A Phase II Single Arm Study of Nivolumab as Maintenance Therapy After Autologous Stem Cell Transplantation in Patients With Hodgkin Lymphoma at Risk of Relapse or Progression
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Sponsor: SCRI Development Innovations, LLC

 
C O N FI D E N TI A L  
T his d oc u me nt is c o nfi de nti al a n d is t he pr o perty of S ar a h C a n n o n Devel o p me nt I n n ov ati o ns,  L L C.  N o p art of t his 
d oc u me nt m ay be tr a ns mitte d, re pr o d uce d, p u blis he d, or use d by ot her pers o ns wit h o ut pri or writte n a ut h oriz ati o n 
fr o m S ar a h C a n n o n Devel o p me nt I n n ov ati o ns, L L C . 
B M T 2 4  
A P h ase II Si n gle Ar m St u d y of Ni v ol u m a b as M ai nte n a nce  Ther a p y after 
A ut ol o g o us S te m Cell T r a ns pl a nt ati o n i n P atie nts wit h H o d g ki n L y m p h o m a 
at R is k of R el a pse or P r o gressi o n 
S A R A H C A N N O N D E V E L O P M E N T 
I N N O V A TI O N S S T U D Y N U M B E R : 
 
B M T 2 4  
S T U D Y  D R U G:  
Ni v ol u ma b  
S P O N S O R:  
Sara h Ca n n o n De vel o p me nt I n n o vati o ns , L L C 
1 1 0 0 Dr. Marti n L . Ki n g Jr. Bl v d. , S uite 8 0 0 
Nas h ville, T N  3 7 2 0 3  
1- 8 4 4 -7 1 0 -6 1 5 7  
as ksara h @sara hca n n o n.c o m  
 
S T U D Y C H AI R : 
Carl os B ac hier, M D  
Sara h Ca n n o n Researc h I nstit ute   
1 1 0 0 Dr. Marti n L . Ki n g Jr. Bl v d. , S uite 8 0 0 
Nas h ville, T N  3 7 2 0 3  
1- 8 4 4 -7 1 0 -6 1 5 7  
 
D A T E FI N A L:  
0 6  J ul y 2 0 1 7  
A M E N D M E N T N U M B E R:  
1  
A M E N D M E N T D A T E:       
2 3 A u g ust 2 0 1 7  
A M E N D M E N T N U M B E R:  
2  
A M E N D M E N T D A T E:       
1 6 Oct o ber  2 0 1 7  
A M E N D M E N T N U M B E R:  
3  
A M E N D M E N T D A T E:       
2 3 Marc h  2 0 1 8  
A M E N D M E N T N U M B E R:  
4  
A M E N D M E N T D A T E:       
2 4  Se pte m ber  2 0 1 8  
A M E N D M E N T N U M B E R:  
5  
A M E N D M E N T D A T E:    
1 6 J a n uar y 2 0 1 9 
A M E N D M E N T N U M B E R:  
6  
A M E N D M E N T D A T E:    
0 7 Fe br uar y 2 0 2 0  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 of 6 9  
 
 
B M T 2 4  
A P h ase II Si n gle Ar m St u d y of Ni v ol u m a b as M ai nte n a nce  T her a p y after 
A ut ol o g o us Ste m C ell Tr a ns pl a nt ati o n i n P atie nts wit h H o d g ki n L y m p h o m a 
at Ris k of Rel a pse or Pr o gressi o n  
 
 T his cli nic al  st u d y s h all be c o n d ucte d i n c o m pli a nce wit h t he pr ot oc ol, as refere nce d herei n, a n d 
all a p plic a ble l oc al, n ati o n al, a n d i nter n ati o n al re g ul at or y re q uire me nts t o i ncl u de, b ut n ot be 
li mite d t o: 
•  
I nter n ati o n al C o u ncil f or  H ar m o nisati o n (I C H) G ui deli nes o n G o o d Cli nic al P r actice 
( G C P) 
•  
Et hic al pri nci ples t h at h a ve t heir ori gi ns i n t he Decl ar ati o n of Helsi n ki  
•  
F o o d a n d Dr u g A d mi nistr ati o n ( F D A) C o de of F e der al Re g ul ati o n ( C F R):  
o  
Title 2 1 C F R P art 5 0 & 4 5 C F R P art 4 6, Pr otecti o n of H u m a n S u bjects 
o  
Title 2 1 C F R P art 5 4, Fi n a nci al Discl os ure b y Cli nic al I n vesti g at ors  
o  
Title 2 1 C F R P art 5 6, I nstit uti o n al Re vie w B o ar ds  
o  
Title 2 1 C F R P art 3 1 2, I n vesti g ati o n al Ne w Dr u g A p plic ati o n 
o  
Titl e 4 5 C F R P arts 1 6 0, 1 6 2, a n d 1 6 4, He alt h I ns ur a nce P ort a bilit y a n d 
Acc o u nt a bilit y Act ( HI P A A)  
 
 
 
 
 
 
 
 
   
  
    
 
   
  
 
 
  
 
  
 
   
   
 
   
    
  
  
  
  
  
   
   
  
  
  
    
  
 
  
  
  
 
   
  
    
  
   
     
  
  
  
  
 
    
  
 
 
 
 

 
 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
Pa ge 3 of 6 9  
 
Cli nic al  St u d y  Si g n at ure A p pr o v al P a ge  
A P h ase II Si n gle Ar m St u d y of Ni v ol u m a b as M ai nte n a nce  T her a p y after 
A ut ol o g o us Ste m  Cell Tr a ns pl a nt ati o n i n P atie nts wit h H o d g ki n L y m p h o m a 
at Ris k of Rel a pse or Pr o gressi o n  
 
S A R A H C A N N O N D E V E L O P M E N T 
I N N O V A TI O N S S T U D Y N U M B E R : 
 
B M T 2 4  
S T U D Y  D R U G:  
Ni v ol u ma b   
D A T E FI N A L:  
0 6  J ul y 2 0 1 7 
A M E N D M E N T N U M B E R:  
1  
A M E N D M E N T D A T E:       
2 3 A u g ust 2 0 1 7  
A M E N D M E N T N U M B E R:  
2  
A M E N D M E N T D A T E:       
1 6 Oct o ber  2 0 1 7  
A M E N D M E N T N U M B E R:  
3  
A M E N D M E N T D A T E:       
2 3 Marc h  2 0 1 8  
A M E N D M E N T N U M B E R  
4  
A M E N D M E N T D A T E:   
2 4 Se pt e m ber  2 0 1 8  
A M E N D M E N T N U M B E R:  
5  
A M E N D M E N T D A T E:    
1 6  J a n uar y 2 0 1 9 
A M E N D M E N T N U M B E R:  
6  
A M E N D M E N T D A T E:    
0 7 Fe br uar y 2 0 2 0  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _         _ _ _ _ _ _ _ _ _ _ _ _ _ _  
St u d y C h ai r  
S ar a h C a n n o n Res e arc h I nstit ute  
St u d y C h ai r  Si g n at ure  
 
D ate  
 
 
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _         _ _ _ _ _ _ _ _ _ _ _ _ _ _  
S p o ns or Re pres e nt ati ve  
S ar a h C a n n o n De vel o p m e nt 
I n n o v ati o ns, L L C 
 
S ar a h C a n n o n De vel o p m e nt I n n o v ati o ns, 
L L C Re pres e nt ati ve Si g n at ure  
 
D ate  
 
 
 
 
 
 
 
 
0 2/ 1 2/ 2 0 2 0
0 9: 3 8 A M E S T
I a m a p pr o vi n g t hi s d o c u m e nt.
C arl o s  B a c hi er, M. D.
S h e et al  K h e d k ar, M. D., M S P H
I a m a p pr o vi n g t hi s
d o c u m e nt.
0 2/ 1 3/ 2 0 2 0
0 8: 5 1 A M E S T
02/13/2020
08:51 AM EST
I am approving this
document.
Sheetal  Khedkar, M.D., MSPH
Carlos  Bachier, M.D.
I am approving this document.
02/12/2020
09:38 AM EST

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 of 6 9  
 
 
Cli nic al St u d y Pri nci p al I n vesti g at or Si g n at ure F or m  
A P h ase II Si n gle Ar m St u d y of Ni v ol u m a b as M ai nte n a nce  T her a p y after 
A ut ol o g o us Ste m  Cell Tr a ns pl a nt ati o n i n P atie nts wit h H o d g ki n L y m p h o m a 
at Ris k of Rel a pse or Pr o gressi o n  
 
S A R A H C A N N O N D E V E L O P M E N T 
I N N O V A TI O N S S T U D Y N UM B E R:  
 
B M T 2 4  
D A T E FI N A L:  
0 6  J ul y 2 0 1 7 
A M E N D M E N T N U M B E R:  
1  
A M E N D M E N T D A T E:       
2 3 A u g ust 2 0 1 7  
A M E N D M E N T N U M B E R:  
2  
A M E N D M E N T D A T E:       
1 6 Oct o ber 2 0 1 7  
A M E N D M E N T N U M B E R:  
3  
A M E N D M E N T D A T E:       
2 3 Marc h  2 0 1 8  
A M E N D M E N T N U M B E R:  
4   
A M E N D M E N T D A T E:       
2 4 Se pte m ber  2 0 1 8  
A M E N D M E N T N U M B E R:  
5  
A M E N D M E N T D A T E:    
1 6  J a n uar y 2 0 1 9 
A M E N D M E N T N U M B E R:  
6  
A M E N D M E N T D A T E:    
0 7 Fe br uar y 2 0 2 0  
B y si g ni n g t his pr ot oc ol acce pta nce pa ge, I c o nfir m I ha ve rea d, u n dersta n d, a n d a gree t o c o n d uct t he 
st u d y i n acc or da nce wit h t he c urre nt pr ot oc ol. 
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _            _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _     _ _ _ _ _ _ _  
P ri nci p al I n vesti g at or N a me  
( Please Pri nt) 
 
P ri nci p al I n vesti g at or Si g n at ure  
 
D ate  
 
Please retai n a c o p y of t his pa ge f or y o ur st u d y fil es a n d ret ur n t h e ori gi nal si g ne d a n d date d 
f or m t o: 
 
Sara h Ca n n o n De v el o p me nt I n n o v ati o ns , L L C 
1 1 0 0 Dr. Marti n L . Ki n g Jr. Bl v d., S uite 8 0 0 
At t n:  B M T 2 4  St u d y Tea m  
Nas h ville, T N 3 7 2 0 3 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 of 6 9  
 
B M T 2 4 S u m m ar y of C h a n ge  
 
A M E N D M E N T N U M B E R:  
6  
A M E N D M E N T D A T E:        0 7 Fe br uar y 2 0 2 0  
Secti o n 5. 0 St u d y Desi g n Fi ve of t he f ort y p atie nts t o be e nr olle d o n t he st u d y will be e nr olle d 
t o a c o ntr ol gr o u p. 
Secti o n 5. 4. 2 I m m u ne R ec o ver y  vers us C o ntr ol Gr o u p Secti o n a d de d t o detail st u d y sc h e d ule 
f or c o ntr ol patie nts. 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 of 6 9  
 
B M T 2 4  P R O T O C O L S Y N O P SI S  
Title of St u d y : 
A P hase II Si n gle Ar m St u d y of Ni v ol u ma b as Mai nte na nce  T hera p y after A ut ol o g o us Ste m  
C ell Tra ns pla ntati o n i n P atie nts wit h H o d g ki n L y m p h o ma at Ris k of Rela pse or Pr o gressi o n  
S ar a h C a n n o n 
De vel o p me nt 
I n n o v ati o ns St u d y  
N u m ber : 
B M T 2 4  
S p o ns or:  
Sara h Ca n n o n De vel o p me nt I n n o vati o ns , L L C –  Nas h ville , T N  
St u d y  D ur ati o n:  
T he t otal d urati o n of t he st u d y is pla n ne d t o be  4 years 
( 2 years e nr oll me nt a n d 2 years ma xi m u m f oll o w -u p).  
P h ase of St u d y :  II 
St u d y  Ce nter s: 
T his st u d y will be  c o n d ucte d at 6  st u d y sites. 
N u m ber of 
P atie nts:  
U p t o  4 0  patie nts are pla n ne d t o be e nr olle d i n t his st u d y: 3 5  will recei ve st u d y treat me nt a n d 
5 patie nts will recei ve sta n dar d-of -care pr oce d ures a n d treat me nt b ot h pre - a n d p ost-
tra ns pla nt. 
O bjecti ves:  
Pri m ar y O bjecti ve  
T he pri mar y o bj ecti ve of t his st u d y is t o:  
•  
E val uate safet y a n d t olera bilit y of ni v ol u ma b as mai nte na nc e earl y after a ut o l o g o us 
ste m cell tra ns pla nt ( A S C T) i n patie nts wit h H o d g ki n L y m p h o ma ( H L) 
Sec o n d ar y O bjecti ves  
T he sec o n dar y o bj ecti ve of t his st u d y is t o: 
•  
E val uate P F S at 1 2 m o nt hs  p ost -tra ns pla nt w he n ni v ol u ma b is a d mi nistere d as 
mai nte na nce i n patie nts wit h H L  after A S C T  
E x pl or at or y O bjecti ves  
T he e x pl orat or y o bj ecti ves of t his st u d y are t o:  
•  
C orrelate efficac y of ni v ol u ma b w he n gi ve n as mai nte na nce after A S C T  wit h 
pr o gra m me d cell deat h pr otei n -1 ( P D - 1) e x pressi o n a n d ot her i m m u ne effect or a n d 
re g ulat or y cells 
•  
C orrelate p ositr o n e missi o n t o m o gra p h y ( P E T )- c o m p ute d t o m o gra p h y ( C T ) 
ne gati vit y wit h P F S  
St u d y  Desi g n : 
T his is a P hase II si n gle -ar m o pe n -la bel st u d y of ni v ol u ma b as mai nte na nce  t hera p y after 
A S C T  i n patie nts wit h H L  at ris k of rela pse or pr o gressi o n.  
St u d y Dr u g s, 
D oses, a n d M o des 
of A d mi nistr ati o n:  
P atie nts will recei ve ni v ol u ma b ( 2 4 0  m g  I V) starti n g Da y 4 5 -1 8 0  p ost -tra ns pla nt (± 1 0 da ys) 
e ver y 2 wee ks f or u p t o a ma xi m u m of 6 m o nt hs of treat me nt.   Fi ve patie nts will recei ve 
sta n dar d-of -care treat me nt pre - a n d p o st-tra ns pla nt as a c o ntr ol gr o u p t o c o m pare i m m u ne 
rec o ver y. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 7 of 6 9  
 
 
B M T 2 4  PR O T O C O L S Y N O P SI S  
I ncl usi o n Criteri a: 
1.  P atie nts 1 8 years of a ge a n d ol der wit h H L  w h o ha ve recei ve d a ut o -H S C T i n t he pre vi o us 
4 5 -1 8 0  da ys.  
2.  C o m plete res p o nse ( C R), partial res p o nse ( P R) o r sta ble disease ( S D) t o sal va ge t hera p y 
pri or t o A S C T  
3.  Hi g h ris k of resi d ual H L p ost -A S C T, as deter mi ne d b y o ne  of t he f oll o wi n g:  
•  
P ositi ve P E T sca n defi ne d b y t he Dea u ville scale 3- 4 ( A p pe n di x C ) a n d wit hi n 2 
m o nt h s of start of hi g h-d ose c he m ot hera p y pri or t o A S C T  
•  
Refract or y t o fr o ntli ne t hera p y  
•  
Rela pse < 1 2 m o nt hs after fr o ntli ne t hera p y  
•  
Rela pse ≥1 2 m o nt hs after fr o ntli ne t hera p y wit h e xtra n o dal disease  
4.  Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) P erf or ma nc e Stat us sc ore of 0 -1 
( A p pe n di x A).  
5.  A de q uate he mat ol o gic f u ncti o n defi ne d as all of t he f oll o wi n g:  
-  
A bs ol ute ne utr o p hil c o u nt ( A N C) ≥1 0 0 0/ μ L  
-  
He m o gl o bi n ( H g b) ≥8 g/ d L (tr a nsf usi o ns t o reac h t his p oi nt are n ot per mitte d)  
-  
Platelets ≥5 0, 0 0 0/ µ L (tra nsf usi o n is n ot per mitte d)  
6.  A de q uate li ver f u ncti o n defi ne d as all of t he f oll o wi n g:  
-  
Ala ni ne a mi n otra nsferase ( A L T) a n d as partate a mi n otra nsferase ( A S T) ≤2. 5 × t he 
u p per li mit of n or mal ( U L N)  
-  
T otal bilir u bi n ≤1. 5 × U L N ( u nless t he patie nt has Gra de 1 bilir u bi n ele vati o n d ue t o 
Gil bert disease or a si milar s y n dr o me i n v ol vi n g sl o w c o nj u gati o n of bilir u bi n)  
7.  A de q uate re nal f u ncti o n defi ne d as ser u m creati ni ne ≤1. 5 m g/ d L ( 1 3 3 μ m ol/ L).  
8.  Fe males of c hil d beari n g p ote ntial m ust ha ve a ne gati ve ser u m or uri ne pre g na nc y test res ult 
wit hi n 7 2 h o urs pri or t o t he first d ose of ni v ol u ma b a n d m ust a gree t o f oll o w i nstr ucti o ns 
f or met h o d(s) of c o ntrace pti o n f or t he d urati o n of treat me nt wit h ni v ol u ma b a n d f or 
7 m o nt hs f oll o wi n g t heir last d ose of st u d y dr u g ( A p pe n di x C).  Fe males of n o n-
c hil d beari n g p ote ntial are t h os e w h o are p ost me n o pa usal gre ater t ha n 1 year or w h o ha ve 
ha d a bilateral t u bal li gati o n or h ysterect o m y.  
9.  Male patie nts wit h fe male part ners of c hil d beari n g p ote ntial a n d w o me n patie nts of 
c hil d beari n g p ote ntial are re q uire d t o use t w o f or ms of acce pt a ble  c o ntrace pti o n, i ncl u di n g 
o ne barrier met h o d, d uri n g t heir partici pati o n i n t he st u d y a n d f or 7 m o nt hs f oll o wi n g last 
d ose of st u d y dr u g.  Male pati e nts m ust als o refrai n fr o m d o nati n g s per m d uri n g t heir 
partici pati o n i n t he st u d y a n d f or 7  m o nt hs f oll o wi n g last d ose of st u d y dr u g ( A p pe n di x C).  
1 0.  Willi n g ness a n d a bilit y t o c o m pl y wit h st u d y a n d f oll o w -u p pr oce d ures.  
1 1.  A bilit y t o u n dersta n d t he nat ur e of t his st u d y a n d gi ve writte n i nf or me d c o nse nt.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 8 of 6 9  
 
B M T 2 4  P R O T O C O L S Y N O P SI S  
E xcl usi o n 
Criteri a:  
1.  P atie nts t hat ha ve recei ve d a n all o ge nic tra ns pla nt.  
2.  Pri or A S C T  or c urre nt t hera p y wit h ot her a nti -ne o plastic or i n vesti gati o nal a ge nts.  
3.  B est res p o nse of pr o gressi ve disease pri or t o A S C T  
4.  P atie nts wit h a n y a ut oi m m u ne disease or a hist or y of a ut oi m m u ne dise ase.  P atie nts wit h 
vitili g o, t y pe I dia betes mellit us, resi d ual h y p ot h yr oi dis m d ue t o a ut oi m m u ne c o n diti o n 
o nl y re q uiri n g h or m o ne re place me nt, ps oriasis n ot re q uiri n g s yste mic treat me nt, or 
c o n diti o ns n ot e x pecte d t o rec ur i n t he a bse nce of a n e xter nal tr i g ger are per mitte d t o 
e nr oll. 
5.  A n y c o n diti o n re q uiri n g s yste mic treat me nt wit h c ortic oster oi ds ( > 1 0 m g dail y pre d nis o ne 
e q ui vale nts) or ot her i m m u n os u p pressi ve me dicati o ns wit hi n 1 4 da ys pri or t o first d ose of 
st u d y dr u g. I n hale d ster oi ds a n d a dre nal re place me nt ster oi d d oses > 1 0 m g dail y 
pre d nis o ne e q ui vale nts are per mitte d i n t he a bse nce of acti ve a ut oi m m u ne disease.  
6.  U se of a st u d y dr u g ≤2 1 da ys or 5 half-li ves ( w hic he ver is s h orter) pri or t o t he first d ose of 
ni v ol u ma b.  F or st u d y dr u gs f or w hic h 5 half -li ves is ≤2 1 da ys, a mi ni m u m of 1 0 da ys 
bet wee n ter mi nati o n of t he st u d y dr u g a n d a d mi nistrati o n of ni v ol u ma b is re q u ire d. 
7.  Wi de -fiel d ra di ot hera p y (i ncl u di n g t hera pe utic ra di ois ot o pes s uc h as str o nti u m 8 9) 
a d mi nistere d ≤2 8 da ys or li mit e d fiel d ra diati o n f or palliati o n ≤7 da ys pri or t o starti n g 
st u d y dr u g or has n ot rec o vere d fr o m si de effects of s uc h t hera p y.  
8.  Maj or s ur g ical pr oce d ures ≤2 8 da ys of be gi n ni n g st u d y dr u g, or mi n or s ur gical pr oce d ures 
≤7 da ys.  N o waiti n g re q uire d f oll o wi n g p ort -a-cat h place me nt.  
9.  Pre vi o usl y u ntreate d brai n metastases.  P atie nts w h o ha ve recei ve d ra diati o n or s ur ger y f or 
brai n metastases are e li gi ble if t hera p y was c o m plete d at least 2 wee ks pri or t o st u d y e ntr y 
a n d t here is n o e vi de nce of ce ntral ner v o us s yste m disease pr o gressi o n, mil d ne ur ol o gic 
s y m pt o ms, a n d n o re q uire me nt f or c hr o nic c ortic oster oi d t herap y.  
1 0.  Pre g na nt or lactati n g  
1 1.  Ac ute or c hr o nic li ver, re nal, or pa ncreatic disease.  
1 2.  U nc o ntr olle d dia betes mellit us  (fasti n g bl o o d gl uc ose > 2 5 0 m g/ d L). 
1 3.  A n y of t he f oll o wi n g car diac diseases c urre ntl y or wit hi n t he last 6 m o nt hs:  
-  
Left v e ntric ular ej ecti o n fracti o n ( L V E F) < 4 5 % as deter mi ne d b y m ult i ple g ate d 
ac q uisiti o n ( M U G A) sca n or ec h ocar di o gra m ( E C H O)  
-  
C orrecte d Q T ( Q T c ) i nter val > 4 8 0 ms o n scree ni n g electr ocar di o gra m ( E C G) 
-  
U nsta ble a n gi na pect oris  
-  
C o n gesti ve heart fail ure ( Ne w Y or k Heart Ass ociati o n ( N Y H A) ≥ Gra de 2 
[ A p pe n di x B])  
-  
Ac ute m y ocar di al i nfarcti o n  
-  
C o n d ucti o n a b n or malit y n ot c o ntr olle d wit h pace ma ker or me dicati o n  
-  
Si g nifica nt ve ntric ular or s u pra ve ntric ular arr h yt h mias ( patie nts wit h c hr o nic rate -
c o ntr olle d atrial fi brillati o n i n t he a bse nce of ot her car diac a b n or malities are eli gi ble)  
-  
Val v ular disease wit h si g nific a nt c o m pr o mise i n car diac f u ncti o n  
1 4.  I na de q uatel y c o ntr olle d h y pert e nsi o n (i.e., s yst olic bl o o d press ure [ S B P] > 1 8 0 m m H g or 
diast olic bl o o d press ure ( D B P) > 1 0 0 m m H g) ( patie nts wit h val ues a b o ve t hese le vels m ust 
ha ve t heir bl o o d  press ure [B P ] c o ntr olle d wit h me dicati o n pri or t o starti n g treat me nt).  
1 5.  Seri o us acti ve i nfecti o n at t he ti me of treat me nt or a n ot her s eri o us u n derl yi n g me dical 
c o n diti o n t hat w o ul d i m pair t he a bilit y of t he patie nt t o recei ve pr ot oc ol treat me nt.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 9 of 6 9  
 
E xcl usi o n 
Criteri a:  
1 6.  K n o w n dia g n osis of h u ma n i m m u n o deficie nc y vir us, he patitis B, or he patitis C.  T esti n g at 
baseli ne is n ot re q uire d.  
1 7.  Prese nce of ot her acti ve ca ncers, or hist or y of treat me nt f or i n vasi ve ca ncer ≤5 years.  
P atie nts wit h Sta ge I ca ncer w h o ha ve recei ve d defi niti ve l ocal treat me nt a n d are 
c o nsi dere d u nli kel y t o rec ur are eli gi ble.  All patie nts wit h pre vi o usl y treate d i n s it u 
carci n o ma (i.e., n o n -i n vasi ve) are eli gi ble, as are patie nts wit h hist or y of n o n-mela n o ma 
s ki n ca ncer. 
1 8.  Ps yc h ol o gical, fa milial, s oci ol o gical, or ge o gra p hical c o n diti o ns t hat d o n ot per mit 
c o m plia nce wit h t he pr ot oc ol.  
St atistic al 
M et h o d ol o g y:  
T he n ull  h y p ot hesis t o be teste d is t hat t he tr ue 1 2 -m o nt h P F S is 5 0 % a gai nst a t w o-si de d 
alter nati ve h y p ot hesis of a 7 0 % P F S rate.  T he 5 0 % 6 -m o nt h P F S rate was o btai ne d fr o m 
Rec o m me n dati o ns f or I nitial E val uati o n, Sta gi n g, a n d Res p o nse Assess me nt of H o d g ki n a n d 
N o n -H o d g ki n L y m p h o ma: T he L u ga n o Classificati o n ( C hes o n et al. 2 0 1 4, see A p pe n di x F ).  A 
t w o-si de d, o ne-sa m ple l o g-ra n k test calc ulate d fr o m a sa m pl e of 3 6 e val ua ble s u bj ects ac hi e ves 
8 0. 3 % p o wer at a 0. 0 5 0 si g nifica nce le vel t o detect a n i m pr o ve me nt of 2 0 % i n 1 2 -m o nt h P F S.  
T h e pr o ba bilit y t hat a s u bj ect e x perie nces a n e ve nt d uri n g t he st u d y is 0. 4 5 7 9.  T he e x pecte d 
n u m ber of e ve nts d uri n g t he st u d y is 1 6.  It is ass u me d t hat t he s ur vi val ti me distri b uti o ns of 
b ot h gr o u ps are a p pr o xi mate d reas o na bl y well b y  t he W ei b ull distri b uti o n wit h a s ha pe 
para meter of 1. 0 0.  T hese pr o p orti o ns ass u me a n e nr oll me nt peri o d of 1 8 m o nt hs a n d a f oll o w -
u p peri o d of 1 2 m o nt hs after t he last s u bj ect is a d de d.  I n or der t o all o w f or a 1 0 % dr o p o ut rate, 
a t otal of 4 0 patie nts wil l be e nr olle d.  T he sa m ple size wa s calc ulate d usi n g P A S S versi o n 1 4. 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 0  of 6 9  
 
B M T 2 4  C O N T A C T I N F O R M A TI O N  
S ar a h C a n n o n De vel o p me nt  I n n o v ati o ns 
C o nt act I nf or m ati o n:  
Sara h Ca n n o n De vel o p me nt  I n n o vati o ns 
1 1 0 0 Dr. Marti n L . Ki n g Jr. Bl v d. , S uite 8 0 0 
Nas h ville, T N  3 7 2 0 3  
1- 8 4 4 -7 1 0 -6 1 5 7  
as ksara h @sara hca n n o n.c o m  
 
St u d y C h air : 
Carl os B ac hier, M D  
Sara h Ca n n o n Researc h I nstit ute  
1 1 0 0 Dr. Marti n L . Ki n g Jr. Bl v d. , S uite 8 0 0 
Nas h ville, T N  3 7 2 0 3  
1- 8 4 4 -7 1 0 -6 1 5 7  
as ksara h @sara hca n n o n.c o m  
 
S afet y De pt.  F a x #:  
S afet y De pt.  E m a il: 
1 -8 6 6 -8 0 7 -4 3 2 5  
C A N N. S A E @ S C RI -I n n o vati o ns.c o m 
Re g ul at or y P h o ne #  
Re g ul at or y E m ail:  
1 -8 4 4 -7 1 0 -6 1 5 7  
S C RI Re g ulat or y @ S C RI -I n n o vati o ns.c o m 
S ar a h C a n n o n De vel o p me nt  In n o v ati o ns  
E nr oll me nt P h o ne #:  
S ar a h C a n n o n De vel o p me nt  I n n o v ati o ns 
E nr oll me nt F a x #:  
S ar a h  C a n n o n De vel o p me nt I n n o v ati o ns 
E nr oll me nt E m ail : 
1 -8 4 4 -7 1 0 -6 1 5 7  
 
1- 8 6 6 -6 9 9 -0 2 5 8  
 
C A N N. S C RII n n o vati o ns E nr @scri -i n n o vati o ns.c o m 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 1  of 6 9  
 
LI S T O F A B B R E VI A TI O N S  
A E  
A d verse e ve nt  
A L P  
Al kali ne p h os p hatase  
A L T  ( S G P T) 
Ala ni ne a mi n otra nsferase  
A N C  
A bs ol ute ne utr o p hil  c o u nt  
A S C T  
A ut ol o g o us ste m cell tra ns pla nt  
A S T ( S G O T) 
A s partate a mi n otra nsferase 
C B C  
C o m plete bl o o d c o u nt  
C F R  
C o de of Fe deral Re g ulati o ns  
cH L  
Classical H o d g ki n L y m p h o ma  
CI  
C o nfi de nce i nter val  
C M P  
C o m pre he nsi ve meta b olic pr ofile  
C R  
C o m plete res p o nse/re missi o n 
C R F  
Case re p ort for m  
C T  
C o m p ute d t o m o gra p h y  
E C G  
Electr ocar di o gra m  
E C O G   
Easter n C o o perati ve O nc ol o g y Gr o u p   
e C R F  
E lectr o nic case re p ort for m  
E F S  
E ve n t-free sur vi val  
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  
HI P A A  
Heal t h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act 
H L  
H o d g ki n L y m p h o ma  
H S C T  
He mat o p oietic ste m cell tra ns pla ntati o n 
I B 
I n vesti gat or B r oc h ure 
I C F 
I nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or  Har m o ni sati o n  
I N R 
I nter nati o nal n or malize d rati o  
I R B 
I nstit uti o nal R e vie w B oar d  
I V 
I ntra ve n o usl y 
N CI C T C A E  
Nati o nal Ca ncer I nstit ute C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts  
N S C L C  
N o n -s mall cell l u n g ca ncer 
O S  
O verall s ur vi val  
 
 
P D -1  
Pr o gra m me d cell deat h pr otei n -1  
P E T  
P ositr o n e missi o n t o m o gra p h y  
P F S  
Pr o gressi o n -free s ur vi val 
P HI  
P r otecte d healt h i nf or mati o n 
P K  
P har mac o ki netics  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 2  of 6 9  
 
 
LI S T O F A B B R E VI A TI O N S  (c o nti n ue d) 
P R  
P artial res p o nse/re missi o n  
R C C  
Re nal cell ca ncer  
S A E  
Seri o us a d verse e ve nt  
S A R  
S us pecte d a d verse reacti o n  
S D  
Sta ble disease  
S U S A R  
S us pecte d u ne x pecte d seri o us a d verse reacti o n  
U L N  
U p per li mit of n or mal  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 3  of 6 9  
 
T A B L E O F C O N T E N T S  
1.  
I N T R O D U C TI O N ................................................................................................. 1 8 
1. 1  
Bac k gr o u n d ........................................................................................................... 1 8  
1. 2  
Treat me nt of Rela pse d or Refract or y H o d g ki n L y m p h o ma .................................. 1 8  
1. 3  
Pr o g n ostic Fact ors i n H o d g ki n L y m p h o ma........................................................... 1 8  
1. 4  
P ost-tra ns pla nt T hera p y f or H o d g ki n L y m p h o ma ................................................. 1 8  
1. 5  
Ni v ol u ma b ............................................................................................................. 1 9  
1. 5. 1  
Cli nical Efficac y  .................................................................................................... 1 9 
1. 5. 2  
Cli nical Safet y  ....................................................................................................... 2 0 
1. 6  
P D - 1 E x pressi o n i n H o d g ki n L y m p h o ma ............................................................. 2 0 
1. 7  
Rati o nale f or t he St u d y .......................................................................................... 2 1  
2.  
S T U D Y O BJ E C TI V E S  ......................................................................................... 2 1 
2. 1  
Pri mar y O bj ecti ve .................................................................................................. 2 1 
2. 2  
Sec o n dar y O bj ecti ves  ............................................................................................ 2 1 
2. 3  
E x pl orat or y O bjecti ves .......................................................................................... 2 1  
2. 4  
E n d p oi nts ............................................................................................................... 2 1  
2. 4. 1  
Safet y E n d p oi nts .................................................................................................... 2 1 
2. 4. 2  
Efficac y E n d p oi nt .................................................................................................. 2 2  
2. 4. 3  
A d diti o nal E n d p oi nt .............................................................................................. 2 2  
3.  
S T U D Y P A TI E N T P O P U L A TI O N A N D DI S C O N TI N U A TI O N  ...................... 2 2 
3. 1  
I n cl usi o n Criteria ................................................................................................... 2 2 
3. 2  
E x cl usi o n Criteria  .................................................................................................. 2 3 
3. 3  
Disc o nti n uati o n fr o m St u d y Treat me nt ................................................................. 2 5  
4.  
P A TI E N T R E GI S T R A TI O N  ................................................................................ 2 5 
5.  
S T U D Y D E SI G N  .................................................................................................. 2 6 
5. 1  
Treat me nt Pla n  ...................................................................................................... 2 6 
5. 1. 1  
Ni v ol u ma b ............................................................................................................. 2 6  
5. 2  
Treat me nt D ur ati o n ............................................................................................... 2 6  
5. 3  
C o nc o mita nt Me dicati o ns...................................................................................... 2 6  
5. 3. 1  
Per mitte d C o nc o mita nt Me dicati o ns  ..................................................................... 2 6 
5. 3. 2  
Pr o hi bite d C o nc o mita nt Me dicati o ns  .................................................................... 2 7 
5. 4  
C orrelati ve St u dies  ................................................................................................ 2 7 
5. 4. 1  
Bi o mar ker A nal ysis ............................................................................................... 2 7  
5. 4. 2  
I m m u ne Rec o ver y v ers us C o ntr ol Gr o u p .............................................................. 2 7 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 4  of 6 9  
 
5. 4. 3  
Ha n dli n g, St ora ge a n d D estr ucti o n of Bi ol o gical Sa m ples ................................... 2 7  
5. 4. 4  
Wit h dra wal of I nf or me d C o nse nt f or D o nate d Bi ol o gical Sa m ples ..................... 2 8  
6.  
D O S E M O DI FI C A TI O N S  .................................................................................... 2 8 
6. 1  
Ma na ge me n t of Ni v ol u ma b-Relate d A d v erse E v e nts  ........................................... 2 9 
6. 1. 1  
Ma na ge me nt of I nf usi o n- Relate d Reacti o ns  ......................................................... 2 9 
7.  
S T U D Y A S S E S S M E N T S A N D E V A L U A TI O N S  .............................................. 3 0 
7. 1  
O ver vie w  ............................................................................................................... 3 0 
7. 2  
Baseli ne St u d y Assess me nts  ................................................................................. 3 0 
7. 3  
St u d y Treat me nt A ssess me nts ............................................................................... 3 1 
7. 3. 1  
Da y 1 of Eac h C ycle ( ± 2 da ys as l o n g as i nter val b et wee n d oses is 1 2- 1 6 
da ys ) ...................................................................................................................... 3 1 
7. 4  
E n d of St u d y Tr eat me nt ........................................................................................ 3 1  
7. 5  
Res p o nse Assess me nt  ............................................................................................ 3 1 
7. 6  
F oll o w- u p .............................................................................................................. 3 2  
8.  
D R U G F O R M U L A TI O N, A V AI L A BI LI T Y, A D MI NI S T R A TI O N, A N D 
T O XI CI T Y I N F O R M A TI O N  ............................................................................... 3 2 
8. 1  
Ni v ol u ma b ............................................................................................................. 3 2  
8. 1. 1  
La b eli n g, Pac ka gi n g, S u p pl y, a n d St ora ge ............................................................ 3 2  
8. 1. 2  
Pre parati o n a n d A d mi nistrati o n of Ni v ol u ma b ..................................................... 3 2  
8. 1. 3  
Preca uti o ns a n d Ris ks Ass ociate d wit h Ni v ol u ma b .............................................. 3 2  
8. 2  
Acc o u nta bilit y f or All St u d y Dr u gs  ...................................................................... 3 2 
9.  
R E S P O N S E E V A L U A TI O N S  A N D M E A S U R E M E N T S  .................................. 3 3 
1 0.  
S T A TI S TI C A L C O N SI D E R A TI O N S  .................................................................. 3 3 
1 0. 1  
Statistical Desi g n  ................................................................................................... 3 3 
1 0. 2  
Sa m ple Size C o nsi derati o ns .................................................................................. 3 3  
1 0. 3  
A nal ysis P o p ulati o n ............................................................................................... 3 3  
1 0. 4  
Data A nal ysis  ........................................................................................................ 3 4 
1 0. 4. 1  
De m o gra p hics a n d Baseli ne C haract eristics  ......................................................... 3 4 
1 0. 4. 2  
Efficac y A nal ysis  .................................................................................................. 3 4 
1 0. 4. 3  
Safet y A nal ysis  ...................................................................................................... 3 4 
1 0. 4. 4  
E x pl orat or y A nal ysis ............................................................................................. 3 5  
1 0. 5  
A nal ysis Ti me P oi nts ............................................................................................. 3 5 
1 0. 5. 1  
Fi nal A nal ysis  ........................................................................................................ 3 5 
1 0. 5. 2  
Pla n ne d I nteri m A nal ysis  ...................................................................................... 3 5 
1 1.  
S A F E T Y R E P O R TI N G A N D  A N A L Y S E S  ......................................................... 3 5 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 5  of 6 9  
 
1 1. 1  
Defi niti o ns  ............................................................................................................. 3 5 
1 1. 1. 1  
A d verse E v e nts  ...................................................................................................... 3 5 
1 1. 1. 2  
Seri o us A d verse E v e nt .......................................................................................... 3 6  
1 1. 1. 3  
A d verse Reacti o n  .................................................................................................. 3 6 
1 1. 1. 4  
S us pecte d A d vers e Reacti o n  ................................................................................. 3 6 
1 1. 1. 5  
Rec or di n g a n d Re p orti n g of A d vers e E ve nts ........................................................ 3 7  
1 1. 1. 6  
Assess me nt of A d vers e E ve nts .............................................................................. 3 8 
1 1. 2  
Seri o us A d verse E v e nt Re p orti n g b y I n vesti gat ors ............................................... 3 8  
1 1. 3  
Rec or di n g of A d v erse E v e nts a n d Seri o us A d vers e E ve nts .................................. 3 9  
1 1. 3. 1  
Dia g n osis vers us Si g ns a n d S y m pt o ms ................................................................. 3 9  
1 1. 3. 2  
Persiste nt or Rec urr e nt A d verse E ve nts  ................................................................ 3 9 
1 1. 3. 3  
A b n or mal La b or at or y Val ues ................................................................................ 3 9  
1 1. 3. 4  
Deat hs  .................................................................................................................... 4 0 
1 1. 3. 5  
H os pitalizati o n, Pr ol o n ge d H os pitalizati o n, or S ur ger y  ........................................ 4 0 
1 1. 3. 6  
Pre -E xisti n g Me dical C o n diti o ns  .......................................................................... 4 0 
1 1. 3. 7  
Ne w Ca ncers .......................................................................................................... 4 1 
1 1. 3. 8  
Pre g n a nc y, A b orti o n, a n d Birt h Defects/ C o n ge nital A n o malies  .......................... 4 1 
1 1. 3. 9  
Ni v ol u ma b O ver d ose ............................................................................................. 4 1  
1 1. 4  
S p o ns or Seri o us A d verse E ve nt Re p orti n g Re q uire me nts .................................... 4 1  
1 1. 4. 1  
S p o ns or Assess me nt of U ne x pecte d...................................................................... 4 2  
1 1. 4. 2  
S p o ns or Re p orti n g f or Cli nical St u dies U n der a n I n ve sti gati o nal N e w Dr u g 
A p plicati o n  ............................................................................................................ 4 2 
1 2.  
Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L  .................................... 4 2 
1 2. 1  
St u d y M o nit ori n g, A u diti n g, a n d I ns pecti n g ......................................................... 4 2  
1 3.  
E T HI C A L, FI N A N CI A L, A N D R E G U L A T O R Y C O N SI D E R A TI O N S  ............ 4 3 
1 3. 1  
I nstit uti o nal Re vie w B oar d A p pr o val.................................................................... 4 3 
1 3. 2  
Re g ulat or y A p pr o val  ............................................................................................. 4 3 
1 3. 3  
I nf or me d C o nse nt .................................................................................................. 4 3 
1 3. 3. 1  
C o nfi de ntialit y  ....................................................................................................... 4 4 
1 3. 4  
Fi na ncial I nf or mati o n  ............................................................................................ 4 5 
1 4.  
R E S E A R C H R E T E N TI O N A N D D O C U M E N T A TI O N O F T H E S T U D Y  ........ 4 5 
1 4. 1  
A me n d me nts t o t he Pr ot oc ol ................................................................................. 4 5  
1 4. 2  
D oc u me ntati o n Re q uire d t o I nitiate t he St u d y  ...................................................... 4 6 
1 4. 3  
St u d y D oc u me ntati o n a n d St ora ge ........................................................................ 4 7  
1 4. 4  
Data C ollecti o n  ...................................................................................................... 4 8 
1 4. 5  
Discl os ure a n d P u blicati o n P olic y ......................................................................... 4 8  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 6  of 6 9  
 
1 5.  
R E F E R E N C E S ...................................................................................................... 5 0  
1 6.  
A P P E N DI C E S  ....................................................................................................... 5 2 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 7  of 6 9  
 
LI S T O F T A B L E S  
Ta ble 1  
D ose Le vel M o dificati o ns ........................................................................ 2 9  
LI S T O F A P P E N DI C E S  
A p pe n di x A:  
E C O G Perf or ma n ce Stat us Criteria  ......................................................... 5 2 
A p pe n di x B:  
Ne w Y or k Heart Ass ociati o n ( N Y H A) Classificati o n of Car diac 
Disease  ..................................................................................................... 5 3 
A p pe n di x C:  
Dea u ville 5 - p oi nt sc ori n g s yste m............................................................. 5 4 
A p pe n di x D:  
G ui deli nes f or Fe male Patie nts of C hil d beari n g P ote ntial a n d Fertile 
Male Patie nts  ............................................................................................ 5 5 
A p pe n di x E:  
Sc he d ule of Assess me nts  ......................................................................... 5 7 
A p pe n di x F:  
Rec o m me n dati o ns f or I nitial E val uati o n, Sta gi n g, a n d Res p o nse 
Assess me nt of H o d g ki n a n d N o n- H o d g ki n L y m p h o ma: T he L u ga n o 
Classificati o n ............................................................................................ 5 9 
A p pe n di x G:  
Ma na ge me nt Al g orit h ms f or I m m u n o- O nc ol o g y A ge nts  ........................ 6 2 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 8  of 6 9  
 
1.  
IN T R O D U C TI O N  
1. 1  
B ac k gr o u n d 
H o d g ki n L y m p h o ma ( H L) is a ca n cer t h at arises fr o m ger mi nal ce nter or p ost -ger mi nal ce nter B 
cells.  T he diseas e has u ni q ue cell ular c o m p ositi o n disti n g uis hi n g it fr o m ot her B cell 
l y m p h o mas a n d c o nsists of s mall n u m bers of mali g na nt Ree d-Ster n ber g cells wit hi n a n e x te nsi ve 
b ut i neffecti ve i nfl a m mat or y a n d i m m u ne -cell i nfiltrate.  H o d g ki n L y m p h o ma acc o u nts f or 
a p pr o xi matel y 1 0 % of all l y m p h o mas, lea di n g t o a b o ut 8 5 0 0 ne w cas es a n d 1 1 2 0 deat hs 
a n n uall y i n t he U nite d States ( Sie gel et al.  2 0 1 6).  H o d g ki n L y m p h o ma has a bi m o dal a ge 
distri b uti o n c ur ve wit h a pea k i n y o u n g a d ults at a p pr o xi matel y 2 0 years of a ge a n d i n ol der 
a d ults ar o u n d a ge 6 5 ( Ries et al. 1 9 9 7 ).  M ost pati e nts affecte d b y t his disease are y o u n g a d ults. 
1. 2  
Tre at me nt of Rel a pse d or Refr act o r y H o d g ki n L y m p h o m a  
T he maj orit y of patie nts wit h H L are c ure d wit h c o m bi nati o n c he m ot hera p y a n d/ or ra diati o n 
t hera p y wit h c o m plete re missi o n attai ne d i n > 8 0 % of patie nts.  Hi g h- d ose t hera p y a n d 
a ut ol o g o us ste m cell tra ns pl a nt ( A S C T) are us e d as sta n dar d of care f or p atie nts wit h pri mar y 
resista nt or rec urr e nt H L .  W hile tra ns pla nt res ults i n a c ure f or s o me patie nts, m ore t ha n 5 0 % 
will e ve nt uall y r ela pse a n d die of t he disease ( Maj hail  et al. 2 0 0 6).  Pr o g n ostic fact ors ha v e bee n 
i de ntifie d t hat aff ect l o n g-ter m o utc o mes after tra ns pla nt f or patie nts wit h H o d g ki n diseas e.  
Ti me -t o-treat me nt f ail ure has bee n f o u n d t o b e a d v ersel y i nfl ue nce d b y a d v a nce d sta ge at 
dia g n osis, c o m ple me nt ar y r a di ot hera p y b ef ore A S C T, a s h ort first c o m plete res p o nse, a n d 
detecta ble disease at A S C T ( S ure da et al. 2 0 0 5 ).  Patie nts w h o pr o gress aft er A S C T ha ve li mite d 
t hera pe utic o pti o ns t o i m pr o ve t he o utc o me of t heir disease. 
1. 3  
Pr o g n osti c F act o rs i n H o d g ki n L y m p h o m a  
Pr o g n ostic fact ors ha v e b ee n i de ntifie d t hat affect l o n g- ter m o utc o me aft er tra ns pla nt f or patie nts 
wit h H o d g ki n diseas e.  P o or o utc o mes p ost- A S C T are ass o ciate d wit h t he prese nce of B 
s y m pt o ms, e xtra n o dal disease, a n d a less t ha n 1 2 m o nt h d urati o n of re missi o n after fr o ntli ne 
c he m ot hera p y.  Patie nts wit h i nter me diate or hi g h -ris k disease h a ve a 5-year e ve nt -free s ur vi val 
(E F S ) r ate of less t ha n 3 0 % c o m par e d t o 6 5 % t o 8 0 % f or patie nts wit h l o w-ris k disease 
(M os k o witz et al. 2 0 0 1 , Maj hail  et al. 2 0 0 6), (S ure da et al. 2 0 0 5 ).  Patie nts w h o pr o gress after 
A S C T ha ve li mite d t hera pe utic o pti o ns t o i m pr o ve t he o utc o me of t heir disease.  M ost rel a pses 
occ ur wit hi n t he first 2  years p ost - A S C T.  I ntr o d u ci n g a n o vel t hera p y t o pre ve nt diseas e 
pr o gressi o n a n d/ or r ela ps e i n i nter me diate - t o hi g h-ris k patie nts p ost- A S C T w o ul d be of be n efit 
f or t hese patie nts. 
1. 4  
P ost -tr a ns pl a nt T her a p y f or H o d g ki n L y m p h o m a  
B ase d o n d ata i n t he A E T H E R A trial, i n A u g ust 2 0 1 5 t he F D A a p pr o ve d bre nt u xi ma b ve d oti n 
f or t he p ost-a ut ol o g o us he mat o p oietic ste m cell tra ns pla ntati o n (a ut o-H S C T ) treat me nt of 
patie nts wit h classical H L at hi g h ris k of rela ps e or pr o gressi o n.  Pr o gressi o n -free s ur vi val (P F S ) 
i n t he bre nt u xi ma b ve d oti n ar m was 4 2. 9 m o nt hs c o m pare d t o 2 4. 1 m o nt hs i n t he place b o ar m 
(M os k o witz et al. 2 01 5 ).  W hile lea di n g t o a si g nifica nt i m pr o ve me nt i n P F S, disc o nti n uati o n of 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 1 9  of 6 9  
 
treat me nt d ue t o a d v erse e ve nts occ urre d i n o ver 3 0 % of patie nts pri maril y d ue t o peri p heral 
se ns or y a n d m ot or ne ur o pat hies (M os k o witz et al. 2 01 5 ).  T his i nt olera nce t o t he o nl y 
esta blis he d t hera p y t o pr e ve nt rela ps e de m o nstrat es t he nee d f or t he de v el o p me nt of n o vel 
treat me nt o pti o ns f or t hese patie nts. 
1. 5  
Ni v ol u m a b 
Ni v ol u ma b (als o ref err e d t o as B M S - 9 3 6 5 5 8 or M D X 1 1 0 6) is a h u ma n m o n ocl o nal a nti b o d y 
( H u M A b; i m m u n o gl o b uli n G 4 [I g G 4]-S 2 2 8 P) t hat tar gets t he pr o gra m me d deat h -1 ( P D -1)  
cl uster of diff ere ntiati o n 2 7 9 ( C D 2 7 9) cell s urface m e m bra ne rece pt or.  P D - 1 is a ne gati ve 
re g ulat or y m olec ul e e x presse d b y acti vat e d T a n d B l y m p h o c yt es (S har p e et al. 2 0 0 7 ).  Bi n di n g 
of P D -1 t o its  li ga n ds, pr o gr a m me d deat h-li ga n d 1 ( P D- L 1) a n d 2 ( P D- L 2), res ults i n t he d o w n-
re g ulati o n of l y m p h o c yte acti vati o n.  I n hi biti o n of t he i nteracti o n bet w ee n P D- 1 a n d its li ga n ds 
pr o m otes i m m u ne res p o nses a n d a nti ge n- s p ecific T-cell res p o ns es t o b ot h f orei g n a nti ge ns as 
well as  self- a nti ge ns.  Ni v ol u ma b is e x presse d i n C hi nese ha mster o var y ( C H O) cells a n d is 
pr o d uce d usi n g sta n dar d ma m malia n cell c ulti vati o n a n d c hr o mat o gra p hic p urificati o n 
tec h n ol o gi es.  T he  cli nical st u d y pr o d u ct is a sterile s ol uti o n f or pare nteral a d mi nistrati o n.  
T he p har mac o ki netics ( P K ), cli nical acti vit y, a n d safet y of ni v ol u ma b ha v e bee n assess e d i n 
s u bjects wit h n o n-s mall cell l u n g ca ncer ( N S C L C), mela n o ma, clear -cell re nal cell carci n o ma 
( R C C), a n d classical H o d g ki n L y m p h o ma (c H L) i n a d diti o n t o ot her t u m or t y pes.  Ni v ol u ma b 
m o n ot hera p y is a p pr o ve d i n m ulti ple c o u ntries, i ncl u di n g t he U S a n d E U, f or u nresecta ble or 
metastatic mela n o ma, pr e vi o usl y treate d metastati c N S C L C, a n d pre vi o usl y treate d a d v a nce d 
R C C . I n a d diti o n, ni v ol u ma b is als o a p pr o ve d f or t he treat me nt of c H L i n t he U S. 
1. 5. 1  
Cli nic al Effic ac y  
Ni v ol u ma b has de m o nstrate d d ura ble res p o nses e x cee di n g 6 m o nt hs as m o n ot hera p y a n d i n 
c o m bi nati o n wit h i pili m u ma b i n se veral t u m or t y p es , i ncl u di n g N S C L C, m ela n o ma, R C C, c H L, 
S C L C, gastric ca n cer, ur ot helial ca ncer, he p at ocell ular carci n o ma, a n d c ol orectal ca ncer .  I n 
c o nfir mat or y trials, ni v ol u ma b as m o n ot hera p y d e m o nstrate d a statisticall y si g nifica nt 
i m pr o ve me nt i n o verall s ur vi val (O S ) c o m pare d wit h t he c urre nt sta n dar d of care i n s u bjects wit h 
a d va nce d or metastatic N S C L C, u nr esecta ble or  m etastatic mela n o ma, a d va nce d  R C C, or 
s q ua m o us cell car ci n o ma of t he hea d a n d nec k (S C C H N ). 
1. 5. 1. 1  
Cli nic al Effic ac y i n H o d g ki n L y m p h o m a  
Ni v ol u ma b m o n ot hera p y has de m o nstrate d cli nical be nefit i n s u bjects wit h c H L w h o ha v e 
rela pse d or pr o gress e d, i ncl u di n g t h ose w h o recei ve d a ut ol o g o us h e mato p oietic ste m cell  
tra ns pla ntati o n a n d p ost-tra ns pla ntati o n bre nt u xi ma b ve d oti n, a n d has bee n a p pr o ve d f or use i n 
t he U S.  T w o st u dies e val uate d t he efficac y of ni v ol u ma b as a si n gl e a ge nt i n patie nts wit h c H L 
after f ail ure of a ut ol o g o us H S C T a n d p ost-tra ns pla ntati o n bre nt u xi ma b ve d oti n.  Patie nts 
recei v e d 2 4 0 m g of ni v ol u ma b a d mi nistere d i ntra v e n o usl y (I V) o v er 6 0 mi n utes e ver y 2 w ee ks 
u ntil disease pr o gressi o n, ma xi mal cli nical be nefit, or u nacce pta ble t o xicit y.  A c ycle  c o nsiste d 
of o ne d ose.  D os e re d u c ti o n was n ot per mitte d. 
Efficac y was e val uate d i n 9 5 patie nts  ( b ot h trials c o m bi ne d) w h o ha d recei ve d bre nt u xi ma b 
ve d oti n after f ail ure of a ut ol o g o us H S C T.  Res p o nse was assess e d usi n g  t h e Re vise d Res p o nse 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 0  of 6 9  
 
Criteria f or Mali g na nt L y m p h o ma ( C hes o n et al. 2 0 0 7 ).  Se ve n patie nts ( 7 %) ha d c o m plet e 
re missi o n ( C R) wit h a 9 5 % c o nfi de n ce i nter v al ( CI , [ 3, 1]) a n d 5 5 ( 5 8 %) patie nts ha d partial 
re missi o n ( P R) wit h a 9 5 % CI ( 4 7, 6 8).  T he o bj ecti ve res p o nse rate ( C R + P R) was 6 2 patie nts 
( 6 5 %).  Me dia n d urati o n of res p o nse ( D o R) was 8. 7 m o nt hs a n d me dia n ti me t o res p o nse w as 
2. 1 m o nt hs. 
1. 5. 2  
Cli nic al S af et y  
T he o ver all safet y e x peri e nce wit h ni v ol u ma b, as a m o n ot hera p y or i n c o m bi nati o n wit h ot her 
t hera pe utics, is bas e d o n e x perie nce i n a p pr o xi mately 1 2, 3 0 0 s u bjects treate d t o date.  F or 
m o n ot hera p y, t he saf et y pr ofile is si milar acr oss t u m or t y pes.  T h ere is n o patter n i n t he 
i nci de nce, se v erit y, or ca usalit y of a d v erse e ve nts ( A Es ) t o ni v ol u ma b d ose le vel.  I n P hase 3 
c o ntr olle d st u dies, t he saf et y pr ofile of ni v ol u ma b m o n ot hera p y is acce pta bl e i n t he c o nte xt of 
t he o bser ve d cli nical efficac y a n d ma na gea ble usi n g esta blis he d s afet y g ui deli nes.  Cli nicall y 
rele va nt A Es t y pical of sti m ulati o n of t he i m m u ne s yste m were i nfre q ue nt a n d ma na gea bl e b y 
dela yi n g or st o p pi n g ni v ol u ma b treat me nt a n d ti mel y i m m u n os u p pressi v e t hera p y or ot her 
s u p p orti ve car e. 
1. 5. 2. 1  
Re n al a n d He p atic I m p air me nt  
T he eff ect of re nal i m pair me nt o n t he cleara nce ( C L ) of ni v ol u ma b w as e v al uate d i n s u bjects 
wit h mil d  (gl o mer ular filtrati o n rate  [G F R ] < 9 0 a n d ≥6 0 m L/ mi n/ 1. 7 3 m 2; n = 3 7 9), m o derate 
( G F R < 6 0 a n d ≥3 0 m L/ mi n/ 1. 7 3 m2; n = 1 7 9), or se vere ( G F R < 3 0 a n d ≥1 5 m L/ mi n/ 1. 7 3 m 2; 
n = 2) re n al i m pair me nt c o m pare d t o  s u bjects wit h n or mal re nal f u n cti o n ( G F R ≥9 0 m L/ mi n/ 1. 7 3 
m 2; n = 3 4 2) i n t he p o p ulati o n p har mac o ki netic (P P K ) a nal ysis.  N o  cli nicall y i m p orta nt 
differe n ces i n t he C L of ni v ol u ma b were f o u n d b et wee n s u bjects wit h mil d or m o derate re nal 
i m pair me nt a n d s u bjects wit h n or mal re nal f u n cti o n.  Data fr o m s u bjects wit h  se vere re nal 
i m pair me nt are to o li mite d t o dra w c o n cl usi o ns o n t his p o p ulati o n. 
T he eff ect of h e patic i m p air me nt o n t he C L of ni v ol u ma b was e val uat e d i n s u bjects wit h mil d  
he patic i m pair me nt (t otal bilir u bi n 1. 0 t o 1. 5 ti mes u p per li mit of n or mal [ U L N ] or as p artate 
a mi n otra nsfer ase [ A S T ] > U L N as d efi ne d usi n g t he  Nati o nal Ca ncer I nstit ute [ N CI] criteria of 
he patic d ysf u ncti o n; n = 9 2) c o m par e d t o s u bjects wit h n or mal he patic f u n cti o n (t otal bilir u bi n 
a n d A S T ≤ U L N; n = 8 0 4) i n t he p o p ulati o n P K a nal yses.  N o cli nicall y i m p orta nt differe nc es i n 
t he C L of ni v ol u ma b w er e f o u n d bet wee n s u bjects wit h mil d he patic i m pair me nt a n d n or mal 
he patic f u ncti o n.  Ni v ol u ma b has n ot bee n st u die d i n s u bjects wit h m o derate (t otal bilir u bi n > 1. 5 
t o 3 ti mes U L N a n d a n y A S T) or se vere he p atic i m pair me nt (t otal bilir u bi n > 3 ti mes U L N a n d 
a n y A S T).  
1. 6  
P D -1 E x pressi o n i n H o d g ki n L y m p h o m a  
St u dies ha ve f o u n d hi g h e x pressi o n of P D- L 1 i n H L  (R oe mer et al  2 0 1 6).  Pr o gra m me d cell 
deat h pr otei n 1 ( P D - 1) bl oc ka de wit h ni v ol u ma b i n cli nical trials e nr olli n g hea vil y pre-treate d 
H L p atie nts ha ve r es ulte d i n res p o nse rat es i n o ver 8 5 % of patie nts ( A nsell  et al. 2 01 5 ).  T he 
m ost c o m m o n dr u g- r elat e d A Es were r as h a n d decreas e d platelet c o u nt wit h 9 % of patie nts 
disc o nti n ui n g d ue t o t o xic eff ects (A ns ell  et al. 2 0 1 5 ).  Data de m o nstrati n g t he t olera bilit y a n d 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 1  of 6 9  
 
efficac y of P D -1 i n hi biti o n i n H L p atie nts ma ke ni v ol u ma b a pr o misi n g t h era p y t o e v al uate i n 
t he p ost-tra ns pla nt setti n g. 
1. 7  
R ati o n ale f or t he St u d y  
T he mali g n a nt Ree d - Ster n ber g cells f o u n d i n H L  ha ve bee n f o u n d t o o vere x press P D- 1 (Gree n  et 
al. 2 0 1 0 ).  Ni v ol u ma b, a n a nti b o d y directe d a gai nst P D - 1, has bee n w ell -t olerate d a n d 
efficaci o us i n t his patie nt p o p ulati o n ( A nsell  et al. 2 01 5 ).  We pr o p ose t o st u d y ni v ol u ma b 
mai nte na nce  t hera p y p ost-A S C T  i n H o d g ki n disease t o see if it is well-t olerate d w he n gi ve n as 
earl y mai nte na n ce t hera p y.  M os k o witz et al. 2 0 1 0  c o n d ucte d a st u d y t o i de ntif y pr o g n ostic 
fact ors f or patie nts wit h r ela pse d or r efract or y H L recei vi n g tra ns pla nt.  I n t his a nal ysis of 
1 5 3 patie nts, it was f o u n d t hat f u ncti o nal i ma gi n g stat us bef ore A S C T was t he o nl y fact or 
si g nifica nt f or E F S  a n d O S a n d clearl y i de ntifi e d a p o o r ris k p o p ulati o n ( 5 year E F S 3 1 % a n d 
7 5 % f or FI - p ositi ve a n d ne gati ve patie nts res pecti vel y).  T his st u d y ai ms t o e nr oll hi g h -ris k 
patie nts as defi ne d b y t his ma n uscri pt t o recei ve ni v ol u ma b t hera p y as c o ns oli dati o n t hera p y 
p ost-tra ns pla nt.  We are als o e x pl ori n g if P F S ca n be pr ol o n ge d i n hi g h- ris k H L p atie nts 
c o m pare d t o hist orical pl ace b o c o ntr ols re p ort e d i n ot her st u dies.  
2.  
S T U D Y  OB J E C TI V E S  
2. 1  
Pri m ar y O bjecti ve  
T he pri mar y o bjecti ve of t his st u d y is t o: 
•  E val uate saf et y a n d t oler a bilit y of ni v ol u ma b as mai n te na nce t hera p y earl y after A S C T  i n 
patie nts wit h H L  
2. 2  
Sec o n d ar y O bjecti ves  
T he sec o n d ar y o bjecti ve  of t his st u d y is t o: 
•  E val uate P F S at 1 2 m o nt hs p ost-tra ns pla nt w he n ni v ol u ma b is a d mi nistere d as 
mai nte na nce t hera p y i n p atie nts wit h H L  after A S C T  
2. 3  
E x pl or at or y O bjecti ves  
T he e x pl orat or y o bj ecti v es of t his st u d y are t o: 
•  C orrelate efficac y of ni v ol u ma b w he n gi ve n as m ai nte na nce t hera p y after A S C T  wit h 
P D - 1 e x pressi o n a n d ot her i m m u ne effect or a n d re g ul at or y cells  
•  C orrelat e p ositr o n e missi o n t o m o gra p h y ( P E T )-c o m pute d t o m o gra p h y ( C T ) ne gati vit y 
wit h P F S  
2. 4  
E n d p oi nts  
2. 4. 1  
S af et y E n d p oi nts  
•  T y pe, i n ci de nce, se verit y, seri o us ness, a n d relate d ness of A E s 
•  La b orat or y a b n or malities  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 2  of 6 9  
 
•  A Es  lea di n g t o disc o nti n uati o n 
2. 4. 2  
Effic ac y E n d p oi nt 
•  Pr o gr essi o n- fr ee s ur vi val 
2. 4. 3  
A d diti o n al E n d p oi nt  
•  P E T - C T ne gati vit y at 1 year p ost-tra ns pla nt 
3.  
S T U D Y  P A TI E N T P O P U L A TI O N A N D D I S C O N TI N U A TI O N 
3. 1  
I ncl usi o n Criteri a 
Patie nts w h o will recei ve st u d y dr u g m ust meet t h e f oll o wi n g criteria i n or der t o be i ncl u de d i n 
t he researc h st u d y: 
1.  Patie nts 1 8  y ears of a ge a n d ol der wit h H L  w h o ha ve recei ve d a ut o- H S C T i n t he pre vi o us 
4 5- 1 8 0 da ys . 
2.  C o m ple te res p o nse (C R ), partial res p o nse ( P R ) or sta ble disease (S D ) t o sal va ge t hera p y 
pri or t o A S C T 
3.  H i g h ris k of resi d ual H L p ost-A S C T , as deter mi ne d b y 1 of t h e f oll o wi n g: 
•  P ositi ve P E T sca n  defi ne d b y t he D ea u ville scale 3- 4 (A p pe n di x C ) a n d wit hi n 2 
m o nt hs of start of hi g h- d ose c he m ot hera p y  pri or t o A S C T 
•  Refract or y t o fr o ntli ne t h era p y  
•  Rela pse < 1 2 m o nt hs after fr o ntli ne t hera p y 
•  Rela pse ≥1 2 m o nt hs after fr o ntli ne t h era p y wit h e xtra n o dal disease  
4.  Easter n C o o per ati ve O nc ol o g y Gr o u p ( E C O G) Perf or ma nce Stat us sc ore of 0 - 1 
( Ap pe n di x A ). 
5.  A d e q uate h e mat ol o gi c  f u ncti o n defi ne d as all of t he f oll o wi n g: 
-  A bs ol ute ne utr o p hil c o u nt ( A N C) ≥10 0 0/ μ L  
-  He m o gl o bi n (H g b) ≥8 g/ d L  (tra nsfusi o ns t o reac h t his p oi nt are n ot per mitte d)  
-  Plate lets ≥5 0 , 0 0 0/ µ L (tra nsf usi o n is n ot per mitte d) 
6.  A de q uate li ver f u ncti o n defi ne d as all of t he f oll o wi n g: 
-  A la ni ne a mi n otra nsf eras e (A L T) a n d as partate a mi n otra nsferas e ( A S T) ≤2. 5 ×  t he 
u p per li mit of n or mal ( U L N) 
-  T otal bilir u bi n ≤1. 5  ×  U L N ( u nless t he patie nt has Gra de 1 bilir u bi n ele v ati o n d ue 
t o Gil bert disease or a si milar s y n dr o me i n v ol vi n g sl o w c o nj u gati o n of bilir u bi n) 
7.  A de q uate r e nal f u n cti o n defi ne d as ser u m creati ni ne ≤1. 5 m g/ d L ( 1 3 3 μ m ol/ L)  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 3  of 6 9  
 
8.  Fe males o f c hil d beari n g p ote ntial m ust ha ve a ne gati ve ser u m or uri n e pre g na nc y test 
res ult wit hi n 72 h o urs pri or t o t he first d ose of ni v ol u ma b a n d m ust a gree t o f oll o w 
i nstr ucti o ns f or met h o d(s) of c o ntrace pti o n f or t h e d urati o n of treat me nt wit h ni v ol u ma b 
a n d f or 7 m o nt hs f oll o wi n g t heir last d ose of st u d y dr u g (A p pe n di x D ).  Fe males of n o n-
c hil d beari n g p ote ntial ar e t h ose w h o are p ost me n o pa usal greater t ha n 1 year or w h o ha v e 
ha d a bilater al t u bal li gati o n or h ysterect o m y.  
9.  Male patie nts wit h fe m al e part ners of c hil d beari n g p ote ntial a n d w o me n p atie nts of 
c hil d beari n g p ote ntial ar e re q uire d t o use t w o f or ms of acce pt a ble  c o ntrace pti o n, 
i ncl u di n g o ne b arrier met h o d, d uri n g t heir p artici p ati o n i n t he st u d y a n d f or 7 m o nt hs 
f oll o wi n g last d ose of st u d y dr u g .  M ale patie nts m ust als o refrai n fr o m d o nati n g s per m 
d uri n g t heir p artici pati o n i n t he st u d y a n d f or 7 m o nt hs f oll o wi n g last d ose of st u d y dr u g 
(A p pe n di x D ). 
1 0.  Willi n g ness a n d a bilit y t o c o m pl y wit h  st u d y a n d f oll o w- u p pr oce d ures. 
1 1.  A bilit y t o u n d ersta n d t he nat ure of t his st u d y a nd gi ve writte n i nf or me d c o nse nt. 
3. 2  
E xcl usi o n Criteri a  
Patie nts  w h o will recei ve st u d y dr u g w h o meet a n y of t he f oll o wi n g criteri a will be e x cl u de d 
fr o m st u d y e ntr y:  
1.  P atie nts t hat ha ve recei ve d a n all o ge nic tra ns pl a nt 
2.  Pri or all o ge n eic ste m cell tra ns pla nt  or c urre nt t hera p y wit h ot her a nti- ne o pl astic or 
i nvesti gati o nal a ge nts  
3.  B est res p o ns e of pr o gressi ve disease pri or t o A S C T 
4.  P atie nts wit h a n y a ut oi m m u ne disease or a hist or y of a ut oi m m u ne di sease.  Patie nts  wit h 
vitili g o, t y pe I di a betes mellit us, resi d ual h y p ot h yr oi dis m d ue t o a ut oi m m u ne c o n diti o n 
o nl y re q uiri n g h or m o ne r e place m e nt, ps oriasis n ot re q uiri n g s yst e mic treat me nt, or 
c o n diti o ns n ot e x pecte d t o rec ur i n t he a bse nce of a n e xter nal tri g ger are per mitte d t o 
e nr oll. 
5.  A n y c o n diti o n re q uiri n g syste mic treat me nt wit h c ortic oster oi ds ( > 1 0 m g dail y 
pr e d nis o ne e q ui val e nts) or ot her i m m u n os u p pressi ve me dicati o ns wit hi n 1 4 da ys pri or t o 
first d ose of st u d y dr u g.  I n h ale d ster oi ds a n d a dre nal re place me nt ster oi d d oses > 1 0 m g 
dail y pr e d nis o ne e q ui val e nts are p er mitte d i n t he a bse nce of acti ve a ut oi m m u ne disease.  
6.  U se of a st u d y dr u g  ≤2 1 da ys or 5 half -li ves ( w hic he ver is s h orter) pri or t o t he first d ose 
of ni v ol u ma b.  F or st u d y dr u gs f or w hic h 5 h alf- li ves is ≤2 1 da ys, a mi ni m u m of 1 0  da ys 
bet wee n ter mi nati o n of t he s t u d y dr u g a n d a d mi nistrati o n of ni v ol u ma b is re q uire d. 
7.  Wi de-fiel d ra di ot hera p y (i ncl u di n g t hera pe utic ra di ois ot o pes s uc h as str o nti u m 8 9) 
a d mi nistere d ≤2 8 da ys or li mite d fiel d ra diati o n f or palliati o n ≤7 da ys pri or t o starti n g 
st u d y dr u g or h as n ot rec o vere d fr o m si de effects of s uc h t hera p y. 
8.  Maj or s ur gical pr o ce d ur es ≤2 8 da ys of b e gi n ni n g st u d y dr u g, or mi n or s ur gical 
pr oce d ur es ≤7 da ys.  N o waiti n g re q uire d f oll o wi n g p ort -a-cat h place me nt.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 4  of 6 9  
 
9.  Pre vi o usl y u ntre ate d br ai n metastases.  Patie nts w h o ha ve recei ve d ra diati o n or s ur ger y 
f or brai n metast ases ar e eli gi ble if t hera p y was c o m plete d at least 2 wee ks pri or t o st u d y 
e ntr y a n d t her e is n o e vi d e nce of ce ntral ner v o us s yste m diseas e pr o gressi o n, mil d 
ne ur ol o gi c s y m pt o ms, a n d n o re q uire me nt f or c hr o nic c ortic oster oi d t hera p y. 
1 0.  Pre g n a nt or lact ati n g  
1 1.  Ac ute or c hr o nic li ver, re nal, or pa ncreatic disease . 
1 2.  U nc o ntr olle d dia betes m ellit us  (fasti n g bl o o d gl u c ose > 2 5 0 m g/ d L). 
1 3.  A n y of t he f oll o wi n g car diac diseases c urre ntl y  or wit hi n t he last 6 m o nt hs:  
-  Left v e ntric ular ejecti o n fracti o n ( L V E F) < 4 5 % as deter mi ne d b y m ulti ple g at e d 
ac q uisiti o n ( M U G A) sca n or ec h ocar di o gra m ( E C H O) 
-  C orrecte d Q T ( Q T c ) i nter val > 4 8 0 ms o n scree ni n g el ectr ocar di o gra m ( E C G ) 
-  U nsta ble a n gi na pect oris  
-  C o n gesti ve heart f ail ure ( Ne w Y or k Heart Ass ociati o n ( N Y H A ) ≥ Gra de 2 
[A p pe n di x B ]) 
-  Ac ute m y ocar dial i nfar cti o n  
-  C o n d ucti o n a b n or malit y n ot c o ntr olle d wit h pace ma ker or me di cati o n 
-  Si g nifica nt ve ntri c ular or s u pra ve ntric ular arr h yt h mias ( p atie nts wit h c hr o nic rate -
c o ntr olle d atrial fi brillati o n i n t he a bse nce of ot her car di ac a b n or malities are 
eli gi ble)  
-  Val v ular diseas e wit h si g nifica nt c o m pr o mise i n car diac f u ncti o n  
1 4.  In a de q uat el y c o ntr olle d h y p erte nsi o n (i.e., s yst olic bl o o d press ure [ S B P] > 1 8 0 m m H g or 
di ast olic bl o o d press ure [ D B P ] > 1 0 0 m m H g) ( pati e nts wit h val ues a b o ve t h ese le vels 
m ust ha ve t heir bl o o d press ure [ B P ] c o ntr olle d wit h me dicati o n pri or t o starti n g 
treat me nt). 
1 5.  S eri o us acti ve i nfecti o n at t he ti me of treat me nt, or a n ot her seri o us u n d erl yi n g me dical 
c o n diti o n t hat w o ul d i m pair t he a bilit y of t he patie nt t o recei ve pr ot oc ol treat me nt . 
1 6.  K n o w n dia g n osis of h u ma n i m m u n o deficie nc y vir us, he patitis B, or he p atitis C.  Testi n g 
at baseli ne is n ot re q uir e d.  
1 7.  Prese nce of ot her acti ve ca ncers, or hist or y of treat me nt f or i n vasi ve ca n cer  ≤5 years.  
Patie nts wit h S ta ge I ca n cer w h o h a ve recei ve d defi niti ve l ocal treat me nt a n d are 
c o nsi dere d u nli kel y t o rec ur ar e eli gi ble.  All patie nts wit h pre vi o usl y treate d i n sit u 
carci n o ma (i.e. , n o n-i n vasi ve) are eli gi ble, as are p atie nts wit h hist or y of n o n-mela n o ma 
s ki n ca ncer. 
1 8.  Ps yc h ol o gical, f a milial, s oci ol o gical, or ge o gra p hi cal c o n diti o ns t hat d o n ot per mit 
c o m plia nce wit h t he pr ot oc ol. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 5  of 6 9  
 
3. 3  
Disc o nti n u ati o n f r 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 f or a n y of t he f oll o wi ng reas o ns:  
•  
Disease pr o gressi o n  
•  
Irre v ersi ble or i nt oler a ble t o xicit y or a b n or mal la b orat or y val ues t h o u g ht t o be relate d t o 
dr u g t o xicit y 
•  
C o n diti o ns re q uiri n g t her a pe utic i nter ve nti o n n ot per mitte d b y t he pr ot oc ol 
•  
I nterc urre nt ill ness (t his will be at t he I n vesti gat or’s discreti o n) 
•  
I n a bilit y of t he p atie nt t o c o m pl y wit h st u d y re q uire me nts 
•  
Patie nt re q uests t o disc o nti n ue treat me nt  
•  
Patie nt wit h dra ws c o nse nt fr o m t he st u d y 
•  
N o n -c o m plia nce/l ost t o f oll o w - u p 
•  
Pre g n a nc y  
After disc o nti n uati o n fr o m pr ot oc ol treat me nt, patie nts m ust be f oll o we d f or A Es f or 1 0 0 d a ys  
after t heir l ast d ose of ni v ol u ma b.  All ne w A Es o cc urri n g d uri n g t his peri o d m ust be re p orte d 
a n d f oll o we d u ntil res ol uti o n, u nless, i n t he o pi ni o n of t he I n vesti gat or, t hes e val ues are n ot 
li kel y t o i m pr o ve, beca us e of t he u n derl yi n g disease.  I n t his case, t he I n vesti gat or m ust rec or d 
his or her reas o ni n g f or t his decisi o n i n t he patie nts’ me dical rec or ds. 
All patie nts w h o ha ve Gr a de 3 or 4 la b orat or y a b n or malities ( per N ati o nal Ca ncer I nstit ute 
C o m m o n Ter mi n ol o g y Criteria f or A d vers e E ve nts [ N CI C T C A E] v 4. 0 3 ) at t he ti me of 
disc o nti n uati o n m ust be f oll o we d u ntil t he la b orat or y v al ues ha v e ret ur n e d t o Gra de 1 or 2, 
u nless it is, i n t he o pi ni o n of t he I n vesti gat or, n ot li kel y t hat t hese v al ues are t o i m pr o ve.  I n t his 
case, t he I n vesti gat or m ust rec or d his or h er reas o ni n g f or m a ki n g t his decisi o n i n t he patie nts’ 
me dical rec or ds.  
4.  
P A TI E N T R E GI S T R A TI O N  
T he patie nt m ust willi n gl y c o ns e nt after bei n g i nf or me d of t he pr o ce d ures t o be f oll o we d, 
e x peri me ntal nat ure  of t h e treat me nt, p ote ntial be n efits, treat me nt alter n ati ves, si de  effects, ris ks , 
a n d disc o mf orts.  I nstit uti o nal Re vie w B o ar d (I R B) a p pr o val of t his pr ot o c ol a n d c o nse nt f or m is 
re q uire d.  Eli gi ble patie nts w h o wis h t o partici pate i n t he st u d y will be e nr olle d i nt o t he st u d y. 
Re gistrati o n m ust occ ur pri or t o t he i nitiati o n of pr ot oc ol t hera p y.  Patie nts eli gi ble t o partici p ate 
i n t he st u d y ma y be e nr olle d t hr o u g h t he Sara h Ca n n o n De vel o p me nt I n n o v ati o ns Ce ntral 
E nr oll me nt Des k.  T he e nr oll me nt des k ma y b e reac he d b y calli n g ( 8 4 4) 7 1 0- 6 1 5 7.  Re gistrati o n 
ma y b e d o ne: 1) via fa x ( 8 6 6) 6 9 9- 0 2 5 8 M o n da y t hr o u g h Fri da y, 8: 3 0 a. m. t o 4: 3 0 p. m., Ce ntral 
Sta n dar d Ti me , or 2) via e mail at C A N N. S C RII n n o vati o ns E nr @scri-i n n o v ati o ns.c o m.  Patie nt 
re gistrati o n will be co nfir me d via e mail wit hi n 2 4  h o urs or b y t he ne xt b usi ness day.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 6  of 6 9  
 
5.  
S T U D Y  DE SI G N  
T his is a P hase II  si n gle- ar m o pe n- la b el st u d y of ni v ol u ma b as mai nte na nce  t hera p y after 
a ut ol o g o us ste m cell tra ns pla ntati o n i n patie nts wit h H L  at ris k of rela ps e or pr o gressi o n . 
Patie nts will recei ve ni v ol u ma b ( 2 4 0 m g  I V) e v er y 2 wee ks ( ± 2  d a ys  as l o n g as i nter val bet w ee n 
d oses is 1 2- 1 6 da ys) starti n g 4 5- 1 8 0 d a ys p ost-tra ns pla nt f or u p t o a ma xi m u m of 6 m o nt hs of 
treat me nt.  T o c o m pare i m m u ne rec o ver y, a c o ntr ol gr o u p of 5 p atients will  recei ve st a n dar d- of-
care pr oce d ures a n d treat me nt b ot h pre- a n d p ost-tra ns pla nt.  Res p o nse t o treat me nt f or p atie nts 
recei vi n g st u d y dr u g will be assesse d  6 m o nt hs a n d 1 year p ost-tra ns pla nt usi n g t he 
Rec o m me n dati o ns f or I nitial E val uati o n, Sta gi n g, a n d  Res p o nse Assess me nt of H o d g ki n a n d 
N o n - H o d g ki n L y m p h o m a: T he L u ga n o Classificati o n (C hes o n et al. 2 0 1 4 , see A p pe n di x F ). 
T he pla n ne d e nr oll me nt f or t his st u d y is 4 0 patie nts: 3 5 patie nts  recei vi n g st u d y dr u g a n d 5 
patie nts will recei ve sta n dar d - of-care pr o ce d ures a n d treat me nt b ot h pre- a n d p ost-tra ns pla nt. 
5. 1  
Tre at me nt Pl a n  
5. 1. 1  
Ni v ol u m a b 
Ni v ol u ma b :  2 4 0 m g  I V Da y 1  of e v er y c ycle (e v er y 2 wee ks ) 
5. 2  
Tre at me nt D ur ati o n  
St u d y treat me nt c o nsists of a ma xi m u m of 6 m o nt hs of treat me nt.  Patie nts m ust recei ve at least 
2 c ycles of ni v ol u ma b t o be e val ua bl e f or efficac y. 
5. 3  
C o nc o mit a nt Me dic ati o ns  
Patie nts  w h o recei v e st u d y dr u g will be i nstr ucte d n ot t o ta ke a n y a d diti o nal me dicati o ns d uri n g 
t he c o urse of t h e st u d y wit h o ut pri or c o ns ultati o n wit h t he researc h tea m.  At eac h visit, t he 
patie nt will be as ke d a b o ut a n y n e w me dicati o ns he /s he is ta ki n g or h as ta k e n after t he start of 
t he st u d y dr u g. 
5. 3. 1  
Per mitte d C o nc o mit a nt Me dic ati o ns  
Pre me dicati o n wit h a nti -e metics is all o we d  acc or di n g to sta n dar d practice g ui deli nes.  
Me dicati o ns ma y be a d mi nistere d f or mai nte n a nce of e xisti n g c o n diti o ns pri or t o st u d y 
e nr oll me nt or f or a ne w c o n diti o n t hat de vel o ps w hile o n st u d y , i ncl u di n g b ut n ot li mite d t o t he 
f oll o wi n g: 
•  Patie nts are per mi tte d t he use of t o pical, oc ular, i ntra-artic ular, i ntra n asal, a n d 
i n halati o nal c ortic oster oi ds ( wit h mi ni mal s yste mi c a bs or pti o n).  A dre nal re place m e nt 
ster oi d d oses ≤1 0 m g d ail y pre d nis o n e are per mitt e d.  A brief (less t ha n 3 wee ks) c o urse 
of c ortic oster o i ds f or pr o p h yla xis  (e. g., c o ntrast d ye aller g y) or f or treat me nt of n o n-
a ut oi m m u ne c o n diti o ns (e. g. , d ela ye d-t y p e h y perse nsiti vit y reacti o n ca use d b y a c o ntact 
aller ge n) is per mitte d.  Ster oi d treat me nt s pecifie d as ≤1 6 m g de x a met has o n e b y m o ut h 
(P O ) dail y t a per e d i n ≤4 wee ks is all o we d o nl y f or t he treat me nt of brai n e de ma.  
Ot her me dicati o ns c o nsi d ere d necessar y f or t h e patie nt’s safet y a n d well -bei n g ma y b e gi ve n at 
t he discreti o n of t he In v esti gat or wit h t he e x ce pti o n of t h ose liste d i n Secti o n  5. 3. 2 . 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 7  of 6 9  
 
5. 3. 2  
Pr o hi bite d C o nc o mit a nt Me dic ati o ns  
T he f oll o wi n g tr eat me nts are pr o hi bite d f or patie nts recei vi n g st u d y dr u g w hile i n t his st u d y:  
•  N o ot her i n vesti gati o nal t hera p y s h o ul d be gi ve n t o patie nts.  N o a ntica ncer a ge nts ot her 
t ha n t he st u d y me dicati o ns s h o ul d be gi ve n t o patie nts.  If s u c h a ge nts are re q uire d f or a 
patie nt, t he n t he patie nt m ust first be wit h dra w n fr o m t he st u d y.  
•  I m m u n os u p pr essi ve a ge nts (e x ce pt t o treat a dr u g-relate d A E ) 
•  I m m u n os u p pr essi ve d oses of s yste mic c ortic oster oi ds (e x ce pt as state d i n Secti o n 5. 3. 1 ) 
5. 4  
C orrel ati v e St u dies  
5. 4. 1  
Bi o m ar ker A n al ysis 
Ma n dat or y p eri p heral b l o o d sa m ples will be c ollecte d fr o m patie nts recei vi n g st u d y dr u g at 
C ycle 1 Da y 1, C ycle 2 Da y 1, C ycle 3 D a y 1, e n d of treat me nt ( E O T  [ 6 m o nt hs]), a n d 1 year 
after t he first d ose of ni v ol u ma b f or fl o w c yt o metric a nal ysis of P D-1 e x pressi o n  of circ ulati n g 
i m m u ne cell s u bsets, i ncl u di n g l y m p h oi d ( C D 4, C D 8, Tre g, N K, B) a n d m yel oi d cells 
( m o n oc yt es, M D S Cs), a n d e x pressi o n of ot her c hec k p oi nt rece pt ors, s uc h as L A G- 3, TI M- 3 
TI GI T, or a g o nists s uc h as I C O S, GI T R, O X- 4 0.  T hese sa m ples will be la bele d wit h a u ni q ue 
st u d y i de ntifier a n d s u bject c o de i n or der t o mai ntai n patie nt c o nfi de ntialit y.  T hes e sa m ples ha v e 
n o cli nical val ue a n d will be use d f or researc h o nl y.  I nf or mati o n o n c ollecti o n, p r ocessi n g 
st ora ge a n d s hi p me nt f or cells a n d plas ma/ser u m will be i n t he la b orat or y ma n ual. 
5. 4. 2  
I m m u ne R ec o v er y vers us C o ntr ol Gr o u p 
C orrelati ve st u dies will c o m pare i m m u ne rec o ver y f or 5 patie nts u n der g oi n g a ut ol o g o us ste m 
cell tra ns pla nt f or H L  b ut n ot recei vi n g ni v ol u ma b (c o ntr ol) wit h patie nts recei vi n g ni v ol u ma b as 
mai nte na nce t hera p y  (treat me nt).  All pre - a n d p ost-tra ns pla nt pr oce d ures i n t he c o ntr ol gr o u p 
will be acc or di n g t o sta n dar d - of-care as d eter mi n e d b y t h eir treati n g p h ysi cia n.  W he n c o m plete 
bl o o d c o u nt ( C B C) a n d c o m pre he nsi ve meta b olic pr ofili n g ( C M P) pa n els are c ollect e d res ults 
will be e ntere d i nt o t he el ectr o nic case re p ort f or m (e C R F) as p art of t he st u d y rec or d.  Bl o o d 
sa m ples i n c o ntr ol patie nts are t o be c ollecte d at:  
•  Bet wee n da ys 4 5- 1 8 0 aft er a ut ol o g o us ste m cell tra ns pla nt 
•  E ver y 2 - 4 w ee ks ( ± 5 d a ys) w hile recei vi n g st u d y treat me nt bas e d o n sta n dar d- of-car e 
sc he d ule 
•  At 6 m o nt hs ( ± 7 da ys) fr o m first sa m ple, a n d 
•  At 1 year ( ± 7 d a ys)  fr o m first sa m ple. 
5. 4. 3  
H a n dli n g, St or a ge a n d D estr ucti o n of B i ol o gic al S a m ples  
O nce testi n g has bee n c o m plete d, sa m ples will be st ore d f or a n a d diti o nal year be y o n d st u d y 
c o m pleti o n.  At t his ti me sa m ples will ha ve all i de ntifiers re m o ve d a n d destr o ye d.  Sa m ples will 
be t ha we d, d ec o nta mi nat e d, s oli difie d, a ut ocla ve d, a n d t he n place d i nt o t he pr o per bi o hazar d 
waste c o ntai ner f or f urt h er dis p osal. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 8  of 6 9  
 
5. 4. 4  
Wit h dr a w al of I nf or me d C o nse nt f or D o n ate d Bi ol o gic al S a m ples  
If a patie nt wit h dr a ws c o nse nt t o t he use of ma n dator y bi ol o gical sa m ples, t he n t he sa m ples will 
be dis p ose d of/ destr o ye d, a n d t he acti o n d oc u m e nte d.  If sa m ples are alrea d y a n al ys e d , Sara h 
Ca n n o n De vel o p me nt I n n o vati o ns is n ot o bli ge d t o destr o y t h e res ults of t his researc h. 
As c ollecti o n of t hese bi ol o gi cal sa m ples is a m a n dat or y p art of t he st u d y, t he patie nt ma y n ot 
c o nti n ue i n t he st u d y.  
6.  
D O S E M O DI FI C A TI O N S  
If t o xicit y o cc urs, t he t o xicit y will be gra d e d utilizi n g t he N CI C T C A E v 4. 0 3 
(htt ps://e vs. nci. ni h. g o v/ft p 1/ C T C A E/ C T C A E _ 4. 0 3/ C T C A E _ 4. 0 3 _ 2 0 1 0 - 0 6-
1 4 _ Q uic k Refere nce _ 8. 5 x 1 1. p df ), a n d a p pr o priate s u p p orti ve care treat me nt will be a d mi nistere d 
t o decrease t he si g ns a n d s y m pt o ms t here of. 
T here will be n o d ose re d ucti o n of ni v ol u ma b; h o we ver, treat me nt dela ys are all o we d.  If t he 
t o xicit y d oes n ot res ol ve t o N CI C T C A E ≤ Gra de 1 after 2 8 d a ys, t he n t he patie nt s h o ul d be 
wit h dra w n fr o m t he st u d y a n d o bs er ve d u ntil res ol uti o n of t he t o xicit y. 
T he d ose m o di ficati o ns t o be use d i n t his st u d y are prese nt e d i n Ta ble 1 . 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 2 9  of 6 9  
 
T a ble 1 
D ose Le vel M o dific ati o ns  
A d verse Reacti o n  
Se verit y *  
D ose M o dificati o n  
C olitis  
Gra de 2 diarr hea or c olitis  
Wit h h ol d d ose
a 
Gra de 3 diarr hea or c olitis  
Wit h h ol d d ose
a 
Gra de 4 diarr hea or c olitis  
P er ma ne ntl y disc o nti n ue  
P ne u m o nitis  
Gra de 2  
Wi t h h ol d d osea 
Gra de 3 or 4  
P er ma ne ntl y disc o nti n ue  
He patitis  
A S T or A L T  > 3 a n d u p t o 5 ×  t he 
U L N or t otal bilir u bi n > 1. 5 a n d u p t o 
3 ×  t he U L N 
Wit h h ol d d ose
a 
A S T or A L T > 5 ×  t he U L N or t otal 
bilir u bi n > 3 ×  t he U L N 
P er ma ne ntl y disc o nti n ue  
H y p o p h ysitis  
Gra de 2 or 3  
Wit h h ol d d ose
a 
Gra de 4  
P er ma ne ntl y disc o nti n ue  
A dre nal  
I ns ufficie nc y 
Gra de 2  
Wit h h ol d d ose
a 
Gra de 3 or 4  
P er ma ne ntl y disc o nti n ue  
T y pe 1 Dia betes  
Mellit us  
Gra de 3 h y per gl yce mia  
Wit h h ol d d ose
a 
Gra de 4 h y per gl yce mia  
P er ma ne ntl y disc o nti n u e  
Ne p hritis a n d Re nal  
D ysf u ncti o n  
Ser u m creati ni ne > 2. 5  a n d u p t o 6 ×  
t he U L N 
Wit h h ol d d ose
a 
Ser u m creati ni ne > 6 ×  t he U L N 
P er ma ne ntl y disc o nti n ue  
Ras h  
Gra de 3  
Wit h h ol d d ose
a 
Gra de 4  
P er ma ne ntl y disc o nti n ue  
E nce p halitis  
Ne w -o nset m o derate or se vere 
ne ur ol o gic si g ns or s y m pt o ms  
Wit h h ol d d ose
a 
I m m u ne-me diate d e nce p halitis  
P er ma ne ntl y disc o nti n ue  
Ot her  
Ot her Gra de 3 a d verse reacti o n  
First occ urre nce  
Rec urre nce of sa me Gra de 3 a d verse 
reacti o ns 
 
Wit h h ol d d ose
a 
P er ma ne ntl y disc o nti n ue  
Life -t hreate ni ng or Gra de 4 a d verse 
reacti o n 
P er ma ne ntl y disc o nti n ue  
Re q uire me nt f or 1 0 m g per da y or 
greater pre d nis o ne or e q ui vale nt f or 
m ore t ha n 1 2 wee ks  
P er ma ne ntl y disc o nti n ue  
P ersiste nt Gra de 2 or 3 a d verse 
reacti o ns lasti n g 1 2 wee ks or l o n ger 
P er ma ne ntl y disc o nti n ue  
* T o xicit y was gra de d per N CI C T C A E v. 4 . 0 3. 
a Res u me treat me nt w he n a d verse reacti o n ret ur ns t o Gra de 0 or 1.  
6. 1  
M a n a ge me nt of Ni v ol u m a b- R el ate d A d verse E ve nts  
M a na ge me nt al g orit h ms f or t he f oll o wi n g ni v ol u ma b-relat e d A Es  are l ocate d i n A p pe n di x G  – 
gastr oi ntesti nal, r e nal, p ul m o nar y, h e patic, e n d o cri n o pat h y, s ki n, a n d n e ur ol o gical.   
6. 1. 1  
M a n a ge me nt of I nf usi o n - Rel ate d R e a cti o ns  
Ni v ol u ma b ca n ca use se v ere i nf usi o n r eacti o ns, w hic h ha ve bee n re p orte d i n less t ha n 1 % of 
patie nts i n  cli nical trials.  Disc o nti n ue ni v ol u ma b i n patie nts wit h Gra de 3 or 4 i nf usi o n 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 0  of 6 9  
 
reacti o ns.  I nterr u pt or sl o w t he rate of i nf usi o n i n patie nts wit h Gra de 1 or 2 i nf usi o n reacti o ns.  
F or ma na ge me nt of i nf usi o n- relate d si de effects, refer t o i nstit uti o nal g ui deli nes. 
7.  
S T U D Y  A S S E S S M E N T S A N D E V A L U A TI O N S  
7. 1  
O ver vie w  
All patie nts s h o ul d visit t he st u d y ce nter o n t h e da ys s pecifie d wit hi n t his pr ot oc ol.  T he 
c o m plete Sc he d ule of Assess me nts f or t his st u d y is s h o w n i n A p pe n di x E .  T he baseli ne p h ysical 
e x a mi nati o n, me dical hist or y, E C O G P S, c o m plet e bl o o d c o u nt ( C B C) wit h  differe ntial a n d 
platelets, c o m pre h e nsi ve meta b olic pr ofile ( C M P ), a n d pr ot hr o m bi n ti me ( P T )/partial 
t hr o m b o plasti n ti me (P T T )/I nt er nati o nal N or malize d Rati o (I N R) s h o ul d b e d o ne ≤7 da ys pri or 
t o i nitiati o n of treat me nt.  A pre g na n c y test m ust be perf or me d wit hi n 7 2 h o urs of C ycl e 1 Da y 1.  
P E T -C T  sca ns s h o ul d be perf or me d ≤6 wee ks  pri or t o i nitiati o n of treat me nt.  E C G a n d researc h 
sa m ples s h o ul d be perf or me d ≤2 8 da ys pri or t o i nitiati o n of st u d y treat me nt.  
7. 2  
B aseli ne  St u d y Assess me nts  
T he f oll o wi n g i nf or mati o n will be c ollecte d a n d pr oce d ures will be perf or me d f or eac h p atie nt at 
scree ni n g: 
•  Writte n i nf or me d c o nse nt pri or t o a n y ot h er st u d y- relate d pr oce d ures ( ≤2 8 da ys pri or t o 
i nitiati o n of treat me nt) 
•  Me dical hist or y  
o  Pri or s yste mic t her a p y a n d ra di ot hera p y f or H L  
o  Res ults of pre- tra ns pla nt P E T-C T (if d o ne) 
•  P h ysical e x a mi nati o n, meas ure m e nts of hei g ht (first visit), wei g ht, a n d vital si g ns (resti n g 
heart r ate, B P, r es pirat or y r ate, a n d oral te m perat ure)  
•  E C O G perf or ma nce stat us (see A p p e n di x A ) 
•  1 2- lea d E C G 
•  C o nc o mita nt me dicati o n re vie w  
•  C B C wit h 3 -part differe ntial a n d platelets  
•  C M P t o i ncl u de: gl uc ose, bl o o d urea nitr o ge n ( B U N), creati ni ne, s o di u m, p otassi u m, 
c hl ori de, cal ci u m, car b o n di o xi de ( C O 2), al kali ne p h os p hatase (A L P ), A S T, A L T , t otal 
bilir u bi n, t otal pr otei n, a n d al b u mi n 
•  C oa g ulati o n a n al ysis:  P T/I N R /P T T  
•  Ser u m or uri ne pr e g na nc y test ( m ust be perf or m e d wit hi n 7 2  h o urs of C ycle 1 Da y 1) 
•  P E T -C T  sca ns ≤6 wee ks pri or t o i nitiati o n of st u d y treat me nt 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 1  of 6 9  
 
•  B o ne marr o w bi o ps y, o nl y if t here is pri or e vi d e nce of b o ne marr o w i n v ol v e me nt.  If 
b o ne marr o w bi o ps y n ee ds t o be re peate d, it s h o ul d be d o ne ≤2 8 da ys pri or t o i nitiati o n 
of st u d y tr eat me nt . 
7. 3  
St u d y Tre at me n t Assess me nts 
7. 3. 1  
D a y 1 of E ac h C ycle  (± 2  d a ys as l o n g as i nter v al bet w ee n d oses is 1 2- 1 6 d a ys) 
•  P h ysical e x a mi nati o n, i ncl u di n g meas ure me nt of wei g ht a n d vital si g ns  
•  E C O G perf or ma nce stat us  
•  A E assess me nt  
•  C o nc o mita nt me dicati o n re vie w  
•  C B C, i ncl u di n g 3- p art diff er e ntial a n d platelets  
•  C M P  
•  Pre - d ose researc h bl o o d sa m ple f or c orrelati ve a n al ysis ( C y cle 1 D a y 1, C ycle 2 D a y 1, 
a n d C ycle 3 D a y 1 o nl y ) 
7. 4  
E n d of St u d y  Tre at me nt  
After wit h dra wal fr o m or c o m pleti o n of pr ot oc ol treat me nt, patie nts m ust be f oll o we d f or A Es 
f or 1 0 0 cal e n dar d a ys aft er t he last d ose of st u d y dr u g.  T h e f oll o wi n g assess me nts will be 
perf or me d : 
•  P h ysical e x a mi nati o n, i ncl u di n g meas ure me nt of wei g ht a n d vital si g ns  
•  E C O G perf or ma nce stat us  
•  A E assess me nt  
•  C o nc o mita nt me dicati o n re vie w  
•  C B C, i ncl u di n g 3- p art differ e ntial a n d platelets  
•  C M P  
•  Ser u m or uri ne pr e g na nc y test 
•  Researc h bl o o d s a m ple f or c orr elati ve a n al ysis  
7. 5  
Res p o nse Assess me nt  
Patie nts s h o ul d ha ve P E T- C T sca ns d o ne p er i nstit uti o n sta n dar d of care.  P E T- C T sca ns are 
re q uire d 1- 3 m o nt hs p ost-A S C T pr i or t o i nitiati o n of t hera p y, 6 m o nt hs p ost- A S C T,  a n d 1 year 
p ost- A S C T.   If t here is pri or e vi de nce of b o ne marr o w i n v ol ve me nt, patie nts s h o ul d als o ha ve 
b o ne marr o w bi o ps y p erf or me d if i n C R at t hese sta gi n g visits t o d oc u me nt res p o nse. 
Patie nts disc o nti n ui n g t hera p y earl y r ecei vi n g > 6 c ycles wit h meas ura ble disease at bas eli ne are 
rec o m me n de d t o h a ve a n E O T P E T- C T.  Patie nts e n di n g treat me nt earl y nee d t o ha ve a P E T -C T  
at 1 year p ost-A S C T  u nless patie nt pr o gresses or st arts a ne w t h era p y. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 2  of 6 9  
 
7. 6  
F oll o w- u p  
Patie n ts will be f oll o we d e ver y m o nt h ( ± 1 wee k ) f or 3 m o nt hs a n d t he n e ver y 3 m o nt hs 
t hereafter fr o m t he date of last d ose of ni v ol u ma b f or u p t o 2 years.  A res earc h bl o o d sa m ple 
will be ta ke n 1 year aft er t he first d ose of ni v ol u ma b.  A p h o ne call ma y be use d t o assess 
s ur vi val a n d t o rec or d i nitiati o n of a n alter nati ve f or m of treat me nt f or l y m p h o ma after res p o nse 
assess me nt at 1 year p ost -A S C T . 
8.  
D R U G F O R M U L A TI O N , A V AI L A BI LI T Y, A D MI NI S T R A TI O N, A N D 
T O XI CI T Y I N F O R M A TI O N  
8. 1  
Ni v ol u m a b 
 
I n vesti g ati o n al Pr o d uct 
D os a ge F or m a n d Stre n gt h 
M a n uf act urer  
Ni v ol u ma b  
1 0 0 m g/ 1 0 m L ( 1 0 m g/ m L)  
Brist ol -M yers S q ui b b  
 
8. 1. 1  
L a beli n g, P ac k a gi n g, S u p pl y, a n d St or a ge 
Ni v ol u ma b will be s u p plie d i n 1 0- cc t y pe I fli nt gl ass vials wit h b ut yl r u b ber st o p pers a n d seale d 
wit h al u mi n u m seals  b y Brist ol- M yers S q ui b b. 
St ore u n der refri gerati o n at 2° C t o 8° C ( 3 6° F t o 4 6° F).  Pr otect fr o m li g ht b y st ori n g i n t he 
ori gi nal pac ka ge u ntil ti me of use.  D o n ot freeze or s ha ke. 
All st u d y dr u gs m ust be ke pt i n a sec ure place u n der a p pr o priate st ora ge c o n diti o ns.  St ora ge 
c o n diti o ns f or ni v ol u ma b are i ncl u de d o n t h e i n vesti gati o nal pr o d uct la b el. 
Sara h Ca n n o n De v el o p me nt I n n o v ati o ns m ust be gra nte d access o n reas o n a ble re q u est t o c hec k 
dr u g st or a ge, dis pe nsi n g pr oce d ur es, a n d acc o u nta bilit y rec or ds. 
8. 1. 2  
Pre p ar ati o n a n d A d mi nistr ati o n of Ni v ol u m a b 
Ni v ol u ma b is a d mi nistere d as a n I V i nf usi o n o ver 6 0 mi n utes.  
Pre parati o n a n d a d mi nistrati o n i nstr ucti o ns will be pr o vi de d i n t he ni v ol u ma b I n v esti gat or ’s 
Br oc h ure (I B).  
8. 1. 3  
Prec a uti o ns a n d Ris ks Ass oci ate d wit h Ni v ol u m a b 
Preca uti o ns a n d ris ks are l ocate d i n t he ni v ol u ma b I B.  Ma n a ge me nt of ni v ol u ma b-relate d A Es is 
pr o vi de d i n A p pe n di x G . 
8. 2  
Acc o u nt a bilit y f or All St u d y D r u gs 
T he P ri nci pal In vesti gat or  (PI, or desi g nee) is res p o nsi ble f or acc o u nta bilit y of all use d a n d 
u n use d st u d y dr u g s u p pli es at t he site. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 3  of 6 9  
 
All st u d y dr u g i n ve nt ories m ust be ma de a vaila ble f or i ns pecti o n b y t he S p o ns or or its 
re pres e ntati ves a n d r e g ul at or y a ge n c y i ns pect ors u p o n re q uest. 
At t he e n d of t he st u d y , all Sara h Ca n n o n De vel o p me nt I nn o v ati o ns Dr u g Acc o u nta bilit y Rec or d 
F or m(s) will be c o m plete d b y t he site a n d s e nt t o t he Sara h Ca n n o n D e vel o p me nt I n n o v ati o ns 
Re g ulat or y De part me nt .  St u d y dr u g  s u p plies m ust n ot be destr o ye d u nless pri or a p pr o val h as 
bee n gra nt e d b y t he S p o ns or or its r e pres e ntati ve.  Please c o ntact Sara h Ca n n o n De vel o p me nt 
I n n o v ati o ns re gar di n g dis p osal of a n y st u d y dr u g. 
9.  
R E S P O N S E E V A L U A TI O N S A N D M E A S U R E M E N T S  
L y m p h o ma pr o gressi o n will be assesse d usi n g t he Rec o m me n dati o ns f or I nitial E val uati o n, 
Sta gi n g, a n d  Res p o nse As sess me nt of H o d g ki n a n d N o n- H o d g ki n L y m p h o ma: T he L u ga n o 
Classificati o n  (C hes o n et al. 2 0 1 4 , see A p p e n di x F ).  Pr o gressi o n will be assesse d  6 m o nt hs 
p ost- A S C T a n d 1 year p ost- A S C T . 
1 0.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
1 0. 1  
St atistic al Desi g n  
T his is a m ultice nter, o pe n -la bel, P hase II st u d y of ni v ol u ma b as mai nte na n ce  t hera p y aft er 
A S C T  i n patie nts wit h H L  at ris k of rela ps e or pr o gressi o n.  T he pri mar y, s ec o n dar y a n d 
e x pl orat or y o bjecti ves a n d e n d p oi nts are f o u n d i n S ecti o n 2 . 
1 0. 2  
S a m ple Size C o nsi der ati o ns  
T he n ull h y p ot hesis t o be teste d is t hat t he tr ue 1 2-m o nt h P F S is 5 0 % a gai nst a t w o -si de d 
alter nati ve h y p ot hesis of a 7 0 % P F S rate .  T he 5 0 % 6 - m o nt h P F S rate w as o btai ne d fr o m t he 
Rec o m me n dati o ns f or I nitial E val uati o n, Sta gi n g, a n d Res p o nse Assess me nt of H o d g ki n a n d 
N o n - H o d g ki n L y m p h o m a: T he L u ga n o Classificati o n (C hes o n et al. 2 0 1 4 , see A p pe n di x F ).  A 
t w o-si de d, o ne-sa m ple l o g-ra n k test calc ulate d fr o m a sa m ple of 3 6 e v al ua ble s u bjects ac hie v es 
8 0. 3 % p o wer at a 0. 0 5 0 si g nifica n ce le v el t o detect a n i m pr o ve me nt of 2 0 % i n 1 2- m o nt h P F S. 
T he pr o ba bilit y t h at a s u bject  e x perie nces a n e ve nt d uri n g t he st u d y is 0. 4 5 7 9.  T he e x pecte d 
n u m ber of e v e nts d uri n g t he st u d y is 1 6.  It is ass u me d t hat t he s ur vi val ti me distri b uti o ns of b ot h 
gr o u ps are a p pr o xi mate d  reas o na bl y w ell b y t h e Wei b ull distri b uti o n wit h a s ha pe para meter of 
1. 0 0.  T hese pr o p orti o ns ass u me a n e nr oll me nt peri o d of 1 8 m o nt hs a n d a f oll o w- u p peri o d of 1 2 
m o nt hs after t he last s u bject is a d de d.  I n or der t o all o w f or a 1 0 % dr o p o ut rate, a t otal of 4 0 
patie nts will be e nr olle d.  T he sa m ple size was calc ulate d usi n g P A S S versi o n 1 4. 
1 0. 3  
A n al ysis P o p ul ati o n 
T he f oll o wi n g a nal ysis p o p ulati o ns will be use d: 
•  F ull A nal ysis Set ( F A S) is defi ne d as all s u bjects w h o ha ve recei v e d at least o ne d ose of 
st u d y me dicati o n. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 4  of 6 9  
 
•  Efficac y -E val u a ble P o p ulati o n ( E F F) is defi ne d as all s u bjects recei vi n g at least t w o 
c ycles of st u d y me dicati o n.  
•  Safet y P o p ulati o n ( S A F) is defi ne d as all patie nts w h o ha ve recei v e d at least o ne d ose of 
st u d y treat me nt.  T his p o p ulati o n will be use d f or t he safet y a n al ysis. 
1 0. 4  
D at a A n al ysis 
Descri pti ve statistics, i ncl u di n g mea n, me di a n, sta n dar d de viati o ns a n d ra n ges f or all c o nti n u o us 
m eas ures will be ta b ulat e d a n d re p ort e d.  Perce nta ges a n d fre q ue nci es f or all cate g orical 
meas ures will als o be pr ese nte d.  Ti me -t o-e v e nts e n d p oi nts will be re p orte d usi n g K a pl a n-Meier 
esti mates, wit h 9 5 %  a CI  f or me dia n ti me t o e ve nt. 
1 0. 4. 1  
D e m o gr a p hics a n d B aseli ne C h ar acteristics  
De m o gra p hic a n d baseli n e disease c har acteristics will be s u m marize d.  Data t o be ta b ulate d will 
i ncl u de de m o gra p hic feat ures s uc h as a ge, se x a n d race, as well as disease-s pecific 
c haracteristics.  
T he n u m ber a n d p erce nta ges of patie nts scr ee ne d, ra n d o mize d, treate d, c o m plete d t he 
treat me nt/st u d y a n d wit h dra w n fr o m treat me nt/st u d y f or a n y reas o ns will b e prese nt e d. 
1 0. 4. 2  
Effic ac y A n al ysis 
T he pri mar y  efficac y a n al ysis will be perf or me d usi n g t he F A S .  Se nsiti vit y a n al ys es will be 
pe rf or me d usi n g the Effi cac y - E val ua ble P o p ulati o n ( E F F). 
•  P r o gr essi o n- Fr ee S ur vi val ( P F S), defi ne d as t he ti me fr o m t he first da y of st u d y dr u g 
a d mi nistrati o n ( Da y 1) t o disease pr o gressi o n as d efi ne d b y t he Rec o m me n dati o ns f or 
I nitial E val uati o n, Sta gi n g, a n d Res p o ns e Assess me nt of H o d g ki n a n d N o n- H o d g ki n 
L y m p h o ma: T he L u ga n o Classificati o n  (C hes o n et al. 2 0 1 4 , see A p pe n di x F ), or d eat h o n 
st u d y.  Patie nts w h o ar e ali ve a n d free fr o m diseas e pr o gressi o n will be ce ns ore d at t he 
date of last t u m or assess me nt.  
F or P F S Ka pl a n -Meier c ur ves will be ge nerate d a n d t he me dia n ti me t o e ve nt a n d t he ass oci ate d 
9 5 % CI  b e pr o vi de d.  K a pla n -M eier esti mat es will als o be pr o d uce d f or t he f oll o wi n g s pecifie d 
ti me p oi nts: 1 2 m o nt hs a n d 2 4 m o nt hs.  T he hazar d rati o a n d t he 9 5 % CI f or t hese e n d p oi nts 
bet wee n t he t w o tr eat me nt gr o u ps will be calc ulat e d.  
1 0. 4. 3  
S af et y A n al ysis 
Safet y will be assesse d t hr o u g h t he a nal ysis of t he re p orte d i nci d e nce of treat me nt -e mer ge nt 
A Es.  Treat me nt -e mer ge nt A Es are t h ose wit h a n o nset o n or after t he i nitiati o n of t hera p y, a n d 
will be gr a de d acc or di n g t o N CI C T C A E v 4. 0 3.  A c o p y of C T C A E sc ori n g s yste m ma y be 
d o w nl oa de d fr o m: htt ps://e vs. nci. ni h. g o v/ft p 1/ C T C A E/ C T C A E _ 4. 0 3/ C T C A E _ 4. 0 3 _ 2 0 1 0 - 0 6-
1 4 _ Q uic k Refere nce _ 8. 5 x 1 1. p df.  
T he A Es will be c o de d usi n g Me dical Dicti o nar y f or Re g ulat or y A cti vities ( Me d D R A), a n d 
s u m marize d usi n g s yste m or ga n class a n d preferre d ter m f or all patie nts i n t he Safet y P o p ulati o n.  
I n a d diti o n, s u m maries of seri o us a d verse e v e nts (S A Es ), A Es lea di n g t o treat me nt 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 5  of 6 9  
 
disc o nti n uati o n, A Es b y ma xi m u m N CI C T C A E gra de, a n d A Es rel ate d t o st u d y treat me nt will 
als o be prese nt e d.  
Ot her saf et y e n d p oi nts i ncl u di n g la b or at or y res ults a n d vital si g ns will be s u m marize d f or all 
patie nts i n t he Safet y P o p ulati o n. 
C o nc o mita nt me dicati o ns will be  liste d a n d s u m marize d a n d c o de d usi n g t h e W orl d Healt h 
Or ga nizati o n -Dr u g Dicti o nar y.  
1 0. 4. 4  
E x pl or at or y A n al ysis 
T he sc o pe a n d details of t he e x pl orat or y a nal ysis, i ncl u di n g c orrelati ve bi o mar ker a nal ysis, will 
be detaile d i n t he Statistical A nal ysis Pla n ( S A P).  
1 0. 5  
A n al ysis Ti me P oi nts  
1 0. 5. 1  
Fi n al A n al ysis  
T he fi nal a n al ysis of t he st u d y will occ ur w he n all e nr olle d s u bjects ha v e recei ve d at least 2 
c ycles of ni v ol u ma b a n d ha ve c o m plete d 1 2 m o nt h p ost- A S C T disease ass ess me nt . 
1 0. 5. 2  
Pl a n ne d I nteri m A n a l ysis 
T here is n o pla n ne d i nteri m a nal ysis f or t his st u d y. 
1 1.  
S A F E T Y R E P O R TI N G A N D  A N A L Y S E S  
Safet y assess me nts will c o nsist of m o nit ori n g a n d rec or di n g pr ot o c ol- defi n e d A Es a n d S A Es, 
meas ure me nt of pr ot oc ol- s pecifie d h e mat ol o g y, cli nical c he mistr y, a n d ot h er pr ot oc ol- s p ecifie d 
tests i n t he e C R Fs t hat ar e dee me d critical t o t he s afet y e v al uati o n of t he st u d y dr u g. 
T he PI  is r es p o nsi ble f or rec o g nizi n g a n d re p orti n g A Es t o t he Sara h Ca n n o n De vel o p me nt 
I n n o v ati o ns Safet y De p art me nt (see Secti o n 1 1. 2 ).  It is t he S p o ns or’s res p o nsi bilit y t o re p ort 
rele va nt S A Es t o t he a p plica ble l ocal, nati o nal, or i nter nati o nal re g ul at or y b o dies.  I n a d diti o n, 
I n v esti gat ors m ust re p ort S A Es a n d f oll o w- u p i nf or mati o n t o t heir res p o nsi ble I R B acc or di n g t o 
t he p olicies of t hat I R B.  
T he PI  is als o res p o nsi ble f or e ns uri n g t h at e ver y staff me m ber i n v ol ve d i n t he st u d y is fa miliar 
wit h t he c o nte nt of t his secti o n. 
1 1. 1  
Defi niti o ns  
1 1. 1. 1  
A d verse E ve nts  
A d verse e ve nt mea ns a n y u nt o war d me dical o cc urre nce a ss oci ate d wit h t he use of a dr u g i n 
h u ma ns, w het her or n ot c o nsi dere d dr u g- relate d.  A n A E  ca n b e a n y u nfa v ora ble a n d u ni nte n d e d 
si g n (e. g., a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or disease te m p oraril y ass o ciate d wit h t he 
use of a dr u g, wit h o ut a n y j u d g me nt a b o ut ca usalit y.   A n A E  ca n arise wit h a n y us e of t he dr u g 
(e. g., off-la bel use, us e i n c o m bi nati o n wit h a n ot her dr u g) a n d wit h a n y r o ut e of a d mi nistrati o n, 
f or m ulati o n, d ose or i ncl u di n g o ver d ose. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 6  of 6 9  
 
1 1. 1. 2  
Seri o us A d verse E ve nt  
A n A E or a s us pecte d a d verse re a cti o n ( S A R) is c o nsi dere d “seri o us ” if it res ults i n a n y of 
t he f oll o wi n g o utc o mes: 
•  De at h  
•  A lif e -t hre ate ni n g A E 
•  I n p atie nt h os pit aliz ati o n of at le ast 2 4- h o urs or pr ol o n g ati o n of e xisti n g 
h os pit aliz ati o n 
•  A persiste nt or si g nific a nt i nc a p acit y or s u bst a nti al disr u pti o n of t he a bilit y t o 
c o n d uct n or m al lif e f u ncti o ns  
•  A c o n ge nit al a n o m al y/ birt h defect 
I m p ort a nt me dical e v e nts t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi dere d seri o us w h e n, base d u p o n a p pr o priate me dical j u d g m e nt, t he y 
ma y je o p ar dize t he patie nt or s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 
o ne of t he o utc o mes liste d i n t his defi niti o n.  E x a m ples of s uc h me dical e v e nts i ncl u de aller gic 
br o nc h os pas m re q uiri n g i nte nsi ve treat me nt i n a n e mer ge n c y r o o m or at h o me, bl o o d d yscrasias 
or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g de pe n de n c y or dr u g 
a b use.  
It is i m p orta nt t o disti n g uis h bet wee n “s eri o us” a n d “se vere” A E, as t he ter ms are n ot 
s y n o n y m o us.  Se verit y is a meas ur e of i nte nsit y; h o we ver, a n A E of s e vere i nte nsit y n ee d n ot 
necessaril y b e c o nsi der e d seri o us.  Seri o us ness ser ves as t he g ui de f or defi ni n g re g ul at or y 
re p orti n g o bli gati o ns.  “ Seri o us” is a r e g ulat or y defi niti o n a n d is base d o n patie nt/e ve nt o utc o me 
or acti o n us uall y ass ociat e d wit h e ve nts t hat p ose a t hreat t o a p atie nt’s life or vital f u ncti o ns.  
F or e x a m ple, na usea w hi c h persists f or se v eral h o urs ma y b e c o nsi dere d se vere na us ea, b ut ma y 
n ot be c o nsi dere d a n S A E.  O n t he ot her ha n d, a str o ke w hic h res ults i n o nl y a li mite d de gree of 
disa bilit y ma y b e c o nsi dere d o nl y a mil d str o ke, b ut w o ul d be c o nsi dere d a n S A E.  Se verit y a n d 
seri o us ness s h o ul d be i n de pe n de ntl y assess e d w he n rec or di n g A Es o n t he e C R F a n d S A Es o n t he 
S A E Re p ort F or m. 
1 1. 1. 3  
A d verse R e acti o n  
A n a d vers e reacti o n mea ns a n y A E  ca us e d b y a dr u g.  A d v erse reacti o ns are a s u bset of all S A Rs  
w here t here is a reas o n t o c o ncl u de t hat t he dr u g ca use d t he e v e nt.  
1 1. 1. 4  
S us pecte d A d verse Re a cti o n  
S us pecte d a d verse r eacti o n mea ns a n y A E  f or w hic h t here is a reas o n a ble p ossi bilit y t hat t he 
dr u g ca use d t h e A E .  Reas o na ble p ossi bilit y mea ns t hat t here is e vi de nce t o s u g gest a ca us al 
relati o ns hi p bet wee n t h e dr u g a n d t he A E .  A n S A R  i m plies a lesser de gree of cert ai nt y a b o ut 
ca usalit y t h a n A E , w hic h mea ns a n y A E  ca use d b y a dr u g.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 7  of 6 9  
 
1 1. 1. 5  
Rec or di n g a n d Re p orti n g of A d verse E ve nts  
Rec or di n g of A d verse E ve nts  
All A Es fr o m a n y patie nt t hat occ ur d uri n g t he c o urse of t he researc h st u d y will be rec or d e d i n 
t he e C R F, a n d t he I n v esti gat or will gi ve his or h er o pi ni o n as t o t he relati o ns hi p of t he A E t o t he 
st u d y dr u g tr eat me nt (i.e., w het her t he e ve nt is rel ate d or u nrelate d t o st u d y dr u g a d mi nistrati o n). 
All A Es s h o ul d be d oc u me nte d.  A descri pti o n of t he e ve nt, i ncl u di n g its date of o nset a n d 
res ol uti o n, w het her it c o nstit utes a S A E or n ot, a n y acti o n ta ke n (e. g., c ha n ges t o st u d y 
treat me nt), a n d o ut c o me, s h o ul d be pr o vi de d, al o n g wit h t he In v esti gat or’s assess me nt of 
ca usalit y (i.e., t he r elati o ns hi p t o t he st u d y treat m e nt[s]).  F or a n A E t o be a s us pecte d treat me nt-
relate d e v e nt t here s h o ul d be at least a reas o n a ble p ossi bilit y of a ca us al rel ati o ns hi p bet wee n t he 
pr ot oc ol treat me nt a n d t h e A E.  A d verse e v e nts will be gra de d acc or di n g t o t he N CI C T C A E 
v 4. 0 3, a n d c ha n ges will be d oc u me nte d. 
If t he A E is seri o us, it s h oul d be re p orte d i m me di atel y t o t he Sara h Ca n n o n De vel o p me nt 
I n n o v ati o ns Safet y De p art me nt.  Ot her u nt o war d e ve nts occ urri n g i n t he fra me w or k of a cli nical 
st u d y ar e t o be r ec or d e d as A Es (i.e., A Es t hat o cc ur pri or t o assi g n me nt of st u d y treat me nt t hat 
are r elate d t o a pr ot oc ol- ma n date d i nter ve nti o n, i ncl u di n g i n vasi ve pr oce d ures s uc h as bi o psies, 
me dicati o n was h o ut, or n o treat me nt r u n- i n). 
A n y cli nicall y si g nifica nt si g ns a n d s y m pt o ms; a b n or mal test fi n di n gs; c h a n ges i n p h ysical 
e x a mi nati o n; h y p erse nsiti v it y; a n d ot her meas ure me nts t hat occ ur will be re p orte d as a n A E, a n d 
c ollecte d o n t he r ele va nt e C R F scree n.  
Test fi n di n gs will be r e p orte d as a n A E if: t he test res ult re q uires a n a dj ust me nt i n t he st u d y 
dr u g(s) or disc o nti n uati o n of treat me nt, a n d/ or t e st fi n di n gs re q uire a d diti o nal testi n g or s ur gi cal 
i nter ve nti o n, a test res ult or fi n di n g is ass o ciate d wit h acc o m pa n yi n g s y m pt o ms, or a test res ult is 
c o nsi dere d t o be a n A E b y t he I n v esti gat or. 
Re p orti n g Peri o d f or A d verse E ve nts  
All A Es , re gar dl ess of seri o us ness or relati o ns hi p t o ni v ol u ma b treat me nt (calle d st u d y 
treat me nt), s pa n ni n g fr o m t he start of st u d y treat me nt u ntil 1 0 0 cale n dar d a ys after 
disc o nti n uati o n or c o m pleti o n of st u d y treat me nt as defi ne d b y t he cli nical st u d y f or t h at patie nt, 
are t o be rec or de d o n t he c orres p o n di n g scree n(s) i ncl u de d i n t he e C R F. 
All A Es res ulti n g i n disc o nti n uati o n fr o m t he st u d y s h o ul d be f oll o w e d u ntil res ol uti o n or 
sta bilizati o n.  All ne w A Es occ urri n g d uri n g t his peri o d m ust be re p ort e d a n d f oll o we d u ntil 
res ol uti o n u nless, i n t he o pi ni o n of t he In v esti gat or, t he A E or la b orat or y a b n or malit y/ies are n ot 
li kel y t o i m pr o ve beca us e of t he u n derl yi n g disease.  I n t his case, t he I n vesti gat ors m ust rec or d 
his or her reas o ni n g f or t his decisi o n i n t he patie nt’s me dical rec or d. 
After 1 0 0 da ys f oll o wi n g t he c o m pleti o n of pr ot oc ol-s pecific treat me nt or disc o nti n uati o n, o nl y 
A Es, S A Es, or deat hs ass esse d b y t he I n v esti gat or as treat me nt -relate d are t o be re p ort e d. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 8  of 6 9  
 
1 1. 1. 6  
Assess me nt of A d verse E ve nts  
All A Es a n d S A Es w het h er v ol u nteer e d b y t he pati e nt, disc o vere d b y st u d y pers o n nel d uri n g 
q uesti o ni n g, or det ecte d t hr o u g h p h ysical e x a mi nati o n, la b orat or y test, or ot her mea ns will be 
re p orte d a p pr o priat el y.  Eac h r e p orte d A E or S A E will be descri be d b y its d urati o n (i.e., start a n d 
e n d dates), r e g ulat or y seri o us ness criteria if a p plica ble, s us pecte d relati o ns hi p t o t he st u d y dr u g 
(see f oll o wi n g g ui da nce), a n d acti o ns ta ke n. 
T o e ns ure c o nsiste n c y of A E a n d S A E ca us alit y assess me nts, I n v esti gat ors s h o ul d a p pl y t he 
f oll o wi n g ge n eral g ui deline:  
Y E S:   T here is a pla usi bl e te m p oral relati o ns hi p bet wee n t he o ns et of t he A E a n d 
a d mi nistrati o n of t he st u d y me dicati o n, a n d t he A E ca n n ot be rea dil y e x plai ne d b y t he 
patie nt’s cli nical state, i nterc urre nt ill ness, or c o nc o mita nt t hera pies, a n d/ or t he A E 
f oll o ws a k n o w n patter n of res p o nse t o t he st u d y dr u g, a n d/ or t he A E a bat es or res ol ves 
u p o n disc o nti n uati o n of t he st u d y dr u g or d ose re d ucti o n a n d, if a p plica ble, rea p pears 
u p o n re- c h alle n ge.  
N O:   E vi de nce e xists t hat t he A E has a n eti ol o g y ot her t ha n t he st u d y dr u g (e. g., pre-
e xisti n g me dical c o n diti o n, u n derl yi n g disease, i nt erc urre nt ill ness, or c o n c o mita nt 
me dicati o n), a n d/ or t he A E has n o pla usi ble te m p oral relati o ns hi p t o st u d y dr u g 
a d mi nistrati o n (e. g., ca n cer dia g n ose d 2 d a ys after first d ose o f st u d y dr u g). 
1 1. 2  
Seri o us A d verse E ve nt Re p orti n g b y I n vesti g at ors  
A d verse e ve nts classifie d b y t he tr eati n g I n vesti gat or as seri o us re q uire e x pe diti o us ha n dli n g a n d 
re p orti n g t o t he Sara h Ca n n o n De vel o p me nt I n n o v ati o ns Safet y De part me nt i n or der t o c o m pl y 
wi t h re g ul at or y re q uire m e nts.  Deter mi nati o n of life-t hreate ni n g or seri o us is base d o n t he 
o pi ni o n of eit her t he S p o ns or or t he I n vesti gat or. 
Seri o us A Es ma y o cc ur at a n y ti me fr o m t he start of st u d y treat me nt t hr o u g h  1 0 0 da ys after t he 
last st u d y treat me nt.  T h e S ar a h C a n n o n De vel o p me nt  I n n o v ati o ns S afet y De p art me nt m ust 
be n otifie d of all S A Es, re g ar dless of c a us alit y, wit hi n 2 4 h o urs of t he first k n o wle d ge of t he 
e ve nt b y t he tre ati n g p h ysici a n or rese arc h pers o n nel.  
T o re p ort a S A E, t he S A E Re p ort F or m s h o ul d be c o m plete d wit h t he necessar y i nf or mati o n. 
T he S A E re p ort s h o ul d b e se nt t o t he Sara h Ca n n o n De vel o p me nt I n n o vati o ns Safet y 
De part me nt via fa x or e mail usi n g t he usi n g t h e f oll o wi n g c o ntact i nf or mati o n ( d uri n g b ot h 
b usi ness a n d n o n- b usi ness h o urs): 
Sara h Ca n n o n De v el o p me nt I n n o v ati o ns Safet y D e part me nt  
Safet y De pt. Fa x #:      1 - 8 6 6- 8 0 7- 4 3 2 5 
Safet y De pt. E mail:      C A N N. S A E @ S C RI -I n n o v ati o ns.c o m 
Tra ns missi o n of t he S A E re p ort s h o ul d be c o nfir me d b y t h e site pers o n nel s u b mitti n g t he re p ort. 
F oll o w- u p i nf or mati o n f or S A Es a n d i nf or mati o n o n n o n-seri o us A Es t hat bec o me seri o us s h o ul d 
als o be re p ort e d t o t he Sara h Ca n n o n De v el o p me nt I n n o vati o ns Safet y De p art me nt as s o o n as it 
is a vaila ble; t hese r e p orts s h o ul d be s u b mitte d usi n g t he Sara h Ca n n o n D e vel o p me nt I n n o vati o ns 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 3 9  of 6 9  
 
S A E Re p ort F or m.  T he detaile d S A E re p orti n g pr ocess will be pr o vi de d t o t he sites i n t he S A E 
re p orti n g g ui deli nes c o nt ai ne d i n t he st u d y refere n ce ma n ual. 
I n v esti gat ors m ust re p ort S A Es a n d f oll o w- u p i nf or mati o n t o t heir res p o nsi ble I R B accor di n g t o 
t he p olicies of t he res p o nsi ble I R B. 
1 1. 3  
Rec or di n g of A d verse E ve nts a n d Seri o us A d verse E ve nts  
1 1. 3. 1  
Di a g n osis vers us Si g ns a n d S y m pt o ms 
All A Es s h o ul d be rec or d e d i n di vi d uall y i n t he patie nt’s o w n w or ds ( v er bati m) u nless, i n t he 
o pi ni o n of t he PI  or d esi g nate d p h ysicia n, t he A Es c o nstit ute c o m p o ne nts of a rec o g nize d 
c o n diti o n, disease, or s y n dr o me.  I n t he latter cas e, t he c o n diti o n, disease, or s y n dr o me s h o ul d b e 
na me d rat her t ha n eac h i n di vi d ual si g n or s y m pt o m.  If a c o nstellati o n of si g ns a n d/ or s y m pt o ms 
ca n n ot be me dicall y c har acterize d as a si n gle di a g n osis or s y n dr o me at t he ti me of re p orti n g, 
eac h i n di vi d ual e v e nt s h o ul d be rec or de d as a n A E or S A E as a p pr o priate o n t he rele va nt f or m(s) 
( S A E Re p ort F or m a n d/ or A E e C R F scree n).  If a dia g n osis is s ubse q ue ntl y esta blis he d, it s h o ul d 
be re p ort e d as f oll o w- u p i nf or mati o n bec o mes  a v aila ble.  If a dia g n osis is d eter mi ne d s u bse q ue nt 
t o t he re p orti n g of t he c o nstellati o n of s y m pt o ms, t he si g ns/s y m pt o ms s h o ul d be u p date d t o 
reflect t he dia g n osis. 
Pr o gr essi o n of mali g n a nc y (i ncl u di n g fatal o utc o m es), if d oc u me nte d b y us e of a p pr o priate 
met h o d (f or e x a m ple, as per L u ga n o C lassificati o n [C hes o n et al. 2 0 1 4 , see A p pe n di x F ]), s h o ul d 
n ot be re p orte d as a n S A E. 
1 1. 3. 2  
Pe rsiste nt or Rec u rre nt A d verse E ve nts  
A persiste nt A E is o ne t h at e xte n ds c o nti n u o usl y, wit h o ut res ol uti o n, bet wee n patie nt e val uati o n 
ti me p oi nts.  S uc h e ve nts s h o ul d o nl y be rec or d e d o nce o n t he S A E Re p ort F or m a n d/ or t he A E 
e C R F scree n.  If a persiste nt A E bec o mes m ore se vere or l esse ns i n se verit y, it s h o ul d be 
rec or d e d o n a se p ar ate S A E Re p ort F or m a n d/ or A E e C R F scree n. 
A rec urre nt A E is o n e t hat occ urs a n d res ol ves b et wee n patie nt e v al uati o n ti me p oi nts a n d 
s u bse q ue ntl y rec urs.  All rec urre nt A Es s h o ul d be rec or d e d o n a n S A E Re p ort F or m a n d/ or A E 
e C R F scree n.  
1 1. 3. 3  
A b n or m al L a b or at or y V al ues 
If a n a b n or mal la b or at or y val u e or vital si g n is ass ociate d wit h cli nical si g ns a n d/ or s y m pt o ms, 
t he si g n or s y m pt o m s h o ul d be re p orte d as a n A E or S A E, a n d t he ass oci ate d la b orat or y v al ue or 
vital si g n s h o ul d be c o nsi dere d a d diti o nal i nf or m ati o n t hat m ust be c ollecte d o n t he rele va nt 
e C R F scree n.  If t h e la b orat or y a b n or m alit y is a si g n of a diseas e or s y n dr o me, o nl y t he dia g n osis 
nee ds t o be r ec or d e d o n t he S A E Re p ort F or m or A E e C R F scree n.  
A b n or mal la b orat or y v al ues will be re p orte d as a n A E if: t he la b orat or y res ult re q uires a n 
a dj ust me nt i n t he st u d y dr u g(s) or disc o nti n uati o n of treat me nt, a n d/ or l a b orat or y fi n di n gs 
re q uire a d diti o nal testi n g or s ur gical i nter v e ntio n, a la b orat or y res ult or fi n di n g is ass ociate d wit h 
acc o m pa n yi n g s y m pt o ms, or a la b or at or y res ult is c o nsi dere d t o be a n A E b y t he I n v esti gat or. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 0  of 6 9  
 
1 1. 3. 4  
De at hs  
Deat hs t hat occ ur d uri n g t he pr ot oc ol-s pecifie d A E re p orti n g peri o d t hat are attri b ute d b y t he 
I n v estigat or s olel y t o pr o gr essi o n of disease will be rec or de d o n t he “ St u d y Disc o nti n uati o n” 
e C R F scree n.  All ot her o n st u d y deat hs, re gar dless of attri b uti o n, will be rec or de d o n a n S A E 
Re p ort F or m a n d e x pe diti o usl y re p orte d t o t he Sara h Ca n n o n De v el o p me nt I n no v ati o ns Safet y 
De part me nt.  
W he n rec or di n g a S A E wit h a n o utc o me of deat h, t he e ve nt or c o n diti o n t hat ca use d or 
c o ntri b ute d t o t he fatal o utc o me s h o ul d be rec or d e d as t he si n gle me dical c o nce pt o n t he S A E 
Re p ort F or m a n d A d vers e E ve nt scr ee n of t h e e C R F.  If t he ca use of deat h is u n k n o w n a n d 
ca n n ot be as cert ai ne d at t he ti me of re p orti n g, rec or d “ Deat h N O S” ( N ot Ot her wise S pecifie d) o n 
t he e C R F A d verse E ve nt scree n.  D uri n g p ost-st u d y s ur vi val f oll o w- u p, deat hs attri b ute d t o 
pr o gressi o n of diseas e will be rec or d e d o nl y o n t he “ After Pr o gressi ve Disease F oll o w-U p” 
e C R F scree n.  
1 1. 3. 5  
H os pit aliz ati o n, Pr ol o n ge d H os pit aliz ati o n, or S ur ger y 
A n y A E t hat res ults i n h os pitalizati o n of > 2 4 h o urs or pr ol o n gati o n of pre- e xisti n g 
h os pitalizati o n s h o ul d be d oc u me nte d a n d re p o rte d as a n S A E u nless s pecificall y i nstr u cte d 
ot her wise i n t his pr ot oc ol.  T here are s o me h os pitalizati o ns t hat d o n ot re q uire re p orti n g as a n 
S A E.  
Treat me nt wit hi n or a d missi o n t o t he f oll o wi n g facilities is n ot c o nsi dere d t o meet t he criteri a of 
“i n patie nt h os pitalizati o n” (alt h o u g h if a n y ot her S A E criteria are met, t he e ve nt m ust still be 
treate d as a n S A E a n d i m me diatel y re p orte d): 
•  E mer ge nc y d e part me nt or emer ge nc y r o o m 
•  O ut patie nt or sa me - d a y s ur ger y u nits 
•  O bser vati o n or s h ort-st a y u nit 
•  Re ha bilitati o n facilit y  
•  H os pice or s kille d n ursi n g f acilit y  
•  N ursi n g h o mes, c ust o dial care or res pite care facilit y 
H os pitalizati o n d uri n g t he st u d y f or a pre- pla n n e d s ur gical or me dical pr oce d ure ( o n e w hic h w as 
pla n ne d pri or t o e ntr y i n t he st u d y) d o es n ot re q uire re p ort i n g as an S A E t o t he Sara h Ca n n o n 
De vel o p me nt I n n o vati o ns Safet y De part me nt.  
1 1. 3. 6  
Pre -E xisti n g Me dic al C o n diti o ns  
A pre - e xisti n g me dical c o n diti o n is o ne t hat is prese nt at t he start of t he st u d y.  S uc h c o n diti o ns 
s h o ul d be rec or de d o n t h e Ge neral Me dical Hist or y e C R F s cree n.  A pre-e xisti n g me dical 
c o n diti o n s h o ul d be rec or de d as a n A E or S A E o nl y if t he fre q u e nc y, se v erit y, or c h aracter of t he 
c o n diti o n w orse ns d uri n g t he st u d y.  W he n rec or di n g s uc h e ve nts o n a n S A E Re p ort F or m a n d/ or 
A E  e C R F scr ee n, it is i m p orta nt t o c o n ve y t he c o n ce pt t hat t he pre-e xisti n g c o n diti o n has 
c ha n ge d b y i ncl u di n g a p plica ble descri pt ors. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 1  of 6 9  
 
1 1. 3. 7  
Ne w C a ncers  
T he de vel o p me nt of a ne w pri mar y ca ncer s h o ul d be re gar de d as a n A E a n d will ge nerall y meet 
at least o ne of t he s eri o us ness criteria (see Secti o n  1 1. 1. 2 ).  Ne w pri mar y ca ncers are t h ose t hat 
are n ot t he pri mar y reas o n f or t he a d mi nistrati o n of t he st u d y treat me nt a n d ha ve de v el o pe d aft er 
t he i ncl usi o n of t he patie nt i nt o t he st u d y.  T h e y d o n ot i ncl u de metastases of t he ori gi nal ca n cer.  
S y m pt o ms of met astasis or t he metastasis itself s h o ul d n ot be re p orte d as a n A E/ S A E, as t he y are 
c o nsi dere d t o be disease pr o gressi o n. 
1 1. 3. 8  
Pre g n a nc y, A b orti o n, a n d Birt h Defects/ C o n ge nit al A n o m alies  
If a patie nt b ec o mes pr e g na nt while e nr olle d i n t he st u d y, a Pre g n a nc y F or m (a pa per re p ort 
f or m, n ot a vaila ble wit hi n t he e C R F) s h o ul d be c o m plete d a n d fa x e d t o t he Sara h Ca n n o n 
De vel o p me nt I n n o vati o ns Safet y De part me nt.  T h e Sara h Ca n n o n D e vel o p me nt I n n o v ati o ns 
Safet y De part me nt s h o ul d be n otifie d e x pe diti o usl y, irres pecti ve of w het h er or n ot it meets t he 
criteria f or e x pe dite d re p orti n g.  A b orti o ns (s p o nt a ne o us, acci de ntal, or t h era pe utic) m ust als o be 
re p orte d t o Sar a h Ca n n o n De vel o p me nt I n n o vati o ns Safet y De part me nt.  
If a f e male part ner of a m ale patie nt bec o m es pre g na nt d uri n g t he m ale pati e nt’s partici pati o n i n 
t his st u d y, t his m ust be re p orte d t o t he Sara h Ca n n o n De vel o p me nt I n n o vati o ns Safet y 
De part me nt i m me diatel y.  E ver y eff ort s h o ul d be ma de t o f oll o w t he pre g n a nc y f or t h e fi n al 
pre g na nc y o ut c o me. 
C o n ge nital a n o malies/ birt h defects al w a ys meet S A E criteria a n d s h o ul d t heref ore be 
e x pe diti o usl y r e p orte d as a n S A E usi n g t he pre vi o usl y descri be d pr o cess f or S A E re p orti n g.  A 
Pre g n a nc y F or m s h o ul d als o ha ve bee n pre vi o usl y c o m plet e d, a n d will nee d t o be u p date d t o 
reflect t he o utc o me of t h e pre g na n c y. 
1 1. 3. 9  
Ni v ol u m a b O ver d ose  
S y m pt o matic a n d n o n-s y m pt o matic o ver d ose m ust be re p orte d i n t he e C R F.  A n y acci d e ntal or 
i nte nti o nal o ver d ose wit h t he st u d y treat me nt t hat is s y m pt o matic, e ve n if n ot f ulfilli n g a 
seri o us ness criteri o n, is t o be re p ort e d t o t he Sara h Ca n n o n De vel o p me nt I n n o vati o ns Safet y 
De part me nt n o gr eater t ha n 2 4 h o urs fr o m first k n o wle d ge of t he e ve nt usi n g t he c orres p o n di n g 
scree ns i n t he e C R F a n d f oll o wi n g t he sa m e pr ocess descri be d f or S A E re p orti n g (see 
Secti o n  1 1. 2 ) if t he o ver d ose is s y m pt o matic. 
F or i nf or m ati o n o n h o w t o ma na ge a n o v er d ose of ni v ol u ma b , see t he I B. 
1 1. 4  
S p o ns or Seri o us A d verse E ve nt Re p orti n g Re q uire me nts  
Sara h Ca n n o n De v el o p me nt I n n o v ati o ns Safet y D e part me nt will f or w ar d S A E i nf or mati o n t o 
B M S Gl o bal P har mac o vi gila nce  at W orl d wi de. Safet y @ b ms .c o m wit hi n 1 b usi ness da y of Sara h 
Ca n n o n De vel o p me nt I n n o vati o ns Safet y De part me nt pers o n nel bec o mi n g a ware of t he S A E. 
Sara h Ca n n o n De v el o p m e nt I n n o v ati o ns is res p o nsi ble f or re p orti n g rele va nt S A Es t o t he 
c o m pete nt a ut h orit y, ot her a p plica bl e re g ulat or y a ut h orities, a n d partici pati n g I n v esti gat ors, i n 
acc or d a nce wit h I nter n ati o nal C o u ncil f or Har m o nisati o n ( I C H) g ui deli nes a n d F D A re g ulati o ns . 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 2  of 6 9  
 
1 1. 4. 1  
S p o ns or Assess me nt of U ne x pecte d  
T he S p o ns or is res p o nsi ble f or assessi n g a n A E  or s us pecte d A E as “ u ne x pecte d .” 
A n A E  or S A R is c o nsi dere d “ u n e x pecte d” w h e n t he f oll o wi n g c o n diti o ns occ ur: 
•  E ve nt(s) is n ot me nti o ne d i n t he I B ( or c urre nt U S Pac ka ge I nsert [ U S PI]) 
•  E ve nt(s) is n ot liste d at t he s pecificit y or s e verit y t hat has bee n o bser ve d 
•  A n e ve nt(s) is n ot c o nsist e nt wit h t he Ge neral I n vesti gati ve Pla n or i n t he c urre nt 
a p plicati o n 
•  I n cl u des A Es or S A R t hat ma y be a ntici pate d fr o m t he p har mac ol o gical pr o perties of t he 
st u d y dr u g, or t h at occ ur wit h me m bers of t he dr u g cl ass, b ut t hat ha ve pre vi o usl y bee n 
o bser ve d u n der i n vesti gati o n 
W he n a p plica ble, a n u n e x pecte d A E ma y als o a p pl y t o a n e v e nt t hat is n ot liste d i n t he c urre nt 
U S PI or a n e ve nt t hat ma y be m e nti o ne d i n t he U S PI, b ut differs fr o m t he e ve nt beca us e of 
gr eater se verit y or s p ecifi cit y.  
K n o w n as S us pecte d U n e x pecte d Seri o us A d vers e Reacti o ns ( S U S A R), t h ese e ve nts s us pecte d 
( b y t he I n vesti gat or or S p o ns or) t o be rel ate d t o t he st u d y dr u g, are u ne x pecte d ( n ot liste d i n t he 
I B), are s eri o us (as d efi n e d b y t h e pr ot oc ol) a n d re q uire e x pe die nt s u b missi o n t o rele va nt healt h 
a ut h orities wit hi n 7 da ys (fatal or lif e -t hreate ni n g e ve nt) or 1 5 d a ys (all seri o us e ve nts), or as 
defi ne d b y la w.  T h e ter m S U S A R is  use d pri maril y i n t he re p orti n g of e ve nts t o re g ulat or y 
a ut h orities.  
E x pecte d A Es are t h ose e ve nts t hat are liste d or c h aract erize d i n t he Pac ka ge I nsert or c urre nt I B.  
1 1. 4. 2  
S p o ns or Re p orti n g f or Cli nic al St u dies U n der a n I n vesti g ati o n al Ne w Dr u g 
A p plic ati o n  
A ll writte n i n vesti gati o nal ne w dr u g (I N D) Safet y Re p orts s u b mitte d t o t he F D A b y t he Sara h 
Ca n n o n De vel o p me nt I n n o vati o ns Safet y De part me nt m ust als o be fa x e d t o p har mace utical 
c o m pa n y(ies) t hat are s u p p orti n g t he st u d y wit h eit her f u n di n g or dr u g s u p pl y: 
B M S Gl o bal P har mac o vi gila nce 
B M S Safet y S A E Fa x #: 6 0 9 - 8 1 8- 3 8 0 4 
W orl d wi de. Safet y @ b ms . c o m 
1 2.  
Q U A LI T Y A S S U R A N C E A N D Q U A LI T Y C O N T R O L  
1 2. 1  
St u d y M o nit ori n g, A u diti n g, a n d I ns pecti n g  
T he In vesti gat or will per mit st u d y -relate d m o nit ori n g, q ualit y a u dits, a n d i ns pecti o ns b y t he 
S p o ns or or its re prese nt ati ve(s), g o ver n m e nt re g ul at or y a ut h orities, a n d t he I R B/ E C of all 
st u d y-r elate d d oc u m e nts (e. g., s o urce d oc u me nts, re g ulat or y d oc u m e nts, data c ollecti o n 
i nstr u me nts, case re p ort f or ms).  T he In v esti gat or will e ns ure t he ca p a bilit y f or i ns pecti o ns of 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 3  of 6 9  
 
a p plica ble st u d y-r elate d f acilities.  T he In vesti gat or will e ns ure t hat t he st u d y m o nit or or a n y 
ot her c o m plia nce or Q ualit y Ass ura n ce re vie w er is gi ve n access t o all st u d y -relate d d o c u me nts 
a n d st u d y- relate d facilities. 
At t he S p o ns or’s discreti o n, S o urce D oc u m e nt Verificati o n ( S D V) ma y b e perf or me d o n all data 
ite ms or a perce nta ge t h ere of. 
Partici pati o n as a n In vesti gat or i n t his st u d y i m plies t he acce pta n ce of p ote ntial i ns pecti o n b y 
g o ver n me nt re g ul at or y a ut h orities, t he S p o n s or or its re prese ntati ve(s). 
1 3.  
E T HI C A L, FI N A N CI A L, A N D R E G U L A T O R Y C O N SI D E R A TI O N S  
T his resear c h st u d y will be c o n d ucte d acc or di n g t o t he sta n dar ds of G o o d Cli nical Practice 
( G C P) o utli ne d i n t he I C H E 6 Tri partite G ui deli n e a n d C F R Title 2 1 part 3 1 2, a p plica b le 
g o ver n me nt re g ul ati o ns, i nstit uti o nal researc h p olicies a n d pr o ce d ures a n d a n y ot h er l ocal 
a p plica ble r e g ulat or y r e q uire me nt(s).  
1 3. 1  
I nstit uti o n al Re vie w B o ar d A p pr o v al 
T he cli nical st u d y pr ot oc ol, i nf or me d c o nse nt f or m ( I C F), I B, a v aila ble safet y i nf or matio n, 
patie nt d oc u me nts (e. g., st u d y diar y), patie nt recr uit me nt pr oce d ures (e. g., a d vertise me nts), 
i nf or mati o n a b o ut pa y me nts (i.e., PI  p a y m e nts) a n d c o m pe nsati o n a vaila ble t o t he patie nts a n d 
d oc u me ntati o n e vi de nci n g t he PI ’s q u alificati o ns s h o ul d be s u b mitte d t o t he I R B f or et hical 
re vie w a n d a p pr o v al if re q uire d b y l o cal re g ulati o ns, pri or t o t he st u d y start. 
T he PI / S p o ns or a n d/ or d esi g nee will f oll o w all necessar y re g ulati o ns t o e ns ure a p pr o priate, 
i nitial, a n d o n- g oi n g , I R B st u d y re vie w.  T he PI / S p o ns or (as a p pr o pri ate) m ust s u b mit a n d, 
w here n ecess ar y, o btai n a p pr o val fr o m t he I R B f or all s u bse q ue nt pr ot oc ol a me n d me nts a n d 
c ha n ges t o t he i nf or m e d c o nse nt d oc u me nt.  I n v esti gat ors will be a d vise d b y t he S p o ns or or 
desi g nee w het h er a n a me n d me nt is c o nsi dere d s u bsta ntial or n o n-s u bsta ntial a n d w het her it 
re q uires s u b missi o n f or a p pr o val or n otificati o n o nl y t o a n I R B. 
Safet y u p dates f or ni v ol u ma b will be pre pare d b y t he S p o ns or or its re pres e ntati ve as re q uire d, 
f or distri b uti o n t o t he I n v esti gat or(s) a n d s ub missi o n t o t he rele va nt I R B. 
1 3. 2  
Re g ul at or y A p pr o v al 
As re q uire d b y l o cal re g ulati o ns, t he S p o ns or will e ns ure all le gal as pects are c o vere d, a n d 
a p pr o val of t he a p pr o pri ate re g ulat or y b o dies o btai ne d, pri or t o st u d y i nitiati o n.  If re q uire d, t he 
S p o ns or will als o e ns ure t hat t he i m ple me ntati o n of s u bsta ntial a me n d me nt s t o t he pr ot oc ol a n d 
ot her rele v a nt st u d y d o c u me nts ha p pe n o nl y after a p pr o val b y t he rele va nt re g ulat or y a ut h orities. 
1 3. 3  
I nf or me d C o nse nt 
I nf or me d c o ns e nt is a pr o cess b y w hic h a p atie nt v ol u ntaril y c o nfir ms his or her willi n g ness t o 
partici pate i n a p artic ular st u d y aft er ha vi n g bee n i nf or me d of all as p ects of t he st u d y t hat are 
rele va nt t o t he patie nt's d ecisi o n t o partici pate.  I nf or me d c o nse nt is d oc u me nte d b y mea ns of a 
writte n, si g ne d, a n d date d I C F. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 4  of 6 9  
 
T he I C F will be s u b mitte d f or a p pr o v al t o t he I R B t hat is res p o nsi ble f or re vie w a n d a p pr o val of 
t he st u d y.  Eac h c o nse nt f or m m ust i ncl u de all of t he rele v a nt ele me nts c urre ntl y re q uire d b y t he 
F D A, as well as l ocal c o u nt y a ut h orit y or state re g u lati o ns a n d nati o nal re q uire me nts. 
Bef ore r ecr uit me nt a n d e nr oll me nt i nt o t he st u d y, eac h pr os p ecti ve ca n di date will be gi ve n a f ull 
e x pla nati o n of t he resear c h st u d y.  O n ce t he esse ntial i nf or mati o n has bee n pr o vi de d t o t he 
pr os pecti ve ca n di date, a n d t he I n v esti gat or is s ure t hat t he i n di vi d ual ca n di date u n dersta n ds t he 
i m plicati o ns of partici pati n g i n t his researc h st u d y, t he ca n di date will be as ke d t o gi ve c o nse nt t o 
partici pate i n t he st u d y b y si g ni n g a n I C F.  A n otati o n t hat writte n i nf or me d c o nse nt has bee n 
o btai ne d will be ma de i n t he patie nt’s me dical rec or d.  A c o p y of t he I C F, t o i ncl u de t he patie nt’s 
si g nat ur e, will be pr o vi de d b y t he In vesti gat or t o t he patie nt.  
If a n a m e n d me nt t o t he pr ot oc ol s u bsta ntiall y alters t he st u d y desi g n or t he p ote ntial ris ks t o t he 
patie nts, t he patie nt’s c o nse nt t o c o nti n ue partici pati o n i n t he st u d y s h o ul d b e o btai ne d. 
1 3. 3. 1  
C o nfi de nti alit y  
1 3. 3. 1. 1  P ati e nt C o nfi de nti alit y  
C o nfi de ntialit y of patie nt’s pers o nal dat a will be pr otecte d i n acc or d a nce wit h t he Healt h 
I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act of 1 9 9 6 ( HI P A A).  HI P A A re g ulati o ns re q uire t hat, 
i n or der t o partici pat e i n t he st u d y, a patie nt m ust si g n a n a ut h orizati o n f or m f or t he st u d y t hat he 
or s he has bee n i nf or me d of f oll o wi n g: 
•  W hat pr otecte d healt h i nf or mati o n ( P HI) will be c ollecte d fr o m patie nts i n t his st u d y 
•  W h o will ha ve access t o t hat i nf or mati o n a n d w h y 
•  W h o will use or discl ose t hat i nf or mati o n  
•  T hat healt h i nf or mati o n ma y b e f urt her discl ose d b y t he reci pie nts of t he i nf or mati o n a n d 
t hat if t he i nf or mati o n is discl ose d t he i nf or mati o n ma y n o l o n ger be pr ot ecte d b y fe deral 
or state pri vac y l a ws  
•  T he i nf or mati o n c ollect e d a b o ut t he researc h st u d y will be ke pt se p arate fr o m t he 
patie nt’s me dical r ec or ds, b ut t he patie nt will be a ble t o o btai n t he researc h rec or ds after 
t he c o ncl usi o n of t he st u d y 
•  W het her t he a ut h orizati o n c o ntai ns a n e x pirati o n date 
•  T he ri g hts of a r esearc h p atie nt t o re v o ke his or her a ut h orizati o n 
I n t he e ve nt t hat a p atie nt re v o kes a ut h orizati o n t o c ollect or use his or h er P HI, t he I n vesti gat or, 
b y r e g ulati o n, retai ns t he a bilit y t o use all i nf or mati o n c ollecte d pri or t o t he re v ocati o n of p atie nt 
a ut h orizati o n.  F or patie nts t hat ha ve re v o k e d a ut h orizati o n t o c ollect or use P HI, atte m pts s h o ul d 
be ma de t o o btai n per missi o n t o c ollect at least vital stat us (i.e., t hat t he patie nt is ali ve) at t he 
e n d of t heir sc h e d ule d st u d y peri o d. 
I n c o m plia nce wit h I C H G C P g ui deli nes a n d a p plica ble parts of 2 1 C F R it is a re q uire me nt t hat 
t he I n v esti gat or a n d i nstit uti o n per mit a ut h orize d re prese nt ati ves of t he S p o ns or, t he re g ulat or y 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 5  of 6 9  
 
a ut h orities a n d t he I R B direct access t o re vie w t he patie nt’s ori gi n al me dical rec or ds at t he site 
f or verifi cati o n of st u d y-r elate d pr oce d ures a n d dat a. 
Meas ures t o pr ot ect c o nfi de ntialit y i ncl u de: o nl y a u ni q ue st u d y n u m ber will i de ntif y patie nts i n 
t he e C R F or ot her d o c u m e nts s u b mitte d t o t he S p o ns or.  T his i nf or mati o n, t o get h er wit h t he 
patie nt’s date of birt h, will be use d i n t he data bas e f or patie nt i de ntificati o n.  Patie nt na mes or 
a d dresses will n ot be e nt ere d i n t he e C R F.  N o  material beari n g a patie nt’s na me will be ke pt o n 
file b y S p o ns or.  Patie nts will be i nf or me d of t heir ri g hts wit hi n t he I C F. 
1 3. 3. 1. 2  I n vesti g at or a n d St aff I nf or m ati o n 
Pers o nal data of t he I n vesti gat ors a n d s u b-I n vesti gat ors m a y be i ncl u de d i n t he Sara h Ca n n o n 
De vel o p me nt I n n o vati o ns data base, a n d s hall be treate d i n c o m plia nce wit h all a p plica ble la ws 
a n d re g ulati o ns.  W he n arc hi vi n g or pr ocessi n g p ers o nal data pertai ni n g t o t he I n vesti gat or or 
s u b-I n vesti gat or, Sar a h Ca n n o n De vel o p me nt I n n o vati o ns s hall ta ke all a p pr o priate meas ures t o 
safe g uar d a n d pr e ve nt access t o t his data b y a n y u na ut h orize d part y. 
1 3. 4  
Fi n a nci al I nf or m ati o n 
T he fi na nces f or t his cli nical st u d y will be s u bject t o a se parate writte n a gree me nt bet wee n t he 
Sara h Ca n n o n De v el o p me nt  I n n o v ati o ns, L L C a n d a p plica ble parties.  A n y I n v esti gat or fi na n cial 
discl os ures as a p plica bl e t o 2 1 C F R Part 5 4 s hall be a p pr o pri atel y pr o vi de d. 
1 4.  
R E S E A R C H R E T E N TI O N A N D D O C U M E N T A TI O N O F T H E S T U D Y  
1 4. 1  
A me n d me nts t o t he Pr ot oc ol  
A me n d me nts t o t he pr ot oc ol s hall be pla n ne d, d oc u me nte d , a n d si g n at ure-a ut h orize d pri or t o 
i m ple me ntati o n. 
If a n a m e n d me nt t o t he pr ot oc ol is re q uire d, t he a me n d me nt will be ori gi n ate d a n d d oc u m e nte d 
b y t he S p o ns or or its r e pr ese ntati ves .  All a me n d m e nts re q uire re vie w a n d a p pr o val of all 
p har mace utical c o m pa ni es a n d t he PI  s u p p orti n g t he st u d y.  T h e writte n a m e n d me nt m ust be 
re vie we d a n d a p pr o ve d b y t he S p o ns or, a n d s u b mitte d t o t he I R B at t he In v esti gat or’s facilit y f or 
t he b oar d’s a p pr o val. 
A me n d me nts s pecificall y i n v ol vi n g c ha n ge t o st u d y desi g n, ris k t o patie nt, i ncreas e t o d osi n g or 
e x p os ure, patie nt n u m ber i ncreas e, a d diti o n or re m o val of ne w tests or pr oce d ures, s hall be 
re vie we d a n d a p pr o ve d b y t he I R B of rec or d f or  t h e I n vesti gat or’s facilit y. 
T he a me n d me nt will be s u b mitte d f or mall y t o t he F D A or ot h er re g ulat or y a ut h orities b y t he 
S p o ns or as a p plica ble, a n d I R B a p pr o v al o btai ne d, a n d s pecificall y w he n a n i ncreas e t o d osi n g or 
patie nt e x p os ure a n d/ or p atie nt n u m ber has bee n pr o p ose d; or, w he n t h e a d diti o n or re m o val of 
a n I n vesti gat or is necessitate d.  
Ite ms r e q uiri n g a pr ot o c ol a me n d me nt a p pr o val fr o m  I R B a n d/ or F D A or ot her re g ulat or y 
a ut h orities i ncl u des, b ut are n ot li mite d t o, t he f oll o wi n g:  
•  C ha n ge t o st u d y desi g n  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 6  of 6 9  
 
•  Ris k t o patie nt 
•  I n crease t o d ose or patie nt e x p os ure t o dr u g 
•  Patie nt n u m ber i ncrea se 
•  A d diti o n or re m o val of tests a n d / or pr oce d ures  
•  A d diti o n/re m o val of a ne w I n vesti gat or  
It s h o ul d be f urt her n ote d t hat, if a n a me n d me nt t o t he pr ot oc ol s u bsta ntiall y alters t he st u d y 
desi g n or t h e p ote ntial ris ks t o t he patie nts, t heir c o nse nt t o c o nti n ue partici pati o n i n t he st u d y 
s h o ul d be o btai ne d. 
1 4. 2  
D oc u me nt ati o n Re q uire d t o I niti ate t he St u d y  
Bef ore t he st u d y ma y b e gi n  certai n d oc u me nt ati o n re q uire d b y F D A re g ul ati o ns a n d I C H G C P  
m ust be pr o vi de d b y t h e I n v esti gat or.  T he re q uire d d oc u me ntati o n s h o ul d be s u b mitte d t o: 
Sara h Ca n n o n De v el o p me nt I n n o v ati o ns 
Re g ulat or y De part me nt  
1 1 0 0 Dr. Marti n L.  Ki n g Jr. Bl v d., S uite 8 0 0 
Nas h ville, T N  3 7 2 0 3 
D oc u me nts at a mi ni m u m re q uire d t o be gi n a st u d y i n t he U S i ncl u de, b ut are n ot li mite d t o, t he 
f oll o wi n g: 
•  A si g nat ur e-a ut h orize d pr ot oc ol a n d c o ntract 
•  A c o p y of t he official I R B a p pr o v al of t he st u d y a n d t he I R B me m bers list  
•  C urre nt C urric ula Vita e f or t he PI  a n d a n y s u b-I n v esti gat or(s) w h o will be i n v ol ve d i n t he 
st u d y 
•  I n dicati o n of a p pr o priate accr e ditati o n f or a n y l a b orat ories t o be use d i n t h e st u d y a n d a 
c o p y of t he n or mal r a n ges f or tests t o be perf or me d b y t hat la b orat or y 
•  Ori gi nal F or m F D A 1 5 7 2 ( State me nt of I n vesti gat or), a p pr o pri atel y c o m pl ete d a n d 
si g ne d 
•  A c o p y of t he I R B- a p pr o ve d c o nse nt f or m (a n d patie nt i nf or mati o n s heet, if a p plica ble) 
c o ntai ni n g p er missi o n f or a u dit b y re prese ntati ves of Sara h Ca n n o n D e vel o p me nt 
I n n o v ati o ns, t he I R B, a n d t he F D A a n d ot her re g ulat or y a ge nci es (as a p plica ble)  
•  Fi na ncial discl os ur e f or ms f or all I n vesti gat ors liste d o n F or m F D A 1 5 7 2 (if a p plica ble) 
•  Site q ualificati o n re p orts, w here a p plica ble  
•  Verificati o n of PI  acce pt a bilit y fr o m l ocal a n d/ or nati o nal de bar me nt list(s)  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 7  of 6 9  
 
1 4. 3  
St u d y  D oc u me nt ati o n a n d St or a ge 
T he PI  m ust mai ntai n a list of a p pr o priatel y q u alifie d pers o ns t o w h o m he/s he has dele gate d 
st u d y d uties a n d s h o ul d e ns ure t hat all pers o ns assisti n g i n t he c o n d uct of t h e st u d y are i nf or me d 
of t heir o bli gati o ns.  All pers o ns a ut h orize d t o ma ke e ntries a n d/ or c orrecti o ns o n t he eC R Fs are 
t o be i ncl u de d o n t his d oc u me nt.  All e ntries i n t he patie nt’s e C R F are t o b e s u p p orte d b y s o urce 
d oc u me ntati o n w her e a p pr o priate. 
S o urce d oc u me nts are t h e ori gi n al d oc u me nts, dat a, rec or ds, a n d certifie d c o pies of ori gi nal 
rec or ds of cli nical fi n di n gs, o bser vati o ns, a n d acti vities fr o m w hic h t h e patie nt’s e C R F data are 
o btai ne d.  T hese ca n i ncl u de, b ut are n ot li mite d t o, h os pital rec or ds, cli nical a n d office c h arts, 
la b orat or y, me dic o-tec h nical de part me nt a n d p har mac y rec or ds, diari es, micr ofic h es, E C G 
traces, c o pies or tra ns cri pti o ns certifie d after verificati o n as bei n g acc urate a n d c o m plete, 
p h ot o gra p hic ne gati ves, micr ofil m or ma g n etic m e dia, X-ra ys, a n d c orres p o n de nce. 
T he PI  a n d eac h st u d y staff me m ber is res p o nsi ble f or mai ntai ni n g a c o m pre he nsi ve a n d 
ce ntralize d fili n g s yste m (e. g., re g ul at or y bi n der or In vesti gat or st u d y file [I S F]) of all st u d y-
relate d ( esse ntial) d oc u m e ntati o n, s uita ble f or i ns p ecti o n at a n y ti me b y re prese ntati ves fr o m t he 
S p o ns or a n d/ or a p plica bl e re g ulat or y a ut h orities.  T he I S F m ust c o nsist of t h ose d oc u me nts t hat 
i n di vi d uall y or c ollecti vel y per mit e v al uati o n of t he c o n d uct of t he st u d y a n d t he q ualit y of t he 
data pr o d uce d.  T he I S F s h o ul d c o ntai n as a mi ni m u m all rele va nt d oc u me nts a n d 
c orres p o n d e nce as o utli ne d i n I C H G C P Secti o n 8 a n d 2 1 C F R Part 3 1 2. 5 7, i ncl u di n g ke y 
d oc u me nts s uc h as t he I B a n d a n y a me n d m e nts, pr ot oc ol a n d a n y a me n d m e nts, si g ne d I C Fs, 
c o pies of c o m plete d e C R Fs, I R B a p pr o val d o c u me nts, patie nt i de ntificati o n lists, e nr oll me nt 
l o gs, dele gati o n of a ut h orit y l o g, staff q ualifi cati o n d oc u me nts, la b orat or y n or mal ra n ges, rec or ds 
relati n g t o t he st u d y dr u g i ncl u di n g acc o u nta bilit y rec or ds.  Dr u g acc o u nta bilit y rec or ds s h o ul d, 
at a mi ni m u m, c o ntai n i nf or mati o n re gar di n g recei pt, s hi p me nt, a n d dis p ositi o n.  Eac h f or m of 
dr u g acc o u nt a bilit y r ec or d, at a m i ni m u m, s h o ul d c o ntai n PI  n a me, date dr u g s hi p pe d/recei v e d, 
date, q ua ntit y a n d batc h/ c o de, or l ot n u m ber f or i de ntit y of eac h s hi p me nt.  I n a d diti o n, all 
ori gi nal s o ur ce d oc u m e nts s u p p orti n g e ntries i n t h e e C R F m ust be mai ntai n e d a n d be rea dil y 
a vaila ble.  
T he S p o ns or s hall mai ntai n a de q uate i n vesti gati o n al pr o d uct rec or ds a n d fi na ncial i nterest 
rec or ds as per 2 1 C F R Part 5 4. 6 a n d Part 3 1 2. 5 7 f or n o less t ha n 2 years aft er t he last mar k eti n g 
a p plicati o n has bee n a p pr o ve d b y t h e F D A; or, i n t he e ve nt t hat t he mar keti n g a p plicati o n has n ot 
bee n a p pr o v e d b y t he F D A, f or n o less t ha n 2 years after t he last s hi p me nt / deli ver y of t he dr u g 
f or i n vesti gati o nal use is disc o nti n ue d a n d t he F D A has bee n n otifie d of t he disc o nti n uati o n. 
T he I R B s h all mai ntai n a de q uate d o c u m e ntati o n / rec or ds of I R B acti vities as per 2 1 C F R Part 
5 6. 1 1 5 f or at least 3 years after c o m pleti o n of t h e researc h. 
T he I n vesti gat or s hall mai ntai n a de q uate rec or ds of dr u g dis p ositi o n, case hist ories, a n d a n y 
ot her st u d y- relat e d rec or ds as per 2 1 C F R Part 3 1 2. 6 2 f or n o less t ha n 2 years after t he last 
mar keti n g a p plicati o n has bee n a p pr o v e d b y t he F D A; or, i n t he e ve nt t hat t he mar keti n g 
a p plicati o n has n ot bee n a p pr o ve d b y t he F D A, f or n o less t ha n 2 years after t he last s hi p me nt / 
deli ver y of t he dr u g f or i n vesti gati o nal use is disc o nti n ue d a n d t he F D A has bee n n otifie d of t he 
disc o nti n uati o n. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 8  of 6 9  
 
T o e na ble e v al uati o ns a n d/ or a u dits fr o m re g ulat or y a ut h orities or fr o m t he S p o ns or or its 
re pres e ntati ve, t he I n v esti gat or a d diti o nall y a grees t o kee p rec or ds, i ncl u di n g t he i de ntit y of all 
partici pati n g p atie nts (s ufficie nt i nf or mati o n t o li n k rec or ds e. g., eC R Fs, m e dical rec or ds), all 
ori gi nal, si g ne d I C Fs, a n d c o pies of all e C R Fs, S A E Re p orti n g f or ms, s o urce d oc u m e nts, 
detaile d rec or ds of tr eat me nt dis p ositi o n, a n d relate d esse ntial re g ulat or y d oc u me nts.  T he 
d oc u me nts liste d a b o ve m ust be retai ne d b y t he I n vesti gat or f or as l o n g as nee de d t o c o m pl y wit h 
nati o nal a n d i nter nati o nal re g ulati o ns ( ge nerall y 2 years after disc o nti n ui n g cli nical de vel o p me nt 
or after  t h e last mar keti n g a p pr o val).  S p o ns or will n otif y t he In v esti gat or(s)/i nstit uti o ns(s) w he n 
t he st u d y-relate d rec or ds are n o l o n ger re q uire d. 
If t he I n vesti gat or rel ocat es, retires, or f or a n y reas o n wit h dra ws fr o m t he st u d y, b ot h t he 
S p o ns or a n d its re prese nt ati ve s h o ul d be pr os pecti vel y n otifie d.  T h e st u d y rec or ds m ust be 
tra nsferre d t o a n acce pta ble desi g n ee, s uc h as a n ot her I n vesti gat or, a n ot her i nstit uti o n, or t o t he 
S p o ns or .  T he I n vesti gat or m ust o btai n t he S p o ns or’s writte n per missi o n bef ore dis p osi n g of a n y 
rec or ds, e ve n if r ete nti o n re q uire me nts ha v e bee n met.  All st u d y files will be mai ntai ne d b y t he 
S p o ns or ( Sara h Ca n n o n De vel o p me nt I n n o vati o ns) t hr o u g h o ut t he st u d y, a n d w ill be hel d b y t he 
S p o ns or at t he c o ncl usi o n of t he st u d y. 
1 4. 4  
D at a C ollecti o n 
T he st u d y eC R F is t he pri mar y d ata c ollecti o n i nstr u me nt f or t he st u d y.  Case re p ort f or ms will 
be c o m plete d usi n g t he E n glis h la n g ua ge a n d s h o ul d be ke pt c urre nt t o e na ble t he S p o ns or t o 
re vie w t he p atie nts’ stat us t hr o u g h o ut t he c o urse of t he st u d y. 
I n or der t o mai ntai n c o nfi de ntialit y, o nl y st u d y n u m ber, patie nt n u m ber, a n d year  of birt h will 
i de ntif y t he p atie nt i n t he e C R F.  If t he p atie nt’s n a me a p pears o n a n y ot h er d oc u me nt (e. g., 
la b orat or y r e p ort), it m ust be o bliterate d o n t he c o p y of t he d oc u me nt t o be s u p plie d t o Sara h 
Ca n n o n De vel o p me nt I n n o vati o ns a n d re place d i nstea d wit h t he patie nt n u m ber a n d patie nt’s 
i nitials.  T he In vesti gat or will mai ntai n a pers o nal patie nt i de ntificati o n list ( patie nt n u m bers wit h 
c orres p o n di n g p atie nt i de ntifiers) t o e na ble rec or ds t o be i de ntifie d a n d verifie d as a ut he ntic.  
Patie nt data/i nf or mati o n will be ke pt c o nfi de ntial, a n d will be ma na ge d acc or di n g t o a p plica ble 
l ocal, state, a n d f e der al r e g ul ati o ns. 
All data re q uest e d i n t he e C R F m ust be s u p p orte d b y a n d b e c o nsiste nt wit h t he patie nt’s s o urce 
d oc u me ntati o n.  All missi n g data m ust be e x plai ne d.  W he n a re q uire d l a b orat or y t est, 
assess me nt, or e v al uati o n has n ot bee n d o ne or a n “ U n k n o w n” b o x is n ot a n o pti o n o n t he e C R F, 
a n ote s h o ul d be cr eate d verif yi n g t hat t he fiel d w as “ N ot D o ne” or “ U n k n o w n. ”  F or a n y e ntr y 
err ors ma d e, t he err or(s) m ust be c orrecte d, a n d a n ote e x plai ni n g t he reas o n f or c ha n ge s h o ul d 
be pr o vi de d. 
T he In vesti gat or will electr o nicall y si g n a n d date t he patie nt e C R F case b o o k i n dicati n g t ha t t he 
data i n t he eC R F has b ee n assesse d.  Eac h c o m plete d e C R F will be si g n e d a n d date d b y t he PI , 
o nce all data f or t hat pati e nt is fi nal.  
1 4. 5  
Discl os ure a n d P u blic ati o n P olic y  
All i nf or mati o n pr o vi de d re gar di n g t he st u d y , as well as all i nf or mati o n c ollecte d/ d oc u me nte d 
d uri n g t he c o urse of t he st u d y, will be re gar d e d as c o nfi de ntial.  T he S p o ns or reser ves t he ri g ht 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 4 9  of 6 9  
 
t o release liter at ure p u bli cati o ns base d o n t he res ults of t he st u d y.  Res ults fr o m t he st u d y will be 
p u blis he d/ prese nte d as p er t he S p o ns or’s p u b licati o n pr ocess.  
I n cl usi o n of t he I n vesti gat or i n t he a ut h ors hi p of a n y m ultice nter p u blicati o n will be base d u p o n 
s u bsta ntial c o ntri b uti o n t o t he desi g n, a nal ysis, i nter pret ati o n of data, drafti n g a n d/ or criticall y 
re visi n g a n y ma n uscri pt(s) deri ve d fr o m t he st u d y.  T he I n vesti gat or ac k n o wle d ges t hat t he st u d y 
is part of a m ultice nter st u d y a n d a grees t hat a n y p u blicati o n b y t he I n v esti gat or of t he res ults of 
t he st u d y c o n d u cte d at r esearc h site s h all n ot be ma de bef ore t he first m ultice nter  p u blicati o n.  I n 
t he e ve nt t her e is n o m ultice nter p u blicati o n wit hi n fiftee n ( 1 5) m o nt hs after t he st u d y h as bee n 
c o m plete d or ter mi nate d at all st u d y sites, a n d all data has bee n recei ve d, t he I n vesti gat or s hall 
ha ve t he ri g ht t o p u blis h its res ults fr o m t he st u d y , su bject  t o t he n otice re q uire me nts descri b e d 
herei n a n d s u bject t o ac k n o wle d ge me nt of t he S p o ns or as a p pr o priate.  I n v esti gat or s h all pr o vi de 
t he S p o ns or t hirt y ( 3 0) d a ys t o r e vie w a ma n uscri pt or a n y p oster prese ntati o n, a bstract or ot her 
writte n or oral m aterial w hic h descri bes t he res ults of t he st u d y f or t he p ur p ose o nl y of 
deter mi ni n g if a n y c o nfi d e ntial or pate nta ble i nf or mati o n is discl ose d t here b y.  If t he S p o ns or 
re q uests i n writi n g, t h e I n vesti gat or s h all wit h h ol d a n y p u blicati o n or pres e ntati o n a n a d diti o nal 
si xt y ( 6 0) d a ys s ol el y t o per mit t he S p o ns or t o see k pate nt pr otecti o n a n d t o re m o ve a n y Sara h 
Ca n n o n De vel o p me nt I n n o vati o ns C o nfi de ntial I nf or mati o n fr o m all p u blicati o ns.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 0  of 6 9  
 
1 5.  
R E F E R E N C E S  
A nsell  et al. 2 0 1 5 
A nsell S M, Les o k hi n A M, B orr ell o I, et al. P D-1 Bl oc ka d e wit h ni v ol u ma b i n r ela pse d or 
refr act or y H o d g ki n’s l y m p h o ma. N E n gl J Me d. 2 0 1 5; 3 7 2( 4): 3 1 1- 1 9. 
C hes o n et al. 2 0 0 7 
C hes o n B D, Pfist ner B, J u wei d M E, et al. Re vise d res p o nse criteria f or m ali g na nt l y m p h o ma. 
J Cli n O nc ol. 2 0 0 7; 2 5( 5): 5 7 9- 8 6. 
C hes o n et al. 2 0 1 4 
C hes o n B D, Fis her RI , Barri n gt o n S F , et al. Rec o m me n dati o ns f or i nitial e val uati o n, s ta gi n g, a n d 
res p o nse ass ess me nt of H o d g ki n a n d n o n-H o d g ki n  l y m p h o m a: the L u ga n o classificati o n. J Cli n 
O nc ol. 2 0 1 4; 3 2( 2 7): 3 0 5 9- 6 7.  
Gree n  et al. 2 0 1 0 
Gre e n M R , M o nti S, R o di g SJ, et al. I nte grati ve a n al ysis re v eals selecti ve 9 p 2 4. 1 a m plificati o n, 
i ncreas e d P D- 1 li ga n d e x pressi o n, a n d f urt h er i n d ucti o n via J A K 2 i n n o d ular scler osi n g H o d g ki n 
l y m p h o ma a n d pri mar y me diasti nal lar ge B-cell l y m p h o ma. Bl o o d. 2 0 1 0( 1 7); 1 1 6: 3 2 6 8- 7 7. 
M aj h ail et al. 2 0 0 6 
Maj hail N S, Weis d orf DJ, Def or T E, et al. L o n g-ter m res ults of a ut ol o g o us ste m cell 
tra ns pla ntati o n f or pri mar y refract or y or rel a pse d H o d g ki n’s l y m p h o ma. Bi ol Bl o o d Marr o w 
Tra ns pla nt. 2 0 0 6; 1 2( 1 0): 1 0 6 5- 7 2. 
M os k o witz et  al. 2 0 0 1 
M os k o witz C H , Ni mer SD , Zele netz AD, et al. A 2 -ste p c o m pre h e nsi ve hi g h- d os e 
c he m ora di ot hera p y sec o n d- li ne pr o gra m f or rel a pse d a n d refract or y H o d g ki n disease: a nal ysis b y 
i nte nt t o treat a n d de vel o p me nt of a pr o g n ostic m o del. Bl o o d. 2 0 0 1; 9 7( 3): 61 6- 2 3. 
M os k o witz et al. 2 0 1 0 
M os k o witz AJ , Ya hal o m J , Ke walra ma ni  T, et al. Pretra ns pla ntati o n f u ncti o nal i ma gi n g pre dicts 
o utc o me f oll o wi n g a ut ol o g o us ste m cell tra ns pla ntati o n f or rela ps e d a n d refract or y H o d g ki n 
l y m p h o ma. Bl o o d. 2 0 1 0; 1 1 6( 2 3): 4 9 3 4- 7. 
M os k o witz  et al. 2 0 1 5 
M os k o witz C H, Na de ma nee A, Masszi  T, et al. Bre nt u xi ma b ve d oti n as c o ns oli dati o n t hera p y 
after a ut ol o g o us ste m- cell tra ns pla ntati o n i n patie nts wit h H o d g ki n's l y m p h o ma at ris k of rel a pse 
or pr o gressi o n ( A E T H E R A): a ra n d o mise d, d o u ble- bli n d, place b o-c o ntr olle d, p hase 3 trial. 
La n cet . 2 0 1 5; 3 8 5( 9 9 8 0): 1 8 5 3- 6 2. 
Ries et al. 1 9 9 7 
Ries L A, K os ar y C L, Ha n ke y B F, et al. ( E ds). S E E R ca ncer statistics re vie w: 1 9 7 3- 1 9 9 4, NI H 
p u bl n o. 9 7- 2 7 8 9, Nati o nal Ca ncer I nstit ute, Bet hes da 1 9 9 7.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 1  of 6 9  
 
R oe mer et al . 2 0 1 6 
R oe mer M, A d va ni R H, Li g o n A H, et al. P D- L 1 a n d P D-L 2 g e netic alterati o ns d efi ne classical 
H o d g ki n l y m p h o ma a n d p re dict o utc o me. J Cli n O nc ol. 2 0 1 6; 3 4( 2 3): 2 6 9 0- 7. 
S h ar pe et al. 2 0 0 7 
S har pe A H, W herr y EJ, A h me d R, et al. T he f u n cti o n of pr o gra m me d cell deat h 1 a n d its li ga n ds 
i n re g ul ati n g a ut oi m m u nit y a n d i nf ecti o n. Nat I m m u n ol . 2 0 0 7; 8( 3): 2 3 9- 4 5. 
Sie gel et al.  2 0 1 6 
Sie gel R L, Miller K D, J e mal A. Ca ncer statistics, 2 0 1 6. C A Ca ncer J Cli n. 2 0 1 6; 6 6( 1): 7- 3 0.  
S ure d a et al. 2 0 0 5 
S ure da A, C o nsta ns M, Iri o n d o A, et al. Pr o g n ostic fact ors affecti n g l o n g -ter m o utc o me after 
ste m cell tra ns pla ntati o n i n H o d g ki n’s l y m p h o ma a ut o grafte d after a first rela pse. A n n O nc ol. 
2 0 0 5; 1 6( 4): 6 2 5- 3 3. 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 2  of 6 9  
 
1 6.  
A P P E N DI C E S  
 
A p pe n di x A: E C O G Perf or m a nce St at us Criteri a  
 
E C O G Perf or m a nce St at us Sc ale  
 
K ar n ofs k y Perf or m a nce Sc ale  
Gr a de  
Descri pti o ns  
Perce nt  
Descri pti o n  
0 
N or mal acti vit y. F ull y acti ve, a ble t o carr y 
o n all pre -disease perf or ma nc e 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 
S y m pt o ms, b ut a m b ulat or y.  R estricte d i n 
p h ysicall y stre n u o us acti vit y, b ut 
a m b ulat or y a n d a ble t o carr y o ut w or k of a 
li g ht or se de ntar y nat ure (e. g., li g ht 
h o use w or k, offi ce 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, 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 
I n be d < 5 0 % of t he ti me.  A m b ulat or y a n d 
ca pa ble of all self -care, 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 his/ her 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 
I n be d > 5 0 % of t he ti me.  Ca p a ble of o nl y  
li mite d self-care, c o nfi ne d t o be d or c hair 
m ore t ha n 5 0 % of wa ki n g h o urs.  
 
4 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 
i n dicate d.  Deat h n o i m mi ne nt. 
4 
1 0 0 % be dri d de n.  C o m pletel y disa ble d.  
Ca n n ot carr y o n a n y self -care.  T otall y 
c o nfi ne d t o be d or c hair.  
 
2 0  
Ver y sic k, h os pitalizati o n i n di cate d.  Deat h 
n ot i m mi ne nt.  
 
1 0  
M ori b u n d, fatal pr ocesses pr o gressi n g 
ra pi dl y. 
5 
Dea d  
0 
Dea d  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 3  of 6 9  
 
 
A p pe n di x B: Ne w Y or k He art Ass oci ati o n ( N Y H A) Cl assific ati o n of C ar di ac Dise ase 
T he f oll o wi n g ta ble prese nts t he N Y H A classificati o n of car diac disease.  
Class  
F u ncti o nal Ca pacit y  
O bj ecti ve Assess me nt  
I 
P atie nts wit h car diac disease b ut wit h o ut res ulti n g li mitati o ns of p h ysical 
acti vit y.  Or d i nar y p h ysical acti vit y d oes n ot ca use u n d ue fati g ue, 
pal pitati o n, d ys p nea, or a n gi nal pai n.  
N o o bj ecti ve e vi de nce of 
car di o vasc ular disease.  
II 
P atie nts wit h car diac disease res ulti n g i n sli g ht li mitati o n of p h ysical 
acti vit y.  T he y are c o mf orta bl e at re st.  Or di nar y p h ysical acti vit y res ults i n 
fati g ue, pal pitati o n, d ys p nea, or a n gi nal pai n. 
O bj ecti ve e vi de nce of 
mi ni mal car di o vasc ular 
disease.  
III 
P atie nts wit h car diac disease res ulti n g i n mar ke d li mitati o n of p h ysical 
acti vit y.  T he y are c o mf orta bl e at rest.  Less t ha n or di nar y a cti vit y ca uses 
fati g ue, pal pitati o n, d ys p nea, or a n gi nal pai n. 
O bj ecti ve e vi de nce of 
m o deratel y se vere 
car di o vasc ular disease.  
I V 
P atie nts wit h car diac disease res ulti n g i n i na bilit y t o carr y o n a n y p h ysical 
acti vit y wit h o ut disc o mf ort.  S y m pt o ms of heart fail ure or t he a n gi nal 
s y n dr o me ma y be prese nt e ve n at rest.  If a n y p h ysical acti vit y is u n derta ke n, 
disc o mf ort is i ncrease d.  
O bj ecti ve e vi de nce of 
se vere car di o vasc ular 
disease.  
S o urce:  T he Criteria C o m mitt ee of Ne w Y or k Heart Ass oci ati o n.  N o me nclat ure a n d Crit eria f or Dia g n osis of 
Diseases of t he Heart a n d Great Vessels.  9t h E d. B ost o n, M A:  Little, Br o w n & C o; 1 9 9 4: 2 5 3 -2 5 6.  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 4  of 6 9  
 
A p pe n di x C: De a u ville 5 - p oi nt sc ori n g s yste m 
T he De a u ville 5 - p oi nt sc ori n g s yste m is a n i nter n ati o nall y acce pt e d a n d utilize d fi ve- p oi nt 
sc ori n g s yste m f or t he fl u or o de o x y gl uc ose ( F D G) a vi dit y of a H o d g ki n's L y m p h o ma or n o n-
H o d g ki n L y m p h o ma t u m or mass as see n o n F D G P E T : 
•  
Sc ore 1: N o u pta ke a b o v e t he bac k gr o u n d 
•  
Sc ore 2:  U pta ke ≤ me di asti n u m  
•  
Sc ore 3: U pta ke > me diasti n u m b ut ≤ li ver  
•  
Sc ore 4: U pta ke m o derat el y i ncreas e d c o m pare d t o t he li ver at a n y site  
•  
Sc ore 5: U pta ke mar ke dl y i ncr eas e d c o m pare d t o t he li ver at a n y site  
•  
Sc ore X: Ne w ar eas of u pta ke u nli kel y t o b e relat e d t o l y m p h o ma 
 
B arri n gt o n et al. 2 0 1 0 
Barri n gt o n S F, Qia n W , S o mer E J, et al. C o nc or da nce b et wee n f o ur E ur o p ea n ce ntres of P E T 
re p orti n g criteria desi g ne d f or use i n m ultice ntre trials i n H o d g ki n l y m p h o ma. E ur J N ucl Me d 
M ol I ma gi n g . 2 0 1 0( 1 0); 3 7: 1 8 2 4 – 3 3. 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 5  of 6 9  
 
A p pe n di x D: G ui deli nes f or Fe m ale P ati e nt s of C hil dbe ari n g  P ote nti al a n d Fertile  M ale 
P ati e nt s 
 
Acce pt a ble C o nt r ace pti o n Met h o ds:  
W o me n of c hil d beari n g p ote ntial, defi ne d as all w o me n p h ysi ol o gicall y ca pa ble of b ec o mi n g 
pre g na nt, m ust use hi g hl y effecti ve c o ntrace pti o n d uri n g t he st u d y a n d f or 7 m o nt hs after 
st o p pi n g treat me nt. 
Hi g hl y effecti ve c o ntrace pti o n is defi ne d as eit her: 
Tr ue A bsti ne nce   
W he n t his is i n li ne wit h t he preferre d a n d us ual lifest yl e of t he s u bject. 
Peri o dic a bsti ne nce (e. g., cale n dar, o v ulati o n, s y m pt ot her mal, p ost-
o v ulati o n met h o ds) a n d wit h dra wal are n ot acce pta ble met h o ds of 
c o ntrace pti o n. 
Steriliz ati o n    
W he n a w o ma n of c hil d b eari n g p ote ntial has h a d s ur gical bilateral 
o o p h orect o m y ( wit h or wit h o ut h yste rect o m y) or t u bal li gati o n at least 
si x wee ks pri or t o st u d y e ntr y.  I n case of o o p h orect o m y al o n e, o nl y 
w he n t he re pr o d ucti ve st at us of t he w o ma n has b ee n c o nfir me d b y 
f oll o w- u p h or m o ne le vel assess me nt. 
M ale P art ner Steriliz ati o n  W he n  t he a p pr o priate p ost- vasect o m y d oc u me ntati o n of t he 
a bse nce of s per m i n t he ejac ulate . 
Use of a c o m bi n ati o n of a n y t w o of t he f oll o wi n g ( o ne fr o m a + o ne fr o m b):  
a)  Place me nt of a n i ntra uteri ne de vice (I U D) or i ntra uteri ne s yste m 
(I U S) or est a blis he d use of oral, i njecte d or i m pla nte d h or m o nal 
met h o ds of c o ntrace pti o n.  
b)  Barrier m et h o ds of c o ntrace pti o n: C o n d o m or Occl usi ve ca p 
( diap hra g m or cer vi cal/ v a ult ca ps) wit h s per mici d al 
f oa m/ gel/fil m/crea m/ va gi nal s u p p osit or y. 
Fertile m ale p atie nts , defi ne d as all males p h ysi ol o gicall y ca pa ble of c o n cei vi n g offs pri n g, 
wit h fe male part ners of c hil d beari n g p ot e ntial m ust use c o n d o ms pl us s per mici dal a ge nt d uri n g 
t he st u d y treat me nt peri o d a n d f or 7 m o nt hs after t he last d ose of st u d y dr u g, a n d s h o ul d n ot 
fat her a c hil d d uri n g t his peri o d. 
Male patie nts m ust als o refrai n fr o m d o nati n g s per m  d uri n g t heir p artici pati o n i n t he st u d y a n d 
f or 7 m o nt hs after t he l ast d ose of st u d y dr u g.  
T he f oll o wi n g are acce pt a ble f or ms of b arrier c o ntr ace pti o n:  
•  Lat e x c o n d o m, dia p hra g m or cer vical/ va ult ca p w he n use d wit h s per mici dal 
f oa m/ gel/fil m/crea m/s u p p osit or y 
U n acce pt a ble C o ntr a ce pti o n Met h o ds:  f or w o m e n of c hil d beari n g p ote ntial i ncl u de: 
•  I U D pr o gest er o ne T 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 6  of 6 9  
 
•  Fe male c o n d o m  
•  Nat ural f a mil y pla n ni n g (r h yt h m met h o d) or breastfee di n g  
•  Fertilit y a ware ness  
•  Wit h dra wal  
•  Cer vical s hiel d  
Pre g n a ncies  
T o e ns ure s u bject safet y, eac h pr e g na n c y i n a s u bj ect o n st u d y treat me nt m ust be re p orte d t o 
t he Sara h Ca n n o n D e vel o p me nt I n n o v ati o ns Safet y De p art me nt wit hi n 2 4 h o urs of lear ni n g of 
its occ urre n ce.  T h e pre g na nc y s h o ul d be f oll o we d u p f or 3 m o nt hs after t h e ter mi nati o n of t he 
pre g na nc y t o d eter mi ne o utc 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 pres e nce or a bse n ce of a n y birt h defects, c o n ge nital a b n or malities, or 
mater nal a n d/ or n e w b or n c o m plicati o ns. 
Pre g n a nc y s h o ul d be rec or de d o n a Cli nical St u d y Pre g n a nc y F or m a n d re p orte d b y t h e 
I n v esti gat or t o S ar a h C a n n o n De vel o p me nt  I n n o v ati o ns S afet y De p art me nt .  Pre g na n c y 
f oll o w- u p s h o ul d be rec or de d o n t he sa me f or m a n d s h o ul d i ncl u de a n assess me nt of t he 
p ossi ble relati o ns hi p t o t he st u d y dr u g  of a n y pre g na n c y o utc o me.  A n y S A E e x perie nce d 
d uri n g pr e g na n c y m ust be re p ort e d o n t he S A E Re p ort F or m. 
Pre g n a nc y o utc o mes m ust be c ollecte d f or t he fe male part ners of a n y m ales w h o t o o k st u d y 
treat me nt i n t his st u d y.  C o nse nt t o re p ort i nf or m ati o n re gar di n g t hes e pre g na n c y o utc o mes 
s h o ul d be o btai ne d fr o m t he m ot her. 
W o me n N ot of C hil d be ari n g P ot e nti al are defi ne d as F oll o ws:  
•  W o me n are c o nsi der e d p ost me n o pa usal a n d n ot of c hil d beari n g p ote ntial if t he y h a ve 
ha d 1 2 m o nt hs of nat ural (s p o nta ne o us) a m e n orr h ea wit h a n a p pr o priate cli nical pr ofile 
(e. g., a ge a p pr o pri ate, hist or y of v as o m ot or s y m pt o ms). 
•  W o me n w h o are per ma n e ntl y sterilize d (e. g., t u bal occl usi o n, h ysterect o m y, bilateral 
sal pi n gect o m y, bilateral o o p h orect o m y) . 
•  W o me n w h o are > 4 5 years  of a ge, n ot usi n g h or m o ne-re pl ace m e nt t hera p y a n d w h o 
ha ve e x perie nce d t otal cessati o n of me nses f or at least 1 2 m o nt hs O R w h o ha ve a 
f ollicle sti m ulati n g h or m o ne ( F S H) v al ue > 4 0 mI U/ m L a n d a n estra di ol val ue 
< 4 0 p g/ m L ( 1 4 0  p m ol/ L) . 
•  W o me n w h o are > 4 5 years  of a ge, usi n g h or m o n e-re place me nt t hera p y a n d w h o ha ve 
e x perie nce d t otal cessati o n of me nses f or at least 1 year O R w h o h a ve ha d d oc u me nte d 
e vi de nce of me n o pa us e b ase d o n F S H > 4 0 mI U/ m L a n d estra di ol < 4 0 p g/ m L  pri or t o 
i nitiati o n of h or m o ne-re place me nt t hera p y. 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 7  of 6 9  
 
A p pe n di x E: Sc he d ule of Assess me nts  f or p atie nts recei vi n g st u d y dr u g 
A S S E S S M E N T S  
B aseli ne a  
 
S T U D Y T R E A T M E N T ( Cycles re pe ate d every 2 wee ks ) 
D a y 1 of e ver y 
c ycle ( ±2 d a ys as 
l o n g as i nter v al 
bet w ee n d oses is 
1 2 -1 6 d a ys ) 
Res p o nse assesse d at 6 
m o nt hs  a n d 1 ye ar p ost -
A S C T  
E n d of Tre at me nt j 
F oll o w -U p k  
Tests a n d O bserv ati o ns  
I nf or me d c o nse nta 
X  
 
 
 
 
Me dical hist or y  
X b 
 
 
 
 
P h ysical e xa m c  
X b 
X  
 
X  
 
Vital Si g ns d 
X b 
X  
 
X  
 
E C O G P S  
X b 
X  
 
X  
 
1 2 -lea d E C G 
X b 
 
 
 
 
A d verse e ve nt e val uati o n  
 
X  
 
X  
X j 
C o nc o mita nt me dicati o n re vie w  
X b 
X  
 
X  
 
St u dy Tre at m e nt  
Ni v ol u ma b  
 
X  
 
 
 
L a b or at ory O bserv ati o ns m  
C B C, 3 -part differe ntial, a n d 
platelets  
X b 
X  
 
X  
 
C M P e 
X b 
X  
 
X  
 
P T/ P T T/I N R f  
X b 
 
 
 
 
Ser u m or Uri ne Pre g na nc y 
T est g 
X b 
 
 
X g 
 
Researc h bl o o d sa m ple h 
 
X ( C 1 D 1 , C 2 D 1, 
a n d C 3 D 1  o nl y)  
 
X  
X  
St a gi n g  
 
 
 
 
 
P E T -C T  sca n 
X b 
 
X i 
 
 
B o ne marr o w bi o ps y l 
X  
 
X  
 
 
S ur vi val  
 
 
 
 
X  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 8  of 6 9  
 
A p pe n di x E: Sc he d ule of Assess me nts (c o nti n ue d)    
 
a 
I nf or me d c o nse nt m ust be o btai ne d ≤2 8 da ys pri or t o t he i nitiati o n of treat me nt. 
b 
T he baseli ne p h ysical e xa mi nati o n, me dical hist or y, E C O G P S, c o m plete bl o o d c o u nts ( C B C) wit h differe ntial a n d platelets, c o m pre he nsi ve meta b olic 
pr ofile ( C M P),  a n d P T/ P T T/I N R s h o ul d be d o ne ≤7  da ys pri or t o i nitiati o n of treat me nt.  H o we ver, if t hese i nitial e xa mi nati o ns are o btai ne d wit hi n 
7 2  h o urs of C ycle 1 Da y 1 t he y d o n ot ha ve t o be re peate d.  A pre g na nc y test m ust be perf or me d wit hi n 7 2 h o urs of C ycle 1 Da y 1.   P E T sca ns s h o ul d 
be perf or me d ≤6 wee ks pri or t o i nitiati o n of treat me nt.  E C G a n d researc h sa m ples s h o ul d be perf or me d ≤2 8 da ys pri or t o i nitiati o n of st u d y treat me nt. 
c 
P h ysical e xa mi nati o n will i ncl u de meas ure me nts of hei g ht ( pretreat me nt visit o nl y), wei g ht, a n d vital si g n s. 
d 
Vital si g ns will i ncl u de resti n g heart rate, bl o o d press ure, res pirat or y rate, a n d te m perat ure.  
e 
C M P will i ncl u de meas ure me nts of gl uc ose, B U N, creati ni ne, s o di u m, p otassi u m, c hl ori de, calci u m, C O 2, A L P , A S T ( S G O T), A L T ( S G P T), t otal 
bilir u bi n, t otal  pr otei n, a n d al b u mi n.  
f 
If P T/ P T T/I N R are n or mal at baseli ne t he y d o n ot nee d t o be re peate d.  P atie nts re q uiri n g t he i nitiati o n of a n a nti-c oa g ul ati o n t hera p y d uri n g st u d y 
treat me nt s h o ul d ha ve c oa g ulati o n tests perf or me d acc or di n g t o sta n dar d practice gui deli nes.  
g 
Ser u m or uri ne pre g na nc y tests are t o be c o n d ucte d i n w o me n of c hil d beari n g p ote ntial.  
h 
A researc h bl o o d sa m ple will be ta ke n at, pre -d ose o n C ycle 1 Da y 1, C ycle 2 Da y 1, C ycle 3 Da y 1 , E O T  (6 m o nt hs),  a n d 1 year after t he first d ose of 
ni v ol u ma b . 
i 
P atie nts s h o ul d ha ve P E T -C T sca ns d o ne per i nstit uti o n sta n dar d of care.  P E T -C T sca ns are re q uire d p ost -A S C T pri or t o i nitiati o n of t hera p y, 6 m o nt hs 
p ost -A S C T , a n d 1 year p ost -A S C T.   P atie nts disc o nti n ui n g t hera p y earl y recei vi n g > 6 c ycl es wit h meas ura ble disease at baseli ne are rec o m me n de d t o 
ha ve a n E O T P E T -C T.  P atie nts  e n di n g treat me nt earl y nee d t o ha ve a P E T -C T sca n  at 1 year  p ost -A S C T  u nless patie nt pr o gresses or starts a ne w 
t hera p y. 
j 
E O T e val uati o ns m ust be c o m plete d wit hi n 3 0 da ys after  t he last d ose of st u d y treat me nt.  P atie nts m ust be f oll o we d f or A Es f or 1 0 0  cale n dar da ys aft er 
t he last d ose of ni v ol u ma b . 
k 
P atie nts will be f oll o we d e ver y m o nt h ( ± 1 wee k ) f or 3 m o nt hs a n d t he n e ver y 3 m o nt hs t hereafter fr o m t he date of last d ose of niv ol u ma b f or u p t o 
2 years.  A p h o ne call ma y be use d t o assess s ur vi val  a n d t o rec or d i nitiati o n of a n alter nati ve f or m of treat me nt f or l y m p h o ma after res p o nse assess me nt 
at 1 year p ost-A S C T . 
 l 
B o ne marr o w bi o ps y is re q ueste d at baseli ne  o nl y i n patie nts  wit h pri or b o ne marr o w i n v ol ve me nt .  At s u bse q ue nt sta gi n g visits, patie nts wit h pri or 
b o ne marr o w i n v ol ve me nt, if i n C R, s h o ul d als o ha ve b o ne marr o w bi o ps y perf or me d  t o d oc u me nt res p o nse . 
m 
La b orat or y sa m ples fr o m c o ntr ol patie nts will be c ollecte d as d escri be d i n Secti o n 5. 4. 2 . 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 5 9  of 6 9  
 
A p pe n di x F: Rec o m me n d ati o ns f or I niti al E v al u ati o n, St a gi n g, a n d Res p o nse Assess me nt of H o d g ki n a n d N o n - H o d g ki n 
L y m p h o m a: T he L u g a n o Cl assific ati o n  
T hese criteria are bas e d u p o n t he criteria fr o m t he Rec o m me n dati o ns f or I nitial E val uati o n, Sta gi n g, a n d Res p o nse Assess me nt of 
H o d g ki n a n d N o n- H o d g ki n  L y m p h o ma: T he L u ga n o Classificati o n (C hes o n et al. 2 0 1 4 ) 
Re vise d Criteria f or Res p o nse Assess me nt  
Res p o nse a n d Site  
P E T -C T – B ase d Res p o nse  
C T -B ase d Res p o nse  
C o m plete  
L y m p h n o des a n d 
e xtral y m p hatic sites  
C o m plete meta b olic res p o nse  
Sc ore 1, 2, or 3 * wit h or wit h o ut a resi d ual mass o n 5 P S †  
It is rec o g nize d t hat i n W al de yer’s ri n g or e xtra n o dal sites wit h hi g h p h ysi ol o gic 
u pta ke or wit h acti vati o n wit hi n s plee n or marr o w (e . g., wit h c he m ot hera p y or 
m yel oi d c ol o n y -sti m ulati n g fa ct ors), u pta ke ma y be greater t ha n n or mal 
me diasti n u m a n d/ or li ver. I n t his circ u msta nce, c o m plete meta b olic res p o nse 
ma y be i nfe rre d if u pta ke at sit es of i nitial i n v ol ve me nt is n o greater t ha n 
s urr o u n di n g n or mal tiss ue e ve n if t he tiss ue has hi g h p h ysi ol o gic 
C o m plete ra di ol o gic res p o nse (all of t he f oll o wi n g)  
T ar get n o des/ n o dal masses m ust re gress t o ≤1. 5 c m i n 
L Di  
N o e xtral y m p hat ic sites of dis ease 
N o n meas ure d lesi o n  
Or ga n e nlar ge me nt  
Ne w lesi o ns  
B o ne marr o w  
N ot a p plica ble  
N ot a p plica ble  
N o ne  
N o e vi de nce of F D G -a vi d dise ase i n marr o w 
A bse nt  
Re gress t o n or mal  
N o ne  
N or mal b y m or p h ol o g y; if i n deter mi nate, I H C ne gati ve  
P artial  
L y m p h  n o des a n d 
e xtral y m p hatic sites  
P artial me tab olic res p o nse 
Sc ore 4 or 5 † wit h re d uce d u pta ke c o m pare d wit h baseli ne a n d resi d ual 
mass(es) of a n y size  
At i nteri m, t hese fi n di n gs s u g gest res p o n di n g disease  
At e n d of treat me nt, t hese fi n di n gs i n dicate resi d ua l disease 
P artial re missi o n (all of t he f oll o wi n g)  
≥5 0 %  decrease i n S P D of u p t o 6 tar get meas ura ble 
n o des a n d e xtra n o dal sites  
W he n a lesi o n is t o o s mall t o meas ure o n C T, assi g n 
5 m m × 5 m m as t he defa ult val ue  
W he n n o l o n ger visi ble, 0 x 0 m m  
F or a n o de  > 5 m m × 5 m m, b ut s maller t ha n n or mal, 
use act ual meas ure me nt f or calc ulati o n  
N o n meas ure d lesi o ns  
Or ga n e nlar ge me nt  
N ot a p plica ble  
N ot a p plica ble  
A bse nt/ n or mal, re gresse d, b ut n o i ncrease  
S plee n m ust ha ve re gresse d b y > 5 0 % i n le n gt h be y o n d 
n or mal  
Ne w le si o ns 
B o ne marr o w  
N o ne  
Resi d ual u pta ke hi g her t ha n u pta ke i n n or mal marr o w b ut re d uce d c o m pare d 
wit h baseli ne ( diff use u pta ke c o m pati ble wit h reacti ve c ha n ges fr o m 
c he m ot hera p y all o we d).  If t here are persiste nt f ocal c ha n ges i n t he marr o w i n 
t he c o nte xt of a n o dal res p o nse, c o nsi derati o n s h o ul d be gi ve n t o f urt her 
e val uati o n wit h M RI or bi o ps y or a n i nter val sca n  
N o ne  
N ot a p plica ble  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 0  of 6 9  
 
Re vise d Criteria f or Res p o nse Assess me nt  
Res p o nse a n d Site  
P E T -C T – B ase d Res p o nse  
C T -B ase d Res p o nse  
N o res p o nse or sta ble 
disease  
T ar get n o des/ n o dal 
masses, e xtra n o dal 
lesi o ns 
N o meta b olic res p o nse  
Sc ore 4 or 5 wit h n o si g ni fica nt c ha n ge i n F D G u pta ke fr o m baseli ne at i nteri m 
or e n d of treat me nt  
Sta ble disease  
˂  5 0 % decrease fr o m baseli ne i n S P D of u p t o 6 
d o mi na nt, meas ura ble n o des a n d e xtra n o dal sites; n o 
criteria f or pr o gressi ve disease are met  
N o n meas ure d lesi o ns  
Or ga n e nlar ge me nt  
Ne w lesi o ns  
B o ne marr o w  
N ot a p plica ble  
N ot a p plica ble  
N o ne  
N o c ha n ge fr o m bas eli ne  
N o i ncrease c o nsiste nt wit h pr o gressi o n  
N o i ncrease c o nsiste nt wit h pr o gressi o n  
N o ne  
N ot a p plica ble  
Pr o gressi ve disease  
I n di vi d ual tar get 
n o des/ n o dal masses  
E xtra n o dal lesi o ns  
Pr o gressi ve meta b olic disease  
Sc ore 4 or 5 wit h a n i ncrease i n i nte nsit y of u pta ke fr o m bas eli ne a n d/ or  
Ne w F D G -a vi d f oci c o nsiste nt wit h l y m p h o ma at i nteri m or e n d -of -treat me nt 
assess me nt  
Pr o gressi ve disease re q uires at least o ne  of t he 
f oll o wi n g: 
P P D pr o gressi o n:  
 
A n i n di vi d ual n o de/lesi o n m ust be a b n or mal wit h:  
L Di > 1. 5 c m a n d  
I ncrease b y ≥5 0 % fr o m P P D na dir a n d  
A n i ncrease i n L Di or S Di fr o m na dir  
0. 5 c m f or lesi o ns ≤2 c m  
1. 0 c m f or lesi o ns > 2 c m  
I n t he setti n g of s ple n o me gal y, t he s ple nic le n gt h m ust 
i ncrease b y > 5 0 % of t he e xte nt of its pri or i ncrease 
be y o n d baseli ne (e . g., a 1 5-c m s plee n m ust i ncrease t o 
> 1 6 c m). If n o pri or s ple n o me gal y, m ust i ncrease b y at 
least 2 c m fr o m baseli ne 
Ne w or rec urre nt s ple n o me gal y  
N o n meas ure d lesi o ns  
N o ne  
Ne w or clear pr o gressi o n of pr e -e xisti n g n o n meas ure d 
lesi o ns 
Ne w lesi o ns  
Ne w F D G -avi d f oci c o nsiste nt wit h l y m p h o ma rat her t ha n a n ot her eti ol o g y 
(e. g., i nfecti o n, i nfla m mati o n).  If u ncertai n re gar di n g eti ol o g y of ne w lesi o ns, 
bi o ps y or i nter val sca n ma y be c o nsi dere d  
Re gr o wt h of pre vi o usl y res ol ve d lesi o ns A ne w n o de 
> 1. 5 c m i n a n y a xi s 
A ne w e xtra n o dal site ˂ 1. 0 c m i n a n y a xis; if > 1. 0 c m 
i n a n y a xis, its prese nce m ust be u ne q ui v ocal a n d m ust 
be attri b uta ble t o l y m p h o ma  
Assessa ble disease of a n y size u ne q ui v ocall y 
attri b uta ble t o l y m p h o ma  
B o ne marr o w  
Ne w or rec urre nt F D G -a vi d f oci 
Ne w  or rec urre nt i n v ol ve me nt  

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 1  of 6 9  
 
A b bre viati o ns: 5 P S, 5 -p oi nt sc ale; C T, c o m p ute d t o m o gra p h y; F D G, fl u or o de o x y gl uc ose; I H C, i m m u n o hist oc he mistr y; L Di, l o n gest tra ns verse dia met er of  a 
lesi o n; M RI, ma g netic res o na nce i ma gi n g; P E T, p ositr o n e missi o n t o m o gra p h y; P P D, cr oss pr o d uct of t he L Di a n d per pe n dic ular dia meter; S Di, s h ortest a xis 
per pe n dic ular  t o t he L Di; S P D, s u m of t he pr o d uct of t he per pe n dic ular dia meters f or m ulti ple lesi o ns. 
* A sc ore of 3 i n ma n y patie nts i n dicates a g o o d pr o g n osis wit h sta n dar d treat me nt, es peciall y if at t he ti me of a n i nteri m s ca n.   H o we ver, i n trials i n v ol vi n g P E T 
w here de -escalati o n is i n vesti gate d, it ma y be prefera ble t o c o nsi der a sc ore of 3 as i na de q uate res p o nse (t o a v oi d u n dertreat me nt).   Meas ure d d o mi na nt lesi o ns: 
U p t o si x o f t he lar gest d o mi na nt n o des, n o dal masses, a n d e xtra n o dal lesi o ns selecte d t o be clearl y meas ura ble i n t w o di a meters.  N o des s h o ul d prefera bl y be 
fr o m dis parate re gi o ns of t he b o d y a n d s h o ul d i ncl u de, w here a p plica ble, me diasti nal a n d retr o perit o neal areas.  N o n -n o dal lesi o ns i ncl u de t h ose i n s oli d or ga ns 
(e. g., li ver, s plee n, ki d ne ys, l u n gs), GI i n v ol ve me nt, c uta ne o us lesi o ns, or t h ose n ote d o n pal pati o n.  N o n meas ure d lesi o ns: A n y disease n ot selecte d as meas ure d, 
d o mi na nt disease a n d tr ul y ass essa ble disease s h o ul d be c o nsi dere d n ot meas ure d.  T hese sites i ncl u de a n y n o des, n o dal masses, a n d e xtra n o dal sites n ot selecte d 
as d o mi na nt or meas ura ble or t hat d o n ot meet t he re q uire me nts f or meas ura bilit y b ut are still c o nsi dere d a b n or mal, as well a s tr ul y assessa ble disease, w hic h is 
a n y site of s us pecte d disease t hat w o ul d be diffic ult t o f oll o w q ua ntitati vel y wit h meas ure me nt, i ncl u di n g ple ural eff usi o ns,  ascites, b o ne lesi o ns, le pt o me ni n geal 
disease, a b d o mi nal masses, a n d ot her lesi o ns t hat ca n n ot be c o nfir me d a n d f oll o we d b y i ma gi n g.   I n W al de yer’s ri n g or i n e xtra n o dal sites (e. g., GI tract, li ver, 
b o ne marr o w), F D G u pta ke ma y be greater t ha n i n t he me diasti n u m wit h c o m plete meta b olic res p o nse, b ut s h o ul d be n o hi g her t ha n s urr o u n di n g n or mal 
p h ysi ol o gic u p ta ke (e. g., wit h marr o w acti vati o n as a res ult of c he m ot hera p y or m yel oi d gr o wt h fact ors). 
† P E T 5 P S: 1, n o u pta ke a b o ve bac k gr o u n d; 2, u pta ke ≤ me di asti n u m; 3, u pta ke > me diasti n u m b ut ≤ li ver; 4, u pta ke m o deratel y >  li ver; 5, u pta ke mar ke dl y 
hi g her t ha n l i ver a n d/ or ne w l esi o ns; X, ne w areas of u pta ke u nli kel y t o be relate d t o l y m p h o ma. 
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 2  of 6 9  
 
A p pe n di x G:  M a n a ge me nt Al g orit h ms f or I m m u n o- O nc ol o g y A ge nts 
T hese ge n eral g ui deli nes c o nstit ute g ui da nce t o t he I n vesti gat or a n d m a y b e s up ple me nte d b y 
disc ussi o ns wit h t he Me dical M o nit or re prese nti n g t he S p o ns or.  T he g ui da nce a p plies t o all 
i m m u n o- o nc ol o g y a ge nts a n d re gi me ns. 
A ge ner al pri nci ple is t hat differe ntial dia g n os es s h o ul d be dili ge ntl y e val u ate d acc or di n g t o 
sta n dar d me dical practice.  N o n -i nfla m mat or y eti ol o gies s h o ul d be c o nsi dere d a n d a p pr o priatel y 
treate d. 
C ortic oster oi ds are a pri mar y t h era p y f or i m m u n o - o nc ol o g y dr u g-relate d A Es .  T he oral 
e q ui vale nt of t he r ec o m me n de d I V d oses m a y be c o nsi dere d f or a m b ulat or y p atie nts wit h l o w-
gr a de t o xicit y.  T he l o w er bi oa vaila bilit y of oral c ortic oster oi ds s h o ul d be ta ke n i nt o acc o u nt 
w he n  s witc hi n g t o t he e q ui vale nt d ose of oral c ortic oster oi ds. 
C o ns ultati o n wit h a me dical or s ur gical s pecialist, es peciall y pri or t o a n i n v asi ve  dia g n ostic or 
t hera pe utic pr oce d ure, is rec o m me n de d. 
T he fre q u e nc y a n d se verit y of t he relate d A Es  c o v ere d b y t hes e  al g orit h ms will de pe n d o n t he 
i m m u n o- o nc ol o g y a ge nt or re gi me n bei n g use d.

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 3  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 4  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 5  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 6  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 7  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 8  of 6 9  
 

 
C O N FI D E N TI A L  
S T U D Y D R U G :  NI V O L U M A B  
    
 
S A R A H C A N N O N D E V E L O P M E N T I N N O V A TI O N S  S T U D Y N U M B E R :   
  
 
B M T  2 4  
FI N A L P R O T O C O L D A T E :  0 7  F E B  2 0 2 0   
  
  
VE R SI O N 7 
P a ge 6 9  of 6 9