A Pivotal, Double-Blind, Randomized, Placebo-Controlled, Multinational Study of SGX942 (Dusquetide) for the Treatment of Oral Mucositis in Patients Being Treated With Concomitant Chemoradiation for the Treatment of Squamous Cell Carcinoma of the Head and Neck
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Oral Cavity and Oropharynx, Oral Mucositis
Sponsor: Soligenix

Pr ot o c ol I D R -O M -0 2 -U S A  
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l
P a g e 1 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
S G X 9 4 2  ( D U S Q U E TI D E) 
I D R- O M-0 2 -U S A  
A PI V O T A L, D O U B L E -B LI N D, R A N D O MI Z E D, P L A C E B O -C O N T R O L L E D , 
M U L TI N A TI O N A L  S T U D Y O F S G X 9 4 2  ( D U S Q U E TI D E) F O R T H E T R E A T M E N T O F 
O R A L M U C O SI TI S I N P A TI E N T S B EI N G  T R E A T E D WI T H C O N C O MI T A N T 
C H E M O R A DI A TI O N F O R T H E T R E A T M E N T O F S Q U A M O U S C E L L C A R CI N O M A 
O F T H E H E A D A N D N E C K   
S p o ns or:  
S oli ge ni x , Inc. 
2 9 E m m o ns Dri ve 
S uite B- 1 0 
Pri ncet o n, NJ 0 8 5 4 0 
( 6 0 9) 5 3 8- 8 2 0 0
D oc u me nt D at e : 
Ori gi n al  
1 1 J a n uar y 2 0 1 7 
A me n d me nt  1 
2 9 N o ve m ber 2 0 1 7  
A me n d me nt 2  
2 2 J a n uar y 2 0 1 8 
A me n d me nt 3
1 7 Se pte m ber 2 0 1 9 
U S I N D N u m ber:  
 
Me dic al M o nit or  
Ric har d Stra u be, M D 
C O N FI D E N TI A LI T Y S T A T E M E N T  
T he i nf or mati o n i n t his d oc u me nt c o ntai ns tra d e secrets a n d c o m mercial i nf or mati o n t hat are 
pri vile ge d or c o nfi d e ntial a n d ma y n ot be discl ose d u nless s uc h discl os ure is re q uire d b y fe deral 
or state la w or re g ulati o ns . I n a n y e ve nt, p ers o ns t o w h o m t he i nf or mati o n is discl ose d m ust be 
i nf or me d t hat t he i nf or m ati o n is pri vile ge d or c o nfi de ntial a n d ma y n ot be f urt her discl ose d b y 
t he m. T hese restri cti o ns o n discl os ure will a p pl y e q uall y t o all f ut ure i nf or mati o n s u p plie d t o 
y o u, w hic h is i n dicat e d as pri vile ge d or c o nfi d e ntial. 
N C T 0 3 2 3 7 3 2 5

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
1.  
P R O T O C O L S Y N O P SI S  
N a me of S p o ns or/ C o m p a n y:  
S oli ge ni x, I nc. 
N a me of I n vesti g ati o n al Pr o d uct:  
S G X 9 4 2 ( d us q ueti de),  
 sterile s ol uti o n f or i ntra ve n o us (I V) i nf usi o n 
N a me of Acti ve I n gre die nt:  
D us q ueti de (researc h na me S G X 9 4),
 f ull y s y nt hetic n o vel pe nta pe pti de 
Title of St u d y:  
A  Pi v otal,  D o u ble -Bli n d,  Ra n d o mize d,  Place b o -C o ntr olle d,  M ulti nati o nal  St u d y  of  S G X 9 4 2  
( D us q ueti de)  f or  t he  Treat me nt of  Oral  M uc ositis  i n  Patie nts  Bei n g  Treate d  wit h  C o nc o mita nt  
C he m ora diati o n f or t he Treat me nt of S q ua m o us Cell Carci n o ma of t he Hea d a n d N ec k 
St u d y Ce nter(s): A t otal of 5 0 -6 0 ce nters i n t he U S A a n d E U  
P ri nci p al I n vesti g at or:
 
St u die d Peri o d ( ye ars):  
Esti mate d date first patie nt e nr olle d: N o ve m ber 2 0 1 7 
Esti mate d date last patie nt e nr olle d: Marc h 2 0 2 0 
P h ase of De vel o p me nt:  
P hase 3 
O bjectives:  
P ri m ar y O bjecti ve:  
•  
T o assess t he efficac y of S G X 9 4 2 c o m pare d t o place b o i n decreasi n g t he d urati o n of se vere oral 
m uc ositis ( S O M; defi ne d as W orl d Healt h Or ga nizati o n [ W H O ] Gra de lesi o n ≥3) i n patie nts 
recei vi n g fracti o nate d ra diati o n treat me nts a n d c o nc o mita nt cis plati n c he m ot hera p y, gi ve n as 8 0-
1 0 0 m g/ m 2 e ver y t hir d wee k, f or t he treat me nt of s q ua m o us cell carci n o ma of t he oral ca vit y or 
or o p har y n x.  
Sec o n d ar y O bjecti ves:  
T o assess t he i m pact of S G X 9 4 2 c o m pare d t o place b o o n t he f oll o wi n g  cli nicall y i m p orta nt sec o n dar y 
o bj ecti ves : 
1.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he Area - U n der-t he-C ur ve ( A U C) f or S O M ( W H O 
Gra de ≥3 ) b y ti me pl ot (se verit y - wei g hte d d urati o n) 
2.  T o assess  t he i m pact t hat S G X 9 4 2 has o n the Area - U n der-t he-C ur ve ( A U C) f or ulcerati ve oral 
m uc ositis ( U O M; defi ne d as W H O Gra de ≥2) b y ti me pl ot (se verit y - wei g hte d d urati o n) 
3.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he i nci de nce of S O M 
4.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he q ualit y of life assess me nt usi n g t he E ur o pea n 
Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer ( E O R T C) Q ualit y of Life Q uesti o n f or 
Hea d a n d Nec k Ca ncer 4 3 q uesti o n ( Q L Q H & N 4 3) i nstr u me nt 
5.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he a m o u nt of  o pi oi ds use d 
 
T o assess t he i m pact of S G X 9 4 2 c o m pare d t o place b o o n t he f oll o wi n g  a d diti o nal sec o n dar y 
o bj ecti ves : 
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he c u m ulati ve n u m ber of da ys of R T brea ks 
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he d urati o n of S O M; i n all ra n d o mize d patie nts 
recei vi n g fracti o nate d R T a n d c o nc o mita nt cis plati n c he m ot hera p y, gi ve n as 8 0-1 0 0 m g/ m 2 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
e ver y t hir d wee k (I T T p o p ulati o n) 
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he d urati o n of U O M 
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he c u m ulati ve a m o u nt of pai n re p orte d b y patie nts 
•  
T he d urati o n of S O M usi n g a n alter nati ve defi niti o n calc ulate d as t he n u m ber of da ys fr o m t he 
first oral e xa mi nati o n wit h W H O gra de ≥3 t hr o u g h t he last assess me nt wit h a W H O sc ore ≥3 
(a n d n ot t o t he first assess me nt wit h a W H O gra de < 3) wit h n o f urt her re p orts of a W H O gra de 
≥3 . 
•  
T he d urati o n of S O M i n t he Per- Pr ot oc ol P o p ulati o n defi ne d as patie nts recei vi n g  a c u m ulati ve 
ra diati o n d ose of at least 5 5 G y a n d ha vi n g recei ve d all st u d y dr u g sc he d ule d. 
S af et y O bj ecti ve: 
Safet y o bj ecti ves will i ncl u de t he f oll o wi n g:  
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he A d verse E ve nts ( A E) a n d seri o us A d verse E ve nts 
( S A E) 
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n c ha n ges i n safet y la b orat or y val ues  
•  
T o assess t he i m pact t hat S G X 9 4 2 has o n t he Res p o nse E val uati o n Criteria i n S oli d T u m ors 
(R E CI S T ) cate g orizati o n of t he pri mar y t u m or at 1 2 wee ks a n d 1 2 m o nt hs p ost - CR T  
•  
T o assess t he i m pact of S G X 9 4 2 o n t he i nci de nce of re p orte d pres u me d bacterial i nfecti o ns 
bet wee n Baseli ne a n d 6 wee ks after c o m pleti o n of ra diati o n t hera p y ( R T) b y t otal n u m ber a n d 
b y se verit y of i nfecti o n, gra de d usi n g t he Nati o nal Ca ncer I nstit ute’s ( N CI’s) C o m m o n 
T er mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E)  
•  
T o assess t he i m pact of S G X 9 4 2 o n 1 2 m o nt h all- ca use m or talit y 
•  
T o assess t he i m pact of S G X 9 4 2 o n pr o gressi o n free s ur vi val t hr o u g h 1 2 m o nt hs 
Met h o d ol o g y:  
A p pr o xi matel y 2 6 0 patie nts wit h s q ua m o us cell carci n o ma of t he oral ca vit y a n d or o p har y n x sc he d ule d 
t o recei ve a mi ni m u m t otal c u m ulati ve ra diati o n d ose of 5 5 G y fracti o nate d as 2. 0- 2. 2 G y per da y a n d 
c o nc o mita nt cis plati n c he m ot hera p y gi ve n as a d ose of 8 0 -1 0 0 m g/ m 2 (e very t hir d wee k ) will be 
e nr olle d. S u bjects will be ra n d o mize d t o recei ve eit her 1. 5 m g/ k g S G X 9 4 2 or place b o gi ve n as a 4-
mi n ute I V i nf usi o n usi n g a n i nf usi o n or s yri n ge p u m p. Bli n de d st u d y dr u g will be starte d wit hi n 3 da ys 
after starti n g R T  a n d c o nti n ue d t wice a wee k ( 2-4 cale n dar da ys a part) t hr o u g h 2 wee ks after 
c o m pleti o n of t he R T . Efficac y will be assesse d b y oral e xa mi nati o n at eac h treat me nt visit a n d t he n at 
t he 3 t hr o u g h 6 wee ks p ost-R T c o m pleti o n visits. O M will be e val uate d usi n g t he W H O Gra de s ys te m 
a n d perf or me d b y o bser vers trai ne d o n t hese meas ure me nts. S O M is defi ne d as a W H O Gra de of ≥3. 
T he d urati o n of S O M is defi ne d as t he first ti me t he patie nt has a W H O Gra de ≥3 u ntil t he first ti me t he 
patie nt has a W H O Gra de of < 3 wit h n o s u bse q ue nt readi n gs ≥3. Patie nts will be ra n d o mize d ( 1: 1; 1. 5 
m g/ k g S G X 9 4 2: place b o) usi n g a n i nteracti ve we b res p o nse s yste m (I W R S). Ra n d o mizati o n will be 
stratifie d b y site, prese nce of pr o p h ylactic gastr ost o m y fee di n g t u be, a n d t u m or h u ma n pa pill o ma vir us 
( H P V) stat us. 
R o uti ne cli nical c he mistr y a n d he mat ol o g y will be o btai ne d at Scree ni n g/ Baseli ne, t he n at 3, 6, a n d 9 
wee ks w hile recei vi n g st u d y dr u g, a n d t he n at t he 4 a n d 6 wee k p ost- R T c o m pleti o n visit. T he sa me 
t y pe of sca n i nitiall y use d t o sta ge t he t u m or (i.e., c o m p ute d t o m o gra p h y [C T ], ma g netic res o na nce 
i ma gi n g [M RI ] or p ositr o n e missi o n t o m o gra p h y [ P E T ]) will be re peate d at 1 2 wee ks  a n d 1 2 m o nt hs 
after c o m pleti o n of t he ra diati o n t hera p y a n d c o m pare d t o t he i nitial sca n usi n g t he R E CI S T 1. 1 
criteria. 
N u m ber o f P atie nts ( pl a n ne d): 
2 6 0 patie nts ( 1 3 0 S G X 9 4 2 treate d a n d 1 3 0 place b o treate d patie nts) will be e nr olle d.  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
Di a g n osis a n d M ai n Criteri a f or I ncl usi o n:  
I ncl usi o n Criteri a 
Patie nts m ust meet all  of t he f oll o wi n g criteria i n or der t o be eli gi ble f or e nr oll me nt:  
1.  Willi n g a n d a ble t o u n dersta n d a n d si g n a n i nf or me d c o nse nt 
2.  Males or fe males a ge greater t ha n or e q ual t o 1 8 years  
3.  Bi o ps y- pr o ve n s q ua m o us cell carci n o ma of t he oral ca vit y or or o p har y n x wit h o ut dista nt or ga n 
metastases  t hat has bee n e val uate d f or h u ma n pa pill o ma vir us ( H P V) 
4.  Sc he d ule d t o recei ve cis plati n c he m ot hera p y of 8 0- 1 0 0 m g/ m² gi ve n e ver y t hir d wee k 
5.  Sc he d ule d t o recei ve a c o nti n u o us c o urse of c o n ve nti o nal e xter nal bea m irra diati o n de li vere d 
b y i nte nsit y - m o d ulate d ra di ot hera p y (I M R T) as si n gle dail y fracti o ns of 2. 0 t o 2. 2 G y, wit h a 
c u m ulati ve ra diati o n d ose bet wee n 5 5 a n d 7 2 G y at eac h site  
6.  Pla n ne d ra diati o n treat me nt fiel ds m ust i ncl u de at least 2 oral sites (retr o m olar tri g o ne, b uc cal 
m uc osa, fl o or of m o ut h, t o n g ue, or s oft palate), wit h eac h site rec ei vi n g ≥5 5 G y  
7.  All w o me n of c hil d beari n g p ote ntial ( W O C B P) a n d males wit h fe male part ners w h o are 
W O C B P m ust a gree t o t he use of effecti ve c o ntrace pti o n d uri n g t he trial.  
•  
W o me n are c o nsi dere d t o be W O C B P f oll o wi n g me narc he a n d u ntil bec o mi n g p ost-
me n o pa usal u nless per ma ne ntl y sterile ( h ysterect o m y, bilateral sal pi n gect o m y a n d bilateral 
o o p h orect o m y). A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use.  
Effecti ve c o ntrace pti o n met h o ds f or W O C B P s h o ul d be starte d pri or t o ra n d o mizati o n a n d 
c o nti n ue d f or a mi ni m u m of 3 5 da ys f oll o wi n g c o m pleti o n of st u d y dr u g a d mi nistrati o n.  
•  
Acce pta ble c o ntrace pti ve met h o ds f or W O C B P are t h ose t hat ac hie ve a fail ure rate of less 
t ha n 1 % per year a n d i ncl u de:  
o  C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n 
ass ociate d wit h i n hi biti o n of o v ulati o n:  
 
 Oral  
 
I ntra va gi nal 
 
Tra ns der mal  
o  Pr o gest o ge n - o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n:  
 
Oral  
 
I nj ecta ble 
 
I m pla nta ble 
o  I ntra uteri ne de vice (I U D)  
o  I ntra uteri ne h or m o ne-releasi n g s yste m ( I U S)  
o  Bilateral t u bal occl usi o n  
o  Vasect o mize d  part ner  
o  Se x ual a bsti ne nce defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g 
t he e ntire peri o d of ris k ass ociate d wit h t he st u d y treat me nts 
•  
Male s u bjects s h o ul d use c o n d o ms d uri n g treat me nt a n d f or 9 8 da ys f oll o wi n g t he last st u d y 
dr u g a d mi nistrati o n peri o d. 
E xcl usi o n Criteri a  
Patie nts wit h a n y of t he f oll o wi n g criteria are N O T  eli gi ble f or e nr oll me nt: 
1.  C urre nt m uc ositis 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 7 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
Criteri a f or Ev al u ati o n:  
Effic ac y:   
Efficac y will be deter mi ne d i n patie nts w h o ha ve recei ve d e n o u g h ra diati o n e x p os ure t o p ut t he m at 
si g nifica nt ris k of de velo pi n g S O M ( defi ne d as a c u m ulati ve ra diati o n d ose of at least 5 5 G y).  
Pri m ary E n d p oi nt: 
T he pri mar y efficac y o utc o me f or t his st u d y is t he d urati o n of S O M, defi ne d as t he n u m ber of da ys 
fr o m t he first oral e xa mi nati o n wit h a W H O Gra de assess me nt of ≥3 u nt il t he first ti me t he patie nt has 
a W H O Gra de of < 3 wit h n o s u bse q ue nt rea di n gs ≥3 .  
Sec o n d ary e n d p oi nts will be a n alyze d i n hier arc hic al or der: 
1.  T he Area - U n der-t he-C ur ve ( A U C) f or S O M ( W H O Gra de ≥3) b y ti me pl ot (se verit y - wei g hte d 
d urati o n) 
2.  T he Area - U n der-t he-C ur ve ( A U C) f or ulcerati ve oral m uc ositis ( U O M; defi ne d as W H O 
Gra de ≥2) b y ti me pl ot (se verit y - wei g hte d d urati o n) 
3.  T he i nci de nce of S O M  
4.  T he q ualit y of life assess me nt usi n g t he E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of 
Ca ncer ( E O R T C) Q ualit y of Life Q uesti o n naire 3 0 q uesti o n m o d ule ( E O R T C Q L Q- C 3 0 
( versi o n 3)) a n d t he E O R T C Hea d a n d Nec k Ca ncer latest 4 3 q uesti o n m o d ule ( Q L Q-H & N 4 3) 
i nstr u me nt 
5.  T he a m o u nt of o pi oi ds use d  
 
T he f oll o wi n g sec o n d ary e n d p oi nts will als o be ex a mi ne d:  
•  
T he c u m ulati ve n u m ber of da ys of ra diati o n treat me nt brea ks 
•  
T he d urati o n of S O M i n all ra n d o mize d patie nts recei vi n g fracti o nate d R T a n d c o nc o mita nt 
cis plati n c he m ot hera p y, gi ve n as 8 0-1 0 0 m g/ m 2 e ver y t hir d wee k (I T T p o p ulati o n) 
•  
T he d urati o n of U O M 
•  
T he c u m ulati ve a m o u nt of pai n re p orte d b y patie nts 
•  
T he d urati o n of S O M usi n g a n alter nati ve defi niti o n calc ulate d as t he n u m ber of da ys fr o m t he 
first oral e xa mi nati o n wit h W H O gra de ≥3 t hr o u g h t he last assess me nt wit h a W H O sc ore ≥3 
(a n d n ot t o t he first assess me nt wit h a W H O gra de < 3) wit h n o f urt her re p orts of a W H O gra de 
≥3.  
•  
T he d urati o n of S O M i n t he Per-Pr ot oc ol P o p ulati o n defi ne d as patie nts recei vi n g a c u m ulati ve 
ra diati o n d ose of at least 5 5 G y a n d all sc he d ule d st u d y dr u g.  
S af et y:  
•  
T he i nci de nce, t y pe, a n d b o d y s yste m cate g orizati o n of A Es 
•  
T he i nci de nce, t y pe, a n d b o d y s yste m cate g orizati o n of S A Es  
•  
T he c ha n ges fr o m B aseli ne f or he mat ol o g y para meters, cli nical c he mistr y para meters, a n d vital 
si g ns 
•  
T u m or stat us at 1 2 wee ks  a n d 1 2 m o nt hs f oll o wi n g c o m pleti o n of R T cate g orize d usi n g t he 
R E CI S T criteria  
•  
T he i nci de nce a n d se verit y of re p orte d i nfecti o ns assesse d b y C T C A E gra di n g  
•  
T he 1 2 m o nt h p ost- R T s ur vi val  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 9 of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
2.  
T A B L E O F C O N T E N T S, LI S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
2. 1.  
T a ble of C o nte nts 
1.  
P R O T O C O L S Y N O P SI S  ..................................................................................................... 3 
2.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F FI G U R E S ..................... 9 
2. 1.  
T A B L E O F C O N T E N T S  ....................................................................................................... 9 
2. 2.  
L I S T O F T A B L E S  ............................................................................................................. 1 2 
2. 3.  
L I S T O F F I G U R E S ............................................................................................................ 1 2 
2. 4.  
A P P E N DI C E S  ................................................................................................................... 1 3 
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 4 
4.  
I N T R O D U C TI O N............................................................................................................... 1 6 
4. 1. 
S G X 9 4 2  ( DU S Q U E TI D E ) ................................................................................................ 1 6 
4. 2.  
T O XI C O L O G Y  ................................................................................................................. 1 6 
4. 3.  
P R E C LI NI C A L P H A R M A C O L O G Y  ..................................................................................... 1 7 
4. 4.  
P H A S E 1  T RI A L  ............................................................................................................... 1 8 
4. 5.  
P H A S E 2  T RI A L I N H E A D A N D N E C K C A N C E R P A TI E N T S  ................................................ 1 9 
 
 
 
4. 7.  
P A TI E N T P O P U L A TI O N  .................................................................................................... 2 7 
5.  
T RI A L O B J E C TI V E S A N D  P U R P O S E  .......................................................................... 2 8 
5. 1.  
P RI M A R Y O BJ E C TI V E  ..................................................................................................... 2 8 
5. 2.  
S E C O N D A R Y O BJ E C TI V E S  ............................................................................................... 2 8 
5. 3.  
S A F E T Y O BJ E C TI V E S  ...................................................................................................... 2 9 
6.  
I N V E S TI G A TI O N A L P L A N ............................................................................................ 3 0 
6. 1.  
O V E R A L L S T U D Y D E SI G N A N D P L A N : D E S C RI P TI O N  ...................................................... 3 0 
6. 2.  
S P E CI FI C A S S E S S M E N T S  ................................................................................................. 3 2 
6. 2. 1  Or al M uc ositis ( O M) Gr a di n g .................................................................................. 3 2  
6. 2. 2  T u m or St at us ............................................................................................................. 3 2  
6. 2. 3  I nfecti o n .................................................................................................................... 3 3 
6. 2. 4  Hist ory of P ai n a n d O pi oi d Use................................................................................ 3 4  
6. 2. 5  L a b or at ory Assess me nts............................................................................................ 3 4  
6. 2. 5. 1. 
Ser u m Pre g n a nc y T est  ...................................................................................... 3 4 
6. 2. 5. 2. 
He mat ol o g y T ests  ............................................................................................. 3 4 
6. 2. 5. 3. 
Cli nical C he mistr y La b orat or y Tests  ................................................................ 3 4 
6. 2. 6  Ot her Assess me nts  .................................................................................................... 3 5 
6. 2. 6. 1. 
Me dical Hist or y  ................................................................................................ 3 5 
6. 2. 6. 2. 
P h ysical E x a mi nati o n ........................................................................................ 3 5 
6. 2. 6. 3. 
Q ualit y of Lif e Q uesti o n naire  ........................................................................... 3 5 
6. 2. 6. 4. 
Vital Si g ns  ......................................................................................................... 3 5 
6. 2. 6. 5.  Hei g ht a n d B o d y M ass I n de x ( B MI) ................................................................ 3 6  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 1 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
1 0. 2. 2. 4. Assess me nt of Pai n  ........................................................................................... 5 0 
1 0. 2. 2. 5.  Alter nati ve Meas ure me nt of t he D urati o n of S O M .......................................... 5 0  
1 0. 2. 2. 6.  D urati o n of S O M i n t he Per- Pr ot oc ol P o p ulati o n ............................................. 5 0  
1 1.  A S S E S S M E N T O F S A F E T Y  ............................................................................................. 5 1 
1 1. 1.  O V E R A L L A S S E S S M E N T S  ................................................................................................ 5 1 
1 1. 1. 1  
Assess me nt of A Es  ................................................................................................. 5 1 
1 1. 1. 2  
Assess me nt of S A Es  ............................................................................................... 5 1 
1 1. 1. 3  
Assess me nt of L a b or at ory a n d Vit al Si g ns ........................................................... 5 1  
1 1. 1. 4  
Assess me nt of T u m or Pr o gressi o n at 1 2 weeks a n d 1 2- m o nt hs P ost- R T  ............. 5 2 
1 1. 1. 5  
I nfecti o ns ............................................................................................................... 5 2 
1 1. 1. 6  
Assess me nt of M ort ality T hr o u g h t he 1 2- m o nt h P ost- R T Cli nic Visit  .................. 5 2 
1 1. 1. 7  
Pr o gressi o n -free S urviv al ..................................................................................... 5 2 
1 1. 2.  S A F E T Y P A R A M E T E R S  .................................................................................................... 5 3 
1 1. 2. 1  
A dverse E x perie nce ( A E)  ...................................................................................... 5 3 
1 1. 2. 2  
Seri o us A dverse E x perie nce ( S A E)  ....................................................................... 5 3 
1 1. 3.  R E L A TI O N S HI P T O S T U D Y D R U G  .................................................................................... 5 3 
1 1. 4.  S E V E RI T Y O F A D V E R S E E V E N T  ...................................................................................... 5 4 
1 1. 5.  R E P O R TI N G A D V E R S E E V E N T S  ....................................................................................... 5 4 
1 1. 5. 1  
A dverse E ve nts  ...................................................................................................... 5 4 
1 1. 5. 2  
Seri o us A dverse E ve nts  ......................................................................................... 5 4 
1 1. 6.  D A T A M O NI T O RI N G C O M MI T T E E  ................................................................................... 5 5 
1 2.  S T A TI S TI C S  ....................................................................................................................... 5 7 
1 2. 1.  O V E R VI E W  ..................................................................................................................... 5 7 
 
 
1 2. 3.  F I N A L A N A L Y SI S  ............................................................................................................ 5 8 
1 2. 4.  S A M P L E S I Z E C A L C U L A TI O N  .......................................................................................... 5 8 
1 2. 5.  S E L E C TI O N O F P RI M A R Y A N A L Y SI S P O P U L A TI O N  .......................................................... 5 8 
1 2. 6.  D I R E C T A C C E S S T O S O U R C E D A T A / DO C U M E N T S  ........................................................... 5 8 
1 2. 6. 1  
St u dy M o nit ori n g .................................................................................................. 5 8  
1 2. 6. 2  
Pre -st u dy Ev al u ati o n ............................................................................................ 5 9 
1 2. 6. 3  
Site I niti ati o n Visit  ................................................................................................ 5 9 
1 2. 6. 4  
M o nit ori n g Visits  .................................................................................................. 5 9 
1 2. 6. 5  
Cl ose- o ut Visit  ....................................................................................................... 6 0 
1 2. 7.  A U DI T S A N D IN S P E C TI O N S  ............................................................................................. 6 0 
1 3.  I N S TI T U TI O N A L R E VI E W B O A R D (I R B)/ E T HI C A L C O M MI T T E E ( E C)  ........... 6 1 
1 4.  Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  ................................................ 6 2 
1 5.  E T HI C S  ............................................................................................................................... 6 3 
1 5. 1.  E T HI C A L R E VI E W O F T RI A L  ........................................................................................... 6 3 
1 5. 2.  E T HI C A L C O N D U C T O F T H E S T U D Y  ................................................................................ 6 3 
1 5. 3.  
W RI T T E N IN F O R M E D C O N S E N T  ...................................................................................... 6 3 
1 5. 4.  S U BJ E C T D A T A P R O T E C TI O N  .......................................................................................... 6 3 
1 5. 5.  F I N A N CI A L D I S C L O S U R E ................................................................................................ 6 3 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 1 4  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
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 
T a ble 2 : A b bre vi ati o ns a n d s peci alist ter ms  
A b bre vi ati o n or s peci alist ter m  
E x pl a n ati o n 
A E  
A d verse e ve nt  
A L T  
Ala ni ne a mi n otra nsferase  
A S T  
As partate a mi n otra nsferase  
A U C  
Area u n der t he c ur ve  
B A L  
Br o nc h oal ve olar la va ge 
B MI  
B o d y mass i n de x  
B U N  
Bl o o d urea nitr o ge n  
C F R  
C o de of fe deral re g ulati o ns 
C ma x  
Ma xi m u m c o nce ntrati o n 
C N S  
Ce ntral ner v o us s yste m  
C O 2 
Car b o n di o xi de 
C P  
C o n diti o nal p o wer  
C R  
C o m plete res p o nse 
C R T  
C he m ora diati o n t hera p y  
C T  
C o m p ute d t o m o gra p h y 
C T C A E  
C o m m o n T er mi n ol o g y Criteria f or A d verse E ve nts  
C V  
Car di o vasc ular  
D L T  
D ose li miti n g t o xicit y  
D M C  
Data m o nit ori n g  c o m mittee 
E C  
Et hics C o m mittee  
E C G  
Electr ocar di o gra m  
e C R F 
Electr o nic case re p ort f or m  
E M A  
E ur o pea n Me dici nes A ge nc y 
E O R T C  
E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer 
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d cli nical practices 
G L P  
G o o d la b orat or y practices  
H E D  
H u ma n e q ui vale nt d ose  
H C G  
H u ma n c h ori o nic g o na d otr o pi n 
H P V  
H u ma n pa pill o ma vir us 
I B 
I n vesti gat or’s br oc h ure 
I C F 
I nf or me d c o nse nt f or m 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 1 5  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
A b bre vi ati o n or s peci alist ter m  
E x pl a n ati o n 
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I D R 
I n nate Defe nse Re g ulat or 
I M R T 
I nte nsit y m o d ulate d ra diati o n t hera p y 
I R B 
I nstit uti o nal Re vie w B oar d 
I T T 
I nte nt t o treat 
I V 
I ntra ve n o us 
I W R S 
I nteracti ve we b res p o nse s yste m 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
mI T T  
M o difie d i nte nt t o treat  
M RI  
Ma g netic res o na nce i ma gi n g  
M T D  
Ma xi m u m t olerate d d ose 
N  
N u m ber  
N CI  
Nati o nal Ca ncer I nstit ute  
N D A  
Ne w dr u g a p plicati o n 
N H P  
N o n - h u ma n pri mate 
N O A E L  
N o o bser ve d a d verse effect le vel 
O M  
Oral m uc ositis  
P E G  
Perc uta ne o us e n d osc o pic gastr o n o m y  
P E T  
P ositr o n e missi o n t o m o gra p h y  
P D  
P har mac o d y na mics  
PI  
Pri nci pal i n vesti gat or  
P K  
P har mac o ki netic  
P P  
Per pr ot oc ol  
P R  
Partial res p o nse  
R B C  
Re d bl o o d cell 
R T  
Ra diati o n t hera p y 
S A E  
Seri o us a d verse e ve nt  
S D  
Sta ble disease  
S O M  
Se vere oral m uc ositis  
T ma x  
Ti me at w hic h t he ma xi m u m bl o o d c o nce ntrati o n was ac hie ve d  
U O M  
Ulcerati ve oral m uc ositis  
W B C  
W hite bl o o d cell  
W H O  
W orl d Healt h Or ga nizati o n 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 1 6  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
4.  
I N T R O D U C TI O N 
T his secti o n  c o ntai ns a brief descri pti o n of t he rati o nale a n d a v aila ble i nf or mati o n c o ncer ni n g t he 
c he mistr y, n o n-cli nical p har mac ol o g y a n d t o xic ol o g y, p har mac o ki netics ( P K), 
p har mac o d y n a mics ( P D), a n d pre vi o us cli nical e x perie nce wit h S G X 9 4 2 . Please refer t o t he 
I n v esti gat or's Br oc h ur e (I B) f or a d diti o nal details a n d i nf or mati o n. 
4. 1.  
S G X 9 4 2 ( Dus q ueti de)  
D us q ueti de is a fi ve a mi n o -aci d pe pti de t hat bi n ds t o t he i ntracell ular p 6 2 pr otei n [ 1] res ulti n g i n 
m o d ulati o n of t he i n nat e i m m u ne res p o nse t o b ot h i nfecti o n a n d tiss ue da m a ge b y re d u ci n g 
i n d ucti o n of i nfla m mati o n a n d i ncreasi n g m acr o p ha ge acti vati o n/ recr uit me nt, res ulti n g i n 
i ncreas e d bact erial cleara nce a n d tiss ue heali n g  [ 2- 4]. T he dr u g is f or m ulat e d as a n  a q ue o us, 
sterile s ol uti o n f or i njecti o n c o ntai ni n g 6 0 m g/ m L of d us q ueti de . T he  f or m ulati o n  c o ntai ns  n o 
preser vati ves  a n d  n o e xci pie nts. T he dr u g will be gi ve n at a d ose of 1. 5 m g/ k g. Dr u g will be 
dil ute d i nt o a n i nf use d v ol u me of 2 5 m L a n d a d mi nistere d as a 4- mi n ute i nf usi o n usi n g eit her a n 
i nf usi o n or s yri n ge p u m p.  
4. 2.  
T o xic ol o g y  
N o n - G L P a n d G L P precli nical t o xic ol o g y a n d s afet y p h ar mac ol o g y st u dies were c o n d ucte d i n 
mice a n d n o n- h u ma n pri mates ( N H Ps). Tra nsie nt, hi g h -d ose ac ute t o xicit y was o bser v e d  i n b ot h 
m o use a n d N H P . Res ol uti o n occ urr e d wit hi n mi n utes i n s ur vi vi n g a ni mals wit h n o l o n g-ter m 
se q uelae. 
P il ot t o xic ol o g y st u dies i n dicate d t hat t he ma xi m u m t olerate d d ose ( M T D) of a si n gl e 
a d mi nistrati o n of d us q ueti de, a d mi nistere d as a n I V i njecti o n o ver 3 0 t o 6 0 sec o n ds, is 8 8 m g/ k g 
i n mice. I n N H P, mil d cli nical si g ns (i.e., s h all o w/la b ore d res pirati o n, decrease d acti vit y, 
partiall y cl ose d e yes , a n d m uscle t witc hes) were n ote d i n 1 or b ot h a ni mals after a d mi nistrati o n 
of 9 0 ( 1 a ni mal), 1 8 0 ( b ot h a ni mals), a n d 2 2 0 ( 1 a ni mal) m g/ k g d us q ueti de d uri n g a n d s h ortl y 
after d osi n g. T hes e res ol ve d wit hi n a fe w mi n utes wit h o ut detecta ble resi d ual effects. 
T he safet y of m ulti ple dail y i njecti o ns of d us q ueti de has als o bee n e val u ate d i n G L P st u dies i n 
mice a n d N H Ps. I n mice, d oses of 2 0, 6 0, or 9 0 m g/ k g/ da y w ere gi ve n I V f or 1 4 da ys. Deat hs 
were o bs er ve d at t he hi g h d ose, prece de d mai nl y b y la b ore d res pirati o n a n d rec u m be n c y. 
Let h alit y w as als o o bser v e d i n 1 a ni mal gi v e n 6 0 m g/ k g b ut n o ot her a ni m als e x hi bite d cli nical 
si g ns at t his d ose. N o test article-r elate d m ortalit y or cli nical si g ns w ere o bser ve d at 2 0 m g/ k g. I n 
s ur vi v ors of all gr o u ps, t here w as n o e vi de n ce of t o xicit y i n a n y or ga n or a b n or mal bi oc he mistr y 
or he mat ol o g y. N o A E s were o bs er ve d at 2 0 m g/ k g a d mi nistere d dail y f or 1 4 da ys. 
D us q ueti de at 2 0, 8 0, or 1 6 0 m g/ k g/ da y was gi ve n I V t o c y n o m ol g us m o n ke ys f or 1 4 da ys. 
Tra nsie nt decrease d acti vit y a n d partiall y cl ose d e yes c o nti n ue d t o be o bser ve d d uri n g a n d 
s h ortl y aft er d osi n g at 1 6 0 m g/ k g f or t he first 3 da ys i n m ost a ni mals, t he n s p ora dicall y 
t hr o u g h o ut t he r e mai ni n g d osi n g peri o d. I n all cas es, t hese cli nical si g ns res ol ve d wit hi n a fe w 
mi n utes. N o A E s were o bser ve d o n a n y ot h er meas ure d para meter or micr osc o picall y i n a n y 
tiss ue. T he a d mi nistrati o n of d us q ueti de at d oses of 2 0 a n d 8 0 m g/ k g/ da y di d n ot res ult i n a ny 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 2 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
T a ble 3: Re p orte d I nfecti o ns  
Tre at me nt Gr o u p  
Pl ace b o  
n = 3 8  
1. 5 m g/ k g 
n = 3 6  
6. 0 m g/ k g 
n = 1 9  
All I nfecti o ns: n 
  ( %) 
  p-v al ue c o m p are d t o pl ace b o 
2 9 
( 7 6 %) 
—  
2 3 
( 6 4 %) 
0. 3 1 1  
8 
( 4 2 %) 
0. 0 1 8  
N o n -f u n g al I nfecti o n: n  
  ( %) 
   p-v al ue c o m p are d t o pl ace b o 
1 7 
( 4 5 %) 
—  
1 0 
( 2 8 %) 
0. 1 5 3  
4 
( 2 1 %) 
0. 1 4 4  
Seri o us I nfecti o n: n  
   ( %) 
   p-v al ue c o m p are d t o pl ace b o 
8 
( 2 1 %) 
—  
7 
( 1 9 %) 
> 0. 9 9 9  
3 
( 1 6 %) 
0. 7 3 5  
 
I n t he mI T T p o p ulati o n, t he n u m ber of p atie nts wit h R E CI S T e val uati o ns cate g orize d as 
c o m plete res p o nses t o t h era p y w as i ncrease d fr o m  1 5/ 3 8 ( 3 9 %) i n t he place b o gr o u p t o 1 7/ 3 6 
( 4 7 %) i n t he 1. 5 m g/ k g S G X 9 4 2 d ose gr o u p, a 2 1 % i ncrease. Disre gar di n g t h ose patie nts wit h 
missi n g or n ot assesse d t u m or stat us, t his i ncrease was 3 4 % i n t he S G X 9 4 2 1. 5 m g/ k g gr o u p. 
T his is c o nsiste nt wit h precli nical st u dies s h o wi n g i m pr o ve d s ur vi val a n d d ecrease d t u m or 
v ol u me size ( 3). O ver t he l o n ger t er m, t he o verall res ol uti o n rate i n t he place b o p o p ulati o n was 
hi g h, ma ki n g f urt h er i m pr o ve me nt diffic ult t o de m o nstrate.  H o we v er, S G X 9 4 2 defi nitel y di d n ot 
decrease t he eff ecti ve ness of C R T t hera p y  (Ta bl e 4 ). Si milarl y, t he o verall 1 -year s ur vi val rate 
was si milar bet wee n gr o u ps a n d m ore fa v ora ble f or t he S G X 9 4 2 treat e d gr o u ps ( Ta ble 5 ).  
T a ble 4: I nci de nce of T u m or C o m plete Res p o nse as a F u ncti o n of Tre at me nt Gr o u p a n d 
Ti me p oi nt  ( S afet y P o p ul ati o n)* 
R E CI S T Res p o nse  
Pl ace b o  
n = 4 1  
1. 5 m g/ k g  
n = 4 2  
3. 0 m g/ k g  
n = 3  
6. 0 m g/ k g  
n = 2 3  
1 -m o nt h f oll o w -u p  
1 5/ 3 2 ( 4 7 %)  
1 7/ 2 7 ( 6 3 %)  
1/ 3 ( 3 3 %)  
4/ 1 6 ( 2 5 %)  
3 -m o nt h f oll o w -u p  
1 7/ 2 7 ( 6 3 %)  
1 8/ 2 7 ( 6 7 %)  
1/ 1 ( 1 0 0 %)  
9/ 1 7 ( 5 3 %)  
6 -m o nt h f oll o w -u p  
1 9/ 2 4 ( 7 9 %)  
1 9/ 2 8 ( 6 8 %)  
1/ 1 ( 1 0 0 %)  
1 0/ 1 4 ( 7 1 %)  
9 -m o nt h f oll o w -u p  
6/ 8 ( 7 5 %)  
1 4/ 1 6 ( 8 8 %)  
2/ 2/ ( 1 0 0 %) 
1/ 3 ( 3 3 %)  
1 2 -m o nt h f oll o w -u p  
2 2/ 2 3 ( 9 6 %)  
1 9/ 2 3 ( 8 3 %)  
1/ 2 ( 5 0 %)  
1 0/ 1 2 ( 8 3 %)  
L O C F * * t hr o u g h 1 2 -m o nt h f oll o w -u p  
2 6/ 3 5 ( 7 4 %)  
2 8/ 3 5 ( 8 0 %)  
1/ 3 ( 3 3 %)  
1 3/ 2 2 ( 5 9 %)  
* P erce nta ge calc ulati o n e xcl u des missi n g/ n ot assesse d e val uati o ns  
* * Last O bser vati o n Carrie d F or war d  
 
T a ble 5: M ort alit y (I T T P o p ul ati o n 1) 
M ort alit y  
Pl ace b o  
n = 4 3  
1. 5 m g/ k g  
n = 4 1  
3. 0 m g/ k g  
n = 3  
6. 0 m g/ k g  
n = 2 4  
T hr o u g h 1 2 -m o nt h f oll o w -u p  
9 ( 2 1 %)  
3 ( 7 %)  
0  
4 ( 1 7 %)  
1 I ncl u des o ne patie nt d yi n g 3 7 3 da ys after recei vi n g t heir last st u d y dr u g d ose 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 2 8  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
5.  
T RI A L O B J E C TI V E S A N D  P U R P O S E  
5. 1.  
Pri m ar y O bjecti ve  
T o assess t he efficac y of S G X 9 4 2 c o m pare d t o place b o i n decreasi n g t he d urati o n of S O M  
(defi ne d as W H O Gra d e lesi o n ≥3) i n patie nts recei vi n g fra cti o nate d ra diati o n treat me nts  a n d 
c o nc o mita nt cis plati n c he m ot hera p y, gi ve n as 8 0- 1 0 0 m g/ m2 e ver y t hir d wee k , f or t he treat me nt 
of s q ua m o us cell carci n o ma of t he oral ca vit y or or o p har y n x.  
5. 2.  
Sec o n d ar y O bjecti ves  
T o assess t he i m pact of S G X 9 4 2 c o m pare d t o place b o o n t he f oll o wi n g cli nicall y i m p orta nt 
sec o n dar y o bj ecti ves: 
1.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he Area- U n der-t he- C ur v e ( A U C) f or S O M 
( W H O Gra de ≥3) b y ti me pl ot (se verit y-w ei g hte d d urati o n) 
2.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he Area- U n der-t he- C ur v e ( A U C) f or 
ulcerati ve oral m uc ositis ( U O M; defi ne d as W H O Gra de ≥2) b y ti me pl ot (se verit y -
wei g ht e d d urati o n) 
3.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he i nci de nce of S O M 
4.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he q ualit y of life assess me nt usi n g t he E O R T C 
Q L Q - C 3 0 ( versi o n 3) a n d Q L Q - H & N 4 3 i nstr u me nt 
5.  T o assess t he i m pact t hat S G X 9 4 2 has o n t he a m o u nt of o pi oi ds use d 
 
T o assess t he i m pact of S G X 9 4 2 c o m pare d t o place b o o n t he f oll o wi n g a d diti o nal sec o n dar y 
o bjecti ves : 
•  T o assess t he i m pact t hat S G X 9 4 2 has o n t he c u m ulati ve n u m ber of da ys of R T brea ks 
•  T o assess t he i m pact t hat S G X 9 4 2 has o n t he d urati o n of S O M; i n all ra n d o mize d 
patie nts recei vi n g fracti o nate d R T a n d c o n c o mita nt cis plati n  c he m ot hera p y,  gi ve n as 8 0-
1 0 0 m g/ m 2 (I T T p o p ulati o n) 
•  T o assess t he i m pact t hat S G X 9 4 2 has o n t he d urati o n of U O M 
•  T o assess t he i m pact t hat S G X 9 4 2 has o n t he c u m ulati ve a m o u nt of pai n re p orte d b y 
patie nts  
•  T he d urati o n of S O M usi n g a n alter nati ve d efi niti o n calc ulate d as t he n u m ber of da ys 
fr o m t he first oral e x a mi nati o n wit h W H O gra d e ≥3 t hr o u g h t he last ass ess me nt wit h a 
W H O sc ore ≥3 (a n d n ot t o t he first assess me nt wit h a W H O gra de < 3) wit h n o f urt her 
re p orts of a W H O gra de ≥3 
•  T he d urati o n of S O M i n t he P er- Pr ot oc ol P o p ulati o n defi ne d as p atie nts recei vi n g a 
c u m ulati ve ra diati o n d os e of at least 5 5 G y a n d st u d y dr u g t wi ce per wee k d uri n g a n d f or 
2 wee ks after r a diati o n t hera p y  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 2 9  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
5. 3.  
S afet y O bjecti ve s 
Safet y o bj ecti ves will i ncl u de t he f oll o wi n g:  
•  T o assess t he i m pact t hat S G X 9 4 2 has o n the A d v erse E ve nts ( A E) a n d seri o us A d verse 
E ve nts ( S A E)  
•  T o assess t he i m pact t hat S G X 9 4 2 has o n c ha n ges i n safet y la b orat or y val u es  
•  T o assess t he i m pact t hat S G X 9 4 2 has o n t he Res p o nse E val uati o n Criteria i n S oli d 
T u m ors ( R E CI S T ) cate g orizati o n of t he pri mar y t u m or at 1 2 wee ks a n d 1 2 m o nt hs C R T  
•  T o assess t he i m pact of S G X 9 4 2 o n t he i nci de nce of re p orte d pres u me d b acterial 
i nfecti o ns bet wee n Baseli ne a n d 6 wee ks after c o m pleti o n of ra diati o n t hera p y ( R T) b y 
t otal n u m ber a n d b y se verit y of i nfecti o n, gra d e d usi n g t he N ati o nal Ca ncer I nstit ute’s 
( N CI’s) C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E) 
•  T o assess t he i m pact of S G X 9 4 2 o n 1 2 m o nt h all- ca use m ortalit y 
•  T o assess t he i m pact of S G X 9 4 2 o n pr o gressi o n free s ur vi val t hr o u g h 1 2 m o nt hs 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 0  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
6.  
I N V E S TI G A TI O N A L P L A N 
6. 1.  
O ver all St u d y Desi g n a n d Pl a n: Descri pti o n  
A p pr o xi matel y 2 6 0 p atie nts will  be e nr olle d i nt o t his P hase 3, place b o -c o ntr olle d, d o u ble- bli n d, 
m ulti nati o nal st u d y t o e v al uate t he efficac y of S G X 9 4 2 c o m pare d t o place b o i n treati n g t he 
d urati o n of S O M  i n patie nts recei vi n g C R T  f or t he treat me nt of hea d a n d n ec k ca n cer. Patie nts 
will be ra n d o mize d i nt o o ne of t w o gr o u ps ( 1. 5 m g/ k g S G X 9 4 2: Place b o) at a 1: 1 rati o. T he y will 
be stratifie d b y site , pres e nce of gastr ost o m y t u b e, a n d H PV stat us . Patie nts will recei ve t heir 
i nitial bli n de d I V st u d y dr u g ( 1. 5 m g/ k g S G X 9 4 2 or place b o) wit hi n 3 da ys of starti n g ra diati o n.  
T he pri mar y efficac y o ut c o me f or t his st u d y is t he d urati o n of S O M, defi ne d as t he n u m ber of 
da ys fr o m t he first or al e x a mi nati o n wit h a W H O Gra de assess me nt of 3 or 4 t hr o u g h t he first 
da y t h at a W H O Gr a de of < 3 is rec or de d wit h n o s u bse q ue nt assess me nts ≥3 . O M  will be 
e val uate d usi n g t he W H O  sc ori n g f or O M .  
Patie nts will be scree ne d t o assess t heir eli gi bilit y pri or t o ra n d o mizati o n. After ra n d o mizati o n, 
s u bjects will be gi n treat me nt wit h st u d y dr u g wit hi n 3 da ys of i nitiati n g R T .  
Patie nts will recei ve st u d y dr u g w hile u n der g oi n g C R T  a n d c o nti n ue t o recei ve st u d y dr u g f or 2 
wee ks  after t he c o m pleti o n of t heir R T . St u d y visit days will be e v er y t hir d da y ( ± 1 da y) . O n 
st u d y visit da ys, p atie nts will recei ve t he 4- mi n ute  i nf usi o n of st u d y dr u g. St u d y dr u g will n ot be 
gi ve n o n t he s a me da y as c he m ot hera p y . St u d y dr u g ca n be gi ve n at a n y ti me d uri n g t he visit 
da y, b ut m ust occ ur o n t h e sa me cale n dar da y t hat is t he st u d y visit da y. T h e st u d y visit cale n d ar 
e xte n ds t o 2 wee ks  p ost-c o m pleti o n of R T .  
Efficac y will be f urt her assesse d at t he 3  t hr o u g h 6 wee k s p ost-R T c o m pleti o n visits. F oll o w - u p 
visits will be c o n d ucte d at 1 2 wee ks a n d 1 2 m o nt hs after t he last ra diati o n d ose t o c o nti n ue t o 
e val uate safet y a n d s ec o n dar y e n d p oi nts. 
Bel o w is a ta bl e o utli ni n g t he st u d y sc h e d ule of pr oce d ures a n d ass ess me nts. T he st u d y w ee k 
desi g nati o ns ass u me a 7- wee k  C R T sc he d ule. T h ese ti mes ma y re q uire a dj ust me nt (as descri be d 
bel o w) if t he treat me nt c o urse is s h orter or if treat me nt brea ks pr ol o n g t he C R T f or m ore t ha n 7 
wee ks.  
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
T a ble 7 : Sc he d ule of E ve nts b y Wee k 
St u d y w ee k  
Scree n  
B ase 2 
1 w 3 
2 w  
3 w  
4 w  
5 w  
6 w  
7 w  
8 w  
9 w  
1 0 w  
1 1 w  
1 2 w  
1 3 w  
1 5 - 5 5 w  
1 9 w  
5 9 w  
P ost -R T 1 
 
 
 
 
 
 
 
 
 
1 w  
2 w  
3 w  
4 w  
5 w 4 
6 w  
2 m -1 1 m 5 
1 2 w  
1 2 m  
M e dic al Hist or y  
X 
X 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X 
2 X 
X 
X 
X 
X 
X  
X  
X 
I nf or me d 
C o nse nt  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
R a n d o miz ati o n  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hist or y of P ai n 
a n d O pi oi d Use  
 
X 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X 
2 X 
X 
X 
X 
X 
 
X  
X 
Assess me nt of 
I nfecti o ns 
 
X 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X 
2 X 
X 
X 
X 
X 
 
 
 
R a di ati o n 6 
 
 
5 X  
5 X  
5 X  
5 X  
5 X  
5 X  
5 X  
 
 
 
 
 
 
 
 
 
Cis pl ati n 6 
 
 
X  
 
 
X  
 
 
X  
 
 
 
 
 
 
 
 
 
A d mi nister 
Dr u g  
 
 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
 
 
 
 
 
 
 
W H O O M
7 
 
X 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
X 
X 
X 
X 
 
 
 
P E G T u be U se 
 
X 
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
X 
X 
X 
X 
 
 
 
V S 8 
X  
X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
X  
X  
X  
X  
 
 
 
P h ysic al E x a m  
X  
X  
 
 
 
 
 
 
 
 
X 1 3 
 
 
 
X  
 
 
 
S afet y L a bs 9 
X  
X 1 2 
 
 
X  
 
 
X  
 
 
X 1 3 
 
X  
 
X  
 
 
 
A Es  
 
X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
2 X  
X  
X  
X  
X  
 
 
 
T u m or Sc a n 1 0 
X 1 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
X 
Ser u m 
Pre g n a nc y  
X 
X 1 2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
H P V St at us  
X 1 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Q u alit y of Life  
 
X 
 
 
 
X 
 
 
 
 
X 1 3 
 
 
 
 
 
 
 
 
1 P ost -R T =  ti me fr o m t h e last ra diati o n t h era p y treat me nt 
2 Baseli ne i nf or mati o n n ee ds t o be o btai n e d pri or t o ( 0 t o 9 6 h o urs b ef ore) t h e first d ose of 
st u d y dr u g 
3 w = wee ks  
4 O nl y t o be d o ne if W H O sc ore is ≥2 at Wee k 4 P ost -R T visit  
5 m = m o nt hs; patie nt c o ntact (cli nic visit, tele p h o n e, or e mail) re q uire d m o nt hl y t hr o u g h 
t he 1 2-m o nt h cli nic visit  
6 Ti mi n g of ra diati o n a n d c h e m ot h era p y at discreti o n of pri mar y care p h ysicia ns  
7 W H O O M = oral m u c ositis gra di n g wit h W H O Oral M u c ositis Gra di n g s yste m  
8 Vital si g ns t o  i ncl u d e te m p erat ure, wei g ht, p ulse, res pirati o ns, a n d seate d bl o o d press ure; 
Hei g ht will be o btai n e d at Baseli ne o nl y  
9 Safet y la bs = he mat ol o g y a n d cli nical c h e mistr y p a n els  
1 0 Sca n = o btai n i nitial sta gi n g C T/ P E T/ M RI sca ns (scree ni n g sca n m ust be wit hi n  6 wee ks 
pri or t o Baseli n e)  
1 1 Nee d t o c o nfir m t h at t h e i nitial dia g n ostic sca ns were C T, P E T, or M RI a n d t he t u m or 
was teste d f or H P V stat us  
1 2 Re p eat test re q uire d if Baseli ne sa m ple > 7  da ys fr o m Scree ni n g  
1 3 T o b e d o n e o nl y o n t h e sec o n d visit i n wee k 2  p ost - R T  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 2  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
It is ass u me d t hat p atie nts will recei ve 7 w ee ks of R T . I n practice, s o me patie nts will ha ve a 
s h orter c o urs e (l o wer pla n ne d ra diati o n d ose) or st o p treat me nt earl y. Si milarl y, p atie nts wit h R T 
brea ks w h o c o m plete 7 w ee ks of R T ma y re q uire treat me nt f or m ore t ha n 7 wee ks. All p ost- R T  
visits will be sc he d ule d fr o m t he last  R T  s o t hat if t he R T  is c o m plete d after 6 wee ks, st u d y dr u g 
will be c o nti n ue d f or t he 2 wee ks f oll o wi n g ( Wee ks 7 a n d 8) a n d t he 1 2 w ee ks  p ost-ra di ati o n 
sca n will be  o btai ne d i n Wee k 18 . Si milarl y, if t here are treat me nt brea ks s uc h t hat R T  c o m pletes 
i n st u d y Wee k 8, t he st u d y dr u g will c o nti n ue f or 2 wee ks ( Wee ks 9 a n d 1 0) a n d t he 1 2 w ee ks 
p ost- ra diati o n sca n will b e o btai ne d at Wee k 2 0. 
6. 2.  
S pecific Assess me nts  
6. 2. 1  
Or al M uc ositis ( O M) Gr a di n g  
O M will be e val uate d b y pers o n nel trai ne d i n t he use of t he W H O Oral M uc ositis Gra di n g 
s yste m w hic h  i ncl u d es b ot h p h ysical a n d f u ncti o n al i nf or mati o n. T his gra di n g s yste m is wi del y 
utilize d i n O M cli nical researc h tri als i ncl u di n g t h e P hase 2 trial a n d is s h o w n i n  Ta ble 8 . 
T a ble 8 : W H O Or al M uc ositis Gr a di n g S yste m 
Sc or e 
Fi n di n gs  
0 
N o fi n di n gs O R  
Pai n or er yt he ma ( n ot b ot h)  
1 
Pai n a n d er yt he ma A N D  
N o ulcer  
2 
Ulcer a n d/ or pse u d o me m bra ne, A N D  
A ble t o eat s oli d f o o d A N D 
A ble t o dri n k  
3 
Ulcer a n d/ or pse u d o me m bra ne, A N D  
N ot a ble t o eat s oli d f o o d A N D 
A ble t o dri n k  
4 
Ulcer a n d/ or pse u d o me m bra ne, A N D  
N ot a ble t o eat s oli d f o o d A N D 
N ot a ble t o dri n k  
O nl y me dical pers o n n el at t he site w h o ha ve u n d er g o n e trai ni n g a n d certifi cati o n i n usi n g t he 
W H O Gra di n g s yst e m will perf or m t he O M ass ess me nts.  
6. 2. 2  
T u m or St at us  
T he t u m or res p o nse t o tr eat me nt will be use d as a safet y e n d p oi nt. Res ults at 1 2 wee ks  a n d 1 2 
m o nt hs p ost- R T will be c o m par e d t o t he Scree ni n g res ults usi n g t he R E CI S T 1. 1 s yste m. T he 
e val uati o n criteri a f or t he tar get lesi o n (t he pri mar y hea d a n d n ec k carci n o ma) are s h o w n i n 
Ta ble 9 ; t he criteria f or n o n-tar get lesi o ns are s h o w n i n Ta ble 1 0 ; a n d t he criteria f or o v erall 
cate g orizati o n of t he t u m or stat us are s h o w n i n T a ble 1 1 . I n a d diti o n, details pertai ni n g t o 
rec urre nce of disease, a d diti o nal t hera p y, or s ur ger y re q uire d  after t he acti ve treat me nt p has e of 
t he trial is c o m plete d will be c ollecte d a n d rec or de d i n t he e C R F t hr o u g h o ut all f oll o w u p visits 
u ntil 1 2 m o nt hs f oll o wi n g t he last R T treat me nt.  
  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 3  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
T a ble 9: R E CI S T E v al u ati o n of t he T ar get Lesi o n 
T ar get Lesi o n Res p o nse  
Me as ure me nt  
C o m plet e Res p o nse ( C R) 
All tar get lesi o ns g o ne  
Partial Res p o nse ( P R)  
> 3 0 % decrease fr o m baseli ne  
Pr o gressi ve Disease  
> 2 0 % i ncrease fr o m s mallest s u m of l o n gest dia meter rec or de d 
si nce treat me nt starte d ( best res p o nse) 
Sta ble Disease ( S D)  
Neit her Pr o gressi ve D isease n or Partial Res p o nse 
 
T a ble 1 0: R E CI S T E v al u ati o n of t he N o n- t ar get Lesi o n 
T ar get Lesi o n Res p o nse  
Me as ure me nt  
C o m plete Res p o nse ( C R)  
All n o n- tar get lesi o ns g o ne 
T u m or mar kers g o ne 
Sta ble Disease ( S D)  
Persiste nce of ≥1 n o n -tar get lesi o n 
T u m or mar ker le vel ele vate d  
Pr o gressi ve Disease  
E nlar ge me nt of n o n -tar get lesi o ns 
 
T a ble 1 1 : O ver all R E CI S T Res p o nse 
T ar get Lesi o ns  
N o n -t ar get Lesi o ns 
Ne w Lesi o ns  
O ver all Res p o nse  
C R  
C R  
N o  
C o m plete Res p o nse  
C R  
S D  
N o  
Partial Res p o nse  
P R  
N o n - Pr o gressi ve 
D isease 
N o  
Partial Res p o nse  
S D  
N o n - Pr o gressi ve 
D isease 
N o  
Sta ble Disease  
P r o gressi ve D isease 
A n y  
Yes or N o  
Pr o gressi ve Disease  
A n y  
P r o gressi ve D isease 
Yes or N o  
Pr o gressi ve Disease  
A n y  
A n y  
Yes  
Pr o gressi ve Disease  
 
6. 2. 3  
I nf ecti o n 
I nfecti o ns will be r e p orte d at eac h cli nic visit t hr o u g h t o t he 6-wee k  p ost-R T visit . A n y i de ntifie d 
i nfecti o n will be cate g orize d as pres u me d  f u n gal, pres u me d viral, or pres u me d bacteri al . T he 
se verit y of eac h r e p orte d infecti o n will be gra d e d 1 t o 5 usi n g t he C T C A E.  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 4  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
6. 2. 4  
Hist or y of P ai n a n d O pi oi d  Use  
E x ce pt f or t he Scree ni n g visit, a t e ver y st u d y visit, t he st u d y staff will re vie w wit h t he patie nt 
t heir c urr e nt pai n le vel as well as t he ca us e of t heir pai n. Eff orts will be ma d e t o differe ntiate  
pai n d ue t o O M  vers us ot her ca us es of pai n. T h e st u d y staff will als o re vie w wit h t he patie nt 
t heir c urr e nt prescri pti o ns f or pai n me dicati o n ( o pi oi ds) wit h s pecial care ta ke n t o re vie w t he as 
nee de d  me di cati o ns t he p atie nts ha ve bee n  gi ve n as well as t he fre q ue nc y  wit h w hic h t he y are 
ta ki n g t he m. D etails f or all of t he a b o ve will be rec or de d i n t he e C R F.  
I n a d diti o n, site staff will re vie w t he st u d y-s pecifi c oral h y gie ne re q uire me nts wit h t he patie nt o n 
a wee kl y b asis.  
6. 2. 5  
L a b or at or y Ass ess me nts  
6. 2. 5. 1.  
Ser u m Pre g n a nc y Test  
Bl o o d sa m ples will be o btai ne d at t he Scree ni n g, Baseli ne  (if Baseli ne > 7 d a ys  fr o m Scree ni n g), 
a n d 6 wee k s p ost-R T  visits f or a ser u m pre g na n c y test  ( h u ma n c h ori o nic g o na d otr o pi n [ HC G])  
f or all w o me n w h o are of c hil d beari n g p ote ntial.  
6. 2. 5. 2.  
He m at ol o g y Tests 
T he he mat ol o g y pa nel will be perf or me d at t he Ce ntral La b orat or y o n sa m ples c ollecte d at  
Scree ni n g,  Baseli ne ( if Scree ni n g tests w ere o bt ai ne d > 7 d a ys  fr o m Bas eli ne), Wee k 3 , Wee k  6, 
a n d at t he 2- w ee k p ost-R T, t he 4- wee k  p ost-R T visit  a n d t he 6-wee k p ost- R T visit s. T he pa nel 
will c o nsist of t he f oll o wi n g tests:  
•  Re d bl o o d cell c o u nt ( R B C) 
•  He mat ocrit  
•  He m o gl o bi n 
•  R B C i n dices  
•  Platelet c o u nt  
•  W hite bl o o d cell c o u nt ( W B C) 
•  W B C differe ntial c o u nt 
6. 2. 5. 3.  
Cli nic al C he mistr y L a b or at or y Tests 
T he cli nical c h e mistr y p a nel will be perf or m e d at t he Ce ntral La b orat or y o n sa m ples c ollecte d at 
Scree ni n g, Baseli ne ( if Scree ni n g tests w ere o bt ai ne d > 7 d a ys  fr o m Bas eli ne), Wee k 3 , Wee k 6, 
a n d at t he 2 - w ee k p ost-R T, t he 4- wee k  p ost-R T a n d t he 6-wee k p ost- R T visit s. T he pa nel will 
c o nsist of t he f oll o wi n g t ests: 
•  Ser u m s o di u m 
•  Ser u m p otassi u m 
•  Ser u m c hl ori de 
•  Ser u m bicar b o nat e ( C O 2) 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 5  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Ala ni ne a mi n otra nsf eras e  ( A L T) 
•  As partate a mi n otra nsferase ( A S T)  
•  T otal bilir u bi n  
•  Al kali ne p h os p hatase 
•  T otal pr otei n  
•  Ser u m creati ni ne  
•  Bl o o d urea nitr o ge n ( B U N) 
6. 2. 6  
Ot her Assess me nts  
6. 2. 6. 1.  
Me dic al Hist or y  
De m o gra p hic i nf or mati o n will be c ollecte d at Scree ni n g a n d i ncl u de t h e f oll o wi n g i nf or mati o n 
t hat will be rec or d e d i n t he Electr o nic Cas e Re p or t F or m (e C R F ): 
•  Birt h date  
•  Se x  
•  Race  
•  Et h nic gr o u p 
•  S m o ki n g hist or y 
•  Alc o h ol c o ns u m pti o n  
At eac h st u d y visit, i nteri m  me dical hist or y will be o btai ne d a n d rec or d e d.  
6. 2. 6. 2.  
P h ysic al E x a mi n ati o n 
A c o m plete p h ysical e x a mi nati o n will be perf or m e d a n d all a b n or m alities n ote d i n t he e C R F at 
Scree ni n g , Baseli ne , the 2- wee k  p ost-R T visit , a n d t he 6- wee k  p ost-R T visit . 
6. 2. 6. 3.  
Q u alit y of Lif e Q uesti o n n aire  
A Q ualit y of Life Q u esti o n naire will be c o m plete d b y eac h p atie nt at Baseli ne, 4 wee ks a n d at 
t he e n d of st u d y dr u g treat me nt ( 2 wee ks p ost-R T) a n d re vi e we d a n d e ntere d b y t h e site 
pers o n nel i nt o t he e C R F. T he E O R T C Q L Q - C 3 0 ( versi o n 3) a n d t he E O R T C Q L Q - H & N 4 3 
i nstr u me nt will be use d f or t hese assess me nts. 
6. 2. 6. 4.  
Vit al Si g ns  
Vital si g ns will be c ollect e d at eac h st u d y visit u p t o a n d i ncl u di n g t he 6-wee k  p ost-R T visit . 
Vital si g ns will i ncl u de t he f oll o wi n g meas ure m e nts: 
•  Heart r ate  
•  Res pirat or y rate  
•  Te m perat ur e  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 6  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Bl o o d press ur e (seate d ) 
•  Wei g h t 
6. 2. 6. 5.  
Hei g ht  a n d B o d y M ass I n de x ( B MI)  
Hei g ht will be c ollecte d at B as eli ne o nl y a n d B o d y Mass I n d e x ( B MI) a ut o maticall y calc ulate d . 
6. 3.  
Visit Sc he d ule  
6. 3. 1  
Scree ni n g  
T he S cree ni n g visit m ust be d o ne wit hi n 4 wee ks pri or t o t he Bas eli ne visit. Pri or t o starti n g t he 
st u d y me dicati o n, t he res ults of all tests m ust be re vie we d t o ass ure t hat t he patie nt meets all 
e ntr y criteri a. Pr oce d ures t o be d o ne at t his visit are: 
•  O btai n I nf or me d C o nse nt F or m (I C F) si g nat ure 
•  Ass ure t hat t he i nitial t u m or i ma gi n g is  c o m pati ble wit h R E CI S T Criteria  ( C T, M RI, or 
P E T sca ns)  
•  Ass ure t hat t he t u m or was e val uate d f or H P V stat us  
•  Assess me nt of e ntr y criteria  
•  C o m plete Me dical Hist or y  
•  C o m plete P h ysi cal E x a mi nati o n  
•  Vital Si g ns  
•  Ser u m H C G pre g na n c y t est ( w o me n o nl y) 
•  He mat ol o g y Pa n el   
•  Cli nical C he mistr y Pa n el  
6. 3. 2  
B aseli ne  D a y  
Baseli ne assess me nt will be c o m plete d pri or t o ra diati o n, c he m ot hera p y,  a n d st u d y dr u g 
a d mi nistrati o n  b ut wit hi n 9 6 h o urs of t he i nitial st u d y dr u g treat me nt. Patie nt will be see n  o n t he 
first da y of st u d y dr u g treat me nt. T he e ntr y criteria will be re vie we d a n d a n i nteri m me dical 
hist or y ta ke n t o ass ure t h at t he patie nt meets all e ntr y criteria. If t he patie nt still q ualifies, t he y 
will u n der g o t he f oll o wi n g pr o ce d ur es: 
•  I nteri m Me dical Hist or y 
•  Ra n d o mizati o n 
•  Vital si g ns  
•  A d verse e ve nts ( be gi n c ollecti n g after ra n d o mizati o n) 
•  P h ysical E x a m   
•  He mat ol o g y Pa n el  (if m ore t ha n 7 d a ys  fr o m Scree ni n g sa m ple) 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 7  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Cli nical C he mistr y Pa n el  (if m ore t ha n 7 d a ys  fr o m Scree ni n g sa m ple) 
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore)  
•  Q ualit y of Lif e  assess me nt  
•  Ser u m Pre g n a nc y  (if m or e t ha n 7 d a ys  fr o m Scree ni n g sa m ple)  
•  Hist or y of p ai n a n d o pi oi d me dicati o n use 
•  Assess me nt of I nf ecti o ns 
6. 3. 3  
St u d y  Dr u g A d mi nistr ati o n Visits D uri n g R T  
St u d y visit da ys occ ur t wice wee kl y (e ver y 3 da ys +/- 1 da y) t hr o u g h t he c o m pleti o n of R T. T he 
first st u d y visit m ust occ ur wit hi n 3 da ys of i nitiati n g R T. T he st u d y visit sc he d ule s h o ul d be 
a d here d t o a n d is i n de pe n de nt of C R T a d mi nistrati o n.  At st u d y dr u g a d mi nistrati o n visits, t he 
f oll o wi n g will be perf or me d: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of p erc uta ne o us e n d osc o pic gastr ost o m y ( P E G ) t u be us e (if a p plica ble) 
•  St u d y Dr u g a d mi nistrati o n  
•  Hist or y of p ai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
•  Q ualit y of Lif e assess me nt  ( Wee k 4 o nl y) 
•  I n a d diti o n t o t he a b o ve, r o uti ne safet y la b oratories will be o btai ne d d uri n g Wee ks 3 a n d 
6 f or:  
o  Bl o o d c ollecti o n f or h e m at ol o g y a n d cli nical c he mistr y pa nel 
6. 3. 4  
St u d y Dr u g A d mi nistr ati o n Wee k 1 After R T  
St u d y visit da ys occ ur t wice wee kl y (e ver y 3 da ys ± 1 da y) f or t he first wee k f oll o wi n g 
c o m pleti o n of R T. At t hese st u d y dr u g a d mi nistrati o n visits, t he f oll o wi n g will be p erf or me d: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of gastr ost o m y t u be use (if a p plica ble ) 
•  St u d y Dr u g a d mi nistrati o n  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 8  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Hist or y of p ai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
6. 3. 5  
St u d y Dr u g A d mi nistr ati o n Wee k 2 After R T  
St u d y visit da ys occ ur t wice wee kl y (e ver y 3 da ys +/- 1 da y) f or t he sec o n d wee k f oll o wi n g 
c o m pleti o n of R T. At t hese st u d y dr u g a d mi nistrati o n visits, t he f oll o wi n g will be p erf or me d: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of gastr ost o m y t u be use (if a p plica ble)  
•  St u d y Dr u g a d mi nistrati o n  
•  Hist or y of p ai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
•  I n a d diti o n, t he fi nal da y of st u d y dr u g a d mi nistrati o n (last visit Wee k 2 p ost-R T) t he 
f oll o wi n g a d diti o nal assess me nts will be perf or me d: 
•  Bl o o d c ollecti o n f or h e m at ol o g y a n d cli nical c he mistr y pa nels 
•  P h ysical e x a mi nati o n  
•  Q ualit y of Lif e assess me nt  
6. 3. 6  
Wee k 3 P ost -R T Visit   
Patie nts will be see n o nce i n t he t hir d wee k f oll o wi n g c o m pleti o n of R T f or t he f oll o wi n g: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d  details of g astr ost o m y t u be use (if a p plica ble)  
•  Hist or y of p ai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
6. 3. 7  
Wee k 4 P ost -R T Visit  
P atie nts will be see n o nce i n t he f o urt h wee k f oll o wi n g c o m pleti o n of R T f or t he f oll o wi n g: 
•  I nteri m Me dical Hist or y  
•  V ital si g ns  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 3 9  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of g astr ost o m y t u be use (if a p plica ble)  
•  Hist or y of Pai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
•  Bl o o d c ollecti o n f or h e m at ol o g y a n d cli nical c he mistr y pa nels 
6. 3. 8  
Wee k 5 P ost- R T Visit  ( o nl y t o be d o ne if W H O sc ore is ≥2 at Wee k 4 P ost -R T)  
Patie nts will be see n o nce i n t he fift h wee k f oll o wi n g c o m pleti o n of R T if t he patie nt ha d a n O M 
gr a de i n W ee k 4 p ost- R T t hat was ≥2  f or t he f oll o wi n g: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of g astr ost o m y t u be use (if a p plica ble)  
•  Hist or y of Pai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
6. 3. 9  
Wee k 6 P ost- R T V isit 
Patie nts will be see n o nce i n t he si xt h wee k f oll o wi n g c o m pleti o n of R T f or t he f oll o wi n g: 
•  I nteri m Me dical Hist or y  
•  Vital si g ns  
•  A d verse e ve nts  
•  Cli nical e val uati o n of m uc ositis ( W H O Sc ore) 
•  Rec or d details of gastr ost o m y t u be use (if a p plica ble) 
•  Bl o o d c ollecti o n f or h e m at ol o g y a n d cli nical c he mistr y pa nels 
•  Hist or y of p ai n a n d o pi oi d use 
•  Assess me nt of I nf ecti o ns 
•  P h ysical e x a mi nati o n  
•  Ser u m H C G pre g na n c y t est ( w o me n o nl y) 
6. 3. 1 0  
M o nt hl y  ( 2- t o 1 1-M o nt h P ost -R T ) F oll o w-u p C o nt acts  
All patie nts will be c o ntacte d at least o nce per m o nt h  ( ± 2 wee ks) t hr o u g h 1 1 m o nt hs (e x ce pt f or 
t he 1 2 wee k/ 3 m o nt h f oll o w- u p visit) f oll o wi n g c o m pleti o n of t heir last R T treat me nt t hr o u g h 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 0  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
eit her cli nic visits or tele p h o ne c o ntacts. F or e ac h c o ntact , t he f oll o wi n g i nf or mati o n t hat will be 
e ntere d i nt o t he e C R F:  
•  Vital stat us  
•  E vi de nce of rec urre n ce of t he pri mar y t u m or 
•  I nitiati o n of a d diti o nal a nti-ca ncer t hera p y 
6. 3. 1 1  
1 2 w ee ks ( 3 -M o nt h ) P ost -R T F oll o w -u p Visit  
Patie nts will ha ve a cli nic visit at 1 2 wee ks ( ± 3 w ee ks)  a n d t h e f oll o wi n g will be perf or me d: 
•  I nteri m Me dical Hist or y  
•  Hist or y of p ai n a n d o pi oi d use 
•  Re peat of t h e sa m e sca ns use d at t he i nitial t u m or sta gi n g t o be use d i n a R E CI S T 1. 1 
c o m paris o n 
•  Rec or d of t u m or stat us i n cl u di n g e vi d e nce of t u m or rec urre n ce a n d a d diti o n al a nti-ca n cer 
t hera pies 
6. 3. 1 2  
1 2 M o nt h  P ost -R T F oll o w -u p Visit  
Patie nts ha ve t heir last st u d y visit at 1 2 m o nt hs ( ± 2 8 da ys) p ost -R T a n d t he f oll o wi n g will be 
perf or me d : 
•  I nteri m Me dical Hist or y  
•  Hist or y of p ai n a n d o pi oi d use 
•  E val uati o n of t u m or stat us 
•  Re peat of t he sa m e sca ns use d a t t he i nitial t u m or sta gi n g t o be use d i n a R E CI S T 1. 1 
c o m paris o n  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
7.  
S E L E C TI O N A N D WI T H D R A W A L O F S U B J E C T S  
7. 1.  
S u bject I ncl usi o n Criteri a  
Patie nts e nr olle d i nt o t his trial m ust meet all  of t he f oll o wi n g criteria:  
1.  Willi n g a n d a ble t o u n dersta n d a n d si g n a n i nf or m e d c o nse nt 
2.  Males or fe m ales a ge grea ter t ha n or e q ual t o 1 8 years 
3.  Bi o ps y- pr o ve n s q u a m o us cell carci n o ma of t he oral ca vit y or or o p har y n x wit h o ut dista nt 
or ga n metastases  t h at has bee n e v al uate d f or h u ma n pa pill o ma vir us ( H P V) 
4.  Sc he d ule d t o recei ve cis plati n c he m ot hera p y of 8 0 - 1 0 0 m g/ m² gi ve n e v er y t hir d wee k  
5.  Sc he d ule d t o recei ve a c o nti n u o us c o urse of c o n v e nti o nal e xter nal bea m irra diati o n 
deli vere d b y I M R T as si n gle d ail y fracti o ns of 2. 0 t o 2. 2 G y, wit h a c u m ulati ve ra diati o n 
d ose bet wee n 5 5 a n d 7 2 G y at eac h site 
6.  Pla n ne d ra diati o n treat me nt fiel ds m ust i ncl u de at least 2 oral sites (retr o m olar tri g o n e, 
b uccal m uc osa, fl o or of m o ut h, t o n g ue, or s oft palate), wit h eac h site recei vi n g ≥5 5 G y  
7.  All w o me n of c hil d beari n g p ote ntial ( W O C B P) a n d males wit h fe male p art ners w h o are 
W O C B P m ust a gree t o t he use of effecti ve c o ntrace pti o n d uri n g t he tri al 
 
•  W o me n are c o nsi der e d t o be W O C B P f oll o wi n g me narc h e a n d u ntil bec o mi n g p ost-
me n o pa usal u nless per m a ne ntl y sterile ( h ysterect o m y, bilateral sal pi n gect o m y a n d 
bilateral o o p h orect o m y). A p ost me n o pa usal state is defi ne d as n o me ns es f or 1 2 
m o nt hs wit h o ut a n alter nati ve me dical ca use.  
 
Effecti ve c o ntrace pti o n met h o ds f or W O C B P s h o ul d be starte d pri or t o ra n d o mizati o n 
a n d c o nti n ue d f or a mi ni m u m of 3 5 da ys f oll o wi n g c o m pleti o n of st u d y dr u g 
a d mi nistrati o n.  
 
•  Ac ce pt a ble c o ntr ace pti ve met h o ds f or W O C B P are t h ose t hat ac hie v e a fail ure rat e of 
less t ha n 1 % per year a n d i ncl u de:  
o  C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n 
ass ociate d wit h i n hi biti o n of o v ulati o n: 
  Oral  
 I ntr a va gi nal 
 Tra ns der m al  
o  Pr o gest o ge n - o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n:  
 Oral  
 I njecta ble 
 I m pla nta bl e 
o  I ntr a uteri ne d e vice (I U D)  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 2  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
o  I ntr a uteri ne h or m o ne-rel easi n g s yst e m ( I U S)  
o  Bilater al t u bal occl usi o n  
o  Vasect o mize d  part ner 
o  Se x ual a bsti ne nce de fi ne d as refrai ni n g fr o m het er ose x ual i nterc o urse 
d uri n g t he e ntire peri o d of ris k ass ociate d wit h t he st u d y treat me nts 
•  M ale s u bject s s h o ul d use c o n d o ms d uri n g treat me nt a n d f or 9 8 da ys f oll o wi n g t he 
last st u d y dr u g a d mi nistrati o n peri o d. 
7. 2.  
S u bject E xcl usi o n  Criteri a  
Patie nts wit h a n y of t he f oll o wi n g criteria are N O T  eli gi ble f or e nr oll me nt:  
1.  C urre nt m uc ositis  
2.  C urre nt  cli nicall y si g nifi ca nt acti ve i nfecti o n  t hat i n t he o pi ni o n of t he I n v esti gat or w o ul d 
ma ke t he m a n u nfit partici pa nt i n t he trial  
3.  Pla n ne d t o re cei v e Er bit u x ™ ( Cet u xi ma b) or si milar tar gete d t hera p y bet wee n baseli ne 
a n d 6 wee ks p ost- ra diati o n t hera p y 
4.  C urre nt use of pr o hi bite d t hera pies liste d i n Secti o n 8. 2  
5.  Pri or ra diati o n t o t he hea d a n d nec k 
6.  C he m ot hera p y treat me nt wit hi n t he pre vi o us 1 2 m o nt hs 
7.  T u m ors of t he li ps, si n uses, sali var y gla n ds, nas o p har y n x, h y p o p har y n x, or lar y n x  
8.  E vi de nce of si g nifica nt r e nal, he patic, h e mat ol o gi c, or i m m u n ol o gic disease deter mi ne d 
b y a n y o n e of t he f oll o wi n g: ( t he b el o w are e x a m ples of e vi de nce of si g nifi ca nt disease, 
n ot re q uire d tests) 
a. Esti mate d creati ni ne cleara nce < 3 0 m L/ mi n  
b.  A L T or A S T le vel gr eater t ha n 1 0 -f ol d t he u p per li mit of n or mal or t otal bilir u bi n 
gr eater t ha n 3 -f ol d t he u p per li mit of n or mal 
c. Ma nifestati o ns of e n d- sta ge li ver disease, s u c h as ascites or he p atic 
e nce p h al o pat h y 
d.  T hr o m b oc yt o p e nia (less t ha n 6 0, 0 0 0 cells/ m m 3) 
e. C D 4 +  T cell c o u nt bel o w 2 0 0 cells per µ L ( verificati o n o nl y re q uire d if t here is a 
cli nical dia g n osis of HI V i nfecti o n)  
9.  E vi de nce of i m me diate life -t hreate ni n g diseas e or a life e x pecta nc y of less t ha n 3 m o nt hs 
1 0.  W o me n w h o are pr e g na nt or breast- fee di n g 
1 1.  Partici pati o n i n a n y st u d y i n v ol vi n g a d mi nistrati o n of a n i n vesti gati o nal a ge nt wit h i n 3 0 
da ys of ra n d o mizati o n i nt o t his st u d y 
1 2.  A n y c o n diti o n t hat, i n t he o pi ni o n of t he I n vesti gat or, w o ul d c o m pr o mise t he safet y of t h e 
s u bject or q ualit y of t he data 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 3  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
7. 3.  
P atie nt  Wit h dr a w al Criteri a  
Patie nts ha ve t he ri g ht t o wit h dra w fr o m t his trial at a n y ti m e (as descri be d i n t he i nf or me d 
c o nse nt d oc u me nt) wit h o ut prej u dice t o f urt her care. A n i n vesti gat or ma y wit h dra w a patie nt 
fr o m t he st u d y at a n y ti me f or a n y of t he f oll o wi n g reas o ns:  
•  T he patie nt wit h dra ws his/ her c o nse nt or ref us es f oll o w- u p e val uati o ns.  
•  T he patie nt is l ost t o f oll o w - u p a n d will n ot atte n d f urt her st u d y visits. 
•  T he i n vesti gat or deter mi nes t hat f urt her p artici pati o n w o ul d be detri me ntal t o t he 
patie nt’s healt h or w ell -b ei n g.  
•  T he patie nt fails t o c o m pl y wit h t he st u d y re q uire me nts t o  ca use har m t o s elf or seri o usl y 
i nterfer e wit h t he vali dit y of t he st u d y res ults. 
•  T he fe mal e patie nt bec o mes pre g na nt d uri n g t he treat me nt peri o d. I n t his case, treat me nt 
s h o ul d be halte d a n d t he patie nt f oll o we d u ntil t he e n d of t he pre g na nc y. If a c hil d is 
b or n, t he i nfa nt s h o ul d be f oll o we d t hr o u g h at least 6 m o nt hs of a ge. 
•  At t he discreti o n of t he site i n vesti gat or if h e/s he feels t hat it is i n t he best me dical 
i nterest of t he patie nt. 
•  T he patie nt misses m ore t ha n 5 c o nsec uti ve s c he d ule d R T sessi o ns. 
•  P atie nts wit h dra w n fr o m t he st u d y will ha ve as ma n y of t he trial assess me nts c o m plete d 
as t he patie nt per mits i ncl u di n g bl o o d tests  a n d sca ns b ut n ot i ncl u di n g O M sc ori n g. All 
ot her t hera pi es i ncl u di n g ra diati o n t hera p y, t h e t y p e a n d fre q ue n c y of c h e m ot hera p y, a n d 
oral treat me nts will re mai n at t he discreti o n of t he cli nical tea m.  Patie nts will be ce ns ore d 
i n t he efficac y a n al ys es at t he ti me of wit h dra wal. 
•  Patie nts wit h dra w n fr o m t he trial will n ot be re place d b ut e nr oll me nt will c o nti n ue u ntil a 
mi ni m u m of 2 6 0 patie nts ha ve bee n e nr olle d. 
7. 4.  
Ter mi n ati o n of t he St u d y  
T he st u d y ma y b e ter mi n ate d earl y f or a n y of t he f oll o wi n g reas o ns: 
•  A healt h a ut h orit y or D M C  re q uests ter mi nati o n of t he st u d y. 
•  It has b ee n d eter mi ne d t h at t he ris k le vel ass oci ate d wit h t he e x peri me ntal dr u g is 
si g nifica nt a n d warra nts t er mi nati o n of t he st u d y.  
•  S oli ge ni x , f or reas o ns ot her t ha n safet y, ma y ter mi nate t he st u d y at a n y ti me b y writte n 
n otice of i nte n de d ter mi nati o n pr o vi de d at least t hirt y ( 3 0) da ys pri or t o ter mi nati o n. 
•  T he i n vesti gat or or I R B/ E C, f or reas o ns ot h er t ha n safet y, ma y ter mi nat e p artici pati o n of 
t his site i n t he st u d y b y writte n n otice of i nte n de d t er mi nati o n pr o vi de d at least t hirt y (3 0) 
da ys pri or t o ter mi nati o n.  
•  A n y ot her cla us e descri be d i n t he i n di vi d ual site St u d y A gree me nt (e. g., if G C Ps or ot her 
re g ulat or y pr o ce d ur es ar e n ot f oll o we d; if e nr oll me nt rate is n ot s ufficie nt t o meet st u d y 
g oa ls). 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 4  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
8.  
T R E A T M E N T O F S U B J E C T S 
8. 1.  
Descri pti o n of  St u d y Dr u g  
A p pr o priate d os es of st u d y dr u g will be a d mi nistere d t o s u bjects wit hi n 3 da ys of t he first da y of 
R T  a n d t he n t wice w ee kl y ( e ver y t hir d d a y ±  1 da y) t hereafter u ntil 2 wee ks after c o m pleti o n of 
R T .  
Patie nts will be see n 3, 4, 5 a n d 6 wee ks  a n d t he n at 1 2 wee ks a n d 1 2 m o nt hs after t he last d ose 
of R T , b ut will n ot be treate d wit h st u d y dr u g at t h ose ti mes. 
8. 2.  
C o nc o mit a nt Me dic ati o ns  
S u bjects will be treate d o n a n o ut patie nt basis. If p atie nts re q uire h os pitalizati o n f or n o n- st u d y 
relate d c o m plicati o ns of t hera p y, all p ossi ble st u d y pr oce d ures will be perf or me d. R T  a n d 
assess me nt of t u m or b ur de n i n all s u bjects will be c o n d ucte d as cli nicall y a p pr o priate, f oll o wi n g 
st u d y-s pecifie d pr ot oc ols. All s u bjects will recei ve c o nc o mita nt cis plati n c h e m ot hera p y ( 8 0- 1 0 0 
m g/ m 2) f or treat me nt of ca ncer of t he oral ca vit y a n d or o p har y n x.  
C o nc o mita nt dr u gs ta ke n b y t he p atie nt d uri n g t h e treat me nt p hase a n d t hr o u g h t he 6- wee k  p ost-
R T  visit s h o ul d be rec or d e d i n t he e C R F. I n ge n eral, t he ge neri c na me of t he dr u g s h o ul d be 
use d. Dr u g na mes, es peci all y c o m bi nati o n pre parati o ns, s h o ul d n ot i ncl u de t he d ose of eac h 
c o m p o ne nt dr u g i n t he na me b ut s h o ul d be n ote d i n t he d ose- Na m e: “ D oc usate/ Se n na” D os e 
“ 5 0/ 8. 6” rat her t ha n N a me: “ D oc usat e 5 0 m g - Se n na 8. 6 m g”. C o m p o ne nts of a n y m o ut h was h 
prescri be d s h o ul d b e liste d- i nstea d of “ M a gic M o ut h was h” rec or de d “ M o ut h was h- 
Maal o x/ Li d o cai ne”.  
T he f oll o wi n g m e dicati o ns/t hera pies s h o ul d N O T  be use d i n e nr olle d p atie nts  (fr o m baseli ne 
t hr o u g h 6 w ee ks p ost-R T) : 
•  A mif osti ne ( Et h y ol ® )  
•  Be nz y d a mi ne h y dr o c hl ori de  
•  Cet u xi ma b ( Er bit u x ® ) 
•  Ce vi meli ne h y dr o c hl ori d e ( E v o x ac ® )  
•  Gl uta mi ne as a pr o p h ylactic a ge nt f or m uc ositis  
•  De vices f or m uc ositis i ncl u di n g Gel Clair, M u Gar d, E pisil a n d Ca p h os ol 
•  G M - C S F (e. g., Le u ki ne® ) 
•  I L- 1 1 ( N e u me ga® )  
•  ‘ Ma gic m o ut h was h’, ‘ Miracle m o ut h was h’ or ot h er m o ut h was h s ol uti o ns c o ntai ni n g a n y 
of t he f oll o wi n g:  
•  C hl or he xi di ne  
•  H y dr o ge n per o xi de  
•  Di p he n h y dra mi ne  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 5  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Tetrac ycli ne  
•  Palifer mi n ( Ke pi va n ce ® ) or ot her kerati n oc yte or fi br o blast gr o wt h fact or 
•  Pil ocar pi ne h y dr oc hl ori d e ( Sala ge n ® )  
•  P o vi d o ne-i o di ne ri nses  
•  Ster oi d ri nses  
•  S ucralfate i n s us pe nsi o n f or m ( use of s u cralfate ta blets is n ot pr oscri be d)  
•  Ot her  bi ol o gic  res p o ns e  m o difiers  – e x ce pt  he mat o p oietic  gr o wt h  fact ors  f or  t h e  
ma na ge me nt of a ne mia or m yel os u p press i o n 
•  L o w le v el laser t h era p y   
•  Ot her i n vesti gati o nal a ge nts f or m uc ositis  
8. 3.  
Tre at me nt C o m pli a nce  
Patie nts will be treate d wit h a n I V i nf usi o n wit nesse d b y site p ers o n nel d uri n g t heir d ail y 
ra diati o n treat me nt cli nic a p p oi nt me nts a n d, t heref ore, c o m plia nce wit h st u d y cli nic visits is 
e x pecte d t o be hi g h w hile t he c he m or a diati o n treat me nts are c o nti n ui n g.  
E ver y eff ort will be ma d e b y t h e patie nt a n d t he st u d y staff t o e ns ure t hat  patie nts ca n c o m plete 
t he assi g n e d tas ks of t he trial o n sc he d ule a n d as p er pr ot oc ol pri or t o b ei n g c o nse nte d. E ver y 
eff ort s h o ul d be ma d e, w he n me dicall y res p o nsi bl e, t o a v oi d treat me nt brea ks or dela ys. 
8. 4.  
R a n d o miz ati o n a n d Bli n di n g  
Patie nts  will be ra n d o mize d 1: 1 t o S G X 9 4 2: place b o usi n g a ra n d o mizati o n c o de ge n erate d b y a n 
i n de pe n de nt statisticia n. Ra n d o mizati o n will be perf or me d usi n g a n I nteracti ve We b Res p o nse 
S yste m (I W R S) i n a d o u ble- bli n d fas hi o n. Eac h vial of S G X 9 4 2  a n d t he i d e nticall y a p peari n g 
place b o vials will be s u p plie d a n d la bele d wit h a u ni q ue bli n de d i de ntif yi n g c o d e. T he I W R S 
will assi g n vial(s) of t h e a p pr o priate st u d y material t o be use d f or eac h pati e nt a n d eac h i nf usi o n 
usi n g t his bli n de d c o de.  
Patie nts will be stratifie d at ra n d o mizati o n b y H P V stat us , prese nce of a gastr ost o m y t u be at 
ra n d o mizati o n, a n d st u d y site. 
Gi ve n t he e xtre mel y s h ort half life of S G X 9 4 2 ( mi n utes), it is a ntici pate d t hat k n o wle d ge of 
w het her t he p atie nt recei ve d place b o or S G X 9 4 2 will rarel y be n e e de d. If, h o we ver, t he PI a n d/ or 
t he pri mar y care cli nical tea m belie ve t hat t his i nf or mati o n is necessar y t o o pti mall y treat a n 
e nr olle d patie nt, t he cli ni cal data ma n a ge me nt tea m ( D S G) s h o ul d be c o ntacte d ( 2 4 h o ur/ 7 da y 
a vaila bilit y) usi n g t he c o ntact di recti o ns a v aila ble i n t he e C R F p ortal. T he st u d y dr u g assi g n me nt 
f or t hat patie nt will be deter mi ne d a n d c o nfir mati o n of t he st u d y dr u g recei ve d will be 
i m me diatel y se nt. 
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 8  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 0.  
A S S E S S M E N T O F E F FI C A C Y  
1 0. 1.  
Pri m ar y Effic ac y E n d p oi nt  
Cli nical e val uati o n of  m uc ositis will be perf or me d a n d gra de d b y trai ne d st u d y e v al uat ors i n 
acc or d a nce wit h W H O Oral M uc ositis Gra di n g s yste m, as detaile d i n Ta ble 8  at eac h st u d y dr u g 
a d mi nistrati o n visit a n d o nce a w ee k t hr o u g h 6 wee ks p ost- R T.  
T he d urati o n of S O M is t he pri mar y e n d p oi nt f or t his cli nical trial.  
S O M is defi ne d a W H O sc ore of ≥3 ( 3 or 4). Res ol uti o n of S O M is defi ne d as t he first 
assess me nt wit h a W H O sc ore < 3 wit h n o f urt her re p orts of a W H O gra de of ≥3. T he d urati o n of 
S O M is defi ne d as t he n u m ber of da ys fr o m t he first W H O sc ore ≥3 t o t he first da y wit h W H O 
sc ore ≤3 wit h n o f urt her occ urr e nce of W H O sc ore ≥3. If t he patie nt h as n ot met t he 
re q uire me nts f or res ol uti o n of S O M b y t he 6- wee k p ost- R T visit, he/s he will be c o nsi dere d 
ce ns ore d at t hat visit ( or p oi nt of disc o nti n uati o n of t he st u d y, if t he p atie nt disc o nti n ues pri or t o 
t hat ti me p oi nt). T o facilitate cal c ulati o n of a l o g -ra n k test wit h o ut ce ns ori n g patie nts wit h 
desira ble o utc o mes ( n o S O M), patie nts w h o d o n ot e x perie nce S O M  will be treate d as ha vi n g a 
d urati o n of S O M  of 0. 0 1 da ys . T h e pri mar y e n d p oi nt a nal ysis will be c o n d u cte d i n t he mI T T 
p o p ulati o n. 
1 0. 2.  
Sec o n d ar y Effic ac y  E n d p oi nts  
1 0. 2. 1  
Pri m ar y Sec o n d ar y A n al yses 
T he pri mar y sec o n d ar y e n d p oi nts are liste d bel o w i n hierarc hical or der a n d will be c o m pare d i n 
t he mI T T p o p ul ati o n. 
1 0. 2. 1. 1.  Se verit y -w ei g hte d D ur ati o n of S O M ( Are a -U n der t he  S O M -Ti me  C ur v e)  
T he se verit y - wei g hte d d urati o n of S O M will be calc ulate d b y t he A U C of t he S O M vers us ti me 
c ur ve. T his will be calc ul ate d b y t he f or m ula f or b aseli ne (t a) t o ti me t he last re p orte d W H O 
sc ore r ec or d e d (t b): 
 
( 
)
( 
)( 
)
∑
−
=
+
+
−
+
=
−
1
1
1
2
b
a
i
i
i
i
i
a
b
t
t
y
y
t
t
A U C
 
w here t i re pr ese nts t he date of t he i t h W H O assess me nt, a n d y
i re prese nts t h e val ue of t he it h W H O 
assess me nt f or W H O ass ess me nts f or w hic h t he s c ore is ≥3.  
1 0. 2. 1. 2.  Se verit y -w ei g hte d D ur ati o n of U O M ( Are a -U n der t he S O M -Ti me C ur ve)  
T he  se verit y- wei g hte d d urati o n of UO M will b e calc ulate d b y t he A U C of t he U O M vers us ti me 
c ur ve. T his will be calc ul ate d b y t he f or m ula f or b aseli ne (t a) t o ti me t he last re p orte d W H O 
sc ore r ec or d e d (t b): 
 
( 
)
( 
)( 
)
∑
−
=
+
+
−
+
=
−
1
1
1
2
b
a
i
i
i
i
i
a
b
t
t
y
y
t
t
A U C
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 4 9  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
w here t i re pr ese nts t he date of t he it h W H O assess me nt, a n d y
i re prese nts t h e val ue of t he it h W H O 
assess me nt f or W H O ass es s me nts f or w hic h t he s c ore is ≥2. 
1 0. 2. 1. 3.  I nci de nce of S O M 
T he i nci de nce of S O M will be calc ulate d as t h e perce nt of p atie nts wit hi n eac h treat me nt gr o u p 
w h o ha ve at least o ne W H O sc ore ≥3.  
1 0. 2. 1. 4.  Q u alit y of Lif e  
A Q ualit y of Life Q u esti o n naire ( Q o L) will be c o m plete d b y eac h p atie nt at Baseli ne, 4 w ee ks 
a n d at t he e n d of st u d y dr u g treat me nt ( 2 w ee ks p ost- R T) a n d re vie we d a n d e ntere d b y t he site 
pers o n nel i nt o t he e C R F. T he E O R T C Q L Q - C 3 0 ( versi o n 3) a n d t he E O R T C Q L Q- H & N 4 3 
i nstr u ment will be use d f or t hese assess me nts.  T h e c ha n ge fr o m Baseli ne i n t he Q o L at t he e n d of 
t he st u d y will be c o m par e d bet wee n treat me nt gr o u ps.  
1 0. 2. 1. 5.  A m o u nt of O pi oi d Me dic ati o n Use d  
At eac h st u d y visit, st u d y pers o n nel will rec or d t he a m o u nt of o pi oi d me dicati o n t hat t he patie nt 
re p orts ha vi n g ta ke n o v er t he pre vi o us 2 4 h o urs. E ac h t y pe of me di cati o n a n d w het her it was 
use d beca us e of O M p ai n or ot her t y pes of p ai n will be n ote d i n t he e C R F. Eac h o pi oi d d ose will 
be c o n vert e d t o a n “ oral m or p hi ne d ose e q ui vale nt d ose” a n d t he t otal a m o u nt of o pi oi d use d f or 
eac h p atie nt s u m me d o ver eac h visit fr o m b aseli ne t o 6 wee ks p ost-c o m pleti o n of t he ra diati o n 
t hera p y. Patie nts wit h missi n g visits will ha ve t heir o pi oi d usa ge esti mate f or t he missi n g data b y 
usi n g a n a ver a ge of t heir o pi oi d use f or t he a vaila ble visits usi n g f or m ula detaile d i n t he S A P. 
T he mea n a n d m e dia n a m o u nt of t otal o pi oi ds use d i n eac h of t he treat me nt gr o u ps will be 
c o m pare d.  
1 0. 2. 2  
Ot her Sec o n d ar y A n al yses  
I n a d diti o n t o t he pri mar y sec o n dar y a nal yses p erf or me d i n hierarc hical or der, se veral a d diti o nal 
sec o n dar y a nal yses will be perf or me d.   
1 0. 2. 2. 1.  C u m ul ati ve N u m ber of Tre at me nt B re a ks  
F or t he a nal ysis p ur p oses f or t his st u d y, treat me nt brea ks will be defi ne d as missi n g 3 or m ore 
sc he d ule d c o nsec uti ve R T treat me nt sessi o ns. T he c u m ulati ve d urati o n of treat me nt brea ks f or 
eac h p atie nt will be calc ulate d b y s u m mi n g t he act ual n u m ber of treat me nt brea k da ys ( ≥3 da ys  
per  brea k) t hr o u g h t he fi nal R T treat me nt a n d c o m pari n g t hes e bet w ee n treat me nt gr o u ps. 
1 0. 2. 2. 2.  D ur ati o n of S O M i n t he I T T P o p ul ati o n 
Usi n g t he a b o ve defi niti o ns, t he d urati o n of S O M will be c o m pare d b et wee n treat me nt gr o u ps i n 
all patie nts ra n d o mize d (I T T p o p ul ati o n). 
1 0. 2. 2. 3.  D ur ati o n of Ulcer ati ve Or al M uc ositis ( U O M)  
U O M is defi ne d as a W H O sc ore ≥2.  Res ol uti o n of U O M is defi ne d as t he first assess me nt wit h 
a W H O sc ore < 2 wit h n o f urt her r e p orts of a W H O gra de of ≥2. T he d urati o n of U O M is defi ne d 
as t he n u m ber of d a ys fr o m t he first W H O sc ore ≥2 t o t he first da y wit h W H O sc ore < 2  wit h n o 
f urt her occ urr e nce of W H O sc ore ≥2. If t he p atie nt has n ot met t he re q uire me nts f or res ol uti o n of 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 0  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
U O M b y t h e 6 - wee k p ost- R T visit, he/s he will be c o nsi dere d ce ns ore d at t h at visit ( or p oi nt of 
disc o nti n uati o n of t he st u d y, if t he p atie nt disc o nti n ues pri or t o t hat ti m e p oi nt). F or statistical 
reas o ns, patie nts w h o d o n ot e x perie nce S O M  will be treate d as ha vi n g a d urati o n of U O M of 
0. 0 1. T he a nal ysis will be d o ne i n t he mI T T p o p ulati o n. 
1 0. 2. 2. 4.  Assess me nt of P ai n  
At eac h st u d y visit, t he patie nt’s assess me nt of t heir pai n o ver t he pre vi o us 2 4 h o urs will be 
rec or d e d b y st u d y pers o n nel usi n g a s cale of 1- 1 0. Patie nts wit h missi n g visits will ha ve t heir 
pai n esti mate d f or t he missi n g data b y a vera gi n g t heir pai n sc ores re p orte d usi n g t he f or m ula 
detaile d i n t he S A P.  
1 0. 2. 2. 5.  Alter n ati ve Me a s ure me nt of t he D ur ati o n of S O M 
T he d urati o n of S O M defi ne d as t he n u m ber of d a ys fr o m t he first oral e x a mi nati o n wit h W H O 
gr a de ≥3 t hr o u g h t he last assess me nt wit h a W H O sc ore ≥3 (a n d n ot t o t he firs t assess me nt wit h 
a W H O gra de < 3) wit h n o f urt her r e p ort s of a W H O gra de ≥3. 
1 0. 2. 2. 6.  D ur ati o n of S O M i n t he Per -Pr ot oc ol P o p ul ati o n  
T he d urati o n of S O M i n t he Per- Pr ot oc ol P o p ulati o n defi ne d as p atie nts recei vi n g a c u m ulati ve 
ra diati o n d ose of at least 5 5 G y a n d ha v i n g recei v e d all sc he d ule d st u d y dr u g d oses.  
 
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 1.  
A S S E S S M E N T O F S A F E T Y  
1 1. 1.  
O ver all Assess me nts  
Safet y i n t his trial will be assesse d  b y t he f oll o wi n g c o m p aris o ns bet wee n treat me nt gr o u ps: 
•  Assess me nt of t he i nci de nce, t y pe, a n d b o d y s yste m cate g orizati o n of A Es 
•  Assess me nt of t he i nci de nce, t y pe, a n d b o d y s yste m cate g orizati o n of S A Es  
•  Assess me nt of t he c h a n ges fr o m baseli ne f or he m at ol o g y para meters, cli nical c he mistr y 
para meters, a n d vital si g ns 
•  Assess me nt of t u m or pr o gr essi o n at 1 2 wee ks  a n d 1 2 m o nt hs f oll o wi n g c o m pleti o n of R T  
classifie d usi n g t h e R E CI S T t u m o r stat us s yste m 
•  T he i nci de nce a n d se v erit y of i nfecti o ns gra d e d usi n g C T C A E  criteria  
•  Assess me nt of m ortalit y t hr o u g h t he 1 2- m o nt h p ost- R T cli nic visit  
1 1. 1. 1  
Assess me nt of A Es  
Site pers o n nel will q uesti o n a n d rec or d i n t he e C R F all re p orte d A Es, as d efi ne d i n Sec ti o n 
1 1. 2. 1  t hat are r e p orte d b et wee n r a n d o mizati o n t hr o u g h t he 6 w ee k p ost- R T visit. T he PI will 
assess  of t he se v erit y of t he A E usi n g t h e C T C A E criteria ( A p pe n di x 1). T he A Es will be c o de d 
as t o preferre d t er mi n ol o g y, a n d b o d y s yste m usi n g t he Me dical Dicti o nar y f or Re g ulat or y 
Acti vities ( Me d D R A) usi n g a c o m p uter a ut o- c o der a n d all assi g n me nts re vi e we d b y  a bli n de d 
me dical re vie wer. T h e n u m ber of e v e nts a n d t he n u m ber of patie nts wit h eac h e ve nt defi ne d b y 
t he pref err e d ter m a n d b y b o d y s yste m cate g or y will be prese nte d. A d diti o n al ta bles will 
c o m pare t he re p ort e d A Es b y pr eferre d ter m a n d b o d y s yste m clas sificati o n classifie d b y 
C T C A E se verit y gra de ( 1 - 5) a n d se p arat el y b y PI assess me nt of rel ati o ns hi p t o st u d y dr u g. 
1 1. 1. 2  
Assess me nt of S A Es  
Site pers o n nel will q uesti o n a n d rec or d i n t he e C R F all re p orte d S A Es, as d efi ne d i n Secti o n 
1 1. 2. 2  t hat are r e p orte d b et wee n r a n d o mizati o n t hr o u g h t he 6 w ee k  p ost-R T visit.  T he S A Es will 
be c o de d as t o pref err e d ter mi n ol o g y, a n d b o d y s yste m usi n g t he Me dical Dicti o nar y f or 
Re g ulat or y  Acti vities ( Me d D R A) usi n g a c o m p uter a ut o- c o d er a n d all assi g n me nts re vie we d b y 
a bli n de d me dical r e vie w er. S u m mar y ta bles i ncl u di n g t he n u m ber of e v e nts a n d t he n u m ber of 
patie nts wit h eac h e v e nt defi ne d b y t he preferre d t er m a n d b y b o d y s yste m cate g or y will be 
prese nte d. A d diti o nall y, t he re p ort e d S A Es b y preferre d t er m a n d b o d y s yst e m classificati o n 
classifie d b y C T C A E se v erit y gra de ( 1 -5) a n d se p aratel y b y PI ass ess me nt of relati o ns hi p t o 
st u d y dr u g. A n arr ati ve s u m mar y of t he patie nt’s S A E will be i ncl u de d i n t he fi nal Cli nical St u d y 
Re p ort. 
1 1. 1. 3  
Assess me nt of L a b or at or y a n d Vit al Si g ns 
Eac h o f t he l a b orat or y t ests o utli ne d i n Secti o n 6. 2. 5  a n d eac h of t he vital si g ns o utli ne d i n 
Secti o n 6. 2. 6. 4  will be s u m marize d f or eac h  c ollecti o n peri o d b y treat me nt gr o u p as: 
•  Gr o u p mea n 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 2  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  Gr o u p sta n dar d d e viati o n 
•  Gr o u p me dia n 
•  Gr o u p ra n ge 
A d diti o nall y, eac h e v al uati o n will be s u m marize d as a c ha n ge fr o m b aseli n e f or eac h p atie nt b y 
treat me nt gr o u p as: 
•  Gr o u p mea n 
•  Gr o u p sta n dar d d e viati o n 
•  Gr o u p me dia n 
•  Gr o u p ra n ge 
Usi n g t he Ce ntr al La b or at or y’s n or mal ra n ges a n d sta n dar d ta ble of n or mal vital si g ns, eac h 
assess me nt will be classifie d as “ n or m al”, “l o w ”, or “ hi g h ” a n d s hift ta bles f or eac h para meter 
s h o w n of eac h assess me nt b y treat me nt gr o u p will be dis pla ye d.  
1 1. 1. 4  
Assess me nt of T u m or Pr o gressi o n  at 1 2 w ee ks  a n d 1 2- m o nt hs P ost- R T  
Sca ns at 1 2 wee ks a n d 1 2 - m o nt hs p ost-R T will be c o m pare d t o t he i nitial i ma ges  usi n g t he 
R E CI S T 1. 1 s yst e m as o utli ne d i n Ta ble 9 , Ta ble 1 0 , a n d Ta ble 1 1 . T h e perce nt of t he p atie nts 
cate g orize d as h a vi n g a “c o m plete t u m or res p o nse” at 1 2 wee ks a n d 1 2 m o nt hs p ost- R T will be 
c o m pare d b et wee n t h e tr eat me nt gr o u ps. A d diti o nall y, t he p erce nt of t he patie nts cate g oriz e d as 
ha vi n g a “c o m plet e t u m or res p o nse” or “ p artial t u m or res p o nse” at 1 2 wee ks  a n d 1 2 m o nt hs 
p ost- R T will be c o m pare d bet wee n t he treat me nt gr o u ps. 
1 1. 1. 5  
Inf ecti o ns  
Patie nts will be assesse d at eac h cli nical visit t hr o u g h t he 6 - wee k p ost-R T visit as t o t he pre se nce 
of pr o ba ble cli nical i nfecti o ns. All cli nical dia g n oses of i nfecti o ns will be classifie d as pres u me d 
f u n gal, pres u me d vir al, or pres u me d bacteri al. T he se verit y of eac h i nfecti o n will be gra de d 
usi n g t he C T C A E ( A p p e n di x 1). T he i nci de nce of all re p orte d i nfecti o ns, t he n u m ber of p atie nts 
wit h re p orte d i nfecti o ns, t he n u m ber of pres u me d f u n gal, t he n u m ber of pres u me d viral a n d t he 
n u m ber of pres u m e d bact erial i nfecti o ns will be c o m pare d bet w ee n treat me nt gr o u ps. T h e 
i nci de nce of eac h t y p e of i nfecti o n (f u n gal, viral, a n d bacterial) b y se verit y gra de ( 1 -5) will be 
dis pla ye d.  
1 1. 1. 6  
Assess me nt of M ort alit y T hr o u g h t he 1 2 -m o nt h P ost- R T Cli nic Visit  
All deat hs t hr o u g h t h e 1 2- m o nt h f oll o w- u p visit will be c ollecte d. T he n u m ber of deat hs i n eac h 
gr o u p will be c o m par e d usi n g a sta n d ar d c hi-s q u are d a nal ysis. T he n u m b er of deat hs o ver ti me 
will be c o m pare d usi n g a Ka pla n -Mei er s ur vi val c ur ve a n d t he s ur vi val c ur ves c o m pare d usi n g a 
l o g-r a n k test. 
1 1. 1. 7  
Pr o g ressi o n -f ree S ur vi v al 
T he d urati o n of pr o gressi o n free s ur vi val will be calc ulate d fr o m t he date of ra n d o mizati o n t o t he 
earliest date of t he f oll o wi n g:  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 3  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
•  T he patie nt die d  
•  T he patie nt ha d a n i ma gi n g r e p ort of t u m or pr o gressi o n ( R E CI S T 1. 1 e val u ati o n of less 
t ha n “ C o m plete Res p o nse”) 
•  T he patie nt c o m plete d t h eir 1 2 m o nt h f oll o w- u p assess me nt.  
Patie nts l ost -t o-f oll o w-u p will be ce ns ore d at t he ti me of t heir last assess me nt.  
1 1. 2.  
S afet y P ar a meters  
1 1. 2. 1  
A d verse E x perie nce ( A E ) 
A n y n o xi o us or u ni nte n de d e ve nt t hat occ urs i n ass ociati o n wit h t he use of a n i n vesti gati o nal 
a ge nt i n h u ma ns , w het her c o nsi dere d rel ate d t o t he i nvesti g ati o n al a ge nt or n ot. T his defi niti o n 
e nc o m passes s y m pt o ms or si g ns r e p orte d b y t he s u bject or detecte d b y t he i n vesti gat or or ot h er 
c o m pete nt o bser v er, as w ell as me dicall y i m p orta nt de viati o ns fr o m n or malit y i n t he res ults of 
a ncillar y i n vesti gati o ns. If prese nt at ti me of first d ose of st u d y dr u g, s uc h A Es m ust be rec or d e d 
as part of t he me di cal hist or y.  
Treat me nt -E mer ge nt A d verse E x perie nce : A n A E t hat is ne w i n o nset or a ggra vate d i n se v erit y 
or fre q u e nc y f oll o wi n g e ntr y i nt o t he st u d y. I n a d diti o n, a n y pat h ol o gical fi n di n g o n p h ysical 
e x a mi nati o n or dia g n ostic pr oce d ure t hat is ne w i n occ urre nce or e x acer bate d i n c o m paris o n wit h 
t he s u bject's stat us at st u d y e ntr y is c o nsidere d a treat me nt -e mer ge nt A E if it re q uires a n y 
me dical or s ur gical i nter ve nti o n w hats oe ver (i ncl u di n g, b ut n ot li mite d t o, a d diti o nal dia g n ostic 
pr oce d ur es or alterati o n of prescri be d t hera p y). 
All A Es, w het her j u d ge d t o be relate d or n ot t o t he st u d y dr u g, s h o ul d be rec or de d i n b ot h t he 
me dical rec or d a n d t he e C R F. T he start a n d res ol uti o n dates, t he j u d g me nt of t he se verit y of t h e 
A E, t he j u d g me nt of t he r elati o ns hi p of t he A E t o t he st u d y dr u g, t h e acti o n ta ke n f or s u bse q u e nt 
d ose of st u d y dr u g, a n d t he o utc o me s h o ul d be n ote d . 
1 1. 2. 2  
Seri o us A d verse E x peri e nce ( S A E)  
A n y A E occ urri n g at a n y d ose t hat res ults i n a n y of t he f oll o wi n g o ut c o mes: 
•  Deat h  
•  A life -t hreate ni n g A E 
•  Pr ol o n gati o n of e xisti n g h os pitalizati o n or s u bse q ue nt nee d f or h os pitalizati o n 
•  A persiste nt or si g nifica nt disa bilit y/i nca p acit y  
•  A c o n ge nital a n o mal y/ birt h defect  
•  A me dical or s ur gical i nte r ve nti o n t o pre v e nt o ne of t he a b o ve 
1 1. 3.  
Rel ati o ns hi p t o St u d y Dr u g  
T he relati o ns hi p of a n A E t o t he assi g ne d st u d y dr u g  is ass esse d usi n g t he f oll o wi n g defi niti o ns: 
N ot Rel at e d : T he dr u g e x perie nce is clearl y relat e d t o ot her fact ors s uc h as t he 
patie nt’s/s u bject’s cli nical state, t hera pe utic i nter v e nti o ns , or c o nc o mita nt dr u gs.  

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 4  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
P ossi bl y Rel ate d: T h e dr u g e x perie nce f oll o ws a reas o na bl e se q ue n ce fr o m t he  ti me of dr u g 
a d mi nistrati o n a n d/ or f oll o ws a k n o w n res p o ns e patter n t o t he st u d y dr u g, b ut c o ul d ha ve bee n 
pr o d uce d b y ot her fact ors s uc h as t he patie nt’s/s u bject’s cli nical state, t hera pe utic i nter ve nti o ns, 
or c o nc o mita nt dr u gs. 
Rel ate d: T he dr u g e x perie nce f oll o ws a reas o n a bl e te m p oral se q u e nce fr o m t he ti me of dr u g 
a d mi nistrati o n , f oll o ws a k n o w n res p o nse p atter n t o t he st u d y dr u g, a n d ca n n ot be reas o n a bl y 
e x plai ne d b y ot her fact ors s uc h as t he patie nt’s/s u bject’s cli nical state, t hera pe utic i nter ve nti o ns, 
or c o nc o mita nt dr u gs.  
1 1. 4.  
Se verit y of A d verse E ve nt  
A cli nical deter mi nati o n of t he i nte nsit y of a n A E  s h o ul d be d o ne f or all re p orte d A Es. T he 
se verit y assess me nt s h o ul d use t he C T C A E gra di n g s yste m t hat assess es t he se verit y of eac h A E 
fr o m gra des 1 - 5. T he gra di n g s yste m ca n b e f o u n d i n A p pe n di x 1. 
1 1. 5.  
Re p orti n g A d verse E ve nts  
1 1. 5. 1  
A d verse E ve nts  
All A Es t hat occ ur after a n y p atie nt/s u bject has b ee n e nr olle d, b ef ore treat me nt, d uri n g 
treat me nt, or wit hi n 6 wee ks ( ± 4 da ys) f oll o wi n g t he cessati o n of R T treat me nt , w het her or n ot 
t he y are relate d t o t he st u d y, m ust be r ec or d ed i n t he e C R F. All A Es s h o ul d be n ote d i n t he e C R F 
wit hi n 3 da ys of b ei n g rec o g nize d. A n y a d vers e e ve nt t hat is eit her a S A E or p ote ntial S A E 
s h o ul d be ha n dle d wit hi n t he ti mefra mes gi ve n i n secti o n 1 1. 5. 2 , bel o w. Eac h treat me nt -
e mer ge nt A E s h o ul d be r e p orte d s p o nta ne o usl y or i n res p o nse t o ge neral, n o n- directe d 
disc ussi o n wit h t he atte n di n g n urse or p h ysicia n (e. g., h as t here bee n a n y c ha n ge i n s u bject stat us 
si nce t he last assess me nt peri o d?). F or eac h treat m e nt -e mer ge nt A E, t he i n v esti gat or s h o ul d 
o btai n all t he i nf or mati o n re q uire d t o c o m plet e t he A E pa ge of t h e cas e re p ort f or m, i n 
acc ord a nce wit h t he g ui deli nes t hat acc o m p a n y it.  
All treat me nt -e mer ge nt A Es, re gar dless of seri o us ness, se verit y, or pres u me d relati o ns hi p t o 
st u d y t her a p y, m ust be rec or de d usi n g me dical ter mi n ol o g y c o nsiste nt wit h t he s o urce d o c u me nt 
a n d o n t he A E pa ge. W he ne ver p ossi ble, dia g n os es s h o ul d be gi v e n w he n si g ns a n d s y m pt o ms 
are d ue t o a c o m m o n eti ol o g y. I n v esti gat ors m ust rec or d t heir o pi ni o n c o n cer ni n g t he 
relati o ns hi p of t he A E t o st u d y t her a p y o n t he A E pa ge. 
All treat me nt -e mer ge nt A Es m ust be f oll o we d u ntil res ol uti o n or u ntil t he 6- m o nt h f oll o w u p 
visit . All meas ures re q uir e d f or A E ma na ge me nt a n d t he ulti mate o utc o me of t he A E m ust be 
rec or d e d i n t he s o urce d o c u me nt a n d re p orte d o n t he A E pa ge. T he res ol uti o n date f or all 
rec or d e d A Es s h o ul d be e ntere d wit hi n 3 da ys of deter mi nati o n t hat t he A E has res ol ve d.  
1 1. 5. 2  
Seri o us A d verse E ve nts  
All S A Es t hat occ ur aft er a n y p atie nt/s u bject has b ee n e nr olle d, b ef ore treat me nt, d uri n g 
treat me nt, or wit hi n six wee ks ( ± 4 d a ys) f oll o wi n g t he last R T , w het h er or n ot t he y are relate d t o 
t he st u d y, m ust be rec or d e d o n f or ms pr o vi de d i n t he eC R F.  
W he n t he i n vesti gat or, or trai ne d desi g nee, bec o m es a ware t hat a s eri o us or p ote ntiall y seri o us 
A E (as defi ne d a b o v e) has occ urr e d, t he site m o nit or or Me dical M o nit or m ust be n otifie d 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 6  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
T he D M C ma y re q u est a n y safet y data i n cl u di n g, b ut n ot li mit e d t o, S A Es, A Es, a n d la b orat or y 
val ues. T he D M C ma y als o re q uest a n y efficac y d ata i ncl u di n g, b ut n ot li mite d t o t he pri mar y 
a n d sec o n dar y o utc o mes t o e val uate be n efit t o ris k.  
T he D M C will re vie w u n bli n de d data at t he i nteri m a nal ys es a n d ma k e rec o m me n d ati o ns t o halt 
t he trial f or o ver w hel mi n g efficac y, or s afet y c o n cer ns, or f or f utilit y; c o nti n ue t he trial as 
writte n; or resize t he trial base d o n t h e place b o d urati o n of S O M. 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 5 9  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
I n acc or da n ce wit h t he G ui deli nes f or t he M o nit ori n g of Cli nical I n vesti gati o ns prese nte d i n t he 
I nter nati o nal C o nfere nce o n Har m o nisati o n (I C H) G ui da nce o n G C Ps ( E 6), S oli ge ni x will select, 
eit her directl y or t hr o u g h s u bc o ntract, q ualifie d i n di vi d uals t o m o nit or t he pr o gress of t he st u d y 
a n d a d her e nce t o pr ot oc ol b y t he i n di vi d ual cli nical sites. 
1 2. 6. 2  
Pre -st u d y E v al u ati o n 
T his i nitial e nc o u nter wit h t he site will esta blis h t hat t he site has all of t he n ecessar y ele me nts t o 
s uccessf ull y partici pate i n t he pr o p ose d pr ot oc ol i ncl u di n g a d e q uate trai ne d staff, a de q u ate free 
ti me of t he staff, a d e q uat e facilities f or s afe a n d pr o per trial c o n d u ct, e vi de n ce f or p ot e ntial 
e nr oll me nt of s uita ble patie nts, a de q uate researc h p har mac y s u p p ort, t he prese nce of a n I R B / E C 
meeti n g t he l o cal a n d F D A re q uire m e nts, a n d a c o m mit me nt f or trai ni n g of all i n v ol ve d staff o n 
t he pr ot oc ol. 
1 2. 6. 3  
Site I niti ati o n Visit  
T he Me dical M o nit or ( or trai ne d des i g nee) will i nitiate t he st u d y after o n- site trai ni n g of t he 
partici pati n g st aff at t he i nstit uti o n. T o pics c o vere d will i ncl u de trai ni n g o n:  
•  T he i n vesti gati o nal stat us of t he st u d y dr u g a n d t he re q u ire me nts f or its acc o u nta bilit y 
•  Bac k gr o u n d o n t he st u d y dr u g 
•  Details of t he pr ot oc ol i n cl u di n g patie nt sel ecti o n, st u d y dr u g a d mi nistrati o n, pr oce d ures 
t o be perf or m e d, a n d visit sc he d ules 
•  Critical nat ure of o btai ni n g i nf or m e d c o nse nt i n acc or da n ce wit h t he D eclarati o n of 
Helsi n ki a n d I C H G ui da nce o n G C Ps ( E 6) bef ore e nr olli n g eac h s u bject i n t he st u d y 
•  T he o bli gati o n t o e ns ur e I R B re vi e w a n d a p pr o val f or t he st u d y, i ncl u di n g t he pr ot oc ol, 
a me n d me nts,  I C F a n d a n y a d v ertise me nts, is o btai ne d pri or t o its i nitiati o n at his/ her 
cli nical site, t o e ns ure c o nti n ui n g re vie w of t he st u d y b y t he I R B, a n d t o k ee p S oli ge ni x 
i nf or me d of s uc h a p pr o v al a n d s u bse q ue nt acti o ns c o ncer ni n g t he st u d y 
1 2. 6. 4  
M o nit ori n g Visits  
S oli ge ni x or t heir trai ne d desi g nee will perf or m o n -site m o nit ori n g visits as fre q ue ntl y as it 
dee ms necessar y. At t hes e visits, t he site m o nit or will c o m pare t he dat a e nt ere d i nt o t he e C R F 
wit h t he s o urce d oc u m e nts a n d c hec k f or pr ot oc ol c o m plia nce i ncl u di n g a rec or d of i nf or me d 
c o nse nt, e nr oll me nt criteria, all s u bject assess me nts, all a d verse e x perie n ces , a n d all c o nc o mita nt 
me dicati o ns. I n a d diti o n, st u d y dr u g a n d s u p p orti n g rec or ds will be re vie w e d. A d diti o nall y, t he y 
ass ure t hat all seri o us, lif e -t hreate ni n g or fatal a d v erse e x perie n ces are bei n g re p orte d 
i m me diatel y [ a n d i n n o case later t h a n t we nt y-f o ur ( 2 4) h o urs after t h e e ve nt] t o t he Me dical 
M o nit or or desi g n ee at S oli ge ni x. 
Fi n di n gs fr o m t hese r e vie ws will be disc usse d wit h t he i n vesti gat or a n d staff. C o m plete d pa ges 
of t he e C R F will be e v al uate d at eac h visit. T he d ates of t he m o nit ori n g visits will be rec or de d i n 
a si g n-i n l o g t hat will be ke pt at t he site. T he st u d y c o or di nat or a n d i n v esti gat or are e x pecte d t o 
be a vaila ble f or q uesti o ns, t he s o urce d o c u me ntati o n rea dil y a vaila bl e, a n d a s uita ble 
e n vir o n me nt pr o vi de d f or re vie w of st u d y- rel ate d d oc u me nts. 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 0  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 2. 6. 5  
Cl ose- o ut Visit  
T he cli nical res ear c h m o nit or(s) will perf or m a n e n d of trial visit t o e ns ure t hat:  
•  All dr u g r ec o n ciliati o n f or ms are acc urate a n d c o m plete.  
•  All u n use d st u d y dr u g is ret ur ne d t o t he a p pr o priat e l ocati o n. 
•  All data iss ues are res ol v e d a n d e C R F are c o m plete d a n d verifie d.  
•  T he I R B h as bee n n otifie d t hat t he st u d y has b ee n c o m plete d. 
•  T he i n vesti gat or at eac h site is a ware t h at t he st u d y has bee n c o m plet e d a n d n o f urt her 
s u bjects are e nr olle d. 
1 2. 7.  
A u dits a n d I ns pecti o ns  
Healt h A ut h orities (e. g., F D A, t he E M A, or c o u ntr y Healt h A ut h orities), i n t he pers o n of a 
trai ne d a n d pr o p erl y a ut h orize d e m pl o yee, ma y re q uest access t o all st u d y rec or ds, i ncl u di n g 
s o urce d oc u m e nts, f or i ns pecti o n a n d c o p yi n g. T h e i n vesti gat or will i m me diatel y n otif y 
S oli ge ni x of a n y u pc o mi n g i ns pecti o ns.  
Peri o dic a u diti n g i ns pecti o ns ma y als o be c o n d uct e d b y a re prese nt ati ve of t he Q ualit y 
Ass ura nce De p art me nt of S oli ge ni x or its trai ne d desi g nee(s). 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 1  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 3.  
I N S TI T U TI O N A L R E VI E W B O A R D (I R B)/ E T HI C A L 
C O M MI T T E E ( E C)  
All partici pati n g ce nters m ust ha ve i n place eit her a n I R B or t h e E C t hat meets all of t he criteria 
o utli ne d i n Secti o n 3 of t he I C H “ G ui da n ce f or I n d ustr y ; E 6 G o o d Cli nical Practice:  
C o ns oli date d G ui da nce”. C o pies of t he I R B/ E C me m bers hi p list a n d pr oce d ures s h o ul d be 
pr o vi de d t o t he S oli ge ni x . 
It is t he r es p o nsi bilit y of t he site’s Pri nci pal I n vesti gat or ( PI) t o o btai n I R B/ E C writte n a p pr o val 
of t he pr ot oc ol, t he I nf or me d C o nse nt F or m, patie nt c o m pe nsati o ns details, a n d a n y 
a d vertise me nts t o be use d i n c o n d uct of t he trial. N o patie n t ca n b e e nr olle d i nt o t he trial pri or t o 
o btai ni n g t hese d o c u me nts. It is als o t he site’s PI res p o nsi bilit y t o : 
Ass ure  t hat n o de viati o ns fr o m, or c ha n ges of, t he pr ot oc ol s h o ul d be i nitiate d wit h o ut pri or 
writte n I R B/ E C a p pr o v al/fa v ora ble o pi ni o n of a n a p pr o priate a me n d me nt, e x ce pt w he n 
necessar y t o eli mi nate i m me diate hazar ds t o t he s u bjects or w he n t he c ha n ge(s) i n v ol ves o nl y 
l o gistical or a d mi nistrati ve as pects of t h e trial (e. g., c h a n ge of m o nit or(s), tele p h o ne n u mber(s))  
Pr o m ptl y re p ort t o t he I R B/ E C:  
o  All d e viati o ns fr o m, or c ha n ges t o, t he pr ot oc ol t o eli mi nate i m me diate hazar ds t o 
t he trial s u bjects 
o  A n y c ha n ges i n creasi n g t he ris k t o s u bjects a n d/ or affecti n g si g nifica ntl y t h e 
c o n d uct of t he trial 
o  All A Es  t hat are b ot h seri o us a n d u ne x pecte d  w het her see n at t hat i nstit uti o n or 
re p orte d fr o m S oli ge ni x  
o  A n y n e w i nf or mati o n t hat ma y affect a d versel y t h e safet y of t h e s u bjects or  t he 
c o n d uct of t he trial. 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 2  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 4.  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  
It is t he r es p o nsibilit y of t he PI or his/ her desi g nee t o ass ure t hat all i nf or mati o n i n t he e C R F is 
acc ur ate a n d c o m plete. T he e C R F will perf or m i m me diate i nter nal c o nsiste nc y c hec ks t o 
mi ni mize p ote ntial f or err o ne o us data (e. g., date of birt h after d ate of ra n d o mizati o n). S oli ge ni x 
will use m o nit ors t o re vie w e ntere d d ata i n t he e C R F a n d ma ke p eri o dic site visits t o c o m pare 
e C R F data wit h s o urce d oc u me nts. Peri o dic i nteri m a u dits fr o m S oli ge ni x’s Q ualit y D e part me nt 
or t heir desi g nee will be c o n d ucte d t o ass ure t hat all I C H g ui deli nes are b ei n g f oll o we d a n d 
i de ntif y a n y s yste mic pr o ble ms wit h t he data or pr oce d ures.  Fi nal a u dits will be c o n d ucte d at 
re pres e ntati ve sites. 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 3  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 5.  
E T HI C S 
1 5. 1.  
Et hic al Re vie w of Tri al  
T he fi nal st u d y pr ot oc ol, i ncl u di n g t he fi nal v ersi o n of t he S u bject I nf or m ati o n a n d C o nse nt 
F or ms, m ust be a p pr o v e d i n writi n g b y I R B / E C bef ore e nr ol l me nt of a n y s u bject i nt o t he st u d y. 
T he PI or t heir desi g nee is res p o nsi ble f or i nf or mi n g t he I R B / E C of a n y S A Es  a n d a me n d me nt(s) 
t o t he pr ot oc ol as per re g ulat or y re q uire m e nts. 
1 5. 2.  
Et hic al C o n d uct of t he St u d y  
T he st u d y will be p erf or me d i n acc or d a nce wit h t he et hical pri nci ples i n t h e Decl arati o n of 
Helsi n ki, G C P s a n d a p plica ble r e g ulat or y re q uire me nts.  
1 5. 3.  
Writte n I nf or me d C o nse nt  
T he I n vesti gat or will e ns ure t hat t he s u bject or a l e gall y a ut h orize d re prese ntati ve of t he s u bject 
are gi ve n f ull a n d a de q u ate oral a n d writte n i nf or mati o n a b o ut t he nat ure, p ur p ose, p ossi ble ris ks 
a n d be nefit s of t he st u d y. S u bjects m ust als o be n otifie d t hat t he y are free t o disc o nti n ue fr o m t he 
st u d y at a n y ti me. T h e s u bject s h o ul d be gi v e n t he o p p ort u nit y t o as k q uesti o ns a n d all o we d ti me 
t o c o nsi der t he i nf or mati o n pr o vi de d. T he s u bject’s si g ne d a n d d ate d i nf or m e d c o nse nt m ust be 
o bt ai ne d bef ore c o n d ucti n g a ny st u dy s pecific pr oce d ure . T he c o nse nt f or m t hat is use d m ust 
meet t he re q uir e me nts as o utli ne d i n t he I C H G ui d a nce o n G C Ps ( E 6) a n d m ust be a p pr o ve d b y 
b ot h t he re vie wi n g I R B / E C a n d b y S oli ge ni x. 
1 5. 4.  
S u bject D at a P r otecti o n 
T he S u bject I nf or m ati o n a n d C o nse nt F or m will e x plai n t hat st u d y data will be st ore d i n a 
c o m p uter data b ase, mai ntai ni n g c o nfi d e ntialit y . S u bjects i n t his data base will be i de ntifie d b y 
i nitials or e nr oll me nt c o de/s u bject n u m ber o nl y. A n a ut h orize d re pres e ntati ve of a re g ulat or y 
a ut h orit y ma y re q uire dir ect access t o parts of t h e trial site rec or ds rele va nt t o t he st u d y, 
i ncl u di n g s u bjects’ me di cal hist or y f or dat a verifi cati o n p ur p oses. 
1 5. 5.  
Fi n a nci al Discl os ure  
T he F D A has iss ue d r e g ulati o ns ( 2 1 C F R Part 5 4) t hat re q uire S p o ns ors (i n t his case S oli ge ni x) 
t o s u b mit c o m plete a n d acc urat e certificati o n or discl os ure state me nts t o certif y t he a bse nce of 
certai n fi n a ncial i nter ests of cli nical i n vesti gat ors a n d/ or discl ose t h ose fi na ncial i nterests, as 
re q uire d, w h e n cli nical st u dies are s u b mitte d t o t he F D A i n s u p p ort of mar keti n g a p pr o val of a 
ne w dr u g a p plicati o n ( N D A). T hes e re g ulati o ns are i nte n de d t o e ns ure t hat fi na ncial i nterests a n d 
arra n ge me nts of cli nical i n vesti gat ors, t hat c o ul d affect relia bilit y of d ata s u b mitte d t o t he F D A 
i n s u p p ort of mar keti n g a p pr o val, ar e i de ntifie d a n d discl ose d b y t he S p o ns or. 
Re gar dless of t he l ocati o n of t he cli nical site, all cli nical i n vesti gat ors partici pati n g i n t his 
cli nical trial s hall be as ke d t o discl ose pr o prietar y (e. g., pate nt, lice nsi n g a gree me nt) a n d 
fi na ncial ( e. g., st oc k o pti o ns, r o yalty) i nterests as t he y p ertai n t o S oli ge ni x, pri or t o partici pati n g 
i n t he st u d y. I n a d diti o n, cli nical i n vesti gat ors will be re q uire d t o c o ns ult wit h S oli ge ni x bef ore 
ac q uiri n g a n y fi n a ncial i nterest i n t he c o m pa n y a n d m ust discl ose a n y c h a n ge i n t heir pr o p rietar y 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 4  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
or fi na ncial i nter ests if it occ urs d uri n g t he c o urse of t he st u d y a n d f or o n e year f oll o wi n g st u d y 
c o m pleti o n. Cli nical i n vesti gat or is defi n e d u n der Title 2 1 C F R Part 5 4 as a n i n vesti gat or or s u b-
i n vesti gat or liste d o n t he F D A F or m 1 5 7 2 t hat is directl y i n v ol ve d i n t he treat me nt or e val uati o n 
of researc h s u bjects. T he re q uire me nt f or pr o pri etar y a n d fi na n cial discl os ure als o i ncl u des a n y 
o w ners hi p b y t he s p o use or a n y de pe n d e nt c hil d of t he i n vesti gat or. 
If t he F D A deter mi nes t hat t he fi na ncial i nterests of a n y cli nical i n vesti gat or raise seri o us 
q uesti o ns a b o ut t he i nte grit y of t he d ata, t he F D A will ta ke a n y acti o n it dee ms necessar y t o 
e ns ure t he r elia bilit y of t he data, i ncl u di n g: 
I nitiati n g a ge n c y a u dits of t he data deri ve d fr o m t he cli nical in vesti gat or i n q uesti o n; 
Re q uesti n g t hat t he S p o ns or s u b mit f urt her a nal ys es of data, e. g., t o e val uat e t he effect of t h e 
cli nical i n vesti gat or’s dat a o n o verall st u d y o utc o me;  
Re q uesti n g t hat t he a p plica nt c o n d uct a d diti o nal i n de pe n de nt st u dies t o c o nfir m t he res ults of t he 
q uesti o ne d st u d y; a n d/ or 
Ref usi n g t o treat t he c o v ere d cli nical st u d y as pr o vi di n g data t hat ca n be t h e basis f or a n a ge n c y 
acti o n. 
If t he S p o ns or d oes n ot i ncl u de certificati o n or discl os ure, or b ot h, if re q uire d, or d oes n ot certif y 
t hat it was n ot p ossi ble t o o btai n t he i nf or mati o n, t he F D A m a y ref use t o fil e t he N D A . 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 5  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 6.  
D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
1 6. 1.  
I ns pecti o n of Rec or ds 
As n ote d i n Secti o n 1 3. 6, it is t he res p o nsi bilit y of t he PI a n d t he partici p ati n g i nstit uti o n t o 
ass ure t hat a p pr o priate tri al -relat e d m o nit ori n g, a u dits, I R B/ E C re vi e w, a n d re g ulat or y 
i ns pecti o n(s) ca n b e carri e d o ut b y ass uri n g direct access t o s o urce d ata/ d oc u me nts. T hese 
i ns pecti o ns ma y b e c o n d ucte d b y S olige ni x  or its desi g nee or re prese ntati v es of t he F D A, E M A, 
or l ocal Healt h A ge ncies.  
1 6. 2.  
Rete nti o n of Rec or ds  
It is t he j oi nt res p o nsi bilit y of b ot h t he site PI a n d t he i nstit uti o n t o ta ke meas ures t o pre v e nt 
acci de nt al or pre mat ure d estr ucti o n of all st u d y d o c u me nts i ncl u di n g t he s o urce d oc u m e nts. 
Esse ntial d oc u me nts s h o ul d be retai ne d u ntil at least 2 years after t he l ast a p pr o val of a 
mar keti n g a p plicati o n i n a n I C H re gi o n a n d u ntil t here are n o p e n di n g or c o nte m plate d mar keti n g 
a p plicati o ns i n a n I C H re gi o n; at least 2 years ha v e ela pse d si nce t he f or mal disc o nti n uati o n of 
cli nical de vel o p me nt of t he i n vesti gati o nal pr o d uct; or 7 years si nce t h e cl ose -o ut of t he cli nical 
trial. S oli ge ni x  will i nf or m t he i n vesti gat or /i nstit uti o n as t o w he n t hese d oc u me nts n o l o n ger 
nee d t o be r etai ne d . 
If t he res p o nsi ble i n vesti gat or retires, rel ocates, or f or ot her reas o n wit h dra ws fr o m t he 
res p o nsi bilit y of kee pi n g t he st u d y r ec or ds, c ust o d y m ust be tra nsferre d t o a pers o n w h o will 
acce pt t he res p o nsi bilit y. S oli ge ni x m ust be n otifie d i n writi n g a n d a ppr o ve of t he na me a n d 
a d dress of t he n e w c ust o dia n. 
1 6. 3.  
P u blic ati o n C o m mittee  
T he S p o ns or, S oli ge ni x, is c o m mitte d t o t he pr o m pt p u blicati o n of t he res ults of t his trial 
re gar dl ess of t he o utc o m e. A P u blicati o n C o m mittee will be a p p oi nte d t o re vie w a n d pre pare a 
ma n uscri pt f or s u b missi o n t o a n a p pr o priat e peer-re vie we d sci e ntific j o ur nal. Me m bers hi p t o t he 
c o m mittee will be offer e d, at a mi ni m u m,  t o t he st u d y’s PI , t he 6 sites e nr olli n g t he hi g hest 
n u m ber of e v al ua ble pati e nts i nt o t he trial, t he st u d y statisti cia n, a n d re prese ntati ves of S oli ge ni x . 
Ot her me m bers ma y b e a p p oi nte d at t he i nitial P u blicati o n C o m mittee meeti n g.  
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
 Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 6  of 6 7  
A m e n d m e nt 1: 2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7  S e pt e m b er 2 0 1 9  
1 7.  
I N V E S TI G A T O R A G R E E M EN T  
 
I h a ve r ea d t he f ore g oi n g pr ot oc ol a n d a gree t hat it c o ntai ns all necessar y d etails f or carr yi n g o ut 
t his st u d y. I will c o n d uct t he st u d y as o utli ne d herei n, i n acc or da n ce wit h l o cal a n d fe deral 
re g ulati o ns, G o o d Cli nical Practices a n d will c o m plete t he st u d y wit hi n t he ti me desi g nate d. 
I will pr o vi de c o pies of t he pr ot oc ol a n d all perti ne nt i nf or mati o n t o all i n di vi d uals res p o nsi ble t o 
me w h o assist i n t he c o n d uct of t his st u d y. I will disc uss t his material wit h t he m t o e ns ure t he y 
are f ull y i nf or m e d re gar di n g t he st u d y dr u gs a n d t he c o n d uct of t he st u d y. 
I will use o nl y t he i nf or me d c o nse nt f or m a p pr o ve d b y t he I nstit uti o nal Re vie w B oar d/ Et hics 
C o m mittee a n d S oli ge ni x a n d will f ulfill all res p o nsi bilities f or s u b mitti n g perti ne nt i nf or mati o n 
t o t he I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee res p o nsi ble f or t his st u d y. 
I f urt her a gree t hat t he H ealt h A ut h orities, S oli ge ni x, or t heir desi g nee(s) s hall ha ve access t o a n y 
s o urce d oc u m e nt fr o m w hic h case re p ort f or m i nf or mati o n ma y h a ve bee n ge n erat e d. 
I a gree t hat I a n d all i n vesti gat ors liste d o n t he F D A F or m 1 5 7 2 s hall i nf or m S oli ge ni x of a n y 
e q uit y i nter est i n t he c o m pa n y pri or t o a n d d uri n g partici pati o n i n t his trial. I f urt her a gree t hat I 
a n d all liste d i n vesti gat ors will c o ns ult wit h S oli ge ni x bef ore ac q uiri n g a n y fi na ncial i nterest i n 
t he c o m pa n y d uri n g t he st u d y a n d f or o ne year aft er t he st u d y’s c o m pleti o n. 
 
 
 
 
 
 
I n v esti gat or's Si g nat ure 
Date  
 
 
 
 
Na me of I n v esti gat or ( T y pe d or Pri nte d) 
 
 
 
 
 
 

Pr ot o c ol I D R -O M -0 2 -U S A  
 
 
Ori gi n al: 1 1 J a n u ar y 2 0 1 7  
C o nfi de nti a l 
P a g e 6 7  of 6 7  
A m e n d m e nt 1:  2 9 N o v e m b er 2 0 1 7   
A m e n d m e nt 2: 2 2 J a n u ar y 2 0 1 8  
A m e n d m e nt 3: 1 7 S e pt e m b er 2 0 1 9  
1 8.  
R E F E R E N C E S  
1.  
Y u, H. B., et al., Se q uest os o me- 1/ p 6 2 is t he key i ntr acell ul ar t ar get of i n n ate defe nse 
re g ul at or pe pti de. J Bi ol C he m, 2 0 0 9. 2 8 4 ( 5 2): p. 3 6 0 0 7- 1 1. 
2.  
N ort h, J. R., et al., A n ovel a p pr o ac h f or e mer gi n g a n d a nti bi otic resist a nt i nfecti o ns: 
I n n ate Defe ns e Re g ul at ors as a n a g n ostic t her a py. J Bi otec h n ol o g y, 2 0 1 6. 2 2 6 : p. 2 4-
3 4. 
3.  
K u dri m oti, M. K., et al., R a n d o mize d, Pl ace b o- C o ntr olle d P h ase 2 a Cli nic al a n d 
Precli nic al D at a De m o nstr ati n g a Si g nific a nt a n d C o nsiste nt Re d ucti o n i n D ur ati o n of 
Or al M uc ositis wit h a N ovel I n n ate D efe nse R e g ul at or.  J Bi otec h n ol o g y, 2 0 1 6. 2 3 9 : p. 
1 1 5- 1 2 5. 
4.  
Sc ott, M. G., et al., A n a nti- i nfective pe pti de t h at selectively m o d ul ates t he i n n ate 
i m m u ne res po nse.  N at Bi otec h n ol, 2 0 0 7. 2 5 ( 4): p. 4 6 5- 7 2. 
5.  
D o ni ni, O., et al., Re d uce d I nfecti o n a n d M uc ositis i n C he m ot her a py- Tre ate d A ni m als 
F oll o wi n g I n n ate Defe nse M o d ul ati o n Usi n g a N ovel Dr u g C a n di d ate.  Bl o o d, 2 0 1 0. 
1 1 6 ( A S H A n n ual Meeti n g A bstracts): p. 3 7 8 1. 
6.  
W H O, W. H. O., W H O H a n d b o ok f or re p orti n g res ults of c a ncer tre at me nt.  1 9 7 9, 
Ge ne va.  
7.  
S o nis, S. T., Ne w t h o u g hts o n t he i niti ati o n of m uc ositis.  Oral Dis, 2 0 1 0. 1 6 ( 7): p. 5 9 7-
6 0 0. 
8.  
Me hta, C. R. a n d S.J. P oc oc k, A d a ptive i ncre as e i n s a m ple size w he n i nte ri m res ults are 
pr o misi n g: a pr actic al g ui de wit h ex a m ples.  Stat Me d, 2 0 1 1. 3 0 ( 2 8): p. 3 2 6 7- 8 4.