  
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 h e i n vesti gat or will kee p rec or ds of la b orat or y tests, cli nical n otes, a n d s u bject 
me dical rec or ds i n t he s u bject files as ori gi nal s o urce d oc u m e nts f or t he st u d y. If re q u este 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 c olla b orat ors, a p plica ble 
re g ulat or y a ge ncies, a n d a p plica ble I R B/I E C wit h direct access t o ori gi nal s o urce d oc u m e nts 
or certifie d c o pies.  
Rec or ds c o ntai ni n g s u bject me dical i nf or mati o n m ust be ha n dle d i n acc or da nce wit h t he 
re q uire me nts of t h e Healt h I nf or mati o n P orta bilit y a n d Acc o u nt a bilit y Act ( HI P A A) Pri vac y 
R ule a n d c o nsiste nt wit h t he ter ms of t he s u bject 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 h e st u d y (t he A ut h orizati o n). Care s h o ul d be ta ke n t o e ns ure t hat 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, cas e re p ort f or ms a n d ot her d oc u me n ts 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 n ce 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 s u bject i de ntities.  
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. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 8  of 6 4  
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 ura n ce, t he p u blicati o n p olic y f or cli nical trial dat a, a n d ot her 
re q uire me nts are s pecifie d i n t he cli nical trial a gree me nt. 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 4 9  of 6 4  
1 1  R E F E R E N C E S  
A d va ni R H, H or witz S M, I yer S P, et al. Res p o nse t o A + C H P b y C D 3 0 e x pressi o n i n t he 
E C H E L O N -2 trial. J Cli n O nc ol.  2 0 1 9; 3 7( S u p pl 1 5): A bstract 7 5 3 8.  
 
A n ders o n J R, Ar mita ge J O, Weise n b ur ger D D. E pi de mi ol o g y of t he n o n -H o d g ki n's 
l y m p h o mas: distri b uti o ns of t he maj or s u bt y p es differ b y ge o gra p hi c l ocati o ns. N o n-
H o d g ki n's L y m p h o ma Cl assificati o n Pr oject. A n n O nc ol. 1 9 9 8; 9( 7): 7 1 7 -2 0.  
 
Ar mita ge J O. T he a g gressi ve peri p heral T -cell l y m p h o mas: 2 0 1 7. A m J He mat ol. 
2 0 1 7; 9 2( 7): 7 0 6 -1 5.  
 
Bellei M, C hiatt o ne C S, L u mi nari S, et al. T -cell l y m p h o mas i n S o ut h a merica a n d e ur o pe. 
Re v Bras He mat ol He m oter. 2 0 1 2; 3 4( 1): 4 2 -7.  
 
B ossar d C, D o b a y M P, Parre ns M, et al. I m m u n o hist oc he mistr y as a val ua ble t o ol t o assess 
C D 3 0 e x pressi o n i n peri p heral T -cell l y m p h o mas: hi g h c orrelati o n wit h m R N A 
le vels. Bl o o d. 2 0 1 4; 1 2 4( 1 9): 2 9 8 3-6.  
 
Ca o A H R, La w C -L, G ar dai SJ. A uristati n -base d a nti b o d y dr u g c o nj u gat es acti vate m ulti ple 
E R stress res p o nse pat h w a ys res ulti n g i n i m m u n o ge nic cell deat h a n d a m plifie d T -
cell res p o nses. Ca n cer R es. 2 0 1 6; 7 6( 1 4 S u p ple me nt).  
 
C hes o n B D, Fis her RI, Barri n gt o n S F, et al. Re c o m me n dati o ns f or i nitial e val uati o n, sta gi n g, 
a n d res p o nse assess me nt of H o d g ki n a n d n o n -H o d g ki n l y m p h o m a: t he L u ga n o 
classificati o n. J Cli n O nc ol. 2 0 1 4; 3 2( 2 7): 3 0 5 9 -6 8.  
 
C hes o n B D, Pfist ner B, J u wei d M E, et al. Re vise d res p o nse criteria f or mali g na nt l y m p h o ma. 
J Cli n O nc ol. 2 0 0 7; 2 5( 5): 5 7 9-8 6.  
 
Cl o p per CJ, Pear s 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 oiffier B, Le pa ge E, Briere J, et al. C H O P c he m ot hera p y pl us rit u xi ma b c o m pare d wit h 
C H O P al o ne i n el derl y p atie nts wit h diff use lar g e -B -cell l y m p h o ma. N E n gl J Me d. 
2 0 0 2; 3 4 6( 4): 2 3 5 -4 2.  
 
d' A m ore F, Rel a n der T, La uritzse n G F, et al. U p -fr o nt a ut ol o g o us ste m-cell tra ns pla ntati o n i n 
peri p heral T -cell l y m p h o ma: N L G -T -0 1. J Cli n O nc ol. 2 0 1 2; 3 0( 2 5): 3 0 9 3 -9.  
 
Dear de n C E, J o h ns o n R, Pette n gell R , et al. G ui deli nes f or t he ma na ge me nt of mat ure T-cell 
a n d N K-cell ne o plas ms ( e x cl u di n g c uta ne o us T -cell l y m p h o ma). Br J Hae mat ol. 
2 0 1 1; 1 5 3( 4): 4 5 1 -8 5.  
 
Elli n F, La n dstr o m J, J er ke ma n M, Rela n der T. Real -w orl d d ata o n pr o g n ostic fact ors a n d 
treat me nt i n peri p heral T-cell l y m p h o mas: a st u d y fr o m t he S we dis h L y m p h o ma 
Re gistr y. Bl o o d. 2 0 1 4; 1 2 4( 1 0): 1 5 7 0 -7.  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 0  of 6 4  
Escal o n M P, Li u N S, Ya n g Y, et al. Pr o g n ostic fact ors a n d treat me nt of patie nts wit h T -cell 
n o n -H o d g ki n l y m p h o ma: t he M. D. A n ders o n Ca ncer Ce nter e x perie nce. Ca ncer. 
2 0 0 5; 1 0 3( 1 0): 2 0 9 1 -8.  
 
F D A. 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. F D A G ui da n ce 
f or I n d ustr y. 2 0 1 8: 1-1 9.  
 
Fe deric o M, Bellei M, L u mi nari S, et al. C D 3 0 + e x pressi o n i n peri p heral T -cell l y m p h o m as 
( P T C Ls): a s u bset a nal ysis fr o m t he i nter nati o nal, pr os pecti ve T -Cell Pr oject. J Cli n 
O nc ol. 2 0 1 5a; 3 3( 1 5 S u p pl): A bstract 8 5 5 2.  
 
Fe deric o M, Bellei M, Pesce E A, et al. T -cell pr oject: a n i nter nati o nal, pr os pecti ve, 
o bser vati o nal st u d y of patie nts wit h a g gressi ve pe ri p heral N K/ T-cell l y m p h o ma. 
Less o n fr o m t he first 1 3 0 8 patie nts. He mat ol O nc ol. 2 0 1 5 b; 3 3( S 1): 1 3 6 -7.  
 
Gar dai S, Heiser R, Ca o A, et al. A d diti o nal, n o n -classical a nti b o d y-dr u g c o nj u gate f u ncti o ns 
c o ntri b ute t o t he a ntit u m or acti vit y of bre nt u xi ma b ve d oti n.  Pr ocee di n gs of 2 0 1 6 
A S H Meeti n g o n L y m p h o ma Bi ol o g y. 2 0 1 6: 8 8 -9.  
 
Glees o n M, Pec kitt C, C u n ni n g ha m D, et al. O utc o mes f oll o wi n g fr o nt -li ne c he m ot hera p y i n 
peri p heral T -cell l y m p h o ma: 1 0 -year e x perie nce at T he R o yal Mars de n a n d T he 
C hristie H os pital. Le u k L y m p h o ma. 2 0 1 8; 5 9( 7): 1 5 8 6 -9 5.  
 
H or witz S, O' C o n n or O A, Pr o B, et al. Bre nt u xi ma b ve d oti n wit h c he m ot hera p y f or C D 3 0 -
p ositi ve peri p heral T -cell l y m p h o ma ( E C H E L O N -2): a gl o b al, d o u ble -bli n d, 
ra n d o mise d, p hase 3 tri al. La n cet. 2 0 1 9; 3 9 3( 1 0 1 6 8): 2 2 9-4 0.  
 
Hsi E D, H or witz S M, Cars o n K R, et al. A nal ysis of peri p heral T -cell l y m p h o ma dia g n ostic 
w or k u p i n t he U nite d States. Cli n L y m p h o ma M yel o ma Le u k. 2 0 1 7; 1 7( 4): 1 9 3 -2 0 0.  
 
J a ga dees h D, H or witz S M, Bartlett N L, et al. Res p o nse t o bre nt u xi ma b ve d oti n b y C D 3 0 
e x pressi o n: r es ults fr o m fi ve trials i n P T C L, C T C L, a n d B -cell l y m p h o m as. J Cli n 
O nc ol. 2 0 1 9; 3 7( S u p pl 1 5): A bstract 7 5 4 3.  
 
Ki m Y H, Ta vallaee M, S u n dra m U, et al. P hase II i n vesti gat or -i nitiate d st u d y of bre nt u xi ma b 
ve d oti n i n m yc osis f u n g oi des a n d Sezar y s y n dr o m e wit h v aria ble C D 3 0 e x pressi o n 
le vel: a m ulti-i nstit uti o n c olla b orati ve pr oj ect. J Cli n O nc ol. 2 0 1 5; 3 3( 3 2): 3 7 5 0-8.  
 
Li F Z X, E m mert o n K, J o nas M, Setter J, Art h ur B, O kele y N, L y o n R, Be nja mi n D, La w C -
L. Relati o ns hi p bet wee n i n vi v o a ntit u m or acti vit y of A D C a n d  pa yl oa d rel ease i n 
precli nical m o dels. Ca ncer Res. 2 0 1 4; 7 4( 1 9 S u p ple me nt).  
 
Merca d al S, Bri o nes J, Xic o y B, et al. I nte nsi ve c h e m ot hera p y ( hi g h -d os e C H O P/ E S H A P 
re gi me n) f oll o we d b y a ut ol o g o us ste m-cell tra ns pla ntati o n i n pre vi o usl y u ntreate d 
patie nts wit h  peri p heral T -cell l y m p h o m a. A n n O nc ol. 2 0 0 8; 1 9( 5): 9 5 8 -6 3.  
 
M os k o witz AJ, L u n ni n g M A, H or witz S M. H o w I treat t he peri p heral T -cell l y m p h o m as. 
Bl o o d. 2 0 1 4; 1 2 3( 1 7): 2 6 3 6 -4 4.  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 1  of 6 4  
M uller P, Marti n K, T he uric h S, et al. Micr ot u b ule -de p ol y merizi n g a ge nts use d i n a nti b o d y-
dr u g c o nj u gates i n d uce a ntit u m or i m m u nit y b y sti m ulati o n of de n dritic cells. Ca ncer 
I m m u n ol Res. 2 0 1 4; 2( 8): 7 4 1-5 5.  
 
N C C N. * R E TI R E D * Refere nce d wit h per missi o n fr o m t he N C C N Cli nical Practice 
G ui deli nes i n O nc ol o g y ( N C C N G ui deli nes ®) f or T -Cell L y m p h o mas Versi o n 
4. 2 0 1 8. © Nati o nal C o m pre he nsi ve Ca ncer Net w or k, I nc. 2 0 1 8.  All ri g hts reser ve d.  
Access e d J ul y 1 8, 2 0 1 8.  T o vie w t he m ost rece nt a n d c o m plete versi o n of t he 
g ui deli ne, g o o nli ne t o N C C N. or g. 2 0 1 8.  
 
Oflaz o gl u E, St o ne IJ, G or d o n K A, et al.  Macr o p ha ges c o ntri b ute t o t he a ntit u m or acti vit y of 
t he a nti-C D 3 0 a nti b o d y S G N -3 0. Bl o o d. 2 0 0 7; 1 1 0( 1 3): 4 3 7 0 -2.  
 
Rei mer P, R u di ger T, G eissi n ger E, et al. A ut ol o g o us ste m -cell tra ns pla ntati o n as first -li ne 
t hera p y i n peri p h eral T-cell l y m p h o mas: res ults of  a pr os pecti ve m ultice nter st u d y. J 
Cli n O nc ol. 2 0 0 9; 2 7( 1): 1 0 6 -1 3.  
 
Sa batti ni E, Pizzi M, Ta ba nelli V, et al. C D 3 0 e x pressi o n i n peri p heral T -cell l y m p h o mas. 
Hae mat ol o gica. 2 0 1 3; 9 8( 8):e 8 1 -2.  
 
Sa va ge KJ. Pr o g n osis a n d pri mar y t hera p y i n p eri p heral T -cell l ym p h o mas. He mat ol o g y A m 
S oc He mat ol E d uc Pr o gra m. 2 0 0 8a: 2 8 0 -8.  
 
Sa va ge KJ, Harris N L, V ose J M, et al. A L K - a na plastic lar ge -cell l y m p h o m a is cli nicall y a n d 
i m m u n o p he n ot y picall y differe nt fr o m b ot h A L K + A L C L a n d peri p heral T-cell 
l y m p h o ma, n ot ot her wise s pecifie d: re p ort fr o m t h e I nter n ati o nal Peri p heral T-Cell 
L y m p h o ma Pr oject. Bl o o d. 2 0 0 8 b; 1 1 1( 1 2): 5 4 9 6 -5 0 4.  
 
Sc h mitz N, Tr u m per L, Zie pert M, et al. Treat me nt a n d pr o g n osis of mat ure T -cell a n d N K -
cell l y m p h o ma: a n a nal ysis of patie nts wit h T -cell l y m p h o ma tre ate d i n st u dies of t he 
Ger ma n Hi g h -Gra d e N o n -H o d g ki n L y m p h o ma St u d y Gr o u p. Bl o o d. 
2 0 1 0; 1 1 6( 1 8): 3 4 1 8 -2 5.  
 
Si m o n A, Pe oc h M, Casass us P, et al. U pfr o nt VI P -rei nf orce d-A B V D ( VI P -r A B V D) is n ot 
s u peri or t o C H O P/ 2 1 i n ne wl y di a g n ose d peri p heral T cell l y m p h o ma. Res ults of t he 
ra n d o mize d p hase III trial G O E L A M S-L T P 9 5. Br J Hae mat ol. 2 0 1 0; 1 5 1( 2): 1 5 9 -6 6.  
 
S ut herla n d M S, Sa n ders o n RJ, G or d o n K A, et al. L ys os o mal traffic ki n g a n d c ystei n e 
pr otease met a b olis m c o nfer tar get -s pecific c yt ot o xicit y b y pe pti de-li n ke d a nti-C D 3 0 -
a uristati n c o nj u gates. J Bi ol C he m. 2 0 0 6; 2 8 1( 1 5): 1 0 5 4 0 -7.  
 
Teras L R, De S a ntis C E, Cer ha n J R, et al. 2 0 1 6 U S l y m p h oi d mali g na n c y statistics b y W orl d 
Healt h Or ga niz ati o n s u bt y p es. C A Ca n cer J Cli n. 2 0 1 6; 6 6( 6): 4 4 3 -5 9.  
 
V ose J, Ar mita ge J, Weise n b ur ger D, I nter n ati o nal T -Cell L y m p h o ma Pr oject. I nt er nati o nal 
peri p heral T -cell a n d nat ural killer/ T -cell l y m p h o ma st u d y: pat h ol o g y fi n di n gs a n d 
cli nical o utc o mes. J Cli n O nc ol. 2 0 0 8; 2 6( 2 5): 4 1 2 4 -3 0.  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 2  of 6 4  
Wi n ber g C D. Peri p heral T -cell l y m p h o m a. M or p h ol o gic a n d i m m u n ol o gi c o bser vati o ns. A m 
J Cli n Pat h ol. 1 9 9 3; 9 9( 4): 4 2 6-3 5.  
 
Zi nz a ni P L, B o nt ha pall y V, H ue b ner D, et al. Pa n o ptic cli nical re vie w of t he c urre nt a n d 
f ut ure treat me nt of rel a ps e d/refract or y T-cell l y m p h o mas: peri p heral T -cell 
l y m p h o mas. Crit Re v O n c ol He mat ol. 2 01 6; 9 9: 2 1 4 -2 7.  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 3  of 6 4  
A P P E N DI X  A: S T U D Y S C H E D U L E   
 
Scree ni n g / Baseli ne 
Treat me nt Peri o d  
E O T visit  
L o n g -ter m F/ U 
M o nt hs after first d ose  
C ycle 1  
C ycles 2 +  
C ycle 4 o nl y  
Last pla n ne d c ycle 
of treat me nt  
9  
1 2  
1 5  
1 8  
2 1  
2 4  
> 2 4  
Visit Wi n d o w  
D -2 8 t o 1  
D -7 t o 1  
D 1  
D 1 ± 1  
Da y 1 5 -2 1  
Da y 1 5 -2 1  
3 0 -3 7 da ys 
p ost last d ose f  
± 1 wk  
E ver y 6 m os  
± 1 wk  
Scree ni n g/ B
aseli ne 
Assess me nts  
I nf or me d c o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
E nr oll me nt  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
Me dical hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital si g ns  
 
 
X  
X  
 
 
 
 
 
 
 
 
 
 
C D 3 0/ hist ol o g y a 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
H T L V -1 stat us  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
H g b A1c   
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
Ec h ocar di o gra m or 
M U G A sca n  
X k 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hei g ht & wei g ht  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
Electr ocar di o gra m  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
Pre g na nc y test  
 
X  
X m  
X m  
 
 
X  
 
 
 
 
 
 
 
Treat me nt  
St u d y treat me nt 
a d mi nistrati o n 
 
 
X  
X  
 
 
 
 
 
 
 
 
 
 
Res p o nse 
Assess me nt  
L y m p h o ma 
assess me nt b 
 
 
X i 
X  
 
X  
X f 
X g 
X g 
X g 
X g 
X g 
X g 
X g 
C T (c hest, nec k, 
a b d o me n, pel vis) 
X  
 
 
 
X  
X  
X f 
X g 
X g 
X g 
X g 
X g 
X g 
X g 
P E T c 
X  
 
 
 
X  
X  
X f 
 
 
 
 
 
 
 
B o ne marr o w bi o ps y  
X d 
 
 
 
X e 
X e 
X e,f 
 
 
 
 
 
 
 
S ur vi val stat us  
 
 
 
 
 
 
 
 
X h 
 
X h 
 
X h 
X h 
Safet y 
Assess me nts  
E C O G perf or ma nce 
stat us 
 
X  
 
X  
 
 
X  
 
 
 
 
 
 
 
C D 4 c o u nt f or HI V 
p ositi ve s u bjects l 
X  
 
  
X l 
 
 
X  
 
 
 
 
 
 
 
HI V viral l oa d f or 
HI V p ositi ve 
s u bjectsl 
X  
 
 
X l 
 
 
X  
 
 
 
 
 
 
 
Ser u m c he mistr y n 
 
X  
X  
X  
 
 
X  
 
 
 
 
 
 
 
C B C wit h differe ntial  
 
X  
X  
X  
 
 
X  
 
 
 
 
 
 
 
Esti mate d gl o mer ular 
filtrati o n rateo 
 
X  
X  
X  
 
 
X  
 
 
 
 
 
 
 
C o n me ds & A Es  
C ollect a n y relate d t o st u d y 
pr ot oc ol pr oce d ures  
C ollect fr o m Da y 1 ( pre d ose) t hr o u g h 3 0 da ys p ost last d ose or  
t hr o u g h E O T visit, whic he ver is later 
 
 
 
 
 
 
 
a. 
T u m or s peci me n m ust be s u b mitte d f or ce ntral pat h ol o g y re vie w wit hi n 3 0 da ys of e nr oll me nt t o 
c o nfir m hist ol o g y a n d C D 3 0 e x pressi o n (s e e Secti o n 7. 1. 1  f or defi niti o n of C D 3 0-p ositi vit y).  
b.  
C o nsists of t he f oll o wi n g: p h ysical e xa mi n ati o n, s u bject me dical hist or y, i ncl u di n g a t h or o u g h re vie w of 
t he s u bject’s c urre nt si g ns a n d s y m pt o ms, B s y m pt o ms, a n d c o nc o mita nt me dicati o ns. See Secti o n 7. 2 . 
c. 
A c o m bi ne d C T/ P E T ma y be o btai ne d t o s atisf y t he re q uire me nts f or C T a n d P E T s ca n ni n g, as l o n g as a 
dia g n ostic q ualit y C T s ca n is o btai ne d; P E T s ca ns ma y als o be o btai ne d a n y ti me d uri n g t he st u d y if 
cli nicall y i n dicate d.  
d.  
O btai ne d wit hi n 6 0 da ys of first d os e of st u d y treat me nt.  
e. 
B o ne marr o w bi o ps y is re q uire d t o c o nfir m res p o ns e if b o ne marr o w is p ositi ve at bas eli ne a n d s h o ul d be 
o btai ne d wit hi n 4  wee ks after d oc u me ntati o n of res p o ns e; d oes n ot nee d t o be re peate d o nce b o ne 
marr o w is ne gati ve.  
g.  
O btai n u ntil s u bject e x perie nces P D per i n vesti gat or ass ess me nt, deat h, or a nal ysis of t he pri mar y 
e n d p oi nt, w hic he ver c o mes first. Visits occ urri n g after 2 4 m o nt hs fr o m first d os e ma y be c o n d ucte d via 
a p h o ne call; i ma gi n g a n d ot her l y m p h o ma ass ess me nts are o pti o nal i n t his s etti n g.  
h.  
S ur vi val stat us is re q uire d e ver y 6 m o nt hs u ntil deat h or st u d y cl os ure, w hic he ver c o mes first. After 3 0 
m o nt hs, t he wi n d o w f or t he ass ess me nt is ± 1  m o nt h. C ollect i nf or mati o n re gar di n g s u bs e q ue nt 
a ntica ncer t hera pies.  
i. 
Wit hi n 4 8 h o urs pri or t o st u d y trea t me nt. 
j. 
N ot re q uire d if s u bject has e x perie nce d P D per i n vesti gat or ass ess me nt  
k.  
M a y be o btai ne d u p t o 1  m o nt h pri or t o t he first d os e of st u d y treat me nt  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 4  of 6 4  
f. 
Res p o nse ass ess me nts at E O T re q uire d if n ot perf or me d at last c ycle of treat me nt. E O T e val uati o ns 
s h o ul d be o btai ne d bef ore t he i nitiati o n of n o n-pr ot oc ol t hera p y. If E O T e val uati o ns ar e c o m plete d 
bef ore 3 0 da ys f oll o wi n g t he last st u d y treat me nt, c o n d uct a p h o ne s cree n 3 0 -3 7 da ys f oll o wi n g t he 
s u bject’s last st u d y treat me nt t o e ns ure t hat n o c ha n ges i n A E pr ofile ha ve occ urre d.  
 
l. 
M o nit ori n g of C D 4 c o u nts a n d HI V viral l o a d will be d o ne at s cree ni n g, C ycle 2 a n d e ver y 4 c ycles 
t hereafter, at E O T, a n d s h o ul d be perf or me d acc or di n g t o i nstit uti o nal sta n dar d of care (s ee 
Secti o n  7. 3. 5 ). 
m.  
T o be perf or me d  pri or t o st u d y treat me nt  
n.  
T he s er u m c he mistr y pa nel 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 hat as e, 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, lactate de h y dr o ge nas e, p h os p h or us, p otassi u m, 
s o di u m, t otal bilir u bi n, uric aci d, a n d gl uc os e. 
o.  
eG F R  ( mL / mi n/ 1. 7 3 m2) b y M D R D . C o n verti n g t o Cr C l ( m L/ mi n) usi n g t he M osteller B S A e q uati o n 
a n d di vi di n g b y 1. 7 3 t o deter mi ne d osi n g h ol ds.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 5  of 6 4  
A P P E N DI X  B: E C O G P E R F O R M A N C E S T A T U S  
Sc ore  
Descri pti o n  
0  
N or mal acti vit y. F ull y acti ve, a ble t o carr y o n all pre -diseas e perf or ma nce wit h o ut 
restricti o n. 
1  
S y m pt o ms, b ut a m b ulat or y. Restri cte d i n p h ysi call y stre n u o us acti vit y, b ut 
a m b ulat or y a n d a ble t o carr y o ut w or k of a li g ht or se de ntar y n at ure (e g, li g ht 
h o use w or k, offi ce w or k).  
2  
I n b e d < 5 0 % of t he ti me. A m b ulat or y a n d ca p a ble of all self -care, b ut u n a ble t o carr y 
o ut a n y w or k acti vities. U p a n d a b o ut m ore t ha n 5 0 % of wa ki n g h o urs.  
3  
I n b e d > 5 0 % of t he ti me. Ca pa ble of o nl y li mite d self-care, c o nfi ne d t o be d or c hair 
m ore t ha n 5 0 % of wa ki n g h o urs.  
4  
1 0 0 %  be dri d de n. C o m pletel y disa bl e d. Ca n n ot carr y o n a n y self -care. T otall y 
c o nfi ne d t o be d or c hair.  
5  
Dea d.  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 6  of 6 4  
A P P E N DI X  C: 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 yl e, is a n acce pta bl e f or m of c o ntrace pti o n. C o m 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 s yste mic e x p os ure (1 2  m o nt hs  after t he last d ose of 
c ycl o p h os p ha mi de or  6 m o nt hs after t he last d ose of ot her st u d y treat me nt, w hic he ver is 
later); see Sec ti o n 4. 1 ). 
A c c e pt a bl e m et h o d s f or hi g hl y  eff e cti v e birt h c o ntr ol ( pr e v e nti n g 
c o n c e 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 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 of t he f oll o wi n g met h o ds ( ple ase see acce pt a ble c o m bi n ati o ns 
bel o w):  
● H or m o nal met h o ds of c o ntrace pti o n (e x cl 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 
● I ntr a uteri ne d e vice wit h f ail ure rat e < 1 % 
● T u bal li gati o n  
● Vasect o m y (at least 9 0 d a 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 az o os per mia)  
● Barrier met h o d ( m ale or fe male c o n d o m wit h or wit h o ut s per mici de, cer vi cal 
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) b  
○ 
All male s u bjects s h o ul d use a c o n d o m ( wit h pre g na nt/ breastfee di n g a n d 
n o n -pre g na nt/ n o n -breastf ee di n g part ners) d uri n g tr eat me nt a n d u ntil t he e n d 
of rele v a nt s yste mic e x p os ure i n t he male s u bject ( 1 2 m o nt hs after t he last  
d ose of c ycl o p h os p h a mi de or 6 m o nt hs after t h e last d ose of ot her st u d y 
treat me nt, w hic he v er is l ater), pl us a f urt her 9 0-da y peri o d  
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 i s defi 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 h e a bse nce of ot h er bi ol o gical, p h ysi ol o gical, or p har mac ol o gical ca uses. A hi g h f ollicle 
sti m ulati n g h or m o ne ( F S H) le vel i n t he p ost me n o pa usal ra n ge ma y be use d t o c o n fir m a p ost me n o pa usal state 
i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or h or m o nal re place me nt t h era p y. H o we ver, i n t h e a bse nce of 
1 2  m o nt hs of a me n orr hea, a si n gle F S H meas ure me nt is i ns ufficie nt.  
b  
A barrier met h o d s h o ul d o nl y be use d wit h a hi g hl y effe cti v e birt h c o ntr ol met h o d t hat is n ot a barrier met h o d. 
Barrier met h o ds al o ne, i ncl u di n g a d o u ble -barrier met h o d, are n ot c o nsi dere d hi g hl y effe cti ve c o ntrac e pti ve 
meas ures (se e u nacce pta ble met h o ds of c o ntrace pti o n).  
Acce pt a ble c o m bi n ati o ns of c o ntr ace pti ve  met h o ds:  
● H or m o nal met h o d a n d vasect o m y  
● H or m o nal met h o d a n d barrier met h o d  
● I ntr a uteri ne d e vice a n d v asect o m y 
● I ntr a uteri ne d e vice a n d b arrier m et h o d 
● T u bal li gati o n a n d v asect o m y  
● T u bal li gati o n a n d b arrier met h o d  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 7  of 6 4  
A c c e pt a bl e m et h o d s f or pr e v e nti n g s e c o n d ar y  e x p o s ur e t o s e 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 a c c e pt a bl e m et h o d s of c o ntr a c e pti o n  
● Peri o dic a bsti ne nce  
● S per mici de o nl y  
● N o met h o d  
● Pr o gesti n -o nl y pills  
● Wit h dra wal  
● C o nc o mita nt use of fe male a n d male c o n d o ms  
● R h yt h m  
● Barrier met h o ds al o n e, i ncl u di n g d o u ble -b arri er 
met h o ds  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi m a b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 8  of 6 4  
A P P E N DI X  D: I N V E S TI G A T O R SI G N A T 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 “ A d ual-c o h ort, o pe n -l a bel, p has e 2 st u d y of 
bre nt u xi ma b ve d oti n a n d C H P ( A + C H P) i n t he fr o ntli ne treat me nt of s u bjects wit h 
peri p heral T -cell l y m p h o ma ( P T C L) wit h less t ha n 1 0 % C D 3 0 e x pressi o n”.  
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 nci pal i n vesti gat or f or t he st u d y. 
 
 
 
 
 
 
I n v esti gat or Si g nat ure 
 
Date  
 
 
 
 
 
 
 
 
 
I n v esti gat or Na me, Pri nt e d 
 
 
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 5 9  of 6 4  
A P P E N DI X  E: D O C U M E N T  HI S T O R Y  
Versi o n  
D ate  
Ori gi nal  
2 9 -Ma y -2 0 2 0  
A me n d me nt 1  
1 3 -A u g -2 0 2 0  
A me n d me nt 2  
2 7 -Oct -2 0 2 0  
 
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6 0  of 6 4  
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 h a n ge  
R ati o n ale  
4. 2  
A d de d “ P artici pati o n i n ot her cli nical trials f or a n y 
c o n diti o n is n ot all o we d, ot her t ha n o bser vati o nal 
st u dies.” 
Clarificati o n  
6. 2 , 7. 1. 1 ,, 
A p pe n di x  A  
Clarifie d t hat t u m or s peci me ns fr o m bi o ps y s h o ul d 
be s u b mitte d wit hi n 3 0  da ys of e nr oll me nt.  
Clarificati o n  
7. 3. 1. 2  
U p date d t he te xt f or “ Pr o gressi o n of  t he 
U n derl yi n g Ca ncer” t o ali g n wit h c urre nt c o m pa n y 
sta n dar ds. 
Clarificati o n  
A p pe n di x  C  
U p date d c o ntrace pti ve g ui da nce.  
I m pr o ve s u bj ect safet y 
T hr o u g h o ut  
Mi n or c orrecti o ns t o f or matti n g, gra m mar, a n d 
s pelli n g. 
Clarificati o n  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)
C CI
C CI
C CI

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6 1  of 6 4  
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 h a n ge  
R ati o n ale  
Title p a ge  
U p date me dical m o nit or  
St u d y u p date  
4. 1, 4. 2  
M o ve d i ncl usi o n criteri o n # 1 2 t o Secti o n 4. 2 as a n 
e xcl usi o n criteri o n.  
C orrecti o n  
7. 3. 1. 2  
A d de d dr u g -i n d uce d li ver i nj ur y defi niti o n, 
re p orti n g, a n d f oll o w-u p i nstr ucti o ns  
S u bj ect safet y  
7. 3. 1. 5  
U p date d t he “ S p o ns or Safet y Re p orti n g t o 
Re g ulat or y A ut h orities”  i nstr ucti o ns 
T o e x pa n d i nstr ucti o ns fr o m 
be y o n d U S o nl y  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6 2  of 6 4  
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 h a n ge  
R ati o n ale  
Title p a ge, 
t hr o u g h o ut 
C ha n ge d S p o ns or na me  “ Seattle Ge netics , I nc.” t o 
“ Sea ge n I nc.”  a n d c ha n ge d “ S eattle Ge netics” t o 
“ Sea ge n”  
S p o ns or u p date  
List of 
A b bre viati o ns  a n d 
Defi niti o ns of 
T er ms  
A d de d a b bre viati o n  a n d defi niti o n f or “ D O R”  
A d de d a b bre viati o n a n d defi niti o n f or “ A L C L”  
A d de d a b bre viati o n a n d defi niti o n f or “ G F R”  a n d 
“e G F R”  
A d de d a b bre viati o n a n d defi niti o n f or “ Cr C l”  
A d de d a b bre viati o n a n d defi niti o n f or “ B S A”  
A d de d a b bre viati o n a n d defi niti o n f or “ M D R D”  
Re m o ve d a b bre viati o n a n d defi niti o n f or “ L D H”  
C orrecti o n  
1  
Re m o ve d a b bre viati o n “ a nti b o d y-de pe n de nt 
cell ular p ha g oc yt osis  ( A D C P)” 
Re m o ve d a b bre viati o n “e n d o plas mic retic ul u m  
( E R)” 
C orrecti o n  
3. 2  
U p date d: “ B ase d o n t he E C H E L O N -2 res ults , 
Sea ge n  belie ves t hat O R R is a s uita ble pri m ar y 
e n d p oi nt t o de m o nstr ate s urr o gate f or cli nical 
be nefit i n t his d ual -c o h ort , si n gle-ar m  trial. T his 
is c o nsiste nt wit h t he rec o m me n d ati o n o utli ne d 
i n F D A ( F D A 2 0 1 8) a n d E M A g ui d a nce ( E M A 
2 0 1 7) f or si n gle -ar m t ri als. Pr o gressi o n -free 
s ur vi val will be a nal yze d as a sec o n dar y e n d p oi nt 
f or s u p p orti ve e vi de nce.”  
Clarificati o n  
3. 2  
A d de d defi niti o n  t o first use of a b bre viati o n 
“ A L C L”  
C orrecti o n  
4. 1 , 7. 3. 3  
C ha n ge d “esti mate d gl o mer ul ar filtrati o n rate 
(eG F R) ≥6 0 > 4 5  m L/ mi n/ 1. 7 3 m 2 usi n g t he 
M o dificati o n of Diet i n Re nal Disease ( M D R D) 
st u d y e q uati o n pr o vi de d bel o w .” 
E x pa n d  s u bj ect i ncl usi o n 
4. 1 , 5. 4 , 7. 3. 3  
A d de d c o n versi o n fr o m e G F R ( m L/ mi n/ 1. 7 3 m 2) 
t o Cr Cl ( m L/ mi n) 
Clarificati o n  
4. 1  
C ha n ge d i ncl usi o n crit eria 9 a n d 1 0 fr o m 
“6  m o nt hs f oll o wi n g t he last d ose of st u d y dr u g ” 
t o “1 2 m o nt hs after t he last d ose of 
c ycl o p h os p ha mi de or 6 m o nt hs after t he last d ose 
of ot her st u d y treat me nt, w hic he ver is later ” 
S u bj ect safet y  
4. 1  
A d de d t o i ncl usi o n criteri o n # 1 1: “If i nf or me d 
c o nse nt is o btai ne d fr o m a le gall y a ut h orize d 
re prese ntati ve f or a s u bj ect 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, b ut t he 
s u bj ect is later a ble t o pr o vi de i nf or me d c o nse nt, 
S u bj ect c o nse nt  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)
C CI
C CI

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6 3  of 6 4  
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 he s u bj ect.”  
4. 2  
A d de d t o e xcl usi o n criteri o n # 5 “ or d o x or u bici n”.  
Clarificati o n  
4. 2  
A d de d e xcl usi o n criteri o n e xcl u di n g s u bj ects wit h 
c o ntrai n dicati o ns t o a n y st u d y dr u g.  
S u bj ect safet y  
4. 2 , 5. 5. 3  
A d de d e xcl usi o n criteri o n of li ve vacci nes 3 0 da ys 
pri or t o t he first d ose of st u d y dr u g a n d 9 0 da ys 
after t he last d ose of st u d y dr u g.  
S u bj ect safet y  
4. 3. 1  
A d de d “ T h e st u d y treat me nt will be disc o nti n ue d 
i n case of pre g na nc y.”  
S u bj ect safet y  
4. 3. 2  
A d de d “ I n case of pre g na nc y, st u d y treat me nt 
m ust b e ter mi nate d , a n d t he s u bj ect m ust be 
wit h dra w n fr o m t he cli nical tri al. ” 
S u bj ect safet y  
5. 2. 5 , 6. 3. 1  
A d de d “ S u bj ects will be m o nit ore d f or a peri o d of 
2 h o urs p ost -i nf usi o n of bre nt u xi ma b ve d oti n.”  
S u bj ect safet y  
5. 3. 1  
A d de d “ Refer t o t he S u m mar y of Pr o d uct 
C haracteristics of c ycl o p h os p ha mi de, d o x or u bici n, 
a n d pre d nis o ne f or f urt her details o n eac h st u d y 
dr u g a n d ass ociate d safet y ris ks.”  
S u bj ect safet y  
6. 2 , A p pe n di x  A  
M U G A sca n t o be all o we d u p t o 1  m o nt h pri or 
(c ha n ge d fr o m 6 m o nt hs)  
S u bj ect safet y  
6. 2. 1 , A p pe n di x  A  
A d de d ser u m c he mistr y pa nel defi niti o n  a n d 
f o ot n ote “ n” 
Clarificati o n  
6. 2. 1 , 
A p pe n di x  A , 
6. 3. 1 , 6. 4  
A d de d eG F R t o baseli ne visit,  e ver y c ycle: Da y 1, 
a n d e n d -of -treat me nt visit 
 
A d de d f o ot n ote “ o”: “ e G F R ( mL / mi n/ 1. 7 3 m2) b y 
M D R D. C o n verti n g t o Cr C l ( m L/ mi n) usi n g t he 
M osteller B S A e q uati o n a n d di vi di n g b y 1. 7 3 t o 
deter mi ne d osi n g h ol ds. ”  
Clarificati o n  
6. 3. 1 , A p pe n di x  A  
A d de d vital si g ns assess me nts a n d pre g na nc y test 
o n Da y 1 of e ver y c ycle bef ore st u d y dr u g 
a d mi nistrati o n 
S u bj ect safet y  
7. 1. 1  
M o difie d “ C uta ne o us , b o ne,  or  b o ne marr o w 
sa m ples, al o ne are u nacce pta ble. F fi ne nee dle 
as pirate s, a n d c yt ol o g y sa m ples are  als o 
u nacce pta ble.  
Clarificati o n  
7. 2  
Re m o ve d a b bre viati o n “ H E E N T  (s ki n, hea d, e yes, 
ears, n ose,  a n d  t hr oat),, l y m p h n o des, heart, l u n gs, 
a b d o me n, bac k, e xtre mities, a n d  ne ur ol o g y ”  
C orrecti o n  
0 9 0 1 7 7 e 1 a 1 3 6 c a 7 4\ A p pr o v e d\ A p pr o v e d O n: 0 8- A pr- 2 0 2 3 0 2: 4 4 ( G M T)
C CI

 
St u d y S G N 3 5 -0 3 2  
Cli nical Pr ot oc ol  
A me n d me nt 3; 1 0 -Mar -2 0 2 1  
Bre nt u xi ma b ve d oti n  
Sea ge n I nc. - C o nfi de ntial  
P a ge 6 4  of 6 4  
7. 3. 1. 2  
“Fa x t he f or m t o t he s p o ns or’s Dr u g Safet y 
De p art me nt wit hi n 4 8  2 4  h o urs of bec o mi n g a ware 
of t he pre g na nc y. ”  
S u bj ect safet y  
7. 3. 1. 4  
Re m o ve d “ , u nless ot her wise i nstr ucte d o n t he 
s p o ns or’s S A E f or m”  
Clarificati o n  
7. 3. 2  
A d de d secti o n detaili n g vital si g n assess me nts  
S u bj ect safet y  
9. 3. 6. 2  
A d de d “ (if a p plica ble, at t he hi g hest se verit y 
gra d e) ” 
 
A d de d “I n a d diti o n, se verit y gra de a n d res ol uti o n 
of eac h A E will be pr o vi de d i n data listi n g.”  
Clarificati o n  
1 0. 3. 2  
A d de d “ T he cli nical trial will n ot be ter mi nate d 
earl y d ue t o e vi de nce of effica c y.”  
Clarificati o n  
A p pe n di x  A  
M o difie d “ C ycle 1  / E nr oll me nt”  
 
A d de d e nr oll me nt r o w i n Scre e ni n g/ Baseli ne 
Assess me nts  
Clarificati o n  
A p pe n di x  C  
C ha n ge d “at least 2 m o nt hs after t he fi nal d ose of 
st u d y dr u g” t o “1 2 m o nt hs aft er t he last d ose of 
c ycl o p h os p ha mi de or 6 m o nt hs after t he last d ose 
of ot her st u d y treat me nt, w hic he ver is later ” 
 
A d de d “ All male s u bj ects s h o ul d use a c o n d o m 
( wit h pre g na nt/ breastfee di n g a n d 
n o n -pre g na nt/ n o n -breastfee di n g part ners)  d uri n g 
treat me nt a n d u ntil t he e n d of rele va nt s yste mic 
e x p os ure i n t he male s u bj ect ( 1 2 m o nt hs after t he 
last d ose of c ycl o p h os p ha mi de or 6 m o nt hs after 
t he last d ose of ot her st u d y treat me nt, w hic he ver is 
later), pl us a f urt her 9 0 -da y peri o d ” 
 
A d de d “ A hi g h f ollicle sti m ul ati n g h or m o ne 
( F S H) le vel i n t he p ost me n o pa usal ra n ge ma y be 
use d t o c o nfir m a p ost me n o pa usal state i n w o me n 
n ot usi n g h or m o nal c o ntrace pti o n or h or m o nal 
re place me nt t hera p y. H o we ver, i n t he a bse nce of 
1 2 m o nt hs of a me n orr hea, a si n gle F S H 
meas ure me nt is i ns ufficie nt. ”  
S u bj ect safet y  
T hr o u g h o ut  
Mi n or c orrecti o ns t o f or matti n g , st yle, a n d 
gra m mar  
Clarificati o n  
 
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