A Phase 2/3, Randomised, Multicentre Study of Tafasitamab With Bendamustine Versus Rituximab With Bendamustine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT)
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Sponsor: Incyte Corporation

Offi ci al   Titl e:  
A  P h as e II/III,   R a n d o  mis e d,   M ulti c e ntr e  St u d y  of   M  O  R 0 0 2 0 8   wit h   B e n d a  m usti n e 
v ers us   Rit u xi  m a b   wit h   B e n d a  m usti n e i n  P ati e nts   wit h   R el a ps e d  or   R efr a ct or y 
Diff us e  L ar g e   B -C ell  L y  m p h o  m a (  R -R   D L  B  C L)   W h o   Ar e   N ot  Eli gi bl e f or   Hi g h -
D os e   C h e  m ot h er a p y (  H  D  C)  a n d   A ut ol o g o us  St e  m -C ell  Tr a ns pl a nt ati o n (  A S  C T) –  
[  B-MI  N  D]  
N  C  T   N u  m b e r:  
N  C T 0 2 7 6 3 3 1 9  
D o c u  m e nt   D at e:  
M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  C T P   A  m e n d  m e nt   N o.  8  1 0 -A pr -2 0 2 4  
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 of  1 3 1  
 
 
 
 
C  LI  NI  C  A  L  T  RI  A  L P  R  O  T  O  C  O  L  
A P h as e II/III,   Ra n d o  mis e d, M ulti c e nt r e   St u d y  of   M  O  R 0 0 2 0 8   wit h 
B e n d a  m usti n e  v e rs us   Rit u xi  m a b   wit h   B e n d a  m usti n e i n P ati e nts   wit h 
R el a ps e d  o r   R ef r a ct o r y   Diff us e   L a r g e   B -C ell   L y  m p h o  m a (  R -  R D  L  B  C  L) W h o 
A r e N ot E li gi bl e f o r H i g h-  Dos e C h e  m ot h e r a p y (  H  D  C) a n d A ut ol o g o us 
S t e  m-  Cell T r a ns pl a nt ati o n (  A S  C  T)   – [  B-MI  N  D ] 
 
 
B ri ef   D es c ri pti o n  of 
St u d y : 
O p e n -l a b el, r a n d o  mis e d tri al t o e v al u at e t h e effi c a c y  a n d s af et y 
of   M  O  R 0 0 2 0 8 wit h b e n d a  m usti n e (  B E  N)  v ers us rit u xi  m a b 
(  R T  X) wit h B E  N i n  a d ult  p ati e nts   wit h R-  R D L  B  C L  
P h as e  of   D e v el o p  m e nt : 
P h as e II/III 
S p o ns o r:  
I n c yt e   C or p or ati o n 
S p o ns o r's   A d d r ess:  
1 8 0 1   A u g usti n e   C ut -Off  
Wil  mi n gt o n,   D E  1 9 8 0 3   U S  A  
St u d y  P r ot o c ol   N u  m b e r:  
M  O  R 2 0 8  C 2 0 4  
I  N  D   N o.: 
1 1 4, 8 5 6  
E u d r a  C  T   N o.:  
2 0 1 4 -0 0 4 6 8 9 -1 1  
D at e  of  P r ot o c ol:  
1 0 -A pr -2 0 2 4  (  V ersi o n 1 1 . 0) 
 
C o nfi d e nti alit y  St at e  m e nt  
T h e  c o n c e pts  a n d i nf or  m ati o n  c o nt ai n e d i n t his  d o c u  m e nt  ar e  c o nsi d er e d  pr o pri et ar y  a n d 
ar e  pr o vi d e d f or t h e e x cl usi v e  us e  of i n v esti g at ors  a n d  ot h er  p ers o ns i n v ol v e d i n t h e st u d y 
w h o  h a v e  a  n e e d t o  k n o  w.  S u bj e ct t o t h e f or e g oi n g, t h e  c o nt e nt  of t his  d o c u  m e nt   m a y  n ot  b e 
dis cl os e d  u nl ess l a  w  or r e g ul ati o ns r e q uir e s u c h  dis cl os ur e,  or I n c yt e   C or p or ati o n  h as  gr a nt e d 
pri or   writt e n  a p pr o v al. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2  of 1 3 1  
I  N  V  E S  TI  G  A  T  O  R' S   A  G  R  E  E  M  E  N  T 
I  h a v e r e a d t h e   M  O  R 2 0 8C 2 0 4  Pr ot o c ol   A  m e n d  m e nt 8  ( d at e d 1 0 -A pr -2 0 2 4 )  a n d  a gr e e t o  c o n d u ct 
t h e st u d y  as  o utli n e d. I  a gr e e t o   m ai nt ai n t h e  c o nfi d e nti alit y  of  all i nf or  m ati o n r e c ei v e d  or 
d e v el o p e d i n  c o n n e cti o n  wit h t his  Pr ot o c ol.  
 
 
 
 
 
( Pri nt e d   N a  m e  of I n v esti g at or) 
 
 
 
 
 
 
 
 
( Si g n at ur e  of I n v esti g at or) 
 
(  D at e) 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 3  of 1 3 1  
P  R  O  T  O  C  O  L   HI S  T  O  R  Y  
V e rsi o n  
D at e  
A  m e n d e d  Pr ot o c ol   C T P  v 1 1. 0  
1 0 -A pr -2 0 2 4  
A  m e n d e d  Pr ot o c ol   C T P  v 1 0. 0  
0 2 -D e c -2 0 2 2  
A  m e n d e d  Pr ot o c ol   C T P  v 9. 0  
2 2 -D e c -2 0 2 1  
A  m e n d e d  Pr ot o c ol   C T P  v 8. 0  
1 4 -F e b -2 0 1 9  
A  m e n d e d  Pr ot o c ol   C T P  v 7. 0  
2 3 -A u g -2 0 1 7  
A  m e n d e d  Pr ot o c ol   C T P  v 6. 0  
2 1 -J ul-2 0 1 7  
A  m e n d e d  Pr ot o c ol   C T P  v 5. 0  
0 5 -A pr -2 0 1 7  
A  m e n d e d  Pr ot o c ol   C T P  v 4. 0  
2 1 -N o v -2 0 1 6  
A  m e n d e d  Pr ot o c ol   C T P  v 3. 0  
0 4 -M ar -2 0 1 6  
A  m e n d e d  Pr ot o c ol   C T P  v 2. 0  
1 8 -D e c -2 0 1 5  
Ori gi n al  Pr ot o c ol   C T P  v 1. 0  
2 5 -N o v -2 0 1 5  
 
A  m e n d e d P r ot o c ol C  T P v 1 1 . 0 (1 0 -A p r -2 0 2 4 ) 
 
O v e r all   R ati o n al e f o r t h e   A  m e n d  m e nt:  
T h e  pri  m ar y  p ur p os e  of t h e a  m e n d  m e nt is t o  u p d at e t h e s p o ns ors hi p fr o  m   M or p h o S ys   A  G t o 
I n c yt e   C or p or ati o n.   
1.  Titl e  P a g e; I n v esti g at o r's   A g r e e  m e nt;  S e cti o n  1,  P r ot o c ol  S y n o psis;  S e cti o n  5,  St u d y 
P u r p os e/  R ati o n al e;  S e cti o n  8. 4,   E n d  of  St u d y;  S e cti o n  1 1. 2,   A d v e rs e   E v e nt  a n d 
S e ri o us   A d v e rs e   E v e nt   R e c o r di n g  a n d   R e p o rti n g;  S e cti o n  1 1. 3,  P r e g n a n ci es; 
S e cti o n  1 3,  St atisti c al   M et h o ds  a n d  Pl a n n e d   A n al ys es ;  S e cti o n  1 4. 4,   R e g ul at o r y  a n d 
Et hi c al   C o nsi d e r ati o ns, I n cl u di n g t h e I nf o r  m e d   C o ns e nt  P r o c ess;  S e cti o n  1 4. 5, 
Q u alit y   C o nt r ol ( St u d y   M o nit o ri n g) ; S e cti o n  1 4. 8,  P u bli c ati o n  P oli c y;  S e cti o n  1 6. 3, 
A p p e n di x   C: O v e r vi e  w  of  p u blis h e d  d at a  o n   N  K  C  C  as  a  p r o g n osti c f a ct o r i n 
D  L  B  C  L  a n d  F  L  
D es c ri pti o n  of  c h a n g e : U p d at e d t h e s p o ns ors hi p fr o  m   M or p h o S ys   A  G t o I n c yt e 
C or p or ati o n . 
R ati o n al e f o r ch a n g e : C h a n g e i n s p o ns ors hi p . 
2.  I n c o r p o r ati o n  of  a d  mi nist r ati v e  c h a n g es. Ot h er  a d  mi nistr ati v e  c h a n g es  h a v e  b e e n 
i n c or p or at e d t hr o u g h o ut t h e  Pr ot o c ol  a n d  ar e  n ot e d i n t h e r e dli n e  v ersi o n  of t h e 
a  m e n d  m e nt. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4  of 1 3 1  
1  P  R  O  T  O  C  O  L S  Y  N  O P SI S  
Titl e  of  St u d y  
A  P h as e II/III,   R a n d o  mis e d,   M ulti c e ntr e  St u d y  of M  O  R 0 0 2 0 8   wit h 
B e n d a  m usti n e  v ers us Rit u xi  m a b   wit h B e n d a  m usti n e i n  P ati e nts   wit h 
R el a ps e d  or   R efr a ct or y   Diff us e  L ar g e   B -C ell  L y  m p h o  m a (  R -R   D L  B  C L) 
W h o   Ar e   N ot  Eli gi bl e f or   Hi g h -D os e   C h e  m ot h er a p y (  H  D  C)  a n d 
A ut ol o g o us  St e  m -C el l  Tr a ns pl a nt ati o n (  A S  C T) –  [B -MI  N  D ] 
P r ot o c ol   N u  m b e r  
M O  R 2 0 8  C 2 0 4  
I  N  D   N u  m b e r 
1 1 4, 8 5 6  
E u d r a  C  T   N u  m b e r  
2 0 1 4 -0 0 4 6 8 9 -1 1  
S p o ns o r  
I n c yt e   C or p or ati o n 
1 8 0 1   A u g usti n e   C ut -Off  
Wil  mi n gt o n,   D E U S  A  1 9 8 0 3  
St u d y  P h as e  
P h as e II/III 
B a c k g r o u n d a n d  St u d y 
R ati o n al e  
D es pit e  a d v a n c es i n t h e first-li n e tr e at  m e nt  of  diff us e l ar g e   B-c ell 
l y  m p h o  m a (  D L  B  C L),  3 0– 4 0  %  of p ati e nts eit h er r el a ps e  or  h a v e r efr a ct or y 
dis e as e.   A p pr o xi  m at el y  5 0  %  of p ati e nts   wit h r el a ps e d or r efr a ct or y (  R-R) 
D L B C L  d o  n ot  a c hi e v e  a l o n g -t er  m r e  missi o n   wit h s u bs e q u e nt t h er a p y  as 
t h e y  eit h er r el a ps e  aft er i nt e nsifi e d  c h e  m ot h er a p e uti c tr e at  m e nt, i n cl u di n g 
hi g h -d os e  c h e  m ot h er a p y (  H  D  C)  a n d  a ut o l o g o us st e  m-c ell tr a ns pl a nt ati o n 
(  A S  C T), or  ar e  n ot  eli gi bl e f or a n i nt e nsifi e d tr e at  m e nt r e gi  m e n. P a ti e nts 
wit h R -R  D L  B  C L  f aili n g i nt e nsifi e d s e c o n d-li n e t h er a p y, or t h os e   w h o  ar e 
i n eli gi bl e f or s u c h t h er a p y, c o nstit ut e  a n  u n  m et   m e di c al  n e e d  as t h e   m e di a n 
o v er all s ur vi v al (  O S) f or t his  p o p ul ati o n is l ess t h a n  o n e  y e ar   wit h  c urr e ntl y 
a v ail a bl e t h er a pi es. 
 
M  O  R 0 0 2 0 8 is  a n  F c -e n h a n c e d ,  h u  m a nis e d,   m o n o cl o n al  a nti b o d y (  m  A b) 
wit h si g nifi c a ntl y  e n h a n c e d  a nti b o d y -d e p e n d e nt  c ell -m e di at e d  c yt ot o xi cit y 
(  A  D  C  C),  a nti b o d y-d e p e n d e nt  c ell -m e di at e d  p h a g o c yt osis (  A  D  C P)  a n d 
dir e ct  c yt ot o xi c  eff e cts ( a p o pt osis)  c o  m p ar e d   wit h its  n o n-e n h a n c e d  
p ar e nt al  a nti b o d y . R es ults  of i n  vitr o  e x p eri  m e nts s u g g est t h at M  O  R 0 0 2 0 8 
l e a ds t o str o n g er   A  D  C  C-m e di at e d t ar g et  c ell l ysis i n  c o  m p aris o n t o 
Rit u xi  m a b (  R T  X)  u n d er  c o n diti o ns i n   w hi c h  n at ur al  kill er (  N  K)  c ells  ar e 
li  mit e d.   B ase d  o n t h e  ass u  m pti o n t h at i n  p ati e nts   wit h l o  w  b as eli n e  n at ur al 
c ell  c o u nt (  N  K  C  C),   N  K  c ell  n u  m b ers  at t h e t u  m o ur sit e   will  n ot  o ut-
n u  m b er t h e  n u  m b er  of t u  m o ur c ells, t h e i n  vitr o  d at a s u p p ort t h e  h y p ot h esis 
t h at   M  O  R 0 0 2 0 8  c o ul d  h a v e  hi g h er t u  m o ur killi n g  c a p a cit y  c o  m p ar e d t o 
rit u xi  m a b i n  p ati e nts   wit h  a  p eri p h er al   N  K  c ell  c o u nt  of  1 0 0 or l ess   N  K 
c ells/ µ L.  M  O  R 0 0 2 0 8  h as s h o  w n  pr eli  mi n ar y  effi c a c y  a n d  a c c e pt a bl e 
t o xi cit y i n p ati e nts   wit h R -R   D L  B  C L, f olli c ul ar l y  m p h o  m a a n d  ot h er 
i n d ol e nt  n o n-H o d g ki n  l y  m p h o  m as (  NH L s).   M  O  R 0 0 2 0 8 is  e x p e ct e d t o 
si g nifi c a ntl y i n cr e as e t h e  cli ni c al  effi c a c y  of  est a blis h e d  c h e  m ot h er a p e uti c 
r e gi  m e ns f or   R-R   D L  B  C L s u c h  as b e n d a  m usti n e ( B E  N ). 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 5 of  1 3 1  
M  O  R 0 0 2 0 8  or taf asit a  m a b 1 (tr a d e  n a  m e   M o nj u vi)  h as  b e e n  a ut h ori z e d f or 
m ar k eti n g i n t h e   U S u n d er t h e  pr o visi o n  of  a c c el er at e d  a p pr o v al  o n 
3 1 -J ul-2 0 2 0  a n d  u n d er t h e tr a d e  n a  m e   Mi nj u vi i n   C a n a d a  ( 1 9-A u g -2 0 2 1) , 
E  U ( 2 6-A u g -2 0 2 1)  a n d   U  K ( 0 8-O ct -2 0 2 1) as  c o n diti o n al  a p pr o v als i n  2 0 2 1 
i n  p ati e nts   wit h   R/  R   D L  B  C L. 
 
T his is  a r a n d o  mi se d, o p e n -l a b el cli ni c al tri al t o  c o  m p ar e t h e s af et y  a n d 
effi c a c y  of   M  O  R 0 0 2 0 8  wit h B E  N v ers us rit u xi  m a b (R T  X) wit h B E  N , a n 
a c c e pt e d st a n d ar d  of  c ar e f or t his  p ati e nt  p o p ul ati o n.  
St u d y   O bj e cti v es  
P RI  M  A  R  Y   O  B J  E  C  TI  V  E : 
T o  d et er  mi n e t h e effi c a c y  of  a  c o  m bi n ati o n  of   M  O  R 0 0 2 0 8  wit h   B E  N  
v ers us  a  c o  m bi n ati o n  of R T  X  wit h B E  N i n t er  ms  of  pr o gr essi o n-fr e e 
s ur vi v al ( P F S) i n:  
•  
A d ult  p ati e nts   wit h   R -R   D L  B  C L  ( o v er all  p o p ul ati o n)  
•  
A s u b gr o u p  of  a d ult  p ati e nts   wit h   R -R   D L  B  C L wit h l o  w  b as eli n e 
p eri p h er al  bl o o d   N  K -c ell  c o u nt (  NK  C  C -l o  w),  d efi n e d  as 1 0 0  or 
l ess   N  K  c ells  p er  µl  bl o o d at  b as eli n e.  
 
S  E  C  O  N  D  A  R  Y   O  B J  E  C  TI  V  E S:  
1.  T o  d et er  mi n e  a n d  c o  m p ar e  b ot h st u d y  ar  ms , M  O  R 0 0 2 0 8  wit h    B E  N 
v ers us   R T  X wit h    B E  N, f or t h e  o v er all  p o p ul ati o n a n d N  K  C  C -l o  w 
s u b gr o u p i n t er  ms  of: 
a) b est o bj e cti v e res p o ns e rat e (  O  R  R  =  c o  m pl et e r es p o ns e [  C  R]  + 
p arti al r es p o ns e [ P  R])  b as e d  o n t h e b est r es p o ns e  a c hi e v e d  at  a n y 
ti  m e  d uri n g t h e st u d y  
b)  d ur ati o n  of res p o ns e (  D o  R)  
c) o v er all sur vi v al (  O S)  
d)  dis e as e  c o ntr ol r at e (  D  C  R  =   C  R  +  P  R  + st a bl e  dis e as e [ S  D])  
e) ti  m e to p r o gr essi o n ( T T P) 
f) ti  m e to n e xt tr e at  m e nt ( T T  N T) 
g)  saf et y , b as e d  o n t h e fr e q u e n c y, i n ci d e n c e a n d s e v erit y  of  a d v ers e 
e v en ts (  A Es) 
h)  q u alit y  of lif e (  Q o L), usi n g  t h e E  O  R T  C   Q L  Q -  C 3 0 a n d  E  Q -5  D -5 L  
q u esti o n n air e s 
2.  T o  ass ess t h e p ot e nti al i  m  m u n o g e ni cit y  of   M  O  R 0 0 2 0 8  
( anti -M  O  R 0 0 2 0 8  a nti b o d y f or  m ati o n)   
3.  T o  ass ess t h e  p h ar  m a c o ki n eti c ( P  K)  pr ofil e  of   M  O  R 0 0 2 0 8 . 
 
E  X P  L  O  R  A  T  O  R  Y   O  B J  E  C  TI  V  E S:  
 
 
 
1 T af asit a  m a b is t h e r e c o  m  m e n d e d I  N  N  a n d   U S  A  N f or   M  O  R 0 0 2 0 8. T af asit a  m a b is  als o  k n o  w n  u n d er t h e  n a  m es 
X  m  A b  ® 5 5 7 4,   M  O  R 2 0 8 , M  O  R 0 0 2 0 8 ,   M o nj u vi  a n d   Mi nj u vi. M  O  R 0 0 2 0 8   w as  n ot r e pl a c e d  i n t his  d o c u  m e nt  as t his is 
a n o n g oi n g tri al. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 6 of  1 3 1  
St u d y   E n d p oi nts  
C  O -P RI  M  A  R  Y  E  N  D P  OI  N  T S : 
1.  P F S  i n t h e o v er all st u d y  p o p ul ati o n ( F  A S) 
2.  P F S i n t h e N  K  C  C -l o  w s u b gr o u p 
 
S  E  C  O  N  D  A  R  Y  E  N  D P  OI  N  T S:  
3.  B est   O  R  R,  D o  R,   O S , D  C  R,  T T P  a n d  T T  N T  
4.  Fr e q u e n c y, i n ci d e n c e  a n d s e v erit y of   A Es  
5.  Q o L  
6.  A nti -M  O  R 0 0 2 0 8  a nti b o d y f or  m ati o n  
7.  P  K  of   M  O  R 0 0 2 0 8  
8.  
 
T h e s e c o n d ar y  e n d p oi nts   will  b e a n al ys e d  i n t h e o v er all  p o p ul ati o n ( F  A S)  
a n d N  K  C  C -lo  w  s u b gr o u p. 
D esi g n  a n d 
M et h o d ol o g y/ P ati e nt 
P o p ul ati o n  
T his is  a r a n d o  mis e d, t  w o -ar  m,   m ulti c e ntr e,  o p e n -l a b el  p h as e II/III effi c a c y 
a n d s af et y st u d y  of M  O  R 0 0 2 0 8 i n  c o  m bi n ati o n   wit h B E  N v ers us   R T  X i n 
c o  m bi n ati o n   wit h B E  N gi v e n t o  a d ult  p ati e nts   w h o  h a v e r el a ps e d  aft er  or 
ar e r efr a ct or y t o  at l e ast  o n e  b ut  n o   m or e t h a n t hr e e   pri or s yst e  mi c t h er a pi es 
a n d h a v e f ail e d ,  or ar e  n ot  c a n di d at es f or   H  D  C  a n d   A S  C T,  a n d  h a v e t h us 
e x h a ust e d t h eir t h er a p e uti c  o pti o ns  of  d e  m o nstr at e d cli ni c al  b e n efit.  At 
l e ast  on e  pri or t h er a p y li n e   m ust  h a v e i n cl u d e d  a   C  D 2 0 -t ar g et e d t h er a p y 
( e. g.   R T  X). 
 
P ati e nts   wit h   R -  R D L  B  C L   w h o   m e et all t h e i n cl usi o n  crit eri a  a n d  h a v e 
n o n e  of t h e  e x cl usi o n  crit eri a   will  b e  e nr oll e d  a n d r a n d o  ml y  assi g n e d t o 
o n e  of t  w o  p ar all el tr e at  m e nt  gr o u ps i n  a r ati o  of  1: 1. B as eli n e   N  K  C  C   will 
b e  d et er  mi n e d  b y fl o  w  c yt o  m etr y.   Hist ol o gi c al  c o nfir  m ati o n  of   D L  B  C L 
di a g n osis ( p ost -r a n d o  mis ati o n)   will  b e  p erf or  m e d  b y  a  c e ntr al  p at h ol o gist. 
 
T h e st u d y   will  b e  p erf or  m e d  a c c or di n g t o  a  gr o u p -s e q u e nti al,  a d a pti v e 
d esi g n   wit h  p ossi bl e s a  m pl e si z e  a dj ust  m e nt  aft er  a  pl a n n e d i nt eri  m 
a n al ysis   wit h  5 0  p er c e nt i nf or  m ati o n r at e.  T h e tri al   will  b e  c o n d u ct e d  at 
a p pr o xi  m at el y  1 8 0 sit es   w orl d  wi d e. 
 
As t h e  c o  m bi n ati o n  of   M  O  R 0 0 2 0 8  a n d   B E  N   will  b e s yst e  m ati c all y 
e v al u at e d f or t h e first ti  m e i n  a  cli ni c al tri al, t h e tri al i n cl u d es  an I niti al 
S af et y E v al u ati o n ( P h as e II  p art  of t h e tri al) w hi c h   will e n a bl e t h e 
I n d e p e n d e nt   D at a   M o nit ori n g   C o  m  mitt e e (I  D  M  C) t o  c o n cl ud e  w h et h er t h e 
c o  m bi n ati o n tr e at  m e nts  ar e s af e. 
 
I n t h e  c o urs e  of I niti al S af et y E v al u ati o n , t h e first t hr e e p ati e nts i n  b ot h 
i n v esti g ati o n al  ar  ms   will  b e  d os e d s e q u e nti all y   wit h  at l e ast  a 4 8  h o urs l a g 
p eri o d  b et  w e e n t h e  e nr o lm e nt s of t  w o  c o ns e c uti v e  p ati e nts  as c o u nt e d fr o  m  
C y cl e  1   D a y   4 (C 1  D 4).   Aft er  c o  m pl eti o n  of t h e first tr e at  m e nt   w e e k 
(  C 1  D8)  b y t h e t hir d  c o ns e c uti v e  p ati e nt i n  e a c h  ar  m ( a p pr o xi  m at el y 
6 p ati e nts i n t ot al) t h e s af et y  d at a   will  b e r e vi e  w e d  b y t h e I  D  M  C.  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 7 of  1 3 1  
F oll o  wi n g  a  p ositi v e r e c o  m  m e n d ati o n of t h e I  D  M  C, s e v e n a d diti o n al 
p ati e nts i n  e a c h  ar  m   m a y  b e  d os e d i n  p ar all el ( a p pr o xi  m at el y  1 4  p ati e nts i n 
t ot al).   A n  a d diti o n al I  D  M  C r e vi e  w   will t a k e  pl a c e  aft er t h e l ast  of 
1 0  p ati e nts i n  e a c h  ar  m ( a p pr o xi  m at el y  2 0  p ati e nts i n t ot al)  h a v e  c o  m pl et e d 
C 3  D 1 visit i n t h eir r es p e cti v e tr e at  m e nt  all o c ati o n  ar  m  ( c o  m pl et e Initi al 
S af et y E v al u ati o n) . 
T h e  e x a ct  n u  m b er  of  p ati e nts  eli gi bl e f or  e v al u ati o n  d e p e n ds  o n t h e 
tr e at  m e nt  all o c ati o n   wit hi n t h e r a n d o  misati o n  bl o c ks.  F or  a s c h e  m ati c  
pr es e nt ati o n  of st u d y  o utli n e , s e e Fi g ur e 1  an d  Fi g ur e   2 i n t h e pr ot o c ol  
S h o ul d t h e I  D  M  C m ai n t ai n t h eir i niti al r e c o  m  m e n d ati o n t hat t h e 
c o  m bi n ati o n tr e at  m e nts  ar e s af e , t he tri al   ma y  pr o c e e d f urt h er   wit h 
r e cr uit  m e nt ( P h as e III  p art  of t h e tri al). S u bs e q u e nt I  D  M  C m e eti n gs   will  b e 
c all e d f or  as o utli n e d i n t h e I  D  M  C C h art er  t hr o u g h o ut t h e  e ntir e tri al. 
E a c h I  D  M  C r e vi e  w   will e n c o  m p ass  t h e  n u  m b er, fr e q u e n c y, s e v erit y a n d 
t y pe of  A Es,  as   w ell  as  cli ni c al l a b or at or y  bi o c h e  mistr y  a n d  h ae  m at ol o g y 
p ar a  m et ers  a n d  ot h er r el e v a nt s af et y  d at a. T h e I  D  M  C   will  als o  a d vis e t h e 
s p o ns or   w h et h er t h e tri al d esi g n r e q uir es   m o difi c ati o ns  or  h as   m et t h e 
pr e- d efi n e d tri al st o p pi n g crit eri a. F urt h er  d et ails ar e  pr o vi d e d i n 
S e cti o ns 9. 8  a nd  1 4. 1  an d t h e I  D  M  C   C h art er. 
F or t h e  p ur p os e  of t h e  pri  m ar y effi c a c y  e n d p oi nt a n al ysis , th e  dis e as e 
r es p o ns e  ass ess  m e nts   will  b e   m a d e c e ntr all y  b y  a n I n d e p e n d e nt 
Ra di ol o g y/ Cli nica l Re vie w C o m mittee (I R C; see Secti o n  1 4. 2 ). 
I n cl usi o n/  E x cl usi o n 
C rit e ri a  
I  N  C  L  U SI  O  N   C  RI  T  E  RI  A: 
Eli gi bl e  p ati e nts   m ust   m e et t h e f oll o  wi n g  crit eri a t o  b e  e nr oll e d i n t h e 
st u d y: 
Di a g n osis/ T ri al P o p ul ati o n  
1.
A g e ≥1 8  y e ars
•
F or  Si n g a p or e  o nl y:  a g e > 2 1  y e ars
2.
Hist ol o gi c all y c o nfir  m e d  di a g n osis,  a c c or di n g t o t h e   W orl d   H e alt h
Or g a ni z ati o n (  W  H  O,  2 0 0 8)  cl assifi c ati o n,  of:
a)
Diff us e l ar g e   B -c ell l y  m p h o  m a  n ot  ot h er  wis e s p e cifi e d (  D L  B  C L
N  O S)
b)
T  c ell/ histi o c yt e ri c h l ar g e   B -c ell l y  m p h o  m a ( T  H  R L  B  C L)
c)
E pst ei n -B arr  vir us ( E  B  V)  p ositi v e   D L  B  C L  of t h e  el d erl y
( E  B  V-p ositi v e   D L  B  C L)
d)
C o  m p osit e l y  m p h o  m a   wit h  a   D L  B  C L  c o  m p o n e nt wit h  a   D L  B  C L
r el a ps e s u bs e q u e nt t o   D L  B  C L tr e at  m e nt
e)
Dis e as e tr a nsf or  m e d fr o  m  a n  e arli er  di a g n osis  of l o  w-gr a d e
l y  m p h o  m a (i. e.  a n i n d ol e nt  p at h ol o g y s u c h  as f olli c ul ar l y  m p h o  m a,
m ar gi n al  z o n e l y  m p h o  m a ) i nt o   D L  B  C L   wit h  a   D L  B  C L r el a ps e
s u bs e q u e nt t o   D L  B  C L tr e at  m e nt.

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 8 of  1 3 1  
3.
Fres h t u m o ur tiss ue for  ce ntral  pa t h ol o g y re vie w  m ust be  pr o vi de d as
a n a dj u nct  to partici pati o n i n t his st u d y. S h o ul d  it n ot  be  p os si ble to
o btai n  a fres h tu m o ur  tiss ue sa m ple, arc hi val  p araffi n e m be d de d
t u m o ur tiss ue ac q uire d ≤3 years pri or t o scree nin g f or t his pr ot oc ol
m ust  b e a vaila ble f or this p ur p ose.
4.
Patie nts m ust  h a ve:
a)
R- R D L B C L (f or defi niti o ns , see Secti o n 8. 1  of  t he pr ot oc ol)
b)
at least o ne bi di me nsi o nall y  m eas ura bl e di sease site. T he lesi o n
m ust ha ve a greatest tra ns verse dia meter of ≥1. 5  c m a nd  g reatest
p er pe n dic ular dia meter of ≥1. 0 c m at baseli ne . T he lesi o n m ust  b e
p o siti ve o n P E T sca n (f or d efi niti o n , see J u wei d et al. (2 0 0 7) ).
c)
recei ve d at least o ne, b ut no m ore  tha n t hree  pre vi o us  syste mic
t hera py  li nes f or t he treat me nt of D L B C L (f or f urt her details see
Secti o ns  8. 6  an d  9. 5 ). At least  o ne pre vi o us  thera p y li ne  must  ha ve
i ncl u de d a CD 2 0 -tar gete d thera p y  (e. g. R T X).
d)
Easter n  C o o perati ve O nc ol o g y  Gro u p  (E C O G)  perf or ma n ce stat us
of  0 t o  2
5 .
Patie nts  after  fail ure of A SC T  or patie nts c o nsi dere d  i n t he o pini o n of
t he i nvesti gat or  c urre ntl y n ot eli gi ble  for  H D C  wit h s ubse q ue nt  A S C T .
D oc u me ntati o n of  the  reas o n f or  ineli gi bilit y f or  AS C T  must  be
prese nt  in  the patie nt’s s o urce data  (f or details , see Secti o n  8. 6 ).
L a b o r at o r y V al u es  
6.
Patie nts m ust  m eet the f oll o wi n g  la b orat or y  criteria at Scr ee ni n g:
a)
abs ol ute ne utr o p hil c o u n t ( A N C) ≥1. 5 × 1 09/ L (u nless sec o n dar y t o 
b o ne  m arr o w  in v ol ve me nt  b y D L B C L  as de m o nstrate d  b y  b o ne  
marr o w  as pirati o n a n d b o ne  m arr o w  bi o ps y  req uire d f or Scree ni n g )
b )
p latelet c o u nt ≥9 0  ×  1 09/ L ( u nless sec o n dar y to  b o n e marr o w  
i n v ol ve me n t b y  D L B C L  as de m o nstrate d b y  b o ne  m arr o w  
as pirati o n a n d b o ne  m arr o w  bi o ps y  req uire d  for  S cree ni n g ) a nd  
a bse nce of  acti ve blee di n g
c)
total ser u m bilir u bi n ≤2. 5  ×  u pper li mit of n o r mal ( U L N) u nless 
sec o n dar y to  Gil bert's  sy n dr o me  (or  pa tter n c o nsiste n t w it h 
Gil bert's)  or d oc u me nte d  li ver in v ol ve me nt  b y l y m p h oma . Patie nts  
w it h Gil bert's  sy n dr o me  or  d oc u me nte d li ver in v ol ve me nt  b y  
l y m p h o ma ma y be i ncl u de d if t heir t o tal bilir u bi n  is ≤5 x U L N
(see e xcl usi o n criteri o n 6e )
d)
alani ne tra nsa mi nase ( A L T), as partate a mi n otra nsferase ( A S T) a n d 
alkali ne p h os p hatase ≤3  ×  U LN  or < 5  ×  U LN  i n case s of  
d oc u me n te d li ver in v ol ve me n t b y l y m p ho ma
e)
ser u m creati ni ne ≤2. 0  x U LN  or  creati ni ne cleara nce m u st b e
≥4 0  m L/ mi n calc ulate d  u si n g a sta n dar d C oc kcr oft - Gault  f or m ula 
( C oc kr oft & Gault , 1 9 7 6 ; see A ppe n di x A  to t he pr o t oc ol)
7.
F or  a fe mal e of  c hil dbeari n g  pote ntial  (F C B P ; f or defi niti o n see  
Secti o n  8 . 9), a negati v e pre g n a nc y t est mu st be c o nfir me d  bef ore  
e nr ol me n t. A n F C B P m ust c o m mit t o  ta ke hi g hl y effecti ve  
c o ntrace pti ve preca uti o ns (see A p pe n di x B ) wit h o ut  interr u pti o n    
d uri n g  the  st u d y a n d f or 3,  6 or  1 2  m o nt hs after  the last  dose  of  
M O R 0 0 2 0 8 , B E N or  RT X  res pecti vel y,  w h ic he ver is later. A n F C B P

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 9 of  1 3 1  
m ust r efr ai n fr o  m  br e astf e e di n g  a n d  d o n ati n g  bl o o d  or  o o c yt es  d uri n g 
t h e  c o urs e  of t h e st u d y  a n d f or  3,  6 or  1 2  m o nt hs  aft er t h e l ast  d os e  of 
M  O  R 0 0 2 0 8,   B E  N  or   R T  X r es p e cti v el y,   w hi c h e v er is l at er.  R estri cti o ns 
c o n c er ni n g  bl o o d  d o n ati o ns  a p pl y  as   w ell t o f e  m al es   w h o  ar e  n ot  of 
c hil d b e ari n g  p ot e nti al.  (A p pli c a bl e i n R e p u bli c  of   K o r e a :  a n  F  C  B P 
m ust c o  m  mit t o t a k e  hi g hl y  eff e cti v e  c o ntr a c e pti v e  pr e c a uti o ns ( s e e 
A p pe n d i x B) wit h o ut  interr u pti o n  an d refrai n  fr o m breastfee di n g a n d 
d o n ati n g  bl o o d  or  o o c yt es  d uri n g t h e  c o urs e  of t h e st u d y  a n d f or 
6 m o nt hs  aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8, 6   m o nt hs  aft er t h e l ast  d os e 
of B E  N  or 1 2   m o nt hs  aft er t h e l ast  d os e  of   R T  X,   w hi c h e v er is l at er.) . 
8.
M al es   m ust  us e   a n eff e cti v e  b arri er   m et h o d  of  c o ntr a c e pti o n wit h o u t
i nt err u pti o n d uri n g t h e st u d y  a n d f or 3, 6 or  1 2 m o nt hs  aft er t h e l ast
d os e of M  O  R 0 0 2 0 8,   B E  N  or   R T  X r es p e cti v el y,   w hi c h e v er is l at er, if
t h e  p ati e nt is s e x u all y  a cti v e   wit h  an  F  C  B P. M al es   m ust r efr ai n fr o  m
d o n ati n g  bl o o d  or s p er  m  d uri n g st u d y  p arti ci p ati o n  a n d f or  3,  6  or
1 2  m o nt hs  aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8,   B E  N  or   R T  X
r es p e cti v el y,   w hi c h e v er is l at er. (A p pli c a bl e i n   R e p u bli c  of   K o r e a :
m al es   m ust r efr ai n fr o  m  d o n ati n g  bl o o d  or s p er  m  a n d, if t h e  p ati e nt is
s e x u all y  a cti v e   wit h  a n  F  C  B P,   m ust  us e  a n  eff e cti v e  b arri er   m et h o d  of
c o ntr a c e pti o n   wit h o ut i nt err u pti o n  d uri n g t h e st u d y  a n d f or  6   m o nt hs
aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8,  6   m o nt hs  aft er t h e l ast  d os e  of B E N
or 1 2   m o nt hs  aft er t h e l ast  d os e  of R T  X,   w hi c h e v er is l at er) .
9.
I n t h e  o pi ni o n  of t h e i n v esti g at or, t h e  p ati e nts   m ust:
a)
b e  a bl e t o  c o  m pl y   wit h  all st u d y -r el at e d  pr o c e d ur es,   m e di c ati o n
us e,  a n d  e v al u ati o ns
b)
b e  a bl e t o  u n d erst a n d  a n d  gi v e  i nf or  m e d  c o ns e nt
c)
n ot b e  c o nsi d er e d t o  b e  p ot e nti all y  u nr eli a bl e  a n d/ or  n ot
c o o p er ati v e.
E X  C  L  U SI  O  N   C  RI  T  E  RI  A:  
Eli gi bl e  p ati e nts   m ust  n ot  h a v e  a n y  of t h e f oll o  wi n g t o  b e  e nr oll e d i n t h e 
st u d y: 
E x cl usi o n a r y Di a g n osis  C rit e ri a  
1.
Patie nts w h o  ha ve:
a)
a n y o t her hist ol o gical ty pe  of  ly m p h o ma  incl u di n g , e. g., pri mar y 
me diasti nal  (t h y mic) lar ge B -cell l y m p h o ma ( P M B L) or B ur kitt’ s 
l y m ph o ma
b)
pri mar y refract or y D L B C L (for  defi niti o n , see Secti o n  8. 1 )
c)
patie nts  wit h kn o w n  "d o u ble/tri ple  h it" D L B C L  ge netics , 
c haracterise d  b y  sim ulta ne o us detecti o n  of  M Y C  wit h  B C L 2     
a n d/ or  B C L 6  tra nsl ocati o n, as defi ne d  b y  fl u oresce nce i n sit u 
h y bri disati o n  ( FI S H). M Y C , B C L 2 , B C L 6  testi n g pri or to st u d y  
e nr ol me nt  is n ot re q uire d .
d )
ce ntral  ne r v o us syste m  (C N S)  ly m p h o ma  in v ol ve me n t in  prese nt 
or  past m e dical  hist or y

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 0  of 1 3 1  
E x cl usi o n a r y P r e vi o us a n d C u r r e nt T r e at  m e nt C rit e ri a  
2.
Patie nts  wh o ha d a  maj or  sur ger y (f or  defi niti o n, see Secti o n  8. 1 ) less 
t ha n 3 0 da ys  pri or  to Da y  1 d osi n g
3.
Pa tie nts wh o ha ve,  wit hin 1 4 da ys  pri or t o Da y 1 d osi n g:
a)
n o t disc o nti n ue d C D 2 0-tar gete d  t hera p y, c he m ot hera p y,  
ra di ot hera p y, i n vesti gati o nal antica ncer  t hera p y or other  
l y m p h o ma-specific t hera p y  (f or e xce pti o ns see Secti o n  9. 5. 3 )
b)
recei ve d  li ve vacci nes (for  defi niti o n , see Secti o n 8. 6 )
c)
req uire d pare nteral  a ntimicr o bial  thera p y  for  acti ve, i nterc urre nt 
s yste mic infecti o ns
4.
Patie nts w h o:
a)
i n t he opi ni o n  of t he i nvesti gat or, ha v e n ot  rec o vere d  s ufficie ntl y 
fr o m the a d verse t o xic effects of  pri or thera pies,  maj or s ur geries 
(f or defi niti o n, see Secti o n 8. 1 ) or  si g nifica nt tra u matic i nj uries
b)
were pre vi o usl y  treate d wit h CD 1 9 -tar gete d  thera p y  or B E N
c)
h a ve  a hist or y of pre vi o us  se vere aller gic reacti o ns  to c o m p o u n ds  
o f si milar biol o gical  or che mical  co m p ositi o n t o  MO R 0 0 2 0 8,  
R T X,  muri ne  protei ns  or B E N , or  the  exci pie nts  co ntai ne d i n t he  
st u d y dr u g f or m ulati o ns
d)
ha ve  u n der g o ne AS C T  wit hi n a p eri o d  of ≤3 m o nt hs  pri or to  
si g ni n g t he inf or me d c o nse nt  for m.  Patie nts  wh o ha ve  a more  
dista nt  hist or y of AS C T  must  ex hi bit  full  hae mat ol o gical  rec o ver y  
bef ore  enr ol me nt  int o t he  st u d y.
e)
ha ve  u n der g o ne pre vi o us  all o ge neic ste m  cell tra ns pla ntati o n
f)
c o nc urre ntl y  use ot her  a ntica ncer or e xperi me ntal  treat me nts (f or 
e xce pti o ns see Secti o n  9. 5. 3 )
E x cl usi o n a r y M e di c al H ist o r y C rit e ri a  
5.
Pri or  hist ory of  mali g na ncies  other  tha n D L B C L,  u nless  the  patie nt has 
b ee n free of  t he di sease f or ≥3  year s pri or  t o Sc ree ni n g. Exce pti o ns  to  
t he ≥3 - year  ti me li mit i ncl u de hist or y of  t he foll o wi n g:
a)
ba sal cell carci n o ma of  the s ki n
b)
s qu a m o us cell  carci n o ma  of the s ki n
c)
carci n o ma i n sit u of  the cer vi x
d )
carci n o ma i n sit u of  the breast
e)
carci n o ma i n sit u of  the  bla d der
f)
i nci de ntal  hist ol o gical fi n di n g of pr ostate  ca ncer
( T u m o ur/ N o de/ Metastasis [ T N M] sta ge of  T1a or  T1 b)
6.
Patie nts  wit h:
a)
p o siti ve he patitis  B a n d/ or C ser ol o g y (for  defi niti o ns , see    
Secti o n  8. 6 )
b)
k n o w n ser o p ositi vit y for  or hist or y of acti ve  viral i nfecti o n wit h 
h u ma n i m m u n o deficie nc y vir us  (HI V)
c)
e vi de nce of  acti ve, se vere u nc o ntr olle d  s yste mic infecti o ns (e. g. , 
t u berc ul osis, o p p ort u nistic i nfecti o ns) or se psis
d)
a hist or y or evi de nce  of se verel y i m m u n oc o m pr o mise d state
e)
a hist or y  or evi de nce of  se vere he patic i m pair me nt (t otal seru m  
bilir u bi n >  3 m g/ d L),  ja u n dice u nless sec o n dar y  to  Gil bert's  
s y n dr o me or  d ocu me nte d l i ver in v ol ve me nt  b y l y m p h o ma  (see 
i ncl usi o n criteri o n 6c)

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 1  of 1 3 1  
f)
a hist or y  or  e vi d e n c e  of cli ni c all y si g nifi c a nt  c ar di o v as c ul ar ,
cere br o vasc ular,  CN S  a n d/ or  other  di sease t hat, i n t he 
i n vesti gat or’s o pini o n , wo ul d  precl u de  partici pati o n i n  the  stu d y or  
c o m pr o mise t he patie nt’s a bilit y t o gi ve i nf or me d c o nse nt (f or 
a d diti o nal  ex pla nati o ns , see Secti on  8. 6 ).
I n v esti g ati o n al   D r u g(s) 
(  N a  m e,   D es c ri pti o n) 
M  O  R 0 0 2 0 8 ( a n  F c -e n h a n c e d ,  h u  m a nis e d,   m o n o cl o n al  a nti b o d y t ar g eti n g 
t h e   B-c ell s urf a c e  a nti g e n   C  D 1 9),   B e n d a  m usti n e (  B E  N: e. g. L e v a ct ® / 
Tr e a n d a ® ) a n d   Rit u xi  m a b (  R T  X: e. g. M a b T h er a
® /  Rit u x a n® ). 
D os e,   R o ut e  of 
A d  mi nist r ati o n, 
T r e at  m e nt   R e gi  m e n  
Tr e at  m e nt wit h st u d y  dr u gs  (M  O  R 0 0 2 0 8  wit h   B E  N  or   R T  X  wit h   B E  N ) 
will  b e  off er e d i n  2 8 -d a y  c y cl es  at s p e cifi e d ti  m e  p oi nts at 
pr ot o c ol -pr es cri b e d d os e l e v els f or  a   m a xi  m u  m  of si x c y cl es.  
T h er e aft er,  p ati e nts   wit h  a r es p o ns e  of  at l e ast  P  R  at t h e  e n d  of   C y cl e  6,  as 
p er l o c al  dis e as e r es p o ns e  ass ess  m e nt, will c o nti n u e anti b o d y m o n ot h er a p y 
tr e at  m e nt (  M  O  R 0 0 2 0 8  or   R T  X) i n  a c c or d a n c e   wit h t h eir  ori gi n al tr e at  m e nt 
all o c ati o n  u ntil dis e as e pr o gr essi o n.  Tr e at  m e nt   m a y  b e st o p p e d  d u e t o 
r e c urr e n c e/ dis e as e  pr o gr essi o n,  u n a c c e pt a bl e t o xi cit y,  d e at h  or 
dis c o nti n u ati o n f or  a n y  ot h er r e as o n,   w hi c h e v er  c o  m es first.  
I n t h e  c as e  of l o c al  c o nfir  m ati o n  of  dis e as e r e c urr e n c e/ pr o gr essi o n, it is  u p 
t o t h e i n v esti g at or t o  d e ci d e  a c c or di n g t o t h e i n di vi d u al ris k/ b e n efit r ati o if 
t h e  p ati e nt s h o ul d  c o nti n u e f urt h er  a nti b o d y tr e at  m e nt (  R T  X  or 
M  O  R 0 0 2 0 8) i n  a c c or d a n c e   wit h t h e i n iti al tr e at  m e nt  all o c ati o n f or  u p t o 
2 4  m o nt hs  i n t ot al (f or  d et ails, s e e S e cti o n  9. 1  of  t h e  pr ot o c ol). 
M  O  R 0 0 2 0 8  d os e : 1 2  m g/ k g  i ntr a v e n o usl y (I  V) 
C y cl e  1 -3: M  O  R 0 0 2 0 8   will  b e  a d  mi nist er e d  o n   D a y  1,   D a y  8,   D a y  1 5  a n d 
D a y  2 2  of  e a c h  c y cl e.   A d diti o n all y , a l o a di n g  d os e   will  b e  a d  mi nist er e d  o n 
D a y  4  of C y cl e  1.  C y cl e 4- u ntil dis e as e pr o gr essi o n :   M  O  R 0 0 2 0 8   will  b e 
a d  mi nist er e d  o n   D a y   1 a n d   D a y  1 5  of  e a c h  c y cl e.  
R  T  X  d os e : 3 7 5   m g/  m 2 I  V 
R T  X   will  b e  a d  mi nist er e d  o n   D a y  1  of  e a c h  c y cl e,   wit h  a  pr e -pl a n n e d 
tr e at  m e nt i nt er v al  of at l e ast 2 8 -d a ys t o t h e s u bs e q u e nt   R T  X 
a d  mi nistr ati o n.  
B  E  N d os e : 9 0   m g/  m 2 I  V 
B E  N   will  b e  a d  mi nist er e d  o n   D a y s  2 +3  of C y cl e  1 . B E  N  a d  mi nistr ati o n  
will  b e r e p e at e d  o n   D a ys  1 + 2  or   D a ys  2 + 3  of t h e s u bs e q u e nt  c y cl es,   wit h  a 
pr e- pl a n n e d tr e at  m e nt i nt er v al of at l e ast 2 8 -d a y s b et  w e e n t h e 
c o  m  m e n c e  m e nt s of t  w o s u c c e e di n g  c y cl es (f or  a d diti o n al i nf or  m ati o n s e e 
Secti o n  9. 1. 3 ). 
B E  N  d os e m a y  b e   m o difi e d i n  a  d e -es c al ati n g f as hi o n  or  dis c o nti n u e d 
b as e d  u p o n  cli ni c al  a n d l a b or at or y fi n di n gs. I n t h e c as e  of  e arl y   B E  N 
dis c o nti n u ati o n , t h e a nti b o d y tr e at  m e nt s h o ul d  c o nti n u e  u nl ess 
c o ntr ai n di c at e d . D et ail e d  g ui d a n c e  o n  h o  w t o   m a n a g e  h ae  m at ol o gi cal 
a n d/ or  ot h er t o xi citi es is pr o vi d e d i n S e cti o n  9. 4  of t h e  pr ot o c ol.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 3  of 1 3 1  
R T  X  wit h B E  N  gr o u p (h a z ar d r ati o [  H  R] of  0. 7 0)  i n t h e  o v er all  p o p ul ati o n. 
A t  w o -st a g e, gr o u p -s e q u e nti al, a d a pti v e  d esi g n   wit h  o n e i nt eri  m  a n al ysis 
will  b e  a p pli e d  usi n g t h e   O’  Bri e n-Fl e  mi n g  a p pr o a c h a n d t h e i n v ers e  n or  m al 
m et h o d f or  pr es er vi n g t h e  o v er all t y p e I  err or r at e (W ass  m er  2 0 0 6 ). 
A t ot al  n u  m b er  of  2 5 6  P F S  e v e nts  ar e r e q uir e d  b as e d  o n  a H  R  of  0. 7 0   wit h 
8 0  %  p o  w er  at fi n al  a n al ysis  f or t h e  F  A S,  usi n g  a t  w o-si d e d l o g-r a n k t est  at 
4. 8  %  al p h a l e v el  a n d  a  1: 1 r a n d o  mi sati o n r ati o  b et  w e e n t h e t  w o tre at  m e nt 
gr o u ps.  T o  g e n er at e t h e r e q uir e d  n u  m b er  of  e v e nts, 2 8 6  e v al u a bl e  p ati e nts 
w o ul d n e e d t o  b e  e nr oll e d , wit h  ass u  m e d  a c cr u al  d ur ati o n  of  1 8   m o nt h s a n d 
a  Foll o  w -  Up  of  1 2   m o nt h s.   A p pl yi n g  a 1 3 %  dr o p -o ut r at e   w o ul d r es ult i n  a 
t ot al  n u  m b er  of e nr oll e d p ati e nts  of  a p pr o xi  m at el y  3 3 0.  
A n i nt eri  m  a n al ysis is  pl a n n e d  aft er t h e  o bs er v ati o n  of  5 0  %  of t h e r e q uir e d 
e v e nts, i. e.,  aft er  1 2 8 P F S e v e nts.  T h e   H  R s will  b e  c al c ul at e d  a n d t hr e e 
o ut c o  m es   will  b e  p ossi b l e  b as e d  o n t h e i nt eri  m r es ult:  T h e st u d y   m a y  b e 
st o p p e d  d u e t o f utilit y, t h e st u d y m a y c o nti n u e   wit h t h e   mi ni  m u  m  pl a n n e d 
n u  m b er  of 3 3 0 p ati e nts  (t o  o bt ai n  2 5 6 P F S e v e nts) ,  or t h e s a  m pl e si z e m a y 
b e i n cr e as e d t o  4 5 0  p ati e nts (t o  o bt ai n  3 6 9  P F S  e v e nts).  E arl y st o p pi n g f or 
effi c a c y is  n ot  all o  w e d.  
T h e s a  m pl e si z e   w as i n cr e as e d t o  4 5 0  p ati e nts  b as e d  o n t h e I  D  M  C 
r e c o  m  m e n d ati o n. 
T h e st u d y i n cl u d es a  c o-pri  m ar y  e n d p oi nt ( P F S i n t h e   N  K  C  C -l o  w 
s u b gr o u p), f oll o  wi n g t h e  e  m er g e n c e  of  d at a s h o  wi n g t h e i  m p ort a n c e  of 
N  K  C  C  as  a  pr o g n osti c f a ct or, a n d p ot e nti all y  a  pr e di cti v e f a ct or  f or 
a nti b o d y  effi c a c y i n   D L  B  C L . 
F or  c o nfir  m at or y  h y p ot h esis t esti n g, t h e  p -v al u es  of t h e st atisti c al t ests f or 
t h e  pri  m ar y  a n d  k e y s e c o n d ar y  e n d p oi nt   will  b e  c o  m bi n e d fr o  m st a g e I 
(i nf or  m ati o n  u p t o I nt eri  m   A n al ysis)  a n d st a g e II (i nf or  m ati o n  b et  w e e n 
int eri  m an al ysis  a n d fi n al an al ysis) of t h e st u d y  usi n g t h e i n v ers e  n or  m al 
m et h o d f or t h e  o v er all  p o p ul ati o n ( F  A S) a n d t h e   N  K  C C- l o  w s u b gr o u p. 
T h e f a  mil y -wis e  err or r at e   will  b e   m ai nt ai n e d  at 4. 8  %  b y s plitti n g t h e  al p h a 
b et  w e e n  F  A S  a n d   N  K  C  C -lo  w s u b gr o u p  a d e q u at el y. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 4  of 1 3 1  
2  T  A B  L  E   O F   C  O  N  T  E  N  T S  
2. 1  O v e r al l   T a bl e  of   C o nt e nts 
TI  T  L  E  P  A  G  E  ........................................................................................................................................... 1 
I  N  V  E S  TI  G  A  T  O  R' S   A  G  R  E  E  M  E  N  T ...................................................................................................... 2 
P  R  O  T  O  C  O  L   HI S  T  O  R  Y  ......................................................................................................................... 3 
1  
P  R  O  T  O  C  O  L S  Y  N  O P SI S  ................................................................................................................ 4 
2  
T  A  B  L  E   O F   C  O  N  T  E  N  T S  ............................................................................................................... 1 4  
2. 1  
O v e r all   T a bl e  of   C o nt e nts  ................................................................................................... 1 4  
2. 2  
List  of   T a bl es  ........................................................................................................................ 1 8  
2. 3  
List  of  Fi g u r es  ....................................................................................................................... 1 8  
3  
LI S  T   O F   A  B  B  R  E  VI  A  TI  O  N S   A  N  D   D  E FI  NI  TI  O  N S   O F   T  E  R  M S  ............................................. 1 9  
4  
B  A  C  K  G  R  O  U  N  D  ............................................................................................................................ 2 4  
4. 1  
O v e r vi e  w  of   N o n -H o d g ki n   L y  m p h o  m as  ............................................................................ 2 4  
4. 2  
T r e at  m e nt  of   D  L  B  C  L  .......................................................................................................... 2 4  
4. 3  
B e n d a  m usti n e i n   D  L  B  C  L   T r e at  m e nt  ................................................................................. 2 5  
4. 4  
O v e r vi e  w  of  n at u r al  kill e r (  N  K)  c ells i n l y  m p h o  m a,  r el e v a n c e t o   M  O  R 0 0 2 0 8  .............. 2 6  
4. 5  
O v e r vi e  w  of   C  D 1 9  e x p r essi o n i n   D  L  B  C  L  a n d t r e at  m e nt   wit h   M  O  R 0 0 2 0 8  .................... 2 7  
4. 5. 1  
T h e   B -c ell   Diff er e nti ati o n   A nti g e n   C  D 1 9 i n  L y  m p h o  m a  .................................... 2 7  
4. 5. 2  
M  O  R 0 0 2 0 8   B a c k gr o u n d  a n d  Pr e cli ni c al   D at a  ..................................................... 2 7  
4. 5. 3  
Cli ni c al  E x p eri e n c e   wit h   M  O  R 0 0 2 0 8  .................................................................. 2 9  
4. 5. 3. 1  
Pr ot o c ol   X  m  A b 5 5 7 4 -0 1  ....................................................................................... 2 9  
4. 5. 3. 2  
O n g oi n g  St u di es  ................................................................................................... 3 0  
4. 5. 4  
S af et y  of   M  O  R 0 0 2 0 8  ........................................................................................... 3 1  
5  
S  T  U  D  Y  P  U  R P  O S  E/  R  A  TI  O  N  A  L  E  ............................................................................................... 3 2  
6  
O  B J  E  C  TI  V  E S ................................................................................................................................ 3 4  
6. 1  
P ri  m a r y   O bj e cti v es  .............................................................................................................. 3 4  
6. 2  
S e c o n d a r y   O bj e cti v es  ........................................................................................................... 3 4  
6. 3  
E x pl o r at o r y   O bj e cti v es  ........................................................................................................ 3 4  
7  
S  T  U  D  Y   E  N  D P  OI  N  T S  .................................................................................................................... 3 5  
7. 1  
C o -P ri  m a r y   E n d p oi nts  ........................................................................................................ 3 5  
7. 2  
S e c o n d a r y   E n d p oi nts  ........................................................................................................... 3 5  
8  
I  N  V  E S  TI  G  A  TIO  N  A  L  P  L  A  N  ........................................................................................................ 3 5  
8. 1  
P r ot o c ol -S p e cifi c   D efi niti o ns  ............................................................................................... 3 5  
8. 2  
St u d y   D esi g n  ......................................................................................................................... 3 6  
8. 3  
St u d y   C o n d u ct  ...................................................................................................................... 3 9  
8. 4  
E n d  of  St u d y  ......................................................................................................................... 3 9  
8. 5  
P ati e nt  S el e cti o n   C rit e ri a  .................................................................................................... 3 9  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 5  of 1 3 1  
8. 5. 1  
I n cl usi o n   Crit eri a ................................................................................................. 3 9  
8. 5. 2  
E x cl usi o n   Crit eri a  ................................................................................................ 4 1  
8. 6  
A d diti o n al   E x pl a n at o r y I nf o r  m ati o n  o n I n cl usi o n  a n d   E x cl usi o n   C rit e ri a .................... 4 2  
8. 7  
R a n d o  mis ati o n  ...................................................................................................................... 4 5  
8. 8  
R e -s c r e e ni n g  P r o c e d u r es ..................................................................................................... 4 6  
8. 9  
D efi niti o n  of  F e  m al e  of   C hil d b e a ri n g  P ot e nti al  ................................................................ 4 7  
9  
T  R  E  A  T  M  E  N  T S .............................................................................................................................. 4 7  
9. 1  
St u d y   T r e at  m e nts  ................................................................................................................. 4 7  
9. 1. 1  
M  O  R 0 0 2 0 8  .......................................................................................................... 4 8  
9. 1. 2  
R T  X ...................................................................................................................... 4 9  
9. 1. 3  
B E  N ...................................................................................................................... 4 9  
9. 2  
P r e  m e di c ati o n f o r  St u d y   D r u g I nf usi o ns ........................................................................... 5 0  
9. 3  
P ati e nt   M o nit o ri n g   D u ri n g  St u d y   D r u g I nf usi o ns  ............................................................ 5 0  
9. 4  
C rit e ri a f o r   D os e   M o difi c ati o ns  a n d  St u d y   D r u g   Dis c o nti n u ati o n  .................................. 5 0  
9. 4. 1  
M a n a g e  m e nt  of  St u d y   Dr u g I nf usi o n -R el at e d   R e a cti o ns  .................................... 5 0  
9. 4. 1. 1  
Gr a d e  2 I  R  Rs f or  p ati e nts r e c ei vi n g   M  O  R 0 0 2 0 8  ................................................. 5 1  
9. 4. 1. 2  
Gr a d e  3 I  R  Rs f or  p ati e nts r e c ei vi n g   M  O  R 0 0 2 0 8  ................................................. 5 2  
9. 4. 1. 3  
Gr a d e  4 I  R  Rs f or  p ati e nts r e c ei vi n g   M  O  R 0 0 2 0 8  ................................................. 5 2  
9. 4. 2  
M a n a g e  m e nt  of  Tr e at  m e nt -R el at e d  T o xi citi es  ..................................................... 5 2  
9. 4. 2. 1  
S af et y -r el at e d   Crit eri a f or   B E  N  Tr e at  m e nt  a n d   B E  N  Tr e at  m e nt 
P ost p o n e  m e nt  ....................................................................................................... 5 3  
9. 4. 2. 2  
A nti b o d y  Tr e at  m e nt   D os e   O  missi o ns/ P ost p o n e  m e nts  ......................................... 5 5  
9. 4. 2. 3  
Tr e at  m e nt   Dis c o nti n u ati o n  ................................................................................... 5 6  
9. 5  
P ri o r  a n d   C o n c o  mit a nt   T h e r a p y  ........................................................................................ 5 7  
9. 5. 1  
Gr o  wt h  F a ct ors  a n d  Tr a nsf usi o n  S u p p ort  ............................................................ 5 8  
9. 5. 2  
I nf e cti o n  Pr o p h yl a xis ........................................................................................... 5 8  
9. 5. 3  
A nti c a n c er  T h er a pi es  ........................................................................................... 5 8  
9. 5. 4  
S yst e  mi c   Gl u c o c orti c ost er oi ds  ............................................................................. 5 8  
9. 5. 5  
M a n a g e  m e nt  of  T u  m o ur  L ysis  S y n dr o  m e  ............................................................ 5 9  
9. 5. 6  
M a n a g e  m e nt  of  P ati e nts   w it h   Hist or y  or  Pr e vi o us  E v e nts  of  F e bril e 
N e utr o p e ni a  .......................................................................................................... 5 9  
9. 5. 7  
A nti  mi cr o bi als/  A nti vir als/  A ntif u n g als  ................................................................. 5 9  
9. 6  
T r e at  m e nt   C o  m pli a n c e  ........................................................................................................ 6 0  
9. 7  
O v e r d os e  of  St u d y   D r u gs  ..................................................................................................... 6 0  
9. 8  
Wit h d r a  w al f r o  m  St u d y   T r e at  m e nt  o r  St u d y/ Sit e   T e r  mi n ati o n  ...................................... 6 0  
9. 8. 1  
Wit h dr a  w al   Crit eri a .............................................................................................. 6 0  
9. 8. 2  
St u d y  or  Sit e  T er  mi n ati o n  .................................................................................... 6 1  
1 0  S  T  U  D  Y  P  R  O  C  E  D  U  R  E S  ................................................................................................................ 6 3  
1 0. 1  S c h e d ul e  of   Visits  a n d  P r o c e d u r es  ...................................................................................... 6 3  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 6  of 1 3 1  
1 0. 2  P r o c e d u r es  ............................................................................................................................ 7 2  
1 0. 2. 1  
Di a g n osti c   Bi o ps y  ................................................................................................ 7 2  
1 0. 2. 2  
D e  m o gr a p hi c   D at a/  R el e v a nt   M e di c al   Hist or y  a n d   C urr e nt   M e di c al 
C o n diti o ns/  B as eli n e,  St a g e  a n d  Pr o g n osti c   Cl assifi c ati o n  ................................... 7 3  
1 0. 2. 3  
Q u alit y  of  Lif e  ...................................................................................................... 7 3  
1 0. 3  S af et y   Ass ess  m e nts  ............................................................................................................... 7 3  
1 0. 3. 1  
Vit al  Si g ns  ............................................................................................................ 7 4  
1 0. 3. 2  
P h ysi c al  E x a  mi n ati o n  ........................................................................................... 7 4  
1 0. 3. 2. 1  
F ull  P h ysi c al  E x a  mi n ati o ns  .................................................................................. 7 4  
1 0. 3. 2. 2  
Li  mit e d  P h ysi c al  E x a  mi n ati o ns  ........................................................................... 7 5  
1 0. 3. 2. 3  
B o d y   M ass,   B o d y S urf a c e   Ar e a (  B S  A)  a n d   H ei g ht   M e as ur e  m e nts  ..................... 7 5  
1 0. 3. 3  
B- S y  m pt o  ms  ........................................................................................................ 7 5  
1 0. 3. 4  
El e ctr o c ar di o gr a  m  ................................................................................................ 7 6  
1 0. 3. 5  
A d v ers e  E v e nt   M o nit ori n g  ................................................................................... 7 6  
1 0. 3. 6  
M o nit ori n g  of  S e c o n d  Pri  m ar y   M ali g n a n ci es  ...................................................... 7 6  
1 0. 3. 7  
L a b or at or y   Ass ess  m e nts  ...................................................................................... 7 6  
1 0. 3. 7. 1  
L a b or at or y  T esti n g  ............................................................................................... 7 6  
1 0. 3. 7. 2  
H e p atitis   Vir us  S er ol o g y  ...................................................................................... 7 9  
1 0. 3. 7. 3  
Pr e g n a n c y  T esti n g  ................................................................................................ 8 0  
1 0. 3. 7. 4  
P  K   Ass ess  m e nts  ................................................................................................... 8 0  
1 0. 3. 7. 5  
I  m  m u n o g e ni cit y ................................................................................................... 8 0  
1 0. 3. 8  
Effi c a c y   Ass ess  m e nts  ........................................................................................... 8 1  
1 0. 3. 8. 1  
T u  m o ur I  m a gi n g  .................................................................................................. 8 1  
1 0. 3. 9  
B o n e   M arr o  w  ....................................................................................................... 8 2  
1 1  S  A F  E  T  Y   M  O  NI  T  O  RI  N  G  .............................................................................................................. 8 3  
1 1. 1  D efi niti o n  of   A d v e rs e   E v e nts,  S e ri o us   A d v e rs e   E v e nts,   A d v e rs e   E v e nts  of  S p e ci al I nt e r est
 ............................................................................................................................................... 8 3  
1 1. 2  A d v e rs e   E v e nt  a n d  S e ri o us   A d v e rs e   E v e nt   R e c o r di n g  a n d   R e p o rti n g  ........................... 8 5  
1 1. 3  P r e g n a n ci es  ........................................................................................................................... 8 6  
1 2  D  A  T  A   H  A  N  D  LI  N  G   A  N  D   A  R  C  HI  VI  N  G  ..................................................................................... 8 8  
1 2. 1  C o  m pl eti n g  a n d  Si g ni n g   C a se   R e p o rt  F o r  ms  .................................................................... 8 8  
1 2. 2  Cli ni c al   D at a   M a n a g e  m e nt  .................................................................................................. 8 8  
1 2. 3  A r c hi vi n g  a n d  Fili n g  ............................................................................................................ 8 8  
1 3  S  T  A  TI S  TI  C  A  L   M  E  T  H  O  D S   A  N  D  P  L  A  N  N  E  D   A  N  A  L  Y S  E S  ..................................................... 8 9  
1 3. 1  P o p ul ati o ns f o r A n al ysis  ...................................................................................................... 8 9  
1 3. 2  G e n e r al  St atisti c al   M et h o ds  ................................................................................................ 9 0  
1 3. 3  P ati e nt   Dis p ositi o n,   B as eli n e  a n d   T r e at  m e nt   C h a r a ct e risti cs  .......................................... 9 0  
1 3. 4  A n al ysis  of   Effi c a c y   D at a  ..................................................................................................... 9 1  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 7  of 1 3 1  
1 3. 4. 1  
Ass ess  m e nt  of  Effi c a c y   V ari a bl es:   C o -Pri  m ar y  E n d p oi nts  .................................. 9 3  
1 3. 4. 2  
A n al ys es  of t h e  S e c o n d ar y  Effi c a c y  E n d p oi nts  ................................................... 9 4  
1 3. 4. 2. 1  
B est   O bj e cti v e   R es p o ns e   R at e  ............................................................................. 9 5  
1 3. 4. 2. 2  
D ur ati o n  of   R es p o ns e  ........................................................................................... 9 6  
1 3. 4. 2. 3  
Dis e as e   C o ntr ol   R at e  ............................................................................................ 9 6  
1 3. 4. 2. 4  
Ti  m e t o  Pr o gr essi o n  ............................................................................................. 9 6  
1 3. 4. 2. 5  
O v er all  S ur vi v al  ................................................................................................... 9 7  
1 3. 4. 2. 6  
Ti  m e t o   N e xt  Tr e at  m e nt  ....................................................................................... 9 7  
1 3. 5  Q u alit y  of   Lif e   Q u esti o n n ai r es   E  O  R  T  C   Q  L  Q -C 3 0  a n d E  Q- 5  D -5  L  ................................ 9 7  
1 3. 6  I  m  m u n o g e ni cit y   A n al ysis .................................................................................................... 9 8  
1 3. 7  P h a r  m a c o ki n eti c   A n al ysis  ................................................................................................... 9 8  
1 3. 8  A n al ysis  of  S af et y   D at a  ........................................................................................................ 9 8  
1 3. 8. 1  
A d v ers e  E v e nts  .................................................................................................... 9 8  
1 3. 8. 2  
Cli ni c al  L a b or at or y  E v al u ati o ns  .......................................................................... 9 9  
1 3. 8. 3  
P h ysi c al  E x a  mi n ati o n  ......................................................................................... 1 0 0  
1 3. 8. 4  
Vit al  Si g ns  .......................................................................................................... 1 0 0  
1 3. 8. 5  
El e ctr o c ar di o gr a  ms ( 1 2 -l e a d  E  C  G) .................................................................... 1 0 0  
1 3. 9  Bi o  m a r k e rs  ......................................................................................................................... 1 0 1  
1 3. 1 0  Ot h e r   D at a  .......................................................................................................................... 1 0 1  
1 3. 1 1  S a  m pl e  Si z e   D et e r  mi n ati o n  ............................................................................................... 1 0 1  
1 3. 1 1. 1  
P ar a  m et ers  a n d   R es ults  of  S a  m pl e  Si z e   D et er  mi n ati o n  ..................................... 1 0 1  
1 3. 1 2  I nt e ri  m   A n al ysis ................................................................................................................. 1 0 5  
1 3. 1 3  P r o c e d u r es f o r   Missi n g,   U n us e d,  a n d  S p u ri o us   D at a  ..................................................... 1 0 5  
1 3. 1 4  R ul es f o r   E x cl u di n g  P ati e nts f r o  m   A n al ysis  .................................................................... 1 0 5  
1 3. 1 5  P r o c e d u r es f o r   R e p o rti n g   D e vi ati o ns f r o  m   O ri gi n al  St atisti c al  Pl a n ............................ 1 0 6  
1 4  S P  E  CI  A  L   R  E  Q  UI  R  E  M  E  N  T S   A  N  D  P  R  O  C  E  D  U  R  E S  ............................................................... 1 0 6  
1 4. 1  I n d e p e n d e nt   D at a   M on it o ri n g   C o  m  mitt e e (I  D  M  C) ........................................................ 1 0 6  
1 4. 2  I n d e p e n d e nt   R a di ol o g y/  Cli ni c al   R e vi e  w   C o  m  mitt e e (I  R  C)  ........................................... 1 0 7  
1 4. 3  P r ot o c ol   A  m e n d  m e nts  a n d   Ot h e r   C h a n g es i n  St u d y   C o n d u ct  ...................................... 1 0 8  
1 4. 4  R e g ul at o r y  a n d   Et hi c al   C o nsi d e r ati o ns, I n cl u di n g t h e I nf o r  m e d   C o ns e nt  P r o c ess ..... 1 0 8  
1 4. 5  Q u alit y   C o nt r ol ( St u d y   M o nit o ri n g)  ................................................................................ 1 0 9  
1 4. 6  Q u alit y   Ass u r a n c e  .............................................................................................................. 1 0 9  
1 4. 7  I ns u r a n c e ............................................................................................................................ 1 0 9  
1 4. 8  P u bli c ati o n  P oli c y  ............................................................................................................... 1 1 0  
1 5  R  E F  E  R  E  N  C  E S ............................................................................................................................. 1 1 1  
1 6  A P P  E  N  DI  C  E S  .............................................................................................................................. 1 1 8  
1 6. 1  A p p e n di x   A:   C o c k c r oft -G a ult  F o r  m ul a  ........................................................................... 1 1 8  
1 6. 2  A p p e n di x   B:   Hi g hl y   Eff e cti v e   C o nt r a c e pti o n  .................................................................. 1 1 9  
1 6. 3  A p p e n di x   C:   O v e r vi e  w  of  p u blis h e d  d at a  o n   N  K  C  C  as  a  p r o g n osti c f a ct o r 
i n D  L  B  C  L  a n d  F  L  .............................................................................................................. 1 2 0  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 8  of 1 3 1  
1 6. 4  A p p e n di x   D:   K a r n ofs k y  P e rf o r  m a n c e  St at us  S c al e  ........................................................ 1 2 2  
1 6. 5  A p p e n di x   E:   N e  w   Y o r k   H e a rt   Ass o ci ati o n  F u n cti o n al   Cl assifi c ati o n  ........................... 1 2 3  
1 6. 6  A p p e n di x  F: I nf o r  m ati o n  o n I n v esti g ati o n al  a n d   R e gist e r e d  P r o d u cts  ........................ 1 2 4  
1 6. 7  A p p e n di x   G:   E q ui v al e nt   D os es f o r   C o rti c ost e r oi ds  ........................................................ 1 2 5  
1 6. 8  A p p e n di x   H:   B o d y  S u rf a c e   A r e a (  B S  A)   C al c ul ati o n  ...................................................... 1 2 6  
1 6. 9  A p p e n di x I:   A n n   A r b o r  St a gi n g - C ots  w ol ds   R e c o  m  m e n d ati o ns  .................................. 1 2 7  
1 6. 1 0  A p p e n di x  J: I nt e r n ati o n al  P r o g n osti c I n d e x (I PI)  .......................................................... 1 2 8  
1 6. 1 1  A p p e n di x   K:   E  C  O  G  P e rf o r  m a n c e  St at us  ........................................................................ 1 2 9  
1 6. 1 2  A p p e n di x   L:   R es p o ns e   C rit e ri a  ........................................................................................ 1 3 0  
 
2. 2  List  of   T a bl es  
( E x cl u di n g t h os e i n t h e  a p p e n di x) 
 
T a bl e  1:  
D efi niti o n  of I nf usi o n-R el at e d   R e a cti o n  ...................................................................... 5 1  
T a bl e  2:  
Crit eri a   R e q uir e d f or t h e I niti ati o n  of   B E  N  Tr e at  m e nts  ............................................... 5 3  
T a bl e  3:  
B E  N   D os e   R e d u cti o n   Crit eri a  ...................................................................................... 5 4  
T a bl e  4:  
B E  N   D os e  L e v els  ......................................................................................................... 5 5  
T a bl e  5:  
S c h e d ul e  of   Ass ess  m e nts  ............................................................................................. 6 4  
T a bl e  6:  
L a b or at or y  E v al u ati o ns  ................................................................................................ 7 8  
T a bl e  7:  
A n al ysis  S ets  ................................................................................................................ 8 9  
T a bl e  8:  
Ass u  m pti o ns f or  S a  m pl e  Si z e  Esti m ati o n ( ori gi n al st u d y  d esi g n  a n d  ass u  m pti o ns)  .. 1 0 2  
T a bl e  9:  
P o  w er   C al c ul ati o n f or   O v er all  P o p ul a ti o n  a n d t h e   N  K  C  C-l o  w  S u b gr o u p ( as  a 
c o ns e q u e n c e  of  al p h a s plitti n g)  u n d er  diff er e nt s c e n ari os  ......................................... 1 0 3  
T a bl e  1 0:  
O p er ati n g   C h ar a ct eristi cs f or   O S  at t h e  Fi n al   A n al ysis .............................................. 1 0 4  
T a bl e  1 1:  
P o  w er   A n al ys es f or   O S  .............................................................................................. 1 0 4  
T a bl e  1 2:  
I  D  M  C   D e cisi o n   G ui d e   B as e d  o n   R es ults  of t h e I nt eri  m   A n al ysis ( n o n-bi n di n g)  ...... 1 0 5  
 
2. 3  List  of  Fi g u r es  
Fi g ur e  1:  
R e cr uit  m e nt  a n d  St u d y  Fl o  w  ........................................................................................ 3 7  
Fi g ur e  2:  
St u d y   D esi g n  ................................................................................................................ 3 8  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 9  of 1 3 1  
3  LI S  T   O F   A  B  B  R  E  VI  A  TI  O  N S   A  N  D   D  E FI  NI  TI  O  N S   O F   T  E  R  M S  
A  B  C  
A cti v at e d   B -c ell 
A  D  C  C  
A nti b o d y -d e p e n d e nt c ell-m e di at e d  c yt ot o xi cit y 
A  D  C P  
A nti b o d y -d e p e n d e nt  c ell -m e di at e d  p h a g o c yt osis  
A E  
A d v ers e  e v e nt  
A E SI  
A d v ers e  e v e nt  of s p e ci al i nt er est  
A L L  
A c ut e l y  m p h o bl asti c l e u k a e  mi a  
A L T  
Al a ni n e tr a ns a  mi n as e  
A  N  C  
A bs ol ut e  n e utr o p hil  c o u nt  
a nti-H  B c  
H e p atitis   B vir us c or e  a nti b o d y  
a nti-H  C  V  
H e p atitis   C  vir us  a nti b o d y  
A S  C T  
A ut ol o g o us st e  m -c ell tr a ns pl a nt ati o n  
A S T  
As p art at e  a  mi n otr a nsf er as e  
A T  C  
A n at o  mi c al  T h er a p e uti c   C h e  mi c al ( cl ass)  
B  C L 2/ 6  
B- c ell   C L L/l y  m p h o  m a  2/ 6  
B  C  R 
B- c ell  a nti g e n r e c e pt or  
B E  N 
B e n d a  m usti n e  
b p  m  
B e ats  p er   mi n ut e ( h e art r at e)  
B S  A  
B o d y s urf a c e  ar e a  
B S  C 
B est s u p p orti v e  c ar e  
C 1  D 4  
C y cl e  1   D a y  4  
C  D  C  
C o  m pl e  m e nt  d e p e n d e nt  c yt ot o xi cit y  
C  D 1 6/ 1 9 / 2 0 
Cl ust er  of  diff er e nti ati o n 1 6/ 1 9 / 2 0 
C  H  O P  
C y cl o p h os p h a  mi d e,  h y dr o x y d a u n or u bi ci n ( als o r ef err e d t o  as  d o x or u bi ci n  or 
a dri a  m y ci n),  o n c o vi n ( vi n cristi n e)  a n d  pr e d nis o n e  or  pr e d nis ol o n e   
CI 
C o nfi d e n c e i nt er v al  
C L L 
C hr o ni c l y  m p h o c yti c l e u k a e  mi a  
C  N S  
C e ntr al  n er v o us s yst e  m  
C  O P  D  
C hr o ni c o bstr u cti v e  p ul  m o n ar y  dis e as e  
C P  H 
C o x  pr o p orti o n al  h a z ar ds  
C  R 
C o  m pl et e r es p o ns e /r e  missi o n 
C  R  O 
C o ntr a ct r es e ar c h o r g a nis ati o n 
C T 
C o  m p ut e d t o  m o gr a p h y  
C T  C  A E 
C o  m  m o n  T er  mi n ol o g y   Crit eri a f or   A d v ers e  E v e nts  
C T F  G  
Cli ni c al  Tri al  F a cilit ati o n   Gr o u p  
D  A -E P  O  C  H -R  
D os e -a dj ust e d  E P  O  C  H -R (et o p osi d e, p r e d nis o n e, o n c o vi n  [ vi n cristi n e], 
cy cl o p h os p h a  mi d e  a nd  h y dr o x y d a u n or u bi ci n  [d o x or u bi ci n ] pl us rit u xi  m a b ) 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 0  of 1 3 1  
D  C  R  
Dis e as e  c o ntr ol r at e  
D  H  A P  
Cis pl ati n,  c yt ar a bi n e,  d e x a  m et h as o n e  
D L  B  C L  
Diff us e l ar g e   B -c ell l y  m p h o  m a  
D L  C  O  
Diff usi o n  c a p a cit y  of t h e l u n g f or  c ar b o n   m o n o xi d e  
D  N  A  
D e o x yri b o n u cl ei c  a ci d  
D o  R  
D ur ati o n  of r es p o ns e  
D P  
Dr u g  pr o d u ct  
E  B  V  
E pst ei n -B arr  vir us  
E  C  G  
El e ctr o c ar di o gr a  m  
E  C  O  G  
E ast er n   C o o p er ati v e   O n c ol o g y   Gr o u p  
e  C  R F  
El e ctr o ni c  c as e r e p ort f or  m  
E  D T  A  
Et h yl e n e di a  mi n et etr a a c eti c  a ci d  
E  M  A  
E ur o p e a n M e di ci n es   A g e n c y  
E  O  R T  C   Q L  Q -C 3 0  
E ur o p e a n   Or g a nis ati o n f or   R es e ar c h  a n d  Tr e at  m e nt  of   C a n c er   Q u alit y  of  Lif e 
Q u esti o n n air e -C or e  3 0  
E  O T  
E n d  of tr e at  m e nt  
E  Q -5  D -5 L  
E ur o  Q ol  fi v e  di  m e nsi o ns  q u alit y  of lif e  q u esti o n n air e,  5 l e v els 
E S  H  A P  
Et o p osi d e,   m et h yl pr e d nis o n e,  c yt ar a bi n e,  cis pl ati n  
E u dr a  C T  
E ur o p e a n   U ni o n   Dr u g   R e g ul ati n g   A ut h oriti es   Cli ni c al  Tri als r e gist er  
F  A S  
F ull  a n al ysis s et  
F  C  B P  
F e  m al e  of  c hil d b e ari n g  p ot e nti al  
F c γ  R  
F c  g a  m  m a r e c e pt or  
F  D  A  
F o o d  a n d   Dr u g   A d  mi nistr ati o n  
F  D  G  
[1 8F]fl u or o d e o x y gl u c os e  
F E  V -1  
F or c e d  e x pir at or y  v ol u  m e i n  1 s e c o n d  
FI S  H  
Fl u or es c e n c e i n sit u h y bri dis ati o n  
F L  
F olli c ul ar l y  m p h o  m a  
F  N  A  
Fi n e  n e e dl e  as pir at e  
F  U  
F oll o  w -u p  
F  V  C  
F or c e d  vit al c a p a cit y 
G  C  B  
G er  mi n al  c e ntr e   B -c ell  
G  C P  
G o o d   Cli ni c al  Pr a cti c e  
G -C S F  
G r a n ul o c yt e  c ol o n y-sti  m ul ati n g f a ct or 
G  G T  
G a  m  m a -gl ut a  m yltr a nsf er as e  
G L P  
G o o d  L a b or at or y  Pr a ct ic e 
H  Bs  A b  
H e p atitis   B vir us s urf a c e  a nti bo d y  
H  Bs  A g  
H e p atitis   B vir us s urf a c e a nti g e n 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 1  of 1 3 1  
H  B  V  
H e p atitis   B  vir us  
H  C  V  
H e p atitis   C  vir us  
H  D  C  
Hi g h -d os e  c h e  m ot h er a p y  
HI  V  
H u  m a n i  m  m u n o d efi ci e n c y  vir us  
H  R  
H a z ar d r ati o  
I  A S 
I  m  m u n o g e ni cit y  a n al ysis s et 
I  B 
I n v esti g at or’s B r o c h ur e 
I  C E 
If osf a  mi d e,  c ar b o pl ati n,  et o p osi d e 
I  C F 
I nf or  m e d c o ns e nt f or  m  
I  C  H 
I nt er n ati o n al   C o nf er e n c e  o n   H ar  m o nis ati o n 
I  D  M  C 
I n d e p e n d e nt   D at a   M o nit ori n g   Co  m  mitt e e  
I E  C 
I n d e p e n d e nt  Et hi cs   C o  m  mitt e e 
I g 
I  m  m u n o gl o b uli n 
I  N  D 
I n v esti g ati o n al   N e  w   Dr u g  a p pli c ati o n 
I  N  N 
I nt er n ati o n al   N o n-pr o pri et ar y   N a  m e  
I PI 
I nt er n ati o n al P r o g n osti c In d e x  
I  R  B 
I nstit uti o n al   R e vi e  w   B o ar d 
I  R  C 
I n d e p e n d e nt   R a di ol o g y/  Cli ni c al   R e vi e  w   C o  m  mitt e e 
I  R  R 
I nf usi o n-r el at e d r e a cti o n 
I  R T 
I nt er a cti v e r es p o ns e t e c h n ol o g y 
I  V 
I ntr a v e n o us(l y) 
L  
Li  mit e d ( p h ysi c al  e x a  mi n ati o n)  
L  D  H  
L a ct at e  d e h y dr o g e n as e  
L E  N  
L e n ali d o  mi d e  
m  A b  
M o n o cl o n al  a nti b o d y  
M  C L  
M a ntl e   C ell  L y  m p h o  m a  
M e d  D  R  A  
M e di c al   Di cti o n ar y f or   R e g ul at or y   A cti viti es  
M  RI  
M a g n eti c r es o n a n c e i  m a gi n g  
M  Y  C  
v -m y c  a vi a n   m y el o c yt o  m at osis  vir al  o n c o g e n e  h o  m o lo g  
N  A b  
N e utr alisi n g  a nti b o d y  
N  CI  
N ati o n al   C a n c er I nstit ut e  
N  H L  
N o n -H o d g ki n l y  m p h o  m a  
N  K  
N at ur al  kill er  
N  K  C  C  
N at ur al  kill er  c ell  c o u nt  
N  K  C  C -hi g h  
Hi g h  b as eli n e  n at ur al  kill er  c ell  c o u nt  
N  K  C  C -l o  w 
L o  w  b as eli n e  n at ur al  kill er  c ell  c o u nt  
N  O S  
N ot  ot h er  wis e s p e cifi e d  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 2  of 1 3 1  
N S  AI  D  
N o nst er oi d al  a nti -i nfl a  m  m at or y  dr u g 
N  Y  H  A  
N e  w   Y or k   H e art   Ass o ci ati o n  
O  R  R  
O bj e cti v e r es p o ns e r at e ( c o  m pl et e r es p o ns e  +  p arti al r es p o ns e) 
O S  
O v er all s ur vi v al  
P  B  M  Cs  
P eri p h er al  bl o o d   m o n o n u cl e ar  c ells  
P  D  
P h ar  m a c o d y n a  mi c (s) 
P E  
P h ysi c al  e x a  mi n ati o n  
P E T  
P ositr o n  e  missi o n t o  m o gr a p h y  
P F S  
Pr o gr essi o n -fr e e s ur vi v al 
P  K  
P h ar  m a c o ki n eti c (s) 
P  K  A S  
P  K  a n al ysis s et  
P L T  
Pl at el et  
P  M  B L  
P ri  m ar y   m e di asti n al l ar g e   B-c ell l y  m p h o  m a 
p. o.  
p er  os ,  by   m o ut h  
P P S  
P er -pr ot o c ol s et  
P  R  
P arti al r es p o ns e /r e  missi o n 
P  R ( E  C  G)  
P  R i nt er v al  
Q o L  
Q u alit y  of lif e  
Q  R S  
Q  R S i nt er v al  
Q T  
Q T i nt er v al  
Q T c  
C orr e ct e d Q T i nt er v al  
Q T c  B  
B a z ett’s Q T i nt er v al c orr e cti o n  
Q T c F  
Fri d eri ci a’s   Q T i nt er v al c orr e cti o n  
R  
R a n d o  mi z ati o n  
R  B  C  
R e d  bl o o d  c ell  
R -C  H  O P  
Rit u xi  m a b  pl us c y cl o p h os p h a  mi d e,  h y dr o x y d a u n or u bi ci n ( als o r ef err e d t o  as 
d o x or u bi ci n  or  a dri a  m y ci n),  o n c o vi n ( vi n cristi n e)  a n d  pr e d nis o n e  or 
pr e d nis ol o n e   
R  N  A  
Ri b o n u cl ei c  a ci d  
rp  m  
R es pir ati o ns  p er   mi n ut e (r es pir ati o n r at e)  
R  R ( E  C  G)  
R el ati v e r at e  
R -R   C L L  
R el a ps e d  or r efr a ct or y  c hr o ni c l y  m p h o c yti c l e u k a e  mi a 
R -R   D L  B  C L  
R el a ps e d  or r efr a ct or y  diff us e l ar g e   B -c ell l y  m p h o  m a  
R -R   N  H L  
R el a ps e d  or r efr a ct or y  n o n -H o d g ki n l y  m p h o  m a  
R T  X  
Rit u xi  m a b  
S  A E  
S eri o us  a d v ers e  e v e nt  
S  A F  
S af et y  a n al ysis s et  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 3  of 1 3 1  
S  A P  
St atisti c al A n al ysis  Pl a n  
S  CI  D  
S e v er e  c o  m bi n e d i  m  m u n o d efi ci e n c y  
S  D  
St a bl e  dis e as e  
S L L  
S  m all l y  m p h o c yti c l y  m p h o  m a  
S  m P  C  
S u  m  m ar y  of  Pr o d u ct   C h ar a ct eristi cs  
S  O  C  
S yst e  m   Or g a n   Cl ass  
S  O P  
St a n d ar d  o p er ati n g  pr o c e d ur e  
S P  D  
S u  m  of t h e  pr o d u ct  of t h e  di a  m et ers  
S P  M  
S e c o n d  pri  m ar y   m ali g n a n c y  
T  B  
T u b er c ul osis  
T E  A E  
Tr e at  m e nt -e  m er g e nt  a d v ers e  e v e nt  
T E  N  
T o xi c  e pi d er  m al  n e cr ol ysis  
T  H  R L  B  C L  
T  c ell/ histi o c yt e ri c h l ar g e   B -c ell l y  m p h o  m a  
T L S  
T u  m o ur l ysis s y n dr o  m e  
T  N  M  
T u  m o ur/  N o d e/  M et ast asis  
T T P  
Ti  m e t o pr o gr essi o n  
T T  N T  
Ti  m e t o  n e xt tr e at  m e nt  
U L  N  
U p p er li  mit  of  n or  m al  
U S  
U nit e d  St at es  
U S  A  N  
U nit e d  St at es   A d o pt e d   N a  m e  
V  A S  
Vis u al a n al o g u e s c al e 
VI  M  
Et o p osi d e, if osf a  mi d e,   m et h otr e x at e  or   mit o x a ntr o n e  
W  B  C  
W hit e  bl o o d  c ell  
W FI  
W at er f or i nj e cti o n 
W  H  O  
W orl d   H e alt h   Or g a ni z ati o n  
β -H  C  G  
B et a -h u  m a n  c h ori o ni c  g o n a d otr o pi n  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 4  of 1 3 1  
4  B  A  C  K  G  R  O  U  N  D  
4. 1  O v e r vi e  w  of   N o n -H o d g ki n   L y  m p h o  m a s 
N o n -  H o d g ki n l y  m p h o  m as (N  H Ls )  a c c o u nt f or  a p pr o xi  m at el y  5  %  of  all  n e  w  c a n c er  c as es  a n d 
c o  m pris e  a  h et er o g e n e o us  gr o u p  of l y  m p h o pr olif er ati v e   m ali g n a n ci es,   w hi c h i n  9 0  %  of  c as es  ar e 
d eri v e d fr o  m   B -c ells. 
 
Diff us e l ar g e   B - c ell l y  m p h o  m a (  D L  B  C L), t h e   m ost  c o  m  m o n   N  H L,  a c c o u nts f or  a p pr o xi  mat el y 
3 0  %  of   N  H Ls (Ar  mit a g e  a n d   W eis e n b ur g er  1 9 9 8 , S  w er dl o  w  et  al.  2 0 0 8 ) a n d  c o  m pris es  6 0  %  of 
all  n e  w l y  m p h o  m as i n t h e  el d erl y (T hi e bl e  m o nt  a n d   C oiffi er  2 0 0 7 ). T h er e is  a sli g ht 
pr e d o  mi n a n c e  of t h e   m al e  g e n d er ( 5 5  %) (M ort o n  et  al.  2 0 0 6 ).   D L  B  C L i n ci d e n c e i n cr e as es   wit h 
a g e, wit h  a   m e di a n  a g e  at  di a g n osis  of  6 4  y e ars (S h e n o y  et  al.  2 0 1 1 ). 
 
At  pr es e nt, D L  B  C L  n ot  ot h er  wis e s p e cifi e d (  N  O S)  c a n  b e f urt h er s u b di vi d e d i nt o  at l e ast 
t  w o   m ol e c ul ar  gr o u ps  b y  g e n e  e x pr essi o n  pr ofili n g:  g er  mi n al  c e ntr e   B-c ell (  G  C  B)  a n d  a cti v at e d 
B- c ell (  A  B  C)  s u bt y p es (R os e n  w al d  et  al.  2 0 0 2 , L e n z  et  al.  2 0 0 8 ). 
 
4. 2  T r e at  m e nt  of   D  L  B  C  L  
First -li n e tr e at  m e nt  e ns ui n g im  m e di at el y  aft er  di a g n osis  a n d st a gi n g  of   D L  B  C L  a n d  c o  m prisi n g 
rit u xi  m a b (  R T  X)  c o  m bi n e d   wit h C  H  O P  c h e  m ot h er a p y  (  R-C  H  O P:   R T  X pl us  c y cl o p h os p h a  mi d e, 
d o x or u bi ci n,  vi n cristi n e,  a n d  pr e d nis o n e ) is  c urr e ntl y t h e st a n d ar d  of  c ar e (C oiffi er  et  al.  2 0 0 2 , 
F e u gi er  et  al.  2 0 0 5 , H a b er  m a n n  et  al.  2 0 0 6).  Th e   R- C  H  O P r e gi  m e n is  a  “ pl atf or  m ”  c o  m bi n ati o n 
t h er a p y,   w hi c h   m a y  b e   m o difi e d i n  or d er t o i n cr e as e its t h er a p e uti c  effi c a c y,  e. g.   D  A-E P  O  C  H -R 
( d os e- a dj ust e d  et o p osi d e,  pr e d nis o n e,  o n c o vi n,  c y cl o-p h os p h a  mi d e  a n d  h y dr o x y d a u n or u bi ci n 
pl us rit u xi  m a b;  Wils o n  et  al. ( 2 0 1 2) .   Ne v ert h el ess,  e v e n   wit h t h e  a v ail a bilit y  of   R -C  H  O P -li k e 
tr e at  m e nt r e gi  m e ns,  a p pr o xi  m at el y  4 0– 5 0  %  of  p ati e nts   will  ulti  m at el y s u c c u  m b t o t h e  dis e as e, 
wit h  3 0 – 4 0  %  of p ati e nts r el a psi n g a n d  1 0  %  h a vi n g  a  di a g n osis  of  pri  m ar y  pr o gr essi v e  dis e as e  or 
b ei n g  n o n-r es p o n d ers (Pfr e u n ds c h u h  et  al.  2 0 0 8 , Pfr e u n ds c h u h  et  al.  2 0 1 1 ). 
 
P ati e nts  pr o gr essi n g  or r el a psi n g  aft er first -li n e tr e at  m e nt   will  b e  e v al u at e d f or t h eir  eli gi bilit y 
f or i nt e nsifi e d s al v a g e tr e at  m e nt str at e gi es   w hi c h  c a n l e a d t o l o n g-t er  m r e  missi o ns.  E x a  m pl es of 
s u c h s al v a g e  c h e  m ot h er a p y i n cl u d e   D  H  A P ( cis pl ati n,  c yt ar a bi n e,  d e x a  m et h as o n e),   VI  M 
( et o p osi d e, if osf a  mi d e,   m et h otr e x at e  or   mit o x a ntr o n e), I  C E (if osf a  mi d e,  c ar b o pl ati n,  et o p osi d e) 
a n d  E S  H  A P ( et o p osi d e,   m et h yl pr e d nis o n e,  c yt ar a bi n e,  cis pl ati n).  F or  p ati e nts   wit h 
c h e  m ot h er a p y- s e nsiti v e  dis e as e,  a ut ol o g o us st e  m-c ell tr a ns pl a nt ati o n  (  A S  C T)  as  c o ns oli d ati o n 
t h er a p y si g nifi c a ntl y i  m pr o v es t h e  o ut c o  m e  of s e c o n d-li n e t h er a p y.   A p pr o xi  m at el y  1 0 – 5 0  %  of 
p ati e nts tr e at e d   wit h a n i nt e nsifi e d r e gi  m e n i n s e c o n d-li n e  a c hi e v e  a l o n g-t er  m r e  missi o n  a n d 
c ur e (P hili p  et  al.  1 9 9 5 ). 
 
U nf ort u n at el y,  o nl y  a p pr o xi  m at el y  5 0  %  of  p ati e nts wit h r el a ps e d  or r efr a ct or y ( R-  R) D L  B  C L  ar e 
eli gi bl e f or a n i nt e nsifi e d tr e at  m e nt str at e g y, d u e   m ai nl y t o  c ar di a c  c o  m or bi diti es,  d e cr e as e d 
h a e  m at o po i eti c r es er v e, r e d u c e d  h e p ati c f u n cti o n or  a d v a n c e d  a g e, r estri cti n g t h e b e n efit  of t his 
a g gr essi v e  a p pr o a c h t o  a r el ati v el y s  m all s u bs et  of  p ati e nts (M orris o n  et  al.  2 0 1 4 ).  Si  mil arl y, 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 5  of 1 3 1  
o nl y  y o u n g er  a n d fit  p ati e nts  c a n  b e  e v al u at e d f or  all o g e n ei c st e  m c ell tr a ns pl a nt ati o n (Tr u el o v e 
et  al.  2 0 1 4). 
 
S e v er al tr e at  m e nt r e gi  m e ns  h a v e  b e e n d es cri b e d f or p ati e nts t h at r el a ps e  aft er i nt e nsifi e d 
s e c o n d-li n e tr e at  m e nt  or   w h o  ar e  n ot  eli gi bl e f or a n i nt e nsifi e d s e c o n d-li n e r e gi  m e n. D es pit e 
r e c e nt  a d v a n c es, t h e tr e at  m e nt  o pti o ns f or  p ati e nts   w h o  h a v e r el a ps e d  or  pr o gr ess e d  aft er 
s e c o n d-li n e tr e at  m e nt  of   D L  B  CL ,  or   w h o  ar e  n ot  eli gi bl e f or   A S  C T r e  m ai n li  mit e d.    
  
 
O n  3 1 J ul y  2 0 2 0, t h e   U. S.  F o o d  a n d   Dr u g   A d  mi nistr ati o n ( F  D  A)  a ut h ori z e d t af asit a  m a b-c xi x 
(  M o nj u vi  ®) i n  c o  m bi n ati o n   wit h l e n ali d o  mi d e f or   m ar k eti n g  u n d er t h e  pr o visi o n  of  ac c el er at e d 
a p pr o v al f or t h e tr e at  m e nt  of  a d ult  p ati e nts   wit h   R/  R   D L  B  C L. T af asit a  m a b -c xi x (  Mi nj u vi ® )  h as 
als o  b e e n  a p pr o v e d f or   m ar k eti n g ( c o n diti o n al  a p pr o v al) i n  E  U  ( 2 6   A u g ust  2 0 2 1), i n   U  K 
( 0 8 O ct o b er  2 0 2 1)   a n d i n   C a n a d a ( 1 9   A u g ust  2 0 2 1) i n  c o  m bi n ati o n   wit h l e n ali d o  mi d e f or t h e 
tr e at  m e nt  of  a d ult  p ati e nts   wit h   R/  R   D L  B  C L. 
 
Alt h o u g h   R T  X is   wi d el y  us e d i n t h e tr e at  m e nt  of   R- R   D L  B  C L f oll o  wi n g   R T  X -b as e d first -li n e 
t h er a p y,  cli ni c al st u di es  h a v e  d e  m o nstr at e d t h at  p ati e nts   w h o  h a v e r e c ei v e d  pri or   R T  X  ar e l ess 
li k el y t o r es p o n d t o   R T  X-c o nt ai ni n g s al v a g e t h er a pi es (M arti n  et  al.  2 0 0 8 , Giss el br e c ht  et  al. 
2 0 1 0 ).  Th er ef or e, t h e  d e v el o p  m e nt  of   m or e  eff e cti v e s al v a g e t h er a p y is  ess e nti al t o i  m pr o v e 
l o n g-t er  m  o ut c o  m es. 
 
M o n o cl o n al  a nti b o d y (  m  A b) t h er a p y   m a y h a v e t h e  p ot e nti al t o i  m pr o v e  o bj e cti v e r es p o ns e r at es 
(  O  R  Rs)  a n d o v er all s ur vi v al ( O S ) i n t his s etti n g wit h o ut i n cr e asi n g  h a e  m at ol o gi c al t o xi cit y.  T his 
p ossi bilit y is s u p p ort e d  b y  d at a fr o  m st u di es i n v esti g ati n g   C  D 1 9   m  A bs, i n cl u di n g   M  D  X- 1 3 4 2, 
S  A  R 3 4 1 9  a n d M E  DI - 5 5 1 (B ar g o u  et  al.  2 0 0 8 , Vi ar d ot  et  al.  2 0 1 1 , Y o u n es  et  al.  2 0 1 2 , 
M atl a  ws k a -  W as o  ws k a  et  al.  2 0 1 3, Ri br a g  et  al.  2 0 1 4 ). 
 
4. 3  B e n d a  m usti n e i n   D  L  B  C  L   T r e at  m e nt  
B e n d a  m usti n e (  B E  N ) is  a  c h e  m ot h er a p e uti c  a g e nt, s y nt h esis e d  as  a  h y bri d  of  a  p uri n e  a n al o g u e 
a n d  a n  al k yl at or. It h as  b e e n  d e  m o nstr at e d  i n  vitr o t h at   B E  N is  a cti v e i n c ell li n es   w hi c h  ar e 
r esist a nt t o s e v er al  ot h er  al k yl ati n g  a g e nts (B alf o u r  a n d   G o a  2 0 0 1, L e o ni  et  al.  2 0 0 8 ).  Th e 
m e c h a nis  m  of  a cti o n  of   B E  N is  n ot f ull y  el u ci d at e d  b ut i n v ol v es t  w o s e p ar at e   m et a b oli c 
p at h  w a ys,  o n e l e a di n g t o  d e o x yri b o n u cl ei c  a ci d (  D  N  A)  d a  m a g e,  pr o v o ki n g  a p o pt osis  a n d 
a n ot h er l e a di n g t o t h e  disr u pti o n  of  c ell  di visi o n.  T h e l att er   m e c h a nis  m is  k n o  w n  as   mit oti c 
c at astr o p h e.  T h e  d u al  eff e ct   m a y  b e  attri b ut a bl e t o t h e  c h e  mi c al str u ct ur e  of t h e   B E  N   m oi et y, 
w hi c h  c o  m pris es  a  2 -c hl or o et h yl a  mi n e  al k yl ati n g  gr o u p,  a  b e n zi  mi d a z ol e ri n g,  a n d  a  b ut yri c  a ci d 
si d e  c h ai n (L e o ni  et  al.  2 0 0 8 , L e o ni  2 0 1 1 ). 
 
B E  N is  a p pr o v e d i n s e v er al c o u ntri es   w orl d  wi d e f or t h e tr e at  m e nt  of  p ati e nts   wit h r el a ps e d 
r efr a ct or y i n d ol e nt l y  m p h o  m as,  c hr o ni c l y  m p h o c yti c l e u k a e  mi a (C L L )  a n d i n s o  m e  c o u ntri es, f or 
m ulti pl e   m y el o  m a.  
 
B E  N   w as  st u di e d  as   m o n ot h er a p y  a n d i n  c o  m bi n ati o n   wit h  ot h er  c h e  m ot h er a p e uti c  a n d/ or 
bi ol o gi c al  a g e nts ( e. g.   R T  X) i n   R-  R a g gr essi v e   N  H L,  yi el di n g O  R  R s fr o  m  3 2% t o  6 2. 7  %, wit h 
m e di a n pr o gr essi o n -fr e e s ur vi v al (P F S ) ti  m es  b et  w e e n  3. 6  a n d  6. 7   m o nt hs. Si  mil arl y , t h e 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 6  of 1 3 1  
c o  m bi n ati o n  of   B E  N  a n d   R T  X  us e d  as first- li n e tr e at  m e nt i n  p ati e nts n ot  eli gi bl e f or i nt e nsi v e 
c h e  m ot h er a p y r e gi  m e ns a c hi e v e d a n O  R  R  of 6 9  %, i n cl u di n g l o n g- l asti n g  c o  m pl et e r e  missi o ns, 
a n d  a   m e di a n  P F S  of  7. 7   m o nt hs (W ei d  m a n n  et  al.  2 0 0 2 , O g ur a  et  al.  2 0 1 1 , H or n  et  al.  2 0 1 2 , 
Ri g a c ci  et  al.  2 0 1 2 , W alt er  et  al.  2 0 1 2 , O h  m a c hi  et  al.  2 0 1 3 , V a cir c a  et  al.  2 0 1 4 ). 
T h er ef or e,  it   m a y  b e  c o n cl u d e d t h at R T  X wit h  B E  N c o  m p ar es f a v o ur a bl y i n t er  ms  of  effi c a c y 
wit h  ot h er r e gi  m e n s f or t his  diffi c ult-t o-tr e at  p ati e nt  p o p ul ati o n (C ol osi a  et  al.  2 0 1 4 ). It is 
es p e ci all y r el e v a nt gi v e n  t h at t h e  c o  m bi n ati o n  of R T  X wit h  B E  N  d e  m o nstr at es  a   m a n a g e a bl e 
t o xi cit y  pr ofil e  a n d c a n t h er ef or e  b e  us e d i n  el d erl y  p ati e nts  a n d/ or  p ati e nts   wit h  c o  m or bi diti es. 
I n t h e t  w o l ar g est  a n d   m ost r e c e ntl y  p u blis h e d st u di es i n   R-R   D L  B  C L , t h e  c o  m bi n ati o n  of R T  X 
wit h    B E  N  e v o k e d  pr e d o  mi n a ntl y  h ae  m at ol o gi cal t o xi citi es i n cl u di n g  n e utr o p e ni a, l e u k o p e ni a, 
t hr o  m b o c yt o p e ni a  a n d  a n ae  mi a.  T h e m y el os u p pr essi o n   w as l ar g el y r e v ersi bl e.   C o  m  m o n 
n o n- h a e  m at ol o gi c al a d v ers e  e v e n ts (A Es ) i n cl u d e d  g astr oi nt esti n al s y  m pt o  ms ( e. g., di arr h o e a, 
c o nsti p ati o n,  n a us e a), i nf e cti o ns  a n d f ati g u e (O h  m a c hi  et  al.  2 0 1 3 , V a cir c a  et  al.  2 0 1 4 ). 
 
D u e t o its f a v ou r a bl e  effi c a c y a n d  a d v a nt a g e o us t o xi cit y  pr ofil e t h e  c o  m bi n ati o n  of R T  X   wit h 
B E  N  b e c a  m e  a st a n d ar d  of  c ar e f or t h e tr e at  m e nt  of p ati e nts   wit h D L  B  C L  o v er r e c e nt y e ars.  
 
4. 4  O v e r vi e  w  of  n at u r al  k ill e r (  N  K) c ells i n l y  m p h o  m a , r el e v a n c e t o 
M  O  R 0 0 2 0 8   
S e v er al  p u blis h e d st u di es  h a v e  e v al u at e d  cli ni c al  o ut c o  m es i n r el ati o n t o  hi g h  or l o  w  b as eli n e 
N  K  C  C i n first -li n e  p ati e nts,  e. g.,  p ati e nts  n e  wl y  di a g n os e d wit h D L  B  C L (Ki  m  et  al.  2 0 1 4 , 
Kl a n o v a  et  al.  2 0 1 7 )  or  pr e vi o usl y  u ntr e at e d  pati e nts wit h f olli c ul ar l y  m p h o  m a ( F L)  (H e  et  al. 
2 0 1 6 , Kl a n o v a  et  al.  2 0 1 7 ).  
I n t h e   M  O  R 2 0 8  C 2 0 1 st u d y  a  c ut-off  1 0 0   N  K  c ells/ µ L   w as  pr o g n osti c f or t h e tr e at  m e nt  o ut c o  m e 
of M  O  R 0 0 2 0 8   m o n ot h er a p y i n   D L  B  C L  a n d  F L,   w hil e  ot h er  bl o o d  c ell  p o p ul ati o ns s u c h  as 
l y  m p h o c yt es  a n d  T  c ells s h o  w e d  n o  ass o ci ati o n   wit h t h e tr e at  m e nt  o ut c o  m e.  E v e n t h o u g h  a 
m ulti v ari at e  a n al ysis   w as  n ot  c o n d u ct e d  d u e t o t h e s  m all s a  m pl e si z e,  a str atifi e d  a n al ysis  di d  n ot 
r e v e al  a n y  o b vi o us  c o nf o u n di n g  of t h e   N  K  C  C s u b gr o u ps   wit h  a n y  ot h er  k e y  b as eli n e 
c h ar a ct eristi cs.  T h er ef or e,   N  K  C  C  p ot e nti all y is a n i n d e p e n d e nt f a ct or f or t h e tr e at  m e nt  o ut c o  m e 
of M  O  R 0 0 2 0 8. 
Si  mil ar t o t h e  o bs er v ati o n f or M  O  R 0 0 2 0 8, t h e   m aj orit y  of t h e  p u blis h e d st u di es f or  a nti- C  D 2 0 
a nti b o di es  als o r e p ort e d  a   N  K  C  C  c ut- off  of  1 0 0  c ells/ µ L,   w hi c h s h o  w e d i n d e p e n d e nt  pr o g n osti c 
v al u e.  T h e  c ut- off   w as  g e n er all y  b as e d  o n   m a xi  mi z e d  diff er e n c es i n  P F S  a n d/ or   O S  b et  w e e n 
p ati e nts   wit h  b as e li n e   N  K  C  C-l o  w  a n d   N  K  C  C- hi g h i n cl u d e d i n t h e r es p e cti v e st u di es (Ki  m  et  al. 
2 0 1 4 , H e  et  al.  2 0 1 6 , Kl a n o v a  et  al.  2 0 1 7 ).  
I n t  w o l ar g e  p h as e III tri als i n  p ati e nts   wit h   N  H L – t h e   G  O  Y  A tri al (  N  C T 0 1 2 8 7 7 4 1) i n  p ati e nts 
wit h  n e  wl y  di a g n os e d   D L  B  C L  a n d t h e   G  A L LI  U  M tri al (  N  C T 0 1 3 3 2 9 6 8) i n  p ati e nts   wit h 
pr e vi o usl y  u ntr e at e d  F L  – t h e  pr o g n osti c  c ut-off  of  1 0 0   N  K  c ells/ µ L   w as  als o  us ef ul t o  pr e di ct 
s u p eri orit y  of  a n  F c- e n h a n c e d  a nti-  C  D 2 0   m o n o cl o n al  a nti b o d y ( o bi n ut u z u  m a b)  v ers us  a 
n o n- e n h a n c e d  a nti   C  D 2 0   m o n o cl o n al  a nti b o d y (  R T  X).  T his  d e  m o nstr at es t h at  a   N  K  C  C  c ut- off 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 7  of 1 3 1  
i d e ntifi e d  vi a t h e  pr o g n osti c  eff e ct  c a n  b e  als o  us ef ul t o  pr e di ct s u p eri orit y  of  o n e   m o n o cl o n al 
a nti b o d y  o v er  a n ot h er. 
T h e s p o ns or  c o n d u ct e d  pr e- cli ni c al  e x p eri  m e nts t o i n v esti g at e t h e i n  vitr o   A  D  C  C  a cti vit y  of t h e 
F c - e n h a n c e d   C  D 1 9-s p e cifi c  a nti b o d y M  O  R 0 0 2 0 8 i n  c o  m p aris o n t o t h e   C  D 2 0-s p e cifi c  a nti b o d y 
rit u xi  m a b f or  a r a n g e  of  eff e ct or t o t ar g et ( E: T) r ati os  of   N  K  c ells  a n d   B-c ell t u  m o ur c ell li n es 
d eri v e d fr o  m   D L  B  C L,   m a ntl e  c ell l y  m p h o  m a (  M  C L)  a n d  c hr o ni c l y  m p h o c yti c l e u k a e  mi a (  C L L). 
T h e r es ults  of t h es e i n  vitr o  e x p eri  m e nts s u g g est t h at M  O  R 0 0 2 0 8 l e a ds t o str o n g er 
A  D  C  C --m e di at e d t ar g et  c ell l ysis i n  c o  m p aris o n t o   R T  X   u n d er  c o n diti o ns i n   w hi c h   N  K  c ells  ar e 
li  mit e d.   B as e d  o n t h e  ass u  m pti o n t h at i n  p ati e nts   wit h l o  w  b as eli n e   N  K  C  C,   N  K  c ell  n u  m b ers  at 
t h e t u  m o ur sit e   will  n ot  o ut- n u  m b er t h e  n u  m b er  of t u  m o ur c ells, t h es e  d at a s u p p ort t h e 
h y p ot h esis t h at M  O  R 0 0 2 0 8  c o ul d  h a v e  hi g h er t u  m o ur  killi n g  c a p a cit y  c o  m p ar e d t o rit u xi  m a b i n 
p ati e nts   wit h  a  p eri p h er al   N  K  c ell  c o u nt  of  1 0 0  or l ess   N  K  c ells/ µ L.  
 
4. 5  O v e r vi e  w  of   C  D 1 9  e x p r essi o n i n   D  L  B  C  L  a n d t r e at  m e nt   wit h   M  O  R 0 0 2 0 8  
4. 5. 1  T h e   B -c ell D iff e r e nti ati o n A nti g e n   C  D 1 9 i n L y  m p h o  m a  
T h e  diff er e nt i ati o n  a nti g e n   C  D 1 9 is  a  5 5 6-a  mi n o a ci d, t y p e I tr a ns  m e  m br a n e  c ell-s urf a c e  pr ot ei n 
wit h  a n i  m p ort a nt r ol e i n  b ot h  n or  m al  a n d   m ali g n a nt   B- c ell  p h ysi ol o g y.   C  D 1 9  b el o n gs t o t h e 
i  m  m u n o gl o b uli n (I g) s u p erf a  mil y  a n d is t h e  d o  mi n a nt si g n al tr a ns d u ci n g   m e  m b er  of t h e   B-c ell 
a nti g e n r e c e pt or (  B  C  R)  c o -r e c e pt or  c o  m pl e x,   w hi c h  als o i n cl u d es  c o  m pl e  m e nt r e c e pt or,   C  D 2 1, 
t h e t etr as p a ni n f a  mil y  pr ot ei n, C  D 8 1 , a n d t h e i nt erf er o n -i n d u c e d tr a ns  m e  m br a n e  pr ot ei n,   C  D 2 2 5 
(C art er  et  al.  2 0 0 2 ). 
 
C  D 1 9 is  e x pr ess e d  e arl y i n   B- c ell  d e v el o p  m e nt at t h e l at e  pr o-B  or  e arl y  pr e -B st a g e , j ust  b ef or e 
t h e I g  h e a v y  c h ai n  g e n e r e arr a n g e  m e nt,  a n d is  pr es e nt t hr o u g h o ut   B-c ell   m at ur ati o n  u ntil 
t er  mi n al  diff er e nti ati o n i nt o  pl as  m a  c ells (A n d ers o n  et  al.  1 9 8 4 ).   As  a l o  w-affi nit y  a nti g e n 
r e c e pt or,   C  D 1 9 f u n cti o ns t o  d e cr e as e t h e  a nti g e n  c o n c e ntr ati o n t hr es h ol d  n e c ess ar y t o tri g g er 
B- c ell  di visi o n  a n d  diff er e nti ati o n.  P ati e nts   wit h  a  h o  m o z y g o us   m ut ati o n i n t h e   C  D 1 9  g e n e 
(C  D 1 9 )  e x hi bit  d e cr e as e d   B- c ell  a cti v ati o n i n r es p o ns e t o   mit o g e n sti  m ul ati o n  a n d  ar e 
h y p o g a  m  m a gl o b uli n a e  mi c,   wit h  n or  m al  n u  m b ers  of  b o n e   m arr o  w  a n d  c ir c ul ati n g 
B -l y  m p h o c yt es (v a n  Z el  m  et  al.  2 0 0 6 ).   CD 1 9 r e g ul at es   B- c ell  pr olif er ati o n  a n d  d e v el o p  m e nt 
t hr o u g h   B  C  R- d e p e n d e nt  a n d i n d e p e n d e nt   m e c h a nis  ms (L esli e  a n d   Y o u n es  2 0 1 3 ). T h er e  ar e  
e  m er gi n g  d at a t h at s u g g est t h at C  D 1 9  pl a ys  a   B  C  R -i n d e p e n d e nt r ol e i n m ali g n a nt   B -c ell 
pr olif er ati o n  b y st a bili si n g  c o n c e ntr ati o ns  of t h e M  Y  C   o n c o pr ot ei n (P o e  et  al.  2 0 1 2 ). 
I  m p ort a ntl y,   C  D 1 9  e x pr essi o n is   m ai nt ai n e d i n l y  m p h o  m as   w hi c h s h o  w a  d o  w n-r e g ul ati o n  of 
C  D 2 0  e x pr essi o n f oll o  wi n g  a nti-  C  D 2 0 t h er a p y (C h u  et  al.  2 0 0 2 ). 
 
4. 5. 2  M  O  R 0 0 2 0 8   B a c k g r o u n d  a n d P r e cli ni c al D at a 
M  O  R 0 0 2 0 8 (s y n o n y  m s:   X  m  A b® 5 5 7 4,   M  O  R 2 0 8 ) is  a n  F c-e n h a n c e d    m  A b t h at  bi n ds t o t h e 
h u  m a n   B- c ell s urf a c e  a nti g e n   C  D 1 9.   M  O  R 0 0 2 0 8  p oss ess es si g nifi c a ntl y i n cr e as e d t u  m o ur 
c yt ot o xi cit y   w h e n  c o  m p ar e d   wit h t h e  p ar e nt al,  n o n -e n h a n c e d ,   m uri n e  4  G 7   C  D 1 9  a nti b o d y.  T h e 
i n cr e as e d  bi n di n g  of   M  O  R 0 0 2 0 8 t o  F c  g a  m  m a r e c e pt ors ( F cγR),  d u e t o t h e  e n gi n e er e d 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 8  of 1 3 1  
m ut ati o ns, si g nifi c a ntl y  e n h a n c es i n  vitr o a nti b o d y-d e p e n d e nt  c ell -m e di at e d  c yt ot o xi cit y 
(A  D  C  C ),  a nti b o d y- d e p e n d e nt  c ell-  m e di at e d  p h a g o c yt osis (A  D  C P),  a n d  dir e ct  c yt ot o xi c  eff e cts 
( a p o pt osis)  o n t h e t u  m o ur  c ells  c o  m p ar e d   wit h t h e  n o n- e n h a nc e d  p ar e nt al   m uri n e  a nti b o d y. 
M  O  R 0 0 2 0 8  h as  n ot  b e e n s h o  w n t o   m e di at e  c o  m pl e  m e nt- d e p e n d e nt  c yt ot o xi cit y (  C  D  C). 
 
M or e s p e cifi c all y, i n  pr e cli ni c al st u di es,   M  O  R 0 0 2 0 8  h as  b e e n s h o  w n t o si g nifi c a ntl y  e n h a n c e 
i n vitr o   A  D  C  C,   A  D  C P,  a n d  dir e ct  c yt ot o xi c  eff e cts ( a p o pt osis)  o n   C  D 1 9 + t u  m o ur  c ell li n es 
s p a n ni n g  a  br o a d r a n g e  of  h u  m a n l y  m p h o  m as  a n d l e u k a e  mi as (  B ur kitt’s l y  m p h o  m a,   C L L,  h air y 
c ell l e u k a e  mi a,   C  D 1 9 +  c hr o ni c   m y el oi d l e u k a e  mi a,   D L  B  C L,  a n d a c ut e l y  m p h o bl asti c l e u k a e  mi a 
[A L L ])  e x pr essi n g l e v els  of   C  D 1 9  a nti g e n r a n gi n g fr o  m  1 5, 0 0 0 t o  1 0 5, 0 0 0   m ol e c ul es/ c ell. 
Si  mil ar  eff e cts   w er e  als o  n ot e d i n r el ati o n t o fr es hl y is ol at e d p ati e nt   C L L  or   A L L  c ells  a n d  ar e 
als o  e x p e ct e d t o tr a nsl at e t o  pri  m ar y   N  H L  c ells , si n c e t h e  e x pr essi o n r a n g e r e p ort e d f or   A L L  a n d 
C L L   B -c ells  c o v ers t h e r a n g e  o bs er v e d f or   N  H L   B -c ells (Gi n al di  et  al.  1 9 9 8 , Ol ej ni c z a k  et  al. 
2 0 0 6 ).   MO  R 0 0 2 0 8  h as  als o s h o  w n s u p eri or  effi c a c y t o its  n o n- e n h a n c e d   p ar e nt al  a nti b o d y i n 
r el ati o n t o its  a bilit y t o i n d u c e  a   m ar k e d r e d u cti o n i n t u  m o ur  gr o  wt h, i n hi bit t u  m o ur  gr o  wt h r at e 
a n d i n cr e as e s ur vi v al i n  vi v o i n  x e n o gr aft   m o d els  of  h u  m a n l y  m p h o  m a i n s e v er e  c o  m bi n e d 
i  m  m u n o d efi ci e n c y ( S  CI  D)   mi c e. ( S e e r el e v a nt s e ctio ns  of I n v esti g at or’s   Br o c h ur e [I  B] .) 
 
T h e  p h ar  m a c o d y n a  mi c ( P  D) i nt er a cti o ns  of   M  O  R 0 0 2 0 8 i n  c o  m bi n ati o n   wit h fl u d ar a bi n e, B E  N, 
a n d l e n ali d o  mi d e (L E  N ) us e d i n t h e tr e at  m e nt  of  p ati e nts   wit h   C L L  a n d   N  H L,   w er e i n v esti g at e d 
i n  a  h u  m a n i ntr a v e n o us (I  V) l y  m p h o  m a   m o d el i n  S  CI  D   mi c e (se e r el e v a nt s e cti o ns  of I  B). I n t his 
ort h ot o pi c   m o d el f or  diss e  mi n at e d   B -c ell   m ali g n a n ci es, t h e   m e di a n s ur vi v al   w as s u p eri or f or  all 
of t h e  gr o u ps r e c ei vi n g   M  O  R 0 0 2 0 8  c o  m bi n ati o n t h er a p y (  wit h fl u d ar a bi n e,   B E  N  or L E  N )   w h e n 
c o  m p ar e d   wit h t h e  gr o u ps r e c ei vi n g   M  O  R 0 0 2 0 8   m o n ot h er a p y.   M or e s p e cifi c all y,   M  O  R 0 0 2 0 8 
( 3. 0   m g/ k g) i n  c o  m bi n ati o n   wit h   B E  N ( 1 3. 0,  1 6. 0   m g/ k g)   w as s u p eri or t o  eit h er t h er a p y  al o n e i n 
t er  ms  of i n cr e as ed m e di a n lif es p a n ( 2 6  %  v ers us  5 7  %).  T h e  eff e ct   w as  cl assifi e d  as  p ot e nti ati o n 
of t h e  effi c a c y  of   M  O  R 0 0 2 0 8,  as   M  O  R 0 0 2 0 8   w as t h e  o nl y  dr u g  a  m o n gst t h e  c o  m bi n ati o n 
p art n ers t est e d t h at  d e  m o nstr at e d  a si g nifi c a nt  eff e ct  o n s ur vi v al  as  a si n gl e  a g e nt.  
 
Tiss u e  cr oss -r ea cti vit y st u di es  h a v e s h o  w n t h at t h e  p att er n  a n d  distri b uti o n  of   M  O  R 0 0 2 0 8 
bi n di n g t o  c y n o  m ol g us   m o n k e y tiss u es  cl os el y  p ar all els t h os e  of  h u  m a n tiss u es.  Fl o  w  c yt o  m etr y 
e x p eri  m e nts s h o  w   M  O  R 0 0 2 0 8  bi n di n g t o  h u  m a n  a n d  c y n o  m ol g us   m o n k e y   B- c ells,  b ut  n ot t o t h e 
B- c ells  of  ot h er  c o  m  m o n l a b or at or y s p e ci es (s u c h  as r at,   m o us e, r a b bit  a n d  d o g).  T h er ef or e, 
p h ar  m a c ol o g y st u di es   w er e r estri ct e d t o  h u  m a n  a n d  c y n o  m ol g us   m o n k e y  c ell- b as e d i n  vitr o 
s yst e  ms,   C  D 1 9 +  h u  m a n   B- c ell t u  m o ur  x e n o gr aft   m o d els i n  S  CI  D   mi c e,  a n d  c y n o  m ol g us 
m o n k e ys i n  vi v o. I n i n  vi v o st u di es i n  c y n o  m ol g us   m o n k e ys,   M  O  R 0 0 2 0 8   w as s h o  w n t o i n d u c e 
B-l y  m p h o c yt e  d e pl eti o n i n  p eri p h er al  bl o o d,  b o n e   m arr o  w, s pl e e n  a n d i n g ui n al l y  m p h  n o d es. 
C y n o  m ol g us   m o n k e ys   w er e  als o j u d g e d t o  b e t h e  o nl y r el e v a nt  c o  m  m o n l a b or at or y s p e ci es f or 
t o xi cit y st u di es. 
 
T h e r es ults  of st u di es  e v al u ati n g t h e  p h ar  m a c o ki n eti cs ( P  K),  P  D  a n d t o xi cit y  of   M  O  R 0 0 2 0 8 i n 
c y n o  m ol g us   m o n k e ys,  ar e  pr o vi d e d i n t h e r el e v a nt s e cti o ns  of t h e I  B.  T h e fi n di n gs i n fi v e 
pr e cli ni c al st u di es   w er e li  mit e d t o t h e  e x p e ct e d  p h ar  m a c ol o gi c al  eff e cts  of   M  O  R 0 0 2 0 8,   wit h  n o 
r e p orts  of  u n a nti ci p at e d t o xi cit y. T h e f i v e st u di es,  all  c o n d u ct e d i n  c y n o  m ol g us   m o n k e ys 
i n cl u d e d:  a  2 6-  w e e k si n gl e  1 0. 0   m g/ k g  d os e,  P  K,  P  D  a n d t o xi cit y st u d y;  a  2 8- d a y si n gl e I  V  d os e, 
d os e- r a n gi n g (0. 3,  1. 0  a n d  3. 0   m g/ k g)  P  K/ P  D st u d y;  a  2 9- d a y, si n gl e- d os e ( 3. 0   m g/ k g) st u d y 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 2 9  of 1 3 1  
c o  m p ari n g   M  O  R 0 0 2 0 8   wit h t  w o  ot h er   C  D 1 9  a nti b o di es   wit h  diff er e nt  F c r e gi o ns;  a n  8- w e e k 
t o xi cit y st u d y i n   w hi c h   M  O  R 0 0 2 0 8   w as  a d  mi nist er e d I  V e v er y  2   w e e ks  at  a  d os e  of  2,  1 0  or 
5 0 m g/ k g f or  8  c o ns e c uti v e   w e e ks   wit h  a  9 0 -d a y r e c o v er y  p eri o d ;  a n d  a  1 3-  w e e k t o xi cit y st u d y 
i n   w hi c h   M  O  R 0 0 2 0 8   w as  a d  mi nist er e d I  V   w e e kl y t o s e x u all y   m at ur e  c y n o  m ol g us   m o n k e ys  at 
d os es  of  1 0,  3 0  or  1 0 0   m g/ k g f or  1 3  c o ns e c uti v e   w e e ks   wit h  a  1 3 2- d a y r e c o v er y p eri o d .  T h e  ai  m 
of t h e l att er   G o o d  L a b or at or y  Pr a cti c e (  G L P) -c o  m pli a nt,   m ulti pl e -d os e t o xi c ol o g y st u d i es w as t o 
s u p p ort t h e  us e  of   M  O  R 0 0 2 0 8 i n  h u  m a n  cli ni c al st u di es. As a n e x p e ct e d  p h ar  m a c ol o gi c al  eff e ct, 
a r e v ersi bl e l a c k  of  g er  mi n al  c e nt r es i n l y  m p h oi d  or g a ns  a n d   m ar k e dl y r e d u c e d  p eri p h er al 
C  D 2 0 +   B  c ell  c o u nts   w er e  o bs er v e d,   w hi c h   w er e  c o nsist e nt   wit h l o  w er e d I g  G l e v els i n s er u  m  as 
w ell  as  a r e v ersi bl e r e d u cti o n i n t h e  T - c ell  d e p e n d e nt  a nti b o d y r es p o ns e.  T h er e   w er e  n o 
M  O  R 0 0 2 0 8-r el at e d  eff e cts  o n  b o d y   w ei g ht,  cli ni c al si g ns, f o o d  c o ns u  m pti o n,  bl o o d  pr ess ur e, 
el e ctr o c ar di o gr a p h y, r es pir at or y r at e,  o p ht h al  m ol o g y,  n e ur o b e h a vi o ur al  o bs er v ati o ns, 
h a e  m at ol o g y,  c o a g ul ati o n,  uri n e  or  c yt o ki n e  a n al ysis.   M  O  R 0 0 2 0 8  h a d  n o  eff e cts  o n   m e nstr u al 
c y cl e l e n gt h i n f e  m al es a n d  n o  hist o p at h ol o g y/  mi cr os c o pi c  c h a n g es t o   m al e  a n d f e  m al e 
r e pr o d u cti v e  or g a ns.   O v er all,   M  O  R 0 0 2 0 8  a d  mi nistr ati o n t o t h e  c y n o  m ol g us   m o n k e y   w as  v er y 
w ell t ol er at e d  at  d os es  u p t o  1 0 0   m g/ k g. I n  a d diti o n,   G L P- c o  m pli a nt tiss u e  cr oss -r e a cti vit y 
st u di es   w er e  p erf or  m e d  o n  n or  m al tiss u e  p a n els fr o  m  h u  m a n  a n d  c y n o  m ol g us   m o n k e y  d o n ors. 
N o s p e cifi c st ai ni n g t o str u ct ur es  ot h er t h a n t h e  e x p e ct e d   m o n o n u cl e ar l e u k o c yt es, l y  m p h o c yt es 
a n d  h a e  m at o p oi eti c  pr e c urs or  c ells   w as  o bs er v e d.  
 
4. 5. 3  Cli ni c al   E x p e ri e n c e   wit h   M  O  R 0 0 2 0 8  
4. 5. 3. 1  P r ot o c ol   X  m  A b 5 5 7 4- 0 1 
A  P h as e   1 St u d y  of   X  m  A b ® 5 5 7 4 t o   E v al u at e t h e  S af et y,   T ol e r a bilit y,  a n d 
P h a r  m a c o ki n eti cs i n  P ati e nts   wit h   R el a ps e d  o r   R ef r a ct o r y   C h r o ni c   L y  m p h o c yti c 
L e u k a e  mi a 
T h e first st u d y i n  h u  m a ns   w as  a  p h as e I tri al e x pl ori n g t h e  us e  of   M  O  R 0 0 2 0 8 ( als o  k n o  w n  as 
X  m  A b ® 5 5 7 4  or M  O  R 0 0 2 0 8) i n  a d ult  p ati e nts  di a g n os e d  a c c or di n g t o I nt er n ati o n al   W or ks h o p  o n 
C L L  g ui d eli n es (H all e k  et  al.  2 0 0 8 ) wit h  a cti v e, tr e at  m e nt -r e q uiri n g   R-R   C L L/ s  m all l y  m p h o c yti c 
l y  m p h o  m a (S L L ).   R es ults  of t h e st u d y   w er e r e p ort e d  b y (W o y a c h  et  al.  2 0 1 4 ). 
 
T  w e nt y -s e v e n  p ati e nts   w er e  e nr oll e d t o  6  es c al ati n g  d os e l e v els,   wit h  e x p a nsi o n  at t h e  hi g h est 
d os e l e v el  of  1 2   m g/ k g.   Ni n e  d os es  of   M  O  R 0 0 2 0 8   w er e i nf us e d  o v er  8   w e e ks.   N o   m a xi  m al 
t ol er at e d  d os e w as r e a c h e d,  a n d t h e  dr u g   w as  g e n er all y   w ell t ol er at e d,   wit h i nf usi o n-r el at e d 
r e a cti o ns (I  R  Rs)  of  gr a d e  1  or  2  b ei n g t h e   m ost  c o  m  m o n t o xi citi es. Tr e at  m e nt -r el at e d  gr a d e  3  or 
4 A Es   o c c urr e d i n fi v e  p ati e nts  a n d i n cl u d e d  n e utr o p e ni a, t hr o  m b o c yt o p e ni a, i n cr e as e d  as p art at e 
a  mi n otr a nsf er as e  (  A S T), f e bril e  n e utr o p e ni a,  a nd t u  m o u r l ysis s y n dr o  m e ( T L S).   M  O  R 0 0 2 0 8 
s h o  w e d  pr eli  mi n ar y  effi c a c y,   wit h  1 8  p ati e nts ( 6 6. 7  %) r es p o n di n g  b y  p h ysi c al  e x a  mi n ati o n 
crit eri a  a n d l a b or at or y st u di es,  a n d  8  p ati e nts ( 2 9. 6  %) r es p o n di n g  b y  c o  m p ut e d t o  m o gr a p h y (  C T) 
crit eri a. M  O  R 0 0 2 0 8 s h o  w e d  a t er  mi n al  eli  mi n ati o n  h alf-lif e  of  a p pr o xi  m at el y  1 4  d a ys. A  d os e of 
1 2   m g/ k g   w as r e c o  m  m e n d e d f or  us e i n s u bs e q u e nt st u di es. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 3 0  of 1 3 1  
4. 5. 3. 2  O n g oi n g  St u di es  
T h e f oll o  wi n g ot h er st u di es  ar e  o n g oi n g. D et ails  of s af et y  a n d  effi c a c y  d at a ar e r e p ort e d i n t h e 
I  B: 
 
P r ot o c ol M  O  R 2 0 8  C 2 0 1  
A  P h as e II a,   O p e n -L a b el,   M ulti c e nt er  St u d y  of  Si n gl e -A g e nt   M  O  R 0 0 2 0 8,  a n  F c -O pti  mis e d 
A nti -C  D 1 9   A nti b o d y, i n  P ati e nts   wit h   R el a ps e d  or   R efr a ct or y   B -C ell   N o n -H o d g ki n’s 
L y  m p h o  m a  
 
P r ot o c ol   M  O  R 2 0 8  C 2 0 3  (  L-MI  N  D)  
A  P h as e II,  Si n gl e -Ar  m,   O p e n -L a b el,   M ult i c e ntr e  St u d y t o  E v al u at e  S af et y  a n d  Effi c a c y  of 
L e n ali d o  mi d e   C o  m bi n e d   wit h   M  O  R 0 0 2 0 8 i n  P ati e nts   wit h   R el a ps e d  or   R efr a ct or y (  R-R) Diff us e 
L ar g e   B -C ell  L y  m p h o  m a  
 
P r ot o c ol   M  O  R 2 0 8  C 2 0 5  (  C  O S  M  O S) 
A  P h as e II,  T  w o -C o h ort,   O p e n -L a b el,   M ulti c e nt er  St u d y t o  E v al u at e t h e  Effi c a c y  a n d  S af et y  of 
M  O  R 0 0 2 0 8   C o  m bi n e d   wit h I d el alisi b  or   V e n et o cl a x i n  P ati e nts   wit h   R el a ps e d  or   R efr a ct or y 
C L L/ S L L  Pr e vi o usl y  Tr e at e d   wit h   Br ut o n’s  T yr osi n e   Ki n as e I n hi bit or  
 
P r ot o c o l   M  O  R 2 0 8  C 1 0 7 ( Fi rst-MI  N  D)  
A  P h as e I b,  o p e n -l a b el, r a n d o  mi z e d st u d y t o  ass ess s af et y  a n d  pr eli  mi n ar y  effi c a c y  of 
T af asit a  m a b i n  a d diti o n t o   R -C  H  O P  or  T af asit a  m a b  pl us  L e n ali d o  mi d e i n  a d diti o n t o   R -C  H  O P i n 
p ati e nts   wit h  n e  wl y  di a g n os e d   Diff us e  L ar g e B -C ell  L y  m p h o  m a (  D L  B  C L)  
 
P r ot o c ol   M  O  R 2 0 8  C 3 1 0 ( F r o nt  MI  N  D)  
A P h as e III,   m ulti c e nt er, r a n d o  mi z e d,  d o u bl e -bli n d,  pl a c e b o -c o ntr oll e d tri al  c o  m p ari n g t h e 
effi c a c y  a n d s af et y  of t af asit a  m a b  pl us l e n ali d o  mi d e i n  a d diti o n t o   R -C  H  O P  v ers us   R -C  H  O P i n 
pr e vi o usl y  u ntr e at e d,  hi g h-i nt er  m e di at e  a n d  hi g h-ris k  p ati e nts   wit h  n e  wl y  di a g n os e d  diff us e 
l ar g e   B-c ell l y  m p h o  m a  
 
P r ot o c ol   M  O  R 2 0 8  C 4 1 4 (  R  E  A  L  MI  N  D)  
A  P h as e I  V,   m ulti c e nt er,  o bs er v ati o n al st u d y t h at   will  c oll e ct  d at a  o n tr e at  m e nts  a n d  o ut c o  m es 
f or  p ati e nts i n t h e   U S   wit h r ela ps e d  or r efr a ct or y  diff us e l ar g e   B -c ell l y  m p h o  m a   w h o  ar e st arti n g 
s e c o n d- or t hir d -li n e t h er a p y  a n d  ar e  n ot r e c ei vi n g  a ut ol o g o us st e  m  c ell tr a ns pl a nt. 
 
P r ot o c ol   M  O  R 2 0 8  C 1 1 5 (  MI  N  D  w a y)  
A  P h as e  1 b/ 2,   O p e n -L a b el,   M ulti c e nt er  St u d y t o  E v al u at e t h e  S af et y  a n d  P h ar  m a c o ki n eti cs  of  a 
M o difi e d  T af asit a  m a b I  V   D osi n g   R e gi  m e n   C o  m bi n e d   wit h  L e n ali d o  mi d e ( L E  N) i n  P ati e nts   wit h 
R el a ps e d  or   R efr a ct or y   Diff us e  L ar g e   B -C ell  L y  m p h o  m a  
 
P r ot o c ol I  N  C  M  O  R 0 2 0 8 -1 0 1 (t o p  MI  N  D)  
A  P h as e  1 b/ 2 a  b as k et st u d y t o  e v al u at e t h e s af et y, t ol er a bi lit y,  p h ar  m a c o ki n eti cs,  a n d  effi c a c y  of 
c o  m bi n ati o n t h er a p y   wit h t h e  a nti -C  D 1 9   m o n o cl o n al  a nti b o d y t af asit a  m a b  a n d t h e  PI 3  K d 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 3 1  of 1 3 1  
i n hi bit or  p ars a clisi b i n  a d ult  p arti ci p a nts   wit h r el a ps e d/r efr a ct or y (  R/  R)  n o n-  H o d g ki n l y  m p h o  m a 
or  c hr o ni c l y  m p h o c yti c l e u k e  mi a 
 
P r ot o c ol I  N  C  M  O  R 0 2 0 8- 1 0 2 ( J- MI  N  D)  
A P h as e  1 b  St u d y  of t af asit a  m a b, t af asit a  m a b  pl us l e n ali d o  mi d e, t af asit a  m a b  pl us  p ars a clisi b, 
a n d t af asit a  m a b  pl us l e n ali d o  mi d e i n  c o  m bi n ati o n   wit h   R -C  H  O P i n J a p a n es e  p arti ci p a nts   wit h 
n o n-  H o d g ki n l y  m p h o  m a.  
 
P r ot o c ol I  N  C  M  O  R 0 2 0 8- 3 0 1 (i n  MI  N  D) 
A  P h as e  3, r a n d o  mi z e d,  d o u bl e- bli n d,  pl a c e b o- c o ntr oll e d,   m ulti c e nt er st u d y t o  e v al u at e t h e 
effi c a c y  a n d s af et y  of t af asit a  m a b  pl us l e n ali d o  mi d e i n  a d diti o n t o rit u xi  m a b  v ers us l e n ali d o  mi d e 
i n  a d diti o n t o rit u xi  m a b i n  p ati e nts   wit h r el a ps e d/r efr a ct or y (  R/  R) f olli c ul ar l y  m p h o  m a  gr a d e  1 t o 
3 a  or   R/  R   m ar gi n al  z o n e l y  m p h o  m a 
 
P r ot o c ol   M  O  R 0 0 2 0 8 II  T   O S  U- 1 3 0 3 1 
P h as e II  St u d y  of  T af asit a  m a b i n   C o  m bi n ati o n   wit h  L e n ali d o  mi d e f or  P ati e nts   wit h   R el a ps e d  or 
R efr a ct or y   C hr o ni c  L y  m p h o c yti c  L e u k e  mi a (  C L L)/ S  m all  L y  m p h o c yti c  L y  m p h o  m a 
( S L L)/ Pr ol y  m p h o c yti c  L e u k e  mi a ( P L L), I n cl u di n g t h os e   w h o  h a v e   R el a ps e d  o n I br uti ni b,  or 
P ati e nts   wit h   U ntr e at e d   C L L/ S L L/ P L L  
 
P r ot o c ol II  R _I  N  T _  D  E _  H ess _  G  O  A  LII  
A  pr os p e cti v e,   m ulti c e nt er  r a n d o  mi z e d  p h as e II tri al i n v esti g ati n g 
G e  m cit a bi n e/  O x ali pl ati n/  Rit u xi  m a b   wit h  or   wit h o ut  T af asit a  m a b (  M  O  R 2 0 8) f or  p ati e nts   wit h 
r el a ps e d/r efr a ct or y   A g gr essi v e  L y  m p h o  m a (  G  O  A L II) 
 
4. 5. 4  S af et y  of   M  O  R 0 0 2 0 8 
M  O  R 0 0 2 0 8  off ers  a  n o v el   m e c h a nis  m  of  a cti o n t h at   m a y  a d d t o t h e  c ar e  of  p ati e nts   wit h   N  H L. 
B as e d  o n t h e  a v ail a bl e  d at a fr o  m t h e  c o  m pl et e d  cli ni c al st u d i es  of   M  O  R 0 0 2 0 8 ( Pr ot o c ol 
X  m  A b ® 5 5 7 4- 0 1  a n d   M  O  R 2 0 8  C 2 0 2),  pr eli  mi n ar y  d at a fr o  m t h e  o n g oi n g cli ni c al st u di es 
M  O  R 2 0 8  C 2 0 1 (J ur c z a k  et  al.  2 0 1 8), M  O  R 2 0 8  C 2 0 3,   M  O  R 2 0 8  C 2 0 4  a n d   M  O  R 2 0 8  C 2 0 5, 
n o n cli ni c al st u di es  a n d  e x p eri  m e nts,  a n d lit er at ur e  d at a  o n   C  D 1 9, t h e s p o ns or is  of t h e  o pi ni o n 
t h at t h e  p ot e nti al  b e n efit  of   M  O  R 0 0 2 0 8  o ut  w ei g hs t h e  p ot e nti al ris ks. It is  e x p e ct e d t h at t h e 
p ot e nti al ris ks   will  b e  a d e q u at el y  c o ntr oll e d  b y t h e  d esi g n  of t his tri al ( e. g.  b y t h e i n cl usi o n  a n d 
e x cl usi o n  crit eri a)  a n d  b y fr e q u e nt   m o nit ori n g  of  p ot e nti al  a d v ers e  dr u g r e a cti o ns t hr o u g h o ut t h e 
e ntir e st u d y.  
 
B as e d  o n t h e s af et y  d at a fr o  m t h e  cli ni c al st u di es list e d  a b o v e t h e  a nti ci p at e d  p ossi bl e ris ks 
ass o ci at e d   wit h   M  O  R 0 0 2 0 8   m o n ot h er a p y i n cl u d e t h e f oll ow i n g A Es  wit h  a s us p e ct e d 
r el ati o ns hi p t o   M  O  R 0 0 2 0 8 tr e at  m e nt (i n ci d e n c e  ≥  3   %): 
•  I  R  Rs (  m ostl y   Gr a d e  1/ 2) 
•  F e bril e  n e utr o p e ni a 
•  N e utr o p e ni a 
•  T hr o  m b o c yt o p e ni a 
•  T u  m o u r lysis s y n dr o  m e 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 3 2  of 1 3 1  
•  U p p er r es pir at or y tr a ct i nf e cti o ns 
•  L o  w er r es pir at or y tr a ct i nf e cti o n  (i n cl u di n g  p n e u  m o ni a  a n d  br o n c hitis) 
•  F ati g u e 
•  C hills  
•  P yr e xi a 
•  N a us e a  
•  Di arr h o e a 
•  H e a d a c h e  
•  R as h  
•  A S T  a n d   A L T i n cr e as es.  
 
Si n c e  a   m aj or  p h ar  m a c ol o gi c al  eff e ct  of   M  O  R 0 0 2 0 8 is   B- c ell  d e pl eti o n, t h e ris ks  ass o ci at e d   wit h 
t h e  us e  of  a p pr o v e d   B- c ell  d e pl eti n g t h er a p e uti cs  b as e d  o n t h e l a b elli n g  of  ot h er  a g e nts   wit h 
si  mil ar  eff e cts s h o ul d  b e  c o nsi d er e d. T h es e   m a y i n cl u d e:   B-c ell  d epl eti o n, l y  m p h o p e ni a, 
n e utr o p e ni a,  h e p atitis   B r e a cti v ati o n,  pr o gr essi v e   m ultif o c al l e u k o e n c e p h al o p at h y, 
m u c o c ut a n e o us r e a cti o ns  a n d i nf e cti o ns. 
 
T h e  a nti ci p at e d ris ks  ass o ci at e d   wit h t h e  a d  mi nistr ati o n  of   M  O  R 0 0 2 0 8  ar e  d es cri b e d i n  d et ail i n 
t h e   M  O  R 0 0 2 0 8 I  B. 
 
 
5  S  T  U  D  Y  P  U  R P  O S  E/  R  A  TI  O  N  A  L  E  
D es pit e r e c e nt i  m pr o v e  m e nts i n t h e   m a n a g e  m e nt  of   D L  B  C L,  a p pr o xi  m at el y  3 0 – 4 0  %  of  p ati e nts 
wit h   D L  B  C L tr e at e d   wit h   R -C  H  O P r el a ps e f oll o  wi n g i niti al i  m  m u n o c h e  m ot h er a p y (C oiffi er  et 
al.  2 0 0 2, F e u gi er  et  al.  2 0 0 5 , S e h n  et  al.  2 0 0 5 , H a b er  m a n n  et  al.  2 0 0 6 , Pfr e u n ds c h u h  et  al.  2 0 0 6 , 
Pfr e u n ds c h u h  et  al.  2 0 1 1 ).   Alt h o u g h  a si g nifi c a nt  n u  m b er  of  p ati e nts  c a n  b e s al v a g e d   wit h 
hi g h- d os e  c h e  m ot h er a p y ( H  D  C ) a n d s u bs e q u e nt   A S  C T, t h e   m aj orit y   will s u c c u  m b t o t h e  dis e as e. 
I n  p arti c ul ar, el d erl y   a n d/ or fr ail  p ati e nts a n d t h os e  wit h   m ulti pl e  c o  m or bi diti es  ar e i n  n e e d  of 
n o v el t h er a p e uti c  a p pr o a c h es as t h e i nt e nsifi e d tr e at  m e nt r e gi  m e ns  c a n n ot  b e  us e d i n t his 
p o p ul ati o n. I  m pr o vi n g t h e t h er a p e uti c  o pti o ns f or t his  gr o u p  of  p ati e nts is  a n i  m p ort a nt  u n  m et 
m e di c al  n e e d . 
 
As   R T  X -b as e d r e gi  m e ns  h a v e  b e c o  m e st a n d ar d first -li n e tr e at  m e nt i n   D L  B  C L, t h e  effi c a c y  of 
R T  X  c o  m bi n e d   wit h  c h e  m ot h er a p y i n t h e s e c o n d- li n e s etti n g  h as  d e cr e as e d  a n d t h er e is  a  n e e d 
f or  n e  w t h er a pi es i n  p ati e nts  pr o gr essi n g  or r el a psi n g aft er first - or s e c o n d -li n e   R T  X-b as e d 
tr e at  m e nt. T h e   C  D 1 9  a nti g e n is  a n  attr a cti v e t ar g et i n   D L  B  C L  as   C  D 1 9 is t y pi c all y  e x pr ess e d i n 
D L  B  C L  c ells,  h as  a si g n alli n g f u n cti o n t h at  c o ntri b ut es t o t h e   m ali g n a nt  p h e n ot y p e  a n d is  n ot 
d o  w n-r e g ul at e d i n p ati e nts   pr e-tr e at e d   wit h   C  D 2 0-t ar g et e d  a g e nts.  T h us, it   mi g ht  b e  p ossi bl e t o 
o v er c o  m e t h e  a bs ol ut e  or r el ati v e   R T  X r esist a n c e i n   R -R   N  H L b y  usi n g   M  O  R 0 0 2 0 8 i nst e a d  of 
R T  X  a n d t h er e b y t o i  m pr o ve  cli ni c al  o ut c o  m e i n t h e   R-  R   N  H L  p ati e nt  p o p ul ati o n. 
 
T h e  eff e cts  of   M  O  R 0 0 2 0 8  a p p e ar t o i n v ol v e   A  D  C  C,   A  D  C P,  a n d  dir e ct  c yt ot o xi c  a cti vit y 
( a p o pt osis).   M  O  R 0 0 2 0 8  a n d   B E  N ar e  a cti v e as si n gl e  a g e nts  a n d i n  c o  m bi n ati o n s h o  w 
s y n er gisti c  a ntil e u k a e  mi c  a n d  a ntil y  m p h o  m a  a cti vit y in  vi v o   a n d i n  vitr o.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 3 3  of 1 3 1  
M O R 0 0 2 0 8 de m o ns trate d si n gle-a ge nt acti vit y i n R -R  C L L/ S L L,  DL B C L,  f ollic ular ly m p h o ma 
a n d ot her i n d ole nt N H L s ( W o yach et al. 2 0 1 4, J urcza k et al. 2 0 1 5,  J urcza k et al. 2 0 1 6). 
M O R 0 0 2 0 8 elicits  o nl y mil d  h ae mat ol o gic al AEs an d ha s a mana gea ble  t o xicit y pr ofile . The  
pre d o mi na nt A Es are  IR R s, a class effect of ma n y  t hera pe utic anti b o dies, w hic h t y picall y occ ur 
d uri n g t he  first to  t hir d a p plicati o n.  Overall , M O R 0 0 2 0 8 is theref ore co nsi dere d t o be a g o o d 
ca n di date for c o m bi na ti on  wit h  esta blis he d  treat me nts, suc h  as B E N , in  D L B C L.  
B E N ha s o n e of the h i g hest anti -l y m p h o ma acti vities of si n gle age nts us e d t o treat R -R D L B C L  
a n d is w ell t olerate d  i n patie nts  wit h D L B C L  wit h a mana gea ble,  mai nl y hae mat ol o gical t o xicit y  
pr ofile  (O h mac hi et al. 2 0 1 3, C ol osia et al. 2 0 1 4, Vacirca et  al. 2 0 1 4 ). As a res ult , t he c urre nt 
o pe n-la bel, ra n d o mise d st u d y w as devel o pe d t o e val uate t he efficac y  an d safet y of M O R 0 0 2 0 8 
wit h  BE N  vers us R T X wit h  B EN i n  ad ult patie nts  wit h R-R D L B C L.  T he  mai n g o al of t his  st u d y 
is t o offer s uc h patie nts  a n o vel treat me nt o pti o n ta ki n g i nt o co nsi derati o n  t hat ma n y  patie nts  are 
frail, of a d va nce d a ge an d/ or ha ve  m ulti ple co m or bi dities.  
A n I nter nati o nal C o nse ns us Pa nel  has rec o m me n de d that  BE N  s h o uld  be a d mi nistere d at a d ose 
of 9 0 m g/ m 2, w he n c o m bi ne d with R T X in t he treat me nt o f a g gressi ve N H L ( C hes o n et al. 2 0 1 0, 
C hes o n et al. 2 0 1 6). The p u bl is he d st u dies in dicate d a co nsiste nt, ma na gea ble an d c o m para ble 
(bet wee n  st u dies) t o xicit y profile  f or patie nts  wit h DL B C L.  Walter  et al. (2 0 1 2) ha ve 
i n vesti gated B E N d os e ra n ges fr o m 6 0 t hr o u g h 1 2 0 m g/ m 2 an d ca me t o t he c o ncl usi o n t hat 
9 0 m g/ m 2 is t he ma xi m u m d os e t hat  ca n  be ac hie ve d  in  the  maj orit y  of p atie nts.  Se veral  stu dies 
ha ve co nfir me d t hat R T X wit h  B E N 9 0 m g/ m 2 is a hig hl y acti ve co m bi nati o n t hera p y a n d a n A E  
pr ofile co m paris o n bet wee n t he 1 2 0 m g/ m 2 an d 9 0 m g/ m 2 d ose le vel s clearl y fa v o ur e d the 
9 0 m g/ m 2 d ose. T heref ore, t he co m bi nati o ns of R T X or M O R 0 0 2 0 8 wit h B E N ( at 9 0 m g/ m 2) 
were  selecte d as t he  m ost  a p pro priate  c o mparat or  a n d e x peri me ntal re gi me ns for this st u d y. 
Si nce M O R 0 0 2 0 8 has n ot be e n pre vi o usl y st u die d i n c o m bi nati o n wit h B E N s yste maticall y in  a 
cli nical trial,  an  I nitial Safet y E v al uati o n  will prece de t he mai n  recr uit me n t i n t his cli nical trial. 
Acc u m ulati n g data (as descri be d  in  Secti o n  4. 4) after  t he st u d y was i nitiate d i ndicate  t hat N K C C 
is an i m p orta nt pr o g n ostic fact or i n D L B C L an d ma y als o affect t he anti-t u m o ur acti vit y  of 
m o n ocl o nal a nti b o dies d irecte d at C D 2 0 a n d/ or C D 1 9 di ffere ntiall y. Acc or di n gl y, t he pr ot oc ol 
was a me n de d  to  e nable t he efficac y  of  M OR 0 0 2 0 8 pl us B E N to be co m pare d wit h t he efficacy of 
R T X pl us B E N in t he  N K C C-l o w su b gr o u p of pa tie nts (defi ne d a t baseli ne ), as well  as i n the 
o verall p o p u lati o n. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 3 6  of 1 3 1  
F or t h e  p ur p os e  of t h e  pr ot o c ol,  m aj o r s u r g e r y is  d efi n e d  as  a n y s ur gi c al  pr o c e d ur e t h at 
i n v ol v es i n its  c o urs e  g e n er al a naest h esi a  or r es pir at or y assist a n c e.  I ntr a v as c ul ar  a c c ess 
pr o c e d ur es  e. g.  c e ntr al li n e  pl a c e  m e nt  or s u b c ut a n e o us  p ort  pl a c e  m e nt,  ar e  n ot  c o nsi d er e d   m aj or 
s ur g er y. 
8. 2  S t u d y D esi g n 
T hi s is a ra n d o mise d, tw o- ar m, m ultice ntre , o pen -la bel, p hase II/III efficac y a n d safet y st u d y of 
M O R 0 0 2 0 8 in c o m bi nati o n wit h B E N  vers us RT X i n c o m bi nati o n wit h B E N . T he st u d y will 
e nr ol a d ult patie nts  wit h D L B C L  wh o  ha ve rela pse d after, or are refract or y  to , at least  o ne b ut n o 
m ore  t ha n t hree pri or s yste mic t hera p y  li nes (f or f urt her details see Secti o n  8. 6 an d  9. 5) a n d 
ha ve faile d or are n ot ca n di dates f or H D C a n d A S C T, a n d ha ve t h us e x ha uste d t heir t hera pe utic 
o pti o ns  of de m o nstrate d cli nical be nefit. At  least  o ne pr i or t hera p y li ne m ust ha ve i ncl u de d a 
C D 2 0 -tar gete d t hera p y (e. g. R T X). 
Patie nts  wit h pri mar y refract or y  DL B C L  (f or defi niti o n, see Secti o n 8. 1), patie nts wit h k n o w n 
" d o u ble/tri ple hit" D L B C L ge netics o r w h o ha ve u n de r g o ne p re vi o us all o ge neic ste m cell 
tra ns pla ntati o n are n ot eli gi ble  f or st u d y partici pati o n. Ad diti o nall y, patie nts  wit h a hist or y of 
A S C T  wit hi n a  perio d ≤3  m o nt hs pr i or to si g ni n g the inf or me d c o nse nt f or m (I C F) ca n n ot be 
i ncl u ded i n t he st u d y. 
T he  co m bi nati o n  o f M O R 0 0 2 0 8 an d  BE N  will be syste maticall y  eval uate d  f or t he first ti me i n a 
cli nical trial. Theref ore,  the trial  i ncl u des a n Initial  S afet y  E val uati o n, w hic h will e na ble t he 
I n de pe n de nt Data M o nit ori n g C o m mittee (I D M C) t o c o ncl u de w het her t he c o m bi nati o n 
treat me nt(s) are safe  (see Fi g ure 1 ). F urt her details  are pro vi de d  i n Secti o n  1 4. 1 an d t he I D M C 
C harter.  
T he  MO R 2 0 8 C 2 0 4  trial will e m pl o y  a parallel - gr o u p desi g n, w here b y patie nts will be ra n d o ml y 
assi g ne d t o t he t w o parallel treat me nt gr o u ps i n a rati o of 1: 1 (see Fi g ure 2 ). The st u d y will be 
perf or me d a cc or di n g t o a gr o u p- se q ue ntial, a dapti ve desi g n  wit h  p ossi ble sa m ple size a dj ust me nt 
after o ne pl a n ne d i nteri m anal ysis. T he interi m anal ysis w ill b e carrie d o ut w he n 1 2 8 P F S eve nts 
( 5 0 % of t he pla n ne d 2 5 6 eve nts) h a ve be e n o bser ve d. If the st u d y is co nti n ue d u ntil co m pleti o n 
a n d n o a da ptati o n is ma de  at i nteri m a nal ysis,  t he sam ple  size will be ap pr o xi matel y  
3 3 0 pa tie nts.  
I n N o ve m ber 2 0 1 9, the  ID M C r ec o mme n de d  to  i ncrease t he sa m ple size t o 4 5 0 patie nts. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 3 7  of 1 3 1  
 
Fi g u r e 1 :  
R e c r uit  m e nt  a n d  St u d y  Fl o  w  
Af ter s cr e e ni n g, eli gi bl e  p ati e nts   will  b e r a n d o  mi z e d i nt o  o n e  of t  w o st u d y  ar  ms.  P ati e nts   will  eit h er r e c ei v e 
M  O  R 0 0 2 0 8  +   B e n d a  m usti n e  or   Rit u xi  m a b  +   B e n d a  m usti n e fr o  m  c y cl e  1 t o  c y cl e  6.  Fr o  m  c y cl e  7  o n  w ar ds, t h e y 
m a y r e c ei v e   M  O  R 0 0 2 0 8  or   Rit u xi  m a b  o nl y.  
D uri n g t h e i niti al s af et y  e v al u ati o n  p h as e  of t h e tri al t h e first  3  p ati e nts i n  b ot h  ar  ms   will  b e  d os e d s e q u e nti all y   wit h 
a  4 8-h o ur l a g  p eri o d  b et  w e e n t h e  e nr ol  m e nts  of  2  c o ns e c uti v e  p ati e nts ( c o u nt e d fr o  m   C 1  D 4).  F oll o  wi n g  a  p ositi v e 
r e c o  m  m e n d ati o n  of t h e I  D  M  C, s e v e n  a d diti o n al  p ati e nts i n  e a c h  ar  m   m a y  b e  d os e d i n  p ar all el.   A n  a d diti o n al I  D  M  C 
r e vi e  w   will t a k e  pl a c e  aft er t h e l ast  of  1 0  p ati e nts i n  e a c h  ar  m  h a v e  c o  m pl et e d   C 3  D 1  visit i n t h eir r es p e cti v e 
tr e at  m e nt  all o c ati o n  ar  m.  S h o ul d t h e I  D  M  C   m ai nt ai n t h eir i niti al r e c o  m  m en d ati o n t h at t h e  c o  m bi n ati o n tr e at  m e nts 
ar e s af e, t h e tri al   m a y  pr o c e e d f urt h er   wit h r e cr uit  m e nt ( P h as e III  p art  of t h e tri al).  
 
A n i nt eri  m  a n al ysis   will  b e  p erf or  m e d  aft er  1 2 8  P F S  e v e nts  h a v e  b e e n  o bs er v e d.  T h e fi n al s a  m pl e si z e w as  a dj ust e d 
aft er t h e i nteri  m  a n al ysis  t o   N = 4 5 0.  T h e fi n al  a n al ysis i n cl u di n g  b ut  n ot li  mit e d t o  pri  m ar y  a n d s e c o n d ar y  e n d  p oi nt 
a n al ys es   will  b e  c o n d u ct e d  at t h e  e n d  of t h e tri al.  
   
A b br e vi ati o ns:   B E  N  =  b e n d a  m usti n e;   C  =   C y cl e ; I  D  M  C  = I n d e p e n d e nt   D at a   M o nit ori n g   C o  m  mitt e e;   M  O  R = 
M  O  R 0 0 2 0 8;   R  = r a n d o  mis ati o n ( 1: 1);   R T  X  = rit u xi  m a b.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

I n c yt e   C or p or ati o n    
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B-  MI  N  D) 
D at e:  1 0-  A pr- 2 0 2 4    
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt   N o.  8,   V ersi o n  1 1. 0     
E u dr a  C T   N u  m b er:  2 0 1 4- 0 0 4 6 8 9- 1 1 
 
V  V-  C LI  N- 0 1 9 4 2 9     
C o nfi d e nti al    
P a g e  3 8  of  1 3 1 
 
 
Fi g u r e  2:    
St u d y   D esi g n 
* S u bs e q u e nt t o t h e  c o  m pl eti o n  of   C o  m bi n ati o n  Tr e at  m e nt,  p ati e nts   wit h  a n  o n g oi n g r es p o ns e  of  at l e ast  P  R  at t h e 
e n d  of   C y cl e  6,  as  ass ess e d l o c all y,   will  c o nti n u e  a nti b o d y   m o n ot h er a p y tr e at  m e nt  u ntil  dis e as e  pr o gr essi o n i n 
a c c or d a n c e   wit h t h e i niti a l tr e at  m e nt  all o c ati o n (  R T  X  or   M  O  R 0 0 2 0 8). 
#B E  N is t o  b e  a d  mi nist er e d  o n   D a ys  2 + 3  of   C y cl e  1.  S u bs e q u e ntl y,   B E  N  c a n  b e  a d  mi nist er e d  o n   D a ys  1 + 2  or 
D a ys  2 + 3  a c c or di n g t o i nstit uti o n al/ p ati e nt/ p h ysi ci a n  c h oi c e. 
N ot e:  Str atifi c ati o n   will  n ot  b e  a p pli e d t o  p ati e nts r a n d o  mis e d  d uri n g I niti al  S af et y  E v al u ati o n (s e e Fi g ur e  1 ). 
A b br e vi ati o ns:   B E  N  =  b e n d a  m usti n e;  E  C  O  G  =  E ast er n   C o o p er ati v e   O n c ol o g y   Gr o u p;   O S  =  o v er all s ur vi v al;  P F S  = 
pr o gr essi o n-fr e e s ur vi v al;   R-  R   D L  B  C L  = r el a ps e d  or r efr a ct or y  diff us e l ar g e   B- c ell l y  m p h o  m a;   R  = r a n d o  mis ati o n 
( 1: 1);   R T  X  = rit u xi  m a b. 
   
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 3 9  of 1 3 1  
8. 3  St u d y    Co n d u ct  
T he  trial will be  co n d ucte d  at a p pr o xi matel y 1 8 0 sites w orl d wi de. 
T he total st u d y d urati o n is ex pecte d t o be ap pr o xi matel y 4 ye ars pl us F oll o w - U p (ass u mi n g n o 
sa m ple size a dj ust me nt  b y  the I D M C) . T he st u d y d urati o n f or an i n di vi d ual patie nt incl u de s 
Scree ni n g ( u p t o 2 8 da ys fr o m t he si g nin g of  t he IC F) , C o m bi nati o n Treat me nt (ma xi m u m 
6 m o nt hs) f oll o we d b y A nti b o d y M o n ot hera p y T reat me nt (u ntil  disease pr o gressi o n). After s t u d y 
treat me nt e n ds , eac h patie nt e nters Foll o w- U p  of a n i n di vi d uall y va r yi n g d urati o n. 
F oll o w- U p  be gi ns  wit h t he E n d  of Treat me nt ( E O T) visit. P atie nts  will als o ha ve a n o n- site 
3 0- da y p ost- treat me nt safet y  eval uati o n  visit ( 3 0-Da y  Safet y  F oll o w- U p visit). F oll o w -U p  f or t he 
pri mar y st u d y e n d p oi nt, i.e. P F S, s h o ul d be pe rf or me d ever y  3 m o nt hs u ntil d isease pr o gressi o n,  
wit h dra wal  of  c o nse nt or deat h, whic he ver  c omes first.  After c o nfir me d  pr o gressi o n,  patie nts 
s h o ul d be foll o we d u p f or O S.
F oll o w- U p  f or O S will be perfor me d  e ver y 3 m o nt hs fr o m t he date  of E O T or  t he last F oll o w-U p  
Visit f or t he pri mar y st u d y e n d p oi nt (i.e. P F S ), as a p plica ble . T he  first F oll o w-U p  f or O S  will be 
a cli nic visit.  S u bse q ue nt F oll o w- U p  for  O S  visits  ma y be p h o ne co ntacts. F or F oll o w- u p of a 
p atie nt w h o bec o mes eli gi ble f or “ F urt her or C o nti n ue d A nti b o d y Treat me nt,”  please refer t o 
Secti o n 1 0. 5.  
8. 4  E n d of St u d y  
T he en d of the st u d y is defi ne d as 3  years after  t he last patie nt w as ra n d o mize d  or after  
a p pr o xi matel y 7 5 %  of p atie nts ha ve  die d, w hic he ver occ urs f irst. U p o n st u d y cl os ure, t he 
s p o ns or will  n otif y t he a p plica ble re g ulat or y a ge nci es i n accor da nce wit h  local  re q uire me nts. 
8. 5  P atie nt Selecti o n Criteri a  
8. 5. 1  Incl usi o n  C riteri a  
Eli gi ble  patie nts m ust meet t he f oll o wi n g criteria t o be enr olle d  i n t he st u d y: 
Di a g n osis/ T ri al Po p ul ati o n 
1.
A g e ≥1 8  y e ars
•
F or  Si n g a p or e  o nl y:  a g e  ≥ 2 1  y e ars
2.
Hist ol o gi c all y   c o nfir  m e d  di a g n osis,  a c c or di n g t o t h e   W orl d   H e alt h   Or g a ni z ati o n (  W  H  O,
2 0 0 8)  cl assifi c ati o n,  of:
a)
Diff us e l ar g e   B -c ell l y  m p h o  m a  n ot  ot h er  wis e s p e cifi e d (  D L  B  C L   N  O S)
b)
T  c ell/ histi o c yt e ri c h l ar g e   B -c ell l y  m p h o  m a ( T  H  R L  B  C L)
c)    E pst ei n -B arr  vir us ( E  B  V)  p ositi v e   D L  B  C L  of t h e  el d erl y ( E  B  V -p ositi v e   D L  B  C L)
d)    C o  m p osit e l y  m p h o  m a   wit h  a   D L  B  C L  c o  m p o n e nt   wit h  a s u bs e q u e nt   D L  B  C L r el a ps e
e)    Dis e as e tr a nsf or  m e d fr o  m  a n  e arli er  di a g n osis  of l o  w- gr a d e l y  m p h o  m a (i. e.  a n i n d ol e nt
p at h ol o g y s u c h  as f olli c ul ar l y  m p h o  m a,   m ar gi n al  z o n e l y  m p h o  m a) i nt o   D L  B  C L   wit h  a
D L  B  C L r el a ps e s u bs e q u e nt t o   D L  B  C L tr e at  m e nt .

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 4 0  of 1 3 1  
3.
Fres h t u m o ur tiss ue f or ce ntral pat h ol o g y re vie w m ust be pr o vi de d as a n a dj u nct t o
partici pati o n i n t his st u d y. S h o ul d it n ot be p ossi ble t o o btai n a fres h t u m o ur tiss ue sa m ple,
arc hi val  paraffi n e m be d de d t u m o ur tiss ue ac q uire d ≤3 years pri or t o scree ni n g f or t his
p ro t oc ol m ust be availa ble  f or t his pur p ose .
4.
Patie nts m ust  ha ve:
a)
R- R  D L B C L (fo r defi niti o ns,  see Secti o n 8. 1 o f t he pr ot oc ol)
b)
at least  on e bi di me nsi o nall y  meas ura ble disease site.  Th e lesi o n must  ha ve a greatest
tra ns verse dia meter of  ≥1. 5  cm  a nd  greatest per pe n dic ular dia meter of ≥1. 0 c m at
baseli ne . T he lesi o n m ust be p ositi ve o n P E T sca n (f or defi niti o n, see Ju wei d  et al.
( 2 0 0 7)).
c)
recei ve d at least one , b ut n o m ore t ha n t hree pre vi o us s yste mic t hera py  li nes f or t he
treat me nt of D L B C L (for  f urt her details see Secti o ns  8. 6 an d  9. 5). At least  one p re vi o us
t hera p y li ne m ust ha ve i ncl u de d a C D 2 0-tar gete d  the ra p y (e. g. R T X).
d)
Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) perf or ma nce stat us of 0 t o 2
5.
Patie nts a fter fail ure of A S C T  or patie nts c o nsi dere d  i n t he o pi ni o n of t he i n vesti gat or
c urre ntl y  n ot eli gi ble f or H D C wit h s u bse q ue nt A S C T . D oc u me ntati o n of t he reas o n f or
i neli gi bilit y f or A S C T m ust be prese nt i n t he patie nt’s  so urce  data  (f or details, see
Secti o n  8. 6 ).
L a b o r at o r y   V al u es  
6.
Patie nts  m ust meet t he f oll o wi n g la b orat or y  criteria at Scree ni n g:
a)
abs ol ute ne utr o p hil c o u nt ( A N C) ≥1. 5 ×  1 09/ L ( u nless sec o n dar y t o b o ne marr o w 
i n v ol ve me nt b y D L B C L as de m o nstrate d b y b o ne marr o w as pirati o n a n d b o ne marr o w  
bi o ps y r e q uir e d f or Scree ni n g)
b ) p latelet c o u n t ≥9 0  ×  1 09/ L ( u nless sec o n dar y t o b o ne marr o w i n v ol ve me nt b y D L B C L as 
de m o nstrate d b y b o ne marr o w as pirati o n a n d b o ne marr o w bi o ps y re q uire d f or  
Scree ni n g ) a n d a bse nce of acti ve blee di n g
c)
total ser u m bilir u bi n ≤2. 5 ×  u pper li mit of n or mal ( U L N) u nless sec o n dar y t o Gil bert’s  
s y n dr o me (o r patter n co nsiste nt wit h  Gil bert’s)  or d oc u me nte d li ver i n v ol ve me nt b y 
l y m p h o ma. Patie nts wit h Gil bert's s y n dr o me or d oc u me nte d li ver i n v ol ve me nt b y 
l y m p h o ma ma y be i ncl u de d if t heir t otal bilir u bi n is ≤5 x  UL N  (see e xcl usi o n criteri o n 
6e )
d ) A L T, A S T a n d al kali ne p h os p hatase ≤3 ×  U L N or < 5 ×  UL N  in  cases of  doc u me nte d  
li ver i n v ol ve me nt b y l y m p h o ma
e)
ser u m creati ni ne ≤ 2. 0 U L N  or creati ni ne cleara n ce m ust b e ≥4 0  m L/ mi n,  calc ulate d  
usi n g a sta n dar d C oc kcr oft- G a ult f or m ula ( Coc kr o ft & Ga ult, 1 9 7 6;  see A p pe n di x A)
7.
F or  a fe male of c hil d beari n g po te ntial ( FC B P; f or defi niti o n  see Secti o n  8. 9 ), a ne gati ve 
pre g na nc y test m ust be c o nfir me d bef ore e nr ol me nt. A n F C B P  m ust  c om mi t to  take  hi g hl y  
effecti ve  c o ntrace pti ve preca uti o ns (see A p pe n di x B) wit h o ut i nterr u pti o n d uri n g t he st u d y 
a n d f or 3, 6 or 1 2 m o n t hs after t he last d ose of M O R 0 0 2 0 8, B E N or R T X res pecti vel y, 
w h ic he ver is later. A n FC B P  must  refrai n fro m b reastfee di n g an d  d o nati n g bl o o d or o oc ytes  
d uri n g t he c o urse of t he st u d y a n d f or 3, 6 or 1 2 m o n t hs after t he last d ose of M O R 0 0 2 0 8, 
B E N or  R T X r es pecti vel y,  wh ic he ver is later. (A p plic a ble  i n Re p u blic  of K ore a: a n FC B P  
m u st co m mit  to  ta ke h i ghl y  effecti ve c ontrace pti ve preca uti o ns (see  A p pe n di x B) wit h o ut 
i nterr u pti o n a n d refrai n fr o m breastfee di n g a n d d o nati n g bl o o d or o oc ytes d uri n g t he c o urse

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 4 1  of 1 3 1  
of t h e st u d y  a n d f or  6   m o nt hs  aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8, 6   m o nt hs  aft er t h e l ast  d os e 
of B E  N  or 1 2   m o nt hs  aft er t h e l ast  d os e  of   R T  X,   w hi c h e v er is l at er.) . 
8.
M al e  p ati e nts   m ust  us e   a n eff e cti v e  b arri er   m et h o d  of  c o ntr a c e pti o n wit h o ut i nt err u pti o n
d uri n g t h e st u d y  a n d f or  3,  6  or  1 2   m o nt hs  aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8,   B E  N  or   R T  X
r es p e cti v el y,   w hi c h e v er is l at er, if t h e  p ati e nt is s e x u all y  a cti v e   wit h  an F  C  B P .   M al es   m ust
r efr ai n fr o  m  d o n ati n g  bl o o d  or s p er  m  d uri n g t h e st u d y  p arti ci p ati o n  a n d f or  3,  6  or  1 2   m o nt hs
aft er t h e l ast  d os e  of M  O  R 0 0 2 0 8,   B E  N  or   R T  X r es p e cti v el y,   w hi c h e v er is l at er. ( A p pli c a bl e
i n   R e p u bli c of   K o r e a : m al es   m ust r efr ai n fr o  m  d o n ati n g  bl o o d  or s p er  m,  a n d if t h e  p ati e nt is
s e x u all y  a cti v e   wit h  a  F  C  B P,   m ust  us e  a n  eff e cti v e  b arri er   m et h o d  of  c o ntr a c e pti o n   wit h o ut
i nt err u pti o n  d uri n g t h e st u d y  a n d f or  6   m o nt hs  aft er t h e l ast  d os e  of   M  O  R 0 0 2 0 8,  6   m o nt hs
aft er t h e l ast  d os e  of B E  N  or 1 2   m o nt hs  aft er t h e l ast  d os e  of R T  X,   w hi c h e v er is l at er) .
9.   I n t h e  o pi ni o n  of t h e i n v esti g at or, t h e  p ati e nts m ust :
a)
b e  a bl e t o  c o  m pl y   wit h  all st u d y -r el at e d  pr o c e dur es,   m e di c ati o n  us e,  a n d  e v al u ati o ns
b)   b e  a bl e t o  u n d erst a n d  a n d  gi v e i nf or  m e d  c o ns e nt
c)
n ot  b e  c o nsi d er e d t o  b e p ot e nti all y  u nr eli a bl e  a n d/ or  n ot  c o o p er ati v e.
8. 5. 2  E x cl usi o n   C rit e ri a  
Eli gi bl e  p ati e nts   m ust  n ot  h a v e  a n y  of t h e f oll o  wi n g t o  b e  e nr oll e d i n t h e st u d y: 
E x cl usi o n a r y   Di a g n osis C rit e ri a  
1.
Patie nts w h o  ha ve:
a)
a n y ot her hist ol o gical t y pe of l y m p h o ma i ncl u di n g, e. g., pri mar y med iasti nal (t h y mic) 
lar ge B-cell ( P M B L ) or B ur kitt’s l ym p h o ma
b ) p ri mar y refract or y  DL B C L  (f or defi niti o n, s ee Secti o n 8. 1)
c)
p atie nts  wit h kn o w n  " do u ble/tri ple  hit" D L B C L  ge netics c h aracterise d by  sim ulta ne o us  
detecti o n of M Y C  wit h  B C L 2  a n d/ or B C L 6  tra nsl ocati o n, as d efi ne d b y  fl u oresce nce i n 
sit u h y bri disati o n (FI S H) . M Y C , B C L 2 , B C L 6  testi n g pri or t o st u d y e nr ol me nt is n ot  
re q uire d.
d ) ce ntral ner v o us s yste m ( C N S) l y m p h o ma i n vol ve me n t i n prese nt or past me dical 
h ist or y
E x cl usi o n a r y P r e vi o us  a n d C u r r e nt T r e at  m e nt C rit e ri a  
2.
Patie nts w h o ha d a maj or s ur ger y (for  defi niti o n, see Secti o n  8. 1 ) less t ha n 3 0 da ys pri or t o 
Da y 1 d osi n g
3.
Patie nt s w h o ha ve, wit hi n 1 4 da ys pri or t o Da y 1 d osi n g:
a)
n ot disc o nti n ue d C D 2 0-tar gete d t hera p y, c he m ot hera p y, ra di ot hera p y, i n vesti gati o nal 
a ntica nce r t hera p y or ot her l y m p h o ma-s pecific t hera p y  (f or e xce p ti o ns see Secti o n 9. 5. 3 )
b ) recei ve d  li ve vacci nes (for defi niti o n,  see Secti o n 8. 6 )
c)
req u ire d pare nteral a nti micr o bial t hera p y  f or acti ve, i nterc urre nt sy ste mic i nfecti o ns
4.
Patie nts w h o:
a)
i n t he o pi ni o n of t he i n vesti gat or, ha ve n ot rec o vere d s ufficie ntl y fr o m t he a d verse t o xic  
effects  of pri or t hera pies, maj or s ur geries (f or defi niti on,  see Secti o n 8. 1 ) or si g nifica nt 
tra u matic  i nj uries
b)
were pre vi o usl y  treate d wit h  CD 1 9 -tar gete d t hera p y or B E N

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 4 2  of 1 3 1  
c)
ha ve a hist or y of pre vi o us se vere aller gic reacti o ns t o c o m p o u n ds of si milar bi ol o gical or
c he mical c o m p ositi o n t o M O R 0 0 2 0 8, R T X, m uri ne pr otei ns or B E N , or the e xci pie nts
c o ntai ne d i n t he st u d y dr u g f or m ulati o ns
d)
ha ve u n der g o ne A S C T w it hi n a peri o d of ≤3 m o nt hs pri or t o si g ni n g t he I C F . Patie nts
w h o  ha ve  a m ore dista nt hist or y of A S C T m ust e x hi bit f ull hae mat ol o gical rec o ver y
bef ore e nr ol me nt i nt o t he st u d y.
e)
ha ve u n der g o ne pre vi o us all o ge nei c ste m  cell tra ns pla ntati o n
f) c o nc urre ntl y  use ot her a ntica ncer  or ex peri me ntal treat me nts  (f or e xce pti o ns see
Secti o n  9. 5. 3 )
E x c l usi o n a r y   Me di c al H ist o r y C rit e ri a  
5.
Pri or hist or y  of mali g na ncies ot her t ha n DL B C L,  u n less t he patie nt has  bee n  free of t he 
disease f or ≥3 years pri or t o S cree ni n g. E xce pti o ns t o t he ≥3 - year ti me  li mit i ncl ude  hist or y 
o f t he f oll o wi n g:
a)
ba sal cell carci n o ma of  t he s ki n
b)
s q ua m o us cell carci n o ma of  t he ski n
c)
carci n o ma  i n sit u of t he  cer vi x
d)
carci no ma  i n sit u of  the breast
e)
carci n o ma  i n sit u of t he bla d der
f) i nci de ntal  hist ol og ical fi n di n g of pr ostate ca ncer (T u m o ur/ N o de/ Metastasis [ T N M]  sta ge 
of T 1a or T 1 b)
6.
Patie nts  wit h:
a)
p o siti ve he patitis  B a n d/ or C ser ol o g y (for  defi niti o ns, see Secti o n  8. 6 )
b ) k n o w n s er o p o siti vit y for or hist or y  of acti ve  viral i nfecti o n wit h  hu ma n  
i m m u n o deficie nc y vir us (HI V)
c)
e vi de nce of  acti ve,  se vere u nc o ntr olle d s yste mi c i nfecti o ns (e. g., t u berc ul osis [ T B], 
o p p ort u nistic i nfecti o ns) or se psis
d ) a hist or y or e vi de nce of se verel y i m m u n oc o m pr o mise d state
e)
a hist or y or e vi de nce  of se vere he patic  im p airme nt (t ota l ser u m bilir u bi n >3  m g/ d L),  
ja u n dice u nless sec o n dar y t o Gil bert’s s y n dr o me or d oc u me nte d l i ver i n v ol ve me nt b y 
l y m p h o ma (see in cl usi o n criteri o n 6c)
f) a hist or y or e vi de nce of cli nicall y  sig nifica nt  car di o v asc ular,  cere br o vasc ular,  CN S  a n d/ or 
o t her disease t hat, i n t he i n vesti gat or’s o pi ni o n, w o ul d precl u de partici pati o n i n t he st u d y 
or c o m pr o mise t he patie nt’s a bilit y t o gi ve i nf or me d c o nse nt (f or a d diti o nal e x pla nati o ns, 
see Secti o n 8. 6 ).
8. 6  A d diti o n al   E x pl a n at o r y I nf o r  m ati o n  o n I n cl usi o n  a n d E x cl usi o n   C rit e ri a  
I n cl usi o n C rit e ri a:   Di a g n osis/  T ri al  P o p ul ati o n  
I n cl usi o n “ 2.   Hist ol o gi c all y  c o nfir  m e d  di a g n osis,  a c c or di n g t o t h e   W orl d   H e alt h   Or g a niz ati o n 
(  W  H  O,  2 0 0 8)  cl assifi c ati o n,  of: 
e)    Dis e as e tr a nsf or  m e d fr o  m  a n  e arli er  di a g n osis  of l o  w- gr a d e l y  m p h o  m a (i. e.  a n
i n d ol e nt  p at h ol o g y s u c h  as f olli c ul ar l y  m p h o  m a,   m ar gi n al z o n e l y  m p h o  m a) i nt o
D L B  C L   wit h  a   D L B  C L r el a ps e s u bs e q u e nt t o   D L B  C L tr e at  m e nt ”

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 4 3  of 1 3 1  
P ati e nts   wit h   Ri c ht er's tr a nsf or  m ati o n  or   Ri c ht er's s y n dr o  m e  ar e  n ot  eli gi bl e f or st u d y 
p arti ci p ati o n.  
In cl usi o n “ 5. P ati e nts  aft er f ail ur e  of  A S  C T   or  p ati e nts  c o nsi d er e d i n t h e  o pi ni o n  of t h e 
i n v esti g at or c urr e ntl y n ot  eli gi bl e f or H  D  C    wit h s u bs e q u e nt  A S  C T.   D o c u  m e nt ati o n  of t h e r e as o n 
f or i n eli gi bilit y f or  A S  C T   m ust  b e  pr es e nt i n t h e  p ati e nt’s s o ur c e  d at a. ” 
A s f or t h e   A SC T, t h e i n d u cti o n,  c o ns oli d a ti o n, st e  m  c ell  c oll e cti o n,  pr e p ar ati v e r e gi  m e n 
i n cl u di n g tr a ns pl a nt ati o n,  a n d   m ai nt e n a n c e   will  b e  c o nsi d er e d  a si n gl e li n e  of t h er a p y. 
F or t h e  p ur p os e  of t his  pr ot o c ol,  p ati e nts   w h o  ar e  n ot  c a n di d at es f or   H  D  C   wit h   A S  C T  ar e 
d efi n e d  b y   m e eti n g  a n y  of t h e f oll o  wi n g  crit eri a  as  e vi d e n c e d i n t h e  p ati e nt’s s o ur c e  d at a : 
1)
I n a d e q u at e  p erf or  m a n c e st at us (  K ar n ofs k y  P erf or  m a n c e  St at us  ≤  8 0  %; s e e A p p e n di x   D )
2)
Dis e as e  n ot r es p o nsi v e t o s al v a g e  c h e  m ot h er a p y.   R es p o nsi v e n ess is  d efi n e d  as  a t u  m ou r
d e  m o nstr ati n g  eit h er C  R  or  P  R t o s al v a g e  c h e  m ot h er a p y.
3)
I n a d e q u at e   m aj or  or g a n f u n cti o n:
a)
S y  m pt o  m ati c  c o n g esti v e  h e art f ail ur e
b)    L u n g f u n cti o n-f or c e d  vit al  c a p a cit y ( F  V  C), f or c e d  e x pir at or y  v ol u  m e i n  1 s e c o n d
( F E  V- 1),  a n d  c orr e ct e d  diff usi o n  c a p a cit y  of t h e l u n g f or  c ar b o n   m o n o xi d e (  D L  C  O)
≤  6 0  %
c)
R e n al f u n cti o n- c r e ati ni n e  cl e ar a n c e  <  6 0   mL /  mi n
d)
Li v er f u n cti o n-t ot al s er u  m  bilir u bi n  a n d tr a ns a  mi n as es  >  2  x   U L  N
e)
S eri o us  a cti v e  or  u n c o ntr oll e d   mi cr o bi al i nf e cti o ns ( e. g.  T  B)
4)    Hist or y  or  e vi d e n c e  of si g nifi c a nt  c o- m or bi d   m e di c al  or  ps y c hi atri c ill n ess   w hi c h   w o ul d
si g nifi c a ntl y  c o  m pr o  mis e t h e  p ati e nt's  cli ni c al c ar e  a n d  c h a n c es  of s ur vi v al
5)
I n a bilit y t o  c oll e ct  a d e q u at e st e  m  c ell  gr aft ( e. g.  <  1- 2  x  1 06 C  D 3 4 +  c ells fr e e  of t u  m o u r
c o nt a  mi n ati o n/ k g r e ci pi e nt  b o d y   w ei g ht)
In cl usi o n   C rit e ri a:   L a b o r at o r y  v al u es 
I ncl usi o n   “ 6.  P ati e nts   m ust   m e et t h e f oll o  wi n g l a b or at or y  crit eri a  at  S cr e e ni n g: 
e)
s er u  m  cr e ati ni n e  ≤ 2. 0 x   U L  N  or cr e ati ni n e  cl e ar a n c e   m ust  b e  ≥ 4 0   m L/  mi n  c al c ul at e d
usi n g  a st a n d ar d   C o c k cr oft-  G a ult f or  m ul a (C o c k cr oft  a n d   G a ult ( 1 9 7 6) ; se e
A p p e n di x  A  to t h e  pr ot o c ol)
G l o  m er ul ar filtr ati o n r at e  c a n  als o  b e  us e d i n  pl a c e  of  cr e ati ni n e  or  cr e ati ni n e  cl e ar a n c e (Cr  Cl).  
E x cl usi o n  c rit e ri a: E x cl usi o n a r y   Di a g n osis   C rit e ri a 
E x cl usi o n   “1. P ati e nts   w h o  h a v e:  
b) pri  m ar y r efr a ct or y   D L B  C L
P r ot o c ol   M  O  R 2 0 8  C 2 0 4  e x cl u d es  pri  m ar y r efr a ct or y  p ati e nts  d efi n e d  as  p ati e nts   w h o  pr o gr ess i n 
t h e  c o urs e  of first li n e tr e at  m e nt  or   wit hi n  6   m o nt hs  of  c o  m pl eti o n  of first li n e tr e at  m e nt.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 4  of 1 3 1  
T h e  pr ot o c ol  all o  ws t h e i n cl usi o n  of: 
1)   D L  B  C L  p ati e nts   wit h  a  hist or y  of  pri  m ar y r efr a ct or y  dis e as e   w h o   w er e r es p o nsi v e t o  a l at er 
tr e at  m e nt li n e,  
2) P ati e nts    wit h r el a ps e d   D L  B  C L  a n d r e  missi o n l asti n g   m or e t h a n  6   m o nt hs  of  pri or 
R T  X - c o nt ai ni n g t h er a p y 
3)   D L  B  C L  p ati e nts   w h o  ar e  n ot r es p o n di n g  or  pr o gr ess  e arl y   w h e n tr e at e d i n  2 n d  a n d  3r d li n e 
i n cl u di n g   R T  X- c o nt ai ni n g r e gi  m e ns. 
 
E x cl usi o n  c rit e ri a: E x cl usi o n a r y P r e vi o us  a n d C u r r e nt T r e at  m e nt  
E x cl usi o n   “3.  P ati e nts   w h o  h a v e,   wit hi n 1 4 d a ys  pri or t o   D a y  1  d osi n g: 
b ) R e c ei v e d li v e  v a c ci n es ” 
 
A d diti o n al i nf or  m ati o n: li v e  v a c ci n es ( e. g.  y ell o  w f e v er  v a c ci n ati o n) m ust n ot  b e  a d  mi nist er e d t o 
p ati e nts  i n t his st u d y.   V a c ci n ati o ns  a g ai nst i nfl u e n z a   wit h i n a cti v at e d  vir us  or  v a c ci n ati o n f or 
p n e u  m o c o c c al  dis e as es  ar e  all o  w e d . 
 
E x cl usi o n  c rit e ri a: E x cl u si o n a r y   Me di c al H ist o r y 
E x cl usi o n   “6. P ati e nts   wit h:  
a)  p ositi v e  h e p atitis  B  a n d/ or   C s er ol o g y ” 
 
I n t h e  c o nt e xt  of t h e  e x cl usi o n  crit eri a, s er o p ositi v e f or  or  a cti v e  vir al i nf e cti o n   wit h   H  B  V 
m e a ns:  
1)  H e p atitis   B  vir us s urf a c e  a nti g e n ( H  Bs  A g ) p ositi v e 
2)  H  Bs  A g n e g ati v e,  a nti -H  B c  p ositi v e  a n d  d et e ct a bl e  vir al   D  N  A (r e g ar dl ess  of   H  Bs  A b 
st at us). 
 
P ati e nts   w h o  e x hi bit t h e  cl assi c al  v a c ci n ati o n  pr ofil e  of   H  Bs  A b  p ositi v e,  a nti -H  B c  n e g ati v e  a n d 
H  Bs  A g  n e g ati v e  ar e  eli gi bl e.  
 
A  p ositi v e  h e p atitis   C t est is  d efi n e d  as  a  p o siti v e t est f or h e p atitis   C  vir us  a nti b o d y ( a nti-H  C  V ) 
a n d  a  p ositi v e t est f or   H  C  V   R  N  A.   T h us,  p ati e nts   wit h  p ositi v e s er ol o g y  b ut  n e g ati v e   H  C  V   R  N  A 
t est r es ults  ar e  eli gi bl e. 
 
Pl e as e r ef er t o S e cti o n 1 0. 3. 7. 2  f or f urt h er i nf or  m ati o n. 
 
b)  “ k n o  w n s er o p ositi vit y f or  or  hist or y  of  a cti v e  vir al i nf e cti o n   wit h  h u  m a n 
i  m  m u n o d efi ci e n c y  vir us (  HI V)” 
 
A d diti o n al i nf or  m ati o n: n o s af et y  d at a  o n t h e  us e  of C  D 1 9  a nti b o di es i n   HI  V  p ositi v e  p ati e nts 
ar e  c urr e ntl y  a v ail a bl e.  
 
c) “ e vi d e n c e  of  a cti v e, s e v er e s yst e  mi c,  u n c o ntr oll e d i nf e cti o ns ( e. g., 
t u b er c ul osis [ T B],  o p p ort u nisti c i nf e cti o ns)  or s e psis 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 5  of 1 3 1  
I nf e cti o ns  c o ntr oll e d  o n  c o n c urr e nt  a nti  mi cr o bi al  a g e nts  a n d/ or  a nti  mi cr o bi al  pr o p h yl a xis  p er 
i nstit uti o n al  g ui d eli n es  ar e  a c c e pt a bl e. 
 
f) “ a hist or y  or  e vi d e n c e  of  cli ni c all y si g nifi c a nt  c ar di o v as c ul ar, 
c er e br o v as c ul ar,   C  N S  a n d/ or  ot h er s yst e  mi c  dis e as e t h at   w o ul d i n t h e 
i n v esti g at or’s  o pi ni o n  pr e cl u d e  p arti ci p ati o n i n t h e st u d y  or  c o  m pr o  mis e t h e 
p ati e nt’s  a bilit y t o  gi v e i nf or  m e d  c o ns e nt. ” 
 
A d diti o n al i nf or  m ati o n:   cli ni c all y si g nifi c a nt  c ar di o v as c ul ar,  c er e br o v as c ul ar,   C  N S  a n d/ or  ot h er 
s yst e  mi c  dis e as e i n cl u d e,  b ut ar e n ot li  mit e d t o:  
1)  a m y o c ar di al i nf ar cti o n   wit hi n  6   m o nt hs  b ef or e  e nr ol  m e nt ,  u n c o ntr oll e d  a n gi n a  p e ct oris, 
el e ctr o c ar di o gr a p hi c  e vi d e n c e  of  a c ut e is c h a e  mi a  
2)  N e  w   Y or k   H e art   Ass o ci ati o n (  N  Y  H  A)  cl ass II  or  hi g h er  c o n g esti v e  h e art f ail ur e  (s e e 
A p p e n di x  E for   N  Y  H  A  cl assifi c ati o n)  
3)  s e v er e  u n c o ntr oll e d or  cli ni c all y si g nifi c a nt  c o n d u cti o n s yst e  m  a b n or  m aliti es  ( e. g. 
v e ntri c ul ar t a c h y c ar di a,  hi g h -gr a d e atri o v e ntri c ul ar - bl o c k). P ati e nts   wit h st a bl e, 
as y  m pt o  m ati c  atri al fi brill ati o n  ar e  all o  w e d i n t h e st u d y  pr o vi d e d t h e y  d o  n ot   m e et t h e 
ot h er  e x cl usi o n  crit eri a  
4)  s e v er e,  u n c o ntr oll e d  c ar di a c  dis e as e i n cl u di n g cli ni c all y si g nifi c a nt  p eri c ar di al  d is e as e 
5)  C  N S l esi o ns /c er e br o v as c ul ar  e v e nt(s)   wit h  cli ni c all y si g nifi c a nt s e q u el a e  
6)  C  N S,   m e ni n g e al  or  e pi d ur al   m ali g n a n ci es ( e. g.,  br ai n   m et ast as es,  k n o  w n   m e ni n g e osis 
l e u k a e  mi a) 
7)  c er e br o v as c ul ar  e v e nt(s)   wit h  cli ni c all y si g nifi c a nt s e q u el a e.  
 
S cr e e ni n g f or  c er e br os pi n al fl ui d   C  N S i n v ol v e  m e nt is  n ot  r e q uir e d  b ut   m a y  b e  p erf or  m e d  at t h e 
dis cr eti o n  of t h e i n v esti g at or.  
 
8. 7  R a n d o  mis ati o n  
D uri n g  S cr e e ni n g,  e a c h  p ati e nt   w h o si g ns t h e I  C F   will  b e  all o c at e d  a  u ni q u e i d e ntifi c ati o n 
n u  m b er.  
 
All  p ati e nts   w h o f ulfil  all i n cl usi o n  crit eri a  a n d   w h o  ar e  n ot  b arr e d  b y  a n y  of t h e  e x cl usi o n 
crit eri a   will  b e r a n d o  ml y  assi g n e d t o tr e at  m e nt  c o  m prisi n g    M  O  R 0 0 2 0 8 wit h B E  N  or   R T  X wit h 
B E  N i n  a  1: 1 r ati o.   R a n d o  mis ati o n   will  b e  d o n e t hr o u g h i nt er a cti v e r es p o ns e t e c h n ol o g y (I  RT ) 
b ef or e t h e  p ati e nt r e c ei v es  a n y st u d y   m e di c ati o n. W hil e  all i n cl usi o n  a n d  e x cl usi o n  crit eri a  n e e d 
t o  b e r e vi e  w e d  a g ai n  pri or t o r a n d o  misati o n, f or  all  crit eri a t h at r ef er t o l a b or at or y  p ar a  m e t ers, 
c e ntr al l a b or at or y r es ults  o bt ai n e d  d uri n g t h e s cr e e ni n g  p eri o d   will  b e  us e d f or  d et er  mi ni n g 
p ati e nt  eli gi bilit y f or st u d y r a n d o  mis ati o n. 
 
R es cr e e ni n g  of  p ati e nts   w h o   w er e  n ot  eli gi bl e f or st u d y  e nr ol  m e nt   will  b e  all o  w e d  u n d er t h e 
c o n diti o ns  d es cri b e d i n S e cti o n  8. 8 . P ati e nts   w h o  ar e r es cr e e n e d   will r e c ei v e  a  n e  w  u ni q u e 
i d e ntifi c ati o n  n u  m b er. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 6  of 1 3 1  
B ef or e r a n d o  mi sati o n,  e nr oll e d  p ati e nts   will  b e str atifi e d  a c c or di n g t o t h e f oll o  wi n g f a ct ors: 
a) Dis e as e r el a ps e/r e c urr e n c e:  e arl y ( ≤ 1 2   m o nt hs)  v ers us l at e ( > 1 2   m o nt hs ) fr o  m t h e 
c o  m pl eti o n  of t h e l ast tr e at  m e nt 
b)  A g e  ≤ 6 5  v ers us  > 6 5  y e ars  
c) E  C  O  G  p erf or  m a n c e st at us  0 -1  v ers us  2  
d)  Pri or s yst e  mi c t h er a p y li n es  ≤ 2 v ers us  > 2.  
 
R a n d o  mis ati o n  d uri n g I niti al S af et y   E v al u ati o n:  D uri n g I niti al  Saf et y E v al u ati o n , p ati e nts   will 
b e  all o c at e d t o tr e at  m e nt  c o  m prisi n g   M  O  R 0 0 2 0 8   wit h   B E  N  or   R T  X   wit h   B E  N vi a si  m pl e 
r a n d o  mis ati o n i n  a  1: 1 r ati o.  T h e i nf or  m ati o n  a b o ut str atifi c ati o n f a ct ors   will  n e v ert h el ess  b e 
c oll e ct e d f or t h es e  p ati e nts  as   w ell t o  b e  us e d i n t h e  a n al ysis  of t h e st u d y  d at a.  
 
8. 8  R e -s c r e e ni n g  P r o c e d u r es 
A  p ati e nt  c a n  b e r e -s cr e e n e d  at t h e  dis cr eti o n  of t h e i n v esti g at or  u n d er  c ert ai n  cir c u  mst a n c es. 
R e -s cr e e ni n g is r estri ct e d t o  o n e  att e  m pt  p er  p ati e nt  a n d  c a n  o nl y  b e  p erf or  m e d if  o n e  of t h e 
f oll o  wi n g  crit eri a is   m et: 
1.  T h e  p ati e nt  h as  alr e a d y  c o ns e nt e d  a n d   m et  all  of t h e i n cl usi o n  a n d  n o n e  of t h e  e x cl usi o n 
crit eri a  a n d  hi s  or  h er  e nr ol  m e nt   w as  d el a y e d  d u e t o  a n  u n e x p e ct e d  c h a n g e i n t h e 
p ati e nt’s  p ers o n al sit u ati o n ( e. g. f a  mil y iss u es) . 
2.  T h e  p ati e nt  pr e vi o usl y f ail e d t o  b e  eli gi bl e  d u e t o  a n y  e v e nt ( e. g.,  pl a n n e d s ur g er y, 
l a b or at or y t est r es ult) or a n y t e c h ni c al/l o gisti c r e as o n ( e. g. s cr e e ni n g  p eri o d  el a ps e d  d u e 
t o u n e x p e ct e d l e a v e  o r a bs e n c e  of  p ati e nt) t h at  h as  b e e n r es ol v e d. 
3.  T h e  p ati e nt f ail e d s cr e e ni n g pr e vi o usl y a n d  b e c o  m es  eli gi bl e f or t h e st u d y  b as e d  o n  a 
c h a n g e i n t h e i n cl usi o n  a n d  e x cl usi o n  crit eri a  as t h e r es ult  of  a  pr ot o c ol  a  m e n d  m e nt. 
4.  T h e p ati e nt f ail e d s cr e e ni n g  d u e t o  n o n -pr o gr ess e d/ n o n -r el a ps e d  dis e as e  at t h e ti  m e  of 
s cr e e ni n g  a n d l at er is  cli ni c all y  di a g n os e d  as  h a vi n g  pr o gr ess e d/r el a ps e d.  
N ot e:   A  p ati e nt s h o ul d  o nl y  b e r e -s cr e e n e d if t h er e is  a  cl e ar i n di c ati o n t h at t h e  p ati e nt   m a y  b e 
eli gi bl e  a c c or di n g t o t h e  c urr e ntl y  v ali d st u d y  pr ot o c ol.  
 
I n t h es e  c as es, if  pr e vi o us s cr e e ni n g  a cti viti es   w er e  dis c o nti n u e d  a n d  e nr ol  m e nt  di d  n ot  o c c ur, 
t h e f oll o  wi n g  pr o c e d ur es s h o ul d  b e i  m pl e  m e nt e d: 
1.  T h e  p ati e nt   m ust si g n  a n d  d at e  a  n e  w I  C F  as  p art  of t h e r e-s cr e e ni n g  pr o c e d ur e 
2.  T h e  eli gi bl e  p ati e nt   will r e c ei v e  a  n e  w  u ni q u e i d e ntifi c ati o n  n u  m b er  vi a t h e I R T  
3.  A  n e  w el e ctr o ni c  c as e r e p ort f or  m ( e  C  R F) will  b e  c o  m pl et e d  
4.  T h e  p ati e nt   will  b e  d o c u  m e nt e d  as r e -s cr e e n e d i n t h e so ur c e  d o c u  m e nts.  
 
A r e -s cr e e n e d  p ati e nt  c a n  b e  e nr oll e d, if  all  of t h e  c urr e nt i n cl usi o n  crit eri a  ar e   m et  a n d  n o n e  of 
t h e  e x cl usi o n  crit eri a  ar e   m et. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 7  of 1 3 1  
8. 9  D efi niti o n  of F e  m al e of   C hil d b e a ri n g P ot e nti al  
A s e x u all y   m at ur e f e  m al e p ati e nt or  a s e x u all y   m at ur e f e  m al e  p art n er  of  a   m al e p ati e nt is 
c o nsi d er e d t o  h a v e  c hil d b e ari n g  p ot e nti al  u nl ess s h e   m e ets  at l e ast o n e  of t h e f oll o  wi n g  crit eri a:  
1.  A g e ≥5 0  y e ars  a n d  n at ur all y a  m e n orr h o ei c f or ≥2 4   m o nt hs (i.e.,  h as n ot h a d   m e ns es  at  
a n y ti  m e i n t h e  pr e c e di n g  2 4  c o ns e c uti v e   m o nt hs).   A m e n orr h o e a f oll o  wi n g  c a n c er 
t h er a p y  d o es  n ot r ul e  o ut  c hil d b e ari n g  p ot e nti al 
2.  Pr e  m at ur e  o v ari a n f ail ur e  c o nfir  m e d  b y  a  g y n a e c ol o gist  
3.  Pr e vi o us  bil at er al s al pi n g o -o o p h or e ct o  m y,  or  h yst er e ct o  m y  
4.  X  Y  g e n ot y p e,  T ur n er s y n dr o  m e,  ut eri n e  a g e n esis . 
 
9  T  R  E  A  T  M  E  N  T S  
9. 1  S t u d y T r e at  m e nts  
T his is  a n  o p e n -l a b el st u d y.  Th e  c o  m bi n ati o n t r e at  m e nt  c o nsisti n g  of M  O  R 0 0 2 0 8 wit h B E  N  or 
R T  X  wit h B E  N will  b e  a d  mi nist er e d  at s p e cifi e d ti  m e p oi nts  at  pr ot o c ol -pr es cri b e d d os e l e v els 
f or  a   m a xi  m u  m  of si x c y cl es . 
 
S u bs e q u e nt t o t h e  c o  m pl eti o n  of t h e C o  m bi n ati o n T r e at  m e nt, p ati e nts wit h  a n  o n g oi n g r es p o ns e 
of  at l e ast  P  R,  as  p er l o c al  dis e as e r es p o ns e  ass ess  m e nt,  at t h e  e n d  of   C y cl e  6   will e nt er   A nti b o d y 
M o n ot h er a p y  Tr e at  m e nt i n  a c c or d a nc e   wit h t h eir  ori gi n al tr e at  m e nt  all o c ati o n u ntil  dis e as e 
pr o gr essi o n .  T h er ef or e, th e d ur ati o n  of   A nti b o d y M o n ot h er a p y T r e at  m e nt   m a y v ar y i n di vi d u all y . 
Tr e at  m e nt   m a y  b e st o p p e d  d u e t o  dis e as e r e c urr e n c e / pr o gr essi o n,   wit h dr a  w al  d u e t o 
u n a c c e pt a bl e t o xi cit y,  dis c o nti n u ati o n f or  a n y  ot h er r e as o n  or  d e at h,   w hi c h e v er  c o  m es first.   
 
I n t h e  c as e  of  dis e as e r e c urr e n c e/ pr o gr essi o n,  as  ass ess e d l o c all y, t h e i n v esti g at or will ,  b as e d  o n 
t h e  p ati e nt`s i n di vi d u al ris k/ b e n efit r ati o,  ali g n wit h t h e  S p o ns or a n d d e ci d e if t h e  p ati e nt s h o ul d 
r e c ei v e “ Furt h er  or C o nti n u e d  tr e at  m e nt   wit h a nti b o d y” i n  a c c or d a n c e   wit h t h e  ori gi n al tr e at  m e nt 
all o c ati o n (  R T  X  3 7 5   m g/  m2 at 2 8 -d a y  i nt er v als  or   M  O  R 0 0 2 0 8 1 2   m g/ k g  at 1 4 -d a y  i nt er v als) f or 
u p t o  2 4  m o nt hs i n t ot al .   M  O  R 0 0 2 0 8   will  b e  pr o vi d e d  b y t h e s p o ns or i n t h e  c o urs e  of t h e tri al. 
H o  w e v er , R T  X i n t hi s  p arti c ul ar  cli ni c al sit u ati o n will  n ot  b e  pr o vi d e d  b y t h e s p o ns or  a n d h as t o 
b e  pr es cri b e d  b y t h e tr e ati n g  p h ysi ci a n  a n d o bt ai n e d fr o  m c o  m  m er ci al s o ur c es. F or  p ati e nts 
r e c ei vi n g  a nti b o d y tr e at  m e nt  d es pit e  dis e as e r e c urr e n c e/ pr o gr essi o n,  b ef or e t h e  a d  mi nistr ati o n  of 
a nti b o di es,  bl o o d  p ar a  m et ers ( h ae  m at ol o g y, s er u  m  c h e  mistr y) s h o ul d  b e  e v al u at e d i n t h e l o c al 
l a b  a c c or di n g t o l o c al  g ui d eli n es/st a n d ar ds  of l o c al   m e di c al  pr a cti c e f or t h e  a d  mi nistr ati o n  of 
m A b s. A  uri n e  pr e g n a n c y t est s h o ul d  b e  p erf or  m e d f or an  F  C  B P . Vit al si g ns s h o ul d  b e   m e as ur e d 
a c c or di n g t o l o c al  pr a cti c e f or t h e  a d  mi nistr ati o n  of   mA b s.  
 
E a c h i n v esti g at or is r es p o nsi bl e f or  e ns uri n g t h at  d eli v eri es  of st u d y  dr u gs  a n d  ot h er st u d y 
m at eri als fr o  m t h e s p o ns or  a n d  ot h er  dr u gs fr o  m t h e  a p pr o pri at e s u p pli ers  ar e  c orr e ctl y r e c ei v e d, 
r e c or d e d, h a n dl e d  a n d st or e d s af el y  a n d  pr o p erl y i n  a c c or d a n c e   wit h  all  a p pli c a bl e r e g ul at or y 
g ui d eli n es,  a n d  us e d i n  a c c or d a n c e   wit h t his  pr ot o c ol.  T h e i n v esti g at or m a y  d el e g at e t h es e t as ks 
t o  a n ot h er  p ers o n ( a c c or di n g t o t h e l o c al l a  ws  a n d r e g ul ati o ns).   Dr u g  a c c ou nt a bilit y f or  ms   will 
b e  k e pt  b y  e a c h sit e  p arti ci p ati n g i n t h e st u d y  a n d   will  b e  c h e c k e d  d uri n g   m o nit ori n g  visits.  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 8  of 1 3 1  
St u d y  dr u g   m ust  b e  h a n dl e d, pr e p ar e d a n d  a d  mi nist er e d as  d es cri b e d i n t h e   Dr u g H a n dli n g 
M a n u al, t h e I  B f or   M  O  R 0 0 2 0 8,  a n d  ot h er s af et y- r el e va nt  d o c u  m e nts ( e. g. , S u  m  m ar y  of  Pr o d u ct 
C h ar a ct eristi cs ( [ S  mP  C ] f or t h e  E ur o p e a n   M e di ci n es   A g e n c y [ E  M  A]  or t h e  Pr es cri bi n g 
I nf or  m ati o n [  U S  Fo o d  a n d   Dr u g   A d  mi nistr ati o n ( F D  A )] f or   B E  N  a n d   R T  X). Pl e as e s e e 
A p p e n di x  F  f or  a d diti o n al i nf or  m ati o n. 
 
T h e i nf usi o n r at es  a n d ti  m es f or st u d y  dr u gs s p e cifi e d i n t h e  pr ot o c ol  a n d t h e   Dr u g   H a n dli n g 
M a n u al ar e r e c o  m  m e n d ati o ns f or t h e i n v esti g ati v e sit es’  us e. If r e q uir e d, t h e i n v esti g at or s h o ul d 
us e  cli ni c al j u d g e  m e nt  a n d i nstit uti o n al  g ui d el i n es t o  o pti  mis e  p ati e nt s af et y  b y  a dj usti n g t h e r at e 
of i nf usi o n  a c c or di n g t o t h e   m e di c al  c o n diti o n  of t h e  p ati e nt.  
 
M  O  R 0 0 2 0 8 will  b e s u p pli e d  b y t h e s p o ns or. B E  N  a n d   R T  X   will  b e a v ail a bl e fr o  m  c o  m  m er ci al 
s o ur c e.   C o n c o  mit a nt   m e di c ati o ns   will  b e  pr o vi d e d  b y t h e i n v esti g ati v e sit e  a n d  n ot  b y t h e 
s p o ns or. 
 
9. 1. 1  M  O  R 0 0 2 0 8 
M  O  R 0 0 2 0 8   D P ( dr u g  pr o d u ct)   m ust  b e st or e d  u n d er r efri g er ati o n  at  2°  C t o  8°  C i n its  ori gi n al 
p a c k a g e i n  a n  a p pr o pri at e st or a g e f a cilit y  e q ui p p e d   wit h t e  m p er at ur e  c o ntr ol, a c c essi bl e  o nl y t o 
t h e  p h ar  m a cist(s), t h e i n v esti g at or,  or  a  d ul y  d esi g n at e d  p ers o n. 
 
M  O  R 0 0 2 0 8   D P  is  a l y o p hilis at e s u p pli e d i n si n gl e- us e  2 0   m L  gl ass  vi als.  E a c h  vi al  c o nt ai ns 
2 0 0   m g  of   M  O  R 0 0 2 0 8 f or r e c o nstit uti o n   wit h  5 m L   w at er f or i nj e cti o n (  W FI).   R e c o nstit uti o n 
yi el ds  4 0   m g/  m L   M  O  R 0 0 2 0 8 i n  2 5 m  M  s o di u  m  citr at e,  2 0 0   m  M tr e h al os e  a n d  0. 0 2  % (  w/ v) 
p ol ys or b at e  2 0  at  p  H  6. 0.  E a c h  pr o d u ct  vi al is i nt e n d e d t o  d eli v er  2 0 0   m g  of   M  O  R 0 0 2 0 8 i n  5   m L 
of r e c o nstit ut e d s ol uti o n.  T h e s ol uti o n  aft er r e c o nstit uti o n is  c ol o url ess t o sli g htl y  y ell o  w  a n d 
ess e nti all y fr e e  of f or ei g n  p arti cl es; it   m a y  c o nt ai n  a f e  w   w hit e t o   w hitis h  pr o d u ct -r el at e d 
p arti cl es.  
 
F or  a d  mi nistr ati o n,   M  O  R 0 0 2 0 8   will  b e  dil ut e d i nt o  a  c o  m  m er ci all y  a v ail a bl e  2 5 0 m L i nf usi o n 
c o nt ai n er   wit h  0. 9  % (  w/ v) s o di u  m  c hl ori d e f or i nj e cti o n. 
 
T h e i n di vi d u al   M  O  R 0 0 2 0 8 i nf usi o n   will  b e  pr e p ar e d  u n d er  as e pti c  c o n diti o ns  a n d  a d  mi nist er e d 
at t h e st u d y sit e,  a c c or di n g t o t h e  dir e cti o ns  of t h e s p o ns or,   w hi c h   will  b e  pr o vi d e d i n  a   Dr u g 
H a n dli n g   M a n u al. I n  g e n er al,  a  vi al  of   M  O  R 0 0 2 0 8   m ust  b e  us e d  as s o o n  as  p ossi bl e  aft er 
r e c o nstit uti o n   wit h   W FI;  a n y s ol uti o n r e  m ai ni n g i n t h e  vi al  h as t o  b e  dis c ar d e d.   Aft er  dil uti o n f or 
i nf usi o n,  a d  mi nistr ati o n  of   M  O  R 0 0 2 0 8 s h o ul d t a k e  pl a c e  as s o o n  as  p ossi bl e.   M a xi  m u  m  all o  w e d 
st or a g e ti  m es  a n d  c o n diti o ns   will  b e  d et ail e d i n t h e   Dr u g   H a n dli n g M a n u al.  
 
M  O  R 0 0 2 0 8    will  b e  a d  mi nist er e d  at  a  d os e  of  1 2. 0   m g/ k g I  V.   D os e r e d u cti o ns  of   M  O  R 0 0 2 0 8  ar e 
n ot  all o  w e d  d uri n g t h e  c o urs e  of t h e st u d y. 
 
F or t h e first t hr e e   m o nt hs (  C y cl e  1 - 3)  of t h e st u d y,  e a c h  c y cl e   will  c o nsist  of  a   M  O  R 0 0 2 0 8 
i nf usi o n  o n   D a y  1,   D a y  8,   D a y  1 5  a n d   D a y  2 2  of t h e  c y cl e.   A d diti o n all y,  a l o a di n g  d os e   will  b e 
a d  mi nist er e d  o n   D a y  4  of   C y cl e  1. T h er e aft er  (  C y cl e  4-u ntil  dis e as e  pr o gr essi o n),  e a c h  c y cl e   will 
c o nsist  of  a   M  O  R 0 0 2 0 8 i nf usi o n  o n   D a y  1  a n d   D a y  1 5. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 4 9  of 1 3 1  
F or t h e first i nf usi o n, t h e I  V i nf usi o n r at e s h o u l d  b e  7 0   m L/ h f or t h e first  3 0   mi n ut es  a n d 
s u bs e q u e ntl y i n cr e as e d t o  a r at e  of  1 2 5   m L/ h; t h e t ot al i nf usi o n  d ur ati o n s h o ul d i d e all y  n ot 
e x c e e d  2. 5  h o urs.   All s u bs e q u e nt   M  O  R 0 0 2 0 8 i nf usi o ns   will  b e  a d  mi nist er e d I  V  at  a  c o nst a nt r at e 
of  1 2 5   m L/ h  o v er  a  2 -h o ur  p eri o d.   M  O  R 0 0 2 0 8 s h o ul d   N  O T  b e  a d  mi nist er e d  as  a n I  V  p us h  or 
b ol us.  
 
U nl ess  c o ntr ai n di c at e d t h e M  O  R 0 0 2 0 8  tr e at  m e nt s h o ul d  c o nti n u e,  e v e n if t h e  p ati e nt 
dis c o nti n u es   B E  N tr e at  m e nt.  
 
9. 1. 2  R  T  X  
S p e cifi c i nf or  m ati o n a b o ut t h e  c h e  mi c al str u ct ur e , pr o p erti es , f or  m ulati o n, st or a g e,  dis p os al a n d 
a d  mi ni str ati o n  of   R T  X ar e  pr o vi d e d i n t h e S  m P  C  ( E  M  A)  a n d  Pr es cri bi n g I nf or  m ati o n (  U S 
F  D  A ). 
 
R T  X s h o ul d  b e  a d  mi nist er e d  o nl y  as  a n  I  V i nf usi o n t hr o u g h  a  d e di c at e d li n e  a n d  n ot  as  a n I  V 
p us h  or  b ol us.  
 
R T  X   will  b e  a d  mi nist er e d  at  a  d os e  of  3 7 5   m g/  m 2 I  V o n   D a y  1  wit h  a  pr e -pl a n n e d tr e at  m e nt 
i nt er v al  of at l e ast 2 8  d a ys t o t h e s u bs e q u e nt   R T  X  a d  mi nistr ati o n.   D os e r e d u cti o ns  of   R T  X  ar e 
n ot  a ll o  w e d  d uri n g t h e  c o urs e  of t h e st u d y. 
 
R T  X   will  b e  a v ail a bl e fr o  m  c o  m  m er ci al  dr u g s u p pli es ( e. g.   M a b T h er a ® /  Rit u x a n® ). 
 
U nl ess  c o ntr ai n di c at e d t h e R T  X  tr e at  m e nt s h o ul d  c o nti n u e,  e v e n if t h e  p ati e nt  dis c o nti n u es   B E  N 
tr e at  m e nt.  
 
9. 1. 3  B  E  N  
S p e cifi c i nf or  m ati o n  a b o ut t h e  c h e  mi c al str u ct ur e,  pr o p erti es, f or  m ul ati o n, st or a g e ,  dis p os al a n d 
a d  mi nistr ati o n  of   B E  N  ar e  pr o vi d e d i n t h e S  m P  C ( E  M  A)  a n d  Pr es cri bi n g I nf or  m ati o n (  U S 
F  D  A) . 
 
B E  N   will  b e  a d  mi nist er e d  at  a  d os e  of  9 0   m g/  m 2 o n   D a y s 2 + 3  of C y cl e  1 . B E  N a d  mi nistr ati o n  
will  b e r e p e at e d  o n D a ys  1 + 2  or  2 + 3  of t h e s u bs e q u e nt  c y cl es,   wit h a  pr e-pl a n n e d  tr e at  m e nt 
i nt er v al  of at l e ast 2 8  d a y s  b et  w e e n t h e  c o  m  m e n cem e nt s of t  w o s u c c e e di n g  c y cl es ,  a c c or di n g t o 
i nstit uti o n al/ p ati e nt/ p h ysi ci a n  c h oi c e. A n  e x c e pti o n t o t his r ul e   m a y  o c c ur i n  c as e t h e B E  N 
a d  mi nistr ati o n s c h e  m e c h a n g es fr o  m   D a ys  2 + 3 t o   D a ys  1 + 2 , or  vi c e  v ers a , i n s u bs e q u e nt  c y cl es.  
 
It is s u g g est e d t h at  d uri n g C o  m bi n ati o n T r e at  m e nt,   B E  N tr e at  m e nt s h o ul d  b e  ali g n e d   wit h t h e 
a d  mi nistr ati o n  of m  A b  o n   D a y  1  o f t h e  c y cl e. W h e n a p pli c a bl e ,   B E  N s h o ul d  b e a d  mi nist er e d 
aft er t h e M  O  R 0 0 2 0 8  or   R T  X  i nf usi o n. 
 
B E  N d os e m a y  b e   m o difi e d i n  a  d e -es c al ati n g f as hi o n  or  dis c o nti n u e d  b as e d  u p o n  cli ni c al  a n d 
l a b or at or y fi n di n gs. I n t h e c as e  of  e arl y B E  N  dis c o nti n u ati o n , t h e  a nti b o d y tr e at  m e nt s h o ul d 
c o nti n u e u nl ess  c o ntr ai n di c at e d .  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 5 0  of 1 3 1  
D et ail e d  g ui d a n c e  o n  h o  w t o   m a n a g e  h a e  m at ol o gi c al a n d/ or  ot h er t o xi citi es is pr o vi d e d i n 
S e cti o n  9. 4. 2 . T h e r e c o  m  m e n d e d i nf usi o n ti  m e is  3 0 t o  6 0   mi n ut es.  T h e  pr e p ar e d   B E  N s ol uti o n 
s h o ul d  b e  a d  mi nist er e d  as  a n I  V i nf usi o n  a n d  n ot  as  a n I  V  p us h  or  b ol us. 
 
B E  N   will  b e  a v ail a bl e fr o  m  c o  m  m er ci al  d r u g s u p pli es ( e. g. L e v a ct ® / Tr e a n d a® ). 
 
9. 2  P r e m e di c ati o n f o r  St u d y   D r u g  I nf usi o ns 
A n y  pr e  m e di c ati o n  gi v e n s h o ul d  b e r e p ort e d i n t h e  e  C  R F. 
 
Pr e  m e di c ati o n f or   R T  X  a n d   B E  N i nf usi o ns s h o ul d f oll o  w i nstit uti o n al  g ui d eli n es  a n d/ or 
pr e  m e di c ati o n  a n d a d  mi nistr ati o n/i nf usi o ns s e cti o ns  of t h e  S  m P  C ( E  M  A)  or  Pr es cri bi n g 
I nf or  m ati o n (U S  F  D  A).  
 
I  R  Rs  h a v e  b e e n r e p ort e d i n  cli ni c al tri als   wit h   M  O  R 0 0 2 0 8.  T h er ef or e,  a r e c o  m  m e n d e d 
pr e  m e di c ati o n r e gi  m e n i n cl u d es  a  hist a  mi n e   H 1 r e c e pt or  bl o c k er ( e. g.,  di p h e n h y dr a  mi n e  5 0   m g 
p er  d os e I  V  or  e q ui v al e nt),  a n  a nti p yr eti c ( e. g.  a c et a  mi n o p h e n [ p ar a c et a  m ol]  1 0 0 0   m g  p er  d os e 
b y   m o ut h [ p. o.]  or I  V  or  e q ui v al e nt)  a n d  gl u c o c orti c ost er oi ds ( e. g.   m et h yl pr e d nis ol o n e  8 0 t o 
1 2 0 m g  p er  d os e I  V  or  e q ui v al e nt).  F or t h e  e q ui v al e nt  c orti c ost er oi d  d os es  pl e as e r ef er t o  
A p p e n di x   G . If r e q uir e d, t h e i n v esti g at or   m a y r e p e at  d os es  of i n di vi d u al  a g e nts  a n d  us e  ot h er 
a g e nts,  d os es  a n d/ or f or  m ul ati o ns i n  a c c or d a n c e   wit h i nstit uti o n al  g ui d eli n es. 
 
Pr e  m e di c ati o n is  m a n d at e d f or t h e first t hr e e   M  O  R 0 0 2 0 8 i nf usi o ns. Pr e  m e di c ati o n f or  p ati e nts 
w h o  d o  n ot  e x p eri e n c e  a n y I  R  Rs t o   M  O  R 0 0 2 0 8  d uri n g t h e first t hr e e i nf usi o ns ( d os es)   will  b e 
o pti o n al f or s u bs e q u e nt   M  O  R 0 0 2 0 8 i nf usi o ns  at t h e  dis cr eti o n  of t h e i n v esti g at or.   Ot h er  wis e, t h e 
pr e  m e di c ati o n s h o ul d  b e  c o nti n u e d f or s u bs e q u e nt  a d  mi nistr ati o ns.  
 
9. 3  P ati e nt   M o nit o ri n g   D u ri n g  St u d y   D r u g I nf usi o ns  
Vit al si g ns s h o ul d b e   m e as ur e d  as  o utli n e d i n  S e cti o n  1 3. 8. 4 . If   m  A b  a n d   B E  N  ar e  b ei n g 
a d  mi nist er e d  o n t h e s a  m e  d a y,  vit al si g ns s h o ul d  b e r e c or d e d i n  e  C  R F f or   m  A b i n f usi o n(s)  o nl y. 
All s u p p orti v e   m e as ur es  c o nsist e nt   wit h  o pti  m al  p ati e nt  c ar e s h o ul d  b e  pr o vi d e d t hr o u g h o ut t h e 
st u d y  a c c or di n g t o i nstit uti o nal st a n d ar ds.  
 
Pr e c a uti o ns f or  a n a p h yl a xis s h o ul d  b e  o bs er v e d  d uri n g st u d y  dr u g  a d  mi nistr ati o n.  E  m er g e n c y 
r es us cit ati o n  e q ui p  m e nt  a n d   m e di c ati o ns s h o ul d  b e r e a dil y  a v ail a bl e. 
 
9. 4  C rit e ri a f o r   D os e   M o difi c ati o ns  a n d St u d y D r u g   Dis c o nti n u ati o n  
9. 4. 1  M a n a g e  m e nt  of  St u d y   D r u g  I nf usi on- R el at e d   R e a cti o ns  
F or I  R  Rs r el at e d t o   B E  N  a n d/ or   R T  X, t h e i n v esti g at or s h o ul d f oll o  w t h e i nstr u cti o ns  c o nt ai n e d 
i n t h e  S  m P  C ( E  M  A)  or  Pr es cri bi n g I nf or  m ati o n (  U S  F  D  A)  of t h e s p e cifi c  pr o d u ct. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 2  of 1 3 1  
If  a  p ati e nt   w h o  d e v el o p e d  a  gr a d e 2 I  R  R r e c ei v es f urt h er i nf usi o ns, t h e n  pr e  m e di c ati o n 
a c c or di n g t o t h e i nstit uti o n al  g ui d eli n es s h o ul d  b e  gi v e n  b ef or e  all s u bs e q u e nt i nf usi o ns. 
9. 4. 1. 2  G r a d e  3 I  R  Rs  f o r  p ati e nts  r e c ei vi n g   M  O  R 0 0 2 0 8 
If  a  p ati e nt  pr es e nts   wit h  a  gr a d e 3 I  R  R:  
•
T h e i nf usi o n s h o ul d  b e st o p p e d i  m  m e di at el y.
•
T h e  p ati e nt   m ust r e c ei v e  a p pr o pri at e tr e at  m e nt   wit h  a n a nti hist a  mi n e  a n d/ or
a c et a  mi n o p h e n ( p ar a c et a  m ol)  or   m et h yl pr e d nis ol o n e ( or  e q ui v al e nt)  a n d, if  n e c ess ar y,
f urt h er   m e di c ati o ns (i. e.  e pi n e p hri n e,  br o n c h o dil at or).
•
O nl y  aft er t h e  c o  m pl et e r es ol uti o n  of  all s y  m pt o  ms (t o  gr a d e ≤1),  a n d  aft er  h a vi n g
r e c ei v e d  a ppr o pri at e  pr o p h yl a cti c   m e di c ati o n(s)  as  d es cri b e d  a b o v e, t h e i nf usi o n   m a y  b e
r es u  m e d  at  a n i nf usi o n r at e  of  2 5  %. If,  aft er  1  h o ur, t h e  p ati e nt’s s y  m pt o  ms  d o  n ot r et ur n
a n d  vit al si g ns  ar e st a bl e, t h e i nf usi o n r at e   m a y  b e i n cr e as e d t o  a   m a xi  m u  m  of  5 0  % .
•
If,  aft er t h e r es u  m pti o n  of i nf usi o n, s y  m pt o  ms r et ur n (irr es p e cti v e  of  gr a d e), t h e i nf usi o n
m ust  b e st o p p e d i  m  m e di at el y  a n d t h e i nf usi o n t u bi n g s h o ul d  b e  dis c o n n e ct e d fr o  m t h e
p ati e nt. B as e d  o n t h e i n v esti g at or’s  d e cisi o n t h e  p ati e nt   m a y r e c ei v e f urt h er st u d y dr u g(s) ,
pr o vi d e d  cli ni c all y  a p pr o pri at e  pr e c a uti o ns  a r e  u n d ert a k e n. If t h e i n v esti g at or  d e ci d es t o
c o nti n u e   wit h f urt h er st u d y  dr u g(s)  a d  mi nistr ati o n, t h e n  pr e  m e di c ati o n  a c c or di n g t o t h e
i nstit uti o n al  g ui d eli n es s h o ul d  b e  gi v e n  b ef or e  all s u bs e q u e nt i nf usi o ns.
9. 4. 1. 3  G r a d e  4 I  R  Rs  f o r  p ati e nts  r e c ei vi n g   M  O  R 0 0 2 0 8 
If  a  p ati e nt  pr es e nts   wit h  a  gr a d e 4 I  R  R:  
•
T h e i nf usi o n s h o ul d  b e st o p p e d i  m  m e di at el y  a n d t h e i nf usi o n t u bi n g s h o ul d  b e
dis c o n n e ct e d fr o  m t h e  p ati e nt .
•
T h e  p ati e nt m ust r e c ei v e  a p pr o pri at e tr e at  m e nt   wit h  a n  a nti hist a  mi n e  a n d/ or
a c et a  mi n o p h e n ( p ar a c et a  m ol) a n d/or   m et h yl pr e d nis ol o n e ( or  e q ui v al e nt)  a n d, if
n e c ess ar y, f urt h er   m e di c ati o ns (i. e.  e pi n e p hri n e,  br o n c h o dil at or) .
•
T h e  p ati e nt   m ust  n ot r e c ei v e f urt h er i nf usi o ns  of t h e st u d y  dr u g t h at is j u d g e d  b y t h e
i n v esti g at or t o  b e t h e  c a us e  of t h e I  R  R,  b ut s h o ul d c o nti n u e tr e at  m e nt   wit h t h e  ot h er st u d y
dr u g  as  p er  pr ot o c ol.
9. 4. 2  M a n a ge me nt of T re at me nt- Rel ate d  To xicities  
T he  f oll o wi n g i nfor mati o n  will s u p p ort t he mana ge me nt of treat m e nt-relate d t o xicities whic h  
ma y res ult i n st u d y dr u g(s) d os e re d ucti o n or p o st p o ne me nt, eit her a t t he start of a ne w cycle  of 
t hera p y or d uri n g a cycle. 
G ui da nce f or d ose p ost p o ne me nt f or B E N a n d d ose re d ucti o n f or B E N is pr o vi de d i n 
Secti o n  9. 4. 2. 1 , gui da nce f or d ose o missi o n/ dela y / p ost p o ne me nt o f MO R 0 0 2 0 8 a n d R T X i n 
Secti o n  9. 4. 2. 2 , an d g ui da nce f or st u d y dr u g(s) treat me nt disc o nti n uati o n i n Secti o n  9. 4. 2. 3.  
All s ce nari os ma y  re q uire t he i m ple me n tati o n of th e p ri nci ples of best s up p orti ve car e ( B S C) 
acc or di n g  t o t he l ocal me dical practice  an d  t he i nstit uti o nal g ui deli nes. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 3  of 1 3 1  
9. 4. 2. 1  S af et y -r el at e d   C rit e ri a f o r   B  E  N   T r e at  m e nt  a n d   B  E  N   T r e at  m e nt  P ost p o n e  m e nt  
P ati e nts  c a n b e gi n  c h e  m ot h er a p y   wit h B E  N   o nl y if t h e  pr e-d os e l o c al l a b or at or y  p ar a  m et ers 
m e as ur e d l o c all y r e  m ai n i n t h e r a n g es s p e cifi e d b el o  w.  F urt h er  m or e,  p ati e nts  c a n r e c ei v e 
s u bs e q u e nt B E  N i nf usi o ns if t h e y  h a v e  p ass e d t h e  n e utr o p hils  a n d  pl at el ets  n a dir  a n d r e c o v er e d 
fr o  m  p ot e nti al B E  N -i n d u c e d  n o n- h ae  m at ol o gi c al t o xi citi es as  d es cri b e d i n T a bl e   2. 
T a bl e   2: 
C rit e ri a   R e q ui r e d f o r t h e I niti ati o n  of   B  E  N   T r e at  m e nts  
P a r a  m et e r  
P ati e nt s h o ul d  o nl y  b e  d os e d if:  
A  N  C  
≥ 1 0 0 0/  m  m 3 ( u nl ess  n e utr o p e ni a is j u d g e d t o  b e s e c o n d ar y t o l y  m p h o  m a 
i nfiltr ati o n  of  b o n e   m arr o  w).  P ati e nt   m a y  h a v e r e c ei v e d  gr o  wt h f a ct or s u p p ort. 
Pl at el ets  
≥ 7 5 0 0 0/  m  m 3 ( u nl ess t hr o  m b o c yt o p e ni a is j u d g e d t o  b e s e c o n d ar y t o l y  m p h o  m a 
i nfiltr ati o n  of  b o n e   m arr o  w). P ati e nt   m a y  h a v e r e c ei v e d tr a nsf usi o n s u p p ort i n 
eit h er sit u ati o n.  
T ot al  bilir u bi n;   A S T;   A L T  
≤  3  x   U L  N ( u nl ess  d u e t o   Gil b ert’s s y n dr o  m e  or  d o c u  m e nt e d li v er i n v ol v e  m e nt 
b y l y  m p h o  m a)  
Ot h er  cli ni c all y si g nifi c a nt  n o n -
h a e  m at ol o gi c al t o xi cit y  
N o  a cti v e  a n d u n c o ntr oll e d i nf e cti o n  
C y cl e  2 -6:  cli ni c all y r el e v a nt,  n o n -h a e  m at ol o gi c al   B E  N -i n d u c e d t o xi cit y  h as 
di  mi nis h e d i n s e v erit y t o  gr a d e  ≤2 or r e c o v er e d t o  b as eli n e l e v el (if t h e  c o n diti o n 
w as  pr e -e xisti n g)  
A b br e vi ati o ns:   A L T  =  al a ni n e tr a ns a  mi n as e;   A  N  C  =  a bs ol ut e  n e utr o p hil  c o u nt;   A S T  =  as p art at e  a  mi n otr a nsf er as e;   B E  N  = 
b e n d a  m usti n e;   U L  N  =  u p p er li  mit  of  n or  m al.  L a b or at or y  p ar a  m et ers  ar e  ass ess e d l o c all y.  
1.
If t he criteria  f or t he i nitiati o n of B E N treat me n t are n o t met,  t he su bse q ue nt B E N  
treat me nt is t o be p ost p o ne d. It is rec o m me n de d t hat t he A E gra de a n d t he hae mat ol o g y  
val ues are s u bse q ue ntl y i n vesti gate d at a ppr o xi matel y  3- da y inter vals.
2.
T here m ust  al wa y s be at least a 2 8- d a y inter val  bet wee n  t he c o m me nce m e nt of
t w o c o nsec uti ve B E N  treat me nt c ycles  (f or a d diti o nal i nf or mati o n  see Secti o n  9. 1. 3 ).
3.
M O R 0 0 2 0 8 or R T X ma y be c o nti n ue d ( please n ote Secti o n  9. 4. 2. 2) wh ile criteria  f or 
B E N  treat me nt are n ot  fulfille d.  For  t hese patie nts,  BE N  treat me nt will occ ur  as s o o n  as 
t he criteria f or re-treat me nt wit h BE N  are f ulfille d.
4.
If base d o n me dical j u d ge me nt, t he treati n g p h ysicia n c o nsi ders cli nical a n d/ or la b orat or y  
para meter c ha n ges n ot t o be st u d y dr u g-relate d t o xicit y, b ut t o re prese nt disease hist or y,  
nat ural fl uct uati o n or pr o gressi o n of t he u n derl yi n g disease, it is at t he p h ysicia n’s  
discreti o n, i n a cc o rda nce  wit h assess me nt of t he i ndi vi d ual r is k/ be nefit r ati o, t o deter mi ne  
w het her  th e n e w BE N  treat me nt s ho ul d  be i nitiate d (see Ta ble 2) or  B EN d o se mai ntai ne d 
(see Ta ble 3) wit h o ut meeti n g t he criteria f or s u bse q ue nt c ycles of  c he m ot hera p y. T he 
decisi o n a n d rati o nale be hi n d t he decisi o n s h o ul d be d oc u me nte d i n t he s o urce data.

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 4  of 1 3 1  
T a bl e   3: 
B  E  N   D os e   R e d u cti o n   C rit e ri a 
N  CI   C  T  C  A  E  c at e g o r y  S e v e rit y  
D os e   m o difi c ati o n  
H a e  m at ol o gi c 
A N  C <  1 0 0 0/ µl (  Gr a d e  ≥ 3)  o n   D a y  1  of 
C y cl es  2 - 6 
B E  N  c y cl e i niti ati o n (  D a y  1)  of   C y cl es  2 
−6 s h o ul d  b e  d el a y e d  u ntil t h e   A  N  C is
≥1 0 0 0/ µl  a n d t h e  P L Ts is  ≥ 7 5 0 0 0/ µl  or
c ell  c o u nts r et ur n t o  b as eli n e l e v el
o bt ai n e d  at s cr e e ni n g r es p e cti v el y *.
If Da y 1 is dela ye d  b y m ore  t ha n 
2 wee ks,  the n  B E N  s h o uld  be  res u me d 
at th e ne xt  lo wer  d o se le vel (see 
Ta ble  4 ). 
Gr o wt h  fact or (e. g. G -C S F)  a n d 
tra nsf usi o n su p p ort  s h o ul d be  c o nsi dere d  
acc or di n g to th e pri nci ples  of  me dical  
practice  a n d t he instit uti o nal  g ui deli nes  
d uri n g t his  a n d  su bse q ue nt  c ycles.   
P L Ts <  7 5 0 0 0/ µl (  Gr a d e  ≥ 2)  o n   D a y  1  of 
C y cl es  2 - 6 
A  N  C <  5 0 0/ µl (  Gr a d e  4)  of  a n y  d ur ati o n 
a c c o  m p a ni e d  b y  b o d y t e  m p er at ur e  of 
≥ 3 8. 3º  C  o n  a si n gl e  o c c asi o n  or  > 3 8º  C  o n 
t  w o  o c c asi o ns   m e as ur e d   wit hi n  1 2 
c o ns e c uti v e  h o urs  or  > 3 8º  C   m ai nt ai n e d 
≥ 1  h o ur  
B E N  c ycle  i nitiati o n ( Da y 1)  of  
C ycles  2- 6  s h o uld be  dela ye d  u ntil t he  
A N C is ≥1 0 0 0/ µl  wit h o u t e vi de nce  of  
fe ver or  i nfecti o n a nd P L Ts is 
≥7 5 0 0 0/ µl *. 
B E N s h o uld t hen b e res ume d  at t he ne xt 
l o wer d ose  le vel (see Ta ble  4 ) 
Gr o wt h  fact or (e. g. G -C S F)  a n d 
tra nsf usi o n su p p ort  s h o ul d be  c o nsi dere d  
acc or di n g to t he pri nc i ples of  me dical  
practice  a n d t he instit uti o nal  g ui deli nes  
d uri n g t his  a n d  su bse q ue nt  c ycles.  
A  N  C <  1 0 0 0/ µl (  Gr a d e  3) l asti n g  ≥  7  d a ys  
P L Ts <  2 5 0 0 0/ µl (  Gr a d e  4) l asti n g  ≥ 7  d a ys 
or  of  a n y  d ur ati o n if  a c c o  m p a ni e d  b y 
cli ni c all y si g nifi c a nt  bl e e di n g  
P L Ts <  1 0 0 0 0/ µl  at  a n y ti  m e  
N a us e a,  e  m esis  or 
di arr h o e a i n t h e 
a bs e n c e  of   m a xi  m u  m 
pr o p h yl a xis  
G r a d e  3 
C o nti n u e B E  N at t h e s a  m e  d os e,  b ut 
i nstit ut e t h e   m a xi  m u  m  pr o p h yl a cti c 
t h er a p y, i n cl u di n g e. g. a  5-H T 3 
a nt a g o nist f or  n a us e a  a n d  e  m esis,  a n d 
l o p er a  mi d e, or  a  c o  m p ar a bl e 
a nti di arr h o e al  a g e nt. 
Gr a d e  4  
Wit h h ol d   B E  N  u ntil r es ol uti o n  of 
t o xi cit y t o   Gr a d e  ≤  2   w hil e  o n   m a xi  m u  m 
pr o p h yl a cti c t h er a p y.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 5  of 1 3 1  
N  CI   C  T  C  A  E  c at e g o r y  S e v e rit y  
D os e   m o difi c ati o n  
N a us e a,  e  m esis  or 
di arr h o e a i n t h e 
pr es e n c e of m a xi  m u  m 
pr o p h yl a xis  
Gr a d e  ≥  3  
Wit h h ol d  B E N  until  t he t o xicit y ret ur ns 
t o Gra de  ≤ 2  or  baseli ne  le vel if t he 
c o n diti o n  was  pre -ex isti n g, a nd  restart 
B E N  at t he ne xt  l o wer d ose  (see    
Ta ble  4 ).  
All  ot h er cli ni c all y 
si g nifi c a nt t o xi citi es 
r el at e d t o   B E  N  
Gr a d e  ≥  3  
A b br e vi ati o ns:   A Es   = a d v ers e  e v e nts;   A  N  C  =  a bs ol ut e  n e utr o p hil  c o u nt; B E  N  = b e n d a  m usti n e;   G -C S F   = gr a n ul o c yt e  c ol o n y -
sti  m ul ati n g f a ct or;  P L Ts =  pl at el ets ( pl at el et  c o u nt) . 
*If  p ati e nts  h a v e f or i nst a n c e  a dis e as e -r el at e d s pl e n o  m e g al y  or   m ar k e d  b o n e   m arr o  w i n v ol v e  m e nt  b y l y  m p h o  m a  as  a  c a us ati v e
f a ct or of  c yt o p e ni as  at s cr e e ni n g, tr e at  m e nt   m a y  c o nti n u e   wit h o ut   m e eti n g t h e  h ae  m at ol o gi c crit eri a f or s u bs e q u e nt  c y cl es  of
c h e  m ot h er a p y. I n s u c h  c as es t h e  d e cisi o n t o  c o nti n u e   B E  N  d osi n g  at t h e  c urr e nt  d os e is  at t h e i n v esti g at or’s  dis cr eti o n.
P ri n ci pl es  of   B  E  N D os e   R e d u cti o n  
T h e  d os e  of   B E  N   m a y  b e r e d u c e d s u c c essi v el y fr o  m t h e st arti n g  d os e of  9 0   m g/  m 2  d ail y 
(T a bl e   4).  F or  a d diti o n al i nf or  m ati o n  pl e as e s e e  S e cti o n 9. 1. 3 . 
T h e   B E  N  d os e   m a y  o nl y  b e  a dj ust e d  o n c e  p er  c y cl e  a n d  b y  o n e  d os e l e v el.   O n c e  a  p ati e nt’s   B E  N 
d os e  h as  b e e n r e d u c e d,  n o  d os e r e- es c al ati o n is  p er  mitt e d.  
T a bl e   4: 
B  E  N D os e   L e v els  
St arti n g  d os e  
9 0   m g/  m 2 d ail y  o n   D a ys  1 + 2  or  2 + 3  e v er y  at l e ast 2 8  d a ys  
D os e  L e v el -  1 
6 0  m g/  m 2 d ail y  o n   D a ys  1 + 2  or  2 + 3 e v er y  at l e ast 2 8  d a ys  
D os e  L e v el -  2 
3 0   m g/  m 2 d ail y  o n   D a ys  1 + 2  or  2 + 3  e v er y at l e ast 2 8  d a ys  
Patie nts w h o  ca n n ot tolerate D ose Le vel  - 2  d ue t o to xiciti es descri be d  in  Ta ble  2 an d  Ta ble  3 
sh o ul d disc o nti n ue B E N treat me nt an d s h o ul d c o nti n ue anti b o d y t hera p y acc or di n g t o t heir i nitial 
treat me nt all ocati o n. 
9. 4. 2. 2  A nti b o d y  Tre at me nt  Dose O missi o ns/ P ost p o ne me nts  
D ose re d ucti o ns of M O R 0 0 2 0 8 or R T X are n ot all o we d d uri n g the co urse o f the st u d y. 
Treat me nt wit h M O R 0 0 2 0 8 or R T X ma y c o nti n ue i n case criteria f or B E N treat me n t are  not 
fu lfille d (see Ta ble  2). 
I n t he case  of cli nicall y si g nifica nt, g ra de 4  t o xicities j u d ge d n ot t o  be rel ate d  t o R T X or  
M O R 0 0 2 0 8: 
1.
R T  X  d os es s h o ul d  b e  p ost p o n e d  u ntil t o xi cit y  di  mi nis h es i n s e v erit y t o ≤g r a d e  3.

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 6  of 1 3 1  
2.
M  O  R 0 0 2 0 8  d os es s h o ul d b e  o  mitt e d  u ntil t o xi cit y  di  mi nis h es i n s e v erit y t o ≤gr a d e  3.
O n e   mi ss e d M  O  R 0 0 2 0 8  d os e s h o ul d  n ot  b e   m a d e  u p f or. If t h e  p ati e nt   miss es  a
s u bs e q u e nt   M  O  R 0 0 2 0 8  d os e, t h e s e c o n d   miss e d  d os e s h o ul d  b e  a d  mi nist er e d
i  m  m e di at el y  aft er t h e t o xi cit y r es ol v es.
In t h e c as e  of  cli ni c all y si g nifi c a nt  gr a d e  ≥ 3 t o xi citi es j u d g e d t o  b e  r el at e d t o R T  X  or 
M  O  R 0 0 2 0 8: 
1.
R T  X  d os es s h o ul d  b e  p ost p o n e d  u ntil t h e t o xi cit y  di  mi nis h es i n s e v erit y t o  gr a d e ≤1  or
r et ur ns t o  a  b as eli n e  gr a d e,  pr o vi d e d t h e  c o n diti o n   w as  pr e-e xisti n g  at  b as eli n e .
2.
M O  R 0 0 2 0 8  d os es s h o ul d b e  o  mitt e d  u ntil t h e t o xi cit y  di  mi nis h es i n s e v erit y t o g r a d e ≤1
or r et ur ns t o  a  b as eli n e  gr a d e,  pr o vi d e d t h e  c o n diti o n   w as  pr e- e xisti n g  at  b as eli n e . O n e
miss e d   M  O  R 0 0 2 0 8  d os e s h o ul d  n ot  b e   m a d e  u p f or. If t h e  p a ti e nt   miss es  a s u bs e q u e nt
M  O  R 0 0 2 0 8  d os e, t h e s e c o n d   miss e d  d os e s h o ul d  b e  a d  mi nist er e d i  m  m e di at el y  aft er t h e
t o xi cit y r es ol v es.
If ba se d o n me dical ju d g me nt , t he treati n g p h ysicia n c o nsi ders a cli nical A E  an d/ or la b orat or y 
para meter  cha n ge n ot  to  be a st ud y dr u g- relate d to xicit y  b ut t o represe nt  nat ural fl uct uati o n  or 
pr o gressi o n of the u n de rl yi n g disease, t he n it is at the p h ys icia n’s di screti o n a n d assess me nt o f 
t he in di vi d ual ris k/ be nefit ratio t o deter mi ne w het her t he pa tie nt sh o ul d be d os e d. T he de cisi o n 
a n d rati o nale be hi n d t he de cisi o n s h o ul d be d oc u me nte d i n t he so urce d ata. 
9. 4. 2. 3  Tre at me nt  Disc o nti n u ati o n  
If t he sa me st u d y dr u g  relate d t o xicit y persists f or m ore tha n 2 8 da ys , the  a d mi nistrati o n  of t his 
partic ular st u d y dr u g s h o ul d be di sc o nti n ue d an d  the pa tie nt sh o ul d c o nti n ue to be d ose d wit h t he 
ot her st u d y dr u g (i.e. t he res pecti ve co m bi nati o n part ner i n t hat treat me nt arm ). 
If t he sa me t o xicit y relate d t o b ot h st u d y dr u gs persists f or m ore t ha n 2 8 da ys, t he n treat me nt 
wit h  b ot h st u d y dr u gs s h o ul d per ma ne ntl y be disc o nti n ue d (see Secti o n  9. 8 ). 
If treat me nt is  i nterr u pte d f or more tha n 2 8 da ys d ue to a n A E an d/ or la b orat or y para meter 
c ha n ge t hat is n ot a st u d y dr u g- relate d t o xicit y, t he ad mi nistrati o n  of t his partic ular st u d y  dru g  
s h o ul d be di sc o nti n ue d a n d t he pa tie nt sh o ul d c o nti n ue t o be d ose d wit h t he ot her st u d y dr u g (i.e. 
t he res pecti ve co m bi nati o n  part ner i n t hat treat me nt ar m).  
If b ot h st u d y dr u gs are te m p oraril y wit h hel d f or m ore t ha n 2 8 da ys d ue t o t he sa me p ersisti n g 
cli nica l AE  an d/ or la b orat or y  para meter c ha n ge  the n treat me nt w it h b oth st u d y dr u gs s h o ul d 
per ma ne nt l y be di sc o nti n ue d.  
All sce nari os  may  req uire  t he im ple me ntati o n  of t he pri nci ples of t he BS C  acc or di n g  t o t he l ocal 
me dical pr actice an d t he instit uti o nal g ui deli nes . T he de cisi o n a n d rati o nale be hi n d t he de cisi o n 
s h o ul d be d o c u me nte d i n the so urce d ata. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 7  of 1 3 1  
9. 5  P ri o r  a n d   C o n c o  mit a nt   T h e r a p y  
A n y pri or, c o nc o mita nt , or pr oce d ural m e dicati o ns or thera p y gi ve n t o or ta ke n b y t he patie nt 
wit hi n  1 m o nt h  pri or t o co m m e nceme n t of t he st u d y an d u p t o  the  En d of  T re at me nt  vi sit 
( E O T) m ust  be rec or de d in  the s o urce d oc u me nts an d t he eC R F al o n g wit h t he i n dicati o n, wa y 
of a d mi nistrati o n/f or m ula  an d d osa ge. S uc h me dicati o ns (i ncl u di n g o ver-t he-c o u nter a ge nts) 
m ust be  liste d o n t he co nc o mita nt  me dicati o ns  f or m i n t he eC R F , wit h t he exce pti o n of [1 8 F] 
fl u or o de o x y gl uc ose (F D G) a n d/ or C T/ M RI c o ntrast a ge nts . 
F or a  patie nt t o be c o me  eli gi ble f or “ F urt her  or C o nti n ue d A nti b o d y  Tre at me nt ”  (if gi ve n 
des pite pr o gressi o n  of disease/rela pse), a n E O T Visit  incl u di n g  all pr ot oc ol prescri be d 
pr oce d ures ne ed t o be perf or me d i n or der t o ca pt ure t he  e ve nt  (i.e. disease pr o gressi o n/rela pse)  
f or the treat me nt t o c o nti n ue furt her. In s uc h cases the 3 0- D a y S afet y F oll o w- U p  will  n ot ta ke 
place as l o n g as anti b o d y t reat me nt c o nti n ues  f urt her. I nstea d, t he 3 0- D a y S afet y F oll o w- U p  
will ta ke  place 3 0 da ys after t he peri o d of “ F urt her  or Co nti n ue d A nti b o d y  Tre atm e nt ”  (if 
g i ve n des pite p ro gressi o n  of disease/rela pse) h as e n de d  (see Secti o n 1 1. 2 ). 
Fr o m t he  3 0- D a y S afet y F oll o w- U p  v isit, a ntica ncer  treat me nts a n d, in  t he case of  a n SA E/
A E SI  assesse d  as relate d  (see Secti o n 1 1. 2 ), ot her rele va nt i nf or mati o n, e. g. c o nc o mita nt 
me dicati o ns s h o ul d be d oc u me nte d. 
T he in vesti gat or sh o ul d i nstr uct the p atie nt n ot to ta ke an y a d diti o nal m e dicati o ns (i ncl u di n g 
o ver the- co u nter-- pr o d ucts) d u rin g t he st u d y wit h o ut pr i or co ns ultati o n. 
I nf or matio n s h o ul d be pr o vi de d o n a n y pre vi o us N H L- s pecific t hera pies si nce t he ti me p oi nt o f 
t he first di a g n osis of N H L. T he ge neric or t he tra de na me ma y be rec or de d. Patie nts sh o ul d n ot 
recei ve a n y D L B C L  s pecific- t hera p y ot her t han st u d y dr u gs ( M O R 0 0 2 0 8, R T X an d B E N) 
d uri n g C o m bi nati o n Treat me nt, d uri n g A nti b o d y M o n ot hera p y Treat me nt an d d uri n g f oll o w u p 
f or P F S .  
Patie nts ma y  c o nti n ue t he me dicati o ns t he y were recei vi n g  at baseli ne. Patie nts ma y  recei ve 
c o nc o mita nt  me dicati o ns  t hat are me dicall y  i n dicate d as sta n dar d care f or t he treat me nt of 
s y m pt o ms a n d interc urre nt  ill nesses. Me dicati o ns t o  treat c o nc o mita nt  d iseases suc h  as dia betes, 
h y perte nsi o n, br o nc hial ast h ma, c hr o nic o bs tr ucti ve p ul m o nar y di sease etc., are all o we d.  Patie nts 
will als o  recei ve  t hera p y t o mi ti gate si de effects of t he  st u d y me dicati o n  as cli nicall y i n dicate d, 
as well as  BS C  as pe r i nstit uti o nal g ui deli nes. This  may  i ncl u de, b ut is n ot li mite d  t o antie metics,  
a nti- diarr h oeals,  a ntic h oli ner gics,  a ntis pas m o dics, a nti p yretics,  a nti hista mi nes,  a nal gesics, 
a nti bi otics, a n d ot her me dicati o ns inte n de d t o treat sy m pt o ms. 
C o ncer ni n g B E N an d R T X, t he S m P C  ( EM A) or Prescri bi n g  I nfor mati o n  ( US  FD A)  sh o ul d  be  
referre d  t o f or i nf or mati o n o n the  ad mi nistrati o n  of c o nc o mita nt me dicati o ns  an d  p ote ntial 
dr u g- dr u g  i nteracti o ns.

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 5 8  of 1 3 1  
9. 5. 1  G r o  wt h  F a ct o rs  a n d   T r a nsf usi o n  S u p p o rt  
Gr o  wt h f a ct ors   m a y  b e  pr es cri b e d  at t h e i n v esti g at or’s  dis cr eti o n,  a c c or di n g t o  t h e pri n ci pl es  of 
m e di c al  pr a cti c e  a n d t h e i nstit uti o n al st a n d ar ds.   Gr o  wt h f a ct ors  or tr a nsf usi o n su p p ort  s h o ul d  n ot 
b e  a d  mi nist er e d  d uri n g S cr e e ni n g s ol el y f or t h e  p ur p os e  of i  m pr o vi n g  a  p ati e nt’s  bl o o d  v al u es i n 
or d er t o   m e et  eli gi bilit y  crit eri a.  
 
9. 5. 2  I nf e cti o n  P r o p h yl a xis 
I n v esti g at ors s h o ul d f oll o  w i nstit uti o n al  g ui d eli n es  c o n c er ni n g i nf e cti o n  c h e  m o pr o p h yl a xis f or 
p ati e nts r e g ar d e d t o  b e  at  hi g h ris k f or i nf e cti o n.  
 
9. 5. 3  A nti c a n c e r   T h e r a pi es  
T h e  us e  of  c o n c urr e nt  a nti n e o pl asti c t h er a pi es  ot h er t h a n st u d y  d r u gs, i n cl u di n g,  b ut  n ot li  mit e d 
t o  c h e  m ot h er a pi es,  h or  m o n al t h er a p y, i  m  m u n ot h er a p y,  bi ol o gi c al r es p o ns e   m o difi ers,   m  A bs   wit h 
or   wit h o ut  c o nj u g ati o n, r a di o -is ot o pi c t h er a pi es,  a n d t ar g et e d s  m all   m ol e c ul es  ar e  n ot  p er  mitt e d 
t hr o u g h o ut C o  m bi n ati o n  T r e at  m e nt, A nti b o d y   M o n ot h er a p y  T re at  m e nt  a n d  d uri n g f oll o  w  u p f or 
P F S . A ll o g e n ei c st e  m c ell tr a ns pl a nt ati o n is  c o nsi d er e d t o  b e a  pr ot o c ol  pr o hi bit e d  a nti c a n c er 
t h er a p y. 
 
Li  mit e d fi el d r a di ot h er a p y f or r e d u ci n g s y  m pt o  m s r el at e d t o t u  m ou r   m ass  eff e ct is  all o  w e d 
d uri n g  S cr e e ni n g.  
 
Pr o vi d e d  all t h e i n cl usi o n  a n d  n o n e  of t h e  e x cl usi o n  crit eri a  a p pl y , at t h e  dis cr eti o n  of t h e 
i n v esti g at or, t h e i ntr at h e c al  pr o p h yl a xis of   C  N S  dis e as e ( e. g.   m et h otr e x at e  a n d  c yt ar a bi n e) is 
all o  w e d i n t h e  c o urs e  of t h e tri al.  T h e s e c o n c o  mit a nt m e di c ati o ns   will  b e  pr o vi d e d  b y t h e 
i n v esti g ati v e sit e  a n d  n ot  b y t h e s p o ns or. 
 
9. 5. 4  S yst e  mi c   Gl u c o c o rti c ost e r oi ds  
Si n gl e -d os e, t o pi c al, i ntr a n as al, i n h al e d c orti c ost er oi ds,  as   w ell  as e y e  dr o ps  or l o c al i nj e cti o ns 
( e. g., i ntr a-arti c ul ar)  c o nt ai ni n g  c orti c ost er oi ds  or  p h ysi ol o gi c r e pl a c e  m e nt  of 
gl u c o c orti c ost er oi ds  ar e  p er  mitt e d  d uri n g st u d y  p arti ci p ati o n.  
 
S yst e  mi c gl u c o c orti c ost er oi ds  i n  d os es  u p t o  2 0   m g/ d a y  pr e d nis o n e  or  e q ui v al e nt (i. e. e q ui p ot e nt 
c orti c ost er oi d)  ar e  p er  mitt e d  b ut  o nl y f or t h e tr e at  m e nt  of  n o n-n e o pl asti c  c o  m or bi d i n di c ati o ns 
( e. g., r h e u  m at oi d  art hritis). 
 
S yst e  mi c gl u c o c orti c ost er oi ds  i n  d os es  a b o v e  2 0   m g/ d a y  pr e d nis o n e  or  e q ui v al e nt (i. e. 
e q ui p ot e nt  c orti c ost er oi d)  ar e  p er  mitt e d f or  a li  mit e d  p eri o d  of ti  m e  u n d er f oll o  wi n g 
cir c u  mst a n c es:  
a) us e  as pr e  m e di c ati o n  
b)  e x a c er b ati o n s of  c hr o ni c  n o n -n e o pl asti c  c o n diti o n s s u c h  as c hr o ni c  o bstr u cti v e 
p ul  m o n ar y  dis e as e (  C  O P  D),  br o n c hi al  ast h  m a  or r h e u  m at oi d  art hritis ,  et c. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 5 9  of 1 3 1  
c)
se vere a n d/ or life-th reate n i n g c o n diti o ns s uc h as a dre nal i n s ufficie nc y, 
c yt o ki ne release s y n dr o me, etc.
d )
a ntie metic pr o p h yla xis f or u p t o 2 4 h o urs
e)
t o ma na ge se ver e D L B C L  ma nifestati o ns (e. g.  c om p ressi ve disease,  ra pi dl y  
pr o gressi n g s y m pt o matic a de n o pat h y) bef ore C ycle 1 Da y 1 as per  
i nstit uti o nal sta n dar ds. The  gl uc ortic oster oi ds d o se nee ds t o  be ta pere d t o 
2 0 m g or less of pre d nis o ne or e q ui vale nt per da y pri or t o st u d y dr u g(s) 
a d mi nistrati o n o n C ycle 1 Da y 1. W here ver p ossi ble , the  fresh t u m o ur  
tiss ue ( Secti on  1 0. 2. 1 ) s ho ul d  be c ollecte d  bef ore st arti n g  the  
a d mi nistr ati o n of gl uc oc ortic oster oi ds i n d oses a b o ve 2 0 m g/ d a y
(pre d nis o ne  or e q ui v ale nt,  ple ase refer t o A p pe n di x  G).
T h e gl u c o c orti c ost er oi d   d os a g e  a n d t h e  all o  w a bl e tr e at  m e nt  p eri o d   will  b e  d et er  mi n e d  b y t h e 
i n v esti g at or  o n  a  c as e- b y-c as e  b asis . T h e i n v esti g at or s h o ul d  dis c uss t h e s yst e  mi c  us a g e  of 
gl u c o c orti c ost er oi ds i n  d os es  a b o v e  2 0   m g/ d a y ( pr e d nis o n e  or  e q ui v al e nt)   wit h t h e   m e di c al 
m o nit or  of t h e st u d y  pri or t o t h e i  m pl e  m e nt ati o n ,   w h e n e v er f e asi bl e. T h e s p e cifi e d s yst e  mi c 
gl u c o c orti c ost er oi d s  us e, if s h ort i n  d ur ati o n, is  n ot li k el y t o  c o nf o u n d t h e tr e at  m e nt eff e ct  a n d 
effi c a c y  a n al ysis.  
Im  m u n os u p pr essi v e t h er a pi es  ot h er t h a n s yst e  mi c  gl u c o c orti c ost er oi ds  as  d es cri b e d  ar e  n ot 
p er  mitt e d.   
9. 5. 5  M a n a g e  m e nt  of   T u  m o u r   L ysis  S y n d r o  m e 
Pr e v e nti o n  a n d t h er a p y  of T L S  s h o ul d  b e  c o n d u ct e d  a c c or di n g t o t h e  dis cr eti o n  of t h e 
i n v esti g at or f oll o  wi n g t h e  pri n ci pl es  of   m e di c al  pr a cti c e  a n d t h e i nstit uti o n al  g ui d eli n es. 
All o p u ri n ol s h o ul d  n ot  b e  gi v e n  o n  d a ys   w h e n   B  E  N is i nf us e d b e c a us e  a n i n c r e as e d  ris k  of 
St e v e n  J o h ns o n s y n d r o  m e  a n d to xi c epi d e r  m al n e c r ol ysis (  T  E  N)  h as  b e e n  r e p o rt e d.  
9. 5. 6  M a n a g e  m e nt  of  P ati e nts   wit h Hist o r y  o r  P r e vi o us E v e nts  of  F e b ril e   N e ut r o p e ni a  
P ati e nts   wit h  a  p ositi v e   m e di c al  hist or y of,  or  pr e vi o us i n ci d e n c es of f e bril e  n e utr o p e ni a    w hil e  o n 
st u d y,  or t h os e wit h  a n i n di vi d u al ris k f or f e bril e  n e utr o p e ni a  > 2 0  %, s h o ul d r e c ei v e  pr o p h yl a cti c 
gr a n ul o c yt e  c ol o n y- sti  m ul ati n g f a ct or (  G-C S F)  a c c or di n g t o t h e  pri n ci pl es  of   m e di c al  pr a cti c e 
a n d t h e i nstit uti o n al  g ui d eli n es.  
9. 5. 7  A nti  mi c r o bi als/ A nti vi r als/ A ntif u n g als  
A nti  mi cr o bi als/ a nti vir als/ a ntif u n g als  s h o ul d  als o  b e  a d  mi nist er e d f or  pr o p h yl a xis  a n d/ or f or 
tr e at  m e nt  a c c or di n g t o t h e  pri n ci pl es  of   m e di c al  pr a cti c e  a n d t h e i nstit uti o n al  g ui d eli n es. 
S yst e  mi c  a ntif u n g al  c o v er a g e is  g e n er all y  n ot r e c o  m  m e n d e d.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 6 0  of 1 3 1  
9. 6  T r e at  m e nt   C o  m pli a n c e  
D osi n g m o dificati o ns d u e to t o xicit y are de scri be d i n Secti o n 9. 4. 2 an d are n ot co vere d here. 
Patie nts will recei ve M O R 0 0 2 0 8, R T X a n d B E N u n der t he direct s u per visi o n of st u d y pers o n nel. 
Eac h a d mi nistrati o n v ol u me or d ose will be c hec ke d a n d t he vial/ o uter pac ka ge c o de a n d v ol u me 
or d ose per a d mi nistrati o n will be rec or de d i n eac h patie nt’s e C R F as well as i n t he s o urce data.  
A pa tie nt w ill be co nsi dere d c o m plia nt w it h t he p r ot oc ol if t he M O R 0 0 2 0 8, R T X an d B E N d os e 
a d mi nistere d is ≥8 0 % t o ≤1 2 0 % of t he assi g ned d osa ge pe r si n gle i nf usi o n. 
Dr u g acc o u nta bilit y will be chec ke d b y t he field m o nit or d ur i n g site v isits an d at the co m pleti o n 
of the st u d y. 
9. 7  O ver d o se of St u d y Dr u gs  
A n o ver d ose of M O R 0 0 2 0 8, R T X or B E N is defi ne d as a d ose e xcee di n g t he pla n ne d d ose b y 
m ore t ha n 2 0 % (for f urt her i nf or mati o n  see Secti o n  1 1. 1 ). For e xact a d vice o n ha n dli n g a B E N 
a n d/ or R T X o ve r d ose please  refer t o Sm P C  (E M A ) or Prescri bi n g In f or mati o n (U S  F D A).  N o 
s pecific treat me nt is rec o m me n de d f or o ver d ose of M O R 0 0 2 0 8. T reat me nt re mai ns at t he 
discreti o n  o f t he i n vesti gat or. 
9. 8  Wit h dr a w a l fro m  St u d y Tre at me nt or  St u d y/Site  Ter mi n ati o n  
9. 8. 1  Wit h dr a w al Criteri a  
Patie nts  may  v ol u ntar il y wit h dra w fr o m t he st u d y or treatme nt. Patie nts ma y be di sc o nti n ue d 
fr o m treat me nt a t t he discreti o n of t he i n vesti gat or at a n y ti me.  
At a  mi ni m u m, all patie nts wh o  disc o nti n ue st u d y treat me nt,  incl u di n g  t h ose wh o  ref use t o ret ur n 
for a  fi nal visit, will be co ntacte d  f or safet y e val uati o ns at t he 3 0- Da y  Safet y  F oll o w- U p  vi sit. 
If s uc h wit h dra wal occ urs, or if t he patie nt fails  t o ret ur n f or visits,  t he i n vesti gat or m ust 
deter mi ne  t he pri mar y reas o n f or a p atie nt´s  pre mat ure wit h dra wal fr o m t he st u d y a n d  rec or d  t he 
i nf or matio n o n t he eC R F.  If t he reas o n f or wit h dra wal is an  A E,  m o nit ori n g sh o ul d  co nti n ue  
u ntil  t he o utc o me is e vi de nt. The s pecific e ve nt  or test res ult(s)  must  be rec or de d i n the e C R F.  At  
t he di screti o n of the sp o ns or, patie nts m a y als o be re m o ve d fr o m the st u d y, f or i nsta nce i n a case 
w he n  it is retr os pecti vel y esta blis he d t hat patie nts d o not f ul fil all i ncl usi o n or meet certai n 
e xcl usi o n  criter ia (e. g., tu m o ur tiss ue  is not  a vaila ble  f or ce ntral pat h ol o g y revie w ). 
It sh o ul d be clearl y d oc u me nte d i n t he so urce d ata, w het he r patie nts wit h dre w t heir co nse nt an d 
w ill n ot e nter Foll o w- U p  or if t he pa tie nt wit h dre w t heir co nse nt for st u d y dr u g treat me nt, b ut 
will c o nti n ue  f urt her partici pati o n i n t he st u d y. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 6 1  of 1 3 1  
E x a  m pl es f or   wit h dr a  w al  crit eri a i n cl u d e  b ut  ar e  n ot li  mit e d t o: 
•
A E (s)
•
A b n or mal la b orat or y val ue(s)
•
A b n or ma l test pr oce d ure res ult(s)
•
U n ma na gea ble t o xicit y relate d t o st u d y dr u g(s) (i ncl u di n g but  not li mite d  t o medical  
e ve nts descri be d i n Secti o ns  9. 4 an d  9. 8. 2)
•
Pr o t oc ol vi olati o n
•
Pa tie nt wit h dra wal of c o nse nt
•
Pre g na nc y o r breast-fee di n g
•
L oss t o f oll o w- u p
•
I na bilit y of t he patie nt t o  co m pl y  wit h st u d y req uire me n ts
•
C o n diti o ns re q uiri n g t hera pe utic i nter ve nti o n n ot per mitte d b y t he pr ot oc ol
•
A d mi nistrati ve  pr o ble ms
•
Ra di ol o gicall y c o nfir me d disease pr o gressi o n
•
Wit h dra wal  of  a patie nt  f or a ny  reas o n  at th e discreti o n of t he i nvesti gat or
P ati e nts   w h o  ar e   wit h dr a  w n f or  a n y r e as o n m ust n ot r e- e nt er t his  cli ni c al st u d y  at  a n y ti  m e.  
F or  p ati e nts   w h o  ar e l ost t o f oll o  w- u p  at l e ast t hr e e  att e  m pts  of  c o nt a ct  b y t h e sit e s h o ul d  b e 
m a d e  a n d  d o c u  m e nt e d i n t h e s o ur c e d at a.  
9. 8. 2  St u d y  o r  Sit e   T e r  mi n ati o n  
T h e i n v esti g at or  a n d t h e s p o ns or  b ot h r es er v e t h e ri g ht t o t er  mi n at e t h e st u d y  at  a n y ti  m e  at  a 
gi v e n  cli ni c al st u d y  c e ntr e.  T h e s p o ns or  als o r es er v es t h e ri g ht t o t er  mi n at e t h e  e ntir e st u d y  or 
t e  m p or aril y i nt err u pt  e nr ol  m ent  a n d/ or  d osi n g  of  alr e a d y  e nr oll e d  p ati e nts f or f urt h er  e v al u ati o n.  
S t o p pi n g  crit eri a f or t his st u d y   will i n cl u d e,  b ut  ar e  n ot li  mit e d t o: 
1.
F or t h e first  1 0  p ati e nts  e nr oll e d i n  c o h ort M  O  R 0 0 2 0 8  +   B E  N  d uri n g t h e s af et y r u n-i n
p h as e:
•
T o xi citi es w hi c h  o c c u r i n t h r e e  o r   m o r e  p ati e nts  (t o xi cit y   m e a ns  a n  a d v ers e  dr u g
r e a cti o n   wit h  a s us p e ct e d  c a us al r el ati o ns hi p t o tri al   m e di c ati o ns  as  ass ess e d  b y t h e
i n v esti g at or  or t h e s p o ns or):

Li v er:   A c ut e  h e p ati c f ail ur e > Gr a d e  4

All er gi c r e a cti o n,  a n a p h yl a xis,  c yt o ki n e r el e as e s y n dr o  m e > Gr a d e  4

A n y  c ar di a c  e v e nt > Gr a d e  4

E  C  G:   Q T c  pr ol o n g ati o n ( T ors a d e  d e  p oi nt es)  > Gr a d e  4

G astr oi nt esti n al:   Di arr h o e a,  n a us e a,  v o  miti n g > Gr a d e  4

A c ut e  ki d n e y i nj ur y  > Gr a d e  4

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 6 2  of 1 3 1  
 
M ulti o r g a n fail ur e  >   Gr a d e  3  
 
P ul  m o n ar y  h a e  m orr h a g e  >   Gr a d e  3  
 
P n e u  m o ni a >  Gr a d e  4  
 
S e psis  ≥   Gr a d e  4  
 
T u  m o u r l ysis s y n dr o  m e >  Gr a d e  4  
• 
A n y  ot h er  u n e x p e ct e d, s us p e ct e d  a d v ers e  dr u g r e a cti o n  of t h e s a  m e  n at ur e   w hi c h is 
≥ Gr a d e  4  a n d   w hi c h  o c c urs i n t hr e e  or   m or e  p ati e nts.  
• 
H a e  m at ol o gi c t o xi cit y   w hi c h  o c c urs i n f o ur  or   m or e  p ati e nts  a n d   w hi c h  h as  n ot 
di  mi nis h e d i n s e v erit y t o  gr a d e  ≤ 2  or r e c o v er e d t o  b as eli n e l e v e l (if t h e  c o n diti o n   w as 
pr e -e xisti n g)   wit hi n  2 8  d a ys (t o xi cit y   m e a ns  a n  a d v ers e  dr u g r e a cti o n   wit h  a 
s us p e ct e d  c a us al r el ati o ns hi p  as  ass ess e d  b y t h e i n v esti g at or  or t h e s p o ns or):  
 
F e bril e  n e utr o p e ni a >  Gr a d e  4  
 
N e utr o p e ni a >  Gr a d e  4  
 
A n ae  mi a >  Gr a d e  4  
 
T hr o  m b o c yt o p e ni a >  Gr a d e  4  
2.  T h er e aft er f or  all  p ati e nts  e nr oll e d i n  c o h ort M  O  R 0 0 2 0 8  +   B E  N:  
• 
≥ 3 0  %  of  p ati e nts  e x p eri e n ci n g  u n e x p e ct e d   Gr a d e  ≥ 4  a d v ers e  dr u g r e a cti o ns  as 
d es cri b e d  a b o v e.  
3.  S p o ns or  d e cisi o n f oll o  wi n g t h e r e c o  m  m e n d ati o n  of I  D  M  C  or t h e  o ut c o  m e  of t h e i nt eri  m 
a n al ysis 
 
S h o ul d  a t er  mi n ati o n  of  a  gi v e n  cli ni c al st u d y  c e ntr e  or t h e   w h ol e st u d y  b e c o  m e  n e c ess ar y, t h e n 
a d e q u at e  pr o c e d ur es   will  b e  arr a n g e d  aft er  c ar ef ul  c o nsi d er ati o n  a n d  c o  m  m u ni c at e d t o  all 
i n v ol v e d  p arti es. I n t er  mi n ati n g  a st u d y  c e ntr e,  or th e  e ntir e st u d y, t h e s p o ns or  a n d t h e 
i n v esti g at ors   will  e ns ur e t h at  a d e q u at e  c o nsi d er ati o n is  gi v e n t o t h e  pr ot e cti o n  of t h e  p ati e nts’ 
i nt er ests. I nstit uti o n al   R e vi e  w   B o ar ds (I  R  Bs)/I n d e p e n d e nt  Et hi cs   C o  m  mitt e es (I E  Cs)  a n d 
c o  m p et e nt  a ut h oriti es   will  b e  n oti fi e d  of  pr e  m at ur e t er  mi n ati o n i n  a c c or d a n c e   wit h  a p pli c a bl e 
r e g ul at or y r e q uir e  m e nts.  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 6 3  of 1 3 1  
1 0  S  T  U  D  Y  P  R  O  C  E  D  U  R  E S  
1 0. 1  S c h e d ul e  of   Visits  a n d  P r o c e d u r es  
T a bl e   5 lists  all s c h e d ul e d ass ess  m e nts,  a n d i n di c at es   wit h  a n  “  X ” t h e  visits  at   w hi c h t h es e 
ass ess  m e nts  ar e  p erf or  m e d. P ati e nts i n  b ot h tr e at  m e nt  ar  ms  ar e s u p p os e d t o f oll o  w t h e s a  m e 
s c h e d ul e  of  visits irres p e cti v e  of tr e at  m e nt  all o c ati o n.  All  d at a  o bt ai n e d fr o  m t h es e  ass ess  m e nts 
m ust  b e s u p p ort e d i n t h e  p ati e nt´s s o ur c e  d o c u  m e nt ati o n. 
 
Visit s c h e d uli n g  c al c ul ati o n:  
E a c h   Visit fr o  m   C y cl e  1   D a y  1  u ntil  a n d i n cl u di n g   C y cl e  7   D a y  1 s h all  b e s c h e d ul e d  b as e d  o n 
t h e  d at e  of t h e   C y cl e  1   D a y  1  visit  a n d i n li n e   wit h t h e  gi v e n  visit   wi n d o  w ( e. g., t h e   C y cl e  2 
D a y   1  visit s h all  b e s c h e d ul e d  2 8  d a ys  aft er t h e  d at e  of   C y cl e  1   D a y  1 ± 3  d a ys; t h e   C y cl e  3   D a y  1 
visit s h all  b e s c h e d ul e d  5 6  d a ys  aft er t h e  d at e  of   C y cl e 1   D a y  1  ± 3  d a ys;   C y cl e  3   D a y  1 5 s h all  b e 
s c h e d ul e d  7 0  d a ys  aft er t h e  d at e  of   C y cl e  1   D a y  1  ± 1  d a ys,  et c.).  
E a c h   Visit fr o  m   C y cl e 7   D a y  1 5  o n  w ar ds s h all  b e s c h e d ul e d  b as e d  o n t h e  d at e  of t h e C y cl e  7  
D a y   1  visit  a n d i n li n e   wit h t h e  gi v e n  visit   wi n d o  w  a n d  n ot  b as e d  o n t h e  d at e  of   C y cl e  1   D a y  1. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 1  of 1 3 1  
4Pr e g n a n c y t ests: f or  F  C  B P:   A s er u  m  pr e g n a n c y t est   m ust  b e  p erf or  m e d  d uri n g S cr e e ni n g. O n C 1  D 1 , a s e c o n d,   m e di c all y s u p er vis e d  uri n e  pr e g n a n c y t est   m ust  b e  p erf or  m e d  pri or 
t o t h e st art  of st u d y  dr u g.  T h e r es ults  of  b ot h t ests   m ust  b e  n e g ati v e i n  or d er t o r e c ei v e C 1  D 1  d osi n g. A β -H  C  G  s er u  m pr e g n a n c y t est s h o ul d  als o  b e  p erf or  m e d at t h e E  O T   visit. At 
all  ot h er i n di c at e d ti  m e  p oi nts,  a  uri n e  pr e g n a n c y t est f or  F  C  B P s h o ul d b e  p erf or  m e d l o c all y  a n d t h e r es ult   m ust  b e  n e g ati v e f or  d osi n g.  
5S a  m pl e t o  b e  c oll e ct e d  a n d  e v al u at e d  i n t h e l o c al l a b or at or y   wit hi n  2 4  h o urs  pri or t o t h e  a d  mi nistr ati o n  of t h e st u d y  dr u g(s) a n d r e vi e  w e d  b y st u d y tr e ati n g  p h ysi ci a n  b ef or e st u d y 
dr u g  a d  mi nistr ati o n.  T h e l o c al  l a b or at or y s a  m pl es   will  als o  b e  c oll e ct e d f or t h e   R T  X +  B E  N  p ati e nts,  d es pit e t h e f a ct t h at t h e y m a y  n ot r e c ei v e st u d y  dr u gs  at  a  p arti c ul ar  visit. 
U n d er s u c h  cir c u  mst a n c es, t h e s a  m pl e  c oll e cti o n ti  m e  p oi nt  o n s u c h  visits is  at t h e i n v esti g at or’s  dis cr eti o n.  
6A nti -  M  O  R 0 0 2 0 8 a nti b o d y s a  m pl es  a n d   M  O  R 0 0 2 0 8  P  K s a  m pl es   will  b e  c oll e ct e d i n t h e   M  O  R 0 0 2 0 8-tr e a t  m e nt  ar  m  o nl y a n d s a  m pl e  c oll e cti o n s h all  b e st o p p e d  aft er   C y cl e  2 3 . 
7S e e  S e cti o n  1 0. 3. 9  f or  d et ails. R e p e at b o n e m arr o  w  bi o ps y  a n d  as pir ati o n t o c o nfir  m  a   C  R a n d o nl y i n t h os e  p ati e nts   w h o  h a d k n o  w n  b o n e   m arr o  w i n v ol v e  m e nt  pri or t o 
r a n d o  mis ati o n. B o n e   m arr o  w  bi o ps y  a n d  as pir ati o n will  o nl y  b e r e p e at e d if r es p o ns e i n  pri or  c y cl es w as  n ot   C  R.  
8M  O  R 0 0 2 0 8  P  K s a  m pl e  (t o  b e  c oll e ct e d i n t h e   M  O  R 0 0 2 0 8 tr e at  m e nt  ar  m  o nl y) t o b e t a k e n  pr e -d os e  a n d  1  h o ur  ± 1 0   mi n  aft er t h e  e n d  of   M  O  R 0 0 2 0 8 i nf usi o n.  
9M  O  R 0 0 2 0 8  P  K s a  m pl es  (t o  b e  c oll e ct e d i n t h e   M  O  R 0 0 2 0 8 tr e at  m e nt  ar  m  o nl y) s h o ul d o pti  m all y  b e  c oll e ct e d  b ef or e   B E  N  a d  mi nistr ati o n  (  w h e n  a p pli c a bl e).  
1 0A nti -M  O  R 0 0 2 0 8  a nti b o d y s a  m pl e  a n d   M  O  R 0 0 2 0 8  P  K s a  m pl e   will  b e  c oll e ct e d pr e- d os e  o nl y i n  o d d  n u  m b er e d A nti b o d y   M o n ot h er a p y Tr e at  m e nt c y cl es of t h e M  O  R 0 0 2 0 8 
tr e at  m e nt  ar  m o nl y (i. e. tr e at  m e nt   C y cl es  7,  9,  1 1 ,  et c. u ntil  a n d i n cl u di n g   C y cl e  2 3 ). N o s a  m pl es t o  b e  c oll e ct e d  aft er   C y cl e  2 3.  
1 1R el e v a nt f or t h e  c o nfir  m ati o n  of   C  R  at   C 6  D 2 8  a n d d uri n g s u bs e q u e nt  dis e as e r es p o ns e  ass ess  m e nts. 
1 2Wit h t h e  e x c e pti o n  of   C 7 D 1 ,  d uri n g   A nti b o d y   M o n ot h er a p y Tr e at  m e nt  a n d F oll o  w -U p f or  P F S,  dis e as e  ass ess  m e nt  usi n g   C T   will  b e  p erf or  m e d  e v er y  3   m o nt hs  ±  2   w e e ks fr o  m 
t h e  pr e vi o us s c a n  u ntil  dis e as e  pr o gr essi o n,  d e at h  or st u d y  dis c o nti n u ati o n (  w hi c h e v er  o c c urs first). Dis e as e r es p o ns e  ass ess  m e nt   m a y  als o i n cl u d e st a n d ar d  of  c ar e  pr o c e d ur es t o 
d et er  mi n e t h e  dis e as e st at us  p er   C h es o n 2 0 0 7 crit eri a ( e. g.  c o nfir  m at or y  bi o ps y, l u  m b ar  p u n ct ur e,  et c f or  P  D)  
1 3I n c as e t h at t h e  p ati e nt is   wit h dr a  w n fr o  m tr e at  m e nt  b ef or e t h e  e n d  of   C y cl e  6  f or r e as o ns  ot h er t h a n  P  D. C T  o nl y   m a y  b e  p erf or  m e d i n li e u  of  P E T/  C T if  E  O T t a k es  pl a c e   wit hi n 
C y cl e  1.  P E T/  C T is  o nl y r e q uir e d  at t h e  E  O T  visit if it   w as  n ot  p erf or  m e d i n t h e  c y cl e  b ef or e t h e  e n d  of tr e at  m e nt.  
1 4F or  a  p ati e nt t o  b e c o  m e  eli gi bl e f or “ F u rt h e r  o r   C o nti n u e d   A nti b o d y   T r e at  m e nt ”  t h e 3 0- D a y  S af et y  F oll o  w -U p  will  n ot t a k e  pl a c e  as l o n g  as  a nti b o d y tr e at  m e nt  c o nti n u es. 
I nst e a d, t h e 3 0- D a y  S af et y  F oll o  w -U p  will t a k e  pl a c e  3 0  d a ys  aft er t h e  p eri o d  of “ F u rt h e r  o r   C o nti n u e d   A nti b o d y   T r e at  m e nt ”  (if  gi v e n  d es pit e  pr o gr essi o n  of  dis e as e/r el a ps e) 
h as  e n d e d. St arti n g f r o  m t h e  3 0-D a y  S af et y  F oll o  w -U p  visit, a nti c a n c er tr e at  m e nts  a n d  S  A E s/  A E SIs ass ess e d  as r el at e d  (s e e  S e cti o n 1 1. 2 ) sh o ul d  b e d o c u  m e nt e d. F or  a n  E  O T  visit 
t a ki n g  pl a c e  b ef or e t h e  e n d  of   C y cl e  6, a n y c o n c o  mit a nt   m e di c ati o n  n e e ds t o  b e r e c or d e d.  
1 5F or  p ati e nts r e c ei vi n g  “ F urt h er  or   C o nti n u e d   A nti b o d y  Tr e at  m e nt ” (if  gi v e n  d es pit e  pr o gr essi o n  of  dis e as e/r el a ps e) f or  u p t o  2 4   m o nt hs i n t ot al :   Bef or e t h e  a d  mi nistr ati o n  of 
a nti b o di es,  bl o o d  p ar a  m et ers ( h a e  m at ol o g y, s er u  m  c h e  mistr y) s h o ul d  b e ass ess e d i n t h e l o c al l a b  a c c or di n g t o l o c al  g ui d eli n es/st a n d ar ds a p pli c a bl e  f or  a d  mi nistr ati o n  of 
m o n o cl o n al  a nti b o di es.   A  uri n e  pr e g n a n c y t est s h o ul d  b e  p erf or  m e d i n  F  C  B P.   Vit al si g ns s h o ul d  b e   m e as ur e d  pri or t o tr e at  m e nt  a n d  a c c or di n g t o l o c al  pr a cti c e a p pli c a bl e f or t h e 
a d  mi nistr ati o n  o f   m o n o cl o n al  a nti b o di es.   Ot h er  pr o c e d ur es  d es cri b e d i n t h e  c ol u  m n   A nti b o d y   M o n ot h er a p y  Tr e at  m e nt   will  n ot  a p pl y f or t his  p ati e nt  p o p ul ati o n. 
1 6H  B  V -D  N  A t o  b e r e-  m e as ur e d  o nl y if  a nti-H  B c   w as p ositi v e d uri n g s cr e e ni n g ( pl e as e s e e  S e cti o n  1 0. 3. 7. 2 ). 
1 7E  O  R T  C   Q L  Q -C 3 0  a n d  E  Q - 5  D-5 L t o  b e  a d  mi nist er e d  o n   D 1  of t h e  o d d -n u  m b er e d   A nti b o d y   M o n ot h er a p y  Tr e at  m e nt  c y cl es  ( e. g.,   C 7  D 1, C 9  D 1,   C 1 1  D 1 , et c). 
1 8First  F  U  visit f or   O S t o  b e p erf or  m e d  as  a  cli ni c  visit.  
1 9D is e as e  ass ess  m e nts a n d t u  m o ur   m e as ur e  m e nts   will  b e   m a d e  b y  p ositr o n  e  missi o n t o  m o gr a p h y ( P E T)  a n d  c o  m p ut e d t o  m o gr a p h y (  C T) or   C T  al o n e wit h  c o ntr ast.  F or  all  p ati e nts , 
n e c k/ c h est/ a b d o  m e n/ p el vis   C T is r e q uir e d.  T h e   C T  p orti o n  of  a  c o  m bi n e d [ 1 8 F]fl u or o d e o x y gl u c os e ( F  D  G) -P E T/  C T s c a n s h o ul d  b e  p erf or  m e d   wit h  c o ntr ast  a n d  c oll e ct e d   wit h 
r es ol uti o n s uffi ci e nt t o  all o  w  a c c ur at e  a n d  c o nsist e nt  c o  m p aris o n  of t ar g et l esi o n   m e as ur e  m e nts   wit h s u bs e q u e nt   C T s c a ns. If a v ail a bl e  a n d  of  a c c e pt a bl e  q u alit y ( e. g.,   C T  p orti o n 
of  P E T/  C T s c a n   w as  p erf or  m e d   wit h  c o ntr ast),  pr e vi o usl y  p erf or  m e d  P E T/  C T  e x a  mi n ati o ns, i n  a c c or d a n c e   wit h t h e st a n d ar d  of  c ar e, t h at   w er e  d o n e  u p t o  4   w e e ks  pri or t o 
S cr e e ni n g   m a y  b e  e  m pl o y e d.  Dis e as e r es p o ns e  ass ess  m e nt   m a y  als o i n cl u d e st a n d ar d  of  c ar e  pr o c e d ur es t o  d et er  mi n e t h e  dis e as e st at us  p er   C h es o n  crit eri a ( e. g.  c o nfir  m at or y 
bi o ps y, l u  m b ar  p u n ct ur e,  et c f or  P  D).  F or f urt h er  d et ails  pl e as e r ef er t o  S e cti o n  1 0. 3. 8. 1 . 
2 0I n t h e  c o urs e  of  F  U f or   O S, Q o L  q u esti o n n air es   will  b e  a p pli e d  o nl y  d uri n g t h e first  F  U f or   O S  visit,   w hi c h   will  b e  a  cli ni c  visit.  
2 1D uri n g   A nti b o d y   M o n ot h er a p y  Tr e at  m e nt,  a li  mit e d  P E   will  b e  p erf or  m e d  o n   D a y  1  of   C y cl es 7, 1 0,  1 3,  1 6,  et c.  
2 2Pr e  m e di c ati o n t o  b e  a d  mi nist er e d  as  o u tli n e d i n S e cti o n  9. 2 . 
2 3 D at a  c oll e cti o n 
   w as st o p p e d  as  of  2 2-J  U  N-2 0 2 0,  b e c a us e s uffi ci e nt  d at a   w as  alr e a d y  c oll e ct e d f or t h e  e x pl or at or y  p ur p os e.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 2  of 1 3 1  
1 0. 2  P r o c e d u r es  
All st u d y -r e q uir e d  pr o c e d ur es s h o ul d  o c c ur  as  o utli n e d i n T a bl e  5. D e vi ati o ns fr o  m t h e ti  mi n g  of 
ass ess  m e nts   will  b e  c o nsi d er e d  pr ot o c ol n o n- c o  m pli a n c es   a n d s h o ul d  b e r e c or d e d i n t h e s o ur c e 
d o c u  m e nts  al o n g   wit h t h e r e as o n f or t h e  e x c ursi o n. 
 
S cr e e ni n g  b e gi ns  o n t h e  d at e t h at t h e I  C F is si g n e d  a n d   will l ast f or  u p t o  2 8  d a ys. I n  e x c e pti o n al 
c as es, t h e s cr e e ni n g  p eri o d   m a y  b e  e xt e n d e d  at t h e  dis cr eti o n  of t h e i n v esti g at or f or  a t ot al  of  u p 
t o  4 2  d a ys  d u e t o  a n y t e c h ni c al/l o gisti c r e as o ns ( e. g.,  e xt e n d e d i  m a gi n g  e q ui p  m e nt  br e a k d o  w n 
a n d/ or s er vi ci n g,  d el a ys i n t h e  d eli v er y  of  c e ntr al l a b or at or y r es ults).  T h e r e as o n f or s u c h 
e xt e nsi o n  al o n g   wit h  a n  e v al u ati o n  b y t h e i n v esti g at or  e ns uri n g t h at s u c h e xt e nsi o n  d o es  n ot  p os e 
a n y  h e alt h ris k f or t h e  p atie nt s h o ul d  b e  d o c u  m e nt e d i n t h e  p ati e nt’s s o ur c e  d at a. T h e I  C F   m ust 
b e si g n e d  pri or t o t h e  c o n d u ct  of  a n y  ass ess  m e nts s ol el y f or t h e  p ur p os e  of t his st u d y.  St a n d ar d 
of  c ar e  ass ess  m e nts  d o n e  o n t h e  d a y  of  c o ns e nt ( b ut  pri or t o si g ni n g t h e I  C F)  d o  n ot  n e e d t o  b e 
r e p e at e d s ol el y f or t h e  p ur p os e  of s cr e e ni n g  a n d   m a y  b e  us e d  as st u d y  d at a, if t h e y  a n d t h eir 
r es ults m e et t h e  pr ot o c ol r e q uir e  m e nts.  
 
O n   C y cl e  1   D a y  1,  p ati e nt  eli gi bilit y   m ust  b e  c o nfir  m e d  b ef or e  dr u g  a d  mi nistr ati o n. 
 
1 0. 2. 1  Di a g n osti c   Bi o ps y  
P ati e nts s h o ul d  b e  eli gi bl e  a n d   willi n g t o  u n d er g o  a  bi o ps y or s ur gi c al  e x cisi o n of  a l y  m p h  n o d e 
a n d/ or  ot h er  p at h ol o gi c al tiss u e,  pr o vi di n g  e n o u g h t u  m o ur tiss u e f or c e ntr al  hist ol o gi c al r e vi e  w 
a n d c orr el ati v e st u di es,  as  a pr er e q uisit e f or   p arti ci p ati o n i n t his st u d y.  S h o ul d it  n ot  b e  p ossi bl e 
t o  o bt ai n  a fr es h t u  m o ur tiss u e s a  m pl e,  ar c hi v al  p ar affi n  e  m b e d d e d t u  m o ur tiss u e  a c q uir e d 
≤ 3  y e ars  pri or t o s cr e e ni n g f or t his  pr ot o c ol   m ust  b e  a v ail a bl e f or t his  p ur p os e.  
 
I n  a d diti o n,  p ati e nts   will  h a v e t h e  o pti o n t o  c o ns e nt f or st or a g e  a n d  us e  of t h eir s u b  mitt e d t u  m o ur 
tiss u e f or f ut ur e l y  m p h o  m a r es e ar c h. 
 
Hist ol o gi c al  c o nfir  m ati o n  of t h e  di a g n osis  of   D L  B  C L   will  b e  p erf or  m e d  b y  a  c e ntr al  p at h ol o gist.  
S ur gi c all y  a c q uir e d tiss u e s a  m pl es  ar e  pr ef err e d,  b ut  c or e  bi o psi es  ar e  p er  mitt e d.  Fi n e  n e e dl e 
as pir at es ( F  N  A)   will  n ot  b e  a c c e pt e d f or  hist ol o gi c al  c o nfir  m ati o n.  
 
C e nt r al  p at h ol o g y  r e vi e  w is   m a n d at o r y ,  b ut r etr os p e cti v e i n  n at ur e.   A n  eff ort s h o ul d  b e   m a d e 
t o s u b  mit tiss u e s a  m pl e(s)   wit hi n  3 0  da ys  of r a n d o  mis ati o n.  P ati e nts  c a n  b e r a n d o  mis e d  pri or t o 
s u b  missi o n  of tiss u e s a  m pl e(s).  T h e l o c al  p at h ol o g y r e p ort i n di c ati n g  a   D L  B  C L  or D L  B  C L   N  O S  
di a g n osis is  a c c e pt a bl e f or  d et er  mi ni n g  a  p ati e nt’s  eli gi bilit y.    O n r e q u est  of t h e i n v esti g at or, t h e 
s p o ns or   m a y f a cilit at e  a n i nt er a cti o n  b et  w e e n t h e i n v esti g at or  a n d t h e  c e ntr al  p at h ol o gist t o 
dis c uss iss u es  c o n n e ct e d t o t h e i niti al  di a g n osis  est a blis h e d l o c all y.  If t h e  q u alit y  of t h e tiss u e 
s a  m pl e  d o es  n ot  all o  w  c e ntr al  p at h ol o g y  a n al ysis,  a n ot h er  ar c hi v al sa  m pl e  of t h e  a p pr o pri at e 
q u alit y   m a y  b e r e q u est e d  b y t h e  S p o ns or. 
 
I n t h e  c as e  of  dis cr e p a n ci es  b et  w e e n t h e  ass ess  m e nts  of t h e l o c al  a n d t h e  c e ntr al  p at h ol o gists, t h e 
ass ess  m e nt  of t h e  c e ntr al  p at h ol o gists   will  b e r el e v a nt f or s e nsiti vit y  a n al ys es  of t h e  pri  m ar y  
effi c a c y   e n d p oi nt  a n al ysis. If t h e   D L  B  C L  di a g n osis  of t h e l o c al  p at h ol o gist  c a n n ot  b e  c o nfir  m e d 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 7 3  of 1 3 1  
b y t he ce ntral pa t h ol o gists, a n d a pa tie nt’s treat me nt ha s alrea d y c o m me nce d, t he pa tie nt ma y 
re mai n  i n t he st u d y at t he  discreti o n of t he  treati n g p h ysicia n. 
B o ne marr o w bi o ps y a n d b o ne marr o w as pirati o n are n ot c o nsi dere d  a de q uate f or t he p ur p ose of 
dia g n ostic bi o ps y i n t his trial (als o see Secti o n  1 0. 3. 9 ). 
1 0. 2. 2  De m o gr a p hic D at a/ Rele v a nt  Me dic al H ist or y a n d  Curre nt  Me dic al 
C o n diti o ns/ B aseli ne, St a ge a n d  Pr o g n ostic Cl assific ati o n  
De m o gra p hic va ria bles t o be rec or de d will incl u de: age, ge n der, r ace , b o d y hei g ht, a n d b o d y 
wei g ht. Wei g ht an d hei g ht sh o ul d be m eas ure d w hile t he pa tie nt is w it h o ut sh oes, b ut dr esse d. 
At the ti me of si g ni n g of the IC F, rele va nt m e dical hi st or y a n d c urre nt m e dical c o n diti o ns sh o ul d 
be  rec or de d.  T he  medical hist or y  of N H L  s h o ul d be d oc u me nte d i n detail, incl u di n g baseli ne 
s y m pt o ms as well as a detaile d  hi st or y of pr i or ca ncer  t hera pies f or NH L , wit h start a n d st o p 
dates,  n u m ber of t hera p y  li ne(s), disease pr o gressi o n d uri n g or after t hera p y, as w ell as 
disc o nti n uati o ns d ue t o i nt olera bilit y or an y ot her cli nicall y si g nifica nt ill ness. A n y pre vi o us 
t hera p y (e. g., c he m ot hera p y, i m m u n ot hera p y, or ra diatio n t hera p y) for D L B C L sh o ul d be 
rec or de d i n t he eC R F. Als o, e xa mi nati o ns lea di n g t o t he d ia g n osis of t he latest p r o gressi o n of 
D L B C L  sh o ul d be d oc u me nte d i n t he pa tie nt’s so urce d oc u me nts. T his ma y i ncl u de, e. g., r es ults  
of la b orat or y  exa mi nati o ns,  i magi n g  res ults or  cli nica l s y m pt o ms relate d  t o DL B C L.  The  
assess me nt of the l y m p h o ma sh o ul d i ncl u de sta gi n g. I n or der t o reflect the patie nt’s  stat us at t he 
ti me of e nr ol me nt, t he sta n dar d sta gi n g s yste m u se d f or D L B C L reflecti n g t he n u m ber of s ites o f 
i n v ol ve me nt an d t heir relatio n t o t he dia p hra g m, t he existe nce of B -s y m pt o ms, a n d the  prese nce 
of extra n o dal di sease, will be d oc u me nte d ( see Ap pe n di x I  for A n n Ar b or S ta gi n g). 
A d d iti o nall y, th e dis ease ris k assess me nt as p er t he I nter nati o nal Pr o g n ostic I n de x (IPI ; see 
A p pe n di x J ) an d  patie nt  stat us as per  EC O G  perf or ma nce stat us criteria ( see A p pe n di x K ) will 
be rec or de d. 
1 0. 2. 3  Q u alit y  of Life  
I n t he co urse of the st u d y, t w o Q o L q uesti o n naires w ill b e us e d: 
a)
th e s t a n d ar dis e d E ur o p e a n   Or g a nis ati o n f or   R es e ar c h  a n d Tr e at  m e nt  of   C a n c er   Q u alit y  of
Lif e   Q u esti o n n air e -C or e  3 0 ( E  O  R T  C  Q L  Q -C 3 0 ).
b)   t h e  E ur o  Q ol fi v e  di  m e nsi o ns  q u alit y  of lif e  q u esti o n n air e wit h 5 l e v els ( E  Q- 5  D- 5 L).
Res ults of  t he c o m plete d Q o L q ue sti o n naires w ill be entere d b y t he site int o t he eC R F. 
1 0 . 3 S afet y Assess me nts  
Saf et y m o nit ori n g  for all  patie nts enr olle d  i n t he st u d y will i ncl u de  la b orat or y  safet y assess me nts  
(e. g., hae mat ol o g y, bl o o d c he mistr y, ur i nal ysis a n d c oa g ulati o n) an d cli nical eval uati o ns (e. g., 
p h ysical e xa mi nati o ns, vital si g ns, 1 2-l ea d electr ocar di o gra m [ EC G ], a n d m o nit ori n g of sec o n d 
pri mar y mali g na nc y [ S P M ] o cc urre nce)  as detaile d  in  the Sc h e d ule of  Assess me nts (Ta ble  5). 
All  A E s an d  S A Es  s h o ul d be rec or de d in t he eC R F. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 4  of 1 3 1  
L a b or at or y  a n d   A E t o xi citi es   will  b e  gr a d e d  a c c or di n g t o   N  CI-  C T  C  A E,  v ersi o n  4. 0 ( or  hi g h er). 
P ati e nts   w h o  e x p eri e n c e  a n y t o xi cit y s h o ul d  b e f oll o  w e d  u ntil t h e t o xi cit y  h as st a bilis e d, t h e 
t o xi cit y  h as r et ur n e d t o t h e  b as eli n e l e v el,  or  a  n e  w tr e at  m e nt  h as  c o  m  m e n c e d. 
S af et y   m o nit ori n g is  d et ail e d i n   S e cti o n 1 1 . 
 
1 0. 3. 1  Vit a l  Si g ns 
Vit al si g ns   will  b e   m e as ur e d  at t h e ti  m e  p oi nts  d es cri b e d i n t h e  S c h e d ul e  of   Ass ess  m e nts  
(T a bl e   5). If   m  A b  a n d   B E  N  ar e  b ei n g  a d  mi nist er e d  o n t h e s a  m e  d a y,  vit al si g ns s h o ul d  b e 
r e c or d e d i n  e  C  R F f or   m  A b i nf usi o n(s)  o nl y.  T h es e  ass ess  m e nts i n cl u d e  b o d y t e  m p er at ur e, 
s yst oli c  a n d  di ast oli c  bl o o d  pr ess ur e r e a di n gs (  m  m  H g),  h e art r at e ( b e ats  p er   mi n ut e [ b p  m]),  a n d 
r es pir at or y r at e (r es pir ati o ns  p er   mi n ut e [r p  m]).   Vit al si g ns   will  be   m e as ur e d  wit hi n  1 5 mi n ut es 
pri or t o i nf usi o n, 1 5  ±  5   mi n ut es  aft er t h e st art  of i nf usi o n,  a n d  3 0  ±  1 0   mi n ut es  aft er t h e st art  of 
i nf usi o n.   Aft er t h e  3 0-mi n ut e  ass ess  m e nt,  vit al si g ns  n e e d t o  b e   m e as ur e d o n c e  e v er y  3 0 t o 
6 0  ± 1 5   mi n ut es  d uri n g t h e i nf usi o n  a n d  at t h e  e n d  of i nf usi o n ( ±  2 0   mi n).  T h e  a ct ual ti  m e  of  vit al 
si g n   m e as ur e  m e nts s h o ul d  b e  a c c ur at el y  d o c u  m e nt e d. If t h e i nf usi o n is i nt err u pt e d  a n d/ or 
s u bs e q u e ntl y r est art e d,  vit al si g ns s h o ul d  b e  ass ess e d  e v er y  6 0  ±  1 5   mi n ut es  aft er t h e first  h o ur. 
D uri n g  visits   w h e n st u d y  dr u g i nf usi o ns  d o  n ot t a k e  pl a c e,  vit al si g ns  n e e d t o  b e   m e as ur e d  o nl y 
o n c e,  at  all  visits  a c c or di n g t o  T a bl e   5. 
 
F or t h e s af et y  of t h e  p ati e nt, i n t h e  c o urs e  of   C y cl e  1   D a y  1 (first   M  O  R 0 0 2 0 8 i nf usi o n)  a n d 
C y cl e  1   D a y  2 (first i nf usi o n  of   B E  N) t h e  p ati e nt   will st a y  at t h e st u d y sit e f or  a p pr o xi  m at el y 
2  h o urs  aft er t h e  e n d  of st u d y  dr u g  a d  mi nistr ati o n f or t h e   m o nit ori n g  of t h e  o c c urr e n c e  of  a c ut e 
t o xi citi es.  
 
T h e fr e q u e n c y  or  d ur ati o n  of   m o nit ori n g   m a y  b e  a d a pt e d as cli ni c all y i n di c at e d,  e. g., if i n t h e 
o pi ni o n  of t h e i n v esti g at or, t h e  vit al si g n r es ults  at t h e ti  m e  of  e v e nt  o ns et  ar e  cli ni c all y 
si g nifi c a nt. I n s u c h  a  c as e, t h e  p ati e nt’s  vit al si g n   m e as ur e  m e nts s h o ul d  c o nti n u e t o  b e r e c or d e d 
u ntil t h e y  h a v e r et ur n e d t o  n or  m al  or  pr e- i nf usi o n l e v els.  S u bs e q u e ntl y, a n   A E s h o ul d  b e 
r e c or d e d. If  p ossi bl e,  b ef or e  vit al si g ns  ar e   m e as ur e d, t h e  p ati e nt s h o ul d  b e r esti n g f or  at l e ast 
5 mi n ut es.  T h e s a  m e  p ositi o n s h o ul d  b e  us e d  e a c h ti  m e  vit al si g ns  ar e   m e as ur e d i n  a  gi v e n 
p ati e nt,  a n d  bl o o d  pr ess ur e s h o ul d  b e   m e as ur e d fr o  m t h e  ar  m  c o ntr al at e r al t o t h e sit e  of st u d y 
dr u g  a d  mi nistr ati o n.   B o d y t e  m p er at ur e s h o ul d  b e   m e as ur e d  a c c or di n g t o  n or  m al i nstit uti o n al 
pr a cti c e.  
 
1 0. 3. 2  P h ysi c al   E x a  mi n ati o n  
1 0. 3. 2. 1  F ull  P h ysi c al   E x a  mi n ati o ns  
A f ull  p h ysi c al  e x a  mi n ati o n ( P E)   will  b e  p erf or  m e d  b y t h e I n v esti g at or  or  a  q u al ifi e d  d esi g n e e 
d uri n g  S cr e e ni n g  a n d  at t h e  E  O T  v isit. 
 
F ull  P E   m ust  b e  p erf or  m e d  a c c or di n g t o t h e  b est st a n d ar ds  of l o c al   m e di c al  pr a cti c e ,  b ut s h o ul d 
i n cl u d e  at l e ast m e as ur e  m e nt  of  vit al si g ns,  p al p a bl e t u  m o ur  ass ess  m e nt  (if  a p pli c a bl e),  g e n er al 
a p p e ar a nc e, s ki n,  h e a d,  e y es,  e ars,  n os e, t hr o at i n cl u di n g   W al d e y er l y  m p h ati c str u ct ur es, l u n gs, 
br e asts  a n d  a xill a e,  c ar di o v as c ul ar s yst e  m,  b a c k  a n d s pi n e,  a b d o  m e n ,  e xtr e  miti es, l y  m p h  n o d es, 
a n d  n e ur ol o gi c al  e x a  mi n ati o n.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 7 5  of 1 3 1  
1 0. 3. 2. 2  Li  mit e d  P h ysi c al   E x a  mi n ati o ns  
Li mite d  P Es ma y be foc use d o n t u m o ur res p o nse assess me nt (l y m p h n o des, li ver, s plee n, etc.) 
a n d A Es at t he i n vesti gat or discreti o n. S uc h li mite d P Es will be  perf or me d as i n dicate d  i n the 
Sc he d ule of  Assess me nts  (Ta ble  5). D uri n g A nti b o d y M o n ot hera p y T reat me nt, a li mite d PE  will 
be pe rf or me d o n Da y 1 of C ycles 7, 1 0, 1 3, 1 6 etc. 
S y m pt o m- dri ve n f ull P Es m a y be pe rf or med as cli nically i n dicate d at an y st u d y visit. Si milarl y, 
t he in vesti gat or m a y e xte n d t he sc o pe of P E at an y visit if c o nsi der e d cli nicall y  rele va nt.  
1 0. 3. 2. 3  B o d y  M ass, Bo d y  Surf ace Are a  (B S A)  a nd  Hei g ht  Me asure me nts  
B o d y mass an d B S A w ill be us e d t o calc ulate t he d oses of M O R 0 0 2 0 8, a n d, R T X an d B E N, 
res pecti vel y.  
B o d y hei g ht w ill be meas ure d o n t he S cree ni n g visit o n l y. 
B o d y mass an d B S A w ill be m eas ure d at least d u ri n g t he S cree ni n g visit an d o n Da y 1 of eac h 
c ycle . T hese va ria bles sh o ul d be us e d to calc ulate t he st u d y dr u g d oses in t he co urse o f a gi ve n 
c ycle an d o n D a y 1 of the succee di n g c ycle, wit h t he exce pti o n of C 1 D 1. O n C 1 D 1, b o d y mass 
a n d B S A m eas ure d o n t hat da y will b e us e d t o calc ulate the d o ses of the st u d y dr u gs.  
B o d y  m ass a n d  BS A  meas ure me nt  ma y ta ke place pre - o r p os t- d ose, with t he exce pti o n of C 1 D 1 
w here t he y  nee d  to  be meas ure d  a nd  calc ulate d  pre - d ose. 
D uri n g t he c o urse of t his st u d y, th e M osteller’ s al g orit h m  s h o ul d be use d  for  BS A  calc ulati o ns 
(see A p pe n di x H). Pr o v i de d t he i nstit uti o nal sta n dar ds req uire  t he use o f a not her sta n dar d B SA 
for m ula , s p o ns or ap pr o v al ma y be o btai ne d  o n a case b y  case basis.  
1 0. 3. 3  B- S y m pt o ms  
T h e pr ot oc ol s pecific defi niti o n  of B-s y m pt o ms is base d o n t he C ots w ol ds Rec o m me n dati o ns 
(see A p pe n di x I). 
B -s y  m pt o  ms  ar e  d efi n e d as  a n y  o n e  or   m or e  of t h e f oll o  wi n g  dis e as e-r el at e d s y  m pt o  ms  or si g ns:
•
U ni nt e nti o n al   w ei g ht l oss  of ≥ 1 0  %   wit hi n t h e  pr e c e di n g  6   m o nt hs or l ess
•
Dr e n c hi n g  ni g ht s  w e ats   wit h o ut si g ns  of i nf e cti o n
•
R e c urr e nt,  u n e x pl ai n e d f e v er   wit h t e  m p er at ur es  a b o v e  3 8°  C   wit h o ut si g ns  of i nf e cti o n
A ss ess  m e nt  of t h e  pr es e n c e  or  a bs e n c e  of   B-s y  m pt o  ms   will  b e  p erf or  m e d  at  v ari o us ti  m e  p oi nts 
as i n di c at e d i n t h e  S c h e d ul e  of   Ass ess  m e nts (s e e  T a bl e   5). 
M e di c al  hist or y  of   B-s y  m pt o  ms s h o ul d  b e  d o c u  m e nt e d. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 6  of 1 3 1  
1 0. 3. 4  El e ct r o c a r di o g r a  m  
St a n d ar d  1 2- l e a d r esti n g  E  C  Gs s h o ul d  b e  o bt ai n e d  at t h e  v ari o us ti  m e  p oi nts  d es cri b e d i n t h e 
S c h e d ul e  of   Ass ess  m e nts (T a bl e   5). If  p ossi bl e, E  C  Gs s h o ul d b e r e c or d e d  aft er t h e  p ati e nt  h as 
r est e d i n  a s u pi n e  p ositi o n f or  at l e ast  5 mi n ut es. H e art r at e  a n d  P  R,   Q  R S ,   R  R  a n d   Q T i nt er v als 
s h o ul d  b e  d et er  mi n e d.   All  E  C  Gs s h o ul d  b e  p erf or  m e d  a n d i nt er pr et e d l o c all y. T h e i n v esti g at or 
s h o ul d e v al u at e t h e  cli ni c al si g nifi c a n c e  of  e a c h  v al u e  o utsi d e t h e r ef er e n c e r a n g es  a c c or di n g t o 
t h e  n at ur e  a n d  d e gr e e  of t h e  o bs er v e d  a b n or  m alit y.   A n y  n e  w  a b n or  m al  v al u es  c o nsi d er e d t o  b e 
cli ni c all y si g nifi c a nt s h o ul d  b e r e p ort e d  as   A Es.  
 
If  cli ni c all y si g nifi c a nt  a b n or  m aliti es  ar e  o bs er v e d  or  art ef a cts  ar e  pr es e nt t h at r es ult i n  a n 
i n a bilit y t o  a d e q u at el y i nt er pr et t h e r es ults, t h e  E  C  G s h o ul d b e r e p e at e d.   A n  a v er a g e  of  all 
i nt er v als   m e as ur e d i n  all  E  C  G tr a ci n gs r e c or d e d  at  a  gi v e n ti  m e  p oi nt   m a y  b e t a k e n if  n e c ess ar y. 
 
1 0. 3. 5  A d v e rs e   E v e nt   M o nit o ri n g  
A Es s h o ul d b e  ass ess e d  at  e a c h  visit  a n d r e p ort e d  as s p e cifi e d i n   S e cti o n 1 1 .  For s cr e e ni n g 
f ail ur e  p ati e nts,  o nly  S  A Es s h o ul d  b e r e c or d e d i n t h e  e  C  R F. 
 
1 0. 3. 6  M o nit o ri n g  of  S e c o n d  P ri  m a r y   M ali g n a n ci es 
S P  Ms   will  b e   m o nit or e d  as  e v e nts  of  s p e ci al i nt er est  a n d s h o ul d  b e i n cl u d e d  as  p art  of t h e 
ass ess  m e nt  of   A Es t hr o u g h o ut t h e  c o urs e  of t h e st u d y. I n v esti g at ors  ar e t o r e p ort  a n y  S P  Ms  as 
A d v ers e  E v e nts  of  S p e ci al I nt er est  (  A E SIs), r e g ar dl ess  of  c a us al r el ati o ns hi p t o t h e st u d y  dr u gs, 
o c c urri n g  at  a n y ti  m e, f or t h e  d ur ati o n  of t h e st u d y, fr o  m   C y cl e  1,   D a y  1  u p t o  a n d i n cl u di n g t h e 
F oll o  w- U p f or  P F S.  E v e nts  of  S P  M  ar e t o  b e r e p ort e d  usi n g t h e  S  A E r e p ort f or  m  a n d   m ust  b e 
c o nsi d er e d  a n i  m p ort a nt   m e di c al  e v e nt  e v e n if  n o  ot h er s eri o us  crit eri a  a p pl y; t h es e  e v e nts   m ust 
als o  b e  d o c u  m e nt e d i n t h e  a p pr o pri at e  p a g e(s)  of t h e  e  C  R F  a n d t h e  p ati e nt’s s o ur c e  d o c u  m e nts. 
 
D o c u  m e nt ati o n  c o n c er ni n g t h e  di a g n osis  of t h e  S P  M   m ust  b e  pr o vi d e d  at t h e ti m e  of r e p orti n g  as 
a n  S  A E ( e. g.,  a n y  c o nfir  m at or y  hist ol o g y  or  c yt ol o g y r es ults,   X- r a ys,   C T s c a ns). 
 
1 0. 3. 7  L a b o r at o r y   Ass ess  m e nts  
D et ail e d i nstr u cti o ns  a n d  a  m o u nts  of  bi ol o gi c al s a  m pl es  n e e d e d f or t h e r es p e cti v e l a b or at or y 
m e as ur e  m e nts   will  b e s u  m  m aris e d i n t h e l a b or at or y   m a n u al.   All s a  m pl es   will  b e  c oll e ct e d  as 
n o n- f asti n g s a  m pl es. 
 
1 0. 3. 7. 1  L a b o r at o r y   T esti n g 
Cli ni c al l a b or at or y p ar a  m et ers   m e as ur e d i n t h e  c o urs e  of t h e st u d y  ar e list e d i n  T a bl e   6.  Lo c al 
a n d  c e ntr al l a b or at ori es   will  b e us e d t hr o u g h o ut t h e st u d y . 
 
C e ntr al l a b or at or y r es ults  ar e r e q uir e d f or  d et er  mi ni n g  p ati e nt  eli gi bilit y f or st u d y  e nr ol  m e nt   a n d 
will  b e  us e d i n t h e   a n al ysis  of t h e st u d y r es ults.   D uri n g t h e  c o urs e  of t h e st u d y,  all s c h e d ul e d 
c e ntr al l a b or at or y r es ults s h o ul d  b e r e vi e  w e d  as s o o n  as  p ossi bl e  aft er   D a y  1  of  e a c h  c y cl e.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 7 7  of 1 3 1  
Patie nts  m ust neit her be q ua lifie d f or stu d y e li gi bility n or ra nd o mise d base d o n t he res ults of t he 
l ocal la b orat or y  assess me nts.  
It is per mitte d  t o re pe at t wice the  ce ntr al la b or at or y assess me nt  of bl o o d  cell c o u nts,  li ver 
e nz y mes,  ser u m electr ol ytes co nce ntrati o n (s o di u m, p otassi u m, calci u m) a n d/ or ser u m cr eati ni ne  
or creati ni ne  cleara nce/ gl o mer ular  filtrati o n rate duri n g Scree ni n g d ue  t o t he varia bilit y of t he  
para meter s an d t heir de pe n de nce o n a mul tit u de of fact ors  (e. g. h y drati o n, m uscle mass). Tha t is, 
pr o vi de d n o safet y c o ncer ns arise an d t hat su c h la b orat or y res ults m i g ht h a ve be e n ca use d b y a 
tra nsie nt , me dicall y pl a usi ble eve nt , whic h res ol ve d s p o nta ne o usl y or as res ult of a me dical 
i nter ve ntio n in t he m ea nti me (e. g. deh y drati o n, v o miti n g, i ma gi n g pr oce d ure w it h a c o ntrast) , or 
tec h nical iss ues. T his pr oce d ure an d t he rati o nale be hi n d it m ust be ex plicitl y d oc u me nte d i n 
s o urce data. 
L ocal la b orat or y  res ults will be  us e d for treat me nt or cli nicall y  relate d de cisi o ns,  or f or t he 
i m me diate safet y n ee ds  of a st u d y patie nt. Local  la b orat or y res ults s h o ul d be re vie we d as so o n as 
p ossi ble  after t heir recei pt a n d  bef ore d osi n g  so  t hat t he  a d mi nistrati o n  of t he i n vesti gati o nal 
me dici nal p r o d uct m a y be adj uste d or interr u pte d if ne cessar y. L oc al la b or at or y  assess me nts 
m a y  be perf or me d  u p t o  2 4  h o urs bef ore a dmi nistr ati o n  of  st u d y dru gs  a nd m a y f all 
o utsi de  of t he pla n ne d visit  wi n d o w. 
In  or de r t o kee p  t he ex peri me ntal c o n diti o ns  as si milar as possi ble , irres pecti ve o f treat me nt 
all ocati o n, t he l ocal la b orat or y sa m ples will als o  be c ollecte d  f or the R T X + B E N  patie nts at  t he 
res pecti ve st u d y visits (see Ta ble 5), des pite t he fact th at t he y ma y n ot necessaril y recei ve st u d y 
dr u gs at  a gi ve n  visit. In  s uc h case t he restricti o n t hat sa m ples  nee d to  be c ollecte d a n d e val uate d 
i n t he l ocal la b orat or y a n d re vie wed b y st u d y treati n g p h ysicia n bef ore st u d y dr u g a d mi nistrati o n 
will n ot ap pl y. 
T he  si g ne d an d  i nterprete d  lab orat or y  res ults ( b ot h l ocal a n d  ce ntral) are  t o be ke pt in t he 
patie nt’s s o urce d oc u me ntati o n. T he la b orat or y res ults s h o ul d be re vie we d, date d a n d si g ne d in a 
ti mel y m a n ner b y  t he i n vesti gat or. A n y  cli nicall y si g nifica nt discre pa ncies bet wee n  local  a n d 
ce ntral  la b orat or y  res ults  will be e val uate d o n a case - b y-case basis.  All b l o o d sa m ples sh o ul d be 
pr ocesse d a n d ha n dle d acc or di n g to sta n dard la b orat or y pr oce d ures. T he ti me of bl o o d c ollecti o n 
s h o ul d be d o c u me nte d i n the eC R F. 
A n y  ab n or mal la b orat or y  fi n din gs  (i de ntifie d eit her t hr o u g h l ocal or ce ntral la b orat or y  anal ysis) 
t hat co nstit ute an A E sh o ul d be re p orte d as s uc h a n d s h o ul d be foll o we d u p u ntil t he o utc o me is 
k n o w n. Als o, a d diti o nal dia g n ostic tests ma y  be i n dicate d  to  deter mi ne  a m ore precise dia g n osis 
of t he  pa tie nt’s co n diti o n  (e. g., orderi n g a w hite b l o o d cell [W B C ] diff ere ntia l co u nt t o  hel p 
c haracterise a hi g h or l o w W B C co u nt, or or deri n g a de ter mi nati o n of re d bl o o d cell [R B C ] 
i n dices t o hel p characterise  a l o w ha e mat ocrit).  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 8  of 1 3 1  
T a bl e   6:     
L a b o r at o r y   E v al u ati o ns 
E v al u ati o n  
A n al ysis  
L o c al  l a b o r at o r y (E  D T  A 
bl o o d  a n d s er u  m s a  m pl e)  
S er u  m  cr e ati ni n e,  h a e  m o gl o bi n,   W  B  Cs, i n cl u di n g   W  B  C  diff er e nti al 1, 
pl at el ets, s o di u  m,  p ot assi u  m,   A S T,   A L T, t ot al  bilir u bi n  
H a e  m at ol o g y  
( E  D T  A  bl o o d) 
W  B  C   wit h  diff er e nti al  c o u nt,  h a e  m at o crit,  h a e  m o gl o bi n,   m e a n 
c or p us c ul ar  v ol u  m e,   m e a n  c or p us c ul ar  h a e  m o gl o bi n, m e a n 
c or p us c ul ar  h a e  m o gl o bi n  c o n c e ntr ati o n,  pl at el et  c o u nt,   R  B  C  c o u nt, 
l y  m p h o c yt es,   m o n o c yt es,  n e utr o p hils,  b a n d  n e utr o p hils,  e osi n o p hils, 
b as o p hils  
S cr e e ni n g: s h o ul d i n cl u d e  a  p eri p h er al  bl o o d s  m e ar 
B a n d  n e utr o p hils  ar e  o nl y r e p ort e d   w h e n  a   m a n u al  diff er e nti al  c o u nt 
p erf or  m e d  a n d  b a n ds  ar e  pr es e nt  
S e r u  m  c h e  mist r y  
(s er u  m s a  m pl e) 
A L T, t ot al  al b u  mi n,  al k ali n e  p h os p h at as e,  a  m yl as e,   A S T,  bi c ar b o n at e, 
bilir u bi n (t ot al),  ur e a, t ot al  c al ci u  m,  c hl ori d e,  cr e ati ni n e,  cr e ati ni n e 
ki n as e, g a  m  m a -gl ut a  m yltr a nsf er as e ( G  G T ),  gl u c os e, l a ct at e 
d e h y dr o g e n as e ( L  D  H ), li p as e,  p h os p h at e,  p ot assi u  m,  pr ot ei n (t ot al), 
s o di u  m,  uri c  a ci d,  β 2-mi cr o gl o b uli n,   C -r e a cti v e  pr ot ei n 
C o a g ul ati o n  p a r a  m et e rs  
(s o di u  m  citr at e  bl o o d) 
A cti v at e d  p arti al t hr o  m b o pl asti n ti  m e,  pr ot hr o  m bi n ti  m e, i nt er n ati o n al 
n or  m alis ati o n r ati o  
I g  c o n c e nt r ati o ns 
(s er u  m s a  m pl e) 
I g  c o n c e ntr ati o ns (I g  G, I g  M, I g  A) 
S e r ol o g y  p a r a  m et e rs  
(s er u  m s a  m pl e) 
H e p atitis   B:   H  Bs  A g,  a nti -H  B c  a n d   H  Bs A b s.   H  B  V D  N  A if  a nti -H  B c 
p ositi v e,  o pti o n al   
H e p atitis   C:   H  C  V  a nti b o d y (  H  C  V   R  N  A  q u a ntifi c ati o n if  a nti -H  C  V  
p ositi v e)  
P r e g n a n c y t est  
(s er u  m or  uri n e s a  m pl es) 
 
β -H  C  G s er u  m  or  uri n e , f e  m al es  of  c hil d b e ari n g  p ot e nti al  o nl y. 
S er u  m s a  m pl es t est e d i n  c e ntr al l a b or at or y  a n d  uri n e s a  m pl es t est e d 
l o c all y 
U ri n al ysis  
A p p e ar a n c e,  c ol o ur,  uri n e  bilir u bi n,  gl u c os e, h a e  m o gl o bi n,  k et o n es, 
p  H,  pr ot ei n, s p e cifi c  gr a vit y,  ur o bili n o g e n .  
Mi cr os c o p y   will  o nl y  b e  p erf or  m e d if  cli ni c all y i n di c at e d . 
G e n ot y pi n g * 
(m u c os al  c h e e k s  w a b, 
o pti o n al)  
F c γ  RII a  a n d  F c γ  RIII a  p ol y  m or p his  m  
I  m  m u n o g e ni cit y 
(s er u  m s a  m pl e) 
 
A nti -M  O  R 0 0 2 0 8  a nti b o di es  
P  K 
(s er u  m s a  m pl e) 
 
M  O  R 0 0 2 0 8  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 7 9  of 1 3 1  
*   M a y  b e  p erf or  m e d  at  a n ot h er ti  m e  p oi nt t h a n   C 1 D 1 if it   w as i n a d v ert entl y    miss e d. 
A b br e vi ati o ns:   A  D  C  C   = a nti b o d y-d e p e n d e nt  c ell -m e di at e d  c yt ot o xi cit y;   A L T   = al a ni n e tr a ns a  mi n as e; a nti-H  B c   = 
h e p atitis   B  c or e  a nti b o d y; a nti-H  C  V  = h e p atitis   C  vir us  a nti b o d y; A S T   = as p art at e a  mi n otr a nsf er as e;  β -H  C  G   = 
b et a -h u  m a n  c h ori o ni c  g o n a d otr o pi n; E  D T  A   = et h yl e n e di a  mi n et etr a a c eti c  a ci d; G  G T   = g a  m  m a -gl ut a  m yltr a nsf er as e; 
H  Bs A b   = h e p atitis   B s urf a c e  a nti b o d y;   H B s  A g  = h e p atitis   B s urf a c e  a nti g e n;  H  B  V   = h e p atitis   B  vir us;  I g  = 
i  m  m u n o gl o b uli n; L D  H   = l a ct at e  d e h y dr o g e n as e;   N  K  = n at ur al  kill er;  P  B  M  Cs  =  p eri p h er al  bl o o d   m o n o n u cl e ar  c ells; 
P  K   = p h ar  m a c o ki n eti cs; R  B  C   = r e d  bl o o d  c ell;   W  B  C  = w hit e  bl o o d  c ells.  
1W  B  C  diff er e nti al  c a n  b e  a ut o  m at e d  or   m a n u al  as  p er i nstit uti o n al st a n d ar ds. R eti c ul o c yt es  (t est e d l o c all y) m a y  b e 
d et er  mi n e d  o nl y   w h e n  cli ni c all y i n di c at e d.  
 
D u e t o t h e  e x pl or at or y  n at ur e  of s o  m e  ass a ys, t h e s p o ns or   m a y  d e ci d e  at  a n y  p oi nt  d uri n g t h e 
st u d y t o t er  mi n at e t h es e  ass ess  m e nts, i n   w hi c h  c as e t h e sit es   will  b e i nf or  m e d  a c c or di n gl y.  
 
1 0. 3. 7. 2  H e p atitis Vi r us  S e r ol o g y  
P ati e nts    will  b e  e x a  mi n e d  a c c or di n g t o t h e s c h e d ul e i n T a bl e   5 f or  vir al  h e p atitis   B  a n d   C 
s er ol o g y. H e p atitis   B  bi o  m ar k ers i n cl u d e   H Bs  A g,  a nti-  H  B c  a n d   H  Bs  A b . P ati e nts   wit h  a  p ositi v e 
t est f or h e p atitis    B  vir us  c or e  a nti b o d y (a nti-H  B c ) c a n  o nl y  b e i n cl u d e d if   H B  V -D  N  A is  n ot 
d et e ct e d. I n t h es e  p ati e nts,   H  B  V -D  N  A s h o ul d  b e  ass ess e d  as  o utli n e d i n  T a bl e   5. 
 
I n t h e  c o nt e xt  of t h e  e x cl usi o n  crit eri a, s er o p ositi v e f or  or a cti v e  vir al i nf e cti o n   wit h   H  B  V  
m e a ns : 
a) H  Bs  A g   p ositi v e 
b)  H  Bs A g  n e g ati v e,  a nti- H  B c  p ositi v e  a n d  d et e ct a bl e  vir al   D  N  A  (r e g ar dl ess  of   H  Bs  A b 
st at us). 
 
P ati e nts   w h o  e x hi bit t h e  cl assi c al  v a c ci n ati o n  pr ofil e  of   H  Bs A b  p ositi v e,  a nti- H  B c  n e g ati v e  a n d 
H  Bs A g  n e g ati v e  a r e  eli gi bl e. 
 
If   H  B  V   D  N  A  b e c o  m es  d et e ct a bl e  d uri n g tr e at  m e nt,  p ati e nts s h o ul d  b e  pr o p h yl a cti c all y tr e at e d 
a n d f oll o  w e d- u p f or  p ot e nti al  h e p atitis   B r e a cti v ati o n  as  p er l o c al   m e di c al  pr a cti c e  or 
i nstit uti o n al  g ui d eli n es f or   C  D 2 0  a nti b o di es s u c h  as   R T  X. If th e   H  B  V  D  N  A  ass a y is  p ositi v e, 
t h e n  p ati e nts  c a n  o nl y st a y i n t h e st u d y if t h e y  ar e  ass ess e d  b y  a  p h ysi ci a n  e x p eri e n c e d i n t h e 
E v al u ati o n  
A n al ysis  
B- /  T-/  N  K  c ell  c o u nti n g 
( h e p ari nis e d bl o o d  a n d E  D T  A 
bl o o d )  
C ell  c o u nts  vi a fl o  w  c yt o  m etr y  
C  D 1 6  e x p r essi o n  o n 
p e ri p h e r al   N  K  c ells  
( h e p ari nis e d  bl o o d)  
C  D 1 6   m ol e c ul es  e x pr ess e d  p er  c ell (  C  D 1 6  a nti b o di es  b o u n d  p er  c ell)  
vi a fl o  w  c yt o  m etr y  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 8 0  of 1 3 1  
treat me nt o f he patitis  B an d  pre-em pti v e treat me nt is i nitiate d, if dee me d ap p r opr iate, an d/ or 
acc or di n g  t o l ocal practice/ g ui deli nes. 
He patitis C ser ol o g y is t o be d o ne at Sc ree ni n g onl y.  He patitis  C bi o mar kers i ncl u d e he patitis  C 
vir us a nti b o d y (a nti- H C V).  For patie nts  w h o  are positi ve  f or a nti- HC V,  H C V R N A s h o ul d be 
meas ure d. 
A p ositi ve he p atitis C  test is defi ne d  as a p o siti ve test f or a nti- HC V  a n d a p ositi ve  test f or H C V 
R N A.  T h us, p atie nts wit h  po siti ve ser ol og y  but  ne gati ve H C V  RN A  test res ults are eli gi ble. 
1 0. 3. 7. 3  Pre g n a nc y  Test i n g 
F or  an F C B P , a pre g na nc y  test will be  perf or me d  at vari o us pre - a n d p ost-treat me nt ti me poi nts 
eit her  b y a uri ne pre g na nc y test or a beta-h u ma n c h ori o nic g o na d otr o pi n ( β - HC G)  test of a  ser u m 
sa m ple (see Ta ble 6). The pre g na nc y test assa y s h o ul d ha ve a mi ni m u m se nsiti vit y of 2 5 I U/ m L. 
At  Scree ni n g a n d t he E O T  visit, a β- HC G ser u m pre g na nc y test s h o ul d be perf or me d f or a n 
F C B P. 
A n F C B P  m ust ha ve t w o ne gati ve pre g na nc y tests pri or t o starti n g t he st u d y dr u g ad mi nistr ati o n. 
T he first pre g na nc y test m ust be perf or me d d uri n g Scree ni n g a n d t he sec o n d pre g na nc y test m ust 
be perf or me d o n C ycle 1 Da y 1 pri or t o t he start of st u d y dr u g. T he patie n t m ust n ot recei ve st u d y 
dr u g u ntil t he st u d y d oct or has verifie d t hat t he res ults of t hese pre g na nc y tests are ne gati ve. 
S u bse q ue nt pre g na nc y tests will be c o n d ucte d as i n dicate d i n t he Sc he d ule of Assess me nts,   
Ta ble  5. 
1 0. 3. 7. 4  P K  Assess me nts 
C o nce ntrati o n-t i me pr ofiles a n d  PK  para meter s will  be assesse d  fo r M O R 0 0 2 0 8 acc or di n g t o t he 
sc he d ule i n Ta ble  5. P K s a m ples w ill not be  collecte d  fr o m patie nts treate d wit h RT X  a n d 
c o nce ntrati o n -ti me pr ofiles or PK  p ara meters will  n ot b e assesse d  for  BE N  or R T X.  P K  sa mple 
c ollecti o n s hall be st o p pe d after C ycle 2 3. 
Ser u m sa m ples f or P K a nal ysis of M O R 0 0 2 0 8 will be ha n dle d a n d st ore d as s pecifie d  in  the 
la borat or y  ma n ual at t he st u d y site u ntil s hi p me nt o n dr y ice t o a n e xter nal a nal ytical la b orat or y. 
At eac h sa m pli n g ti me p oi nt, t he o btai ne d ser u m sa m ple s h o ul d be s plit i nt o tw o  ali q u ots ( o ne 
pri mar y a n d o ne b ac k - up  sa mple). 
1 0. 3. 7. 5  I mm u n o ge nicit y 
Ser u m sa m ples  f or a nti- M O R 0 0 2 0 8 a nti b o d y a nal ysis will be c ollecte d acc or di n g t o t he sc he d ule 
i n Ta ble 5. Anti- dr u g a nti b o d y sa m ples will n o t b e collecte d  fr om patie nts  treate d  wit h R T X. 
Ser u m sa m ple  c ollecti o n  f or a nti- M O R 0 0 2 0 8 a nti b o d y a nal ysis s hall be st o p pe d  after C ycle 2 3. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 1  of 1 3 1  
S er u  m s a  m pl es f or  a nti -  M  O  R 0 0 2 0 8  a nti b o d y  a n al ysis   will  b e  h a n dl e d  a n d st or e d  as s p e cifi e d i n 
t h e l a b or at or y   m a n u al  at t h e st u d y sit e  u ntil s hi p  m e nt  o n  dr y i c e t o  a n  e xt er n al  a n al yti c al 
l a b or at or y.   At  e a c h s a  m pli n g ti  m e  p oi nt, t h e  o bt ai n e d s er u  m s a  m pl e s h o ul d  b e s plit i nt o t hr e e 
ali q u ots ( o n e  pri  m ar y  a n d  t  w o b a c k - u p s a  m pl es). 
 
1 0. 3. 8  Effi c a c y   Ass ess  m e nts  
T h e  pri  m ar y effi c a c y e n d p oi nt a n al ysis   will  b e e v al u at e d t hr o u g h c e ntr al r e vi e  w  b y a n 
I n d e p e n d e nt   R a di ol o g y/  Cli ni c al   R e vi e  w   C o  m  mitt e e (I  R  C) t h at   will  a p pl y   C h es o n  crit eri a (s e e 
A p p e n di x L ). T h e r e vi e  w pr o c ess will  b e  d efi n e d i n t h e I  R  C   C h art er.  
 
Effi c a c y   will  b e  e v al u at e d i n t er  ms  of  P F S  ( pri  m ar y  e n d p oi nt), b est O  R  R,   D  C R,   D o  R,   O S,  T T P 
a n d  T T  N T  (s e c o n d ar y  e n d p oi nts).  F or  d efi niti o ns, s e e  S e cti o n 1 3. 4 . 
 
L o c al  ass ess  m e nt  of  effi c a c y r es p o ns e (  C h es o n  crit eri a) will  b e r e q uir e d i n  a d diti o n t o  c e ntr al 
r e vi e  w  at t h e  b e gi n ni n g  of   C y cl e  3,   C y cl e  5  a n d  at t h e  E  O T  visit t o  d et er  mi n e   w h et h er t h e 
dis e as e  h as  pr o gr ess e d.  L o c al  effi c a c y  ass ess  m e nt   will  als o  b e  p erf or  m e d  at t h e  e n d  of   C y cl e  6 
f or t h e  d e cisi o n   w h et h er tr e at  m e nt   will  c o nti n u e  as   A nti b o d y   M o n ot h er a p y  Tr e at  m e nt fr o  m 
C y cl es  7 o n  w ar ds. Dis e as e r es p o ns e  ass ess  m e nt  as i n di c at e d i n  T a bl e   5 m a y  als o i n cl u d e 
st a n d ar d  of  c ar e  pr o c e d ur es t o  d et er  mi n e t h e  dis e as e st at us  p er   C h es o n  crit eri a ( e. g.  c o nfir  m at or y 
bi o ps y, l u  m b ar  p u n ct ur e,  et c f or  P  D) .   D at a fr o  m t h es e  pr o c e d ur es is  c oll e ct e d  a n d pr o vi d e d t o t h e 
I  R  C  as  d efi n e d i n t h e I  R  C   C h art er. 
 
1 0. 3. 8. 1  T u  m o u r I  m a gi n g  
D uri n g t h e  c o urs e  of t h e st u d y, dis e as e  a n d r es p o ns e  ass ess  m e nts  as   w ell  as t u  m o ur 
m e as ur e  m e nts   will  b e  p erf or  m e d.  
 
I niti al  dis e as e  a n d  dis e as e r es p o ns e  ass ess  m e nts will  b e   m a d e  b y p ositr o n  e  missi o n t o  m o gr a p h y 
(P E T )  a n d c o  m p ut e d t o  m o gr a p h y ( C T ) at S cr e e ni n g  a n d   D a y  2 8 ( ± 4  d a ys)  of   C y cl e  6  a n d  at t h e 
E  O T v isit, i n t h e  c as es   w h er e  a  p ati e nt is   wit h dr a  w n fr o  m tr e at  m e nt  b ef or e t h e  e n d  of   C y cl e  6 f or 
r e as o ns  ot h er t h a n  pr o gr essi v e  dis e as e. 
 
T h e   C T  p orti o n  of  a  c o  m bi n e d [ 1 8F]fl u or o d e o x y gl u c os e ( F  D  G )-P E T/  C T s c a n s h o ul d  b e 
p erf or  m e d   wit h  c o ntr ast  a n d  c oll e ct e d   wit h r es ol uti o n s uffi ci e nt t o  all o  w  a c c ur at e  a n d  c o nsist e nt 
c o  m p aris o n  of t ar g et l esi o n   m e as ur e  m e nts   wit h s u bs e q u e nt   C T s c a ns.  
 
T u  m o ur   m e as ur e  m e nts  a n d  dis e as e r es p o ns e  ass ess  m e nt  will als o  b e  p erf or  m e d  as i n di c at e d i n 
T a bl e   5 b y   C T  wit h  c o ntr ast . 
 
M a g n eti c r es o n a n c e i  m a gi n g (  M  RI)   m a y  b e  us e d i n li e u  of   C T,  a n d P E T/  M  RI i n li e u  of  P E T/  C T 
f or  p ati e nts   wit h  c o ntr ai n di c ati o ns t o t h e  a d  mi nistr ati o n  of  c o ntr ast  a g e nts,  or  d u e t o  ot h er 
m e di c al r e as o ns,  at t h e s a  m e ti  m e  p oi nts  as   C T,  or i n  a d diti o n t o   C T,  at t h e  dis cr eti o n  of t h e 
i n v esti g at or (i n t his  c as e,   M  RI   m a y  b e  p erf or  m e d  as/  w h e n  a p pr o pri ate).  T h e   m et h o d  us e d  at 
b as eli n e s h o ul d  b e  us e d t hr o u g h o ut t h e st u d y  u nl ess  ot h er  wis e   m e di c all y i n di c at e d. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 8 2  of 1 3 1  
If a vaila ble a n d of  acce pta ble q ualit y  (e. g., CT  p orti o n of P E T/ C T sca n  was perfor me d  wit h  
c o ntrast) , pre vi o usl y perf or me d PE T/ C T  exa mi nati o ns,  i n acc or da nce w it h t he sta n dar d of care, 
t hat w ere d o ne u p t o 4  wee ks pr i or t o Scree ni n g ma y  be use d for  a patie nt’s baseli ne  ce ntral  
ra di ol o g y assess me nt. A d diti o nal P E T/ C T  or C T/ M RI exa mi nati o ns ma y be pe rf or med b y t he 
i n vesti gat or d uri n g t h e co ur se of the st u d y, if d ee me d necessar y (e. g., t o c o nfir m the o cc urre nce 
of  a C R or  di sease pr o gressi o n or t o ma ke  i m p orta nt treat me nt-relate d decisi o ns).   
If t he p atie nt di sc o nti n ues fr o m treat me nt, a PE T/ C T  sca n  is o nl y  req uire d  at t he E O T  vi sit if 
s uc h sca n was n ot pe rf or me d in t he cycle pr i or t o the en d of treat me nt. C T m a y be pe rf or med i n 
lie u o f P E T/ C T if t he pa tie nt disc o nti n ues fr om treat me nt wit hi n  Cycle  1. 
T he sa me sca n  mo dalit y  s h o ul d be use d for  all assess me nts, a nd  all patie nts are re q uire d  t o have  
sca ns of the ne c k/c hest/a b d o me n/ pel vis. 
If it is i m p ossi ble f or t he patie nt t o  have  t heir P E T exa mi nati o n  i n faste d state, ade q uate  
pr oce d ures sh o ul d be in place t o meas ure an d c o ntr ol b l o o d gl uc ose le vel. 
I n a d diti o n t o t he Inter nati o nal W or ki n g Gr o u p 2 0 0 7 ( C hes o n et al. 2 0 0 7) e val uati o n 
c o m p o ne nts,  radi ol o gists  f ulfilli n g t he r oles of ce ntral re vie wers will rec ord  t he classificati o n of 
P E T/ C T  sca ns acc or di n g to  the 5 -p oi nt scale  q ualitati ve rati n g an d  meas ure me nt of t he  vertical 
le n gt h of the splee n. T hese as pects of the L u ga n o  Classificati o n ( C hes o n et al. 2 0 1 4) are n ot a 
dir ect c o m p o ne nt of  t he I nter nati o nal W or ki n g Gr o u p 2 0 0 7 re vie w an d are inte n de d as 
s u p ple me ntal i nf or mati o n o nly.  
1 0. 3. 9  B o ne M arr o w  
At t he Scree ni n g visit, a u ni- or  bilateral b o ne marr o w bio ps y a n d a s pirate s h o ul d be o btai ne d t o 
assess b o ne marr o w i n v ol ve me nt. Res ults fr o m a b o ne marr o w e xa mi nati o n d o ne u p t o 4 w ee ks 
pri or t o Scree ni n g a re acce pta ble pro vi de d t he patie nt’s disease has bee n sta ble si nce t he n . 
T he ac hie ve me nt  of C R  in  the c o urse  of M O R 2 0 8 C 2 0 4 st u d y m ust be c o nfir me d l ocall y, b y 
cli nical a n d ra di ol o gic eval uati o n al o n g wit h b o ne m arr o w co nfir mati o n.  The latter  a p plies o n l y 
i n case t he b o ne m arr o w w as in v ol ve d b y l y m p h o ma be f ore the ra n d o misati o n. If b o ne m arr o w 
was n ot in v ol ve d b y l y m p h o ma be f ore co m me nci n g t he st u d y treat me nt, t he n b o ne m arr o w 
c o nfir mati o n bi o ps y a n d as piratio n is n ot re q uire d. T he re peate d b o ne m arr o w exa mi nati o n is 
als o  n ot  re q uire d f or patie nts i n wh o m b o ne  ma rr o w ha s alrea d y bee n cleare d of  t he i nfiltrate at 
pre vi o us eval uati o n, i.e . t heir pr e vi o us b o ne m arr o w res p o nse was C R.  
Hist o l o gical exa mi nati o n  of t he bo ne  marr o w bi o ps y a n d as pirate s h o ul d be perf or me d l ocall y 
at t he pr ot o c ol s pecifie d time  p oi nts  (see Ta ble  5 ). 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 3  of 1 3 1  
1 1  S  A F  E  T  Y   M  O  NI  T  O  RI  N  G  
T h e  p ati e nts   will  b e  cl os el y  o bs er v e d  a n d  q u esti o n e d f or  a n y  ki n d  of   A E  d uri n g t h e st u d y 
pr o c e d ur es  a n d  at f oll o  w -u p  a p p oi nt  m e nts t hr o u g h o ut t h e st u d y  p eri o d   wit h  n o n -l e a di n g 
q u esti o ni n g ( e. g. , “  H o  w  d o  y o u f e el ? ”).   A Es  als o   m a y  b e  d et e ct e d   w h e n t h e y  ar e  v ol u nt e er e d  b y 
t h e  p ati e nt  d uri n g  or  b et  w e e n st u d y  visits  or t hr o u g h  p h ysi c al  e x a  mi n ati o n, l a b or at or y t ests,  or 
ot h er  ass ess  m e nts.  
 
St u d y  p ers o n n el   m ust r e  m ai n  vi gil a nt f or t h e  o c c urr e n c e  of   A Es,  p arti c ul arl y t h os e t h at   m a y  b e 
lif e-t hr e at e ni n g.  P ers o n n el   w h o  ar e tr ai n e d i n t h e  a c ut e   m a n a g e  m e nt  of I  R  Rs,  c yt o ki n e r el e as e 
s y n dr o  m e,  a n a p h yl a xis,  a n d  ot h er  e  m er g e n ci es,  a n d   w h o  h a v e  a c c ess t o  a p pr o pri at e  cli ni c al 
s u p pli es, s h o ul d  b e r e a dil y  a v ail a bl e. 
 
All   A Es s h o ul d  b e tr e at e d  a p pr o pri at el y.  S u c h tr e at  m e nt   m a y i n cl u d e  c h a n g es i n st u d y  dr u g 
tr e at  m e nt i n cl u di n g  p ossi bl e i nt err u pti o n  or  dis c o nti n u ati o n, st arti n g  or st o p pi n g  c o n c o  mit a nt 
tr e at  m e nts,  c h a n g es i n t h e fr e q u e n c y  or  n at ur e  of  ass ess  m e nts,  h os pit alis ati o n,  or  a n y  ot h er 
m e di c all y r e q uir e d i nt er v e nti o n.   O n c e  a n   A E is  d et e ct e d, it s h o ul d  b e f oll o  w e d  u p,  a n d  a n 
ass ess  m e nt s h o ul d  b e   m a d e  at  e a c h  visit ( or   m or e fr e q u e ntl y, if  n e c ess ar y)  of  a n y  c h a n g es i n its 
s e v erit y, its s eri o us n ess, its s us p e ct e d r el ati o ns hi p t o t h e st u d y  dr u g(s),  a n y  of t h e i nt er v e nti o ns 
r e q uir e d t o tr e at it,  a n d its  o ut c o  m e.  
 
1 1. 1  D efi niti o n  of   A d v e rs e   E v e nts,  S e ri o us   A d v e rs e  E v e nts,  A d v e rs e  E v e nts  of  
S p e ci a l Int e r est  
A n   A E is  d efi n e d  as  a n y  u nt o  w ar d   m e di c al  o c c urr e n c e i n  a  p ati e nt  a d  mi ni st er e d  a   m e di ci n al 
pr o d u ct,   w hi c h  d o es  n ot  n e c ess aril y  h a v e  a  c a us al r el ati o ns hi p t o t his tr e at  m e nt.  
 
A n   A E  c a n t h er ef or e  b e  a n y  u nf a v o ur a bl e  a n d  u ni nt e n d e d si g n (i n cl u di n g  a n  a b n or  m al l a b or at or y 
fi n di n g), s y  m pt o  m,  or  dis e as e t e  m p or all y  ass o ci at e d   wit h t h e us e  of  a st u d y  dr u g,   w h et h er  or  n ot 
it is  c o nsi d er e d r el at e d t o t h at st u d y  dr u g. 
 
A Es i n cl u d e  a n y  cli ni c all y si g nifi c a nt  d et eri or ati o n  of  a  p ati e nt’s   m e di c al st at us  aft er t h e si g ni n g 
of t h e I  C F.   Als o,  a n i n cr e as e i n t h e fr e q u e n c y  or i nt e nsit y  of  a  pr e -e xisti n g  e pis o di c  e v e nt  or 
c o n diti o ns  a n d  e v e nts r es ulti n g fr o  m  pr ot o c ol   m a n d at e d  pr o c e d ur es ( e. g. i n v asi v e  pr o c e d ur es) 
f all  u n d er t h e  d efi niti o n  of   A Es. I n  a d diti o n,  o v er d os es ( d efi n e d  as  e x c e e di n g t h e  pl a n n e d  d os e 
b y > 2 0 %) s h o ul d  b e r e c or d e d  as   A Es.  
 
As f ar  as  p ossi bl e,  e a c h   A E s h o ul d  b e  e v al u at e d t o  d et er  mi n e t h e f oll o  wi n g:  
•  R el ati o ns hi p t o t h e st u d y  dr u g (s us p e ct e d/ n ot s us p e ct e d)  
•  D ur ati o n (st art  a n d  e n d  d at e , or if  c o nti n ui n g  at  e n d  of st u d y)  
•  Int e nsit y: t h e i nt e nsit y  of  all   A Es   will  b e  gr a d e d  as   mil d,   m o d er at e,  or s e v er e  usi n g t h e 
f oll o  wi n g  d efi niti o ns: 
o  mil d:  
 t ol er a bl e 
o  m o d er at e:  
i nt erf er es   wit h  n or  m al  a cti vit y 
o  s e v er e:  
 i n c a p a cit ati n g ( c a us es i n a bilit y t o  p erf or  m  us u al  a cti viti es  or w or k)  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 4  of 1 3 1  
•  S e v erit y i. e. t o xi cit y  gr a d e:  d et er  mi n e d  a c c or di n g t o t h e   N  CI-C T  C  A E  v ersi o n  4. 0  of 
M a y  2 8,  2 0 0 9,  usi n g t h e f oll o  wi n g  d efi niti o ns:  
o  gr a d e  1:   mil d;  as y  m pt o  m ati c  or   mil d s y  m pt o  ms;  cli ni c al  or  di a g n osti c  
 
 o bs er v ati o ns  o nl y; i nt er v e nti o n  n ot i n di c at e d  
o  gr a d e  2:  m o d er at e;   mi ni  m al, l o c al  or n o n -i n v asi v e i nt er v e nti o n i n di c ate d;   
 li  miti n g  a g e-a p pr o pri at e i nstr u  m e nt al  a cti viti es  of  d ail y li vi n g  
 
 (r ef ers t o  pr e p ari n g   m e als, s h o p pi n g f or  gr o c eri es  or  cl ot h es,  
 
 usi n g t h e t el e p h o n e,   m a n a gi n g   m o n e y,  et c.)  
gr a d e  3:  s e v er e  or   m e di c all y si g nifi c a nt  b ut  n ot i  m  m e di at el y lif e-t hr e ate ni n g; 
h os pit alis ati o n  or  pr ol o n g ati o n  of  h os pit alis ati o n i n di c at e d;  dis a bli n g; li  miti n g 
s elf-c ar e  a cti viti es  of  d ail y li vi n g  
o  gr a d e  4:  lif e-t hr e at e ni n g  c o ns e q u e n c es;  ur g e nt i nt er v e nti o n i n di c at e d 
o  gr a d e  5:  d e at h r el at e d t o   A E  
•  O ut c o  m e  
•  A cti o n t a k e n ( n o  a cti o n t a k e n; st u d y  dr u g t e  m p or aril y i nt err u pt e d; st u d y  dr u g 
p er  m a n e ntl y  dis c o nti n u e d  d u e t o t his   A E;  c o n c o  mit a nt   m e di c ati o n t a k e n;  n o n -dr u g 
t h er a p y  gi v e n;  h os pit alis ati o n/ pr ol o n g e d  h os pit alis ati o n) 
•  S eri o us n ess:   w h et h er it is s eri o us,   w h er e  a  S  A E is  d efi n e d  as o n e t h at:  
o  r es ults i n  d e at h 
o  is lif e-t hr e at e ni n g 
o  r e q uir es i n-p ati e nt  h os pit alis ati o n  or  pr ol o n g ati o n  of  e xisti n g  h os pit alis ati o n 
( h os pit alis ati o n si g nifi es t h at t h e  p ati e nt   w as  a n i n-p ati e nt f or  at l e ast  o n e 
o v er ni g ht st a y)  u nl ess  h os pit alis ati o n is f or:  
 r o uti n e tr e at  m e nt  or   m o nit ori n g  of t h e st u di e d i n di c ati o n,  n ot  ass o ci at e d   wit h 
d et eri or ati o n  of s y  m pt o  ms r el at e d t o   N  H L  
 el e cti v e  or  pr e -pl a n n e d tr e at  m e nt f or  a  pr e -e xisti n g  c o n diti o n t h at is  u nr el at e d 
t o   N  H L  a n d  h as  n ot   w ors e n e d si n c e si g ni n g  of t h e i nf or  me d  c o ns e nt 
 s o ci al r e as o n  a n d r es pit e  c ar e i n t h e  a bs e n c e  of  a n y  d et eri or ati o n i n t h e 
p ati e nt’s  g e n er al  c o n diti o n  
o  r es ults i n  p ersist e nt  or si g nifi c a nt  dis a bilit y  or i n c a p a cit y 
o  is  a  c o n g e nit al  a n o  m al y  or  birt h  d ef e ct 
o  is   m e di c all y si g nifi c a nt, i. e.  d efi n e d  as a n  e v e nt t h at j e o p ar dis es t h e  p ati e nt  or   m a y 
r e q uir e   m e di c al i nt er v e nti o n t o  pr e v e nt  o n e  of t h e  o ut c o  m es list e d  pr e vi o usl y. 
 
T h e t er  m  “lif e -t hr e at e ni n g ” r ef ers t o  a n  e v e nt i n   w hi c h t h e  p ati e nt   w as, i n t h e  vi e  w  of t h e 
r e p orti n g i n v esti g at or,  at i  m  m e di at e ris k  of  d e at h  at t h e ti  m e  of t h e  e v e nt; it  d o es  n ot r ef er t o  a n 
e v e nt t h at  h y p ot h eti c all y   mi g ht  h a v e  c a us e d  d e at h if it   w er e   m or e s e v er e.   M e di c al j u d g  m e nt 
s h o ul d  b e  e x er cis e d i n  d e ci di n g   w h et h er  a n   A E is s eri o us i n  ot h er sit u ati o ns: i  m p ort a nt   A Es t h at 
ar e  not i  m  m e di at el y lif e -t hr e at e ni n g  or  d o  n ot r es ult i n  d e at h  or  h os pit alis ati o n  b ut   m a y 
j e o p ar dis e t h e  p ati e nt  or   m a y r e q uir e i nt er v e nti o n t o  pr e v e nt  o n e  of t h e  ot h er  o ut c o  m es list e d i n 
t h e  pr e vi o us  d efi niti o ns s h o ul d  als o  b e  c o nsi d er e d  as s eri o us. 
 
A E SI s ar e T L S,  S P  M, I  R  Rs  a n d all er gi c r e a cti o ns t o st u d y  dr u g  ≥ gr a d e  3 ,  c yt o ki n e r el e as e 
s y n dr o  m e  a n d  o v er d os es. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 8 5  of 1 3 1  
U nli ke r o uti ne safet y  assess me nts,  SA Es a n d  A E SI s are m o nit ore d c o nti n u o usl y a n d ha ve s pecial 
re p orti n g re q uire me nts (see Secti o n  1 1. 2 ). 
T he  i n vesti gat or sh o ul d  de ter mi ne t he ca usalit y  (relati o nshi p t o t he stu d y dr u g) ba sed o n his/ her 
cli nica l e x perie nce  an d  o n  t he i nf or mati o n gi ve n in  t he I B. T he  ca usal relati o ns hi p  of all A Es t o 
t he st u d y d r u g will be j u d ge d as eit her  s uspecte d  or n ot s us pecte d.  A s uspecte d  ca usal  
relati o ns hi p  mea ns  at least a reas o na ble p os si bilit y t hat the eve nt is ca use d b y t he st u d y dr u g. If 
n o relati o ns hi p has be e n pr o vi de d b y the in vesti gat or , t he eve nt w ill b e co nsi dere d as relate d t o 
t he st u d y dr u g. 
I nf or matio n a b o ut ad verse dr u g reacti o ns alread y k n o w n a b o ut the i n vesti gati o nal st u d y dr u g ca n 
be fo u n d i n t he IB (M O R 0 0 2 0 8), S m P C an d/ or P rescri bin g I nf or matio n ( B E N, R T X), or will be  
c o m m u nicate d  i n t he f or m of I n vesti gat or N otificati o ns. This  i nfor mati o n  will be i ncl u de d i n t he 
patie nt IC F a n d s h o ul d be di sc ussed wit h t he pa tie nt d ur i n g t he st u d y, as n ee de d. 
1 1 . 2 A d ver se E v e nt a n d Seri o us A d vers e E ve nt Rec or di n g  an d Re p orti n g  
All  AEs (e xce pt  n o n-seri o us A Es  f or scree ni n g  fail ures) t hat occ ur after t he pr o visi o n of 
i nf or me d c o nse nt an d u p to 3 0 da ys after last dr u g ad mi nistrati o n  will be rec or de d i n t he eC R F  
a n d i n t he p atie nt’s me dical rec or ds, w het her or n ot the y are c o nsi dere d b y t he in vesti gat or t o be 
relate d to t he st u d y dr u g. T hereafter, o nl y S A Es / A E SIs assesse d  as relate d  t o a n y st u d y dr u g 
s h o ul d be rec or de d. All A Es sh o ul d be rec or de d usi n g acce pta ble di a g n oses, if p os si ble. F or 
scree ni n g fail ure pa tie nts, n o n-seri o us A Es w ill n ot be rec or de d i n t he e C R F b ut o nl y i n t he 
patie nt’s  medical rec or ds.   
I n a d diti o n, all S A Es an d A E SI s will be rec or de d o n t he S A E re p ort f or m. St u d y ce ntres a n d 
i n vesti gat ors are i nstr ucte d t o re p ort all S A Es a n d A ESI s t o t he s p o ns or ( or desi g nee) w it hi n 
2 4 h o urs, usi n g t he st u d y- s pecific S A E re p ort f or m. 
Ge nerall y, t he di a g n osis instea d of the in di vi d ual sy m pt o ms s h o ul d be re p orte d as t he eve nt ter m. 
If a di a g n osis ha s be e n re p orte d as an A E, it is n ot ne cessar y to re p ort eac h i n di vi d ual si g n a n d 
s y m pt o m of  t hat AE  as a  se parate A E. For  e xam ple,  if a fe brile ne utr o pe nia is re p orte d as a n  AE,  
t here is n o nee d t o re p ort ne utr o p hil co u nt de crease an d f e ver ab o ve 3 8° C , or ot her relate d si g ns, 
s y m pt o ms, or la b orat or y val ues as se parate A Es. H o we ver, if s uc h e ve nts occ ur in is olati o n, a n d 
fe brile ne utr o pe nia is n ot di a g n ose d, t he n eac h e ve nt sh o ul d be re p orte d as an A E. 
I RR s a n d aller gic reacti o ns to st u d y dr u gs gr a de 3 or hi g her, o r c yto ki ne release s y n dr o me,  
w hic h  are A ESI s in t his st u d y, s h o ul d be re p orte d as di a g n osis al o n g wit h t heir res pecti ve 
s y m pt o ms i n o ne eve nt  ter m  (e. g., ‘I R R w it h sy m pt o ms  of hi ves, c hills a n d fe ver’ f or IR R s). F or 
o ver d oses , t he di a g n osis an d if ap plica ble t he acc o m pa n yi n g sy m pt o ms ca use d b y t he o ve r d ose 
s h o ul d be re p orte d. 
All n o n- seri o us A Es m ust be foll o we d u p f or a fi nal o u tc o me. A n o utc o me of “u n k n o w n” is n ot 
c o nsi dere d t o be an acce pta ble fi nal o utc o me. A n o utc o me o f “n ot ye t res ol ve d” is an acce pta ble 
fi nal o ut c o me for n o n- seri o us A Es at t he e n d of a patie nt’s partici pa ti o n in t he st u d y. All S A Es 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 6  of 1 3 1  
m ust  b e f oll o  w e d  u p f or  a fi n al  o ut c o  m e  u ntil r es ol uti o n  or, if r es ol uti o n  b e c o  m es  u nli k el y,  u ntil 
st a bilis ati o n  or  d e at h.  
 
E v e nts t h at  ar e  cl e arl y  c a us e d  b y  pr o gr essi o n  of t h e  u n d erl yi n g  dis e as e ( e. g. tr a nsf or  m ati o n t o 
m or e  a g gr essi v e t u  m ou r hist ol o g y or   B -s y  m pt o  ms) s h o ul d  n ot  b e r e c or d e d  as   A Es  or  S  A Es. 
T h es e  d at a   will  b e  c a pt ur e d  as  effi c a c y  ass ess  m e nt  d at a  o nl y. If t h er e is  a n y  u n c ert ai nt y  as t o 
w h et h er  a n  e v e nt is  d u e t o  dis e as e  pr o gr essi o n, it s h o ul d  b e r e c or d e d  as  a n   A E or  S  A E . 
 
D e at hs t h at  o c c ur  d uri n g t h e  pr ot o c ol-s p e cifi e d  a d v ers e  e v e nt r e p orti n g  p eri o d t h at  ar e cl e arl y 
attri b ut e d t o  pr o gr essi o n  of t h e  u n d erl yi n g  dis e as e s h o ul d  n ot  b e r e c or d e d  as  S  A Es.   All  ot h er 
o n-st u d y  d e at hs, r e g ar dl ess  of r el ati o ns hi p t o st u d y  dr u g,   m ust  b e r e c or d e d  o n t h e   A d v ers e  E v e nt 
e  C  R F  a n d i  m  m e di at el y r e p ort e d  o n t h e  S  A E r e p ort f or  m t o t h e  S p o ns or.   D e at h s h o ul d  b e 
c o nsi d er e d  a n  o ut c o  m e  a n d  n ot  a  disti n ct  e v e nt.  T h e  e v e nt  or  c o n diti o n t h at  c a us e d t h e f at al 
o ut c o  m e s h o ul d  b e r e c or d e d  as t h e si n g l e   m e di c al  c o n c e pt  o n t h e   A d v ers e  E v e nt  e  C  R F. 
G e n er all y,  o nl y  o n e s u c h  e v e nt s h o ul d  b e r e p ort e d. 
 
D uri n g  F oll o  w- U p  f or   O v er all  S ur vi v al, t h e f oll o  wi n g s h o ul d  b e r e p ort e d: 
•  D e at hs  attri b ut e d t o  pr o gr essi o n  of t h e  u n d erl yi n g  dis e as e s h o ul d  b e r e p ort e d  vi a t h e 
e  C  R F . 
•  S  A Es/  A E SIs  t h e i n v esti g at or  b e c o  m es  a  w ar e  of  a n d  c o nsi d ers t o  b e r el at e d t o  a n y st u d y 
dr u g s h o ul d  b e r e p ort e d i n t h e  e  C  R F  a n d o n t h e  S  A E r e p ort f or  m vi a f a x t o t h e   C  R  O (s e e 
b el o  w). 
 
N otifi c ati o n  of i niti al  or f oll o  w - u p  S  A E/  A E SI i nf or  m ati o n ( b y  usi n g t h e st a n d ar d  S  A E f or  m 
pr o vi d e d  b y t h e s p o ns or)   m ust  b e s e nt  b y e  m ail  or f a x t o t h e s p o ns or ( or  d esi g n e e).  
 
1 1. 3  P r e g n a n ci es  
As  d et ail e d i n t h e  S c h e d ul e  of   Ass ess  m e nts (T a bl e   5) a n d  S e cti o n  1 0. 3. 7. 3 , s er u  m  pr e g n a n c y 
t esti n g   will  b e  c arri e d  o ut  at t h e  S cr e e ni n g  a n d E  O T  v isits.   D uri n g t h e tr e at  m e nt  p eri o d  of t h e 
st u d y,  uri n e  pr e g n a n c y t esti n g   will  b e  p erf or  m e d l o c all y  a n d  c a n  b e r e p e at e d if r e q uir e d.   A n y 
pr e g n a n c y t h at  o c c urs  d uri n g st u d y  p arti ci p ati o n ( aft er si g n at ur e  of t h e i nf or  m e d  c o ns e nt f or  m 
u ntil 3,  6  or  1 2   m o nt hs aft er l ast  d os e  of M  O  R 0 0 2 0 8,   B E  N  or   R T  X r es p e cti v el y,   w hi c h e v er is 
l at er) s h o ul d  b e r e p ort e d  usi n g  a   Cli ni c al  Tri al  Pr e g n a n c y  F or  m. Li k e  wis e, if  a f e  m al e s e x u al 
p art n er  of a p ati e nt  p arti ci p ati n g i n t his tri al b e c o  m es  pr e g n a nt   wit hi n  3,  6  or  1 2   m o nt hs  aft er l ast 
d os e  of   M  O  R 0 0 2 0 8,   B E  N  or   R T  X r es p e cti v el y,   w hi c h e v er is l at er, t his  pr e g n a n c y s h o ul d  b e 
r e p ort e d. (A p pli c a bl e i n   R e p u bli c  of   K o r e a : a n y  pr e g n a n c y t h at  o c c urs  d uri n g st u d y 
p arti ci p ati o n ( aft er si g n at ur e  of t h e i nf or  m e d  c o ns e nt f or  m  u ntil  6   m o nt hs  aft er l ast  d os e  of 
M  O  R 0 0 2 0 8, 6   m o nt hs  aft er t h e l ast  d os e  of   B E  N  or  1 2   m o nt hs  aft er t h e l ast  d os e  of R T  X) s h o ul d 
b e r e p ort e d  usi n g  a   Cli ni c al  Tri al  Pr e g n a n c y  F or  m.  Li k e  wis e, if  a f e  m al e s e x u al  p art n er  of  a 
p ati e nt  p arti ci p ati n g i n t his tri al  b e c o  m es  pr e g n a nt   wit hi n  6   m o nt hs  aft er l ast  d os e  of 
M  O  R 0 0 2 0 8,  6   m o nt hs  aft er t h e l ast  d os e  of B E  N  or  1 2   m o nt hs  aft er t h e l a st  d os e  of   R T  X, t his 
pr e g n a n c y s h o ul d  b e r e p ort e d.) 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 7  of 1 3 1  
T o  e ns ur e  p ati e nt s af et y,  e a c h  pr e g n a n c y  of  a st u d y  p ati e nt  or  a f e  m al e s e x u al p art n er  of  a st u d y 
p ati e nt   m ust  als o  b e r e p ort e d   wit hi n  2 4  h o urs  of l e ar ni n g  of its  o c c urr e n c e  b y e  m ail  or f a x t o 
s p o ns or ( or d esi g n e e).  
 
S t u d y  p ati e nts   w h o  b e c o  m e  pr e g n a nt   m ust  b e   wit h dr a  w n fr o  m t h e st u d y tr e at  m e nt. A   m al e 
p ati e nt   w h os e  s e x u al p art n er  b e c o  m es  pr e g n a nt   m a y  c o nti n u e st u d y  p arti ci p ati o n.  
 
A  n e  wl y  di a g n os e d  pr e g n a n c y i n  a  p ati e nt  or f e  m al e s e x u al p art n er  of  a st u d y  p ati e nt   w h o  h as 
r e c ei v e d st u d y   m e di c ati o n is  n ot  c o nsi d er e d  an  S  A E  u nl ess it   m e ets  a n y  crit eri a  of s eri o us n ess  or 
it is s us p e ct e d t h at t h e st u d y   m e di c ati o n i nt er a ct e d   wit h  a  c o ntr a c e pti v e   m et h o d  a n d l e d t o 
pr e g n a n c y.  
 
If t h e  pr e g n a n c y r es ults i n cli ni c al  c o ns e q u e n c es/ c o  m pli c ati o ns i n   m ot h er  or  c hil d,  e. g. if t h e 
c hil d is  b or n   wit h  a  birt h  d ef e ct, t his s h o ul d  b e r e p ort e d  as  a n  S  A E  of   m ot h er  or  c hil d  as 
a p pli c a bl e. 
 
T h e  pr e g n a n c y s h o ul d  b e f oll o  w e d  u p t o  d et er  mi n e  o ut c o  m e, i n cl u di n g s p o nt a n e o us  or  v ol u nt ar y 
t er  mi n ati o n,  d et ails  of  birt h,  a n d t h e  pr es e n c e  or  a bs e n c e  of  a n y  birt h  d ef e cts  or  c o n g e nit al 
a b n or  m aliti es  or   m at er n al  a n d  n e  w b or n  c o  m pli c ati o ns.  E v er y i nf a nt  h as t o  b e f oll o  w e d  u p f or 
2  m o nt hs  aft er  d eli v er y.  
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 8 8  of 1 3 1  
1 2  D  A  T  A   H  A  N  D  LI  N  G   A  N  D   A  R  C  HI  VI  N  G  
1 2. 1  C o  m pl e ti n g  a n d  Si g ni n g   C as e   R e p o rt  F o r  ms 
A n  e  C  R F  will  b e  us e d i n t his st u d y. T h e i n v esti g at or will  b e r es p o nsi bl e f or  a c c ur at e  a n d ti  m el y 
d at a  e ntr y a n d  d at a  cl arifi c ati o ns i n t h e  e  C  R F.   D at a  e ntr y   m a y  b e  d el e g at e d t o  a d e q u at el y tr ai n e d 
sit e  p ers o n n el. A n y  err ors s h o ul d  b e  c orr e ct e d   wit hi n t h e  el e ctr o ni c s yst e  m. I n t h e c as e  of 
missi n g  d at a,  a r e as o n s h o ul d  b e  gi v e n. T h e  a u dit tr ail   will r e c or d  all  c h a n g es   m a d e, t h e  d at e  a n d 
ti  m e  of t h e  c orr e cti o n,  a n d t h e  p ers o n  c orr e cti n g t h e  err or.  T h e  a p pr o pri at e  el e ctr o ni c si g n at ur e 
will  b e  pr o vi d e d.  T h e i n v esti g at or   will r e c ei v e  a  c o p y  of t h eir  e  C  R F i n  a r e a d a bl e f or  m at  aft er 
d at a b as e l o c k f or  ar c hi vi n g.  
 
1 2. 2  Cli ni c al   D at a   M a n a g e  m e nt  
T h e   C  R  O   will  b e r es p o nsi bl e f or t h e  pr o c essi n g  a n d  q u alit y  c o nt r ol  of t h e  d at a  a c c or di n g t o t h e 
C  R  O’s st a n d ar d  o p er ati n g  pr o c e d ur es ( S  O Ps).   D at a   m a n a g e  m e nt   will  b e  c arri e d  o ut  b y t h e C  R  O. 
T h e  h a n dli n g  of  d at a, i n cl u di n g  d at a  q u alit y  c o ntr ol,   will  c o  m pl y   wit h  all  a p pli c a bl e r e g ul at or y 
g ui d eli n es.  
 
D et ails f or  d at a  v ali d ati o n  a n d  e dit  c h e c ks   will  b e  d es cri b e d i n  a p pr o pri at e  d at a   m a n a g e  m e nt 
d o c u  m e nts.   Q u eri es   will  b e  h a n dl e d  vi a t h e  e  C  R F s yst e  m.   D at a  cl e a ni n g   will  c o nti n u e  u ntil  all 
q u eri es  ar e r es ol v e d.  
 
M e di c al  c o di n g   will  us e   M e di c al   Di cti o n ar y f or   R e g ul at or y   A cti viti e s (  M e d  D  R  A),   V ersi o n  1 8.1 
(or  hi g h er ) f or   A Es  a n d   m e di c al  hist or y  a n d t h e   W  H  O D r u g D i cti o n ar y E n h a n c e d f or 
m e di c ati o n.  
 
1 2. 3  A r c hi vi n g  a n d  Fili n g  
All st u d y  d o c u  m e nt ati o n  at t h e i n v esti g at or sit e  a n d s p o ns or sit e   will  b e  ar c hi v e d i n  a c c or d a n c e 
wit h I nt er n ati o n al C o nf er e n c e  o n   H ar  m o nis ati o n (I  C  H)  E 6   G o o d   Cli ni c al  Pr a cti c e (  G  C P) 
g ui d a n c e  a n d t h e  cli ni c al tri al  a gr e e  m e nt.  
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 8 9  of 1 3 1  
1 3  S  T  A  TI S  TI  C  A  L   M  E  T  H  O  D S   A  N  D  P  L  A  N  N  E  D   A  N  A  L  Y S E S 
T h e  d at a   will  b e a n al ys e d   b y t h e s p o ns or a n d/ or  d esi g n e e.   A n y  d at a  a n al ysis  c arri e d  o ut 
i n d e p e n d e ntl y  b y t h e i n v esti g at or s h o ul d  b e s u b  mitt e d t o I n c yt e   C or p or ati o n  b ef or e  p u bli c ati o n 
or  pr es e nt ati o n. 
It is  pl a n n e d t h at t h e  d at a fr o  m  p arti ci p ati n g c e ntr es  i n t his  pr ot o c ol   will  b e  c o  m bi n e d, s o t h at  a n 
a d e q u at e  n u  m b er  of  p ati e nts   will  b e  a v ail a bl e f or  a n al ysis . 
T h e f oll o  wi n g  a n al ys es  ar e  pl a n n e d: 
•
I nteri m A n al ysis: pla n ne d t o ta ke place after a p pr o xi matel y 1 2 8 P F S e ve nts ( base d o n  
I R C assess me nt) ha ve bee n o bser ve d i n t he o verall p o p ulati o n ( F A S) .
Fi n a l A n al ysis: pla n ne d t o ta ke place at t he e n d of t he st u d y (f or defi niti o n see      
Secti o n  8. 4 ), i n de pe n de nt of h o w ma n y I R C P F S  e ve nts ha v e bee n  obser ve d  at that  poi nt  
i n time.  All e n d p oi nts as descri be d i n Secti o n  7 w ill b e a nal yze d .
A d diti o n al s af et y  a n al ys es   m a y  b e  p erf or  m e d t o s u p p ort i nt er a cti o ns   wit h r e g ul at or y  a ut h oriti es.  
1 3. 1  P o p ul ati o ns f o r   A n al ysis  
T a bl e   7 d et ails t h e  d efi n e d  a n al ysis  s ets. 
T a bl e   7: 
A n al ysis  S ets  
A n al ysis s et  
D es c ri pti o n  
F ull  a n al ysis s et ( F  A S)  
All  p ati e nts   w h o   w er e r a n d o  mis e d t o  eit h er tr e at  m e nt  ar  m.  
A n al ys es  usi n g t h e  F  A S   will  b e  b as e d  u p o n t h e tr e at  m e nt 
t o   w hi c h  e a c h  p ati e nt   w as r a n d o  mis e d. 
P er -pr ot o c ol s et ( P P S)  
All  p ati e nts i n t h e  F  A S,  h a vi n g  at l e ast  o n e  d os e  of 
M  O  R 0 0 2 0 8  or   R T  X,  a n d   B E  N.  
P ati e nts   wit h o ut  a n y  p ost -b as eli n e  ass ess  m e nt  of   D L  B  C L 
r es p o ns e  or   wit h s p e cifi c  k e y pr ot o c ol  d e vi ati o ns   will  b e 
e x cl u d e d fr o  m t h e  P P S.  
S af et y  a n al ysis s et ( S  A F)  
All  p ati e nts   w h o r e c ei v e d  at l e ast  o n e  d os e  of   M  O  R 0 0 2 0 8 
or   R T  X  or   B E  N.  
A n al ys es  usi n g t h e  S  A F   will  b e  b as e d  o n t h e a ct u al 
tr e at  m e nt r e c ei v e d. 
P  K  a n al ysis s et ( P  K  A S)  
T h e P  K   po p ul ati o n   will i n cl u d e  all  p ati e nts   w h o  h a v e  at 
l e ast  o n e  q u a ntifi a bl e s er u  m   M  O  R 0 0 2 0 8  c o n c e ntr ati o n 
( P  K  p ar a  m et ers   will  b e  c al c ul at e d  as  d at a  p er  mit.) 
I  m  m u n o g e ni cit y  a n al ysis s et (I  A S) 
All  p ati e nts   w h o  w er e r a n d o  mis e d  a n d h a v e  at l e ast  o n e 
a nti-M  O  R 0 0 2 0 8  a nti b o d y  ass ess  m e nt.  
A b br e vi ati o ns:   B E  N   = b e n d a  m usti n e;  P  K   = p h ar  m a c o ki n eti cs;   R T  X   = rit u xi  m a b. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 0  of 1 3 1  
1 3. 2  G e n e r al  St atisti c al   M et h o ds  
T a b ul ati o ns  of s u  m  m ar y st atisti cs,  gr a p hi c al  pr es e nt ati o ns,  a n d st atisti c al  a n al ys es   will  b e 
p erf or  m e d  usi n g  S  A S ®  s oft  w ar e  v ersi o n  9. 3  or  hi g h er. 
 
C o nti n u o us,  q u a ntit ati v e  v ari a bl e s u  m  m ari es   will i n cl u d e t h e  n u  m b er  of  p ati e nts (  N) (  wit h 
n o n -missi n g  v al u es/ v ali d  c as es),   m e a n, st a n d ar d  d e vi ati o n,   mi ni  m u  m,  2 5t h  q u artil e,   m e di a n,  7 5t h 
q u artil e  a n d   m a xi  m u  m,  e x c e pt f or  P  K   m etri cs,   w h er e  a d diti o n al st atisti cs m a y  b e  us e d.  
 
C at e g ori c al,  q u al it ati v e  v ari a bl e s u  m  m ari es   will i n cl u d e t h e fr e q u e n c y  a n d  p er c e nt a g e  of 
p ati e nts/ e ntri es i n t h e  p arti c ul ar  c at e g or y.  
 
D efi niti o n  of  b as eli n e  v al u e: t h e l ast  pr e -a d  mi nistr ati o n  o bs er v ati o n   will  b e  us e d  as t h e  b as eli n e 
v al u e f or  c al c ul ati n g  p ost -a d  mi nistr ati o n  c h a n g es fr o  m  b as eli n e.  
 
All  d at a  o bt ai n e d vi a  t h e  e  C  R F  a n d  e nt er e d i nt o t h e  d at a b as e   will  b e  pr o vi d e d i n s e p ar at e  d at a 
listi n gs s h o  wi n g i n di vi d u al  p ati e nt  v al u es.  T h e  pl a n ni n g  a n d r e p orti n g  of st atisti c al  a n al ys es   will 
b e  c arri e d  o ut  as  d es cri b e d i n t h e   C  R  O’s  S  O Ps.   A S t atisti c al A n al ysis P l a n ( S  A P)  det aili n g t h e 
st atisti c al  a n al ys es   will  b e  pr e p ar e d a n d si g n e d  off b ef or e t h e d at a b as e l o c k.  
 
1 3. 3  P ati e nt   Dis p ositi o n,   B as eli n e  a n d   T r e at  m e nt   C h a r a ct e risti cs  
T h e  n u  m b er  of  p ati e nts s cr e e n e d, r a n d o  mis e d,  a n d i n cl u d e d i n  e a c h  a n al ysis  p o p ul ati o n   will  b e 
s u  m  m arised. I n  a d diti o n , t h e  n u  m b er  of  p ati e nts t h at  dis c o nti n u e tr e at  m e nt  d uri n g t h e 
C o  m bi n ati o n T r e at  m e nt  or t h e A nti b o d y M o n ot h er a p y T r e at  m e nt  or F oll o  w -U p will  b e 
s u  m  m arise d, al o n g   wit h r e as o ns f or  dis c o nti n u ati o n.  
 
T h e  n u  m b er  of  p ati e nts  c o  m pl eti n g C o  m bi n ati o n T r e at  m e nt ( 1/ 2/ 3/ 4/ 5/ 6  c y cl es),  a n d t h e  n u  m b er 
of  p ati e nts i n cl u d e d i n A nti b o d y M o n ot h er a p y T r e at  m e nt (cy cl es  > 7)  a n d F oll o  w -U p will  b e 
s u  m  m arise d  a n d list e d. 
 
D e  m o gr a p hi c i nf or  m ati o n   will  b e s u  m  m aris e d f or t h e f ull  a n al ysis s et (F  A S ) a n d s af et y a n al ysis 
s et (S  A F ) p o p ul ati o ns  usi n g  d es cri pti v e st atisti cs. D e  m o gr a p hi c i nf or  m ati o n will  als o  b e 
s u  m  m aris e d f or t h e N  K  C  C -l o  w s u b gr o u p. G e n d er  a n d r a c e will  b e s u  m  m aris e d  b y  c o u nts  a n d 
p er c e nt a g es.  
 
M e di c al  hist or y  will  b e s u  m  m aris e d  b y  c o u nts  a n d  p er c e nt a g es  usi n g   M e d  D  R  A s yst e  m  or g a n 
cl ass ( S  O  C)  a n d  pr ef err e d t er  m  cl assifi c ati o ns.   C o n c o  mit a nt   m e di c ati o ns   will  b e r e c or d e d  a n d 
c o d e d  usi n g t h e   W  H  O   Dr u g   Di cti o n ar y  E n h a n c e d  a n d  gr o u p e d  b y   A n at o  mi c al  T h er a p e uti c 
C h e  mi c al (  A T  C) cl ass es.  T a b ul ati o ns   wit h  c o u nts/ p er c e nt a g es   will s h o  w t h e n u  m b er  of 
m e di c ati o ns/ p er c e nt a g e  us e d i n  e a c h  cl ass.  
 
T h e N  H L -s p e cifi c   m e di c al  hist or y   will  b e s u  m  m aris e d f or t h e  d ur ati o n  of  dis e as e si n c e i niti al 
di a g n osis,  n u  m b er  of  pr e vi o us t h er a pi es  (t h er a p y li n es), t y p e  of  pr e vi o us t h er a p y,  a n d  b est 
r es p o ns e f oll o  wi n g  pr e vi o us N  H L -s p e cifi c t h er a p y.   Dis e as e st a gi n g  a n d  dis e as e ris k  ass ess  m e nt 
will  b e  e v al u at e d  b y fr e q u e n c y t a b ul ati o ns  as   w ell.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 1  of 1 3 1  
1 3. 4  A n al ysis  of   Effi c a c y   D at a  
I n t his st u d y t  w o  c o- pri  m ar y  e n d p oi nts ( P F S i n F  A S  a n d  P F S i n   N  K  C  C -l o  w s u b gr o u p) a nd t  w o 
k e y s e c o n d ar y  e n d p oi nts (  O  R  R  a n d   O S) i n t h e F  A S  or   N  K  C  C -l o  w s u b gr o u p will  b e t est e d   wit h 
i nf er e nti al st atisti cs.  
 
T h e f oll o  wi n g s c h e  m e   will  b e f oll o  w e d t o t est t h e  c o - pri  m ar y  e n d p oi nts  a n d t h e s e c o n d ar y 
e n d p oi nts: 
 
1)  F or  c o nfir  m at or y  h y p ot h esis t esti n g  at t h e fi n al  a n al ysis , t h e  p-v al u es  of t h e st atisti c al t ests 
f or t h e  pri  m ar y  a n d  k e y s e c o n d ar y  e n d p oi nt will  b e c o  m bi n e d fr o  m st a g e I ( i nf or  m ati o n  u p t o 
t h e int eri  m an al ysis)  a n d st a g e II ( i nf or  m ati o n b et  w e e n t h e i nt er i  m an al ysis  a n d fi n al 
a n al ysis)  of t h e st u d y  usi n g t h e i n v ers e  n or  m al   m et h o d f or t h e  o v er all  p o p ul ati o n ( F  A S)  a n d 
t h e N  K  C  C -l o  w s u b gr o u p.  T his  pr o c e d ur e  pr es er v es t h e  o v er all ( e x p eri  m e nt- wis e) t y p e I  err or 
r at e  of  α  =  0. 0 5 (t  w o-si d e d) (W ass  m er  2 0 0 6 ). 
 
T h e  pr e-s p e cifi e d   w ei g hts t o  b e  us e d f or  c o  m bi ni n g t h e  p- v al u es fr o  m t h e t  w o st a g es s h o ul d 
s atisf y t h e  c o n diti o n t h at t h e s u  m  of t h e s q u ar e  of t h e w ei g hts  a d d  u p t o  1.   T h e s q u ar e  of t h e 
w ei g ht at st a g e I   will  b e  e q u al t o  0. 4  a n d  at st a g e II   will  b e  e q u al t o  0. 6. 
 
2)  T h e t ot al  T y p e I  err or i n t his st u d y  c o nsisti n g  of  4. 8  % will  b e  distri b ut e d  o v er t h e t  w o 
c o- pri  m ar y  e n d p oi nts  a n d t h e  k e y s e c o n d ar y  e n d p oi nts  a c c or di n g t o t h e f oll o  wi n g s c h e  m e: 
 
𝜶𝜶𝟐𝟐
∗ is s u c h t h at st u d y   wis e   T y p e I  e r r o r  r at e is   m ai nt ai n e d  at  4. 8  % 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 2  of 1 3 1  
T h e  al p h a (t  w o -si d e d) t o  b e s p e nt f or t h e t  w o  c o- pri  m ar y  e n d p oi nts   will  d e p e n d  o n t h e 
o ut c o  m e  of si  m ul ati o ns  d e  m o nstr ati n g t y p e I  err or  c o ntr ol f or  eit h er  of t h e t  w o s c e n ari os: 
a) C o ns er v ati v el y  all o c ati n g  al p h a f oll o  wi n g  a stri ct   B o nf err o ni -t y p e s plit  of  3. 4  % for t h e 
o v er all  p o p ul ati o n ( F  A S)  a n d  a   m a xi  m u  m  of  1. 4  % f or N  K C  C-l o  w . W ass  m er ( 2 0 1 1)  an d 
S u git a ni  et  al. ( 2 0 1 6) , c o ul d  d e  m o nstr at e t h at  c o  m bi ni n g i n v ers e  n or  m al   m et h o d  a n d 
B o nf err o ni t y p e  p artiti o n  of  al p h a i nt o   m ulti pl e  h y p ot h esis  c o ns er v es t h e t o t al st u d y   wis e 
T y p e I  err or r at e i n t h e str o n g s e ns e.  
 
b)  Al p h a  all o c at e d t o t h e N  K  C  C -l o  w s u b gr o u p  d e p e n di n g  o n t h e  c orr el ati o n  b et  w e e n t h e 
o v er all  p o p ul ati o n ( F  A S)  a n d t h e N  K  C  C -l o  w s u b gr o u p (S pi ess e ns  a n d   D e b ois  2 0 1 0 ).  Th e 
c orr el ati o n  d e p e n ds  o n t h e  pr o p orti o n  of  P F S  e v e nts  o bs er v e d i n t h e N  K  C  C -l o  w 
s u b gr o u p  v ers us t h e t ot al  n u  m b er  of  P F S  e v e nts  o bs er v e d i n t h e  o v er all  p o p ul ati o n 
( F  A S).  F or  e x a  m pl e, if t h e N  K  C  C -l o  w s u b gr o u p  c o nt ai ns  5 0  % ( or  5 5  %)  of t h e  e v e nts 
o bs er v e d i n t h e  o v er all  p o p ul ati o n ( F  A S),  al p h a   will  b e  a   m a xi  m u  m  of  2. 2  % ( or  2. 3  %) f or 
t h e   N  K  C  C-l o  w s u b gr o u p  a n d  3. 4  % f or t h e  o v er all  p o p ul ati o n ( F  A S).   
 
3)  If t h e  pri  m ar y  e n d p oi nt is   m et f or t h e  o v er all  p o p ul ati o n ( F  A S), t h e s e c o n d ar y  e n d p oi nts   will 
b e  hi er ar c hi c all y t est e d f or t h e o v er all  p o p ul ati o n ( F  A S)   wit h t h e  al p h a t h at   w as  pr o vi d e d f or 
F  A S  (i. e.,  3. 4  %). If  a n y  k e y-s e c o n d ar y  e n d p oi nt is  n ot   m et i n t h e F  A S, t h e c o-pri  m ar y 
e n d p oi nt  of  P F S  a n d t h e  k e y-s e c o n d ar y  e n d p oi nts   will  b e t est e d f oll o  wi n g t h e s a  m e 
hi er ar c hi c al  pl a n i n t h e   N  K  C  C -l o  w s u b gr o u p  at t h e  all o c at e d  al p h a. 
 
4)  If t h e  pri  m ar y  e n d p oi nt is  n ot   m et f or t h e  F  A S ,  b ut is   m et i n t h e N  K  C  C -l o  w s u b gr o u p, t h e 
s e c o n d ar y  e n d p oi nts   will  b e  hi er ar c hi c all y t est e d f or t h e N  K  C  C -l o  w s u b gr o u p  d e p e n di n g  o n 
t h e  o ut c o  m e  of t h e si  m ul ati o ns   m e nti o n e d  pr e vi o usl y, t h at is 
a) wit h t h e  al p h a t h at   w as  all o c at e d t o t h e N  K  C  C -l o  w s u b gr o u p   wit h t h e  c o ns er v ati v e 
B o nf err o ni-t y p e s plit ( 2 a),  or 
 
b)  t h e  al p h a  all o c at e d f or  e a c h  k e y s e c o n d ar y  e n d p oi nt   will  b e t h e   mi ni  m u  m  of t h e  al p h a 
( 2 b) 
i. t h at   w as  all o c at e d t o t h e N  K  C  C -l o  w s u b gr o u p  a n d  
ii. t h e  al p h a t h at   will  b e  c al c ul at e d  c o nsi d eri n g  c orr el ati o n  of t h e  gi v e n  e n d p oi nt 
b et  w e e n t h e N  K  C  C -l o  w s u b gr o u p  a n d t h e  o v er all  p o p ul ati o n ( F  A S).  
 
F or t h e  k e y- s e c o n d ar y  e n d p oi nts c orr el ati o n will  b e c al c ul at e d  a c c or di n g t o t h e  
f oll o  wi n g: 
o  F or   O  R  R:  b as e d  o n t h e  pr o p orti o n  of  p ati e nts i n   N  K  C  C- l o  w  vs  F  A S 
o  F or   O S:  b as e d  o n t h e  pr o p orti o n  of  e v e nts i n   N  K  C  C- l o  w  vs  F  A S 
 
T h e  a d e q u a c y  of t h e  c o  m bi n e d  us e  of t h e  
•  i n v ers e  n or  m al   m et h o d f or t h e  a d a pti v e d esi g n 
•  al p h a s p e n di n g f or t h e t  w o  c o- pri  m ar y  e n d p oi nts ( as st at e d  a b o v e) 
•  hi er ar c hi c al t esti n g  pr o c e d ur e  of s e c o n d ar y  e n d p oi nts i n t h e N  K  C  C -l o  w 
s u b gr o u p 
i n r es p e ct t o t h e t y p e I  err or  c o ntr ol   will  b e  pr o v e n  b y si  m ul ati o ns  a n d r e p ort e d i n t h e 
S  A P ,   w hic h   will b e fi n ali z e d  pri or t o t h e int eri  m an al ysis.   T h e  al p h a t o  b e  all o c at e d t o t h e 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 3  of 1 3 1  
N  K  C  C -lo  w s u b gr o u p   will  d e p e n d  o n t h e r es ult  of t h es e si  m ul ati o ns  a n d   will  b e  d e ci d e d 
f oll o  wi n g t h e  c o ns er v ati v e  a p pr o a c h  of  a d e q u at el y  c o ntr olli n g t h e st u d y-wis e ty p e I  err or 
r at e  of  4. 8  %.  
 
1 3. 4. 1  Ass ess  m e nt  of E ffi c a c y V a ri a bl es : C o -P ri  m a r y   E n d p oi nt s 
T h e  pri  m ar y  effi c a c y  e n d p oi nt   will  b e  P F S,  d efi n e d  as t h e ti  m e  el a ps e d  b et  w e e n r a n d o  mis ati o n 
a n d I  R  C -ass ess e d ti  m e  of t u  m o ur  pr o gr essi o n  or  d e at h fr o  m  a n y  c a us e.  T h e  d at e  of  pr o gr essi o n 
will  b e  d e e  m e d t o  b e t h e first  d at e w h e n  pr o gr essi v e  dis e as e   w as  di a g n os e d . P ati e nts w it h  n o 
dis e as e  pr o gr essi o n  as  of t h e  a n al ysis  c ut -off  d at e   will  b e  c e ns or e d  at t h e  d at e  of t h e l ast t u  m o ur 
ass ess  m e nt.  
 
P ati e nts l ost  t o f oll o  w-u p   will  b e  c e ns or e d  at t h e l ast  a v ail a bl e t u  m o ur  ass ess  m e nt.  P ati e nts   wit h 
n o  p ost -b as eli n e  ass ess  m e nt   will  b e  c e ns or e d  at t h e ti  m e  of r a n d o  misati o n. 
 
P ati e nts w h o r e c ei v e  n o n -st u d y a ntic a n c er tr e at  m e nt  b ef or e  dis e as e  pr o gr essi o n,  or p ati e nts wit h 
cli ni c al  b ut  n ot r a di ol o gi c al e vi d e n c e  of  pr o gr e ssio n   will  b e  c e ns or e d  at t h e  d at e  of t h e l ast 
e v al u a bl e t u  m o ur  ass ess  m e nt.   A d diti o n al  c e ns ori n g  d et ails   will  b e  o utli n e d i n t h e  S  A P.  
 
T h e fi n al a n al ysis   will  b e p erf or  m e d o n t h e  F  A S  a n d t h e   N  K  C  C -l o  w s u b gr o u p  of t h e  F  A S, t h e 
l att er d efi n e d  as p ati e nts  h a vi n g 1 0 0  or l ess   N  K  c ells  p er  µl  bl o o d  at  b as eli n e . 
 
P ati e nts t o  b e i n cl u d e d i n t h e   N  K  C  C -l o  w s u b gr o u p   m ust  h a v e  a n  e v al u a bl e  b as eli n e   N  K  C  C 
v al u e.  
 
P F S   will  b e  c o  m p ar e d  b et  w e e n tr e at  m e nt  gr o u ps i n t h e F  A S p o p ul ati o n  a n d   N  K  C  C -lo  w  
s u b gr o u p usi n g t h e str atifi e d l o g -r a n k t est.  T h e  esti  m at e  of t h e  h a z ar d r ati os (  HR s) a n d 
c orr es p o n di n g  9 5  % c o nfi d e n c e i nt er v al ( CI ) will  b e  pr o vi d e d  usi n g  a   C o x  pr o p orti o n al  h a z ar ds  
(  C P  H) m o d el i n cl u di n g tr e at  m e nt  a n d t h e str atifi c ati o n f a ct ors ( dis e as e r el a ps e/r e c urr e n c e: 
≤ 1 2  m o nt hs  v ers us  > 1 2   m o nt hs fr o  m l ast tr e at  m e nt,  E  C  O  G  p erf or  m a n c e st at us:  0 -1  v ers us  2 , 
a g e ≤  6 5  y e ars  v ers us > 6 5  y e ars  a n d t h e n u  m b er  of  pr e vi o us s yst e  mi c t h er a p y li n es  ≤ 2  v ers us  > 2) . 
T h e str atifi c ati o n f a ct ors   will  b e  d efi n e d  as  p er t h eir r a n d o  mi sati o n  assi g n  m e nt.  P F S f or  e a c h  ar  m  
a n d  a n al ysis  p o p ul ati o n  will  b e s u  m  m ari se d  usi n g t h e K a pl a n -M ei er  m et h o d . 
 
V ari o us s u p p orti v e  a n al ys es m a y  b e  p erf or  m e d  usi n g t h e  F  A S a n d   N  K  C  C -lo  w  s u b gr o u p ( u nl ess 
ot h er  wis e  n ot e d):  
 
1.  T h e  pri  m ar y  effi c a c y  e n d p oi nt  a n al ysis  as  o utli n e d  a b o v e   will  b e  c o n d u ct e d  usi n g t h e 
P P S . 
2.  A n  u n str atifi e d l o g-r a n k t est   will  b e  c al c ul at e d,  a n d  a   C P  H   m o d el fit, wit h  o nl y tr e at  m e nt 
i n t h e   m o d el. 
3.  M ulti v ari at e  a n al ysis   will  b e  p erf or  m e d i n cl u di n g t h e str atifi c ati o n f a ct ors,  b o n e   m arr o  w 
i n v ol v e  m e nt,  a n d t h e f oll o  wi n g s et  of p ot e nti al  pr o g n osti c /pr e di cti v e f a ct ors: r a c e,   G  C  B 
v ers u s  n o n-G  C B  D L  B  C L, I PI ,  pri or A S  C T ,  n u  m b er  of  pri or t h er a p y li n es: 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 9 4  of 1 3 1  
a)    A st e p -wis e s el e cti o n  pr o c ess   will  b e  us e d t o i d e ntif y  a fi n al s u bs et  of f a ct ors t o  b e
i n cl u d e d.   O n c e t h e s u bs et is est a blis h e d, t h e n tr e at  m e nt   will  b e  a d d e d t o t h e   m o d el t o
ass ess its  eff e ct .
b)
A n  e x pl or at or y  a n al ysis  of tr e at  m e nt  b y f a ct or i nt er a cti o ns  usi n g t h e   C P  H   m o d el   will
b e  c arri e d  o ut.  F urt h er  d et ails   will  b e  pr o vi d e d   wit hi n t h e  S  A P .
4.    A n al ys es   will  b e  d o n e f or t h e s u b gr o u ps  of t h e str atifi c ati o n f a ct ors  a n d  b o n e   m arr o  w
i n v ol v e  m e nt,  as   w ell  as  a n y  ot h er  pr o g n osti c f a ct ors i d e ntifi e d i n t h e  a b o v e   m ulti v ari at e
a n al ysis.  T h e H  R a n d  9 5  %   CI   will  b e  pr es e nt e d f or  e a c h s u b gr o u p.
V ari o us s e nsiti vit y  a n al ys es r e g ar di n g   missi n g  d at a   will  b e  p erf or  m e d  usi n g t h e  F  A S  a n d 
N  K  C  C -l o  w s u b gr o u p: 
1. P ati e nts l ost  t o f oll o  w- u p,  b ut  h a vi n g  a n  a v ail a bl e  d e at h  d at e,   will  b e i n cl u d e d i n t h e
ti  m e-t o-e v e nt  a n al ysis  as  a n  e v e nt.  T his   will  a c c o u nt f or  a  p ossi bl e i  m b al a n c e i n  d e at hs,
w hi c h  c o ul d  bi as t h e  P F S   m e as ur e  m e nt  b y  o v er esti  m ati n g t h e  P F S i n t h e tr e at  m e nt  ar  m
wit h l ess  d o c u  m e nt e d f oll o  w - u p.
2. I nt er v al  c e ns ori n g   will  b e  a p pli e d.   Diff er e nt  c o nsi d er ati o ns f or i nt er v al  c e ns ori n g   will  b e
c o nsi d er e d   wit h  d et ails s p e cifi e d  i n t h e  S  A P.
3. A n  a n al ysis   will  b e  d o n e  as  p er t h e  pri  m ar y effi c a c y  e n d p oi nt a n al ysis  b ut   wit h  c e ntr al
r e a d er  b as eli n e  di a g n osis r es ults.  T his is t o  as c ert ai n t h at l o c al  a n d  c e ntr al r e a d er
diff er e n c es  d o  n ot  aff e ct t h e r es ults.
4. T h e   m et h o d  of   m ulti pl e i  m p ut at i o n   m a y  b e  a p pli e d t o  a c c o u nt f or   N  K  C  C  v al u es   missi n g  at
b as eli n e.  T his   will  b e i  m pl e  m e nt e d i n  c as e  of   m or e t h a n  1 0  %   missi n g  b as eli n e   N  K  C  C
v al u es.
5. C o x  P  H   M o d el t o  esti  m at e t h e   H  R i n F  A S  a n d N  K  C  C -lo  w s u b gr o u p   m a y i n cl u d e t h e
a d diti o n al  c of a ct or  of   N  K  C  C -l o  w b as eli n e  st at us i n t h e   m o d el.
6. T o  a c c o u nt f or  a  p ossi bl e i  m b al a n c e  b et  w e e n tr e at  m e nt  ar  ms i n t h e   N  K  C  C -l o  w s u b gr o u p,
b al a n ci n g  of  c o v ari at es  vi a  Pr o p e nsit y  S c or e   w ei g hti n g   m et h o d ( Li  et  al.  2 0 1 8)   m a y  b e
a p pli e d.
F urt he r t y pes of a nal yses  o n P F S m a y be spe cifie d i n t he SA P.  
1 3. 4. 2  A n al ys es of  th e Sec o n d ar y  Effic ac y  En d p oi nts  
Hierarc hical testi n g will be em pl o ye d f or ke y sec o n dar y e n d p oi nts, w it h t he pri mar y e n d p oi nt 
P F S s er vi n g  as a  gate kee per. T he T y pe I err or rate w ill be a dj uste d acc or di n gl y t o s u p p ort 
la belli n g clai ms for ke y sec o n dary e n d p oi nts.  
S pecificall y,  t he f oll o wi n g proce d ures  will be i m ple me nte d to  ma i ntai n t he o ve rall T y pe I err or 
rate acr oss t h e pri mar y an d  t w o ke y sec o n dar y e n d p oi nts of t he st u d y at a n a dj uste d t w o -si de d 
si g nifica nce le vel al p ha fo r t he fi nal a nal ysis (for details  see Secti on  1 3. 1 1. 1 ). 
T he  pr i mar y efficac y  e nd p oi nt  a nal ysis will serve as t he gate kee per  f or the ke y s ec o n dar y  
e n d p oi nt a nal yses,  i.e., the  pr i mary  efficac y h y p ot hesis m us t be  rejecte d at t he t w o-si de d 
a dj uste d  si g nifica nce le vel al p ha bef ore t he efficac y  h y p otheses f or  the  sec o n dar y  efficac y 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 9 5  of 1 3 1  
e n d p oi nts  c a n  b e t est e d.  T h e k e y s e c o n d ar y  e n d p oi nts   will  b e t h e f oll o  wi n g (i n t h e or d er  of 
d es c e n di n g i  m p ort a n c e): 
•
K e y s e c o n d ar y  1: b est O  R  R
•
K e y s e c o n d ar y  2 :   O S
If t he pri mar y h y p othesis  is rejecte d, the  t w o key s ec o n dar y e n d p oi nts w ill be se q ue ntiall y teste d 
at the  t w o-si de d a dj uste d si g nifica nce le vel al p ha i n t he or der liste d ab o ve . If a n ul l h y p ot hesis is 
n ot rejecte d, for mal se q ue ntial testi n g  will be st op pe d  an d  o nly  n o m i nal si g nifica nce will be  
me nti o ne d f or the re mai ni n g sec o n dar y e n d p oi nts. A nal yses a n d p- val ues  will be re p orte d f or all 
t he efficac y e n d p oi nts, i ncl u di n g t he pri mar y e n d p oi nt, t he ke y s ec o n dar y e n d p oi nts, a n d a ll 
ot her sec o n dar y en d p oi nts liste d i n Secti o n  7. 2.  
N ot e t hat if t he primar y  en d p oi nt is  met f or  t he o verall (F A S)  p o p ulati o n, t he sec o n dar y 
e n d p oi nts  will be hierarc hicall y  teste d f or t he F A S p o p ul ati o n w it h t he al p ha that w as pr o vi de d 
for F A S .  
If t he pri mar y en d p oi nt  is n ot met f or t he F A S p o p ul ati o n, b ut is met i n t he NK C C -lo w 
s u b gr o u p, t he n t he sec o n dar y e n d p oi nts will be hierarc hicall y teste d f or t he N K C C -l o w s u b gr o u p 
wit h t he al p ha t hat was pr o vi de d f or t he N K C C -l o w s u b gr o u p (see Secti o n 1 3. 4. 1 ), ta ki n g i nt o 
acc o u nt t he c orrelati o n bet wee n t he s u b gr o u p a n d the o ve rall p o p ulati o n (F A S)  wit h  regar ds  t o 
t he sec o n dar y e n d p oi nt co nsi dere d. . 
If the p ri mar y e n d p oi nt is n ot m et in t he o ve rall p o p ulati o n 
 
, t here w ill n ot be an y al p ha left to carr y o ve r for t he sec o n dar y e n d p oi nt s. I n t his 
sit uati o n, a nal ysis o f the sec o n dar y e n d p oi nts w ill be pe rf or me d f or the 
 
 as e x pl orat ory a nal yses. T he p- val ues  will be prese nte d  f or ill ustrati ve 
p ur p oses o nl y. 
1 3. 4. 2. 1  Best  O bjecti ve  Res po nse R ate 
O bjecti ve res p o nse is defi ne d  whe n  a patie nt  is classifie d as ha vi n g  a C R  or PR  after D L B C L  
e val uati o n usi n g t he I nter nati o nal W or ki n g Gr o u p r es p o nse  criteria f or mali g na nt l y m p h o ma  
( C hes o n et al. ( 2 0 0 7); see A p pe n di x L ). 
F or eac h  visit a vaila ble, the n u m ber (c o u nts an d perce nta ges) of pa tie nts i n eac h of t he foll o wi n g 
cate g ories will  be pres e nte d  in  a ta ble: pr o gressi ve disease, S D,  PR , C R  a n d o bj ecti ve res p o nse 
( C R or P R ). Ta b ulati o n will  s h o w missi n g res p o nse e val uati o ns as well, i ncl u di n g these patie nts 
i n t he den o mi nat or f o r calc ulati n g  the  rates. DL B C L  res p o nse assess me nts of lo cal a n d I RC 
e val uati o ns will be ta b ulate d. 
T he  best  O R R is defi ne d as t he pr o p orti o n of pati e nts  wit h CR  or P R (see Secti o n 6. 2 ). 
T he de n o mi nat or for calc ulati n g t he rate s/ perce nta ges will be base d u p o n t he total n u m ber of 
patie nts in t he F A S p o p ulati o n (a n d i n t he N K C C-l o w su b gr o u p of the F A S). Patie nts w it h n o 
p ost- baseli ne assess me nt  of res p o nse  will be i ncl u de d as n o nres p o n ders.  Res p o nse rates will  be 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 6  of 1 3 1  
e v al u at e d  usi n g t h e l o c al  a n d t h e  c e ntr al  e v al u ati o n  of t h e I  R  C. F or t h e I  R  C  e v al u ati o ns t h e b est 
O  R  R  f or  e a c h tr e at  m e nt  ar  m   will  b e t h e r at e  of  p ati e nts   w h o   m et t h e o bj e cti v e r es p o ns e 
d efi niti o n  u p  u ntil t h e l ast  a v ail a bl e t u  m ou r  ass ess  m e nt.  T h e  n u  m b er  of  p ati e nts  cl assifi e d  as 
r es p o n d ers  a n d t h e r es p e cti v e r at es  as   w ell  as  9 5  % CI s (  Cl o p p er-P e ars o n)   will  b e  pr es e nt e d. T h e 
b est O  R  R s will  als o  b e  c o  m p ar e d  b et  w e e n tr e at  m e nts  usi n g t h e   C o chr a n -M a nt el -H a e ns z el t est 
str atifi e d  b y r a n d o  mis ati o n str at a. 
 
B est r es p o ns e   will  b e  d et er  mi n e d   wit h r es p e ct t o  all r es p o ns e  e v al u ati o ns  gi v e n  u ntil l ast 
a v ail a bl e t u  m o u r  ass ess  m e nt.   B est r es p o ns e r at es   will  b e  d es cri pti v el y t a b ul at e d  as t h e b est O  R  R, 
disti n g uis hi n g  b et  w e e n t h e l o c al  a n d t h e  c e ntr al r a di ol o gi c al  e v al u ati o n. 
 
T h e  b est O  R  Rs   m a y  als o  b e  e x pl or e d   wit hi n f urt h er s u b gr o u ps ot h er t h a n   N  K  C  C -l o  w.   D et ails 
will  b e  pr o vi d e d   wit hi n t h e  S  A P.  
 
1 3. 4. 2. 2  D u r ati o n  of R es p o ns e  
D o  R is d efi n e d  as t h e ti  m e el a ps e d b et  w e e n t h e i niti al ti  m e  p oi nt  of t u  m o ur r es p o ns e (  C  R  or  P  R) 
a n d t h e ti  m e  of d o c u  m e nt e d t u  m o ur  pr o gr essi o n.   R es p o ns e  d ur ati o n   will  b e t a b ul at e d f or r es ults 
gi v e n  b y t h e l o c al  ass ess  m e nt  as   w ell  as  b y t h e  c e ntr al  ass ess  m e nts  of t h e I  R  C. D es cri pti v e 
a n al ysis   will  b e  d o n e f or   D  O  R  a  m o n g  p ati e nts   w h o r es p o n d e d i n  e a c h  ar  m f or t h e  o v er all 
p o p ul ati o n  a n d f or t h e   N  K  C  C -l o  w s u b gr o u p. 
 
1 3. 4. 2. 3  Dis e as e C o nt r ol R at e  
D  C  R is  d efi n e d  as  h a vi n g  a r es p o ns e  of   C  R,  P  R  or  S  D (  D  C  R  =   O  R R  +  S  D).  T h e   D  C  R   will  b e 
e v al u at e d  as f or t h e  b est   O  R  R.  
 
1 3. 4. 2. 4  Ti  m e t o  P r o g r essi o n  
T T P is  d efi n e d  as t h e ti  m e fr o  m r a n d o  mi sati o n  u ntil  d o c u  m e nt e d   D L  B  C L  pr o gr essi o n  or  d e at h  as 
a r es ult  of l y  m p h o  m a.  T h e  e v e nt  of i nt er est is  o nl y  dis e as e  pr o gr essi o n  a n d  d e at h fr o  m 
l y  m p h o  m a;  d e at h fr o  m  ot h er  c a us es   will  n ot  b e  c o nsi d er e d i n r elati o n t o t h e  T T P  e v al u ati o n.  
 
P ati e nts  n ot  e x p eri e n ci n g  dis e as e  pr o gr essi o n   will  b e  c e ns or e d  at t h e l ast a v ail a bl e D L  B  C L 
ass ess  m e nt. P ati e nts  d yi n g fr o  m  ot h er  c a us es   will  b e  c e ns or e d  at t h e ti  m e  of  d e at h.  E arl y 
dr o p -o uts   wit h o ut  a n y  d o c u  m e nt e d  d at e  of  pr o gr essi o n   will  b e  c e ns or e d  at t h e l ast a v ail a bl e 
D L  B  C L  ass ess  m e nt.  
 
T T P   will  b e  a n al ys e d  usi n g t h e s a  m e  e v e nt  a n al ysis s ets  as f or t h e  pri  m ar y effi c a c y  e n d p oi nt 
a nal ysis  of  P F S.  St atisti cs t o  b e r e p ort e d  a n d  gr a p hi c al vis u alis ati o ns   will  b e t h e s a  m e  as f or t h e 
pri  m ar y  effi c a c y  p ar a  m et er.  
 
T T P o n -st u d y will  b e  c o  m p ar e d   wit h t h e T T P  o n  e a c h  p ati e nt’s   m ost r e c e nt pri or t h er a p y  vi a 
t a b ul ate d d es cri pti v e st atisti cs.   A d diti o n all y, T T P  o n t h e p ati e nt’s m ost r e c e nt  pri or t h er a p y  will 
b e t est e d  as  a f a ct or i n  a C P  H m o d el   wit h str at ifi c ati o n f a ct ors  a n d  b o n e   m arr o  w i n v ol v e  m e nt t o 
d et er  mi n e if t his si g nifi c a ntl y i nfl u e n c es t h e  T T P of  p ati e nts u n d er st u d y tr e at  m e nt.  
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 7  of 1 3 1  
1 3. 4. 2. 5  O v e r all S u r vi v al  
O S is  d efi n e d  as t h e ti  m e fr o  m r a n d o  mis ati o n t o t h e  d at e  of  d e at h.  P ati e nts   w h o  ar e  ali v e  or   w h o 
dr o p  o ut  e arl y   will  b e  c e ns or e d  at t h e l ast  a v ail a bl e st u d y  visit  ass ess  m e nt.   A n al ysis str at e gi es 
will f oll o  w t h os e  a p pli e d f or t h e  pri  m ar y  effi c a c y  p ar a  m et er.  
 
1 3. 4. 2. 6  Ti  m e t o N e xt T r e at  m e nt  
T T  N T is  d efi n e d  as t h e t i  m e fr o  m r a n d o  mis ati o n t o t h e ti  m e  of i nstit uti o n  of  n e xt t h er a p y f or  a n y 
r e as o n i n cl u di n g  dis e as e  pr o gr essi o n, tr e at  m e nt t o xi cit y  a n d  p ati e nt  pr ef er e n c e.  T T  N T   will  b e 
s u  m  m arise d  b y tr e at  m e nt  gr o u p  a n d  pr es e nt e d  usi n g   K a pl a n -M ei er  c ur v es.  T T  N T  will  als o  b e 
a n al ys e d i n  a si  mil ar   m a n n er t o t h e  pri  m ar y effi c a c y  e n d p oi nt a n al ysis  usi n g  a str atifi e d l o g -r a n k 
t est  a n d  a   C P  H   m o d el.  S e nsiti vit y  a n al ys es   m a y  b e  p erf or  m e d  a n d   w o ul d  b e  o utli n e d i n t h e  S  A P. 
 
1 3. 5  Q u alit y  of   Lif e   Q u esti o n n ai r e s E  O  R  T  C   Q  L  Q -C 3 0  a n d  E  Q -5  D -5  L  
T h e E  O  R T  C   Q L  Q -C 3 0 is  c o  m p os e d  of  b ot h   m ulti -it e  m s c al es  a n d si n gl e-it e  m   m e as ur es.  T h es e 
i n cl u d es fi v e f u n cti o n al s c al es ( p h ysi c al f u n cti o ni n g, r ol e f u n cti o ni n g,  e  m oti o n al f u n cti o ni n g, 
c o g niti v e f u n cti o ni n g, s o ci al f u n cti o ni n g), t hr e e s y  m pt o  m s c ales (f ati g u e,  n a us e a  a n d  v o  miti n g, 
p ai n),  a gl o b al  h e alt h st at us/  Q o  L s c al e  a n d si x si n gl e it e  ms ( d ys p n o e a, i ns o  m ni a, l oss  of 
a p p etit e,  c o nsti p ati o n,  di arr h o e a, fi n a n ci al  diffi c ulti es).  E a c h  of t h e   m ulti -it e  m s c al es i n cl u d es  a 
diff er e nt s et  of it e  ms –  n o it e m  o c c urs i n   m or e t h a n  o n e s c al e.   A  hi g h s c al e s c or e r e pr es e nts  a 
hi g h er r es p o ns e l e v el. T h us,  a  hi g h s c or e f or  a f u n cti o n al s c al e r e pr es e nts  a  hi g h  or  h e alt h y l e v el 
of f u n cti o ni n g,  a  hi g h s c or e f or t h e  gl o b al  h e alt h st at us r e pr es e nts  a  hi g h  q u alit y  of lif e ,  b ut  a 
hi g h s c or e f or  a s y  m pt o  m s c al e  or s y  m pt o  m it e  m r e pr es e nts  a  hi g h l e v el  of s y  m pt o  m at ol o g y  a n d 
f u n cti o n al i  m p air  m e nt. 
 
T h e  E  Q -5  D -5 L  q u esti o n n air e  c o  m pris es  a  d es cri pti v e s yst e  m  a n d  a  vis u al  a n al o g u e s c al e (  V  A S). 
T h e  E  Q -5  D -5 L  c o nt ai ns fi v e  q u esti o ns ( m o bilit y, s elf -c ar e,  us u al  a cti viti es,  p ai n/ dis c o  mf ort,  a n d 
a n xi et y/ d e pr essi o n).   R es p o n d e nts  c o ul d  c h o os e  o n e  of t h e fi v e l e v els t o  d es cri b e t h eir  h e alt h 
st at e  o n t h e  d a y  of s ur v e y.  T h es e fi v e l e v els i n cl u d e  “ n o  pr o bl e  m ”,  “sli g ht  pr o bl e  ms ”,  “  m o d er at e 
pr o bl e  ms ”  a n d  “s e v er e  pr o bl e  ms ” i n  all fi v e  di  m e nsi o ns,  a n d  “ u n a bl e ” i n   m o bilit y, s elf -c ar e  a n d 
us u al  a cti viti es  or  “ e xtr e  m e  pr o bl e  ms ” i n  p ai n/ dis c o  mf ort  a n d  a n xi et y/ d e pr essi o n. T h e  h e alt h  of 
t h e r es p o n d e nt is i n di c at e d  b y  a ti c k  or  a  cr oss i n t h e  b o x  a g ai nst th e   m ost  a p pr o pri at e st at e  m e nt 
i n  e a c h  of t h e  5  di  m e nsi o ns.  T his  d e cisi o n r es ults i n  a  1-di git  n u  m b er  e x pr essi n g t h e l e v el 
s el e ct e d f or t h at  di  m e nsi o n.  T h e  di gits f or  5  di  m e nsi o ns  c a n  b e  c o  m bi n e d i n  a  5 -di git  n u  m b er 
d es cri bi n g t h e r es p o n d e nt’s  h e alt h st at e.  E  Q -5  D -5 L  h e alt h st at es,  d efi n e d  b y t h e  E  Q -5  D -5 L 
d es cri pti v e s yst e  m,   m a y  b e  c o n v ert e d i nt o  a si n gl e i n d e x  v al u e.  
 
A  v erti c al,  h as h -m ar k e d  vis u al  a n al o g u e s c al e ( E  Q -V  A S) is  a n c h or e d  b y  0 (t h e   w orst i  m a gi n a bl e 
h e alt h st at e)  at t h e  b ott o  m  a n d  1 0 0 (t h e  b est i  m a gi n a bl e  h e alt h st at e)  o n t h e t o p f or r es p o n d e nts 
t o r at e t h eir  o v er all  h e alt h. A  cr oss i n t h e  E  Q -5  D -5 L   V  A S s c al e i n di c at es  h o  w t h e r es p o n d e nt 
h e alt h is t o d a y  a n d t h e n t h e  n u  m b er is tr a ns cri b e d i n a b o x.  
 
S c ori n g  of  e a c h s c al e   will  b e  c al c ul at e d, f oll o  wi n g t h e r es p e cti v e   m a n u als.  T h e  b as eli n e 
ass ess  m e nt is t h e l ast  a v ail a bl e  ass ess  m e nt  b ef or e first i nf usi o n  of st u d y   m e di c ati o n.   D es cri pti v e 
st atisti cs f or  e a c h  of t h e s c or es   will  b e t a b ul at e d.   Als o,  c h a n g es f r o  m  b as eli n e f or  e a c h s c or e,  a n d 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 8  of 1 3 1  
n u  m b ers  of  p ati e nts   wit h i  m pr o v e  m e nt  a n d  d et eri or ati o n   will  b e s u  m  m aris e d  b y  visit.  F urt h er 
d et ail   will  b e  pr o vi d e d i n t h e  S  A P.  
 
1 3. 6  I  m  m u n o g e ni cit y   A n al ysis 
O n e  of t h e s e c o n d ar y o bj e cti v es will  b e t o  e v al u at e t h e  p ot e nti al i  m  m u n o g e ni cit y  of M  O  R 0 0 2 0 8  
i n t h e i  m  m u n o g e ni cit y  a n al ysis s et (I  A S).  T h e  a n al ysis   will s h o  w  b ot h t h e a bs ol ut e  n u  m b er  a n d 
p er c e nt a g e  of  p ati e nts   w h o  d e v el o p  a nti -M  O  R 0 0 2 0 8  a nti b o di es.   R es ults  of s e  mi -q u a ntit ati v e 
a nti-M  O  R 0 0 2 0 8  a nti b o d y titr e  d et er  mi n ati o ns  of  c o nfir  m e d  p ositi v e s a  m pl es   will  b e t a b ul at e d , as 
w ell  as t h e n u  m b er  a n d  p er c e nt a g e  of  p ati e nts  h a vi n g  p ositi v e  ass ess  m e nts.  C o nfir  m e d  p ositi v e 
a nti-M  O  R 0 0 2 0 8  a nti b o d y s a  m pl es   will  b e  c h ar a ct eri se d   wit h r es p e ct t o  n e utr ali si n g  c a p a cit y i n  a 
n e utr ali si n g  a nti b od y (  N  A b)  ass a y. 
 
1 3. 7  P h a r  m a c o ki n eti c   A n al ysis  
O n e  of t h e s e c o n d ar y  o bj e cti v es   will  b e t o i n v esti g at e t h e  P  K  pr ofil e  of   M  O  R 0 0 2 0 8  usi n g t h e  P  K 
a n al ysis s et ( P  K  A S) . P  K  p ar a  m et ers f or   M  O  R 0 0 2 0 8   will  b e  c o  m p ut e d  b as e d  o n  n o n -
c o  m p art  m e nt al  d at a  a n al ysis  a n d s u  m  m aris e d  usi n g  d es cri pti v e st atisti cs ( s u c h  as n,   m e a n, 
g e o  m etri c   m e a n, st a n d ar d  d e vi ati o n,  c o effi ci e nt  of  v ari ati o n,   m e di a n,   mi ni  m u  m  a n d   m a xi  m u  m). 
M e a n c o n c e ntr ati o ns ( o n  ori gi n al  a n d  o n l o g -li n e ar s c al e)  of M  O  R 0 0 2 0 8  will  b e  vis u alis e d i n 
fi g ur es.  F urt h er  d et ails  of  P  K  a n al ysis   will  b e s p e cifi e d i n t h e  S  A P. 
 
I n  a d diti o n, a p o p ul ati o n P  K  a n al ysis of   M  O  R 0 0 2 0 8  will  b e c o n d u ct e d .  T h e  pl a n n e d m et a -
a n al ysis   will  e n c o  m p ass P  K  d at a fr o  m   M  O  R 2 0 8  C 2 0 4  a n d  ot h er  cli ni c al tri als   wi t h   M  O  R 0 0 2 0 8. 
T h e  a n al ysis will  pr o vi d e  a n  u n d erst a n di n g  of t h e  p o p ul ati o n P  K of   M  O  R 0 0 2 0 8 a n d  d et er  mi n e  
t h e i nfl u e n c e  of i ntri nsi c  a n d  e xtri nsi c f a ct ors (s u c h  as  b ut  n ot li  mit e d t o  a g e,  g e n d er, r a c e, l e v el 
of  h e p ati c  or r e n al f u n cti o n  a n d  pr es e n c e  of  a nti -d r u g  a nti b o di es) t h at   m a y i nfl u e n c e P  K 
v ari a bilit y.  D et ails  of t h e i nt e n d e d p o p ul ati o n P  K a n al ysis  will  b e  d es cri b e d i n  a s e p ar at e 
p o p ul ati o n  P  K pr ot o c ol  a n d t h e r es ults will  b e  d es cri b e d i n  a s e p ar at e p o p ul ati o n  P  K st u d y  
r e p ort. 
 
1 3. 8  A n al ysis  of  S af et y   D at a  
1 3. 8. 1  A d v e rs e   E v e nts  
O n e  of t h e s e c o n d ar y  e n d p oi nts is t h e  e v al u ati o n  of t h e fr e q u e n c y, i n ci d e n c e,  a n d s e v erit y  of 
A Es.  
 
A Es   will  b e  c o d e d  a c c or di n g t o   M e d  D  R  A  S  O  C  a n d  pr ef err e d t er  ms. I n ci d e n c e a n d fr e q u e n c y of 
all   A Es   will  b e s u  m  m aris e d  b y  S  O  C,  pr ef err e d t er  m, r e l ati o ns hi p t o tr e at  m e nt, s e v erit y  a n d 
s eri o us n ess. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 9 9  of 1 3 1  
A n   A E s u  m  m ar y t a bl e   will  b e  pr es e nt e d s h o  wi n g t h e  n u  m b er  of  e v e nts,  n u  m b er  of  p ati e nts  a n d 
t h e  p er c e nt a g e  of  p ati e nts  h a vi n g: 
 
•  T r e at  m e nt-e  m er g e nt  a d v ers e  e v e nts ( T E  A Es)  
•  S  A Es  
•  D r u g-r el at e d  T E  A Es (s plit  b y   B E  N-,   M  O  R 0 0 2 0 8- a n d   R T  X -r el at e d  a n d  o v er all) 
•  D r u g-r el at e d  T E  A Es i n  e a c h s e v erit y/t o xi cit y  gr a di n g ( a c c or di n g t o N  CI -C T  C  A E ) 
•  T E  A Es t h at l e d t o st u d y  dis c o nti n u ati o n  
•  I  R  Rs  b y  gr a d e. 
 
I n  a d diti o n, t h e i n ci d e n c e r at e  of   A Es i n  e a c h  of t h e a b o v e-m e nti o n e d  c at e g ori es   will  b e 
pr es e nt e d   wit h  9 5  % CI s  b as e d  o n t h e  n u  m b er  of  p ati e nts  a n d t h e  n u  m b er  of   A Es. 
 
T h e  n u  m b er  of   A Es, i n r el ati o n t o t h e  n u  m b er  a n d  p er c e nt a g e  of  p ati e nts   wit h  o n e  or   m or e 
T E  A E s, will  b e s u  m  m aris e d  b y   M e d  D  R  A  S  O  C  a n d  pr ef err e d t er  m f or  e a c h tr e at  m e nt  ar  m.  S u c h 
s u  m  m ari es   will  b e  dis pl a y e d f or  all  T E  A Es,  T E  A Es  b y   m a xi  m u  m s e v erit y/t o xi cit y,  a n d  T E  A Es 
b y r el ati o ns hi p t o st u d y  dr u gs,  S  A Es,  dr u g -r el at e d  T E  A Es  a n d  T E  A Es t h at l e d t o st u d y 
dis c o nti n u ati o n.  
 
T h e s p o ns or   will  d es cri b e   A E SI s, i n  a d diti o n t o t h os e r e p ort e d  as  S  A Es.   A E SI t a b ul ati o ns   will  b e 
a n al o g o us t o t h e t a b ul ati o n  of  T E  A Es.  
 
1 3. 8. 2  Cli ni c al   L a b o r at o r y   E v al u ati o ns  
T h e  a n al ysis  of c e ntr al l a b or at or y  p ar a  m et ers f or  e a c h tr e at  m e nt  ar  m   will  be  pr es e nt e d, s e p ar at e d 
i nt o  bl o o d  p ar a  m et ers (e. g., h a e  m at ol o g y, s er u  m  c h e  mistr y,  c o a g ul ati o n)  a n d  uri n e  p ar a  m et ers 
( uri n al ysis).   All  d at a c oll e ct e d i n t h e  c o u rs e  of t h e st u d y will  b e list e d.  
 
D es cri pti v e s u  m  m ari es  of  a ct u al ( a bs ol ut e)  v al u es  a n d  c h a n g e -fro  m -b as eli n e  v al u es   will  b e 
pr es e nt e d ,  e. g., f or h a e  m at ol o g y  a n d s er u  m  c h e  mistr y f or t h e S  A F  b y  visit . 
 
E a c h  a b n or  m al  v al u e  m e as ur e d i n t h e  c e ntr al l a b or at or y will  b e fl a g g e d t o s h o  w   w h et h er it is  a 
v al u e  b el o  w  or  a b o v e t h e r ef er e n c e r a n g e.  F or t h e  ass ess  m e nt  of l a b or at or y  v ari a bl es, t h e 
i n v esti g at or   will  n e e d t o j u d g e t h eir  cli ni c al si g nifi c a n c e. 
T h e  ass ess  m e nt  of t h e  cli ni c al r el e v a n c e of c e ntr al l a b or at or y  v ari a bl es will  b e t a b ul at e d  b y ti  m e 
p oi nt f or  e a c h  cli ni c al l a b or at or y  a n al yt e  usi n g fr e q u e n c y t a b ul ati o ns. A d diti o n all y, f or  e a c h 
l a b or at or y  p ar a  m et er, s hifts i n  ass ess  m e nts fr o  m  b as eli n e t o s el e ct e d  p ost-a d  mi nistr ati o n ti  m e 
p oi nts   will  b e  pr es e nt e d.  F urt h er  d et ail s   will  b e  pr o vi d e d i n t h e  S  A P. 
 
If   N  CI-C T  C  A E  gr a d es  ar e  a v ail a bl e f or  a  cli ni c al l a b or at or y  a n al yt e, t h e y   will  b e  d eri v e d 
a c c or di n g t o   N  CI -C T  C  A E,   V ersi o n  4. 0  ( or  hi g h er),  a n d us e d t o  pr es e nt  a d diti o n al fr e q u e n c y  a n d 
s hift t a bl es  b as e d  o n   N  CI-C T  C  A E  gr a d es.  
 
T h e  ass ess  m e nt  of  c at e g ori c al  uri n al ysis  v ari a bl es   will  b e t a b ul at e d  b y ti  m e  p oi nt f or  e a c h  uri n e 
p ar a  m et er f or t h e S  A F  (fr e q u e n c y t a bl es). A d diti o n all y, f or  e a c h  of t h es e , uri n e  p ar a  m et er s hifts 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 0  of  1 3 1  
i n  ass ess  m e nts fr o  m  b as eli n e t o s el e ct e d  p ost-a d  mi nistr ati o n ti  m e  p oi nts   will  b e  pr es e nt e d (s hift 
t a bl es). 
 
C e ntr al l a b or at or y  v al u es t h at  ar e  o utsi d e t h e r ef er e n c e r a n g e   will  als o  b e fl a g g e d i n t h e  d at a 
listi n gs,  al o n g   wit h t h e  c orr es p o n di n g r ef er e n c e r a n g es. 
 
1 3. 8. 3  P h ysi c al   E x a  mi n ati o n  
B as eli n e P Es will  b e s u  m  m aris e d b y  b o d y s yst e  m.   N e  w  a n d   w ors e ni n g  a b n or  m al P E  fi n di n gs 
d uri n g t h e st u d y   will  b e  e nt er e d  as   A E s  a n d  a n al ys e d   wit hi n t h e   A E t a bl es. 
 
1 3. 8. 4  Vit al  Si g ns  
D es cri pti v e s u  m  m ari es  of  a ct u al  v al u es  a n d  c h a n g es fr o  m  b as eli n e   will  b e  c al c ul at e d f or  vit al 
si g ns.  T h es e s u  m  m ari es   will  b e  pr es e nt e d f or t h e S  A F  at  all ti  m e  p oi nts.  E a c h  a b n or  m al  v al u e 
will  b e fl a g g e d t o s h o  w   w h et h er it is  a  v al u e  b el o  w  or  a b o v e t h e  n or  m al li  mit. 
 
1 3. 8. 5  El e ct r o c a r di o g r a  ms ( 1 2 -l e a d   E  C  G) 
S u  m  m ar y  E  C  G  ass ess  m e nt ( c at e g ori es: ‘ n or  m al ’; ‘ a b n or  m al, cli ni c all y si g nifi c a nt ’; ‘ a b n or  m al, 
n ot  cli ni c all y si g nifi c a nt ’)   will  b e t a b ul at e d  b y ti  m e  p oi nt  usi n g fr e q u e n c y t a b ul ati o ns. 
 
E a c h r es ult  of t h e  1 2 -l e a d  EC  G ( P  R,   Q  R S,   R  R  a n d   Q T  i nt er v al  v al u es)   will  b e fl a g g e d t o s h o  w 
w h et h er it is  a  v al u e  b el o  w  or  a b o v e t h e  n or  m al li  mit.  
 
S u  m  m ar y st atisti cs f or  all ti  m e  p oi nts   will  b e  dis pl a y e d f or   Q T  a n d  b ot h   Q T c  c orr e cti o n   m et h o ds. 
T h e   B a z ett’s  c orr e cti o n   m et h o d (B a z ett  1 9 2 0 ) f or   Q T c   will  b e  a p pli e d  as f oll o  ws: 
 
B a z ett’s   C orr e cti o n (  Q T c B) 
R R
Q T
Q T c B
m s e c
=
 
 
T h e  Fri d eri ci a  c orr e cti o n   m et h o d (Fri d eri ci a  1 9 2 0 ) f or   Q T c   will  b e  a p pli e d  as f oll o  ws: 
 
Fri d eri ci a’s   C orr e cti o n (  Q T c F)  
3
s e c
R R
Q T
Q T c F
m
=
 
 
W h er e  r el ati v e r at e (  R  R)  =  6 0/ h e art r at e 
 
Als o, t h e  n u  m b er  a n d  p er c e nt a g e  of  p ati e nts   wit h   Q T c  v al u es  a b o v e t h e  n or  m al li  mit ( > 4 5 0   ms, 
> 4 8 0   ms,  > 5 0 0   ms)  a n d t h e  n u  m b er  a n d  p er c e nt a g e  of  p ati e nts   w h o  e x p eri e n c e d  a  c h a n g e 
≥ 3 0  ms  or  a  c h a n g e  ≥ 6 0  ms   will  b e  pr es e nt e d  b y ti  m e  p oi nt.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 1  of  1 3 1  
1 3. 9  Bi o  m a r k e rs  
1 3. 1 0  O t h e r D at a  
All  ot h er  d at a  as  d o c u  m e nt e d i n t h e  e  C  R F   will  b e list e d  a n d/ or t a b ul at e d  usi n g  d es cri pti v e 
st atisti cs  or  c o u nts/ p er c e nt a g es,  d e p e n di n g  o n t h e  n at ur e  of  d at a. 
 
1 3. 1 1  S a  m pl e  Si z e   D et e r  mi n ati o n  
A p pr o xi  m at el y  3 3 0  p ati e nts   wit h   R-  R   D L  B  C L   w h o   m e et t h e i n cl usi o n  crit eri a  a n d  h a v e  n o n e  of 
t h e  e x cl usi o n  crit eri a   will  b e r a n d o  mis e d i nt o  o n e  of t h e t  w o  p ar all el tr e at  m e nt  gr o u ps i n  a r ati o 
of  1: 1.  T h e st u d y   will  b e  p erf or  m e d  a c c or di n g t o  a t  w o- st a g e,  gr o u p-s e q u e nti al,  a d a pti v e  d esi g n 
wit h  a  p ossi bl e s a  m pl e si z e  a dj ust  m e nt  aft er  a  pl a n n e d i nt eri  m  a n al ysis   wit h  a  c h e c k f or f utilit y.  
  
T h e t  w o -st a g e,  gr o u p-s e q u e nti al,  a d a pti v e  d esi g n   wit h  o n e i nt eri  m  a n al ysis  a n d  a si n gl e  pri  m ar y 
e n d p oi nt   w as  e v al u at e d  b y si  m ul ati o ns t o i n v esti g at e t h e  a p pr o pri at e n ess  of t his  a p pr o a c h f or t h e 
st u d y  o bj e cti v es,  at t h e ti  m e  of t h e  ori gi n al st u d y  d esi g n.   Det ails  of t h e s e si  m ul ati o ns   will  b e 
gi v e n i n t h e  S  A P.  Pri or t o t h e i nt eri  m  a n al ysis , t h e st u d y  d esi g n   w as   m o difi e d t o i n c or p or at e o n e  
a d diti o n al c o-pri  m ar y  e n d p oi nt  ( b as e d  o n t h e   N  K  C  C-l o  w s u b gr o u p). F urt h er si  m ul ati o ns   w er e 
c o n d u ct e d  a n d  d et ails  of t h es e   will  als o  b e  pr o vi d e d i n t h e  S  A P. 
 
1 3. 1 1. 1  
P a r a  m et e rs  a n d R es ults  of S a  m pl e S i z e D et e r  mi n ati o n  
St u d y s a  m pl e si z e  esti  m ati o ns  a n d  ass u  m pti o ns b as e d  o n t h e  ori gi n al st u d y  d esi g n (i. e., wit h  a 
si n gl e  pri  m ar y  e n d p oi nt) ar e s u  m  m aris e d i n  T a bl e   8. T h e  pri  m ar y  o bj e cti v e  of t h e st u d y is t o 
d et e ct  a st atisti c all y si g nifi c a nt  diff er e n c e i n  P F S f or t h e  e x p eri  m e nt al tr e at  m e nt  ar  m r el ati v e t o 
t h e  c o  m p ar at or  ar  m.   At t h e ti  m e  of t h e  ori gi n al st u d y  d esi g n, it w as ass u  m e d t h at t h e   m e di a n  P F S 
i n t h e   M  O  R 0 0 2 0 8 wit h   B E  N   gr o u p   w o ul d  e q u al  7. 0   m o nt hs  v ers us  4. 9   m o nt hs i n t h e  c o  m p ar at or 
st a n d ar d tr e at  m e nt   R T  X wit h   B E  N gr o u p ( H  R   of  0. 7 0),  b as e d  o n lit er at ur e  d at a (O h  m a c hi  et  al. 
2 0 1 3 , V a cir c a  et  al.  2 0 1 4 ). A t  w o -st a g e,  gr o u p-s e q u e nti al,  a d a pti v e  d esi g n   wit h  o n e i nt eri  m 
a n al ysis w as  pl a n n e d .  T esti n g  of t h e  n ull  h y p ot h esis  at t h e fi n al  a n al ysis w o ul d  b e  b as e d  o n t h e 
i n v ers e  n or  m al   m et h o d  a p pl yi n g   O’  Bri e n- Fl e  mi n g  b o u n d ar y (O'  Bri e n  a n d  Fl e  mi n g  1 9 7 9 , 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 2  of  1 3 1  
W ass  m er  2 0 0 6 ).  T his  pr o c e d ur e  pr es er v es t h e  o v er all ( e x p eri  m e nt-wis e) t y p e I  err or r at e  of  α = 
0. 0 5 i n  a str o n g s e ns e f or  d at a- dri v e n  c h a n g es i n  d esi g n  aft er i nt eri  m  a n al ysis  of s ur vi v al tri als.  
 
B as e d  o n t h e  ori gi n al st u d y  d esi g n  a n d  ass u  m pti o ns,  a t ot al  n u  m b er  of  2 5 6  P F S  e v e nts  ar e 
r e q uir e d  b as e d  o n  a   H  R  of  0. 7 0   wit h  8 0  %  p o  w er  at fi n al  a n al ysis, usi n g  a t  w o -si d e d l o g-r a n k t est 
at  a n  al p h a l e v el  of  4. 8  %  a n d  a  1: 1 r a n d o  mis ati o n r ati o  b et  w e e n t h e t  w o tr e at  m e nt gr o u ps.   B as e d 
o n  1 8   m o nt hs  of  e nr ol  m e nt  a n d  a  1 2-  m o nt h  F oll o  w-  U p,  2 8 6 e v al u a bl e  p ati e nts  n e e d t o  b e 
e nr oll e d.   A p pl yi n g  a  1 3  %  dr o p- o ut r at e   w o ul d r es ult i n  a t ot al  n u  m b er  of  p ati e nts  of 
a p pr o xi  m at el y  3 3 0. 
 
T a bl e   8: 
Ass u  m pti o ns  f o r  S a  m pl e  Si z e   Esti  m ati o n ( o ri gi n al st u d y  d esi g n  a n d 
ass u  m pti o ns)  
P ar a  m et er f or s a  m pl e siz e  esti  m ati o n  
 
M  O  R 0 0 2 0 8   wit h   B E  N tr e at  m e nt  ar  m: m e di a n P F S  
7. 0   m o nt hs  
R T  X   wit h   B E  N tr e at  m e nt  ar  m: m e di a n P F S  
4. 9   m o nt hs  
H a z ar d r ati o ( e x p eri  m e nt al/ c o  m p ar at or)  
0. 7 0  
O v er all si g nifi c a n c e l e v el ( o v er all t y p e I  err or r at e  of  α) 
5. 0  %  
A dj ust e d si g nifi c a n c e l e v el  at i nt eri  m  a n al ysis ( O’  Bri e n- Fl e  mi n g)  
0. 5 2  %  
A dj ust e d si g nifi c a n c e l e v el  at fi n al  a n al ysis ( O’  Bri e n- Fl e  mi n g)  
4. 8  %  
P o  w er  
8 0  %  
E nr ol  m e nt  d ur ati o n (  m o nt hs)  
1 8  
F oll o  w -u p  d ur ati o n (  m o nt hs)  
1 2  
A c cr u al r at e  
A b o ut  1 7  p ati e nts/  m o nt h  
E v e nts r e q uir e d  
2 5 6  
E v al u a bl e  p ati e nts t o  b e  e nr oll e d  
2 8 6  
O v e r all  p ati e nt  n u  m b e r (i n cl u di n g  1 3 %  d r o p - o ut) 
3 3 0  
 
Wit h  pr o p os e d i ntr o d u cti o n  of  c o- pri  m ar y  e n d p oi nt i n   N  K  C  C-l o  w s u b gr o u p,  a n d  a s plit  of t ot al 
al p h a  of  4. 8  % i n t h e  o v er all ( F  A S)  p o p ul ati o n  a n d t h e N  K  C  C -l o  w s u b gr o u p, t h er e   will  b e  a 
c h a n g e i n t h e  p o  w er  of t h e t  w o- si d e d l o g r a n k t est if t h e t ot al  n u  m b er  of  o v er all ( F  A S) P F S 
e v e nts is  k e pt  u n c h a n g e d  at  2 5 6.  T h e t a bl e  b el o  w  pr es e nts t h e  ass u  m pti o ns  a n d t h e  p o  w er  as  a 
c o ns e q u e n c e  of  al p h a-s plitti n g  a n d i ntr o d u cti o n  of t h e  c o- pri  m ar y  e n d p oi nt: 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 3  of  1 3 1  
T a bl e   9: 
P o  w e r C al c ul ati o n f o r O v e r all  P o p ul ati o n  a n d t h e N  K  C  C -lo  w  S u b g r o u p ( as  a 
c o ns e q u e n c e  of a l p h a splitti n g)  u n d e r  diff e r e nt s c e n a ri os  
O v er all  P o p ul ati o n 
Ass u  m pti o n  
N =  3 3 0  
N = 4 5 0  
M e di a n  P F S  =  7  m  vs.  4. 9  m  
M e di a n  P F S  =  7  m  vs.  4. 9  m  
H a z ar d r ati o  =  0. 7  
H a z ar d r ati o  =  0. 7  
E v e nts  =  2 5 6  
E v e nts  = 3 6 9  
Al p h a  =  3. 4  %  
Al p h a  =  3. 4  %  
P o  w er  =  7 7  %  
P o  w er  =  9 0  %  
P ossi bl e  S c e n ari os f or   N  K  C  C -l o  w  S u b gr o u p  
O v er all  P o p ul ati o n  S a  m pl e 
Si z e  
N =  3 3 0  
N = 4 5 0  
N  K  C  C -l o  w S a  m pl e  Si z e  
1 3 2 ( 4 0  %)  
1 4 8 ( 4 5  %)  
1 6 5 ( 5 0  %)  
1 8 0 ( 4 0  %)  
2 0 2 ( 4 5  %)  
2 2 5 ( 5 0  %)  
M e di a n  P F S  (  m o nt hs) 
5  vs.  3  
5  vs.  3  
5  vs.  3  
5  vs.  3  
5  vs.  3  
5  vs.  3  
H a z ar d   R ati o  
0. 6  
0. 6  
0. 6  
0. 6  
0. 6  
0. 6  
E v e nts  
1 0 9  
1 2 3  
1 3 7  
1 5 4  
1 7 1  
1 9 1  
Al p h a (t  w o -si d e d) 
1. 4  %  
1. 4  %  
1. 4  %  
1. 4  %  
1. 4  %  
1. 4  %  
P o  w er  
0. 5 8  
0. 6 5  
0. 7 0  
0. 7 6  
0. 8 1  
0. 8 6  
 
Pr o p orti o n  of t ot al ev e nts  
0. 4 3  
0. 4 8  
0. 5 4  
0. 4 2  
0. 4 6  
0. 5 2  
Al p h a  a dj ust e d (t  w o -si d e d) * 
2. 0  %  
2. 2  %  
2. 3  %  
2. 0  %  
2. 1  %  
2. 2  %  
P o  w er  a dj ust e d  
0. 6 3  
0. 7 1  
0. 7 6  
0. 8  
0. 8 5  
0. 8 9  
*   Ass u  mi n g  c orr el ati o n  b et  w e e n t h e s u b gr o u p  a n d t h e  o v er all  p o p ul ati o n (S pi ess e ns  a n d   D e b ois  2 0 1 0 ). 
 
As  o utli n e d i n  S e cti o n  1 3. 1 2 ,  at t h e ti  m e  of t h e i nt eri  m  a n al ysis, t h e I  D  M  C   will  h a v e t h e  o pti o n 
of r e c o  m  m e n di n g  a n i n cr e as e i n s a  m pl e si z e t o  4 5 0  p ati e nts.  T h e st atisti c al  d et ails f or  a s a  m pl e 
si z e i n cr e as e t o  4 5 0  p ati e nts,  b as e d  o n t h e r e vis e d st u d y  d esi g n (i. e.,   wit h t  w o c o-pri  m ar y 
e n d p oi nts  a n d  al p h a s p e n di n g )  ar e s u  m  m ari z e d i n t h e  S  A P.  
 
I n  a d diti o n t o  P F S,   O S is  c o nsi d er e d  a n i  m p ort a nt  e n d p oi nt t o i nf or  m  b ot h  effi c a c y  a n d s af et y.  
T a bl e 1 0  b e l o  w  pr o vi d es  d et ails  o n t h e  o p er ati n g  c h ar a ct eristi cs f or   O S at t h e ti  m e  of  Fi n al 
A n al ysis: 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 4  of  1 3 1  
T a bl e 1 0 :  
O p e r ati n g   C h a r a ct e risti cs f o r   O S  at t h e  Fi n al   A n al ysis  
S a  m pl e  Si z e   C o nsi d e r ati o ns  
D et ails  
S a  m pl e  Si z e  
4 5 0  
M e di a n   O S i n  c o ntr ol  ar  m (  R T  X   wit h   B E  N)  
F ull  p o p ul ati o n:  1 0   m o nt hs  
N  K  C  C -l o  w s u b gr o u p:  7   m o nt hs 
M e di a n   O S i n  e x p eri  m e nt al  ar  m ( M  O  R 0 0 2 0 8  wit h   B E  N)  
F ull  p o p ul ati o n:  1 4. 3   m o nt hs  
N  K  C  C -l o  w s u b gr o u p:  1 1. 7 m o nt hs  
Ass u  m e d   O S   H  R  
F ull  p o p ul ati o n:  0. 7  
N  K  C  C -l o  w s u b gr o u p:  0. 6 
T est 
2- si d e d str atifi e d l o g-r a n k t est 
Gl o b al si g nifi c a n c e l e v el  
t  w o-si d e d  5  % 
E x p e ct e d   O S  e v e nts 1  
F ull  p o p ul ati o n:  3 3 8 1 
N  K  C  C -l o  w s u b gr o u p:  1 3 52 
L o c al t  w o -si d e d si g nifi c a n c e l e v el 
F ull  p o p ul ati o n:  3. 4  %  
N  K  C  C -l o  w s u b gr o u p:  1. 4  % 
P o  w er  at t h e ti  m e  of  Fi n al   A n al ysis  
F ull  p o p ul ati o n:  8 8  %  
N  K  C  C -l o  w s u b gr o u p:  7 0  %  
1 T h es e  n u  m b ers  ar e  b as e d  o n t h e  ass u  m pti o n t h at  Fi n al   A n al ysis   will  o c c ur   w h e n  a p pr o xi  m at el y  7 5  %  of  p ati e nts  h a v e  di e d  b ut 
usi n g l o c al si g nifi c a n c e l e v els  as st at e d i n  Fi g ur e  9 -1  of t h e  S  A P.  
2 Ass u  mi n g  4 0  %  of  all  p ati e nts  b el o n g t o t h e   N  K  C  C -l o  w s u b gr o u p. 
 
I n  c o n n e cti o n   wit h t h e  a b o v e, T a bl e 1 1  pr o vi d es t h e  p o  w er  c al c ul ati o ns f or   O S  gi v e n t h e 
diff er e nt  n u  m b er  of  p ossi bl e   O S  e v e nts i n t h e  F  A S  a n d t h e   N  K  C  C -l o  w s u b gr o u p: 
 
T a bl e 1 1 :  
P o  w e r   A n al ys es f o r   O S  
F ull  p o p ul ati o n  
N  K  C  C -l o  w s u b g r o u p 
N u  m b e r  of   O S 
e v e nts 
Inf o r  m ati o n 
f r a cti o n 
P o  w e r  
N u  m b e r  of   O S 
e v e nts 
I nf o r  m ati o n 
f r a cti o n 
P o  w e r  
2 5 0  
9 1  %  
7 6  %  
1 0 0  
6 1  %  
5 4  %  
2 7 5  
1 0 0  %  
8 0  %  
1 2 5  
7 6  %  
6 6  %  
3 0 0  
1 0 9  %  
8 4  %  
1 3 6  
( pr oj e ct e d f or 
Fi n al   A n al ysis)  
8 2  %  
7 0  %  
3 2 5  
1 1 8  %  
8 7  %  
1 5 0  
9 1  %  
7 5  %  
3 4 0  
( pr oj e ct e d f or 
Fi n al   A n al ysis)  
1 2 0  %  
8 8  %  
1 6 5  
1 0 0  %  
8 0  %  
3 5 0  
1 2 7  %  
8 9  %  
1 7 5  
1 0 6  %  
8 3  %  
* at t  w o -si d e d  al p h a  of  3. 4  % f or t h e  F  A S,  a n d  1. 4  % f or t h e   N  K  C  C-l o  w s u b gr o u p.  T h e  c al c ul ati o ns  ar e  b as e d  o n f oll o  wi n g 
ass u  m pti o ns:   m e di a n   O S f or   B  R i n  F  A S:  1 0   m o nt hs, tr u e  h a z ar d r ati o  of  0. 7;   m e di a n   O S f or   B  R i n   N  K  C  C -l o  w:  7   m o nt hs, tr u e 
h a z ar d r ati o  of  0. 6 .   
 
T h e  i nf or  m ati o n fr a cti on i n t h e  a b o v e t a bl e r ef ers t o t h e  n u  m b er  of   O S  e v e nts t h at   mi g ht  b e 
o bs er v e d  c o  m p ar e d t o t h e  c al c ul at e d  b e n c h  m ar k  n u  m b er  of   O S  e v e nts  at  8 0  %  p o  w er. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 5  of  1 3 1  
1 3. 1 2  I nt e ri  m A n al ysis  
T h e i nt eri  m  a n al ysis is  pl a n n e d  aft er t h e  o bs er v ati o n  of  5 0  %  o f t h e r e q uir e d  e v e nts, i. e.,  aft er 
1 2 8 P F S e v e nts.  T h e   H  R   will  b e  c al c ul at e d  a n d t hr e e  o ut c o  m es   will  b e  p ossi bl e  b as e d  o n t h e 
i nt eri  m r es ult.  T h e st u d y   m a y  b e st o p p e d  d u e t o f utilit y, t h e st u d y   m a y  c o nti n u e   wit h t h e 
mi ni  m u  m  pl a n n e d  n u  m b er  of  3 3 0  p ati e nts ( 2 5 6 P F S e v e nts),  or t h e s a  m pl e si z e m a y b e i n cr e as e d  
t o  4 5 0  p ati e nts (t o  o bt ai n  3 6 9  P F S  e v e nts). E arl y st o p pi n g f or  effi c a c y is  n ot  all o  w e d.  
 
T h e  p ossi bl e s c e n ari os  of  c o  m bi n ati o n  of  o bs er v e d  P F S  h a z ar d r ati os (  M  O  R 0 0 2 0 8  pl us   B E  N 
v ers us   R T  X  pl us   B E  N) i n t h e  F  A S  a n d   N  K  C  C -l o  w s u b gr o u p  a n d  p ot e nti al I  D  M  C 
r e c o  m  m e n d ati o ns b as e d  o n t h e  m ar e s u  m  m ari z e d i n T a bl e  1 2 .  
 
T a bl e   1 2:  
I  D  M  C D e cisi o n G ui d e B as e d  o n R es ults  of t h e Int e ri  m A n al ysis ( n o n -
bi n di n g)  
S c e n a ri o  
O bs e r v e d  P F S  h a z a r d  r ati o  at i nt e ri  m 
a n al ysis  
( e x p e ri  m e nt al  vs  c o  m p a r at o r  a r  m) 
I  D  M  C  r e c o  m  m e n d ati o n 
 
O v e r all  p o p ul ati o n  
N  K  C  C -l o  w 
s u b g r o u p 
 
1 
≤ 0. 7 5  
≤ 0. 6 5  
C o nti n u e tri al   wit h o ut s a  m pl e si z e   m o difi c ati o n  
( S S  = 3 3 0) , if  b ot h  c o n diti o ns  ar e   m et. 
2 
> 0. 8 5  
> 0. 7 5  
St o p f or f utilit y , if  b ot h  c o n diti o ns  ar e   m et. 
3 
All  ot h er s c e n ari os  
I n cr e as e s a  m pl e si z e t o  4 5 0 
 
I n  a d diti o n, t h e I  D  M  C   will r e c o  m  m e n d t o  c o nti n u e  or  n ot c o nti n u e t h e  d e v el o p  m e nt  of  a 
c o  m p a ni o n  di a g n osti c.  G ui d a n c e f or I  D  M  C r e c o  m  m e n d ati o ns   will   b e  pr o vi d e d i n t h e I  D  M  C 
c h art er. 
F or  c o nfir  m at or y  h y p ot h esis t esti n g  at t h e fi n al  a n al ysis, t h e i n v ers e  n or  m al   m et h o d  of 
c o  m bi ni n g t h e  p- v al u es   will  b e  us e d.  T his  pr o c e d ur e  pr es er v es t h e  o v er all ( e x p eri  m e nt -wis e) 
t y p e I  err or r at e  of  α  =  0. 0 5 (t  w o-si d e d). 
 
1 3. 1 3  P r o c e d u r es f o r   Missi n g,   U n us e d,  a n d  S p u ri o us   D at a  
Missi n g  v al u es   will  n ot  b e s u bstit ut e d  b y  esti  m at e d  v al u es  b ut   will  b e tr e at e d  as   missi n g i n t h e 
st atisti c al  e v al uati o n.   All  d at a fr o  m  all  p ati e nts r a n d o  mis e d i n t h e st u d y   will  b e i n cl u d e d i n  all 
listi n gs,  pl ots, s u  m  m ar y t a bl es,  a n d st atisti c al  a n al ys es   wit h r es p e ct t o t h e  a n al ysis  p o p ul ati o ns 
assi g n e d t o t h e  v ari o us  o bj e cti v es.  
 
1 3. 1 4  R ul es f o r   E x cl u di n g  P ati e nts f r o  m A n al ysis  
All  d os e d  p ati e nts   will  b e i n cl u d e d i n t h e  a n al ys es  u nl ess  n ot  ot h er  wis e s p e cifi e d ( e. g. , wit h 
r es p e ct t o t h e  diff er e nt  a n al ysis  p o p ul ati o n  d efi niti o ns). 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 0 6  of  1 3 1  
1 3 . 15  Pr oce d ures  f or Re p orti n g De vi ati o ns fr o m  Ori gi n al  St atistic al Pl a n 
Details of  the a nal yses  t o be perfor me d  o n data fr o m t his st u d y will be pr o vi de d i n a se parate 
S A P. A n y de viati o ns fr o m the statistical anal ysis o utli ne d i n t his pr ot oc ol will be de scri be d, a n d 
reas o ns f or t he deviati o ns  liste d, i n t he fi nal cli nical st u d y re p ort. 
1 4  S P E CI A L  RE Q UI R E M E N T S  AN D  P R O C E D U R E S  
1 4 . 1 I n de pe n dent D at a M o nit ori n g C o m mittee  (I DM C)  
T he de sig n of the stu d y s pecifies t he esta blis h me nt of a n  I DM C  acc or di n g  t o t he I C H E 9  
g ui deli ne an d i n li ne w it h t he rec o m me n dati o ns of the U S  F D A G ui da nce o n “ Est a blis h me nt a n d 
O per ati o n  o f Cli nic al Tri al D at a M onit ori n g  Co m mittees ” (Marc h 2 0 0 6 ). The  ID M C  will be  
res p o nsi ble f or pe ri o dically m o nit ori n g st u d y e nr ol me nt statistics, c o m plia nce, a n d efficac y a n d 
safet y data fr o m the o n g oi n g trial a n d f or alerti n g t he sp o ns or of p os sible c o ncer ns relate d t o the 
c o n d uct of t he trial. 
T he sp o ns or w ill ap p oi nt the I D M C pri or to t he ra n d o mi sati o n of t he first patie nt i nt o  the  st u d y. 
As  t he co m bi nati o n  of M O R 0 0 2 0 8 an d  BE N  w ill be syste maticall y  e val uate d  f or t he first ti me i n 
a setti n g  of a cli nical trial, I DM C  revie w  will be ma n date d d uri n g I nitia l Sa fet y E val uati o n 
(P h ase  II of t he trial) t o c o ncl u de w het her t he c o m bi nati o n treat me nts  are safe (see Fi g ure 1 ). 
I n t he co urse of I nitial Safet y E val uati o n, t he  first t hree patie nts in b ot h i n vesti gati o nal ar ms 
( M O R 0 0 2 0 8 + B E N a n d R T X + B E N)  will be d ose d se q ue ntiall y wit h a 4 8- h o ur la g peri o d 
bet wee n t he enr ol me nt s of tw o c o nsec uti ve p atie nts (c o u nte d fr o m C 1 D 4). 
Af ter c o m pleti o n o f t he first treat me nt wee k ( C1 D 8) b y  t he thir d  co nsec uti ve  pa tie nt i n eac h  ar m 
(a p pr o xi matel y 6 patie nts in t otal) the safet y data w ill be re vie we d b y t he I D M C. 
F oll o wi n g a p ositi ve rec o m me n dati o n of the ID M C, se ve n a d diti o nal pa tie nts i n eac h  ar m  ma y 
be  d ose d i n paralle l (a p pr o xi matel y  14  pa tie nts i n t otal). A n  ad diti o nal I D M C  revie w  will ta ke  
place  after t he last of 1 0 pa tie nts i n eac h  ar m (a p pr o xi matel y 2 0  patie nts in  t otal) ha ve co m plete d  
C 3 D 1  visit i n t heir res pecti ve treat me nt all ocati o n ar m (c o m plete I nitial Safet y Eval uati o n).  
T he e xact n u m ber of patie nts eli gi ble f or e val uati o n de pe n ds o n t he treat me nt all ocati o n w it hi n 
t he ra n d o misati o n bl oc ks. Furt her m ore, f or e ver y patie nt w h o wit h dra ws or disc o nti n ues i n t he 
c o urse of I nitial Safet y E val uati o n bef ore ha vi n g recei ve d st u d y dr u g o n C ycle 3 Da y 1, a ne w 
patie nt ma y be ra n d o mise d. F or a  sc he matic prese ntati o n of t he st u d y o utli ne, see Fi g ure 1 an d 
Fi g ure 2. 
S h o ul d  t he ID M C  mai ntai n t heir i nitial rec o m me n dati o n t hat t he co m bi nati o n  treat me nts are 
safe, t he trial ma y procee d  fur t her wit h recr uit me nt  (P hase  III of the  trial). S u bse q ue nt ID M C 
meeti n gs w ill be calle d f or as o ut li ne d i n t he I D M C C harter t hr o u g h o ut t he entire trial. 
Recr uit me nt  w ill c o nti n ue sea mlessl y be t wee n meeti n gs u nles s s pecificall y re q ueste d b y I D M C. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 7  of  1 3 1  
E a c h I  D  M  C r e vi e  w   will  e n c o  m p ass t h e  n u  m b er , fr e q u e n c y, s e v erit y a n d t y p e  of   A Es,  as   w ell  as 
cli ni c al l a b or at or y  bi o c h e  mistr y  a n d  h ae  m at ol o g y  p ar a  m et ers  a n d  ot h er r el e v a nt s af et y  d at a.  T h e 
I  D  M  C   will  als o a d vis e t h e s p o ns or w h et h er t h e tri al  d esi g n r e q uir es   m o difi c ati o ns  or  h as   m et t h e 
pr e- d efi n e d tri al st o p pi n g r ul es . 
 
I n  a d diti o n, t h e I  D  M  C   will  b e  e ntr ust e d t o  c o n d u ct t h e tri al’s  pl a n n e d i nt eri  m  a n al ysis  as  a 
c o nfi d e nti al  pr o c ess.   Alt h o u g h t h e tri al   will  b e  c o n d u ct e d i n  a n  o p e n- l a b el f as hi o n,   w h er e 
i n v esti g at ors  a n d  p ati e nts  ar e  a  w ar e  of i n di vi d u al tr e at  m e nt  assi g n  m e nt  a n d  o ut c o  m e  at t h eir sit e, 
t h e r es ults  of t h e  c o  m p ar ati v e i nt eri  m  a n al ysis (tr e at  m e nt  ar  m  v ers us  c o  m p ar at or  ar  m)   will  o nl y 
b e  a v ail a bl e t o I  D  M  C   m e  m b ers. T his f ulfils t h e  n e e d  of r estri cti n g t h e  a n al ysis  c o n d u ct  a n d t h e 
dis cl os ur e  of  t h e i nt eri  m  a n al ysis r es ults t o  o nl y  a li  mit e d  a n d  pr e d et er  mi n e d  n u  m b er  of  p e o pl e 
f or t h e  p ur p os e  of   m ai nt ai ni n g t h e i nt e grit y  of t h e tri al. T h e ID  M  C   will  o p er at e  u n d er  a   C h art er 
t h at  d es cri b es t h e c o  m p ositi o n, r ol es  a n d r es p o nsi biliti es  of t h e  c o  m  mitt e e  a n d i d e ntifi es t h e 
m e  m b e rs  a n d t h e  c o nt a ct  p ers o ns r el e v a nt t o t h e tri al. All  ot h er  p ers o ns i n v ol v e d i n t h e tri al 
c o n d u ct   will r e  m ai n  bli n d e d t o t h e i nt eri  m  a n al ysis r es ults  u ntil t h e r e g ul ar  e n d  of t h e tri al  h as 
b e e n r e a c h e d ,  or  u ntil t h e tri al  h as  b e e n st o p p e d  e arli er ( d u e t o f utilit y,  or  b y  d e cisi o n  of t h e 
s p o ns or).   
 
T h e I  D  M  C   will  b e  a d vis or y t o t h e s p o ns or. T h e sp o ns or   will  b e r es p o nsi bl e f or r e vi e  wi n g t h e 
I  D  M  C r e c o  m  m e n d ati o ns, t o  d e ci d e   w h et h er t o  c o nti n u e  or t er  mi n at e t h e tri al  d u e t o f utilit y,  a n d 
t o  d et er  mi n e   w h et h er a n y  a  m e n d  m e nt t o t h e  pr ot o c ol  or  c h a n g es i n st u d y  c o n d u ct  ar e r e q uir e d. 
 
T h e i nf or  m ati o n  a b o ut f urt h er st u d y  c o n d u ct  aft er t h e i nt eri  m  a n al ysis   will  b e  us e d f or  a  p ossi bl e 
a  m e n d  m e nt  of t h e  e xisti n g tri al  pr ot o c ol  or  as  n e e d e d  b y t h e r e g ul at or y  a ut h oriti es. 
 
If t h e s p o ns or  d e ci d es t o st o p t h e tri al  d u e t o f utilit y,  dis cl os ur e  of t h e r es ults will  b e  p erf or  m e d 
as  us u al f oll o  wi n g t h e  d efi n e d  pri n ci pl es  at  a fi n al  a n al ysis. If t h e s p o ns or  d e ci d es t o  c o nti n u e t h e 
tri al  or t o  c o nti n u e t h e tri al   wit h   m o difi c ati o ns, th e i nt eri  m r es ults   will  b e  k e pt  c o nfi d e nti al. 
I n v esti g at ors   will  o nl y  b e i nf or  m e d  a b o ut t h e  d e cisi o n t o  c o nti n u e/t o  c o nti n u e   wit h 
m o difi c ati o ns/ or t o  dis c o nti n u e t h e tri al.  
 
1 4. 2  I n d e p e n d e nt   R a di ol o g y/  Cli ni c al   R e vi e  w   C o  m  mitt e e  (I  R  C) 
T h e  pri  m ar y  e n d p oi nt, P F S ,   will  b e e v al u at e d t hr o u g h c e ntr al r e vi e  w  b y t h e I  R  C.  T h e  pr o c ess 
will  b e  d efi n e d i n d et ails i n t h e t e xt  of t h e I  R  C   Ch art er . 
 
F or r a di ol o g y ass ess  m e nt, t  w o  pri  m ar y r e vi e  w ers (  R a di ol o g y   R e vi e  w ers   1  a n d  2)   will 
i n d e p e n d e ntl y r e vi e  w  e a c h  p ati e nt’s s c a ns  a c c or din g t o t h e I nt er n ati o n al   W or ki n g   Gr o u p 2 0 0 7 
r es p o ns e  crit eri a (C h es o n  et  al.  2 0 0 7 ).   A dj u di c ati o n   will  b e r e q uir e d if R a di ol o g y   R e vi e  w ers  1 
a n d  2  dis a gr e e  o n t h e  o ut c o  m es,  n a  m el y   D at e  of  Pr o gr essi o n,   B est   R es p o ns e,  a n d/ or   D at e  of 
I niti al   R es p o ns e. I n  or d er t o r es ol v e  dis cr e p a n ci es,   R e vi e  w er  3 (  A dj u di c at or)   will i n d e p e n d e ntl y 
e v al u at e t h e  c as e  i n  q u esti o n.   R e vi e  w er  3   will  h a v e si  m ult a n e o us a c c ess t o  all i  m a g es  a n d 
pr e vi o us  ass ess  m e nts (i . e., i  m a g es, i  m a g e  o v erl a ys, ti  m e  p oi nt  e v al u ati o ns,  a n d s u  m  m ar y 
fi n di n gs fr o  m  b ot h  pri  m ar y re vi e  w ers).   R e vi e  w er i d e ntit y   will  b e f ull y  bli n d e d.   R e vi e  w er  n a  m es 
will  n ot  b e a d d e d t o t h e i nf or  m ati o n  pr o vi d e d f or  a dj u di c ati o n,  a n d f urt h er  m or e, t h e  or d er i n 
w hi c h t h eir fi n di n gs  ar e  pr es e nt e d   will  b e r a n d o  mis e d  a cr oss  c as es t o  pr e v e nt  c o n diti o n e d  bi as. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 8  of 1 3 1  
R e vi e  w er  3   will  c h o os e t h e  ass ess  m e nt t h at  h e  or s h e  c o nsi d ers t o r e pr es e nt t h e   m or e  c orr e ct 
ass ess  m e nt  of t h e  o ut c o  m es i n t h e f oll o  wi n g  or d er  of  pr e c e d e n c e:   D at e  of  Pr o gr essi o n,   B est 
R es p o ns e,  a n d   D at e  of I niti al   R es p o ns e.  
 
F oll o  wi n g r a di o l o g y r e vi e  w, t h e fi n al r a di ol o g y  ass ess  m e nts  a n d  p ati e nt  cli ni c al  d at a   will  b e 
pr es e nt e d t o t h e  cli ni c al  o n c ol o gist   w h o   will d et er  mi n e t h e fi n al  o ut c o  m e f or  e a c h  p ati e nt  b as e d 
o n r e vi e  w  of  b ot h i  m a gi n g  a n d  cli ni c al  d at a.  
 
T h e  o ut c o  m e  of t his r e vi e  w is  eit h er t h e  P F S  d at e  or  a  c e ns or i n g d at e,   w hi c h is t h e  d at e  of l ast 
f oll o  w-u p   wit h o ut  e vi d e n c e  of  dis e as e  pr o gr essi o n f or  all  p ati e nts s u b  mitt e d f or r e vi e  w.  
 
1 4. 3  P r ot o c ol   A  m e n d  m e nts  a n d   Ot h e r   C h a n g es i n  St u d y   C o n d u ct  
A n y  c h a n g es t o t h e  pr ot o c ol   will  b e   m a d e i n t h e f or  m  of  a n  a  m e n d  m e nt. 
 
C h a n g es t o t h e  c o n d u ct  of t h e st u d y  ar e  n ot  p er  mitt e d.   A n y  u nf or es e e n  c h a n g es i n t h e st u d y 
c o n d u ct   will  b e r e c or d e d i n t h e  cli ni c al st u d y r e p ort.  
 
1 4. 4  R e g ul at o r y  a n d   Et hi c al   C o nsi d e r ati o ns, I n cl u di n g t h e I nf o r  m e d   C o ns e nt 
P r o c ess  
Pri o r t o i niti ati o n  of  a st u d y sit e, I n c yt e   C or p or ati o n will  o bt ai n f a v o ur a bl e  o pi ni o n/ a p pr o v al 
fr o  m t h e  a p pr o pri at e r e g ul at or y  b o di es/l o c al  h e alt h  a ut h oriti es (i n  a c c or d a n c e   wit h l o c al 
r e g ul ati o ns)  a n d t h e I  R  B/I E  C t o  c o n d u ct t h e st u d y i n  a c c or d a n c e   wit h I  C  H   GC P  a n d  a p pli c a bl e 
c o u ntr y -s p e cifi c r e g ul at or y r e q uir e  m e nts. 
 
N o s u bst a nti al  c h a n g es t o t h e fi n al  a p pr o v e d  pr ot o c ol   will  b e i niti at e d   wit h o ut t h e I  R  B’s/I E  C’s 
pri or   writt e n  a p pr o v al  or f a v o ur a bl e  o pi ni o n  a n d  a p pr o v al  b y t h e r e g ul at or y  b o di es/l o c al  h e alt h 
a uth oriti es,  e x c e pt   w h e n  n e c ess ar y t o  eli  mi n at e i  m  m e di at e  h a z ar ds t o t h e  p ati e nts  or   w h e n t h e 
c h a n g e i n v ol v es  o nl y l o gisti cs  or  a d  mi nistr ati o n.  
 
T his  cli ni c al st u d y   w as  d esi g n e d  a n d s h all  b e  c o n d u ct e d  a n d r e p ort e d i n  a c c or d a n c e   wit h t h e 
pr ot o c ol,   wit h I  C  H E 6   G  C P  g ui d eli n es,   wit h  a p pli c a bl e l o c al r e g ul ati o ns,  a n d   wit h t h e  et hi c al 
pri n ci pl es l ai d  d o  w n i n t h e   D e cl ar ati o n  of   H elsi n ki, i n cl u di n g,  b ut  n ot li  mit e d t o:  
•  I  R  B/I E  C r e vi e  w  a n d f a v o ur a bl e  o pi ni o n/ a p pr o v al  of t h e st u d y  pr ot o c ol  a n d  a n y 
s u bs e q u e nt  a  m e n d  m e nts 
•  P ati e nt i nf or  m e d  c o ns e nt  
•  In v esti g at or r e p orti n g r e q uir e  m e nts . 
 
T h e i n v esti g at or   will  o bt ai n fr e el y  gi v e n   writt e n  c o ns e nt fr o  m  e a c h  p ati e nt  aft er  a n  a p pr o pri at e 
e x pl a n ati o n  of t h e  ai  ms,   m et h o ds,  a nti ci p at e d  b e n efits,  p ot e nti al  h a z ar ds  a n d  a n y  ot h er  as p e ct  of 
t h e st u d y t h at is r el e v a nt t o t h e  p ati e nt's  d e cisi o n t o  p arti ci p at e. 
 
I nf or  m e d co ns e nt   m ust  b e  gi v e n  b y t h e  p ati e nt  b ef or e t h e  p ati e nt is  e x p os e d t o  a n y st u d y -r el at e d 
pr o c e d ur e, i n cl u di n g s cr e e ni n g t ests f or  eli gi bilit y.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 0 9  of 1 3 1  
1 4. 5  Q u alit y   C o nt r ol ( St u d y   M o nit o ri n g)  
St u d y   m o nit ori n g   will  b e  p erf or  m e d i n  a c c or d a n c e   wit h I  C  H  E 6   G  C P  g ui d eli n es, t h e s p o ns or’s 
a n d   C  R  O’s  S  O Ps, t h e s p o ns or’s  a n d   C  R  O’s   writt e n i nstr u cti o ns, t h e  pr ot o c ol,  a n d  all  a p pli c a bl e 
l a  ws  a n d r e g ul ati o ns.  
 
T h e s p o ns or’s   m o nit ors   will  c o nt a ct t h e si t e  pri or t o t h e st art  of t h e st u d y t o r e vi e  w   wit h t h e sit e 
st aff t h e  pr ot o c ol, st u d y r e q uir e  m e nts,  a n d t h eir r es p o nsi biliti es t o s atisf y r e g ul at or y,  et hi c al,  a n d 
t h e s p o ns or’s r e q uir e  m e nts.  
 
I n c yt e   C or p or ati o n a n d t h e   C  R  O  will   m o nit or t h e st u d y t o  e ns ur e t h at t h e: 
•  D at a  ar e  a ut h e nti c,  a c c ur at e,  a n d  c o  m pl et e  
•  S af et y  a n d ri g hts  of  p ati e nts  ar e  b ei n g  pr ot e ct e d  
•  S t u d y is  c o n d u ct e d i n  a c c or d a n c e   wit h t h e  c urr e ntl y  a p pr o v e d  pr ot o c ol  a n d  a n y  ot h er 
st u d y  a gr e e  m e nts,   G  C P,  a n d  all  a p pli c a bl e r e g ul at or y r e q uir e  m e nts. 
 
T h e i n v esti g at or  a n d t h e  h e a d  of t h e   m e di c al i nstit uti o n (  w h er e  a p pli c a bl e)  a gr e e t o  all o  w t h e 
m o nit or  dir e ct  a c c ess t o  all s o ur c e  d at a  d o c u  m e nts.  
 
1 4. 6  Q u alit y   Ass u r a n c e  
A c c or di n g t o I  C  H  E 6   G  C P  g ui d eli n es, t h e s p o ns or  or r e g ul at or y  a ut h oriti es   m a y  a u dit t h e 
i n vesti g ati o n al sit es.  T h e s p o ns or’s   Q u alit y   Ass ur a n c e   U nit  a n d/ or t h eir  a ut h oris e d 
r e pr es e nt ati v e(s), i n d e p e n d e nt  of t h e   Cli ni c al   O p er ati o ns  a n d   Cli ni c al   D e v el o p  m e nt 
D e p art  m e nt s,  ar e r es p o nsi bl e f or  a u diti n g t h e st u d y.  T h e i n v esti g at or   m ust  a c c e pt s u c h  a u dits  b y 
t h e s p o ns or’s   Q u alit y   Ass ur a n c e   U nit  a n d/ or t h eir  a ut h oris e d r e pr es e nt ati v e(s)  a n d  e ns ur e  a c c ess 
t o  all s o ur c e  d at a/ d o c u  m e nts. 
 
T h e i n v esti g at or   m ust  a c c e pt t h at r e g ul at or y  a ut h oriti es   m a y  c o n d u ct  a n i ns p e cti o n t o  v erif y 
c o  m pli a n c e  of t h e st u d y wit h   G  C P  g ui d eli n es. If i nf or  m e d t h at  a r e g ul at or y i ns p e cti o n   will t a k e 
pl a c e, t h e i n v esti g at or   m ust i nf or  m t h e s p o ns or   wit h o ut  d el a y.  
 
1 4. 7  I ns u r a n c e 
T his st u d y is  c o v er e d  u n d er t h e s p o ns or’s  Li a bilit y I ns ur a n c e  P oli c y  c o v eri n g d a  m a g e t o  p ati e nts 
a c c or di n g t o a p pli c a bl e l e g al r e q uir e  m e nts .   A  c o p y  of t h e   C ertifi c at e  of I ns ur a n c e  a n d/ or  a n 
i nf or  m ati o n l e afl et  c o nt ai ni n g  ess e nti al i nf or  m ati o n  a b o ut t h e i ns ur a n c e  c o v er a g e   will  b e 
pr o vi d e d t o t h e i n v esti g at or  as r e q uir e d  b y   R e g ul at or y   A ut h oriti es, I  R  Bs  or I E  Cs.  
 
T h e  i n v esti g at or   m ust i nf or  m t h e  p ati e nts  a c c or di n gl y  a n d   m ust  als o  p oi nt  o ut t h at t h e  p ati e nts 
ar e  all o  w e d t o  u n d er g o  ot h er   m e di c al tr e at  m e nt ( e x c e pt i n  a n  e  m er g e n c y)  o nl y   wit h t h e 
i n v esti g at or’s  pri or  a p pr o v al  or t o r e c ei v e  a d diti o n al   m e di c ati o n  o nl y   wit h th e i n v esti g at or’s  pri or 
a p pr o v al. 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 0  of  1 3 1  
1 4. 8  P u bli c ati o n  P oli c y  
A n y  pr es e nt ati o n  or  p u bli c ati o n  of  d at a fr o  m t his st u d y   will  b e i nt e n d e d  as  a j oi nt  p u bli c ati o n  b y 
t h e i n v esti g at or(s)/ a p pr o pri at e st u d y  c e ntr e  p ers o n n el  a n d  a p pr o pri at e s p o ns or  p ers o n n el. 
A ut h ors hi p   wi ll f oll o  w t h e I nt er n ati o n al   C o  m  mitt e e  of   M e di c al J o ur n al  E dit ors 
R e c o  m  m e n d ati o ns f or t h e   C o n d u ct,  R e p orti n g,  E diti n g,  a n d  P u bli c ati o n  of  S c h ol arl y   W or k i n 
M e di c al  J o ur n als  (htt p://  w  w  w.i c  mj e. or g/r e c o  m  m e n d ati o ns/ )  a n d   will  b e  d efi n e d  pri or t o t h e first 
p u bli c ati o n. 
 
F or   m ulti c e ntr e st u di es, it is   m a n d at or y t h at t h e first  p u bli c ati o n  b e  b as e d  o n  d at a fr o  m  all 
c e ntr es,  a n d t h at t h e  d at a  ar e  a n al ys e d  a n d s u b  mitt e d  as sti p ul at e d i n t h e  pr ot o c ol  b y  a st atisti ci a n 
assi g n e d  b y t h e s p o ns or. 
 
T h us,  n o i n v esti g at or  or i nstit uti o n   m a y  p u blis h  a n y r es ults  of t h e st u d y  c o n d u ct e d  at t h eir sit e, 
b ef or e s u c h  a first   m ulti c e ntr e  p u bli c ati o n is   m a d e   w hi c h  c o v ers t h e  d at a fr o  m  all  c e n tr es. T h e 
a ut h ors  h a v e t h e fi n al r es p o nsi bilit y f or t h e  d e cisi o n t o s u b  mit t h eir   m a n us cri pt  a n d s h all  b e 
gi v e n f ull  a c c ess t o t h e  d at a r es ulti n g fr o  m t h e st u d y.  
 
T h e  c o or di n ati n g i n v esti g at or  a n d/ or  a ut h ors s h all  c o or di n at e  a n y i nt e n d e d  p u bli c ati o n  of st u d y 
r es ults   wit h t h e s p o ns or, t o  e n a bl e t h e s p o ns or t o  e ns ur e t h at r es ults  ar e  pr es e nt e d i n  a 
r es p o nsi bl e  a n d  c o h er e nt   m a n n er. 
 
T h e s p o ns or r es er v es t h e ri g ht t o r e vi e  w  all   m a n us cri pts  a n d  a bstr a cts  at l e ast  6 0  d a ys  b ef or e 
t h eir s u b  missi o n f or  p u bli c ati o n  or pr es e nt ati o n.  T his is  n ot i nt e n d e d t o r estri ct  or  hi n d er 
p u bli c ati o n  or  pr es e nt ati o n,  b ut is t o  all o  w t h e s p o ns or t o  pr ot e ct t h e  c o nfi d e nti alit y  of 
i nf or  m ati o n  a n d t o  pr o vi d e  c o  m  m e nts t h at   m a y  n ot  y et  b e  a v ail a bl e t o t h e i n v esti g at or. 
 
At t h e s p o ns or’s r e q u est,  a n y  c o nfi d e nti al i nf or  m ati o n ( ot h er t h a n st u d y r es ults)   will  b e  d el et e d 
a n d  all r e as o n a bl e  c o  m  m e nts   m a d e  b y t h e s p o ns or   will  b e i n c or p or at e d  pri or t o t h e s u b  missi o n 
f or  p u bli c ati o n  or  pr es e nt ati o n. I n t h e r ar e  e v e nt t h at s u c h  p u bli c ati o n   w o ul d  aff e ct t h e 
p at e nt a bilit y  of  a n y i n v e nti o n t o   w hi c h t h e s p o ns or  h as ri g hts, t h e s p o ns or  h as t h e ri g ht t o r e q u est 
a n  a d diti o n al  d el a y t o t h e  pr o p os e d  p u bli c ati o n  of  n o   m or e t h a n  9 0 d a ys s o  as t o  all o  w t h e 
s p o ns or t o  pr ot e ct its i nt ell e ct u al  pr o p ert y ri g hts. 
 
T h e r es ults  of t h e st u d y   m a y  b e  us e d  b y I n c yt e   C or p or ati o n f or t h e  p ur p os es  of  n ati o n al  a n d 
i nt er n ati o n al r e gistr ati o n,  p u bli c ati o n,  a n d i nf or  m ati o n f or   m e di c al  pr of essi o n als. If  n e c ess ar y, 
t h e  a ut h oriti es   will  b e  n otifi e d  of t h e i n v esti g at ors’  n a  m es,  a d dr ess es,  q u alifi c ati o ns,  a n d  e xt e nt 
of i n v ol v e  m e nt. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 1  of 1 3 1  
1 5  R  E F  E  R  E  N  C  E S  
A n d ers o n   K  C,   B at es   M P,  Sl a u g h e n h o u pt   B L,  Pi n k us   G S,  S c hl oss  m a n  S F  a n d   N a dl er  L  M. 
E x pr essi o n  of  h u  m a n   B  c ell -ass o ci at e d  a nti g e ns  o n l e u k e  mi as  a n d l y  m p h o  m as:  a   m o d el  of 
h u  m a n   B  c ell diff er e nti ati o n. Bl o o d  1 9 8 4; 6 3 ( 6):  1 4 2 4-1 4 3 3.  
Ar  mit a g e J  O  a n d   W eis e n b ur g er   D  D.   N e  w  a p pr o a c h t o  cl assif yi n g  n o n -H o d g ki n's l y  m p h o  m as: 
cli ni c al f e at ur es  of t h e   m aj or  hist ol o gi c s u bt y p es.   N o n -H o d g ki n's  L y  m p h o  m a   Cl assifi c ati o n 
Pr oj e ct. J   Cli n   O n c ol 1 9 9 8; 1 6 ( 8): 2 7 8 0 -2 7 9 5.  
B alf o ur J  A  a n d   G o a   K L. B e n d a  m usti n e. Dr u gs  2 0 0 1; 6 1 ( 5):  6 3 1-6 3 8;  dis c ussi o n  6 3 9 -6 4 0.  
B ar g o u   R,  L e o  E,  Z u g  m ai er   G,   Kli n g er   M,   G o e b el er   M,   K n o p  S,  et  al. T u  m or r e gr essi o n i n 
c a n c er  p ati e nts  b y  v er y l o  w  d os es  of  a  T  c ell -e n g a gi n g  a nti b o d y. S ci e n c e  2 0 0 8; 3 2 1 ( 5 8 9 1):  9 7 4-
9 7 7.  
B a z ett   H  C.   A n  a n al ysis  of t h e ti  m e ‐r el ati o ns  of t h e  el e ctr o c ar di o gr a  ms. H e art  1 9 2 0; 7 :  3 5 3-3 7 0.  
C ar b o n e  P P,   K a pl a n   H S,   M uss h off   K,  S  mit h ers   D  W  a n d  T u bi a n a   M.   R e p ort  of t h e   C o  m  mitt e e 
o n   H o d g ki n's   Dis e as e  St a gi n g   Cl assifi c ati o n. C a n c er   R es  1 9 7 1; 3 1 ( 1 1):  1 8 6 0-1 8 6 1.  
C art er   R  H,   W a n g   Y  a n d   Br o o ks  S.   R ol e  of   C  D 1 9 si g n al tr a ns d u cti o n i n   B  c ell  bi ol o g y. I  m  m u n ol 
R es  2 0 0 2; 2 6 ( 1-3):  4 5 -5 4.  
C h es o n   B  D,   Br u g g er   W,   D a  m aj   G,   Dr e yli n g   M,   K a hl   B,   Ki  m b y  E,  et  al. O pti  m al  us e  of 
b e n d a  m usti n e i n  h e  m at ol o gi c  dis or d ers:  Tr e at  m e nt r e c o  m  m e n d ati o ns fr o  m  a n i nt er n ati o n al 
c o ns e ns us  p a n el - a n  u p d at e. L e u k  L y  m p h o  m a  2 0 1 6; 5 7 ( 4):  7 6 6-7 8 2.  
C h es o n   B  D,  Fis h er   RI,   B arri n gt o n  S F,   C a v alli  F,  S c h  w art z  L  H,  Z u c c a  E,  et  al. 
R e c o  m  m e 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 r es p o ns e  ass ess  m e 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 h e  L u g a n o  cl assifi c ati o n. J   Cli n   O n c ol 2 0 1 4; 3 2 ( 2 7):  3 0 5 9-3 0 6 8.  
C h es o n   B  D,  Pfist n er   B, J u  w ei d   M E,   G as c o y n e   R  D,  S p e c ht  L,   H or ni n g  SJ,  et  al.   R e vis e d 
r es p o ns e  crit eri a f or   m ali g n a nt l y  m p h o  m a. J   Cli n   O n c ol 2 0 0 7; 2 5 ( 5):  5 7 9-5 8 6.  
C h es o n B  D,   W e n dt n er   C  M,  Pi e p er   A,   Dr e yli n g   M,  Fri e d b er g J,   H o el z er   D,  et  al.   O pti  m al  us e  of 
b e n d a  m usti n e i n  c hr o ni c l y  m p h o c yti c l e u k e  mi a,  n o n -H o d g ki n l y  m p h o  m as,  a n d   m ulti pl e 
m y el o  m a: tr e at  m e nt r e c o  m  m e n d ati o ns fr o  m  a n i nt er n ati o n al  c o ns e ns us  p a n el. Cli n  L y  m p h o  m a 
M y el o  m a  L e u k  2 0 1 0; 1 0 ( 1):  2 1-2 7.  
C h u  P  G,   C h e n   Y  Y,   M oli n a   A,   Ar b er   D  A  a n d   W eiss  L  M.   R e c urr e nt   B -c ell  n e o pl as  ms  aft er 
Rit u xi  m a b t h er a p y:  a n i  m  m u n o p h e n ot y pi c  a n d  g e n ot y pi c st u d y. L e u k  L y  m p h o  m a  2 0 0 2; 4 3 ( 1 2): 
2 3 3 5 -2 3 4 1.  
Cli ni c al  Tri al  F a cilit ati o n   Gr o u p (  C T F  G).   R e c o  m  m e n d ati o ns r el at e d t o  c o ntr a c e pti o n  a n d 
pr e g n a n c y t esti n g i n  cli ni c al tri als.   1 5  S e pt e  m b er  2 0 1 4.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 2  of 1 3 1  
C o c k cr oft   D  W  a n d   G a ult   M  H.  Pr e di cti o n  of  cr e ati ni n e  cl e ar a n c e fr o  m s er u  m  cr e ati ni n e. N e p hr o n  
1 9 7 6; 1 6 ( 1):  3 1-4 1.  
C oiffi er   B,  L e p a g e  E,   Bri er e J,   H er br e c ht   R ,  Till y   H,   B o u a b d all a h   R,  et  al.   C  H  O P  c h e  m ot h er a p y 
pl us rit u xi  m a b  c o  m p ar e d   wit h   C  H  O P  al o n e i n  el d erl y  p ati e nts   wit h  diff us e l ar g e -B -c ell 
l y  m p h o  m a. N  E n gl J   M e d  2 0 0 2; 3 4 6 ( 4):  2 3 5-2 4 2.  
C ol osi a   A,   Nj u e   A,  Tr as k  P  C,   Oli v ar es   R,   K h a n  S,   A b b e   A,  et  al.   Cli ni c al  e ffi c a c y  a n d s af et y i n 
r el a ps e d/r efr a ct or y  diff us e l ar g e   B-c ell l y  m p h o  m a:  a s yst e  m ati c lit er at ur e r e vi e  w. Cli n 
L y  m p h o  m a   M y el o  m a  L e u k  2 0 1 4; 1 4 ( 5):  3 4 3-3 5 5. e 3 4 6.  
F e u gi er  P,   V a n   H o of   A,  S e b b a n   C,  S ol al -C eli g n y  P,   B o u a b d all a h   R,  F er  m e   C,  et  al.  L o n g -t er  m 
r es ults of t h e   R -C  H  O P st u d y i n t h e tr e at  m e nt  of  el d erl y  p ati e nts   wit h  diff us e l ar g e   B -c ell 
l y  m p h o  m a:  a st u d y  b y t h e   Gr o u p e  d' Et u d e  d es  L y  m p h o  m es  d e l'  A d ult e. J   Cli n   O n c ol 
2 0 0 5; 2 3 ( 1 8):  4 1 1 7-4 1 2 6.  
Fri d eri ci a  L S. Di e s yst ol e n d a u er i  m  el e ktr o k ar di o gr a  m  m  b ei  n or  m al e n   m e ns c h e n  u n d  b ei 
h er z kr a n k e n. A ct a   M e d  S c a n d  1 9 2 0; 5 3 :  4 6 9-4 8 6.  
Gi n al di  L,   D e   M arti nis   M,   M at ut es  E,  F ar a h at   N,   M orill a   R  a n d   C at o vs k y   D.  L e v els  of 
e x pr essi o n  of   C  D 1 9  a n d   C  D 2 0 i n  c hr o ni c   B  c ell l e u k a e  mi as . J   Cli n  P at h ol 1 9 9 8; 5 1 ( 5):  3 6 4-3 6 9.  
Giss el br e c ht   C,   Gl ass   B,   M o u ni er   N,  Si n g h   Gill   D,  Li n c h   D  C,  Tr n e n y   M,  et  al.  S al v a g e r e gi  m e ns 
wit h  a ut ol o g o us tr a ns pl a nt ati o n f or r el a ps e d l ar g e   B -c ell l y  m p h o  m a i n t h e rit u xi  m a b  er a. J   Cli n 
O n c ol  2 0 1 0; 2 8 ( 2 7):  4 1 8 4-4 1 9 0.  
H a b er  m a n n  T  M,   W ell er  E  A,   M orris o n   V  A,   G as c o y n e   R  D,   C assil et h  P  A,   C o h n J  B,  et  al. 
Rit u xi  m a b -C  H  O P  v ers us   C  H  O P  al o n e  or   wit h   m ai nt e n a n c e rit u xi  m a b i n  ol d er  p ati e nts   wit h 
diff us e l ar g e   B -c ell l y  m p h o  m a. J   Cli n   O n c ol 2 0 0 6; 2 4 ( 1 9):  3 1 2 1-3 1 2 7.  
H all e k   M,   C h es o n   B  D,  C at o vs k y   D,   C ali g aris -C a p pi o  F,   Di g hi er o   G,   D o h n er   H,  et  al.   G ui d eli n es 
f or t h e  di a g n osis  a n d tr e at  m e nt  of  c hr o ni c l y  m p h o c yti c l e u k e  mi a:  a r e p ort fr o  m t h e I nt er n ati o n al 
W or ks h o p  o n   C hr o ni c  L y  m p h o c yti c  L e u k e  mi a  u p d ati n g t h e   N ati o n al   C a n c er I nstit ut e -W or ki n g 
Gr o u p  1 9 9 6  g ui d eli n es. Bl o o d  2 0 0 8; 1 1 1 ( 1 2):  5 4 4 6-5 4 5 6.  
H e  L,  Z h u   H  Y,   Qi n  S  C,  Li   Y,   Mi a o   Y,  Li a n g J  H,  et  al. L o  w  n at ur al  kill er (  N  K)  c ell  c o u nts i n 
p eri p h er al  bl o o d  a d v ers el y  aff e ct  cli ni c al  o ut c o  m e  of  p ati e nts   wit h f olli c ul ar l y  m p h o  m a. Bl o o d 
C a n c er J  2 0 1 6 ;6 ( 8):  e 4 5 7. 
H or n J,   Kl e b er   M,   Hi e k e  S,  S c h  mitt -Gr aff   A,   W as c h   R  a n d  E n g el h ar dt   M.  Tr e at  m e nt  o pti o n  of 
b e n d a  m usti n e i n  c o  m bi n ati o n   wit h rit u xi  m a b i n  el d erl y  a n d fr ail  p ati e nts   wit h  a g gr essi v e   B -n o n -
H o d g ki n l y  m p h o  m a: r ati o n al,  effi c a c y,  a n d t ol er a n c e. A n n   H e  m at ol 2 0 1 2; 9 1 ( 1 0):  1 5 7 9-1 5 8 6.  
I nt er n ati o n al   N o n-H o d g ki n's  L y  m p h o  m a  Pr o g n osti c  F a ct ors  Pr oj e ct.   A  pr e di cti v e   m o d el f or 
a g gr essi v e  n o n -H o d g ki n's l y  m p h o  m a. N  E n gl J   M e d  1 9 9 3; 3 2 9 ( 1 4):  9 8 7-9 9 4.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 3  of 1 3 1  
J ur c z a k   W,  Zi n z a ni  P L  a n d   G ai d a n o   G.  S u b gr o u p  a n al ys es  of  diff us e l ar g e   B-c ell l y  m p h o  m a 
(  D L  B  C L)  a n d i n d ol e nt l y  m p h o  m a  c o h orts fr o  m  a  p h as e II a st u d y  of si n gl e-a g e nt   M  O  R 2 0 8 i n 
p ati e nts   wit h r el a ps e d  or r efr a ct or y  n o n -H o d g ki n’s l y  m p h o  m a (  R -R   N  H L. J   Cli n   O n c ol 
2 0 1 6; 3 4 (s u p pl;  a bstr  7 5 4 5). 
J ur c z a k   W,  Zi n z a ni  P L,   G ai d a n o   G,   G oy   A,  Pr o v e n ci o   M,   N a g y  Z,  et  al.  P h as e II a st u d y  of t h e 
C  D 1 9  a nti b o d y   M  O  R 2 0 8 i n  p ati e nts   wit h r el a ps e d  or r efr a ct or y   B -c ell  n o n-H o d g ki n's 
l y  m p h o  m a. A n n   O n c ol  2 0 1 8; 2 9 ( 5):  1 2 6 6-1 2 7 2.  
J ur c z a k   W,  Zi n z a ni  P L  a n d   G o y   A.  P h as e II a st u d y  of si n gl e -a g e nt   M  O  R 2 0 8 i n p ati e nts   wit h 
r el a ps e d  or r efr a ct or y   B-c ell  n o n-H o d g ki n’s l y  m p h o  m a (  N  H L). J   Cli n   O n c ol 2 0 1 5; 3 3 (s u p pl; 
a bstr  8 5 0 0).  
J u  w ei d   M E,  Str o o b a nts  S,   H o e kstr a   O S,   M ott a g h y  F  M,   Di etl ei n   M,   G u er  m a zi   A,  et  al.   Us e  of 
p ositr o n  e  missi o n t o  m o gr a p h y f or r es p o ns e  ass ess  m e nt  of l y  m p h o  m a:  c o ns e ns us  of t h e I  m a gi n g 
S u b c o  m  mitt e e  of I nt er n ati o n al   H ar  m o ni z ati o n  Pr oj e ct i n  L y  m p h o  m a. J   Cli n   O n c ol 2 0 0 7; 2 5 ( 5): 
5 7 1 -5 7 8.  
K ar n ofs k y   D  A  a n d   B ur c h e n a J  H.  T h e   Cli ni c al  E v al u ati o n  of   C h e  m ot h er a p e uti c   A g e nts i n 
C a n c er. E v al u ati o n  of   C h e  m ot h er a p e uti c   A g e nts .   M a c L e o d   C  M.   N e  w   Y or k,   C ol u  m bi a 
U ni v ersit y  Pr ess.  1 9 4 9 : 1 9 6.  
Ki  m J  K,   C h u n g J S,  S hi n   HJ,  S o n g   M  K,   Yi J  W,  S hi n   D  H,  et  al. I nfl u e n c e  of   N  K  c ell  c o u nt  o n t h e 
s ur vi v al  of  p ati e nts   wit h  diff us e l ar g e   B-c ell l y  m p h o  m a tr e at e d   wit h   R -C  H  O P. Bl o o d   R es  
2 0 1 4; 4 9 ( 3):  1 6 2-1 6 9.  
Kl a n o v a   M,   O est er g a ar d   M Z,  Tr n ě n ý   M,   Hi d d e  m a n n   W,   M ar c us   R,  S e h n  L  H,  et  al.  L o  w 
P eri p h er al   Bl o o d   N  K   C ell   C o u nt Is   Ass o ci at e d   wit h   W ors e   Cli ni c al   O ut c o  m e i n  P ati e nts   wit h 
F olli c ul ar  L y  m p h o  m a ( F L)  a n d   Diff us e  L ar g e   B -C ell  L y  m p h o  m a (  D L  B  C L)  T r e at e d   wit h 
I  m  m u n o c h e  m ot h er a p y:   R es ults fr o  m t h e  Fr o ntli n e  P h as e  3   G  A L LI  U  M  a n d   G  O  Y  A  Tri als. Bl o o d  
2 0 1 7; 1 3 0 ( S u p pl  1):  7 2 7. 
L e n z   G,   Wri g ht   G  W,  E  mr e   N  C,   K o hl h a  m  m er   H,   D a v e  S S,   D a vis   R E,  et  al.   M ol e c ul ar s u bt y p es 
of  diff us e l ar g e   B -c ell l y  m p h o  m a  aris e  b y  disti n ct  g e n eti c  p at h  w a ys. Pr o c   N atl   A c a d  S ci   U  S   A  
2 0 0 8; 1 0 5 ( 3 6):  1 3 5 2 0-1 3 5 2 5.  
L e o ni  L  M.  T h e  e v ol vi n g r ol e  of  b e n d a  m usti n e i n l y  m p h oi d   m ali g n a n c y:  u n d erst a n di n g t h e  dr u g 
a n d its   m e c h a nis  m  of  a cti o n --i ntr o d u cti o n. S e  mi n   H e  m at ol  2 0 1 1; 4 8  S u p pl  1 :  S 1-3.  
L e o ni  L  M,   B ail e y   B,   R eif ert J,   B e n d all   H  H,  Z ell er   R  W,   C or b eil J,  et  al.   B e n d a  m usti n e ( Tr e a n d a) 
dis pl a ys  a  disti n ct  p att er n  of  c yt ot o xi cit y  a n d  u ni q u e   m e c h a nisti c f e at ur es  c o  m p ar e d   wit h  ot h er 
al k yl ati n g  a g e nts. Cli n   C a n c er   R es  2 0 0 8; 1 4 ( 1):  3 0 9-3 1 7.  
L esli e  L  a n d   Y o u n es   A.   A nti -C  D 1 9 str at e gi es i n  h e  m at ol o gi c al   m ali g n a n ci es. Dr u gs  of t h e 
F ut ur e  2 0 1 3; 3 8 ( 1 2):  8 3 5. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 4  of 1 3 1  
List er  T  A,   Cr o  wt h er   D,  S ut cliff e  S  B,   Gl atst ei n  E,   C a n ell os   G P,   Y o u n g   R  C,  et  al.   R e p ort  of  a 
c o  m  mitt e e  c o n v e n e d t o  dis c uss t h e  e v al u ati o n  a n d st a gi n g  of  p ati e nts   wit h   H o d g ki n's  dis e as e: 
C ots  w ol ds   m e eti n g. J   Cli n   O n c ol 1 9 8 9; 7 ( 1 1):  1 6 3 0-1 6 3 6 . 
M arti n   A,   C o n d e  E,   Ar n a n   M,   C a n al es   M  A,   D e b e n   G,  S a n c h o J  M,  et  al. R -E S  H  A P  as s al v a g e 
t h er a p y f or  p ati e nts   wit h r el a ps e d  or r efr a ct or y  diff us e l ar g e   B-c ell l y  m p h o  m a: t h e i nfl u e n c e  of 
pri or  e x p os ur e t o rit u xi  m a b  o n  o ut c o  m e.   A   G E L/ T  A  M  O st u d y. H a e  m at ol o gi c a  2 0 0 8; 9 3 ( 1 2): 
1 8 2 9 -1 8 3 6.  
M atl a  ws k a -W as o  ws k a   K,   W ar d  E,  St e v e ns  S,   W a n g   Y,   H er bst   R,   Wi nt er  S S,  et  al.   M a cr o p h a g e 
a n d   N  K-m e di at e d  killi n g  of  pr e c urs or -B  a c ut e l y  m p h o bl asti c l e u k e  mi a  c ells t ar g et e d   wit h  a -
f u c os yl at e d  a nti-C  D 1 9  h u  m a ni z e d  a nti b o di es. L e u k e  mi a  2 0 1 3; 2 7 ( 6):  1 2 6 3-1 2 7 4.  
M orris o n   V  A,   H a  mli n  P,  S o u b e yr a n  P,  St a u d er   R,   W a d h  w a  P,   A a pr o   M,  et  al. Diff us e l ar g e   B -
c ell l y  m p h o  m a i n t h e  el d erl y: I  m p a ct  of  pr o g n osis,  c o  m or bi diti es,  g eri atri c  ass ess  m e nt,  a n d 
s u p p orti v e  c ar e  o n  cli ni c al  pr a cti c e.   A n I nt er n ati o nal  S o ci et y  of   G eri atri c   O n c ol o g y ( SI  O  G) 
E x p ert  P ositi o n  P a p er. J   G eri atr   O n c ol 2 0 1 4.  
M ort o n  L  M,   W a n g  S S,   D e v es a  S S,   H art g e  P,   W eis e n b ur g er   D  D  a n d  Li n et   M S.  L y  m p h o  m a 
i n ci d e n c e  p att er ns  b y   W  H  O s u bt y p e i n t h e   U nit e d  St at es,  1 9 9 2-2 0 0 1. Bl o o d  2 0 0 6; 1 0 7 ( 1):  2 6 5-
2 7 6.  
M ost ell er   R  D.  Si  m plifi e d  c al c ul ati o n  of  b o d y -s urf a c e  ar e a. N  E n gl J   M e d  1 9 8 7; 3 1 7 ( 1 7):  1 0 9 8. 
O'  Bri e n  P  C  a n d  Fl e  mi n g  T  R.   A   m ulti pl e t esti n g  pr o c e d ur e f or  cli ni c al tri als. Bi o  m etri cs  
1 9 7 9; 3 5 ( 3):  5 4 9-5 5 6.  
O g ur a   M,   A n d o   K,  T a ni  w a ki   M,   W at a n a b e  T,   U c hi d a  T, O h  m a c hi   K,  et  al. F e asi bilit y  a n d 
p h ar  m a c o ki n eti c st u d y  of  b e n d a  m usti n e  h y dr o c hl ori d e i n  c o  m bi n ati o n   wit h rit u xi  m a b i n r el a ps e d 
or r efr a ct or y  a g gr essi v e   B  c ell  n o n -H o d g ki n's l y  m p h o  m a. C a n c er  S ci  2 0 1 1; 1 0 2 ( 9):  1 6 8 7-1 6 9 2.  
O h  m a c hi   K,   Niits u   N,   U c hi d a  T,   Ki  m  SJ ,   A n d o   K,  T a k a h as hi   N,  et  al.   M ulti c e nt er  p h as e II st u d y 
of  b e n d a  m usti n e  pl us rit u xi  m a b i n  p ati e nts   wit h r el a ps e d  or r efr a ct or y  diff us e l ar g e   B -c ell 
l y  m p h o  m a. J   Cli n   O n c ol 2 0 1 3; 3 1 ( 1 7):  2 1 0 3-2 1 0 9.  
O k e n   M  M,   Cr e e c h   R  H,  T or  m e y   D  C,   H ort o n J,   D a vis  T E,   M c F a d d e n E T,  et  al.  T o xi cit y  a n d 
r es p o ns e  crit eri a  of t h e  E ast er n   C o o p er ati v e   O n c ol o g y   Gr o u p. A  m J   Cli n   O n c ol  1 9 8 2; 5 ( 6):  6 4 9-
6 5 5.  
Ol ej ni c z a k  S  H,  St e  w art   C  C,   D o n o h u e   K  a n d   C z u c z  m a n   M S.   A  q u a ntit ati v e  e x pl or ati o n  of 
s urf a c e  a nti g e n  e x pr essi o n i n  c o  m  m o n   B-c ell   m ali g n a n ci es  usi n g fl o  w  c yt o  m etr y. I  m  m u n ol 
I n v est 2 0 0 6; 3 5 ( 1):  9 3-1 1 4.  
Pfr e u n ds c h u h   M.   H o  w I tr e at  el d erl y  p ati e nts   wit h  diff us e l ar g e   B -c ell l y  m p h o  m a. Bl o o d  
2 0 1 0; 1 1 6 ( 2 4):  5 1 0 3-5 1 1 0.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 5  of 1 3 1  
Pfr e u n ds c h u h   M,   K u h nt  E,  Tr u  m p er  L,   Ost er b or g   A,  Tr n e n y   M,  S h e p h er d  L,  et  al. C  H  O P -li k e 
c h e  m ot h er a p y   wit h  or   wit h o ut rit u xi  m a b i n  y o u n g  p ati e nts   wit h  g o o d -pr o g n osis  diff us e l ar g e -B -
c ell l y  m p h o  m a:  6 -y e ar r es ults  of  a n  o p e n -l a b el r a n d o  mis e d st u d y  of t h e   M a b Th er a I nt er n ati o n al 
Tri al (  MI n T)   Gr o u p. L a n c et   O n c ol  2 0 1 1; 1 2 ( 1 1):  1 0 1 3-1 0 2 2.  
Pfr e u n ds c h u h   M,  S c h u b ert J,  Zi e p ert   M,  S c h  mits   R,   M o hr e n   M,  L e n gf el d er  E,  et  al. Si x  v ers us 
ei g ht  c y cl es  of  bi -w e e kl y   C  H  O P -1 4   wit h  or   wit h o ut rit u xi  m a b i n  el d erl y  p ati e nts   wit h  a g g r essi v e 
C  D 2 0 +   B -c ell l y  m p h o  m as:  a r a n d o  mis e d  c o ntr oll e d tri al (  RI  C  O  V E  R -6 0). L a n c et   O n c ol  
2 0 0 8; 9 ( 2):  1 0 5-1 1 6.  
Pfr e u n ds c h u h   M,  Tr u  m p er  L,   Ost er b or g   A,  P ett e n g ell   R,  Tr n e n y   M, I  mri e   K,  et  al. C  H  O P -li k e 
c h e  m ot h er a p y  pl us rit u xi  m a b  v ers us   C  H  O P -li k e  c h e  m ot h er a p y al o n e i n  y o u n g  p ati e nts   wit h 
g o o d -pr o g n osis  diff us e l ar g e -B -c ell l y  m p h o  m a:  a r a n d o  mis e d  c o ntr oll e d tri al  b y t h e   M a b T h er a 
I nt er n ati o n al  Tri al (  MI n T)   Gr o u p. L a n c et   O n c ol  2 0 0 6; 7 ( 5):  3 7 9-3 9 1.  
P hili p  T,   G u gli el  mi   C,   H a g e n b e e k   A,  S o  m ers   R,   V a n  d er  L eli e   H,   Br o n  D,  et  al.   A ut ol o g o us 
b o n e   m arr o  w tr a ns pl a nt ati o n  as  c o  m p ar e d   wit h s al v a g e  c h e  m ot h er a p y i n r el a ps es  of 
c h e  m ot h er a p y -s e nsiti v e  n o n-H o d g ki n's l y  m p h o  m a. N  E n gl J   M e d  1 9 9 5; 3 3 3 ( 2 3):  1 5 4 0-1 5 4 5.  
Pl o n q u et   A,   H ai o u n   C, J ais J P,   D e b ar d   A L,  S all es   G,   B e n e   M  C,  et  al. P eri p h er al  bl o o d  n at ur al 
kill er  c ell  c o u nt is  ass o ci at e d   wit h  cli ni c al  o ut c o  m e i n  p ati e nts   wit h  a aI PI  2 -3  diff us e l ar g e   B -c ell 
l y  m p h o  m a. A n n   O n c ol  2 0 0 7; 1 8 ( 7):  1 2 0 9-1 2 1 5.  
P o e J  C,   Mi n ar d -C oli n   V,   K o u nti k o v  EI,   H a as   K  M  a n d  T e d d er  T F.   A  c -M y c  a n d s urf a c e   C  D 1 9 
si g n ali n g  a  m plifi c ati o n l o o p  pr o  m ot es   B  c ell l y  m p h o  m a  d e v el o p  m e nt  a n d  pr o gr essi o n i n   mi c e. J 
I  m  m u n ol 2 0 1 2; 1 8 9 ( 5):  2 3 1 8-2 3 2 5.  
Ri br a g   V,   D u p uis J,  Till y   H,   M ors c h h a us er  F,  L ai n e  F,   H o u ot   R,  et  al.   A  d os e -es c al ati o n st u d y  of 
S  A  R 3 4 1 9,  a n  a nti -C  D 1 9  a nti b o d y   m a y t a nsi n oi d  c o nj u g at e,  a d  mi nist er e d  b y i ntr a v e n o us i nf usi o n 
o n c e   w e e kl y i n  p ati e nts   wit h r el a ps e d/r efr a ct or y   B -c ell  n o n-H o d g ki n l y  m p h o  m a. Cli n   C a n c er 
R es  2 0 1 4; 2 0 ( 1):  2 1 3-2 2 0.  
Ri g a c ci  L,  P u c ci ni   B,   C ort el a z z o  S,   G ai d a n o   G,  Pi c ci n   A,   D'  Ar c o   A,  et  al.   B e n d a  m ust i n e   wit h  or 
wit h o ut rit u xi  m a b f or t h e tr e at  m e nt  of  h e a vil y  pr etr e at e d  n o n -H o d g ki n's l y  m p h o  m a  p ati e nts :   A 
m ulti c e nt er r etr os p e cti v e st u d y  o n  b e h alf  of t h e It ali a n  L y  m p h o  m a  F o u n d ati o n ( FI L). A n n 
H e  m at ol  2 0 1 2; 9 1 ( 7):  1 0 1 3-1 0 2 2.  
R os e n  w al d   A,   Wri g ht   G,   C h a n   W  C,  C o n n ors J  M,   C a  m p o  E,  Fis h er   RI,  et  al.  T h e  us e  of 
m ol e c ul ar  pr ofili n g t o  pr e di ct s ur vi v al  aft er  c h e  m ot h er a p y f or  diff us e l ar g e -B -c ell l y  m p h o  m a. N 
E n gl J   M e d  2 0 0 2; 3 4 6 ( 2 5):  1 9 3 7-1 9 4 7.  
S e h n  L  H,   D o n al ds o n J,   C h h a n a b h ai   M,  Fit z g er al d   C,   Gill   K,   Kl as a   R,  et  al. I ntr o d u cti o n  of 
c o  m bi n e d   C  H  O P  pl us rit u xi  m a b t h er a p y  dr a  m ati c all y i  m pr o v e d  o ut c o  m e  of  diff us e l ar g e   B -c ell 
l y  m p h o  m a i n   Britis h   C ol u  m bi a. J   Cli n   O n c ol 2 0 0 5; 2 3 ( 2 2):  5 0 2 7-5 0 3 3.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 6  of 1 3 1  
S h af er   D ,  S  mit h   M  R,   B or g h a ei   H,   Mill e ns o n   M  M,  Li  T,  Lit  wi n  S,  et  al.  L o  w   N  K  c ell  c o u nts i n 
p eri p h er al  bl o o d  ar e  ass o ci at e d   wit h i nf eri or  o v er all s ur vi v al i n  p ati e nts   wit h f olli c ul ar 
l y  m p h o  m a. L e u k   R es  2 0 1 3; 3 7 ( 1 0):  1 2 1 3-1 2 1 5.  
S h e n o y  PJ,   M ali k   N,   N o o k a   A,  Si n h a   R,   W ar d   K  C,   Br a  wl e y   O  W,  et  al.   R a ci al  diff er e n c es i n t h e 
pr es e nt ati o n  a n d  o ut c o  m es  of  diff us e l ar g e   B -c ell l y  m p h o  m a i n t h e   U nit e d  St at es. C a n c er  
2 0 1 1; 1 1 7 ( 1 1):  2 5 3 0-2 5 4 0.  
S pi ess e ns   B  a n d   D e b ois   M.   A dj ust e d si g nifi c a n c e l e v els f or s u b gr o u p  a n al ys es i n  cli ni c al t ri als. 
C o nt e  m p   Cli n  Tri als  2 0 1 0; 3 1 ( 6):  6 4 7-6 5 6.  
S u git a ni  T,   Br et z  F  a n d   M a ur er   W.   A si  m pl e  a n d fl e xi bl e  gr a p hi c al  a p pr o a c h f or  a d a pti v e  gr o u p -
s e q u e nti al  cli ni c al tri als. J   Bi o p h ar  m  St at 2 0 1 6; 2 6 ( 2):  2 0 2-2 1 6.  
S  w er dl o  w  S  H,   C a  m p o  E,   H arris   N L  et  al.,  E ds. W  H  O Cl assifi c ati o n  of  T u  m o urs  of 
H a e  m at o p oi eti c  a n d  L y  m p h oi d  Tiss u es .  2 0 0 8;  L y o n,  Fr a n c e, I  A  R  C  Pr ess. 
T hi e bl e  m o nt   C  a n d   C oiffi er   B.  L y  m p h o  m a i n  ol d er  p ati e nts. J   Cli n   O n c ol 2 0 0 7; 2 5 ( 1 4):  1 9 1 6-
1 9 2 3.  
Tr u el o v e  E,  F o x   C,   R o bi ns o n  S,  P e ar c e   R,  P err y J,   Kir kl a n d   K,  et  al.   C ar  m usti n e,  Et o p osi d e, 
C yt ar a bi n e,  a n d   M el p h al a n (  B E  A  M) -C a  m p at h   All o g e n ei c  St e  m   C ell  Tr a ns pl a nt ati o n f or 
A g gr essi v e   N o n -H o d g ki n  L y  m p h o  m a:   A n   A n al ysis  of   O ut c o  m es fr o  m t h e   Britis h  S o ci et y of 
Bl o o d  a n d   M arr o  w  Tr a ns pl a nt ati o n. Bi ol   Bl o o d   M arr o  w  Tr a ns pl a nt  2 0 1 4.  
V a cir c a J L,   A cs  PI,  T a b b ar a I  A,   R os e n  PJ,  L e e  P  a n d  L y n a  m  E.   B e n d a  m usti n e  c o  m bi n e d   wit h 
rit u xi  m a b f or  p ati e nts   wit h r el a ps e d  or r efr a ct or y  diff us e l ar g e   B  c ell l y  m p h o  m a. A n n   H e  m at ol  
2 0 1 4; 9 3 ( 3):  4 0 3-4 0 9.  
v a n  Z el  m   M  C,   R eisli I,  v a n  d er   B ur g   M,   C ast a n o   D,  v a n   N o es el   CJ,  v a n  T ol   MJ,  et  al.   A n 
a nti b o d y-d efi ci e n c y s y n dr o  m e  d u e t o   m ut ati o ns i n t h e   C  D 1 9  g e n e. N  E n gl J   M e d  2 0 0 6; 3 5 4 ( 1 8): 
1 9 0 1 -1 9 1 2.  
Vi ar d ot   A,   G o e b el er   M,   N o p p e n e y   R,   Kr a us e  S  W,   K a ll ert  S,  F erstl   B,  et  al.   Bli n at u  m o  m a b 
M o n ot h er a p y  S h o  ws  Effi c a c y i n  P ati e nts   wit h   R el a ps e d   Diff us e  L ar g e   B   C ell  L y  m p h o  m a. Bl o o d  
2 0 1 1; 1 1 8 ( 2 1):  1 6 3 7. 
W alt er  E,  S c h  mitt  T,   Di etri c h  S,   H o   A  a n d   Wit z e ns -H ari g   M.   Rit u xi  m a b  a n d  b e n d a  m usti n e i n 
p ati e nts   wit h   C  D 2 0 +  diff us e l ar g e   B -c ell l y  m p h o  m a  n ot  eli gi bl e f or  c y cl o p h os p h a  mi d e, 
d o x or u bi ci n,  vi n cristi n e  a n d  pr e d nis o n e -li k e  c h e  m ot h er a p y. L e u k  L y  m p h o  m a  2 0 1 2; 5 3 ( 1 1): 
2 2 9 0 -2 2 9 2.  
W ass  m er   G.  Pl a n ni n g  a n d  a n al y zi n g  a d a pti v e  gr o u p s e q u e nti al s ur vi v al tri als. Bi o  m J  
2 0 0 6; 4 8 (4):  7 1 4 -7 2 9.  
W ass  m er   G.   O n s a  m pl e si z e  d et er  mi n ati o n i n   m ulti -ar  m e d  c o nfir  m at or y  a d a pti v e  d esi g ns. J 
Bi o p h ar  m  St at  2 0 1 1; 2 1 ( 4):  8 0 2-8 1 7.  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 7  of 1 3 1  
W ei d  m a n n  E,   Ki  m  S Z,   R ost   A,  S c h u p p ert   H,  S ei p elt   G,   H o el z er   D,  et  al. B e n d a  m usti n e is 
eff e cti v e i n r el a ps e d  or r efr a ct or y  a g gr essi v e  n o n -H o d g ki n's l y  m p h o  m a. A n n   O n c ol  2 0 0 2; 1 3 ( 8): 
1 2 8 5 -1 2 8 9.  
Wils o n   W  H, J u n g  S  H,  P or c u  P,   H ur d   D, J o h ns o n J,   M arti n  S E,  et  al.   A   C a n c er  a n d  L e u k e  mi a 
Gr o u p   B   m ulti -c e nt er st u d y  of   D  A -E P  O  C  H -rit u xi  m a b i n  u ntr e at e d  diff us e l ar g e   B-c ell 
l y  m p h o  m a   wit h  an al ysis  of  o ut c o  m e  b y   m ol e c ul ar s u bt y p e. H a e  m at ol o gi c a  2 0 1 2; 9 7 ( 5):  7 5 8-7 6 5.  
W o y a c h J  A,   A  w a n  F,  Fli n n I  W,   B er d ej a J  G,   Wil e y  E,   M a ns o or  S,  et  al.   A  p h as e  1 tri al  of t h e  F c -
e n gi n e er e d   C  D 1 9  a nti b o d y   X  m  A b 5 5 7 4 (  M  O  R 0 0 2 0 8)  d e  m o nstr at es s af et y  a n d  pr eli  mi n ar y 
effi c a c y i n r el a ps e d   C L L. Bl o o d  2 0 1 4; 1 2 4 ( 2 4):  3 5 5 3-3 5 6 0.  
Y o u n es   A,   Ki  m  S,   R o  m a g u e r a J,   C o p el a n d   A,  F ari al  S d e   C,   K  w a k  L  W,  et  al.  P h as e I   m ulti d os e-
es c al ati o n st u d y  of t h e  a nti -C  D 1 9   m a yt a nsi n oi d i  m  m u n o c o nj u g at e  S  A  R 3 4 1 9  a d  mi nist er e d  b y 
i ntr a v e n o us i nf usi o n  e v er y  3   w e e ks t o  p ati e nts   wit h r el a ps e d/r efr a ct or y   B-c ell l y  m p h o  m a. J   Cli n 
O n c ol  2 0 1 2; 3 0 ( 2 2):  2 7 7 6-2 7 8 2.  
 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 1 8  of  1 3 1  
1 6  A P P  E  N  DI  C  E S  
1 6. 1  A p p e n di x   A:   C o c k c r oft -G a ult  F o r  m ul a  
C o c k c r oft -G a ult   E q u ati o n:  
T his f or m ula pres u mes wei g ht t o be meas ure d i n  kil o gra ms an d c reati ni ne t o  be meas u re d in 
m g/ d L. 
W he n  seru m  creati ni ne is  meas ure d  in  µm ol/ L:  
W h er e C o nst a nt  is 1. 2 3  f or   m e n  a n d 1. 0 4  f or   w o  m e n. 
S o ur c e:  C o c k cr oft  a n d   G a ult ( 1 9 7 6) . Pr e di cti o n  of  cr e ati ni n e  cl e ar a n c e fr o  m s er u  m  cr e ati ni n e. 
N e p hr o n.  1 9 7 6; 1 6( 1)  3 1- 4 1. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 1 9  of  1 3 1  
1 6. 2  A p p e n di x   B:   Hi g hl y   Eff e cti v e   C o nt r a c e pti o n  
 
M et h o ds t h at  c a n  a c hi e v e  a f ail ur e r at e  of l ess t h a n  1  %  p er  y e ar   w h e n  us e d  c o nsist e ntl y  a n d 
c orr e ctl y  ar e  c o nsi d er e d  as  hi g hl y  eff e cti v e  birt h  c o ntr ol   m et h o ds.  S u c h   m et h o ds i n cl u d e: 
•  C o  m bi n e d ( o estr o g e n  a n d  pr o g est o g e n  c o nt ai ni n g)  h or  m o n al  c o nt r a c e pti o n  ass o ci at e d 
wit h i n hi biti o n  of  o v ul ati o n: 
o  or al 
o  i ntr a v a gi n al 
o  tr a ns d er  m al 
•  Pr o g est o g e n- o nl y  h or  m o n al  c o ntr a c e pti o n  ass o ci at e d   wit h i n hi biti o n  of  o v ul ati o n: 
o  or al 
o  i nj e ct a bl e 
o  i  m pl a nt a bl e 
•  Intr a ut eri n e  d e vi c e  
•  Intr a ut eri n e h or  m o n e- r el e asi n g s yst e  m 
•  B il at er al t u b al  o c cl usi o n 
•  V as e ct o  mis e d p art n er 
•  S e x u al  a bsti n e n c e 
 
S o ur c e:  Cli ni c al  Tri al  F a cilit ati o n   Gr o u p (  C T F  G) ( 1 5  S e pt e  m b er  2 0 1 4) .   Re c o  m  m e n d ati o ns 
r el at e d t o  c o ntr a c e pti o n  a n d  pr e g n a n c y t esti n g i n  cli ni c al tri als. 
 
N  O T E: P eri o di c  a bsti n e n c e ( e . g.,  c al e n d ar,  o v ul ati o n, s y  m pt ot h er  m al,  p ost-o v ul ati o n   m et h o ds) 
a n d   wit h dr a  w al  ar e  n ot  hi g hl y  eff e cti v e   m et h o ds  of  c o ntr a c e pti o n. 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 0  of  1 3 1  
1 6. 3  A p p e n di x   C:   O v e r vi e  w  of  p u blis h e d  d at a  o n   N  K  C  C  as  a  p r o g n osti c 
f a ct o r i n D  L  B  C  L  a n d  F  L  
 
P u bli c ati o n  
(st u d y  n a  m e) 
St u d y t y p e  
N u  m b e r  of 
p ati e nts  
P ati e nt 
p o p ul ati o n  
T r e at  m e nt  
N  K  C  C 
c ut - off 
( c ells/ µ  L) 
T r e at  m e nt  eff e ct  b as e d 
o n   N  K  C  C  
(  N  K  C  C-l o  w  vs.   N  K  C  C-
hi g h  c o  m p a ris o n *)  
Kl a n o v a  et  al. 
( 2 0 1 7) 
(  G  O  Y  A) 
Pr os p e cti v e, 
r a n d o  mi z e d 
p h as e III  
n = 1 2 8 7  
N e  wl y 
di a g n os e d 
D L  B  C L 
R- C  H  O P  
vs  
o bi n ut u z u  m a b -
C  H  O P  
1 0 0  
U ni v ari at e   A n al ysis - P F S 
H  R ( 9 5  %   CI):  
1. 3 6 ( 1. 0 7 -1. 7 2)  
I n v ers e:  0. 7 4 ( 0. 5 8-0. 9 3)  
p = 0. 0 1  
Kl a n o v a  et  al. 
( 2 0 1 7) 
(  G  A L LI  U  M) 
Pr os p e cti v e, 
r a n d o  mi z e d 
p h as e III  
n = 1 0 6 4  
Pr e vi o usl y 
u ntr e at e d  
F L  
R- c h e  m o  
vs  
o bi n ut u z u  m a b - 
c h e  m o  
1 0 0  
U ni v ari at e   A n al ysis:  P F S 
H  R ( 9 5  %  CI):  
1. 5 7 ( 1. 1 0 -2. 2 5)  
I n v ers e: 0. 6 4 ( 0. 4 4-0. 9)  
p = 0. 0 1  
Ki  m  et  al. ( 2 0 1 4)  R etr os p e cti v e  
n = 7 2  
N e  wl y 
di a g n os e d 
D L  B  C L 
R- C  H  O P  
1 0 0  
U ni v ari at e  a n al ysis:  P F S 
H  R ( 9 5  %   CI):  
6. 0 3 ( 1. 7 9 -1 3. 5 5)  
I n v ers e:  0. 1 7 ( 0. 0 7-0. 5 6)  
p < 0. 0 0 1  
Pl o n q u et  et  al. 
( 2 0 0 7)  
( L  N  H 9 8  B 3) 
Pr os p e cti v e 
r a n d o  mi z e d 
p h as e II 
( aft er   A S  C T) 
n = 1 3 6  
N e  wl y 
di a g n os e d 
D L  B  C L 
A S  C T f oll o  w e d 
b y 
r a n d o  mi z ati o n 
t o   R T  X  or  n o 
R T  X 
8 0  
U ni v ari at e  a n al ysis  E F S 
H  R ( 9 5  %   CI):  
1. 8 5 ( 1. 1 4 -3)  
I n v ers e: 0. 54 ( 0. 3 3 -0. 8 8)  
 p  =  0. 0 1  
H e  et  al. ( 2 0 1 6)  
R etr os p e cti v e  
n = 1 1 4  
Pr e vi o usl y 
u ntr e at e d  
F L  
R T  X- c o nt ai ni n g 
t h er a p y 
1 0 0  
U ni v ari at e  a n al ysis:  P F S 
H  R ( 9 5  %  CI)  
U ni v ari at e  a n al ysis:  P F S 
H  R ( 9 5  %   CI)  
3. 4 9 ( 1. 6 -7. 6 3)  
I n v ers e:  0. 2 9 ( 0. 1 3-0. 6 2)  
p = 0. 0 0 2  

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 1  of  1 3 1  
P u bli c ati o n  
(st u d y  n a  m e) 
St u d y t y p e  
N u  m b e r  of 
p ati e nts  
P ati e nt 
p o p ul ati o n  
T r e at  m e nt  
N  K  C  C 
c ut - off 
( c ells/ µ  L) 
T r e at  m e nt  eff e ct  b as e d 
o n   N  K  C  C  
(  N  K  C  C-l o  w  vs.   N  K  C  C-
hi g h  c o  m p a ris o n *)  
S h af er  et  al. 
( 2 0 1 3) 
R etr os p e cti v e  
n = 7 5  
N e  wl y 
di a g n os e d 
F L  
R a di ot h er a p y 
( 1 1  p ati e nts) 
a n d/ or si n gl e 
a g e nt  or   R T  X -
c o nt ai ni n g 
r e gi  m e ns,  or 
o bs er v ati o n 
( n = 3 5) 
1 5 0  
M ulti v ari at e  a n al ysis:   O S 
H  R ( 9 5  %   CI)  
6. 7 3 ( 0. 7 6 – 5 9)  
I n v ers e:  0. 1 5 ( 0. 0 1 7-1. 3 ) 
p  = 0. 0 8  
J ur c z a k  et  al. 
( 2 0 1 8) a n d 
M or p h o S ys /I n c yt e 
d at a  o n fil e  
(  M  O  R 2 0 8  C 2 0 1) 
Pr os p e cti v e 
p h as e II 
( n = 3 1) 
R-  R 
D L  B  C L 
M  O  R 0 0 2 0 8 
m o n ot h er a p y  
1 0 0  
U ni v ari at e  a n al ysis  P F S 
H  R ( 9 5  %   CI) 
0. 2 4 ( 0. 0 9,  0. 7 0)  
Pr os p e cti v e 
p h as e II 
( n = 3 1) 
R- R i  N  H L, 
( p o ol e d  F L 
&  ot h er 
i  N  H L 
p ati e nts)  
U ni v ari at e  a n al ysis  P F S 
H  R ( 9 5  %   CI)  
 0. 3 9 ( 0. 1 2,  1. 2 5)  
*   N ot e t h at i n r a n d o  mi z e d st u di es,  h a z ar d r ati os s h o  w n i n t his  c ol u  m n  ar e f or t h e   N  K  C  C -l o  w  v ers us t h e   N  K  C  C-hi g h 
s u b gr o u p  usi n g  p o ol e d  d at a fr o  m  b ot h tr e at  m e nt  ar  ms  
A S  C T:  a ut ol o g o us st e  m  c ell tr a ns pl a nt;   CI:  c o nfi d e n c e i nt er v als;   D L  B  C L:  diff us e l ar g e   B  c ell l y  m p h o  m a;  E F S: 
e v e nt-fr e e s ur vi v al;  F L: f olli c ul ar l y  m p h o  m a;  F LI PI: f olli c ul ar l y  m p h o  m a I nt er n ati o n al  Pr o g n osti c I n d e x;   H  R: 
h a z ar d r ati o;   N  K  C  C:  n at ur al  kill er  c ell  c o u nt;   O S:  o v er all s ur vi v al;  P F S:  pr o gr essi o n -fr e e s ur vi v al;   R-C  H  O P; 
rit u xi  m a b,  c y cl o p h os p h a  mi d e,  d o x or u bi ci n,  vi n cristi n e,  a n d  pr e d nis o n e/ pr e d nis ol o n e;   R-R: r el a ps e d/r efr a ct or y; 
R T  X: rit u xi  m a b  
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 2  of  1 3 1  
1 6. 4  A p p e n di x   D: K a r n o fs k y  P e rf o r  m a n c e  St at us  S c al e 
 
D efi niti o n  of   R ati n g (  %)   C rit e ri a  
 
A bl e t o  c arr y  o n  n or  m al  a cti vit y  a n d t o   w or k;  n o 
s p e ci al  c ar e  n e e d ed.  
1 0 0   N or  m al  n o  c o  m pl ai nts;  n o  e vi d e n c e  of 
dis e as e.  
9 0  
A bl e t o  c arr y  o n  n or  m al  a cti vit y;   mi n or 
si g ns  or s y  m pt o  ms  of  dis e as e. 
8 0  
N or  m al  a cti vit y   wit h  eff ort; s o  m e si g ns  or 
s y  m pt o  ms  of  dis e as e.  
U n a bl e t o   w or k;  a bl e t o li v e  at  h o  m e  a n d  c ar e f or   m ost 
p ers o n al  n e e ds;  v ar yi n g  a  m o u nt  of  assist a n c e  n e e d e d.  
7 0  
C ar es f or s elf;  u n a bl e t o  c arr y  o n  n or  m al 
a cti vit y  or t o  d o  a cti v e   w or k.  
6 0  
R e q uir es  o c c asi o n al  assist a n c e,  b ut is  a bl e 
t o  c ar e f or   m ost  of  his  p ers o n al  n e e ds. 
5 0  
R e q uir es  c o nsi d er a bl e  assist a n c e  a n d 
fr e q u e nt   m e di c al  c ar e.  
U n a bl e t o  c ar e f or s elf; r e q uir es  e q ui v al e nt  of 
i nstit uti o n al  or  h os pit al  c ar e;  dis e as e   m a y  b e 
pr o gr essi n g r a pi dl y.  
4 0  
Dis a bl e d; r e q uir es s p e ci al  c ar e  a n d 
assist a n c e.  
3 0  
S e v er el y  dis a bl e d;  h os pit al  a d  missi o n is 
i n di c at e d  alt h o u g h  d e at h  n ot i  m  mi n e nt. 
2 0  
V er y si c k;  h os pit al  a d  missi o n  n e c ess ar y; 
a cti v e s u p p orti v e tr e at  m e nt  n e c ess ar y.  
1 0  
M ori b u n d; f at al  pr o c ess es  pr o gr essi n g 
r a pi dl y. 
0  
D e a d  
S o ur c e:  K ar n ofs k y  a n d   B ur c h e n a ( 1 9 4 9) . T h e   Cli ni c al  E v al u ati o n  of   C h e  m ot h er a p e uti c   A g e nts i n   C a n c er. I n: 
M a c L e o d   C  M ( e d).  E v al u ati o n  of   C h e  m ot h er a p e uti c   A g e nts.   N e  w   Y or k:   C ol u  m bi a   U ni v ersit y  Pr ess;  1 9 4 9:  1 9 6.  
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 3  of 1 3 1  
1 6. 5  A p p e n di x E : N e  w   Y o r k   H e a rt   Ass o ci ati o n  F u n cti o n al   Cl assifi c ati o n  
 
C rit e ri a f o r N  Y  H  A  F u n cti o n al   Cl assifi c ati o n  
N  Y  H  A 
Cl ass  
C rit e ri a  
I 
N o s y  m pt o  ms  a n d  n o li  mit ati o n i n  or di n ar y  p h ysi c al  a cti vit y; s h ort n ess  of  br e at h   w h e n 
w al ki n g, st air  cli  m bi n g,  et c.  
II 
Mil d s y  m pt o  ms (  mil d s h ort n ess  of  br e at h  a n d/ or  a n gi n a  p ai n)  a n d sli g ht li  mit ati o n  d uri n g 
or di n ar y  a cti vit y  
III 
M ar k e d li  mit ati o n i n  a cti vit y  d u e t o s y  m pt o  ms,  e v e n  d uri n g l ess -t h a n-or di n ar y  a cti vit y ( e. g. 
w al ki n g s h ort  dist a n c es,  a p pr o xi  m at el y  > 2 0 – 1 0 0  m et ers); c o  mf ort a bl e  o nl y  at r est  
I  V 
S e v er e li  mit ati o ns;  p ati e nt  e x p eri e n c es s y  m pt o  ms  e v e n   w hil e  at r est,   m ostl y  b e d b o u n d  
A b br e vi ati o n:   N  Y  H  A,   N e  w   Y or k   H e art   Ass o ci ati o n  
 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 4  of 1 3 1  
1 6. 6  A p p e n di x F : I nf o r  m ati o n  o n I n v esti g ati o n al  a n d   R e gist e r e d  P r o d u cts 
 
T h e I n v esti g at or’s   Br o c h ur e f or   M  O  R 0 0 2 0 8, a n d S u  m  m ar y  of  Pr o d u ct   C h ar a ct eristi cs ( E  M  A)  or 
Pr es cri bi n g I nf or  m ati o n (  U S  F  D  A) f or R T  X  a n d   B E  N, will  b e s u p pli e d t o t h e st u d y sit es.  
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 5  of 1 3 1  
1 6. 7  A p p e n di x G : E q ui v al e nt   D os es f o r   C o rti c ost e r oi ds  
 
E q ui v al e nt  d os es f o r  c o rti c ost e r oi ds  
 
N a  m e (I  N  N)  
E x a  m pl e  
E q ui v al e nt  d os es f o r 
8 0 –  1 0 0 –  1 2 0   m g 
m et h yl p r e d nis ol o n e  
P ot e n c y  
H y dr o c ortis o n e  
H y dr o c ort o n e  ®  
4 0 0 –  5 0 0 –  6 0 0   m g  
1  
Pr e d nis o n e  
D e c orti n  ®  
1 0 0 –  1 2 5 –  1 5 0   m g  
4  
Pr e d nis ol o n e  
D e c orti n  ®   H  
1 0 0 –  1 2 5 –  1 5 0   m g  
4  
M et h yl pr e d nis ol o n e  
Ur b as o n  ®  
8 0 –  1 0 0 –  1 2 0   m g  
5  
D e x a  m et h as o n e  
F ort e c orti n  ®  
1 4 –  1 6 –  2 0   m g  
3 0  
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 6  of 1 3 1  
1 6. 8  A p p e n di x H :   B o d y  S u rf a c e   A r e a (  B S  A)   C al c ul ati o n 
 
T h e  al g orit h  m t o  b e  us e d i n t his st u d y is:  
 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 7  of  1 3 1  
1 6. 9  A p p e n di x I:   A n n   A r b o r  St a gi n g - C ots  w ol ds   R e c o  m  m e n d ati o ns  
 
St a g e I: i n v ol v e  m e nt  of  a si n gl e l y  m p h ati c r e gi o n (I),  or l o c alis e d i n v ol v e  m e nt  of  a si n gl e e xtr a 
l y  m p h ati c or g a n  or sit e (I E).  
 
St a g e II: i n v ol v e  m e nt  of t  w o  or   m or e l y  m p h ati c r e gi o ns  o n t h e s a  m e si d e  of  di a p hr a g  m (II)  or 
l o c alis e d i n v ol v e  m e nt  of  a n e xtr a l y  m p h ati c  or g a n  or sit e  a n d  o n e  or   m or e l y  m p h  n o d e r e gi o ns 
t h e s a  m e si d e  of  di a p hr a g  m (II E). 
 
St a g e III: i n v ol v e  m e nt  of t  w o  or   m or e l y  m p h ati c r e gi o ns  o n  b ot h si d es  of  di a p hr a g  m (III)   w hi c h 
m a y  als o  b e  a c c o  m p a ni e d  eit h er  b y l o c alis e d i n v ol v e  m e nt  of  a n  e xtr a l y  m p h ati c or g a n  or sit e 
(III E),  or  b y i n v ol v e  m e nt  of t h e s pl e e n (III S). 
 
St a g e I  V: Diff us e  or  diss e  mi n at e d i n v ol v e  m e nt  of  o n e  or   m or e  e xtr a l y  m p h ati c  or g a ns  or tiss u e, 
wit h  or   wit h o ut  ass o ci at e d l y  m p h  n o d e i n v ol v e  m e nt.  
B o n e   m arr o  w  or li v er i n v ol v e  m e nt   will  al  w a ys  b e  c o nsi d er e d  as st a g e I  V.  
 
 
C rit e ri a f o r   B -s y  m pt o  ms 
T h e  pr es e n c e  of: ( a)  u ni nt e nti o n al   w ei g ht l oss  of   m or e t h a n  1 0  %   wit hi n t h e  pr e vi o us  6   m o nt hs 
a n d/ or ( b) f e v ers  of  gr e at er t h a n  1 0 0. 5°  F  or  3 8. 0°   C f or  at l e ast  3  c o ns e c uti v e  d a ys   wit h o ut  ot h er 
e vi d e n c e of i nf e cti o n  a n d/ or ( c)  dr e n c hi n g  ni g ht s  w e ats   wit h o ut e vi d e n c e  of i nf e cti o n, is  d e n ot e d 
b y t h e s uffi x l ett er ‘  B’. ‘  A’ i n di c at es t h e  a bs e n c e  of t h es e s y  m pt o  ms.  
 
 
 
S o ur c es:  
 
A n n   Ar b or  St a gi n g 
C ar b o n e  et  al. ( 1 9 7 1) . R e p ort  of t h e  c o  m  mitt e e  o n   H o d g ki n's  dis e as e st a g i n g  cl assifi c ati o n. 
C a n c er   R es; 3 1: 1 8 6 0- 6 1. 
 
C ots  w ol ds   R e c o  m  m e n d ati o ns 
List er  et  al. ( 1 9 8 9) .  St a gi n g f or   H o d g ki n's  dis e as e.   R e p ort  of  a  c o  m  mitt e e  c o n v e n e d t o  dis c uss 
t h e  e v al u ati o n  a n d st a gi n g  of  p ati e nts   wit h   H o d g ki n's  dis e as e:   C ots  w ol ds   m e eti n g. J   Cli n 
O n c ol; 7: 1 6 3 0- 3 6 [ Err at u  m; J   Cli n   O n c ol.  1 9 9 0; 8: 1 6 0 2]. 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
V  V -C LI  N -0 1 9 4 2 9
C o nfi d e nti al  
P a g e 1 2 8  of  1 3 1  
1 6. 1 0  A p p e n di x J : I nt e r n ati o n al  P r o g n osti c I n d e x (I PI) 
O n e  p oi nt is  assi g n e d f or  e a c h  of t h e f oll o  wi n g c h ar a ct eristi cs : 
•
A ge ol der t ha n 6 0
•
Lactate de h y dr o ge nase le vel hi g her t ha n n or mal
•
E C O G  p erf or ma nce  stat us sc ore  of 2 or greate r (see A p pe n di x K )
•
St a ge III  or I V disease
•
M o re t ha n one i n v o l ve d e xtra n o dal  disease site
T h e t ot al s c or e r a n ges fr o  m  z er o t o fi v e,  c orr es p o n di n g t o t h e f oll o  wi n g ris k  gr o u ps: 
•
L o w ris k:  0 – 1  p oi nts
•
L o  w- i nt er  m e diat e ris k:  2  p oi nts
•
Hi g h-i nt er  m e di at e ris k:  3  p oi nts
•
H i g h ris k:  4– 5  p oi nts.
S o ur c e:  I nt er n ati o n al   N o n-  H o d g ki n's  L y  m p h o  m a  Pr o g n osti c  F a ct ors  Pr oj e ct ( 1 9 9 3). A  pr e di cti v e 
m o d el f or  a g gr essi v e  n o n-  H o d g ki n's l y  m p h o  m a.   N  E n gl J   M e d.  1 9 9 3; 3 2 9( 1 4): 9 8 7- 9 4. 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 2 9  of  1 3 1  
1 6. 1 1  A p p e n di x K: E  C  O  G  P e rf o r  m a n c e  St at us  
 
E  C  O  G  P e rf o r  m a n c e  St at us   G r a d es  
G r a d e  
E  C  O  G  
0 
F ull y  a cti v e,  a bl e t o  c arr y  o n  all  pr e -dis e as e  p erf or  m a n c e   wit h o ut r estri cti o n  
1 
R estri ct e d i n  p h ysi c all y str e n u o us a cti vit y  b ut  a  m b ul at or y  a n d  a bl e t o  c arr y  o ut   w or k  of 
a li g ht  or s e d e nt ar y  n at ur e,  e. g., li g ht  h o us e   w or k,  offi c e   w or k  
2 
A  m b ul at or y  a n d  c a p a bl e  of  all s elf c ar e  b ut  u n a bl e t o  c arr y  o ut  a n y   w or k  a cti viti es. 
U p  a n d  a b o ut   m or e t h a n  5 0  %  of   w a ki n g  h o urs  
3 
C a p a bl e  of  o nl y li  mit e d s elf c ar e,  c o nfi n e d t o  b e d  or  c h air   m or e t h a n  5 0  %  of   w a ki n g 
h o urs  
4 
C o  m pl et el y  dis a bl e d.   C a n n ot  c arr y  o n  a n y s elf c ar e.  T ot all y  c o nfi n e d t o  b e d  or  c h air  
5 
D e a d  
 
S o ur c e : O k e n  et  al. ( 1 9 8 2) .  To xi cit y  a n d   R es p o ns e   Crit eri a  of t h e  E ast er n   C o o p er ati v e   O n c ol o g y 
Gr o u p.   A  m J   Cli n   O n c ol.  1 9 8 2; 5( 6): 6 4 9- 5 5. 
Cr e dit: T h e   E ast er n   C o o p er ati v e   O n c ol o g y   Gr o u p,   R o b ert   C o  mis   M.  D.,   Gr o u p   C h air. 
 
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0- A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 3 0  of  1 3 1  
1 6. 1 2  A p p e n di x L: R es p o ns e   C rit e ri a  
T h e r es p o ns e  crit eri a i n t his st u d y  ar e t h os e  d efi n e d i n t h e t a bl e  b el o  w.   All  of t h e  m  ar e  b as e d  o n 
t h e I nt er n ati o n al   W or ki n g   Gr o u p r es p o ns e  crit eri a (C h es o n  et  al.  2 0 0 7 ). 
 
D efi niti o n  of R es p o ns e   C rit e ri a  
R es p o ns e  D efi niti o n  
N o d al   m ass es  
S pl e e n, li v e r  
B o n e   m a r r o  w  
C  R 
Dis a p p e ar a n c e  of  all 
e vi d e n c e  of  dis e as e  
a) F  D  G -a vi d  or  P E T 
p ositi v e  pri or t o 
t h er a p y;   m ass  of 
a n y si z e  p er  mitt e d 
if  P E T  n e g ati v e 
b) V ari a bl e  F  D  G -a vi d 
or  P E T  n e g ati v e; 
r e gr essi o n t o 
n or  m al si z e  o n   C T  
N ot  p al p a bl e, 
n o d ul es 
dis a p p e ar e d  
I nfiltr at e 
cl e ar e d  o n 
r e p e at  bi o ps y; 
if 
i n d et er  mi n at e 
b y 
m or p h ol o g y, 
i  m  m u n o hist o-
c h e  mistr y 
s h o ul d  b e 
n e g ati v e  
P  R  
R e gr essi o n  of   m e as ur a bl e 
dis e as e  a n d  n o  n e  w sit es  
≥ 5 0  %  d e cr e as e i n 
S P  D  of  u p t o  6 
l ar g est  d o  mi n a nt 
m ass es;  n o i n cr e as e 
i n si z e o n   C T  
a) F  D  G -a vi d  or  P E T 
p ositi v e  pri or t o 
t h er a p y;  o n e  or 
m or e  P E T  p ositi v e 
at  pr e vi o usl y 
i n v ol v e d sit e 
b) V ari a bl e  F  D  G -a vi d 
or  P E T  n e g ati v e; 
r e gr essi o n  o n   C T 
≥ 5 0  %  d e cr e as e 
i n  S P  D  of 
n o d ul es (f or 
si n gl e  n o d ul e i n 
gr e at est 
tr a ns v ers e 
di a  m et er);  n o 
i n cr e as e i n si z e 
of li v er  or 
s pl e e n 
Irr el e v a nt if 
p ositi v e  pri or 
t o t h er a p y;  c ell 
t y p e s h o ul d  b e 
s p e cifi e d 
S  D  
F ail ur e t o  att ai n   C  R/ P  R  or 
P  D  
a) F  D  G -a vi d  or  P E T 
p ositi v e  pri or t o 
t h er a p y;  P E T 
p ositi v e  at  pri or 
sit es  of  dis e as e  a n d 
n o  n e  w sit es  o n   C T 
or  P E T  
b) V ari a bl e  F  D  G -a vi d 
or  P E T  n e g ati v e; 
n o  c h a n g e i n si z e 
of  pr e vi o us l esi o ns 
o n   C T  
 
 

I n c yt e   C or p or ati o n 
Pr ot o c ol   N u  m b er:   M  O  R 2 0 8  C 2 0 4 (  B -MI  N  D)  
D at e: 1 0 -A pr -2 0 2 4  
I  N  D   N u  m b er:  1 1 4, 8 5 6 
C T P   A  m e n d  m e nt N o. 8 ,   V ersi o n 1 1 . 0 
E u dr a  C T   N u  m b er: 2 0 1 4 -0 0 4 6 8 9 -1 1  
 
V  V -C LI  N -0 1 9 4 2 9  
C o nfi d e nti al  
P a g e 1 3 1  of 1 3 1  
D efi niti o n  of R es p o ns e   C rit e ri a  
R es p o ns e  D efi niti o n  
N o d al   m ass es  
S pl e e n, li v e r  
B o n e   m a r r o  w  
R el a ps e d 
dis e as e  or 
P  D  
A n y  n e  w l esi o n  or i n cr e as e 
b y ≥5 0  %  of  pr e vi o usl y 
i n v ol v e d sit es fr o  m  n a dir 
A p p e ar a n c e  of  a  n e  w 
l esi o n(s)  > 1. 5  c  m i n 
a n y  a xis, ≥ 5 0  % 
i n cr e as e i n  S P  D  of 
m or e t h a n  o n e  n o d e, 
or  ≥ 5 0  % i n cr e as e i n 
l o n g est  di a  m et er  of  a 
pr e vi o usl y i d e ntifi e d 
n o d e  > 1  c  m i n s h ort 
a xis 
L esi o ns  P E T  p ositi v e 
if  F  D  G-a vi d 
l y  m p h o  m a  or  P E T 
p ositi v e  pri or t o 
t h er a p y 
> 5 0  % i n cr e as e 
fr o  m  n a dir i n 
t h e  S P  D  of  a n y 
pr e vi o us l esi o ns  
N e  w  or 
r e c urr e nt 
i n v ol v e  m e nt 
A b br e vi ati o ns:   C  R  =  c o  m pl et e r es p o ns e;  F  D  G  =  [1 8F]fl u or o d e o x y gl u c os e;  P E T  =  p ositr o n  e  missi o n t o  m o gr a p h y; 
C T  =  c o  m p ut e d t o  m o gr a p h y;  P  R  =  p arti al r es p o ns e;  S P  D  =  s u  m  of t h e  pr o d u ct  of t h e  di a  m et ers;  S  D =  st a bl e 
dis e as e;  P  D  =  pr o gr essi v e  dis e as e . 
 
 
 

Si g nat ure Pa ge f or V V- C LI N- 0 1 9 4 2 9 v 3. 0
Si g nat ure Pa ge f or V V- C LI N- 0 1 9 4 2 9 v 3. 0
A p pr o val Tas k
o ver
 O nc ol o g y Tar gete d T hera pe utics
1 0- A pr- 2 0 2 4 1 5: 2 2: 4 7 G M T + 0 0 0 0
A p pr o val Tas k
 Cli nical Researc h Scie ntist
1 0- A pr- 2 0 2 4 1 5: 4 5: 3 0 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
 Se ni or Cli nical Trial Hea d
1 0- A pr- 2 0 2 4 1 7: 0 4: 5 3 G M T + 0 0 0 0
A p pr o val Tas k
A p pr o ver
 Bi ostatistics
1 1- A pr- 2 0 2 4 0 9: 4 7: 1 7 G M T + 0 0 0 0