A Phase Ib/II Study of Selinexor Plus Pembrolizumab in Cisplatin-Ineligible or Cisplatin-Refractory Patients With Advanced Urothelial Carcinoma
Phase: PHASE1
Conditions: Advanced Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Refractory Urothelial Carcinoma
Sponsor: Mamta Parikh

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1  of 6 8  
A P H A S E I B /II S T U D Y O F S E LI N E X O R P L U S P E M B R O LI Z U M A B I N  
CI S P L A TI N -I N E LI GI B L E O R CI S P L A TI N-R E F R A C T O R Y P A TI E N T S WI T H  
A D V A N C E D U R O T H E LI A L C A R CI N O M A  
 
Pr ot oc ol N u m ber:    
U C D C C # 2 8 9  (I S T # x x x x x) 
I n dic ati o n: 
A d va nce d U r ot helial C arci n o ma 
P h ase : 
Ib /II 
F u n di n g S o urce:    
Kar y o p har m  T hera pe utics , I nc. 
A ge nt : 
Seli ne x or  ( K P T-3 3 0 ), pe m br oliz u ma b 
Pri nci p al I n vesti g at or : 
Ma mta Pari k h , M D, M S  
Di visi o n of He mat ol o g y/ O nc ol o g y  
U C Da vis C o m pre he nsi ve Ca ncer Ce nter  
 
 
 
 
 
C o -I n vesti g at or(s):   
Pri m o N Lara, M D  
U C Da vis C o m pre he nsi ve Ca ncer Ce nter  
 
 
 
Maria M u dr yj, P h D  
De part me nt of Me dical Micr o bi ol o g y a n d I m m u n ol o g y  
U ni versit y of C alif or nia,  Da vis  
 
 
St atistici a n:  
S usa n L. Ste wart, P h D  
Di visi o n of Bi ostatistics  
U ni versit y of Calif or nia, Da vis  
  
 
I N D # : 
E xe m pt  
I N D S p o ns or:  
U C  Da vis C o m pre he nsi ve Ca ncer Ce nter  
Pr ot oc ol Hist or y:    
Versi o n 1. 0    
0 4/ 2 1/ 2 0 2 0  
Versi o n 2. 0    
0 7/ 2 0/ 2 0 2 0  
Versi o n 3. 0    
0 9/ 0 7/ 2 0 2 0  
Versi o n 4. 0   
( 06 / 0 3/ 2 0 2 2) 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2  of 6 8  
 
P R O T O C O L S Y N O P SI S  
St u d y Title:    
A P hase I b /II st u d y of seli ne x or pl us pe m br oliz u ma b i n cis plati n -i neli gi ble or cis plati n -refract or y patie nts 
wit h a d va nce d ur ot helial carci n o ma.  
Pr ot oc ol N o.:    
U C D C C # 2 8 9  
P h ase of De v .:   
P h I b /II 
I n vesti g ati o n al 
Pr o d uct, D os a ge 
F or m, R o ute, a n d 
D ose Re gi me n  
S eli ne x or 6 0  m g  or  8 0 m g  orall y ( P O)  
Pe m br oliz u ma b 2 0 0 m g i ntra ve n o usl y  (I V) o nce e ver y 3 wee ks 
D ose Le vel    
Pe m br oliz u m a b  
Seli ne x or  
1  (starti n g d ose) 2 0 0 m g I V e ver y 3  wee k s ( D 1)   
8 0 m g P O o nce wee kl y  ( D 1, D 8, D 1 5)  
-1    
2 0 0 m g I V e ver y 3  wee k s ( D 1)   
6 0 m g P O o nce wee kl y  ( D 1, D 8, D 1 5)  
* Eac h c ycle is 2 1 da ys  
 
Pri m ar y 
O bjecti ve:  
•  Ib: I de ntif y Rec o m me n de d P hase 2 D ose ( R P 2 D) of seli ne x or i n c o m bi nati o n wit h sta n dar d 
d ose pe m br oliz u ma b i n patie nts wit h a d va nce d ur ot helial carci n o ma w h o are cis plati n -
i neli gi ble or cis plati n -refract or y, as defi ne d b y d ose-li miti n g t o xicit y 
•  II: C haracterize t he efficac y of seli ne x or at R P 2 D i n c o m bi nati o n wit h pe m br oliz u ma b b y 
o bjecti ve res p o nse rate as defi ne d b y R E CI S T criteria.  
Sec o n d ar y 
O bjecti ve s: 
1.  E val u ate t he t o xicit y of t he c o m bi nati o n of seli ne x or wit h sta n dar d-d ose pe m br oliz u ma b i n 
patie nts wit h a d va nce d ur ot helial carci n o ma w h o are cis plati n -i neli gi ble or cis plati n -
refract or y. 
2.  E val uate pr o gressi o n -free s ur vi val i n patie nts treate d wit h t he c o m bi nati o n of seli ne x or 
wit h sta n dar d -d ose pe m br oliz u ma b at t he R P 2 D.  
E x pl or at or y 
O bjecti ves:  
1.  E val uate t he fre q ue nc y of p ositi ve X P O 1 e x pressi o n b y I H C a m o n g patie nts wit h cis plati n -
i neli gi ble a d va nce d ur ot helial carci n o ma. 
2.  T o e val uate t he relati o ns hi p bet wee n X P O 1 e x pre ssi o n b y I H C a n d res p o nse t o t he 
c o m bi nati o n of seli ne x or a n d pe m br oliz u ma b.  
3.  T o e val uate t he relati o ns hi p bet wee n P D -L 1 e x pressi o n b y I H C a n d res p o nse t o t he 
c o m bi nati o n seli ne x or a n d pe m br oliz u ma b.  
4.  T o a nal yze pre - a n d p ost-treat me nt bl o o d sa m ples/ peri p heral bl o o d m o n o n uclear cells 
( P B M Cs) f or c ha n ges i n N K a n d T-cells. 
St u d y D esi g n a n d 
I n vesti g ati o n al 
Pl a n/ Met h o d ol o g y  
T his P hase I b st u d y will i nitiall y e nr oll 3 patie nts wit h l ocall y a d va nce d or metastatic ur ot helial 
carci n o ma w h o are cis plati n -i neli gi ble a n d treat me nt -naï ve i n t he a d va nce d setti n g t o recei ve 
seli ne x or 8 0 m g P O wee kl y a n d pe m br oliz u ma b 2 0 0 m g I V q 3 wee k s ( D ose Le vel [ D L] 1 ). 
Usi n g a 3 + 3 a p pr oac h, t he f oll o wi n g d ose de -escalati o n pla n will pr ocee d , a n d t he R P 2 D will be 
t he hi g hest d ose le vel at w hic h 0/ 3 or 1/ 6 patie nts ha ve D L T: 
N u m ber of P atie nts wit h D L T 
at a G i ve n D ose L e vel 
De -esc al ati o n D ecisi o n R ule  
0 o ut of 3  
E nr oll 3 patie nts t o sa me d ose le vel  
0 o ut of 6  
R P 2 D  
1 o ut of 3  
E nr oll 3 patie nts t o sa me D L  
1 o ut of 6  
R P 2 D  
2 o ut of 3  
If D L 1 , de-escalate o ne d ose le vel  
If D L -1 , st o p st u d y 
2 o ut of 6  
If D L 1, de-escalate o ne d ose le vel  
If D L -1 , st o p st u d y 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3  of 6 8  
O nce t he R P 2 D c o h ort is i de ntifie d, a P hase II e x pa nsi o n c o h ort will be e nr olle d f or a t otal of 2 7  
e val ua ble patie nts t o furt her e val uate t o xic it y, a n d t o e val uate efficac y as defi ne d b y o bjecti ve 
res p o nse rate. 
Patie nts will be assesse d e ver y 3 wee ks cli nicall y f or t o xicit y, a n d t he D L T assess me nt wi n d o w  
d uri n g t he P hase I b p orti o n of t he st u d y  will be 6 wee ks. Patie nts will be assesse d e ver y 6 wee ks 
f or res p o nse or pr o gressi o n  t o t hera p y f or t he first 1 2 wee ks (after w hic h t he y will u n der g o 
ra di o gra p hic i ma gi n g e ver y 1 2 wee ks) a n d will c o nti n ue o n treat m e nt u ntil t he ti me of 
u nacce pta ble t o xicit y or u ntil e vi de nce of pr o gressi ve disease b y R E CI S T o n ra di o gra p hic 
i ma gi n g.  
Pre -treat me nt bi o ps y will be re q uire d f or a n y patie nt w h o d oes n ot ha ve arc hi val tiss ue a vaila ble. 
Pre -treat me nt bl o o d sa m ples will be dra w n, a n d a d diti o nal researc h bl o o d dra w s will be 
perf or me d o n patie nts o n trial  a n d w he n patie nts c o me off st u d y . 
 
St u d y P o p ul ati o n 
a n d S a m ple Size:  
T his st u d y’s p o p ulati o n is patie nts wit h l ocall y a d va nce d or metastatic ur ot helial carci n o ma, w h o 
are cis plati n-i neli gi ble or w h o ha ve pr o gresse d o n o ne plati n u m -base d c he m ot hera p y re gi me n . 
Patie nts ma y ha ve recei ve d s yste mic t hera p y i n t he ne oa dj u va nt  or a dj u va nt  setti n g, a n d ma y 
ha ve recei ve d i ntra vesical t hera p y i n t he past.  
T he sa m ple si ze f or t his st u d y  will re q uire 6 -1 2  patie nts f or t he 3 + 3 p orti o n , a n d a n a d diti o nal 
e x pa nsi o n  t o e val uate 27  patie nts at t he R P 2 D , f or a t otal e nr oll me nt of u p t o 3 3  patie nts.  
Ass u mi n g a res p o nse rate of 2 0 % f or pe m br oliz u ma b al o ne i n t his st u d y p o p ulati o n base d o n 
hist ori cal c o ntr ols, a sa m ple size of 2 7  e val ua ble patie nts will all o w f or detecti o n  of a n 
i m pr o ve me nt of  O R R t o 4 5 % wit h  8 0 % p o wer  at t he 0. 0 5 le vel ( 2 -si de d). 
Eli gi bilit y 
Criteri a  
Patie nts will meet t he f oll o wi n g i ncl usi o n criteria:  
•  A ge ≥ 1 8 years  
•  H ist ol o gicall y c o nfir me d l ocall y a d va nce d, u nresecta ble, or metastatic ur ot helial carci n o ma 
w h o ha ve meas ura ble disease b y R E CI S T 1. 1 criteria  
•  W ill ha ve arc hi val tiss ue a vaila ble or a willi n g ness t o u n der g o pre-treat me nt bi o ps y 
•  E C O G  perf or ma nce stat us 0 -2  
•  N ot eli gi ble t o recei ve cis plati n -base d c he m ot hera p y d ue t o re nal d ysf u ncti o n, peri p heral 
ne ur o pat h y, ot ot o xicit y or u n willi n g ness of patie nt t o recei ve cis plati n  O R pr o gresse d o n o ne 
plati n u m -base d c he m ot hera p y re gi me n.  
•  M a y ha ve ha d ne oa dj u va nt  or a dj u va n t plati n u m -base d c he m ot hera p y or i ntra vesical t hera p y 
i n t he past 
•  A de q uate he mat ol o gic f u ncti o n  - see Secti o n 3. 1  
•  A de q uate or ga n f u ncti o n  - see Secti o n 3. 1  
Patie nts are i neli gi ble if t he f oll o wi n g e xcl usi o n criteria are met:  
•  Ra diati o n treat me nt t o a fiel d c o nsi dere d part of t he selecte d tar get lesi o ns, recei ve d <  1 4 
da ys pri or t o e nr oll me nt 
•  S yste mic  ca ncer  t hera p y recei ve d ≤ 2 1 da ys pri or t o e nr oll me nt  
•  C o nc o mita nt dia g n osis of a d diti o nal mali g na nc y i n t he past 2 years, wit h t he e xce pti o n of 
pr ostate ca ncer wit h de m o nstrate d P S A <  4  or n ot re q uiri n g s yste mic t hera p y , a n d of 
c uta ne o us mali g na ncies w hic h ha ve bee n resecte d s uc h as basal cell carci n o ma or s q ua m o us 
cell carci n o ma of t he s ki n , a n d ca ncers t hat ha ve bee n treate d wit h c urati ve i nte nt a n d are i n 
cli nical re missi o n f or at least 2 years . 
•  A ut oi m m u ne dis or der re q uiri n g acti ve t hera p y as defi ne d b y c ortic oster oi ds at a d ose ≥ 1 0 
m g oral pre d nis o ne or t he e q ui vale nt or re q uiri n g i m m u n os u p pressi ve t hera p y.  
•  Use of c ortic oster oi ds at d ose of ≥ 1 0 m g oral p re d nis o ne or t he e q ui vale nt per da y ≤ 1 4 da ys 
pri or t o e nr oll me nt.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4  of 6 8  
•  Recei ve d a n y pri or i m m u ne c hec k p oi nt i n hi bit or t hera p y (a nti-P D -1, a nti -P D -L 1, or  a nti-
C T L A 4 directe d t hera p y)  
E n d p oi nts:  
Pri mar y e n d p oi nt:  
•  Rec o m me n de d P hase 2 D ose as defi ne d b y D ose -Li miti n g T o xicit y  
•  O bjecti ve res p o nse rate  ( O R R), i.e. patie nts wit h c o m plete res p o nse ( C R), partial res p o nse 
( P R), sta ble disease ( S D), pr o gressi ve disease ( P D) b y R E CI S T criteria 
Sec o n dar y e n d p oi nt:  
•  Gra de 3 or hi g her a d verse e ve nts ( A Es) as defi ne d b y N CI C T C A E criteria  
•  Pr o gressi o n -free s ur vi val 
E x pl orat or y e n d p oi nt:  
•  X P O 1 e x pressi o n b y I H C of t u m or s peci me ns   
•  P D -L 1 e x pressi o n b y I H C of t u m or s peci me ns  
•  Pre - a n d p ost -treat me nt N K a n d C D 4 +, C D 8 + cells 
St atistic al 
C o nsi der ati o ns  
T o esta blis h t he R P 2 D, a 3 + 3 de -escalati o n  desi g n is e m pl o ye d; t his will re q uire a mi ni m u m o f 6  
patie nts a n d u p t o 1 2  patie nts.  A d diti o nal  patie nts will be e nr olle d  at R P 2 D  f or a t otal of 27  
e val ua ble patie nts t o f urt her c haracterize t o xicit y a n d t o e val uate efficac y . Ass u mi n g a r es p o nse 
rate of 2 0 % f or pe m br oliz u ma b al o ne i n t his st u d y p o p ulati o n, base d o n hist orical c o ntr ols, a 
sa m ple size of 27  patie nts will all o w  f or detecti o n of a n i m pr o ve me nt t o O R R of 4 5 %.  
C orrel ati ves:  
E x pl orat or y o bjecti ves will re q uire pre -treat me nt tiss ue, eit her arc hi val or c ollecte d pri or t o 
treat me nt o n trial, a n d pre-treat me nt researc h bl o o d sa m ple as well as researc h bl o o d sa m ples f or 
all patie nts o n treat me nt a n d w he n patie nts c o me off st u d y . Researc h bl o o d sa m ples will be 
ba n ke d.  
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6  of 6 8  
LI S T O F A B B R E VI A TI O N S  A N D T E R M S  
A b bre vi ati o n/ Ter m    
Defi niti o n  
C  
de grees Celsi us  
M  
M icr o m olar 
A E  
a d verse e ve nt 
A N C  
a bs ol ute ne utr o p hil c o u nt  
A L T  
ala ni ne tra nsa mi nase  
A S T  
as partate tra nsa mi nase  
C LI A  
Cli nical La b orat or y I m pr o ve me nt A me n d me nts  
C R  
c o m plete res p o nse  
C R C  
cli nical researc h c o or di nat or  
C R F  
case re p ort f or m  
C T  
c o m p ute d t o m o gra p h y  
C T C A E  
( N CI) C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts 
D L T  
d ose -li miti n g t o xicit y 
D S M B  
Data a n d Safet y M o nit ori n g B oar d  
D S M C  
Data a n d Safet y M o nit ori n g C o m mittee  
D S M P  
Data a n d Safet y M o nit ori n g Pla n  
E C O G  
Easter n C o o perati ve O nc ol o g y Gr o u p  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
G G T  
ga m ma -gl uta m yl tra nsferase  
G L P  
G o o d La b orat or y Practice  
I C H 
I nter nati o nal C o u ncil f or  Har m o nisati o n  
I E C 
i n de pe n de nt et hics c o m mittee 
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 
I V 
Intra ve n o us  
Ki  
i n hi bit or y c o nsta nt 
l bs 
P o u n ds  
L D H  
lactate de h y dr o ge nase 
m 2 
s q uare meters 
m g  
M illi gra m 
Mi n  
M i n ute 
m L  
M illiliter 
M RI  
ma g netic res o na nce i ma gi n g 
M T D  
m U C  
ma xi m u m t olerate d d ose  
metastatic ur ot helial carci n o ma  
N CI  
Nati o nal Ca ncer I nstit ute  
O C R  
Office of Cli nical Researc h  
O S  
o verall s ur vi val  
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  
PI  
pri nci pal i n vesti gat or 
P R  
partial res p o nse  
R E CI S T  
Res p o nse E val uati o n Criteria I n S oli d T u m ors  
S A E  
seri o us a d verse e ve nt 
S R C  
Scie ntific Re vie w C o m mittee  
U C D  
U ni versit y of Calif or nia, Da vis ( U C Da vis)  
U C D C C C  
U C Da vis C o m pre he nsi ve Ca ncer Ce nter  
U S  
U nite d States  
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 7  of 6 8  
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  
S T U D Y S C H E M A ........................................................................................................................................ 5  
LI S T O F A B B R E VI A TI O N S A N D T E R M S  ............................................................................................... 6  
T A B L E O F C O N T E N T S  .............................................................................................................................. 7  
LI S T O F T A B L E S  ........................................................................................................................................ 9  
LI S T O F FI G U R E S  ...................................................................................................................................... 9  
1. 0    
S T U D Y O BJ E C TI V E S  .................................................................................................................. 1 0  
1. 1  
Pri mar y O bjecti ve  ........................................................................................................................... 1 0  
1. 2  
Sec o n dar y O bjecti ves  ...................................................................................................................... 1 0  
1. 3  
E x pl orat or y or C orrelati ve O bjecti ves  ............................................................................................ 1 0  
2. 0    
B A C K G R O U N D  ........................................................................................................................... 1 0  
2. 1  
Scie ntific Rati o nale  ......................................................................................................................... 1 1  
2. 1. 1  Pe m br oliz u ma b  .................................................................................................................... 1 1  
2. 1. 2  Seli ne x or  .............................................................................................................................. 1 1  
2. 1. 3  Seli ne x or a n d Pe m br oliz u ma b C o m bi nati o n  ....................................................................... 1 2  
2. 2  
Disease  ............................................................................................................................................ 1 3  
2. 2. 1  Treat me nt O pti o ns  ............................................................................................................... 1 3  
2. 3  
I n vesti gati o nal Pr o d uct Na me a n d Descri pti o n ............................................................................... 1 3  
2. 3. 1  Seli ne x or  .............................................................................................................................. 1 3  
2. 3. 2  Pe m br oliz u ma b  .................................................................................................................... 1 4  
2. 4  
S u m mar y of N o ncli nical Data  ......................................................................................................... 1 4  
2. 4. 1  P har mac ol o g y  ...................................................................................................................... 1 4  
2. 4. 2  T o xi c ol o g y ........................................................................................................................... 1 5  
2. 5  
S u m mar y of Cli nical Data  ............................................................................................................... 1 6  
2. 5. 1  P har mac o ki netics a n d Pr o d uct Meta b olis m  ......................................................................... 1 6  
2. 5. 2  S u m mar y of Cli nical Safet y ................................................................................................. 1 7  
2. 5. 3  Ris ks  .................................................................................................................................... 1 8  
3. 0    
S U BJ E C T S E L E C TI O N  ................................................................................................................ 1 9  
3. 1  
I ncl usi o n Criteria ............................................................................................................................ 1 9  
3. 2  
E x cl usi o n Criteria  ........................................................................................................................... 2 0  
4. 0    
S T U D Y D E SI G N  .......................................................................................................................... 2 2  
4. 1  
P hase I b  ........................................................................................................................................... 2 2  
4. 1. 1  Defi niti o n of D ose Li miti n g T o xicit y  .................................................................................. 2 3  
4. 1. 2  Defi niti o n of R P 2 D  .............................................................................................................. 2 3  
4. 2  
P hase II E x pa nsi o n at R P 2 D  ........................................................................................................... 2 3  
5. 0    
T R E A T M E N T O F S U BJ E C T S  ..................................................................................................... 2 4  
5. 1  
St u d y Treat me nt A d mi nistrati o n  ..................................................................................................... 2 4  
5. 2  
Seli ne x or  ......................................................................................................................................... 2 4  
5. 2. 1  D osi n g a n d A d mi nistrati o n  .................................................................................................. 2 4  
5. 2. 2  F or m ulati o n, Pac ka gi n g, a n d Ha n dli n g  ............................................................................... 2 5  
5. 2. 3  Pre parati o n  ........................................................................................................................... 2 5  
5. 2. 4  H o w S u p plie d  ...................................................................................................................... 2 5  
5. 3  
Pe m br oliz u ma b  ............................................................................................................................... 2 5  
5. 3. 1  F or m ulati o n, Pac ka gi n g, a n d Ha n dli n g  ............................................................................... 2 6  
5. 3. 2  Pre parati o n  ........................................................................................................................... 2 6  
5. 3. 3  H o w S u p plie d  ...................................................................................................................... 2 6  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 8  of 6 8  
5. 3. 4  Dis p osal a n d Destr ucti o n  ..................................................................................................... 2 6  
5. 4  
M o nit ori n g  ...................................................................................................................................... 2 6  
5. 5  
D ose M o dificati o n a n d Ma na ge me nt of T o xicit y  ........................................................................... 2 7  
5. 5. 1  D ose Dela y a n d Disc o nti n uati o n  ......................................................................................... 2 7  
5. 5. 2  T o xicities Necessitati n g D ose M o dificati o n or Dela y  ......................................................... 2 7  
5. 5. 3  Seli ne x or D ose M o dificati o ns  ............................................................................................. 3 0  
5. 5. 1  Criteria t o Res u me Treat me nt  .............................................................................................. 3 5  
5. 6  
I nstr ucti o ns f or I nitiati o n of Eac h C ycle ......................................................................................... 3 6  
6. 0    
T R E A T M E N T D U R A TI O N  ......................................................................................................... 3 6  
6. 1  
Disc o nti n uati o n Criteria  .................................................................................................................. 3 6  
6. 1. 1  Disc o nti n uati o n fr o m St u d y Treat me nt  ............................................................................... 3 6  
6. 1. 2  Disc o nti n uati o n D ue t o A Es  ................................................................................................ 3 7  
6. 2  
D urati o n of F oll o w U p  .................................................................................................................... 3 7  
6. 3  
Ter mi nati o n of Treat me nt a n d St u d y Partici pati o n  ......................................................................... 3 7  
7. 0    
C O N C O MI T A N T A N D E X C L U D E D M E DI C A TI O N  ................................................................ 3 8  
7. 1  
C o nc o mita nt T hera p y  ...................................................................................................................... 3 8  
7. 2  
E xcl u de d T hera p y  ........................................................................................................................... 3 8  
7. 3  
Per mitte d T hera p y  ........................................................................................................................... 3 8  
8. 0    
S T U D Y C A L E N D A R  ................................................................................................................... 3 9  
9. 0    
S T U D Y E V A L U A TI O N S  ............................................................................................................. 4 0  
9. 1  
Scree ni n g P hase  .............................................................................................................................. 4 0  
9. 2  
Treat me nt P hase  .............................................................................................................................. 4 0  
9. 3  
E n d of Treat me nt Visit  .................................................................................................................... 4 0  
9. 4  
F oll o w -u p P hase  .............................................................................................................................. 4 0  
9. 5  
Efficac y  ........................................................................................................................................... 4 1  
9. 5. 1  Res p o nse Criteria  ................................................................................................................. 4 1  
9. 6  
Safet y  .............................................................................................................................................. 4 3  
9. 6. 1  A d verse E ve nts  .................................................................................................................... 4 3  
1 0. 0   
C O R R E L A TI V E S  ......................................................................................................................... 4 4  
1 0. 1  
Bl o o d  ............................................................................................................................................... 4 7  
1 0. 2  
Tiss ue  .............................................................................................................................................. 4 7  
1 1. 0   
S T A TI S TI C A L C O N SI D E R A TI O N S  ........................................................................................... 4 8  
1 1. 1  
Sa m ple Size  ..................................................................................................................................... 4 8  
1 1. 2  
Statistical A nal ysis Pla n  .................................................................................................................. 4 8  
1 1. 3  
Safet y  .............................................................................................................................................. 4 9  
1 1. 4  
Efficac y  ........................................................................................................................................... 4 9  
1 1. 5  
S u bject C o urse  ................................................................................................................................ 5 0  
1 2. 0   
S A F E T Y A N D R E P O R TI N G R E Q UI R E M E N T S  ........................................................................ 5 0  
1 2. 1  
A d verse E ve nts  ............................................................................................................................... 5 0  
1 2. 1. 1  Se verit y of A d verse E ve nts  ................................................................................................. 5 0  
1 2. 1. 2  Ca usalit y ( Attri b uti o n) of A d verse E ve nts  .......................................................................... 5 1  
1 2. 1. 3  Seri o us A d verse E ve nts  ....................................................................................................... 5 1  
1 2. 1. 4  La b orat or y Test A b n or malities  ............................................................................................ 5 2  
1 2. 2  
Pr oce d ures f or Ha n dli n g S pecial Sit uati o ns  .................................................................................... 5 2  
1 2. 2. 1  Pre g na nc y a n d Breastfee di n g  .............................................................................................. 5 2  
1 2. 2. 2  O ver d ose  .............................................................................................................................. 5 3  
1 2. 2. 3  A b use, Mis use, or Me dicati o n Err or  .................................................................................... 5 4  
1 2. 3  
Pr oce d ures f or Re p orti n g A d verse E ve nts  ...................................................................................... 5 4  
1 2. 3. 1  Met h o ds a n d Ti mi n g f or Assessi n g a n d Rec or di n g Safet y Varia bles  .................................. 5 4  
1 2. 3. 2  A d verse E ve nt Re p orti n g Peri o d  ......................................................................................... 5 4  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 9  of 6 8  
1 2. 3. 3  Pr oce d ures f or S A E Re p orti n g  ............................................................................................ 5 5  
1 3. 0   
E T HI C A L C O N SI D E R A TI O N S A N D A D MI NI S T R A TI V E P R O C E D U R E S  ........................... 5 7  
1 3. 1  
Et hics a n d G o o d Cli nical Practice  ................................................................................................... 5 7  
1 3. 2  
I nstit uti o nal Re vie w B oar d ............................................................................................................. 5 8  
1 3. 3  
Patie nt I nf or mati o n a n d I nf or me d C o nse nt  ..................................................................................... 5 8  
1 3. 4  
Patie nt C o nfi de ntialit y  .................................................................................................................... 5 8  
1 3. 5  
St u d y Re gistrati o n  ........................................................................................................................... 5 8  
1 3. 6  
Pr ot oc ol C o m plia nce a n d De viati o ns  .............................................................................................. 5 9  
1 3. 7  
Rec or d Rete nti o n  ............................................................................................................................ 5 9  
1 3. 8  
Q ualit y Ass ura nce a n d C o ntr ol  ....................................................................................................... 5 9  
1 4. 0   
O V E R SI G H T A N D M O NI T O RI N G ............................................................................................. 5 9  
1 4. 1  
Data a n d Safet y M o nit ori n g  ............................................................................................................ 5 9  
1 4. 2  
I n vesti gat or M o nit ori n g G ui deli nes ................................................................................................ 6 0  
1 5. 0   
R E F E R E N C E S  .............................................................................................................................. 6 1  
1 6. 0   
A P P E N DI C E S  ............................................................................................................................... 6 3  
1 6. 1  
E C O G a n d Kar n ofs k y Perf or ma nce Stat us Sc ores 1, 2 ...................................................................... 6 3  
1 6. 2  
C oc kcr oft -Ga ult Esti mati o n of Cr Cl  ............................................................................................... 6 4  
1 6. 3  
St u d y Re gistrati o n  ........................................................................................................................... 6 4  
1 6. 4  
Data C ollecti o n F or ms  .................................................................................................................... 6 5  
1 6. 5  
N CI C T C Versi o n 5. 0  ..................................................................................................................... 6 6  
1 6. 6  
Pill Diar y f or Seli ne x or  ................................................................................................................... 6 7  
1 6. 7  
C orrelati ve Sa m ple C ollecti o n a n d Ha n dli n g  .................................................................................. 6 8  
 
 
LI S T O F T A B L E S  
Ta ble 1. R ules f or D ose De -escalati o n  ........................................................................................................................ 2 2  
Ta ble 2. D ose Le vels  ................................................................................................................................................... 2 2  
Ta ble 3: D ose F or ms of St u d y Treat me nts  .................................................................................................................. 2 4  
Ta ble 4. D ose M o dificati o n D ue t o I m m u ne -Me diate d T o xicit y  ................................................................................ 2 8  
Ta ble 5. D ose M o dificati o n D ue t o N o n -I m m u ne Me diate d T o xicit y ......................................................................... 2 9  
Ta ble 6. Pre -s pecifie d D ose M o dificati o ns f or A Es Relate d t o Seli ne x or Treat me nt  ................................................. 3 1  
Ta ble 7. S u p p orti ve Care a n d Seli ne x or D ose A dj ust me nt G ui deli nes f or A Es  Relate d t o Seli ne x or  ....................... 3 1  
Ta ble 8. Best O verall Res p o nse E val uati o n  ................................................................................................................. 4 2  
Ta ble 9. C orrela ti ve St u dies ........................................................................................................................................ 4 4  
Ta ble 1 0. P he n ot y pic Mar kers f or A nal ysis of Vari o us I m m u ne Cells  ....................................................................... 4 5  
 
LI S T O F FI G U R E S  
Fi g ure 1: T 2 4 Bla d der Ca ncer Cell Li ne Treate d wit h Seli ne x or 2 5 0 n M f or 2 Da ys;  P D L 1 E x pressi o n b y q P C R  .. 1 2  
 
 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 0  of 6 8  
1. 0   
S T U D Y O B J E C TI V E S  
1. 1   
Pri m ar y O bjecti ve  
T here are c o -pri mar y o bjecti ves i n t his st u d y. T he pri mar y o bjecti ve of t he P hase I b p orti o n of 
t he st u d y is t o dete r mi ne t he rec o m me n de d P hase 2 d ose ( R P 2 D) of seli ne x or i n c o m bi nati o n 
wit h sta n dar d -d ose p e m br oliz u ma b i n patie nts wit h a d va nce d ur ot helial carci n o ma w h o are 
cis plati n-i neli gi ble or plati n u m -refract or y. T he pri mar y o bjecti ve of t he P hase II p orti o n of t he 
st u d y is t o deter mi ne t he o bjecti ve res p o nse rate ( O R R) of seli ne x or i n c o m bi nati o n wit h 
pe m br oliz u ma b i n patie nts wit h a d va nce d ur ot h elial carci n o ma w h o are cis plati n -i neli gi ble or 
plati n u m -refract or y. 
1. 2   
Sec o n d ar y O bjecti ves  
1.    
T o f urt her e val uate t he t o xicit y pr ofile of t he c o m bi nati o n of seli ne x or wit h 
pe m br oliz u ma b i n patie nts wit h a d va nce d ur ot h elial carci n o ma . 
2.    
T o f urt her e val uate t he efficac y of t he c o m bi nati o n of seli ne x or wit h pe m br oliz u ma b i n 
patie nts wit h a d va nce d ur ot helial carci n o ma as defi ne d  b y pr o gressi o n -free s ur vi val 
( P F S). 
1. 3   
E x pl or at or y or C orrel ati ve O bjecti ves  
1.    
T o e val uate t he fre q u e nc y of p ositi ve X P O 1 e x pressi o n b y I H C a m o n g pati e nts wit h 
cis plati n-i neli gi ble a d va n ce d ur ot helial carci n o ma. 
2.    
T o e val uate t he relati o ns hi p bet wee n X P O 1 e x pressi o n b y I H C a n d res p o nse t o t he 
c o m bi nati o n of seli ne x or a n d pe m br oliz u ma b . 
3.    
T o e val uate t he relati o ns hi p bet wee n P D -L 1 e x pressi o n b y I H C a n d res p o nse t o t he 
c o m bi nati o n of seli ne x or a n d pe m br oliz u ma b  
4.    
T o a nal yze pre - a n d p ost -treat me nt bl o o d sa m ples / peri p heral bl o o d m o n o n uclear cells 
( P B M Cs) f or c ha n ges i n N K a n d T -cells.  
 
2. 0   
B A C K G R O U N D  
T he a d ve nt of i m m u ne c hec k p oi nt i n hi bit or t hera pies has res ulte d i n ne w o pti o ns f or bla d der 
ca ncer patie nts w h o h a ve pr o gresse d after cis plati n -base d t hera p y or are cis plati n -i neli gi ble. Yet, 
vari o us F D A a p pr o ve d a nti -P D -1 a n d a nti -P D -L 1 a nti b o dy  t hera pies ha ve de m o nstrate d m o dest 
o bjecti ve res p o ns e rates ( O R R) ra n gi n g fr o m 1 6 -3 5 % [ 8 -1 3 ]. T h us, t here re mai ns a nee d f or 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 1  of 6 8  
i m pr o ve me nt of t he res p o nse of c hec k p oi nt i n hi biti o n i n patie nts wit h metastatic ur ot helial 
carci n o ma (m U C ). 
T he n uclear e x p orti n -1/ c hr o m os o me re gi o n mai nte na nce 1 ( X P O 1) pr otei n is i m plicate d i n t he 
tra ns p ort of n u mer o us t u m or s u p press or pr otei ns ( T S Ps) a n d cell c ycle re g ulat ors i ncl u di n g R B, 
p 5 3, B R C A 1, a n d p 2 1, o ut of t he cell n ucle us, a n d t h us c o ul d pla y a ke y re g ulat or y r ole i n t u m or 
cell pr oliferati o n  [ 1 4-1 5] . Precli nical data gat here d at U C Da vis i n dicate t hat X P O 1 is 
o vere x presse d i n ur ot heli al carci n o ma c o m pare d t o n or mal bla d der tiss ue.  X P O 1 i n hi biti o n i n 
bla d der ca ncer cell li nes arreste d cell c ycle pr o gressi o n [ 2 3 ]. T h us, X P O 1 is a tar get t hat c o ul d 
ha ve p ote ntial be n efit i n patie nts wit h m U C.  
2. 1   
Scie ntific R ati o n ale  
2. 1. 1    
Pe m br oliz u m a b  
Pe m br oliz u ma b is a selecti ve, h u ma nize d a nti -P D 1 m o n ocl o na l a nti b o d y. It was st u die d i n t w o 
maj or trials i n m U C. I n t he first P hase III st u d y, plati n u m pre -treat e d patie nts were ra n d o mize d 
t o recei ve eit her pe m br oliz u ma b or c he m ot hera p y ( paclita xel, d oceta xel or vi nfl u ni ne) [8 ]. T he 
st u d y met its pri mar y e n d p oi nts, de m o nstrati n g a me dia n o verall s ur vi val ( O S) be nefit of 
pe m br oliz u ma b c o m pare d t o c he m ot hera p y ( 1 0. 3 v s 7. 4 m o nt hs), t h o u g h t here was n o si g nifica nt 
differe n ce i n pr o gressi o n -free s ur vi val ( P F S). I n t he sec o n d P hase II trial, 3 7 0 cis plati n-i neligi ble 
patie nts wit h a d va nce d or metastatic U C, were treate d wit h pe m br oliz u ma b u ntil pr o gressi o n, 
wit h a n o verall res p o nse rate ( O R R) of 2 4 % [9 ]. T he res p o nse rate was hi g her (~ 3 5 %) a m o n gst 
patie nts wit h P D -L 1 e x pressi o n ≥ 1 0 %.  
2. 1. 2    
Seli ne x or  
Seli ne x or ( K P T -3 3 0) is a n orall y bi oa vaila ble, first -i n-class i n hi bit or of X P O 1, a n d has 
de m o nstrate d a t olera ble safet y pr ofile i n b ot h s oli d t u m ors a n d he mat ol o gic mali g na ncies, a n d 
sh o w n  e nc o ura gi n g efficac y i n a variet y of he m at ol o gic mali g na ncies [ 1 6 -2 2 ]. It was rece ntl y 
a p pr o ve d b y t he F D A f or t he treat me nt of refract or y m ulti ple m yel o ma. T o date, it has n ot bee n 
st u die d cli nicall y i n ur ot helial carci n o mas. 
W or k fr o m t he M u dr yj la b ( U C Da vis) has e val uate d t he effect of seli ne x or i n hi g h -gra de 
bla d der mali g na nci es [ 2 3 ]. B y e val uati n g O N C O MI N E datasets of n or mal bla d der tiss ue a n d 
tiss ue fr o m bla d der t u m ors, X P O 1 tra nscri pt le vels were s h o w n t o b e hi g her i n t u m or tiss ue t ha n 
i n n or mal bla d der. I n f o ur m uscle-i n vasi ve bla d der ca ncer cell li nes, seli ne x or le d t o decrease d 
cell via bilit y a n d decreas e d X P O 1 le vels. I n all cell li nes teste d, X P O 1 i n hi biti o n retar de d cell 
c ycle pr o gressi o n b y decreasi n g S p hase, i n d uci n g G 1 arrest, or i n d uci n g G 2/ M arrest. I n se veral 
m o dels of bla d der ca ncer treate d wit h seli ne x or i n vitr o, t he la b als o o bser ve d i ncrease d 
a p o pt osis, e val uate d b y c ha n ges i n P A R P clea va ge. I n m o use xe n o graft m o dels, oral ga va ge of 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 2  of 6 8  
seli ne x or res ulte d i n decrease d t u m or gr o wt h c o m pare d t o c o ntr ol. Als o de m o nstrate d i n t hese 
m o dels were X P O 1 i n hi biti o n, i ncrease d e x pressi o n of p 2 7, a n d decrease of c ycli n A [ 2 3 ].  
O n t he w h ole, t hese res ults s u g gest t hat seli ne x or has p ote ntial efficac y i n patie nts wit h m U C.  
2. 1. 3    
Seli ne x or a n d Pe m br oliz u m a b C o m bi n ati o n  
Data s u g gest t hat t he c o m bi nati o n of i m m u ne c hec k p oi nt i n hi biti o n wit h seli ne x or ma y e n ha nce 
t he acti vit y of seli ne x or. A precli nical trial of seli ne x or de m o nstrate d i ncrease d C T L A 4 a n d 
P D C D 1 ( w hic h e nc o d es P D -1) ge ne e x pressi o n i n le u k oc ytes, a n d i n mela n o ma m o dels 
seli ne x or i n c o m bi nati o n wit h a nti-P D -1 or wit h a nti -P D L -1 a nti b o dies decrease d t u m or gr o wt h 
rates [2 4 ]. I n fact, t he c o m bi nati o n als o i ncrease d N K cells a n d C D 4 + T cells. I n a d diti o n, Dr. 
M u dr yj’s la b als o e val uat e d t he effect of seli ne x or o n 4 bla d der ca ncer cell li nes; i n t hree of 
t hese cell li nes, P D-L 1 a n d P D -L 2 e x pressi o n was i ncrease d b y seli ne x or ( u n p u blis he d d at a, 
ex a m ple i n Fi g ure 1 b el o w ), f urt her s u p p orti n g t he c o m bi nati o n of seli ne x or wit h 
pe m br oliz u ma b i n treat m e nt of ur ot helial carci n o mas.  
 
Fi g ure 1 : T 2 4 B l a d der C a ncer C ell L i ne T re ate d wit h S eli ne x or 2 5 0 n M f or 2 D a ys;  
P D L 1 E x pressi o n b y q P C R  
 
 
 
0
0. 5
1
1. 5
2
2. 5
T 2 4 C o ntr ol P DL 1 Ex pr essi o n  
T 2 4 K P T P DL 1 Ex pr essi o n
T 2 4 P DL 1 Ex pr essi o n

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 3  of 6 8  
2. 2   
Dise ase  
A p pr o xi matel y 7 9, 0 0 0 ne w cas es of bla d der ca ncer are dia g n ose d a n n uall y, wit h nearl y 1 7, 0 0 0 
patie nts d yi n g d ue t o t he disease e v er y year [ 1 ]. T he pr o g n osis f or patie nts w h o de vel o p dista nt 
disease re m ai ns p o or, wit h 5 -year s ur vi val c urre ntl y esti mate d at 5. 2 %. Cis plati n -base d 
c o m bi nati o n c he m ot hera p y re gi me ns ha ve bee n t h e mai nsta y f or metast atic ur ot helial carci n o ma 
( m U C) f or deca des; w hil e res p o nse rates are e nc o ura gi n g, o nl y 1 0-1 5 % of patie nts s ur vi ve l o n g 
ter m fr o m t hese treat me nts [ 2 -7 ]. M ore o ver, nearl y half of patie nts wit h m U C ca n n ot be treate d 
wit h cis plati n -base d c he m ot hera p y d ue t o c o m or bi dities or p o or perf or ma nce stat us . 
2. 2. 1    
Tre at me nt  O pti o ns  
T he c urre nt treat me nt o pti o ns f or patie nts wit h plati n u m -refract or y ur ot h elial carci n o ma is 
treat me nt wit h a n a nti-P D -1 or a nti -P D -L 1 a ge nt, b ut res p o nse rat es are ge nerall y ar o u n d 2 0 % 
[ 8, 1 0-1 2]. I n t he l ast year, er dafi ni b has bee n a p pr o ve d f or use i n p atie nts wit h a d va nce d 
ur ot helial carci n o ma w h o ha ve pr o gresse d after plati n u m -c o ntai ni n g c he m ot hera p y if t he y ha ve a 
s usce pti ble F G F R 3 or F G F R 2 ge netic alterati o n. W hile t he res p o nse rate i n t hese patie nts is 
pr o misi n g at ~ 4 0 %, a li mite d n u m ber of patie nts h a ve t his ge netic alterati o n.  
2. 3   
I n vesti g ati o n al Pr o d uct N a me a n d Descri pti o n 
2. 3. 1    
Seli ne x or  
Seli ne x or  is a first-i n-class, selecti ve i n hi bit or of n uclear e x p ort ( SI N E)  c o m p o u n d. It f u ncti o ns 
b y bi n di n g wit h, a n d i n hi biti n g, t he n uclear e x p ort pr otei n, X P O 1.   
2. 3. 1. 1   
Mec h a nis m of Acti o n  
X P O 1 is o vere x presse d i n a lar ge v ariet y of mali g na ncies i ncl u di n g m ulti ple m yel o ma ( M M), 
oste osarc o ma, pa ncreatic ca ncer, o varia n ca ncer, gli o m a, le u ke mia, a n d l y m p h o ma a n d 
c orrel ates wit h a d va n ce d disease, resista nce t o t hera p y, a n d p o or s ur vi val. X P O 1 e x p orts t u m or 
s u p press or pr otei ns ( T S Ps; e g, p 5 3, p 7 3, p R b, F O X Os, A P C, P T E N) a n d gr o wt h re g ulat or y 
pr otei ns ( G R Ps; e g, p 2 1, p 2 7, s ur vi vi n) o ut o f t he n ucle us. T hese pr otei n car g os me diate t heir 
cell c ycle c hec k p oi nt/t u m or s u p pressi o n f u ncti o ns wit hi n t he n ucle us. T heref ore, n uclear t o 
c yt o plas mic tra ns p ort of t hese pr otei ns b y X P O 1 l ea ds t o t heir f u ncti o nal i nacti vati o n. X P O 1 
als o re g ulates t he c y t o plas mic l ocalizati o n a n d, i n t ur n, tra nslati o n of ke y pr ot o o nc o ge nic 
m R N As (e g, M yc, B C L 2, B C L 6 a n d c ycli n D) t hat c o m ple x wit h t he X P O 1 car g o pr otei n, 
e u kar y otic i nitiati o n fact or 4 E (eI F 4 E). I n a d diti o n, X P O 1 is i n v ol ve d i n re g ulati n g n uclear 
le vels of t he gl uc oc ortic oi d rece pt or ( G R). 
I n hi biti o n of X P O 1 b y seli ne x or pr o m otes a p o pt osis i n mali g na nt cells b y bl oc ki n g eac h of t he 
a b o ve X P O 1 -me di ate d mec ha nis ms. Beca us e t hese mec ha nis ms are rele va nt t o a n y ne o plastic 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 4  of 6 8  
cell, seli ne x or has t he p ot e ntial t o e ffecti vel y treat a ra n ge of mali g na ncies. N or mal cells u n der g o 
re versi ble cell c ycl e arrest f oll o wi n g i n hi biti o n of X P O 1 a n d rec o ver w he n t he bl oc k is re m o ve d. 
Seli ne x or is ( 2 Z )-3 -{ 3 -[ 3, 5-bis(trifl u or o met h yl) p he n yl] -1 H -1, 2 4 -triaz ol-1 -yl } -N ’-( pr yazi n-2 —
yl) p r o p-2 -e n e h y drazi de. It is a w hite t o off -w hite p o w der a n d has t he m olec ular f or m ula 
C 1 7H 1 1F 6N 7 0 a n d a m olec ular mass of 4 4 3. 3 1 g/ m ol.  Eac h seli ne x or ta bl et c o ntai ns 2 0 m g of 
seli ne x or as t he acti ve i n gre die nt. Seli ne x or ta blets are bl ue, r o u n d, bi-c o n ve x, fil m-c oate d 
ta blets wit h “ K 2 0” de b osse d o n o ne si de a n d n ot hi n g o n t he ot her si de. T he i nacti ve i n gre die nts 
are c oll oi dal silic o n di o xi de, cr oscar mell ose s o di u m, ma g nesi u m stearate, micr ocr ystalli ne 
cell ul ose, O pa dr y 2 0 0 clear, O pa dr y II bl ue, p o vi d o ne K 3 0 , a n d s o di u m la ur yl s ulfate. 
2. 3. 2    
Pe m br oliz u m a b  
Pe m br oliz u ma b  is a m o n ocl o nal I g G 4 ka p pa a nti b o d y bl oc ki n g t he P D -1 rece pt or. T he a nti b o d y 
has a n a p pr o xi mat e m olec ular wei g ht of 1 4 9 k Da. It is pr o d uce d i n rec o m bi na nt C hi nese ha mster 
o var y ( C H O) cells. It is a n i ntra ve n o us t hera p y a d mi nistere d at a d ose of 2 0 0 m g i ntra ve n o usl y 
(I V) o v er 3 0 mi n utes e ver y 3 wee ks , pr o vi de d as a 1 0 0 m g/ 4 m L s ol uti o n i n a si n gle-d ose vial . It 
is a p pr o ve d f or us e i n t he treat me nt of patie nts wit h ad va nce d ur ot helial carci n o ma.  
Pe m br ol iz u ma b f or i njecti o n is a sterile, preser vati ve-free, w hite t o off-w hit e l y o p hilize d p o w der 
i n si n gle-d ose vials f or i ntra ve n o us use. Eac h 2 m L of rec o nstit ute d s ol uti o n c o ntai ns 5 0 m g of 
pe m br oliz u ma b a n d is f or m ulate d i n L -histi di ne ( 3. 1 m g), p ol ys or bate  8 0 ( 0. 4 m g) a n d s ucr ose 
( 1 4 0 m g). ma y c o ntai n h y dr oc hl oric aci d/s o di u m h y dr o xi de t o a dj ust p H t o 5. 5. 
Pe m br oliz u ma b i njecti o n is als o pr o d uce d as a sterile, preser vati ve -free, clear t o sli g htl y 
o palesce nt, c ol orless t o sli g htl y yell o w s ol uti o n f or i ntra ve n o us use. Eac h vi al c o ntai ns 1 0 0 m g 
of pe m br oliz u ma b i n 4 m L of s ol uti o n. Eac h 1 m L of s ol uti o n c o ntai ns 2 5 m g of pe m br oliz u m a b 
a n d is f or m ulate d i n: L -histi di ne ( 1. 5 5 m g), p ol ys or bate 8 0 ( 0. 2 m g), s ucr ose ( 7 0 m g), a n d water 
f or i njecti o n, U S P. 
2. 4   
S u m m ar y of N o ncli nic al  D at a  
2. 4. 1    
P h ar m ac ol o g y  
2. 4. 1. 1   
Seli ne x or  
I n n o n cli nical st u dies, seli ne x or re v ersi bl y i n hi bits n uclear e x p ort of t u m or s u p press or pr otei ns 
( T S Ps), gr o wt h re g ulat ors, a n d m R N As of o nc o ge nic pr otei ns b y bl oc ki n g e x p orti n 1 ( X P O 1). 
X P O 1 i n hi biti o n b y seli ne x or lea ds t o acc u m ulati o n of T S Ps i n t he n u clear, re d ucti o ns i n se veral 
o nc o pr otei ns, s uc h as c -m yc a n d c ycli n D 1, cell c ycle arrest, a n d a p o pt osis of ca ncer cells. 
Seli ne x or de m o nstrate d pr o -a p o pt otic acti vit y i n vitr o i n m ulti ple m yel o ma cell li nes a n d patie nt 
t u m or sa m ples, a n d i n m uri ne xe n o graft m o dels. Seli ne x or e x p os ure-res p o nse relati o ns hi ps a n d 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 5  of 6 8  
t he ti me c o urse of p har mac o d y na mics res p o nses are u n k n o w n. T he effect of seli ne x or o n Q Tc 
i nter val was e v al uate d i n patie nts wit h hea vil y pretreate d he mat ol o gic mali g na ncies at a d ose 2. 2 
ti mes t he ap pr o ve d rec o m me n de d d ose t wice wee kl y, wit h n o lar ge effect o n Q Tc i nter val at t he 
t hera pe utic d os e le vel. 
2. 4. 1. 2   
Pe m br oliz u m a b  
B y bi n di n g t o t he P D -1 li ga n ds, lea di n g t o P D -L 1 a n d P D -L 2 bl oc ka de, a n d t o t he P D -1 rece pt or 
f o u n d o n T cells, pe m br oliz u ma b i n hi bits T cell pr oliferati o n a n d c yt o ki ne pr o d ucti o n. 
U pre g ulati o n of P D -1 li g a n ds occ urs i n s o me t u m ors a n d si g nali n g t hr o u g h t his pat h wa y ca n 
c o ntri b ute t o i n hi biti o n of acti ve T -cell i m m u ne s ur veilla nce of t u m ors. Pe m br oliz u ma b is a 
m o n ocl o nal a nti b o d y t hat bi n ds t o t he P D -1 rece pt or a n d bl oc ks its i nteracti o n wit h P D -L 1 a n d 
P D -L 2, releasi n g P D -1 p at h wa y -me diat e d i n hi biti o n of t he i m m u ne res p o nse, i ncl u di n g t he a nti -
t u m or i m m u ne res p o nse. I n s y n g e neic m o use t u m or m o dels, bl oc ki n g P D-1 acti vit y res ulte d i n 
decrea se d t u m or gr o wt h. 
2. 4. 2    
T o xic ol o g y  
2. 4. 2. 1   
Seli ne x or  
Carci n o ge nicit y st u dies ha ve n ot bee n c o n d ucte d wit h seli ne x or. It was n ot m uta ge nic i n vitr o i n 
a bacterial re v erse m utati o n ( A mes) ass a y a n d was n ot clast o ge nic i n eit her t he i n vitr o 
c yt o ge netic ass a y i n h u ma n l y m p h oc ytes or i n t he i n vi v o rat micr o n ucle us assa y. Fertilit y 
st u dies i n a ni mals ha ve n ot bee n c o n d uct e d wit h seli ne x or. I n re peat -d ose oral t o xicit y st u dies, 
seli ne x or was a d mi nistere d f or u p t o 1 3 wee ks i n rats a n d m o n ke ys. Re d uce d s per m, s per mati ds, 
a n d ger m cells i n e pi di d y mi des a n d testes were o bser ve d i n rats at ≥ 1 m g/ k g, decrease d o varia n 
f ollicles were o bs er ve d i n rats at ≥ 2 m g/ k g, a n d si n gle cell necr osis of testes was o bser ve d i n 
m o n ke ys at ≥ 1. 5 m g/ k g. T hese d ose le vels res ulte d i n s yste mic e x p os ures a p pr o xi matel y 0. 1 1, 
0. 2 8, a n d 0. 5 3 ti mes, res pecti vel y, t he e x p os ure ( A U Clast) i n h u ma ns at t he rec o m me n de d 
h u ma n d ose of 8 0 m g.  
2. 4. 2. 2   
Pe m br oliz u m a b  
N o st u dies ha ve bee n perf or me d t o test t he p ote ntial of pe m br oliz u ma b f or carci n o g e nicit y or 
ge n ot o xicit y. F ertilit y st u dies ha ve n ot bee n c o n d ucte d wit h pe m br oliz u ma b. I n 1 -m o nt h a n d 6 -
m o nt h re peat -d ose t o xic ol o g y st u dies i n m o n ke ys, t here were n o n ota ble effects i n t he male a n d 
fe male re pr o d ucti ve or ga ns; h o we ver, m ost a ni mals i n t hese st u dies were n ot se x ually mat ure.  
I n a ni mal m o dels, i n hi biti o n of P D-1 si g nali n g res ulte d i n a n i ncreas e d se verit y of s o me 
i nfecti o ns a n d e n h a nce d i nfla m mat or y res p o nses. M t u berc ul osis-i nfect e d P D-1 k n oc k o ut mice 
e x hi bit mar ke dl y decreas e d s ur vi val c o m pare d wit h wil d -t y pe c o ntr ols, w hic h c orrelate d wit h 
i ncreas e d bact erial pr oliferati o n a n d i nfla m mat or y res p o nses i n t hese a ni mals. P D-1 k n oc k o ut 
mice ha ve als o s h o w n decreas e d s ur vi val f oll o wi n g i nfecti o n wit h l y m p h oc ytic c h ori o me ni n gitis 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 6  of 6 8  
vir us ( L C M V). A d mi nistrati o n of pe m br oliz u m a b i n c hi m pa nzees wit h nat urall y occ urri n g 
c hr o nic he p atitis B i nfecti o n res ulte d i n t w o o ut of f o ur a ni mals wit h si g nifica ntl y i ncrease d 
le vels of ser u m A L T, A S T, a n d G G T, w hic h persiste d f or at least 1 m o nt h after disc o nti n uati o n 
of pe m br oliz u ma b.  
2. 5   
S u m m ar y of Cli nic al D at a  
2. 5. 1    
P h ar m ac o ki netics a n d Pr o d uct Met a b olis m  
2. 5. 1. 1   
Seli ne x or  
F oll o wi n g a si n gle -d ose a d mi nistrati o n of seli ne x or 8 0 m g, t he mea n (sta n dar d de viati o n) pea k 
plas ma c o nce ntrati o n ( C ma x) was 6 8 0 ( 1 2 4 n g/ m L) a n d t he mea n A U C was 
5 3 8 6  ( 1 1 1 6) n g -h/ m L. Seli ne x or C ma x a n d A U C i ncreas e d pr o p orti o nall y o ver d oses fr o m 
3  m g/ m 2 t o 8 5 m g/ m2 ( 0. 0 6 t o 1. 8 ti mes t he a p pr o ve d rec o m me n de d d ose base d o n 1. 7 m 2 b o d y 
s urface area). N o cli nicall y rele va nt acc u m ulati o n at stea d y state was o bser ve d.  T he C ma x is 
reac h ed wit hi n 4 h o urs f oll o wi n g oral a d mi nistrati o n of seli ne x or. C o nc o mita nt a d mi nistrati o n of 
hi g h -fat meals di d n ot affect t he p har mac o ki netics of seli ne x or t o a cli nicall y si g nifica nt e ve nt. 
T he a p pare nt v ol u me of distri b uti o n of seli ne x or is 1 2 5 L i n patie nts wit h ca ncer.  
T he pr otei n bi n di n g of seli ne x or is 9 5 %. F oll o wi n g a si n gle d ose of seli ne x or, t he mea n half -life 
is 6 t o 8 h o urs. T he a p pare nt t otal cleara nce of seli ne x or is 1 7. 9 L/ h i n patie nts wit h ca ncer. 
Seli ne x or is meta b olize d b y C Y P 3 A 4, m ulti ple  U D P -gl uc ur o n os yltra nsferases ( U G Ts) a n d 
gl utat hi o ne S -tra nsferases ( G S Ts). N o cli nicall y si g nifica nt differe nce i n t he P K of seli ne x or 
were o bs er ve d b ase d o n a ge ( 1 8 -9 4 y ears ol d), se x, et h nicit y, mil d t o se vere re nal i m pair me nt 
( C Lcr: 1 5-8 9 m L/ mi n b y C oc kcr oft -Ga ult). T he effect of e n d -sta ge re nal disease ( C Lcr < 1 5 
m L/ mi n) or he m o dial ysis o n seli ne x or P K is u n k n o w n. Mil d he patic i m pair me nt ha d n o 
cli nicall y si g nifica nt effect o n t he P K of seli ne x or. T he effect of m o d erate a n d se vere he patic 
i m pair me nt o n seli ne x or P K is u n k n o w n. Seli ne x or is a s u bstrate of C Y P 3 A 4 a n d of U G Ts a n d 
G S Ts. It i n hi bits O A T P 1 B 3 b ut d oes n ot i n hi bit ot her s ol ute carrier ( S L C) tra ns p orters. It is n ot a 
s u bstrate d of P-g p, B C R P, O A T P 1 B 1, O A T P 1 B 3, O A T 1, O A T 3, O C T 1, O C T 2, M A T E 1, or 
M A T E 2 -K. F or mal dr u g -dr u g i nteracti o n st u dies ha ve n ot bee n perf or me d.  
2. 5. 1. 2   
Pe m br oliz u m a b  
T he p har mac o ki netics ( P K) of pe m br oliz u ma b was c haracterize d usi n g a p o p ulati o n P K a nal ysis 
wit h c o nce ntrati o n dat a c ollecte d fr o m 2 9 9 3 patie nts wit h vari o us ca ncers w h o rece i ve d 
pe m br oliz u ma b d oses of 1 t o 1 0 m g/ k g e ver y 2 wee ks, 2 t o 1 0 m g/ k g e ver y 3 wee ks, or 2 0 0 m g 
e ver y 3 wee ks. Stea d y -state c o nce ntrati o ns of pe m br oliz u ma b were reac he d b y 1 6 wee ks of 
re peat e d d osi n g wit h a n e ver y 3-wee k re gi me n a n d t he s yste mic acc u m ulati o n was 2. 1 -f ol d. T he 
pea k c o n ce ntrati o n ( C ma x), tr o u g h c o nce ntrati o n ( C mi n), a n d area u n der t he plas ma 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 7  of 6 8  
c o nce ntrati o n vers us ti me c ur ve at stea d y state ( A U Css) of pe m br oliz u ma b i ncreas e d d ose 
pr o p orti o nall y i n t he d ose ra n ge of 2 t o 1 0 m g/ k g e ver y 3 wee ks.  
T he ge o metric mea n val u e ( C V %) f or v ol u me of distri b uti o n at stea d y state is 6. 0 L ( 2 0 %). 
Pe m br oliz u ma b cleara nce ( C V %) is a p pr o xi matel y 2 3 % l o wer at stea d y state t ha n t hat after t he 
first d ose; t his decrease i n cleara nce wit h ti me is n ot c o nsi dere d cli nicall y i m p orta nt. T he 
ter mi nal half-life (t1/ 2) is 2 2 da ys ( 3 2 %). N o cli nicall y i m p orta nt effect o n t he C L of 
pe m br oliz u ma b was see n i n re gar ds t o: a ge (ra n ge 1 5 -9 4 years), se x, race ( 8 9 % w hite), re nal 
i m pair me nt, mil d he patic i m pair me nt (t otal bilir u bi n ≤ U L N a n d A S T > U L N or t otal bilir u bi n 
bet wee n 1 -1. 5 x U L N a n d a n y A S T), or t u m or b ur de n. T he i m pact of m o d erate t o se vere he patic 
i m pair me nt o n t he P K of pe m br oliz u ma b is u n k n o w n. 
2. 5. 2    
S u m m ar y of Cli nic al S afet y  
2. 5. 2. 1   
Seli ne x or  
Seli ne x or was st u die d cli nicall y at a d os e of 8 0 m g i n a P hase 2 st u d y i n c o m bi nati o n wit h 
de xa met has o ne 2 0 m g, wit h b ot h dr u gs gi ve n o n Da ys 1 a n d 3 of e ver y wee k. T he me dia n 
d urati o n of seli ne x or treat me nt was 8 wee ks ( 1 -6 0 wee ks). T he me dia n d os e was 
1 1 5. 4  ( 3 6-2 0 0  m g) per wee k. T he treat me nt d isc o nti n uati o n rate d ue t o a d verse reacti o ns was 
2 7 %; 5 3 % of patie nts ha d a re d ucti o n i n t he seli ne x or d ose a n d 6 5. 3 % ha d a d ose i nterr u pti o n. 
T he m ost fre q ue nt a d verse reacti o ns re q uiri n g per ma ne nt disc o nti n uati o n i n 4 % or greater of 
patie nts w h o recei ve d  seli ne x or i ncl u de d fati g ue, na usea, a n d t hr o m b oc yt o pe nia. T he rate of fatal 
a d verse reacti o ns was 8. 9 %. T he m ost c o m m o n ( ≥1 0 % of patie nts) a d verse reacti o ns Gra de  ≥ 3  
re p orte d i n patie nts wit h rela pse d a n d refract or y m ulti ple m yel o ma w h o recei ve d seli ne x or a n d 
de xa met has o ne  i n cl u de d t hr o m b oc yt o pe nia, a ne mi a, h y p o natre mia, a n d ne utr o pe nia (see 
I n v esti gat or’s Br oc h ure). 
 
2. 5. 2. 2   
Pe m br oliz u m a b  
T he safet y of pe m br oliz u ma b was i n vesti gate d i n K E Y N O T E -0 5 2, a si n gle -ar m trial t hat 
e nr olle d 3 7 0 patie nts wit h l ocall y a d va n ce d or metastatic ur ot helial carci n o ma w h o were n ot 
eli gi ble f or cis plati n -c o nt ai ni n g c he m ot hera p y. Patie nts wit h a ut oi m m u ne disease or me di cal 
c o n diti o ns t hat re q uire d s yste mic c ortic oster oi ds or ot her i m m u n o s u p pressi ve me dicati o ns were 
i neli gi ble. Patie nts recei v e d pe m br oliz u ma b 2 0 0 m g I V e ver y 3 wee ks u ntil u nacce pta ble 
t o xicit y or eit her ra di o gra p hic or cli nical disease pr o gressi o n. T he me dia n d urati o n of e x p os ure 
t o pe m br oliz u ma b was 2. 8 m o nt hs ( 1 da y-1 5. 8 m o nt hs).  
Pe m br oliz u ma b was disc o nti n ue d d ue t o  a d verse reacti o ns i n 1 1 % of patie nts. Ei g htee n patie nts 
( 5 %) die d fr o m ca us es ot her t ha n diseas e pr o gressi o n. Fi ve patie nts ( 1. 4 %) w h o were treat e d 
wit h pe m br oliz u ma b e x p erie nce d se psis w hic h le d t o deat h, a n d t hree patie nts ( 0. 8 %) 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 8  of 6 8  
e x perie n ce d p ne u m o nia t hat le d t o deat h. A d verse reacti o ns lea di n g t o i nterr u pti o n of 
pe m br oliz u ma b occ urre d i n 2 2 % of patie nts; t he m ost c o m m o n ( ≥1 %) were li ver e nz y me 
i ncreas e, diarr hea, uri nar y tract i nfecti o n, ac ute ki d ne y i nj ur y, fati g ue, j oi nt pai n, a n d p ne u m o nia. 
Seri o us a d verse reacti o ns occ urre d i n 4 2 % of patie nts. T he m ost fre q ue nt seri o us a d verse 
reacti o ns (≥2 %) were uri nar y tract i nfecti o n, he m at uria, ac ut e ki d ne y i nj ur y, p ne u m o nia, a n d 
ur ose psis.  
I m m u ne-relat e d a d verse reacti o ns t hat re q uire d s yste mic gl uc oc ortic oi ds occ urre d i n 8 % of 
patie nts, use of h or m o nal s u p ple me ntati o n d ue t o a n i m m u ne -relate d a d verse reacti o n occ urre d 
i n 8 % of patie nts, a n d 5 % of patie nts re q uire d at least o ne ster oi d d ose ≥ 4 0 m g oral pre d nis o ne 
e q ui vale nt.  
2. 5. 3    
Ris ks  
2. 5. 3. 1   
Seli ne x or  
Base d o n fi n di n gs i n a ni mal st u dies a n d its mec ha nis m of acti o n, seli ne x or ca n ca use fetal har m 
w he n a d mi nistere d t o a pre g na nt w o ma n. T here are n o a vaila ble data i n pre g na nt w o me n t o 
i nf or m t he dr u g-ass o ciate d ris k. I n a ni mal re pr o d ucti o n st u dies, a d mi nistrati o n of seli ne x o r t o 
pre g na nt rats d uri n g or ga n o ge nesis res ulte d i n str uct ural a b n or m alities a n d alterati o ns t o gr o wt h 
at e x p os ures t hat were b el o w t h ose occ urri n g cli nicall y at t he rec o m me n de d d ose. Pre g na nt 
w o me n m ust be a d vise d t o t he ris ks t o a fet us. T he esti mate d ba c k gr o u n d ris k of maj or birt h 
defects a n d miscarri a ge f or t he i n dicate d p o p ulati o n is u n k n o w n. T here is n o i nf or mati o n 
re gar di n g t he prese n ce of seli ne x or or its meta b olites i n h u ma n mil k, or t heir effects o n t he 
breastfe d c hil d or mil k pr o d ucti o n, t h us w o m e n are a d vise d n ot t o breastfee d d uri n g treat me nt 
wit h seli ne x or a n d f or 1 wee k after last d ose. Safet y a n d effecti ve ness h a ve n ot bee n esta blis he d 
i n t he pe diatric p o p ulati o n. Patie nts ≥ 7 5 years ol d ha d a hi g her i nci de nce of disc o nti n uati o n d ue 
t o a d verse reacti o ns ( 4 4 % vs 2 7 %), hi g her i n ci de nce of S A Es ( 7 0 % vs 5 8 %) a n d hi g her 
i nci de nce of fatal A Es ( 1 7 % vs 9 %) c o m pare d t o y o u n ger patie nts.  
2. 5. 3. 2   
Pe m br oliz u m a b  
Base d o n its mec ha nis m of acti o n, pe m br oliz u ma b ca n ca use fetal har m w he n a d mi nistere d t o a 
pre g na nt w o ma n. N o a vaila ble h u ma n data is a vail a ble i nf or mi n g t he ris k of e m br y o -fet al 
t o xicit y. I n a ni mal m o dels, t he P D-1/ P D -L 1 si g nali n g pat h wa y is i m p orta nt i n t he mai nte na nce 
of pre g na n c y t hr o u g h i n d ucti o n of mater nal i m m u ne t olera nce t o fetal tiss u e. H u ma n I g G 4 are 
k n o w n t o cr oss t he place nta. T here are n o data o n t he prese nce of pe m br oliz u ma b i n eit her 
a ni mal or h u ma n mil d or its effect o n t he breastfe d c hil d or o n mil k pr o d ucti o n; w o me n are 
a d vise d n ot t o breastf ee d d uri n g treat me nt a n d f or 4 m o nt hs after fi nal d ose a d mi nistrati o n.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 1 9  of 6 8  
3. 0   
S U B J E C T S E L E C TI O N  
S u bjects will be recr uite d fr o m t he U C Da vis C o m pre he nsi ve Ca ncer Ce nt er.  
3. 1   
I ncl usi o n Criteri a 
Patie nts m ust meet all of t he foll o wi n g criteria  t o b e eli gi ble f or st u d y e ntr y. 
1.  Pat h ol o gicall y c o nfir me d l ocall y a d va nce d or met astatic ur ot helial carci n o ma b y 
hist ol o g y.  
2.  Meas ura ble dis ease b y R E CI S T v 1. 1 criteria.  
3.  N ot eli gi ble t o recei ve cis plati n -base d c he m ot hera p y d ue t o re nal d ysf u ncti o n  ( defi ne d as 
Cr Cl <  6 0 m L/ mi n) , >  Gra de 2 peri p heral n e ur o pat h y, or ot ot o xici t y ( defi ne d as 
>  Gra d e  2 heari n g l oss) ; O R u n willi n g ness of patie nt t o recei v e cis plati n; O R pr o gresse d 
o n o ne plati n u m -base d c he m ot hera p y re gi me n  f or a d va nce d disease. 
4.  Ma y ha ve ha d ne oa dj u va nt or a dj u va nt plati n u m -base d c he m ot hera p y or i ntra vesical 
t hera py i n t he past  
5.  Me n a n d w o me n ≥1 8 years of a ge.  
6.  E C O G  perf or ma nce st at us sc ore of 0, 1 or 2 (see A p pe n di x ). 
7.  Life e x pecta nc y ≥ 3 m o nt hs . 
8.  He mat ol o g y para m eters defi ne d b y:  
a. A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 0  × 1 0 9/ L,  
b.  Platelet c o u nt ≥ 7 5 × 1 0 9/ L ( patie nts f or w h o m < 5 0 % of b o ne marr o w n ucl eate d 
cells are pl as ma cells) or ≥5 0, 0 0 0/ m m 3 ( patie nts f or w h o m ≥5 0 % of b o ne marr o w 
n ucleate d cells are pl as ma cells) , a n d  
c. He m o gl o bi n ≥ 9 g/ d L ( ma y ha ve bee n tra nsf use d)  
9.  Bl o o d c he mistr y le vels defi ne d b y:  
a. T otal bilir u bi n le ve l ≤ 1. 5 × t he u p per li mit of n or mal ( U L N) ra n ge (e xce pt 
patie nts wit h Gil bert’s s y n dr o me w h o m ust ha ve a t otal bilir u bi n of < 3 × U L N)  
b.  A S T a n d A L T le vels ≤ 2. 5 × U L N, or A S T a n d A L T le vels ≤ 5 × U L N  
(f or s u bjects wit h d oc u m e nte d metastatic diseas e t o t he li ver) 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 0  of 6 8  
c. Creati ni ne cleara n ce ≥ 3 0 m L/ mi n b y C oc kcr oft -Ga ult f or m ula  
1 0.  S u bjects wit h acti ve he patitis B vir us ( He p B) are all o we d if a nti viral t hera p y f or he patitis 
B has bee n gi ve n f or > 8 we e ks a n d viral l oa d is < 1 0 0 I U/ m L  pri or t o first d ose of trial 
treat ment. S u bjects wit h u ntreate d he patitis C vir us ( H C V) are all o we d. S u bjects wit h 
H u ma n I m m u n o deficie nc y Vir us ( HI V) w h o ha ve C D 4 + T -cell c o u nts ≥ 3 5 0 cells/ µ L 
a n d n o hist or y of AI D S -d efi ni n g o p p ort u nistic i nfecti o ns i n t he last year are all o we d.  
1 1.  Willi n g ness t o u n der g o ma n dat or y pre-treat me nt bi o ps y ( u nless t here is a de q uate arc hi val 
t u m or s peci me n a vaila bl e f or P D-L 1 I H C e val uati o n).   
1 2.  Fe male s u bjects w h o are of n o n -re pr o d ucti ve p ote ntial (i.e., p ost-me n o pa us al b y hist or y - 
n o me nses f or ≥1 year; O R hist or y o f h ysterect o m y; O R hist or y of bilateral t u bal li gati o n; 
O R hist or y of bilateral o o p h orect o m y). Or, f e male s u bjects of c hil d beari n g p ote ntial m ust 
ha ve a n e gati ve ser u m or uri ne pre g na nc y test wit hi n 7 2 h o urs pri or t o t he first st u d y dr u g 
a d mi nistrati o n . 
1 3.  Ma le a n d fe male s u bjects w h o are of re pr o d ucti ve p ote ntial m ust a gree t o use hi g hl y 
effecti ve met h o d of birt h c o ntr ol (e. g. , i m pla nts, i njecta bles, birt h c o ntr ol pills wit h t w o 
h or m o nes , i ntra uteri ne de vices [I U Ds], c o m plete a bsti ne nce or sterilize d part ner, a n d 
fe male sterilizati o n) a n d a barri er met h o d (e. g., c o n d o ms, va gi nal ri n g, s p o n ge, etc.)  
d uri n g t he peri o d of t hera p y a n d f or 4 m o nt hs after t he last d ose of st u d y dr u g . 
1 4.  A bilit y t o u n dersta n d a n d willi n g ness t o si g n a n i nf or me d c o nse n t f or m. 
1 5.  A bilit y t o a d here t o t he st u d y visit sc he d ule a n d ot her pr ot oc ol re q uire me nts.  
1 6.  M ust be a ble t o s wall o w st u d y dr u g.  
3. 2   
E xcl usi o n Criteri a  
Patie nts w h o meet a n y of t he f oll o wi n g criteria will be e xcl u de d fr o m st u d y e ntr y.  
1.  Recei vi n g ra diati o n ≤ 1 4 da ys pri or t o e nr oll me nt t o t he site of selecte d tar get lesi o ns. 
2.  S yste mic t hera p y f or ca n cer ≤ 2 1 da ys pri or t o e nr oll me nt . 
3.  A ut oi m m u ne dis or der re q uiri n g acti ve t hera p y as defi ne d b y c ortic oster oi ds at a d ose 
≥ 1 0 m g oral pre d nis o ne or t he e q ui vale nt or re q uiri n g c hr o nic i m m u n os u p pressi ve 
t hera p y.  
4.  Use of c ortic oster oi ds ≤ 1 4 da ys pri or t o e nr oll me nt at a d ose of ≥ 1 0 m g oral pre d nis o ne 
or t he e q ui vale nt per da y . 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 1  of 6 8  
5.  Recei ve d i m m u ne c h ec k p oi nt i n hi bit or t hera p y (a nti -P D -1, a nti -P D -L 1, or a nti -C T L A 4 
directe d t hera p y) o n a pri or cli nical trial.  
6.  Has recei ve d seli ne x or or a n ot her X P O 1 i n hi bit or pre vi o usl y . 
7.  A n y acti ve gastr oi ntesti n al d ysf u ncti o n t hat c o ul d i nterfere wit h a bs or pti o n of st u d y 
treat me nt i n t he o pi ni o n of t he i n vesti gat or. 
8.  Pre g na nt or lact ati n g w o me n . 
9.  A n y c o n diti o n t hat w o ul d pr o hi bit t he u n dersta n di n g or re n deri n g of i nf or me d c o nse nt . 
1 0.  A n y c o n diti o n i ncl u di n g a d diti o nal mali g na ncies, la b orat or y a b n or malities, or ps yc hiatric 
ill ness t hat i n t he o pi ni o n of t he i n vesti gat or w o ul d i nterfere wit h t he patient’s safet y or 
c o m plia nce w hile o n trial.  
1 1.  Se vere i nfecti 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 nterfere wit h patie nt safet y 
or c o m plia nce o n tri al wit hi n 4 wee ks pri or t o e nr oll me nt.   
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 2  of 6 8  
4. 0   
S T U D Y D E SI G N   
T his is a P hase I b /II st u d y usi n g a 3 + 3 de -escalati o n desi g n t o i de ntif y  t he R P 2 D of seli ne x or i n 
c o m bi nati o n wit h fi xe d d ose pe m br oliz u ma b  d uri n g t he P hase I b p orti o n . D ue t o t o xicit y 
o bser ve d at t he c urre ntl y a p pr o ve d d ose of seli ne x or i n patie nts wit h refract or y m ulti ple 
m y el o ma, t he st u d y will i nitiate wit h a l o wer d ose of seli ne x or t hat has bee n pre vi o usl y 
esta blis he d t o be well -t ol erate d, wit h all o wa nce f or o ne d ose le vel de-es cal ati o n.  
4. 1   
P h ase I b  
Patie nts wit h  plati n u m -refract or y or cis plati n-i neli gi ble a d va nce d ur ot helial carci n o ma wit h 
meas ura ble disease  (as d efi ne d b y R E CI S T v 1. 1), will be e nr olle d t o t his trial if t he y meet all 
ot her eli gi bilit y criteria  (see Secti o ns 3 . 1, 3 . 2).  
Arc hi val tiss ue  will be re q uire d pri or t o treat me nt o n t he st u d y. F oll o wi n g a 3 + 3 st u d y des i g n, 
i nitiall y 3 patie nts will be e nr olle d, wit h t he pr o p ose d d ose  de -escal ati o n pla n  s h o w n i n Ta ble 1 
a n d d ose le vels s h o w n i n Ta ble 2. T he R P 2 D will be t he hi g hest d ose le vel at w hic h 0/ 3 or 1/ 6 
patie nts ha ve D L T.  
T a ble 1 . R ules f or  D ose De -es c al ati o n  
N u m ber of P atie nts wit h D L T 
at a G i ve n D ose L e vel 
De -esc al ati o n D ecisi o n R ule  
0 o ut of 3  
E nr oll 3 patie nts t o sa me D L  
0 o ut of 6  
R P 2 D  
1 o ut of 3  
E nr oll 3 patie nts t o sa me D L  
1 o ut of 6  
R P 2 D  
2 o ut of 3  
If D L 1 , deescalate o ne d ose le vel  
If D L -1 , st o p st u d y 
2 o ut of 6  
If D L 1, de-escalate o ne d ose le vel  
If D L -1 , st o p st u d y 
T a ble 2 . D ose Le vels 
D ose Le vel  
Pe m br oliz u m a b  
Seli ne x or  
1   
(S tarti n g D ose)  
2 0 0 m g I V e ver y 3 wee k s ( D 1)   
8 0 m g P O o nce wee kl y  
( D 1, D 8, D 1 5)  
-1    
2 0 0 m g I V e ver y 3 wee k s ( D 1)   
6 0 m g P O o nce wee kl y  
( D 1, D 8, D 1 5)  
* Eac h c ycle is 2 1 da ys  
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 3  of 6 8  
 
Eac h treat me nt c ycle will be 2 1 da ys i n d urati o n. S u bjects will recei v e c o m bi nati o n t hera p y f or 
u p t o 2 4  m o nt hs or u ntil pr o gressi o n or i nt olera bl e t o xicit y. Patie nts will be assesse d f or t o xicit y 
e ver y 3 wee ks  wit h cli nical a n d la b m o nit ori n g , a n d t he peri o d  f or assessi n g d ose-li miti n g 
t o xicit y ( D L T) will be t he first 6 wee ks of treat me nt.  
4. 1. 1    
Defi niti o n of D ose Li miti n g T o xicit y  
D ose -li miti n g t o xicit y is defi ne d as a n y cli nicall y si g nifica nt Gra de 3 or hi g her n o n -he m at ol o gic 
t o xicit y re q uiri n g i nter ve nti o n as defi ne d b y N CI C T C A E versi o n 5. 0 a n d a n y Gra de 4 or hi g her 
he mat ol o gic t o xicit y as defi ne d b y N CI C T C A E versi o n 5. 0 wit h t he e xce pti o n of t he f oll o wi n g:  
•  Im m u ne -relat e d Gra de 3 or hi g her a d verse e ve nt ( A E) t hat res ol ves t o Gra de 2 or less 
wit hi n 2 1 da ys wit h  gl uc oc ortic oi ds  
•  Gra de 3 or hi g her e n d ocri n o pat hies t hat res ol ve t o Gra de 2 or less wit h or wit h o ut 
p har mac ol o gic i nter ve nti o n wit hi n 2 1 da ys  
•  Gra de 3 or hi g her na usea, v o miti n g t hat res ol ves t o Gra de 2 or less wit h p har mac ol o gic 
i nter ve nti o n wit hi n 7 da ys  
•  Gra de 3 h y p o n atre mia t h at res ol ves wit hi n 7 da ys  
 
S u bjects w h o are n ot e val ua ble f or t o xicit y will be re place d f or D L T assess me nt. If s u bjects are 
u na ble t o recei ve at least 7 5 % of t he i nte n de d seli ne x or d ose  f or reas o ns ot her t ha n t o xicit y a n d 
di d n o t e x perie nce a D L T, t h ose s u bjects will be re place d t o all o w f or m ore acc urate D L T 
assess me nt.  S u bjects w h o recei v e  at least o ne d ose of pe m br o liz u ma b are e val ua ble f or D L T. 
H ol di n g dr u g d ue t o t o x icit y d oes  n ot me et t he defi niti o n of D L T as l o n g as t he s ubject recei ves 
at least 7 5 % of t he i nte n de d seli ne x or d ose .  
4. 1. 2    
Defi niti o n of R P 2 D  
T he Rec o m me n de d P has e 2 D ose ( R P 2 D) is t he hi g hest d ose of seli ne x or i n c o m bi nati o n wit h 
pe m br oliz u ma b at w hic h t here are 0 or 1/ 6 D L Ts o bser ve d d uri n g t he D L T assess me nt wi n d o w 
(first 2 c ycles). 
4. 2   
P h ase II E x p a nsi o n at R P 2 D  
After i de ntificati o n of t he R P 2 D, a n e x pa nsi o n c o h ort will be e nr olle d  t o recei ve c o m bi nati o n 
t hera p y at t he esta blis he d R P 2 D. A d diti o nal patie nts will be e nr olle d i n t he P hase II p orti o n of 
t he st u d y t o accru e a t otal of 2 7 patie nts at t he R P 2 D  t o f urt her e val uate t o xicit y a n d t o e val uate 
efficac y as d efi ne d b y o bjecti ve res p o nse rate .  C o m bi ne d seli ne x or a n d pe m br oliz u ma b will 
c o nti n ue f or 2 4  m o nt hs or u ntil pr o gress i o n or u nacce pta ble t o xicit y.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 4  of 6 8  
S u bjects  will be assesse d e ver y 3 wee ks cli nicall y f or t o xicit y. S u bjects  will be assesse d e ver y 6 
wee ks f or res p o nse or pr o gressi o n t o t hera p y f or t he first 1 2 wee ks (after w hic h t he y will 
u n der g o ra di o gra p hic i m a gi n g e ver y 1 2 wee ks) a n d will c o nti n ue o n treat me nt u ntil t he ti me of 
u nacce pta ble t o xicit y or u ntil e vi de nce of pr o gressi ve disease b y R E CI S T v 1. 1 o n ra di o gra p hic 
i ma gi n g.  
B l o o d sa m ples will be dra w n o n D a y 0, D a y 8  (± 3  da ys ) a n d D a y 2 1  (± 3  da ys ) of C ycle 1, a n d 
w he n s u b jects c o me off st u d y (± 7 da ys ). 
5. 0   
T R E A T M E N T O F S U B J E C T S  
5. 1   
St u d y Tre at me nt  A d mi nistr ati o n   
T a ble 3 : D ose F or ms of St u d y T re at me nts  
Pr o d uct N a m e & P ote nc y  
D os a ge F or m  
Pe m br oliz u ma b 5 0 m g (si n gle use vial)  
L y o p hilize d P o w der f or I njecti o n  
Pe m br oliz u ma b 1 0 0 m g/ 4 m L (si n gle use vial)    
S ol uti o n f or I njecti o n  
Seli ne x or 2 0 m g  
Oral ta blets  
 
5. 2   
Seli ne x or  
5. 2. 1    
D osi n g a n d A d mi nistr ati o n  
Seli ne x or starti n g d ose f or t his st u d y will be 8 0 m g ( f o ur 2 0 m g ta blets) o n D a y 1, D a y 8, a n d 
D a y 1 5 of a 2 1 -da y c y cle. Seli ne x or a n d pe m br o li z u ma b m ust be a d mi nistere d o n D a y 1 , b ut t he 
se q ue nce of a d mi nistrati o n  is at t he discreti o n of t he treati n g p h y sicia n. 
Seli ne x or ta blets s h o ul d be ta ke n orall y wit h at least 1 2 0 m L ( 4 o u nces) of water at 
a p pr o xi matel y t he sa me ti me eac h d a y. It ca n be ta ke n wit h or wit h o ut f o o d. Seli ne x or ta blets 
s h o ul d be s wall o we d w h ole ( n ot cr us he d) t o pre ve nt a n i ncrease d ris k of der mat ol o gic t o xicit y if 
t he p o w der c o m es i n c o ntact wit h s ki n.  
All patie nts will be gi ve n a diar y t o rec or d t he ti mi n g of ta ki n g seli ne x or o ver 2 1 da ys (see 
A p pe n di x); t he patie nt di ar y will be re vi e we d at eac h cli nic visit.  
I n or der t o mi ni mize na usea, all patie nts s h o ul d recei ve 5 -H T 3 a nta g o nists ( o n da nsetr o n 8 m g or 
e q ui vale nt), u nless c o ntrai n dicate d, a p pr o xi matel y 3 0 mi n utes pri or t o  a n d c o nti n ue d 2 -3 ti mes 
dail y f or 3 da ys after seli ne x or d osi n g. Alter nati ve a ntie metic a ge nts ma y be use d if t he patie nt 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 5  of 6 8  
d oes n ot t olerate or h as i na de q uate a ntie metic effect wit h 5 -H T 3 a nt a g o nist.  I n a d diti o n, patie nts 
s h o ul d recei ve ol a nza pi n e 2. 5 m g oral Q H S  starti n g o n Da y 1 f or at least t he first 2 c ycles. T he 
ola nza pi ne d ose m a y be re d uce d t o dail y P R N d ue t o si de effects or st o p pe d after 2 m o nt hs if 
na usea is well c o ntr olle d .  
Misse d or V o mite d D oses  
If a patie nt misses a d os e of seli ne x or, t he n t hat d ose s h o ul d be re place d if t he s u bject re m e m bers 
wit hi n a 3 da y wi n d o w  ( wit hi n 7 2 h o urs of misse d d ose). Ot her wise, patie nts s h o ul d ta ke t he 
ne xt d ose t he f oll o wi n g wee k, wit h o ut c o m pe nsati n g f or t he misse d d ose. D o n ot d o u ble d ose. 
Misse d d oses s h o ul d be rec or de d i n t he e C R F. If a  patie nt misses a n i nf usi o n of pe m br oliz u ma b, 
d ose ma y be re place d wit hi n 3 da ys.  
If a d ose of seli ne x or is v o mite d wit hi n 1 h o ur of i n gesti o n, it ma y  be re place d ,  b ut s u bject will 
nee d t o n otif y st u d y tea m . If v o miti n g occ urs m ore t ha n 1 h o ur after d osin g, it will be c o nsi dere d 
a c o m plete d ose a n d t he d ose ca n n ot be re place d  
5. 2. 2    
F or m ul ati o n, P ac k a gi n g, a n d H a n dli n g  
Seli ne x or  is f or m ulate d as a bl ue, r o u n d, bi -c o n ve x, fil m -c oate d i m me diate release 2 0 m g ta blet 
wit h “ K 2 0” de b osse d o n o ne si de a n d n ot hi n g o n t he ot her si de. Seli ne x or 2 0 m g ta blets f or oral 
a d mi nistrati o n  will be pac ka ge d  i n w allet-size d c hil d-resista nt blister pac ks. Eac h blister pac k 
has 1 2 ta blets  (see I S T P har mac y M a n ual f or m ore i nf or mati o n). Ta bl ets s h o ul d be st ore d at or 
bel o w 3 0 o C ( 8 6 o F) . 
5. 2. 3    
Pre p ar ati o n  
Refer t o t he I S T P har mac y Ma n ual f or details of seli ne x or f or m ulati o n, pre parati o n, a n d 
a d mi nistrati o n.  
5. 2. 4    
H o w S u p plie d  
Seli ne x or  will be s u p plie d b y Kar y o p har m a t n o c ost t o st u d y patie nts.  
5. 3   
Pe m br oliz u m a b  
Pe m br oliz u ma b will be a d mi nistere d at a d ose of 2 0 0 m g as a n I V i nf usi o n o ver 3 0 mi n utes o n 
D 1 ( ±  3 da ys) of a 2 1 -da y  c ycle pr o vi de d b ot h st u d y dr u gs are t a ke n o n t he sa me da y . 
Dela ye d i nf usi o ns: If a p atie nt misses a n i nf usi o n of pe m br oliz u ma b, t he n t hat d ose s h o ul d be 
re placed wit hi n 3 da ys. Ot her wise, t his will be c o nsi dere d a misse d d ose.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 6  of 6 8  
5. 3. 1    
F or m ul ati o n, P ac k a gi n g, a n d H a n dli n g  
Pe m br oliz u ma b f or i njecti o n as a clear t o sli g htl y o palesce nt, c ol orless t o sli g htl y yell o w s ol uti o n 
is pac ka ge d i n a cart o n c o ntai ni n g o ne 1 0 0 m g/ 4 m L ( 2 5 m g/ m L), si n gle-d ose vial ( N D C 0 0 0 6 -
3 0 2 6 -0 2). Vials s h o ul d be st ore d u n der refri gerati o n at 2 -8 oC ( 3 6 -4 6 o F) i n ori gi nal cart o n t o 
pr otect fr o m li g ht. T he vi als s h o ul d n ot be fr oze n  a n d s h o ul d n ot be s ha ke n.  
5. 3. 2    
Pre p ar ati o n  
Refer t o t he Pe m br oliz u ma b prescr i bi n g i nf or m ati o n f or a d diti o nal g ui da nce o n st u d y dr u g 
st ora ge, pre p arati o n a n d ha n dli n g. 
5. 3. 3    
H o w S u p plie d  
Pe m br oliz u ma b is c o m merciall y a vaila ble a n d will be  l ocall y s o urce d fr o m c o m mercial, sta n dar d 
of care s u p plies.  
5. 3. 4    
Dis p os al a n d Destr ucti o n  
Res p o nsi bilit y  f or dr u g acc o u nta bilit y is o n t he i n vesti gat or a n d t he assi g ne d p har macist or 
desi g nee. Dr u g s u p pl y will be dis p ose d of acc or di n g t o i nstit uti o nal  sta n dar d o perati n g 
pr oce d ure s. Acc urat e rec or ds of all i n vesti gati o nal pr o d uct recei ve d at  a n d dis pe nse d fr o m t he 
st u d y site s h o ul d be rec or de d o n t he Dr u g L o g.  
5. 4   
M o nit ori n g  
Safet y will be e val uat e d i n t his st u d y t hr o u g h t he m o nit ori n g of all seri o us a n d n o n -seri o us A Es, 
defi ne d a n d gra de d acc or di n g t o N CI C T C A E v 5. 0.   Patie nts will be assesse d f or safet y 
(i ncl u di n g la b orat or y val ues) acc or di n g t o t he St u d y Cale n dar.  Patie nts will be f oll o we d f or 
pr ot oc ol -relat e d t o xicit y f or 3 0  da ys f oll o wi n g t he last d ose o f st u d y treat m e nt, w hic he ver c o mes 
first. Ge neral safet y assess me nts will i ncl u de serial i nter val hist ories, p h ysical e xa mi nati o ns, a n d 
s pecific la b orat or y st u dies, i ncl u di n g ser u m c he mistries a n d bl o o d c o u nts (see St u d y Cale n dar 
f or t he list a n d ti mi n g of st u d y assess me nts).  All  seri o us a d verse e ve nts ( S A Es) will be 
re p orte d i n a n e x pe dite d f as hi o n . I n a d diti o n, t he i n vesti gat ors will re vie w a n d e val u ate 
o bser ve d A Es o n a re g ul ar basis.  
Patie nts w h o ha ve a n o n g oi n g st u d y treat me nt -relate d A E u p o n st u d y c om pleti o n or at 
disc o nti n uati o n fr o m t he st u d y will be f oll o we d u ntil t he e ve nt has res ol ve d t o baseli ne gra de, t he 
e ve nt is assesse d b y t he i n vesti gat or as sta ble, ne w a ntica ncer treat me nt is i nitiate d, t he patie nt is 
l ost t o f oll o w-u p, t he patie nt wit h dra ws c o ns e nt, or u ntil it has bee n deter mi ne d t hat st u d y 
treat me nt or partici pati o n is n ot t he ca use of t he A E. 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 7  of 6 8  
5. 5   
D ose M o dific ati o n a n d M a n a ge me nt of T o xicit y  
5. 5. 1    
D ose  Del a y  a n d Disc o nti n u ati o n  
T o xicit y necessitati n g d ose m o dificati o n or de la y is base d o n N CI C T C AE v 5. 0  T o xicit y Gra de. 
T he I n vesti gat or will ass ess w het her eac h A E is relate d or n ot t o eac h of t he st u d y dr u gs. E ve nts 
t hat are j u d ge d defi nitel y, pr o ba bl y or p ossi bl y rel ate d are c o nsi dere d relate d A Es. E ve nts t hat 
are c o nsi d ere d u nli kel y or defi nitel y n ot relate d are c o nsi dere d n ot relate d A Es. Fact ors t o be 
ta ke n i nt o c o nsi derati o n i ncl u de t he te m p oral relati o ns hi p bet wee n a d mi nistrati o n of st u d y dr u g 
a n d t he o nset of t he A E, ot her p ote ntial ca us es of t he A E i ncl u di n g t he s u bject’s u n derl yi n g 
me dical c o n diti o n a n d c o nc o mita nt me dicati o ns, w het her t he A E is c o nsiste nt wit h k n o w n A Es 
pre vi o usl y attri b ute d t o a st u d y dr u g, w het her t he A E decreases or res ol v es u p o n wit h h ol di n g or 
re d uci n g t he d ose of t he st u d y dr u g, or w het her t h e A E rec urs u p o n rei ntr o d ucti o n of t he st u d y 
dr u g.   
5. 5. 2    
T o xicities Necessit ati n g D ose M o dific ati o n or Del a y  
T he f oll o wi n g acti o n i n Ta ble 4  a n d Ta ble 5  s h o ul d be ta ke n f or a n y st u d y dr u g-relate d t o xicit y 
o utli ne d bel o w, di vi de d i nt o im m u ne -me diate d A Es ( Ta ble 4 ) a n d n o n-im m u ne me diate d A Es 
( Ta ble 5 ). 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 8  of 6 8  
T a ble 4 . D ose M o dific ati o n D ue t o  I m m u ne-Me di ate d T o xicit y  
A d verse Re acti o n  
Se verit y  
D ose M o dific ati o n  
I m m u ne-me diate d 
p ne u m o nitis  
Gra de 2  
Wit h h ol d pe m br oliz u ma b  
Gra de 3 or 4 or rec urre nt Gra de 2  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b  
I m m u ne-me diate d 
c olitis  
Gra des 2 or 3  
Wit h h ol d pe m br oliz u ma b a n d seli ne x or u ntil 
res ol uti o n 
Gra de 4  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b. 
C o nti n ue seli ne x or at o ne d ose le vel l o wer.  
I m m u ne-me diate d 
he patitis  
A S T or A L T greater t ha n 3 b ut n o m ore t ha n 5 
ti mes t he U L N or t otal bilir u bi n greater t ha n 1. 5 
b ut n o m ore t ha n 3 ti mes t he U L N  
Wit h h ol d pe m br oliz u ma b  
A S T or A L T greater t ha n 5 ti mes U L N or t otal 
bilir u bi n greater t ha n 3 ti mes U L N 
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b  
I m m u ne-me diate d 
e n d ocri n o pat hies 
Gra de or 4  
Wit h h ol d pe m br oliz u ma b u ntil cli nicall y 
sta ble, c o nti n ue seli ne x or 
I m m u ne-me diate d 
ne p hritis  
Gra de 2  
Wit h h ol d pe m br oliz u ma b, c o nti n ue 
seli ne x or 
Gra de 3 or 4  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b, 
c o nti n ue seli ne x or  
I m m u ne-me diate d 
s ki n a d verse 
reacti o ns 
Gra de 3 or s us pecte d Ste ve ns -J o h ns o n 
S y n dr o me ( SJ S) or t o xic e pi der mal necr ol ysis 
( T E N) 
Wit h h ol d pe m br oliz u ma b a n d seli ne x or u ntil 
res ol uti o n. Res u me seli ne x or at sa me d ose 
le vel. 
Gra de 4 or c o nfir me d SJ S or T E N  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b, 
res u me seli nex or at o ne d ose le vel l o wer.  
Ot her i m m u ne -
me diate d a d verse 
reacti o ns 
Gra de 2 or 3 base d o n t he se verit y a n d t y pe of 
reacti o n 
Wit h h ol d pe m br oliz u ma b, ca n c o nti n ue 
seli ne x or if A E is n ot relate d t o seli ne x or 
Gra de 3 base d o n t he se verit y a n d t y pe of 
reacti o n or Gra de 4 
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b  
Rec urre nt i m m u ne -
me diate d a d verse 
reacti o ns 
Rec urre nt Gra de 2 p ne u m o nitis  
 
Rec urr e nt Gra de 3 or 4  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b. 
H ol d seli ne x or u ntil res ol uti o n of s y m pt o ms, 
t he n res u me. 
I na bilit y t o ta per 
c ortic oster oi d 
Re q uire me nt f or >  1 0 m g per da y pre d nis o ne or 
e q ui vale nt f or m ore t ha n 1 2 wee ks after last 
d ose of pe m br oliz u ma b  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b. 
C o nti n ue seli ne x or.  
I nf usi o n-relate d 
reacti o ns 
Gra de 1 or 2  
I nterr u pt or sl o w rate of i nf usi o n of 
pe m br oliz u ma b. C o nti n u e seli ne x or. 
Gra de 3 or 4  
Per ma ne ntl y disc o nti n ue pe m br oliz u ma b, 
c o nti n ue seli ne x or  
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 2 9  of 6 8  
T a ble 5 . D ose M o dific ati o n D ue t o N o n-I m m u ne Me di ate d T o xicit y 
A d verse Re acti o n    
Occ urre nce  
Acti o n *  
He m at ol o gic A d verse Re acti o ns  
T hr o m b oc yt o pe ni a  
Platelet c o u nt 2 5, 0 0 0 t o 
less t ha n 7 5, 0 0 0/ mc L 
A n y    
Re d uce seli ne x or b y 1 d ose le vel  
Platelet c o u nt 2 5, 0 0 0 t o 
less t ha n 7 5, 0 0 0/ mc L wit h 
c o nc urre nt blee di n g  
A n y    
- h ol d seli ne x or a n d pe m br oliz u ma b  
- res u me pe m br oliz u ma b a n d res u me seli ne x or at 1 d ose le vel l o wer 
after res ol uti o n of blee di n g  
Platelet c o u nt less t ha n 
2 5, 0 0 0/ mc L  
A n y    
- h ol d seli ne x or a n d pe m br oliz u ma b  
- res u me pe m br oliz uma b a n d res u me seli ne x or at 1 d ose le vel l o wer 
after platelet c o u nt > 5 0, 0 0 0/ mc L  
Ne utr o pe ni a  
A bs ol ute ne utr o p hil c o u nt 
of 0. 5 - 1. 0 x 1 0 9/ L wit h o ut 
fe ver 
A n y    
Re d uce seli ne x or b y 1 d ose le vel  
C o nti n ue pe m br oliz u ma b  
A bs ol ute ne utr o p hil c o u nt 
less t ha n 0. 5 x 1 09/ L O R 
fe brile ne utr o pe nia 
A n y    
H ol d seli ne x or  
M o nit or u ntil ne utr o p hil c o u nt r et ur ns t o 1. 0 x 1 0 9/ L or hi g her  
Res u me seli ne x or at o ne d ose le vel l o wer  
C o nti n ue pe m br oliz u ma b  
A ne mi a  
Gra de 3  
A n y    
A d mi nister bl o o d tra nsf usi o ns  
Re d uce seli ne x or b y o ne d ose le vel  
C o nti n ue pe m br oliz u ma b  
Gra de 4  
A n y    
Disc o nti n ue seli ne x or  
H ol d pe m br oliz u ma b u ntil A E <  Gra de 2, t he n res u me  
H y p o n atre mi a  
S o di u m le vel < 1 3 0 
m m ol/ L  
A n y    
H ol d seli ne x or a n d pe m br oliz u ma b  
M o nit or u ntil s o di u m le vels ret ur n t o 1 3 0 m m ol/ L or hi g her  
Res u me seli ne x or at 1 d ose le vel l o wer, res u me pe m br oliz u ma b  
F ati g ue  
Gra de 2 lasti n g greater 
t ha n 7 da ys or Gra de 3 
 
H ol d seli ne x or a n d pe m br oliz u ma b  
M o nit or u ntil fati g ue res ol ves t o Gra de 1 or baseli ne  
Res u me seli ne x or at 1 d ose le vel l o wer; res u me pe m br oliz u ma b  
N a use a a n d V o miti n g  
Gra de 1 or 2 na usea ( oral 
i nta ke decrease d wit h o ut 
si g nifica nt wei g ht l oss, 
de h y drati o n or 
mal n utriti o n) O R Gra de 1 
or 2 v o miti n g ( 5 or fe wer 
e pis o des per da y)  
A n y    
C o nti n ue seli ne x or a n d pe m br oliz u ma b, a d d a d diti o nal a nti -na usea 
me dicati o ns.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 0  of 6 8  
Gra de 3 na usea or Gra de 3  
or hi g her v o miti n g  
A n y    
H ol d seli ne x or.  
M o nit or u ntil s y m pt o ms res ol ve t o Gra de 2 or l o wer  
A d d a d diti o nal a nti -na usea me dicati o ns  
Res u me seli ne x or at o ne d ose le vel l o wer  
Di arr he a  
Gra de 2  
1 st 
occ urre nce  
wit h o ut 
s u p p orti ve 
care 
C o nti n ue seli ne x or a n d pe m br oliz u ma b  
A d d s u p p orti ve care  
2 n d a n d 
a d diti o nal 
occ urre nce  
wit h o pti mal 
ma na ge me nt  
Re d uce seli ne x or b y o ne d ose le vel, c o nti n ue pe m br oliz u ma b  
C o nti n ue s u p p orti ve care  
Gra de 3 or hi g her    
A n y    
H ol d seli ne x or; h ol d pe m br oliz u ma b if a n y s us pici o n of c olitis 
A d d s u p p orti ve care  
M o nit or u ntil res ol uti o n t o Gra de 2 or less  
Res u me seli ne x or at o ne d ose le vel l o wer, c o nti n ue pe m br oliz u ma b  
Wei g ht l oss a n d A n ore xi a  
Wei g ht l oss of 1 0 % t o less 
t ha n 2 0 % O R a n ore xia 
ass ociate d wit h si g nifica nt 
wei g ht l oss or mal n utriti o n  
A n y    
H ol d seli ne x or, c o nti n ue pe m br oliz u ma b  
M o nit or u ntil wei g ht >  9 0 % of baseli ne wei g ht  
Res u me seli ne x or at o ne d ose le vel l o wer  
Wei g ht l oss of > 2 0 %    
A n y    
Disc o nti n ue  
I nfecti o ns  
Acti ve u nc o ntr olle d or 
s us pecte d i nfecti o ns 
A n y    
H ol d u ntil t he i nfecti o n has cli nicall y res ol ve d a n d/ or t he patie nt is 
cli nicall y sta ble. W he n rea d y t o res u me d osi n g, treat me nt ma y c o nti n ue 
at t he ori gi nal d ose  (see secti o n 5. 5. 3. 1) 
*st u d y dr u gs ca n be h el d f or u p t o 1 2 wee ks, after w hic h patie nt m ust c o me off st u d y  
5. 5. 3    
Seli ne x or  D ose M o dific ati o ns  
D ose re d u cti o ns d ue t o i nt olera ble t o xicit y are all o we d per Secti o n 5. 5 . 2 a b o ve. S c he d ule 
m o dificati o ns are all o we d i n s o me cases per treati n g i n vesti gat or. F or s o me A Es, d ose 
i nterr u pti on a n d/ or re d u cti o n is rec o m me n de d. See Ta ble 6  f or pre-s pecifi e d d ose m o dificati o ns 
f or A Es relate d t o st u d y treat me nt a n d see Ta bl e 5  f or d ose re d ucti o n a n d i nterr u pti o n 
rec o m me n dati o ns. 
W hile dr u g -relate d maj or or ga n t o xicities are n ot pr o mi ne nt, t hr o m b oc yt o pe nia a n d a n u m ber of 
c o nstit uti o nal si de effects ca n li mit d osi n g wit h seli ne x or. T heref ore, patie nts s h o ul d als o be 
treate d wit h s u p p orti ve care t o re d uce t o xicities. I n a d diti o n, it s h o ul d be n ote d t hat t he 
c o nstit uti o nal si de effects ofte n atte n uat e o ver t he first 4 t o 6 wee ks of d osi n g. Fi nall y, s o me 
patie nts wit h ra pi d t u m or res p o nses e x perie nce si g nifica nt fati g ue, na usea, malaise a n d/ or 
ast he nia after o ne  or m ore d oses of seli ne x or. T his effect has n ot bee n ass ociate d wit h t y pical 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 5  of 6 8  
5. 5. 3. 1   
Seli ne x or D ose A dj ust me nt i n t he S etti n g of I nfecti o n  
Patie nts wit h acti ve u nc o ntr olle d or s us pecte d i nfecti o ns s h o ul d ha ve treat me nt wit h hel d u ntil t he 
i nfecti o n has cli nicall y res ol ve d a n d/ or t he patie nt is cli nicall y sta ble. W he n rea d y t o res u me 
d osi n g, treat me nt ma y c o nti n ue at t he ori gi nal d ose. Misse d d oses will n ot be re place d. Patie nts 
ma y c o nti n ue a nti bi otics f or pr ol o n ge d peri o ds w hile re -i nitiati n g t heir treat me nt at t he discreti o n 
of t he I n vesti gat or.  
5. 5. 3. 2   
C o n diti o ns N ot Re q uiri n g Seli ne x or D ose Re d ucti o n  
T he f oll o wi n g c o n diti o ns ar e e x ce pti o ns t o t he d ose -m o dificati o n g ui deli nes. Seli ne x or d oes n ot 
nee d t o be i nterr u pte d or re d uce d i n t he f oll o wi n g cases:  
•  Al o pecia of a n y gra d e  
•  Electr ol yte or ser u m a nal yte (e g, urate) a b n or malities e xce pt f or h y p o natre mia t hat are 
re versi ble wit h stan d ar d i nter ve nti o ns  
•  Is olat e d val ues of Gra d e ≥3 al kali ne p h os p hatase. Deter mi nati o n of li ver vers us b o ne 
eti ol o g y s h o ul d be ma de, a n d e val uati o n of ga m ma -gl uta m yl tra nsferase, 5' n ucle oti dase, 
or ot her li ver e n z y mes s h o ul d be perf or me d.  
 
5. 5. 1    
Criteri a t o Res u me  Tre at me nt  
S u bjects ma y res u me treat me nt wit h st u d y dr u g w he n t he dr u g -relate d A E(s) o utli ne d i n Ta ble 4  
a n d Ta ble 5  res ol ve t o Gra de ≤ 1 or bas eli ne val ue, wit h t he f oll o wi n g e xce pti o ns:  
•  S u bjects w h o ha ve e x p erie nce d a Gra de 3 dr u g -rel ate d s ki n A E t hat is dee me d t o re q uire 
treat me nt h ol d ma y res u me treat me nt i n t he pres e nce of Gra de 2 s ki n t o xicit y.  
•  Dr u g -relate d p ul m o nar y t o xicit y t hat is dee me d t o re q uire treat me nt h ol d m u st ha ve 
res ol ve d t o baseli ne b ef ore treat me nt is res u me d.  
•  A n y e xce pti o n o utli ne d i n Ta ble 4  a n d Ta ble 5  
•  S u bjects ma y res u me pe m br oliz u ma b if st u d y dr u g is hel d d ue t o seli ne x or -attri b uta ble 
t o xicit y. Patie nts ca n c o nti n ue seli ne x or if hel d d u e t o pe m br oliz u ma b-attri b uta ble 
t o xicit y. 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 6  of 6 8  
5. 6   
I nstr ucti o ns f or I niti ati o n of E ac h C ycle 
Eac h c y cle of treat me nt ma y be gi n o n t he sc he d ul e d Da y 1 of a ne w c ycle if:  
•  T he A N C is ≥ 1 0 0 0/ m m³;  
•  T he platelet c o u nt is ≥ 7 5 , 0 0 0/ m m³ ( patie nts f or w h o m < 5 0 % of b o ne marr o w n ucleate d 
cells are pl as ma cells) or ≥5 0, 0 0 0/ m m 3 ( patie nts f or w h o m ≥5 0 % of b o ne marr o w 
n ucleate d cells are pl as ma cells) ;   
•  N o e vi de nce of life -t hreate ni n g i nfecti o n.  
 
If t hese c o n diti o ns are n ot met o n Da y 1 of a ne w c ycle, t he s u bject will be e val uate d wee kl y a n d 
a ne w c y cle of treat me nt will n ot be i nitiate d u ntil t he t o xicit y has res ol ve d as descri be d a b o ve.   
6. 0   
T R E A T M E N T D U R A TI O N  
S u bjects will recei ve c o m bi nati o n t hera p y f or u p t o 2 4  m o nt hs u nless o ne of t he f oll o wi n g 
criteria a p plies:  
•  C o nfir me d d isease pr o gressi o n per R E CI S T  v 1. 1  
•  I nterc urre nt ill ness t hat pre ve nts f urt h er a d mi nistrati o n of treat me nt 
•  U nacce pta ble a d verse e v e nts  
•  Patie nt wit h dra wal fr o m st u d y ( patie nt c h oice)  
•  Pre g na nc y  
•  Patie nt recei ves alter nati ve ca n cer -direct e d treat m e nt 
•  St u d y ter mi nati o n  
•  P h ysicia n Discreti o n  
 
6. 1   
Disc o nti n u ati o n Criteri a  
6. 1. 1    
D isc o nti n u ati o n fr o m St u d y Tre at me nt  
Patie nts will be disc o nti n ue d fr o m st u d y treat me nt d ue t o disease pr o gressi o n per R E CI S T v 1. 1 
criteria, d u e t o u nacce pta ble t o xicit y eit her i n t he o pi ni o n of t he i n vesti gat or or t he patie nt, or if 
t he patie nt wit h dra ws c o nse nt.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 7  of 6 8  
6. 1. 2    
Disc o nti n u ati o n D ue t o A Es  
Patie nts will disc o nti n ue st u d y treat me nt d ue  t o u nacce pta ble t o xicit y  per secti o n 4. 1. 1 at a n y 
ti me w hile o n st u d y treat me nt, b ut patie nts will c o nti n ue cli nical f oll o w -u p u ntil disease 
pr o gressi o n or i nitiati o n of ne w treat me nt. I n t he case of A Es Gra de > 3, if i n t he o pi ni o n of t he 
i n vesti gat or or t he patie nt, t he patie nt ca n n o l o n g er be ass esse d cli nicall y d ue t o se verit y of 
ill ness, t he patie nt will be disc o nti n ue d fr o m t he trial, b ut will be i ncl u de d i n t he t o xicity 
e val uati o n f or t he st u d y.  
6. 2   
D ur ati o n of F oll o w U p  
All patie nts will be f oll o we d f or 3 0  d a ys after t he last d ose of treat me nt or u ntil all treat me nt 
relate d t o xicities res ol ve t o baseli ne or G ra de ≤ 1. A d verse e ve nts wit h attri b uti o n of p ossi ble, 
pr o ba ble , or defi nite will be re p orte d f oll o wi n g g ui deli nes f or a d verse e ve nt re p orti n g , a n d all 
S A Es will be re p orte d f or 3 0  da ys after t he last d ose.    
Patie nts will be f oll o we d e ver y 3 m o nt hs per S O C  f or d oc u me nte d pr o gressi o n, P F S, u ntil deat h, 
l oss t o f oll o w u p, c o nse nt wit h dra wal, or st u d y ter mi nati o n.  
Patie nts w h o disc o nti n ue st u d y treat me nt earl y will be f oll o we d f or pr o gressi o n free s ur vi val 
( P F S) e ver y 3 m o nt hs  as part of t heir r o uti ne S O C ma na ge me nt . 
6. 3   
Ter mi n ati o n of Tre at me nt a n d St u d y P artici p ati o n  
Patie nts will be i nf or me d t hat t he y ha ve t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me f or a n y 
reas o n, wit h o ut prej u dice t o t heir me dical care. T he i n vesti gat or als o has t h e ri g ht t o wit h dra w 
patie nts fr o m t he st u d y f or safet y, b e h a vi oral or a d mi nistrati ve reas o ns.  
T he I n vesti gat or will ma ke e ver y reas o na ble eff ort t o kee p eac h patie nt i n t he st u d y u nless it is i n 
t he patie nt’s best i nterests t o disc o nti n ue partici pati o n.  If a patie nt is re m o ve d fr o m t he st u d y or 
decli nes f urt he r partici p ati o n, all E n d of Treat me nt e val uati o ns s h o ul d be perf or me d if t he patie nt 
is willi n g a n d a ble t o be assesse d.  A des cri pti o n of t he reas o n(s) f or wit h dra wal fr o m t he st u d y 
m ust be rec or de d o n t he case re p ort f or m ( C R F).  T he I n vesti gat or s h o ul d als o e ns ure t hat all 
patie nts are f oll o we d u p f or s ur vi val stat us after t h e E n d of Treat me nt  Visit.  
Patie nts w h o disc o nti n ue f oll o wi n g e ntr y will ha ve rele va nt i nf or mati o n c o m plete d a n d rec or de d 
o n t he C R F.  All patie nts w h o disc o nti n ue beca us e of a d verse e ve nts or cli nicall y si g nifica nt 
la b orat or y a b n or malities s h o ul d be f oll o we d u p u ntil t he y rec o ver or sta bilize, a n d t he 
s u bse q ue nt o utc o me will be rec or de d. T he ca us e of deat h s h o ul d be rec or de d i n detail, wit hi n 2 4 
h o urs, o n a seri o us a d v erse e ve nt ( S A E)  f or m a n d re p orte d t o i nstit uti o nal, fe deral, a n d a n y ot her 
c o m mittees a n d/ or f u n di n g s o urce as a p pr o priate . 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 8  of 6 8  
7. 0   
C O N C O MI T A N T A N D E X C L U D E D M E DI C A TI O N  
7. 1   
C o nc o mit a nt  T her a p y  
Pr o p h ylactic c o nc o mita nt treat me nt wit h a 5 -H T 3 a nta g o nist a n d/ or ot her a nti -na usea a ge nts  
pri or t o a n d d uri n g treat me n t wit h seli ne x or will be a d mi nistere d.  Alter nati ve treat me nt ma y be 
pr o vi de d if t he patie nt d o es n ot t olerate 5 -H T 3 a nt a g o nists . I ntra ve n o us h y drati o n ma y als o be 
offere d t o patie nts w hile o n t hera p y.  
N o c o nc o mita nt t hera p y is re q uire d d uri n g treat me nt wit h pe m br oliz u ma b.  
7. 2   
E xcl u de d  T her a p y  
Patie nts m ust n ot ta ke  pre d nis o ne at a d ose  of  greater t ha n 1 0 m g P O dail y  ( or e q ui vale nt d ose of 
a n y ot her c ortic oster oi d ). 
Patie nts  are pr o hi bite d fr o m ta ki n g i m m u n os u p pressi ve a ge nts s uc h as c ycl os p ori ne, 
met h otre xate, m yc o p h e n olate m ofetil, i nfli xi ma b.  
7. 3   
Per mitte d T her a p y  
Pre d nis o ne  is per mitte d at a d ose ≤ 1 0 m g P O per  da y . 
 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 3 9  of 6 8  
8. 0   
S T U D Y C A L E N D A R  
E v al u ati o n  
Pre -Tre at me nt  
Tre at me nt 
C ycles  
(3 -wee k c ycles ) 
E n d of 
Tre at me nt 9 
P ost -
Tre at me nt 1 1 
 
Scree ni n g 1  
( # da ys pri or t o first d ose) 
All C ycles 3   
Safet y Visit  
Sc he d uli n g Wi n d o w ( da ys)  
≤ 2 8    
≤ 1 4  
± 3  
± 7  
Hist or y  
 
 
 
Me dical Hist or y  
X    
 
X  
X  
Cli nic al/ L a b or at or y/ Assess m e nts  
 
 
P h ysical E xa m  
   
X  
X  
X  
Vital S i g ns 
   
X  
X  
X  
A E  a n d C o nc o mita nt M e dicati o ns  
 
 
C o nti n u o usl y  
He mat ol o g y ( C B C wit h D iffere ntial)   
   
X  
X  
X  
Ser u m C he mistr y ( C M P )1 2 
   
X  
X  
X  
T S H  
   
X  
X  
X  
He p B/ C, HI V  
X    
 
 
 
 
Pre g na nc y T est (if a p plica ble)6 
   
X  
 
 
 
C hest/ A b d o me n/ Pel vis C T Ima gi n g
2   
X  
 
X  
 
C orrel ati ves  
Pre -treat me nt T iss ue B i o ps y 
X 4  
 
 
 
 
Bl o o d S a m ple 
   
X  
X 5 
 
St u d y Tre at m e nt A d mi nistr ati o n  
Seli ne x or 7 
 
 
X  
 
Pe m br oliz u ma b 8 
 
 
X  
 
1.  Scree ni n g: Scree ni n g cli nical safet y la b orat or y e val uati o ns ca n be use d f or C ycle 1 Da y 1 assess me nts if 
perf or me d ≤ 1 4 da ys pri or t o first d ose.  
2.  I ma gi n g will be acce pte d if perf or me d ≤ 6 0 da ys pri or t o first d ose. C T i ma gi n g assess me nt will be perf or me d 
e ver y 6 wee ks f or first 4 c ycles of treat me nt, t he n e ver y 1 2 wee ks.  
3.  D L T assess me nt wi n d o w is 6 wee ks . 
4.  Pre -treat me nt tiss ue bi o ps y is re q uire d o nl y if patie nt d oes n ot ha ve a vaila ble arc hi val tiss ue. See Secti o n 1 0. 0.  
5.  Bl o o d sa m ples f or c orrelati ve st u dies will be o btai ne d o n D a y 0, D a y 8  (± 3  da ys ) a n d Da y 2 1  (± 3  da ys ) of 
C ycle 1, a n d w he n s u bjects c o me off st u d y (± 7 da ys ). 
6.  F or fe males of c hil d beari n g p ote ntial, a ne gati ve ser u m h u ma n c h ori o nic g o na d otr o pi n ( h C G) pre g na nc y test 
m ust be o btai ne d wit hi n 3 da ys bef ore t he first d ose of st u d y treat me nt.  D uri n g trial treat me nt, uri ne pre g na nc y 
tests s h o ul d be perfor me d as cli nicall y i n dicate d . 
7.  Seli ne x or is ta ke n o n Da y 1, Da y 8, a n d Da y 1 5 of eac h c ycle.  
8.  Pe m br oliz u ma b  is a d mi nistere d o n D 1 of eac h c ycle. Pe m br oliz u ma b s h o ul d  ta ke n o n t he sa me da y as 
Seli ne x or.  
9.  E n d of Treat me nt is at t he ti me t he decisi o n is ma de t o ta ke t he s u bject off st u d y treat me nt .  
1 0.  Safet y Visit: 2 8 da ys after s u bject is ta ke n off st u d y treat me nt. 
1 1.  F oll o w u p: E ver y 3  m o nt hs fr o m E n d of Treat me nt per sta n dar d of care f or s ur vi val f oll o w u p a n d  P F S . P F S 
will be assesse d usi n g R E CI S T 1. 1 criteria . 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 0  of 6 8  
1 2.  Deter mi nati o n of li ver vers us b o ne eti ol o g y s h o ul d be ma de, a n d e val uati o n of ga m ma -gl uta m yl tra nsferase, 5' 
n ucle oti dase, or ot her li ver e nz y mes s h o ul d be perf or me d  (see secti o n 5. 5. 3. 2). 
9. 0   
S T U D Y E V A L U A T I O N S 
9. 1   
Scree ni n g P h ase  
T he scree ni n g p hase is d efi ne d as t he ti me i nter val bet wee n w he n  t he s u bject si g ns t he i nf or me d 
c o nse nt (I C F) a n d t he ti me  of re gistrati o n.   
D uri n g Scree ni n g, eli gi bilit y criteria will be re vie we d a n d a c o m plete cli ni cal e val u ati o n wil l be 
perf or me d as s pecifie d i n t he St u d y Cale n dar. Scree ni n g pr oce d ures will be perf or me d ≤ 2 8  da ys 
pri or t o first d ose, u nless ot her wise s pecifie d. I ma gi n g will be acce pt e d  if perf or me d ≤ 6 0 da ys  
pri or t o first d ose. Scree ni n g cli nical safet y la b orat or y e val uati o ns ca n be us e d f or C ycle 1 Da y 1 
assess me nts if perf or me d ≤ 1 4 da ys pri or t o  first d ose.  
9. 2   
Tre at me nt P h ase  
O ne c ycl e of treat me nt is 2 1  da ys i n w hic h t he s u bject will recei v e t he c o m bi nati o n t hera p y , a n d 
t he treat me nt p hase is u p t o a t otal of 2 4  m o nt hs.  
T he Treat me nt P hase will be gi n at C ycle 1 Da y 1 a n d will c o nti n ue u ntil t he st u d y dr u g is 
disc o nti n ue d. T he last meas ure m e nts ta ke n o n D a y 1 of C ycle 1 bef ore a d mi nistrati o n of t he 
st u d y dr u g or at scree ni n g ( w hic he ver val ue was l ast) will be defi ne d as t he baseli ne val u es.  
9. 3   
E n d of Tre at me nt Visit  
A n e n d-of -treat me nt (E o T ) visit s h o ul d be at t he ti me t he decisi o n is ma de t o ta ke t he s u bject  off 
st u d y treat me nt. If a s u bj ect is u na ble t o ret ur n t o t he site f or t he E o T visit, t he s u bject s h o ul d be 
c o ntacte d t o c ollect A Es t hat occ urre d wit hi n 3 0 da ys  after t he last d ose of st u d y dr u g.  
9. 4   
F oll o w -u p P h ase  
T he safet y f oll o w -u p p hase is t he i nter val bet wee n t he e n d of treat me nt visit a n d sc he d ule d 
safet y f oll o w u p visit w hic h will occ ur 2 8  ( ± 7 da ys) da ys after disc o nti n uati o n of c o m bi nati o n 
t hera p y. Patie nts will be f oll o we d e ver y 3 m o nt hs per S O C f or d oc u me nte d pr o gressi o n, P F S, 
u ntil deat h, l oss t o f oll o w u p, c o nse nt wit h dra wal, or st u d y ter mi nati o n. Patie nts w h o disc o nti n ue 
st u d y treat me nt earl y will be f oll o we d f or pr o gressi o n free s ur vi val ( P F S) e ver y 3 m o nt hs as part 
of t heir r o uti ne S O C ma n a ge me nt.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 1  of 6 8  
If t he s u bject starts o n a ne w a ntica n cer dr u g bef ore 3 0  ( ± 7 da ys) da ys after disc o nti n uati o n of 
st u d y dr u gs, t he safet y f oll o w u p visit s h o ul d be pri or t o t he start of ne w t hera p y. If t he s u bj ect 
disc o nti n ues treat me nt wit h o ut disease pr o gressi o n, t he s u bject will be f oll o we d e ver y 3 m o nt hs  
( or patie nt sta n dar d of care sc he d ul e) b y i ma gi n g t o m o nit or disease stat us. O nce t he s u bject 
starts a ne w t hera p y or h as pr o gressi o n of disease, t he s u bject’s s ur vi val stat us s h o ul d be 
f oll o we d wit h c hart re vie w, tele p h o ne, or e mail u ntil deat h or wit h dra wal of c o n se nt. 
9. 5   
Effic ac y  
Res p o nse a n d pr o gressi o n will be e val uate d i n t his st u d y usi n g t he ne w i nter nati o nal criteria 
pr o p ose d b y t he re vise d Res p o nse E val uati o n Criteria i n S oli d T u m ors ( R E CI S T) g ui deli ne 
( versi o n 1. 1) [1 ]. Cha n ges i n t he lar gest dia meter ( u ni di me nsi o nal m eas ure me nt) of t he t u m or 
lesi o n is use d i n t he R E CI S T criteria  [ 2 5]. 
9. 5. 1    
Res p o nse Criteri a  
9. 5. 1. 1   
E v al u ati o n of T ar get Lesi o ns b y R E CI S T 1. 1  
•  C o m plete Res p o nse ( C R) : Disa p peara nce of t he tar get lesi o n  
•  P arti al Res p o nse ( P R) :  At least a 3 0 % decrease i n t he s u m of t he L D of tar get lesi o ns, 
ta ki n g as refere n ce t he baseli ne s u m L D  
•  Pr o gressi ve Dise ase ( P D) : At least a 2 0 % i ncrease i n t he s u m of t he L D of tar get lesi o n, 
or t he a p peara n ce of o ne or m ore ne w lesi o ns  
•  St a ble Dis e ase ( S D): Neit her s ufficie nt s hri n ka ge t o q ualif y f or P R n or s ufficie nt 
i ncreas e t o q ualif y f or P D, ta ki n g as refere nce t h e s mallest s u m L D si nce t he treat me nt 
starte d 
 
9. 5. 1. 2   
E v al u ati o n of Best O ver all Res p o nse  
T he best o verall res p o nse is t he best res p o nse re c or de d fr o m t he start of t he treat me nt u ntil 
disease pr o gressi o n/rec urre nce (ta ki n g as refere nce f or P D t he s mallest meas ure me nts rec or de d 
si nce t he treat me nt starte d). I n ge neral, t he patie nt's best res p o nse assi g n me nt will de pe n d o n t he 
ac hie ve m e nt of b o t h meas ure me nt a n d c o nfir mati o n criteria. 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 2  of 6 8  
T a ble 8 . Best O ver all Res p o nse E v al u ati o n  
Best O ver all Res p o nse E v al u ati o n  
T ar get Lesi o n    
Ne w Lesi o n    
O ver all Res p o nse  
C R  
N o  
C R  
P R  
N o  
P R  
S D  
N o  
S D  
P D  
Yes or N o  
P D  
 
Patie nts  wit h  a gl o bal  deteri orati o n  of  healt h  stat us re q uiri n g disc o nti n uati o n  of  treat me nt 
wit h o ut  o bjecti ve  e vi de nce of  disease  pr o gressi o n  at t hat ti me s h o ul d be  classifie d as ha vi n g  
“s y m pt o matic deteri orati o n”.  E ver y  eff ort s h o ul d be  ma de  t o d oc u me nt  t he o bjecti ve  pr o gressi o n  
e ve n after disc o nti n uati o n  of  treat me nt.  
I n s o me circ u msta n ces  it ma y  be  diffic ult  t o disti n g uis h  resi d ual disease  fr o m n or mal  tiss ue. 
W he n  t he e v al uati o n  of  c o m plete res p o nse de pe n ds  o n  t his deter mi nati o n,  it is rec o m me n de d t hat 
t he resi d ual lesi o n be i n v esti gate d  (fi ne nee dle  as pirate/ bi o ps y)  t o c o nfir m t he c o m plete res p o nse 
stat us.  
9. 5. 1. 3   
C o nfir m ati o n  
T he  mai n  g oal  of  c o nfir mati o n  of  o bjecti ve  res p o nse is t o a v oi d o veresti mati n g  t he res p o nse rate 
o bser ve d.  F or re p orti n g t he st u d y  o utc o me s t he res p o nse rate a n d c o nfir me d res p o nse rate will be 
ma de clear . T o  be  assi g ne d  t he stat us of  c o nfir m e d  res p o nses m ust  be  c o nfir me d  b y  re peat 
assess me nts  t hat s h o ul d be  perf or me d  n o  less t ha n 4  wee ks  after t he criteria f or res p o nse are first 
met.  L o n ger  i nter vals as deter mi ne d  b y  t he st u d y pr ot oc ol  ma y  als o be  a p pr o priate.  I n t he cas e of  
S D,  f oll o w-u p  meas ure m e nts  m ust  ha ve  met  t he S D  criteria at least o nce  after st u d y e ntr y at a 
mi ni m u m  i nter val (i n ge neral,  n ot  less t ha n 6 -8  wee ks)  t hat is defi ne d  i n t he st u d y pr ot oc ol . F or 
P D all res ults s h o ul d be c o nfir me d as des cri be d i n secti o n 6 . 2.  
9. 5. 1. 4   
D ur ati o n of O ver all Res p o nse  
T he  d urati o n  of  o verall  res p o nse is meas ure d  fr o m t he ti me meas ure me nt  criteria are met  f or C R  
or  P R  ( w hic he ver st at us is rec or de d first) u ntil  t he first date  t hat rec urre nce or  P D  is o bjecti vel y  
d oc u me nte d,  ta ki n g as refere n ce f or P D  t he s mallest meas ure me nts  rec or de d si nce t he treat me nt 
starte d.  
9. 5. 1. 5   
D ur ati o n of St a ble Dise ase  
S D  is meas ure d  fr o m t he start of  t he treat me nt u ntil  t he criteria f or diseas e  pr o gressi o n  are met,  
ta ki n g as refere n ce t he s mallest meas ure me nts  rec or de d si nce t he treat me nt starte d. T he  cli nical 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 3  of 6 8  
rele va n ce of  t h e d urati o n  of  S D  varies  f or differe nt  t u m or t y pes a n d gra des.  T heref ore,  it is 
hi g hl y  rec o m me n de d t hat t he pr ot oc ol  s pecif y t he mi ni mal  ti me i nter val re q uire d bet wee n  t w o 
meas ure me nts  f or deter mi nati o n  of  S D.  T his  ti me i nter val s h o ul d ta ke i nt o acc o u nt  t he e x pecte d 
cli nical be nefit  t hat s uc h a stat us ma y  bri n g  t o t he p o p ulati o n  u n der  st u d y.  
9. 5. 1. 6   
O bjecti ve Res p o nse R ate  
O R R is defi ne d as t he perce nta ge of patie nts t hat ac hie v e P R or C R.  
9. 5. 1. 7   
Dise ase C o ntr ol R ate ( D C R)  
D C R is defi ne d as t he perce nta ge of patie nts t hat ac hie ve a n o bjecti ve t u m or res p o nse or ha ve 
sta ble disease t o t hera p y c o nfir me d b y i ma gi n g 6 wee ks a part . 
9. 5. 1. 8   
R e p orti n g of Res ults  
All  patie nts  i ncl u de d i n t he st u d y m ust  be  assesse d f or res p o ns e t o treat me nt, e ve n if t here are 
maj or  pr ot oc ol  treat me nt de viati o ns  or  if t he y are i neli gi ble. Eac h  patie nt  will  be  assi g ne d o ne  of  
t he f oll o wi n g cate g ori es:  1)  c o m plete res p o nse, 2)  partial  res p o nse, 3)  sta ble disease,  4)  
pr o gressi ve  disease,  5)  earl y deat h  fr o m mali g na nt  disease,  6)  earl y deat h  fr o m t o xicit y, 7)  earl y 
deat h  beca use  of  ot h er  ca use,  or  9)  u n k n o w n  ( n ot assessa ble, i ns uffi cie nt data).   
All  of  t he patie nts  w h o  met  t he eli gi bilit y criteria s h o ul d be  i ncl u de d i n t he mai n  a nal ysis of  t he 
res p o nse rate. Patie nts  i n res p o nse cate g ories 4 -9  s h o ul d be  c o nsi dere d  as faili n g t o res p o n d t o 
treat me nt ( diseas e pr o gressi o n).  T h us,  a n i nc orrect treat me nt sc he d ul e or  dr u g  a d mi nistrati o n , or 
fail ure t o c o m plete all prescri be d st u d y t hera p y, d oes  n ot  res ult i n e xcl usi o n fr o m t he a nal ysis of  
t he res p o nse rate. All  c o n cl usi o ns  s h o ul d be  base d  o n  all eli gi ble p atie nts. S u b a nal yses  ma y  t he n 
be  perf or me d  o n  t he basis  of  a s u bset of  patie nts,  e xcl u di n g  t h ose f or w h o m  maj or  pr ot oc ol  
de viati o ns  ha ve  bee n  i de ntifie d (e. g., earl y deat h  d ue  t o ot her  reas o ns, earl y disc o nti n uati o n  of  
treat me nt, maj or  pr ot oc ol  vi olati o ns,  etc.). T he  reas o ns f or e xcl u di n g patie nts  fr o m t he a nal ysis 
s h o ul d be  clearl y re p orte d.   
9. 6   
S afet y  
Safet y assess me nts will c o nsist of m o nit ori n g a n d rec or di n g all a d verse e ve nts, i ncl u di n g seri o us 
a d verse e ve nts, t he m o nit ori n g of he mat ol o g y, bl o o d c he mistr y, a n d t he re g ular m o nit ori n g of 
vital si g ns, a n d p h ysical c o n diti o n as s h o w n i n c orres p o n di n g ta bles. F or details o n A E c ollecti o n 
a n d re p orti n g, refer t o t he Safet y secti o n i n t he pr ot oc ol  ( Secti o n 1 2). 
9. 6. 1    
A d verse E ve nts  
P ote ntial A Es will be re p orte d b y t he s u bject ( or, w he n a p pr o priate, b y a care gi ver, s urr o gat e, or 
t he s u bject's le gall y acce pta ble re prese ntati ve) be gi n ni n g  at i nitiati o n of st u d y treat me nt a n d 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 4  of 6 8  
e n di n g 3 0 da ys  f oll o wi n g t he last a d mi nistrati o n of st u d y treat me nt or st u d y 
disc o nti n uati o n/ter mi nati o n, w hic he ver is earlier . In vesti gat ors will deter mi ne if t he e ve nts are 
rec or de d as A Es. A Es will be f oll o we d b y t he i n vesti gat or as s pecifi e d i n Secti o n 12 . 
1 0. 0  
C O R R E L A TI V E S  
We h y p ot hesize t h at ( 1) X P O 1 e x pressi o n wil l be ass ociate d wit h res p o ns es t o t hera p y o n t his 
trial, ( 2) t he fre q ue n c y of C D 4 + T-cells a n d I N F-ga m ma + pr o d uci n g C D 4 T cells will i ncreas e 
wit h treat me nt wit h pe m br oliz u ma b a n d Seli ne x or.  
I n t his st u d y, pre-treat me nt t u m or bi o ps y or arc hi v al F F P E tiss ue will be re q uire d f or e val uati o n 
of c orrelati ve st u dies. I n a d diti o n, bl o o d sa m ples will be c ollecte d  f or o pti o nal i m m u n ol o gic a n d 
m olec ular c orrelati ve st u dies  o n D a y 0, D a y 8  (± 3  da ys ) a n d D a y 2 1  (± 3  da ys ) of C ycle 1, a n d 
w he n s u bjects c o me off st u d y  (± 7  da ys ). Pre -treat me nt t u m or bi o ps y a n d pre- a n d post -treat me nt 
bl o o d sa m ples will be o btai ne d as o utli ne d i n Secti o n 1 0. 1 & 1 0. 2 . Bl o o d a n d t u m or tiss ue will 
be  ba n ke d f or  c orrelati ve st u dies.  
T a ble 9 . C orrel ati ve St u dies  
Bi o m ar k er 
N a m e a 
A N D Le a d PI 
a n d Site  
Ass a y  
( C LI A: 
Y/ N)  
Use (I nte gr al, I nte gr ate d, or 
E x pl or at or y) A N D P ur p ose b  
Tiss ue/ B o d y Fl ui d 
Teste d  
a n d Ti mi n g of Ass a y  
M a n d at or y  
/ O pti o n al 
F u n di n g 
S o urce(s)  
C D 4 + a n d C D 8 + 
T cells   
 
Fl o w 
c yt o metr y 
C LI A: N  
I nte grate d 
Assess a bs ol ute i ncrease i n C D 4 
d ue t o Seli ne x or + 
pe m br oliz u ma b  
P B M C  
D 0, 8, 2 1, off st u d y  
O    
Kar y o p har m - 
pe n di n g  
C D 4 +  a n d C D 8 + 
T cells/I N F -
ga m ma pr o d uci n g  
 
Fl o w 
c yt o metr y 
C LI A: N  
I nte grate d 
Assess i ncrease i n I N F -
pr o d uci n g C D 4 d ue t o Seli ne x or 
+ pe m br oliz u ma b  
P B M C  
D 0, 8, 2 1, off st u d y  
O    
Kar y o p har m - 
pe n di n g  
I N F-ga m ma  
 
E LI S A  
C LI A: N  
I nte grate d 
Assess a bs ol ute i ncrease i n I N F 
d ue t o Seli ne x or + 
pe m br oliz u ma b  
P B M C  
D 0, 8, 2 1, off st u d y  
O    
Kar y o p har m - 
pe n di n g  
N K, T cell a n d 
m o n oc yte 
f u ncti o nal assa ys  
 
Vari o us 
tec h ni q ues  
 
C LI A: N  
E x pl orat or y  
Assess t he effect of Seli ne x or + 
pe m br oliz u ma b o n T a n d N K 
cell f u ncti o n 
P B M C  
D 0, 8, 2 1, off st u d y  
O    
Kar y o p har m - 
pe n di n g  
N K cell killi n g 
assa y  
 
A D C C 
assa y  
C LI A: N  
E x pl orat or y  
Assess t he effect of Seli ne x or 
a n d pe m br oliz u ma b o n  N K cell 
f u ncti o n 
P B M C  
D 0, D 8, D 2 1, off st u d y  
O  
Kar y o p har m - 
pe n di n g  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 5  of 6 8  
 
Distri b uti o n, p he n ot y pe, a n d fre q u e nc y of m o n o n uclear cell s u bsets, ser u m a n d T -cell s pecific 
c yt o ki nes will be e xa mi n e d a t t he i n dicate d ti me p oi nts s u m marize d i n t he ta ble a b o ve. After 
pre parati o n of P B M Cs via sta n dar d pr oce d ure, cells will be a nal yze d usi n g a m ulti -para meter, 
Hi -D F A C S t o deter mi ne t he fre q u e nc y a n d p he n ot y pe of m o n o n uclear s u bsets i ncl u di n g: B 
cells, hel p er T cells, c yt ot o xic T cells, re g ulat or y T cells, naï ve T cells, me m or y T cells, N K T 
cells, N K cells (a n d s u bt y pes).  
T a ble 1 0 . P he n ot y pic M ar kers f or A n al ysis of V ari o us Im m u ne C ells  
Cell S u bset  
 
P he n ot y pe M ar k er  
T cell  
C D 4 +  hel per T cell  
C D 3 + C D 4 +   ( +/- I N F) 
C D 8 +  c yt ot o xic T cell    
C D 3 + C D 8 +  ( +/- I F N) 
Re g ulat or y T cells  
C D 3 + C D 4 + C D 2 5 + F o x p 3 +  
Naï ve T cell  
C D 4 + / C D 8+ C D 4 5 R A + C D 1 1a +  
Me m or y T cell  
C D 4 + / C D 8+ C D 4 5 R O + C D 1 1a +  
N K T cell  
C D 3 + C D 5 6 + C D 1 6 +  
i N K T cell 
C D 3 + C D 5 6 + C D 1 6 + 6 B 1 1 + C D 1 d +  
 
 
C D 4 + , & C D 8+  / P D-1 + , & P D L-1 +  
 
 
C D 4 + , & C D 8+  Ti m -3 + , & La g-3 +  
N K cell  
 
C D 3 - C D 5 6 + C D 1 6 +   +/ _ Gra nz y me B  
B cell  
B 2 cell  
C D 1 9 + I g D+ C D 1 1 b - C D 5 - 
B 1a cell  
C D 1 9 + I g M+ C D 1 1 b + C D 5 +  
B 1 b cell  
C D 1 9 + I g M+ C D 1 1 b + C D 5 - 
 
F u ncti o nal A nal ysis  
N K, T, a n d m o n oc yte f u ncti o n will be assa ye d at i n dicate d ti me p oi nts. Assa y of P B M C’s f or T 
cell a n d m o n oc yte acti vati o n: P B M C’s will be p urifie d fr o m bl o o d usi n g fic ol/ h y pa q ue a n d 
( 1 x 1 0 5cells/ well i n 2 0 0 µ L c ult ure me dia) will b e c ult ure d i n q ua dr u plicate 9 6 -well U -b ott o m 
plates f or eac h c o n diti o n: c ult ure me di u m al o ne or me di u m s u p ple me nte d wit h C D 3/ C D 2 8 m A b 
( 0. 5 µ g/ ml), or P H A ( 5 µ g/ ml) f or T cell acti vati o n a n d L P S ( 1 mc g/ ml) f or m o n oc yte acti vati o n. 
Cells will be i nc u bate d f or 3 -5 d a ys at 3 7C, 5 % C O 2. T he c ult ure s u per nata nts will be c ollecte d 
a n d st ore d at -7 0° C.  T he s u per nata nts will be assa ye d f or se veral c yt o ki nes/c he m o ki nes (e. g. I L -
2, I F N -γ, I L-1 7, I L -1 0, I L -4, T N F -α, T G F -β) usi n g t he M ulti ple x Bea d -bas e d L u mi ne x ® 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 6  of 6 8  
Tec h n ol o g y,  C yt o ki ne H u ma n 1 0 -Ple x Pa nel ( or if batc he d wit h ot her sa m ples, t he C yt o ki ne 
H u ma n 2 5 -Ple x Pa nel) (I n vitr o ge n, Carls ba d, C A), see bel o w.  
N K f u ncti o nal ass a y: H u ma n N K cells will be i de ntifie d as descri be d N K ( C D 3 -C D 5 6 + C D 1 6 +), 
N K T ( C D 3 + C D 5 6 + C D 1 6 +) a n d i N K T cells will be s orte d fr o m bl o o d. T he s orte d N K/ N K T cells 
will be sti m ulate d wit h p ol y I C f or 1 2 a n d 2 4 h. i N K T cells will be sti m ulate d wit h i N K T cell -
s pecific li ga n d, -Gal Cer. S u per nata nts will be c ollecte d t o a nal yze t he le vels of I F N -ga m ma, 
I L-6 a n d I L -8 usi n g t he B D c yt o metric bea d arra y kit per t he ma n ufact urer’s rec o m me n dati o ns. 
I F N-g a m ma a n d I L -4 will be meas ure d b y C B A kit or i ntracell ular stai ni n g. Sera c yt o ki ne  will 
be meas ure d b y C B A kit.  
N K Cell Killi n g Acti vit y:  N K cells bi n d t o, a n d kill K 5 6 2 cells (a h u ma n m yel o ge n o us cell li ne, 
A T C C) t h us f or mi n g t he basis of t his f u ncti o nal killi n g assa y; t his fl o w c yt o metric assa y ca n 
detect bi n di n g a n d killi n g.  
K 5 6 2 c ells. S p o nta ne o us l ysis will be teste d at eac h ti me p oi nt usi n g e q ui vale ntl y c ult ure d K 5 6 2 
cells i n t he a bse nce of effect ors. If we e nc o u nter a n y pr o ble ms wit h t his assa y, a sta n dar d 5 1 Cr -
releas e assa y will be d o ne, testi n g gr o u ps e q ui vale nt t o t h ose descri be d a b o ve. 
Ser u m bi o mar kers: Ser u m will be arc hi ve d fr o m patie nts pri or t o, d uri n g a n d after treat me nt wit h 
Seli ne x or a n d pe m br oliz u ma b.  
M ulti ple x Be a d -b ase d L u mi ne x ® Tec h n ol o g y : T he micr o bea d m ulti ple x detecti o n s yste m 
de vel o pe d b y I n vitr o ge n) e na bles de tecti o n of n u mer o us c yt o ki nes si m ulta ne o usl y i n a si n gle 
reacti o n c o nt ai ner.  I n t his tec h n ol o g y, m olec ular reacti o ns ta ke place o n t h e s urface of 
micr osc o pic plastic bea ds ( 2 u m).  F or eac h reacti o n, ca pt ure m olec ules (i. e., m o n o -s pecific 
a nti b o dies) are c o vale ntl y attac he d t o t he s urface of i nter nall y c ol or -c o de d micr o bea ds.  T he 
assi g ne d c ol or -c o de i de ntifies t he reacti o n i n a s pecific micr o bea d p o p ulati o n t hr o u g h o ut t he test.  
M ulti ple x ca pa bilit y i n v ol ves mi xi n g se veral p o p ulati o ns of micr o bea ds, eac h wit h a s pecifi c 
ca pt ure m olec ule, i nt o o ne reacti o n vessel at t he st art of t he test.  T he ma g nit u de of t he 
bi o m olec ular reacti o n is meas ure d usi n g a re p orter m olec ule w hic h si g nals t he e xte nt of t he 
reacti o n b y attac hi n g t o t he test m olec ules ca pt ure d o n the micr o bea ds. T o perf or m a t est, t he 
c ol or-c o d e d micr o bea ds, re p orter m olec ules, a n d s a m ple (e. g., t u m or cell l ysate) are mi xe d a n d 
t he n i njecte d i nt o t he L u mi ne x fl o w c yt o meter w here lasers ill u mi nate t he c ol ors i nsi de a n d o n 
t he s urface of eac h micr o bead. T his met h o d is ra pi d, se nsiti ve, a n d q ua ntitati ve, a n d le n ds itself 
t o hi g h-t hr o u g h p ut i n a n ec o n o mical fas hi o n.   
Ser u m C yt o ki nes : T he L u mi ne x assa y f or i m m u n ol o gic a nal ytes will i ncl u de 3 7 differe nt 
c yt o ki nes a n d gr o wt h fact ors (i ncl u di n g I L -1, 2, 4, 5, 6, 7, 1 0, 1 2, 1 7, T N F, I N F -γ, T G F-beta, 
G M -C S F, P D G F, a n d V E G F) (I n vitr o ge n). T his test will all o w f or t he ultrase nsiti ve 
deter mi nati o n of c yt o ki n es i n t he ser u m of patie nts bef ore a n d d uri n g treat me nt wit h Seli ne x or 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 7  of 6 8  
a n d pe m br oliz u ma b . T his will all o w f or t he i de ntificati o n of p ote ntial bi o mar kers t hat mi g ht 
pre dict a res p o nse t o t he c o m bi nati o n of Seli ne x or a n d pe m br oliz u ma b.  
I N F-g a m m a pr o d uci n g C D 4 + a n d C D 8 + T cells: P B M Cs is olate d at i n dicate d ti me p oi nts will 
be assesse d f or I F N -g a m ma pr o d ucti o n f or m  b ot h C D 8 + a n d  C D 4 + T cells u si n g i ntracell ular 
fl o w c yt o metr y. A p pr o xi matel y 1 0 6 P B M C’s will be stai ne d wit h fl u or oc hr o me -c o nj u gate d 
a nti b o d y f or detecti o n of C D 4  a n d C D 8 ( Da k o) f or 3 0-6 0 mi n utes a n d was h e d wit h 
fi xati o n/ per mea bilizati o n s ol uti o n (e Bi oscie nce). Cells will be t he n was he d wit h per mea bilz ati o n 
b uffer after ce ntrif u gati o n, bl oc ke d wit h 2 % rat/ m o use ser u m f oll o we d b y a d di n g t he 
rec o m me n de d a m o u nt of a nti-I N F-ga m ma fl ur oc hr o me -c o nj u gate d a nti b o d y ( Da k o) f or 3 0 
mi n utes. Cells will be was he d t wice w it h per mea bilizati o n b uffer f oll o we d b y res us pe nsi o n i n 
Fl o w C yt o metr y Stai ni n g b uffer (e Bi oscie nce)  a n d a nal yze d b y fl o w c yt o m etr y ( B D C o ulter). 
Data will be c ollecte d usi n g a F A C S A RI A ( B D Bi oscie nces) a n d a nal y ze d b y " Fl o wj o" fl o w 
c yt o metr y data a n al ysi s s oft ware ( Tree Star I nc, As hla n d, O R). 
1 0. 1  
Bl o o d  
O ne 1 0 m L E D T A t u be of w h ole bl o o d will be c ollecte d at scree ni n g a n d pr ocesse d b y t he 
M olec ular P har mac ol o g y S hare d Res o urce ( M P S R ).  W h ole bl o o d will be ce ntrif u ge d at 
2 0 0 0  x  g f or 1 5 mi n utes t o se parat e pla s ma fr o m b uff y c oat a n d re d bl o o d cells ( R B C).  Plas ma 
will be discar de d, a n d b uff y c oat will be c ollecte d ~ 2 m L a n d mi xe d well a n d place d i nt o 
2  x  1  m L cr y ot u bes, st ore d at -8 0 °C u ntil deli ver y t o Dr. Ma vera kis ’s la b.  T u bes will be la bele d 
wit h st u d y, st u d y I D, dat e a n d ti me of c ollecti o n. ( See a b o ve f or st u dies i nte n de d) 
1 0. 2  
Tiss ue  
Tiss ue will be c ollecte d fr o m  a pre-treat me nt bi o ps y or arc hi val s p eci me n if t he latter is 
a vaila ble.  Ur ot helial carci n o ma  tiss ue will be  c ollecte d fr o m F F P E bl oc ks pr oc esse d b y t he 
sta n dar d pr ot oc ols of t he De part me nt of Pat h ol o g y. A b oar d certifie d pat h ol o gist will i de ntif y 
t u m or o n t he cli nical H & E sli des. Paraffi n secti o ns a n d c ores will be pre pare d b y t he 
Bi ore p osit or y s hare d res o urce.  We will re q u est 5 F F P E sli des secti o ne d at 5 micr o ns or 
3 m m  x  5 m m c ores ( if p ossi ble) base d o n t u m or v ol u me. Pla n ne d st u dies i ncl u de P D -L 1 
e x pressi o n b y I H C a n d X P O 1 e x pressi o n b y I H C. Usi n g i nstit uti o nal sta n dar ds, X P O 1 I H C 
a nal ysis sta n dar ds will be vali date d pri or t o p erf or mi n g t his  st u d y’s a nal ysis. Usi n g esta blis he d 
De part me nt of Pat h ol o g y g ui deli nes, P D -L 1 e x pressi o n b y I H C a nal ysis will als o be perf or me d.  
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 8  of 6 8  
1 1. 0  
S T A TI S TI C A L C O N SI D E R A TI O N S  
1 1. 1  
S a m ple Size  
T o esta blis h t he R P 2 D, a 3 + 3  de -es calati o n  st u d y desi g n is e m pl o ye d; t his will re q uire a 
mi ni m u m of 6 patie nts a n d u p t o 1 2  patie nts.  O nl y t w o d ose le vels are i ncl u de d i n t his trial. 
T hese were c h os e n beca use t he first d ose le vel is a re d uce d d os e fr o m t he F D A -a p pr o ve d le vel 
t hat has bee n re p orte d t o be well-t olerate d i n patie nts wit h m ultiple m yel o ma. We a ntici pate it t o 
be well -t olerate d i n c o m bi nati o n wit h pe m br oliz u ma b, b ut ha ve i ncl u de d o ne d ose le vel 
re d ucti o n i n t he e ve nt t hat u ne x pecte d t o xicit y is o bser ve d. O ur h y p ot hesis is t hat a d ose le vel 
re d ucti o n bel o w 6 0 m g w ee kl y of seli ne x or w o ul d i n dicate t hat t he c o m bi nati o n of seli ne x or a n d 
pe m br oliz u ma b is n ot well -t olerate d a n d s h o ul d n ot be f urt her de vel o pe d. O nce R P 2 D is 
esta blis he d, ad diti o nal patie nts will be e nr olle d f or a t otal of 2 7  patie nts at t he R P 2 D e val ua ble 
f or res p o ns e assess me nt. T his will pr o vi de f urt her e val uati o n of tr ue t o xicit y - f or e xa m ple, if t he 
tr ue A E rat e is 1 0 %, t he n t he pr o ba bilit y of o bser vi n g at least o ne a d verse e ve nt as a f u ncti o n of 
tr ue rate a n d n u m ber of patie nts o n trial is 4 7 % wit h a 6 patie nt c o h ort as w o ul d be o btai ne d i n 
t he 3 + 3 d ose-d e -es calati o n. T he i ncl usi o n of a n a d diti o nal, at mi ni m u m , 1 2 patie nts w o ul d 
i m pr o ve t he pr o ba bilit y of o bser vi n g at least o n e A E as a f u ncti o n of tr ue rate a n d n u m ber of 
patie nts t o 8 5 % if t he tr ue A E rat e is 1 0 %.  
Ass u mi n g a res p o nse rate of 2 0 % f or pe m br oliz u ma b al o ne i n t his st u d y p o p ulati o n base d o n 
hist orical c o ntr ols, a sa m ple size of 2 7  patie nts will all o w f or detecti o n of a n i m pr o ve me nt t o 
O R R of 4 5 % wit h  8 0 % p o wer , at t he 0. 0 5 le vel ( 2 -si de d) base d o n t his si n gle sta ge P hase II 
desi g n . 
1 1. 2  
St atistic al A n al ysis Pl a n  
T he R P 2 D is defi ne d i n Secti o n 4. 1. 2 . Dose li miti n g t o xicities  will be liste d acc or di n g t o d ose 
le vel. All e nr olle d patie nts w h o i nitiate c o m bi nati o n t hera p y will be c o nsi dere d, u nless t he 
patie nt st o ps t hera p y d uri n g t he D L T assess me nt peri o d f or a reas o n ot her t ha n D L T . 
Se paratel y b y d ose l e vel a n d t he e x pa nsi o n c o h ort (as well as f or t he t otal R P 2 D c o h ort), A Es 
will be s u m marize d as n u m ber of patie nts acc or di n g t o N CI C T C A E ter m a n d g ra de, w here 
gra de is t he ma xi m u m acr oss a patie nt’s treat me nt peri o d. Gra de 3 a n d hi g h er A Es will be liste d, 
acc or di n g t o d ose l e vel a n d patie nt. T he n u m ber ( %) of patie nts w h o e x perie nce ≥ 1 Gra de 3 -5 
A Es will be re p orte d , as well as t he pr o p orti o n wit h exact bi n o mial  9 5 % CI  
F or re p orti n g of A Es, t he safet y -e v al ua ble patie nts are t h ose w h o recei ve d at least o ne d ose of 
b ot h seli ne x or a n d pe m br oliz u ma b.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 4 9  of 6 8  
O bjecti ve res p o ns e rat e ( O R R) will be  re p orte d as a pri mar y  e n d p oi nt f or all e val ua ble patie nts - 
e val ua ble p atie nts are c o nsi dere d patie nts w h o recei ve d at least o ne d ose of t he R P 2 D of 
seli ne x or a n d sta n dar d-d ose pe m br oliz u ma b a n d ha d at least o ne i ma gi n g assess me nt after 
e nr oll me nt. O bjecti ve res p o nse rate, calc ulate d as t he t otal n u m ber of patie nts wit h a c o nfir me d 
C R or P R, will be re p orte d as a perce nta ge of t otal e val ua ble patie nts. Disease c o ntr ol rate, 
calc ulate d as t he t otal n u m ber of patie nts wit h a c o nfir me d C R, P R or sta ble disease, will be 
re p orte d as a perce nt a ge of t otal e val ua ble patie nts at t he R P 2 D. Eac h will be re p orte d wit h e xact 
bi n o mial 9 5 % CI . Pr o gressi o n -free s ur vi val ( P F S) will be re p orte d as defi ne d as ti me fr o m 
e nr oll me nt t o trial t o ti me of disease pr o gressi o n or deat h fr o m a n y ca us e , a n d will be re p orte d 
wit h e xact bi n o mial 9 5 % CI.  
E x pl orat or y a nal ys es of t u m or tiss ue sa m ple will be u n derta ke n u p o n c o m pleti o n of st u d y 
f oll o w-u p. T u m or tiss ue will be a nal yze d f or X P O 1 e x pressi o n b y I H C ( per Pat h ol o g y 
De part me nt vali dat e d ass a y); t h ose patie nts wit h I H C 2 + will be re p orte d  as p ositi ve. T he 
fre q ue n c y of X P O 1 e x pressi o n p ositi vit y a m o n g patie nts i n t his st u d y will be re p orte d wit h 9 0 % 
CI . A d escri pti ve ta ble e val uati n g X P O 1 e x pressi o n ( p ositi ve or ne gati ve) vers us o bjecti ve 
res p o nse ( y es or n o) will be pr o d uce d wit h o ut f or mal statistical testi n g. Si milar a nal ysis will be 
u n derta ke n t o e val uate t h e relati o ns hi p bet wee n P D -L 1 e x pressi o n a n d o bj ecti ve res p o ns e. Usi n g 
fl o w c yt o metr y, a n al yzi n g P B M Cs deri ve d fr o m bl o o d sa m ples, baseli ne a n d p ost -treat me nt N K, 
C D 4, a n d  C D 8 T -cell le vels  will be meas ure d f or eac h patie nt. Pre - a n d p ost -treat me nt T-cell 
le vels will be re p orte d d escri pti vel y  ( q ua ntitati vel y a n d as a % c ha n ge bet wee n pre- a n d p ost-
treat me nt) a n d gra p hicall y first f or all patie nts o n trial, a n d t he n se paratel y a m o n g t h ose w h o 
ha ve a n o bjecti ve res p o nse rate, a n d t h ose w h o d o n ot ha ve a n o bjecti ve res p o nse rate. T hese 
st u dies will be c o n d ucte d o nce accr ual a n d f oll o w-u p is c o m plete, ass u mi n g a vaila bilit y of 
a de q uate res o urces.  
1 1. 3  
S afet y  
N CI C T C A E v 5. 0 criteria will be use d t o d oc u me nt safet y data  b y patie nt a n d b y d ose le vel . 
1 1. 4  
Effic ac y  
As  a pri mar y e n d p oi nt , all res p o nses will be re p orte d usi n g  R E CI S T 1. 1 defi niti o ns. O bjecti ve 
res p o nse rate will be s u m marize d b y e xac t bi n o mial c o nfi de nce i nter vals. Pr o g ressi o n-free 
s ur vi val will be ca pt ure d as a sec o n d ar y e n d p oi nt, wit h a Ka pla n-M eier pl ot a n d esti mate of 
me dia n P F S wit h 9 5 % c o nfi de nce i nter val . 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 0  of 6 8  
1 1. 5  
S u bject C o urse  
I nf or mati o n re g ar di n g t h e s u bject’s c o urse s uc h as c o m pleti n g t he st u d y treat me nt, d ose dela ys, 
pre mat ure disc o nti n uati o n a n d maj or pr ot oc ol vi ol ati o n will be ta b ulate d a n d s u m marize d.  
 
1 2. 0  
S A F E T Y A N D R E P O R TI N G R E Q UI R E M E N T S  
1 2. 1  
A d verse E ve nt s 
A n a d verse e ve nt ( A E) is defi ne d as a n y ne w u nt o war d me dical occ urre nce or w orse ni n g of a 
pree xisti n g me dical c o n dit i o n i n a cli nical i n vesti gati o n partici pa nt a d mi nistere d st u d y dr u g a n d 
t hat d oes n ot necessaril y ha ve a ca usal relati o ns hi p wit h t his treat me nt. A n A E ca n t heref ore be 
a n y u nfa v ora ble a n d u ni nte n de d si g n (s uc h as a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or 
disease te m p orall y ass o ciate d wit h t he use of i n vesti gati o nal pr o d uct, w het h er or n ot c o nsi dere d 
relate d t o t he i n vesti gati o nal pr o d uct.  
1 2. 1. 1    
Se verit y of A d verse E ve nts  
T he se verit y of a n A E is gra de d as f oll o ws:  
Gr a de 1  ( Mil d): 
T he e ve nt ca uses disc o mf ort t hat affects n or mal dail y 
acti vities. 
Gr a de 2  (M o derate ):   
T he e ve nt ma kes t he pati e nt u na ble t o perf or m n or mal dail y 
acti vities or si g nifica ntl y affects his/ her cli nical stat us.  
Gr a de 3  (Se vere):    
T he e ve nt ma kes t he pati e nt u na ble t o perf or m n or mal dail y 
acti vities or si g nifica ntl y affects his/ her cli nical stat us.  
Gr a de 4  (Life -t hreate ni n g): T he patie nt was at ris k of deat h at t he ti me of t he e ve nt.  
Gr a de 5  (Fatal ): 
T he e ve nt ca use d deat h.  
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 1  of 6 8  
1 2. 1. 2    
C a us alit y ( Attri b uti o n) of A d verse E ve nts  
T he i n vesti gat or is t o assess t he ca usal relati o n of all A Es (i.e., w het her t here is a reas o na ble 
p ossi bilit y t hat t he st u d y dr u g ca use d t h e e ve nt) usi n g t he f oll o wi n g defi niti o ns:  
N ot Rel ate d:    
A n ot her ca us e of t he A E is m ore pla usi ble; a te m p oral se q ue nce ca n n ot be 
esta blis he d wit h t he o nset of t he A E a n d a d mi nistrati o n of t he 
i n vesti gati o nal pr o d uct; or, a ca us al relati o ns hi p is c o nsi dere d bi ol o gicall y 
i m pla usi ble. 
U nli kel y:    
T he c urre nt k n o wle d ge or i nf or mati o n a b o ut t he A E i n dicates t hat a 
relati o ns hi p t o t he i n vesti gati o nal pr o d uct is u nli kel y. 
P ossi bl y Rel ate d:  T here is a cli nicall y pla usi ble ti me se q ue nce bet wee n o nset of t he A E a n d 
a d mi nistrati o n of t he i n vesti gati o nal pr o d uct, b ut t he A E c o ul d als o be 
attri b ute d t o c o n c urre nt or u n derl yi n g disease, or t he use of ot her dr u gs or 
pr oce d ures.  P ossi bl y relate d s h o ul d be use d w he n t he i n vesti gati o nal 
pr o d uct is o ne of se veral bi ol o gicall y pla usi ble A E ca uses.  
Pr o b a bl y 
Rel ate d:  
T he A E is li kel y relate d t o i n vesti gati o nal pr o d uct. 
Rel ate d:    
T he A E is clearl y relate d t o use of t he i n vesti gati o nal pr o d uct.  
 
A n y ot her A E n ot liste d as a n e x pecte d e ve nt i n t he I n vesti gat or’s Br oc h ure or i n t his pr ot oc ol 
will be c o nsi dere d u n e x p ecte d.  
1 2. 1. 3    
Seri o us A d verse E ve nt s 
Seri o us a d verse e ve nt ( S A E) mea ns a n y u nt o war d me dical occ urre nce t hat at a n y d ose:  
•  Res ults i n de at h . 
•  Is life-t hre ate ni n g ( N ote: t he ter m “life-t hreate ni n g” refers t o a n e ve nt/reacti o n i n w hic h 
t he patie nt was at ris k of deat h at t he ti me of t he e ve nt/reacti o n.  It d o es n ot refer t o a n 
e ve nt/reacti o n w hic h h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere).  
•  Re q uires i n patie nt h os pit aliz ati o n or pr ol o n g ati o n of a n e xisti n g h os pit aliz ati o n   
•  Res ults i n persiste nt or si g nific a nt dis a bilit y or i nc a p a cit y. ( Disa bilit y is defi ne d as a 
s u bsta ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct n or mal life f u ncti o ns).  
•  Is a c o n ge nit al a n o m al y/ birt h defect . 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 2  of 6 8  
•  Is a me dic all y i m p ort a nt e ve nt or re acti o n . Me dical a n d scie ntific j u d g m e nt s h o ul d be 
e xercis e d i n deci di n g w het her ot her sit uati o ns s h o ul d be c o nsi dere d s eri o us, s uc h as 
i m p orta nt me dical e ve nts t hat mi g ht n ot be i m me diatel y life-t hreate ni n g or res ult i n deat h 
or h os pitalizati o n, b ut mi g ht je o par dize t he patie nt or mi g ht re q uire i nter ve nti o n t o 
pre ve nt  o ne of t he ot her o utc o mes liste d i n t he defi niti o n a b o ve.  
 
 
 
1 2. 1. 4    
L a b or at or y Test A b n or m alities  
All la b orat or y test res ults ca pt ure d as part of t h e st u d y s h o ul d be rec or de d f oll o wi n g i nstit uti o nal 
pr oce d ures.  
1 2. 2  
Pr oce d ures f or H a n dli n g S peci al Sit u ati o ns  
1 2. 2. 1    
Pre g n a nc y  a n d Bre astfee di n g  
Pre g na nt patie nts are n ot per mitte d t o e nr oll i n t his trial. D uri n g scree ni n g f or e nr oll me nt, all 
w o me n of re pr o d ucti ve p ote ntial will u n der g o uri ne pre g na nc y testi n g a n d will be e xcl u de d fr o m 
partici pati o n if f o u n d t o be pre g na nt. If a  patie nt bec o mes pre g na nt d uri n g treat me nt, t he patie nt 
will ha ve t o disc o nti n ue st u d y treat me nt i m me diatel y, b ut w o ul d c o nti n ue wit h f oll o w -u p 
assess me nt per st u d y.  
N ote: Pre g na nc y p er se is n ot c o nsi dere d t o be a n A E; h o we ver, it is disc usse d here beca u se of 
t he i m p orta nce of re p orti n g pre g na nci es t hat occ ur d uri n g st u dies a n d beca use a me dical 
occ urre nce o bser ve d i n t he m ot her or fet us/ ne w b or n w o ul d be classifie d as a n A E.  
Fe male p atie nts of c hil d b eari n g p ote ntial a n d fertil e male patie nts will be i nf or me d as t o t he 
p ote ntial ris k of c o nce pti o n w hile partici pati n g i n t his st u d y a n d will be a d vise d t hat t he y m ust 
use hi g hl y effecti ve c o ntrace pti o n liste d bel o w (i.e., res ults i n a l o w fail ure rate w he n us e d 
c o nsiste ntl y a n d c orrectl y) d uri n g t he d osi n g per i o d a n d f or a peri o d of at least 4  m o nt hs after t he 
e n d of treat me nt.  
A list of hi g hl y effecti ve met h o ds of c o ntrace pti o n is pr o vi de d i n t he A p pe n di x.  
A pre g na n c y test will be perf or me d o n eac h pre m e n o pa usal fe male patie nt of c hil d beari n g 
p ote ntial ≤ 3 da y s pri or t o t he first d ose of st u d y dr u g . D uri n g trial treat me nt, uri ne pre g na nc y 
tests s h o ul d be perf or me d as cli nicall y i n dicate d. A ne gati ve pre g na nc y t est m ust be d oc u me nte d 
pri or t o a d mi nistrati o n of st u d y dr u g.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 3  of 6 8  
If a patie nt is c o nfir me d pre g na nt d uri ng t he st u d y, st u d y dr u g a d mi nistrati o n m ust be 
disc o nti n ue d i m me diatel y. T he I n vesti gat or m ust i m me diatel y n otif y t he S p o ns or S p o ns or 
i n vesti gat or of t his e ve nt a n d rec or d t he Pre g na nc y o n t he Pre g na nc y F or m. T he i nitial 
i nf or mati o n re gar di n g a pre g na nc y m ust be f or war de d t o Kar y o p har m’s P har mac o vi gila nce 
De part me nt b y e m ail or fa x wit hi n 2 4 h o urs of first k n o wle d ge of its occ urre nce. A pre g na nc y 
re p ort f or m is pr o vi de d b y Kar y o p har m P har mac o vi gila nce. 
T he pre g n a nc y s h o ul d be f oll o we d u p t o deter mi n e t he o ut c o me, i ncl u di n g s p o nta ne o us or 
v ol u ntar y ter mi nati o n, details of t he birt h, a n d t he prese nce or a bs e nce of a n y birt h defects, 
c o n ge nital a b n or malities, or mater nal a n d/ or ne w b or n c o m plicati o ns.  
All pre g na ncies occ urri n g wit hi n 4 m o nt hs after t he patie nt’s  last d ose of st u d y dr u g m ust be 
re p orte d t o K ar y o p har m, re gar dless of w het h er t he patie nt recei ve d t he Kar y o p har m st u d y dr u g 
or ot her st u d y dr u gs, wit h dra ws fr o m t he st u d y, or t he st u d y is c o m plete d. Patie nts s h o ul d be 
i nstr ucte d t o i nf or m t he I n vesti gat or re gar di n g a n y pre g na nci es.  
A n y S A E t hat occ urs d uri n g pre g na nc y m ust be rec or de d o n t he S A E re p ort f or m (e g, mater nal 
seri o us c o m plicati o ns, t hera pe utic a b orti o n, ect o pi c pre g na nc y, still birt h, ne o natal deat h, 
c o n ge nital a n o mal y, or birt h defect) a n d re p orte d wit hi n 2 4 h o urs i n acc or da nce wit h t he 
pr oce d ure f or re p orti n g S A Es ( descri be d i n Secti o n 9. 2. 3).  
A pre g na n c y i n a fe male part ner of a male patie nt m ust be re p orte d t o Kar y o p har m 
P har mac o vi gila nce wit hi n 2 4 h o urs of lear ni n g of its occ urre nce. Pre g n a nci es i n fe male part ners 
s h o ul d o nl y be f oll o we d if t he male patie nt is bei n g treate d wit h a s eli ne x or -c o ntai ni n g re gi me n. 
C o nse nt t o re p ort i nf or m ati o n re gar di n g t hese pre g na nc y o utc o mes s h o ul d be o btai ne d fr o m t he 
fe male part ner. 
It is n ot k n o w n w het h er s eli ne x or passes i nt o t he breast mil k. M ot hers s h o ul d n ot breastfee d 
w hile bei n g treate d wit h a seli ne x or -c o ntai ni n g re gi me n.  
1 2. 2. 2    
O ver d ose  
A n o ver d ose is a deli berate or acci de ntal a d mi nistrati o n of a n y Kar y o p har m st u d y dr u g t o a 
st u d y patie nt, at a d ose greater t ha n t h at w hic h was assi g ne d t o t hat patie nt per t he st u d y 
pr ot oc ol. If a n o v er d ose occ urs, Kar y o p har m P har mac o vi gila nce s h o ul d be n otifie d i m me diatel y, 
a n d t he patie nt s h o ul d be o bser ve d cl os el y f or A Es. Res ulti n g s y m pt o ms s h o ul d be treate d, as 
a p pr o priate, a n d t he i nci d e nt of o ver d ose a n d relate d A Es a n d/ or treat me nt s h o ul d be rec or de d. 
I nf or mati o n re g ar di n g t h e o ver d ose is t o be rec or de d o n Kar y o p har m’s S A E re p ort f or m a n d se nt 
t o Kar y o p har m P har mac o vi gila nce re gar dless of w het her or n ot a n A E or S A E has occ urre d d ue 
t o t he o ver d ose. If t he o ver d ose is ass oci ate d wit h a n S A E, t he S A E re p ort f or m m ust be 
s u b mitte d t o Kar y o p har m P har mac o vi gila nce wit hi n 2 4 h o urs of a ware ness. If t here is n o A E or 
S A E, t he re p ort m ust be s u b mitte d wit hi n 2 4 h o urs of a war e ness.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 4  of 6 8  
As seli ne x or is meta b olize d b y G S H c o nj u gati o n, it is p ossi ble, b ut n ot de m o nstrate d, t hat 
he patic G S H de pleti o n mi g ht occ ur i n cas e of e xtre me o ver d ose. T heref ore, i n o ver d ose cases, if 
patie nts de vel o p li ver f u ncti o n test a b n or malities, s u p p orti ve  meas ures s u c h as S A M or ot her 
dr u gs t hat ca n re place G S H mi g ht be c o nsi dere d as part of t he o verall ma na ge me nt pla n.  
1 2. 2. 3    
A b use, Mis use, or Me dic ati o n Err or  
A b use is t he persiste nt or s p ora dic, i nte nti o nal e xcessi ve use of t he Kar y o p har m st u d y dr u g 
w hic h is acc o m pa ni e d b y har mf ul p h ysical or ps yc h ol o gical effects.  
A me dicati o n err or is a n y pre ve nta ble i n ci de nt t hat ma y ca use or lea d t o i na p pr o priate st u d y 
treat me nt use or p atie nt har m w hile t he st u d y treat me nt is i n t he c o ntr ol of t he healt h care 
pr ofessi o nals or patie nts. S uc h i nci de nt ma y be d ue t o healt h care pr ofessi o nal practice, pr o d uct 
la beli n g, pac ka gi n g a n d pre parati o n, pr oce d ures f or a d mi nistrati o n, a n d s yste ms, i ncl u di n g t he 
f oll o wi n g: prescri bi n g, or der c o m m u nicati o n, n o me nclat ure, c o m p o u n di n g, dis pe nsi n g, 
distri b uti o n, a d mi nistrati o n, e d ucati o n, m o nit ori n g, a n d use.  
All occ urre nces of a b use, mis use, or me dicati o n err or wit h t he Kar y o p har m st u d y dr u g are t o be 
rec or de d o n Kar y o p har m’s S A E re p ort f or m a n d s e nt t o Kar y o p har m P har mac o vi gila nce 
re gar dless of w het h er or n ot a n A E or S A E has occ urre d d ue t o t he a b use, mis use, or me dicati o n 
err or. If t he a b us e, mis use, or me dicati o n err or is ass ociate d wit h a n S A E, t he S A E re p ort f or m 
m ust be s u b mitte d t o Kar y o p har m P har mac o vi gila nce wit hi n 2 4 h o urs of a ware ness. If t here is 
n o A E or S A E, t he re p ort m ust be s u b mitte d wit hi n 2 4  h o urs of a ware ness.  
1 2. 3  
Pr oce d ures f or Re p orti n g A d verse E ve nts   
1 2. 3. 1    
Met h o ds a n d Ti mi n g f or Assessi n g a n d Rec or di n g S afet y V ari a bles  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat all A Es a n d S A Es t hat are o bser ve d or re p orte d 
d uri n g t he st u d y are c ollecte d a n d re p orted t o t he I R B a n d t o t he F D A i n acc or da nce wit h C F R 
3 1 2. 3 2 (I N D Safet y Re p orts).  
1 2. 3. 2    
A d verse E ve nt Re p orti n g Peri o d  
•  
A E will be re p orte d a n d rec or de d fr o m t he ti me of t he first d ose of st u d y dr u g t hr o u g h 3 0 
da ys after t he last d ose of st u d y dr u g or u ntil t he start of s u bse q ue nt a nti ne o plastic 
t hera p y, w hic h e ver occ urs first.  T hat is, if a patie nt be gi ns a ne w a nti ne o pl astic t hera p y, 
t he A E re p orti n g peri o d f or n o nseri o us A Es e n ds at t he ti me t he ne w treat m e nt is starte d.  
•  
S A Es will be re p orte d t o Kar y o p har m fr o m t he first d ose of st u d y dr u g t hr o u g h 3 0 da ys 
after a d mi nistrati o n of t he last d ose of st u d y dr u g a n d rec or de d i n t he e C R F.   All S A Es 
m ust als o be re p orte d t o Kar y o p har m P har mac o vi gila nce  
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 5  of 6 8  
I n v esti gat ors are n ot o bli gate d t o acti vel y see k i nf or mati o n re gar di n g t he occ urre nce of ne w 
S A Es be gi n ni n g after t he 3 0 -da y p ost last d ose  peri o d. H o we ver, if t h e i n vesti gat or lear ns of 
s uc h a n S A E a n d t hat e v e nt is dee me d rele va nt t o t he use of st u d y treat me nt, he/s he s h o ul d 
pr o m ptl y d oc u me nt a n d re p ort t he e ve nt.  
1 2. 3. 3    
Pr oce d ures f or S A E Re p orti n g  
1 2. 3. 3. 1  
I niti al a n d F oll o w u p Re p orts 
E ver y S A E, re g ar dless of t he ca usal relati o ns hi p t o t he Kar y o p har m st u d y dr u g, occ urri n g after 
t he patie nt has si g ne d i nf or me d c o nse nt u ntil at least 3 0 da ys after t he patie nt has st o p pe d the 
Kar y o p har m st u d y dr u g m ust be re p orte d t o t he Kar y o p har m P har mac o vi gila nce De part me nt 
wit hi n 2 4 h o urs of lear ni n g of its occ urre nce. T he i n vesti gati o nal site pers o n nel m ust use t he 
S A E Re p ort F or m pr o vi d e d b y Kar y o p har m f or re p orti n g a n y S A E t o t he Kar y o p har m 
P har mac o vi gila nce De part me nt.  
U p o n c o m pleti o n, t he S A E Re p ort F or m m ust be i m me diatel y e maile d or fa xe d t o:  
P har mac o vi gila nce De part me nt  
Kar y o p har m T hera pe utics I nc.  
E mail: p har mac o vi gila nce @ ka r y o p har m.c o m 
Fa x:  
+ 1 -6 1 7 -3 3 4 -7 6 1 7 ( U S A)  
+ 4 9 -8 9 -9 2 1 8 -5 6 5 0 ( Ger ma n y)  
 
Kar y o p har m will re p ort a p plica ble S A Es t o ot her a p plica ble re g ulat or y a ut h orities a n d 
I n v esti gat ors utilizi n g seli ne x or, as ma y be re q uire d. 
1 2. 3. 3. 2  
A d diti o n al I n vesti g at or Res p o nsi bilities o n F ol l o w-u p of S A Es  
T he i n vesti gat or a n d s u p p orti n g pers o n nel res p o nsi ble f or patie nt care s h o ul d i nstit ute a n y 
s u p ple me ntal i n vesti gati o ns of S A Es base d o n t h eir cli nical j u d g me nt of li kel y ca usati ve fact ors. 
T his ma y i ncl u de e xtra cli nical la b orat or y tests, p h ysical e xa mi nati o ns or c o ns ulti n g a n 
a p pr o priate s pecialist. If a patie nt dies d uri n g t he f oll o w -u p peri o d f or t he S A E, t he e ve nt 
ca usi n g t he deat h will be re p orte d as part of t hat S A E. T he rel ati o ns hi p bet wee n t he S A E a n d t he 
deat h s h o ul d be s pecifi call y  a d dresse d.  
1 2. 3. 3. 3  
A d diti o n al Re p orti n g Re q uire me nts f or I N D H ol ders  
F or I n v esti gat or S p o ns ore d I N D St u dies t here are s o me a d diti o nal re p orti n g re q uire me nts f or t he 
F D A i n acc or da nce wit h t he g ui da nce set f ort h i n 2 1 C F R 3 1 2. 3 2.   

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 6  of 6 8  
S p o ns or -i n vesti gat ors of st u dies c o n d ucte d u n der a n I N D are re q uire d t o re p ort all seri o us, 
u ne x pecte d , a n d rel ate d a d verse e v e nts directl y t o t he F D A o n a Me d Watc h F or m F D A 3 5 0 0 A 
wit hi n 7 (if fatal or life -t hreate ni n g) or 1 5 cal e n dar da ys of first a ware ness, as descri be d bel o w.  
Bef ore s u b mitti n g t his re p ort, t he  s p o ns or nee ds t o e ns ure t hat t he e ve nt m eets all t hree of t he 
defi niti o ns c o ntai ne d i n t he re q uire me nt:  
•  S us pecte d a d verse reacti o n  
•  Seri o us  
•  U ne x pect e d  
 
T he S p o ns or -I n vesti gat or will n otif y t he F D A acc or di n g t o t he f oll o wi n g ti meli nes: 
•  wit hi n 7 c ale n d ar  d a ys  of a n y u ne x pecte d fatal or life -t hreat e ni n g a d verse e ve nt wit h 
p ossi ble relati o ns hi p t o st u d y dr u g;  
•  wit hi n 1 5 c ale n d ar d a ys  of a n y e ve nt t hat is c o nsi dere d: 1) seri o us, 2) u ne x pecte d, a n d 
3) at least p ossi bl y relate d t o st u d y partici pati o n.  
 
F D A fa x n u m ber f or I N D Safet y Re p orts: ( 8 0 0) F D A-0 1 7 8  or ( 8 0 0) 3 3 2-0 1 7 8  
If t he a d v erse e ve nt d oes n ot meet all t hree of t he defi niti o ns, it s h o ul d n ot be s u b mitte d as a n 
e x pe dite d I N D safet y re p ort t o t he F D A.  F or a d verse e ve nts t hat are eit her seri o us b ut d o n’t 
meet t he criteria f or e x pe dite d re p orti n g or are n ot seri o us, t he F D A will be n otifie d at t he ti me 
of t he I N D A n n ual Re p ort.  
Me d W atc h F or m F D A 3 5 0 0 A Re p orti n g G ui deli nes  
I n a d diti o n t o c o m pleti n g a p pr o priate de m o gra p hi c a n d s us pect me di cati o n i nf or mati o n, t he 
re p ort s h o ul d i ncl u de t he f oll o wi n g i nf or mati o n wit hi n t he E ve nt Descri pti o n of t he Me d Watc h 
F or m F D A 3 5 0 0 A:  
•  Treat me nt re gi me n ( d osi n g, fre q ue nc y, c o m bi nati o n t hera p y)  
•  Pr ot oc ol descri pti o n (i ncl u de n u m ber if assi g ne d)  
•  Descri pti o n of e v e nt, se verit y, tr eat me nt, a n d o utc o me, if k n o w n  
•  S u p p orti ve dia g n ostic a n d la b orat or y res ults  
•  I n v esti gat or’s ass ess me nt of t he relati o ns hi p of t he S A E t o eac h i n vesti gati o nal pr o d uct 
a n d s us pect me dicati o n  
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 7  of 6 8  
F oll o w -u p i nf or mati o n:  
•  A d diti o nal i nf or mati o n ma y be a d de d t o a pr e vi o usl y s u b mitte d re p ort b y a n y of t he 
f oll o wi n g met h o ds: 
•  A d di n g t o t he ori gi nal Me d Watc h F or m F D A 3 5 0 0 A a n d s u b mitti n g it as f oll o w -u p  
•  A d di n g s u p ple me ntar y s u m mar y i nf or mati o n a n d s u b mitti n g it as f oll o w -u p wit h t he 
ori gi nal Me d Watc h F or m F D A 3 5 0 0 A  
S u m ma rizi n g ne w i nf or mati o n a n d s u b mitti n g it wit h a c o ver letter i ncl u di n g s u bject i de ntifiers 
(i.e., D O B, i nitials, s u bject n u m ber), pr ot oc ol d escri pti o n a n d n u m ber, s us pect dr u g, brief 
a d verse e ve nt descri pti o n, a n d n otati o n t hat a d diti o nal or f oll o w -u p i nf o r mati o n is bei n g 
s u b mitte d 
 
1 2. 3. 3. 4  
Re p orti n g t o t he I nstit uti o n al Re vie w B o ar d  
B ot h seri o us a n d n o n -seri o us a d verse e ve nts will be re p orte d i n accor da nce wit h U C D I R B 
A d mi nistrati o n a n d U C D  C o m pre he nsi ve Ca ncer Ce nter’s ( U C D C C C)  Office of Cli nical 
Researc h  (O C R ) p olicies. T he U C Da vis I R B ca n be reac he d at ( 9 1 6) 7 0 3 -9 1 5 1.  
Partici pati n g site(s) will re p ort a d verse e ve nts per i nstit uti o n’s I R B g ui deli nes.   
1 3. 0  
E T HI C A L C O N SI D E R A TI O N S A N D A D MI NI S T R A TI V E  P R O C E D U R E S  
1 3. 1  
Et hics a n d G o o d Cli nic al Pr actice  
T his st u d y m ust be carrie d o ut i n c o m plia nce wit h t he pr ot oc ol a n d G o o d Cli nical Practice, as 
descri be d i n:  
1.  I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) Har m o nize d Tri partite G ui deli nes f or G o o d 
Cli nical Practice 1 9 9 6.  
2.  Directi ve 9 1/ 5 0 7/ E E C, T he R ules G o v er ni n g Me dici nal Pr o d ucts i n t he E ur o pea n 
C o m m u nit y.  
3.  U S 2 1 C o de of Fe d eral R e g ulati o ns deali n g wit h cli nical st u dies (i ncl u di n g parts 5 0 a n d 5 6 
c o ncer ni n g i nf or me d c o nse nt a n d I R B re g ulati o ns).  
4.  Declarati o n of Helsi n ki, c o ncer ni n g me di cal res earc h i n h u ma ns  ( Rec o m m e n dati o ns 
G ui di n g P h ysicia ns i n Bi o me dical Researc h I n v ol vi n g H u ma n S u bjects, Helsi n ki 1 9 6 4, 
a me n de d T o k y o 1 9 7 5, Ve nice 1 9 8 3, H o n g K o n g 1 9 8 9, S o merset West 1 9 9 6).  
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 8  of 6 8  
T he i n vesti gat or a grees, w he n si g ni n g t he pr ot oc ol, t o a d here t o t he i nstr ucti o ns a n d pr oce d ures 
descri be d i n it a n d t here b y t o a d here t o t he pri nci ples of G o o d Cli nical Practice t hat it c o nf or ms t o.  
1 3. 2  
I nstit uti o n al Re vie w B o ar d 
Bef ore i m ple me nti n g t his st u d y, t he pr ot oc ol, t he pr o p ose d i nf or me d c o nse nt f or m a n d ot her 
i nf or mati o n t o s u bjects, m ust be re vie we d b y a pr o perl y c o nstitute d I nstit uti o nal Re vie w B oar d 
(I R B). 
1 3. 3  
P atie nt I nf or m ati o n a n d I nf or me d C o nse nt 
After t he st u d y has b ee n f ull y e x plai ne d, writte n i nf or me d c o ns e nt will be o btai ne d fr o m eit her 
t he patie nt or his g uar dia n or le gal represe nt ati ve pri or t o st u d y partici pati o n.  T he met h o d of 
o btai ni n g a n d d oc u me nti n g t he i nf or me d c o nse nt a n d t he c o nte nts of t he c o nse nt will c o m pl y 
wit h I C H -G C P a n d all a p plica ble re g ulat or y re q uire me nt(s).  I n acc or da nce wit h U C D O C R  
p olic y a n ori gi nal s i g ne d a n d date d partici pa nt I nf or me d C o nse nt d oc u me nt will resi de i n a 
sec ure d l o cati o n wit hi n t he U C D O C R .  C o pies of t he si g ne d a n d date d I nf or me d C o nse nt 
d oc u me nt will be pr o vi de d t o t he st u d y partici pa nt a n d U C D Healt h S yste m I nf or mati o n 
Ma na ge me nt f or  i ncl usi o n i n t he partici pa nt’s U C D Healt h S yste m Me dical Rec or d . 
1 3. 4  
P atie nt C o nfi de nti alit y  
I n or der t o mai ntai n patie nt pri vac y, all st u d y re p orts a n d c o m m u nicati o ns will i de ntif y t he 
patie nt b y i nitials a n d t he assi g ne d patie nt n u m ber.  Data ca pt ure rec or d s a n d dr u g acc o u nt a bilit y 
rec or ds will be st ore d i n sec ure ca bi nets i n t he U C DC C C  O C R .  Me dical rec or ds of patie nts will 
be mai ntai ne d i n strict c o nfi de nce acc or di n g t o le gal re q uire m e nts. T he pati e nt’s c o nfi de ntialit y 
will be mai ntai ne d a n d will n ot be ma de p u blicl y a vaila ble t o t he e xte nt per mitte d b y t he 
a p plica ble la ws a n d re g ul ati o ns.  
1 3. 5  
St u d y Re gistr ati o n  
O nce si g ne d, i nf or me d c o nse nt has bee n o btai ne d a n d all pretreat me nt e val uati o ns ha ve bee n 
perf or me d, p atie nts will be e ntere d o n st u d y acc or di n g t o U C D Office of Cli nical Researc h  
(O C R ) p olic y. T o re gister a patie nt, t he dat a ma na ger or desi g nee m ust c o m plete t he Eli gi bilit y 
C hec klist a n d t he Patie nt Re gistrati o n F or m.  A fter verif yi n g t he eli gi bilit y, t he O C R c o or di nat or 
will re gister t he patie nt o nt o t he st u d y a n d assi g n a patie nt accessi o n.  A d mi nistrati o n of st u d y 
dr u g ma y n ot be i nitiate d u ntil t he patie nt is re gistere d  ( See A p pe n di x).   

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 5 9  of 6 8  
1 3. 6  
Pr ot oc ol C o m pli a nce  a n d De vi ati o ns  
T he i n vesti gat or will c o n d uct t he st u d y i n c o m plia nce wit h t he pr ot oc ol gi ve n a p pr o val/fa v ora bl e 
o pi ni o n b y t he I R B a n d t he a p pr o priate re g ul at or y a ut h orit y(ies).   
All pr ot oc ol de viati o ns will be re p orte d i n acc or da nce wit h U C D I R B A d mi nistrati o n a n d U C D 
Ca ncer Ce nter O C R  p olicies.  A n y de p art ures fr o m t he pr ot oc ol m ust be f ull y d oc u me nte d i n t he 
s o urce d oc u m e nts.   
1 3. 7  
Rec or d Rete nti o n  
T he i n vesti gat or will mai ntai n all st u d y rec or ds acc or di n g t o I C H -G C P a n d a p plica ble re g ulat or y 
re q uire me nt(s).  
1 3. 8  
Q u alit y Ass ur a nce a n d C o ntr ol  
Q ualit y ass ura nce a u dits of select patie nts a n d s o urce d oc u m e nts ma y be c o n d ucte d b y t he U C 
Da vis C o m pre he nsi ve Ca ncer Ce nter Q ualit y Ass ura nce C o m mittee as o utli ne d i n t he U C Da vis 
Ca ncer Ce nter Dat a a n d Safet y M o nit ori n g pla n.  Q ualit y c o ntr ol will be mai ntai ne d b y t he O C R  
Q ualit y Ass ura nce tea m acc or di n g t o O C R  p olic y.  
1 4. 0  
O V E R SI G H T  A N D M O NI T O RI N G  
1 4. 1  
D at a a n d S afet y M o nit ori n g  
I n a d diti o n t o t he re q uire me nts f or a d verse e ve nt re p orti n g, t his pr ot oc ol is als o s u bject t o t he U C 
Da vis C o m pre he nsi ve Ca ncer Ce nter’s ( U C D C C C ) Data a n d Safet y M o nit ori n g Pla n. T he 
U C D C C C is c o m mitte d t o p urs ui n g hi g h -q ualit y patie nt -orie nte d cli nical researc h a n d has 
esta blis he d mec ha nis ms t o e ns ure b ot h scie ntific ri g or a n d patie nt safet y i n t he c o n d uct of 
cli nical researc h st u dies. T he U C D C C C relies o n a m ulti -tiere d c o m mittee s yste m t hat re vie ws 
a n d m o nit ors all ca ncer cli nical trials a n d e ns ures t he safet y of its partici pa nts, i n c o m plia nce 
wit h i nstit uti o nal a n d fe d eral re q uire me nts o n a d verse e ve nt ( A E) re p orti n g, verificati o n of data 
acc urac y, a n d a d here n ce t o pr ot oc ol eli gi bilit y re q ui re me nts, treat me nt g ui deli nes, a n d rel ate d 
matters. T he Scie ntific R e vie w C o m mittee ( S R C) ass u mes o verall o versi g ht of ca ncer st u dies, 
wit h assista nce a n d i n p ut fr o m t w o i n de pe n de nt, b ut i nteracti n g, c o m mittees: t he Q ualit y 
Ass ura nce C o m mittee a n d t he Data  Safet y M o nit ori n g C o m mittee. A m ulti -le vel re vie w s yste m 
stre n gt he ns t he a bilit y of t he U C D CC C t o f ulfill its missi o n i n c o n d ucti n g hi g h q ualit y cli nical 
ca ncer researc h.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 0  of 6 8  
As per U C D C C C  Office of Cli nical Researc h  (O C R ) sta n dar d o perati n g pr oce d ure s t h e pri nci pal 
i n vesti gat or ( PI) a n d cli nical researc h c o or di nat or ( C R C) meet at least m o nt hl y f or o n g oi n g st u d y 
i nf or mati o n, t o disc uss patie nt data a n d a d verse e ve nts, a n d t o deter mi ne if d ose de -es calati o n is 
warra nte d, w he n a p plica ble . 
Acc or d i n g t o t he U C D CC C Data a n d Safet y M o nit ori n g Pla n ( D S M P), a n y ne w seri o us a d verse 
e ve nts relat e d t o t he dr u gs bei n g use d o n t his trial are re vie we d m o nt hl y b y t he U C D C C C Data 
a n d Safet y M o nit ori n g C o m mittee ( D S M C) a n d a n y a p plica ble c ha n ges t o t he st u d y ar e 
rec o m me n de d t o t he PI, if necess ar y. 
T he U C D C C C Scie ntific Re vie w C o m mittee ( S R C) deter mi nes if a U C D C C C Data a n d Safet y 
M o nit ori n g B oar d ( D S M B) is re q uire d.  If re q uire d, t he D S M C will a p p oi nt a D S M B. T he 
D S M B is res p o nsi ble f or re vie wi n g st u d y accr ual l o gs, a d verse e ve nt i nf or mati o n, a n d d ose de -
escalati o n meeti n g mi n utes ( w here a p plica ble) t o e ns ure s u bject s afet y a n d c o m plia nce wi t h 
pr ot oc ol defi ne d g ui deli n es.  
1 4. 2  
I n vesti g at or M o nit ori n g G ui deli nes 
I n v esti gat ors will c o n d uct c o nti n u o us re vie w of patie nt safet y. P atie nts will be m o nit ore d 
m o nt hl y  d uri n g t he st u d y.  All patie nts o n acti ve treat me nt will be disc usse d at wee kl y 
c o nfere nces t hat are hel d at t he U ni versit y of Calif or nia , Da vis . Per Ca ncer Ce nter g ui deli nes, a 
trial ca n n ot pr ocee d t o t h e ne xt d ose le vel u ntil a D L T meeti n g is c o n d ucte d t o c o m pre he nsi vel y 
re vie w all t o xicit y data a n d a p pr o ve t he d ose de -escalati o n. T he disc ussi o n will i ncl u de f or eac h 
d ose le vel: t he n u m ber of patie nts, si g nifica nt t o xicities as descri be d i n t he pr ot oc ol, d oses 
a dj ust me nts, a n d res p o ns es o bser ve d. 
 
 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 1  of 6 8  
1 5. 0  
R E F E R E N C E S  
1.  Sie gel R L, Mill der K D, Je mal A. Ca ncer statistics 2 0 1 7. C A Ca ncer J Cli n 2 0 1 7; 6 7: 7 -
3 0.  
2.  Ster n ber g C N, Ya g o d a A, Sc her HI, et al. Met h otre xate, vi n blasti ne, d o x or u bici n a n d 
cis plati n f or a d va n ce d tra nsiti o nal cell carci n o ma of t he ur ot heli u m. Efficac y a n d patter ns 
of res p o nse a n d rel a pse. Ca ncer 1 9 8 9 ; 6 4: 2 4 4 8-5 8.  
3.  L oe hrer PJ Sr, Ei n h or n L H, Els o n PJ, et al. A ra n d o mize d c o m paris o n of cis plati n al o ne 
or i n c o m bi nati o n wit h met h otre xate, vi n blasti ne, a n d d o x o r u bici n i n patie nts wit h 
metastatic ur ot helial carci n o ma: a c o o perati ve gr o u p st u d y. J Cli n O nc ol 1 9 9 2; 1 0: 1 0 6 6 -
7 3.  
4.  Sa x ma n S B, Pr o pert KJ, Ei n h or n L H, et al. L o n g -t er m f oll o w-u p of a p hase III i nter gr o u p 
st u d y of cis plati n al o ne or i n c o m bi nati o n wit h meth otre xate, vi n blasti ne, a n d 
d o x or u bici n i n patie nts wit h metastatic ur ot helial carci n o ma: a c o o perati ve gr o u p st u d y. J 
Cli n O nc ol 1 9 9 7; 1 5: 2 5 6 4 -9.  
5.  v o n der Maas e H, Ha nse n S W, R o berts J T, et al. Ge mcita bi ne a n d cis plati n vers us 
met h otre xate, vi n blasti ne, d o x or u bici n, a n d cis plati n i n a d va nce d or metastatic bla d der 
ca ncer: res ults of a l ar ge, ra n d o mize d, m ulti nati o nal, m ultice nter, P hase III st u d y. J Cli n 
O nc ol 2 0 0 0; 1 8: 3 0 6 8 -7 7.  
6.  Ster n ber g C N, de M ul der P H, Sc h or na gel J H, et al. Ra n d o mize d p hase III trial of  hi g h -
d ose i nte nsit y met h otre xate, vi n blasti ne, d o x or u bi ci n, a n d cis plati n ( M V A C) 
c he m ot hera p y a n d rec o m bi na nt h u ma n gra n ul oc yte c ol o n y -sti m ulati n g fact or vers us 
classic M V A C i n a d va n ce d ur ot helial tract t u m ors: E ur o pea n Or ga nizati o n f or Researc h 
a n d Treat me nt of Ca ncer Pr ot oc ol n o 3 0 9 2 4. J Cli n O nc ol 2 0 0 1; 1 9: 2 6 3 8 -4 6.  
7.  Ster n ber g C N. Se ve n y ear u p date of a n E O R T C p hase III trial of hi g h -i nte nsit y M-V A C 
c he m ot hera p y a n d G -C S F vers us classic M -V A C i n a d va nce d ur ot helial tract t u m o urs. 
E ur J Ca ncer 2 0 0 6; 4 5: 5 0 -4.  
8.  Bell m u nt J, de Wit R, Va u g h n DJ, et al. Pe m br oliz u ma b as sec o n d -li ne t hera p y f or 
a d va nce d ur ot helial carci n o ma. N E n gl J Me d 2 0 1 7; 3 7 6: 1 0 1 5 -2 6.  
9.  Balar A V, Castella n o D, O’ D o n nell P H, et al. First -li ne pe m br oliz u ma b i n cis plati n-
i neli gi ble patie nts with l ocall y a d va nce d a n d u nres ecta ble or metastatic ur ot helial ca ncer 
( K E Y N O T E-0 5 2): a m ultice ntre, si n gle -ar m, p has e 2 st u d y. La ncet O nc ol 2 0 1 7; 1 8: 
1 4 8 3 -9 2.  
1 0.  R ose n ber g J E, H off ma n -Ce nsits J, P o wles T, et al. Atez oliz u ma b i n patie nts wit h l ocall y 
a d va nce d a n d metastatic ur ot helial carci n o ma w h o ha ve pr o gresse d f oll o wi n g treat me nt 
wit h plati n u m -base d c he m ot hera p y: a si n gle -ar m, m ultice nter, p hase 2 trial. La ncet 2 0 1 6; 
3 8 7: 1 9 0 9 -2 0.  
1 1.  A p ol o A B, I nfa nte J R, Bal ma n o u kia n A, et al. A vel u ma b, a n a nti -pr o gra m me d deat h -
li ga n d 1 a nti b o d y, i n patie nts wit h refract or y metastatic ur ot helial carci n o ma: res ults fr o m 
a m ultice nter, P hase I b st u d y. J Cli n O nc ol 2 0 1 7; 3 5: 2 1 1 7 -2 4.  

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 2  of 6 8  
1 2.  S har ma P, Retz M, Sief ker -Ra dt ke A, et al. Ni v ol u ma b i n metastatic ur ot helial carci n o ma 
after plati n u m t hera p y ( C hec k mate 2 7 5): a m ultice ntre, si n gle -ar m, p hase 2 trial. La ncet 
O nc ol 2 0 1 7; 1 8: 3 1 2 -2 2.  
1 3.  P o wles T, O’ D o n nell P H, Massar d C, et al. Efficac y a n d safet y of d ur val u ma b i n l ocall y 
a d va nce d or metastatic ur ot helial carci n o ma: u p date d res ults fr o m a P hase 1/ 2 o pe n la bel 
st u d y. J A M A O nc ol 2 0 1 7: E 1 7 2 4 1 1 (e P u b) 
1 4.  M u q bil I, Ka uff ma n M, Sc ha m S, et al. U n dersta n di n g X P O 1 tar get net w or ks usi n g 
s yste ms bi ol o g y a n d mat he matical m o deli n g. C urre nt P har mace utical Desi g n 2 0 1 4;  2 0: 
5 6 -6 5.  
1 5.  Ta n D S, Be dar d P L, K ur u vil la J, et al. Pr o misi n g SI N Es f or e m bar g oi n g n uclear-
c yt o plas mic e x p ort as a n a ntica ncer strate g y. Ca ncer Disc o ver y 2 0 1 4; 4: 5 2 7 -3 7.  
1 6.  K oji ma K, K or n bla u S M, R u v ol o V, et al. Pr o g n ostic i m pact a n d tar geti n g of C R M 1 i n 
acut e le u ke mia.  2 0 1 3; 1 2 1: 4 1 6 6 -7 4.  
1 7.  Raza k A R, Ma u -S ore nse nse n M, Ga brail N Y, et al. First -i n-class, first-i n-h u ma n P hase I 
st u d y of seli n x or, a selecti ve i n hi bit or of n uclear e x p ort, i n patie nts wit h a d va nce d s oli d 
t u m ors. J Cli n O nc ol 2 0 1 6; 3 4: 4 1 4 2-5 0.  
1 8.  Garz o n R, Sa v o na  M, Baz R, et al. A P hase 1 cli ni cal trial of si n gle -a ge nt s eli ne x or i n 
ac ute m yel oi d le u ke mia. Bl o o d 2 0 1 7; 1 2 9: 3 1 6 5 -7 4.  
1 9.  K ur u villa J, Sa v o na M, Baz R, et al. Selecti ve i n hi biti o n of n uclear e x p ort wit h seli ne x or 
i n patie nts wit h n o n-H o d g ki n l y m p h o ma. Bl o o d 2 0 1 7; 1 2 9: 3 1 7 5 -8 3.  
2 0.  C he n C, Sie gel D, G utierrez M, et al. Safet y a n d efficac y of seli ne x or i n rel a pse d or 
refract or y m ulti ple m yel o ma a n d Wal d e nstr o m’s macr o gl o b uli ne mia. Bl o o d 2 0 1 7 ( A S H 
a bstract).  
2 1.  Ya n g A Y, Wi n er H, Gree n M, et al. A P hase I st u d y of sel i ne x or i n c o m bi nati o n wit h 
hi g h -d ose c ytara bi ne a n d mit o xa ntr o ne f or re missi o n i n d ucti o n i n patie nts wit h ac ute 
m yel oi d le u ke mia. J He mat ol O nc ol 2 0 1 8; 1 1: 4 (e p u b).  
2 2.  V o gl D T, Di n gli D, C or nell R F, et al. Selecti ve i n hi biti o n of n uclear e x p ort wit h oral 
seli ne x or f or treat me nt of rela pse d or refract or y m ulti ple m yel o ma. J Cli n O nc ol 2 0 1 8; 
3 6: 1 -8.  
2 3.  Bae k H B, L o m bar d A P, Li berti ni SJ, et al. X P O 1 i n hi biti o n b y seli ne x or i n d uces p ote nt 
c yt ot o xicit y a gai nst hi g h -gra de bla d der mali g na ncies. O nc otar get 2 0 1 8; 9: 3 4 5 6 7 -3 4 5 8 1.  
2 4.  Farre n M R, He n n esse y R C, S ha k ya R, et al. T he E x p orti n -1 i n hi bit or seli ne x or e xerts 
s u peri or a ntit u m or acti vit y w he n c o m bi ne d wit h T-cell c hec k p oi nt i n hi bit ors. M ol Ca ncer 
T her 2 0 1 7; 1 6: 4 1 7 -2 7.  
2 5.  Eise n ha uer, E A, et al. Ne w res p o nse e val uati o n criteria i n s oli d t u m o urs: re vise d R E CI S T 
g ui deli ne ( versi o n 1. 1). E ur J Ca ncer, 2 0 0 9; 4 5: 2 2 8 -4 7.  
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 3  of 6 8  
1 6. 0  
A P P E N DI C E S  
1 6. 1  
E C O G a n d K ar n ofs k y Perf or m a nce St at us Sc ores 1, 2 
 
E C O G P E R F O R M A N C E S T A T U S  
K A R N O F S K Y P E R F O R M A N C E S T A T U S  
0 — F ull y acti ve, a ble t o carr y o n all pre -disease 
perf or ma nce wit h o ut restricti o n  
1 0 0 — N or mal, n o c o m plai nts; n o e vi de nce of disease  
 9 0 — A ble t o carr y o n n or mal acti vit y; mi n or si g ns or 
s y m pt o ms of disease 
1 — Restricte d i n p h ysicall y stre n u o us acti vit y b ut 
a m b ulat or y a n d a ble t o ca rr y o ut w or k of a 
li g ht or se de ntar y nat ure, e. g., li g ht h o use 
w or k, office w or k  
 8 0 — N or mal acti vit y wit h eff ort, s o me si g ns or 
s y m pt o ms of disease 
 7 0 — Cares f or self b ut u na ble t o carr y o n n or mal 
acti vit y or t o d o acti ve w or k  
2 — A m b ulat or y a n d ca pa ble of all selfcare b ut 
u na ble t o carr y o ut a n y w or k acti vities; u p 
a n d a b o ut m ore t ha n 5 0 % of wa ki n g h o urs  
 6 0 — Re q uires occasi o nal assista nce b ut is a ble t o care 
f or m ost of pers o nal nee ds 
 5 0 — Re q uires c o nsi dera ble assista nce a n d fre q ue nt 
me dical care  
3 — Ca pa ble of o nl y li mite d selfcare; c o nfi ne d t o 
be d or c hair m ore t ha n 5 0 % of wa ki n g h o urs  
 4 0 — Disa ble d; re q uires s pecial care a n d assista nce  
 3 0 — Se verel y disa ble d; h os pitalizati o n is i n dicate d 
alt h o u g h deat h n ot i m mi ne nt  
4 — C o m pletel y disa ble d; ca n n ot car r y o n a n y 
selfcare; t otall y c o nfi ne d t o be d or c hair 
 2 0 — Ver y ill; h os pitalizati o n a n d acti ve s u p p orti ve 
care necessar y  
 1 0 — M ori b u n d  
5 — Dea d  
  0 — Dea d  
 
1.  Kar n ofs k y D, B urc he nal J, T he cli nical e val uati o n of c he m ot hera pe utic a ge nts i n ca ncer. I n: Mac Le o d C, e d. 
E val uati o n of C he m ot hera pe utic A ge nts. Ne w Y or k, N Y: C ol u m bia U ni versit y Press; 1 9 4 9: 1 9 1 – 2 0 5.  
2.  Z u br o d C, et al. A p praisal of met h o ds f or t he st u d y of c he m ot hera p y i n ma n: C o m parati ve t hera pe utic trial of 
nitr o ge n m ustar d a n d t hi o p h os p h ora mi de . J o ur nal of C hr o nic Diseases; 1 9 6 0: 1 1: 7-3 3.  
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 4  of 6 8  
1 6. 2  
C oc kcr oft -G a ult E sti m ati o n of Cr Cl 
 
C oc kcr oft -Ga ult esti mati o n of creati ni ne cleara nce ( Cr Cl):  
( C oc kcr oft, 1 9 7 6; L u ke 1 9 9 0) 
 
Cr Cl ( m L/ mi n) =    
    ( 1 4 0 –  a ge) x ( wei g ht, k g) _ _           
   (M ales )   
   
7 2 x (ser u m creati ni ne, m g/ d L)  
 
Cr Cl ( m L/ mi n) =    
    ( 1 4 0 –  a ge) x ( wei g ht, k g)     x 0. 8 5          
   (Fe m ales )    
7 2 x (ser u m creati ni ne, m g/ d L)  
 
 
 
1 6. 3  
St u d y Re gistr ati o n  
O nce si g ne d, i nf or me d c o nse nt has b ee n o btai ne d; patie nts will be e ntere d o n st u d y.  T o re gister 
a patie nt, t he st u d y c o or di nat or m ust c o m p lete t he Eli gi bilit y C hec klist. T he st u d y c o or di nat or 
will re gister t he patie nt o nt o t he st u d y a n d assi g n a u ni q ue patie nt n u m ber.    
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 5  of 6 8  
1 6. 4  
D at a C ollecti o n  F or ms   
All data will be c ollecte d usi n g U C Da vis data c ollecti o n f or ms. A n y a n d all s o urce 
d oc u me ntati o n s hall be mai ntai ne d.  
 
 
 
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 6  of 6 8  
1 6. 5  
N CI C T C Versi o n 5 . 0 
T o xicit y will be sc ore d usi n g N CI C T C V ersi o n 5. 0 f or t o xicit y a n d a d verse e vent re p orti n g.  A 
c o p y of t he N CI C T C V ersi o n 5. 0  ca n be d o w nl oa de d fr o m t he C T E P  h o me pa ge: 
( htt p://cte p.i nf o. ni h. g o v).  All a p pr o priate treat me nt areas h a ve access t o a c o p y of t he C T C  
versi o n.  
 
 
 

Seli ne x or pl us P e m br oliz u m a b  
 
Cli nic al St u d y Pr ot oc ol U C D C C # 2 8 9  
 
 
Versi o n 4. 0 ( 0 6 / 0 3/ 2 0 2 2) 
U C D a vis C o m pre he nsi ve C a ncer Ce nter  
 
 
C O N FI D E N TI A L  
 
P a ge 6 8  of 6 8  
1 6. 7  
C orrel ati v e S a m ple C ollecti o n a n d H a n dli n g  
Bl o o d sa m ples will be c ollecte d pre - a n d p ost -treat me nt a n d will be st ore d i n t he U C Da vis 
Bi ore p osit or y, wit h assista nce fr o m A nt h o n y Marti nez.