Drug Use Surveillance for Cabometyx Tablets "Renal Cell Carcinoma"
Conditions: Renal Cell Carcinoma
Sponsor: Takeda

Cli nic al St u d y Pr ot oc ol
Cli nic al St u d y Pr ot oc ol  
N C T N u m b e r: N C T 0 4 8 0 4 8 1 3  
Titl e: C A B O M E T Y X T a bl et s G e n er al Dr u g U s e R e s ult s S ur v eill a nc e St u d y “ R e n al C ell 
C arci n o m a"  
St u d y N u m b er : C a b o z a nti ni b -5 0 0 1  
D oc u m e nt Ver si o n a n d D at e: Versi o n 4  / 1 2 -D E C -2 0 2 2  
C ert a i n  i nf or m ati o n  wit hi n  t hi s  d oc u m e nt  h a s  b e e n  r e d act e d  (i e,  s p ecific  c o nt e nt  i s  
m a s k e d  irr e v er si bl y fr o m vi e w) t o pr ot ect eit h er p er s o n all y i d e ntifi a bl e i nf or m ati o n or 
c o m p a n y c o nfi d e nti al i nf or m ati o n.  
A s u m m ar y  of  c h a n g e s  t o  pr e vi o u s  pr ot oc ol  v er si o n s  i s  a p p e n d e d  t o  t h e  e n d  of  t h e  
d oc u m e nt.  
N ot e; T h i s d oc u m e nt w a s tr a n sl at e d i nt o E n gli s h a s  t h e l a n g u a g e o n  ori gi n al v er si o n  
w a s J a p a n e s e.  

Ge ner al use -res ults s ur veill a nce st u d y pr ot oc ol
C A B O M E T Y X  T a blets ge ner al dr u g -use s ur ve ill a n ce
“ Re n al cell c arci n o m a ”
S p o ns or
Ta ke d a P h ar m ace utic al C o m p a n y Li mite d.
Pr ot oc ol N u m ber
C a b oz a nti ni b -5 0 0 1
V ersi o n N u m ber
Versi o n 4
D ate of pre p ar ati o n  
Dece m ber 1 2, 2 0 2 2
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

T A B L E O F C O N T E N T S  
1. 0  
Bac k gr o u n d of i m ple me ntati o n  .................................................................................................................. 1 
2. 0  
O bjecti ves  ..................................................................................................................................................... 1 
3. 0  
Safet y s pecificati o n  ...................................................................................................................................... 1 
4. 0  
Pla n ne d sa m ple size a n d rati o nale  ................................................................................................................ 1 
4. 1  Pla n ne d sa m ple size  .......................................................................................................................... 1 
4. 2  Rati o nale  ........................................................................................................................................... 2 
5. 0  
St u d y p o p ulati o n  ........................................................................................................................................... 2 
6. 0  
D osa ge a n d a d mi nistrati o n  ........................................................................................................................... 2 
7. 0  
Pla n ne d n u m ber of me dical i nstit uti o ns b y de part me nt  ................................................................................ 2 
8. 0  
Met h o ds  ........................................................................................................................................................ 3 
8. 1  O bser vati o n peri o d  ........................................................................................................................... 3 
8. 2  Re q uest t o st u d y sites a n d c o ntract  ................................................................................................... 3 
8. 3  Patie nt c o nse nt  .................................................................................................................................. 3 
8. 4  Patie nt e nr oll me nt met h o d  ................................................................................................................ 3 
8. 5  Pre parati o n a n d s u b missi o n of s ur ve y f or ms  .................................................................................... 4 
9. 0  
Pla n ne d st u d y peri o d  .................................................................................................................................... 4 
1 0. 0  I n vesti gati o n ite ms ....................................................................................................................................... 4 
1 0. 1  Patie nt re gistrati o n  ............................................................................................................................ 4 
1 0. 2  Patie nt c haracteristics  ....................................................................................................................... 4 
1 0. 3  Details of treat me nt  .......................................................................................................................... 5 
1 0. 4  Test/ o bser vati o n ite ms  ...................................................................................................................... 5 
1 0. 4. 1  A ntit u m or effect  ................................................................................................................. 5 
1 0. 4. 2  Ot her O bser vati o ns  ............................................................................................................ 5 
1 0. 5  A d verse E ve nts  ................................................................................................................................. 5 
1 1. 0  A nal ysis Ite ms a n d Met h o ds ......................................................................................................................... 8 
1 1. 1  Matters relate d t o patie nt c o m p ositi o n  ............................................................................................. 8 
1 1. 2  Patie nt c haracteristics  ....................................................................................................................... 8 
1 1. 3  Details  of treat me nt .......................................................................................................................... 8 
1 1. 4  Matters c o ncer ni n g safet y  ................................................................................................................. 8 
1 1. 4. 1  I nci de nce of a d verse e ve nts ............................................................................................... 8 
1 1. 4. 2  Fact ors t hat ma y affect safet y ............................................................................................. 8 
1 1. 5  Matters c o ncer ni n g efficac y  ............................................................................................................. 8 
1 2. 0  Re gistrati o n of s ur ve y i nf or mati o n  ............................................................................................................... 8 
1 3. 0  Or ga nizati o nal Str uct ure  ............................................................................................................................... 9 
1 3. 1  Or ga nizati o nal str uct ure f or p ost -mar keti n g s ur veilla nce, etc.  ......................................................... 9 
1 4. 0  Me dical A d vis or  ........................................................................................................................................... 9 
1 5. 0  C o ntract Researc h Or ga nizati o n  ................................................................................................................... 9 
1 6. 0  Sc he d ule d ti mi n g of milest o nes f or e val uati o n of t he i m ple me ntati o n stat us of t he s ur ve y a n d o btai ne d 
res ults, or re p orti n g t o t he P har mace uticals a n d Me dical De vices A ge nc y, a n d its rati o nale....................... 9 
1 7. 0  A D DI TI O N A L M E A S U R E S T H A T M A Y B E I M P L E M E N T E D B A S E D O N T H E S U R V E Y R E S U L T S 
A N D C RI T E RI A F O R D E T E R MI NI N G T H E I NI TI A TI O N  ..................................................................... 9 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

1 8. 0  Ot her necessar y matters  .............................................................................................................................. 1 0  
1 8. 1  Re visi o n of t he pr ot oc ol  ................................................................................................................. 1 0  
1 8. 2  Acti o ns t o be ta ke n if a n y pr o ble m or q uesti o n is o bser ve d  ........................................................... 1 0  
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

1. 0  
B A C K G R O U N D O F I M P L E M E N T A TI O N  
I n  t he  Ja pa nese  a n d  o verseas  cli nical  st u dies  of  C A B O M E T Y X  Ta blets  ( Herei nafter  referre d  t o  as  
Ca b o met y x  i n patie nts wit h re nal cell carci n o ma, he patic f u ncti o n dis or der a p plica ble t o H y's La w N ote  was 
n ot re p orte d, b ut he patic e nz y me i ncrease d s uc h as ala ni ne a mi n otra nsferase ( Herei nafter referre d t o as A L T) 
i ncrease d a n d as partate a mi n otra nsferase ( Herei nafter referre d t o as A S T) i ncrease d was fre q ue ntl y o bser ve d. 
I n  a d diti o n,  a m ylase  i ncrease d  a n d  li pase  i ncrease d  ha ve  occ urre d  at  a  certai n  i nci de nce,  a n d  seri o us 
pa ncreatic  e nz y me  i ncrease d,  pa ncreatitis,  a n d  a c ute  pa ncreatitis  f or  w hic h  a  ca usal  relati o ns hi p  wit h  
Ca b o met y x  c o ul d n ot be r ule d o ut ha ve als o bee n re p orte d.  
W he n usi n g Ca b o met y x , earl y detecti o n b y a p pr o priate m o nit ori n g, a p pr o priate ma na ge me nt t hr o u g h d ose 
re d ucti o n/i nterr u pti o n,  a n d  s u p p orti ve  care  bef ore  a n  e ve nt  bec o mes  se vere  is  i m p orta nt  t o  a v oi d  t he  
pr o gressi o n t o seri o us he patic d ysf u ncti o n or pa ncreatitis. T heref ore, a d d iti o nal p har mac o vi gila nce acti vities 
are necessar y t o c o nfir m t he occ urre nce (fre q ue nc y a n d se verit y), cli nical c o urse, t hera pe utic meas ures, a n d 
pr o gressi o n t o se vere diseases of he patic d ysf u ncti o n, pa ncreatitis, a n d i ncrease d la b orat or y val ue ( A L T, A S T,  
a m ylase, li pase) i n cli nical practice, a n d t o c ollect i nf or mati o n o n t he a p pr o priate ness of t he safet y meas ures 
ta ke n i n cli nical practice f or Ca b o met y x . 
F or  t he  c o m bi nati o n  t hera p y  wit h  ni v ol u ma b  ( ge netical  rec o m bi nati o n)  ( Herei nafter  referre d  t o  as  
ni v ol u ma b),  si nce  t he  i nci de nce  of  he patic  e nz y me  i ncrease d  was  hi g her  t ha n  t hat  wit h  Ca b o met y x  
m o n ot hera p y i n t he gl o bal p hase 3 st u d y ( St u d y C A 2 0 9 9 E R), it was c o ncl u de d t hat t he sa me i nf or mati o n as 
t he a b o ve s h o ul d be c ollecte d. 
T heref ore, a ge neral dr u g use -res ults s ur veilla nce st u d y i n patie nts wit h u nresecta ble or metastatic re nal cell 
carci n o ma i n r o uti ne cli nical practice ( Herei nafter referre d t o as t his i n vesti gati o n) was pl a n ne d. T his st u d y 
will be c o n d ucte d i n c o m plia nce wit h G P S P Or di na nce a n d all a p plica ble re g ulat or y re q uire me nts.  
N ot e) A L T or A S T > 3 × U L N a n d t otal bilir u bi n > 2 × U L N, pl us al kali ne p h os p hatase ( Herei nafter referre d 
t o as A L P) < 2 × U L N 
2. 0  
O BJ E C TI V E S  
To i n vesti gate t he occ urre nce stat us of a d verse reacti o ns (a d verse e ve nts), es peciall y he patic fail ure, he patic 
f u ncti o n dis or der, a n d pa ncreatitis (I nf or mati o n o n i nci de nce, se verit y, treat me nt, c o urse, o utc o me, etc.) i n 
patie nts wit h u nresecta ble or meta static re nal cell carci n o ma u n der act ual use stat us of Ca b o met y x . 
3. 0  
S A F E T Y S P E CI FI C A TI O N  
He patic fail ure, he patic f u ncti o n dis or der, pa ncreatitis  
4. 0  
P L A N N E D S A M P L E SI Z E A N D R A TI O N A L E  
4. 1  
P L A N N E D S A M P L E SI Z E  
Ca b o met y x  m o n ot hera p y: 3 0 0 patie nts (as re gistere d patie nts)  
Patie nts treate d wit h ni v ol u ma b c o m bi nati o n t hera p y: 5 0 patie nts (as t he n u m ber of e nr olle d patie nts)  
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
4. 2  
R A TI O N A L E  
Ca b o met y x  M o n ot hera p y Cases: I n St u d y Ca b oza nti ni b -2 0 0 1, 7/ 3 5 ( 2 0. 0 %) patie nts ha d A L T or A S T 
ele vati o ns > 3 × U L N. Si nce it was c o nsi dere d p ossi ble t o e val uate t he e ve nt at a certai n le vel b y c ollecti n g 
at least 5 0 patie nts, t he pla n ne d sa m ple size was set at 3 0 0 patie nts t o c ollect 5 0 patie nts, ass u mi n g t he 
i nci de nce of he patic d ysf u ncti o n t o be 2 0. 0 % a n d ta ki n g wit h dra wals/ dr o p o uts i nt o acc o u nt. 
T he i nci de nce of pa ncreatitis or ac ute pa ncreatitis A Es was 4/ 3 3 1 ( 1. 2 %) a n d 1/ 3 5 ( 2. 9 %) patie nts i n St u d y 
X L 1 8 4 -3 0 8 a n d St u d y Ca b oza nti ni b -2 0 0 1, res pecti vel y. I ncreases i n pa ncreatic e nz y mes s uc h as a m ylase 
a n d li pase were a m ylase i ncrease d i n 5/ 3 5 s u bjec ts ( 1 4. 3 %), li pase i ncrease d i n 3/ 3 5 s u bjects ( 8. 6 %), a n d 
pa ncreatic e nz y mes i ncrease d i n 1/ 3 5 s u bjects ( 2. 9 %) i n St u d y Ca b oza nti ni b -2 0 0 1. T heref ore, it is c o nsi dere d 
p ossi ble t o c o nfir m a d verse e ve nts c orres p o n di n g t o “ pa ncreatitis” or“  ac ute pa ncreatitis  ” i n at least 1 s u bject 
wit h a pr o ba bilit y of 9 5 % or hi g her a n d e val uate a certai n n u m ber of a d verse e ve nts relate d t o “ pa ncreatitis 
(i ncl u di n g pa ncreatic e nz y me i ncrease d) ” b y c ollecti n g 3 0 0 cases. 
Patie nts recei vi n g ni v ol u ma b c o m bi nati o n t hera p y: I n St u d y C A 2 0 9 9 E R, i ncreases i n A L T or A S T t o m ore 
t ha n 3 ti mes t he u p per li mit of n or mal were o bser ve d i n 7/ 2 2 patie nts ( 3 1. 8 %) i n t he Ja pa nese p o p ulati o n. 
Si nce it was c o nsi dere d p ossi ble t o e val uate t he e ve nt at a certai n le vel b y c ollecti n g at least 1 5 patie nts wit h 
t he e ve nt, t he pla n ne d sa m ple size was set t o be 5 0 patie nts t o c ollect 1 5 patie nts ass u mi n g t hat t he i nci de nce 
of he patic d ysf u ncti o n i n t his s ur ve y is 3 0. 0 %. Ac ute pa ncreatitis occ urre d i n 1/ 3 2 0 s u bjects ( 0. 3 %) i n St u d y 
C A 2 0 9 9 E R. I n t he Ja pa nese p o p ulati o n, li pase i ncrease d was o bser ve d i n 7/ 2 2 patie nts ( 3 1. 8 %) a n d a m ylase 
i ncrease d i n 2/ 2 2 patie nts ( 9. 1 %). T heref ore, a d verse e ve nts relate d t o " pa ncreatitis (i ncl u di n g pa ncreatic 
e nz y me i ncrease d)" ca n be e val uate d t o a certai n e xte nt b y c ollecti n g data fr o m 5 0 patie nts.  
 
5. 0  
S T U D Y P O P U L A TI O N  
To be c o n d ucte d i n patie nts wit h u nresecta ble or metastati c re nal cell carci n o ma. H o we ver, patie nts w h o 
meet a n y of t he f oll o wi n g e xcl usi o n criteria will n ot be i ncl u de d i n t he st u d y. Refer t o t he pac ka ge i nsert.  
  
 E xcl usi o n Criteria  
T he s u bject has a hist or y of h y perse nsiti vit y t o a n y i n gre die nts of Ca b o met y x . 
 
6. 0  
D O S A G E A N D A D MI NI S T R A TI O N  
T he us ual a d ult d osa ge is 6 0 m g of ca b oza nti ni b  a d mi nistere d orall y o nce dail y i n t he faste d state. T he d ose 
ma y be re d uce d acc or di n g t o t he patie nt's c o n diti o n.  
W he n a d mi nisteri n g i n c o m bi nati o n wit h ni v ol u ma b ( ge netical rec o m bi nati o n), t he us ual a d ult d osa ge is 4 0 
m g of ca b oza nti ni b a d mi nistere d orall y o nce dail y i n t he faste d state. T he d ose ma y be re d uce d acc or di n g t o 
t he patie nt's c o n diti o n. 
 
7. 0  
P L A N N E D N U M B E R O F M E DI C A L I N S TI T U TI O N S B Y D E P A R T M E N T  
De part me nt of Ne p hr ol o g y a n d Ur ol o g y, etc.  
A p pr o xi matel y 1 5 0 sites  
 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
8. 0  
M E T H O D S  
8. 1  
O B S E R V A TI O N P E RI O D  
2 6 wee ks  
If a d mi nistrati o n of Ca b o met y x  is disc o nti n ue d f or a n y reas o n, patie nts will be m o nit ore d u ntil 3 0 da ys after 
disc o nti n uati o n of a d mi nistrati o n of Ca b o met y x  or t he start of s u bse q ue nt s yste mic a ntica ncer t hera p y, 
w hic he ver c o mes first. If a patie nt is l ost t o f oll o w -u p ( dr o p o ut), t he o bser vati o n peri o d will e n d at t he ti me 
p oi nt w he n t he patie nt is deter mi ne d t o be l ost t o f oll o w -u p.  
 
* Rati o nale f or t he o bser vati o n peri o d  
T he me dia n ( mi ni m u m -ma xi m u m) ti me t o o nset of a d verse e ve nts relate d t o he patic f u ncti o n dis or der was 
2 8 da ys ( 1 t o 1 1 1 9 da ys) a n d 1 5 da ys ( 4 t o 1 1 4 da ys) i n St u dies X L 1 8 4 -3 0 8 a n d Ca b oza nti ni b -2 0 0 1, 
res pecti vel y. T he res pecti ve 3 4 q ua ntile ( Q 3) was 5 6 a n d 2 5 da ys. 
T he  me dia n  ( mi ni m u m -ma xi m u m)  ti me  t o  o nset  of  a d verse  e ve nts  relate d  t o  " pa ncreatitis  (i ncl u di n g  
pa ncreatic e nz y me i ncrease d)" was 2 9 da ys ( 1 t o 7 5 7 da ys) i n St u d y X L 1 8 4 -3 0 8 a n d 2 9 da ys ( 2 t o 2 5 5 da ys) 
i n St u d y Ca b oza nti ni b-2 0 0 1. T he c orres p o n di n g 3 4 q ua ntile ( Q 3) was 8 3 a n d 5 3 da ys, res pecti vel y.  
Base d o n t he a b o ve, m ost of t he e ve nts o bser ve d ca n be i de ntifie d if t he o bser vati o n peri o d is set at 2 6 wee ks 
after t he start of treat me nt.  
Re gar di n g t he ti me t o o nset of a d verse e ve nts relate d t o t he safet y s pecificati o n " He patic fail ure, he patic 
f u ncti o n dis or der" a n d " pa ncreatitis," a certai n n u m ber of e ve nts ca n be i de ntifie d wit hi n 2 6 wee ks of 
ni v ol u ma b c o m bi nati o n t hera p y base d o n t he res ults of St u d y C A 2 0 9 9 E R, as wit h Ca b o met y x  m o n ot hera p y.  
 
8. 2  
R E Q U E S T T O S T U D Y SI T E S A N D C O N T R A C T  
Ta ke da P har mace utical C o m pa n y Li mite d. will c o ncl u de a writte n c o ntract wit h eac h st u d y site pri or t o t he 
c o n d uct of t his o bser vati o nal st u d y.  
 
8. 3  
P A TI E N T C O N S E N T  
Pri or t o patie nt e nr oll me nt, t he i n vesti gat or will e x plai n t he c o nte nts of t he i nf or me d c o nse nt f or m t o t he 
patie nt ( or his/ her le gall y acce pta ble re prese ntati ve) a n d o btai n oral or writte n c o nse nt fr o m t he patie nt ( or 
his/ her le gall y acce pta ble re prese nta ti ve) t o pr o vi de i nf or mati o n f or t his st u d y. 
W he n writte n i nf or me d c o nse nt is o btai ne d, t he patie nt ( or le gall y acce pta ble re prese ntati ve) m ust si g n a n d 
date t he i nf or me d c o nse nt f or m. T he i n vesti gat or s hall retai n t he ori gi nal si g ne d c o nse nt f or m.  
T he i nf or me d c o nse nt f or m will descri be t he o utli ne of t he st u d y, t he ha n dli n g of t he patie nt's pers o nal a n d 
pers o nal healt h i nf or mati o n i n t he st u d y, a n d t he fact t hat t he patie nt is free t o wit h dra w fr o m t he st u d y at 
a n y ti me wit h o ut gi vi n g a reas o n a n d wit h o ut prej u dice t o his/ her f urt her me dical care.  
A n i de ntificati o n n u m ber is assi g ne d t o eac h patie nt w h o si g ns t he i nf or me d c o nse nt f or m.  
 
8. 4  
P A TI E N T E N R O L L M E N T M E T H O D  
T he st u d y will be c o n d ucte d b y a “ce ntral re gistrati o n met h o d ” usi n g a n electr o nic data ca pt ure s yste m 
( Herei nafter referre d t o as E D C) via We b. 
F or patie nts t o w h o m Ca b o met y x  is prescri be d after t he first da y of t he c o ntract peri o d wit h t he me dical 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
i nstit uti o n, t he i n vesti gat or or a pers o n desi g nate d b y t he i n vesti gat or will e nter i nf or mati o n relate d t o patie nt 
re gistrati o n i n E D C b y 3 0 da ys after t he start date of prescri pti o n of Ca b o met y x  ( T he start date of prescri pti o n 
is defi ne d as “ Da y 0, ” a n d t he da y after t he start date of prescri pti o n is defi ne d as“ Da y 1. ”), a n d t he 
i n vesti gat or will p ut a n electr o nic si g nat ure.  
 
8. 5  
P R E P A R A TI O N A N D S U B MI S SI O N O F S U R V E Y F O R M S  
I nf or mati o n will be c ollecte d usi n g E D C. 
T he i n vesti gat or or a pers o n desi g nate d b y t he i n vesti gat or will e nter data i n E D C f or all re gistere d patie nts 
pr o m ptl y after perf or mi n g necessar y o bser vati o ns, a n d t he i n vesti gat or will p ut a n electr o nic si g nat ure. If t he 
a d mi nistrati o n of Ca b o met y x  ca n n ot be c o nfir me d, e nter t his fact ( n o nee d t o e nter ot her ite ms).  
If a d mi nistrati o n of Ca b o met y x  is disc o nti n ue d d uri n g t he o bser vati o n peri o d d ue t o t he o nset of a n a d verse 
e ve nt, o bser vati o n will be c o nti n ue d after disc o nti n uati o n of a d mi nistrati o n u ntil t he a d verse e ve nt res ol ves 
or is res ol vi n g as m uc h as p ossi ble, a n d t he e ve nt will be e ntere d i n E D C.  
 
9. 0  
P L A N N E D S T U D Y P E RI O D  
S tudyperiod: March 2021 to March 2024  
Patie nt re gistrati o n peri o d: Marc h 2 0 2 1 t o 2 0 2 3  A u g ust  N ote)  
 
N ote) E ve n patie nts f or w h o m Ca b o met y x  is prescri be d b y A u g ust 3 1, 2 0 2 3 , patie nt re gistrati o n (e ntr y i n 
E D C) will n ot be acce pte d o n a n d after Se pte m ber 1, 2 0 2 3 . 
If t he n u m ber of re gistere d patie nts f or t he e ntire st u d y reac hes t he pla n ne d n u m ber bef ore A u g ust 3 1, 
2 0 2 3 , t he re gistrati o n will be cl ose d bef ore t he e n d of t he patie nt re gistrati o n peri o d. If t he patie nt 
re gistrati o n peri o d is s h orte ne d, t he st u d y peri o d will als o be c ha n ge d acc or di n g t o t he s h orte ne d peri o d.  
 
1 0. 0  
I N V ES TI G A TI O N I T E M S  
T he i n vesti gat or or a pers o n desi g nate d b y t he i n vesti gat or will e nter t he f oll o wi n g ite ms i n E D C.  
 
1 0. 1  
P A TI E N T R E GI S T R A TI O N  
1) I n vesti gati o n ite ms  
Date of prescri pti o n of Ca b o met y x , patie nt i de ntificati o n n u m ber, se x, a ge (at t he ti me of prescri pti o n 
of Ca b o met y x ), prese nce or a bse nce of c o nse nt ( ver bal or writte n), assess me nt of e xcl usi o n criteria, 
prese nce or a bse nce of pri or s yste mic dr u g t hera p y f or re nal cell carci n o ma, prese nce or a bse nce of 
c o nc o mita nt use of ni v ol u ma b  
2) Ti mi n g of st u d y 
At patie nt e nr oll me nt  
 
1 0. 2  
P A TI E N T C H A R A C T E RI S TI C S  
1) I n vesti gati o n ite ms  
Ti mi n g of dia g n osis of re nal cell carci n o ma, dia g n osis of hist ol o gical t y pe, cli nical sta ge (sta ge), 
treat me nt cate g or y (at t he start of treat me nt wit h Ca b o met y x ), Kar n ofs k y Perf or ma nce Stat us, I M D C 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
ris k classificati o n, c o m plicati o ns ( prese nce/a bse nce a n d details), me dical hist or y ( prese nce/a bse nce a n d 
details), hei g ht, wei g ht, treat me nt hist or y bef ore t he start of treat me nt wit h Ca b o met y x  
( prese nce/a bse nce a n d details), metastases ( prese nce/a bse nce a n d details) 
2) Ti mi n g of st u d y 
At t he start of a d mi nistrati o n of Ca b o met y x  
 
1 0. 3  
D E T AI L S O F T R E A T M E N T  
1) I n vesti gati o n ite ms  
A d mi nistrati o n stat us of Ca b o met y x  ( Start date, date of i nterr u pti o n, date of d ose c ha n ge, date of 
c o m pleti o n, dail y d ose, reas o n f or disc o nti n uati o n), a d mi nistrati o n stat us of c o nc o mita nt me dicati o n * 
( Prese nce/a bse nce, dr u g na me, a n d treat me nt peri o d), ra di ot hera p y ( prese nce/a bse nce a n d details) 
*I n t his st u d y, o nl y t hera pe utic dr u gs f or t he pri mar y disease are t o be i n vesti gate d. 
2) Ti mi n g of st u d y 
Peri o d fr o m t he start of a d mi nistrati o n of Ca b o met y x  t o Wee k 2 6 ( or disc o nti n uati o n of a d mi nistrati o n) 
 
1 0. 4  
T E S T /O B S E R V A TI O N I T E M S  
W he n eac h e xa mi nati o n/ o bser vati o n is perf or me d at eac h ti me p oi nt u n der t he act ual use stat us i n dail y 
me dical practice, it s h o ul d be e ntere d i n E D C.  
1 0. 4. 1  
A ntit u m or effect  
1) Para meter  
Best o verall res p o nse referri n g t o t he R E CI S T 1. 1 e xtract a n d t he date of t he assess me nt  
2) Ti mi n g of s t u d y 
Peri o d fr o m i nitiati o n of Ca b o met y x  treat me nt t o Wee k 2 6 ( or 3 0 da ys after disc o nti n uati o n of 
treat me nt or start of s u bse q ue nt s yste mic a ntica ncer t hera p y, w hic he ver c o mes first) 
 
1 0. 4. 2  
Ot her O bser vati o ns  
1) O bser vati o n Ite ms  
Prese nce/a bse nce of pre g na nc y [ o nl y f or fe male patie nts], wit h dra wal of c o nse nt [ o nl y f or patie nts w h o 
wit h dre w c o nse nt]  
2) Ti mi n g of s st u d y 
Peri o d fr o m t he start of a d mi nistrati o n of Ca b o met y x  t o Wee k 2 6 ( or disc o nti n uati o n of a d mi nistrati o n) 
 
1 0. 5  
A D V E R S E E V E N T S  
1) A d verse e ve nts  
A d verse e ve nts (see Ta ble 1) t hat meet a n y of t he f oll o wi n g criteria will be c ollecte d: 
・Safet y s pecificati o n: he patic fail ure, he patic i m pair me nt, pa ncreatitis  
- F ul mi na nt he patitis, he patic fail ure, he patic f u ncti o n a b n or mal (a c o n diti o n i n w hic h t here is 
a b n or malit y i n li ver f u ncti o n s uc h as meta b olic or s y nt hetic ca pacit y), la b orat or y a b n or malities i n 
li ver f u ncti o n ( A L T i ncrease d *, A S T i ncrease d *, bilir u bi n i ncrease d, etc.), etc. ( T hese A E ter ms are 
e xa m ples o nl y, t he m ost me dicall y rele va nt A E ter m will be e ntere d i n E D C)  
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
- Ac ute pa ncreatitis, pa ncreatic e nz y me la b orat or y a b n or malities ( Li pase i ncrease d * *, a m ylase 
i ncrease d * *, etc.) 
・Seri o us A d verse E ve nts  
・A d verse E ve nts Lea di n g t o Disc o nti n uati o n of Ca b o met y x  
・A d verse e ve nts of C T C A E Gra de * * * 3 or hi g her  
*I n t his st u d y, patie nts wit h ele vati o ns of A L T or A S T > 3 ti mes t he u p per li mit of n or mal will be 
i ncl u de d i n t he st u d y. Patie nts wit h A L T or A S T > 3 ti mes t he u p per li mit of n or mal bef ore t he 
start of treat me nt will be i ncl u de d i n t he i n vesti gati o n if cli nicall y si g nifica nt ele vati o ns are 
o bser ve d.  
* * I n t his st u d y, a n y i ncrease i n a m ylase or li pase > 1. 5 ti mes t he u p per li mit of n or mal will be 
i ncl u de d i n t he st u d y. Patie nts wit h a m ylase or li pase > 1. 5 ti mes t he u p per li mit of n or mal bef ore 
t he start of treat me nt will be i ncl u de d i n t he i n vesti gati o n if a cli nicall y si g nifica nt i ncrease is 
o bser ve d.  
* * * E val uate acc or di n g t o Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse 
E ve nts ( N CI C T C A E, Versi o n 5. 0).  
2) I n vesti gati o n ite ms  
Prese nce or a bse nce of a d verse e ve nts, na me of a d verse e ve nt, date of o nset, C T C A E Gra de ( w orst 
val ue), seri o us ness a n d reas o n f or seri o us ness (see Ta ble 2), c ha n ge i n d osa ge a n d a d mi nistrati o n of 
Ca b o met y x  ( prese nce or a bse nce a n d details), ot her acti o n ta ke n f or t he e ve nt ( prese nce or a bse nce a n d 
details), date of o utc o me assess me nt, o utc o me, ca usal relati o ns hi p wit h Ca b o met y x  * (see Ta ble 3), 
c ha n ges o ver ti me i n li ver f u ncti o n la b orat or y val ues ( A S T, A L T, A L P, t otal bilir u bi n, a n d P T-I N R) * *, 
li ver virus tests ( H A V ( H A -I g M A b), H B V ( H Bs A g, H Bc A b, H Bs A b, H B V-D N A), H C V ( H C V A b, 
H C V -R N A), a n d H E V ( H E V -I g A A b)) * *, c ha n ges o ver ti me i n pa ncreatic e nz y me la b orat or y val ues 
(a m ylase a n d li pase) * * *, stat us of dr u g a d mi nistrati o n at t he o nset of e ve nts relate d t o t he safet y 
s pecificati o ns, a n d c o urse of a d verse e ve nts relate d t o t he safet y s pecificati o ns [ o nl y seri o us a d verse 
e ve nts]  
If t he o utc o me is assesse d as “ n ot rec o vere d ” or“ u n k n o w n, ” f oll o w-u p s h o ul d be perf or me d as m uc h 
as p ossi ble.  
*If t he ca usalit y wit h Ca b o met y x  is N ot Relate d, c ollect t he rati o nale f or t he deter mi nati o n. 
* * To be c ollecte d o nl y f or e ve nts relate d t o safet y s pecificati o ns ( He patic fail ure, he patic f u ncti o n 
dis or der).  
To be c ollecte d o nl y f or e ve nts relate d t o * * * Safet y S pecificati o n ( pa ncreatitis).  
3) Ti mi n g of st u d y 
Peri o d fr o m i nitiati o n of Ca b o met y x  treat me nt t o Wee k 2 6 ( or 3 0 da ys after disc o nti n uati o n of 
treat me nt or start of s u bse q ue nt s yste mic a ntica ncer t hera p y, w hic he ver c o mes first) 
 
 
 
 
 
 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
u n derl yi n g diseases, c o m plicati o ns, c o nc o mita nt dr u gs a n d c o nc urre nt 
treat me nts. 
 
1 1. 0  
A N A L Y SI S I T E M S A N D M E T H O D S  
1 1. 1  
M A T T E R S R E L A T E D T O P A TI E N T C O M P O SI TI O N  
T he n u m ber of patie nts e nr olle d, t he n u m ber of patie nts w h ose case st u d y  f or ms are c ollecte d, t he n u m ber 
of patie nts e val uate d f or safet y a n d eff ecti ve ness, t he n u m ber of patie nts e xcl u de d fr o m t he e val uati o n, 
reas o ns f or e xcl usi o n, etc. will be ta b ulate d. 
 
1 1. 2  
P A TI E N T C H A R A C T E RI S TI C S  
Patie nt c haracteristics s uc h as ge n der, a ge, disease d urati o n, cli nical sta ge, pri or treat me nt hist or y, a n d 
prese nce or a bse nce of he patic i m pair me nt will be ta b ulate d.  
 
1 1. 3  
D E T AI L S O F T R E A T M E N T  
T he  a d mi nistrati o n  stat us  of  Ca b o met y x  a n d  t hera pe utic  dr u gs  f or  re nal  cell  carci n o ma  ot her  t ha n  
Ca b o met y x will be ta b ulate d.  
 
1 1. 4  
M A T T E R S C O N C E R NI N G S A F E T Y  
T he f oll o wi n g a nal yses will be perf or me d i n t he safet y a nal ysis set. A d verse e ve nts were c o de d usi n g 
Me d D R A/J a n d classifie d b y preferre d ter m ( P T).; preferre d ter m ( P T) a n d s yste m or ga n class ( S yste m Or ga n 
Class); S u m marize d i n S O C).  
 
1 1. 4. 1  
I nci de nce of a d verse e ve nts 
T he fre q ue ncies of a d verse e ve nts t o be i n vesti gate d t hat occ ur d uri n g t he o bser vati o n peri o d will be 
ta b ulate d b y t y pe, ti me of o nset, se verit y ( C T C A E Gra de), seri o us ness, acti o n ta ke n f or a d mi nistrati o n of 
Ca b o met y x , ca usal relati o ns hi p t o Ca b o met y x , etc. 
 
1 1. 4. 2  
Fact ors t hat ma y affect safet y  
Fre q ue ncies of tar get a d verse reacti o ns t hat occ ur d uri n g t he o bser vati o n peri o d will be ta b ulate d b y 
patie nt bac k gr o u n d fact or ( Ge n der, a ge, prese nce or a bse nce of c o nc urre nt re nal/ he patic i m pair me nt, etc.) 
a n d Ca b o met y x  m o n ot hera p y or ni v ol u ma b c o m bi nati o n t hera p y.  
 
1 1. 5  
M A T T E R S C O N C E R NI N G E F FI C A C Y  
A ntit u m or  effects  d uri n g  t he  o bser vati o n  peri o d  will  be  ta b ulate d  f or  Ca b o met y x  m o n ot hera p y  a n d  
ni v ol u ma b c o m bi nati o n t hera p y i n t he eff ecti ve ness a nal ysis set.  
 
1 2. 0  
R E GI S T R A TI O N O F S U R V E Y I N F O R M A TI O N  
I nf or mati o n o n t his st u d y will be re gistere d o n t he f oll o wi n g p u blic we bsite bef ore t he start of t his st u d y. 
・Cli nical researc h pr ot oc ol/researc h s u m mar y discl os ure s yste m: Ja pa n Re gistr y of Cli nical Trials  
・Nati o nal I nstit utes of Healt h Cli nical Trials Re gistr y: Cli nical Trials. g o v  
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
1 3. 0  
O R G A NI Z A TI O N A L S T R U C T U R E  
1 3. 1  
O R G A NI Z A TI O N A L S T R U C T U R E F O R P O S T -M A R K E TI N G S U R V EI L L A N C E , E T C . 
See Attac h me nt  
 
1 4. 0  
M E DI C A L A D VI S O R  
 
 
 
Acti vit y:  
・To gi ve a d vice o n t he pre parati o n a n d re visi o n of t he st u d y pr ot oc ol, etc.  
・To gi ve a d vice o n t he pre parati o n a n d re visi o n of t he cli nical st u d y re p ort  
・Ot her a d vice re q uiri n g vari o us me dical j u d g me nts f or t he c o n d uct of t his i n vesti gati o n  
 
1 5. 0  
C O N T R A C T R E S E A R C H O R G A NI Z A TI O N  
( 1)
 
 
Details of o perati o ns: Data ma na ge me nt o perati o ns, E D C c o nstr ucti o n o perati o ns, st ora ge o perati o ns of 
rec or ds, etc., s u p p ort o perati o ns relate d t o p ost-mar keti n g s ur veilla nce  
 
( 2) 
 
 
Acti vit y: E D C setti n g ma na ge me nt  
 
( 3) 
 
 
Acti vit y: M o nit ori n g, statistic al a nal ysis  
 
1 6. 0  
S C H E D U L E D  TI MI N G  O F  MI L E S T O N E S  F O R  E V A L U A TI O N  O F  T H E  I M P L E M E N T A TI O N  
S T A T U S  O F  T H E  S T U D Y  A N D  O B T AI N E D  R E S U L T S,  O R  R E P O R TI N G  T O  T H E  
P H A R M A C E U TI C A L S A N D M E DI C A L D E VI C E S A G E N C Y, A N D I T S R A TI O N A L E  
At t he ti me of peri o dic safet y re p orti n g: To c o m pre he nsi vel y e xa mi ne safet y i nf or mati o n.  
9 m o nt hs after st u d y c o m pleti o n (at t he ti me of pre parati o n of t he fi nal re p ort):  
Fi nal ta b ulati o n will be perf or me d after data l oc k of all re gistere d patie nts, a n d t he fi nal re p ort will be 
pre pare d a n d s u b mitte d.  
 
1 7. 0  
A D DI TI O N A L M E A S U R E S T H A T M A Y B E I M P L E M E N T E D B A S E D O N T H E S T U D Y  R E S U L T S 
A N D C RI T E RI A F O R D E T E R MI NI N G T H E I NI TI A TI O N  
T he Ris k Ma na ge me nt Pla n i ncl u di n g t he f oll o wi n g c o nte nts will be re vie we d at milest o nes.  
・T he necessit y f or c ha n gi n g t he c o nte nts of t he pla n of t his st u d y, i ncl u di n g t he prese nce or a bse nce of ne w 
safet y s pecificati o ns, will be e xa mi ne d. 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

 
 
・Re vie w t he necessit y of f or m ulati n g a ris k mi ni mizati o n pla n f or ne w safet y s pecificati o ns.  
 
1 8. 0  
O T H E R N E C E S S A R Y M A T T E R S  
1 8. 1  
R E VI SI O N O F T H E P R O T O C O L  
D uri n g t he st u d y peri o d, t he pr o gress stat us, occ urre nce of a d verse reacti o ns/seri o us a d verse reacti o ns 
u ne x pecte d fr o m Preca uti o ns, prese nce or a bse nce of i ncrease d i nci de nce of s pecific a d verse reacti o ns, 
a p pr o priate ness of st u d y ite ms, etc. will be m o nit ore d, a n d if necessar y, t his pr ot oc ol will be re vie we d a n d 
re vise d. If t he a p pr o val f or partial c ha n ges i n t he d osa ge a n d a d mi nistrati o n or i n dicati o ns is o btai ne d d uri n g 
t he i m ple me ntati o n peri o d, t he necessit y of re visi o n of t his pr ot oc ol will be e xa mi ne d as necessar y, a n d t he 
pr ot oc ol will be re vise d as necessar y.  
 
1 8. 2  
A C TI O N S T O B E T A K E N I F A N Y P R O B L E M O R Q U E S TI O N I S O B S E R V E D  
If a n y safet y or effecti ve ness iss ue is f o u n d, acti o ns will be c o nsi dere d after cl ose e xa mi nati o n of t he data. 
 
 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e

D oc u me nt Hist or y  
 
Ve r si o n 
D ate 
C o m me nts  
ori gi nal versi o n 
2 0 2 1/ 2/ 8 
Ne w d oc u me nt 
2 n d versi o n 
2 0 2 1/ 9/ 1 
1. 0 
B A C K G R O U N D O F I M P L E M E N T A TI O N  
4. 1 
P L A N N E D S A M P L E SI Z E  
4. 2 
R A TI O N A L E  
6. 0 
D O S A G E A N D A D MI NI S T R A TI O N  
8. 1 
O B S E R V A TI O N P E RI O D  
1 0. 1 
P A TI E N T R E GI S T R A TI O N  
1 1. 4. 2 
F A C T O R S T H A T M A Y A F F E C T S A F E T Y  
1 1. 5 
M A T T E R S C O N C E R NI N G E F FI C A C Y  
1 4. 0 
M E DI C A L A D VI S O R  
3r d versi o n 
2 0 2 2/ 5/ 9 
1 3. 0 
O R G A NI Z A TI O N A L S T R U C T U R E  
4t h versi o n 
2 0 2 2/ 1 2/ 1 2 
9. 0 
P L A N N E D S T U D Y P E RI O D  
 
Pr o p ert y of T a k e d a: F or n o n- c o m m er ci al u s e o nl y a n d s u bj e ct t o t h e a p pli c a bl e T er m s of U s e