MAGNETISMM-1 A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH IMMUNOMODULATORY AGENTS IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)
Phase: PHASE1
Conditions: Multiple Myeloma
Sponsor: Pfizer

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M A G N E TI S M M - 1
A P H A S E I, O P E N L A B E L S T U D Y T O E V A L U A T E T H E S A F E T Y, 
P H A R M A C O KI N E TI C, P H A R M A C O D Y N A MI C A N D C LI NI C A L A C TI VI T Y O F 
E L R A N A T A M A B ( P F -0 6 8 6 3 1 3 5 ), A B-C E L L M A T U R A TI O N A N TI G E N 
( B C M A) - C D 3 BI S P E CI FI C A N TI B O D Y, A S A SI N G L E A G E N T A N D I N 
C O M BI N A TI O N WI T H I M M U N O M O D U L A T O R Y A G EN T S I N P A TI E N T S WI T H 
R E L A P S E D/ R E F R A C T O R Y A D V A N C E D M U L TI P L E M Y E L O M A ( M M )
I n vesti g ati o n al Pr o d uct N u m ber:
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I n vesti g ati o n al Pr o d uct N a me:
Elra nata ma b 
U nite d S t ates ( U S) I n vesti g ati o n al Ne w 
Dr u g ( I N D) N u m ber:
1 3 3 ,9 4 0
E ur o pe a n Cli nic al Tri al s D at a b ase 
( E u dr a C T) N u m ber:
2 0 1 9 -0 0 0 8 2 2 -2 4
Cli nic al Tri als. g o v N C T :
N C T 0 3 2 6 9 1 3 6
Pr ot oc ol N u m ber:
C 1 0 7 1 0 0 1
P h ase:
1
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t h ese d oc u me nt s, yo u  a gree t o h ol d t his 
i nf or mati o n i n c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or 
use it f or u na ut h orize d p ur p oses.  I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer 
m ust be pr o m ptl y n otifie d .
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D oc u me nt Hist or y
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
Ori gi nal 
pr ot oc ol
1 0 Ma y
2 0 1 7  
N/ A
A me n d me nt 1
2 8 Se pte m ber 2 0 1 7
1. S u m mar y , Secti o ns 3. 1, 3. 3, a n d 9. 2. 1: 
Re vise d D L T rate t o 2 5 % wit h a n acce pta ble 
e q ui vale nce i nter val of ( 2 0%- 3 0 %) f oll o wi n g 
fee d bac k fr o m t he F D A. 
2. S u m mar y , Secti o n 3. 1: Re m o ve d Part 2 B 
c o m bi nati o n t hera p y secti o n si nc e details of 
c o m bi nati o n p orti o n will o nl y be pr o vi de d i n a 
f ut ure a me n d me nt.
3. Sc he d ule of acti vities: Clarifie d t hat res ults 
fr o m t he patie nt’s last b o ne marr o w 
assess me nts ma y be utilize d f or scree ni n g if t he 
res ults were c ollecte d wit hi n 3 m o nt hs fr o m
pla n ne d st u d y  dr u g treat me nt.
4. Sc he d ule of acti vities a n d Secti o n 3. 1: A d de d 
7 2 hr h os pitalizati o n o n C y cle 1 Da y 1 ( C 1 D 1) 
f or patie nts i n Part 1 a n d 7 2 hr h os pitalizati o n 
o n C y cle 1 Da y 8 ( C 1 D 8) f or patie nts i n Part 
1 A , per re q uest fr o m t he F D A .
5 . Secti o n 3. 1. 4. a n d A p pe n di x 8 : D ose decisi o n 
r ules ha ve bee n re vise d f oll o wi n g a c ha n ge i n 
D L T tar get rate.
6. Secti o n 3. 2: D ose li miti n g t o xicit y  ( D L T) 
criteria ha ve bee n re vise d f oll o wi n g F D A’s 
rec o m me n dati o ns. 
7. Secti o n 3. 5: A ne w st o p pi n g criteria sect i o n 
has bee n i ncl u de d t o pr o vi de r ules f or st o p pi n g 
t he st u d y i n Part 2 d ose e x pa nsi o n.
8. Secti o n 4. 1: A d mi nistrati ve e dits were ma de 
t o clarif y i ncl usi o n criteria # 1 t o e ns ure t hat 
o nl y  patie nts wit h meas ura ble disease a n d eit her 
a bi o ps y pr o ve n plas mac yt o ma or b o ne marr o w 
plas ma cells > 2 0 % will be i ncl u de d. Criteria 
f or pri or t hera p y ha ve bee n m o ve d t o criteria # 2 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
s o t hat all patie nts are n o w re q uire d t o meet 
t hese criteria.
9. Secti o n 5. 5. 3 Ta ble 3 : Re vise d d ose 
m o dificati o n criteria f or n o n -he mat ol o gi cal 
t o xicities gra des 3 a n d 4 s uc h t hat a gra de 3 
e ve nt w o ul d re q uire d ose - de- escalati o n a n d 
gra de 4 e ve nts will re q uire disc o nti n uati o n, per 
g ui da nce fr o m t he F D A.
1 0. Secti o n 7. 1. 2: A d de d treat me nt g ui da nce f or 
patie nts w h o ha ve recei ve d a n all o ge neic b o ne 
marr o w tra ns pla nt.
1 1. Secti o n 7. 1. 3: A d de d o pti o n f or sites t o 
a nal yz e c yt o ki nes l ocally s h o ul d t his be 
re q uire d f or patie nt ma na ge me nt. 
1 2. Secti o n 7. 2. 1: Pr o vi de d i nf or mati o n 
re gar di n g p ote ntial darat u m u ma b i nterfere nce 
i nf or mati o n a n d clarifie d t hat t he F L C assa y 
s h o ul d be utilize d if darat u m u ma b treat me nt 
was gi ve n < 1 1 4 da y s pri or t o pla n ne d treat me nt 
da y  ( C 1 D 1). 
A me n d me nt 2
2 5 A pril 2 0 1 8
1. Pr ot oc ol S u m mar y  a n d Secti o n 3: A d diti o n 
of s u bc uta ne o us ( S C) c o h orts i n Part 1 a n d Part 
1 A t o all o w f or e val uati o n of S C d osi n g. 
E val uati o n of 1 hr i nf usi o n has bee n re vise d 
s uc h t hat it will n o w occ ur i n Part 2 as a lea d-i n 
c o h ort. 
2. Pr ot oc ol S u m mar y  a n d Sectio n 2:
A d mi nistrati ve c ha n ges ha ve bee n ma de t o t he 
w or di n g i n e x pl orat or y  bi o mar ker e n d p oi nts.
3. Sc he d ule of assess m e nt A a n d B a n d Secti o n 
5. 8. 6: A d diti o n of l ocal site i njecti o n 
t olera bilit y assess me nt t o e val uate i njecti o n site 
reacti o ns (IS R).
4. Sc he d ule of assess me nt A a n d B : Re visi o n of 
bi oc he mical disease assess me nts fr o m wee kl y 
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
t o per c ycle ti mefra me t o acc o u nt f or half -life
of M -pr otei ns a n d t o re d uce b ur de n o n sites.
5. Sc he d ule of assess me nt A a n d B a n d Secti o n 
7. 1. 5: Tri plicate E C Gs will o nl y  be ta ke n o n 
C 1 D 1 u ntil C 2 D 1 5. All ot her assess me nts will 
be base d o n a si n gle E C G.
6. Sc he d ule of assess me nt A a n d B a n d 
Secti o n 7. 2. 2: A d mi nistrati ve e dits t o b o ne 
marr o w c ollecti o n a n d assess me nt t o e ns ure 
ali g n me nt bet wee n t he sc he d ule of assess me nts 
an d S ecti o n 7. 2. 2. 
7. Sc he d ule of assess me nt A a n d B: Re d uce d 
n u m ber of uri nal ys is assess me nts s uc h t hat it
will o nl y  be perf or me d w he n cli nicall y 
i n dicate d.
8. Sc he d ule of assess me nt B : Re m o val of 
wee kl y wei g ht assess me nt i n Sc he d ule of 
assess me nt B t o al i gn wit h Sc he d ule of 
assess me nt A a n d Secti o n 5. 4. 1 w here wei g ht is 
e val uate d o n Da y 1 of eac h c ycle.
9. Secti o n 1. 2. 4: S C n o n -cli nical safet y 
i nf or mati o n has bee n a d de d t o j ustif y 
i nc or p orati o n of S C d osi n g i n t his st u d y.
1 0. Secti o n 1. 2. 6. 2: S C starti n g d ose rati o nale 
has bee n a d de d t o s u p p ort t he a d diti o n of S C 
a d mi nistrati o n. 
1 1. Secti o n 4: I ncl usi o n criteria has bee n 
re vise d s uc h t hat bi o psy pr o ve n plas mac y t o ma 
a n d ≥2 0 % plas ma cells i n b o ne marr o w is n o
l o n ger a re q uire me nt si nce t his will e x pa n d t he 
n u m ber of p ote ntial rela pse/ refract or y  m ulti ple 
m y el o ma patie nts t hat ma y be e nr olle d.
1 2 . Secti o n 4 a n d Secti o n 5. 8. 1 4 : I ncl usi o n 
criteria ha ve bee n re vise d s uc h t hat tra nsf usi o n 
s u p p ort will be all o we d d uri n g scree ni n g.  
S pecificall y, Secti o n 5. 8. 1 4 has bee n a d de d t o 
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
clarif y w he n tra nsf usi o n s u p p ort will be 
all o we d. 
1 1. Secti o n 4: Clarificati o n has bee n ma de t o 
patie nts treate d wit h el ot uz u ma b or ot her 
a nti-S L A M F 7 rece pt or (als o k n o w n as 
a nti-C D 3 1 9 ) t hera py s uc h t hat t he y  will o nly be 
e xcl u de d if last d ose of t hera p y is less t ha n 3 0 
da y s fr o m e nr oll me nt i nt o st u d y.
1 2. Secti o n 4: E xcl usi o n criteria f or pri or 
B C M A t hera pies has bee n clarifie d f or Part 1 
a n d Part 1 A s uc h t hat k n o w n B C M A ne gati ve 
patie n ts will n ot be eli gi ble b ut patie nts wit h 
B C M A p ositi ve rela pse ma y  be all o we d 
f oll o wi n g disc ussi o n wit h t he s p o ns or. F or Part 
2, t he e xcl usi o n criteria ha ve bee n clarifie d t o 
all B C M A tar gete d t hera p y.
1 3 . Secti o n 7. 1. 3 a n d 7. 5. 4: Tar gete d pa nel f or 
a d hoc ce ntral c yt o ki ne pa nel has bee n re place d 
wit h t he f ull pa nel t o ali g n wit h t he ce ntral 
assess me nts t hat will be c o m plete d.
1 4 . A p pe n di x 9: Ad de d : t o pr o vi de g ui da nce o n 
s u bc uta ne o us i njecti o ns.
A me n d me nt 3
0 7 Fe br uar y  2 0 1 9 
1. E u dra C T n u m ber 2 0 1 9- 0 0 0 8 2 2 - 2 4 was 
a d de d t o t he c o ver pa ge
2.
Pr ot oc ol S u m mar y : F or t he p ur p ose of 
clarit y, refere nce t o Secti o n 3. 1. 1. 3 (I V 
Pri mi n g a n d Mai nte na nce D ose Escalati o n) 
is n o w liste d wit h eac h s u m mar y descri bi n g 
d osi n g gr o u ps.
3.
Pr ot oc ol S u m mar y : F or t he p ur p ose of
clarit y, t he P art 2 e x pa nsi o n para gra p h ha d 
la n g ua ge re m o ve d w hic h was re peate d i n 
Secti o n 3. 1. 2.
4.
Pr ot oc ol S u m m ar y a n d T a ble 1 i n Secti o n 
3. 1. 4: A d diti o n of 9 0 a n d 2 7 0 µ g/ k g d oses 
f or t he I V c o h orts ( Part 1) b ase d o n 
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E T M F C o py of:
 
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
e mer gi n g data t hat T B D ha ve bee n 
i de ntifie d.
5.
Secti o n 1. 2. 6: Title was u p date d t o Starti n g 
D ose Rati o nale t o clarif y t he c o nte nt of t he 
secti o n.
6.
Pr ot oc ol s u m mar y  a n d Secti o n 1. 2. 6. 2: 
C larifie d la n g ua ge f or s u bc uta ne o us starti n g 
d ose rati o nale e x plai ne d i n detail i n S ecti o n 
3. 1. 1. 2. 
7.
Secti o n 1. 2. 6. 3: U p date d title a n d m o difie d 
la n g ua ge t o clarif y se nte nce t hat t he pri mi n g 
a n d mai nte na nce p art ma y be e val uate d 
pri or t o reac hi n g M T D.
8.
Secti o n 3. 1: U p date d st u d y  sc he ma t o 
reflect st u d y desi g n a n d a d de d f o ot n ote t o 
s pecif y t hat t he n o lea d-i n c o h ort will be 
c o n d ucte d if t he s u bc uta ne o us r o ute is 
selecte d f or Part 2.
9.
Secti o n 3. 1. 1. 3 : A d de d g ui da nce f or 
pri mi n g a n d mai nte na nce d ose f or P art 1 A 
I V c o h orts.
1 0. Pr ot oc ol S u m mar y , Secti o n 1. 2. 6. 2 Secti o n 
1. 2. 6. 3, Secti o n 3. 1. 1. 1, Secti o n 3. 1. 1. 2, 
Secti o n 3. 2 a n d A p pe n di x 5: Clarifie d 
la n g ua ge t o re m o ve tociliz u ma b a n d/ or 
vas o press ors fr o m t he ma na ge me nt of C R S 
a n d re place d ( w here a p pr o priate) wit h 
la n g ua ge t hat w o ul d e na ble t he treat me nt 
wit h sta n dar d of care per t he i nstit uti o n’s, 
i n vesti gat or’s or treati n g ph y sicia n’s 
g ui deli nes.
1 1. Pr ot oc ol S u m mar y  Sc he d ule of Acti vities 
B: F o ot n ote # 2 1 was c orrecte d fr o m C y cle 1 
Da y  1 t o C ycle 1 Da y 8 f or t he mai nte na nce 
d ose.
1 2. Secti o n 3. 1. 1. 1: C ha n ge d la n g ua ge t o clarif y  
t hat d oses a b o ve 2 7 0 µ g/ K g will be 
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E T M F C o py of:
 
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P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
e x pl ore d a n d a d de d lan g ua ge t hat P art 1 
s u bc uta ne o us or I V mai nte na nce ma y be 
i nitiate d.
1 3. Secti o n 3. 1. 1. 2: M o difie d la n g ua ge t o start 
t he s u bc uta ne o us part i n de pe n de nt of G ra de 
3 C R S a n d all o w S C starti n g d ose at hi g her 
d ose le vel base d o n c urre nt I V preli mi nar y  
safety, P K , a n d C R S data.
1 4. Secti o n 3. 1. 1. 3: Re vise d te xt t o lea ve o nl y  
Pri mi n g a n d Mai nte na nce f or Part 1 A I V.
1 5. Secti o n 3. 1. 1. 4: Delete d secti o n f or Part 1 A 
s u bc uta ne o us a d mi nistrati o n.
1 6. Secti o n 3. 1. 1. 5: Delete d secti o n f or Part 1 A 
I V a d mi nistrati o n.
1 7. Secti o n 3. 1. 4: M o di fie d la n g ua ge s o t hat 
hi g her d oses i n t he I V a d mi nistrati o n 
c o h orts ca n be e val uate d.
1 8. Secti o n 3. 1. 2: A d de d a state me nt t hat , base d 
o n e mer gi n g cli nical data fr o m t he Part 1 
d ose escalati o n, eit her I V or S C 
a d mi nistrati o n , i ncl u di n g pri mi n g a n d 
mai nte na nce d ose , will be selecte d f or t he 
Part 2 d ose e x pa nsi o n.  A d diti o nall y , a 
se nte nce was a d de d t hat n o lea d -i n c o h ort 
will be c o n d ucte d if s u bc uta ne o us r o ute is 
selecte d f or Part 2 e x pa nsi o n.
1 9. Secti o n 3. 2: T he D ose Li miti n g T o xicit y  
Defi niti o n was u p date d f or Gr a de 4 
thr o m b oc y t o pe nia t o acc o u nt f or s u bjects 
t hat ha ve a platelet c o u nt bet wee n 2 5, 0 0 0 
a n d 5 0, 0 0 0 a n d a d de d for Gra de 4 
t hr o m b oc yt o pe nia wit h ≥
Gra de 2 
blee di n g .
2 0. Secti o n 4. 1: Reflect t he f oll o wi n g 
clarificati o ns: 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
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D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
2 1. I ncl usi o n criteri o n # 1a a n d A p pe n di x 2: 
L o were d t he M- pr otei n t o greater t ha n or 
e q ual t o 0. 5 g/ d L f or Part 1 a n d greater t ha n 
or e q ual t o 1. 0 g/ d L f or Part 2.
2 2. I ncl usi o n criteri o n # 1c: Up date d t o reflect 
meas ura ble disease f or F L C.
2 3. I ncl usi o n criteri o n # 2 a n d Secti o n 3. 1. 1. 1:
C larifie d t hat patie nts m ust ha ve recei ve d 
pri or t hera pies wit h pr oteas o me i n hi bit ors, 
I Mi D dr u gs , a n d a nti -C D 3 8 m o n ocl o nal 
a nti b o dies, w here a p pr o ve d a n d a vaila ble. 
2 4. I ncl usi o n criteri o n # 2: Re vise d t o s pecif y 
t hat patie nts m ust ha ve pr o gresse d o n or are 
i nt olera nt of esta blis he d t hera pies k n o w n t o 
pr o vi de cli nical be nefit i n m ulti ple 
m y el o ma.
2 5. I ncl usi o n criteri o n # 5: L o were d t he platelet 
c o u nt t o 2 5, 0 0 0/ m m 3, clarifie d t hat 
he m o gl o bi n ma y  be greater t ha n or e q ual t o 
8 g/ d L, tra nsf usi o n s u p p ort is all o we d f or 
b ot h sit uati o ns if c o m plete d pri or t o pla n ne d 
C 1 D 1. 
2 6. I ncl usi o n criteri o n # 6:
Mo difie d t he 
creati ni ne cleara nce t o ≥3 0 m L / mi n a n d 
ser u m creati ni ne t o ≤2. 5 m g/ d L.
2 7. E xcl usi o n criteri o n # 6:  M o difie d t o i ncl u de 
a d diti o nal ≥
Gra de 3 i m m u ne -me diate d 
a d verse e ve nt s a n d a d de d e xce pti o ns f or 
i m m u ne-relate d a d verse e ve nts 
a p pr o priatel y ma na ge d b y c hec k p oi nt 
i n hi bit ors.
2 8. E xcl usi o n criteri o n # 1 4: C larifie d t o reflect 
t he la n g ua ge re gar di n g patie nts wit h rela pse 
f oll o wi n g B C M A tar gete d t hera py 
eli gi bilit y. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
2 9. E xcl usi o n criteri o n # 1 5: E li mi nate d t he 
re q uire me nt f or pri or B C M A t hera pies i n 
Part 2 o nl y . 
3 0. Secti o n 5. 3. 1: D osa ge F or m(s) a n d 
Pac ka gi n g:  title was re vise d t o reflect t he 
P har mace utical f or m a n d refer t o t he 
I n vesti gati o nal Pr o d uct Ma n ual a n d 
I n vesti gat or’s Br oc h ure f or a d diti o nal 
details re gar di n g P F -0 6 8 6 3 1 3 5.
3 1. Secti o n 5. 3. 2: Re m o ve d t he p hr ase 
“I n vesti gati o nal Pr o d uct Ma n ual” a n d 
a b bre viate d t he na me as it was pre vi o usl y 
s pelle d i n t he pri or para gra p h.
3 2. Secti o n 5. 5. 2: Clarifie d sit uati o n i n w hic h 
patie nts re q uire disc o nti n uati o n of t he st u d y 
dr u g f or m ore t ha n 4 2 da ys, clarifie d t hat it 
w o ul d be fr o m Da y  1 of t he c urre nt c ycle.
3 3. Secti o n 5. 5. 3: A d de d > 4 2 da y s f or patie nts 
e x perie nci n g a D L T of pr ol o n ge d 
m y el os u p pressi o n.
3 4. A p pe n di x 2: ( See i ncl usi o n criteria f or 
m o dificati o ns) was a d de d i n t he I M W G 
res p o nse criteria f or ser u m M -pr otei n.
3 5. A d diti o nal a d mi nistrati ve c ha n ges a n d 
clarificati o ns were ma de t h ro u g h o ut t he 
pr ot oc ol.
A me n d me nt 4
3 1 Oct o ber 2 0 1 9
T he p ur p ose of t his a me n d me nt is pri maril y  t o 
e na ble e val uati o n of c o m bi nati o ns of 
P F - 0 6 8 6 3 1 3 5 wit h a nti-P D 1 a nti b o d y  
P F - 0 6 8 0 1 5 9 1 or wit h le nali d o mi de a n d all o w 
t he o pti o n of s u bc uta ne o us e ver y 2 wee k d osi n g 
of P F - 0 6 8 6 3 1 3 5. I n a d diti o n, clarificati o ns, 
a d mi nistrati ve a n d t yp o gra p hical m o dificati o ns 
were ma d e.
1.
Pr ot oc ol S u m mar y , bac k gr o u n d a n d 
rati o nale: A d de d la n g ua ge t o i n dicate t he 
c o m bi nati o n of P F-0 6 8 6 3 1 3 5 wit h a n 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
a nti-P D -1 a nti b o d y  or a n I Mi D will be 
i n vesti gate d.
2.
Pr ot oc ol S u m mar y , st u d y desi g n, St u d y 
O bjecti ves a n d E n d p oi nts, Sc he d ule of 
Acti vities B, Secti o ns 2, 3. 1. 1, 3. 1. 1. 2, 
3. 1. 1. 3, 3. 1. 1. 4, 5. 4. 1, 9. 6 a n d Fi g ure 6: 
re na me d Part 1 A Pri mi n g a n d Mai nte na nce 
D ose Escalati o n t o Part 1. 1 Pri mi n g a n d 
Mai nte na nce D os e Escalati o n.
3.
Pr ot oc ol S u m mar y , st u d y desi g n a n d 
Secti o n 3 a n d Fi g ure 6: A d de d la n g ua ge t o 
s pecif y w hat eac h Part of t he st u d y will 
eac h i n vesti gate a n d t he n u m ber of patie nt s
t hat eac h Part will e nr oll.
4.
Pr ot oc ol S u m mar y , st u d y desi g n a n d Fi g ure 
6: Clarifie d t he d ose escalati n g d oses of P F-
0 6 8 6 3 1 3 5 f or Parts 1 I V a n d S C .
5.
Pr ot oc ol S u m mar y , st u d y desi g n: A d de d a 
state me nt t hat clarifies t he 7 2- h o ur
h os pitalizati o n peri o d o n C 1 D 1 f or all 
m o n ot hera p y d ose escalati o n c o h orts a n d t o 
f urt her e val uate t he h os pitalizati o n peri o d i n 
t he e x pa nsi o n c o h orts.
6.
Pr ot oc ol S u m mar y , st u d y desi g n: A d de d 
la n g ua ge f or Part 1 m o n ot hera py t o s pecif y 
D L T peri o d a n d s pecif y  peri o d f or i ntra-
patie nt d ose escalati o n a n d restricti o ns t o 
e nr oll t he sa me patie nt i nt o differe nt Parts 
of t he st u d y.
7.
Pr ot oc ol S u m mar y , St u d y Desi g n, Sc he d ule 
of Acti vities B , secti o ns 3. 1. 1. 3: M o difie d 
t he pri mi n g sc he d ule t o start o n C 0 D 1 a n d 
mai nte na nce o n C 1 D 1.
I n a d diti o n, a n 
alter nati ve ste p -u p re gi me n a n d 
pr o p h y lactic ster oi d o pti o ns were a d de d t o 
t he sc hed ule.
8.
Pr ot oc ol S u m mar y , st u d y desi g n, sc he d ule 
of acti vities B , secti o ns 3. 1. 1. 3, 5. 4. 2: a d de d 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
s u bc uta ne o us r o ute f or pri mi n g a n d 
mai nte na nce . I ncl u de d le nali d o mi de a n d 
P F -0 6 8 0 1 5 9 1 i n t his Part . Ad de d t w o wee k 
sc he d ule o pti o n f or m o n ot hera py, 
le nali d o mi de a n d P F- 0 6 8 0 1 5 9 1. Re m o ve d 
da y s 9 a n d 1 0 fr o m c ycle 1, c ha n ge d 
sc he d ule t o a 4 wee k c ycle.
9.
Pr ot oc ol S u m mar y , st u d y o bjecti ves a n d 
e n d p oi nts a n d Secti o n 2: A d de d la n g ua ge 
t hat defi nes t he o bjecti ves a n d e n d p oi nts f or 
eac h c o m bi nati o n d ose fi n di n g a n d 
e x pa nsi o n Part s of t he st u d y .
1 0. Pr ot oc ol S u m mar y , Sc he d ule of acti vities 
A: Re na me d s o t hat all wee kl y i ntra ve n o us 
a n d s u bc uta ne o us m o n ot hera p y d ose 
escalati o n sc he d ules f oll o w eit her S O A A or 
B, rearra n ge d t he pr oce d ures b y sect i o n, 
clarifie d t he visit wi n d o w i n t he 
p har mac o ki netic, s ol u ble fact or a n d 
c yt o ki ne acti vities.
1 1. Pr ot oc ol S u m mar y , Sc he d ule of acti vities C: 
Was create d t o reflect ne w c o m bi nati o n 
d ose fi n di n g, e x pa nsi o n m o n ot hera p y a n d 
c o m bi nati o n c o h orts, clarifie d t o c he c k f or 
M R D w he n a patie nt ac hie ves c o m plete 
res p o nse.
1 2. Pr ot oc ol S u m mar y , Sc he d ule of acti vities 
A, B, C, Secti o ns 5. 9 . 3, 5.9 . 4, A p pe n di x 5, 
Ta bles 1 2, 1 4: A d de d ne w A S T C T 
c o nse ns us criteria f or C R S a n d I C A N S 
ma na ge me nt of c y t o ki ne release s yn dr o me 
( C R S) a n d i m m u ne effect or cell ass ociate d 
ne ur ot o xicit y  sy n dr o me (I C A N S).
1 3. St u d y  desi g n, sc he d ule of acti vities A, B 
a n d C: Clarifie d t hr o u g h o ut t he 
p har mac o d y n a mic, p har mac o ki netic, 
s ol u ble fact or a n d c yt o ki ne assess me nts 
ta bles w he n b o ne marr o w s h o ul d be 
c ollecte d f or t he i ntra ve n o us r o ute a n d 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
a d de d clarificati o n o n w he n t hese 
pr oce d ures s h o ul d be ta ke n relati ve t o 
C 1 D 1.
1 4. Secti o ns 1 I ntr o d ucti o n: U p date d t o a d d 
s u p p orti n g bac k gr o u n d pre-cli nical 
i nf or mati o n a n d cli nical data re gar di n g 
c o m bi nati o n of C D 3 bis pecifics a n d 
a nti-P D 1/ L 1 or le nali d o mi de.
1 5. Secti o ns 1. 2. 8. 1, 1. 2. 8. 4, 3. 1. 1. 4, 3. 1. 2 a n d
3. 1. 4, 5. 4. 3: U p date d t o i n dicate t hat a fi xe d 
d ose a p pr oac h will be use d f or 
P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n d ose fi n di n g 
i n all e x pa nsi o n c o h orts. 
1 6. Secti o n 1. 2. 8. 3: A d de d t o s pecify t he 
starti n g d oses f or all c o m bi nati o n Parts.
1 7. Secti o n 1. 2. 8. 5: A d de d t o all o w a Q 2 W 
d osi n g i nter val o pti o n f or patie nts treate d 
wit h wee kl y d osi n g at least 6 m o nt hs . 
1 8. Secti o n 3: St u d y  desi g n sc he me was create d 
t hat reflects all ne w c o m bi nati o n d ose 
fi n din g a n d e x pa nsi o n c o h orts.
1 9. Secti o n 3. 1. 1. 2: U p date d t o reflect act ual 
starti n g d ose of Part 1 s u bc uta ne o us 
m o n ot hera p y.
2 0. Secti o n 3. 1. 1. 4 descri bes c o m bi nati o n d ose 
fi n di n g c o h orts.
2 1. Secti o n 3. 1. 2: Was u p date d t o descri be t he 
c o m bi nati o n e x pa nsi o n c o h orts.
2 2. Sec ti o n 3. 1. 4: Ta ble 1 was u p dated t o 
i ncl u de d oses use d i n t he i ntra ve n o us d ose 
escalati o n. Ta ble 2 was a d de d t o i ncl u de 
s u bc uta ne o us pla n ne d d oses a n d la n g ua ge 
was a d de d t o clarif y  wee kl y a n d e ver y t w o 
wee k d osi n g i nter vals. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
2 3. Secti o n 3. 2: T he D L T defi niti o n was 
u p date d t o s pecif y  D L T peri o ds f or 3 a n d 4 
wee k c ycles. D L T defi niti o ns were re vise d 
t o pr o vi de clarity f or Gra de 4 ne utr o pe nia, 
fe brile ne utr o pe nia a n d is olate d Gra de 3 
la b orat or y a b n or malities. 
2 4. Secti o n 3. 2. 1: L ate t o xicit y e val uati o n 
sc he d ules were clarifie d f or c o m bi nati o n 
a n d m o n ot hera p y d ose escalati o n c o h orts. 
2 5. Secti o n 3. 4: Re vise d t o pr o vi de clarit y 
re gar di n g deter mi nati o n of t he 
rec o m me n de d p hase 2 d ose of P F- 0 6 8 6 3 1 3 5 
i n c o m bi nati o n c o h orts.
2 6. Secti o ns 4. 1 was a n d 4. 2 were re vise d as 
f oll o ws:

I ncl usi o n Criteria # 1a: Re vise d t o ha ve a 
ser u m M-pr otei n of 0. 5 g/ d L f or b ot h, 
Part 1 a n d 2.

I ncl usi o n Criteria # 5: Re vise d t o clarif y  
t he re q uire me nts f or a de q uate 
he mat ol o gical f u ncti o n f or A N C a n d 
platelet c o u nt f or Part 1 C a n d 2 C of t he 
st u d y. 

I ncl usi o n Criteria # 6 : Re vise d t o 
s pecif y t he creati ne cleara nce f or Part 
1 C a n d 2 C of t he st u d y .

I ncl usi o n Criteria # 8: Re vise d t o 
pr o vi de clarit y f or he patitis B a n d C 
testi n g.

I ncl usi o n Criteria # 1 2: La n g ua ge was 
u p date d t o reflect ne w te m plate pr ot oc ol 
i nf or mati o n re gar di n g i nf or me d c o nse nt 
re q uire me nts.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges

I ncl usi o n Criteria 1 4: A d de d T S H, T 3 
a n d T 4 f or patie nts e nr olle d i n Part 1 B 
a n d 2 B.

E xcl usi o n criteria # 1 1: Pr o vi de d clarit y 
f or a nti b o dy base d t hera pies.

E xcl usi o n Criteria # 1 4: Clarifie d 
re q uire me nts f or patie nts t hat ha ve 
recei ve d pri or B C M A t hera py.

E xcl usi o n Criteria # 1 6: A d de d ne w 
te m plate la n g ua ge f or re q uire me nts o n 
E C G res ults.

E xcl usi o n Criteria # 2 0: Re vise d t o 
i ncl u de re q uire me nts f or P F- 0 6 8 0 1 5 9 1. 

E xcl usi o n Criteria # 2 3: A d de d disease 
restricti o ns f or patie nts e nr olle d i nt o 
Part s 1 B a n d 2 B.

E xcl usi o n Criteria # 2 4: A d de d 
restricti o n re gar di n g t he use of 
c ortic oster oi ds a n d 
i m m u n os u p pressa nts.

E xcl usi o n Criteria # 2 5: A d de d t o 
e xcl u de patie nts wit h Gra de ≥3 
a na p h yl actic reacti o ns t o a nti b o dies .

E xcl usi o n Criteria # 2 6: A d de d a 
restricti o n f or Parts 1C a n d 2 C f or 
patie nts w h o ha d pre vi o us le nali d o mi de 
d ose re d ucti o ns.
2 7. Secti o n 4. 3: A d de d t hat 2 hi g hl y effecti ve 
met h o ds of c o ntrace pti o n are re q uire d f or 
Parts 1 C a n d 2 C.
2 8. Secti o n 5. 3. 3 : Re vise d la n g ua ge t o 
refere nce t he I P ma n ual a n d I B f or 
P F -0 6 8 6 3 1 3 5.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
2 9. Secti o n 5. 3. 2: Clarifie d t he pre parati o n a n d 
dis pe nsi n g f or b ot h, P F -0 6 8 6 3 1 3 5 a n d P F -
0 6 8 0 1 5 9 1. 
3 0. Secti o n 5. 3: A d de d le nali d o mi de as a n
i n vesti gati o nal pr o d uct. 
3 1. Secti o n 5. 4. 1: A d de d clarit y  t o w he n a n d 
h o w t he o pti o n of 2 wee k i nter val d osi n g 
ca n be d o ne f or P F -0 6 8 6 3 1 3 5 I V 
a d mi nistrati o n.
3 2. Secti o n 5. 4. 2: A d de d clarit y  t o w he n a n d 
h o w o pti o n of 2 wee k i nter val d osi n g ca n be 
d o ne f or P F -0 6 8 6 3 1 3 5 S C a d mi nistrati o n.
3 3. Secti o n 5. 4. 3: A d de d i nstr ucti o ns o n t he 
a dmi nistrati o n of P F -0 6 8 0 1 5 9 1.
3 4. Secti o n 5. 5: A d de d d ose m o dificati o ns t hat 
ca n occ ur f or P F- 0 6 8 0 1 5 9 1 a n d 
le nali d o mi de. 
3 5. Secti o n 5. 7 a n d 5. 7. 1: Re vise d titles t o 
i ncl u de n o n-i n vesti gati o nal pr o d ucts.
3 6. Secti o n 5. 9 . 1 0: Re m o ve d restricti o n o n t he 
use of he mat o p oietic gr o wt h fact ors o nl y at 
c ycle 2 a n d be yo n d.
3 7. Secti o n 5. 9 . 1 5: Re m o ve d restricti o n o n 
tra nsf usi o n s u p p ort d uri n g c ycle 1 a n d 
wit hi n 1 4 da y s pri or t o c ycle 1.
3 8. Secti o n 6. 4: A d de d re q uire me nt f or f oll o w-
u p of late i m m u ne relate d a d verse e ve nts i n 
Pa rts 1 B a n d 2 B.
3 9. Secti o n 7. 1. 3: Delete d d u plicate d 
i nf or mati o n. Clarifie d he patitis tests, a d de d 
T S H, T 4 re q uire me nts i n ta ble 8. 
4 0. Secti o n 7. 1. 5: All o we d disc ussi o n wit h 
s p o ns or f or c o nti n uati o n of st u d y treat me nt 
f or patie nts t hat e x perie nce tra nsie nt 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
pr ol o n ge d Q Tc F if t he i n vesti gat or belie ves 
it is i n t he best i nterest of t he patie nt.
4 1. Secti o n 7. 1. 7 a n d a p pe n di x 9: Pr o vi de d 
i nf or mati o n o n t he use of a b d o mi nal 
q ua dra nts f or t he s u bc uta ne o us 
a d mi nistrati o n of P F -0 6 8 6 3 1 3 5 a n d 
P F - 0 6 8 0 1 5 9 1.
4 2. Secti o n 7. 2. 2: Clarif ie d assa ys t o be use d 
f or M R D testi n g.
4 3. Secti o n 7. 3: A d de d a bl o o d 
p har mac o ki netics sa m ple c ollecti o n f or P F-
0 6 8 0 1 5 9 1.
4 4. Secti o n 7. 4: A d de d a nti -dr u g a nti b o d y  
a nal ys is f or P F-0 6 8 0 1 5 9 1. 
4 5. Secti o n 7. 5: A d de d clarificati o n f or b o ne 
marr o w sa m ples at 6 a n d 9 m o nt h
ti me p oi nts.
4 6. Secti o n 7. 5. 2: A d de d t hat P D- 1 rece pt or 
occ u pa nc y  will be e val uate d i n Parts 1 B a n d 
2 B.
4 7. Secti o n 7. 5. 4: Re vise d la n g ua ge t o pr o vi de 
clarit y o n c ollecti o n of sa m ples f or C R S 
assess me nt.
4 8. Secti o n 8. 1. 4: A d de d la n g ua ge t o s pecif y  
a d verse e ve nt c oll ecti o n peri o d f or 
P F -0 6 8 0 1 5 9 1 i n Parts 1 B a n d 2 B. 
4 9. Secti o n 9. 1: A d de d defi niti o n f or 
p har mac o ki netic a n d i m m u n o ge nicit y tests 
i n Parts 1 B a n d 2 B.
5 0. Secti o n 9. 3: A d de d clarificati o n t o s u p p ort 
t he calc ulati o n of sa m ple sizes f or 
c o m bi nati o n d ose escalati o n a n d e x pa nsi o n 
c o h orts.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
5 1. Secti o n 9. 5. 1 a n d 9. 5. 2: A d de d 
p har mac o ki netic a nal ys is f or Parts 1 B an d 
2 B. 
5 2. A p pe n di x 1 0: A d de d ma na ge me nt f or 
i m m u ne-relate d a d verse e ve nts i n Parts 1 B 
a n d 2 B.
A me n d me nt 5
1 3 J ul y 2 0 2 0
T he pri mar y  p ur p ose of t his a me n d me nt is t o 
a d d p o mali d o mi de as a c o m bi nati o n t hera p y  
wit h P F - 0 6 8 6 3 1 3 5.  I n a d diti o n, clarificati o ns, 
a d mi nistrati ve, a n d t yp o gra p hical m o dificati o ns 
were ma de.
1.
C orrecte d ite m 3 0 i n list of S u m mar y  of 
C ha n ges f or A me n d me nt 4. T he c orrect 
secti o n n u m ber s h o ul d be 5. 3 a n d 
le nali d o mi de s h o ul d ha ve bee n liste d as 
i n vesti gati o nal pr o d uct.
2.
Gl o bal: Re place d P F -0 6 8 0 1 5 9 1 wit h 
sasa nli ma b. W here nee de d f or clarit y  a d de d 
t he f oll o wi n g “sasa nli ma b (f or merly 
P F -0 6 8 0 1 5 9 1)”.
3.
Pr ot oc ol S u m mar y Sc he d ules of Acti vities 
A, B, a n d C f o ot n ote # 3 7, Secti o ns 3. 1, 6. 3, 
a n d 6. 6: I ncrease d treat me nt d urati o n/f oll o w 
u p wit h P F -0 6 8 6 3 1 3 5 fr o m 1 2 u p t o 
2 4 m o nt hs after t he last patie nt first d ose as 
ot her B C M A -tar geti n g a ge nts ha ve see n 
re p orte d res p o nse d urati o n be yo n d 1 ye ar. 
4.
Pr ot oc ol S u m mar y a n d Gl o ball y ( where 
a p plica ble, i ncl u di n g st u d y O bjecti ves
Secti o n 2 ): A d de d p o mali d o mi de t o list of 
c o m bi nati o n a ge nts ( Part 1 D a n d Part 2 D).
5.
Pr ot oc ol S u m mar y  a n d Gl o ball y ( w here 
i n dicate d f or clarity): S pecifie d Par ts 1 B 
a n d 2 B will be c o n d ucte d e x -U S o nl y .
6.
Pr ot oc ol S u m mar y  a n d Gl o bal Secti o ns (as 
a p plica ble, i ncl u di n g Sc he ma): A d de d 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
Parts 1 D a n d 2 D ( p o mali d o mi de 
c o m bi nati o n c o h orts) .
7.
Pr ot oc ol S u m mar y  a n d Gl o ball y ( where 
a p plica ble), i ncl u de d “ or ma xi m u m 
a d mi nistere d d ose ( M A D) ” or “/ M A D”
after ma xi m u m t olerate d d ose ( M T D).
8.
Pr ot oc ol S u m mar y  a n d Gl o ball y: Re vise d 
d oses f or Part 1 s u bc uta ne o us ( S C)
a d mi nistrati o n (c ha n ge d 2 0 0 t o 2 1 5 µ g/ k g, 
c ha n ge d 3 0 0 t o 3 6 0 µ g/ k g, a n d a d de d d oses 
of 6 0 0 a n d 1 0 0 0 µ g/ k g ).
9.
Pr ot oc ol S u m mar y a n d Secti o n 3. 1 : A d de d: 
U p o n reac hi n g M T D/ M A D, u p t o 
a p pr o xi matel y 6 - 1 2 patie nts t otal at selecte d 
le vel(s) bel o w t he M T D/ M A D wee kly a n d 
Q 2 W d osi n g u p t o t he sa me d ose i nte nsit y  
as t he M T D/ M A D wee kl y re gi me n ma y be 
e val uate d f urt her t o s u p p ort t he R P 2 D 
d ecisi o n.
1 0. Pr ot oc ol S u m mar y : S pecifie d t hat t he safet y 
c o h ort f or Part 1 B will use a 
d ose -escalati o n/ de -escalati o n a p pr oac h f or 
P F -0 6 8 6 3 1 3 5 starti n g at least 1 d ose le vel 
bel o w t he m o n ot hera p y M T D/ M A D or t he 
R P 2 D, w hic he ver is l o wer a n d will be 
c o m bi ne d with a fi xe d S C d ose of 3 0 0 m g 
sasa nli ma b. 
1 1. Pr ot oc ol S u m mar y , Secti o n 3. 1 , a n d 9. 3: 
U p date d patie nt n u m bers. A p pr o xi matel y  
1 0 0 patie nts are e x pecte d t o be e nr olle d i nt o 
Parts 1/ 1. 1/ 1 B, 1 C, a n d 1 D. Parts 2 A, 2 B, 
2 C, a n d 2 D will e nr oll a p pr o xi matel y  
2 0 patie nts eac h. U p date d sa m ple size 
calc ulati o n secti o n. 
1 2. Pr ot oc ol S u m mar y  a n d Secti o n 2 : A d de d 
“a n d b o ne marr o w b y fl o w c yt o metr y 
a nal ys is” t o t he t hir d Tertiar y/ E x pl orat or y 
E n d p oi nt b ullet.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
1 3. Sc he d ules of Acti vities: A d de d refere nce t o 
A p pe n di x 1 1 f or alter nati ve meas ure 
g ui deli nes d ue t o C O VI D - 1 9.
1 4. Clarifie d d osi n g i n Sc he d ule of Acti vities
C f o ot n ote # 7 f or Part 1 S C Q 2 W.
1 5. Clarifie d h os pitalizati o n as o pti o nal i n 
Sc he d ule s of Acti vities B f o ot n ote # 7 f or 
Parts 2 A, 2 B, 2 C , a n d 2 D at C 1 D 1.
1 6. Clarifie d ti mi n g of pre g na nc y testi n g f or 
patie nts i n Parts 1 C, 1 D, 2 C, a n d 2 D i n 
Sc he d ule of Acti vities B, a n d C 
f o ot n ote # 2 0 a n d Secti o n 7. 1. 1 per 
le nali d o mi de a n d p o mali d o mi de 
re q uire me nts f or pre g na nc y testi n g. 
1 7. Sc he d ules of Acti vities A, B, a n d C 
f o ot n ote # 2 4, Secti o n 7. 2. 2, a n d A p pe n di x 
3: C larifie d patie nt stat us f or assess me nt of 
M R D ( mi ni mal resi d ual disease)
a n d a d de d 
clarif yi n g la n g ua ge f or ce ntral a n d l ocal 
assess me nt f or M R D.
1 8. Sc he d ule s of A cti vities A, B, a n d C
f o ot n ote # 2 5 , re vise d te xt re gar di n g ti mi n g 
of assess me nts f or fl u or o de o x ygl uc ose 
( F D G) p ositr o n e missi o n t o m o gra p hy 
( P E T)/c o m p uterize d t o m o gra p hy ( C T).
Delete d “as cli nicall y i n dicate d” i n t he 
Sc he d ule of Acti vities Visit I de ntifier 
c ol u m n.
Ali g ne d Secti o n 7. 2. 3.
1 9. A d de d la n g ua ge t o Sc he d ules of Acti vities 
A, B, a n d C f o ot n ote # 2 8 a n d Secti o n 7. 6. 2 
re gar di n g ge netic a nalys is; a d de d b o ne 
marr o w as pirates will be e val uate d at t he 
l ocal la b, a n d i nstr ucti o ns f or w he n 
assess me nts ca n n ot be d o ne . Clarifie d 
ti mi n g. 
2 0. A d de d clarif yi n g la n g ua ge t o f o ot n ote # 3 5 
i n Sc he d ule of Acti vities B t o i ncl u de 
Part s 1 a n d 2 B as part of t he o ne -m o nt h 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
f oll o w-u p a n d late f oll o w - u p f or late 
i m m u ne-relate d a d verse e ve nts. A d de d 
“ 2 B” t o f o ot n ote # 3 5 i n Sc he d ule of 
Acti vities C. 
2 1. Sc he d ule of Acti vities C: A d de d Parts 1 D 
a n d 2 D t o t he title an d descri pti o n , a d de d 
r o w f or p o mali d o mi de a d mi nistrati o n 
( Parts 1 D a n d 2 D) a n d a d de d a f o ot n ote 
wit h a d diti o nal details (i ncl u di n g d ose). 
2 2. Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities C: A d de d 
Parts 1 D a n d 2 D t o title a n d descri pti o n, 
a d de d r o ws f or sa m ple c ollecti o n f or 
le nali d o mi de a n d p o mali d o mi de P K
(ali g ne d Secti o n 7. 3). Ali g ne d s B C M A 
sa m ple c ollecti o n f or Part 2 wit h P K 
c ollecti o n f or Part 2.
2 3. T o e ns ure c o nsiste nc y  wit h ti mi n g of 
sa m ples i n Part 2, ad de d C y cles 1 a n d 2
Da y 2 2 0 hr ti me p oi nts f or t he c ollectio n of
sa m ples f or P F-0 6 8 6 3 1 3 5 a n d s ol u ble 
B C M A i n t he Sc he d ule of 
P har mac o ki netics, S ol u ble fact or , a n d 
C y t o ki ne Assess me nts A cti vities B. 
2 4. C orrecti o n t o t he li n ks of t he Sc he d ule of 
P har mac o ki netic, S ol u ble Fact or a n d 
C y t o ki ne Assess me nts s o t he y c orrectly li n k 
t o t heir res pecti ve Sc he d ule of Acti vities B 
or C.
2 5. Secti o ns 1. 2. 3. 1. 1. 2. 3. 1. 1, 1. 2. 3. 1. 2, a n d 
1. 2. 3. 2 : A d de d safety a n d efficac y data as of 
1 5 A pril 2 0 2 0 f or patie nts i n Part 1 treate d 
wit h P F - 0 6 8 6 3 1 3 5.
2 6. Secti o n 1. 2. 7: A d de d e x -U S s o urces f or 
le nali d o mi de pr o d uct i nf or mati o n (a n d 
a d de d t o refere nce list). A d de d rati o nal e f or 
w h y  de xa met has o ne will n ot be 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
a d mi nistere d wit h le nali d o mi de i n Parts 1 C 
a n d 2 C.
2 7. Secti o n 1. 2. 8: A d de d descri pti o n of 
p o ma li d o mi de a n d refere nces f or c o m plete 
i nf or mati o n.
2 8. Secti o n 1. 2. 9. 1: A d de d li n k t o 
Secti o n 1. 2. 9. 4 f or a d diti o nal details of t he 
fi xe d-d osi n g a p pr oac h. 
2 9. Secti o n 1. 2. 9. 3: A d de d Parts 1 C a n d 1 D 
pr o vi de d details o n p o mali d o mi de d ose. 
3 0. Secti o n 1. 2. 9. 4: A d de d preli mi nar y  
p o p ulati o n P K data f or P F -0 6 8 6 3 1 3 5 t o 
s u p p ort fi xe d d osi n g a p pr oac h. 
3 1. Secti o n 3. 1. 1: A d de d la n g ua ge f or t he 
e val uati o n of u p t o 6-1 2 patie nts t otal at 
selecte d le vel(s) bel o w t he M T D/ M A D 
wee kl y a n d Q 2 W d osi n g u p t o t he sa me 
d ose i nte nsit y  as t he M T D/ M A D wee kly 
re gi men ma y  be e val uate d f urt her t o s u p p ort 
t he R P 2 D decisi o n.
3 2. Secti o n 3. 1. 1. 3: C orrecte d err or (see 
stri ket hr o u g h te xt): T he 4 8 hr o bser vati o n 
peri o d f or t he first patie nt i n eac h d ose le vel 
i n Part 1. 1 will be gi n o n C 1 0 D 1 d uri n g t he 
sec o n d h os pitalizati o n peri o d.
3 3. Secti o n 3. 1. 1. 4: Re vise d Part 1 c o m bi nati o n 
d ose fi n di n g te xt re gar di n g M A D a n d R P 2 D 
starti n g d ose a n d de-escalati o n, clarifie d 
t hat t he fi xe d d ose of 3 0 0 m g w o ul d be 
a d mi nistere d S C , a n d a d de d a para gra p h f or 
Part 1 D.
3 4. Secti o n 3. 1. 2: A d de d te xt re gar di n g 
s u bc uta ne o us fi xe d d ose of P F- 0 6 8 6 3 1 3 5 
f or patie nts i n Part 2 A, a d de d para gra p h f or 
Part 2 D , a n d re m o ve d para gra p h f or 
i ntra ve n o us a d mi nistrati o n si nce I V is n o 
l o n ger c o nsi dere d f or d ose e x pa nsi o n. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
Re m o ve d refere nce t o “I V o nl y” fr o m 
S C H E D U L E O F P H A R M A C O KI N E TI C, 
S O L U B L E F A C T O R A N D C Y T O KI N E 
A C TI VI TI E S C (i ncl u di n g f o ot n ote * ) t o 
ali g n. 
3 5. Secti o n 3. 1. 4 : Delete d last r o w of Ta ble 1 
( d ose le vel 8 a n d u p, d ose T B D), m o difie d 
Ta ble 2 d oses f or d ose le vels 3, 4, a n d 5 a n d 
a d de d a 6 t h d ose le vel, delete d 
n o na p plica ble para gra p h. Clarifie d t hat i n 
Part 1. 1, t he starti n g mai nte na nce d ose will 
be n o m ore t ha n 2- f ol d a b o ve t he pri mi n g 
d ose esta blis he d fr o m Part 1. 
3 6. Secti o n 3. 2. 1: Clarifie d start of late 
t o xicities. 
3 7. Secti o n 3. 3: A d de d Ma xi m u m A d mi nistere d
D ose t o secti o n title, a d de d defi niti o n of 
M A D.
3 8. Secti o n 4. 1: I ncl usi o n criteri o n # 5 , a d de d 
platelet c o u nt f or Parts 1 D a n d 2 D, 
c orrecti o n ma de t o i ncl usi o n criterio n # 8 t o 
e xcl u de patie nts wit h acti ve he patitis B or
C.
3 9. Secti o n 4. 2: E xcl usi o n criteri o n # 4, a d de d 
refere nce t o A p pe n di x 1 1 f or a d diti o nal 
clarificati o n as it relates t o S A R S -C o V 2 
i nfecti o n, # 2 0, a d de d re q uire me nt f or 
c o ntrace pti o n d urati o n f oll o wi n g t he last 
d ose of le nali d o mi de a n d p o mali d o mi de .
4 0. Secti o n 4. 2: A d de d criteria # 2 7, 2 8, a n d 2 9 
descri bi n g e xcl usi o ns f or patie nts e nr olli n g 
i n p o mali d o mi de c o m bi nati o n c o h orts 
Parts 1 D a n d 2 D ( patie nts pre vi o usl y  
recei ve d p o mali d o mi de, patie nts recei vi n g 
str o n g C Y P 1 A 2 i n hi bit ors, a n d patie nts wit h 
a n y le vel of he patic i m pair me nt t hat w o ul d 
re q uire d ose re d ucti o n of p o mali d o mi de, 
res pecti vely) .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
4 1. Secti o n 4. 3: U p date d c o ntrace pti o n f or 
fe males of c hil d beari n g p ote ntial t o i ncl u de 
a list of hi g hl y effecti ve met h o ds a n d 
i nc or p orate d p o mali d o mi de a n d 
le nali d o mi de w here ap pr o priate. A d de d 
t hat a n y ris k a n d e val uati o n a n d miti gati o n 
strate g y re q uire d by l oca l re g ulati o ns f or 
le nali d o mi de a n d p o mali d o mi de m ust be 
f oll o we d. 
4 2. Secti o n 4. 1: T he last I ncl usi o n Criteri o n ha d 
bee n mer ge d i nt o t he hea der f or t he 
E xcl usi o n Criteria secti o n. It n o w rea ds as 
I ncl usi o n criteria # 1 4.
4 3. Secti o n 5. 3. 1: Re vise d le nali d o mi de 
para gra p h, a d de d para gra p h f or 
p o mali d o mi de.  
4 4. Secti o n 5. 4. 2: Delete d para gra p h descri bi n g 
d urati o n of a d mi nistrati o n of sasa nli ma b.
4 5. Secti o n 5. 5. 2: A d de d A N C a n d platelet
val ues f or p o mali d o mi de, a d de d refere nce 
t o A p pe n di x 1 1 f or g ui deli nes f or d ose 
dela y s of P F-0 6 8 6 3 1 3 5 f or partici pa nts wit h 
acti ve or pres u me d S A R S -C o V 2 i nfecti o n. 
4 6. Secti o n 5. 5. 3: M o difie d Ta ble 4. 
L y m p h o pe nia will n ot be i ncl u de d i n 
he mat ol o gical t o xici t y as t his e x pecte d as 
part of P F - 0 6 8 6 3 1 3 5 mec ha nis m of acti o n .  
A d de d te xt a n d T a ble 8 f or d ose 
m o dificati o ns f or p o mali d o mi de.
4 7. Secti o n 5. 9 : A d de d dr u g-dr u g i nteracti o n 
( D DI) te xt f or le nali d o mi de a n d 
p o mali d o mi de. Secti o n 5. 9 a n d 
A p pe n di x 1 2: A d de d D DI te xt f or 
P F - 0 6 8 6 3 1 3 5.
4 8. Secti o n 5. 9. 1 0: A d de d ca uti o nar y  te xt f or 
t he use of a ge nts t hat ma y i ncrease t he ris k 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 4
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
of t hr o m b osis i n patie nts recei vi n g 
le nali d o mi de. 
4 9. Secti o n 6. 4: Re place d “st u d y dr u g” wit h 
sasa nli ma b.
5 0. Secti o n 7. 2: A d de d te xt descri bi n g t he 
d isease res p o nse assess me nt. 
5 1. Secti o n 7. 2. 1: A d de d te xt t o free li g ht c hai n 
a nal ys is descri bi n g ti mi n g f or patie nts 
treate d wit h darat u m u ma b. A d de d t his te xt 
t o f o ot n ote # 2 2 of Sc he d ules of 
Acti vities A, B, a n d C t o ali g n. Delete d 
“ o nl y” fr o m Beta -2 micr o gl o b uli n b ullet f or 
clarit y. 
5 2. Secti o n 7. 2. 2: A d de d t hat I n case of 
s us pecte d stri n ge nt C o m plete Res p o nse 
(s C R), t he prese nce/a bse nce of cl o nal cells 
o n i m m u n o hist oc he mistr y s h o ul d als o be 
e val uate d t o b o ne marr o w bi o ps y  para gra p h.
5 3. Secti o n 8. 1. 4. 2: A d de d te xt s pecif y i n g t he 
start of t he c ollecti o n peri o d f or n o nseri o us 
A Es a n d S A Es. A d de d i nstr ucti o nal te xt f or 
patie nts e x perie nci n g c y t o ki ne release 
s yn dr o me.
5 4. Secti o n 8. 4. 3. 1: Re place d i nsta nce of 
“ partici pa nt” wit h patie nt t o ali g n wit h 
pr ot oc ol ter mi n ol o g y . 
5 5. Secti o n 9. 2. 1: A d de d “If t he M T D is n ot 
reac he d, t he n t he M A D will be ma xi m u m 
d ose t hat is e val uate d i n t he st u d y ” f or 
clarit y. 
5 6. Secti o n 9. 3: U p date d sa m ple size 
deter mi nati o n secti o n f or a d diti o nal c o h orts.
5 7. Secti o n 9. 5. 1: A d de d Parts 1 D a n d 2 D t o 
a nal y sis of P F-0 6 8 6 3 1 3 5, re place d i nsta nce 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
of “ partici pa nts” wit h patie nts t o ali g n wit h 
ot her pr ot oc ol secti o ns. 
5 8. Secti o n 9. 5. 2: A d de d le nali d o mi de a n d 
p o mali d o mi de , 1 C a n d 2 C a n d 1 D a n d 2 D 
as a p pr o priate t o t he secti o n title. A d de d 
le nali d o mi de a n d p o mali d o mi de t o t he 
a nal ys is of c o nce ntrati o n-ti me data. 
5 9. Secti o n 9. 5. 6: Delete d first para gra p h 
descri bi n g a nal ys is of bl o o d a n d b o ne 
marr o w bi o mar ker sa m ples. A d de d 
para gra p h f or a nal ys is a n d re p orti n g of 
tertiar y/e x pl orat or y a nalyses.
6 0. Secti o n 9. 6. 2. 1: A d de d t hat t he se verity of 
I m m u ne Effect or Cell-Ass ociate d 
Ne ur ot o xicit y  Sy n dr o me ( I CA N S ) s h o ul d 
be gra de d acc or di n g t o t he A merica n 
S ociet y  f or Tra ns pla ntati o n a n d Cell ular 
T hera p y ( A S T C T ) c o nse ns us criteria.
6 1. Secti o n 1 3. 1: A d de d refere nce t o 
Secti o n 6. 6 f o r m ore i nf or mati o n o n h o w 
e n d of st u d y is deter mi ne d. 
6 2. A p pe n di x 2: Re m o ve d re d u n da nt te xt i n 
I M W G criteria c ol u m n i n Pr o gressi ve 
Disease ( P D) r o w a n d ad de d clarif y i n g 
la n g ua ge pri or t o b ullete d list. C orrecte d 
f o ot n ote n u m ber refere nce i n t hir d b ullet i n 
Cli nical Rela pse r o w . 
6 3. A p pe n di x 1 1: A d de d a p pe n di x t o pr o vi de 
g ui da nce f or alter nati ve meas ures d uri n g 
p u blic e mer ge ncies.
6 4. A p pe n di x 1 2: A d de d dr u g- dr u g i nteracti o n 
a p pe n di x.
A me n d me nt 6
( C o u ntr y 
s pecific 
1 7 Dece m ber 2 0 2 0
T he pri mar y  p ur p ose of t his a me n d me nt is t o 
a d dress re q uests recei ve d fr o m re g ulat or y  
a ge nc y Pa ul -E hrlic h -I nstit ut
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 6
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
A me n d me nt, 
Ger ma n y)
( P EI). T he c ha n ges f or A me n d me nt 6 are 
s pecific o nly t o Ger ma n y.
1. Re m o ve d Parts 1 B a n d 2 B (c o m bi nati o n wit h 
Sasa nli ma b) t hr o u g h o ut t he pr ot oc ol.
2. Secti o n 3. 2: Re m o ve d last b ullet i n dicati n g 
t hat Inf usi o n Relate d Reacti o ns (I R Rs) a n d 
I njecti o n Site Reacti o ns (I S Rs) will n ot be 
a dj u dicate d as D L Ts.
3 . Secti o n 3. 4: Secti o n was u p date d wit h 
Rec o m me n de d P hase 2 D ose f or m o n ot hera p y 
a n d fi xe d (flat) d ose a d diti o nal details .
4. Secti o n 5. 5. 3: P o mali d o mi de disc o nti n uati o n 
criteria ha ve bee n u p date d t o i ncl u de  
a na p h yl actic reacti o ns, a n gi oe de ma, 
pr o gressi ve m ultif ocal le u k oe nce p hal o pat h y 
( P M L), or ras h ( Gra de 4 or blisteri n g).
5 . Secti o n 5. 9. 6: Re m o ve d last para gra p h 
i n dicati n g t hat I nf usi o n Relate d Reacti o ns 
(IR Rs) will n ot be c o nsi dere d as D L Ts .
6. Secti o n 5. 9. 7: Re m o ve d last para gra p h 
i n dicati n g t hat I njecti o n Site Reacti o ns (IS Rs)
will n ot be c o nsi dere d as D LTs .
A me n d me nt 7
1 5 Ja n uar y 2 0 2 1
T he pri mar y  p ur p ose of t his a me n d me nt is t o 
i nc or p orate c ha n ges pre vi o usl y i ncl u de d i n 
c o u ntr y s pecific A me n d me nt 6 ( Ger ma n y). I n 
a d diti o n, b eca use de xa met has o ne is a ke y 
c o m p o ne nt of sta n dar d a nti-m y el o ma t hera pies 
a n d its effect o n t he safet y  a n d efficacy of T-
cell e n ga gi n g bis pecific a ge nts is n ot k n o w n, 
P F - 0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h 
de xa met has o ne will be i n vesti gate d i n Part s 1 E
a n d 2 E.
Clarificati o ns, a d mi nistrati ve, a n d 
t yp o gra p hical m o dificati o ns were ma de. 
1.
C ha n ges pre vi o usl y i ncl u de d i n c o u ntr y  
s pecific A me n d me nt 6 ( Ger ma ny) as descri be d 
a b o ve.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 7
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
2.
Pr ot oc ol S u m mar y  (St u d y  desi g n) a n d 
Secti o n 3. 1: A d de d la n g ua ge t o e na ble P F -
0 6 8 6 3 1 3 5 c o m bi nati o n wit h de xa met has o ne i n 
Part 1 E a n d e x pa nsi o n Part 2 E , t o e val uate its 
p ote ntial t o miti gate i m m u ne effect or cell -
ass ociate d t o xicities a n d m o d ulate efficac y  of 
P F -0 6 8 6 3 1 3 5. Part 1 E will e nr oll ~ 9 - 1 6 
patie nts . If t he c o m bi nati o n re gi me n wit h 
de xa met has o ne i n Part 1 E is well t olerate d, Part 
2 E will e nr oll ~ 2 0 patie nts.
3.
St u d y  O bjecti ves a n d E n d p oi nts 
( Pr ot oc ol S u m mar y a n d Secti o n 2. 1): U p date 
la n g ua ge t o i ncl u de e val uati o n P F- 0 6 8 6 3 1 3 5 
c o m bi nati o n wit h de xa met has o ne a n d t o clarif y  
t hat plas ma will be c ollecte d f or P K a nalys is. 
4.
Pr ot oc ol S u m mar y  (St u d y  Desi g n),
Secti o n 3. 1 . 1, Secti o n 3.1 . 1. 3 a n d Secti o n 
3. 1. 1. 4 : F or t he p ur p ose of clarity, a d de d 
la n g ua ge t o s pecif y t hat patie nts will be 
h os pitalize d o n C 1 D 1 a n d re m o ve d 7 2 hrs, as 
h os pitalizati o n re q uire me nts are descri be d i n 
detail i n S c he d ule o f A cti vities f or s pecific Parts 
of t he st u d y .
5.
Secti o n 3. 1. 1: U p date d t o clarif y  D L T 
o bser vati o n peri o d ta ki n g i nt o acc o u nt d osi n g 
sc he d ule f or c o h orts t hat i m ple me nt 4 wee ks 
c ycle wit h pri mi n g.
6.
Pr ot oc ol S u m mar y  (St u d y  Desi g n), 
Secti o n 3. 1 a n d Secti o n 3. 1 . 1. 4: U p date t o 
i n dicate t hat if t he c o m bi nati o n re gi me n wit h 
de xa met has o ne i n Part 1 E is well t olerate d as 
g ui de d b y m T PI, Part 2 E ma y be i nitiate d .
7.
Pr ot oc ol S u m mar y , Secti o n 3. 1 ( St u d y 
desi g n) Secti o n 3. 1. 1. 4 a n d Secti o n 9. 3: 
U p date d t otal patie nt n u m bers f or t he st u d y, t o 
acc o u nt f or a d diti o n of de xa met has o ne c o h ort s
Part 1 E a n d 2 E. A p pr o xi matel y  1 2 0 patie nts are 
e x pecte d t o be e nr olle d i nt o Parts 1/ 1. 1, 1 C, 1 D , 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 8
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
a n d 1 E a n d a p pr o xi matel y 8 0 i n c o m bi nati o n 
c o h orts of Part 2.
8. 
Sc he d ule of Acti vities A, B, C: A d de d 
“ De m o gra p h y”  as re q uire d assess me nt a n d 
pr o vi de d a d diti o nal i nf or mati o n re gar di n g M R D 
assess me nt re q uire me nts f or clarit y.
9.
Sc he d ule of Acti vities A, B, C: F or t he 
p ur p ose of clarit y , f o ot n ote 2 4 u p date d t o 
i ncl u de a d diti o nal i nf or mati o n re gar di n g M R D
assess me nt re q uire me nts f or clarit y.
1 0. 
Sc he d ule of Acti vities A, B, a n d C: 
F o ot n ote 2 5 u p date d t o i ncl u de t hat o nl y  M RI is 
all o we d t o be use d as i ma gi n g m o dalit y f or 
patie nts b y  sites i n Ger ma n y.
1 1.
Sc he d ule of Acti vities B: U p date d t o 
i ncl u de de xa met has o ne i n c o m bi nati o n wit h 
P F -0 6 8 6 3 1 3 5 i n Parts 1 E a n d 2 E .
1 2.
Sc he d ule of Acti vities B a n d f o ot n ote 7: 
U p date d t o i n dicate t hat all patie nts recei vi n g a 
pri mi n g d ose will be h os pitalize d f or at least 
2 4 hrs o n C 0 D 1 a n d f or at least 2 4 hrs o n C 1 D 1.
H os pitalizati o n o n C 1 D 2 a n d C 1 D 3 a n d C 1 D 4 
visits (i ncl u di n g assess me nts) ha ve bee n 
re m o ve d fr o m Part 1. 1 a n d a n y part usi n g 
pri mi n g d ose, f oll o we d b y mai nte na nce.
1 3.
Sc he d ule of Acti vities B (f o ot n ote 4 1): 
A d de d la n g ua ge t o e na ble de xa met has o ne 
a d mi nistrati o n f or Parts 1 E a n d 2 E as nee de d 
a n d pr o vi de f urt her i nf or mati o n re gar di n g 
d osi n g, disc o nti n uati o n , a n d d urati o n of 
treat me nt.
1 4.
Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities B (f o ot n ote 2): 
U p date d t o i n dicate t hat P K sa m ple s h o ul d be
c ollecte d if t he h os pitalizati o n peri o d is 
e xte n de d be y o n d 2 4 h o urs o n C 0 D 1 or C 1 D 1.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 9
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
1 5.
Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities B: U p date d t o 
i n dicate t hat C 1 D4 a n d C 2 D 4 visits (i ncl u di n g 
assess me nts) ha ve bee n re m o ve d .
1 6.
Sc he d ul e of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities B ( i ncl u di n g 
f o ot n ote 5): U p date d t o pr o vi de i nstr ucti o ns a n d 
clarificati o n a b o ut bl o o d sa m ple c ollecti o n f or 
le nali d o mi de a n d p o mali d o mi de c o nce ntrati o n 
a nal ys is. 
1 7. 
Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities B (i ncl u di n g 
f o ot n ote 6): U p date d t o pr o vi de i nstr ucti o ns f or 
bl o o d sa m ple c ollecti o n f or de xa met has o ne 
c o nce ntrati o n a nal ys is.
1 8.
Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities C (f o ot n ote 3): 
Clar ificati o n pr o vi de d a b o ut bl o o d sa m ple 
c ollecti o n f or le nali d o mi de a n d p o mali d o mi de 
c o nce ntrati o n a nal ys is.
1 9.
Secti o n 1. 2. 3. 1: U p date d base d o n 
c urre nt safet y data. Safet y  data f or b ot h I V a n d 
S C c o h orts c o ns oli date d u n der Secti o n 1. 2. 3. 1.
2 0.
Secti o n 1. 2. 3. 2: U p date d base d o n 
c urre nt efficac y data. Efficac y  data f or b ot h I V 
a n d S C c o h orts c o ns oli date d u n der Secti o n 
1. 2. 3. 2.
2 1.
Secti o n 1. 2. 6: U p date d t o i n dicate t hat 
le nali d o mi de ca n ca use e m br yo- fetal t o xicit y. 
Re m o ve d refere nce t o de xa met has o ne, as 
de xa met has o ne is e na ble d i n Parts 1 E a n d 2 E t o 
u n dersta n d its effects o n t he safet y a n d efficac y 
of P F - 0 6 8 6 3 1 3 5.
2 2.
Secti o n 1. 2. 7: U p date d t o i n dicate t hat 
p o mali d o mi de ca n ca use e m br y o- fetal t o xicit y. 
Re m o ve d refere nce t o de xa met has o ne, as 
de xa met has o ne is e na ble d i n Part E t o 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 0
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
u n dersta n d effects of t his bac k b o ne a nti -
m y el o ma a ge nt o n t he safet y a n d efficac y of 
P F - 0 6 8 6 3 1 3 5
2 3.
Secti o n 1. 2. 8: I ntr o d uce d secti o n t o 
descri be t he rati o nale f or c o m bi ni n g P F -
0 6 8 6 3 1 3 5 wit h de xa met has o ne.
2 4.
Secti o n 1. 2. 9. 3: U p date d secti o n t o 
i n dicate t hat Part 1 E will e val uate t he R P 2 D 
d ose le vel of P F 0 6 8 6 3 1 3 5 wit h
de xa met has o ne. 
2 5.
Secti o n 3. 1 ( St u d y  Sc he ma/ Fi g ure 4): 
U p date d t o i ncl u de c o m bi nati o n wit h 
de xa met has o ne, Part 1 E (≈9- 1 6 patie nts) a n d 
Part 2 E (≈2 0 patie nts).
2 6.
Secti o n 3. 1 ( St u d y  Sc he ma/ Fi g ure 4): 
U p date d t o descri be Part 1. 1 pri mi n g c o h orts, 
i ncl u di n g pri mi n g a n d mai nte na nce ( Q 1 W a n d 
Q 2 W ).
2 7.
Secti o n 3. 1. 1: U p date d hea di n g wit h 
pri mi n g a n d mai nte na nce c o h orts f or clarit y.
2 8.
Secti o n 3. 1. 1. 4: U p date d t o i ncl u de 
R P 2 D f or P F -0 6 8 6 3 1 3 5 as a si n gle a ge nt a n d a 
ta ble detaili n g p ote ntial fi xe d d oses t o be 
a d mi nistere d i n m o n ot hera p y a n d c o m bi nati o n 
ar ms wit h p o mali d o mi de, le nali d o mi de a n d 
de xa met has o ne. Pr o vi de detaile d i nf or mati o n 
f or P F-0 6 8 6 3 1 3 5 a d mi nistrati o n i n c o m bi nati o n 
wit h de xa met has o ne.
2 9. 
Secti o n 3. 1. 2 a n d 3. 1. 4: A d de d la n g ua ge 
t o i ntr o d uce Part 1 E a n d 2 E as nee de d a n d 
pr o vi de f urt her i nf or mati o n re gar di n g d osi n g 
a n d de-escalati o n. 
3 0. 
Secti o n 3. 1. 1, 3. 1. 1. 3, 3. 2 a n d 3. 2. 1: 
Base d o n e mer gi n g data t hat t here was n o 
si g nifica nt late t o xicit y, late t o xicit y e val uati o n 
of patie nts f or a mi ni m u m of 6 0 da y s was 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 1
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
rem o ve d as re q uire me nt f or t he p ur p ose of 
M T D/ M A D deter mi nati o n.
3 1. 
Secti o n 3. 1. 1. 3: U p date d hea di n g wit h 
pri mi n g a n d mai nte na nce c o h orts a n d re m o ve d 
d ose escalati o n f or clarit y. 
3 2.
Secti o n 3. 4 : U p date d t o i ncl u de R P 2 D 
f or P F-0 6 8 6 3 1 3 5 as a si n gle a ge nt a n d 
prel i mi nar y data s u g gesti n g t hat a d mi nistrati o n 
of pri mi n g d ose re d uces d urati o n of C R S.
3 3.
Secti o n 4. 1: Restricte d Easter n 
C o o perati ve O nc ol o g y  Gr o u p ( E C O G) 
Perf or ma nce Stat us ( P S) t o 0- 1 f or Part 2 A a n d 
t o 0-2 f or all ot her c o h orts (i ncl usi o n 4).
3 4.
Secti o n 4. 1: Clarifie d i ncl usi o n criteria 
f or platelet c o u nts f or b ot h Part 1 E a n d Part 2 E 
(i ncl usi o n 5).
3 5.
Secti o n 4. 2: Pr o vi de d clarit y  f or 
re q uire me nt f or sys te mic i m m u ne s u p pressi ve 
me dicati o n i n (e xcl usi o n 1 2).
3 6.
Secti o n 4. 2: Pr o vi de d clarit y  re gar di n g 
p ote ntial C O VI D vacci nati o n (e xcl usi o n 1 8).
3 7. 
Secti o n 4. 3: Pr o vi de d a d diti o nal clarit y  
re gar di n g pre g na nc y pre ve nti o n pr o gra m f or 
le nali d o mi de a n d p o mali d o mi de.
3 8.
Secti o n 5 (st u d y  treat me nts), Secti o n 
5. 2 a n d Secti o n 5. 3. 1: I ncl u de d de xa met has o ne 
as i n vesti gati o nal m e dici nal pr o d uct.
3 9.
Secti o n 5. 5: U p date d t o i ncl u de 
de xa met has o ne a n d clarif y  t hat if a d ose of P F-
0 6 8 6 3 1 3 5 is dela y e d or i nterr u pte d, t he n 
de xa met has o ne s h o ul d n ot be a d mi nistere d u ntil 
P F -0 6 8 6 3 1 3 5 a d mi nistrati o n is restarte d .
4 0.
Secti o n 5. 5. 2 ( D ose dela ys): U p date d t o 
i ncl u de de xa met has o ne. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 2
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
4 1.
Secti o n 5. 5. 3 ( D ose re d ucti o ns): 
U p date d t o i ncl u de g ui da nce f or d ose dela y s f or 
de xa met has o ne relate d t o xicities, i ncl u di n g 
Ta ble 1 0. U p date d t o i ncl u de g ui da nce f or d ose 
m o dificati o n f or P F -0 6 8 6 3 1 3 5 relate d t o xicities. 
S pecificall y, f or a n y patie nt w h o recei ves fi xe d 
d oses of P F -0 6 8 6 3 1 3 5, t he ne xt d ose le vel of 
P F -0 6 8 6 3 1 3 5 will be 2 5 % l o wer .
4 2.
Secti o n 5. 9: U p date d t o i ntr o d uce 
de xa met has o ne as m o derate i n d ucer of C Y P 
3 A 4.
4 3.
Secti o n 5. 9. 1 3: U p date d t o i n dicate t hat , 
e xce pt as s pecifie d i n t he pr ot oc ol,
c ortic oster oi ds f or palliati ve or s u p p orti ve 
p ur p oses are per mitte d o nl y  f oll o wi n g 
disc ussi o n a n d a gree me nt bet wee n t he 
i n vesti gat or a n d s p o ns or.
4 4.
Secti o n 7. 2. 2: U p date d t o f urt her clarif y  
M R D assess me nt pr ocess a n d re q uire me nts.
4 5.
Secti o n 7. 2. 3: U p date d t o i ncl u de t hat 
o nl y  M RI is all o we d t o be use d as i ma gi n g 
m o dalit y  b y sites i n Ger ma n y.
4 6. 
Secti o n 9 . 3: U p date d t o i ncl u de Part 1 E 
a n d 2 E i n t he sa m ple size deter mi nati o n.
4 7.
Secti o n 9. 4: U p date d t o e na ble 
i n de pe n de nt ce ntral re vie w f or efficac y 
e n d p oi nts as nee de d. Secti o n u p date d t o clarif y 
t hat c o nfir me d res p o nses are re q uire d, mi ni mal 
res p o nse ( M R) is n ot i ncl u de d i n t he O R R 
res p o nse defi niti o n a n d sta ble disease ( S D) is 
n ot i ncl u de d i n c li nical be nefit ( C B) defi niti o n.
4 8.
S ecti o n 9. 5. 1: U p date d t o i ncl u de bl o o d 
sa m ple c ollecti o n f or P F - 0 6 8 6 3 1 3 5 i n Part 1 E 
a n d 2 E.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 3
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
4 9.
Secti o n 9. 5. 2: U p date d t o i ncl u de bl o o d 
sa m ple c ollecti o n f or de xa met has o ne i n Part 1 E 
a n d 2 E.
5 0.
Secti o n 1 6: U p date d Refere nces as 
nee de d .
5 1.  
A p pe n di x 1: U p date d a b bre viati o ns as 
nee de d .
A me n d me nt 8
0 6 J u ne 2 0 2 1
T he pri mar y  p ur p ose of t his a me n d me nt is t o 
i nc or p orate c ha n ges relate d t o peri p heral 
ne ur o pat h y, i ncl u di n g miti gati o n meas ures.
1.
Pr ot oc ol S u m mar y  ( St u d y Desi g n) a n d 
St u d y  O ver vie w ( St u d y Desi g n): U p date d t o 
clarif y t hat e nr ollme nt i n st u d y  C 1 0 7 1 0 0 1 
has bee n c o m plete d, as cli nical de vel o p me nt 
pr o gra m f or P F- 0 6 8 6 3 1 3 5 has bee n 
e x pa n de d wit h de dicate d st u dies t hat will 
f urt her i n vesti gate b ot h m o n ot hera py a n d 
c o m bi nati o n t hera p y. 
2.
Beca use le nali d o mi de bel o n gs t o t he sa me 
dr u g class as p o mali d o mi de, t he ma xi m u m 
d ose of le nali do mi de was re d uce d t o 1 5 m g, 
as descri be d t hr o u g h o ut t he d oc u me nt. T he 
d ose a dj ust me nt ta bles (Ta ble 6 a n d 
Ta ble 7 ) i n Secti o n 5. 5. 3 w ere m o difie d
acc or di n gl y.
3.
I n or der t o f oc us o n t he data m ost i m p orta nt 
f or i n vesti gat ors, Secti o n 1. 2. 3. 1 a n d 
Secti o n 1. 2. 3. 2 were u p date d wit h safety 
a n d efficac y data, res pecti vel y.
4.
Clarifie d t hat n e urol o gical assess me nts 
occ ur at eac h p h ys ical e xa mi nati o n i n t he 
S o As a n d Secti o n 7. 1. 4 .
5.
Sc he d ule of P har mac o ki netic, S ol u ble 
Fact or a n d C yt o ki ne Acti vities B (f o ot n ote 
5): Pr o vi de d g ui da nce a b o ut bl o o d sa m ple 
c ollecti o n f or le nali d o mi de a n d 
p o mali d o mi de c o nce ntrati o n a nal y sis f or 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 4
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
patie nts tra nsiti o ne d t o m o n ot hera p y wit h 
P F - 0 6 8 6 3 1 3 5.
6.
Clarifi cati o n a d de d f or d ose dela y s i n 
Secti o n 5. 5. 2 a n d 5. 5. 3 .
7.
D ose m o dificati o ns of P F - 0 6 8 6 3 1 3 5 f or 
peri p heral ne u r o pat hy were a d de d t o 
Ta ble 5 i n Secti o n 5. 5. 3 .
8.
C o nsi derati o ns re gar di n g c o nc o mita nt 
me dicati o ns wer e i ncl u de d i n Secti o n 5. 9 .
9.
Secti o n 5. 9. 1 a n d 5. 9. 4 : U p date d t o descri be
pre me dicati o n f or C R S.
1 0. Rec o m me n de d e val uati o n f or peri p heral 
ne ur o pat h y was a d de d t o Secti o n 8. 4. 4 .
1 1. Criteria f or i nterr u pti o n of st u d y  treat me nt 
were a d de d i n Secti o n 9. 7 .
1 2. Bi o mar ke r c ollecti o ns f or M R D assess me nt 
b y  N G S were clarifie d i n t he t he S o A.
1 3. Pre g na nc y tests a n d c o ntrace pti o n c hec ks, 
al o n g wit h A E assess me nts were e xte n d e d 
t o 9 0 da ys after t he last d ose of 
i n vesti gati o nal pr o d uct.
1 4. T he Title Pa ge was u p date d t o i ncl u de t he 
ne w Pfizer l o g o, t he st u d y na me
( MA G N E TI S M M - 1), t he ge neric na me
(elra n ata ma b), a n d t he N C T n u m ber.
1 5. U p date d refere nces as nee de d i n Secti o n 1 6 .
1 6. F or c o nsiste nc y  bet wee n A p pe n di x 5 , 
Secti o n 5. 9. 4 a n d rest of t he pr ot oc ol, it has 
bee n c larifie d t hr o u g h o ut t he d oc u me nt t hat 
C R S will be assesse d acc or di n g t o t he 
gra di n g descri be d b y Lee et al. 2 0 1 4 a n d 
2 0 1 9 (see A p pe n di x 5 ) as i nitiall y descri be d 
i n pr ot oc ol a me n d me nt 7.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 5
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
1 7. Ge neral f or matti n g a n d c o p y e diti n g were
perf or me d t hr o u g h o ut t he d oc u me nt .
A me n d me nt 9
2 8 Marc h 2 0 2 3
T he pri mar y  p ur p ose of t his a me n d me nt is t o 
e xte n d t he d urati o n of t he st u d y b y  ~ 6 m o nt hs, 
re d uce sa m ple c ollecti o ns f or e x pl orat or y 
e n d p oi nts, a n d e xte n d c o ntrace pti o n peri o d p ost 
last d ose.
1. S o A A (f o ot n ote # 3 7), S o A B (f o ot n ote # 3 7) ,
S o A C (f o ot n ote # 3 6 ), Secti o n 3. 1 ( St u d y 
O ver vie w), Secti o n 6. 3 ( F oll o w -u p), Secti o n 
6. 5 ( E n d of St u d y ): E n d of st u d y  f or all patie nts 
will be deat h or u p t o a p pr o xi matel y  3 0 m o nt hs 
after last patie nt first d ose, f oll o we d b y a n y 
re q uire d f oll o w-u p visits ; S ur vi val f oll o w- u p 
has bee n u p date d acc or di n gl y. B y  re visi n g e n d 
of st u d y , acti ve patie nts will c o nti n ue recei vi n g 
si g nifica nt cli nical be nefit fr o m t hera py wit h 
elra nata ma b. 2 2 Fe br uar y  2 0 2 3 P A C L
2. S o A A (f o ot n ote # 2 0 ), S o A B (f o ot n ote # 20 ),
S o A C (f o ot n ote # 1 9 ), Secti o n 4. 2 ( E xcl usi o n 
Criteria ), Secti o n 4. 3 ( Lifest y le Re q uire me nts): 
Re vise d c o ntrace pti o n re q uire me nts base d o n 
rece ntly u p date d P K data as descri be d i n I B.
3 . S o A A (f o ot n ote # 2 1), S o A B (f o ot n ote # 2 1) ,
S o A C (f o ot n ote # 2 0 ), Secti o n 1. 2. 9. 5 ( D osi n g 
I nter val), Secti o n 3. 1. 1. 4 ( Part 1 C o m bi nati o n 
D ose Fi n di n g), Secti o n 5. 4 ( A d mi nistrati o n): I n 
or der t o re d uce partici pa nt b ur de n of fre q ue nt 
visits, d osi n g o nce per c ycle ( C X D 1) is all o we d 
u p o n c o ns ultati o n wit h t he s p o ns or .
4 . S o A A (i ncl u di n g f o ot n otes #2 9, 3 1- 3 3 ), S o A 
B (i ncl u di n g f o ot n otes # 2 9, 3 1 - 3 3), S o A C 
(i ncl u di n g f o ot n otes #2 8, 3 0- 3 2 ), Secti o n 1. 2. 1 0 
( Bi o mar kers), Secti o n 2 ( St u d y O bjecti ves a n d 
E n d p oi nts ), Secti o n 7. 5 (Bi o mar kers a n d 
P har mac o d y na mics Assess me nt; Ta ble 1 2) : I n 
or der t o li mit t he b ur de n of fre q ue nt sa m ple 
c ollecti o ns, bl o o d sa m ple a n d b o ne marr o w 
as pirate c ollecti o ns are re d uce d (e x pl orat or y 
e n d p oi nts ). 1 9 A u g ust 2 0 2 1 P A C L
5 . I n or der t o f oc us o n t he data m ost i m p orta nt 
f or i n vesti gat ors, Secti o n 1. 2. 3. 1 a n d Secti o n 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 6
D oc u me nt  
Versi o n D ate
S u m m ar y of C h a n ges
1. 2. 3. 2 were u p date d wit h safet y a n d efficac y 
data, res pecti vel y.
6. I n or der t o ali g n wit h Pfizer pr ocesse s a n d 
pr ot oc ol te m plate re q uire me nts, Secti o n s 1 1. 1, 
1 1. 3, 1 2. 1, 1 5. 1 a n d 1 5. 2 were u p date d.
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d i nstit uti o nal re vie w b oar ds (IR Bs)/et hics c o m mittees 
(E Cs) a n d a n y pr ot oc ol a d mi nistrati ve c ha n ge letter(s) .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 7
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 ...................................................................................................................4 4
LI S T O F FI G U R E S ................................................................................................................. 4 4
A P P E N DI C E S ......................................................................................................................... 4 5
S C H E D U L E O F A C TI VI TI E S A: P A R T 1 I V A N D S C W E E K L Y M O N O T H E R A P Y 
( N O P RIMI N G D O S E) ....................................................................................................... 5 4
S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E F A C T O R A N D C Y T O KI N E 
A C TI VI TI E S A: P A R T 1 I V A N D S C W E E K L Y M ON O T H E R A P Y ( N O 
P RI MI N G D O S E) ............................................................................................................... 6 2
S C H E D U L E O F A C TI VI TI E S B: P A R T 1. 1 A N D A N Y P A R T U SI N G P RI MI N G 
D O S E A N D M AI N T E N A N C E .......................................................................................... 6 5
S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E F A C T O R A N D C Y T O KI N E 
A C TI VI TI E S B: P A R T 1 . 1 A N D A N Y O T H E R P A RT U SI N G P RI MI N G D O S E
A N D M AI N T E N A N C E ...................................................................................................... 7 6
S C H E D U L E O F A C TI VI TI E S C: P A R T S 1 S C Q 2 W , 1 C, A N D 1 D ( D O S E 
E S C A L A TI O N C O M BI N A TI O N) A N D 2 A, 2 C A N D 2 D ( D O S E E X P A N SI O N 
C O H O R T S) WI T H O U T P RI MI N G D O S E ........................................................................ 8 0
S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E F A C T O R A N D C Y T O KI N E 
A C TI VI TI E S C: P A R T S 1 S C Q 2 W, 1 C A N D 1 D ( D O S E E S C A LA T I O N 
C O M BI N A T I O N) A N D 2 A, 2 C A N D 2 D ( D O S E E X P A N SI O N C O H O R T S) 
WI T H O U T P RI MI N G D O S E ............................................................................................. 9 0
1. I N T R O D U C TI O N ............................................................................................................... 9 4
1. 1. Mec ha nis m of Acti o n/I n dicati o n ............................................................................. 9 4
1. 2. Bac k gr o u n d a n d Rati o nale ...................................................................................... 9 4
1. 2. 1. M ulti ple M y el o ma ...................................................................................... 9 4
1. 2. 2. Bis pecific A nti b o dies .................................................................................. 9 5
1. 2. 3. P F -0 6 8 6 3 1 3 5............................................................................................... 9 6
1. 2. 3. 1. Safet y ......................................................................................... 9 6
1. 2. 3. 2. Efficac y ..................................................................................... 9 7
1. 2. 3. 3. M o n ocl o nal A nti b o d y  Interfere nce of La b orat or y  
E val uati o n of M y el o ma ..................................................................... 9 7
1. 2. 4. N o ncli nical Safet y I nf or mati o n .................................................................. 9 7
1. 2. 5. P F -0 6 8 6 3 1 3 5 Precli nical Efficac y ..............................................................9 8
1. 2. 5. 1. I n Vitr o Acti vit y  of P F-0 6 8 6 3 1 3 5............................................. 9 8
1. 2. 5. 2. Si n gle A ge nt A nti -t u m or Efficac y of P F-0 6 8 6 3 1 3 5 i n 
Ort h ot o pic M ulti ple M y el o ma M o dels T u m or M o dels ..................... 9 8
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 8
1. 2. 5. 3. A nti- t u m or Efficac y of P F-0 6 8 6 3 1 3 5 i n C o m bi nati o n wit h 
t he Im m u n o m o d ulat or y  Dr u g Le nali d o mi de i n Ort h ot o pic a n d 
S u bc uta ne o us M y el o ma M o dels ........................................................ 9 9
1. 2. 6. L e nali d o mi de ............................................................................................ 1 0 0
1. 2. 7. P o mali d o mi de ........................................................................................... 1 0 1
1. 2. 8. De xa met has o ne ......................................................................................... 1 0 1
1. 2. 9. Starti n g D ose Rati o nale ............................................................................ 1 0 2
1. 2. 9. 1. I ntra ve n o us (I V) Starti n g D ose Rati o nale ............................... 1 0 2
1. 2. 9. 2. S u bc uta ne o us ( S C) Starti n g D ose Rati o nale ........................... 1 0 3
1. 2. 9. 3. Starti n g D ose f or C o m bi nati o n Safet y  C o h orts ( Parts 1 C, 
1 D a n d 1 E) ....................................................................................... 1 0 3
1. 2. 9. 4. Fi xe d D osi n g A p pr oac h .......................................................... 1 0 4
1. 2. 9. 5. D osi n g I nter val ........................................................................ 1 0 4
1. 2. 9. 6. Pri mi n g a n d Mai nte na nce D ose Rati o nale .............................. 1 0 5
1. 2. 1 0. Bi o mar ker Rati o nale ............................................................................... 1 0 5
1. 2. 1 0. 1. Ba n ke d Bi os peci me ns ........................................................... 1 0 6
2. S T U D Y O BJ E C TI V E S A N D E N D P OI N T S ..................................................................... 1 0 7
2. 1. Part 1 I V a n d S C m o n ot hera p y D ose Escalati o n, Part 1. 1 Pri mi n g a n d 
Mai nte na nce D ose Escalati o n a n d Parts 1 C, 1 D a n d 1 E D ose 
Escalati o n/ Fi n di n g ...................................................................................................1 0 7
2. 2. Part 2 D ose E x pa nsi o n .......................................................................................... 1 0 9
3. S T U D Y D E SI G N ............................................................................................................... 1 1 0
3. 1. St u d y  O ver vie w..................................................................................................... 1 1 0
3. 1. 1. Part 1 M o n ot hera p y  D ose Escalati o n a n d Part 1. 1 Pri mi n g a n d 
Mai nte na nce C o h orts ..................................................................................... 1 1 2
3. 1. 1. 1. Part 1 I ntra ve n o us (I V) A d mi nistrati o n .................................. 1 1 3
3. 1. 1. 2. Part 1 S u bc uta ne o us ( S C) A d mi nistrati o n .............................. 1 1 3
3. 1. 1. 3. Part 1. 1 Pri mi n g a n d Mai nte na nce C o h orts ............................ 1 1 4
3. 1. 1. 4. Part 1 C o m bi nati o n D ose Fi n di n g ........................................... 1 1 5
3. 1. 2. Part 2 D ose E x pa nsi o n .............................................................................. 1 1 7
3. 1. 3. Starti n g D ose ............................................................................................ 1 1 8
3. 1. 4. Criteria f or D ose Escalati o n/ De -Escalati o n .............................................. 1 1 8
3. 1. 4. 1. Criteria f or I ntra patie nt D ose Escalati o n ................................. 1 2 0
3. 2. D ose L i miti n g T o xicit y ( D L T) Defi niti o n............................................................ 1 2 1
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 9
3. 2. 1. L ate T o xicities .......................................................................................... 1 2 3
3. 3. Ma xi m u m T olerate d a n d Ma xi m u m A d mi nistere d D ose ( M T D a n d M A D) 
Defi niti o ns ............................................................................................................... 1 2 3
3. 4. Rec o m me n de d P hase 2 D ose ( R P 2 D) Defi niti o n ................................................. 1 2 4
3. 5. St o p pi n g Criteria i n Part 2 D ose E x pa nsi o n .......................................................... 1 2 4
4. P A TI E N T E LI GI BI LI T Y C RI T E RI A ............................................................................... 1 2 5
4. 1. I ncl usi o n Criteria ................................................................................................... 1 2 5
4. 2. E xcl usi o n Criteria .................................................................................................. 1 2 7
4. 3. L ifest yle Re q uire me nts ......................................................................................... 1 3 0
4. 4. S p o ns or’s Q ualifie d Me dical Pers o n nel ................................................................ 1 3 1
5. S T U D Y T R E A T M E N T S ................................................................................................... 1 3 2
5. 1. All ocati o n t o Treat me nt ........................................................................................ 1 3 2
5. 2. Patie nt C o m plia nce ...............................................................................................1 3 2
5. 3. I nvesti gati o nal Pr o d uct S u p plies ........................................................................... 1 3 3
5. 3. 1. P har mace utical F or m(s) a n d Pac ka gi n g ................................................... 1 3 3
5. 3. 2. Pre parati o n a n d Dis pe nsi n g ...................................................................... 1 3 3
5. 4. A d mi nistrati o n .......................................................................................................1 3 3
5. 4. 1. I V A d mi nistrati o n P F - 0 6 8 6 3 1 3 5.............................................................. 1 3 3
5. 4. 2. S C A d mi nistrati o n P F -0 6 8 6 3 1 3 5 ............................................................. 1 3 4
5. 5. Rec o m me n de d D ose M o difica ti o ns ...................................................................... 1 3 5
5. 5. 1. D osi n g I nterr u pti o ns ................................................................................. 1 3 6
5. 5. 2. D ose Dela y s ..............................................................................................1 3 7
5. 5. 3. D ose Re d ucti o ns ....................................................................................... 1 3 7
5. 5. 4. I ntra - Patie nt D ose Escalati o n f or P F-0 6 8 6 3 1 3 5 ....................................... 1 4 3
5. 6. Per ma ne nt Disc o nti n uati o n ................................................................................... 1 4 4
5. 7. I n vesti gati o nal Pr o d uct St ora ge ............................................................................ 1 4 4
5. 8. I n vesti gati o nal a n d N o n -I n vesti gati o nal Pr o d uct Acc o u nta bility......................... 1 4 5
5. 8. 1. Destr ucti o n of I n vesti gati o nal a n d N o n -I n vesti gati onal Pr o d uct 
S u p plies .......................................................................................................... 1 4 5
5. 9. C o nc o mita nt Treat me nt(s) ..................................................................................... 1 4 5
5. 9. 1. Pre me dicati o n Re q uire d f or C yt o ki ne Release S y n dr o me Pr o p h yl a xis ... 1 4 6
5. 9. 2. Ot her A nti -t u m or/ A nti-ca ncer or E x peri me ntal Dr u gs .............................1 4 7
5. 9. 3. S u p p orti ve Care ........................................................................................ 1 4 7
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 0
5. 9. 4. C y t o ki ne Release S yn dr o me ..................................................................... 1 4 7
5. 9. 5. I m m u ne Effect or Cell -Ass ociate d Ne ur ot o xicit y  S yn dr o me I C A N S ....... 1 4 7
5. 9. 6. T u m or L y sis Sy n dr o m e ( T L S) .................................................................. 1 4 8
5. 9. 7. I nf usi o n Relate d Reacti o ns (I R R) .............................................................1 4 8
5. 9. 8. I njecti o n Site Reacti o ns (I S R) .................................................................. 1 4 9
5. 9. 9. H y perse nsiti vit y  T ypes 1 a n d 3 ................................................................ 1 4 9
5. 9. 1 0. E xtra vasati o n .......................................................................................... 1 4 9
5. 9. 1 1. He mat o p oietic Gr o wt h Fact ors ...............................................................1 4 9
5. 9. 1 2. A nti -Diarr heal, A nti -E metic T hera p y..................................................... 1 5 0
5. 9. 1 3. A nti- I nfla m mat or y T hera p y.................................................................... 1 5 0
5. 9. 1 4. C ortic oster oi ds ........................................................................................ 1 5 0
5. 9. 1 5. S ur ger y .................................................................................................... 1 5 0
5. 9. 1 6. Tra nsf usi o n S u p p ort ................................................................................ 1 5 0
6. S T U D Y P R O C E D U R E S ................................................................................................... 1 5 0
6. 1. Scree ni n g ............................................................................................................... 1 5 0
6. 2. St u d y  Peri o d .......................................................................................................... 1 5 1
6. 3. F oll o w -u p.............................................................................................................. 1 5 1
6. 4. E n d of Treat me nt ................................................................................................... 1 5 1
6. 5. E n d of St u d y .......................................................................................................... 1 5 1
6. 6. Patie nt Wit h dra wal ................................................................................................ 1 5 2
7. A S S E S S M E N T S ................................................................................................................ 1 5 3
7. 1. Safet y Assess me nt ................................................................................................. 1 5 4
7. 1. 1. Pre g na nc y  Testi n g .................................................................................... 1 5 4
7. 1. 2. A d verse E ve nts ......................................................................................... 1 5 4
7. 1. 3. La b orat or y  Safety Assess me nt ................................................................. 1 5 5
7. 1. 4. Vital Si g ns a n d P h ysical E xa mi nati o n ...................................................... 1 5 6
7. 1. 5. ( 1 2 -Lea d) Electr ocar di o gra m ....................................................................1 5 6
7. 1. 6. Ec h ocar di o gra m ( Ec h o) or M ulti gate d Ac q uisiti o n Sca n ( M U G A)......... 1 5 7
7. 1. 7. L ocal Site I njecti o n T olera bilit y  Assess me nt ( S C O nl y) ......................... 1 5 7
7. 2. Disease Res p o nse Assess me nt .............................................................................. 1 5 8
7. 2. 1. L a b orat or y E val uati o n of Disease Res p o nse............................................ 1 5 8
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 1
7. 2. 2. B o ne Marr o w Plas ma Cell E val uati o n a n d B o ne Marr o w Sa m ple 
C ollecti o n .......................................................................................................1 5 9
7. 2. 3. Fl u or o de o x y gl uc ose ( F D G) P ositr o n E missi o n T o m o gra p h y 
( P E T)/ C o m p ute d T o m o gra p hy ( C T) I ma gi n g ............................................... 1 6 1
7. 3. P har mac o ki netics Assess me nts ............................................................................. 1 6 2
7. 4. I m m u n o ge nicit y A nal yses ..................................................................................... 1 6 3
7. 5. Bi o mar ker a n d P har mac o d y na mic Assess me nts ................................................... 1 6 3
7. 5. 1. B o ne Marr o w Bi o mar kers ........................................................................ 1 6 5
7. 5. 2. W h ole Bl o o d P har mac o d y na mic Mar kers ................................................ 1 6 5
7. 5. 3. S hi p me nt of P har mac o d y na mic Sa m ples ................................................. 1 6 5
7. 5. 4. C y t o ki ne Assess me nts .............................................................................. 1 6 5
7. 5. 5. S ol u ble B C M A Assess me nts .................................................................... 1 6 6
7. 6. P har mac o ge n o mics ................................................................................................ 1 6 6
7. 6. 1. Ge n ot y pi n g A nal ysis ................................................................................ 1 6 6
7. 6. 2. Ge netic A nal y sis ....................................................................................... 1 6 7
7. 7. Ba n ke d Bi os peci me ns ........................................................................................... 1 6 7
7. 7. 1. A d diti o nal Researc h .................................................................................. 1 6 8
8. A D V E R S E E V E N T R E P O R TI N G .................................................................................... 1 6 8
8. 1. Re q uire me nts ......................................................................................................... 1 6 8
8. 1. 1. A d d iti o nal Details O n Rec or di n g A d verse E ve nts o n t he C R F................ 1 6 9
8. 1. 2. Eliciti n g A d verse E ve nt I nf or mati o n ........................................................ 1 6 9
8. 1. 3. Wit h dra wal Fr o m t he St u d y  D ue t o A d verse E ve nts................................ 1 6 9
8. 1. 4. Ti me Peri o d f or C ollecti n g A E/ S A E I nf or mati o n .................................... 1 7 0
8. 1. 4. 1. Re p orti n g S A Es t o Pfizer Safet y ............................................. 1 7 0
8. 1. 4. 2. Rec or di n g N o n -seri o us A Es a n d S A Es o n t he C R F ............... 1 7 0
8. 1. 5. Ca usalit y  Assess me nt ............................................................................... 1 7 1
8. 1. 6. S p o ns or’s Re p orti n g Re q uire me nts t o Re g ulat or y  A ut h orities................1 7 1
8. 2. Defi niti o ns............................................................................................................. 1 7 1
8. 2. 1. A d v erse E ve nts ......................................................................................... 1 7 1
8. 2. 2. A b n or mal Test Fi n di n gs ........................................................................... 1 7 2
8. 2. 3. Seri o us A d verse E ve nts ............................................................................ 1 7 3
8. 2. 4. H os pitalizati o n .......................................................................................... 1 7 3
8. 3. Se verit y  Assess me nt..............................................................................................1 7 5
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 2
8. 4. S pecial Sit uati o ns ..................................................................................................1 7 5
8. 4. 1. P ote ntial Cases of Dr u g -I n d uce d Li ver I nj ur y.......................................... 1 7 5
8. 4. 2. E x p os ure t o t he I n vesti gati o nal Pr o d uct D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure ................................................... 1 7 7
8. 4. 2. 1. E x p os ure D uri n g Pre g na nc y  ( E D P) ........................................ 1 7 7
8. 4. 2. 2. E x p os ure D uri n g Breastfee di n g .............................................. 1 7 8
8. 4. 2. 3. Occ u pati o nal E x p os ure ........................................................... 1 7 8
8. 4. 3. Me dicati o n Err ors ..................................................................................... 1 7 8
8. 4. 3. 1. Me dicati o n Err ors .................................................................... 1 7 9
8. 4. 4. Peri p heral ne ur o p at h y ............................................................................... 1 7 9
9. D A T A A N A L Y SI S/ S T A TI S TI C A L  M E T H O D S.............................................................1 8 0
9. 1. A nal y sis Sets ......................................................................................................... 1 8 0
9. 2. Statistical Met h o ds a n d Pr o perties ........................................................................ 1 8 1
9. 2. 1. Statistical Met h o ds f or D ose Escalati o n/ De -Escalati o n ........................... 1 8 1
9. 2. 2. Statistical Met h o d f or Esti mati n g t he M T D/ M A D ................................... 1 8 2
9. 3. Sa m ple Size Deter mi nati o n ................................................................................... 1 8 3
9. 4. Efficac y  A nalys is .................................................................................................. 1 8 3
9. 5. A nal y sis of P har mac o ki netics a n d P har mac o d yna mics ........................................ 1 8 5
9. 5. 1. P F -0 6 8 6 3 1 3 5 P K A nal y sis ....................................................................... 1 8 5
9. 5. 2. L e nali d o mi de, P o mali d o mi de, a n d De xa met has o ne P har mac o ki netic 
A nal y sis ( Parts 1 C a n d 2 C, Parts 1 D a n d 2 D, Parts 1 E a n d 2 E as 
a p pr o priate) .................................................................................................... 1 8 5
9. 5. 3. P o p ulati o n P har mac o ki netic A nal ys is of P har mac o ki netics 
( P K)/ P har mac o dy n a mic M o deli n g ................................................................ 1 8 5
9. 5. 4. A nal y sis of Im m u n o ge nicit y ..................................................................... 1 8 5
9. 5. 5. A nal y sis of P har mac o d yna mics ................................................................ 1 8 6
9. 5. 6. A nal y sis of Bi o mar ker E n d p oi nts .............................................................1 8 6
9. 6. Safet y A nal ys is...................................................................................................... 1 8 6
9. 6. 1. A nal y sis of t he Pri mar y E n d p oi nt f or Part 1 ............................................ 1 8 6
9. 6. 2. A nal y sis of Sec o n dar y Safety E n d p oi nts .................................................. 1 8 6
9. 6. 2. 1. A d verse E ve nts ........................................................................ 1 8 6
9. 6. 2. 2. La b orat or y  Test A b n or malities ............................................... 1 8 7
9. 6. 2. 3. Electr ocar di o gra m ................................................................... 1 8 7
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 3
9. 7. I nteri m A nal ys is.................................................................................................... 1 8 8
9. 8. D ata M o nit ori n g C o m mittee ................................................................................. 1 8 9
1 0. 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 ............................................... 1 8 9
1 1. 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 8 9
1 1. 1. Case Re p ort F or ms/ Electr o nic Data Rec or d ....................................................... 1 8 9
1 1. 2. Rec or d Rete nti o n ................................................................................................. 1 9 0
1 1. 3. Data Pr otecti o n .................................................................................................... 1 9 0
1 2. E T HI C S ............................................................................................................................ 1 9 1
1 2. 1. Re g ulat or y  a n d Et hical C o nsi derati o ns...............................................................1 9 1
1 2. 2. Patie nt I nf or mati o n a n d C o nse nt ......................................................................... 1 9 2
1 2. 3. Re p orti n g of Safet y I ss ues a n d Seri o us Breac hes of t he Pr ot oc ol or I CH 
G C P ......................................................................................................................... 1 9 2
1 3. D E FI NI TI O N O F E N D O F T RI A L ................................................................................. 1 9 3
1 3. 1. E n d of Trial i n All Partici pati n g C o u ntries ......................................................... 1 9 3
1 4. S P O N S O R DI S C O N TI N U A TI O N C RI T E RI A ..............................................................1 9 3
1 5. P U B LI C A TI O N O F S T U D Y R E S U L T S ........................................................................ 1 9 3
1 5. 1. Disse mi nati o n of Cli nical St u d y  Data................................................................. 1 9 3
1 5. 2. P u blicati o n P olic y ...............................................................................................1 9 4
1 6 . R E F E R E N C E S ................................................................................................................1 9 6
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 4
LI S T O F T A B L E S
Ta ble 1.
Ta ble of P ote ntial Fi xe d D ose Le vels .....................................................1 1 6
Ta ble 2.
Ta ble of P ote ntial D ose Le vels i n Part 1 I V A d mi nistrati o n .................. 1 1 9
Ta ble 3.
Ta ble of P ote ntial D ose Le vels i n Part 1 S C A d mi nistrati o n ................. 1 1 9
Ta ble 4.
Decisi o n R ules ........................................................................................ 1 2 0
Ta ble 5.
D ose M o dificati o ns f or P F -0 6 8 6 3 1 3 5 Pr o d uct -Relate d T o xicit y  an d 
f or Peri p heral Se ns or y or M ot or Ne ur o pat hy * * * ................................... 1 3 8
Ta ble 6.
Le nali d o mi de D ose A dj ust me nt f or T hr o m b oc y t o pe nia........................ 1 4 0
Ta ble 7.
Le nali d o mi de D ose A dj ust me nt f or Ne utr o pe nia................................... 1 4 0
Ta ble 8.
Le nali d o mi de D ose A dj ust me nt f or Re nal I m pair me nt .......................... 1 4 1
Ta ble 9.
D ose M o dificati o n I nstr ucti o ns f or P o mali d o mi de f or He mat ol o gic 
T o xicities ................................................................................................1 4 1
Ta ble 1 0.
D ose M o dificati o n I nstr ucti o ns f or De xa met has o ne T o xicities ............. 1 4 2
Ta ble 1 1.
Safet y  La b orat or y Tests.......................................................................... 1 5 5
Ta ble 1 2.
Bi o mar ker Assa y s a n d Sa m ple S o urces ................................................. 1 6 4
Ta ble 1 3.
Lee et al 2 0 1 4 C R S re vise d gra di n g s ys te m2 .......................................... 2 1 4
Ta ble 1 4.
Defi niti o n of Hi g h D ose Vas o press or ..................................................... 2 1 5
Ta ble 1 5.
A S T C T C R S re vise d gra di n g s ys te m3 .................................................... 2 1 5
Ta ble 1 6.
I m m u ne Effect or Cell-Ass ociate d E nce p hal o pat h y  (IC E) Sc ore ........... 2 1 8
Ta ble 1 7.
A S T C T I C A N S Gra di n g ......................................................................... 2 1 9
LI S T O F FI G U R E S
Fi g ure 1.
P F -0 6 8 6 3 1 3 5 Acti vit y  In Vitr o ................................................................. 9 8
Fi g ure 2.
P F -0 6 8 6 3 1 3 5 Acti vit y  i n a n O P M-2 M M Ort h otr o pi c T u m or M o del .....9 9
Fi g ure 3.
Efficac y  of P F-0 6 8 6 3 1 3 5 i n C o m bi nati o n wit h L e nali d o mi de i n 
M M. 1 S a n d M O L P- 8 Ort h ot o pic T u m or M o dels ................................... 1 0 0
Fi g ure 4.
C 1 0 7 1 0 0 1 St u d y  Desi g n.........................................................................1 1 0
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 5
A P P E N DI C E S
A p pe n di x 1. A B B R E VI A TI O N S ...........................................................................................2 0 1
A p pe n di x 2. T H E I N T E R N A TI O N A L M Y E L O M A W O R KI N G G R O U P (I M W G) 
R E S P O N S E C RI T E RI A F O R M U L TI P L E M Y E L O M A ...................... 2 0 9
A p pe n di x 3. I M W G MI NI M A L  R E SI D U A L DI S E A S E ( M R D) Criteria............................ 2 1 2
A p pe n di x 4. E C O G P E R F O R M A N C E S T A T U S ................................................................. 2 1 3
A p pe n di x 5. C R S A N D I C A N S MI TI G A TI O N A N D M A N A G E M E N T ............................ 2 1 4
A p pe n di x 6. I N T E R N A TI O N A L M Y E L O M A W O R KI N G G R O U P (I M W G) 
M U L TI P L E M Y E L O M A DI A G N O SI S C RI T E RI A 4 5 .......................... 2 2 4
A p pe n di x 7. M A N A G E M E N T O F I N F U SI O N R E L A T E D R E A C TI O N S, 
I N CL U DI N G A L L E R GI C R E A C TI O N S O R A N A P H Y L A XI S .......... 2 2 5
A p pe n di x 8. D E T AI L E D D O S E E S C A L A TI O N/ D E -E S C A L A TI O N S C H E M E F O R 
m T PI  D E SI G N........................................................................................ 2 2 7
A p pe n di x 9. S U B C U T A N E O U S I NJ E C TI O N SI T E L O C A TI O N S .................................... 2 3 0
A p pe n di x 1 0. Alter nati ve Meas ures D uri n g P u blic E mer ge ncie s ......................................... 2 3 1
A p pe n di x 1 1. Pr o hi bite d C o nc o mita nt Me dicati o ns w hic h ma y  Res ult i n Dr u g-Dr u g 
I nteracti o n ( D DI) ....................................................................................2 3 4
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 6
P R O T O C O L S U M M A R Y
B ac k gr o u n d a n d R ati o n ale
Des pite a n u m ber of rece nt treat me nt a d va nces f or M ulti ple M y el o ma ( M M), m ost patie nts 
are e x pecte d t o rela pse.  M M is n ot c o nsi dere d c ura ble a n d e ac h li ne of t hera p y re n ders t he 
patie nt m ore refract or y  t o treat me nt.  F or e xa m ple , t he me dia n o verall s ur vi val of patie nts 
wit h M M w h o rela pse d f oll o wi n g i m m u n o m o d ulat or y dr u g (IMi D ) a n d b ortez o mi b 
(Velca de ) t hera pies is 9 m o nt hs .1 It is t heref ore clear t hat a d diti o nal treat me nt a p pr oac hes 
are re q uire d f or rela pse d/refract or y  M M.
B y  directl y tar geti n g c yt ot o xic T-cells t o t u m ors, bis pecific a nti b o dies offer a n o vel 
i m m u n ot hera pe utic a p pr oac h f or ca ncer.  T hese a nti b o dies ha ve t w o se parate a nti ge n 
rec o g niti o n d o mai ns: a d o mai n t hat rec o g nizes a t u m or a nti ge n a n d a n ot her t hat rec o g nizes 
cl uster of differe ntiati o n ( C D ) 3 e x presse d o n T -cells.  Bis pecific a nti b o dies are t heref ore 
a ble t o si m ulta ne o usl y bi n d t o C D 3 a n d t he t u m or a nti ge n at t he sa me ti me, t here b y i nitiati n g 
a c yt ot o xic res p o nse t o war ds t he b o u n d t u m or cell.  P F-0 6 8 6 3 1 3 5 is a heter o di mer ic 
h u ma nize d f ull -le n gt h bis pecific a nti b o dy c o m prise d of o ne B -cell Mat urati o n A nti ge n 
( B C M A) bi n di n g ar m a n d o ne C D3 bi n di n g ar m paire d t hr o u g h hi n ge m utati o n tec h n ol o g y . 
Strate gies t o f urt her e n ha nce t he i m m u ne effects of P F- 0 6 8 6 3 1 3 5 ha ve bee n s u p p orte d b y  
pre -cli nical data s h o wi n g e n ha nce d t u m or gr o wt h i n hi biti o n b y c o m bi ni n g P F-0 6 8 6 3 1 3 5 wit h 
a n i m m u n o m o d ulat or y dr u g (I Mi D).
I n t his first i n patie nt ( FI P) cli nical st u d y, P F-0 6 8 6 3 1 3 5 will be e val uate d f or t he treat me nt of 
a d ult patie nts wit h rela pse d /refract ory m ulti ple m y el o ma, w h o ha ve recei ve d a pr oteas o me 
i n hi bit or, a n IMi D a n d a n a nti C D 3 8 m o n ocl o nal a nti b o d y ( m A b) eit her i n c o m bi nati o n wit h
le nali d o mi de, p o mali d o mi de , de xa met has o ne, or as a si n gle a ge nt.
St u d y Desi g n:
T his is a P hase 1 o pe n -la bel, m ulti -d ose, m ulti -ce nter, d ose escalati o n, safet y, 
p har mac o ki netic ( P K) a n d p har mac o d y n a mic st u d y of P F- 0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de , p o mali d o mi de or de xa met has o ne i n a d ult patie nts wit h 
a d va nce d M M
w h o ha ve rela pse d fr o m or are refract or y t o sta n dar d t hera p y.  T his st u d y  will 
be di vi de d i nt o d ose escalati o n /fi n di n g part ( Part 1) a n d d ose e x pa nsi o n part ( Part 2). 
Part 1 d ose escalati o n /fi n di n g ( wit h eit her m o n ot hera py or c o m b inati o n t hera pies) i n or der t o 
deter mi ne t he rec om me n de d P hase 2 d ose (R P 2 D ) is f urt her di vi de d i nt o :

Part 1 i ntra ve n o us (I V) m o n ot hera p y a n d Part 1 s u bc uta ne o us ( S C) m o n ot hera p y 
c o h orts as well as Part 1. 1 pri mi n g a n d mai nte na nce c o h ort s .

Part 1 C le nali d o mi de c o m bi nati o n, Part 1 D p o mali d o mi de c o m bi nati o n a n d Part 1 E 
de xa met has o ne c o m bi nati o n c o h orts. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 7
Part 2 d ose e x pa nsi o n p hase will be di vi de d i nt o 4 c o h orts as f oll o ws: 

Part 2 A ( P F -0 6 8 6 3 1 3 5 as m o n ot hera p y).

Part 2 C ( P F - 0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de).

Part 2 D ( P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h p o mali d o mi de) .

Part 2 E ( P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h de xa met has o ne).
After t he si n gle -a ge nt P F -0 6 8 6 3 1 3 5 ma xi m u m t olerate d d ose ( M T D) or ma xi m u m 
a d mi nistere d d ose ( M A D) a n d R P 2 D as well as prefer re d r o ute of a d mi nistrati o n has bee n 
dete r mi ne d i n t he Part 1 m o n ot hera p y  d ose escalati o n, safet y c o h orts e val uati n g 
c o m bi nati o ns of P F -0 6 8 6 3 1 3 5 wit h eit her le nali d o mi de, p o mali d o mi de or de xa met has o ne 
ma y  be i nitiate d i n Parts 1 C, 1 D or Part 1 E res pecti vel y.  F oll o wi n g i de ntificati o n of t he 
M T D / M A D a n d R P 2 D as m o n ot hera p y a n d i n eac h c o m bi nati o n c o h ort, d ose e x pa nsi o n
c o h orts testi n g m o n ot hera p y  a n d c o m bi nati o n s wit h le nali d o mi de , p o mali d o mi de or 
de xa met has o ne will be i nitiate d (e x pa nsi o n c o h orts Parts 2 A, 2 C , 2 D, or 2 E res pecti vely ).
I V a n d S C a d mi nistrati o n of P F - 0 6 8 6 3 1 3 5 will be e val uate d d uri n g t he Part 1 d ose 
escalati o n. A n alter nati ve mai nte na nce d ose escalati o n p hase ( Part 1. 1), w hic h i nc or p orates 
t he usa ge of a pri mi n g d ose d uri n g C y cle 0 D a y 1 ( C0 D 1) f oll o we d by a mai nte na nce d ose 
1 wee k later at C 1 D 1 f or all s u bse q ue nt d oses, ma y als o be i nitiate d. Part 1 will be 
i m ple me nte d as f oll o ws:

Part 1 I V st u dies escalati n g d oses of P F -0 6 8 6 3 1 3 5 a d mi nistere d i ntra ve n o usl y  
( 0. 1, 0. 3, 1, 3, 1 0, 3 0, 5 0 µ g/ k g or hi g her if i n dicate d ) wee kl y  (see Secti o n 3. 1. 1. 3 ).  
A d diti o nal d ose le vels (l o wer, i nter me diate or hi g her ) m a y  be e val uate d [see 
Secti o n 3. 1. 4 ].

After Part 1 I V 5 0 µ g/ k g d ose was cleare d , Part 1 S C a d mi nistrati o n (8 0, 1 3 0, 2 1 5, 
3 6 0, 6 0 0, a n d 1 0 0 0 µ g/ k g ) wee kly w as o pe ne d base d o n t he e mer gi n g cli nical a n d P K 
data fr o m Part 1 I V c o h orts (see Secti o n 3. 1. 1. 3 ). U p o n reac hi n g M T D/ M A D, u p t o 
6- 1 2 patie nts t otal at selecte d le vel(s) bel o w t he M T D/ M A D wee kly a n d Q 2 W d osi n g 
u p t o t he sa me d ose i nte nsit y as t he M T D/ M A D
wee kl y re gi me n m a y  be e val uate d 
f urt her t o s u p p ort t he R P 2 D decisi o n.

A n alter nati ve Part 1 . 1 pri mi n g a n d mai nte na nce d os i n g f or m o n ot hera p y  I V or S C
a d mi nistrati o n ma y be tri g gere d if ≥Gra de 3 c yt o ki ne release sy n dr o me ( C R S ) e ve nts
(lasti n g f or > 2 4 h o urs des pite treat me nt wit h sta n dar d of care per t he i nstit uti o n’s, 
I n vesti gat or’s, or treati n g p h ysicia n’s g ui deli nes f or t he ma na ge me nt of C R S) are
o bser ve d (see Secti o n 3. 1. 1. 3 ). A p ri mi n g d ose (C yc le 0) w o ul d be gi ve n o ne wee k 
pri or t o C ycle 1 of mai nte na nce d osi n g a n d i ncl u de a ma n dat or y o ver ni g ht 
h os pitalizati o n o n C 0 D 1. Alter nati ve strate g ies f or i ncreasi n g d osi n g s uc h as a 
ste p-u p re gi me n or pr o p h y lactic ster oi ds m a y  als o be c o nsi dere d a n d i m ple me nte d t o 
f urt her i m pr o ve t olera bilit y if nee de d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 8

F or all patie nts i n m o n ot hera p y Part 1 c o h orts, t o cl osel y  ma na ge a n d m o nit or ac ute 
t o xicities, patie nts will be h os pitalize d o n C 1 D 1. T he nee d f or ma n dat or y  
h os pitalizati o n as well as its le n gt h will be re -assesse d f or patie nts e nr olle d i n Part 2 A 
base d o n safet y data fr o m Part 1 after a gree me nt of s p o ns or a n d i n vesti gat ors at t he 
ti me of m o n ot hera py M T D/ M A D a n d R P 2 D
deter mi nati o n .

A sta g gere d e nr oll me nt strate g y will be a p plie d f or all patie nts i n t he m o n ot hera p y 
Part 1 c o h ort at eac h d ose le vel: whe n a d ose le vel o pe ns f or e nr ol l me nt, t he 
first patie nt will be d ose d a n d o bser ve d f or 4 8 h o urs.   I n Part 1, if n o safety c o ncer ns 
arise d uri n g t his 4 8 hr peri o d fr o m start of treat me nt, t he n s u bse q ue nt patie nts will be 
e nr olle d i nt o t he sa me d ose le vel. I n Part 1. 1, if n o safety c o nce r ns arise 4 8 hrs after 
recei vi n g t he mai nte na nce d ose o n C 1 D1 , s u bse q ue nt patie nts will be e nr olle d i nt o 
t he sa me mai nte na nce d ose le vel.

All patie nts i n t he m o n ot hera py c o h orts of Part 1 will be m o nit ore d cl osel y f or d ose 
li miti n g t o xicities ( D LTs, see Secti o n 3. 2 ), u ntil t he e n d of C ycle 1 .  
Eit her I V or S C a d mi nistrati o n of P F - 0 6 8 6 3 1 3 5 eit her wit h or wit h o ut a pri mi n g d ose will be 
selecte d t o m o ve f or war d i n c o m bi nati o ns wit h le nali d o mi de, p o mali d o mi de , or 
de xa met has o ne.

Part 1 C will i n vesti gate P F- 0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de , Part 1 D will 
i n vesti gate P F-0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h p o mali d o mi de .

T h ese safety c o h ort s ( Parts 1 C a n d 1 D) will use a d ose -escalati o n/ de -escalati o n 
a p pr oac h f or P F -0 6 8 6 3 1 3 5 starti n g wit h t he d ose le vel M T D -1/ M A D -1 or R P 2 D 
( w hic he ver is l o wer) of P F-0 6 8 6 3 1 3 5 fr o m Part 1 d ose escalati o n c o m bi ne d wit h 
1 5 m g le nali d o mi de , or 4 mg p o mali d o mi de .  If safe a n d well t olerate d 
P F -0 6 8 6 3 1 3 5 will t he n be escalate d t o t he m o n ot hera p y M T D/ R P 2 D , if 
a p plica ble, a gai n i n c o m bi nati o n wit h 1 5 m g le nali d o mi de , or 4 m g p o mali d o mi de
i n or der t o select t he c o m bi nati o n R P 2 D.  I f t he c o m bi nati o n re gi me n is n ot well 
t olerate d d ue t o P F-0 6 8 6 3 1 3 5, P F - 0 6 8 6 3 1 3 5 m a y  be de -escalate d i n c o m bi nati o n 
acc or di n g t o m T PI desi g n.  Eac h c y cle of t he c o m bi nati o n of P F-0 6 8 6 3 1 3 5 a n d 
le nali d o mi de or p o mali d o mi de starti n g wit h C yc le 1 will be 2 8 d a y s. 

T o cl osel y  ma na ge ac ute t o xicities, patie nts will be h os pitalize d o n C 1 D 1.
T he 
nee d f or ma n dat or y  h os pitalizati o n as well as its le n gt h will be re -assesse d f or 
patie nts e nr olle d i n Parts 2 C a n d 2 D base d o n safet y  data fr o m Parts 1 C a n d 1 D, 
res pecti vely.

A sta g gere d e nr oll me nt strate g y  will be a p plie d f or Parts 1 C a n d 1 D: w he n a d ose 
le vel o pe ns f or e nr oll me nt, t he first patie nt wi ll be d ose d, a n d o bser ve d f or 
9 6 h o urs after C 1 D 1.  If n o safet y c o ncer ns arise d uri n g t his 9 6 hr peri o d fr o m 
C 1 D 1 , s u bse q ue nt patie nts will be e nr olle d i nt o t he sa me d ose le vel a n d 
c o m bi nati o n .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 9

U p o n reac hi n g M T D/ M A D, u p t o a p pr o xi matel y 6- 1 2 patie nts t otal at selecte d 
le vel(s) bel o w t he M T D/ M A D ma y be e val uate d f urt her t o s u p p ort t he R P 2 D 
decisi o n .

Part 1 E will i n vesti gate P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h de xa met has o ne.  
De xa met has o ne w o ul d be gi n o n C 0 D 1 a n d it will be d ose d as pre me dicati o n pri or t o 
P F -0 6 8 6 3 1 3 5 a d mi nistrati o n .

T his safet y c o h ort will e val uate t he R P 2 D of P F -0 6 8 6 3 1 3 5 wit h de xa met has o ne at 
a d ose of 4 0 m g. F or s u bjects ol der t ha n 7 5 ye ars or u n der wei g ht ( b o d y mass 
i n de x [ B MI] < 1 8. 5), de xa met has o ne pre me dicati o n ma y be gi ve n pri or t o 
P F - 0 6 8 6 3 1 3 5 at a d ose of 2 0 m g. P F - 0 6 8 6 3 1 3 5 ma y  be de- escalate d acc or di n g t o 
m o difie d t o xicit y  pr o ba bilit y i nter val ( m T PI) desi g n. If t he c o m bi nati o n re gi me n 
is n ot well t olerate d as g ui de d b y m T PI, Part 2 E ma y n ot be i nitiate d. Eac h c y cle 
of t he c o m bi nati o n of P F -0 6 8 6 3 1 3 5 a n d de xa met has o ne starti n g wit h C ycle 1 will 
be 2 8 d a y s. 

T o cl osel y  ma na ge ac ute t o xicities, patie nts i n Part 1E will be h os pi talize d o n
C 1 D 1. T he nee d f or h os pitalizati o n as well as its le n gt h will be re- assesse d f or 
patie nts e nr olle d i n Part 2 E base d o n safet y data fr o m Part 1 E after a gree me nt of 
s p o ns or a n d i n vesti gat ors.

F or Part 1 E or Part 2 E , patie nts wit hi n t hese parts ma y  e nr oll c o nc urre ntl y.

It is e x pecte d t hat Part 1 E will e nr oll a p pr o xi matel y 9-1 6 patie nts .
A m o difie d t o xicit y  pr o ba bilit y i nter val ( m T PI) met h o d, tar getin g a D L T rate of 2 5 % a n d a n 
acce pta ble e q ui vale nce i nter val of 2 0 % - 3 0 % will be utilize d f or d ose escalati o n i n Part 1.  
All patie nts will als o be m o nit ore d cl osel y f or D L Ts u ntil t he e n d of C ycle 1. All patie nts 
will be m o nit ore d f or late t o xicities f oll owi n g t he i nitial D L T peri o d u p t o Da y 6 0 fr o m first 
d ose (see Secti o n 3. 2. 1 ).  O nce a d ose le vel has bee n declare d safe, patie nts at l o wer d ose 
le vels w h o ha ve c o m plete d t he 6 0 d a y  late t o xicit y o bser vati o n peri o d ma y escalate t o t he 
ne xt hi g her d ose le vel, if criteria o utli ne d i n Secti o n 3. 1. 4. 1 Criteria f or I ntra patie nt D ose
Escalati o n ha ve bee n met .  A d diti o nal i ntra -patie nt d ose escalati o ns will als o be per mitte d 
after a mi ni mal i nter val of 6 0 d a y s.  N o cr oss o ver is all o we d, h o we ver, bet wee n patie nts 
assi g ne d t o m o n ot hera p y P F - 0 6 8 6 3 1 3 5 a n d t he differe nt c o m bi nati o n re gi me ns.
F oll o wi n g t he deter mi nati o n s of t he R P 2 D of m o n ot hera p y a n d c o m bi nati o ns wit h 
le nali d o mi de or p o mali d o mi de i n Part 1, t he res pecti ve e x pa nsi o n c o h orts i n Part 2 will 
c o m me nce. I n a d diti o n, if t he c o m bi nati o n wit h de xa met has o ne i n Part 1 E is well t olerate d as 
g ui de d b y m T PI, Part 2 E ma y be i nitiate d.
Part 2 d ose e x pa nsi o n p hase will be di vi de d i nt o 4 c o h orts as f oll o ws: Part 2 A ( P F - 0 6 8 6 3 1 3 5 
as m o n ot hera p y), Part 2 C ( P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de) , Part 2 D 
( P F-0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h p o mali d o mi de ) a n d Part 2 E ( P F -0 6 8 6 3 1 3 5 i n 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 0
c o m bi nati o n wit h de xa met has o ne) w hic h will e val uate safet y a n d a nti -m y el o ma acti vit y of 
P F -0 6 8 6 3 1 3 5 at R P 2 Ds deter mi ne d i n Part 1 .
A p pr o xi matel y  1 2 0 patie nts ha d bee n pla n ne d t o e nr oll i nt o Parts 1/ 1 . 1, 1 C, 1 D, 1 E wit h
a p pr o xi matel y 8 0 patie nts pla n ne d t o e nr oll i nt o Part 2. Parts 1 C, 1 D a n d 1 E were pla n ne d t o 
e nr oll a p pr o xi matel y 9- 1 6 patie nts wit h P arts 2 A, 2 C , 2 D a n d 2 E pla n ne d t o e nr oll 
a p pr o xi matel y 2 0 patie nts eac h.
T he cli nical de vel o p me nt pr o gra m f or P F - 0 6 8 6 3 1 3 5 has bee n e x pa n de d wit h de dicate d 
st u dies t hat will f urt her i n vesti gate b ot h m o n ot hera p y a n d c o m bi nati o n t hera p y. Theref ore, 
t he S p o ns or has deter mi ne d t hat e nr ollme nt i n st u d y  C 1 0 7 1 0 0 1 has bee n c o m plete d.
St u d y O bjecti ves a n d E n d p oi nts
P art 1 I V a n d S C m o n ot her a p y D ose Esc al ati o n , P art 1 . 1 Pri mi n g a n d M ai nte n a nce 
D ose Esc al ati o n a n d P art s 1 C, 1 D a n d 1 E C o m bi n ati o n D ose Esc al ati o n/ Fi n di n g
Pri m ar y O bjecti ves: 
Pri m ar y E n d p oi nts: 

T o assess safet y a n d t olera bilit y at i ncreasi n g 
d ose le vels of P F -0 6 8 6 3 1 3 5 as m o n ot hera p y 
a n d i n c o m bi nati o n wit h le nali d o mi de,
p o m ali d o mi de, or d e xa met has o ne i n 
s uccessi ve c o h orts of patie nts wit h m ulti ple 
m yel o ma i n or der t o esti mate t he Ma xi m u m 
T ol erate d D ose ( M T D) or Ma xi m u m 
A d mi nistere d D ose ( M A D) a n d select t he 
Rec o m me n de d P hase 2 D ose ( R P 2 D).

N u m ber of D L Ts f oll o wi n g treat me nt wit h 
escalati n g d oses of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o m ali d o mi de , or de xa met has o ne .
Sec o n d ar y O bjecti ves: 
Sec o n d ar y E n d p oi nts: 

T o e val uate t he o verall safet y pr ofile. 

A d verse E ve nts as c haracterize d b y t y pe, 
fre q ue nc y, se verit y as gra de d b y Nati o nal 
Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria 
f or A d verse E ve nts ( N CI C T C A E) versi o n 4. 0 3, 
ti mi n g, seri o us ness, a n d relati o ns hi p t o 
P F -0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de, p o m ali d o mi de ,
or de xa met has o ne .  T he se verit y of c yt o ki ne 
release s y n dr o me ( C R S) will be assesse d 
acc or di n g t o t he gra di n g descri be d b y Lee et al. 
( 2 0 1 4 a n d 2 0 1 9 ,2 ,3 See A p pe n di x 5 );

La b orat or y a b n or malities as c haracterize d b y 
t ype, fre q ue nc y, se verit y (as gra de d b y N CI 
C T C A E versi o n 4. 0 3), a n d ti mi n g.

T o e val uate a nti -m yel o ma acti vit y of  
P F -0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de,
p o m ali d o mi de, or d e xa met has o ne.

O bjecti ve res p o nse rate ( O R R) usi n g t he 
i nter nati o nal m yel o ma w or ki n g gr o u p (I M W G) 
res p o nse criteria f or m ulti ple m yel o ma4 ,5 (see 
A p pe n di x 2 );

Ti m e t o e ve nt e n d p oi nts: ti me t o res p o nse 
(T T R ), c o m plete res p o nse rate ( C R R), d urati o n 
of res p o nse (D O R ), d urati o n of c o m plete 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 1
res p o nse ( D o C R), d urati o n of sta ble disease 
(D O S D ), pr o gressi o n -free s ur vi val (P F S ), 
o verall s ur vi val ( O S ), as assesse d b y I M W G 
criteria f or res p o nse 4 ,5 (see A p pe n di x 2 );

Rate of patie nts wit h n o mi ni mal resi d ual disease 
( M R D) after treat me nt wit h P F-0 6 8 6 3 1 3 5 usi n g 
I M W G M R D criteria5 (see A p pe n di x 3 ).

T o e val uate si n gle d ose a n d m ulti ple d ose P K 
of P F -0 6 8 6 3 1 3 5 gi ve n as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de ,p o m ali d o mi de,
a n d de xa met has o ne . A d diti o nall y, P K of 
le nali d o mi de, p o m ali d o mi de, a n d 
de xa met has o ne will be e val uate d w he n 
c o m bi ne d wit h P F -0 6 8 6 3 1 3 5 ( Parts 1 C , 1 D ,
a n d 1 E , res pecti vel y).

P har m ac o ki netic para meters of P F -0 6 8 6 3 1 3 5 : 
C y cle 1 Da y 1 d ose a n d C ycle 2 Da y 1 d ose 
ma xi m u m c o nce ntrati o n ( C ma x ), area u n der t he 
c o nce ntrati o n vers us ti me c ur ve fr o m ti me zer o 
t o t he last q ua ntifia ble ti me p oi nt pri or t o t he 
ne xt d ose ( A U C last) a n d if data per mit, cleara nce 
( C L) or cleara nce after n o n -i ntra ve n o us 
a d mi nistrati o n ( C L/ F ), v ol u me of distri b uti o n at 
stea d y state ( Vss) or a p pare nt v ol u me of 
distri b uti o n after o n -i ntra ve n o us a d mi nistrati o n 
(Vss/ F ), a n d ter mi nal eli mi nati o n t 1/ 2.

P las ma le nali d o mi de, p o mali d o mi de, a n d 
de xa met has o ne c o nce ntrati o ns at selecte d ti me 
p oi nts ( Parts 1 C, 1 D, a n d 1 E , res pecti vel y).

T o e val uate i m m u n o ge nicit y of  P F -0 6 8 6 3 1 3 5
as m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de,  p o m ali d o mi de , or 
de xa met has o ne, .

I nci de nce a n d titers of a nti-dr u g a nti b o dies 
( A D A) a n d ne utralizi n g a nti b o dies ( Na b ) a gai nst 
P F -0 6 8 6 3 1 3 5 .

T o c haracterize t he i m pact of P F -0 6 8 6 3 1 3 5 as 
a mo n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o m ali d o mi de, or 
de xa met has o ne o n s yste mic s ol u ble i m m u ne 
fact ors.

Pre - a n d p ost-d ose q ua ntificati o n of s ol u ble 
c yt o ki nes i n ser u m.
Terti ar y/ E x pl or at or y O bjecti ves: 
Terti ar y/ E x pl or at or y E n d p oi nts: 

E val uate t he effect of P F -0 6 8 6 3 1 3 5 as a 
m o n o t hera p y a n d i n c o mbi n ati o n wit h 
le nali d o mi de, p o m ali d o mi de, or 
de xa met has o ne o n plas ma cell, T a n d B cell 
c o m part me nts.

B C M A e x pressi o n o n plas ma cell s i n b o ne 
marr o w , as assesse d b y m ulti para meter fl o w 
c yt o metr y a n d i m m u n o hist oc he mistr y;

Pre - a n d p ost-d ose le vels of s ol u ble B C M A;

E n u merati o n of T, B, a n d nat ural killer ( N K )
s u bt y pes i n w h ole bl o o d a n d b o ne marr o w b y 
fl o w c yt o metr y a nal ysis;

T- cell i m m u n o p he n ot y pi n g, i ncl u di n g b ut n ot 
li mite d t o pr oliferati o n a n d acti vati o n mar kers i n 
w h ole bl o o d a n d b o ne marr o w b y fl o w 
c yt o metr y a nal ysis;

T- cell e n ga ge me nt, i ncl u di n g b ut n ot li mite d t o 
pr oliferati o n a n d acti vati o n mar kers i n b o ne 
marr o w  b y i m m u n o hist oc he mistr y;

T he relati ve e x pressi o n of (ri b o n ucleic aci d) 
R N A tra nscri pts, i ncl u di n g b ut n ot li mite d t o, 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 2
t h ose ass ociate d wit h i mm u ne acti vati o n a n d 
i m m u ne re g ulati o n i n b o ne marr o w;

T he a b u n da nce a n d di versit y of T -cell cl o nes i n 
b o ne marr o w .

T o c ollect ba n ke d bi os peci me ns f or 
e x pl orat or y researc h, u nless pr o hi bite d b y 
l ocal re g ulati o ns or et hics c o m mittee decisi o n.  

C ollecti o n of ba n ke d bi os peci me ns u nless 
pr o hi bite d b y l ocal re g ulati o ns or et hics 
c o m mittee decisi o n.  A d diti o nal i nf or mati o n o n 
c ollecti o n a n d p ote ntial use is pr o vi de d i n t he 
Ba n ke d Bi os peci me ns Secti o n 7. 7 .
P art 2 D ose E x p a nsi o n
Pri m ar y O bjecti ves: 
Pri m ar y E n d p oi nts: 

T o assess preli mi nar y cli nical efficac y at 
R P 2 D f or P F-0 6 8 6 3 1 3 5 as m o n ot hera p y a n d
i n c o m bi nati o n wit h le nali d o mi de,  
p o m ali d o mi de, or de xa met has o ne .

O R R a n d D O R , as assesse d b y I M W G criteria 
f or res p o nse4 ,5 (see A p pe n di x 2 )
Sec o n d ar y O bjecti ves: 
Sec o n d ar y E n d p oi nts: 

T o f urt her c haracterize t he safet y a n d 
t olera bilit y of P F-0 6 8 6 3 1 3 5 as m o n ot hera p y 
a n d i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

A d verse E ve nts as c haracterize d b y t y pe, 
fre q ue nc y, se verit y (as gra de d b y N CI C T C A E 
versi o n 4. 0 3), ti mi n g, seri o us ness, a n d 
relati o ns hi p t o P F -0 6 8 6 3 1 3 5 as m o n ot hera p y a n d 
i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne . T he se verit y 
of C R S will be assesse d acc or di n g t o t he gra di n g 
descri be d b y Lee et al. ( 2 0 1 4 a n d 2 0 1 9 ,2 ,3 See 
A p pe n di x 5 );

La b orat or y a b n or malities as c haracterize d b y 
t ype, fre q ue nc y, se verit y (as gra de d b y N CI 
C T C A E versi o n 4. 0 3), a n d ti mi n g.

T o f urt her e val uate a nti -m yel o ma efficac y of 
P F -0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

Ti m e t o e ve nt e n d p oi nts: C R R, D o C R, T T R, 
D O S D, P F S, O S, as assesse d b y I M W G criteria 
f or res p o nse4 ,5 (see A p pe n di x 2 );

Rate of patie nts wit h n o mi ni mal resi d ual diseas e 
( M R D) after treat me nt wit h P F-0 6 8 6 3 1 3 5 usi n g 
I M W G M R D criteria5 (see A p pe n di x 3 ).

T o e val uate P K of P F -0 6 8 6 3 1 3 5 at R P 2 D as 
m o n ot hera p y a n d i n c o mbi nati o n wit h 
le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne . A d diti o nall y, t o c ollect 
le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne c o nce ntrati o n data whe n 
c o m bi ne d wit h P F -0 6 8 6 3 1 3 5.

C o nce ntrati o ns of P F -0 6 8 6 3 1 3 5 , le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne f or selecte d 
ti me p oi nts. 

T o e val uate i m m u n o ge nicit y of  P F -0 6 8 6 3 1 3 5
as m o n ot hera p y a n d i n c o mbi nati o n wit h 

I nci de nce a n d titers of a nti-dr u g a nti b o dies 
( A D A a n d ne utralizi n g a nti b o dies ( Na b ) a gai nst 
P F -0 6 8 6 3 1 3 5 .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 3
le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne .

T o c haracterize t he i m pact of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o m ali d o mi de or 
de xa met has o ne o n s yste mic s ol u ble i m m u ne 
fact ors.

Pre - a n d p ost-d ose q ua ntificati o n of s ol u ble 
c yt o ki nes i n ser u m.
Terti ar y/ E x pl or at or y O bjecti ves: 
Terti ar y/ E x pl or at or y E n d p oi nts: 

E val uate t he effect of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o m ali d o mi de, or 
de xa met has o ne o n plas ma cell, T a n d B cell 
c o m part me nts.

B C M A e x pressi o n o n plas ma cells i n b o ne 
marr o w , as assesse d b y m ulti para meter fl o w 
c yt o metr y a n d i m m u n o hist oc he mistr y;

Pre - a n d p ost-d ose le vels of s ol u ble B C M A;

E n u merati o n of T, B, a n d N K s u bt y pes i n w h ole 
bl o o d a n d b o ne marr o w b y fl o w c yt o metr y 
a nal ysis ;

T- cell i m m u n o p he n ot y pi n g, i ncl u di n g b ut n ot 
li mite d t o pr oliferati o n a n d acti vati o n mar kers i n 
w h ole bl o o d a n d b o ne marr o w b y fl o w 
c yt o metr y a nal ysis;

T- cell e n ga ge me nt, i ncl u di n g b ut n ot li mite d t o 
pr oliferati o n a n d acti vati o n mar kers i n b o ne 
marr o w  b y i m m u n o hist oc he mistr y;

T he relati ve e x pressi o n of R N A tra nscri pts, 
i ncl u di n g b ut n ot li mite d t o, t h ose ass ociate d 
wit h i m m u ne acti vati o n a n d i m m u ne re g ulati o n 
i n b o ne marr o w;

T he a b u n da nce a n d di versit y of T -cell cl o nes i n 
b o ne marr o w .

T o c ollect ba n ke d bi os peci me ns f or 
e x pl orat or y researc h, u nless pr o hi bite d b y 
l ocal re g ulati o ns or et hics c o m mittee decisi o n.  

C ollecti o n of ba n ke d bi os peci me ns u nless 
pr o hi bite d b y l ocal re g ulati o ns or et hics 
c o m mittee decisi o n.  A d diti o nal i nf or mati o n o n 
c ollecti o n a n d p ote ntial use is pr o vi de d i n t he 
Ba n ke d Bi os peci me ns Secti o n 7. 7 .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 7
Sc he d ule of Acti vities A
Visit I de ntifier
Scree ni n g 1
D a ys pri or t o 
e nr oll me nt
Tre at m e nt Peri o d
1 m o nt h 
F oll o w -u p 3 5
S ur vi v al 
F oll o w -u p 3 7
C ycle 1
( 1 C ycle = 3 
wee ks)
C ycle 2
C ycle 3 
o n w ar ds
E O T 3 6
St u d y D a y
-2 8 t o - 1 
-1 4 
t o - 1
1
2
3
4 * 8
1 5 1
4 * 8
1 5 1
8
1 5
Visit Wi n d o w ( d a ys)
± 1 ± 1 ± 1 ± 1
± 1 ± 2 ± 2 ± 2 ± 2
+ 7
± 1 4
p ol y merase c hai n reacti o n; R N A = ri b o n ucleic aci d; SI F E = ser u m i m m u n ofi xati o n electr o p h oresis; S P E P = ser u m pr otei n electr o p h oresis; T C R = T-cell 
rece pt or; T B N K = T, B, a n d N K l y m p h oc ytes; UI F E = 2 4 hr uri ne i m m u n ofi xati o n electr o p h oresis ; U P E P = 2 4 hr uri ne pr otei n electr o p h oresis.
* P lease see Sc he d ule o f P har mac o ki netic, S ol u ble Fact or a n d C yt o ki ne Assess me nts A f or a d diti o nal assess me nts o n C ycle 1 Da y 4 ( C 1 D 4) a n d C ycle 2 Da y 4 
( C 2 D 4).
F o ot n otes f or Sc he d ule of Acti vities A
1.
Scree ni n g: T o be c o m plete d wit hi n 2 8 da ys pri or t o start of st u d y treat me nt.
2.
I nf or me d C o nse nt: M ust be o btai ne d pri or t o u n der g oi n g a n y st u d y s pecific pr oce d ures, a n d be c o m plete d wit hi n 2 8 da ys pri or t o start of st u d y treat me nt.
3.
M y el o m a H ist or y: wi ll be c ollecte d wit hi n 2 8 da ys d uri n g scree ni n g pri or t o start of st u d y treat me nt.  I ncl u des hist or y of disease u n der st u d y i ncl u di n g 
details of pri mar y dia g n osis, bi o ps y i nf or mati o n, a n d treat me nt hist or y.
4.
Me dic al Hist or y:
I ncl u des hist or y of disease pr ocess ot her t ha n t he ca ncer u n der st u d y (acti ve or res ol ve d) a n d c o nc urre nt ill ness.  I ncl u des pri or 
treat me nts a n d a n y c urre nt me dical treat me nts f or a n y c o n diti o n.
5.
B aseli ne Si g ns & S y m pt o ms: Patie nts will be as ke d a b o ut a n y si g ns a n d s y m pt o ms e x perie nce d w it hi n t he 2 8 da ys pri or t o C 1 D 1.  D uri n g t he st u d y, a n y 
ne w or w orse ne d c o n diti o ns s i nce baseli ne will be rec or de d o n t he A d verse E ve nts ( A E) case re p ort f or m ( C R F) pa ge. 
6.
Re gistr ati o n : Patie nt n u m ber a n d d ose le vel all ocati o n assi g ne d b y Pfizer I nc. 
7.
P atie nt h os pit aliz ati o n: All patie nts i n Part 1 I V or S C m o n ot hera p y d ose escalati o n wil l be h os pitalize d f or 7 2 hrs fr o m C ycle 1 Da y 1 ( C 1 D 1).  
H os pitalizati o n peri o d ma y be e xte n de d if t he patie nt e x perie nces a b n or mal la b orat or y fi n di n gs or o n g oi n g a d verse e ve nts t hat
re q uire f urt her 
h os pitalizati o n.
8.
P h ysic al e x a mi n ati o n ( P E): P h y sical e xa mi nati o n i ncl u des ne ur ol o gical assess me nt a n d, at scree ni n g , will als o i ncl u de hei g ht.
9.
Wei g ht:
Wei g ht will be meas ure d pri or t o d osi n g.
1 0. Vit al Si g ns: I ncl u des te m perat ure ( oral, t y m pa nic, te m p oral or a xillar y), bl o o d press ure ( B P), a n d p ulse rate t o be rec orde d i n t he sitti n g p ositi o n after 
5 mi n utes of rest.
1 1. Perf or m a nce St at us: Use Easter n C o o perati ve O nc ol o g y Gr o u p ( E C O G) – see A p pe n di x 4 .
1 2. 1 2 -Le a d el ectr oc ar di o gr a m ( E C G): At scree ni n g, si n gle 1 2-lea d E C G will be perf or me d.  O n C 1 D 1 u ntil C 2 D 1 5, tri plicate 1 2-lea d E C Gs will be 
perf or me d t o deter mi ne mea n Q Tc F i nter val.  O n Da y 1, 8 , a n d 1 5 of C ycles 1 a n d 2, E C Gs will be perf or me d pri or t o i n vesti gati o nal pr o d uct 
a d mi nistrati o n ( u p t o 6 0 mi n utes bef ore d osi n g), a n d t he e n d of i nf usi o n or s u bc uta ne o us i njecti o n.  F or s u bc uta ne o us a d mi nistrati o n o nl y, tri plicate 1 2 -lea d 
E C Gs will als o be perf or me d o n Da y 4 of C ycles 1 a n d 2.  Fr o m C ycle 3 o n war ds, si n gle 1 2 -lea d E C G will be perf or me d o n Da y 1 of eac h c ycle pri or t o 
i n vesti gati o nal pr o d uct a d mi nistrati o n ( u p t o 6 0 mi n utes bef ore d osi n g).  W he n c oi nci di n g wit h bl o o d sa m ple dra ws f or p har maco ki netics ( P K), E C G 
assess me nt s h o ul d be perf or me d pri or t o bl o o d sa m ple c ollecti o n, s uc h t hat t he bl o o d sa m ple is c ollecte d at t he n o mi nal ti me.  If t he mea n Q Tc F is 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 8
Sc he d ule of Acti vities A
Visit I de ntifier
Scree ni n g 1
D a ys pri or t o 
e nr oll me nt
Tre at m e nt Peri o d
1 m o nt h 
F oll o w -u p 3 5
S ur vi v al 
F oll o w -u p 3 7
C ycle 1
( 1 C ycle = 3 
wee ks)
C ycle 2
C ycle 3 
o n w ar ds
E O T 3 6
St u d y D a y
-2 8 t o - 1 
-1 4 
t o - 1
1
2
3
4 * 8
1 5 1
4 * 8
1 5 1
8
1 5
Visit Wi n d o w ( d a ys)
± 1 ± 1 ± 1 ± 1
± 1 ± 2 ± 2 ± 2 ± 2
+ 7
± 1 4
pr ol o n ge d ( > 5 0 0 msec), t he E C Gs s h o ul d be re -e val uate d b y a q ualifie d pers o n at t he i nstit uti o n f or c o nfir mati o n.  A d diti o nal tri plicate E C Gs ma y be 
perf or me d as cli nicall y i n dicate d. 
1 3. Ec h oc ar di o gr a m  ( Ec h o) or m ulti g ate d ac q uisiti o n sc a n ( M U G A): Ec h o or M U G A will be e val uate d i n patie nts wit h pre vi o us hist or y of car diac e ve nts.  
F or t hese patie nts, a n Ec h o or M U G A will be perf or me d at scree ni n g, w he n cli nicall y i n dicate d a n d at t he e n d of treat me nt ( E O T) visit.
1 4. H e m at ol o g y : N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 3 d a y s pri or t o t hat date.  All sa m ples will be c ollecte d pri or t o 
i n vesti gati o nal pr o d uct a d mi nistrati o n o n da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d.  See Assess me nts Secti o n 7. 1. 3 f or La b orat or y Tests 
list.
1 5. Bl o o d C he m istr y: N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 3 da ys pri or t o t hat date.  All sa m ples will be c ollecte d pri or t o 
i n vesti gati o nal pr o d uct a d mi nistrati o n o n da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d.  See Assess me nts Secti o n 7. 1. 3 f or La b orat or y Tests 
list.
1 6. C o a g ul ati o n : N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 3 d a y s pri or t o t hat date.  All sa m ples will be c ollecte d pri or t o 
i n vesti gati o nal pr o d uct a d mi nistrati o n o n da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d.  See Assess me nts Secti o n 7. 1. 3 f or La b orat or y Tests 
list.
1 7. He p atitis assess me nt : Scree ni n g tests f or he patitis B ( H B V) a n d C ( H C V) s h o ul d be perf or me d i ncl u di n g he patitis B s urface a nti ge n ( H Bs A g), he patiti s B 
c ore a nti b o d y ( H Bc A b), a n d he patitis C vir us ( H C V) a nti b o d y.  I n t he case of a p pare nt o n g oi n g H B V or H C V i nfecti o n, refle x ser u m D N A or R N A viral 
l oa d testi n g, res pecti vel y, will be perf or me d.  See Assess me nts Secti o n 7. 1. 3 f or La b orat or y Tests list.
1 8. M ulti ple x c yt o ki ne ass a ys : see S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E F A C T O R A N D C Y T O KI N E acti vities A ta ble.  See assess me nts
Secti o n 7. 5. 4 f or la b orat or y tests list.
1 9. Uri n al ysis : Di pstic k is acce pta ble.  Micr osc o pic a nal yses if di pstic k a b n or mal.  N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 3 da ys 
pri or t o t hat date.  F oll o wi n g C 1 D 1, o nl y o btai n as cli nicall y i n dicate d u ntil E O T.  See Assess me nts Secti o n 7. 1. 3 f or La b orat or y Tests list.
2 0. Pre g n a nc y Test a n d c o ntr ace pti o n c hec k :  Ser u m pre g na nc y test f or fe males of c hil d beari n g p ote ntial (see Pre g na nc y Testi n g Secti o n 7. 1. 1 ).  
C o ntrace pti o n use will be c hec ke d t o c o nfir m t hat c o ntrace pti o n is use d t hr o u g h o ut t he st u d y a n d f or 5 m o nt hs after t he last d ose of st u d y treat me nt 
c o nsiste ntl y a n d c orrectl y. C o ntrace pti o n o nl y re q uire d f or W O C B P.
2 1. Tre at m e nt wit h i n vesti g ati o n al pr o d uct P F -0 6 8 6 3 1 3 5 : I n vesti gati o nal pr o d uct will be a d mi nistere d o n Da y 1, 8 a n d 1 5 of eac h c ycle (see A d mi nistrati o n 
Secti o n 5. 4 ). If a patie nt has recei ve d treat me nt wit h e ver y wee k d osi n g ( Q 1 W) P F-0 6 8 6 3 1 3 5 f or at least 6 m o nt hs, a n d disease assess me nts ha ve re mai ne d 
sta ble o ver at least 2 m o nt hs, c o nsi derati o n may be gi ve n t o i ncreasi n g d ose i nter vals fr o m wee kl y t o e ver y 2 w ee ks or o nce e ver y t hree wee ks ( o nce per 
c ycle; o nl y C X D 1 d osi n g a n d acti vities a p plica ble) after c o ns ultati o n wit h s p o ns or.  C ycles wo ul d re m ai n t he sa me le n gt h wit h a n y s ki p pe d w ee kl y d oses 
n ote d.  If t he patie nt s u bse q ue ntl y be gi ns t o ha ve i ncrease of disease b ur de n, d ose i nter vals s h o ul d ret ur n t o wee kl y d osi n g.
2 2. Ser u m i m m u n ofi x ati o n electr o p h oresis ( SI F E), ser u m  pr otei n electr o p h oresis ( S P E P), ser u m free li g ht c h ai n a n al ysis ( F L C) tests a n d bet a -2 
mi cr o gl o b uli n tests : N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt perf or me d wit hi n 3 da ys pri or t o t hat date.  See Assess me nts Secti o n 7. 2. 1 f or 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 9
Sc he d ule of Acti vities A
Visit I de ntifier
Scree ni n g 1
D a ys pri or t o 
e nr oll me nt
Tre at m e nt Peri o d
1 m o nt h 
F oll o w -u p 3 5
S ur vi v al 
F oll o w -u p 3 7
C ycle 1
( 1 C ycle = 3 
wee ks)
C ycle 2
C ycle 3 
o n w ar ds
E O T 3 6
St u d y D a y
-2 8 t o - 1 
-1 4 
t o - 1
1
2
3
4 * 8
1 5 1
4 * 8
1 5 1
8
1 5
Visit Wi n d o w ( d a ys)
± 1 ± 1 ± 1 ± 1
± 1 ± 2 ± 2 ± 2 ± 2
+ 7
± 1 4
la b orat or y disease assess me nt tests list.  Beta 2 micr o gl o b uli n will be c ollecte d o n C 1 D 1 ( ot her ti me p oi nts are o pti o nal).  N ote t hat SI F E will o nl y be 
c o m plete d at baseli ne w he n electr o p h oresis s h o ws n o meas ura bl e pr otei n, at s us pecte d C R, a n d at s us pecte d pr o gressi o n (cli nical or bi oc he mical).  W he n a 
c o m plete res p o nse ( C R) or a cli nical or bi oc he mical pr o gressi o n is s us pecte d, S P E P, SI F E, a n d ser u m free li g ht c hai n a nal ysis ( F L C) tests will be re peate d 
wit hi n 1 t o 4 we e ks.  F or patie nts sc he d ule d t o be d ose escalate d, sa m ples will als o be c ollecte d w it hi n 1 wee k pri or t o recei vi n g t he firs t hi g her d ose.  All 
sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n o n da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d.   If patie nts were 
treate d wit h darat u m u ma b less t ha n 1 1 4 da ys pri or t o pla n ne d treat me nt da y, darat u m u ma b will i nterfere wit h S P E P, U P E P, SI F E a n d UI F E assa ys.  
T heref ore, f or t hese patie nts, F L C assa y s h o ul d be c o m plete d at scree ni n g, C 1 D 1, a n d all s u bse q ue nt disease assess me nts. I n t hese patie nts w h o pre vi o usl y 
recei ve d darat u m u ma b ser u m a n d uri ne M-s pi ke if meas ura ble at baseli ne i n t hese patie nts s h o ul d als o be f oll o we d at t he sa me ti me p oi nts as F L C wit h t he 
m o st re prese ntati ve mar ker of disease stat us use d f or deter mi nati o n I M W G assess me nt.
2 3. 2 4 hr uri ne i m m u n ofi x ati o n electr o p h oresis ( UI F E), 2 4 hr uri ne pr otei n electr o p h oresis ( U P E P) : N o nee d t o re peat o n C 1 D 1 if baseli ne assess me nt 
perf or me d wit hi n 3 d a y s pri or t o t hat date.  See Assess me nts Secti o n 7. 2. 1 f or la b orat or y disease assess me nt tests list.  N ote t hat UI F E will o nl y be 
c o m plete d at baseli ne w he n electr o p h oresis s h o ws n o meas ura ble pr otei n, at s us pecte d C R, a n d at s us pecte d pr o gres si o n (cli nical or bi oc he mical).  W he n a 
C R or a cli nical or bi oc he mical pr o gressi o n is s us pecte d, U P E P a n d UI F E will be re peate d wit hi n 1 t o 4 w ee ks.  F or patie nts s c he d ule d t o be d ose escalate d, 
sa m ples will als o be c ollecte d wit hi n 1 wee k pri or t o recei v i n g t he first hi g her d ose.  If sa m ples c ollecti o n da y c oi nci des wit h da ys w here b y i n vesti gati o nal 
pr o d uct is t o be a d mi nistere d, sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n.
2 4. B o ne M arr o w C ollecti o n a n d Assess me nts : F or C 1 D 1 a n d o n treat me nt b o ne marr o w c ollecti o ns a n d assess me nts, see- Secti o n 7. 2. 2 .  Sa m ple f or C ycle 1 
D a y 1 ( C 1 D 1) ma y be ta ke n u p t o 7 da ys bef ore st u d y treat me nt.   B o ne marr o w  c ollecti o ns a n d l ocal plas ma cell assess me nts s h o ul d be fi xe d acc or di n g t o 
t he cale n dar, re gar dless of treat me nt dela ys.  B o ne marr o w  e val uati o n c o nsisti n g of b o ne marr o w as pirate a n d/ or b o ne marr o w bi o psies will be perf or me d t o 
f oll o w disease res p o nse.  W he n b o ne marr o w plas macell i nfiltrati o n is assesse d b y b ot h b o ne marr o w as pirate a n d b y b o ne marr o w bi o ps y, t he hi g hest 
val ue of b o ne marr o w  -plas macell i nfiltrati o n s h o ul d be utilize d f or res p o nse e val uati o n.  B o ne marr o w  as pirates will als o be c ollecte d a n d plas ma cells will 
be e val uate d at ti me of s us pecte d c o m plete res p o nse ( C R) a n d o pti o nal at ti me of s us pecte d disease pr o gressi o n.  B o ne marr o w  bi o ps y will als o be c ollecte d 
a n d plas ma cells will be e val uate d w he n c o nfir mati o n of stri n ge nt c o m plete res p o nse (s C R -) is re q uire d.  F or patie nts w h o e x perie nce a platea u or C R, 
a d diti o nal B M as pirates at 9 m o nt hs after C 1 D 1 a n d o n war ds w ill be o pti o nal.  O pti o nal b o ne marr o w as pirate a n d bi o ps y sa m ples will als o be ta ke n at 
disease pr o gressi o n if a sa m ple w as n ot ta ke n wit hi n t he past 4 wee ks.  If a patie nt is sc he d ule d f or escalati o n t o t he ne xt hi g hest d ose le vel c o h ort f oll o w i n g 
6 0 da y late t o xicit y e val uati o n, a b o ne marr o w as pirate will be c ollecte d w it hi n 1 wee k bef ore d ose escalati o n, u nless a n -o ntreat me nt - sa m ple was c ollecte d 
wit hi n t he past 2 8 da ys or t he i n vesti gat or assesses t hat t here i n a n u nj ustifia ble ris k f or t he patie nt, a n d/ or t he patie nt ref uses t o u n der g o a b o ne marr o w 
pr oce d ure.  A b o ne marr o w as pirate sa m ple will be c ollecte d f or ce ntral M R D assess me nt usi n g t he ne xt ge nerati o n se q ue nci n g ( N G S) assa y w he n patie nt 
is i n s us pecte d C R or act ual C R. A C 1 D 1 b o ne marr o w  as pirate m ust als o be c ollecte d i n all patie nts as t he baseli ne M R D
refere nce sa m ple. Sa m ples f or
M R D assess me nts s h o ul d be ali q u ote d fr o m t he first b o ne marr o w as pirate p ull. S a mples at 1 a n d 3 m o nt hs after C 1 D 1 will be c ollecte d 7 da ys; sa m ples 
at 9 m o nt hs after C 1 D 1 a n d later will be c ollecte d 1 4 da ys .  
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6 0
Sc he d ule of Acti vities A
Visit I de ntifier
Scree ni n g 1
D a ys pri or t o 
e nr oll me nt
Tre at m e nt Peri o d
1 m o nt h 
F oll o w -u p 3 5
S ur vi v al 
F oll o w -u p 3 7
C ycle 1
( 1 C ycle = 3 
wee ks)
C ycle 2
C ycle 3 
o n w ar ds
E O T 3 6
St u d y D a y
-2 8 t o - 1 
-1 4 
t o - 1
1
2
3
4 * 8
1 5 1
4 * 8
1 5 1
8
1 5
Visit Wi n d o w ( d a ys)
± 1 ± 1 ± 1 ± 1
± 1 ± 2 ± 2 ± 2 ± 2
+ 7
± 1 4
2 5. Dise ase asse ss me nts b y fl u or o de o x y gl uc ose ( F D G) p ositr o n e missi o n t o m o gr a p h y ( P E T)/ c o m p uterize d t o mo gr a p h y ( C T): See Assess me nts 
Secti o n 7. 2. 3 .  Ra di o gra p hic assess me nts o btai ne d per t he patie nt’s sta n dar d of care pri or t o e nr oll me nt i nt o t he st u d y d o n ot nee d t o be re peate d a n d are 
acce pta ble t o be use d as baseli ne e val uati o n, if, ( 1) o btai ne d wit hi n 2 8 da ys bef ore C 1 D 1 , ( 2) t he sa me tec h ni q ue/ m o dalit y ca n be use d t o f oll o w i de ntifie d 
lesi o ns t hr o u g h o ut t he trial f or a gi ve n patie nt, a n d ( 3) a p pr o priate d oc u me ntati o n i n dicati n g t hat t hese ra di o gra p hic t u m or assess me nts were perf or me d as 
sta n dar d of care is a vaila ble i n the patie nt’s s o urce n otes.  F or all patie nts, i ma ges are re q uire d at scree ni n g, s us pecte d C R, w he n disease pr o gressi o n is 
s us pecte d (e g, s y m pt o matic deteri orati o n), e n d of treat me nt visit (if n ot d o ne i n pre vi o us 4 w ee ks) a n d w he n ot her wise cli nicall y i n di cate d.   I n patie nts wit h 
meas ura ble tar get lesi o ns at scree ni n g, i ma ges at 1 a n d 3 m o nt hs after C 1 D 1 will be c ollecte d ± 7 da ys; i ma ges at 9 m o nt hs after C 1 D 1 a n d e ver y 6 m o nt hs 
t hereafter will be c ollecte d ± 1 4 da ys . F or sites i n Ger ma n y: O nl y M RI is all o wed t o be use d as i ma gi n g m o dalit y f or partici pa nts.
2 6. A d verse E ve nt ( A E) Assess me nts : A Es s h o ul d be d oc u me nte d a n d rec or de d at eac h visit usi n g t he Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y 
Criteria f or A d verse E ve nts ( N CI C T C A E) versi o n 4. 0 3.  H o w e ver, t he se verit y of c yt o ki ne release s y n dr o me ( C R S) will be assesse d acc or di n g t o t he 
gra di n g descri be d b y Lee et al. ( 2 0 1 4 a n d 2 0 1 9 2 ,3 See A p pe n di x 5 ) i nstea d of C T C A E. I n a d diti o n, A merica n S ociet y f or Tra ns pla ntati o n a n d Cell ular 
T hera p y ( A S T C T) c o nse ns us gra di n g of C R S a n d i m m u ne effect or cell -ass ociate d ne ur ot o xicit y (I C A N S) 3will be ca pt ure d se paratel y fr o m t he A E 
assess me nts ( See A p pe n di x 5 ). T he ti me peri o d f or acti vel y eliciti n g a n d c ollecti n g A Es a n d S A Es ( “acti ve c ollecti o n peri o d”) f or eac h patie nt be gi ns fr o m 
t he ti me t he patie nt pr o vi des i nf or me d c o nse nt t hr o u g h a n d i ncl u di n g a mi ni m u m of 9 0 cale n dar da ys after t he last i n vesti gati o nal pr o d uct a d mi nistrati o n.  
If t he patie nt be gi ns a ne w a ntica ncer t her a p y, t he peri o d f or rec or di n g n o n-seri o us A Es o n t he case re p ort f or m ( C R F) e n ds at t he ti me t he ne w treat me nt is 
starte d.  H o we ver, a n y S A Es occ urri n g d uri n g t he acti ve c ollecti o n peri o d m ust still be re p orte d t o Pfizer Safet y a n d rec or de d o n t he C R F, ir res pecti ve of 
a n y i nter ve ni n g treat me nt.
2 7. C o nc o m it a nt Tre at me nts: all c o nc o mita nt me dicati o ns a n d N o n dr u g S u p p orti ve I nter ve nti o ns s h o ul d be rec or de d o n t he C R F.
2 8. Ge netic A n al ysis : B o ne marr o w as pirates ta ke n o n C 1 D 1 will be e val uate d at l ocal la b f or t( 4; 1 4)( p 1 6; q 3 2), t( 1 4; 1 6)( q 3 2; q 2 3), 1 7 p 1 3 deleti o ns, 
t( 1 1; 1 4)( q 1 3; q 3 2), c hr o m os o me 1 3 deleti o n, pl oi d y cate g or y, a n d c hr o m os o me 1 a b n or malities . If s o me of t hese c yt o ge netic assess me nts ca n n ot be d o ne, 
site s h o ul d pr o vi de patie nt’s m ost rece nt c yt o ge netic testi n g res ults a n d e nter i nt o e C R F.  Sa m ple m a y be ta ke n u p t o 7 da ys bef ore t he start of st u d y 
treat me nt.
2 9. B C M A + e x pressi o n o n m ulti ple m y el o m a cells i n b o ne m arr o w: E x pressi o n of B C M A will be e val uate d o n fres h b o ne marr o w  as pirates ( b y fl o w 
c yt o metr y) a n d bio psies ( b y I H C).  E x pressi o n of a d diti o nal mar kers i ncl u di n g C D 1 3 8 will als o be e val uate d.  A d diti o nal a nal yses ma y be perf or me d o n 
b o ne marr o w  bi o psies, i ncl u di n g i m m u n o p he n ot y pi n g of i nfiltrati n g i m m u ne cells a n d e x pl orat or y m olec ular a nal yses. If t he sa mple c ollecti o n da y 
c oi nci des wit h da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d, sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n .  Sa m ple 
f or C ycle 1 Da y 1 ( C 1 D 1) ma y be ta ke n u p t o 7 da ys bef ore st u d y treat me nt ; sa m p les at 1 a n d 3 m o nt hs after C 1 D 1 will be c ollecte d pre -d ose 7 da ys; 
sa m ples at 9 m o nt hs after C 1 D 1 will be c ollecte d pre -d ose 1 4 da ys.  .
3 0. S ol u ble B C M A : See Sc he d ule of P har mac o ki netic, S ol u ble Fact or a n d C yt o ki ne Acti viti es A.  S ol u ble B C M A will be meas ure d i n plas ma b y mass 
s pectr o metr y. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6 1
Sc he d ule of Acti vities A
Visit I de ntifier
Scree ni n g 1
D a ys pri or t o 
e nr oll me nt
Tre at m e nt Peri o d
1 m o nt h 
F oll o w -u p 3 5
S ur vi v al 
F oll o w -u p 3 7
C ycle 1
( 1 C ycle = 3 
wee ks)
C ycle 2
C ycle 3 
o n w ar ds
E O T 3 6
St u d y D a y
-2 8 t o - 1 
-1 4 
t o - 1
1
2
3
4 * 8
1 5 1
4 * 8
1 5 1
8
1 5
Visit Wi n d o w ( d a ys)
± 1 ± 1 ± 1 ± 1
± 1 ± 2 ± 2 ± 2 ± 2
+ 7
± 1 4
3 1. T B N K a n d I m m u n o p he n ot y pi n g: e n u merati o n a n d p he n ot y pes of T -cell s u bsets b y m ulti para meter fl o w c yt o metr y.  If sa m ple c ollecti o n da y c oi nci des 
wit h da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d, sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d m i nistrati o n.  B o ne marr o w  
sa mple f or C ycle 1 Da y 1 ( C 1 D 1) ma y be ta ke n u p t o 7 da ys bef ore st u d y treat me nt ; sa m ples at 1 m o nt h or 3 m o nt hs after C 1 D 1 will be c ollecte d 7 da ys.  
. 
3 2. Ge ne e x pressi o n ri b o n ucleic aci d ( R N A) pr ofile: ge ne e x pressi o n ass ociate d wit h acti vati o n state a n d a nti -t u mor acti vit y will be meas ure d b y  R N A 
se q ue nci n g i n b o ne marr o w.  If sa m ple c ollecti o n da y c oi nci des wit h da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistered, sa m ples will be c ollecte d 
pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n.  B o ne marr o w sa m ple f or C ycle 1 Da y 1 ( C 1 D 1) ma y be ta ke n u p t o 7 d a y s bef ore st u d y treat me nt; sa m ples 
at 1 m o nt h or 3 m o nt hs after C 1 D 1 will be c ollecte d 7 da ys; sa m ples at 9 m o nt hs after C 1 D 1 will be c ollecte d 1 4 da ys.  W he n b o ne marr o w as pirate 
sa m ples are ta ke n f or disease res p o nse e val uati o n,  sa m ples f or ge ne e x pressi o n a nal ysis will als o be ac q uire d.
3 3. T -cell rece pt or ( T C R) se q ue nci n g : cl o nal e x pa nsi o n, c o ntracti o n a n d di versit y a n d its ass ociati o n wit h acti vit y a n d d ura bilit y will be assesse d b y 
de o x yri b o n ucleic aci d ( D N A) se q ue nci n g of T C R i n b o ne marr o w .  If sa m ple c ollecti o n da y c oi nci des wit h da ys w here b y i n vesti gati o nal pr o d uct is t o be 
a d mi nistere d, sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n.  B o ne marr o w sa m ple f or C ycle 1 Da y 1 ( C 1 D 1) ma y be ta ke n u p t o 
7 da ys bef ore s t u d y treat me nt; sa m ples at 1 m o nt h or 3 m o nt hs after C 1 D 1 will be c ollecte d 7 da ys; sa m ples at 9 m o nt hs after C 1 D 1 will be c ollecte d
1 4 da ys.  W he n b o ne marr o w as pirate sa m ples are ta ke n f or disease res p o nse e val uati o n, sa m ples f or T C R se q u e nci n g will als o be ac q uire d.
3 4. Ge n o mic b a n ke d bi os peci me ns Pre p D 1: If n ot c ollecte d o n C 1 D 1, c ollect at t he ne xt a vaila ble ti me p oi nt w he n bi os peci me ns are bei n g c ollecte d i n 
c o nj u ncti o n wit h a patie nt visit.
3 5. O ne m o nt h f oll o w -u p: At least 2 8 cale n dar da ys, a n d n o m ore t ha n 3 5 cale n dar da ys, after disc o nti n uati o n of treat me nt, patie nts will ret ur n t o u n der g o 
re vie w of c o nc o mita nt treat me nts, vital si g ns, a n d assess me nt f or res ol uti o n of a n y treat me nt-relate d t o xicit y.  Patie nts c o nti n ui n g t o e xperie nce t o xicit y at 
t his p oi nt f oll o wi n g disc o nti n uati o n of treat me nt will c o nti n ue t o be f oll o we d at least e ver y 4 we e ks u ntil res ol uti o n or deter mi nati o n, i n t he cli nical 
j u d g me nt of t he i n vesti gat or, t hat n o f urt her i m pr o ve me nt is e x pecte d.  If t he patie nt c o m pletes t he f oll o w-u p visit pri or t o c o m pleti o n of t he 6 0 d a y  l o n g 
ter m d ose li miti n g t o xicit y ( D L T) o bser vati o n peri o d, a f oll o w u p p h o ne call will be c o m plete d o n at least Da y 6 0, a n d n o m ore t ha n Da y 6 5.
3 6. E n d of Tre at me nt ( E O T) Visit: O btai n t hese assess me nts if n ot c o m plete d i n t he last wee k (last 4 wee ks f or disease assess me nts).
3 7. S ur vi v al f oll o w u p: F oll o w i n g disc o nti n uati o n of st u d y treat me nt ( u nless patie nts are l ost t o f oll o w u p, c o nse nt is wit h dra w n, or st u d y is disc o nti n ue d b y 
t he s p o ns or), s ur vi val stat us will be c ollecte d b y tele p h o ne e ver y 3 m o nt hs u ntil deat h, or u p t o a p pr o xi matel y 3 0 m o nt hs after last patie nt first d ose, 
w hic he ver c o mes first.  S u bse q ue nt a nti -ca ncer t hera pies a n d rele va nt tra ns pla nt i nf or mati o n will als o be c ollecte d. A n y sta n dar d of care ( S O C) disease 
assess me nts o btai ne d bet wee n E O T a n d s u bse q ue nt a nti -ca ncer t hera p y will be c ollecte d. 
3 8. L oc al Site I njecti o n T oler a bilit y Assess me nt ( S C A d mi nistr ati o n C o h ort O nl y): Assess me nt of i njecti o n site s h o ul d be c o n d ucte d at 1 t o 4 h o urs 
f oll o wi n g treat me nt a d mi nistrati o n o n Da y 1, 8 a n d 1 5 f or t he first c ycle.  If i njecti o n site pai n or i njecti o n site reacti o n (I S R) c haracteristics c o nti n ue t o 
persist after t he first c ycle, l ocal site i njecti o n t olera bilit y assess me nts s h o ul d c o nti n ue u ntil t he s y m pt o ms res ol ve.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6 2
S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E F A C T O R A N D C Y T O KI N E A C T I VI TI E S A: P A R T 1 I V A N D S C 
W E E K L Y M O N O T H E R A P Y ( N O P RI MI N G D O S E )
T he sc he d ule of p har mac o ki netic, s ol u ble fact or a n d c y t o ki ne acti vities ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d 
pr oce d ures.  T his sc he d ule of acti vities is a p plica ble t o Part 1 I V a n d S C m o n ot hera py d ose escalati o n c o h orts .  T he i n vesti gat or ma y  
sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d i n t he sc he d ule of activities ta ble i n or der t o c o n d uct e val uati o ns or 
assess me nts re q uire d t o pr otect t he well -bei n g of t he patie nt.   See A p pe n di x 1 0 f or alter nati ve meas ure g ui deli nes d ue t o C O VI D- 1 9.
Visit 
I de ntifier
U p t o 7 
d a ys 
pri or t o 
C 1 D 1
Tre at m e nt Peri o d
E O T
C ycle 1
C ycle 2
C ycle 3 o n w ar ds
St u d y D a y
D 1  
D 2  
D 4  
D 8
D 1 5
D 1  
D 4  
D 8
D 1 5
D 1
H o urs Pre/ 
after d osi n g †
0 
2 *
4 *
8
2 4 
7 2
0 
2 *
4 *
0 
2 *
0 
2 *
4 *
7 2
0 
2 *
0 
2 *
0 
2 *
Visit wi n d o w
0. 5 
hr
1 
hr
3 
hrs
2 4 
hrs
0. 5 
hr
1 hr
2 4 
hrs
C y t o ki ne 
e val uati o n i n 
ser u m1
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
X
3 ( 7 da ys) 
a n d 
9 m o nt hs 
(1 4 da ys) 
after C 1 D 1
Sa m ples f or 
P F - 0 6 8 6 3 1 3 5 
bl o o d le vel 2
X  
X  
X  
X  
X  
X  
X
(I V 
o nl y)
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X
(I V 
o nl y)
X  
X  
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X 2
X 2
(I V 
o nl y
)
X
Bl o o d sa m ples 
f or A D A a n d 
N A b a gai nst 
P F -0 6 8 6 3 1 3 5 3
X
X  
X
X 3
X
S ol u ble B C M A 
a n d ot her 
fact ors4
X  
X  
X  
X  
X  
X  
X  
X
(I V 
o nl y)
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X
(I V 
o nl y)
X  
X  
X
(I V 
o nl y)
X  
X
(I V 
o nl y)
X 4
X 4
(I V 
o nl y
)
X
A b bre viati o ns: A nti -P F -0 6 8 6 3 1 3 5 a nti b o dies = A D A; B C M A = B -cell mat urati o n a nti ge n; D = Da y; E O T = e n d of treat me nt; ne utralizi n g a nti b o dies = N A b.
* F or i ntra ve n o us (I V) a d mi nistrati o n, t he 2-h o ur sa m ple s h o ul d be ta ke n i m me diatel y ( u p t o 1 5 mi n utes bef ore) bef ore t he e n d of P F -0 6 8 6 3 1 3 5 i nf usi o n; if 
t he i nf usi o n is l o n ger t ha n 2 h o urs ( or s h orter if a 1 h o ur i nf usi o n is teste d), t he c ollecti o n ti me of t his sa m ple s h o ul d be a dj uste d acc or di n gl y f or t he sa m ple t o 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6 3
Visit 
I de ntifier
U p t o 7 
d a ys 
pri or t o 
C 1 D 1
Tre at m e nt Peri o d
E O T
C ycle 1
C ycle 2
C ycle 3 o n w ar ds
St u d y D a y
D 1  
D 2  
D 4  
D 8
D 1 5
D 1  
D 4  
D 8
D 1 5
D 1
H o urs Pre/ 
after d osi n g †
0 
2 *
4 *
8
2 4 
7 2
0 
2 *
4 *
0 
2 *
0 
2 *
4 *
7 2
0 
2 *
0 
2 *
0 
2 *
be c ollecte d i m me diatel y bef ore t he act ual e n d of P F -0 6 8 6 3 1 3 5 i nf usi o n.  F or s u bc uta ne o us a d mi nistrati o n, t he 2-h o ur sa m ple s h o ul d be ta ke n at 2 h o urs 
p ost -i njecti o n 1 2 mi n utes ; als o f or S C a d mi nistrati o n, wit h t he e xce pti o n of c yt o ki ne sa m ples, 2 a n d 4 hr sa m ples are n ot nee de d ot her t ha n o n C ycle 1 D 1 .  
† Sa m pli n g ti mes are relate d t o t he start of t he i nf usi o n.  All eff orts will be ma de t o o btai n t he p har mac o ki netic ( P K) sa m ples at t he e xact n o mi nal ti me 
relati ve t o d osi n g.  H o we ver, sa m ples o btai ne d wit hi n t he wi n d o w s pecifie d will be c o nsi dere d acce pta ble.  
F o ot n otes f or Sc he d ule of P h ar m ac o ki netic, S ol u ble F act ors a n d C yt o ki ne Acti vities A
1.
C yt o ki ne e v al u ati o n i n ser u m: See C yt o ki ne Assess me nts Secti o n 7. 5. 4 f or a f ull list of c yt o ki ne assess me nts.  All sa m ples will be a nal yze d ce ntrall y.  
All 0 h o ur sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n o n da ys w here b y i n ves ti gati o nal pr o d uct is t o be a d mi nistere d.  If C R S 
is s us pecte d, a n a d h oc c yt o ki ne sa m ple will be c ollecte d(see Secti o n 7. 1. 3 La b orat or y Safet y Assess me nts).  S h o ul d t he site re q uire c yt o ki ne i nf or mati o n 
f or patie nt ma na ge me nt, t he site will ha ve t he o pti o n of c ollecti n g a n a d diti o nal sa m ple f or l ocal a nal ysis. If a sa m ple f or c yt o ki ne pa nel e val uati o n is d ue 
t o be c ollecte d o n t he sa me da y as t he da y a s us pecte d C R S e ve nt occ urs, t he n a n a d h oc sa m ple f or ce ntral a nal ysis is n ot req uire d/c ollecte d. H o w e ver, 
a n a d h oc sa m ple f or l ocal a nal ysis ma y still be c oll ecte d f or patie nt ma na ge me nt.  
2.
Bl o o d s a m ple f or P F -0 6 8 6 3 1 3 5 bl o o d le vel: A p pr o xi matel y 5 m L sa m ple of w h ole bl o o d (t o pr o vi de a p pr o xi matel y 2 m L of ser u m) will be c ollecte d at 
eac h ti me p oi nt f or P K a nal ysis of P F -0 6 8 6 3 1 3 5.  After C ycle 8, pre - a n d p ost- dose P K sa m ples will be c ollecte d o nl y o n e ver y 4 t h c ycle ( C ycle 8, 
C y cle 1 2, C ycle 1 6, etc.).  A n a d diti o nal P K sa m ple s h o ul d als o be ta ke n if C R S is s us pecte d, a n d a P K sa m ple is n ot alrea d y sc he d ule d t o be ta ke n 
(e g, C ycle 3 o n war ds).
3.
A nti P F -0 6 8 6 3 1 3 5 A n ti b o dies ( A D A) a n d Ne utr alizi n g A nti b o dies ( N A b): C ollecti o n of t w o 1 m L pre -d ose ser u m sa m ples (fr o m 5 m L t otal w h ole 
bl o o d) t o detect t he prese nce of a nti b o dies t o P F -0 6 8 6 3 1 3 5 is t o be o btai ne d pri or t o t he start of treat me nt.  Patie nts ha vi n g a n u nres ol ve d a d verse e ve nt 
t hat is p ossi bl y relate d t o a nti-P F -0 6 8 6 3 1 3 5 a nti b o dies at t heir last assess me nt will be as ke d t o ret ur n t o t he cli nic f or A D A a n d dr u g c o nce ntrati o n bl o o d 
sa m pli n g at a p pr o xi matel y 3-m o nt h i nter vals u ntil t he a d verse e ve nt or its se q uela e res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d 
s p o ns or.  After C ycle 4, pre -d ose A D A a n d N A b sa m ples will be c ollecte d o nl y o n C ycles 6, 8, a n d e ver y 4 t h c ycle t hereafter ( C ycle 8, C ycle 1 2, 
C y cle 1 6, etc.).
4.
S ol u ble B C M A a n d ot her f ac t ors: A p pr o xi matel y 3 m L sa m ple of w h ole bl o o d (t o pr o vi de a p pr o xi matel y 1
m L of plas ma) will be c ollecte d at eac h 
ti me p oi nt f or a nal ysis of s ol u ble B C M A a n d ot her fact ors b y mass s pectr o metr y.  All 0 h o ur sa m ples will be c ollecte d pri or t o i n vesti gati o na l pr o d uct 
a d mi nistrati o n o n da ys w here b y i n vesti gati o nal pr o d uct is t o be a d mi nistere d.  After C ycle 8, pre - a n d p ost-d ose P K sa m ples will be c ollecte d o nl y o n 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6 4
Visit 
I de ntifier
U p t o 7 
d a ys 
pri or t o 
C 1 D 1
Tre at m e nt Peri o d
E O T
C ycle 1
C ycle 2
C ycle 3 o n w ar ds
St u d y D a y
D 1  
D 2  
D 4  
D 8
D 1 5
D 1  
D 4  
D 8
D 1 5
D 1
H o urs Pre/ 
after d osi n g †
0 
2 *
4 *
8
2 4 
7 2
0 
2 *
4 *
0 
2 *
0 
2 *
4 *
7 2
0 
2 *
0 
2 *
0 
2 *
e ver y 4 t h c ycle ( C ycle 8, C ycle 1 2, C ycle 1 6, etc.).  A n a d diti o nal s ol u ble B C M A/ ot her fact or sa m p le s h o ul d als o be ta ke n if C R S is s us pecte d, a n d a 
sa m ple is n ot alrea d y sc he d ule d t o be ta ke n (e g, C ycle 3 o n war ds).
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9 4
1. I N T R O D U C TI O N
1. 1.
Mec h a nis m of Acti o n/ I n dic ati o n
P F -0 6 8 6 3 1 3 5 is a bis pecific m o n ocl o nal a nti b o d y  a gai nst B-cell mat urati o n a nti ge n ( B C M A, 
als o k n o w n as t u m or necr osis fact or rece pt or s u perfa mil y  me m ber 1 7 [ T N F R S F 1 7] or cl uster 
of differe ntiati o n [ C D] 2 6 9) a n d C D 3.  Tar gete d T- cell me diate d c yt ot o xicit y f oll o ws t he 
bi n di n g of o ne e pit o pe of P F -0 6 8 6 3 1 3 5 t o C D 3 e x pressi n g T -cells, a n d a sec o n d e pit o pe t o 
B C M A e x pressi n g m ulti ple m y el o ma cells.  I n t his cli nical st u d y , P F-0 6 8 6 3 1 3 5 will be 
e val uate d f or t he treat me nt of a d ult patie nts wit h rela pse d or refract or y m ulti ple m y el o ma as 
m o n ot hera p y a n d i n c o m bi nati o n wit h le nali d o mi de, p o mali d o mi de , or de xa met has o ne .
1. 2. B ac k gr o u n d a n d R ati o n ale
1. 2. 1. M ulti ple M yel o m a
M ulti ple m y el o ma ( M M) is a he mat ol o gical mali g na nc y  t hat is c haracterize d b y u nc o ntr olle d 
e x pa nsi o n of b o ne marr o w plas ma cells.  A p pr o xi matel y  1 1 4, 0 0 0 ne w cases of M M are 
dia g n ose d w orl d wi de eac h y ear, a n d 8 0, 0 0 0 patie nts will die fr o m t heir disease. 6 I n t he U S, 
t he i nci de nce of M M has i ncrease d fr om 4. 9 1 per 1 0 0, 0 0 0 i n 1 9 7 5, t o 6. 7 9 per 1 0 0, 0 0 0 i n 
2 0 1 3. 7  M ore patie nts are dia g n ose d at a n ol der a ge; 3 4. 4 per 1 0 0, 0 0 0
dia g n ose d at 
a ge 6 5 a n d o ver, w hilst 2. 4 per 1 0 0, 0 0 0 are dia g n ose d u n der t he a ge of 6 5.
M M is a disease t hat e v ol ves fr o m a pre- mali g na nt sta ge of m o n ocl o nal ga m m o pat h y  of 
u n deter mi ne d cli nical si g nifica nce ( M G U S), t o as y m pt o matic s m ol deri n g m y el o ma, t o 
s ym pt o matic acti ve m yel o ma .8 D uri n g t he acti ve sta ge of disease, a maj orit y  of patie nts 
de vel o p pai nf ul b o ne lesi o ns a n d or ga n d ys f u ncti o n, lea di n g t o a ne mia, re nal i ns ufficie nc y 
a n d h y percalce mia.  W hilst patie nts wit h s m ol deri n g m yel o ma d o n ot re q uire pri mar y 
t hera py, t he treat me nt re gi me n f or patie nts wit h acti ve disease is c urre ntl y de pe n de nt o n t he 
patie nt’s eli gi bilit y  t o recei ve a n a ut ol o g o us ste m cell tra ns pla nt ( A S C T).  F or patie nts 
< 7 0 ye ars ol d wit h n o c o m or bi dities, i n d ucti o n t hera p y (eit her pr oteas o me i n hi bit or- base d or 
i m m u n o m o d ulati o n-base d re gi me ns) c o m bi ne d wit h a n A S C T is t he s u g geste d a p pr oac h, 
wit h 2 -ye ar s ur vi val ac hie ve d i n 8 0 % of patie nts. 8 ,9 Still, e ve n i n t his y o u n ger a ge gr o u p, t he 
rate of t o xicit y f oll o wi n g tra ns pla nt is hi g h, wit h 5 % m ortalit y d ue t o a d verse e ve nts re p orte d 
i n cli nical st u dies.1 0  I n ol der patie nts ie, t h ose > 7 0 ye ars, a d verse e ve nt relate d m ortalities 
f oll o wi n g A S C T is a sta g geri n g 1 9 %.1 0 T h o u g h i n t he or y all o ge neic ste m cell tra ns pla nt has 
a c urati ve p ote ntial, it is n ot a rec o m me n de d re gi me n f or t his p o p ulati o n as n o s ur vi val 
a d va nta ges ha ve bee n de m o nstrate d i n ra n d o mize d st u dies d ue t o i ncrease d t o xicities .1 1 F or 
tra ns pla nt i neli gi ble patie nts, i m m u n o m o d ulati o n base d re gi me n of b ortez o mi b, 
le nali d o mi de, a n d de xa met has o ne is t he pri mar y preferre d treat me nt o pti on as it was 
de m o nstrate d i n t he P hase III S o ut h west O nc ol o g y  Gr o u p (S W O G ) S 0 7 7 7 st u d y  t hat a n 
o bjecti ve res p o nse rate ( O R R), of 7 1 %, a n d pr o gressi o n free s ur vi val of 4 3 m o nt hs ca n be 
ac hie ve d .9 ,1 2 H o we ver, t o xicit y  re mai ns t o be a c o ncer n, wit h Gra de 3 or hi g her ne ur o pat h y  
re p orte d i n 2 4 % of patie nts. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9 5
Des pite a n u m ber of rece nt a d va nces, t he maj orit y of patie nts are e x pecte d t o rela pse, e ve n 
f or t h ose w h o res p o n d i nitiall y t o treat me nt.  E ve n f or patie nts w h o are eli gi ble t o recei ve 
a ut ol o g o us ste m cell tra ns pla nts, t he me dia n ti me t o rela pse was 1 7. 2 m o nt hs .1 3 Si milarl y , 
f or patie nts t hat are treate d wit h n o vel pr oteas o me i n hi bit or-base d or
i m m u n o m o d ulati o n-base d c o m bi nati o n re gi me ns as fr o nt li ne treat me nt, t he me dia n ti me t o 
rela pse is 1 6. 4 m o nt hs .1 4
Patie nts wit h rela pse d refract or y  m ulti ple m yel o ma w h o res p o n d p o orl y t o pr oteas o me 
i n hi bit or- base d or i m m u n o m o d ulati o n-base d re gi me ns s h o w a me dia n o verall s ur vi val of 
o nl y  1. 5 ye ars.1 5 I n t his rela pse d setti n g, a p pr o xi matel y 5 0 % treat me nt-relate d a d verse 
e ve nts ( A E) a n d 2 0 % seri o us a d verse e ve nts ( S A E) ha ve bee n re p orte d .1 6 F urt her m ore, eac h 
s u bse q ue nt li ne of t hera p y re n ders t he patie nt m ore refract or y t o treat me nt.  F or e xa m ple, 
patie nts w h o are d o u ble -refract or y t o pr oteas o me i n hi bit or- base d or i m m u n o m o d ulati o n 
re gi me ns ha ve a me dia n o verall s ur vi val of 9 a n d 5 m o nt hs .1 7 It is t heref ore clear t hat 
a d diti o nal treat me nt a p pr oac hes are re q uire d f or rela pse d/ refract or y  M M.
1. 2. 2. Bis pecific A nti b o dies
F u ncti o nal l ocal a n d s y ste mic i m m u nit y is ofte n s u p presse d i n a M M patie nt.  Im paire d 
i m m u nit y res ults fr o m t he disr u pti o n of n or mal he mat o p oiesis f oll o wi n g b o ne marr o w 
i n vasi o n b y plas ma cl o nes.  T he p ote ntial f or T-cell base d i m m u n ot hera p y f or M M has bee n 
hi g hli g hte d b y t he a bilit y f or graft i m m u ne reacti ve T -cells t o era dicate m yel o ma cells 
f oll o wi n g all o ge neic ste m cell tra ns pla ntati o n.1 8 It ma y t heref ore be p ossi ble t o rest ore 
i m m u ne-reacti ve T- cells, pre ve nt mali g na nt cell gr o wt h a n d decrease disease rec urre nce wit h 
i m m u n ot hera pe utic a p pr oac hes.
Bis pecific a nti b o dies offer a n o vel i m m u n ot hera pe utic a p pr oac h t hat all o ws t he direct 
tar geti n g of c yt ot o xic T- cells t o t u m or cells.  T hese a nti b o dies are e n gi neere d wit h t w o 
se parate a nti ge n rec o g niti o n d o mai ns; o ne t hat rec o g nizes a t u m or a nti ge n a n d a n ot her t hat 
rec o g nizes C D 3 e x presse d o n T- cells.  Si m ulta ne o us bi n di n g of C D 3 a n d t he t u m or a nti ge n 
i nitiates a c yt ot o xic res p o nse t o war ds t he b o u n d t u m or cell.  U nli ke n or mal T- cell
c yt ot o xicit y, bis pecific a nti b o d y me diate d c yt ot o xicit y is i n de pe n de nt t o t he prese nce of 
a nti ge n prese nti n g cells ( A P Cs), e x pre ssi o n of maj or hist oc o m pati bilit y c o m ple x ( M H C) 
I m olec ules b y  t he t u m or, a n d t he prese nce of c osti m ulat or y m olec ules.  Bli nat u m o ma b, a 
C D 1 9/ C D 3 bis pecific a nti b o d y , was t he first bis pecific a nti b o d y t o be a p pr o ve d b y t he 
U nite d States ( U S) F o o d a n d Dr u g A d mi nistrati o n ( F D A) .1 9 I n a P hase 2 trial of rela pse or 
refract or y B cell ac ute l y m p h o blastic le u ke mia ( A L L) patie nts, 3 3 % ac hie ve d c o m plete 
res p o nse ( C R) a n d 1 0 % ac hie ve d C R wit h i nc o m plete he mat ol o gical rec o ver y.1 9 It ma y 
t heref ore be p ossi ble t o use t he sa me a p pr oac h f or M M wit h a m yel o ma-restricte d a nti ge n.
B- cell mat urati o n a nti ge n ( B C M A, als o k n o w n as T N F R S F 1 7 a n d C D 2 6 9) is a ca n di date f or 
bis pecific a nti b o d y base d i m m u n ot hera p y.  B C M A e x pressi o n is u pre g ulate d d uri n g B-cell 
mat urati o n i nt o plas ma blasts a n d plas ma cells, b ut it is n ot e x presse d o n naï ve B cells, 
he mat o p oietic ste m cells or n or mal tiss ues s uc h as t he heart, l u n g, ki d ne y , or t o nsil.2 0 ,2 1
B C M A k n oc k o ut mice s h o w n or mal de vel o p me nt, a n d are a ble t o elicit a n or mal h u m oral 
i m m u ne res p o nse.2 2 ,2 3 I n m ulti ple m yel o ma, B C M A e x pressi o n was i de ntifie d at eac h 
disease sta ge, a n d o n patie nts wit h differi n g c y t o ge netic ris ks.2 0 F urt her m ore, B C M A 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9 6
e x pressi o n was n ot i nfl ue nce d b y treat me nt wit h a ut ol o g o us ste m cell tra ns pla nt ( A S C T) or 
c he m ot hera p y. 2 0 ,2 1 I n vi v o, bis pecific a nti b o dies a gai nst B C M A ha ve bee n s h o w n t o i n d uce 
T- cell acti vati o n, re d uce t u m or b ur de n a n d pr ol o n g s ur vi v al.2 4 -2 6 A P hase 1 d ose escalati o n 
st u d y wit h a B C M A bis pecific a nti b o dy ( BI 8 3 6 9 0 9) has bee n i nitiate d.  As of A u g ust 2 0 1 9, 
4 3 patie nts ha ve bee n e n r olle d.2 6
1. 2. 3. P F -0 6 8 6 3 1 3 5
P F -0 6 8 6 3 1 3 5 is a heter o di meric h u ma nize d f ull -le n gt h bis pecific a nti b o dy c o m prise d of o ne 
B -cell Mat urati o n A nti ge n ( B C M A) bi n di n g ar m a n d o ne cl uste r of differe ntiati o n ( C D 3) 
bi n di n g ar m paire d t hr o u g h hi n ge m utati o n tec h n ol o g y .  It utilizes a m o difie d h u ma n I g G 2 Da 
fra g me nt cr ystalliza ble ( Fc) re gi o n.  T he half-life of P F-0 6 8 6 3 1 3 5 was 3 d a y s i n a 
n o n- h u ma n pri mate m o del , a n d P F-0 6 8 6 3 1 3 5 has a pr ojecte d ter mi nal half -life of 1 0 d a y s i n 
h u ma ns. 
1. 2. 3. 1. S afet y
T he safet y, efficac y, a n d P K of elra nata ma b were i nitiall y e val uate d i n P hase 1 st u d y 
( C 1 0 7 1 0 0 1) as m o n ot hera p y (IV a n d S C) or i n c o m bi nati o n wit h le nali d o mi de or 
p o mali d o mi de. 
As of t he 2 2 J u ne 2 0 2 2 data c ut off date, 1 0 1 partici pa nts ha ve bee n e nr olle d i n t he st u d y  as 
f oll o ws: 2 3 i n Part 1 IV d ose escalati o n, 3 0 i n Part 1 S C d ose escalati o n, 2 0 i n Part 1. 1 S C 
pri mi n g d ose c o h orts, 1 5 i n Part 2 A: S C d ose d ose e x pa nsi o n, 4 i n Part 1 C: elra nata ma b + 
le nali d o mi de a n d 9 i n Part 1 D: elra nata ma b + p o mali d o mi de. In Part 1. 1, t o miti gate t he ris k 
of C R S a n d I C A N S, partici pa nts recei ve d a pri mi n g d ose of 6 0 0 µ g/ k g elra nata ma b 
(e q ui vale nt t o 4 4 m g) o n Da y 1 pri or t o t he first f ull d ose of 1 0 0 0 µ g/ k g (e q ui valent t o 7 6 
m g) o n Da y  8. I n Part 2 A, i n a d diti o n t o t he pri mi n g d ose of elra nata ma b, partici pa nts 
recei ve d pre-me dicati o n wit h de xa met has o ne, aceta mi n o p he n a n d di p he n h y dra mi ne pri or t o 
t he first 2 d oses, pri mi n g d ose a n d first f ull d ose res pecti vel y. 
Base d o n t he data fr o m t his st u d y , 7 6 m g Q W a d mi nistere d S C was selecte d as t he R P 2 D of 
elra nata ma b f or f ut ure st u dies. T his secti o n will f oc us o n safet y data fr o m partici pa nts w h o 
recei ve d elra nata ma b m o n ot hera py at t he f ull 1 0 0 0 μ g/ k g or 7 6 m g [ Q W or Q 2 W] d osi n g 
re gi me n ( N = 4 1) re gar dless of pri mi n g d ose or pre me dicati o n.
I n t he 4 1 partici pa nts w h o recei ve d elra nata ma b m o n ot hera py at t he f ull 1 0 0 0 μ g/ k g or 7 6 m g 
[ Q W or Q 2 W] d osi n g re gi me n , t he m ost c o m m o n all ca usalit y T E A Es (fre q ue nc y ≥2 0 %) 
were C R S ( 8 7. 8 %), n e utr o pe nia ( 7 8. 0 %), a ne mia ( 6 3. 4 %), I S R ( 5 6. 1 %), t hr o m b oc y t o pe nia 
a n d fati g ue (eac h 4 8. 8 %), diarr hea, h y p o p h os p hate mia a n d l y m p h o pe nia (eac h 3 9. 0 %), 
decrease d a p petite a n d dr y s ki n (eac h 3 6. 6 %), bac k pai n ( 3 4. 1 %), na usea a n d 
h y p o ma g nesae mia (eac h 3 1. 7 %), A S T i ncrease d a n d le u k o pe nia (eac h 2 6. 8 %), A L T 
i ncrease d, fall, hy p o kale mia, p yre xia, v o miti n g, pai n i n e xtre mit y a n d wei g ht decrease d (eac h 
2 4. 4 %), art hral gia, c o u g h, d y s p n oea, hea dac he a n d p ne u m o nia (eac h 2 2. 0 %).
F or a d diti o nal i nf or mati o n , refer t o t he si n gle refere nce safety d oc u me nt ( S R S D), w hic h f or 
t his st u d y is t he In vesti gat or’s B r oc h ure. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9 7
1. 2. 3. 2. Effic ac y
Cli nical acti vit y  has bee n o bser ve d i n St u d y C 1 0 7 1 0 0 1. As of t he 2 2 J u ne 2 0 2 2 data c ut off 
date , t he c o nfir me d o bjecti ve res p o nse rate at t he f ull 1 0 0 0 μ g/ k g or 7 6 m g [ Q W or Q 2 W 
d osi n g re gi me n ( N = 4 1)] was 6 3. 4 % ( 9 5 % CI, 4 8. 1, 7 6. 4), p er I M W G criteria . Res p o nses 
were d ura ble a n d dee pe ne d o ver ti me. Me dia n d urati o n of f oll o w -u p f or all 4 1 patie nts 
treate d at t he f ull 1 0 0 0 μ g/ k g or 7 6 m g ( Q W or Q 2 W d osi n g re gime n) was 1 0. 9 4 m o nt hs 
( 0. 3 0, 2 4. 4 1). F or res p o n di n g partici pa nts, t he me dia n d urati o n of res p o nse ( 9 5 % CI) was 
1 1. 6 ( 7. 2, N E) m o nt hs. T he me dia n pr o gressi o n -free s ur vi val ( 9 5 % CI) was 1 0. 4 ( 4. 7, 1 5. 2) 
m o nt hs .
A d diti o nal i nf or mati o n f or t his c o m p o u n d ma y  be f o u n d i n t he si n gle refere nce safet y 
d oc u me nt ( S R S D), w hic h f or t his st u d y  is t he In vesti gat or’s B r oc h ure. 
1. 2. 3. 3. M o n ocl o n al A nti b o d y I nterfere nce of L a b or at or y E v al u ati o n of M yel o m a
Wit h t he i ncreasi n g use of t hera pe utic i m m u n o gl o b uli n G ka p pa (I g Gk) m A bs , eit her as a 
treat me nt f or m ulti ple m yel o ma itself, or f or ot her reas o ns, t he iss ue of m A b i nterfere nce a n d 
ass ociate d false-p ositi ve res ults i n t he m o n ocl o nal s pi ke (M- s pi ke) assa y f or patie nts wit h 
I g Gk m ulti ple m y el o mas has bee n n ote d. O n b ot h ser u m pr otei n electr o p h oresis (S P E P ) a n d 
ser u m i m m u n ofi xati o n electr o p h oresis (SI F E ) met h o ds, a visi ble a n d q ua ntifia ble m y el o ma 
pr otei n ( M- pr otei n ) c orres p o n di n g t o t he t hera pe utic a nti b o d y  ma y mi grate wit h si milar 
c haracteristics t o t he patie nt’s o w n M -s pi ke. T his has pr o m pte d t he i nter nati o nal m yel o ma 
w or ki n g gr o u p (I M W G) t o iss ue a n u p date d defi niti o n of C R t hat w he n l o o ki n g at detecta ble 
m y el o ma pr otei n ( M- pr otei n ) i n peri p heral bl o o d, t he prese nce or a bse nce of m o n ocl o nal
ba n ds b y  S P E P a n d SI F E m ust be ma de o nl y  i n refere nce t o t he patie nt’s ori gi nal M-pr otei n 
secrete d by pat h ol o gic plas ma cells .2 7  T his s pea ks t o t he i m p orta nce of ha vi n g a baseli ne 
sa m ple fr o m t he patie nt’s ori gi nal disease cl o ne a n d als o t he nee d f or e x perie nce d rea ders 
w h o ca n rec o g nize c haracteristic mi grati o n patter ns of cert ai n t hera pe utic m A bs. St u dies 
re p ort t he detecti o n li mit i n S P E P a n d SI F E assa ys usi n g sa m ples s pi ke d wit h t hera pe utic 
m A bs t o be 1 0 0 g/ ml; a c o nce ntrati o n t hat is well e xcee de d i n t he circ ulati o n at t hera pe utic 
d oses .2 8  P F -0 6 8 6 3 1 3 5, h o we ver, is pre dicte d t o reac h a ma xi mal ser u m c o nce ntrati o n of 
1 0 0 µ g/ ml o nl y  at d oses of 2 5 0 0 μ g/ k g a n d a b o ve; he nce t here is n o e x pectati o n of 
t hera pe utic m A b i nterfere nce i n t he M-s pi ke assa y i n t his i nsta nce.
1. 2. 4. N o ncli nic al S afet y I nf or m ati o n
I n n o ncli nical safet y st u dies c o n d ucte d i n c yn o m ol g us m o n ke y s wit h P F-0 6 8 6 3 1 3 5 
a d mi nistere d b y eit her t he I V or S C r o ute f or u p t o 1 -m o nt h i n d urati o n, t he ke y  effects were 
c yt o ki ne ele vati o ns t hat were occasi o nall y acc o m pa nie d b y e mesis d uri n g t he first 6 h o urs 
after t he first dr u g a d mi nistrati o n a n d mi ni mal t o m o derate i nfla m mati o n at t he i njecti o n 
site. Decreases i n B cells a n d plas ma cells as well as fl uct uati o ns i n peri p heral T- cell
n u m bers were o bser ve d i n I V st u dies w here i m m u n o p he n ot y pi n g meas ure me nts were 
i ncl u de d. All of t hese effects were c o nsi dere d relate d t o t he mec ha nis m of acti o n.
I n 
a d diti o n, re d s ki n disc ol orati o n was n ote d i n a s u bset of a ni mals a d mi nistere d P F - 0 6 8 6 3 1 3 5 
b y  t he I V r o ute. N o ne of t he effects were c o nsi dere d a d verse.
T h us, t he n o o b ser ve d a d verse 
effect le vel ( N O A E L) i n t he pi v otal t o xicit y  st u d y was 0. 3 m g/ k g i n m o n ke y s [ hi g hest d ose 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9 9
M O L P- 8 (a m ulti ple m yel o ma cell li ne wit h t( 1 1; 1 4)( q 1 3; q 3 2) c hr o m os o mal a b n or malit y  
a n d ne gati ve f or C D 2 8) t u m or m o dels. 
Fi g ure 2.
P F- 0 6 8 6 3 1 3 5 Acti vit y i n a n O P M -2 M M Ort h otr o pic T u m or M o del
1. 2. 5. 3. A nti -tu m or Effic ac y of P F -0 6 8 6 3 1 3 5 i n C o m bi n ati o n wit h t he 
I m m u n o m o d ul at or y Dr u g Le n ali d o mi de i n Ort h ot o pic a n d S u bc ut a ne o us M yel o m a 
M o dels 
I n vi v o st u dies were perf or me d i n T cell e n grafte d h u ma n m yel o ma ort h ot o pic t u m or -beari n g 
mice t o e val uate t he c o m bi nati o n of P F -0 6 8 6 3 1 3 5 wit h t he i m m u n o m o d ulat or y  dr u g (I Mi D) 
le nali d o mi de (P F -0 6 8 6 3 1 3 5 _ 2 9 A pr 1 9 _ 0 9 3 4 0 4) .
I n t he hi g h B C M A e x pressi n g M M. 1 S m o del, P F -0 6 8 6 3 1 3 5 treat me nt res ulte d i n s u peri or 
a nti-t u m or res p o nse vers us le nali d o mi de al o ne. T u m or gr o wt h i n hi biti o n i n d uce d b y  
P F -0 6 8 6 3 1 3 5 was e n ha nce d w he n gi ve n i n c o m bi nati o n wit h le nali d o mi de c o m pare d t o 
si n gle a ge nt treat me nts, alt h o u g h it was n ot sta tisticall y si g nifica nt (Fi g ure 3 A) . Usi n g b o d y 
wei g ht as a meas ure me nt of p ote ntial f or t o xicit y , t here were n o i n dicati o ns t hat t he 
si n gle-a ge nt or c o m bi nati o ns t hera p ies ha d ne gati ve effects o n t he ge neral healt h of t he 
a ni mals d uri n g t he st u d y.   I n t he M O LP - 8 m o del, w hic h e x presses l o w le vels of B C M A, 
tu m or gr o wt h i n hi biti o n was statisticall y si g nifica ntl y e n ha nce d i n t he P F-0 6 8 6 3 1 3 5 + 
le nali d o mi de c o m bi nati o n c o m pare d t o ot her treat me nts (Fi g ure 3 B) .  T he h u ma n T cell 
e n grafte d m yel o ma m o dels ha ve a li mite d re pert oire of h u ma n i m m u ne cells e n grafte d a n d 
t heref ore t he y ca n n ot be use d t o c o m pre he nsi vely reca pit ulate all p ote ntial mec ha nis ms of 
acti o n of le nali d o mi de.  Per ha ps beca use of t his, t he e n ha nce me nt i n a nti -t u m or acti vit y was 
n ot statisticall y  si g nifica nt i n t he M M. 1 S m o del c o m pare d to si n gle a ge nt P F - 0 6 8 6 3 1 3 5 
treat me nt gr o u ps. E ve n s o, e n ha nce d t u m or acti vit y  of t he c o m bi nati o n of P F- 0 6 86 3 1 3 5 a n d 
le nali d o mi de was o bser ve d i n b ot h t he M M. 1 S a n d M O LP - 8 m o dels, s u g gesti n g t he p ote ntial 
f or sy ner g y i n t he h u ma n setti n g.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 1
i nfecti o n, d ys p nea, dizzi ness, t hr o m b oc yt o pe nia, tre m or a n d ras h. Le nali d o mi de, a 
t hali d o mi de a nal o g ue, ca n ca use e m br y o-fetal t o xicit y.
Le nali d o mi de will be d ose d at 1 5 m g orall y dail y da y s 1-2 1 of e ver y  2 8 da ys starti n g C 1 D 1. 
C o m plete i nf or mati o n f or t his c o m p o u n d ca n be f o u n d i n t he Cel ge ne U S PI, Re vli mi d®
(le nali d o mi de), S u m mit, Ne w Jerse y w hic h is t he S R S D f or t his st u d y .3 0 I n t he E U, 
Re vli mi d ® ca n be f o u n d at t he E ur o pea n Me dici nes A ge nc y  S P C.3 1 I n Ca na da t his 
c o m p o u n d ca n be f o u n d i n t he Cel ge ne Pr o d uct M o n o gra p h, R e vli mi d ® (le nali d o mi de) 
Mississa u ga, O ntari o .3 2
1. 2. 7. P o m ali d o mi de
P o mali d o mi de ( P o mal y st ® i n t he U S a n d I m n o vi d i n t he E U) is a t hali d o mi de a nal o g ue 
w hic h has direct a nti -m y el o ma t u m orici dal acti vit y, i n hi bits str o ma l cell s u p p ort f or M M 
t u m or cell gr o wt h a n d has i m m u n o m o d ulat or y acti vities.3 3  A d diti o nall y , p o mali d o mi de 
i n d uces t u m or cell deat h i n b ot h, le nali d o mi de-se nsiti ve a n d le nali d o mi de-resista nt cell li nes.  
P o mali d o mi de is i n dicate d i n c o m bi nati o n wit h de xa met has o ne f or patie nts wit h M M w h o 
ha ve recei ve d at least 2 pri or t hera pies i ncl u di n g le nali d o mi de a n d a pr oteas o me i n hi bit or 
a n d ha ve de m o nstrate d disease pr o gressi o n o n or wit hi n 6 0 da y s of c o m pleti o n of t he last 
t hera py. M ost c o m m o n si de effects i ncl u de fati g ue a n d ast he nia, ne utr o pe nia, a ne mia, 
c o nsti pati o n, na usea, diarr hea, d ys p nea, u p per -res pirat or y tract i nfecti o ns, bac k pai n, a n d 
p y re xia. Ras h, c o u g h, peri p heral e de ma, m uscle s pas ms, a n d h y p ot h y r oi dis m ca n als o be 
c o m m o n si de effects.  P o mali d o mi de, a t hali d o mi de a nal o g ue, ca n ca use e m br y o -fetal t o xicit y. 
A d ose of 4 m g  of p o mali d o mi de will be a d mi nistere d orall y o n Da ys 1- 2 1 of e ver y  2 8 d a y s
starti n g C 1 D 1. C o m plete i nf or mati o n f or t his c o m p o u n d ca n be f o u n d i n t he Cel ge ne U S PI, 
P o mal y st® ( p o mali d o mi de), S u m mit, Ne w Jerse y (t he S R S D f or t his st u d y).3 4 I n t he E U, 
I m n o vi d® ca n be f o u n d at t he E ur o pea n Me dici nes A ge nc y  S P C.3 5  I n Ca na da t his c o m p o u n d 
ca n be f o u n d i n t he Cel ge ne Pr o d uct M o n o gra p h, P o mal y st® ( p o mali d o mi de), Mississa u ga, 
O ntari o .3 6
1. 2. 8. De x a met h as o ne
De xa met has o ne is a c ortic oster oi d w hic h has i m m u n o m o d ulat or y  pr o perties a n d a nti-
ne o plastic acti vit y  a gai nst l ym p h oi d mali g na ncies i ncl u di n g m ulti ple m y el o ma. 3 7
De xa met has o ne has bee n use d i n t he pre ve nti o n a n d treat me nt of i m m u ne effect or cell -
ass ociate d t o xicities i ncl u di n g c y t o ki ne release sy n dr o me .3 8 ,3 9 I n a d diti o n t o its 
i m m u n o m o d ulat or y pr o perties, de xa met has o ne e x hi bits a nti-m y el o ma acti vit y a n d has bee n 
i nte grate d i nt o sta n dar d c o m bi nati o n re gi me ns s uc h as
b ortez o mi b/le nali d o mi de/ de xa met has o ne a n d
darat u m u ma b/le nali d o mi de/ de xa met has o ne. 4 0 ,4 1  Beca use t he effect of de xa met has o ne o n t he 
safety a n d efficac y of T -cell e n ga gi n g bis pecific a ge nts is n ot k n o w n, t he a d diti o n of 
de xa met has o ne t o P F -0 6 8 6 3 1 3 5 will be i n vesti gate d i n Part 1 E a n d P art 2 E .  T he m ost 
c o m m o n a d verse reacti o ns are car di o vasc ular, der mat ol o gic, e n d ocri ne, fl ui d a n d electr ol yt e 
dist ur ba nces, gastr oi ntesti nal, meta b olic, m usc ul os keletal, ne ur ol o gical/ ps yc hiatric, 
o p ht hal mic, a b n or mal fat de p osits, decrease d resista nce t o i nfecti o n, hicc u ps, i ncrease d or 
decrease d m otilit y  a n d n u m ber of s per mat oz oa, malaise, m o o n face, a n d wei g ht gai n.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 2
De xa met has o ne will be d ose d as pre me dicati o n at 4 0 m g orall y  6 0 ± 3 0 mi n utes pri or t o P F-
0 6 8 6 3 1 3 5 a d mi nistrati o n.  F or s u bjects ol der t ha n 7 5 ye ars or u n der wei g ht ( b o d y  mass i n de x 
[ B MI] < 1 8. 5), de xa met has o ne ma y be d ose d as pre me dicati o n at 2 0 m g  orall y 6 0 ± 3 0 
mi n utes pri or t o P F -0 6 8 6 3 1 3 5 a d mi nistrati o n. If a d ose of P F-0 6 8 6 3 1 3 5 is hel d or s ki p pe d, 
t he n de xa met has o ne s h o ul d n ot be a d mi nistere d. F or patie nts recei vi n g de xa met has o ne
pre me dicati o n, de xa met has o ne s h o ul d be disc o nti n ue d after 6 m o nt hs u nless cli nical 
rati o nale t o c o nti n ue de xa met has o ne is pr o vi de d b y i n vesti gat or a n d a p pr o ve d b y s p o ns or.
1. 2. 9. St arti n g D ose R ati o n ale
1. 2. 9. 1. I ntr a ve n o us (I V) St ar ti n g D ose R ati o n ale
T he selecti o n of t he starti n g d ose f or t his first -i n-patie nt ( FI P) st u d y  was base d o n t he 
mi ni m u m a ntici pate d bi ol o gical effect le vel ( M A B E L) i n acc or da nce wit h t he I nter nati o nal 
C o nfere nce o n Har m o nizati o n (I C H) S 9 G ui da nce, gi ve n t hat P F -0 6 8 6 3 1 3 5 is a bi -s pecific 
T- cell-e n ga gi n g a ge nt wit h i m m u ne a g o nistic pr o perties.  T he i n vitr o bi ol o gical acti vities f or 
P F -0 6 8 6 3 1 3 5 were deter mi ne d via T- cell acti vati o n, c yt o ki ne release, a n d c yt ot o xicit y 
e x peri me nts.  Base d o n e x p os ure -res p o nse a nal yses, ei g ht o ut of te n assa y meas ures ac hie ve d 
2 0 % ma xi mal effect (effecti ve c o nce ntrati o n [ E C] 2 0) a b o ve 1. 9 n g/ m L.  All te n assa y  
meas ures als o ac hie ve d 5 0 % ma xi mal effect ( E C 5 0) a b o ve 1. 9 n g/ m L.  T his E C 2 0 val ue i n 
c o m bi nati o n wit h t he pr ojecte d P F - 0 6 8 63 1 3 5 h u ma n p har mac o ki netics ( P K) base d o n 
all o metric scali n g of m o n ke y P K data were use d f or pr ojecti n g t he M A B E L d ose.  
S pecificall y, t he M A B E L d ose was calc ulate d b y setti n g t he ma xi m u m ( or pea k) ser u m 
c o nce ntrati o n ( C ma x ) less t ha n or e q ual t o t he 1. 9 n g/ m L t hres h ol d (ass u mi n g pea k c y t o ki ne 
release a n d C D 3 + T- cell acti vati o n is dri ve n b y ma xi m u m dr u g e x p os ure).  I n a d diti o n, 
rece pt or occ u pa nc y ( R O) was calc ulate d base d o n i n vitr o bi n di n g affi nities (e q uili bri u m 
diss ociati o n c o nsta nt or K D ) of P F- 0 6 8 6 3 1 35 ( 3 8 p M a gai nst B C M A a n d 1 7 n M a gai nst 
C D 3) t o f urt her e ns ure t hat t he rec o m me n de d M A B E L starti n g d ose will res ult i n mi ni m u m 
rece pt or bi n di n g.
Base d o n t his M A B E L a p pr oac h, t he cli nical starti n g d ose selecte d f or t he st u d y  is 0. 1 μ g/ k g 
gi ve n as a 2 - h o ur i ntra ve n o us i nf usi o n gi ve n wee kl y i n 3 wee k c y cles.  As P F -0 6 8 6 3 1 3 5 has 
a pr ojecte d half -life of 3. 5 da y s i n h u ma ns, a wee kl y re gi me n, wit h a pr ojecte d < 1. 3 3 -f ol d 
e x p os ure acc u m ulati o n rati o at stea d y state acr oss t he pla n ne d d ose escalati o n ra n ge was 
c hose n t o mai ntai n a hi g her a vera ge c o nce ntrati o n o ver t he d osi n g i nter val (a p ote ntial dri ver 
of efficac y ) relati ve t o Cma x .  T he h u ma n C ma x f or u n b o u n d P F -0 6 8 6 3 1 3 5 at t he starti n g d ose 
of 0. 1 μ g/ k g is pr ojecte d t o be a p pr o xi matel y 1. 1 n g/ m L, w hic h is e x pec te d t o res ult i n 
mi ni mal bi ol o gical effec t.  T his free c o nce ntrati o n pr ojecti o n acc o u nts f or bi n di n g t o t y pical 
le vels of ser u m s ol u ble B C M A ( 2. 5 7 n g/ m L) i n healt h y  h u ma ns.  Beca use t he ser u m s ol u ble 
B C M A le vels are ele vate d i n rela pse d/refract or y  M M patients, t he u n b o u n d P F -0 6 8 6 3 1 3 5 
c o nce ntrati o ns at C ma x ma y  be l o wer.  I n a d diti o n, t he rec o m me n de d starti n g d ose of 
0. 1 g/ k g is e x pecte d t o res ult i n mi ni m u m rece pt or bi n di n g, as t he t he oretical rece pt or 
occ u pa nc y  (R O ) val ues at t he pr ojecte d Cma x are less t ha n 1 7 % f or B C M A a n d 0. 0 5 % C D 3.
A b o d y  wei g ht-base d d osi n g a p pr oac h (g/ k g ) will be a p plie d f or t he d ose -escalati o n part 
( Part 1) of FI P st u d y  of P F-0 6 8 6 3 1 3 5 wit h t he g oal t o re d uce i nter -i n di vi d ual variati o ns i n 
P K e x p os ure.  Fi xe d -d osi n g a p pr oac h will be a p plie d i n d ose -fi n di n g f or c o m bi nati o n a n d
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 3
als o i n all e x pa nsi o n parts of t he st u d y (see Secti o n 1. 2. 9. 4 f or m ore details). Pfizer i nte n ds 
t o c o n d uct p o p ulati o n P K a nalys is of P F- 0 6 8 6 3 1 3 5 after s ufficie nt data ha ve bee n c ollecte d 
t o i nf or m o pti mal d osi n g a p pr oac h f or f ut ure st u dies.
1. 2. 9. 2. S u bc ut a ne o us ( S C) St arti n g D ose R ati o n ale
T he pr o p ose d starti n g d ose f or S C a d mi nistrati o n is 8 0 µ g/ k g, o ne d ose le vel hi g her (“ D ose 
I V + 1”) t ha n t he pre vi o usl y teste d I V d ose le vel ( 5 0 µ g/ k g) i n Part 1 I V a d mi nistrati o n t hat is 
dee me d safe.   Ta ki n g e x pecte d bi oa vaila bilit y  f or S C vers us IV i nt o c o nsi derati o n, t he 
8 0 µ g/ k g S C d ose is e x pecte d t o ha ve l o wer e x p os ure t ha n 5 0 µ g/ k g I V. A vaila ble a n d 
e mer gi n g safet y data fr o m c o m plete d a n d i nitiate d I V a d mi nistrati o n c o h orts i n t he d ose 
escalati o n Part 1 I V i nf or me d a n d s u p p orte d t he decisi o n t o i nitiate S C a d mi nistrati o n.
Base d o n a n ass u me d bi oa vaila bilit y  ≤1 0 0 % a n d sl o we d u pta ke t o t he s ys te mic circ ulati o n 
wit h S C a d mi nistrati o n, t he s y ste mic e x p os ure Cma x a n d area u n der t he c ur ve ( A U C ) after S C 
a d mi nistrati o n at t he starti n g d ose di d n ot e xcee d e x p os ures of “ D ose I V - + 1” f or S C d ose
escalati o n.  C o nse q ue ntl y, relati ve t o t he ne xt pr o p ose d d ose le vel i n Part 1 I V, t he S C 
starti n g d ose c o h ort is e x pecte d t o e x hi bit c o m para ble or less se vere sys te mic a d verse e ve nts, 
i ncl u di n g C R S.  T his s h o ul d re d uce t he p ote ntial f or t o xicit y wit h t he i nitial tra nsiti o n fr o m 
I V t o S C d osi n g. T he s p o ns or ma y  deci de t o disc o nti n ue or pa use t he I V d ose escalati o n a n d 
o nl y  deter mi ne an M T D / M A D f or t he S C r o ute. 
I n c yn o m ol g us m o n ke y s, P F- 0 6 8 6 3 1 3 5 was well t olerate d f oll o wi n g re peate d I V d oses u p t o 
3 0 0 µ g/ k g or f oll o wi n g re peate d S C d oses u p t o 3 0 0 µ g/ k g. F or refere nce, f oll o wi n g S C 
a d mi nistrati o n of P F -0 6 8 6 3 1 3 5 at 1 0 0 µ g/ k g wee kl y  i n h u ma ns a n d ass u mi n g 
1 0 0 % bi oa vaila bilit y , t he s yste mic ma xi m u m c o nce ntrati o n ( C ma x ) is pre dicte d t o be 
a p pr o xi matel y 3 3. 4 % a n d 5 7. 0 % of t he Cma x o bser ve d f oll o wi n g a d mi nistrati o n of 3 0 0 µ g/ k g 
I V a n d 3 0 0 µ g / k g S C, res pecti vel y i n c yn o m ol g us m o n ke y s.  Si milarl y, t he area u n der t he 
c o nce ntrati o n-ti me c ur ve f or the first d osi n g i nter val ( A U C 0 - 1 6 8) f oll o wi n g si n gle S C 
a d mi nistrati o n of P F -0 6 8 6 3 1 3 5 at 1 0 0 µ g/ k g wee kl y  i n h u ma ns is pre dicte d t o be 
a p pr o xi matel y 5 7. 6 % a n d 4 9. 8 % of t he A U C deter mi ne d f oll o wi n g t he a d mi nistrati o n of 
3 0 0 µ g/ k g I V a n d 3 0 0 µ g/ k g S C, res pec ti vel y, i n c yn o m ol g us m o n ke y s. T h us, e x p os ures of 
P F -0 6 8 6 3 1 3 5 f oll o wi n g S C a d mi nistrati o n u p t o 1 0 0 µ g/ k g are pr ojecte d t o be l o wer t ha n 
t h ose o bser ve d to be well t olerate d i n c y n o m ol g us m o n ke y .
1. 2. 9. 3. St arti n g D ose f or C o m bi n ati o n S afet y C o h orts ( P arts 1 C, 1 D a n d 1 E ) 
T he d ose fi n di n g e val uati o n wit h P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de or 
p o mali d o mi de is pla n ne d t o be i nitiate d after t he P F-0 6 8 6 3 1 3 5 m o n ot hera p y  d ose escalati o n, 
a n d t he M T D/ M A D a n d R P 2 D
of P F -0 6 8 6 3 1 3 5 m o n ot hera p y has bee n deter mi ne d .  T he 
starti n g d ose of P F-0 6 8 6 3 1 3 5 f or t he c o m bi nati o n wit h le nali d o mi de or p o mali d o mi de 
t hera py will be 1 d ose le vel bel o w t he M T D / M A D if t he M T D/ M A D a n d R P 2 D of 
m o n ot hera p y P F -0 6 8 6 3 1 3 5 are e q ual, a n d t he d ose of P F -0 6 8 6 3 1 3 5 will be d ose escalate d t o 
t he m o n ot hera p y M T D/ M A D or R P 2 D . If t he m o n ot hera py R P 2 D is alrea d y at least 1 d ose 
le vel bel o w t he M T D/ M A D, t he n t he R P 2 D will be use d as t he starti n g d ose of P F- 0 6 8 6 3 1 3 5 
i n c o m bi nati o n wit h le nali d o mi de or p o mali d o mi de , a n d n o d ose escalati o n will be pla n ne d.
Le nali d o mi de will be d ose d at 1 5 m g orall y dail y da y s 1-2 1 of e ver y  2 8 da y s starti n g C 1 D 1. 
P o mali d o mi de will be d ose d at 4 m g orall y dail y D a ys 1-2 1 of e ver y  2 8 da ys starti n g C 1 D 1.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 4
Part 1 E will i n vesti gate P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h de xa met has o ne .  De xa met has o ne 
w o ul d be gi n o n C 0 D 1 a n d it will be d ose d as pre me dicati o n pri or t o P F - 0 6 8 6 3 1 3 5
a d mi nistrati o n. D ue t o n o n -o verla p pi n g t o xicit y  bet wee n P F - 0 6 8 6 3 1 3 5 a n d de xa met has o ne,
this safet y  c o h ort will e val uate t he R P 2 D of P F-0 6 8 6 3 1 3 5 m o n ot hera p y a n d a fi xe d d ose of 
de xa met has o ne, at a d ose of 4 0 m g. F or s u bjects ol der t ha n 7 5 years or u n der wei g ht ( b o d y 
mass i n de x [ B MI] < 1 8. 5), de xa met has o ne pre me dicati o n ma y  be gi ve n pri or t o P F - 0 6 8 6 3 1 3 5
at a fi xe d d ose of 2 0 m g. If a d ose of P F-0 6 8 6 3 1 3 5 is hel d or s ki p pe d, t he n de xa met has o ne 
s h o ul d n ot be a d mi nistere d. F or patie nts recei vi n g de xa met has o ne pre me dicati o n, 
de xa met has o ne s h o ul d be disc o nti n ue d after 6 m o nt hs u nless cli nical rati o nale t o c o nti n ue 
de xa met has o ne is pr o vi de d b y i n vesti gat or a n d a p pr o ve d b y  s p o ns or.
1. 2. 9. 4. Fi xe d D osi n g A p pr o ac h 
A fi xe d-d ose a p pr oac h will be a p plie d f or P F -0 6 8 6 3 1 3 5 i n Part s 1 C, 1 D a n d 1 E a n d Part 2 
gi ve n t hat a fi xe d d osi n g a p pr oac h was s h o w n t o pr o vi de si milar P K varia bilit y c o m pare d t o 
b o d y - wei g ht a dj uste d d osi n g w he n e val uate d f or m o n ocl o nal a nti b o dies, t hera pe utic 
pe pti des, a n d pr otei ns. 4 2 ,4 3 I n a d diti o n, fi xe d d osi n g offers ease of pre parati o n a n d less 
c ha nce of d osi n g err ors. Base d o n t he preli mi nar y p o p ulati o n P K a nal y sis of P F- 0 6 8 6 3 1 3 5 
i n 4 1 patie nts u p t o 3 6 0 µ g/ k g d ose, t here is n o cli nicall y mea ni n gf ul effect of b o d y wei g ht 
(ra n ge: 4 7. 9 t o 1 2 0 k g) or b o d y  s urface area (ra n ge: 1. 3 7 t o 2. 3 6 m 2), o n t he P F- 0 6 8 6 3 1 3 5 
cleara nce a n d f urt her j ustifies fi xe d d osi n g a p pr oac h f or e x pa nsi o n parts of t he o n g oi n g 
st u d y. Als o, a ge (ra n ge: 4 7 t o 8 2 years) or se x ( 2 0 males vs 2 1 fe males) were n ot cli nicall y 
mea ni n gf ul c o variate s o n P F -0 6 8 6 3 1 3 5 e x p os ure .
1. 2. 9. 5. D osi n g I nter v al
T he i nitial Q 1 W d osi n g fre q ue nc y of P F -0 6 8 6 3 1 3 5 i n t hi s st u d y was selecte d base d o n t he 
pr ojecte d t1/ 2 of 4- 8 da y s in h u ma ns . Base d o n e mer gi n g P K, P D, a n d safet y data, re gi me ns 
wit h alter nati ve d osi n g fre q ue ncies (e g, Q 2 W or Q 4 W) ma y  als o be c o nsi dere d. I n or der t o 
re d uce t he b ur de n of wee kl y visits, if a patie nt has recei ve d treat me nt wit h Q 1 W 
P F - 0 6 8 6 3 1 3 5 f or at least 6 m o nt hs, a n d disease assess me nts ha ve re mai ne d sta ble o ver at 
least 2 m o nt hs, c o nsi derati o n ma y be gi ve n t o i ncreasi n g d ose i nter vals fr o m wee kly t o e ver y 
2 wee ks or o nce per c y cle ( C X D 1) after c o ns ultati o n wit h t he s p o ns or. C y cles w o ul d re mai n 
t he sa me le n gt h. It w o ul d be prefera ble t o s ki p d osi n g of P F-0 6 8 6 3 1 3 5 o n da y s 8 a n d 2 2 of 
eac h c ycle if c ycles are 4 wee ks i n le n gt h . If t he patie nt s u bse q ue ntl y be gi ns t o ha ve a n 
i ncrease of disease b ur de n, d ose i nter vals s h o ul d ret ur n t o wee kl y d osi n g.
I n a d diti o n, if P K data at a n y p oi nt d uri n g S C Q 1 W d ose escalati o n s u g gests t hat a Q 2 W 
d ose sc he d ule ma y  be a ble t o ac hie ve s ufficie nt tr o u g h c o nce ntrati o ns a n d pr o vi de a de q uate 
s yste mic e x p os ure, a Q 2 W d osi n g sc he d ule w o ul d re place Q 1 W at the ne xt hi g her d ose le vel
if M T D or M A D ha ve n ot bee n reac he d. If it is p ossi ble a n d warra nte d t o c o nti n ue d ose 
escalati o n wit h S C Q 2 W e ve n if M T D / M A D has bee n reac he d f or S C Q 1 W, Part 1. 1 ma y  be 
use d wit h pri mi n g d ose at t he M T D / M A D of S C Q 1 W a n d s u bse q u e nt escalati o n t o ne xt 
hi g her d ose le vel wit h S C Q 2 W d osi n g as mai nte na nce, pr o vi de d t hat t he ne xt hi g her d ose 
le vel gi ve n Q 2 W w o ul d n ot e xcee d t he o verall e x p os ure t hat ha d bee n ac hie ve d at 
M T D / M A D of S C Q 1 W.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 5
C y cles f or Q 2 W d osi n g w o ul d be 4 wee ks. B ot h Q 1 W a n d Q 2 W d osi n g will be c o nsi dere d 
f or R P 2 D deter mi nati o n fr o m Part 1.
1. 2. 9. 6. Pri mi n g a n d M ai nte n a nce D ose R ati o n ale
I n a P hase 2 trial of bli nat u m o ma b i n a d ults patie nts wit h rela pse/refract or y ac ute 
l ym p h o blastic le u ke mia ( A L L), d ose li miti n g t o xicities of Gra de 4 c yt o ki ne release 
s yn dr o me ( C R S) were re p orte d i n 2 o ut of 7 patie nts treate d at 1 5 g/ m 2/ da y .4 4 It was f o u n d 
t hat if treat me nt was i nterr u pte d f or 1- 2 wee ks, patie nts rec o vere d s ufficie ntl y  f or treat me nt 
t o res u me.  T his le d t o t he i m ple me ntati o n of a l o wer starti n g d ose ( pri mi n g d ose) of 
5 g / m 2/da y  f or t he first wee k, escalati n g t o 1 5 a n d 3 0 g/ m 2 per da y s u bse q ue ntl y.  Of t he 
1 1 patie nts treate d wit h t his a p pr oac h wit hi n t he sa me st u d y , 2 patie nts de vel o pe d Gra de 3 
C R S , b ut n o d ose li miti n g Gra de 4 or 5 C R S was o bser ve d. 4 4 W he n t his
ste p wise a p pr oac h 
was a p plie d t o a sec o n d P hase 2 st u d y , o nl y 3 patie nts o ut of 1 8 9 treate d e x perie nce d C R S
( Gra de 3) b ut n o Gra de 4 or 5 C R S was o bser ve d .1 8 T h us, it was c o ncl u de d t hat t he 
i m ple me ntati o n of a pri mi n g d ose a p pr oac h is effecti ve i n a meli orati n g C R S t hr o u g h 
b uil di n g t olera nce , a n d it has bec o me t he rec o m me n de d treat me nt re gi me n f or A L L patie nts.  
Base d o n pri mi n g f oll o we d b y  mai nte na nce bei n g de m o nstrate d t o be p ote ntiall y s uccessf ul 
i n re d uci n g C R S, t his a p pr oac h ma y be e val uate d pri or t o reac hi n g an M T D / M A D (see 
Secti o n 3. 1. 1. 3 ). T his a p pr oac h ma y  be i m ple me nte d t o re d uce C R S relate d t o xicities if 
i n dicate d f or patie nt safet y.
1. 2. 1 0. Bi o m ar ker R ati o n ale
T he o bjecti ves of t he bi o mar ker assess me nts will be t o u n dersta n d t he relati o ns hi p bet wee n 
t he p har mac o ki netics ( P K), tar get l oa d, i m m u ne cell p he n oty pes, a n d p har mac o d y na mic 
acti vit y of P F- 0 6 8 6 3 1 3 5, wit h a n d wit h o ut c o m bi nati o n part ners, a n d its a nti-t u m or acti vit y 
a n d safet y pr ofile.  T his u n dersta n di n g will i n t ur n i nf or m t he selecti o n of a t hera pe utic d ose, 
as well as p ote ntiall y i de ntif y a p he n ot y pic pr ofile t hat ma xi mizes a nti -t u m or acti vit y w hile 
mi ni mizi n g t he ris k of t o xicit y . 
Tar get l oa d will be assesse d usi n g a fl o w c y t o metr y assa y t o meas ure cell s urface B C M A o n 
m ulti ple m y el o ma cells i n fres h b o ne marr o w as pirates at baseli ne.  Le vels of circ ulati n g 
s ol u ble B C M A will be meas ure d fr o m plas ma sa m ples bef ore a n d after P F-0 6 8 6 3 1 3 5 usi n g 
mass s pectr o metr y .  T he relati o ns hi p bet wee n tar get l oa d a n d t he p har mac o ki netics of 
P F -0 6 8 6 3 1 3 5 will pr o vi de g ui da nce f or d ose selecti o n f or P F -0 6 8 6 3 1 3 5.  T he g oal of t his 
a nal ys is will be t o select d oses t hat e x hi bit a n acce pta ble safety pr ofile, a n d p ote ntiall y  
pr o vi d e e vi de nce of a nti -t u m or acti vit y.  T he p har mac o d yna mic effect of B C M A: C D 3 
e n ga ge me nt b y P F -0 6 8 6 3 1 3 5 will b e i n vesti gate d i n t he b o ne marr o w f or all patie nts.  
P ote ntial effects of P F- 0 6 8 6 3 1 3 5 o n T- cell s u bset perce nta ges , pr oliferati o n a n d s ur vi val, a n d 
acti vati o n mar kers will be assesse d b y fl o w c yt o metr y.  I n a d diti o n t o t hese fl o w c yt o metr y 
a nal ys es, b o ne m arr o w bi o ps y tiss ue sa m ples will be assesse d f or si milar e n d p oi nts i ncl u di n g 
B C M A e x pressi o n a n d T- cell s u bset i m m u n o p he n ot ypi n g b y  i m m u n o hist oc he mistr y (I H C).  
T he s patial relati o ns hi p of m y el o ma cells a n d T- cells ma y be i nterr o gate d .  T hereafter, 
material a n d assa y  per mitti n g, a d diti o nal e x pl orat or y a nalys es ma y be u n derta ke n t o f urt her 
e val uate mec ha nis m of acti o n a n d/ or resista nce. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 6
T o m o nit or f or p ote ntial i m m u ne acti vati o n or i nfla m mati o n res ulti n g fr o m t he 
i m m u n osti m ulat or y effects of d osi n g wit h P F -0 6 8 6 3 1 3 5, ser u m will be c ollecte d t o meas ure 
c yt o ki nes a n d c he m o ki nes, a n d w h ole bl o o d a bs ol ute cell c o u nts (T, B, a n d N K [ nat ural 
killer] l ym p h oc y tes or T B N K) will be meas ure d. 
T he m ost c halle n gi n g o bjecti ve of t he bi o mar ker pla n wi ll be t o disc o ver mar kers t hat 
i de ntif y patie nts at baseli ne m ost li kel y t o res p o n d t o P F-0 6 8 6 3 1 3 5 t hera p y wit h mi ni mal ris k 
of t o xicit y .  E x pl orat or y a nalys es ma y be u n derta ke n t o u n dersta n d t he bi ol o gical basis f or 
res p o nse t o B C M A: C D 3 e n ga ge me nt.  T hese meas ures will atte m pt t o a d dress w het her 
baseli ne le vels or c ha n ges i n b o ne marr o w ri b o n ucleic aci d ( R N A) e x pressi o n, a n d T- cell
cl o nal di versit y c orrelate wit h t u m or res p o nse.  B o ne marr o w sa m ple ma y  be s u b mitte d t o 
R N A pr ofili n g a nal ys is t o i nterr o gate t he bala nce bet wee n i m m u ne tra nscri pts ass ociate d 
wit h i m m u ne acti vati o n a n d i m m u ne re g ulati o n.  T -cell re pert oire di versit y ma y be assesse d 
b y  hi g h t hr o u g h p ut se q ue nci n g of T-cells fr o m b o ne marr o w tiss ue a n d/ or peri p heral bl o o d.  
W h ole bl o o d a n d, s a m ple per mitti n g, a p orti o n of t he b o ne marr o w sa m ple ma y  be use d f or 
de o x yri b o n ucleic aci d (D N A ) is olati o n f or e x pl orat or y a nalys es s uc h as p har mac o ge n o mics.  
T hese assess me nts ma y  be a nalyz e d i n t he c o nte xt of cli nical res p o nse data t o p ote ntiall y  
i de ntif y patie nts wit h t he hi g hest pr o ba bilit y of res p o n di n g t o B C M A: C D 3 e n ga ge me nt.  All 
of t hese meas ures will be c orrelate d wit h meas ures of t o xicit y  a n d a nti-t u m or acti vit y t o 
ascertai n t heir usef ul ness as p ote ntial bi o mar kers of cli nical be nefit.
1. 2. 1 0. 1. B a n ke d Bi os pec i me ns
Ba n ke d b i os peci me ns will be c ollecte d f or t he p ur p ose of c o n d ucti n g researc h; s pecific uses 
are descri be d i n t he B a n ke d B i os peci me ns Secti o n 7. 7 .  C o m pari n g t he D N A, R N A, pr otei n, 
a n d meta b olite variati o n patter ns of patie nts w h o res p o n d well a n d t h ose w h o res p o n d p o orl y 
t o treat me nt ma y hel p t o better defi ne t he m ost a p pr o priate gr o u p of patie nts i n w hic h t o 
tar get a gi ve n treat me nt.  C ollecti n g bi os peci me ns f or e x pl orat or y 
p har mac o ge n o mic/ ge n o mic/ bi o mar ker a nal yses a n d retai ni n g t he m i n t he Bi os peci me n 
Ba n ki n g S ys te m ( B B S) ma ke it p ossi ble t o better u n dersta n d t he i n vesti gati o nal pr o d uct’s 
mec ha nis m of acti o n a n d t o see k e x pla nati o ns f or differe nces i n, f or e xa m ple, e x p os ure, 
t olera bilit y, safety, a n d/ or efficac y n ot a ntici pate d pri or t o t he be gi n ni n g of t he st u d y .
Ba n ke d b i os peci me ns retai ne d i n t he B B S als o ca n be use d i n research o n M M .
Pr o vi di n g t hese bi os peci me ns is a re q uire d st u d y acti vit y f or st u d y sites a n d patie nts, u nless 
pr o hi bite d b y  l ocal re g ulati o ns or et hics c o m mittee ( E C) decisi o n.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 7
2. S T U D Y O B J E C TI V E S A N D E N D P OI N T S
2. 1. P art 1 I V a n d S C m o n ot her a p y D ose Esc al ati o n , P art 1 . 1 Pri mi n g a n d M ai nte n a nce D ose Esc al ati o n
a n d P art s 1 C, 1 D a n d 
1 E D ose Esc al ati o n/ Fi n di n g
Pri m ar y O bjecti ves: 
Pri m ar y E n d p oi nts: 

T o assess safet y a n d t olera bilit y at i ncreasi n g d ose 
le vels of P F-0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne i n s uccessi ve c o h orts of patie nts wit h 
m ulti ple m yel o ma i n or der t o esti mate t he Ma xi m u m 
T olerate d D ose ( M T D) or Ma xi m u m A d mi nistere d 
D ose ( M A D) a n d select t he Rec o m me n de d P hase 2 
D ose ( R P 2 D).

N u m ber of D L Ts f oll o wi n g treat me nt wit h escalati n g d oses of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h le nali d o mi de, p o mali d o mi de, or de xa met has o ne .
Sec o n d ar y O bjecti ves: 
Sec o n d ar y E n d p oi nts: 

T o e val uate t he o verall safet y pr ofile. 

A d verse E ve nts as c haracterize d b y t y pe, fre q ue nc y, se verit y as gra de d b y N CI C T C A E 
versi o n 4. 0 3, ti mi n g, seri o us ness, a n d relati o ns hi p t o P F -0 6 8 6 3 1 3 5 treat me nt as 
m o n ot hera p y a n d i n c o m bi nati o n wit h le nali d o mi de, p o m ali d o mi de, or de xa met has o ne .  
T he se verit y of C R S will be assesse d acc or di n g t o t he gra di n g descri be d b y Lee et al. ( 2 0 1 4
a n d 2 0 1 9 ,2 ,3 See A p pe n di x 5 );

La b orat or y a b n or malities as c haracterize d b y t y pe, fre q ue nc y, se verit y (as gra de d b y N CI 
C T C A E versi o n 4. 0 3), a n d ti mi n g.

T o e val uate a nti -m yel o ma acti vit y of  P F-0 6 8 6 3 1 3 5 as 
m o n ot hera p y an d i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

O bjecti ve res p o nse rate ( O R R) usi n g t he i nter nati o nal m yel o ma w or ki n g gr o u p (I M W G) 
res p o nse criteria f or m ulti ple m yel o ma4 ,5 (see A p pe n di x 2 );

Ti m e t o e ve nt e n d p oi nts: ti me t o res p o nse ( T T R), c o m plete res p o nse rate ( C R R), d urati o n 
of res p o nse ( D O R), d urati o n of c o m plete res p o nse ( D o C R), d ur ati o n of sta ble dise ase 
( D O S D), pr o gressi o n -free s ur vi val ( P F S), o verall s ur vi val ( O S), as assesse d b y I M W G 
criteria f or res p o nse 4 ,5 (see A p pe n di x 2 );

Rate of patie nts wit h n o M R D after treat me nt wit h P F -0 6 8 6 3 1 3 5 usi n g I M W G M R D 
criteria 5 (see A p pe n di x 3 ).

T o e val uate si n gle d ose a n d m ulti ple d ose P K of 
P F -0 6 8 6 3 1 3 5 gi ve n as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de or p o mali d o mi de.
A d diti o nall y, P K of le nali d o mi de, p o mali d o mi de, a n d 

P har m ac o ki netic para meters of P F -0 6 8 6 3 1 3 5 : C y cle 1 Da y 1 d ose a n d C ycle 2 D a y 1 d ose 
ma xi m u m c o nce ntrati o n ( C ma x ), area u n der t he c o nce ntrati o n vers us ti me c ur ve fr o m ti me 
zer o t o t he last q ua ntifia ble ti me p oi nt pri or t o t he ne xt d ose ( A U C last) a n d if data per mit, 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 8
de xa met has o ne will be e val uate d w he n c o m bi ne d wit h 
P F -0 6 8 6 3 1 3 5 ( Parts 1 C, 1 D , a n d 1 E, res pecti vel y).
cleara nce ( C L or C L/ F ), v ol u me of distri b uti o n at stea d y state ( Vss or Vss/ F ), a n d ter mi nal 
eli mi nati o n t 1/ 2..

P las ma le nali d o mi de, p o mali d o mi de, a n d de xa met has o ne c o nce ntrati o ns at selecte d ti me 
p oi nts ( Parts 1 C, 1 D , a n d 1 E , res pecti vel y). 

T o e val uate i m m u n o ge nicit y of  P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h , le nali d o mi de,
p o m ali d o mi de. or de xa met has o ne .  

I nci de nce a n d titers of a nti-dr u g a nti b o dies (A D A ) a n d ne utralizi n g a nti b o dies ( Na b) 
a gai nst P F -0 6 8 6 3 1 3 5 .

T o c haracterize t he i m pact of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o m i de, or de xa met has o ne, o n s yste mic s ol u ble 
i m m u ne fact ors.

Pre - a n d p ost-d ose q ua ntificati o n of s ol u ble c yt o ki nes i n ser u m .
Terti ar y/ E x pl or at or y O bjecti ves: 
Terti ar y/ E x pl or at or y E n d p oi nts: 

E val uate t he effect of P F -0 6 8 6 3 1 3 5 as a m o n ot hera p y 
a n d i n c o m bi nati o n wit h le nali d o mi de, p o mali d o mi de,
or  de xa met has o ne o n plas ma cell, T a n d B cell 
c o m part me nts.

B C M A e x pressi o n o n plas ma cells i n b o ne marr o w , as assesse d b y m ulti para meter fl o w 
c yt o metr y a n d i m m u n o hist oc he mistr y;

Pre - a n d p ost-d ose le vels of s ol u ble B C M A;

E n u merati o n of T, B, a n d N K s u bt y pes i n w h ole bl o o d a n d b o ne marr o w b y  fl o w 
c yt o metr y a nal ysis;

T- cell i m m u n o p he n ot y pi n g, i ncl u di n g b ut n ot li mite d t o pr oliferati o n a n d acti vati o n 
mar kers i n w h ole bl o o d a n d b o ne marr o w  b y fl o w c yt o metr y a nal ysis;

T- cell e n ga ge me nt, i ncl u di n g b ut n ot li mite d t o pr oliferati o n a n d acti vati o n mar kers i n 
b o ne marr o w  b y i m m u n o hist oc he mistr y;

T he relati ve e x pressi o n of R N A tra nscri pts, i ncl u di n g b ut n ot li mite d t o, t h ose ass ociate d 
wit h i m m u ne acti vati o n a n d i m m u ne re g ulati o n i n b o ne marr o w;

T he a b u n da nce a n d di versit y of T- cell cl o nes i n b o ne ma rr o w.

T o c ollect ba n ke d bi os peci me ns f or e x pl orat or y 
researc h, u nless pr o hi bite d b y l ocal re g ulati o ns or 
et hics c o m mittee decisi o n.  

C ollecti o n of ba n ke d bi os peci me ns u nless pr o hi bite d b y l ocal re g ulati o ns or et hics 
c o m mittee decisi o n.  A d diti o nal i nf or mati o n o n c ollecti o n a n d p ote ntial use is pr o vi de d i n 
t he Ba n ke d Bi os peci me ns Secti o n 7. 7 .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 9
2. 2. P art 2 D ose E x p a nsi o n
Pri m ar y O bjecti ves: 
Pri m ar y E n d p oi nts: 

T o assess preli mi nar y cli nical efficac y at 
R P 2 D f or P F-0 6 8 6 3 1 3 5 as m o n ot hera p y a n d
i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

O R R a n d D o R , as assesse d b y I M W G criteria f or 
res p o nse4 ,5 (see A p pe n di x 2 ).
Sec o n d ar y O bjecti v es: 
Sec o n d ar y E n d p oi nts: 

T o f urt her c haracterize t he safet y a n d 
t olera bilit y of P F-0 6 8 6 3 1 3 5 as m o n ot hera p y 
a n d i n c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

A d verse E ve nts as c haracterize d b y t y pe, 
fre q ue nc y, se verit y (as gra de d b y N CI C T C A E 
versi o n 4. 0 3), ti mi n g, seri o us ness, a n d 
relati o ns hi p t o P F -0 6 8 6 3 1 3 5 treat me nt as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
p o m ali d o mi de, le nali d o mi de, or de xa met has o ne .  
T he se verit y of C R S will be assesse d acc or di n g 
t o t he gra di n g descri be d b y Lee et al. ( 2 0 1 4 a n d 
2 0 1 9 ,2 ,3 See A p pe n di x 5 );

La b orat or y a b n or malities as c haracterize d b y 
t ype, fre q ue nc y, se verit y (as gra de d b y N CI 
C T C A E versi o n 4. 0 3), a n d ti mi n g.

T o f urt her e val uate a nti -m yel o ma efficac y of 
P F -0 6 8 6 3 1 3 5 as m o n ot hera p y a n d i n 
c o m bi nati o n wit h le nali d o mi de, 
p o m ali d o mi de, or de xa met has o ne .

Ti m e t o e ve nt e n d p oi nts: C R R, D o C R, T T R, 
D O S D, P F S, O S, as assesse d b y I M W G criteria 
f or res p o nse4 ,5 (see A p pe n di x 2 );

Rate of patie nts wit h n o M R D after treat me nt 
wit h P F -0 6 8 6 3 1 3 5 usi n g I M W G M R D criteria 5
(see A p pe n di x 3 ).

E val uate P K of P F -0 6 8 6 3 1 3 5 at R P 2 D as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne . A d diti o nall y, t o c ollect
le nali d o mi de, p o mali d o mi de, a n d 
de xa met has o ne c o nce ntrati o n data whe n 
c o m bi ne d wit h P F -0 6 8 6 3 1 3 5.

C o nce ntrati o ns of P F -0 6 8 6 3 1 3 5 , le nali d o mi de, 
p o m ali d o mi de, a n d de xa met has o ne at selecte d 
ti me p oi nts.

T o e val uate i m m u n o ge nicit y of  P F -0 6 8 6 3 1 3 5
as m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o m ali d o mi de, or
de xa met has o ne . 

I nci de nce a n d titers of a nti-dr u g a nti b o dies 
(A D A ) a n d ne utralizi n g a nti b o dies ( Na b ) a gai nst 
P F -0 6 8 6 3 1 3 5.

T o c haracterize t he i m pact of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o mali d o mi de, or 
de xa met has o ne o n s yste mic s ol u ble i m m u ne 
fact ors.

Pre - a n d p ost-d ose q ua ntificati o n of s ol u ble 
c yt o ki nes i n ser u m.
Terti ar y/ E x pl or at or y O bjecti ves: 
Terti ar y/ E x pl or at or y E n d p oi nt): 

E val uate t he effect of P F -0 6 8 6 3 1 3 5 as 
m o n ot hera p y a n d i n c o m bi nati o n wit h 
le nali d o mi de, p o mali d o mi de, or 

B C M A e x pressi o n o n plas ma cells i n b o ne 
marr o w , as assesse d b y m ulti para meter fl o w 
c yt o metr y a n d i m m u n o hist oc he mistr y;
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 0
de xa met has o ne o n plas ma cell, T a n d B cell 
c o m part me nts.

Pre - a n d p ost-d ose le vels of s ol u ble B C M A;

E n u merati o n of T, B, a n d N K s u bt y pes i n w h ole 
bl o o d a n d b o ne marr o w b y fl o w c yt o metr y 
a nal ysis ;

T- cell i m m u n o p he n ot y pi n g, i ncl u di n g b ut n ot 
li mite d t o pr oliferati o n a n d acti vati o n mar kers i n 
w h ole bl o o d a n d b o ne marr o w b y fl o w 
c yt o metr y a nal ysis;

T- cell e n ga ge me nt, i ncl u di n g b ut n ot li mite d t o 
pr oliferati o n a n d acti vati o n mar kers i n b o ne 
marr o w  b y i m m u n o hist oc he mistr y;

T he relati ve e x pressi o n of R N A tra nscri pts, 
i ncl u di n g b ut n ot li mite d t o, t h ose ass ociate d 
wit h i m m u ne acti vati o n a n d i m m u ne re g ulati o n 
i n b o ne marr o w;

T he a b u n da nce a n d di versit y of T- cell cl o nes i n 
b o ne marr o w .

T o c ollect ba n ke d bi os peci me ns f or 
e x pl orat or y researc h, u nless pr o hi bite d b y 
l ocal re g ulati o ns or et hics c o m mittee decisi o n.  

C ollecti o n of ba n ke d bi os peci me ns u nless 
pr o hi bite d b y l ocal re g ulati o ns or et hics 
c o m mittee decisi o n.  A d diti o nal i nf or mati o n o n 
c ollecti o n a n d p ote ntial use is pr o vi de d i n t he 
Ba n ke d Bi os peci me ns Secti o n 7. 7 .
3. S T U D Y D E SI G N
3. 1. St u d y O ver vie w
Fi g ure 4.
C 1 0 7 1 0 0 1 St u d y Desi g n
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 1
T his is a P hase 1, o pe n -la bel, m ulti-d ose, m ulti -ce nter, d ose escalati o n, safet y, 
p har mac o ki netic ( P K) a n d p har mac o d y n a mic ( P D) st u d y of P F- 0 6 8 6 3 1 3 5 as m o n ot hera p y 
a n d i n c o m bi nati o n wit h le nali d o mi de , p o mali d o mi de or de xa met has o ne i n a d ult patie nts 
wit h a d va nce d m ulti ple m y el o ma w h o ha ve rela pse d fr o m or are refract or y  t o sta n dar d 
t hera py.  T his st u d y will be di vi de d i nt o d ose escalati o n /fi n di n g ( Part 1) a n d d ose e x pa nsi o n 
( Part 2) . Intra ve n o us (I V) a n d s u bc uta ne o us ( S C) a d mi nistrati o n of P F-0 6 8 6 3 1 3 5 will be 
e val uate d d uri n g t he Part 1 d ose escalati o n.   A n alter nati ve mai nte na nce d ose escalati o n 
p hase ( Part 1. 1), w hic h i nc or p orates t he usa ge of a pri mi n g d ose d uri n g C y cle 0 D a y 1 
( C0 D 1) 1 wee k pri or t o a mai nte na nce d ose f or all s u bse q ue nt d oses ma y  als o be i nitiate d if 
e xcessi ve t o xicit y occ urs or t he M T D / M A D is reac he d earlier t ha n desire d (see 
Secti o n 3. 1. 1. 3 ). U p o n reac hi n g M T D/ M A D, u p t o a p pr o xi matel y 6 - 1 2 patie nts t otal at 
selecte d le vel(s) bel o w t he M T D/ M A D wee kly a n d Q 2 W d osi n g u p t o t he sa me d ose 
i nte nsit y as t he M T D/ M A D wee kl y re gi me n m a y be e val uate d f urt her t o s u p p ort t he R P 2 D 
decisi o n. T he r o ute of P F -0 6 8 6 3 1 3 5 a d mi nistrati o n f or Parts 1 C, 1 D a n d Part 1 E a n d Part 2
will be deci de d o nce t he I V a n d S C d ose escalati o ns ha ve bee n c o m plete d, a n d a n R P 2 D has 
bee n selecte d.
F oll o wi n g t he deter mi nati o ns of t he R P 2 D of m o n ot hera p y a n d c o m bi nati o ns wit h 
le nali d o mi de or p o mali d o mi de i n Part 1, t he res pecti ve e x pa nsi o n c o h orts i n Part 2 will 
c o m me nce. I n a d diti o n, if t he c o m bi nati o n re gi me n wit h de xa met has o ne is well t olerate d as 
g ui de d b y m T PI i n Part 1 E , Part 2 E ma y be i nitiate d.
T he Part 2 d ose e x pa nsi o n p hase will be di vi de d i nt o 4 c o h orts as f oll o ws: Part 2 A 
(P F - 0 6 8 6 3 1 3 5 as m o n ot hera p y), Part 2 C ( P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de) ,
Part 2 D ( P F - 0 6 8 6 3 1 3 5 i n c o m bi natio n wit h p o mali d o mi de) , a n d Part 2 E (P F -0 6 8 6 3 1 3 5 i n 
c o m bi nati o n wit h de xa met has o ne), w hic h will e val uate safet y a n d a nti -m y el o ma acti vit y of 
P F -0 6 8 6 3 1 3 5 at t he R P 2 Ds deter mi ne d i n Part 1 (see Secti o n 3. 1. 1 , 3. 1. 1. 3 a n d 3. 1. 2 ).
A p pr o xi matel y 1 2 0 patie nts ha d bee n pla n ne d t o e nr oll i nt o Parts 1/ 1 . 1, 1 C, 1 D a n d 1E wit h
a p pr o xi matel y 8 0 patie nts pla n ne d t o e nr oll i nt o Part 2. Parts 1 C ,1 D a n d 1 E were pla n ne d t o
e nr ol l a p pr o xi matel y 9-1 6 patie nts wit h Part s 2 A, 2 C , 2 D a n d 2E pla n ne d t o e nr oll 
a p pr o xi matel y 2 0 patie nts eac h .
T he cli nical de vel o p me nt pr o gra m f or P F - 0 6 8 6 3 1 3 5 has bee n e x pa n de d wit h de dicate d 
st u dies t hat will f urt her i n vesti gate b ot h m o n ot hera p y a n d c o m bi nati o n t hera p y. T heref ore, 
t he S p o ns or has deter mi ne d t hat e nr ollme nt i n st u d y  C 1 0 7 1 0 0 1 has bee n c o m plete d.
All patie nts will c o m plete u p t o 4 wee ks of scree ni n g f or all Parts. 
F oll o wi n g t he i nitial d ose, treat me nt wit h i n vesti gati o nal pr o d uct will c o nti n ue u ntil disease 
pr o gressi o n, patie nt wit h dra wal of c o nse nt or u nacce pta ble t o xicit y  occ urs.  A f oll o w-u p visit 
a p pr o xi matel y 4 wee ks after t he last d ose f or a d verse e ve nt ( A E) a n d seri o us A E ( S A E) 
c ollecti o n will be c o n d ucte d.  If t he patie nt c o m plet es t he 1 m o nt h f oll o w- u p visit pri or t o 
c o m pleti o n of t he 6 0 da y l o n g ter m D L T o bser vati o n peri o d (see Secti o n 3. 2. 1 ), a f oll o w u p 
p h o ne call will be c o m plete d o n at least Da y 6 0, a n d n o m ore t ha n Da y 6 5. Patie nts f o u n d t o 
ha ve a nti -dr u g a nti b o dies ( A D A) at t heir fi nal st u d y  visit a n d a n o n g oi n g A E p ossi bl y relate d 
t o A D A will be as ke d t o ret ur n t o t he cli nic f or A D A assess me nt at a p pr o xi matel y 3 m o nt h 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 2
i nter vals (if feasi ble gi ve n t he u n derlyi n g disease) u ntil t he a d verse e ve nt or its se q uelae 
ret ur n t o baseli ne or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or.
F oll o wi n g disc o nti n uati o n of st u d y  treat me nt ( u nless patie nts are l ost t o f oll o w u p, c o nse nt is 
wit h dra w n, or st u d y is disc o nti n ue d b y t he s p o ns or), s ur vi val stat us will be c ollecte d b y 
tele p h o ne e ver y 3 m o nt hs u ntil deat h, or u p t o a p pr o xi matel y 3 0 m o nt hs after first treat me nt 
of t he last patie nt, w hic he ver c o mes first.  S u bse q ue nt a nti -ca ncer t hera pies a n d rele va nt 
tra ns pla nt i nf or mati o n will als o be c ollecte d.
Treat me nt wit h i n vesti gati o nal pr o d uct will c o nti n ue u ntil disease p r o gressi o n, patie nt ref usal 
or u nacce pta ble t o xicit y  occ urs.  T he last st u d y treat me nt will be u p t o a p pr o xi matel y 
3 0 m o nt hs after first treat me nt of t he last patie nt , a n d t he st u d y w o ul d t he n e n d after a ny 
a d diti o nal f oll o w -u p visits re q uire d after t he l ast st u d y treat me nt.
3. 1. 1. P art 1 M o n ot her a p y D ose Esc al ati o n a n d P art 1. 1 Pri mi n g a n d M ai nte n a nce 
C o h orts
S C H E D U L E O F A C TI VI TI E S A a n d S C H E D U L E O F P H A R M A C O KI N E TI C, S O L U B L E 
F A C T O R A N D C Y T O KI N E acti vities A will be utilize d i n Part 1. 
T o cl osel y  ma na ge ac ute t o xicities, all patie nts e nr olle d i nt o Part 1 d ose escalati o n p hase will 
be h os pitalize d o n C 1 D 1 ( Als o f or at least 2 4 hrs if a pri mi n g d ose is gi ve n o n C 0 D 1). T he 
h os pitalizati o n peri o d ma y be e xte n de d if t he patie nt e x perie nces a b n or mal la b orat or y  
fi n di n gs or o n g oi n g a d verse e ve nts t hat re q uire f urt her h os pitalizati o n.  T he nee d f or 
ma n dat or y  h os pitalizati o n as well as its le n gt h will be re-assesse d f or patie nts e nr olle d i n 
Part s 2 A, 2 C , a n d 2 D base d o n safet y data fr o m Part 1 after a gree me nt of s p o ns or a n d 
i n vesti gat ors at t he ti me of m o n ot hera py M T D / M A D/ a n d R P 2 D deter mi nati o n
F or safet y reas o ns, a sta g gere d e nr oll me nt strate g y will be a p plie d f or Parts 1 a n d 1. 1 at eac h 
d ose le vel ; t he first patie nt will be d ose d a n d o bser ve d f or 4 8 h o urs. If n o safety c o ncer ns 
arise d uri n g t his 4 8 hr peri o d fr o m start of treat me nt, t he n s u bse q ue nt patie nts will be 
e nr olle d i nt o t he sa me d ose le vel. All patie nts i n Part 1 a n d Part 1. 1 will be m o n it ore d 
cl osel y f or d ose li miti n g t o xicities ( D LTs, see Secti o n 3. 2 ).  Decisi o ns f or d ose escalati o n
will be ma de ba se d o n D L Ts o bser ve d wit hi n t he D L T o bser vati o n peri o d . A m o difie d 
t o xicit y pr o ba bilit y i nter val ( m T PI) met h o d, tar geti n g a D L T rate of 2 5 % a n d a n acce pta ble 
e q ui vale nce i nter val of 2 0 % -3 0 % will be utilize d f or d ose escalati o n Part 1 (see 
Secti o n 3. 1. 4 ).  At least 6, u p t o 1 6 patie nts m ust be e nr olle d i nt o a d ose le vel t hat is 
deter mi ne d t o be M T D / M A D. U p o n reac hi n g M T D/ M A D, u p t o a p pr o xi matel y 
6- 1 2 patie nts t otal at selecte d le vel(s) bel o w t he M T D/ M A D wee kl y a n d Q 2 W d osi n g u p t o 
t he sa me d ose i nte nsit y as t he M T D/ M A D wee kl y re gi me n m a y  be e val uate d f urt her t o 
s u p p ort t he R P 2 D decisi o n.
Assess me nt of late t o xicities will als o be c o m plete d after t he D L T o bser vati o n peri o d t o 
6 0 da y s after C 1 D 1 f or all patie nts. O nce a d ose le vel has bee n declare d safe, patie nts at 
l o wer d ose le vels w h o ha ve c o m plete d t he 6 0 d a y  late t o xicit y o bser vati o n peri o d ma y  
escalate t o t he ne xt hi g her d ose le vel, if criteria o utli ne d i n Secti o n 3. 1. 4. 1 Criteria f or
I ntra patie nt D ose Escalati o n ha ve bee n met .  A d diti o nal i ntra -patie nt d ose escalati o ns will 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 3
als o be per mitte d after a mi ni mal i nter val of 6 0 da ys.  N o cr oss o ver is all o we d, h o we ver, 
bet wee n m o n ot hera p y P F -0 6 8 6 3 1 3 5 a n d t he differe nt c o m bi nati o n re gi me ns.
3. 1. 1. 1. P art 1 I ntr a ve n o us (I V) A d mi nistr ati o n
I n Part 1, P F -0 6 8 6 3 1 3 5 will i nitiall y be st u die d as a n I V f or m ulati o n i n se q ue ntial d ose le vels 
( 0. 1, 0. 3, 1, 3, 1 0, 3 0, 5 0 g/ k g or hi g her if i n dicate d ) i n a d ult patie nts wit h 
rela psed /refract ory m ulti ple m y el o ma, w h o ha ve recei ve d a pr oteas o me i n hi bit or, a n 
i m m u n o m o d ulat or y dr u g (IMi D ) a n d a n a nti C D 3 8 m o n ocl o nal a nti b o d y ( m A b) w here 
a p pr o ve d a n d a vaila ble eit her i n c o m bi nati o n or as a si n gle a ge nt.  A d diti o nal d ose le vels 
(l o wer, i nter me diate or hi g her) m a y  be e val uate d.  If t o xicit y is o bser ve d at t he starti n g d ose 
le vel of 0. 1 g/ k g, 0. 0 3 g/ k g will be e val uate d .  S u bse q ue nt t o t he starti n g d ose le vel, if 
d ose de -escalati o n is rec o m me n de d b y  t he m T PI m o del after D L T e val uati o n, i nter me diate 
d ose le vels bet wee n t he pre vi o us d ose a n d c urre nt d ose ma y  be st u die d.  De pe n di n g o n t he 
o bser ve d safet y a n d t olera bilit y pr ofile of P F -0 6 8 6 3 1 3 5, d ose le vels a b o ve 5 0 g/ k g or 
hi g her if i n dicate d m a y  be e x pl ore d.  All patie nts will als o be m o nit ore d fr o m Da y 2 2 t o 
Da y 6 0 f or late t o xicities (see Secti o n 3. 2. 1 ).
If wit hi n 2 1 d a y s after t he i nitial i nf usi o n a d ose le vel i n d uces sy m pt o ms c o nsiste nt wit h
Gra de 3 C R S a n d lasts f or > 2 4 h o urs des pite sta n dar d of care treat me nt f or t he 
ma na ge me nt of C R S per t he g ui deli nes of t he i nstit uti o n, I n vesti gat or, or treati n g p h ys icia n, 
a n d it is c o nsi dere d n ot t o be d ue t o a n I R R, aller gic reacti o n, a na p h yl a xis or ot her ca uses, 
e val uati o n of Part 1 S C or Part 1 . 1 I V Mai nte na nce a d mi nistrati o n ma y be i nitiate d.
3. 1. 1. 2. P art 1 S u bc ut a ne o us ( S C) A d mi nistr ati o n
Part 1 S C a d mi nistrati o n has be e n tri g gere d base d o n t he e mer gi n g cli nical a n d P K data fr o m 
I V c o h orts at 8 0 µ g/ k g, o ne d ose le vel hi g her (“ D ose I V + 1”) t ha n t he teste d I V d ose le vel of 
5 0 µ g/ k g i n Part 1 I V a d mi nistrati o n t hat is dee me d safe a n d has n ot e x perie nce d a G ra de 3 
C R S e ve nt.
De pe n di n g o n t he o bser ve d safet y a n d t olera bilit y pr ofile of P F- 0 6 8 6 3 1 3 5, eac h d ose le vel 
f or S C a d mi nistrati o n will be i ncrease d by a ma xi m u m of 3- f ol d. 
De pe n di n g o n e val uati o n of i m m u n o ge nicit y, safet y , efficac y, P K a n d/ or P D data t he S C 
a d mi nistrati o n p orti o n ma y be place d o n h ol d or disc o nti n ue d a n d Part 1. 1 Pri mi n g a n d 
Mai nte na nce D ose Escalati o n a d mi nistrati o n ma y be re-i nitiate d if a p pr o priate. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 4
3. 1. 1. 3. P art 1 . 1 Pri mi n g a n d M ai nte n a nce C o h orts
Part 1 . 1 is a n alter nati ve d osi n g re gi me n t hat will be i nitiate d o nl y if a pri mi n g d ose f or I V or 
S C has bee n declar e d i n Part 1.  T he decisi o n t o e val uate a re gi me n t hat i ncl u des a pri mi n g 
d ose ma y  be ma de b y t he i n vesti gat ors a n d s p o ns or pri or t o reac hi n g an M T D / M A D usi n g 
t he f oll o wi n g criteria as g ui da nce:

If a d ose le vel i n d uces sy m pt o ms c o nsiste nt ≥ Gra de 3 C R S lasti n g f or > 2 4 h o urs 
(des pite treat me nt wit h sta n dar d of care per t he i nstit uti o n’s, I n vesti gat or’s , or 
treati n g p hys icia n’s g ui deli nes f or t he ma na ge me nt of C R S) c o nsi dere d n ot t o be d ue 
t o a n i nf usi o n relate d reacti o n (IR R), aller gic reacti o n, a na p h y la xis or ot her ca uses, 
t he n a l o wer d ose, w hic h has bee n e val uate d i n at least 2-4 patie nts, will be c h ose n as 
a pri mi n g d ose ( D ose Pri me) f or s u bse q ue nt c o h orts. 

If a D ose Pri me is selecte d, d ose escalati o n will c o nti n ue t o deter mi ne t he 
M T D / M A D of a d ose re gi me n t hat i ncl u des a pri mi n g d ose. 

If a d ose le vel i n d uces c o nfir me d C R S of Gra de 4 c o nsi dere d n ot t o be d ue t o a n IR R, 
aller gic reacti o n, a na p h yl a xis or ot her ca uses, t he n a l o wer d ose, w hic h has bee n 
e val uate d i n at least 2 - 4 patie nts, will be c h ose n as a pri mi n g d ose ( D ose Pri me) f or 
s u bse q ue nt c o h orts.

I n a d diti o n, o bser vati o n of a c o nfir me d C R S eve nt t hat meets t he a b o ve q ualificati o ns 
f oll o wi n g later i nf usi o ns (ie, after C ycle 1 Da y 1) or C R S e ve nts t hat are a p pr oac hi n g 
t he li mit of t olera bilit y ma y pr o m pt t he i n vesti gat ors a n d s p o ns or t o i ncl u de 
e val uati o n of a D ose Pri me f or s u bse q ue nt c o h orts.
After c o nfir mati o n of t he safet y of D ose Pri me, t he treat me nt sc he d ule will i m ple me nt t he 
i ncl usi o n of t he fi xe d pri mi n g d ose as t he first d ose ( C0 D 1) f oll o we d b y a mai nte na nce d ose
1 wee k later ( C 1 D1 ) t hat will c o nti n ue t o be escalate d i n s u bse q ue nt c o h orts f oll o wi n g a n 
m T PI  met h o d.  T he starti n g mai nte na nce d ose le vel will be n o greater t ha n 2 -f ol d a b o ve t he 
pri mi n g d ose (see Secti o n 3. 1. 4 ). De pe n di n g o n t he o bser ve d safet y a n d t olera bilit y pr ofile 
of P F -0 6 8 6 3 1 3 5, eac h mai nte na nce d ose le vel a d mi nistrati o n will be i ncrease d b y  a 
ma xi m u m of 2 -f ol d. After t he M T D / M A D h a s bee n esta blis he d, t he pri mi n g d ose ma y 
p ote ntiall y  be f urt her verifie d i n c o n necti o n t o t he esta blis he d M T D/M A D/ R P 2 D, i ncl u di n g 
c o nsi derati o n of m ore t ha n o ne pri mi n g ste p, if i n dicate d, usi n g i nf or mati o n fr o m all patie nts 
w h o were i ncl u de d i n t he i nitia l pri mi n g d ose deter mi nati o n as well as t h ose e nr olle d i n 
s u bse q ue nt d osi n g c o h orts.
S C H E D U L E O F A C TI VI TI E S B: WI T H P RI MI N G D O S E A N D S C H E D U L E O F 
P H A R M A C O KI N E TI C , S O L U B L E F A C T O R A N D C Y T O KI N E A C TI VI TI E S B will t he n 
be utilize d i n Part 1 . 1.  I n Part 1 . 1, patie nts will recei ve t he pri mi n g d ose o n C0 D 1 d uri n g t he 
pr i mi n g d ose p orti o n of C ycle 0. T he pri mi n g d ose will re mai n t he sa me f or all d ose le vel 
c o h orts. T he mai n te na nce d ose will be a d mi nistere d o ne wee k later o n C 1 D 1 a n d f or 
s u bse q ue nt c ycles. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 5
T o cl osel y  ma na ge ac ute t o xicities, all patie nts recei vi n g a pri mi n g d ose will be h os pitalize d 
f or at least 2 4 hrs o n b ot h C 0 D 1, a n d C 1 D 1.  T he h os pitalizati o n peri o d ma y be e xte n de d if 
t he patie nt e x perie nces a b n or mal la b orat or y fi n di n gs or o n g oi n g a d verse e ve nts t hat re q uire 
f urt her h os pitalizati o n. 
F or safet y reas o ns, a sta g gere d start will be e m pl o ye d at eac h d ose le vel; t he first pati e nt will 
be d ose d, a n d o bser ve d f or 4 8 h o urs. T he 4 8 hr o bser vati o n peri o d f or t he first patie nt i n 
eac h d ose le vel i n Part 1 . 1 will be gi n o n C 1 D 1 d uri n g t he sec o n d h os pitalizati o n peri o d. If 
n o safet y c o ncer ns arise d uri n g t his 4 8 hr peri o d fr o m start of treat me nt, t he n s u bse q ue nt 
patie nts will be e nr olle d i nt o t he sa me mai nte na nce d ose le vel. 
Decisi o ns f or mai nte na nce d ose escalati o n will be ma de base d o n t o xicities o bser ve d wit hi n 
t he D L T o bser vati o n peri o d ( C ycles 0 a n d 1) .  S u bse q ue nt t o starti n g t h e mai nte na nce d ose 
le vel, if d ose de-escalati o n is rec o m me n de d b y t he m T PI  m o del after e val uati o n, i nter me diate 
d ose le vels bet wee n t he pre vi o us d ose a n d c urre nt d ose ma y  be st u die d.  At least 6, u p t o 
a p pr o xi matel y 1 6 patie nts m ust be e nr olle d i nt o a mai n te na nce d ose le vel t hat is deter mi ne d 
t o be t he ma xi m u m t olerate d d ose ( M T D)/M A D . 
O nce a d ose le vel has bee n declare d safe, patie nts at l o wer d ose le vels w h o ha ve c o m plete d 
6 0 da y  late t o xicit y o bser vati o n peri o d ma y  escalate t o t he ne xt hi g her d ose le vel, if criteria 
o utli ne d i n Secti o n 3. 1. 4. 1 Criteria f or I ntra patie nt D ose Escalati o n ha ve bee n met .  
A d diti o nal i ntra -patie nt mai nte na nce d ose escalati o ns will als o be per mitte d after a mi ni mal 
i nter val of 6 0 d a y s fr o m first a d mi nistrati o n of mai nte na nce d ose.  
Alter nati ve strate gies f or i ncreasi n g d osi n g s uc h as a ste p -u p re gi me n or pr o p h y lactic ster oi ds 
ma y als o be c o nsi dere d a n d i m ple me nte d t o f urt her i m pr o ve t olera bilit y  if nee de d.
3. 1. 1. 4. P art 1 C o m bi n ati o n D ose Fi n di n g
Parts 1 C, 1 D a n d 1E , are d ose fi n di n g safety c o h orts f or P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h 
le nali d o mi de, p o mali d o mi de or de xa met has o ne , res pecti vely.  U p o n deter mi ni n g t he 
P F - 0 6 8 6 3 1 3 5 R P 2 D/ M T D / M A D a n d r o ute of a d mi nistrati o n as m o n ot hera p y eit her wit h or 
wit h o ut pri mi n g d ose i n Part 1, Parts 1 C, 1 D a n d 1E will be i nitiate d t o st u d y t he safety of
P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de , p o mali d o mi de , or de xa met has o ne .  Parts 1 C
a n d 1 D will be starte d wit h P F -0 6 8 6 3 1 3 5 o ne d ose le vel bel o w t he M T D / M A D a n d escalate d 
o ne d ose le vel u nless t he R P 2 D is bel o w t he M T D / M A D i n w hic h case t he R P 2 D will be 
use d as t he starti n g d ose of P F- 0 6 8 6 3 1 3 5 . If i n Parts 1 C, or 1 D, t he c o m bi nati o n is n ot well 
t olerate d, d oses of P F -0 6 8 6 3 1 3 5 ma y  be de- escalate d t o a l o wer d ose le vel bel o w t he starti n g 
d ose of P F -0 6 8 6 3 1 3 5 use d i n c o m bi nati o n . Part 1 E will be a c o m bi nati o n of P F -0 6 8 6 3 1 3 5 at 
R P 2 D/ M T D/ M A D a n d de xa met has o ne. If t his c o m bi nati o n is n ot well t olerate d, Part 2 E ma y 
n ot be i nitiate d.  
As descri be d i n Secti o n 3. 4 , a d ose of 1 0 0 0 µ g/ k g S C wee kl y has bee n selecte d as t he R P 2 D 
f or P F-0 6 8 6 3 1 3 5 as a si n gle a ge nt. T his si n gle a ge nt R P 2 D will be a d mi nistere d as a fi xe d 
d ose of 7 6 m g ( a fi xe d d ose e q ui vale nt of 1 0 0 0 µ g/ k g; see Secti o n 1. 2. 9. 4 f or rati o nale) 
f oll o wi n g a pri mi n g d ose of 4 4 m g (a fi xe d d ose e q ui vale nt of 6 0 0 µ g/ k g) a d mi nistere d o ne 
wee k earlier. Si milarl y, Part 1 c o m bi nati o n d ose fi n di n g ( Part 1 C a n d Part 1 D) will be 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 6
a d mi nistere d as fi xe d d oses f or P F- 0 6 8 6 3 1 3 5 wit h mai nte na nce d os es starte d o ne wee k after 
t he pri mi n g d ose; t he starti n g d ose is o ne d ose le vel bel o w t he si n gle a ge nt R P 2 D as 
descri be d i n Ta ble 1:
T a ble 1. 
T a ble of P ote nti al Fi xe d D ose Le vels 
D ose le vel a
Pri mi n g D ose
(m g )
M ai nte n ace D ose
( mg)
0
2 4
3 2
1 (starti n g)
3 2
4 4
2 b
4 4
7 6
a. D ose le vel refers t o desi g nate d d ose le vels f or Part 1 C a n d Part 1 D
b. Desi g nate d d ose le vel f or Part 1 E
Part 1 C will i n vesti gate P F- 0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de i n se q ue ntiall y 
escalati n g d oses of P F- 0 6 8 6 3 1 3 5 . T his safet y c o h ort will start wit h t he d ose le vel 
M T D- 1 / M A D- 1 or R P 2 D ( w hic he ver is l o wer) of P F -0 6 8 6 3 1 3 5 fr o m t he Part 1 d ose
escalati on a n d 1 5 m g d ose of le nali d o mi de i n or der t o select t he c o m bi nati o n R P 2 D. If t he 
c o m bi nati o n re gi me n is n ot well t olerate d, a d ose t hat is l o wer t ha n t he R P 2 D deter mi ne d f or 
si n gle-a ge nt P F-0 6 8 6 3 1 3 5 ma y  be e val uate d i n c o m bi nati o n bef ore pr ocee di n g t o Par t 2. If 
necessar y , de-escalati o n will be g ui de d b y a n m T PI desi g n . P F - 0 6 8 6 3 1 3 5 will be 
a d mi nistere d o n C 1 D 1 a n d wee kl y or e ver y  2 wee ks or o nce per c y cle ( C X D 1) t hereafter
wit h or wit h o ut a pri mi n g d ose . A d ose of 1 5 m g of le nali d o mi de will be a d mi niste re d orally 
o n Da y s 1- 2 1. P F -0 6 8 6 3 1 3 5 a n d le nali d o mi de will be a d mi nistere d o ver a c y cle of 2 8 d a y s.
A sta g gere d e nr oll me nt strate g y  will be a p plie d at eac h d ose le vel: w he n a d ose le vel o pe ns 
f or e nr oll me nt, t he first patie nt wi ll be d ose d, a n d o bser ve d f or 9 6 h o urs be y o n d C 1 D 1 .  If n o 
safet y c o ncer ns arise d uri n g t his 9 6 hr peri o d fr o m C 1 D 1 of P F - 0 6 8 6 3 1 3 5 a n d le nali d o mi de, 
s u bse q ue nt patie nts will be e nr olle d i nt o t he sa me d ose le vel.  T o cl osel y ma na ge ac ute 
t o xicities, patie nts will be h os pitalize d o n C 1 D 1.   It is e x pecte d t hat Part 1 C will e nr oll 
a p pr o xi matel y 9- 1 6 patie nts.
Part 1 D will i n vesti gate P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h p o mali d o mi de i n de -escalati o n 
d oses.  T his safet y c o h ort will e val uate t he M T D -1/ M A D - 1 or R P 2 D d ose le vel ( w hic he ver 
is l o wer) of P F - 0 6 8 6 3 1 3 5 fr o m Part 1 d ose escalati o n a n d a sta n dar d of care d ose of 
p o mali d o mi de i n or der t o select t he c o m bi nati o n R P 2 D.  I f t he c o m bi nati o n re gi me n is n ot 
well t olerate d, a d ose t hat is l o wer t ha n t he R P 2 D deter mi ne d f or si n gle -a ge nt P F- 0 6 8 6 3 1 3 5 
ma y  be e val uate d i n c o m bi nati o n bef ore pr ocee di n g t o Part 2.  If necessar y, de-escalati o n 
will be g ui de d b y m T PI.  T he first d ose of P F -0 6 8 6 3 1 3 5 will be a d mi nistere d o n C 1 D 1 a n d 
wee kl y t hereafter.  A d ose of 4 m g of p o mali d o mi de will be a d mi nistere d oral l y o n 
D a y s 1-2 1.  P F -0 6 8 6 3 1 3 5 a n d p o mali d o mi de will be a d mi nistere d o ver a c y cle of 2 8 d a y s.  A 
sta g gere d e nr oll me nt strate g y will be a p plie d at eac h d ose le vel: w he n a d ose le vel o pe ns f or 
e nr oll me nt, t he first patie nt will be d ose d, a n d o bser ve d f or 9 6 h o urs.  If n o safet y c o ncer ns 
arise d uri n g t his 9 6 hr peri o d fr o m C 1 D 1 of P F -0 6 8 6 3 1 3 5 a n d p o mali d o mi de, s u bse q ue nt 
patie nts will be e nr olle d i nt o t he sa me d ose le vel.  T o cl osel y ma na ge ac ute t o xicities, 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 7
patie nts will be h os pitalize d o n C 1 D 1.  It is e x pected t hat Part 1 D will e nr oll a p pr o xi matel y  
9 - 1 6 patie nts.
Part 1 E will i n vesti gate P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h de xa met has o ne. T his safet y c o h ort 
will e val uate t he R P 2 D fi xe d d ose le vel of P F -0 6 8 6 3 1 3 5 m o n ot hera p y a n d a fi xe d d ose of 
de xa met has o ne , at a d ose of 4 0 m g .  F or s u bjects ol der t ha n 7 5 years or u n der wei g ht ( b o d y 
mass i n de x [ B MI] < 1 8. 5), de xa met has o ne pre me dicati o n ma y  be gi ve n pri or t o P F - 0 6 8 6 3 1 3 5
at a d ose of 2 0 m g. If t he c o m bi nati o n re gi me n is n ot well t olerate d d ue t o P F- 0 6 8 6 3 1 3 5, 
P F - 0 6 8 6 3 1 35 ma y  be de-escalate d i n c o m bi nati o n acc or di n g t o m o difie d t o xicit y  pr o ba bility 
i nter val ( m T PI) desi g n. Eac h c ycle of t he c o m bi nati o n of P F-0 6 8 6 3 1 3 5 a n d de xa met has o ne 
starti n g wit h C ycle 1 will be 2 8 d a y s. If t he c o m bi nati o n re gi me n is n ot well t olerate d as 
g ui de d b y m T PI, Part 2 E ma y  n ot be i nitiate d. De xa met has o ne w o ul d be gi n o n C 0 D 1 a n d it 
will be d ose d as pre me dicati o n pri or t o P F -0 6 8 6 3 1 3 5 a d mi nistrati o n. If a patie nt has recei ve d 
de xa met has o ne f or 6 m o nt hs or P F -0 6 8 6 3 1 3 5 is disc o nti n ue d, t he n de xa met ha s o ne s h o ul d be 
disc o nti n ue d u nless cli nical rati o nale t o c o nti n ue de xa met has o ne is pr o vi de d b y  i n vesti gat or 
a n d a p pr o ve d b y s p o ns or . Patie nts w h o nee d t o disc o nti n ue treat me nt wit h de xa met has o ne 
ma y  c o nti n ue t o recei ve treat me nt wit h P F -0 6 8 6 3 1 3 5 . If a d ose of P F -0 6 8 6 3 1 3 5 is hel d or 
s ki p pe d, t he n de xa met has o ne s h o ul d n ot be a d mi nistere d u ntil P F- 0 6 8 6 3 1 3 5 is restarte d. It is 
e x pecte d t hat Part 1 E will e nr oll a p pr o xi matel y  9- 1 6 patie nts.
3. 1. 2. P art 2 D ose E x p a nsi o n 
Part 2 d ose e x pa nsi o n p hase will be di vi de d i nt o 4 c o h orts as f oll o ws: Part 2 A ( P F -0 6 8 6 3 1 3 5 
as m o n ot hera p y), Part 2 C ( P F - 0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h le nali d o mi de), Part 2 D 
(P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h p o mali d o mi de), a n d Part 2 E (P F -0 6 8 6 3 1 3 5 i n 
c o m bi nati o n wit h d e xa met has o ne) w hic h will e val uate safety a n d a nti -m y el o ma acti vit y of 
P F -0 6 8 6 3 1 3 5 at t he m o n ot hera p y /c o m bi nati o n R P 2 D .
Base d o n e mer gi n g cli nical data fr o m t he Part 1 d ose escalati o n, eit her I V or S C 
a d mi nistrati o n i ncl u di n g pri mi n g a n d mai nte na nce d ose Q 1 W or Q 2 W will be selecte d f or 
t he Part 2 d ose e x pa nsi o n.
If t he S C a d mi nistrati o n is selecte d f or Part 2 d ose e x pa nsi o n, all patie nts i n 2 C, 2 D a n d 2 E 
will recei ve a s u bc uta ne o us fi xe d d ose of P F -0 6 8 6 3 1 3 5 at t he Q 1 W R P 2 D ( wit h or wit h o ut a 
pri mi n g d ose gi ve n at C 0 D 1 1 wee k pri or t o C 1 D 1). Part 2 A patie nts will als o recei ve a 
s u bc uta ne o us fi xe d d ose of P F- 0 6 8 6 3 1 3 5 at eit her t he R P 2 D Q 1 W or Q 2 W sc he d ule, 
de pe n di n g o n e mer gi n g cli nical data i n Part 1. 
F or le nali d o mi de, Part 2 C, 1 5 m g orall y ( P O ) will be a d mi nistere d dail y o n da y s 1– 2 1 o f a
2 8 da y  c ycle starti n g C 1 D 1 i n c o m bi nati o n wit h t he M T D/M A D
or R P 2 D of P F - 0 6 8 6 3 1 3 5 
deter mi ne d i n Part 1 C ( wit h or wit h o ut a pri mi n g d ose of P F-0 6 8 6 3 1 3 5 gi ve n at C 0 D 1 ,
1 wee k pri or t o C 1 D 1) .
F or p o mali d o mi de , Part 2 D, 4 m g P O will be a d mi nistere d dail y  o n days  1– 2 1 of a 2 8-d a y  
c ycle starti n g C 1 D 1 i n c o m bi nati o n wit h t he M T D/M A D
or R P 2 D of P F -0 6 8 6 3 1 3 5 
deter mi ne d i n Part 1 D ( wit h or wit h o ut a pri mi n g d ose of P F -0 6 8 6 3 1 3 5 gi ve n at C 0 D 1 
1 wee k pri or t o C 1 D 1).
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 8
F or de xa met has o ne, Part 2 E, 4 0 m g P O will be a d mi nister e d as pre me dicati o n 6 0 ± 3 0 
mi n utes pri or t o P F - 0 6 8 6 3 1 3 5 starti n g C 0 D 1 i n c o m bi nati o n wit h t he M T D/ M A D/ R P 2 D 
fi xe d d ose of P F-0 6 8 6 3 1 3 5 deter mi ne d i n Part 1. F or s u bjects ol der t ha n 7 5 y ears or 
u n der wei g ht ( b o d y mass i n de x [ B MI ] < 1 8. 5), de xa met has o ne pre me dicati o n ma y be gi ve n 
6 0 ± 3 0 mi n utes pri or t o P F - 0 6 8 6 3 1 3 5 at a d ose of 2 0 m g.
T he R P 2 D selecte d will be base d o n t he M T D or t he M A D , a n d f urt her e val uati o n of ot her 
c o variates s uc h as disease b ur de n, s ol u ble plas ma B C M A le vel, a n d b o d y s ize i nf or mati o n
will als o be utilize d .  S electi o n of 1 hr or 2 hr i ntra ve n o us a d mi nistrati o n (if utilize d i n 
P art 2) will be base d o n t he i nci de nce of I R Rs.  A p pr o xi mat el y 8 0 patie nts ma y be e nr olle d 
i nt o Part 2 (see Secti o n 9. 3 Sa m ple Size Deter mi nati o n ) wit h a p pr o xi matel y 2 0 patie nts i n 
Part s 2 A, 2 C , 2 D, a n d 2 E. Patie nts fr o m t he d ose fi n di n g c o m bi nati o n c o h orts of Parts 1 C, 
a n d 1 D treate d at t he d ose le vels selecte d f or Part 2 ma y be c o u nte d t o war ds sa m ple size of 
t he c orres p o n di n g c o h orts of Part 2.
P reli mi nar y data fr o m t he Part 2 d ose e x pa nsi o n ma y  pr o vi de g ui da nce i n t he S p o ns or’s 
decisi o n t o a dj ust t he sa m ple size of eac h ar m, t o a d d ot her a vaila ble treat me nt c o m bi nati o ns
i n a f ut ure a me n d me nt, or t o i nitiate a d diti o nal cli nical st u dies.
3. 1. 3. St arti n g D ose
T he starti n g d ose f or Part 1 I V a d mi nistrati o n will be 0. 1 g/ k g gi ve n wee kl y  i n 3 wee k
c ycles. 
3. 1. 4. Criteri a f or D ose Esc al ati o n / De- Esc al ati o n
T he st u d y  has bee n desi g ne d t o esta blis h t he M T D / M A D defi ne d as t he d ose t hat y iel ds 
a p pr o xi matel y 2 5% pr o ba bilit y  of D L T a n d c o nsi ders e q ui vale nt d oses t hat yiel d pr o ba bility 
of D L T i n t he i nter val ( E q ui vale nce I nter val) 2 0 % t o 3 0 %. 
All d ose escalati o n/ de -escalati o ns will be g ui de d b y t he m T PI desi g n a n d t heref ore 
2- 4 patie nts will be e nr olle d i n eac h c o h ort (see Secti o n 3. 1 St u d y  O ver vie w).
T he p ote ntial d ose le vels t o be e val uate d f or Part 1 I V a d mi nistrati o n are liste d i n Ta ble 2 .  
T he p ote ntial d ose le vels t o be e val uate d f or Part 1 S C a d mi nistrati o n are liste d i n Ta ble 3 . 
D ose esc alati o n f or Part 1 I V a n d S C will start at d ose le vel 1 f or eac h (Ta ble 2 a n d Ta ble 3 ).
I n Part 1, f or b ot h I V a n d S C a d mi nistrati o n, t he ma xi m u m d ose i ncrease will be 
a p pr o xi matel y 3 f ol d if n o D LTs are o bser ve d; per m T PI , i nter me diate or hi g her d oses ma y  
be e val uat e d base d o n cli nical fi n di n gs.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 9
T a ble 2.
T a ble of P ote nti al D ose Le vels i n P art 1 I V A d mi nistr ati o n
D ose le vel
D ose
( μ g/ k g)
1
0. 1
2
0. 3
3
1. 0
4
3. 0
5
1 0. 0
6
3 0. 0
7
5 0. 0
T a ble 3 .
T a ble of P ote nti al D ose Le vels i n P art 1 S C A d mi nistr ati o n
D ose le vel
D ose
( μ g/ k g)
0
5 0
1
8 0
2
1 3 0
3
2 1 5
4
3 6 0
5
6 0 0
6
1 0 0 0
I n Part 1 . 1, t he starti n g mai nte na nce d ose will be n o m ore t ha n 2-f ol d a b o ve t he pri mi n g d ose 
esta blis he d fr o m Part 1. Ma xi m u m mai nte na nce d ose i ncreases will be 2 -f ol d ( 1 0 0 %).
Q 2 W d osi n g w o ul d be e val uate d u p o n reac hi n g M T D/ M A D. C y cles f or Q 2 W d osi n g w o ul d 
be 4 wee ks rat her t ha n t he 3 wee ks wit h Q 1 W d osi n g. B ot h Q 1 W a n d Q 2 W d osi n g ma y  be 
c o nsi dere d f or Part 2 A e x pa nsi o n fr o m Part 1.
O nce t he first D L T is o bser ve d, t he ma xi m u m i ncrease w o ul d i ncrease n o m ore t ha n 2- f ol d
u p t o 3 µ g/ k g , a n d n o m ore t ha n 6 7 % b e y o n d 3 µ g/ k g .
Part s 1 C, a n d 1 D will c o m bi ne escalati n g d oses of P F -0 6 8 6 3 1 3 5 starti n g at t he m o n ot hera p y 
M T D- 1 /M A D - 1 or R P 2 D ( w hic he ver is l o wer) d ose le vel a n d i ncreasi n g t o t he m o n ot hera py 
R P 2 D / M T D, if a p plica ble, i n c o m bi nati o n wit h a sta n dar d d ose of le nalid o mi de or 
p o mali d o mi de, res pecti vel y. D e -escalati o n of P F -0 6 8 6 3 1 3 5 t o a l o wer d ose le vel ma y  occ ur 
if necessar y.
I n Part 1 E, t he c o h ort t hat i ncl u des de xa met has o ne will e val uate P F-0 6 8 6 3 1 3 5 at a pri mi n g 
d ose of 4 4 m g f oll o we d b y a mai nte na nce d ose of 7 6 m g a d mi nistere d.  De -escalati o n of 
P F -0 6 8 6 3 1 3 5 t o a l o wer d ose le vel ma y  occ ur if necessar y.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 1
a n d/ or t he patie nt ref uses t o u n der g o a b o ne marr o w pr oce d ure ; if a b o ne marr o w 
as pirate or bi o ps y was perf or me d wit hi n t he past 2 8 da y s pri or t o pla n ne d start of 
escalate d d ose, o nly disease sta gi n g l a b tests m ust be perf or me d );
4.
A disc ussi o n bet wee n t he i n vesti gat or a n d s p o ns or has bee n c o m plete d, a n d it is 
a gree d t hat t his will be i n t he patie nt’s best i nterest .
A patie nt w h ose d ose has bee n escalate d will n ot c o ntri b ute t o t he assess me nt of t he n u m ber 
of D L Ts at t he escalate d d ose le vel.
3. 2. D ose Li miti n g T o xicit y ( D L T ) Defi niti o n
M o nit ori n g f or D L Ts
will occ ur d uri n g Part 1. Se verit y  of a d verse e ve nts ( A Es) will be 
gra de d acc or di n g t o Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse 
E ve nts ( C T C A E ) versi o n 4. 0 3.  T he se verit y  of c yt o ki ne release s yn dr o me ( C R S) will be 
assesse d acc or di n g t o t he gra di n g descri be d b y Lee et al. ( 2 0 14 a n d 2 0 1 9 ,2 ,3 See A p pe n di x 5 ).
F or t he p ur p ose of d ose escalati o n, t he D L T o bser vati o n peri o d will be u p t o t he e n d of C ycle 
1 i n eac h patie nt. F or t h ose patie nts recei vi n g a pri mi n g d ose, C ycle 0 a n d C y cle 1 w o ul d be 
i ncl u de d i n t he D L T o bser vati o n peri o d.  D L T e val ua ble patie nts will i ncl u de patie nts t hat 
ha ve e x perie nce d a D L T i n t he D LT o bser vati o n peri o d or . D L T e val ua ble patie nts will als o 
i ncl u de t h ose w h o recei ve d all of t heir pla n ne d d oses of P F - 0 6 8 63 1 3 5 i n t he i nitial D LT 
o bser vati o n peri o d if Q 2W d osi n g is bei n g e val uate d or at least all b ut o ne of t heir pla n ne d 
d oses of P F -0 6 8 6 1 3 5 if Q 1 W d osi n g is bei n g e val uate d , pr o vi de d a d ose was n ot misse d d ue 
t o t o xicit y attri b ute d t o st u d y dr u g. Safet y i nf or mati o n fr o m a n y patie nts t hat d o n ot meet 
D L T e val ua ble criteria c o ul d still be c o nsi dere d f or o verall d ose escalati o n decisi o ns 
alt h o u g h t he y w o ul d n ot fact or i nt o m T PI decisi o n r ules.
A n y  of t he f oll o wi n g a d verse e ve nts o bser ve d wit hi n t he D LT o bser vati o n peri o d c o nsi dere d 
relate d t o P F- 0 6 8 63 1 3 5 or P F -0 6 8 6 3 1 3 5 i n c o m bi nati o n wit h
le nali d o mi de, p o mali d o mi de, 
de xa met has o ne, will be classifie d as D L Ts: 
He m at ol o gic al:

Gra de 4 ne utr o pe nia lasti n g > 5 d a y s. E xce pt i n le nali d o mi de c o m bi nati o n c o h ort 
w here it ca n be ma na ge d b y  d ose re d ucti o n of le nali d o mi de i n t he ne xt c ycle.

Fe brile ne utr o pe nia ( defi ne d as a n a bs ol ute ne utr o p hil c o u nt [ A N C] < 1 0 0 0/ m m 3 wit h 
a si n gle te m perat ure of > 3 8. 3 C [ 1 0 1 F] , or a s ustai ne d te m perat ure of 3 8 C
[ 1 0 0. 4F] f or m ore t ha n o ne h o ur). If fe ver is d eter mi ne d t o be a s y m pt o m of C R S 
c o nfir me d b y cli nical c o urse a n d c yt o ki ne le vels a n d res ol ves i n a ma n ner c o nsiste nt 
wit h C R S, t his w o ul d n o l o n ger be c o nsi dere d a D L T, a n d t he patie nt ma y  res u me 
treat me nt.

Gra de 3 ne utr o pe nia wit h i nfecti o n . 

Gra de 4 t h r o m b oc yt o pe nia ( u nless t he st u d y e ntr y baseli ne c o u nt was ≥2 5, 0 0 0 a n d 
< 5 0, 0 0 0 t o ta ke i nt o acc o u nt b o ne marr o w s u p pressi o n d ue t o m ulti ple m yel o ma, i n 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 2
t his case gra de 4 t hr o m b oc yt o pe nia nee ds t o be acc o m pa nie d b y ≥Gra de 2 blee di n g 
t o be a D L T).  For su bjects w h o e x perie nce a platelet c o u nt < 1 0 , 0 0 0/ m m3, t his is 
c o nsi dere d a D L T irres pecti ve of ot her fact ors wit h t he e xce pti o n of le nali d o mi de-
relate d Gra de 4 t hr o m b oc yt o pe nia ma na gea ble b y platelet tra nsf usi o ns a n d 
le nali d o mi de d ose re d ucti o n i n t he ne xt c ycle. 

Gra de 3 t hr o m b oc y t o pe nia wit h ≥Gra de 2 blee di n g.
N o n -he m at ol o gic al:

Gra de 4 A d verse E ve nts ( A Es).

Gra de 3 A E lasti n g ≥5 d a y s des pite o pti mal s u p p orti ve care, wit h t he e xce pti o n of A E 
attri b ute d t o a C R S e ve nt (i e, Gra de 3 tra nsa mi nitis).

Gra de 3 C R S , e xce pt t h ose C R S t hat ha ve i) n ot bee n ma xi mall y  treate d (ie, lac k of
a d mi nistrati o n of sta n dar d of care treat me nt per t he i nstit uti o n’s, I n vesti gat or’s, or 
treati n g p hys icia n’s g ui deli nes f or t he ma na ge me nt of C R S) or ii) i m pr o ve d t o 
≤Gra de 1 wit hi n 4 8 h o urs .

Gra de 4 C R S.

C o nfir me d dr u g -i n d uce d li ver i nj ur y ( DI LI) meeti n g H y’s la w criteria o utli ne d i n 
Secti o n 8. 4. 1 .

Gra de 4 la b orat or y  a b n or malities dee me d cli nicall y si g nifica nt b y  t he i n vesti gat or 
s hall be re p orte d as Gra de 4 A E as descri be d i n Secti o n 8. 2. 2 .

Cli nicall y  i m p orta nt or persiste nt t o xicities (e g, t o xicities res p o nsi ble f or si g nifica nt 
d ose dela y ) t hat are n ot i ncl u de d i n t he a b o ve criteria ma y als o be c o nsi dere d a D L T 
f oll o wi n g re vie w b y t he i n vesti gat ors a n d t he S p o ns or.  All D L Ts nee d t o re prese nt a 
cli nicall y si g nifica nt s hift fr o m baseli ne.
T he f oll o wi n g A Es will n ot be a dj u dicate d as D L Ts:

Is olate d Gra de 3 la b orat or y  a b n or malities t hat are n ot ass ociate d wit h cli nical 
se q uelae a n d are c orrecte d wit h s u p ple me ntati o n/a p pr o priate ma na ge me nt wit hi n 
7 2 h o urs of t heir o nset or dee me d cli nicall y i nsi g nifica nt b y  t he i n vesti gat or.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 3
3. 2. 1. L ate T o xicities
Late t o xicities are A Es t hat meet t he sa me gra di n g criteria as D L T criteria a n d occ ur fr o m 
C y cle 2 Da y 1 t hr o u g h t he 6 0 d a y  assess me nt peri o d.  If late t o xicities occ ur t h ose m a y be 
i nc or p orate d i n t he m T PI a p pr oac h a n d e nr oll me nt i nt o a n y hi g her d ose le vel c o h orts ma y be 
place d o n te m p oraril y h ol d.  All safet y data will be re vie we d, a n d a decisi o n will be ma de t o 
eit her:

C o nti n ue e nr oll me nt i n hi g her d ose le vel c o h orts.

I ncrease t he n u m ber of patie nts at t he d ose le vel i n w hic h t he late t o xicities occ urre d 
t o satisf y t he m T PI decisi o n r ules (Secti o n 3. 1. 4 ).  All patie nts will be f oll o we d f or at 
least 6 0 d a y s t o assess safet y at t his d ose le vel.  If t he m T PI decisi o n r ule of 
d ose -escalati o n is reac he d, e nr oll me nt i n hi g her d ose le vel c o h orts ma y  res u me.  If 
after t he e nr oll me nt of a d diti o nal s u bjects t he m T PI rec o m me n ds t o de -escalate t he 
d ose, t he o pti o n t o de-escalate t he d ose will be disc usse d.

Per ma ne ntl y  st o p e nr oll me nt i n hi gher d ose le vel c o h orts, a n d declare t he d ose le vel 
t o be a b o ve M T D/ M A D.  Increase t he n u m ber of patie nts at t he d ose le vel i n w hic h 
t he late t o xicities occ urre d t o satisf y t he m T PI decisi o n r ules (Secti o n 3. 1. 4 ).

St o p t he st u d y . 
F or a n y gi ve n patie nt t hat is o n -treat me nt at d ose le vels t hat are s u bse q ue ntl y c o nsi dere d t o 
be a b o ve t he M T D / M A D, t he o pti o n t o d ose re d uce will be disc usse d.  If a patie nt t olerate d 
t he a b o ve M T D/ M A D d ose le vel well a n d is be nefiti n g, c o nti n uati o n of treat me nt at t he 
a b o ve M T D/ M A D d ose le vel will re q uire re -c o nse nti n g.
3. 3. M a xi m u m T oler ate d a n d M a xi m u m A d mi nistere d D ose ( M T D
a n d M A D )
Defi niti o n s
T he M T D is defi ne d as t he hi g hest d ose wit h tr ue t o xicit y pr o ba bilities i n t he e q ui vale nce 
i nter val (EI ) w here t he EI is defi ne d as 2 0 %- 3 0 %.
E ve n t h o u g h t he m T PI m o del ma y  select a n M T D wit h a n i nci de nce of D L Ts t hat is hi g her 
t ha n 3 0 % si nce m T PI decisi on r ules are base d o n u nit pr o ba bilit y  mass ( U P M) a n d n ot o n 
p oi nt esti mates of t he D L T rate (see Secti o n 9. 2. 1 ), d oses wit h a n i nci de nce of D L T 
> 3 0 % (e g, 3 o ut of 9) ca n n ot be declare d as t he M T D.   I n practice, m o del rec o m me n dati o ns 
ma y  be o verri d de n b y cli nical j u d g me nt, a n d M T D wit h a n i nci de nce of D L Ts t hat is hi g her 
t ha n 3 0 % will n ot be c o nsi dere d acce pta ble t o be selecte d as M T D.  T he M T D will be t he 
hi g hest d ose ass ociate d wit h t he occ urre nce of D L Ts ≤3 0 % (e g, < 3 of 9 e val ua ble patie nts 
e x perie nce a D L T).
If t he M T D is n ot reac he d, t he n t he M A D will be ma xi m u m d ose t hat is e val uate d i n t he 
st u d y.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 4
3. 4. Rec o m me n de d P h ase 2 D ose ( R P 2 D) Defi niti o n
B ase d o n preli mi nar y  safet y, efficac y, P K, a n d p har mac o d y n a mics data fr o m Part 1 
( m o n ot hera py d ose escalati o n) , a d ose of 1 0 0 0 µ g/ k g S C wee kl y has bee n selecte d as t he 
R P 2 D f or P F - 0 6 8 6 3 1 3 5 as a si n gle a ge nt . Briefl y , si n gle-a ge nt a nti-m y el o ma acti vit y has 
bee n o bser ve d at d oses ≥2 1 5 µ g/ k g S C wit h a n acce pta ble safet y pr ofile acr oss all d ose 
le vels. T he o verall res p o nse rate ( O R R) f or t he 2 1 5, 3 6 0, 6 0 0, a n d 1 0 0 0 µ g/ k g S C d ose le vels 
w as 7 5 % ( 3 / 4), 7 5 % (3/ 4 ), 6 6. 7 % (4/ 6 ) a n d 8 3 % (5/ 6 ), res pecti vely. I n a d diti o n, p reli mi nar y 
e x p os ure -efficac y a nalys es i n dicate d t hat hi g her P F - 0 6 8 6 3 1 3 5 e x p os ure (a vera ge 
c o nce ntrati o n at stea d y state ) m a y  be ass ociate d wit h hi g her pr o ba bilit y of o bjecti ve 
res p o nse, es pecially i n patie nts wit h hi g h baseli ne s ol u ble B C M A . O verall, t he data s up p ort
1 0 0 0 µ g/ k g S C wee kl y as a t olera ble d ose t hat pr o vi de s cli nical be nefit f or t he maj orit y of 
patie nts wit h rela pse d or refract or y M M , i ncl u di n g t h ose wit h hi g h baseli ne sol u ble B C M A .
Alt h o u g h o nl y Gra de 1 or Gra de 2 C R S was re p orte d d uri n g d ose escalati o n , 2 of 6 patie nts 
e x perie nce d Gra de 1 C R S e ve nts t hat laste d f or 9 da ys wit h t he first d ose of 1 0 0 0 µ g/ k g . T he 
l o n gest d urati o n of C R S i n t he 6 0 0 µ g/ k g S C c o h ort was 4 da ys, w hic h occ urre d i n 1 patie nt 
a n d was Gra de 1. T heref ore, Part 1. 1 of t his st u d y e val uat es w het her t he d urati o n of C R S ca n
be miti gate d b y a si n gle pri mi n g d ose of 6 0 0 µ g/ k g gi ve n o ne wee k pri or t o 1 0 0 0 µ g/ k g 
mai nte na nce d osi n g (see Secti o n 1. 2. 9. 6 f or rati o nale). Base d o n preli mi nar y safety data fr o m 
Part 1. 1, a d mi nistrati o n of a pri mi n g d ose ( 6 0 0 µ g/ k g) re d uces d urati o n of C R S ass ociate d 
wit h s u bse q ue nt mai nte na nce d osi n g (1 0 0 0 µ g / k g). Theref ore , a pri mi n g strate g y will be 
a d o pte d for b ot h P F -0 6 8 6 3 1 3 5 m o n ot hera p y  a n d c o m bi nati o n t hera py i n t his st u d y as well as
ot her st u dies .
F or m o n ot hera p y d osi n g wit h P F - 0 6 8 6 3 1 3 5, the R P 2 D of 1 0 0 0 µ g/ k g will be a d mi nistere d as 
a fi xe d d ose of 7 6 m g S C wee kl y (see Secti o n 1. 2. 9. 4 f or rati o nale) f oll o wi n g a si n gle 
pri mi n g d ose of 4 4 m g (fi xe d d ose e q ui vale nt of 6 0 0 µ g/ k g ) a d mi nistere d o ne wee k bef ore 
i nitiati o n of mai nte na nce d osi n g .
T he c o m bi nati o n R P 2 D f or P F -0 6 8 6 3 1 3 5 will be deter mi ne d se paratel y f or eac h c o m bi nati o n 
t hera py .
3. 5. St o p pi n g Criteri a i n P art 2 D ose E x p a nsi o n
If t he f oll o wi n g criteria liste d bel o w are met i n a n y of t he c o h orts i n Part 2 d ose e x pa nsi o n , 
f urt her e nr oll me nt i nt o t he c o h ort meeti n g t he criteria will be place d o n h ol d , a n d a decisi o n 
t o st o p t he c o h ort ma y be ma de f oll o wi n g a re vie w of all safet y i nf or mati o n:

Gra de 5 treat me nt -relate d A E ≥1 0 %; or

Gra de 4 - 5 treat me nt-relate d n o n-he mat ol o gica l A E > 2 5 %.
A d verse e ve nt i nf or mati o n c ollecte d d uri n g d ose escalati o n of patie nts treate d at t he sa me 
d ose le vels will be i ncl u de d i n t he e val uati o n.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 5
4. P A TI E N T E LI GI BI LI T Y C RI T E RI A
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate patie nts are e nr olle d.  T he f oll o wi n g 
eli gi bilit y criteria are desi g ne d t o select patie nts f or w h o m partici pati o n i n t he st u d y is 
c o nsi dere d a p pr o priate.  All rele va nt me dical a n d n o n me dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het her a partic ular pat ie nt is s uita ble f or t his pr ot oc ol.
4. 1. I ncl usi o n Criteri a
Patie nts m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or e nr oll me nt i n t he 
st u d y:
1.
Patie nts wit h rela pse d or refract or y  m ulti ple m yel o ma, as defi ne d b y t he i nter nati o nal 
m y el o ma w or ki n g gr o u p ( I M W G) u p date d criteria 2 0 1 44 5 (see A p pe n di x 6 ), a n d 
meas ura ble disease o n e nr oll me nt (st u d y  e ntr y) as defi ne d b y o ne or m ore of t he 
a b n or malities liste d i n a t o c bel o w:
a.
Ser u m m y el o ma ( M)-pr otei n greater t ha n or e q ual t o 0. 5 g/ d L ( 5 g/ L).   
b.
Uri ne M -pr otei n greater or e q ual t o 2 0 0 m g/ 2 4 h.
c.
F or patie nts wit h o ut meas ura ble ser u m a n d uri ne M- pr otei n le vels or if t he ser u m 
a n d uri ne M -pr otei n le vels are u ni nter preta ble d ue t o assa y  i nterfere nce b y pri or 
treat me nt wit h darat u m u ma b o nl y : free li g ht c hai n (F L C ) is co nsi dere d t o be 
meas ura ble i n patie nts w h ose i n v ol ve d li g ht c hai n (eit her ka p pa or la m b da) 
is  > 1 0 0  m g/ L ( 1 0  m g/ d L) a n d w h o ha ve a n a b n or mal ka p pa:la m b da rati o 
(a b n or mal is o utsi de t he ra n ge . 2 6 t o 1. 6 5).
2.
Patie nts m ust ha ve pr o gresse d o n or are i nt olera nt o f esta blis he d t hera pies k n o w n t o 
pr o vi de cli nical be nefit i n m ulti ple m y el o ma i ncl u di n g pr oteas o me i n hi bit or, a n IMi D 
dr u g a n d a n a nti -C D 3 8 m A b, w here a p pr o ve d a n d a vaila ble , eit her i n c o m bi nati o n or 
as a si n gle a ge nt.  Patie nts m ust n ot be ca n di date f or r e gi me ns k n o w n t o pr o vi de 
cli nical be nefit i n rela pse or refract or y  m ulti ple m yel o ma base d o n t he i n vesti gat or’s 
j u d g me nt.  If a patie nt decli nes s uc h t hera py, t his m ust be rec or de d i n t he st u d y  files.
3.
Fe male or male patie nts a ge 1 8 years. 
4.
Easter n C o o pera ti ve O nc ol o g y Gr o u p ( E CO G) Perf or ma nce Stat us ( P S) (see
A p pe n di x 4 ).

F or Part 2 A: Easter n C o o perati ve O nc ol o g y  Gr o u p ( E C O G) Perf or ma nce Stat us 
( P S) 0- 1.

F or all ot her Parts: Easter n C o o perati ve O nc ol o g y  Gr o u p ( E C O G) Perf or ma nce 
Stat us ( P S) 0 - 1. P S -2 is per mitte d if P S is d ue t o u n derl yi n g m yel o ma.  
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 6
5.
A de q uate he mat ol o gical f u ncti o n i ncl u di n g:

A bs ol ute ne utr o p hil c o u nt ( A N C) 1, 0 0 0/ m m 3 .

F or P F - 0 6 8 6 3 13 5 m o n ot hera p y , Part 1 E a n d 2 E : Platelet c o u nt ≥2 5 , 0 0 0/ m m3
(tra nsf usi o n s u p p ort is per mitte d if c o m plete d pri or t o pla n ne d start of d osi n g ).
F or Parts 1 C a n d 2 C platelet c o u nt ≥3 0 , 0 0 0/ m m3. F or Parts 1 D a n d 2 D platelet 
c o u nt ≥5 0 , 0 0 0/ m m3.

He m o gl o bi n ≥8. 0 g/ d L (tra nsf usi o n s u p p ort is per mitte d if c o m plete d pri or t o 
pla n ne d start of d osi n g) .
6.
A de q uate Re nal F u ncti o n, i ncl u di n g:

F or n o n -le nali d o mi de parts of t he st u d y: Esti mate d creati ni ne cleara nce
3 0 m L / mi n as calc ulate d usi n g t he met ho d sta n dar d f or t he i nstit uti o n.  (If a n 
esti mate d creati ni ne cleara nce [ C r Cl] is belie ve d t o be i nacc urate f or a patie nt, 
2 4- h o ur uri ne c ollecti o n wit h act ual assess me nt of Cr Cl is all o we d); F or Parts 1 C 
a n d 2C , esti mate d creati ni ne cleara nce 6 0 m L / mi n.

Ser u m creati ni ne ≤2. 5 m g/ d L;

N ot dial y sis- de pe n de nt.
7.
A de q uate Li ver F u ncti o n, i ncl u di n g:

As partate a n d ala ni ne a mi n otra nsferase ( A S T a n d A L T) ≤2. 5 x u p per li mit of 
n or mal ( U L N ); ≤5. 0 x U L N if t here is li ver i n v ol ve me nt b y  t he t u m or. 

Al kali ne p h os p hatase ≤2. 5 x U L N (5 x U L N i n case of b o ne metastasis). 

T otal bilir u bi n ≤2. 0 m g/ d L, e x ce pt i n patie nts wit h Gil bert S y n dr o me w h o m ust 
ha ve a t otal bilir u bi n less t ha n 3. 0 m g/ d L.
8.
N o acti ve he patitis B ( H B V) or he patitis C ( H C V) i nfecti o n.
9.
Res ol ve d ac ute effects of a n y  pri or t hera py t o baseli ne se verit y or C T C A E Gra de ≤1, 
wit h t he e xce pti o n of peri p heral ne ur o pat h y attri b uta ble t o b ortez o mi b i n t he li mit of 
Gra de ≤2.
1 0. Ser u m pre g na nc y  test (f or fe males of c hil d beari n g p ote ntial) ne gati ve at scree ni n g.
1 1. Fe male patie nts of n o n -c hil d beari n g p ote ntial m ust meet at least 1 of t he f oll o wi n g 
criteria:

Ac hie ve d p ost me n o pa usal stat us, defi ne d as f oll o ws: cessati o n of re g ular me nses 
f or at least 1 2 c o nsec uti ve m o nt hs wit h n o alter nati ve pat h ol o gical or 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 7
p h y si ol o gical ca use; stat us ma y be c o nfir me d wit h a ser u m f ollicle sti m ulati n g 
h or m o ne ( F S H) le vel c o nfir mi n g t he p ost me n o pa usal state.

Ha ve u n der g o ne a d oc u me nte d h y sterect o m y a n d/ or bilateral o o p h orect o m y. 

Ha ve me dicall y  c o nfir me d o varia n fail ure. 

All ot her fe male patie nts (i ncl u di n g fe male pat ie nts wit h t u bal li gati o ns) are 
c o nsi dere d t o be of c hil d beari n g p ote ntial. 
1 2. Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt as descri be d i n A p pe n di x 1 , w hic h 
i ncl u des c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he inf or me d 
c o nse nt d oc u me nt (I C D) a n d i n t his pr ot oc ol.
1 3. Willi n g a n d a ble t o c o m pl y  wit h sc he d ule d visits, treat me nt pla n, la b orat or y tests, a n d 
ot her pr oce d ures.
4. 2. E xcl usi o n Criteri a
Patie nts wit h a n y  of t he f oll o wi n g c haracteristics/c o n diti o ns will n ot be i ncl u de d i n t he st u d y:
1.
Patie nts wit h ot her mali g na ncies i n a d diti o n t o m ulti ple m y el o ma are n ot eli gi ble if 
t he ot her mali g na nc y has re q uire d treat me nt wit hi n t he past 3 ye ars or is n ot i n 
c o m plete re missi o n wit h t he e xce pti o ns of s uccessf ull y  treate d n o n-metastatic basal 
cell or s q ua m o us cell s ki n carci n o ma.
2.
Hist or y  of acti ve a ut oi m m u ne dis or ders (i ncl u di n g b ut n ot li mite d t o: Cr o h n’s 
disease, r he u mat oi d art hritis, scler o der ma, s ys te mic l u p us er yt he mat os us, Gra ve’s 
disease) a n d ot her c o n diti o ns t hat c o m pr o mise or i m pair t he i m m u ne s y ste m.
3.
A n y  f or m of pri mar y i m m u n o deficie nc y (s uc h as Se vere C o m bi ne d 
I m m u n o deficie nc y Disease).
4.
Patie nts wit h acti ve u nc o ntr olle d bacterial, f u n gal or viral i nfecti o n, i ncl u di n g k n o w n 
h u ma n i m m u n o deficie nc y vir us ( HI V) i nfecti o n or ac q uire d i m m u n o deficie nc y  
s yn dr o me ( AI D S) relate d ill ness. See A p pe n di x 1 0 f or a d diti o nal clarificati o n as it 
relates t o S A R S -C o V 2 i nfecti o n .  
5.
Patie nts wit h e vi de nce of acti ve m uc osal or i nter nal blee di n g.
6.
Hist or y  of C T C A E Gra de ≥3 i m m u ne -me diate d a d verse e ve nt (i ncl u di n g he patitis,
pa ncreatitis, c olitis, p ne u m o nitis, car ditis, a n d c yt o ki ne release sy n dr o me) t hat was 
c o nsi dere d relate d t o pri or i m m u ne -m o d ulat or y  t hera p y (e xce pti o ns: i m m u ne-relate d 
a d verse e ve nts sec o n dar y t o c hec k p oi nt i n hi bit ors t hat ha ve bee n a p pr o priatel y 
ma na ge d or res ol ve d s uc h as h y p o p h y sitis a n d h y p ot h y r oi dis m).
7.
Maj or s ur ger y  wit hi n 4 wee ks pri or t o st u d y e ntr y.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 8
8.
Ra diati o n t hera p y wit hi n 2 wee ks pri or t o st u d y e ntr y ( b o ne lesi o ns re q uiri n g 
ra diati o n ma y be treate d wit h li mite d [ie, ≤2 5 % of b o ne marr o w i n fiel d] ra diati o n 
t hera py d uri n g t his peri o d).
9.
Patie nts wit h a hist or y  of ste m cell tra ns pla nt (a ut ol o g o us or all o ge neic) wit hi n 
1 0 0 da y s pri or t o st u d y  e nr oll me nt.
1 0. D o n or L y m p h oc y te I nf usi o n ( D LI) wit hin 3 0 d a y s pri or t o st u d y e ntr y.
1 1. Ti me bet wee n t he last d oses of pre vi o us s ys te mic a nti-ca ncer t hera p y is less t ha n 
5 ti mes t he eli mi nati o n half-life of pre vi o us t hera p y or less t ha n 3 0 d a y s after last 
d ose of a nti b o d y  base d t hera pies (e g, el ot uz u ma b, darat u m u ma b).
1 2. Re q uire me nt f or s ys te mic i m m u ne s u p pressi ve me dicati o n e xce pt as per mitte d i n t he 
st u d y pr ot oc ol.
1 3. C urre nt re q uire me nt f or c hr o nic bl o o d pr o d uct s u p p ort.
1 4. Patie nts wi t h k n o w n rela pse f oll o wi n g B C M A tar gete d t hera py (e xce pt f or 
P F -0 6 8 6 3 1 3 5) m a y be eli gi ble f oll o wi n g disc ussi o n wit h t he s p o ns or. H o we ver, 
patie nts w h o ha d recei ve d ale mt uz u ma b pre vi o usl y or w h o ha ve n ot rec o vere d w hite 
bl o o d cell c o u nts t o baseli ne after c o n diti o ni n g c he m ot hera p y f or pri or c hi meric 
a nti ge n rece pt or ( C A R) T cell t hera p y are e xcl u de d.
1 5. Patie nt k n o w n t o be refract or y  t o platelet or re d bl o o d cell tra nsf usi o ns.
1 6. Baseli ne 1 2 -lea d electr ocar di o gra m ( E C G) t hat de m o nstrates cli nicall y rele va nt 
a b n or malities t hat ma y affect patie nt safety or i nter pretati o n of st u d y res ults 
(e g, baseli ne c orrecte d Q T [ Q Tc] i nter val > 4 7 0 msec, c o m plete left b u n dle bra nc h 
bl oc k [ L B B B], si g ns of a n ac ute or i n deter mi nate -a ge m y ocar dial i nfarcti o n , S T-T 
i nter val c ha n ges s u g gesti ve of acti ve my o car dial isc he mia, sec o n d - or t hir d -de gree 
atri o ve ntric ular [ A V] bl oc k, or seri o us bra d yarr h yt h mias or tac h yarr h yt h mias). If t he 
baseli ne u nc orrecte d Q T i nter val is > 4 7 0 msec, t his i nter val s h o ul d be rate- c orrecte d 
usi n g t he Fri dericia met h o d a n d t he res ulti n g C orrecte d Q T i nter val b y  Fre dericia
(Q Tc F ) s h o ul d be use d f or decisi o n ma ki n g a n d re p orti n g.  If Q Tc e xcee ds 4 7 0 msec, 
or Q R S e xcee ds 1 2 0 msec, t he E C G s h o ul d be re peate d 2 m ore ti mes a n d t he a vera ge 
of t he 3 Q Tc or Q R S val ues s h o ul d be use d t o deter mi ne t he patie nts eli gi bilit y. 
C o m p uter -i nter prete d E C Gs s h o ul d be o verrea d by a p h ysicia n e x perie nce d i n 
rea di n g E C Gs bef ore e xcl u di n g partici pa nts.  Cases m ust be disc usse d i n detail wit h 
s p o ns or’s me dical m o nit or t o j u d ge eli gi bilit y .
A n y  of t he f oll o wi n g i n t he pre vi o us 6 m o nt hs: m yocar dial i nfarcti o n, l o n g Q T 
s yn dr o me, T orsa de de P oi ntes, arr h y t h mias (i ncl u di n g s ustai ne d ve ntric ular 
tac hyarr h yt h mia a n d ve ntric ular fi brillati o n), seri o us c o n d ucti o n s y ste m a b n or malities 
(e g, left a nteri or he mi bl oc k, left b u n dle bra nc h bl oc k), u nsta ble a n gi na, 
c or o nar y/ peri p heral arter y b y pass graft, s y m pt o matic c o n gesti ve heart fail ure ( C H F, 
Ne w Y or k Heart Ass ociati o n class III or I V), cere br o vasc ular acci de nt, tra nsie nt 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2 9
ische mic attac k, s y m pt o matic p ul m o nar y  e m b olis m, a n d/ or ot her cli nical si g nifica nt 
e pis o de of t hr o m b oe m b olic disease, o n g oi n g car diac d ys r hyt h mias of Nati o nal 
Ca ncer I nstit ute ( N CI) C T C A E > Gra de 2, atrial fi brillati o n of a n y  gra de ( > Gra de 2 
i n t he case of as ym pt o matic l o ne atrial fi brillati o n). If a partici pa nt has a car diac 
r h yt h m de vice/ pace ma ker place d a n d Q Tc F > 4 7 0 msec, t he partici pa nt ca n be 
c o nsi dere d eli gi ble.  S u bjects wit h car diac r h yt h m de vice/ pace ma ker m ust be 
disc usse d i n detail wit h s p o ns or’s me dical m o nit or t o j u d ge eli gi bilit y .
1 7. H y perte nsi o n t hat ca n n ot be c o ntr olle d b y  me dicati o ns ( > 1 5 0/ 1 0 0 m m H g des pite 
o pti mal me dical t hera p y).
1 8. Partici pati o n i n ot her st u dies i n v ol vi n g i n vesti gati o nal dr u g(s) wit hi n 4 wee ks pri or t o 
st u d y e ntr y.  Patie nt m a y  be i ncl u de d if 5 ti mes eli mi nati o n half-life of dr u g has 
passe d. N ote: C O VI D -1 9 vacci nati o n ma y  be c o nsi dere d a n e xce pti o n a n d s h o ul d be 
disc usse d wit h t he s p o ns or o n a n i n di vi d ual basis.
1 9. K n o w n or s us pecte d h y p erse nsiti vit y t o m uri ne a n d b o vi ne pr o d ucts. 
2 0. Fe rtile male patie nts a n d fe male patie nt s of c hil d beari n g p ote ntial w h o are u n willi n g 
or u na ble t o use a hi g hl y effecti ve met h o d of c o ntrace pti o n as o utli ne d i n t his 
pr ot oc ol . 
2 1. Ot her ac ute or c hr o nic me dical or ps yc hi atric c o n diti o n, i ncl u di n g rece nt ( wit hi n t he 
past y ear) or acti ve s uici dal i deati o n or be ha vi or or la b orat or y  a b n or malit y t hat ma y 
i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or i n vesti gati o nal pr o d uct 
a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of st u d y res ults a n d, i n t he 
j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he patie nt i na p pr o priate f or e ntr y i nt o t his 
st u d y.
2 2. I n vesti gat or site staff me m bers directly i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir 
fa mil y me m bers , site staff me m bers ot her wise s u per vise d b y t he i n vesti gat or, or 
patie nts w h o are Pfizer e m pl o y ees, i ncl u di n g t heir fa mil y me m bers, directl y i n v ol ve d 
i n t he c o n d uct of t he st u d y.
2 3. F or e nr oll me nt i n le nali d o mi de c o m bi nati o n c o h orts Parts 1 C a n d 2 C , patie nts w h o 
ha d pre vi o usl y recei ve d le nali d o mi de a n d were d ose re d uce d t o less t ha n 2 5 m g dail y 
f or t hr o m b oc yt o pe nia, ne utr o pe nia or re nal i m pair me nt.
2 4. F or e nr oll me nt i n p o mali d o mi de c o m bi nati o n c o h orts Parts 1 D a n d 2 D, patie nts w h o 
ha d pre vi o usl y recei v e d p o mali d o mi de a n d were d ose re d uce d t o less t ha n 4 m g dail y 
f or t hr o m b oc yt o pe nia, ne utr o pe nia, se vere re nal i m pair me nt, or he patic i m pair me nt.
2 5. F or e nr oll me nt i n p o mali d o mi de c o m bi nati o n c o h orts Parts 1 D a n d 2 D, patie nts w h o 
are recei vi n g str o n g C Y P 1 A 2 i n hi bit ors ( eg, ci pr ofl o xaci n a n d fl u v o xa mi ne ).
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 0
2 6. F or patie nts o n p o mali d o mi de c o m bi nati o n Parts 1 D a n d 2 D, patie nts w h o ha ve a n y 
le vel of he patic i m pair me nt ( C hil d-P u g h A -C) t hat w o ul d re q uire d ose re d ucti o n of 
p o mali d o mi de.
4. 3. Life st yle Re q uire me nts
All fertil e fe male patie nts w h o are of c hil d beari n g p ote ntial w h o are, i n t he o pi ni o n of t he 
i n vesti gat or, se x uall y acti ve a n d at ris k f or pre g na nc y wit h t heir part ner(s) m ust a gree t o use 
a hi g hl y effecti ve met h o d of c o ntrace pti o n c o nsiste ntl y  a n d c orrectly f or t he d urati o n of t he 
acti ve treat me nt peri o d a n d f or at least 5 m o nt hs after t he last d ose of P F -0 6 8 6 3 1 3 5 .
N o c o ntrace pti o n met h o ds are re q uire d f or male partici pa nts w h o recei ve P F - 0 6 8 6 3 1 3 5 i n 
t his st u d y, as t he calc ulate d safety mar gi n is ≥1 0 0 ‑f ol d bet wee n t he esti mate d mater nal 
e x p os ure d ue t o se mi nal tra nsfer a n d t he esti mate d M A B E L ( mi ni mal a ntici pate d bi ol o gical 
effect le vel) use d as c o nser vati ve esti mate of e x p os ure t hat ma y  res ult i n seri o us 
ma nifestati o ns of de vel o p me ntal t o xicit y .
I n a d diti o n t o c o ntrace pti o n re q uire me nts t o P F-0 6 8 6 3 1 3 5, f or Parts 1 C , 2 C, 1 D a n d 2 D , t he 
ma n ufact urer’s ( Brist ol Me y ers S q ui b b’s) pre g na nc y pre ve nti o n pr o gra ms ( P P P) f or 
le nali d o mi de a n d p o mali d o mi de m ust be f oll o we d. All fe males of c hil d beari n g p ote ntial , as 
defi ne d p er P P P, m ust use at least 2 acce pta ble met h o d s of c o ntrace pti o n as s pecifie d i n t he 
P P P i ncl u di n g at least o ne hi g hly effecti ve met h o d (t u bal li gati o n, I U D, h or m o nal [ birt h 
c o ntr ol pills, h or m o nal patc hes, i njecti o ns, va gi nal ri n gs, or i m pla nts], or part ner’s
vasect o m y) a n d at least o ne a d diti o nal effecti ve met h o d of birt h c o ntr ol ( male late x or 
s ynt hetic c o n d o m, dia p hra g m, or cer vical ca p e ver y  ti me t he y ha ve se x wit h a male, or 
a bstai ni n g fr o m se x wit h a male) f or at least 4 wee ks bef ore le nali d o mi de or p o ma li d o mi de 
t hera py (i ncl u di n g d uri n g d osi n g i nterr u pti o ns) , d uri n g le nali d o mi de or p o mali d o mi de 
t hera py, a n d u ntil at least 4 wee ks after t he last d ose of le nali d o mi de or p o mali d o mi de 
t hera py, a n d me n m ust al wa y s use a late x or s ynt hetic c o n d o m d uri n g a n y  sex ual c o ntact 
wit h fe males of c hil d beari n g p ote ntial d uri n g le nali d o mi de or p o mali d o mi de t hera py
(i ncl u di n g d uri n g d osi n g i nterr u pti o ns) a n d u ntil at least 4 wee ks after disc o nti n ui n g 
le nali d o mi de or p o mali d o mi de . I n a d diti o n, P P P re q uire me nts relate d t o pr o hi biti o n of bl o o d, 
se me n, a n d s per m d o nati o n d uri n g le nali d o mi de a n d p o mali d o mi de treat me nt a n d f or at least 
4 wee ks after disc o nti n ui n g treat me nt m ust be f oll o we d.
T he i n vesti gat or or his or her desi g nee, i n c o ns ultati o n wit h t he patie nt , will c o nfir m t hat t he 
patie nt has selecte d a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual patie n t a n d his 
or her part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds (see bel o w) a n d will 
c o nfir m t hat t he patie nt has bee n i nstr ucte d i n its c o nsiste nt a n d c orrect use.  At ti me p oi nts 
i n dicate d i n t he S C H E D U L E O F A C TI VI TI E S (i ncl u di n g t he re q uire d c o ntrace pti o n peri o d 
[t hr o u g h 5 m o nt hs p ost last d ose of P F - 0 6 8 6 3 1 3 5 f or W O C B P]), t he i n vesti gat or or desi g nee 
will i nf or m t he patie nt o f t he nee d t o use hi g hly effecti ve c o ntrace pti o n c o nsiste ntl y  a n d 
c orrectl y a n d d oc u me nt t he c o n versati o n a n d t he patie nt ’s affir mati o n i n t he patie nt ’s c hart 
(patie nts nee d t o affir m t heir c o nsiste nt a n d c orrect use of t he selecte d met h o ds of 
c o ntrace pti on).  I n a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he patie nt t o call 
i m me diatel y if t he selecte d c o ntrace pti o n met h o d is disc o nti n ue d or if pre g na nc y  is k n o w n or 
s us pecte d i n t he patie nt or part ner. I n a d diti o n t o re p orti n g re q uire me nts o utli ne d i n Secti o ns
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 1
8. 4. 2 a n d 8. 4. 2. 1 , f or Parts 1 C, 2 C, 1 D a n d 2 D, a d diti o nal re p orti n g re q uire me nts as defi ne d 
i n t he P P P f or le nali do mi de a n d p o mali d o mi de m ust be f oll o we d, i ncl u di n g i m me diate 
re p orti n g of p ote ntial pre g na nc y e x p os ure t o t he ma n ufact urer, f oll o w-u p re p orti n g t o t he 
ma n ufact urer eac h tri mester u ntil o utc o me, a n d i nfa nt f oll o w- u p t o t he ma n ufact urer e ver y  
q uarter f or 1 year after birt h ( pe n di n g c o nse nt of t he fe male partici pa nt or fe male part ner).
Hi g hl y effecti ve met h o ds of c o ntrace pti o n are t h ose t hat, al o ne or i n c o m bi nati o n, res ult i n a 
fail ure rate of less t ha n 1 % per ye ar w he n use d c o nsiste ntl y a n d c orrectl y (ie, perfect use) a n d 
i ncl u de t he f oll o wi n g:
1.
Esta blis he d use of h or m o nal met h o ds of c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n (e g, oral, i nserte d, i n jecte d, i m pla nte d, tra ns der mal), pr o vi de d t he patie nt or 
male patie nt ’s fe male part ner pla ns t o re mai n o n t he sa me treat me nt t hr o u g h o ut t he 
e ntire st u d y a n d has bee n usi n g t hat h or m o nal c o ntrace pti ve f or a n a de q uate peri o d of 
ti me t o e ns ure effecti ve ness. 
2.
C orrectl y place d c o p per -c o ntai ni n g i ntra uteri ne de vice (I U D).
3.
Male c o n d o m or fe male c o n d o m use d WI T H a se parate s per mici de pr o d uct (ie, f oa m, 
gel, fil m, crea m, or s u p p osit or y ).  F or c o u ntries w here s per mici de is n ot a vaila ble or 
c o n d o m pl us s per mici de is n ot acce pte d as hi g hl y effecti ve c o ntrace pti o n, t his o pti o n 
is n ot a ppr o priate.
4.
Male sterilizati o n wit h a bse nce of s per m i n t he p ost vasect o m y ejac ulate.
5.
Bilateral t u bal li gati o n/ bilateral sal pi n gect o m y or bilateral t u bal occl usi ve pr oce d ure 
( pr o vi de d t hat occl usi o n has bee n c o nfir me d i n acc or da nce wit h t he de vice’s la bel).
N O T E: Se x ual a bsti ne nce, defi ne d as c o m pletel y a n d persiste ntl y refrai ni n g fr o m all 
heter ose x ual i nterc o urse (i ncl u di n g 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) ma y o b viate t he nee d f or c o ntrace pti o n O N L Y if t his is t he preferre d a n d us ual 
lifest yle of t he patie nt .
4. 4. S p o ns or ’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q ualifie d me dical pers o n nel f or t he 
st u d y is d oc u me nte d i n t he st u d y c o ntact list l ocate d i n t he s u p p orti n g st u d y d oc u me ntati o n . 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel o n st u d y- relate d me dical 
q uesti o ns or pr o ble ms, patie nts are pr o vi de d wit h a c o ntact car d. T he c o ntact car d c o ntai ns, 
at a mi ni m u m, pr ot oc ol a n d i n vesti gati o nal pr o d uct i de ntifiers, patie nt st u d y n u m bers, 
c o ntact i nf or mati o n f or t he i n vesti gator site, a n d c o ntact details f or a c o ntact ce nter i n t he 
e ve nt t hat t he i n vesti gator site staff ca n n ot be reac he d t o pr o vi de a d vice o n a me dical 
q uesti o n or pr o ble m ori gi nati n g fr o m a n ot her healt hcare pr ofessi o nal n ot i n v ol ve d i n t he 
patie nt’s partici pati o n i n t he st u d y . T he c o ntact n u m ber ca n als o be use d b y  i n vesti gator staff 
if t he y are see ki n g a d vice o n me dical q uesti o ns or pr o ble ms; h o we ver, it s h o ul d be use d o nl y  
i n t he e ve nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he i n vesti gator site a n d 
t he st u d y tea m are n ot a vaila ble. It is t heref ore i nte n de d t o a u g me nt, b ut n ot re place, t he 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 2
esta blis he d c o m m u nicati o n pat h wa y s bet wee n t he i n vesti gator site a n d t he st u d y tea m f or 
a dvice o n me dical q uesti o ns or pr o ble ms t hat ma y arise d uri n g t he st u d y .  T he c o ntact 
n u m ber is n ot i nte n de d f or use b y t he patie nt directl y, a n d if a patie nt calls t hat n u m ber, he or 
s he will be directe d bac k t o t he i n vesti gator site.
5. S T U D Y T R E A T M E N T S
F or t he p ur p oses of t his st u d y , a n d per I nter nati o nal C o nfere nce o n Har m o nizati o n (IC H) 
g ui deli nes, i n vesti gati o nal pr o d uct is defi ne d as a p har mace utical f or m of a n acti ve 
i n gre die nt or place b o bei n g teste d or use d as a refere nce/c o m parat or i n a cli nical trial, 
i ncl u di n g a pr o d uct wit h a mar keti n g a ut h orizati o n w he n use d or asse m ble d (f or m ulate d or 
pac ka ge d) i n a wa y  differe nt fr o m t he a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d 
i n dicati o n, or w he n use d t o gai n f urt her i nf or mati o n a b o ut a n a p pr o ve d use (IC H E 6 1. 3 3).
F or t his st u d y , t he i n vesti gati o nal me dici nal pr o d uct s i ncl u de P F - 0 6 8 6 3 1 3 5, le nali d o mi de,
p o mali d o mi de a n d de xa met has o ne.  F or d ose le vel i nf or mati o n, please see Secti o n 3. 1 .
5. 1. All oc ati o n t o Tre at me nt
D ose le vel all ocati o n will be perf or me d b y t he s p o ns or after patie nts ha ve gi ve n t heir writte n 
i nf or me d c o nse nt a n d ha ve c o m plete d t he necessar y baseli ne assess me nts. T he site staff will
e-mail a c o m plete Re gistrati o n F or m t o t he desi g nate d s p o ns or st u d y  tea m me m ber or 
desi g nee .  T he s p o ns or will assi g n a patie nt i de ntificati o n n u m ber a n d s u p pl y t his n u m ber t o 
t he site.  T he patie nt i de ntificati o n n u m ber will be use d o n all st u d y -relate d d oc u me ntati o n at 
t he site.
N o patie nt s hall recei ve i n vesti gati o nal pr o d uct u ntil t he i n vesti gat or or desi g nee has recei ve d 
t he f oll o wi n g i nf or mati o n i n writi n g fr o m t he s p o ns or:

C o nfir mati o n of t he patie nt’s e nr oll me nt;

S pecificati o n of t he d ose le vel f or t hat patie nt a n d ;

P er missi o n t o pr ocee d wit h d osi n g t he patie nt .
T he s p o ns or or desi g nee will n otif y  t he ot her sites of t he i ncl usi o n of a ne w patie nt, a n d will 
i nf or m st u d y sites a b o ut t he ne xt p ossi ble e nr oll me nt date.
5. 2. P atie nt C o m pli a nce
All d oses of P F -0 6 8 6 3 1 3 5 will be a d mi nistere d b y t he a p pr o priatel y desi g nate d st u d y staff at 
t he i n vesti gati o nal site. Oral me dicati o ns le nali d o mi de ,p o mali d o mi de , a n d de xa met has o ne, 
if a p plica ble, will be ta ke n b y t he patie nt eit her at t he site or at h o me.
T he site will c o m plete re q uire d d osa ge Pre parati o n R ec or d l ocate d i n t he I n vesti gati o nal 
Pr o d uct ma n ual (I P ma n ual).  T he use of t he Pre parati o n Rec or d is preferre d b ut it d oes n ot 
precl u de t he use of a n e xisti n g a p pr o priate cli nical site d oc u me ntati o n s y ste m.  T he e xisti n g 
cli nical site's d oc u me ntati o n s y ste m s h o ul d ca pt ure all perti ne nt/re q uire d i nf or mati o n o n t he 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 3
pr e parati o n a n d a d mi nistrati o n of t he d ose.  T his ma y  be use d i n place of t he Pre parati o n 
Rec or d after a p pr o val fr o m t he s p o ns or a n d/ or desi g nee. 
5. 3. I n vesti g ati o n al Pr o d uct S u p plies
5. 3. 1. P h ar m ace utic al F o r m(s) a n d P ac k a gi n g
P F - 0 6 8 6 3 1 3 5 is prese nte d as a sterile a q ue o us b uffere d s ol uti o n f or 
i ntra ve n o us/s u bc uta ne o us a d mi nistrati o n .  Please c o ns ult t he In vesti gati o nal Pr o d uct Ma n ual
(IP ma n ual) a n d I n vesti gat or’s Br oc h ure f or f urt her details.
Le nali d o mi de ( Re vli mi d ® ) is a n oral me dicati o n a p pr o ve d i n t he U S, E U, a n d Ca na da f or t he 
treat me nt of m ulti ple m yel o ma. Please c o ns ult t he Re vli mi d ® U S pac ka ge I nsert ( U S PI) or 
E U Pac ka ge I nsert or S P C f or f urt her details.3 0 -3 2
P o mali d o mi de ( U S P o mal y st® , E U a n d Ca na da I mn o vi d ® ) is a n oral me dicati o n a p pr o ve d i n 
t he U S, E U, a n d Ca na da f or t he treat me nt of m ulti ple m y el o ma. Please c o ns ult t he 
P o mal y st® U S pac ka ge I nsert ( U S PI) or E U pac ka ge i nsert or S P C f or f urt her details.3 4 -3 6
De xa met has o ne is a n oral me dicati o n a p pr o ve d i n t he U S, E U, a n d Ca na da.3 7
5. 3. 2. Pre p ar ati o n a n d Dis pe nsi n g
F or P F -0 6 8 6 3 1 3 5 , see t he I P man ual f or i nstr ucti o ns o n h o w t o pre pare t he i n vesti gati o nal 
pr o d uct f or a d mi nistrati o n.  I n vesti gati o nal pr o d uct s h o ul d be pre pare d a n d dis pe nse d b y a n 
a p pr o priatel y q ualifie d a n d e x perie nce d me m ber of t he st u d y  staff (e g, p h y sicia n, n urse, 
p h y sicia n’s assista nt, n urse practiti o ner, p har mac y assista nt/tec h nicia n, or p har macist) as 
all o we d b y l ocal, state, a n d i nstit uti o na l g ui da nce.
O nl y  q ualifie d pers o n nel w h o are fa miliar wit h pr oce d ures t hat mi ni mize u n d ue e x p os ure t o 
t he msel ves a n d t o t he e n vir o n me nt s h o ul d u n derta ke t he pre parati o n, ha n dli n g, a n d safe 
dis p osal of bi ot hera p y a ge nts.
5. 4. A d mi nistr ati o n
5. 4. 1. I V A d mi nistr ati o n P F -0 6 8 6 3 1 3 5
P F - 0 6 8 6 3 1 3 5 will be a d mi nistere d o n Da y 1, 8 a n d 1 5 of eac h c y cle per t he IP ma n ual as a n 
i ntra ve n o us (I V) i nf usi o n o ver 2 hrs (1 5 mi n utes).   If t he patie nt is assi g ne d t o t he lea d-i n 
c o h ort i n Part 2 t hat is s pecifically desi g ne d t o e val uate re d uce d i nf usi o n ti me, P F- 0 6 8 6 3 1 3 5
ma y  be a d mi nistere d as a n I V i nf usi o n o ver 1 hr (1 0 mi n utes) .  F or m o n ot hera p y, eac h 
c ycle will be 3 wee ks i n d urati o n, a n d eac h patie nt will be treate d 3 ti mes d uri n g eac h c ycle, 
u nless d ose dela y s or i nterr u pti o ns occ ur (see Secti o ns 5. 5. 1 a n d 5. 5. 2 ).  O n C 1 D 1 f or all 
patie nts, a n d o n C 0 D 1 f or patie nts recei vi n g a pri mi n g d ose, P F-0 6 8 6 3 1 3 5 will be 
a d mi nistere d o n a n i n patie nt basis.  O n all ot her da ys, P F -0 6 8 6 3 1 3 5 will be a d mi nistere d o n 
a n o ut patie nt basis. ).  O n C 1 D 1 f or all patie nts, a n d o n C 0 D 1 f or patie nts recei vi n g a pri mi n g 
d ose , P F- 0 6 8 6 3 1 3 5 will be a d mi nistere d o n a n i n patie nt basis.  O n all ot her da y s, 
P F -0 6 8 6 3 1 3 5 will be a d mi nistere d o n a n o ut patie nt basis.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 4
Details f or P F - 0 6 8 6 3 1 3 5 i nf usi o n are pr o vi de d i n t he c urre nt P F - 0 6 8 6 3 1 3 5 I P Ma n ual . T he 
d ose le vel will be assi g ne d b y  t he s p o ns or (see Secti o n 5. 1 All ocati o n t o Treat me nt).   F or 
m o n ot hera p y Part 1, all patie nts s h o ul d be wei g he d wit hi n 7 2 h o urs pri or t o Da y 1 of eac h 
c ycle t o e ns ure t he y di d n ot e x perie nce eit her a wei g ht l oss or gai n >1 0 % fr o m t he pri or 
wei g ht use d t o calc ulate t he a m o u nt of P F -0 6 8 6 3 1 3 5 re q uire d f or d ose pre parati o n. If t he 
patie nt e x perie nce d eit her a wei g ht l oss or g ai n > 1 0 % c o m pare d t o t he pri or wei g ht use d t o 
calc ulate t he i nitial d ose or d ose i n t he pre vi o us c ycle , t he a m o u nt of P F -0 6 8 6 3 1 3 5 re q uire d 
f or pre parati o n a n d a d mi nistrati o n f or t he c urre nt c ycle m ust be recalc ulate d usi n g t hi s m ost 
rece nt wei g ht o btai ne d. S h o ul d t he i nstit uti o nal p olic y  be s uc h t hat t he d ose is re q uire d t o be 
calc ulate d if a patie nt e x perie nces a wei g ht gai n of < 1 0 %, t his will be all o we d. Fi xe d d osi n g 
a p pr oac h will be a p plie d i n d ose -fi n di n g f or c o m bi nati o n a n d als o-d osi n g a p pr oac h will be 
a p plie d i n d ose- fi n di n g f or c o m bi nati o n a n d als o i n all e x pa nsi o n parts of t he st u d y ( See 
Secti o n 1. 2. 9. 4 ).
T he use of a n i nf usi o n or s y ri n ge p u m p is t he preferre d met h o d of a d mi nistrati o n t o e ns ure 
acc urate deli ver y of t he i n vesti gati o nal pr o d uct.  Please refer t o t he I P ma n ual f or i nf usi o n 
rate a n d d urati o n.
Eac h patie nt ma y  recei ve P F-0 6 8 6 3 1 3 5 u ntil disease pr o gressi o n, u nacce pta b le t o xicit y, 
wit h dra wal of c o nse nt, or st u d y  ter mi nati o n. If a patie nt has recei ve d treat me nt wit h Q 1 W 
P F -0 6 8 6 3 1 3 5 f or at least 6 m o nt hs , a n d disease assess me nts ha ve re mai ne d sta ble o ver at 
least 2 m o nt hs, c o nsi derati o n ma y  be gi ve n t o i ncreasi n g d ose i nter vals fr o m wee kly t o e ver y 
2 wee ks or o nce per c y cle ( o nl y C X D 1 d osi n g a n d acti vities a p plica ble) after c o ns ultati o n 
wit h s p o ns or . C y cles w o ul d re mai n t he sa me le n gt h wit h a n y  s ki p pe d wee kl y d oses n ote d. If 
t he patie nt s u bse q ue ntly be gi ns t o ha ve i ncr ease of disease b ur de n, d ose i nter vals s h o ul d
ret ur n t o wee kl y d osi n g.
5. 4. 2. S C A d mi nistr ati o n P F - 0 6 8 6 3 1 3 5
Q ualifie d a n d trai ne d i n vesti gat or site pers o n nel will a d mi nister P F - 0 6 8 6 3 1 3 5 t o patie nts b y 
S C i njecti o n.  I deall y, eac h i njecti o n m a y be u p t o 2 m L  i n v ol u me. H o we ver, if t he 
ma xi m u m v ol u me all o we d per i nstit uti o n’s p olic y  is l o wer, t he n u m ber of i njecti o ns ma y 
i ncrease t o acc o m m o date t his differe nce i n v ol u me t o e ns ure t he c orrect fi nal d ose is 
deli vere d .
St u d y  dr u g s h o ul d be a d mi nistere d t o t he a b d o me n ( wit h prefere nce gi ve n t o t he l o wer 
q ua dra nts w he n p ossi ble). Refer t o A p pe n di x 9 for details o n a d mi nistrati o n of m ulti ple 
i njecti o ns t o t he a b d o me n.  St u d y staff s h o ul d refer t o t he I P Ma n ual f or s pecific i nstr ucti o ns 
o n t he ha n dli n g a n d pre parati o n of st u d y  dr u g.
Si mila r t o I V d osi n g, d uri n g m o n ot hera p y d ose escalati o n wit h Q 1 W S C P F - 0 6 8 6 3 1 3 5 o nl y
eac h c ycle will be 3 wee ks i n d urati o n, a n d eac h patie nt will be treate d 3 ti mes d uri n g eac h 
c ycle, u nless d ose dela ys or i nterr u pti o ns occ ur (see Secti o ns 5. 5. 1 a n d 5. 5. 2 .  If patie nts are 
e nr olle d i nt o Q 2 W S C d osi n g c o h orts d uri n g d ose escalati o n, eac h c y cle will be 4 wee ks i n 
d urati o n, a n d eac h patie nt will be tre ate d t wice d uri n g eac h c y cle. O n C 1 D 1 f or all patie nts, 
a n d o n C 0 D 1 f or patie nts recei vi n g a pri mi n g d ose, P F- 0 6 8 6 3 1 3 5 will be a d mi nistere d o n a n 
i n patie nt basis.  O n all ot her da ys, P F-0 6 8 6 3 1 3 5 will be a d mi nistere d o n a n o ut patie nt basis ).  
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 5
If patie nts are e nr olle d i nt o Q 2 W S C d osi n g c o h orts d uri n g d ose escalati o n, eac h c ycle will 
be 4 wee ks i n d urati o n, a n d eac h patie nt will be treate d t wice d uri n g eac h c ycle. O n C 1 D 1 
f or all patie nts, a n d o n C0 D 1 f or patie nts recei vi n g a pri mi n g d ose, P F 0 6 8 6 3 1 3 5 will be 
a d mi nistere d o n a n i n patie nt basis.  O n all ot her da ys, P F 0 6 8 6 3 1 3 5 will be a d mi nistere d o n 
a n o ut patie nt basis.
Details f or P F - 0 6 8 6 3 1 3 5 i njecti o ns are pr o vi de d i n t he c urre nt P F -0 6 8 6 3 1 3 5 I P Ma n ual. T he 
d ose le vel will be assi g ne d b y  t he s p o ns or (see Secti o n 5. 1 All ocati o n t o Treat me nt).  F or 
m o n ot hera p y Part 1, all patie nts s h o ul d be wei g he d wit hi n 7 2 h o urs pri o r t o Da y 1 of eac h 
c ycle t o e ns ure t he y di d n ot e x perie nce eit her a wei g ht l oss or gai n > 1 0 % fr o m t he pri or 
wei g ht use d t o calc ulate t he a m o u nt of P F -0 6 8 6 3 1 3 5 re q uire d f or d ose pre parati o n.  If t he 
patie nt e x perie nce d eit her a wei g ht l oss or gai n > 1 0 % c o m pare d t o t he pri or wei g ht use d t o 
calc ulate t he i nitial d ose or d ose i n t he pre vi o us c ycle , t he a m o u nt of P F -0 6 8 6 3 1 3 5 re q uire d 
f or pre parati o n a n d a d mi nistrati o n f or t he c urre nt c ycle m ust be recalc ulate d usi n g t his m ost 
rece nt wei g ht o btai ne d. S h o ul d t he i nstit uti o nal p olic y be s uc h t hat t he d ose is re q uire d t o be 
calc ulate d if a patie nt e x perie nces a wei g ht gai n of < 1 0 %, t his will be all o we d. Fi xe d -d osi n g 
a p pr oac h will be a p plie d i n d ose -fi n di n g f or c o m bi nati o n a n d als o i n all e x pa nsi o n parts of 
t he st u d y ( See Secti o n 1. 2. 9. 4 ).
Eac h patie nt ma y  recei ve P F- 0 6 8 6 3 1 3 5 u ntil disease pr o gressi o n, u nacce pta ble t o xicit y , 
wit h dra wal of c o nse nt, patie nt n o l o n ger willi n g t o partici pate i n trial, or st u d y  ter mi nati o n.
If a patie nt has recei ve d treat me nt wit h Q 1 W P F - 0 6 8 6 3 1 3 5 f or at least 6 m o nt hs, a n d disease 
assess me nts ha ve re mai ne d sta ble o ver at lea st 2 m o nt hs, c o nsi derati o n ma y be gi ve n t o 
i ncreasi n g d ose i nter vals fr o m wee kly t o e ver y 2 wee ks or o nce per c y cle ( o nl y C X D 1 d osi n g 
a n d acti vities a p plica ble) after c o ns ultati o n wit h s p o ns or . C y cles w o ul d re mai n t he sa me 
le n gt h wit h a ny s ki p pe d wee kl y d oses n ote d. If t he patie nt s u bse q ue ntly be gi ns t o ha ve 
i ncrease of disease b ur de n, d ose i nter vals s h o ul d ret ur n t o wee kly d osi n g.
F or Parts 1 C, 1 D, 1 E a n d Part 2 d ose e x pa nsi o n : P F - 0 6 8 6 3 1 3 5 will be a d mi nistere d as 
descri be d f or m o n ot hera p y  P F- 0 6 8 6 3 1 3 5, a n d e ac h c ycle will be 4 wee ks i n d urati o n.  O n 
C 1 D 1 f or all patie nts a n d C 0 D 1 f or patie nts recei vi n g a pri mi n g d ose, P F -0 6 8 6 3 1 3 5 will be 
a d mi nistere d o n a n i n patie nt basis.  O n all ot her da ys, P F- 0 6 8 6 3 1 3 5 will be a d mi nistere d o n 
a n o ut patie nt basis.
If a patie nt has recei ve d treat me nt wit h Q 1 W P F -0 6 8 6 3 1 3 5 f or at least 6 m o nt hs, a n d disease 
assess me nts ha ve re mai ne d sta ble o ver at least 2 m o nt hs, c o nsi derati o n ma y be gi ve n t o 
i ncreasi n g d ose i nter vals fr o m wee kly t o e ver y 2 wee ks or o nce per c y cle ( o nl y CX D 1 d osi n g 
a n d acti vities a p plica ble) after c o ns ultati o n wit h s p o ns or . C y cles w o ul d re mai n t he sa me 
le n gt h wit h a ny s ki p pe d wee kl y d oses n ote d. F or e ver y  2 wee k d osi n g, it w o ul d be 
prefera ble t o s ki p d osi n g of P F -0 6 8 6 3 1 3 5 o n da y s 8 a n d 2 2 of eac h c ycle. If t he patie nt 
s u bse q ue ntl y be gi ns t o ha ve i ncrease of disease b ur de n, d ose i nter vals s h o ul d ret ur n t o 
wee kl y d osi n g.
5. 5. Rec o m me n de d D ose M o dific ati o ns
E ver y  eff ort s h o ul d be ma de t o a d mi nister i n vesti gati o nal pr o d uct o n t he pla n ne d d ose a n d 
sc he d ule.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 6
I n t he e ve nt of si g nifica nt t o xicit y, d osi n g ma y  be dela ye d a n d/ or re d uce d as descri be d 
bel o w.  I n t he e ve nt of m ulti ple t o xicities, d ose m o dificati o n s h o ul d be base d o n t he w orst 
t o xicit y o bser ve d.  Patie nts are t o be i nstr ucte d t o n otif y i n vesti gat ors at t he first occ urre nce 
of a n y a d verse s y m pt o m.
D ose m o dificati o ns of P F - 0 6 8 6 3 1 3 5, le nali d o mi de, p o mali d o mi de a n d de xa met has o ne, m a y  
occ ur i n o ne of t hree wa ys:

Wit hi n a c y cle: d osi n g i nterr u pti o n u ntil a de q uate rec o ver y a n d d ose re d ucti o n, if 
re q uire d, d uri n g a gi ve n treat me nt c ycle; 

Bet wee n c y cles: ne xt c ycle a d mi nistrati o n ma y be dela ye d d ue t o persisti n g t o xicit y 
w he n a ne w c y cle is d ue t o start;

I n t he ne xt c ycle: d ose re d ucti o n ma y be re q uire d i n a s u bse q ue nt c ycle base d o n 
t o xicit y e x perie nce d i n t he pre vi o us c y cle.
I n Parts 1 E a n d 2 E, if a d ose of P F-0 6 8 6 3 1 3 5 is dela y e d or i nterr u pte d, t he n de xa met has o ne 
s h o ul d n ot be a d mi nistere d u ntil P F-0 6 8 6 3 1 3 5 a d mi nistrati o n is restarte d.
5. 5. 1. D os i n g I nterr u pti o ns
Patie nts e x perie nci n g Gra de 3 or 4 p ote ntiall y treat me nt -relate d t o xicit y or i nt olera ble 
dr u g -relate d Gra de 2 t o xicit y  des pite s u p p orti ve care s h o ul d ha ve t heir treat me nt i nterr u pte d. 
A p pr o priate f oll o w- u p assess me nts s h o ul d be d o ne u ntil a de q uate rec o ver y occ urs as 
assesse d b y t he i n vesti gat or.  Criteria re q uire d bef ore treat me nt ca n res u me are descri be d i n 
t he D ose Dela y s Secti o n 5. 5. 2 .
D oses ma y  be hel d as nee de d u ntil t o xicit y res ol uti o n.  De pe n di n g o n w he n t he a d verse e ve nt 
res ol ve d, a treat me nt i nterr u pti o n ma y lea d t o t he patie nt missi n g all s u bse q ue nt pla n ne d 
d oses wit hi n t hat sa me c y cle or e ve n t o dela y t he i nitiati o n of t he s u bse q ue nt c ycle. 
If t he a d verse e ve nt t hat le d t o t he treat me nt i nterr u pti o n rec o vers wit hi n t he sa me c ycle, t he n 
re-d osi n g i n t hat c y cle is all o we d.  D oses o mitte d f or t o xicit y are n ot re place d wit hi n t he 
sa me c ycle. T he nee d f or a d ose re d ucti o n at t he ti me of treat me nt res u m pti o n s h o ul d be 
base d o n t he criteria defi ne d i n t he D ose Re d ucti o ns Secti o n 5. 5. 3 , u nless e x pressl y a gree d 
ot her wise f oll o wi n g disc ussi o n bet wee n t he i n vesti gat or a n d t he s p o ns or. 
I n t he e ve nt of a treat me nt i nterr u pti o n f or reas o ns ot her t ha n treat me nt-relate d t o xicit y 
(e g, electi ve s ur ger y) lasti n g > 3 wee ks, treat me nt res u m pti o n will be deci de d i n c o ns ultati o n 
wit h t he s p o ns or.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 7
5. 5. 2. D ose Del a ys
Re -treat me nt f oll o wi n g treat me nt i nterr u pti o n f or treat me nt-relate d t o xicit y or at t he start of 
a n y ne w c ycle s h o ul d n ot occ ur u ntil all of t he f oll o wi n g para meters ha ve bee n met:

A N C ≥1, 0 0 0/ m m 3 f or P F- 0 6 8 6 3 1 3 5, de xa met has o ne, a n d le nali d o mi de; ≥5 0 0/ m m 3
f or p o mali d o mi de;

Platelets c o u nt ≥2 5 , 0 0 0/m m 3 f or P F - 0 6 8 6 3 1 3 5 a n d de xa met has o ne; ≥3 0, 0 0 0/ m m3 f or 
le nali d o mi de; ≥5 0, 0 0 0/ m m3 f or p o mali d o mi de ;

N o n -he mat ol o gic t o xicities ha ve ret ur ne d t o baseli ne or Gra de 1 se verit y  ( or, at t he 
i n vesti gat or’s discreti o n, Gra de 2 if n ot c o nsi dere d a safet y ris k f or t he patie nt).

Rec o ver y  of treat me nt-e mer ge nt peri p heral ne ur o pat h y t o Gra de ≤1 se verit y .
If a treat me nt dela y  res ults fr o m w orse ni n g of he mat ol o gic or bi oc he mical para meters, t he 
fre q ue nc y of rele va nt bl o o d tests s h o ul d be i ncrease d as cli nically i n dicate d.
If t hese c o n diti o ns are met wit hi n 3 wee ks of treat me nt i nterr u pti o n or c y cle dela y, st u d y 
treat me nt m a y  be res u me d.  R efer t o t he D ose Re d ucti o ns Secti o n 5. 5. 3 f or a d verse e ve nts 
re q uiri n g d ose re d ucti o n at t he ti me of treat me nt res u m pti o n. 
If t hese c o n diti o ns are n ot met, treat me nt res u m pti o n m ust be dela y e d u p t o a ma xi m u m of 
3 wee ks .  If patie nts re q uire disc o nti n uati o n of st u d y treat me nt f or m ore t ha n 4 2 da y s of 
D a y 1 of t he c urre nt c ycle, t he n st u d y treat me nt s h o ul d be per ma ne ntly disc o nti n ue d, u nless 
t he i n vesti gat or’s be nefit/ris k assess me nt s u g gests ot her wise after disc ussi o n wit h t he 
S p o ns or’s me dical m o nit or.
If a treat me nt i nterr u pti o n c o nti n ues be yo n d t he last da y of t he c urre nt c y cle, t he n t he da y 
w he n treat me nt is restarte d will be c o u nte d as Da y 1 of t he ne xt c y cle. 
Rec o m me n de d g ui deli nes f or d ose dela y s of P F -0 6 8 6 3 1 3 5 f or partici pa nts w h o ha ve acti ve 
[c o nfir me d ( p ositi ve b y re g ulat or y a ut h ority- a p pr o ve d test) or pres u me d (test 
pe n di n g/cli nical s us pici o n)] S A R S -C o V 2 i nfecti o n ca n be f o u n d i n A p pe n di x 1 0 .
5. 5. 3. D ose Re d ucti o ns
F oll o wi n g d os i n g i nterr u pti o n or c ycle dela y d ue t o t o xicit y, t he P F -0 6 8 6 3 1 3 5 d ose ma y  nee d 
t o be re d uce d w he n treat me nt is res u me d.
N o s peci fic d ose a dj ust me nts f or P F- 0 6 8 6 3 1 3 5 are rec o m me n de d f or Gra de 1/ 2 
treat me nt-relate d t o xicit y.  H o we ver, i n vesti gat ors s h o ul d al wa ys ma na ge t heir patie nts 
acc or di n g t o t heir me dical j u d g me nt base d o n t he partic ular cli nical circ u msta nces.
Patie nts e x perie nci n g rec urre nt a n d i nt olera ble Gra de 2 t o xicit y  m a y res u me d osi n g at t he 
ne xt l o wer d ose le vel of P F - 0 6 8 6 3 1 3 5 o nce rec o ver y  t o Gra de 1 or baseli ne is ac hie ve d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 8
D ose re d ucti o n of P F -0 6 8 6 3 1 3 5 b y  1 a n d, if nee de d, 2 d ose le vels will be all o we d de pe n d i n g 
o n t he t y pe a n d se verit y  of t o xicit y e nc o u ntere d.  Patie nts e nr olle d i n t he first ( 0. 1 g/ k g ) 
c o h ort will be all o we d 1 d ose re d ucti o n if re q uire d.  Patie nts re q uiri n g m ore t ha n 2 d ose 
re d ucti o ns ( or 1 d ose re d ucti o n f or t he first c o h ort) will be disc o nti n ue d fr o m t he treat me nt 
a n d e ntere d i nt o t he f oll o w -u p p hase, u nless ot her wise a gree d bet wee n t he i n vesti gat or a n d 
t he s p o ns or. If d ose re d ucti o n of P F - 0 6 8 6 3 1 3 5 is nee de d for a n y patie nt w h o recei ve s fi xe d 
d oses of P F - 0 6 8 6 3 1 3 5 ( Parts 1 C, 1 D, 1 E, 2 A, 2 C, 2 D, 2 E), t he ne xt d ose le vel of 
P F -0 6 8 6 3 1 3 5 will be 2 5 % l o wer t ha n t he c urre nt d ose le vel (e g, fr o m 3 2 m g t o 2 4 m g, or 
fr o m 2 4 m g t o 1 6 m g). All d ose m o dificati o ns/a dj ust me nts m ust be clearl y d oc u me nte d i n 
t he patie nt's s o urce n otes a n d case re p ort f or m ( C R F ). 
O nce a d ose has bee n re d uce d f or a gi ve n patie nt, all s u bse q ue nt c y cles s h o ul d be 
a d mi nistere d at t hat d ose le vel, u nless f urt her d ose re d ucti o n is re q uire d.  I ntra patie nt dose 
re-escalati o n is n ot all o we d.
Patie nts e x perie nci n g a D L T m a y  res u me d osin g at t he ne xt l o wer d ose le vel (if a p plica ble) 
o nce a de q uate rec o ver y  is ac hie ve d.  Patie nts e x perie nci n g a D L T of pr ol o n ge d 
m y el os u p pressi o n ( > 4 2 da ys) m a y  n ot res u me treat me nt e ve n if a de q uate rec o ver y is 
ac hie ve d.  N o d ose re d ucti o ns are pla n ne d f or pa tie nts e x perie nci n g t o xicities ot her t ha n 
t h ose liste d as D LTs.  H o we ver, patie nts e x perie nci n g rec urre nt a n d i nt olera ble Gra de 2 
t o xicit y ma y res u me d osi n g at t he ne xt l o wer d ose le vel o nce rec o ver y t o Gra de 1 or 
baseli ne is ac hie ve d.  Patie nts w h ose he mat ol o gic i n dices i m pr o ve pri or t o meeti n g t he 
criteria f or pr ol o n ge d m yel os u p pressi o n > 4 2 d a y s ma y res u me d osi n g at t he ne xt l o wer d ose 
le vel or per ma ne ntl y disc o nti n ue fr o m treat me nt at t he discreti o n of t he i n vesti gat or.
Rec o m me n de d d ose re d ucti o ns f or P F- 0 6 8 6 3 1 3 5 are descri be d i n Ta ble 5.
T a ble 5.
D ose M o dific ati o ns f or P F -0 6 8 6 3 1 3 5 Pr o d uct -Rel ate d T o xicit y a n d f or 
Peri p her al Se ns or y or M ot or Ne ur o p at h y * * *
T o xicit y
Gr a de 1
Gr a de 2
Gr a de 3
Gr a de 4
N o n -he mat ol o gic 
(e xcl u di n g peri p heral 
ne ur o pat h y -see bel o w)
C o nti n ue at t he 
sa me d ose 
le vel.
C o nti n ue at t he sa me 
d ose le vel. 
Wit h h ol d d ose u ntil 
t o xicit y is 
G ra de ≤1, or has 
ret ur ne d t o 
baseli ne, t he n 
re d uce t he d ose b y 
1 le vel.*
Per m a ne ntl y 
disc o nti n ue .*
H e m at ol o gic e xce pt f or 
l y m p h o pe nia, w hic h is 
e x pecte d as part of 
P F -0 6 8 6 3 1 3 5 
mec ha nis m of acti o n
C o nti n ue at t he 
sa me d ose 
le vel.
C o nti n ue at t he sa me 
d ose le vel.
Wit h h ol d d ose u ntil 
t o xicit y is 
G ra de ≤2, or has 
ret ur ne d t o 
baseli ne, t he n 
res u me treat me nt at 
t he sa me d ose 
le vel.* *   If t o xicit y 
re occ urs, d osi n g 
ma y be re d uce d b y 
1 d ose le vel.   If 
Wit h h ol d d ose u ntil 
t o xicit y is G ra de ≤2, 
or has ret ur ne d t o 
baseli ne, t he n 
re d uce t he d ose b y 
1 le vel a n d res u me 
treat me nt.* *   If 
t o xicit y re occ urs 
des pite d ose 
re d ucti o n, d osi n g 
ma y be re d uce d b y 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3 9
T a ble 5.
D ose M o dific ati o ns f or P F -0 6 8 6 3 1 3 5 Pr o d uct -Rel ate d T o xicit y a n d f or 
Peri p her al Se ns or y or M ot or Ne ur o p at h y * * *
T o xicit y
Gr a de 1
Gr a de 2
Gr a de 3
Gr a de 4
t o xicit y re occ urs 
after a ma xi m u m of 
2 d ose le vel 
re d ucti o ns ( 1 f or 
patie nts i n first 
c o h ort), patie nt 
ma y be 
per ma ne ntl y 
disc o nti n ue d fr o m 
treat me nt.
F or platelets, 
wit h h ol d d ose if 
t o xicit y 
≤2 5, 0 0 0 m m 3 a n d 
re-start w he n 
platelets ha ve 
ret ur ne d t o 
≥2 5, 0 0 0 m m 3 or 
baseli ne
1 m o re d ose le vel.  
If t o xicit y re occ urs, 
patie nt ma y be 
per ma ne ntl y 
disc o nti n ue d fr o m 
treat me nt.
Peri p heral se ns or y or 
m o t or ne ur o pat h y (all 
ca usalit y)
See 
Secti o n 8. 4. 4 f or 
rec o m me n de d wor k - u p.
C o nti n ue at t he 
sa me d ose 
le vel.
C o nti n ue t o 
m o nit or t he 
partici pa nt f or 
si g ns of 
w orse ni n g 
ne ur o pat h y
Wit h h ol d d ose u ntil 
res ol uti o n t o Gra de ≤1, 
t he n res u me at a 
re d uce d d ose le vel. 
C o nti n ue t o m o nit or t he 
partici pa nt s f or si g ns of 
w orse ni n g ne ur o pat h y.
If G ra de ≥2 ne ur o pat h y
reocc urs , per ma ne ntl y 
disc o nti n ue 
elra nata ma b.
P er ma ne ntl y 
disc o nti n ue 
elra nata ma b.
Per m a ne ntl y 
disc o nti n ue 
elra nata ma b
* Na usea, v o miti n g, or diarr hea m ust persist at Gra de 3 or 4 des pite ma xi mal me dical t hera p y t o re q uire d ose 
m o dificati o n.
* * C ycle will n ot be e xte n de d t o c o ver f or t he missi n g d os es.
* * * D ose re d ucti o ns f or le n ali do mi de s h o ul d als o f oll o w t he rec o m me n dati o ns i n t his ta ble.
D oses ma y  be hel d as nee de d u ntil t o xicit y res ol uti o n. A p pr o priate f oll o w-u p assess me nts 
s h o ul d be d o ne u ntil a de q uate rec o ver y occ urs as assesse d b y t he i n vesti gat or.
D ose m o dificati o ns f or le nali d o mi de (ie, f or ne utr o pe nia, t hr o m b oc yt o pe nia, re nal 
i m pair me nt, gra de 3 or 4 t o xicities j u d ge d t o be relate d t o le nali d o mi de) per ma n ufact urer’s 
g ui deli nes is per mitte d. Please see , Ta ble 7 a n d Ta ble 8 he mat ol o gic t o xicities a n d re nal 
i m pair me nt f or d ose m o dificati o ns. Please c o ns ult t he Re vli mi d ® U S pac ka ge I nsert ( U S PI) 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 0
f or f urt her details.3 0 F or E ur o pe, please c o ns ult t he Re vli mi d ® S u m mar y  of Pr o d uct 
C haracteristics ( S P C) f or f urt her details. 3 1  F or Ca na da, please c o ns ult t he Re vli mi d ® Pr o d uct 
M o n o gra p h f or f urt her details.
3 2
T a ble 6.
Le n ali d o mi de D ose A dj ust me nt f or T hr o m b oc yt o pe ni a
Pl atelet C o u nt
Rec o m me n de d C o urse of Acti o n

W he n c o u nt first falls t o < 3 0 , 0 0 0 mc L.

W he n c o u nt ret ur ns t o ≥3 0, 0 0 0 mc L .

I nterr u pt le nali d o mi de treat me nt, f oll o w c o m plete
bl o o d c o u nt ( C B C) wee kl y .

Res u me le nali d o mi de at 1 0 m g .

F or eac h s u bse q ue nt dr o p i n c o u nt t o < 3 0, 0 0 0 mc L .

W he n c o u nt ret ur ns t o ≥3 0, 0 0 0 mc L .

I nterr u pt le nali d o mi de treat me nt.

Res u me le nali d o mi de at t he ne xt l o wer d ose le vel 
( 5 m g) o nce dail y. D o n ot dec rease d ose bel o w 5 
m g o nce dail y .
T a ble 7. 
Le n ali d o mi de D ose A dj ust me nt f or Ne utr o pe ni a
Ne utr o p hil C o u nt
Rec o m me n de d C o urse of Acti o n

W he n c o u nt first falls t o < 1, 0 0 0/ mc L .

W he n c o u nt ret ur ns t o ≥1, 0 0 0/ mc L a n d ne utr o pe nia 
is t he o nl y  o bser ve d t o xicit y.

W he n c o u nt ret ur ns t o ≥1, 0 0 0/ mc L a n d ot her 
t o xicit y is o bser ve d.

I nterr u pt le nali d o mi de treat me nt, start G-C S F 
treat me nt, f oll o w C B C wee kl y .

Res u me le nali d o mi de at 1 5 m g o nce dail y .

Res u me le nali d o mi de at 1 0 m g o nce dail y.

F or eac h s u bse q ue nt dr o p i n c o u nt t o < 1, 0 0 0/ mc L .

W he n c o u nt ret ur ns t o ≥1, 0 0 0/ mc L .

I nterr u pt le nali d o mi de treat me nt.

Res u me le nali d o mi de at t he ne xt l o wer d ose le vel 
( 1 0 m g or 5 m g) o nce dail y. D o n ot decrease d ose 
bel o w  5 m g o nce dail y.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 1
T a ble 8. 
Le n ali d o mi de D ose A dj ust me nt f or Re n al I m p air me nt
C ate g or y
Re n al F u ncti o n
D ose
M o derate re nal i m pair me nt
Cr Cl a 3 0 -6 0 m L/ mi n
1 0 m g e ver y o nce dail y
Se vere re nal i m pair me nt
Cr Cl a < 3 0 m L/ mi n ( n ot re q uiri n g 
dial ysis)
1 5 m g e ver y ot her da y
E n d -sta ge re nal disease
Cr Cl a < 3 0 m L/ mi n (re q uiri n g 
dial ysis)
5 m g o nce dail y. O n dial ysis da ys, 
a d mi nister t he d ose after dial ysis
Ke y: Cr Cl = creati ni ne cleara nce.
a Esti mate d b y creati ni ne cleara nce as calc ulate d b y t he C oc kcr oft -Ga ult e q uati o n.
F or r ec o m me n de d le nali d o mi de d ose m o dificati o ns f or peri p heral ne ur o pat h y (all ca usality) , 
refer t o Ta ble 5 .
D ose m o dificati o ns f or p o mali d o mi de (ie, f or ne utr o pe nia, t hr o m b oc y t o pe nia, str o n g 
C Y P 1 A 2 i n hi bit ors, se vere re nal i m pair me nt, or he patic i m pair me nt) per ma n ufact urer’s 
g ui deli nes is per mitte d.  Please see Ta ble 9 he mat ol o gic t o xicities f or d ose m o dificati o ns.  
Please c o ns ult t he P o mal yst ® U S pac ka ge I nsert ( U S PI ) f or f urt her details.3 4  F or E ur o pe, 
please c o ns ult t he I m n o vi d ® S u m mar y  of Pr o d uct C haracteristics ( S P C) f or f urt her details.3 5
F or Ca na da, please c o ns ult t he P o mal y st ® Pr o d uct M o n o gra p h f or f urt her details. 3 6
T a ble 9 .  
D ose M o dific ati o n I nstr ucti o ns f or P o m ali d o mi de f or He m at ol o gic T o xicities
I nterr u pti o n/res u m pti o n t hres h ol d
D ose M o dific ati o n
Ne utr o pe nia
A N C * < 5 0 0 per mc L or Fe brile ne utr o pe nia (fe ver ≥ t o 
3 8. 5° C a n d A N C < 1, 0 0 0 per mc L)
A N C ret ur n t o ≥5 0 0/ mc L
I nterr u pt p o mali d o mi de treat me nt, f oll o w C B C wee kl y.  
Res u me p o mali d o mi de at 3 m g dail y.
F or eac h s u bse q ue nt dr o p < 5 0 0/ mc L
Ret ur n t o ≥5 0 0/ mc L
I nterr u pt p o mali d o mi de treat me nt.
Res u me p o mali d o mi de at 1 m g less t ha n t he pre vi o us 
d ose
T hr o m b oc yt o pe nia
Platelets < 2 5, 0 0 0/ mc L
Platelets ret ur n t o > 5 0, 0 0 0/ mc L
I nterr u pt p o mali d o mi de treat me nt, f oll o w C B C wee kl y. 
Res u me p o mali d o mi de treat me nt at 3 m g dail y.
F or eac h s u bse q ue nt dr o p < 2 5, 0 0 0/ mc L
Ret ur n t o m ore t ha n or e q ual t o 5 0, 0 0 0/ mc L
I nterr u pt p o mali d o mi de treat me nt.
Res u me p o mali d o mi de at 1 m g less t ha n pre vi o us d ose.
* N ote: A N C = A bs ol ute Ne utr o p hil C o u nt
F or ot her Gra de 3 or 4 t o xicities (e xce pt as n ote d bel o w), h ol d treat me nt a n d restart treat me nt 
at 1 m g less t ha n t he pre vi o us d ose w he n t o xicit y  has res ol ve d t o less t ha n or e q ual t o Gra de 
2 at t he p h y sicia n’s discreti o n. F or a na p h ylactic reacti o ns, a n gi oe de ma, pr o gressi ve 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 2
m ultif ocal le u k oe nce p hal o pat h y  ( P M L), or ras h ( Gra de 4 or blisteri n g), p o mali d o mi de s h o ul d 
be per ma ne ntl y  disc o nti n ue d.
T o i nitiate a ne w c y cle of p o mali d o mi de, t he ne utr o p hil c o u nt m ust be at least 5 0 0 per mc L, 
t he platelet c o u nt m ust be at least 5 0, 0 0 0 per mc L.  If t o xicities occ ur after d ose re d ucti o ns t o 
1 m g, t he n disc o nti n ue p o mali d o mi de.

D osa ge A dj ust me nt f or Str o n g C Y P 1 A 2 I n hi bit ors:

A v oi d c o nc o mita nt use of p o mali d o mi de wit h str o n g i n hi bit ors of C Y P 1 A 2. 
C o nsi der alter nati ve treat me nts. If a str o n g C Y P 1 A 2 i n hi bit or m ust be use d, 
re d uce p o mali d o mi de d ose b y 5 0 %.

D osa ge A dj ust me nt f or Patie nts wit h Se vere Re nal I m pair me nt o n He m o dial y sis:

F or patie nts wit h se vere re nal i m pair me nt re q uiri n g dial ys is, t he rec o m me n de d 
starti n g d ose is 3 m g dail y ( 2 5 % d ose re d ucti o n).  Ta ke p o mali d o mi de after 
c o m pleti o n of dial ysis pr oce d ure o n he m o dialys is da ys.

D osa ge A dj ust me nt f or Patie nts wit h He patic I m pair me nt:

F or patie nts wit h mil d or m o derate he patic i m pair me nt ( C hil d- P u g h classes A or 
B), t he rec o m me n de d starti n g d ose is 3 m g dail y ( 2 5 % d ose re d ucti o n). F or 
patie nts wit h se vere he patic i m pair me nt ( C hil d -P u g h class C), t he rec o m me n de d 
d ose is 2 m g ( 5 0 % d ose re d ucti o n).
De xa met has o ne will be a d mi nistere d at a d ose of 4 0 m g wee kl y. F or s u bjects ol der t ha n 7 5 
ye ars or u n der wei g ht ( b o d y mass i n de x [ B MI ] < 1 8. 5), t he de xa met has o ne d ose ma y be 
a d mi nistere d at a d ose of 2 0 m g wee kl y. De xa met has o ne ma y  be re d uce d, if necessar y, 
acc or di n g t o Ta ble 1 0.
T a ble 1 0.
D ose M o dific ati o n I nstr ucti o ns f or De x a met h as o ne T o xicities
C T A C A E C ate g or y
T o xicit y
D ose M o dific ati o n
Gastr oi ntesti nal
Gra de 1 -2 D ys pe psia, gastric or d u o de nal
ulcer, gastritis re q uiri n g me dical 
ma na ge me nt
Treat w it h H 2 bl oc kers, s ucralfate, or 
o m e praz ole. If
s y m pt o ms persist des pite a b o ve 
meas ure, decrease
de xa met has o ne d ose b y 5 0 %.
≥Gra de 3 re q uiri n g
h os pitalizati o n or s ur ger y
H ol d de xa met has o ne u ntil s y m pt o ms 
a de q uatel y c o ntr olle d. Restart at 5 0 % 
of c urre nt d ose al o n g wit h c o nc urre nt 
t hera p y wit h H 2 bl oc kers, s ucralfate or 
o m e praz ole. If s y m pt o ms persist 
des pite a b o ve meas ure, disc o nti n ue 
de xa met has o ne a n d d o n ot res u me.
Ac ute pa ncreatitis
Disc o nti n ue de xa met has o ne a n d d o 
n ot res u me
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 3
T a ble 1 0.
D ose M o dific ati o n I nstr ucti o ns f or De x a met h as o ne T o xicities
C T A C A E C ate g or y
T o xicit y
D ose M o dific ati o n
Car di o vasc ular
≥Gra de 3 E de ma li miti n g f u ncti o n a n d
u nres p o nsi ve t o t hera p y or a nasarca
Di uretics as nee de d a n d decrease 
de xa met has o ne d ose b y 2 5 %; if e de ma 
persists des pite a b o ve meas ures, 
decrease d ose t o 5 0 % of i nitial d ose; 
disc o nti n ue de xa met has o ne a n d d o n ot 
res u me if s y m pt o ms persist des pite 
5 0 % re d ucti o n
Ne ur ol o g y/ Ps yc hiatric
≥Gra de 2 i nterferi n g wit h f u ncti o n b ut n ot
i nterferi n g wit h acti vities of dail y li vi n g
H ol d de xa met has o ne u ntil s y m pt o ms 
a de q uatel y c o ntr olle d. Restart at 5 0 % 
of c urre nt d ose. If s y m pt o ms persist 
des pite a b o ve meas ure, disc o nti n ue 
de xa met has o ne a n d d o n ot res u me
M usc ul os keletal
≥Gra de 2 M uscle w ea k ness S y m pt o matic
a n d i nterferi n g wit h f u ncti o n b ut n ot
i nterferi n g wit h acti vities of dail y li vi n g
Decrease de xa met has o ne d ose b y 
2 5 %; if wea k ness persists des pite 
a b o ve meas ures, decrease d ose t o 5 0 % 
of i nitial d ose; disc o nti n ue 
de xa met has o ne a n d d o n ot res u me if 
s y m pt o ms persist des pite 5 0 %
Meta b olic
≥Gra de 3 H y per gl yce mia
Treat me nt wit h i ns uli n or oral 
h y p o gl yce mic a ge nts as nee de d. If 
u nc o ntr olle d des pite a b o ve meas ure, 
decrease d ose b y 2 5 % decre me nts 
u ntil le vels are satisfact or y
5. 5. 4. I ntr a-P atie nt D ose Esc al ati o n f or P F- 0 6 8 6 3 1 3 5
O nce a patie nt c o m pletes t heir 6 0 d a y  late t o xicit y o bser vati o n peri o d , if t he patie nt di d n ot 
e x perie nce a n y ≥Gra de 3 dr u g relate d t o xicities, t he patie nt ma y  escalate t o t he ne xt hi g her 
d ose le vel if t he hi g her d ose le vel is alrea d y bee n declare d safe f oll o wi n g 6 0-d a y  late t o xicit y 
e val uati o n, a n d criteria o utli ne d i n Secti o n 3. 1. 4. 1 Criteria f or I ntra patie nt D ose Escalati o n
ha ve bee n met .
A d diti o nal i ntra -patie nt d ose escalati o ns will als o be per mitte d o nce a d diti o nal 6 0 d a y  late 
t o xicit y e val uati o n has bee n c o m plete d , a n d if t he patie nt di d n ot e x perie nce a n y ≥Gra de 3 
dr u g relate d t o xicities.  N o cr oss o ver is all o we d, h o we ver, bet wee n m o n ot hera p y  
P F - 0 6 8 6 3 1 3 5 a n d t he differe nt c o m bi nati o n re gi me ns.
A mai nte na nce d ose le vel will be declare d safe f oll o wi n g D L T e val uati o n of patie nts f or a 
mi ni m u m of 6 0 da y s.  O nce a mai nte na nce d ose le vel has bee n declare d safe, patie nts at 
l o wer d ose le vels w h o ha ve c o m plete d t he 6 0 d a y  late t o xicit y o bser vati o n peri o d ma y  
escalate t o t he ne xt hi g her d ose le vel, if criteria o utli ne d i n Secti o n 3. 1. 4. 1 Criteria f or 
I ntra patie nt D ose Escalati o n ha ve bee n met .  N o cr oss o ver is all o we d, h o we ver, bet wee n 
m o n ot hera p y P F -0 6 8 6 3 1 3 5 a n d t he differe nt c o m bi nati o n re gi me ns.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 4
5. 6. Per m a ne nt Disc o nti n u ati o n
T he st u d y will st o p if all d oses e x pl ore d a p pear t o be o verl y t o xic as deter mi ne d b y st u d y 
s p o ns or a n d i n vesti gat ors.  F or ot her s p o ns or disc o nti n uati o n criteria, please refer t o 
Secti o n 1 4 .  F or patie nt wit h dra wal criteria, please refer t o Secti o n 6. 6 .
N ote t hat disease pr o gressi o n as deter mi ne d b y la b orat or y  assess me nts c o m plete d wit hi n t he 
first c ycle ca n n ot be a reas o n f or st u d y wit h dra wal.
D ose escalati o n ma y  als o st o p if:

T he ma xi m u m sa m ple size has bee n ac hie ve d;

A p pr o xi matel y 6 - 1 6 patie nts ha ve bee n e nr olle d at a d ose t hat is pre dicte d t o be t he 
M T D / M A D;

All d oses e x pl ore d a p pear t o be o verl y t o xic a n d t he M T D / M A D ca n n ot be 
deter mi ne d. 
5. 7. I n vesti g ati o n al P r o d uct St or a ge 
T he i n vesti gat or, or a n a p pr o ve d re prese ntati ve, e g, p har macist will e ns ure t hat all 
i n vesti gati o nal pr o d ucts are st ore d i n a sec ure d area wit h c o ntr olle d access u n der re q uire d 
st ora ge c o n diti o ns a n d i n acc or da nce wit h a p plica ble re g ulat or y re q uire me nts.
In vesti gati o nal pr o d uct s s h o ul d be st ore d i n t heir ori gi nal c o ntai ner s a n d i n acc or da nce wit h 
t he la bels. 
See t he I P m a n ual f or st ora ge c o n diti o ns of t he pr o d uct o nce rec o nstit ute d.
A n y  st ora ge co n diti o ns state d i n t he S R S D will be s u perse de d b y t he st ora ge c o n diti o ns 
state d o n t he pr o d uct la bel. 
Site s y ste ms m ust be ca pa ble of meas uri n g a n d d oc u me nti n g (f or e xa m ple, via a l o g), at a 
mi ni m u m, dail y  mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns (as 
a p plica ble, i ncl u di n g fr oze n, refri gerate d , a n d/ or r o o m -te m perat ure pr o d ucts).  T his s h o ul d 
be ca pt ure d fr o m t he ti me of i n vesti gati o nal pr o d uct recei pt t hr o u g h o ut t he st u d y.  E ve n f or 
c o nti n u o us-m o nit ori n g s y ste ms, a l o g or site pr oce d ure t hat e ns ures acti ve e val uati o n f or 
e xc ursi o ns s h o ul d be a vaila ble.  T he i nte nt is t o e ns ure t hat t he mi ni m u m a n d ma xi m u m 
te m perat ure is c hec ke d eac h b usi ness da y t o c o nfir m t hat n o e xc ursi o n occ urre d si nce t he l ast 
e val uati o n a n d t o pr o vi de t he site wit h t he ca pa bilit y t o st ore or vie w t he mi ni m u m/ ma xi m u m
te m perat ure f or all n o n w or ki n g da ys u p o n ret ur n t o n or mal o perati o ns.  T he o perati o n of t he 
te m perat ure m o nit ori n g de vice a n d st ora ge u nit (f or e xa m ple, refri gerat or), as a p plica ble, 
s h o ul d be re g ularly i ns pecte d t o e ns ure t h e y are mai ntai ne d i n w or ki n g or der.
A n y  e xc ursi o ns fr o m t he pr o d uct la bel st ora ge c o n diti o ns s h o ul d be re p orte d t o Pfizer u p o n 
disc o ver y .  T he site s h o ul d acti vel y  p urs ue o pti o ns f or ret ur ni ng t he pr o d uct t o t he st ora ge 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 5
c o n diti o ns descri be d i n t he la beli n g , as s o o n as p ossi ble.  De viati o ns fr o m t he st ora ge 
re q uire me nts, i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o Pfizer .
O nce a n e xc ursi o n is i de ntifie d, t he i n vesti gati o nal pr o d uct m ust be q uara nti ne d a n d n ot use d 
u ntil t he Pfizer pr o vi des per missi o n t o use t he i n vesti gati o nal pr o d uct. It will n ot be 
c o nsi dere d a pr ot oc ol de viati o n if Pfizer a p pr o ves t he use of t he i n vesti gati o nal pr o d uct after 
t he te m perat ure e xc ursi o n.  Us e of t he i n vesti gati o nal pr o d uct pri or t o Pfizer a p pr o val will be 
c o nsi dere d a pr ot oc ol de viati o n. 
S pecific details re gar di n g i nf or mati o n t he site s h o ul d re p ort f or eac h e xc ursi o n will be 
pr o vi de d t o t he site. 
Recei pt of materials, d o or o pe ni n g a n d cl osi n g, a n d ot her r o uti ne ha n dli n g o perati o ns w here 
t he pr o d ucts are briefly o ut of t he te m perat ure ra n ge descri be d i n t he la beli n g are n ot 
c o nsi dere d e xc ursi o ns. 
5. 8. I n vesti gati o n al a n d N o n -I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y 
T he i n vesti gat or site m ust mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, or 
ot her dis p ositi o n of t he i n vesti gati o nal a n d n o n -i n vesti gati o nal pr o d uct s u p plies.  All 
i n vesti gati o nal a n d n o n -i n vesti gati o nal pr o d ucts will be acc o u nte d f or usi n g a dr u g 
acc o u ntabilit y  f or m/rec or d.
5. 8. 1. Destr ucti o n of I n vesti g ati o n al a n d N o n -I n vesti g ati o n al Pr o d uct S u p plies 
T he s p o ns or or desi g nee will pr o vi de g ui da nce o n t he destr ucti o n of u n use d i n vesti gati o nal 
a n d n o n -i n vesti gati o nal pr o d uct (e g, at t he site).  If destr ucti o n is a ut h orize d t o ta ke place at 
t he i n vesti gat or site, t he i n vesti gat or m ust e ns ure t hat t he materials are destr o ye d i n 
c o m plia nce wit h a p plica ble e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial 
i nstr ucti o ns pr o vi de d b y Pfizer, a n d all destr ucti o n m ust be a de q uatel y d oc u me nte d.
5. 9. C o nc o mit a nt Tre at me nt (s)
C o nc o mita nt treat me nt c o nsi dere d necessar y  f or t he patie nt’s well -bei n g m a y  be gi ve n at 
discreti o n of t he treati n g p h y sicia n.
All c o nc o mita nt treat me nts, bl o o d pr o d ucts, as well as n o n dr u g i nter ve nti o ns recei ve d by 
patie nts fr o m scree ni n g u ntil t he e n d of st u d y  visit will be rec or de d o n t he C R F.
P F - 0 6 8 6 3 1 3 5 has bee n de m o nstrate d t o tra nsie ntl y i ncrease c yt o ki ne le vels (e g, I L- 6) i n vi v o 
i n m o n ke ys a n d h u ma n s (als o de m o nstrate d via i n vitr o assa ys) w hic h is e x pecte d wit h 
C D 3 -tar gete d bis pecifics. C y t o ki nes ha ve bee n s h o w n t o res ult i n m o dest i n hi biti o n of s o me 
c yt oc hr o me P 4 5 0 e nz ymes. T heref ore, treat me nt wit h P F- 0 6 8 6 3 1 3 5 has a p ote ntialt o
i ncrease t he e x p os ure of c o nc o mita nt me dicati o ns t hat are s u bstrates f or t hese e nz ymes. 
Ca uti o n s h o ul d be use d u p o n c o nc o mita nt use of se nsiti ve s u bstrates of c yt oc hr o me P 4 5 0 
e nz ymes wit h narr o w t hera pe utic i n de x (e g , C Y P 3 A 4: alfe nta nil, c y cl os p ori ne, 
di h y dr oer g ota mi ne, er g ota mi ne, fe nta n yl , pi m ozi de, q ui ni di ne, sir oli m us a n d tacr oli m us; 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 6
C Y P 2 C 9: p he n y t oi n, warfari n) es pecially d uri n g t he i nitial treat me nt c y cle. A d diti o nal 
details are pr o vi de d i n A p pe n di x 1 1 .
Le nali d o mi d e w he n c o -a d mi nistere d wit h di g o xi n has de m o nstrate d a n i ncrease i n di g o xi n 
C ma x a n d A U C i nf b y  1 4 %.3 0 Le v els of di g o xi n f or patie nts recei vi n g b ot h dr u gs m ust be 
m o nit ore d i n Parts 1 C a n d 2 C i n acc or da nce wit h cli nical j u d g me nt a n d base d o n sta n da r d 
cli nical practice i n patie nts recei vi n g di g o xi n . Refer t o le nali d o mi de la bel re gar di n g dr u gs 
t hat are pr o hi bite d f or use c o nc o mita ntly. 
P o mali d o mi de e x p os ure ma y  be i ncrease d b y str o n g C Y P 1 A 2 i n hi bit ors (e g, ci pr ofl o xaci n 
a n d fl u v o xa mi ne). If c o-a d ministrati o n is u na v oi da ble i n Parts 1 D a n d 2 D, re d uce t he 
p o mali d o mi de d ose per i nstr ucti o ns i n P o mal y st la bel3 4 a n d Secti o n 5. 5. 3 .
Dr u gs w hic h i n d uce C Y P 3 A 4 e nz y me acti vit y  (e. g., bar bit urates, p he nyt oi n, car ba maze pi ne, 
rifa m pi n) ma y e n ha nce t he meta b olis m of c ortic oster oi ds a n d re q uire t hat t he d osa ge of t he 
c ortic oster oi d be i ncrease d. Dr u gs w hic h i n hi bit C Y P 3 A 4 (e. g., ket oc o naz ole, macr oli de 
a nti bi otics s uc h as er yt hr o m yci n) ha ve t he p ote ntial t o res ult i n i ncrease d plas ma 
c o nce ntrati o ns of c ortic oster oi ds. De xa met has o ne is a m o derate i n d ucer of C Y P 3 A 4. C o -
a d mi nstrati o n wit h ot her dr u gs t hat are meta b olize d b y C Y P 3 A 4 (e. g., i n di na vir, 
er yt hr o m y ci n) ma y i ncrease t heir cleara nce, res ulti n g i n decrease d plas ma c o nce ntrati o n.
All C O VI D - 1 9 vacci nes are per mitte d a n d s h o ul d be rec or de d as c o nc o mita nt me dicati o ns 
(sta n dar d A E c ollecti o n a n d re p orti n g pr ocesses s h o uld be f oll o we d) .  T he ti mi n g of 
C O VI D - 1 9 vacci ne a d mi nistrati o n relati ve t o st u d y i nter ve nti o n is at t he discreti o n of t he 
i n vesti gat or, alt h o u g h, if p ossi ble, it is best t o a v oi d vacci ne a d mi nistrati o n wit hi n 4 8 h o urs 
bef ore or after t he first a n d sec o n d d oses of st u d y i nter ve nti o n.
T he a d mi nistrati o n of dr u gs k n o w n t o ca use peri p heral ne ur o pat h y  s h o ul d be caref ully 
c o nsi dere d, a n d if p ossi ble, a v oi de d b y t he i n vesti gat or.
5. 9. 1. Pre me dic ati o n Re q uire d f or C yt o ki ne Rele ase S y n dr o me Pr o p h yl a xis
F or b ot h t he pri mi n g d oses a n d first f ull d ose ( 7 6 m g), a d mi nister t hese me dicati o ns 
6 0 mi n utes ( ± 1 5 mi n utes) pri or t o elra nata ma b d ose:   

aceta mi n o p he n 6 5 0 m g ( or paraceta m ol 5 0 0 m g) *

di p he n h y dra mi ne 2 5 m g ( or e q ui vale nt) *, oral or I V

de xa met has o ne 2 0 m g ( or e q ui vale nt), oral or I V
* Differe nt b ut c o m para ble d oses d ue t o l ocal stre n gt h variati o ns are per missi ble.
Si milar pre me dicati o ns f or d oses at ot her ti me p oi nts ma y  be gi ve n at t he discreti o n of  t he 
i n vesti gat or.
See A p pe n di x 5 f or ma na ge me nt of C R S a n d IC A N S .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 7
5. 9. 2. Ot her A nti -t u m or/A nti - ca ncer or E x peri me nt al Dr u gs
N o a d diti o nal a nti -ca ncer t hera p y will be per mitte d w hile patie nts are recei vi n g st u d y 
treat me nt.  A d diti o nall y , t he c o nc urre nt use of select vita mi ns or her bal s u p ple me nts is n ot 
per mitte d . Palliati ve ra di ot hera p y o n st u d y is per mitte d f or t he treat me nt of pai nf ul b o n y 
lesi o ns pr o vi de d t hat t he lesi o ns were k n o w n at t he ti me of st u d y e ntr y a n d t he i n vesti gat or 
clearl y i n dicates t hat t he nee d f or palliati ve ra di ot hera p y is n ot i n dicati ve of disease 
pr o gressi o n.  I n vie w of t he c urre nt lac k of data a b o ut t he i nteracti o n of P F - 0 6 8 6 3 1 3 5 wit h
ra di ot hera py, P F -0 6 8 6 3 1 3 5 treat me nt s h o ul d be i nterr u pte d d uri n g palliati ve ra di ot hera p y , 
st o p pi n g 7 d a y s bef ore a n d res u mi n g treat me nt after 7 d a y s.
5. 9. 3. S u p p orti ve C are 
Palliati ve a n d s u p p orti ve care f or disease relate d s y m pt o ms ma y  be a d mi nistere d at t he 
i n vesti gat or’s discreti o n a n d acc or di n g t o a ny a vaila ble A merica n S ociet y  of Cli nical 
O nc ol o g y ( A S C O) g ui deli nes. 
All o p uri n ol/ras b uricase ma y  be a d mi nistere d as nee de d f or t u m or l ysis pr o p h yla xis or 
treat me nt. 
5. 9. 4. C yt o ki ne Rele ase S y n dr o me
S y m pt o ms ass ociate d wit h C R S var y  greatl y a n d ma y be diffic ult t o disti n g uis h fr o m ot her 
c o n diti o ns.  T he m ore c o m m o n s y m pt o ms i ncl u de fe ver, na usea, hea dac he, tac h y car dia, 
h y p ote nsi o n, ras h a n d s h ort ness of breat h.  T he se verit y  of s ym pt o ms ca n be mil d t o life 
t hreate ni n g a n d t h us t here s h o ul d be a hi g h s us pici o n f or C R S if t hese s ym pt o ms occ ur.   If 
C R S is s us pecte d, c yt o ki nes will be a nal yz e d at ce ntral la b orat ories t o deter mi ne if c yt o ki ne 
ele vati o n c o nsiste nt wit h C R S is o bser ve d (see Secti o n 7. 1. 3 ).  T he se verit y of c y t o ki ne 
release s yn dr o me ( C R S) will be assesse d acc or di n g t o t he m o difie d gra di n g descri be d b y  Lee 
et al. i n 2 0 1 4 2 as well as t he m ore rece nt c o nse ns us gra din g fr o m t he A merica n S ociet y f or 
Tra ns pla ntati o n a n d Cell ular T hera p y ( A S T C T )3 b ut o nl y A S T C T will be use d f or 
ma na ge me nt of C R S 3 8 ,3 9 (A p pe n di x 5 ). 
F or C R S D L T criteria, please see Secti o n 3. 2 .
5. 9. 5. I m m u ne Effect or Cell-Ass oci ate d Ne ur ot o xicit y S y n dr o me I C A N S
I C A N S is defi ne d as “a dis or der c haracterize d by a pat h ol o gic pr ocess i n v ol vi n g t he ce ntral 
ner v o us s ys te m f oll o wi n g a ny i m m u ne t hera p y t hat res ults i n t he acti vati o n or e n ga ge me nt of 
e n d o ge n o us or i nf use d T cells a n d/ or ot her i m m u ne effect or cells. S y m pt o ms or si g ns ca n be 
pr o gressi ve a n d ma y  i ncl u de a p hasia, altere d le vel of c o nsci o us ness, i m pair me nt of c o g niti ve 
s kills, m ot or wea k ness, seiz ures, a n d cere bral e de ma. 3 It has bee n o bser ve d f oll o wi n g 
a d mi nistrati o n of s o me c hi meric a nti b o d y rece pt or ( C A R) T cells a n d bis pecific a nti b o dies
a n d ca n occ ur i n de pe n de ntl y  of C R S. T he se verit y of I CA N S s h o ul d be gra de d acc or di n g t o 
t he A S T C T c o nse ns us criteria,3 a n d ma na ge me nt g ui deli nes are pr o vi de d i n A p pe n di x 5 .3 8 ,3 9
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 8
5. 9. 6. T u m or L ysis S y n dr o me ( T L S)
T u m or l y sis is a gr o u p of meta b olic c o m plicati o ns t hat ca n occ ur after treat me nt of ca ncer.  
T u m or l y sis s yn dr o me ( T L S) occ urs w he n t u m or cells release t heir c o nte nts i nt o t he 
bl o o dstrea m, eit her s p o nta ne o usl y or i n res p o nse t o t hera p y , lea di n g t o t he c haracteristic 
fi n di n gs of hy p er urice mia, h yper kale mia, h y p o p h os p hate mia , a n d hy p ocalce mia.   T hese 
electr ol yt e a n d meta b olic dist ur ba nces ca n pr o gress t o cli nical t o xic effects, i ncl u di n g re nal 
i ns ufficie nc y, car diac arr h yt h mias, seiz ures, a n d deat h d ue t o m ulti -or ga n fail ure.  T he 
i nci de nce a n d se verit y of t he T LS de pe n d o n t he ca ncer mass, t he p ote ntial f or l y sis of t u m or
cells, t he c haracteristics of t he patie nt, a n d s u p p orti ve care.
O pti mal m a na ge me nt of T LS s h o ul d i n v ol ve preser vati o n of re nal f u ncti o n.   Ma na ge me nt 
s h o ul d als o i ncl u de pre ve nti o n of d ysr hyt h mias a n d ne ur o m usc ular irrita bilit y .  All patie nts 
w h o are at ris k f or T L S s h o ul d recei ve i ntra ve n o us h y drati o n t o ra pi dl y  i m pr o ve re nal 
p erf usi o n a n d gl o mer ular filtrati o n a n d t o mi ni mize aci d osis.   Re d uci n g t he le vel of uric aci d, 
wit h t he use of all o p uri n ol a n d partic ularl y wit h t he use of ras b uricase, ca n preser ve or 
i m pr o ve re nal f u ncti o n a n d re d uce ser u m p h os p h or us le vels as a sec o n dary be neficial effect. 
H y per kale mia re mai ns t he m ost da n ger o us c o m p o ne nt of T L S beca use it ca n ca use s u d de n 
deat h d ue t o car diac d ys r h yt h mia.  Patie nts s h o ul d li mit p otassi u m a n d p h os p h or us i nta ke 
d uri n g t he ris k peri o d f or T L S.   Fre q ue nt meas ure me nt of p otassi u m le vels (e ver y 4 t o 
6 h o urs), c o nti n u o us car diac m o nit ori n g, a n d t he a d mi nistrati o n of oral s o di u m p ol y st yre ne 
s ulf o nate are rec o m me n de d i n patie nts wit h T LS a n d ac ute ki d ne y  i nj ur y.  H y p ocalcae mia 
ca n als o lea d t o life-t hreate ni n g d ysr hyt h mias a n d n e ur o m usc ular irrita bilit y; c o ntr olli n g t he 
ser u m p h os p h or us le vel ma y pre ve nt h yp ocalce mia.   S y m pt o matic h y p ocalce mia s h o ul d be 
treate d wit h calci u m at t he l o west d ose re q uire d t o relie ve sy m pt o ms.   H y p ocalce mia n ot 
acc o m pa nie d b y si g ns or s y m pt o ms d oes n o t re q uire treat me nt.
5. 9. 7. I nf usi o n Rel ate d Re acti o ns (I R R)
F oll o wi n g t he first i nf usi o n of s o me m o n ocl o nal a nti b o d y  t hera pe utics, s o me patie nts 
e x perie nce fe ver, hea dac he, na usea, v o miti n g or h y p ote nsi o n.  T hese a d verse e ve nts ( A Es) 
are ge nerall y ascri be d t o l ysis of cell ular tar gets, c yt o ki ne release, or c o m ple me nt acti vati o n. 
Inf usi o n relate d reacti o n is c haracterize d b y  fe ver a n d c hills, a n d less c o m m o nl y 
h y p ote nsi o n, eit her e x perie nce d b y  a partic ular patie nt or if see n i n ot her patie nts, 
pretreat me nt me dic ati o n s h o ul d be a d mi nistere d t o re d uce t he i nci de nce a n d se verit y.  A 
re gi me n is s u g geste d here; h o we ver, if l ocal sta n dar d of care is a differe nt re gi me n, t his will 
be all o we d.  I n cases of i nf usi o n reacti o ns, patie nts s h o ul d be pretreate d wit h aceta mi n o p he n 
a n d di p he n h y dra mi ne ( or ot her a nti hista mi ne) a p pr o xi matel y  0. 5 t o 2 h o urs bef ore 
i n vesti gati o nal pr o d uct a d mi nistrati o n.  T he pretreat me nt me dicati o ns will n ot be s u p plie d b y 
Pfizer.  S u g geste d starti n g d oses are 6 5 0 t o 1 0 0 0 m g aceta mi n o p he n a n d 5 0 m g 
di p he n h y dra mi ne ( or e q ui vale nt f or ot her a nti hista mi nes) eit her I V or oral.  T w o ( 2) 
a d diti o nal d oses of aceta mi n o p he n ma y  be a d mi nistere d a p pr o xi matel y e ver y 4- 6 h o urs after 
t he i nitial pretreat me nt or as nee de d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 9
Detaile d g ui da nce o n treat me nt, d ose i nter r u pti o ns a n d p ote ntial retreat me nt is pr o vi de d i n 
A p pe n di x 7 .
5. 9. 8. I njecti o n Site Re acti o ns (I S R)
I S R is a ty pe of h y p erse nsiti vit y reacti o n t hat ma y be i m me diate, alt h o u g h it us uall y a p pears 
wit hi n 2 4 -4 8 hrs after i njecti o n. I S R, b y  defi niti o n, i ncl u des t he f oll o wi n g er yt he ma, pr urit us , 
pai n, i nfla m mati o n, ras h, i n d urati o n, itc hi n g a n d e de ma at t he i njec ti o n site. T o e val uate 
I S Rs, site t olera bilit y assess me nts will be perf or me d per S C H E D U L E O F A C TI VI TI E S .
5. 9. 9. H y perse nsiti vit y T y pes 1 a n d 3
T y pe 1 h y perse nsiti vit y  or aller gic (e g, s h ort ness of breat h, urticaria, a na p h yla xis, 
a n gi oe de ma) reacti o ns are t he oreticall y  p ossi ble i n res p o nse t o a n y i njecte d pr otei n.  Im m u ne 
c o m ple x me diate d T ype 3 h y perse nsiti vit y  reacti o ns are si milar t o t he a d verse e ve nts ( A Es) 
of T y p e 1 reacti o n s b ut are li kel y t o be dela ye d fr o m t he ti me of i nf usi o n a n d ma y  i ncl u de 
s ym pt o ms s uc h as ras h, urticaria, p ol ya rt hritis, m y al gia, p olys y n o vitis, fe ver, a n d, if se vere, 
gl o mer ul o ne p hritis. 
All patie nts s h o ul d be cl osel y  o bser ve d w hile recei vi n g i n vesti gati o nal pr o d uct i nf usi o ns a n d 
m o nit ori n g f or cli nical si g ns of a s ys te mic reacti o n will c o nti n ue t hereafter f or cli nical si g ns 
of aller gic reacti o ns/ h y perse nsiti vit y . 
I n t he case of a hy p erse nsiti vit y reacti o n, t he s u bject will be treate d sy m pt o maticall y  wit h 
s u p p orti ve care, f urt her m o nit ori n g, a n d treat me nt wit h a nti-hista mi nes a n d/ or 
c ortic oster oi ds.  St u d y i nf usi o ns ma y be st o p pe d a n d t he s u bject will be f oll o we d u ntil t he 
e n d of t he st u d y. 
Detaile d g ui da nce o n treat me nt, d ose i nterr u pti o ns a n d p ote ntia l retreat me nt is pr o vi de d i n 
A p pe n di x 7 .
5. 9. 1 0. E xtr a v as ati o n
I n t he e ve nt of e xtra vasati o n, i nf usi o n s h o ul d be st o p pe d i m me diatel y a n d t he i n vesti gat or 
n ee ds t o be c o ns ulte d i m me diatel y .  Treat me nt of e xtra vasati o n s h o ul d f oll o w l ocal sta n dar d 
of care. 
5. 9. 1 1. He m at o p oietic Gr o wt h F act ors
Pri mar y  pr o p h ylactic use of gra n ul oc yte-c ol o n y sti m ulati n g fact ors is n ot per mitte d d uri n g 
C ycle 1, b ut t he y  ma y be use d t o treat treat me nt e mer ge nt ne utr o pe nia as i n dicate d b y t he 
c urre nt A merica n S ociet y of Cli nical O nc ol o g y  g ui deli nes.4 6  
Use of er yt hr o p oieti n gr o wt h fact ors is all o we d as nee de d t o treat a ne mia.  Er y t hr o p oietic 
a ge nts or ot her a ge nts t hat ma y  i ncrease t he ris k of t hr o m b osis s h o ul d be use d wit h ca uti o n 
after ma ki n g a be nefit -ris k assess me nt i n patie nts recei vi n g le nali d o mi de.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 0
5. 9. 1 2. A nti -Di arr he a l, A nti-E metic T her a p y
Pri mar y  pr o p h y la xis of diarr hea, na usea a n d v o miti n g is per mitte d i n t he first c y cle. Pri mar y  
pr o p h y la xis i n s u bse q ue nt c ycles is at t he i n vesti gat or’s discreti o n. T he c h oice of t he 
pr o p h y lactic dr u g as well as t he d urati o n of treat me nt is u p t o t he i n vesti gat or wit h s p o ns or 
a p pr o val ass u mi n g t here is n o k n o w n or e x pecte d dr u g - dr u g i nteracti o n a n d ass u mi n g t he 
dr u g is n ot i ncl u de d i n t he C o nc o mita nt Treat me nt(s) Secti o n 5. 9 .
5. 9. 1 3. A nti -Infl a m m at or y T her a p y
A nti- i nfla m mat or y or narc otic a nal gesic ma y be offere d as nee de d ass u mi n g t here is n o 
k n o w n or e x pecte d dr u g- dr u g i nteracti o n a n d ass u mi n g t he dr u g is n ot i ncl u de d i n t he 
C o nc o mita nt Treat me nt (s) Secti o n 5. 9 . 
5. 9. 1 4. C ortic oster oi ds 
C hr o nic s y ste mic c ortic oster oi d use f or palliati ve or s u p p orti ve p ur p oses, e xce pt as s pecifie d 
i n t he pr ot oc ol, is per mitte d o nl y  f oll o wi n g disc ussi o n a n d a gree me nt bet wee n t he 
i n vesti gat or a n d s p o ns or. Ac ute e mer ge nc y  a d mi nistrati o n, t o pical a p plicati o ns, i n hale d 
s pra ys, e ye dr o ps , or l ocal i njecti o ns of c ortic oster oi ds are all o we d.
5. 9. 1 5. S ur ger y 
Ca uti o n is a d vise d o n t he oretical gr o u n ds f or a n y s ur gical pr oce d ures d uri n g t he st u d y.  T he 
a p pr o priate i nter val of ti me bet wee n s ur ger y  a n d P F - 0 6 8 6 3 1 3 5 re q uire d t o mi ni mize t he ris k 
of i m paire d w o u n d heali n g a n d blee di n g has n ot bee n deter mi ne d.  St o p pi n g P F - 0 6 8 6 3 1 3 5 is 
rec o m me n de d at least 7 d a y s pri or t o s ur ger y.  P ost o perati vely, t he decisi o n t o rei nitiate 
P F - 0 6 8 6 3 1 3 5 treat me nt s h o ul d be base d o n a cli nical assess me nt of satisfact or y  w o u n d 
heali n g a n d rec o ver y  fr o m s ur ger y.
5. 9. 1 6. Tr a nsf usi o n S u p p ort
Pri mar y  pr o p h ylactic use of tra nsf usi o n s u p p ort f or a ne mia is all o we d t o treat a ne mia, as 
i n dicate d by t he c urre nt A merica n S ociet y of Cli nical O nc ol o g y  a n d A merica n Ass ociati o n 
of Bl o o d Ba n ks ( A A B B) g ui deli nes .4 7
Pri mar y  pr o p h y lactic use of tra nsf usi o n s u p p ort f or t hr o m b oc y t o pe nia is all o we d d uri n g 
scree ni n g if t he tra nsf usi o n is c o m plete d pri or t o pla n ne d st u d y treat me nt start. Pri mar y  
pr o p h y lactic use of tra nsf usi o n s u p p ort f or t hr o m b oc yt o pe nia is all o we d t o treat 
t hr o m b oc yt o pe nia, as i n dicate d b y t he c urre nt A merican S ociet y of Cli nical O nc ol o g y. 4 8
6. S T U D Y P R O C E D U R E S 
6. 1. Scree ni n g
F or scree ni n g pr oce d ures see t he S C H E D U L E O F A C TI VI TI E S a n d Assess me nts Secti o n 7 .
All patie nts bei n g c o nsi dere d f or t he st u d y a n d eli gi ble f or scree ni n g m ust si g n a n i nf or me d 
c o nse nt f or t he st u d y bef ore c o m pleti n g a n y st u d y-s pecific pr oce d ures.  A patie nt 
i de ntificati o n n u m ber will be assi g ne d.  T he i n vesti gat or ( or a p pr o priate dele gate at t he site) 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 1
will o btai n i nf or me d c o nse nt fr o m eac h patie nt i n acc or da nce wit h t he pr oce d ures descri be d 
i n t he S C H E D U L E O F A C TI VI TI E S a n d o n I nf or me d C o nse nt.
All patie nts will be scree ne d wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he first d ose  t o 
c o nfir m t hat t he y meet t he patie nt selecti o n criteria f or t he st u d y.
T he re q uire d scree ni n g assess me nts a n d la b orat or y tests are s u m marize d i n t he S C H E D U L E 
O F A C TI VI TI E S a n d Secti o n 7. 1. 3 .  F ollo wi n g c o m pleti o n of t he scree ni n g assess me nts a n d 
c o nfir mati o n of eli gi bilit y, patie nts ma y be e nr olle d.
6. 2. St u d y Peri o d
F or t he treat me nt peri o d pr oce d ures, see t he S C H E D U L E O F A C TI VI TI E S a n d Secti o n 7 .
6. 3. F oll o w -u p 
F or f oll o w -u p pr oce d ures see t he S C H E D U L E O F A C TI VI TI E S a n d Assess me nts Secti o n 7 .
At least 2 8 cale n dar d a y s, a n d n o m ore t ha n 3 5 cale n dar da ys, after disc o nti n uati o n of 
treat me nt, patie nts will ret ur n t o u n der g o re vie w of c o nc o mita nt treat me nts, vital si g ns, a n d 
assess me nt f or res ol uti o n of a n y treat me nt relate d t o xicit y .  Patie nts c o nti n ui n g t o e x perie nce 
t o xicit y at t his p oi nt f oll o wi n g disc o nti n uati o n of treat me nt will c o nti n ue to be f oll o we d at 
least e ver y 4 wee ks u ntil res ol uti o n or deter mi nati o n, i n t he cli nical j u d g me nt of t he 
i n vesti gat or, t hat n o f urt her i m pr o ve me nt is e x pecte d.  Patie nts f o u n d t o ha ve A D A at t heir 
fi nal st u d y visit a n d a n o n g oi n g A E p ossi bly relate d t o A D A will be as ke d t o ret ur n t o t he 
cli nic f or A D A assess me nt at a p pr o xi matel y  3 m o nt h i nter vals (if feasi ble gi ve n t he 
u n derl y i n g disease) u ntil t he a d verse e ve nt or its se q uelae ret ur n t o baseli ne or sta bilize at a 
le vel acce pta ble t o t he i n vesti gat or a n d s p o ns or. If t he patie nt c o m pletes t he 1 m o nt h f oll o w 
u p visit pri or t o c o m pleti o n of t he 6 0 d a y  l o n g ter m D LT o bser vati o n peri o d, a f oll o w u p 
p h o ne call will be c o m plete d o n Da y 6 0 a n d n o m ore t ha n Da y 6 5.
F oll o wi n g disc o nti n uati o n of st u d y  treat me nt ( u nless patie nts are l ost t o f oll o w u p, c o nse nt is 
wit h dra w n, or st u d y is disc o nti n ue d b y t he s p o ns or), s ur vi val stat us will be c ollecte d b y 
tele p h o ne e ver y 3 m o nt hs u ntil deat h, or u p t o a p pr o xi matel y 3 0 m o nt hs after first treat me nt 
of t he last patie nt, w hic he ver c o mes first.  S u bse q ue nt a nti -ca ncer t hera pies a n d rele va nt 
tra ns pla nt i nf or mati o n will als o be c ollecte d.
6. 4. E n d of Tre at me nt
E n d of treat me nt is defi ne d as t he date i n w hic h t he patie nt c o m pletes t he e n d of treat me nt 
( E O T) visit ( u nless patie nts are l ost t o f oll o w u p, c o nse nt is wit h dra w n, or st u d y is 
disc o nti n ue d b y  t he s p o ns or). N ote t hat t he patie nt ma y  c o nti n ue o n t he st u d y f or t heir 
f oll o w u p a n d s ur vi val f oll o w u p visits.
6. 5. E n d of St u d y 
E n d of st u d y  f or all patie nts will be deat h or u p t o a p pr o xi matel y 3 0 m o nt hs after last patie nt 
first d ose, f oll o we d by a n y re q uire d f oll o w -u p visits.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 2
6. 6. P atie nt Wit h dr a w al
Wit h dr a w al of co nse nt: 
Patie nts w h o re q uest t o disc o nti n ue recei pt of st u d y treat me nt will re mai n i n t he st u d y a n d 
m ust c o nti n ue t o be f oll o we d f or pr ot oc ol s pecifie d f oll o w- u p pr oce d ures. T he o nl y  
e xce pti o n t o t his is w he n a patie nt s pecificall y wit h dra ws c o nse nt f or a n y f urt her c o ntact wit h 
hi m or her or pers o n s pre vi o usl y a ut h orize d b y t he patie nt t o pr o vi de t his i nf or mati o n. 
Patie nts s h o ul d n otif y t he i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt fr o m 
f ut ure f oll o w-u p, w he ne ver p ossi ble. T he wit h dra wal of c o nse nt s h o ul d be e x plai ne d i n 
detail i n t he me dical rec or ds b y  t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y  fr o m 
f urt her recei pt of i n vesti gati o nal pr o d uct or als o fr o m st u d y  pr oce d ures a n d/ or p ost treat me nt
st u d y f oll o w- u p, a n d e ntere d o n t he a p pr o priate case re p ort f or m ( C R F ) pa ge. I n t he e ve nt 
t hat vital stat us ( w het her t he patie nt is ali ve or dea d) is bei n g meas ure d, p u blicl y a vaila ble 
i nf or mati o n s h o ul d be use d t o deter mi ne vital stat us o nl y as a p pr o priately directe d i n 
acc or da nce wit h l ocal la w.
L ost t o foll o w - up: 
All reas o na ble eff orts m ust be ma de t o l ocate patie nts t o deter mi ne a n d re p ort t heir o n g oi n g 
stat us. T his i ncl u des f oll o w- u p wit h pers o ns a ut h orize d b y  t he patie nt as n ote d a b o ve. L ost 
t o f oll o w-u p is defi ne d b y  t he i na bility t o reac h t he patie nt after a mi ni m u m of 2 d oc u me nte d 
p h o ne calls, fa xes, or e - mails as well as lac k of res p o nse by t he patie nt t o 1 re gistere d mail 
letter. All atte m pts s h o ul d be d oc u me nte d i n t he patie nt’s me dical rec or ds.
If it is 
deter mi ne d t hat t he patie nt has die d, t he site wi ll use l ocall y per missi ble met h o ds t o o btai n 
t he date a n d ca use of deat h. If t he i n vesti gat or’s use of a t hir d-part y re prese ntati ve t o assist 
i n t he f oll o w-u p p orti o n of t he st u d y  has bee n i ncl u de d i n t he patie nt’s i nf or me d c o nse nt, 
t he n t he i n vesti gat or ma y use a sp o ns or -retai ne d t hir d-part y re prese ntati ve t o assist site staff 
wit h o btai ni n g t he patie nt’s c o ntact i nf or mati o n or ot her p u blic vital stat us data necessar y  t o 
c o m plete t he f oll o w-u p p orti o n of t he st u d y . T he site staff a n d re prese ntati ve will c o ns ult 
p u blicl y  a vaila ble s o urces, s uc h as p u blic healt h re gistries a n d data bases, i n or der t o o btai n 
u p date d c o ntact i nf or mati o n. If, after all atte m pts, t he patie nt re mai ns l ost t o f oll o w-u p, t he n 
t he last-k n o w n -ali ve date as deter mi ne d b y t he i n vesti gat or s h o ul d be re p orte d a n d 
d oc u me nte d i n t he patie nt’s me dical rec or ds.
Patie nts ma y  wit h dra w fr o m treat me nt at a ny ti me at t heir o w n re q uest, or t he y  m a y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or or s p o ns or f or safet y (see als o t he 
Wit h dra wal Fr o m t he St u d y  D ue t o A d verse E ve nts secti o n) or be ha vi oral reas o ns, or t he 
i na bilit y of t he patie nt t o c o m pl y wit h t he pr ot oc ol -re q uire d sc he d ule of st u d y visits or
pr oce d ures at a gi ve n i n vesti gat or site. 
Reas o ns f or wit h dra wal of st u d y  treat me nt ma y i ncl u de:

O bjecti ve disease pr o gressi o n ( n ote t hat disease pr o gressi o n as deter mi ne d b y 
la b orat or y assess me nts c o m plete d wit hi n t he first c ycle ca n n ot be a reas o n f or st u d y 
wit h dra wal) ;
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 3

Gl o bal deteri orati o n of healt h stat us re q uiri n g disc o nti n uati o n;

U nacce pta ble t o xicit y ;

Pre g na nc y ;

Si g nifica nt pr ot oc ol vi olati o n;

L ost t o f oll o w - u p;

Patie nt ref use d f urt her treat me nt;

St u d y  ter mi nate d b y s p o ns or;

Deat h.
Reas o ns f or wit h dra wal fr o m st u d y f oll o w-u p ma y i ncl u de:

C o m plete d st u d y  f oll o w- u p;

St u d y  ter mi nate d b y s p o ns or;

L ost t o f oll o w - u p;

Ref us e d f urt her f oll o w-u p;

Deat h.
N ote t hat disc o nti n uati o n of st u d y treat me nt d oes n ot re prese nt wit h dra wal fr o m t he st u d y .  If 
st u d y treat me nt is defi niti vel y disc o nti n ue d, t he partici pa nt will re mai n i n t he st u d y If a 
patie nt d oes n ot ret ur n f or a sc he d ule d vi sit, e ver y eff ort s h o ul d be ma de t o c o ntact t he 
patie nt.  All atte m pts t o c o ntact t he patie nt a n d i nf or mati o n recei ve d d uri n g c o ntact atte m pts 
m ust be d oc u me nte d i n t he patie nt’s me dical rec or d.
I n a ny circ u msta nce, e ver y  eff ort 
s h o ul d be ma de t o d oc u me nt patie nt o utc o me, if p ossi ble.  T he i n vesti gat or s h o ul d i n q uire 
a b o ut t he reas o n f or wit h dra wal, re q uest t hat t he patie nt ret ur n f or a fi nal visit, if a p plica ble, 
a n d f oll o w u p wit h t he patie nt re gar di n g a n y u nres ol ve d A Es .
If t he patie nt ref uses f urt her visits, t he patie nt s h o ul d c o nti n ue t o be f oll o we d f or s ur vi val 
u nless t he patie nt wit h dra ws c o nse nt f or discl os ure of f ut ure i nf or mati o n or f or f urt her 
c o ntact.  I n t his case, n o f urt her st u d y-s pecific e val uati o ns s h o ul d be perf or me d a n d n o 
a d diti o nal data s h o ul d be c ollecte d.  T he s p o ns or ma y  retai n a n d c o nti n ue t o use a n y data 
c ollecte d bef ore s uc h wit h dra wal of c o nse nt.
7. A S S E S S M E N T S
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat t he pr ot oc ol -re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d. H o we ver , it is a ntici pate d t hat fr o m ti me t o ti me t here ma y be 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 4
circ u msta nces o utsi de of t he c o ntr ol of t he i n vesti gat or t hat ma y  ma ke it u nfeasi ble t o 
perf or m t he test. I n t hese cases t he i n vesti gat or will ta ke all ste ps necessar y t o e ns ure t he 
safety a n d well - bei n g of t he patie nt . W he n a pr ot oc ol
-re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t his a n d a n y c orrecti ve a n d pre ve nti ve acti o ns t hat 
he or s he has ta ke n t o e ns ure t hat n or mal pr ocesses are a d here d t o as s o o n as p ossi b le. T he 
st u d y tea m will be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner .
F or sa m ples bei n g c ollecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, s hi p me nt 
i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or t o i nitiati o n 
of t he st u d y .
7. 1. S afet y Assess me nt
Safet y  assess me nts will i ncl u de c ollecti o n of A Es, seri o us a d verse e ve nts (S A Es ), vital si g ns 
a n d p h ysical e xa mi nati o n, electr ocar di o gra m (E C G [1 2- lea d]), la b orat or y assess me nts, 
i ncl u di n g pre g na nc y tests a n d verificati o n of c o nc o mita nt treat me nts.  See A p pe n di x 1 0 f or 
alter nati ve meas ure g ui deli nes d ue t o C O VI D -1 9. 
7. 1. 1. Pre g n a nc y Testi n g
F or fe male patie nts of c hil d beari n g p ote ntial, a ser u m pre g na nc y  test, wit h se nsiti vit y of at 
least 2 5 mI U/ m L , will be perf or me d at scree ni n g a n d o n Da y 1 of eac h c y cle.
A ne gati ve pre g na nc y  test res ult is re q uire d bef ore t he patie nt m a y  recei ve t he i n vesti gati o nal 
pr o d uct .  Pre g na nc y tests will als o be d o ne w he ne ver 1 me nstr ual c y cle is misse d d uri n g t he 
acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y  is ot her wise s us pecte d).  Pre g na nc y 
tests ma y als o be re peate d if re q ueste d by i nstit uti o nal re vie w b oar ds (I R Bs)/et hics 
c o m mittees ( E Cs) or if re q uire d b y  l ocal re g ulati o ns.
I n a d diti o n, f or P arts 1 C, 1 D, 2 C, a n d 2 D, pre g na nc y  testi n g s h o ul d occ ur at C 1 D 1 a n d 
wee kl y d uri n g first c ycle, a n d if me nstr ual c ycles are irre g ular s h o ul d occ ur e ver y 2 wee ks
t hereafter. I n a d diti o n, pre g na nc y  pre venti o n pr o gra ms ( P P P) f or le nali d o mi de a n d 
p o mali d o mi de m ust be f oll o we d.  
7. 1. 2. A d verse E ve nts
Assess me nt of a d verse e ve nts will i ncl u de t he t y pe, i nci de nce, se verit y  ( gra de d b y t he 
Nati o nal Ca ncer I nstit ute [ N CI ] C T C A E versi o n 4. 0 3 ) ti mi n g, seri o us ness, a n d relate d ness.  
T he se verit y of c y t o ki ne release s yn dr o me ( C R S) will be assesse d acc or di n g t o t he gra di n g 
descri be d b y Lee et al. ( 2 0 1 4 a n d 2 0 1 9 ,2 ,3 see A p pe n di x 5 ).
Patie nts w h o ha ve u n der g o ne all o ge neic ste m cell tra ns pla nt > 1 0 0 da y s bef ore t he first d ose 
of st u d y  treat me nt will be m o nit ore d f or c hr o nic graft -vers us -h ost disease ( G v H D ) acc or di n g 
t o i nstit uti o nal g ui deli nes.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 5
7. 1. 3. L a b or at or y S afet y Assess me nt
He mat ol o g y , bl o o d c he mistr y , viral, c oa g ulati o n a n d pre g na nc y  assess me nts will be dra w n at 
t he ti me p oi nts descri be d i n t he S C H E D U L E O F A C TI VI TI E S a n d a nal yz e d at l ocal 
la b orat ories.  If C R S is s us pecte d, a n a d h oc c yt o ki ne sa m ple will be c ollecte d a n d e val uate d 
ce ntrall y ( See Secti o n 7. 5. 4 ).  S h o ul d t he site re q uire c y t o ki ne i nf or mati o n f or patie nt 
ma na ge me nt, t he site will ha ve t he o pti o n of c ollecti n g a n a d diti o nal sa m ple f or l ocal 
a nal ys is. If a sa m ple f or p har mac o d y n a mic c yt o ki ne pa nel e val uati o n is d ue t o be c ollecte d 
o n t he sa me da y  as a s us pecte d C R S e ve nt occ urs , t he n a n a d h oc sa m ple f or ce ntral a nalys is 
is n ot re q uire d/c ollecte d. H o we ver, a n a d h oc sa m ple f or l ocal a nal ys is ma y still be c ollecte d 
f or patie nt ma na ge me nt .  L o cal c yt o ki ne a nalys is ma y i ncl u de i nterle u ki n (I L)-6, I L -1 , 
t u m or necr osis fact or –al p ha ( T N F ), a n d/ or I L-1 0 or ot her c y t o ki nes t hat will hel p t he 
i n vesti gat or wit h patie nt ma na ge me nt.
If T L S is s us pecte d, a s u b-set of c he mistr y tests will be c o m plete d (ie, t otal calci u m, 
creati ni ne, p h os p h or us or p h os p hate, p otassi u m a n d uric aci d) t o c o nfir m dia g n osis if t he 
tests were n ot perf or me d wit hi n t he last 2 4 hrs.
T a ble 1 1.
S afet y L a b or at or y Tests
He m at ol o g y
C he mi str y
Vir al
C o a g ul ati o n
Uri n al ysis
Pre g n a nc y 
Test
A d h oc C e ntr al 
L a b C yt o ki ne 
A n al ysis †
He m o gl o bi n
A L T
H Bs A g 
a n d 
H Bc A b) 
wit h 
refle xi ve 
D N A 
testi n g
P T  or I N R
Uri ne 
di pstic k f or 
uri ne 
pr otei n: If 
p ositi ve, 
c ollect 2 4 -hr 
a n d 
micr osc o pic 
( Refle x 
Testi n g)
F or fe male 
patie nts of 
c hil d beari n g 
p ote ntial, 
ser u m.
I L-6, I L -1 0, 
I L-2, sI L 2 R, 
I L-1 2, I L -4, 
I L-5, I L --1 3, 
I L-1 7, I L -1 b, 
I L-8, I F N , a n d 
T N F -
Platelets
A S T
H C V 
a nti b o d y 
wit h 
refle xi ve 
R N A 
testi n g.
P T T
W B C
bicar b o nate
A bs ol ute 
Ne utr o p hils
C R P
A bs ol ute 
L y m p h oc ytes
Al k P h os
A bs ol ute 
M o n oc ytes
S o di u m
A bs ol ute 
E osi n o p hils
P otassi u m
O pti o n al A d 
h oc L oc al L a b 
C yt o ki ne 
A n al ysis †
A bs ol ute 
Bas o p hils
Ma g nesi u m
Uri ne 
di pstic k f or 
uri ne bl o o d: 
If p ositi ve, 
c ollect a 
micr osc o pic 
( Refle x 
Testi n g)
C hl ori de
I L-6
T otal calci u m
I L-1 
T otal 
bilir u bi n * * *
I L-1 0
T otal Pr otei n
T N F 
B U N or Urea
Ot her c yt o ki nes
Creati ni ne
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 6
T a ble 1 1.
S afet y L a b or at or y Tests
He m at ol o g y
C he mi str y
Vir al
C o a g ul ati o n
Uri n al ysis
Pre g n a nc y 
Test
A d h oc C e ntr al 
L a b C yt o ki ne 
A n al ysis †
Uric Aci d
Gl uc ose 
( n o nfaste d)
L D H
Al b u mi n
P h os p h or us or 
P h os p hate
A b bre viati o ns: A l kali ne p h os p hatase = Al k P h os; ala ni ne A mi n otra nsferase = A L T; as partate 
a mi n otra nsferase = A S T; bl o o d urea nitr o ge n = B U N; C -reacti ve pr otei n = C R P; he patitis B = H B V; 
he patitis C = H C V; i nterfer o n-ga m ma = I F N ; I L = i nterle u ki n; I nter nati o nal N or malize d = I N R; lactate 
de h y dr o ge nase = L D H; partial t hr o m b o plasti n ti me = P T T; ; T N F = T u m or necr osis fact or - al p ha; w hite 
bl o o d cells = W B C .
* * * F or p ote ntial H y's La w cases, i n a d diti o n t o re peati n g A S T a n d A L T, la b orat or y tests s h o ul d i ncl u de 
al b u mi n, creati ne ki nase, t otal bilir u bi n, direct a n d i n direct bilir u bi n, ga m ma -gl uta m yl tra nsferase, 
pr ot hr o m bi n ti me ( P T)/I N R, al kali ne p h os p hatase, t otal bile aci ds a n d aceta mi n o p he n dr u g a n d/ or pr otei n 
a d d uct le vels. 
† A d h oc c yt o ki nes f or ce ntral la b e val uati o n will be c ollecte d if C R S is s us pecte d a n d c oi nci des wit h a da y 
p har mac o d y na mic sa m ples are n ot c ollecte d per t he Sc he d ule of Acti vities .  L ocal la b e val uati o n of 
c yt o ki ne is o nl y  re q uire d if t he site re q uire t his i nf or mati o n f or patie nt ma na ge me nt.
7. 1. 4. Vit al Si g ns a n d P h ysic al E x a mi n ati o n
Patie nts will ha ve a p h y sical e xa mi nati o n t o i ncl u de ne ur ol o gical assess me nt, wei g ht, vital 
si g ns, p ulse rate, assess me nt of E C O G perf or ma nce stat us (A p pe n di x 4 ) a n d hei g ht; hei g ht 
will be meas ure d at scree ni n g o nl y.
7. 1. 5. ( 1 2-Le a d) E lectr oc ar di o gr a m
Electr ocar di o gra m ( E C G): Tri plicate 1 2 -lea d (wit h a 1 0 -sec o n d r h yt h m stri p) traci n g will be 
use d f or E C Gs c ollecte d i n C ycles 1 a n d 2 .  Si n gle E C Gs will be c ollecte d at scree ni n g a n d 
fr o m C ycle 3 o n war ds. It is prefera ble t hat t he mac hi ne use d has a ca pacity t o calc ulate t he 
sta n dar d i nter vals a ut o maticall y.  At eac h ti me p oi nt i n C ycles 1 a n d 2 (see t he S C H E D U L E 
O F A C TI VI TI E S ), 3 c o nsec uti ve E C Gs will be perf or me d at a p pr o xi matel y 2 mi n utes a part 
t o deter mi ne t he mea n Q Tc F i nter val.  If t he mea n Q Tc F is pr ol o n ge d ( >5 0 0 msec, 
ie, C T C A E Gra de 3), t he n t he E C Gs s h o ul d be re- e val uate d b y a q ualifie d pers o n at t he site 
f or c o nfir mati o n as s o o n as t he fi n di n g is ma de, i ncl u di n g verificati on t hat t he mac hi ne 
rea di n g is acc urate.  If ma n ual rea di n g verifies a Q Tc F of > 5 0 0 msec , i m me diate c orrecti o n 
f or re versi ble ca uses (i ncl u di n g electr ol yte a b n or malities, h yp o xia a n d c o nc o mita nt 
me dicati o ns f or dr u gs wit h t he p ote ntial t o pr ol o n g t he Q Tc F i nter val) s h o ul d be perf or me d.  
I n a d diti o n, re peat E C Gs s h o ul d be i m me diatel y perf or me d h o urly f or at least 3 h o urs u ntil 
t he Q Tc F i nter val falls bel o w 5 0 0 msec.  If Q Tc F i nter val re verts t o less t ha n 4 8 0 msec, a n d 
i n t he j u d g me nt of t he i n vesti gat or(s) an d s p o ns or is deter mi ne d t o be d ue t o ca use(s) ot her 
t ha n i n vesti gati o nal pr o d uct, treat me nt ma y be c o nti n ue d wit h re g ular E C G m o nit ori n g.  If i n 
t hat ti mefra me t he Q Tc F i nter vals rise a b o ve 5 0 0 msec t he i n vesti gati o nal pr o d uct will be 
hel d u ntil t he Q Tc F i nter val decreases t o 4 8 0 msec.  Patie nts will t he n restart t he 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 7
i n vesti gati o nal pr o d uct at t he ne xt l o west d ose le vel.  If t he Q Tc F i nter val has still n ot 
decrease d t o ≤4 8 0 msec after 2 wee ks, or if at a n y ti me a patie nt has a Q Tc F i nter val 
> 5 1 5 msec or b ec o mes s ym pt o matic, t he patie nt will be re m o ve d fr o m t he st u d y u nless t he 
i n vesti gat or belie ves t hat it is i n t he best i nterest of t he patie nt t o c o nti n ue a n d it has bee n 
a gree d u p o n after disc ussi o n wit h t he s p o ns or.  A d diti o nal tri plicate E C Gs ma y  be perf or me d 
as cli nicall y i n dicate d. 
Pri or t o c o ncl u di n g t hat a n e pis o de of pr ol o n gati o n of t he Q Tc F i nter val is d ue t o 
i n vesti gati o nal pr o d uct, t h or o u g h c o nsi derati o n s h o ul d be gi ve n t o p ote ntial preci pitati n g 
fact ors (e g, c ha n ge i n patie nt cli nical c o n diti o n, effect of c o nc urre nt me dicati o n, electr olyt e 
dist ur ba nce) a n d p ossi ble e val uati o n b y s pecialist.
If a patie nt e x perie nces a car diac or ne ur ol o gic A E (s pecificall y  sy n c o pe, dizzi ness, seiz ures, 
or str o ke), a n E C G (tri plicate) s h o ul d be o btai ne d at t he ti m e of t he e ve nt. 
W he n matc he d wit h P K sa m pli n g, t he E C G s h o ul d be carrie d o ut bef ore eac h P K sa m ple 
dra wi n g s uc h t hat t he P K sa m ple is c ollecte d at t he n o mi nal ti me (ie, t he ti mi n g of t he P K 
c ollecti o ns o verri des t he ti mi n g of t he E C G c ollecti o ns). 
7. 1. 6. Ec h oc ar di o gr a m ( Ec h o) or M ulti g ate d Ac q uisiti o n Sc a n ( M U G A)
Ec h ocar di o gra m ( Ec h o) or m ulti gate d ac q uisiti o n sca n ( M U G A) will be e val uate d i n patie nts 
wit h pre vi o us hist or y  of car diac e ve nts.  F or t hese patie nts, a n ec h ocar di o gra m or M U G A
will be perf or me d at scree ni n g, w he n cli nicall y i n dicate d, a n d at t he e n d of treat me nt ( E O T) 
visit.  T he f oll o wi n g para meters will be e val uate d: ve ntric ular f u ncti o n (i ncl u di n g left 
ve ntric ular ejecti o n fracti o n [ L V E F], e n d s ys t olic v ol u me [ E S V] a n d e n d diast olic v ol u me 
[ E DV]), q ualitati ve e val uati o n of c ha m ber size, a n d wall m oti o n.  A D o p pler e xa mi nati o n 
will be c o m plete d a n d s h o ul d i ncl u de a n assess me nt of mitral val ve, atria, ri g ht ve ntricle, 
tric us pi d val ve, a ortic val ve, p ul m o nic val ve, great vessels, a n d pericar di u m. 
7. 1. 7. L oc al Site I njecti o n T oler a bilit y Assess me nt ( S C O nl y)
Assess me nts ma de of t he i njecti o n sites i n t he a b d o mi nal fat f ol d t o m o nit or l ocal t olera bilit y 
t o P F- 0 6 8 6 3 1 3 5 S C i njecti o ns will be perf or me d 1 t o 4 h o urs f oll o wi n g st u d y dr u g 
a d mi nistrati o n, as per t he S C H E D U L E O F A C TI VI TI E S .  If S C i njecti o ns i n t he a b d o mi nal 
l ocati o n are n ot p ossi ble, S C i njecti o ns ca n be a d mi nistere d i n a distri b ute d ma n ner i n t he 
t hi g hs.  S C i njecti o ns i n t he u p per e xtre mities (e g, delt oi d, u p per a n d lo wer ar m) are n ot 
per mitte d.  Refer t o A p pe n di x 9 f or m ore details.
Site t olera bilit y  assess me nts s h o ul d c o nti n ue at re g ularl y s c he d ule d visits if i njecti o n site 
pai n or i njecti o n site reacti o n (I S R) c haracteristics c o nti n ue t o persist.  T he assess me nts 
s h o ul d c o nti n ue u ntil t he s ym pt o ms res ol ve.  T he i njecti o n sites will be assesse d f or 
er yt he ma, i n d urati o n, ecc h y m osis, i njecti o n site pai n, i njecti o n site pr urit us, or ot her 
o bser ve d c haracteristics after st u d y dr u g d osi n g.  T he dia meter of t he affecte d area will be 
meas ure d a n d t he c o n diti o n of t he i njecti o n site will be rec or de d o n t he S C I njecti o n Site 
Assess me nt C R F.  A n y o bser ve d a b n or malit y at t he i njecti o n site will be j u d ge d b y t he 
i n vesti gat or t o deter mi ne w het her a c orres p o n di n g A E s h o ul d be re p orte d.  I S Rs s h o ul d be 
i m me diatel y p h ot o gra p he d i n c ol or, wit h scale d r uler place d by t he reacti o n, a n d t hese 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 8
p h ot o gra p hs s h o ul d be i ncl u de d i n t he pa tie nt’s s o urce d oc u me ntati o n.  W he n a p pr o priate, at 
t he discreti o n of t he i n vesti gat or, a patie nt wit h a n IS R ma y  be referre d f or a der mat ol o gical 
c o ns ultati o n a n d s ki n bi o ps y  ma y be o btai ne d f or f ut ure e xa mi nati o n of t he IS R.  T he 
der mat ol o g y  c o ns ultati o n is e x pecte d t o ta ke place at t he der mat ol o gist’s practice l ocati o n, or 
ma y  occ ur wit hi n t he sa me i nstit uti o n w here t his st u d y is c o n d ucte d.
7. 2. Dise ase Res p o nse Assess me nt 
A nti- ca ncer assess me nts a n d res p o nse will be assesse d acc or di n g t o t he I nter nati o nal 
M yel o ma W or ki n g Gr o u p (I M W G) res p o nse criteria f or m ulti ple m yel o ma 4 ,5 ( M M, See 
A p pe n di x 2 ).  Disease res p o nse assess me nt s h o ul d be c o nti n ue d t o e n d of treat me nt if e n d of 
treat me nt reas o n is disease pr o gressi o n. Patie nts t hat e n d treat me nt wit h o ut pr o gressi o n a n d 
re mai n i n f oll o w-u p o n st u d y  s h o ul d c o nti n ue t o ha ve disease res p o nse assess me nts t hat are 
o btai ne d per sta n dar d of care re p orte d u ntil disease pr o gressi o n , start of ne w a nti-m y el o ma 
t hera py, or e n d of f oll o w -u p o n st u d y wit h res p o nse assess me nts rec or de d i n t he st u d y  
data base .
7. 2. 1. L a b or at or y E v al u ati o n of Dise ase Res p o nse
La b orat or y  tests f or disease res p o nse will be use d t o e x pl ore early si g nals of a nti-ca ncer 
acti vit y (see A p pe n di x 2 ).4 ,5 T he se la b orat or y tests will be c o m plete d per S C H E D U L E O F 
A C TI VI TI E S , i ncl u di n g assess me nts at s us pecte d C R, w he ne ver disease pr o gressi o n is 
s us pecte d (e g, s ym pt o matic deteri orati o n), a n d at wit h dra wal fr o m treat me nt if n ot d o ne i n 
t he pre vi o us 4 wee ks.  F or patie nts sc he d ule d t o be d ose escalate d, sa m ples will als o be 
c ollecte d wit hi n 1 wee k b ef ore t he pla n ne d start of t he escalate d d ose .  Assess me nts will 
i ncl u de: 

Ser u m pr otei n electr o p h oresis ( S P E P) f or t he meas ure me nt of ser u m al b u mi n a n d 
M -pr otei ns ( al p ha 1 gl o b uli ns, al p ha 2 gl o b uli ns, beta 1 gl o b uli ns, beta 2 gl o b uli ns [beta 
gl o b uli ns if la b is u na ble t o se parate beta 1 a n d beta 2 gl o b uli ns ], a n d/ or ga m ma 
gl o b uli ns ).

Ser u m i m m u n ofi xati o n electr o p h oresis ( SI F E) f or defi niti ve i de ntificati o n of s pecific 
M- pr otei ns (i ncl u di n g i m m u n o gl o b uli n [I g]G, I g A, I g M, a n d t w o li g ht c hai ns ka p pa 
a n d la m da).  SI F E will o nl y  be c o m plete d at baseli ne w he n electr o p h oresis s h o ws n o 
meas ura ble pr otei n at s us pecte d C R, a n d at s us pecte d pr o gressi o n (cli nical or 
bi oc he mical) .

2 4 hr uri ne pr otei n electr o p h oresis ( U P E P) f or t he meas ure me nt of uri ne al b u mi n a n d 
M - pr otei ns ( al p ha 1 gl o b uli ns, al p ha 2 gl o b uli ns, beta 1 gl o b uli ns, beta 2 gl o b uli ns, 
[ beta gl o b uli ns if la b is u na ble t o se parate beta 1 a n d beta 2 gl o b uli ns], a n d/ or ga m ma 
gl o b uli ns ).

2 4 hr uri ne i m m u n ofi xati o n electr o p h oresis ( UI F E) f or defi niti ve i de ntificati o n of 
s pecific M- pr otei ns (i ncl u di n g I g G, I g A, I g M, a n d t w o li g ht c hai ns ka p pa a n d la m da).  
UI F E will o nl y be c o m plete d at baseli ne w he n electr o p h oresis s h o ws n o meas ura ble 
pr otei n at s us pecte d C R, a n d at s us pecte d pr o gressi o n (cli nical or bi oc he mical).
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 9

I n v ol ve d a n d u ni n v ol ve d ser u m free li g ht c hai n a nal ysis ( F L C) o nly w he n b ot h ser u m 
a n d uri ne M -c o m p o ne nts are dee me d n o n -meas ura ble (i ncl u di n g at s us pecte d C R).
Ser u m free ka p pa, free l a m b da a n d free ka p pa/la m b da rati o s h o ul d be rec or de d. 

If patie nts were treate d wit h darat u m u ma b less t ha n 1 1 4 da y s pri or t o pla n ne d 
treat me nt da y, darat u m u ma b will i nterfere wit h S P E P, U P E P, SIF E a n d UI F E 
assa ys.  T heref ore, f or t hese patie nts, F L C assa y  s h o ul d be c o m plete d at 
scree ni n g, C 1 D 1, a n d all s u bse q ue nt disease assess me nts. I n t hese patie nts w h o 
pre vi o usl y  recei ve d darat u m u ma b ser u m a n d uri ne M- s pi ke if meas ura ble at 
baseli ne i n t hese patie nts s h o ul d als o be f oll o we d at t he sa me ti me p oi nts as F L C
wit h t he m ost re prese ntati ve mar ker of disease stat us use d f or deter mi nati o n 
I M W G assess me nt.

Beta -2 micr o gl o b uli n . T his will be c ollecte d o n t he first da y of treat me nt.
All sa m ples will be c ollecte d pri or t o i n vesti gati o nal pr o d uct a d mi nistrati o n o n da y s w here b y 
i n vesti gati o nal pr o d uct is t o be a d mi nistere d.  I n patie nts wit h t w o M-pr otei n ba n ds at t he 
start of t hera py, u nless t he sec o n d ba n d is d ue t o darat u m u ma b or ot her t hera pe utic m A b
i nterfere nce, t he s u m of t he t w o s pi kes s h o ul d be use d f or m o nit ori n g of disease.  W he n a 
c o m plete res p o nse ( C R) , or a cli nical or bi oc he mical pr o gressi o n is s us pecte d, S P E P, ser u m 
SI F E, U P E P, UI F E a n d F L C tests will be re peate d wit hi n 1 t o 4 wee ks . 
N ote t hat if a patie nt ha d meas ura ble ser u m or uri ne M-s pi ke at baseli ne, u nless t he ba n d is 
d ue t o darat u m u ma b or meas ure me nt of M -s pi ke is c o nf o u n de d b y t he prese nce of 
darat u m u ma b or ot her t hera pe utic m A b , pr o gressi o n ca n n ot be defi ne d b y  i ncreases i n ser u m 
F L C al o ne.   Ser u m F L C le vels s h o ul d o nl y  be use d f or res p o nse assess me nt w he n b ot h t he 
ser u m a n d uri ne M-c o m p o ne nt le vels are dee me d n ot meas ura ble or u ni nter preta ble.  
F urt her m ore, caref ul atte nti o n s h o ul d be gi ve n t o ne w p ositi ve i m m u n ofi xati o n res ults 
a p peari n g i n patie nts w h o ha ve ac hie ve d a C R, w he n t he is ot ype is differe nt.   T his ma y  
re prese nt oli g ocl o nal i m m u ne rec o nstit uti o n a n d s h o ul d n ot be c o nf use d wit h rela pse; t hese 
ba n ds t y picall y  disa p pear o ver ti me.
7. 2. 2. B o ne M arr o w Pl as m a Cell E v al u ati o n a n d B o ne M arr o w S a m ple C ollecti o n
B o ne marr o w e val uati o n of plas ma cells i n b o ne marr o w as pirate a n d/ or b o ne marr o w 
bi o psies will be perf or me d t o f oll o w disease res p o nse. 
U nilateral b o ne marr o w as pirate sa m ples will be c ollecte d a n d t he perce nta ge of plas ma cells
will be e val uate d at t he f oll o wi n g ti mes: 
a.
First p re-d ose f irst da y of st u d y treat me nt or u p t o 7 da y s bef ore st u d y treat me nt);
b.
At 1 m o nt h after C 1 D 1 ± 7 da y s; 
c.
At 3 m o nt h s after C 1 D 1 ± 7 da y s;
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 0
d.
W he n s u bject is f o u n d i m m u n ofi xati o n ne gati ve i n b ot h ser u m a n d uri ne t o c o nf ir m 
a n y c o m plete res p o nse ( C R);
e.
At ti me of s us pecte d disease pr o gressi o n ( o pti o nal) ; 
f.
Wit hi n 1 wee k p ri or t o escalati n g t o t he ne xt hi g her d ose le vel c o h ort f oll o wi n g 
6 0- d a y  late t o xicit y e val uati o n ( u nless t he i n vesti gat or assesses t hat t her e i n a n 
u nj ustifia ble ris k f or it a n d/ or t he patie nt ref uses t o u n der g o a b o ne marr o w 
pr oce d ure ; if a b o ne marr o w as pirate or bi o ps y  was perf or me d wit hi n t he past 
4 wee ks pri or t o pla n ne d start of escalate d d ose, o nl y  disease sta gi n g la b tests m ust be 
perf or me d );
g.
At 9 m o nt hs after C 1 D 1 a n d e ver y 6 m o nt hs t hereafter u nless a platea u or C R is 
o bser ve d.   F or patie nts w h o e x perie nce a platea u or C R, a d diti o nal sa m ples at 9 
m o nt hs after C 1 D 1 a n d o n war ds will be o pti o nal. A ± 1 4 da y  wi n d o w a p plies f or 
t hese c ollecti o ns.
B o ne marr o w bi o psies will als o be c ollecte d a n d t he perce nta ge of plas ma cells wit hi n t he 
bi o ps y  sa m ples will als o be e val uate d at t he f oll o wi n g ti mes .  I n case of s us pecte d stri n ge nt 
C o m plete Res p o nse (s C R), t he prese nce/a bse nce of cl o nal cells o n i m m u n o hist oc he mistr y  
s h o ul d als o be e val uate d.
a.
First da y  of st u d y treat me nt ( or u p t o 7 d a y s bef ore st u d y treat me nt); 
b.
At 1 m o nt h after C 1 D 1 ± 7 da y s;
c.
At 3 m o nt hs (o pti o nal) after C 1 D 1 ± 7 da y s;
d.
At 9 m o nt hs ± 1 4 da y s ( o pti o nal) after C 1 D 1 a n d e ver y 6 m o nt hs ± 1 4 da y s t hereafter 
( o pti o nal);
e.
At s us pecte d stri n ge nt C o m plete Res p o nse (s C R) ;
f.
At ti me of s us pecte d disease pr o gressi o n ( o pti o nal). 
Assess me nts s h o ul d be fi xe d acc or di n g t o t he cale n dar, re gar dless of treat me nt dela ys.  W he n 
b o ne marr o w plas ma cell i nfiltrati o n is assesse d b y b ot h b o ne marr o w as pirate a n d b y b o ne 
marr o w bi o ps y, t he hi g hest val ue of b o ne marr o w plas ma cell i nfiltrati o n s h o ul d be utilize d 
f or res p o nse e val uati o n.
T he sa me b o ne marr o w l ocati o n use d f or c haracterizati o n at baseli ne s h o ul d be e m pl o y e d i n 
p ost -baseli ne b o ne marr o w sa m pli n g if cli nicall y feasi ble . 
W he n b o ne marr o w as pirate a n d bi o ps y sa m ples are ta ke n f or disease res p o nse e val uati o n, 
sa m ples f or bi o mar ker a nal ysis will als o be ac q uire d (see B o ne Marr o w Bi o mar kers 
Secti o n 7. 5. 1 ).  I n a d diti o n, if a s u bject is i m m u n ofi xati o n ne gati ve i n b ot h ser u m a n d uri ne 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 1
a n d fl o w c yt o metr y is n ot a vaila ble, bi o ps y sa m ple will be re q uire d f or I H C stai ni n g t o assess 
cl o nalit y. 
B o ne marr o w as pirates will als o be e val uate d ce ntrall y f or mi ni mal resi d ual disease ( M R D,
see A p pe n di x 3 )5 usi n g a ne xt ge nerati o n se q ue nci n g ( N G S) assa y w he n a patie nt is i n 
s us pecte d C R or act ual C R. B o ne marr o w as pirates will be c ollecte d f oll o wi n g t he sa m ple 
c ollecti o n sc he d ule descri be d i n Sc he d ule of Acti vities A, B, a n d C. A C 1 D 1 ( patie nts 
wit h o ut pri mi n g d ose ) or C 0 D 1 ( patie nts wit h pri mi n g d ose) b o ne marr o w as pirate m ust als o 
be c ollecte d a n d s u b mitte d f or all patie nts as t he baseli ne refere nce of t he N G S M R D test.
Sa m ples f or M R D assess me nts s h o ul d be ali q u ote d fr o m t he first b o ne marr o w as pirate p ull.
L ocal M R D testi n g is n ot e nc o ura ge d. I n t he case t hat M R D assess me nt is perf or me d l ocall y 
usi n g a n a nal yt ically vali date d fl o w c yt o metr y M R D assa y  t hat meets t he I M W G se nsiti vit y 
criteria (i.e. se nsiti vit y of o ne i n 1 05 n ucleate d cells), res ults of s uc h test s h o ul d be pr o vi de d 
t o t he s p o ns or b y rec or di n g i n t he st u d y data base. N G S M R D testi n g s h o ul d n ot be 
perf or me d l ocall y. .
7. 2. 3. Fl u or o de o x y gl uc ose ( F D G) P ositr o n E missi o n T o m o gr a p h y ( P E T)/ C o m p ute d 
T o m o gr a p h y ( C T) Im a gi n g 
Fl u or o de o x y gl uc ose -P E T/ C T ( 1 8F- F D G -P E T/ C T) i ma gi n g will be use d t o e x pl ore early 
si g nals of a nti-ca ncer acti vit y.  F D G -P E T/ C T is a f u ncti o nal i ma gi n g met h o d i n w hic h t he 
u pta ke of 1 8 F -F D G b y  cells reflects t he tiss ue u pta ke of gl uc ose, t h us re veali n g s pecific 
t ypes of tiss ue meta b olis m.   I n M M, f u ncti o nal i ma gi n g o n hy bri d sca n ners (c o m bi nati o n of 
P E T a n d C T i ma gi n g) rat her t ha n o n P E T sca n ners al o ne are re q uire d.  T he ass ociati o n of 
a b n ormal F D G u pta ke pr o vi de d b y  P E T i ma gi n g a n d t he assess me nt of b o ne str uct ure 
pr o vi de d b y C T i ma gi n g lea ds t o a n o pti mal e val uati o n of disease.
I ma gi n g st u dies will be c ollecte d per S C H E D U L E O F A C TI VI TI E S . F or all patie nts, 
i ma ges are re q uire d at scree ni n g, s us pecte d C R, w he n disease pr o gressi o n is s us pecte d 
(e g, s ym pt o matic deteri orati o n), e n d of treat me nt visit (if n ot d o ne i n pre vi o us 4 wee ks) a n d 
w he n ot her wise cli nicall y  i n dicate d.  I n patie nts wit h meas ura ble tar get lesi o ns at scree ni n g, 
i ma ges are re q uire d at 1, 3, a n d 9 m o nt hs after C 1 D 1 a n d e ver y 6 m o nt hs t hereafter.
T he scree ni n g P E T/ C T will be use d t o deter mi ne e val ua ble tar get lesi o ns f or eac h patie nt.  
T u m or bac k gr o u n d rati os ( T B Rs ) a n d de vel o p me nt of ne w sites of a b n or malit y will be 
rec or de d. 
If i ma gi n g is use d i n disease assess me nt, t he sa me i ma gi n g tec h ni q ue use d t o c haracterize 
eac h i de ntifie d a n d re p orte d lesi o n at baseli ne will be e m pl o y e d i n p ost -baseli ne disease 
assess me nts.  A n y s oft tiss ue plas mac y t o ma d oc u me nte d at baseli ne m ust u n der g o serial 
m o nit ori n g ; ot her wise, t he patie nt will be classifie d as u ne v al ua ble.  Plas mac y t o ma t hat has 
bee n irra diate d will n ot be s uita ble f or res p o nse assess me nt; h o we ver, it m ust be m o nit o re d 
f or pr o gressi ve disease.
Ra di o gra p hic st u dies are n ot re q uire d t o satisf y  res p o nse a n d M R D re q uire me nts, e xce pt if 
C R or i ma gi n g M R D - ne gati ve stat us is s us pecte d (see A p pe n di x 3 ). 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 2
Disease res p o nse assess me nts will be base d u p o n I M W G criteria
4 ,5 (see A p pe n di x 2 ). 
All patie nts’ files a n d ra di ol o gic i ma ges a n d pat h ol o g y  sa m ples m ust be a vaila ble f or s o urce 
verificati o n a n d f or p ote ntial peer re vie w or i n de pe n de nt ce ntral re vie w . 
Ra di o gra p hic assess me nts o btai ne d per t he patie nt’s sta n dar d of care pri or t o e nr oll me nt i nt o 
t he st u d y d o n ot nee d t o be re peate d a n d are acce pta ble t o be use d as baseli ne e val uati o n, if, 
( 1) o btai ne d wit hi n 2 8 da y s bef ore start of st u d y treat me nt, ( 2) t he sa me tec h ni q ue/ m o dalit y 
ca n be u se d t o f oll o w i de ntifie d lesi o ns t hr o u g h o ut t he trial f or a gi ve n patie nt, a n d ( 3) 
a p pr o priate d oc u me ntati o n i n dicati n g t hat t hese ra di o gra p hic t u m or assess me nts were 
perf or me d as sta n dar d of care is a vaila ble i n t he patie nt’s s o urce n otes.
N ote: F or sites i n Ger ma n y, o nly M RI is all o we d t o be use d as i ma gi n g m o dalit y f or 
partici pa nts wit h e xtra me d ullar y  disease.
7. 3. P h ar m ac o ki netics Assess me nts
Bl o o d sa m ples f or t he a nal y sis of P F-0 6 8 6 3 1 3 5 c o nce ntrati o ns will be c ollecte d i nt o 
a p pr o priatel y la bele d t u bes at t he ti mes s pecifie d i n t he S C H E D U L E O F A C TI VI TI E S of t he 
pr ot oc ol.   If C R S is s us pecte d, a n d if a P K sa m ple is n ot alrea dy sc he d ule d t o be ta ke n 
(eg, fr o m C ycle 3 o n war ds), a P K sa m ple s h o ul d als o be ta ke n.  F or eac h a nal y sis, 
a p pr o xi m atel y 5 m L  of bl o o d sa m ples will be c ollecte d t o pr o vi de a p pr o xi matel y 2 m L  
ser u m.  T he P K sa m pli n g sc he d ule ma y  be m o difie d base d o n e mer gi n g P K data. Bl o o d 
sa m ples (a p pr o xi matel y 3 m L ) t o pr o vi de a p pr o xi matel y 1. 5 m L  plas ma f or t he a nalys is of
le nali d o mi de, p o mali d o mi de , a n d de xa met has o ne co nce ntrati o ns will be c ollecte d i n Parts 1 C
a n d 2C , Parts 1 D a n d 2 D, a n d Parts 1 E a n d 2 E, res pecti vel y, of t he st u d y as o utli ne d i n t he
S C H E D U L E O F A C TI VI TI E S .
I n a d diti o n t o sa m ples c ollecte d at t he sc he d ule d ti mes, a n a d diti o nal bl o o d sa m ple f or 
P F - 0 6 8 6 3 1 3 5 s h o ul d be c ollecte d fr o m patie nts e x perie nci n g u ne x pecte d a n d/ or seri o us A Es 
a n d t he date a n d ti me of bl o o d sa m ple c ollecti o n a n d of last d osi n g pri or t o P K c ollecti o n 
s h o ul d be d oc u me nte d i n t he C R F.   W here n ote d i n t he S C H E D U L E O F A C TI VI TI E S , 
bl o o d sa m ples f or P F -0 6 8 6 3 1 3 5 c o nce ntrati o ns will be c ollecte d at a p pr o xi matel y  t he sa me 
ti me as ot her assess me nts s uc h as p har mac o dy na mic sa m ples w he ne ver p ossi ble.
All eff orts will be ma de t o o btai n t he p har mac o ki netic sa m ples at t he e xact n o mi nal ti me 
relati ve t o d osi n g.  All bl o o d sa m ples s h o ul d be ta ke n fr o m t he c o ntralateral i nf usi o n ar m o n 
d osi n g da y s.  H o we ver, t he e xact ti me of t he sa m ple c ollecti o n will al wa y s be n ote d o n t he 
C R F.   Sa m ples o btai ne d wit hi n t he s pecifie d visit wi n d o w will be n ot be ca pt ure d as a 
pr ot oc ol de viati o n.   T he 2 hr sa m ples s h o ul d be c ollecte d i m me diatel y  bef ore t he i nf usi o n 
e n ds ( n ot m ore t ha n 1 5 mi n utes pri or) fr o m t he c o ntra -lateral ar m of t he i nf usi o n.  If a 
sc he d ule d bl o o d sa m ple c ollecti o n ca n n ot be c o m plete d f or a ny reas o n, t he misse d sa m ple 
ti me ma y be re-sc he d ule d wit h a gree me nt of cli nical i n vesti gat ors, patie nt a n d S p o ns or.  
A d diti o nal i nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p pi n g will be 
pr o vi de d i n t he la b ma n ual.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 3
P K sa m ples will be assa ye d f or P F- 0 6 8 6 3 1 3 5, le nali d o mi de, a n d p o mali d o mi de usi n g a 
vali date d a nal yt ical met h o d i n c o m plia nce wit h Pfizer sta n dar d o perati n g pr oce d ures.  Details 
re gar di n g t he collecti o n, pr ocessi n g, st ora ge a n d s hi p pi n g of t he bl o o d sa m ples will be 
pr o vi de d i n t he st u d y  ma n ual.
As part of u n dersta n di n g t he p har mac o ki netics of t he i n vesti gati o nal pr o d uct sa m ples ma y  be 
use d f or e val uati o n of t he bi oa nal y tical met h o d, as well as for ot her i nter nal e x pl orat or y  
p ur p oses.   T hese data will n ot be i ncl u de d i n t he cli nical st u d y re p ort. 
7. 4. I m m u n o ge nicit y A n al yses
Bi oa nal ys is t o assess f or a nti-dr u g ( P F - 0 6 8 6 3 1 3 5) a nti b o dies ( A D A) will be perf or me d.  
Sa m ples will be a nal y ze d usi n g a vali date d a nal yt ical met h o d i n c o m plia nce wit h Pfizer
sta n dar d o perati n g pr oce d ures (S O Ps ).  All sa m ples t hat are p ositi ve i n a scree ni n g assa y  will 
be f urt her c haracterize d i n ter ms of a nti b o d y  s pecificit y.  A tiere d a p pr oac h t o scree ni n g, 
c o nfir mati o n a n d titer/ q ua ntitati o n will be utilize d. A scree ni n g assa y wit h c o m petiti ve 
c o nfir mat or y ste ps f oll o we d b y a titer assa y will be use d.  Sa m ples ma y  als o be a nalyz e d i n 
ne utralizi n g a nti b o d y ( N A b) assa ys.  Patie nts f o u n d t o ha ve a nti - dr u g a nti b o dies at t heir fi nal 
st u d y visit a n d a n o n g oi n g A E p ossi bly relate d t o A D A will be as ke d t o ret ur n t o t he cli nic 
f or A D A a n d dr u g c o nce ntrati o n bl o o d sa m pli n g at a p pr o xi matel y 3 m o nt h i nter vals u ntil t he 
a d verse e ve nt or it s se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d 
s p o ns or.
Bl o o d sa m ples (a p pr o xi matel y  5 m L ) t o pr o vi de a p pr o xi matel y 1 m L  of ser u m eac h f or A D A 
a n d N A b a gai nst P F-0 6 8 6 3 1 3 5 a nal ys is will be c ollecte d i nt o a p pr o priately la bele d t u bes at 
ti mes s pecifie d i n t he sc he d ule of acti vities of t his pr ot oc ol.  A d diti o nal i nstr ucti o ns f or 
sa m ple c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p pi n g will be pr o vi de d i n t he la b ma n ual.
T he i m m u n o ge nicit y sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he i nstr ucti o ns 
pr o vi de d t o t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y . A n y de viati o ns fr o m t he 
i m m u n o ge nicity sa m ple ha n dli n g pr oce d ure (e g, sa m ple c ollecti o n a n d pr ocessi n g ste ps, 
i nteri m st ora ge or s hi p pi n g c o n diti o ns), i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d 
re p orte d t o t he s p o ns or.  O n a case-b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as 
t o w het her sa m ple i nte grit y has bee n c o m pr o mise d.  A n y  de viati o n fr o m t he s pecifie d sa m ple 
ha n dli n g pr oce d ure res ulti n g i n c o m pr o mise d sa m ple i nte grit y will be c o nsi dere d a pr ot oc ol 
de viati o n.
As part of u n dersta n di n g t he i m m u n o ge nicit y of t he i n vesti gati o nal pr o d uct, sa m ples ma y be 
use d f or e val uati o n of t he bi oa nal y tical met h o d a n d/ or a d diti o nal c haracterizati o n of a n 
o bser ve d i m m u n o ge nicit y  res p o nse.  T hese data will be use d f or i nter nal e x pl orat or y  
p ur p oses a n d will n ot be i ncl u de d i n t he cli nical st u d y re p ort (C S R ).  Sa m ples c ollecte d f or 
t his p ur p ose will be retai ne d i n acc or da nce t o l ocal re g ulati o ns a n d if n ot use d wit hi n t his 
ti mefra me, will be destr o ye d.
7. 5. Bi o m ar ker a n d P h ar m ac o d y n a mic Assess me nts
O ne of t he ke y  ele me nts of t his st u d y is t he p ossi bilit y t o e val uate p ote ntial m olec ular tar gets 
t hat c o ul d be m o difie d b y P F-0 6 8 6 3 1 3 5 , as a m o n ot hera py a n d i n c o m bi nati o n.  Tiss ue 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 4
sa m ples (i ncl u di n g b ut n ot li mite d t o b o ne marr o w bi o ps y, b o ne marr o w as pirate, peri p heral 
bl o o d, ser u m a n d plas ma) will be c ollecte d bef ore a n d after P F-0 6 8 6 3 1 3 5 d osi n g f or 
bi o mar ker e val uati o n a n d p har mac o d y n a mic assess me nts.  Sa m ples o btai ne d pre a n d p ost 
P F -0 6 8 6 3 1 3 5 a d mi nistrati o n will be ma n dat or y f or all patie nts (e xce pt f or b o ne marr o w 
bi o ps y  sa m ples c ollecte d at 1, 3 a n d 9 m o nt hs after C 1 D 1( o pti o nal) a n d e ver y 6 m o nt hs 
t hereafter ( o pti o nal), or f or b o ne marr o w as pirate sa m ples fr o m 9 m o nt hs after C 1 D 1 a n d 
e ver y 6 m o nt hs t hereafter f or patie nts w h o e x perie nce a platea u or C R). If t he c ollecti o n of a 
b o ne marr o w bi o ps y is n ot re q uire d f or disease res p o nse assess me nt, a n d t he i n vesti gat or 
deter mi nes t hat t he ris k ass ociate d wit h t he b o ne marr o w bi o psy is n ot a p pr o priate f or a 
researc h setti n g e g, base d o n c o m plicati o ns d uri n g a pre vi o us pr oce d ure, after c o ns ultati o n 
wit h t he s p o ns or’s me dical m o nit or , t he c ollecti o n of a n y i m pe n di n g b o ne marr o w bi o psies 
ma y  be o mitte d. 
Ta ble 1 2 s u m marizes re prese ntati ve assa ys t o be use d a n d t he sa m ple s o urce.  Refer t o t he 
S C H E D U L E O F A C TI VI TI E S   f or details pertai ni n g t o s pecific da ys a n d ti mes of sa m ple 
c ollecti o n a n d t o t he La b Ma n ual f or details of sa m ple pre parati o n, st ora ge, a n d s hi p me nt.  
T he bi o mar ker st u dies will be use d t o hel p u n dersta n d t he mec ha nis m of acti o n of 
P F -0 6 8 6 3 1 3 5 al o ne a n d i n c o m bi nati o n as well as p ote n tial mec ha nis ms of resista nce.  T he 
st u dies ma y hel p i n t he f ut ure de vel o p me nt of P F-0 6 8 6 3 1 3 5.
T a ble 1 2.
Bi o m ar ker Ass a ys a n d S a m ple S o urces
Bi o m ar ker
M atri x
Ass a y
S ol u ble i m m u ne fact ors
S er u m
I m m u n oassa y
S ol u ble B C M A/relate d fact ors
Plas ma
Mass s pectr o metr y
B C M A e x pressi o n
B M as pirate 
Fl o w  c yt o metr y 
B M bi o ps y
I H C
T B N K
W h ole bl o o d 
Fl o w  c yt o metr y 
B M as pirate 
Fl o w  c yt o metr y
I m m u ne cell p he n ot y pi n g
W h ole bl o o d 
Fl o w  C yt o metr y 
B M as pirate 
Fl o w  C yt o metr y 
B M bi o ps y 
I H C
R N A pr ofili n g
B M as pirate a n d/ or 
bi o ps y ( p ossi ble)
R N A Se q ue nci n g
T- cell re pert oire a nal ysis
W h ole bl o o d 
D N A Se q ue nci n g 
B M as pirate a n d/ or 
Bi o ps y ( p ossi ble)
D N A Se q ue nci n g
A b bre viati o ns: B C M A = B -cell mat urati o n a nti ge n; B M = b o ne marr o w ; de o x yri b o n ucleic aci d = D N A; 
T, B, a n d N K cells = T B N K 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 5
7. 5. 1. B o ne M arr o w Bi o m ar kers
Patie nts will be re q uire d t o pr o vi de b o ne marr o w bi o ps y  a n d as pirate sa m ples f or bi o mar ker 
a nal ys is at ti mes s pecifie d i n t he S C H E D U L E O F A C TI VI TI E S (see als o Secti o n 7. 2. 2 B o ne 
Marr o w E val uati o n ). 
W he n b o ne marr o w as pirate a n d bi o psy sa m ples are ta ke n f or disease 
res p o nse e val uati o n, sa m ples f or bi o mar ker a nalys is will als o be ac q uire d. T his i ncl u des 
b o ne marr o w t a ke n f oll o wi n g a C R, s C R or f oll o wi n g disease pr o gressi o n .
A nal y ses will be c o n d ucte d at fl o w c yt o metr y a n d I H C refere nce la bs t o assess tar get 
e x pressi o n a n d e n u merati o n a n d p he n ot y pi n g of plas ma cells, i nfiltrati n g T- cell s u bsets a n d 
a d diti o nal i m m u ne cells.  F urt her I H C, i m m u n ofl u oresce nce or m ulti ple x i ma gi n g assa ys f or 
a d diti o nal i m m u ne cell p o p ulati o ns a n d/ or i m m u ne acti vati o n a n d re g ulati o n mar kers, a n d/ or 
e pi ge netic assa ys f or i m m u ne cell q ua ntificati o n ma y  be perf orme d t o assess a d diti o nal 
p har mac o d y n a mic effects, if bi o ps y materials s uffice.  T u m or tiss ue ma y als o be s u b mitte d t o 
R N A, T-cell rece pt or ( T C R ), a n d ot her m olec ular pr ofili n g of dr u g res p o nse b y n ucle oti de 
se q ue nci n g. 
I nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he 
la b orat or y ma n ual.
7. 5. 2. W h ole Bl o o d P h ar m ac o d y n a mic M ar kers
W h ole bl o o d sa m ples f or circ ulati n g T, B, N K l y m p h oc yte assa y ( T B N K), a n d T- cell
i m m u n o p he n ot ypi n g will be c ollecte d at ti mes s pecifie d i n t he S C H E D U L E O F 
A C TI VI TI E S of t his pr ot oc ol.  T he T B N K assa y  deter mi nes t he a bs ol ute c o u nts a n d 
perce nta ges f or T, B, N K l y m p h oc y te p o p ulati o ns as well as C D 4 + a n d C D 8 + T- cell s u bset 
rati os i n peri p heral bl o o d.  T-cell i m m u n o p he n ot y pi n g will use m ulti para meter fl o w 
c yt o metr y t o e val uate mar kers s uc h as pr oliferati o n a n d s ur vi val, acti vati o n, a n d e x ha usti o n 
i n C D 4 + a n d C D 8 + naï ve a n d me m or y T-cell s u bsets.  
W h ole bl o o d sa m ples f or e x pl orat or y  m olec ular a nal ysis a n d bi o ba n ki n g will be c ollecte d at 
ti mes s pecifie d i n t he S C H E D U L E O F A C TI VI TI E S of t his pr ot oc ol.
I nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he 
la b orat or y ma n ual.
Sa m ples ma y  be use d f or fl o w assa y de vel o p me nt.  Sa m ples c ollecte d f or t his p ur p ose will be 
retai ne d i n acc or da nce t o l ocal re g ulati o ns a n d if n ot use d wit hi n t his ti mefra me, will be 
destr o y e d.
7. 5. 3. S hi p me nt of P h ar m ac o d y n a mic S a m ples
T he s hi p me nt a d dress a n d assa y  la b c o ntact i nf or mati o n are pr o vi de d i n t he la b orat or y 
ma n ual .
7. 5. 4. C yt o ki ne Assess me nts
Sa m ples will be c ollecte d f or ce ntral e val uati o n of c y t o ki nes at t he ti me p oi nts s pecifie d i n 
t he S C H E D U L E O F A C TI VI TI E S a n d Secti o n 7. 1. 3 .  I nstr ucti o ns f or sa m ple c ollecti o n, 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 6
pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he st u d y  ma n ual.  All sa m ples will be 
a nal yz e d ce ntrall y.  If C R S is s us pected a nd c oi nci des wit h a da y  p har mac o d yna mic sa m ples 
are n ot c ollecte d per t he Sc he d ule of Acti vities , a n a d h oc c y t o ki ne sa m ple s h o ul d be 
c ollecte d (see Secti o n 7. 1. 3 La b orat or y Safet y Assess me nts ).  I n a d diti o n, sh o ul d t he site 
re q uire c yt o ki ne i nf or matio n f or patie nt ma na ge me nt, t he site will ha ve t he o pti o n of 
c ollecti n g a n a d diti o nal sa m ple f or l ocal a nal ys is. 
7. 5. 5. S ol u ble B C M A Assess me nts
W h ole bl o o d sa m ples (a p pr o xi matel y  3 m L ) t o pr o vi de a p pr o xi matel y 1 m L plas ma f or 
s ol u ble B C M A assess me nt will be c ollecte d at t he ti mes s pecifie d i n t he S C H E D U L E O F 
A C TI VI TI E S of t his pr ot oc ol.   A n a d diti o nal s ol u ble B C M A/ ot her fact or sa m ple s h o ul d als o 
be ta ke n if C R S is s us pecte d, a n d a sa m ple is n ot alrea d y  sc he d ule d t o be ta ke n (eg, fr o m 
C ycle 3 o n war ds).   I nstr ucti o ns f or sa m ple c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will 
be pr o vi de d i n t he st u d y ma n ual.
S ol u ble B C M A le vels will be deter mi ne d b y a mass s pectr o metr y assa y, a n d sa m ples ma y b e 
use d f or f urt her e val uati o n of t he bi oa nal yt ical met h o d, as well as f or ot her i nter nal 
e x pl orat or y p ur p oses i ncl u di n g deter mi nati o n of relate d s ol u ble fact ors s uc h as A 
Pr oliferati o n -In d uci n g L i ga n d (A P RI L ).  T hese data will n ot be i ncl u de d i n t he cli nic al 
re p ort.  Sa m ples c ollecte d f or t his p ur p ose will be retai ne d i n acc or da nce t o l ocal re g ulati o ns 
a n d if n ot use d wit hi n t his ti mefra me, will be destr o y e d.
7. 6. P h ar m ac o ge n o mics
7. 6. 1. Ge n ot y pi n g A n al ysis 
Bl o o d sa m ples f or ge n ot y pi n g m a y  be e xa mi ne d t o assess t he i m pact of allelic varia nts of 
ge nes pr o p ose d t o i m pact res p o nse t o P F -0 6 8 6 3 1 3 5, as well as mec ha nis ms of acti o n a n d/ or 
resista nce.  A d diti o nall y, t hese sa m ples ma y als o be use d f or retr os pecti ve e val uati o n of 
a d diti o nal ge netic varia nts ass ociate d wit h variati o n i n P K or t o e x pl ore A Es s h o ul d t hese be 
o bser ve d.  Sa m ples will be retai ne d f or a peri o d of u p t o 3 ye ars after re g ulat or y a p pr o val.
A 4 -m L  bl o o d sa m ple will be c ollecte d fr o m eac h patie nt i nt o a plastic di p otassi u m e detic
aci d et h yl e ne dia mi netetraacetic aci d ( K 2E D T A) t u be at ti mes s pecifie d i n t he S C H E D U L E 
O F A C TI VI TI E S secti o n of t he pr ot oc ol. 
Sa m ples will be a nal y ze d usi n g a n o n- c haracterize d assa y ( n o n-vali date d ).  T hese data will 
be use d f or i nt er nal e x pl orat or y p ur p oses a n d will n ot be i ncl u de d i n t he C S R .
T he p har mac o ge n o mic ( P G x ) sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d i n t he 
i nstr ucti o ns pr o vi de d t o t he i n vesti gat or site t o mai ntai n sa m ple i nte grit y. A n y  de viati o ns 
fr o m t he P G x processi n g ste ps, i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d 
re p orte d t o t he s p o ns or. O n a case -b y -case basis, t he s p o ns or ma y  ma ke a deter mi nati o n as 
t o w het her sa m ple i nte grit y has bee n c o m pr o mise d. A n y  sa m ple dee me d o utsi de of 
esta blis he d sta bi lit y, or of q uesti o na ble i nte grity, will be c o nsi dere d a pr ot oc ol de viati o n.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 7
7. 6. 2. Ge netic A n al ysis 
B o ne marr o w as pirates ta ke n bef ore t he start of st u d y treat me nt will be e val uate d at l ocal la b 
f or t( 4; 1 4)( p 1 6; q 3 2), t( 1 4; 1 6)( q 3 2; q 2 3), 1 7 p 1 3 deleti o ns, t( 1 1; 1 4)( q 1 3; q 3 2), c hr o m os o me 
1 3 deleti o n, pl oi d y  cate g or y, a n d c hr o m os o me 1 a b n or malities . If s o me of t hese c yt o ge netic 
assess me nts ca n n ot be d o ne, site s h o ul d pr o vi de patie nt’s m ost rece nt c y t o ge netic testi n g 
res ults a n d e nter i nt o e C R F. Sa m ple s ma y  be ta ke n u p t o 7 d a y s bef ore t he start of st u d y 
treat me nt.
7. 7. B a n ke d Bi os peci me ns 
Ba n ke d b i os peci me ns will be c ollecte d fr o m patie nts f or e x pl orat or y researc h relati n g t o t he 
dr u g res p o nse a n d M M .  T hese c ollecti o ns are n ot t ypicall y ass ociate d wit h a pla n ne d 
assess me nt descri be d i n t he pr ot oc ol.  T he y  will be ha n dle d i n a ma n ner t hat pr otects eac h 
patie nt’s pri vac y  a n d c o nfi de ntialit y.  Ba n ke d b i os peci me ns will be assi g ne d t he patie nt’s 
st u d y i de ntificati o n c o de (I D) at t he site.  T he data ge nerated fr o m t hese b a n ke d 
b i os peci me ns will als o be i n de xe d b y t his I D.  Bi os peci me ns will be ke pt u ntil destr ucti o n i n 
facilities wit h access li mite d t o a ut h orize d pers o n nel, a n d bi os peci me n-deri ve d data will be 
st ore d o n pass w or d-pr otecte d c o m p uter s ys te ms.  The ke y  bet wee n t he patie nt’s I D a n d t he 
patie nt’s direct pers o nall y  i de ntif yi n g i nf or mati o n (e g, na me, a d dress) will be hel d at t he 
st u d y site.  Bi os peci me ns will be use d o nl y f or t he p ur p oses descri be d i n t he pr ot oc ol a n d 
i nf or me d c o nse nt d oc u me nt; a n y other uses re q uire a d diti o nal et hical a p pr o val.  U nless a 
ti me li mitati o n is re q uire d b y l ocal re g ulati o ns or et hical re q uire me nts, bi os peci me ns will be 
st ore d f or ma ny ye ars ( n o ti me li mit) t o all o w f or researc h i n t he f ut ure, i ncl u di n g researc h 
c o n d ucte d d uri n g t he le n gt h y dr u g -de vel o p me nt pr ocess a n d als o p ost -mar keti n g researc h.  
Patie nts ma y  wit h dra w t heir c o nse nt f or t he use of t heir ba n ke d b i os peci me ns at a n y ti me b y 
ma ki n g a re q uest t o t he i n vesti gat or; i n t his case, a n y re mai ni n g bi os peci me ns will be
destr o ye d, b ut data alrea d y  ge nerate d fr o m t he bi os peci me ns will c o nti n ue t o be a vaila ble t o 
pr otect t he i nte grit y of e xisti n g a nal ys es. 
U nless pr o hi bite d b y  l ocal re g ulati o ns or et hics c o m mittee decisi o n, a 4- m L bl o o d ge n o mic 
b a n ke d b i os peci me n Pre p D 1 (di p ot assi u m e detic aci d [et h yle ne di a mi netetr a acetic aci d] 
[ K2E D T A] w h ole -bl o o d c ollecti o n o pti mize d f or D N A a n al ysis) will be c ollecte d at t he 
ti me s pecifie d i n t he S C H E D U L E O F A C TI VI TI E S secti o n of t he pr ot oc ol t o be retai ne d f or 
p ote ntial p har mac o ge n o mic/ ge n o mic/ bi o mar ker a nal ys es relate d t o dr u g res p o nse a n d M M .  
F or e xa m ple, p utati ve safet y  bi o mar kers, dr u g-meta b olizi n g e nz y me ge nes, dr u g -tra ns p ort 
pr otei n ge nes, or ge nes t h o u g ht t o be relate d t o t he mec ha nis m of dr u g acti o n ma y be 
e xa mi ne d.  T he pri mar y p ur p ose is t o e xa mi ne D N A; h o we ver, t he bi os peci me n ma y als o be 
use d t o st u d y  ot her m olec ules (e g, R N A, pr otei ns, a n d meta b olites).
T he b a n ke d b i os peci me ns will be c ollecte d fr o m all patie nts u nless pr o hi bite d b y l ocal 
re g ulati o ns or I R B/ E C decisi o n.
It is p ossi ble t hat t he use of t hese bi os peci me ns ma y res ult i n c o m merciall y via ble pr o d ucts.  
Patie nts will be a d vise d i n t he i nf or me d c o nse nt d oc u me nt t hat t he y  will n ot be c o m pe nsate d 
i n this e ve nt.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 8
7. 7. 1. A d diti o n al Rese arc h
U nless pr o hi bite d b y  l ocal re g ulati o ns or I R B/ E C decisi o n, patie nts will be as ke d t o i n dicate 
o n t he c o nse nt f or m w het her t he y will all o w b a n ke d b i os peci me ns t o als o be use d t o desi g n 
a n d c o n d uct researc h i n or der t o gai n a f urt her u n dersta n di n g of ot her diseases a n d t o 
a d va nce scie nce, i ncl u di n g de vel o p me nt of ot her me dici nes f or patie nts.
Patie nts nee d n ot pr o vi de a d diti o nal bi os peci me ns f or t he uses descri be d i n t his secti o n; t he 
bi os peci me ns s pecifie d i n t he B a n ke d B i os peci me ns Secti o n 7. 7 will be use d.  Patie nts ma y  
still partici pate i n t he st u d y if t he y elect n ot t o all o w t heir b a n ke d b i os peci me ns t o be use d 
f or t he a d diti o nal p ur p oses descri be d i n t his secti o n.
8. A D V E R S E E V E N T R E P O R TI N G
8. 1. Re q uire me nts
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g safet y e ve nts o n t he C R F a n d f or 
re p orti n g safet y e ve nts o n t he Cli nical Trial ( C T) Seri o us A d verse E ve nt ( S A E) Re p ort F or m 
t o Pfizer Safet y.  T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: 1) S A Es; 
2) n o n- seri o us a d verse eve nts ( A Es); a n d 3) e x p os ure t o t he i n vesti gati o nal pr o d uct u n der 
st u d y d uri n g pre g na nc y or breastfee di n g, a n d occ u pati o nal e x p os ure. 
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T 
S A E Re p ort F or m t o 
Pfizer S afet y Wit hi n 
2 4 H o urs of A w are ness
S A E
All
All
N o n -seri o us A E
All
N o ne
E x p os ure t o t he 
i n vesti gati o nal pr o d uct u n der 
st u d y d uri n g pre g na nc y or 
breastfee di n g, a n d 
occ u pati o nal e x p os ure
All (re gar dless of w het her 
ass ociate d wit h a n A E), 
e xce pt occ u p ati o n al 
e x p os ure
E x p os ure d uri n g 
pre g na nc y , e x p os ure via 
breastfee di n g, 
occ u pati o nal e x p os ure 
(re gar dless of w het her 
ass ociate d wit h a n A E)
All o bser ve d or v ol u nteere d e ve nts re gar dless of tre at me nt gr o u p or s us pecte d ca usal 
relati o ns hi p t o t he i n vesti gati o nal pr o d uct(s) will be re p orte d as descri be d i n t he f oll o wi n g 
para gra p hs.
E ve nts liste d i n t he ta ble a b o ve t hat re q uire re p orti n g t o Pfizer Safet y o n t he cli nical trial 
seri o us a d verse e ve nt (C T S A E ) Re p ort F or m wit hi n 2 4 h o urs of a ware ness of t he e ve nt b y 
t he i n vesti gat or are t o be re p orte d re g ar dless of w het her t he e ve nt is deter mi ne d b y t he 
i n vesti g at or t o be rel ate d t o a n i n vesti g ati o n al pr o d uct u n der st u d y.  In partic ular, if t he 
S A E is f atal or life-t hreate ni n g, n otificati o n t o Pfizer Safety m ust be ma de i m me diatel y, 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 9
irres pecti ve of t he e xte nt of a vaila ble e ve nt i nf or mati o n.  T his ti me fra me als o a p plies t o 
a d diti o nal ne w (f oll o w-u p) i nf or mati o n o n pre vi o usl y  f or war de d re p orts.  I n t he rare sit uati o n 
t hat t he i n vesti gat or d oes n ot bec o me i m me diately a ware of t he occ urre nce of a n e ve nt, t he 
i n vesti gat or m ust re p ort t he e ve nt wit hi n 2 4 h o urs after lear ni n g of it a n d d oc u me nt t he ti me 
of his/ her first a ware ness of t he e ve nt.
F or eac h e ve nt, t he i n vesti gat or m ust p urs ue a n d o btai n a de q uate i nf or mati o n b ot h t o 
deter mi ne t he o utc o me a n d t o assess w het her it meets t he criteria f or classificati o n as a n S A E 
(see t he Seri o us A d verse E ve nts Secti o n 8. 2. 3 bel o w).  I n a d diti o n, t he i n vesti gat or ma y  be 
re q ueste d by Pfizer Safet y t o o btai n s pecific f oll o w -u p i nf or mati o n i n a n e x pe dite d fas hi o n.  
T his i nf or mati o n is m ore detaile d t ha n t hat rec or de d o n t he C R F .  I n ge neral, t his will i ncl u de 
a descri pti o n of t he e ve nt i n s ufficie nt detail t o all o w f or a c o m plete me dical assess me nt of 
t he case a n d i n de pe n de nt deter mi nati o n of p ossi ble ca usalit y.  A n y i nf or mati o n rele va nt t o 
t he e ve nt, s uc h as c o nc o mita nt me dicati o ns a n d ill nesses, m ust be pr o vi de d.  In t he case of a 
patie nt deat h, a s u m mar y of a vaila ble a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble 
t o Pfizer Safet y .  A ny perti ne nt a d diti o nal i nf or mati o n m ust be re p orte d o n t he C T S A E 
Re p ort F or m; a d diti o nal s o urce d oc u me nts (e g, me dical rec or ds, C R F, la b orat or y  data) are t o 
be se nt t o Pfizer Safet y O N L Y u p o n re q uest.
As part of o n g oi n g safet y re vie ws c o n d ucte d b y  t he s p o ns or, a n y n o n-seri o us A E t hat is 
deter mi ne d b y t he s p o ns or t o be seri o us will be re p orte d b y t he s p o ns or as a n S A E.  T o assist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
8. 1. 1. A d diti o n al Det ails O n Rec or di n g A d verse E ve nts o n t he C R F
All e ve nts detaile d i n t he ta ble a b o ve will be rec or de d o n t he A E pa ge(s) of t he C R F .  It 
s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf or mati o n is n ot t he 
sa me as t he A E pa ge of t he C R F.  W he n t he sa me data are c ollecte d, t he f or ms m ust be 
c o m plete d i n a c o nsiste nt ma n ner.   A Es s h o ul d be rec or de d usi n g c o ncise me dic al 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b ot h t he C R F a n d t he C T S A E Re p ort 
F or m f or re p orti n g of S A E i nf or mati o n.
8. 1. 2. Eliciti n g A d verse E ve nt I nf or m ati o n
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d A Es a n d all A Es s p o nta ne o usl y
re p orte d by t he st u d y patie nt.  I n a d diti o n, eac h st u d y  patie nt will be q uesti o ne d a b o ut t he 
occ urre nce of A Es i n a n o n -lea di n g ma n ner.
8. 1. 3. Wit h dr a w al Fr o m t he St u d y D ue t o A d verse E ve nts 
S ee als o t he Patie nt Wit h dra wal
Secti o n 6. 6 .
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca uses, 
acc or di n g t o t he defi niti o n of A E n ote d bel o w, a n d rec or de d o n t he C R F. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 0
W he n a patie nt wit h dra ws fr o m t he st u d y  beca use of a n S A E, t he S A E m ust be rec or de d o n 
t he C R F a n d re p orte d, as a p pr o priate, o n t he C T S A E Re p ort F or m, i n acc or da nce wit h t he 
Re q uire me nts secti o n a b o ve.
8. 1. 4. Ti me Peri o d f or C ollecti n g A E/ S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g A Es a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h patie nt be gi ns fr o m t he ti me t he patie nt pr o vi des i nf or me d c o nse nt, w hic h 
is o btai ne d bef ore t he patie nt’s partici pati o n i n t he st u d y (ie, bef ore u n der g oi n g a ny 
st u d y-relate d pr oce d ure a n d/ or recei vi n g i n vesti gati o nal pr o d uct), t hr o u g h a n d i ncl u di n g a 
mi ni m u m of 9 0 cale n dar da ys after t he last a d mi nistrati o n of P F - 0 6 8 6 3 1 3 5.  If t he 1-m o nt h 
f oll o w u p visit is c o m plete d bef ore t he 6 0 d a y  late t o xicit y e val uati o n peri o d is c o m plete d, 
the A E / S A E c ollecti o n peri o d will be e xte n de d u ntil t he late t o xicit y e val uati o n is c o m plete d.
F or patie nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
8. 1. 4. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a patie nt d uri n g t he acti ve c ollecti o n peri o d are re p orte d t o Pfizer 
Safet y  o n t he C T S A E Re p ort F or m.
S A Es occ urri n g i n a patie nt after t he acti ve c ollecti o n peri o d has e n de d are re p orte d t o Pfizer 
Safet y  if t he i n vesti gat or bec o mes a ware of t he m; at a mi ni m u m, all S A Es t hat t he 
i n vesti gat or belie ves ha ve at least a reas o na ble p ossi bilit y of bei n g relate d t o i n vesti gati o nal 
pr o d uct m ust be re p orte d t o Pfizer Safet y .
F oll o w u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut a n d after t he acti ve c ollecti o n peri o d a n d 
u ntil t he e ve nt or its se q uelae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or, a n d 
Pfizer c o nc u rs wit h t hat assess me nt.
If a patie nt be gi ns a ne w a ntica ncer t hera p y, S A Es occ urri n g d uri n g t he a b o ve-i n dicate d 
acti ve c ollecti o n peri o d m ust still be re p orte d t o Pfizer Safet y  irres pecti ve of a n y i nter ve ni n g 
treat me nt.
8. 1. 4. 2. Rec or di n g N o n -seri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a patie nt d uri n g t he acti ve c ollecti o n peri o d, 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt as descri be d i n Secti o n 8. 1. 4 , will be rec or de d 
o n t he A E secti o n of t he C R F. A n y  si g ns a n d sy m pt o ms e ntirel y  d ue t o C R S (e g, fe ver, 
h y p o xia, h y p ote nsi o n) s h o ul d be rec or de d wit hi n t he C R S assess me nt C R F . A si n gle ter m of 
C y t o ki ne release s yn dr o me gra de d b y m o difie d Lee et al 2 0 1 4 criteria 2 s h o ul d t he n be 
rec or de d i n t he A E C R F. A n y  si g ns a n d sy m pt o ms e ntirel y  d ue t o I C A N S (e g, c o nf usi o n, 
seiz ure) s h o ul d be rec or de d wit hi n t he IC A N S assess me nt C R F. A si n gle ter m of I m m u ne 
cell- ass ociate d ne ur ot o xicit y gra de d by A S T C T criteria 3 s h o ul d t he n be rec or de d i n t he A E 
C R F. I njecti o n site assess me nts c o ntai ni n g A Es s h o ul d ha ve t he ter m of I njecti o n site 
reacti o n rec or de d wit h C T C A E 4. 0 3 gra di n g i n t he A E C R F.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 1
F oll o w -u p b y  t he i n vesti gat or ma y be re q uire d u ntil t he e ve nt or its se q uelae res ol ve or 
sta bilize at a le vel acce ptable t o t he i n vesti gat or, a n d Pfizer c o nc urs wit h t hat assess me nt.
If a patie nt be gi ns a ne w a ntica ncer t hera py, t he rec or di n g peri o d f or n o n -seri o us A Es e n ds at 
t he ti me t he ne w treat me nt is starte d; h o we ver, S A Es m ust c o nti n ue t o be rec or de d o n t he 
C R F d u ri n g t he a b o ve -i n dicate d acti ve c ollecti o n peri o d.
8. 1. 5. C a us alit y Assess me nt
T he i n vesti gat or’s assess me nt of ca usalit y m ust be pr o vi de d f or all A Es (seri o us a n d 
n o n-seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p o n t he C R F, a n d re p ort s uc h 
a n assess me nt i n acc or da nce wit h t he S A E re p orti n g re q uire me nts, if a p plica ble.  A n 
i n vesti gat or’s ca usality assess me nt is t he deter mi nati o n of w het her t here e xists a reas o na ble 
p ossi bilit y  t hat t he i n vesti gati o nal pr o d uct ca use d or c o ntri b ute d t o a n A E; ge nerally t he facts 
(e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p s h o ul d be pr o vi de d.  If t he 
i n vesti gat or d oes n ot k n o w w het her or n ot t he i n vesti gati o nal pr o d uct ca use d t he e ve nt, t he n 
t he e ve nt will be ha n dle d as “relate d t o i n vesti gati o nal pr o d uct” f or re p orti n g p ur p oses, as 
defi ne d b y t he s p o ns or.  If t he i n vesti gat or's ca usalit y assess me nt is “ u n k n o w n b ut n ot 
relate d” t o i n vesti gati o nal pr o d uct, t his s h o ul d be clearly d oc u me nte d o n st u d y  rec or ds. 
I n a d diti o n, if t he i n vesti gat or deter mi nes t hat a n S A E is ass ociate d wit h st u d y pr oce d ures, 
t he i n vesti gat or m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d 
re p ort s uc h a n assess me nt i n t he de dicate d secti o n of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
8. 1. 6. S p o ns or’s Re p orti n g Re q uire me nts t o Re g ul at or y A ut h orities
A E re p orti n g, i ncl u di n g s us pecte d u ne x pecte d seri o us a d verse reacti o ns, will be carrie d o ut 
i n acc or da nce wit h a p plica ble l ocal re g ulati o ns.
8. 2. Defi niti o ns
8. 2. 1. A d verse E ve nts
A n A E is a n y u nt o war d me dical occ urre nce i n a st u d y  patie nt a d mi nistere d a pr o d uct or 
me dical de vice; t he e ve nt nee d n ot necessaril y ha ve a ca usal relati o ns hi p wit h t he treat me nt 
or usa ge.  E xa m ples of A Es i ncl u de, b ut are n ot li mite d t o: 

A b n or mal test fi n di n gs;

Cli n icall y si g nifica nt si g ns a n d s ym pt o ms;

C ha n ges i n p h ys ical e xa mi nati o n fi n di n gs;

H y perse nsiti vit y ;

Dr u g a b use;

Dr u g de pe n de nc y .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 2
A d diti o nall y , A Es ma y i ncl u de si g ns a n d sy m pt o ms res ulti n g fr o m:

Dr u g o ver d ose;

Dr u g wit h dra wal;

Dr u g mis use; 

Dr u g i nteracti o ns;

E xtra vasati o n;

E x p os ure d uri n g pre g na nc y  ( E D P);

E x p os ure via breastfee di n g;

Me dicati o n err or;

Occ u pati o nal e x p os ure.
W orse ni n g of si g ns a n d s y m pt o ms of t he mali g na nc y  u n der st u d y s h o ul d be rec or de d as A Es 
i n t he a p pr o priate secti o n of t he C R F.  Disease pr o gressi o n assesse d by meas ure me nt of 
mali g na nt lesi o ns o n ra di o gra p hs or ot her met h o ds s h o ul d n ot be re p orte d as A Es.
8. 2. 2. A b n or m al Test Fi n di n gs
A b n or mal o bjecti ve test fi n di n gs s h o ul d be rec or de d as A Es w he n a n y of t he f oll o wi n g 
c o n diti o ns are met: 

Test res ult is ass ociate d wit h acc o m pa nyi n g s y m pt o ms; a n d/ or

Test res ult re q uires a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n; 
a n d/ or

Test res ult lea ds t o a c ha n ge i n st u d y d osi n g ( o utsi de of a n y pr ot oc ol -s pecifie d d ose 
a dj ust me nts) or disc o n ti n uati o n fr o m t he st u d y, si g nifica nt a d diti o nal c o nc o mita nt 
dr u g treat me nt, or ot her t hera p y;  a n d/ or

Test res ult is c o nsi dere d t o be a n A E b y t he i n vesti gat or or s p o ns or.
Merel y re peati n g a n a b n or mal test, i n t he a bse nce of a n y of t he a b o ve c o n diti o ns, d o es n ot 
c o nstit ute a n A E.  A n y a b n or mal test res ult t hat is deter mi ne d t o be a n err or d oes n ot re q uire 
rec or di n g as a n A E.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 3
8. 2. 3. Seri o us A d verse E ve nts
A seri o us a d verse e ve nt is a n y  u nt o war d me dical occ urre nce at a n y d ose t hat:

Res ults i n deat h;

Is life-t hreate ni n g (i m me diate ris k of deat h);

Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n;

Res ults i n persiste nt or si g nifica nt disa bilit y /i nca pacit y (s u bsta ntial disr u pti o n of t he 
a bilit y t o c o n d uct n or mal life f u ncti o ns);

Res ults i n c o n ge nital a n o mal y/ birt h defect.
Or t hat is c o nsi dere d t o be:

A n i m p orta nt me dical e ve nt.
Me dical a n d scie ntific j u d g me nt is e xercise d i n deter mi ni n g w het her a n e ve nt is a n i m p orta nt 
me dical e ve nt.  A n i m p orta nt me dical e ve nt ma y  n ot be i m me diatel y life-threate ni n g a n d/ or 
res ult i n deat h or h os pitalizati o n.  H o we ver, if it is deter mi ne d t hat t he e ve nt ma y je o par dize 
t he patie nt or ma y re q uire i nter ve nti o n t o pre ve nt o ne of t he ot her A E o utc o mes, t he 
i m p orta nt me dical e ve nt s h o ul d be re p orte d as seri o us.
E x a m ples of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y r o o m or at h o me f or 
aller gic br o nc h os pas m; bl o o d d yscrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n; 
or de vel o p me nt of dr u g de pe n de nc y  or dr u g a b use.
Pr o gressi o n of t he mali g na nc y  un der st u d y (i ncl u di n g si g ns a n d sy m pt o ms of pr o gressi o n) 
s h o ul d n ot be re p orte d as a n S A E u nless t he o utc o me is fatal wit hi n t he acti ve c ollecti o n
peri o d.  H os pitalizati o n d ue t o si g ns a n d s y m pt o ms of disease pr o gressi o n s h o ul d n ot be 
re p orte d as a n S A E.  If t he mali g na nc y has a fatal o utc o me d uri n g t he st u d y or wit hi n t he 
acti ve c ollecti o n peri o d, t he n t he e ve nt lea di n g t o deat h m ust be rec or de d as a n A E o n t he 
C R F, a n d as a n S A E wit h 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) 
Gra de 5 (see t he Secti o n 8. 3 Se verit y  Assess me nt).
8. 2. 4. H os pit aliz ati o n
H os pitalizati o n is defi ne d as a n y i nitial a d missi o n (e ve n less t ha n 2 4 h o urs) i n a h os pital or 
e q ui vale nt healt hcare facilit y, or a n y pr ol o n gati o n of a n e xisti n g a d missi o n.  A d missi o n als o 
i ncl u des tra nsfer wit hi n t he h os pital t o a n ac ute/i nte nsi ve care u nit (e g, fr o m t he ps yc hiatric 
wi n g t o a me dical fl o or, me dical fl o or t o a c or o nar y  care u nit, or ne ur ol o gical fl o or t o a 
t u berc ul osis u nit).  A n e mer gen c y  r o o m visit d oes n ot necessaril y c o nstit ute a h os pitalizati o n; 
h o we ver, t he e ve nt lea di n g t o t he e mer ge nc y  r o o m visit is assesse d f or me dical i m p orta nce.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 4
H os pitalizati o n d oes n ot i ncl u de t he f oll o wi n g:

Re ha bilitati o n facilities;

H os pice facilities;

Res pite care (e g, care gi ver relief);

S kille d n ursi n g facilities;

N ursi n g h o mes;

Sa me -d a y  s ur geries (as o ut patie nt/sa me-d a y /a m b ulat or y pr oce d ures).
H os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n t he a bse nce of a preci pitati n g cli nical 
A E is n ot i n it self a n S A E.  E xa m ples i ncl u de: 

A d missi o n f or treat me nt of a pree xisti n g c o n diti o n n ot ass ociate d wit h t he 
de vel o p me nt of a ne w A E or wit h a w orse ni n g of t he pree xisti n g c o n diti o n (e g, f or 
w or k u p of a persiste nt pretreat me nt la b orat or y  a b n or malit y);

S ocia l a d missi o n (e g, patie nt has n o place t o slee p);

A d mi nistrati ve a d missi o n (e g, f or ye arl y p h ys ical e xa mi nati o n);

Pr ot oc ol -s pecifie d a d missi o n d uri n g a st u dy (e g, f or a pr oce d ure re q uire d b y t he st u d y 
pr ot oc ol);

O pti o nal a d missi o n n ot ass ociate d wit h a prec i pitati n g cli nical A E (e g, f or electi ve 
c os metic s ur ger y);

H os pitalizati o n f or o bser vati o n wit h o ut a me dical A E;

Pre pla n ne d treat me nts or s ur gical pr oce d ures.  T hese s h o ul d be n ote d i n t he baseli ne 
d oc u me ntati o n f or t he e ntire pr ot oc ol a n d/ or f or t he i n di vi d ual patie nt;

A d missi o n e xcl usi vel y  f or t he a d mi nistrati o n of bl o o d pr o d ucts.
Dia g n ostic a n d t hera pe utic n o ni n vasi ve a n d i n vasi ve pr oce d ures, s uc h as s ur ger y , s h o ul d n ot 
be re p orte d as S A Es.  H o we ver, t he me dical c o n diti o n f or w hic h t he pr oce d ure was 
perf or me d s h o ul d be re p orte d if it meets t he defi niti o n of a n S A E.  F or e xa m ple, a n ac ute 
a p pe n dicitis t hat be gi ns d uri n g t he re p orti n g peri o d s h o ul d be re p orte d if t he S A E 
re q uire me nts are met, a n d t he res ulti n g a p pe n dect o m y s h o ul d be rec or de d as treat me nt of t he 
A E.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 5
8. 3. Se verit y Assess me nt
G R A D E
Cli nical Descri pti o n of Se verit y
0  
N o c ha n ge fr o m n or mal or refere nce ra n ge ( T his gra de is n ot i ncl u de d i n t he 
Versi o n 4. 0 3 C T C A E d oc u me nt b ut ma y  be use d i n certai n circ u msta nces.)
1
MI L D a d verse e ve nt
2
M O D E R A T E a d verse e ve nt
3
S E V E R E a d verse e ve nt
4
LI F E -T H R E A T E NI N G c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d
5
D E A T H R E L A T E D T O a d verse e ve nt
N ote t he disti ncti o n bet wee n t he se verit y a n d t he seri o us ness of a n A E.  A se vere e ve nt is n ot necessaril y 
a n S A E.  F or e xa m ple, a hea dac he ma y be se vere (i nterferes si g nifica ntl y wit h t he patie nt’s us ual f u ncti o n) 
b ut w o ul d n ot be classifie d as seri o us u n less it met o ne of t he criteria f or S A Es, liste d a b o ve.
8. 4. S peci al Sit u ati o ns
8. 4. 1. P ote nti al C ases of Dr u g -I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y, b ut a da pt 
are ter me d “a da pt ors.”  I n s o me patie nts, tra nsa mi nase ele vati o ns are a har bi n ger of a m ore 
seri o us p ote ntial o utc o me.  T hese patie nts fail t o a da pt a n d t heref ore are "s usce pti ble" t o 
pr o gressi ve a n d seri o u s li ver i nj ur y, c o m m o nl y referre d t o as dr u g-i n d uce d li ver i nj ur y 
( DI LI).  Patie nts w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 ti mes t he u p per li mit of 
n or mal ( × U L N) s h o ul d be m o nit ore d m ore fre q ue ntl y  t o deter mi ne if t he y are a n “a da pt or” 
or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n as partate a mi n otra nsferase ( A S T) a n d/ or ala ni ne 
a mi n otra nsferase ( A L T) prece de t otal bilir u bi n ( T Bili) ele vati o ns ( > 2 × U L N) b y  se veral 
da y s or wee ks.  T he i ncrease i n T Bili t ypicall y occ urs w hile A S T/ A L T is/are still ele vate d 
a b o ve 3 × U L N (ie, A S T/ A L T a n d T Bili val ues will be ele vate d wit hi n t he sa me la b sa m ple).  
I n rare i nsta nces, by t he ti me T Bili ele vati o ns are detecte d, A S T/ A L T val ues mi g ht ha ve 
decrease d.  T his occ urre nce is still re gar de d as a p ote ntial DI LI.  T heref ore, a b n or mal 
ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T Bili t hat meet t he criteria o utli ne d bel o w 
are c o nsi dere d p ote ntial DI LI (assesse d per H y ’s la w criteria) cases a n d s h o ul d al wa ys be 
c o nsi dere d i m p orta nt me dical e ve n ts, e ve n bef ore all ot her p ossi ble ca uses of li ver i nj ur y 
ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he patie nt’s 
i n di vi d ual baseli ne val ues a n d u n derlyi n g c o n diti o ns.  Patie nts w h o prese nt wit h t he 
f oll o wi n g la b orat or y a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI ( H y’s la w) 
cases t o defi niti vel y deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y  val ues:

Patie nts wit h A S T/ A L T a n d T Bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q uentl y  prese nt wit h A S T O R A LT val ues > 3 × U L N A N D a T Bili val ue 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 6
> 2 × U L N wit h n o e vi de nce of he m ol ys is a n d a n al kali ne p h os p hatase val ue 
< 2 × U L N or n ot a vaila ble;

F or patie nts wit h baseli ne A S T O R A L T O R T Bili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T or A L T 
val ues > 2 ti mes t he baseli ne val ues A N D > 3 × U L N; or > 8 × U L N ( w hic he ver is 
s maller).

Pree xisti n g val ues of T Bili a b o ve t he n or mal ra n ge: T Bili le vel i ncrease d fr o m 
baseli ne val ue b y a n a m o u nt of at least 1 × U L N o r if t he val ue reac hes 
> 3 × U L N ( w hic he ver is s maller).
Rises i n A S T/ A L T a n d T Bili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or. 
T he patie nt s h o ul d ret ur n t o t he i n vesti gat or site a n d b e e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults.  T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt. 
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A LT a n d T Bili , la b orat or y tests s h o ul d 
i ncl u de al b u mi n, creati ne ki nase ( C K), direct a n d i n direct bilir u bi n, ga m ma-gl uta m yl  
tra nsferase ( G G T), pr ot hr o m bi n ti me ( P T)/i nter nati o nal n or malize d rati o (I N R), t otal bile 
aci ds, al kali ne p h os p hatase a n d aceta mi n o p he n dr u g a n d/ or pr otei n a d d uct le vels.  
C o nsi derati o n s h o ul d als o be gi ve n t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n 
a ntic oa g ulate d t u be of bl o o d f or f urt her testi n g, as nee de d, f or f urt her c o nte m p ora ne o us 
a nal ys es at t he ti me of t he rec o g nize d i nitial a b n or ma lities t o deter mi ne eti ol o g y.  A detaile d 
hist or y , i ncl u di n g rele va nt i nf or mati o n, s uc h as re vie w of et ha n ol, aceta mi n o p he n (eit her b y 
itself or as a c of or m ulate d pr o d uct i n prescri pti o n or o ver-t he-c o u nter me dicati o ns) , 
recreati o nal dr u g, s u p ple me nt ( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, 
tra vel hist or y, hist or y of c o ntact wit h a ja u n dice d pers o n, s ur ger y, bl o o d tra nsf usi o n, hist or y 
of li ver or aller gic disease, a n d p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be 
c ollecte d.  F urt her testi n g f or ac ute he patitis A, B, C, D, a n d E i nfecti o n a n d li ver i ma gi n g 
(e g, biliar y tract) ma y be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T Bili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y ’s la w) cases if n o 
ot her reas o n f or t he li ver f u ncti o n tests (L F T ) a b n or malities has yet bee n f o u n d.  S uc h 
p ote nti al DI LI ( H y’s l a w) c ases are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y 
of all t he res ults of t he i n vesti g a ti o ns perf or me d t o deter mi ne eti ol o g y of t he L F T 
a b n or m alities.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 7
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
8. 4. 2. E x p os ure t o t he I n vesti g ati o n al Pr o d uct D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E x p os ure t o t he i n vesti gati o nal pr o d uct u n der st u d y  d uri n g pre g na nc y or breastfee di n g a n d 
occ u pati o nal e x p os ure are re p orta ble t o Pfizer Safet y  wit hi n 2 4 h o urs of i n vesti gat or 
a ware ness.
8. 4. 2. 1. E x p os ure D uri n g Pre g n a nc y ( E D P)
F or b ot h u na p pr o ve d/ u nlice nse d pr o d ucts a n d f or mar kete d pr o d ucts, a n E D P occ urs if:

A fe male bec o mes, or is f o u n d t o be, pre g na nt eit her w hile recei vi n g or ha vi n g bee n 
e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he i n vesti gati o nal 
pr o d uct; or t he fe male bec o mes or is f o u n d t o be pre g na nt after disc o nti n ui n g a n d/ or 
bei n g e x p ose d t o t he i n vesti gati o nal pr o d uct;

A n e xa m ple of e n vir o n me ntal e x p os ure w o ul d be a case i n v ol vi n g direct c o ntact 
wi t h a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a n urse re p orts t hat s he is pre g na nt 
a n d has bee n e x p ose d t o c he m ot hera pe utic pr o d ucts).

A male has bee n e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he 
i n vesti gati o nal pr o d uct pri or t o or aro u n d t he ti me of c o nce pti o n a n d/ or is e x p ose d 
d uri n g his part ner’s pre g na nc y .
If a patie nt or patie nt’s part ner bec o mes or is f o u n d t o be pre g na nt d uri n g t he patie nt’s 
treat me nt wit h t he i n vesti gati o nal pr o d uct, t he i n vesti gat or m ust re p ort t his i nf or mati on t o 
Pfizer Safet y  o n t he C T S A E Re p ort F or m a n d a n E D P s u p ple me ntal f or m, re gar dless of 
w het her a n S A E has occ urre d.  I n a d diti o n, t he i n vesti gat or m ust s u b mit i nf or mati o n 
re gar di n g e n vir o n me ntal e x p os ure t o a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a patie nt 
re p orts t hat s he is pre g na nt a n d has bee n e x p ose d t o a c yt ot o xic pr o d uct b y i n halati o n or 
s pilla ge) t o Pfizer Safet y usi n g t he E D P s u p ple me ntal f or m.  T his m ust be d o ne irres pecti ve 
of w het her a n A E has occ urre d a n d wit hi n 2 4 h o urs of a ware ness of t he e x p os ure.  T he 
i nf or mati o n s u b mitte d s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or 
i nf or mati o n relate d t o ter mi nati o n of pre g na nc y).
F oll o w -u p is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me.  T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w- u p t o t he i nitial E D P s u p ple me ntal f or m.  I n t he case of a li ve birt h, t he str uct ural 
i nte grity of t he ne o nate ca n be assesse d at t he ti me of birt h.  I n t he e ve nt of a ter mi nati o n, t he 
reas o n(s) f or ter mi nati o n s h o ul d be s pecifie d a n d, if cli nicall y p ossi ble, t he str uct ural 
i nte grity of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless 
pre -pr oce d ure test fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs are 
re p orte d).
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 8
If t he o utc o me of t he pre g na nc y meets t he criteria f or a n S A E (ie, ect o pic pre g na nc y, 
s p o nta ne o us a b orti o n, i ntra uteri ne fetal de mise, ne o natal deat h, or c o n ge nital a n o maly [i n a 
li ve-b or n ba b y, a ter mi nate d fet us, a n i ntra uteri ne fetal de mise, or a ne o natal deat h]), t he 
i n vesti gat or s h o ul d f oll o w t he pr oce d ures f or re p orti n g S A Es.
A d diti o nal i nf or mati o n a b o ut pre g na nc y  o utc o mes t hat are re p orte d t o Pfizer Safet y as S A Es 
f oll o ws: 

S p o nta ne o us a b orti o n i ncl u des miscarria ge a n d misse d a b orti o n;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es.  I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he i n vesti gati o nal pr o d uct. 
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he s p o ns or.  F urt her 
f oll o w-u p of birt h o utc o mes will be ha n dle d o n a case- b y -case basis (e g, f oll o w- u p o n 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela y s).  In t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he patie nt wit h t he Pre g na nt Part ner Release of I nf or mati o n F or m 
t o deli ver t o his part ner.  T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u me nts t hat t he 
patie nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his part ner.
8. 4. 2. 2. E x p os ure D uri n g Bre astfee di n g
Sce nar i os of e x p os ure d uri n g breastfee di n g m ust be re p orte d, irres pecti ve of t he prese nce of 
a n ass ociate d S A E, t o Pfizer Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s a ware ness, usi n g t he 
C T S A E Re p ort F or m.  A n e x p os ure d uri n g breastfee di n g re p ort is n ot create d w he n a Pfizer 
dr u g s pecificall y  a p pr o ve d f or use i n breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n 
acc or d wit h a ut h orize d use.  H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h 
a dr u g’s a d mi nistrati o n, t he S A E is re p orte d t o get her wi t h t he e x p os ure d uri n g breastfee di n g.
8. 4. 2. 3. Occ u p ati o n al E x p os ure
A n occ u pati o nal e x p os ure occ urs w he n, d uri n g t he perf or ma nce of j o b d uties, a pers o n 
( w het her a healt hcare pr ofessi o nal or ot her wise) gets i n u n pla n ne d direct c o ntact wit h t he 
pr o d uct, w hic h ma y  or ma y n ot lea d t o t he occ urre nce of a n A E.
A n occ u pati o nal e x p os ure is re p orte d t o Pfizer Safet y  wit hi n 2 4 h o urs of t he i n vesti gat or’s 
a ware ness, usi n g t he C T S A E Re p ort F or m, re gar dless of w het her t here is a n ass ociate d 
S A E.  Si nce t he i nf or mati o n d oes n o t pertai n t o a patie nt e nr olle d i n t he st u d y, t he 
i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he c o m plete d C T S A E Re p ort 
F or m is mai ntai ne d i n t he i n vesti gat or site file.
8. 4. 3. Me dic ati o n Err ors
Ot her e x p os ures t o t he i n vesti gati o nal pr o d uct u n der st u d y m a y occ ur i n cli nical trial setti n gs, 
s uc h as me dicati o n err ors .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 9
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T 
S A E Re p ort F or m t o 
Pfizer S afet y Wit hi n 
2 4 H o urs of A w are ness
Me dicati o n err ors
All (re gar dless of w het her 
ass ociate d wit h a n A E)
O nl y  if ass ociate d wit h 
a n S A E
8. 4. 3. 1. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he i n vesti gati o nal 
pr o d uct b y t he wr o n g patie nt, or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h. 
Me dicati o n err ors i ncl u de :

Me dicati o n err ors i n v ol vi n g patie nt e x p os ure t o t he i n vesti gati o nal pr o d uct;

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he partici pati n g patie nt.
S uc h me dicati o n err ors occ urri n g t o a st u d y pa tie nt are t o be ca pt ure d o n t he me dicati o n err or 
pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
I n t he e ve nt of me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d i m me diatel y.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, t he me dicati o n err or is rec or de d o n t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o n -seri o us, are rec or de d o n a n A E pa ge of t he 
C R F. 
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y  wit hi n 2 4 h o urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E .
8. 4. 4. Peri p her al ne ur o p at h y
Peri p heral ne ur o pat h y is a c o m m o n c o m plicati o n of M M a n d its treat me nt. Peri p heral 
ne ur o pat h y ca n be ca use d b y M M itself, eit her b y t he para ne o pl astic effects of t he 
m o n ocl o nal pr otei n ( p ol y ne ur o pat h y is a n esse ntial feat ure of P O E M S s y n dr o me) or i n t he 
f or m of ra dic ul o pat hy fr o m direct c o m pressi o n, a n d partic ularl y b y certai n t hera pies, 
i ncl u di n g I Mi Ds a n d pr oteas o me i n hi bit ors. S y m pt o ms are us ua ll y sy m metric a n d i ncl u de 
parest hesias, n u m b ness, b ur ni n g se nsati o n a n d m uscle wea k ness; t hese are ge nerall y mil d, 
b ut i n rare cases ca n be disa bli n g or e ve n life -t hreate ni n g. Treat me nt -e mer ge nt peri p heral 
ne ur o pat h y s y m pt o ms are us uall y  sy m metric, distal a n d pr o gressi ve. 4 9 Rece ntl y , peri p heral 
ne ur o pat h y has bee n descri be d f oll o wi n g a d mi nistrati o n of B C M A -directe d bis pecifi c T-cell 
e n ga gers. 5 0  
Peri p heral ne ur o pat h y (i ncl u di n g G B S) is c o nsi dere d a n i m p orta n t p ote ntial ris k of 
elra nata ma b.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 0
W or k -u p f or ne w or w orse ni n g Gra de ≥2 peri p heral ne ur o pat h y  s h o ul d i ncl u de a ne ur ol o g y 
c o ns ult, i ma gi n g (e g, M RI  of t he s pi ne), N C V/ E M Gs, a n d l u m bar p u nct ure t o assess C S F.  I n 
c o ns ultati o n wit h a ne ur ol o gist, a p pr o priate t hera p y f or peri p heral ne ur o pat h y (e g, ster oi ds 
a n d/ or I V i m m u n o gl o b uli n) s h o ul d be c o nsi dere d.
Cl osel y  m o nit or partici pa nts f or si g ns a n d sy m pt o ms of ne ur o pat h y  f oll o wi n g i nfecti o ns or 
f oll o wi n g t he a d mi nistrati o n of a ny vacci ne. 
F or rec o m me n de d d ose m o d ificati o ns f or peri p heral ne ur o pat h y (all ca usalit y), refer t o 
Ta ble 5 .
9. D A T A A N A L Y SI S/ S T A TI S TI C A L M E T H O D S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c ollecte d i n t his st u d y 
is o utli ne d here a n d f urt her detaile d i n a statistical a nalys is pla n ( S A P), w hic h will be 
mai ntai ne d b y  t he s p o ns or.  T he S A P ma y  m o dif y w hat is o utli ne d i n t he pr ot oc ol w here 
a p pr o priate; h o we ver, a n y maj or m o dificati o ns of t he pri mar y  e n d p oi nt defi niti o ns or t heir
a nal ys es will als o be reflecte d i n a pr ot oc ol a me n d me nt.
9. 1. A n al ysis S ets 
Treate d patie nt safety a nal ysis set:
T he safet y a nal ys is set i ncl u des all e nr olle d patie nts w h o recei ve at least o ne d ose of 
st u d y treat me nt.
F ull a nal ys is set:
T he f ull a nal ys is set i ncl u des all e nr olle d patie nts.
Per- pr ot oc ol a nal ysis set (e val ua ble f or M T D/ M A D):
T he per -pr ot oc ol a nal y sis set i ncl u des all e nr olle d patie nts w h o recei ve at least o ne 
d ose of st u d y  treat me nt a n d w h o d o n ot ha ve maj or treat me nt de viati o ns d uri n g D L T 
o bser vati o n peri o d.  Patie nts wit h maj or treat me nt de viati o ns d uri n g D L T o bser vati o n 
peri o d are n ot e val ua ble f or t he M T D / M A D assess me nt a n d will be re place d as nee de d 
t o per mit M T D/ M A D esti mati o n. 
P F - 0 6 8 6 3 1 3 5 P K a nal ys is sets:
T he P K para meter a nal ys is p o p ulati o n is defi ne d as all e nr olle d patie nts treate d w h o 
ha ve s ufficie nt i nf or mati o n t o esti mate at least 1 of t he P K para meters of i nterest.
T he P K c o nce ntrati o n p o p ulati o n is defi ne d as all e nr olle d patie nts w h o are t reate d 
wit h P F -0 6 8 6 3 1 3 5, ha ve n o pr ot oc ol de viati o ns affecti n g t he P K assess me nt, a n d ha ve 
at least 1 p ost-d ose c o nce ntrati o n meas ure me nt.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 1
Bi o mar ker a nal ys is set(s):
T he bi o mar ker a nal ys is set i ncl u des all e nr olle d patie nts wit h at least o ne of t he 
p har mac o d y n a mic/ bi o mar ker para meters e val uate d at pre- or p ost -d ose.
Ef ficac y mo difie d i nte nt t o treat (I T T) a nal ys is set:
I ncl u des all Patie nts w h o ha ve recei ve d at least o ne d ose of st u d y  treat me nt.
Efficac y  Per-Pr ot oc ol a nal y sis set:
T he efficac y  per -pr ot oc ol a nal ys is set i ncl u des all treate d patie nts w h o d o n ot ha ve 
maj or treat me nt de viati o ns a n d are e val ua ble at least f or t he first t u m or assess me nt. 
P F -0 6 8 6 3 1 3 5 I m m u n o ge nicit y a nal ysis set:
T he i m m u n o ge nicit y a nal y sis set is defi ne d as patie nts w h o recei ve at least 1 d ose of 
st u d y treat me nt a n d ha ve at least 1 A D A sa m ple c ollecte d.
9. 2. St atistic al Met h o ds a n d Pr o perties
9. 2. 1. St atistic al Met h o ds f or D ose Esc al ati o n/ De- Esc al ati o n
T his st u d y  has bee n desi g ne d t o esta blis h t he Ma xi m u m T olerate d D ose ( M T D)/ M A D.  T he 
M T D is
defi ne d as t he d ose t hat y iel ds a p pr o xi matel y 2 5% pr o ba bilit y  of D L T a n d c o nsi ders 
e q ui vale nt d oses t hat yi el d pr o ba bilit y of D L T i n t he i nter val ( E q ui vale nce I nter val) 2 0 % t o 
3 0 %.  T he 2 5 % tar get was c h ose n base d o n safet y c o nsi derati o ns a n d is c o nsi dere d 
a p pr o priate base d o n si m ulati o ns a n d e x pert i n p ut. 
T he m T PI  desi g n5 1 -5 3 uses a B a y esia n statistics fra me w or k a n d a beta/ bi n o mial hierarc hical 
m o del t o c o m p ute t he p osteri or pr o ba bilit y  of 3 d osi n g i nter vals t hat reflect t he relati ve 
differe nce bet wee n t he t o xicit y  rate of eac h d ose le vel t o t he tar get rate (tar get pr o ba bilit y 
[ p T] = 0. 2 5).  If t he t o xicit y rate of t he c urre ntly use d d ose le vel is far s maller t ha n p T, t he 
m T PI  will rec o m me n d escalati n g t he d ose le vel; if it is cl ose t o p T, t he m T PI will 
rec o m me n d c o nti n ui n g at t he c urre nt d ose; if it is far greater t ha n p T, t he m T PI will 
rec o m me n d de-escalati n g t he d ose le vel.  T hese r ules are c o nce pt uall y  si milar t o t h ose use d 
b y  t he 3 + 3 desi g n, e xce pt t he decisi o ns of a n m T PI desi g n are base d o n p osteri or 
pr o ba bilities calc ulate d u n der a c o here nt pr o ba bilit y  m o del. 
Bei n g a m o del -base d desi g n, m T PI a ut o maticall y a n d a p pr o priatel y tail ors d ose -escalati o n 
a n d de-escalati o n decisi o ns f or differe nt st u dies wit h differe nt t o xicit y  para meters.  M ore 
i m p orta ntl y, all t he d ose-escalati o n decisi o ns f or a gi ve n st u d y ca n be pre -calc ulate d u n der 
t he m T PI desi g n a n d prese nte d i n a t w o-w a y  ta ble (see A p pe n di x 8 ).  T h us, c o m pare d t o 
ot her a d va nce d m o del -base d desi g ns p u blis he d i n t he literat ure, t he m T PI desi g n is 
l o gisticall y less c o m plicate d a n d easier t o i m ple me nt. 
Decisi o n r ules are base d o n calc ulati n g u nit pr o ba bilit y  mass ( U P M) of 3 d osi n g i nter vals 
c orres p o n di n g t o u n der, pr o per, a n d o ver d osi n g i n ter ms of t o xicit y.  S pecificall y , t he 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 2
u n der d osi n g i nter val is defi ne d as ( 0; p T -e1), t he o ver-d osi n g i nter val ( p T +e 2, 1), a n d t he 
pr o per -d osi n g i nter val ( p T - e1, p T + e2), w here e1 a n d e 2 are s mall fracti o ns.  In st u d y , e1 a n d 
e 2 are selecte d as 0. 0 5, t h eref ore, t he tar get i nter val f or t he D L T rate is ( 0. 2 0, 0. 3 0 ).  T he 
2 5 % tar get, t he s y m metr y  of t he E q ui vale nce I nter val a n d its u p per li mit were c h ose n base d 
o n safet y c o nsi derati o ns.  T he pri or distri b uti o n of D L T is set as a beta ( 0. 5, 0. 5), a n d t he 
t hres h ol d pr o ba bilit y f or early ter mi nati o n a n d d ose e xcl usi o n is set t o 0. 9 5. 
T he 3 d osi n g i nter vals are ass ociate d wit h 3 differe nt d ose -escalati o n decisi o ns.  T he 
u n der d osi n g i nter val c orres p o n ds t o a d ose -escalati o n ( E), o ver d osi n g c orres p o n ds t o a d ose 
de-escalati o n ( D), a n d pr o per d osi n g c orres p o n ds t o re mai ni n g at t he c urre nt d ose ( R).  Gi ve n 
a d osi n g i nter val a n d a pr o ba bilit y  distri b uti o n, t he u nit pr o ba bilit y mass ( U P M) of t hat 
d osi n g i nter val is defi ne d as t he pr o ba bilit y of a patie nt bel o n gi n g t o t hat d osi n g i nter val 
di vi de d b y  t he le n gt h of t he d osi n g i nter val.  E ve n t h o u g h t he m T PI ma y select a n 
M T D / M A D wit h a n i nci de nce of D L Ts t hat is hi g her t ha n 3 0 %, d oses wit h a n i nci de nce of 
D L T > 3 0 % (e g, 4 o ut of 9) ca n n ot be declare d as t he M T D / M A D. 
If t he M T D is n ot reac he d, t he n t he M A D will be ma xi m u m d ose t hat is e val uate d i n t he 
st u d y.
9. 2. 2. St atistic al Met h o d f or Esti m ati n g t he M T D / M A D
As pre vi o usl y  descri be d, t he esti mate d M T D is t he hi g hest teste d d ose le vel wit h D LT rate
0. 3 0 i n at least 6 D L T -e val ua ble patie nts (ie, per pr ot oc ol a nal ys is set).  It is ass u me d t hat 
hi g her d oses res ult i n hi g her t o xicit y  rates.  B ut, d ue t o t he relati vely l o w n u m ber of patie nts 
t hat ma y be p ote ntiall y all ocate d t o a ny d ose, t his ass u m pti o n ma y  be vi olate d.
T o est i mate t he M T D/ M A D the st u d y  will c o nti n ue accr ui n g u ntil o ne of t he t hree st o p pi n g 
c o n diti o ns bel o w is tri g gere d:
1.
T he ma xi m u m sa m ple size has bee n ac hie ve d.
2.
M T D / M A D has bee n i de ntifie d wit h s ufficie nt acc urac y : 6 t o 1 6 patie nts ha ve bee n 
acc u m ulate d o n a dose t hat is c urre ntl y esti mate d t o be t he M T D / M A D; or
3.
All d oses e x pl ore d a p pear t o be o verl y t o xic a n d t he M T D / M A D ca n n ot be 
deter mi ne d. 
Cli nical j u d g me nt will be e xercise d i n ta ki n g f or war d d oses t o t he e x pa nsi o n c o h ort(s), i n 
case n o clear c h oice e xists bet wee n m ore t ha n 1 c o m peti n g M T D/ M A D.  T his decisi o n will 
be base d u p o n t he c o m bi nati o n of data relate d t o safet y, a nti -t u m or acti vit y, a n d cli nical 
j u d g me nt of t he i n vesti gat ors a n d t he s p o ns or.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 3
9. 3. S a m ple Size Deter mi n ati o n
D ue t o t he d y na mic nat ure of t he Ba yesia n all ocati o n pr oce d ure, t he sa m ple size of t he m T PI  
a p pr oac h ca n n ot be deter mi ne d i n a d va nce.  It is esti mate d a p pr o xi matel y 1 0 0 D L T e val ua ble 
patie nts ma y  be e nr olle d i n t he d ose escalati o n sta ge i n or der t o ha ve a relia ble a n d acc urate 
esti mate of t he M T D/ M A D a n d R P 2 D .  At least 6 a n d u p t o 16 patie nts s h o ul d be e nr olle d at 
a d ose le vel t hat is pre dicte d t o be t he M T D / M A D as per t he m T PI met h o d. H o we ver, 
a d diti o nal c o h orts bel o w M T D/ M A D ma y  als o be c o nsi dere d f or e nr oll me nt u p t o 
a p pr o xi matel y 6- 1 2 patie nts f or t he p ur p ose of c o nfir mi n g t he R P 2 D.
It is a ntici pate d t hat Parts 1 C, 1 D a n d 1 E will eac h ha ve a p pr o xi matel y 9-1 6 patie nts 
e nr olle d. H o we ver, t he t otal n u m ber of patie nts will de pe n d o n t he n u m ber of d ose le vels 
nee de d t o deter mi ne t he M T D / M A D f or eac h c o m bi nati o n a n d n u m ber of patie nts e val ua ble 
f or D L T at eac h c o h ort.
S u bse q ue nt patie nts will e nter a n e x pa nsi o n c o m p o ne nt, Part 2, ai me d at e val uati n g safet y 
a n d a nti -m y el o ma acti vit y of P F-0 6 8 6 3 1 3 5 at t he R P 2 D i n m o n ot hera p y (Part 2 A ) a n d i n 
c o m bi nati o n wit h le nali d o mi de , p o mali do mi de , or de xa met has o ne (Parts 2 C, 2 D a n d 2E,
c orres p o n di n gl y) .  A p pr o xi matel y 2 0 patie nts are e x pecte d t o be e nr olle d i nt o eac h of 
Parts 2 A, 2 C, 2 D a n d 2 E, b ut e nr oll me nt of patie nts ma y be disc o nti n ue d earlier if mi ni mal 
or n o a nti -t u m or acti vit y is o bser ve d.
C o h ort sa m ple size is deter mi ne d as f oll o ws.
Part 2 A - m o n ot hera p y : Ass u mi n g a n o n-i nf or mati ve pri or (ie, Jeffre y’s pri or) if 1 2 o ut of 
2 0 partici pa nts ha ve t u m or res p o nse, t his w o ul d pre dict a p osteri or pr o ba bilit y 
( Beta Bi n o mial) e q ual t o 0. 8 1 4 t hat tr ue res p o nse rate is n ot i nferior t o tar get res p o nse rate of 
5 0 % a n d a p oste ri or pr o ba bilit y e q ual t o 0. 0 0 3 t hat tr ue res p o nse rate is i nferi or t o 
be nc h mar k rat e of 3 0 %.  
Part s 2 C, 2 D , a n d 2 E – c o m bi nati o n wit h le nali d o mi de, p o mali d o mi de, a n d de xa met has o ne
res pecti vely : Ass u mi n g a n o n-i nf or mati ve pri or (ie, Jeffre y’s pri or) if 1 4 o ut of 2 0
partici pa nts ha ve t u m or res p o nse, t his w o ul d pre dict a p osteri or pr o ba bil it y ( Beta Bi n o mial) 
e q ual t o 0. 8 1 8 t hat tr ue res p o nse rate is n ot i nferi or t o t he tar get res p o nse rate of 6 0 % a n d a 
p oste ri or pr o ba bilit y e q ual t o 0. 0 0 0 1 t hat tr ue res p o nse rate is i nferi or t o be nc h mar k rate of 
3 0 %.
9. 4. Effic ac y A n al ysis
I n t his First i n Patie nt st u d y , a nti-m y el o ma acti vit y is a sec o n dar y o bjecti ve i n Part 1 d ose 
escalati o n.  O bjecti ve res p o nse rate ( OR R) a n d d urati o n of res p o nse ( D OR) are pri mar y 
o bjecti ves i n Part 2 d ose e x pa nsi o n .  Ot her efficac y e n d p oi nts are sec o n dar y o bjecti ves i n 
Pa rt 2.  T he a nal ys is p o p ulati o n is defi ne d i n Secti o n 9. 1 A nal y sis Sets.
I ma gi n g st u dies, rele va nt la b orat or y assess me nts, a n d b o ne marr o w pat h ol o g y  ma y be 
c ollecte d t o s u p p ort i n de pe n de nt ce ntral re vie w f or efficac y e n d p oi nts.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 4
Disease res p o nse will be prese nte d i n t he f or m of patie nt data listi n gs t hat i ncl u de, b ut are n ot 
li mite d t o starti n g d ose, disease res p o nse at eac h visit, a n d best o verall res p o nse.  I n a d diti o n, 
pr o gressi o n date, deat h date, date of first res p o nse a n d last disease assess me nt date, a n d date 
of last c o ntact will be liste d.
Best o ver all res p o nse ( B O R) will be assesse d base d o n re p o rte d o verall res p o nses at 
differe nt e val uati o n ti me p oi nts usi n g I M W G res p o nse criteria (see A p pe n di x 2 ).4 ,5

C o m plete Res p o nse will e nc o m pass c o nfir me d stri n ge nt C o m plete Res p o nse (s C R) 
a n d C o m plete Res p o nse ( C R).

O ver all Res p o nse ( O R) will e nc o m pass c o nfir me d s C R, C R, V G P R ( ver y g o o d 
partial res p o nse ) a n d partial res p o nse ( P R ).

Cli nic al Be nefit ( C B) will e nc o m pass c o nfir me d s C R, C R, VG P R, P R a n d M R.
Pr o gressi o n -free s ur vi v al ( P F S) is t he ti me fr o m start date of st u d y  treat me nt t o date of 
first d oc u me ntati o n of pr o gressi o n, or deat h d ue t o a n y ca use.  Pr o gressi o n is defi ne d as t he 
a p peara nce of l ocal, re gi o nal or dista nt disease of t he sa me t ype after c o m plete res p o nse or 
pr o gressi o n of pre -e xisti n g lesi o ns.  It d oes n ot i ncl u de sec o n d pri mar y  mali g na ncies of 
u nrelate d t y pes. 
O ver all s ur vi v al ( O S) is t he ti me fr o m start date of st u d y  treat me nt t o date of deat h d ue t o 
a n y ca use.
D ur ati o n of C o m plete Re missi o n is defi ne d f or patie nts wit h c o nfir me d c o m plete res p o nse 
(s C R, C R) as t he ti me fr o m t he first d oc u me ntati o n of c o m plete res p o nse t o t he first 
d oc u me ntati o n of o bjecti ve t u m or pr o gressi o n or t o deat h d ue t o a n y ca use, w hic he ve r occ urs 
first.
D ur ati o n of Res p o nse ( D O R) is defi ne d f or patie nts wit h c o nfir me d o bjecti ve res p o nse (as 
defi ne d a b o ve i n o verall res p o nse) as t he ti me fr o m t he first d oc u me ntati o n of o bjecti ve 
t u m or res p o nse t o t he first d oc u me ntati o n of o bjecti ve t u m or pr o gressi o n or t o deat h d ue t o 
a n y ca use, w hic he ver occ urs first.
D ur ati o n of St a ble Dise ase ( D O S D) is defi ne d f or patie nts wit h c o nfir me d sta ble disease as 
t he ti me fr o m t he first d oc u me ntati o n of o bjecti ve sta ble disease t o t he first d oc u me ntati o n of 
o bje cti ve t u m or pr o gressi o n or t o deat h d ue t o a n y ca use, w hic he ver occ urs first.
Ti me t o Res p o nse ( T T R) is defi ne d f or patie nts wit h c o nfir me d o bjecti ve res p o nse (as 
defi ne d a b o ve i n o verall res p o nse) as t he ti me fr o m t he first d oc u me ntati o n of o bjecti ve 
t u m or res p o nse.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 5
9. 5. A n al ysis of P h ar m ac o ki netics a n d P h ar m ac o d y n a mics 
9. 5. 1. P F -0 6 8 6 3 1 3 5 P K A n al ysis
T he c o nce ntrati o ns of P F -0 6 8 6 3 1 3 5 will be s u m marize d b y  descri pti ve statistics ( n, mea n, 
sta n dar d de viati o n, c oefficie nt of variati o n, me dia n, mi ni m u m ma xi m u m, a n d ge o metric 
mea n) b y d osi n g c o h ort, c ycle, a n d n o mi nal ti me.   I ndi vi d ual patie nt a n d me dia n pr ofiles of 
t he c o nce ntrati o n-ti me data will be pl otte d b y d osi n g c o h ort a n d c ycle usi n g n o mi nal ti mes.   
Me dia n pr ofiles will be prese nte d o n b ot h li near-li near a n d l o g -li near scales.
F or patie nts fr o m Parts 1, 1. 1 , 1 C, 1 D, a n d 1 E, i n di vi d ual c o nce ntrati o n-ti me data of 
P F -0 6 8 6 3 1 3 5 f oll o wi n g t he C y cle 0 Da y 1 d ose (o nl y  f or patie nts recei v i n g pri mi n g d ose),
C y cle 1 Da y 1 d ose a n d C y cle 2 Da y 1 d ose (I V o nl y) will be a nal yz e d se paratel y usi n g 
n o n- c o m part me ntal a nal ysis t o esti mate t he P K para meters.  T he P K para meters esti mate d 
will i ncl u de C ma x , ti me t o ma xi m u m c o nce ntrati o n ( Tma x ), a n d c o nce ntrati o n vers us ti me 
c ur ve (A U C last).  If data per mit or if c o nsi dere d a p pr o priate, mi ni m u m c o nce ntrati o n ( C mi n ), 
ter mi nal eli mi nati o n half-life (t1/ 2), cleara nce (C L or C L / F), vol u me of distri b uti o n at stea d y 
state (V ss or V ss/ F), a n d acc u m ulati o n rati o ( Rac) will be als o esti mate d f or C ycle 1 Da y 1 a n d 
C y cle 2 Da y 1.  Act ual sa m ple c ollecti o n ti mes will be use d f or t he para meter calc ulati o ns.   
T he P K para meters will be s u m marize d descri pti vel y  b y d osi n g c o h ort, a n d c ycle.
F or patie nts e nr olle d i n Part s 2 A, 2 C , 2 D, a n d 2 E of t he st u d y , tr o u g h P F-0 6 8 6 3 1 3 5
c o nce ntrati o ns w ill be s u m marize d descri pti vel y b y c ycle.
9. 5. 2. Le n ali d o mi de , P o m ali d o mi de , a n d De x a met h as o ne P h ar m ac o ki netic A n al ysis
( P arts 1 C a n d 2 C, P arts 1 D a n d 2 D , P arts 1 E a n d 2 E as a p pr o pri ate )
T he c o nce ntrati o n -ti me data of le nali d o mi de, p o mali d o mi de, a n d de xa met has o ne will be 
s u m marize d b y descri pti ve statistics ( n, mea n, sta n dar d de viati o n, c oefficie nt of variati o n, 
me dia n, mi ni m u m, ma xi m u m, a n d ge o metric mea n) acc or di n g t o d osi n g c o h ort a n d ti me f or 
eac h part of t he st u d y.  
9. 5. 3. P o p ul ati o n P h ar m ac o ki netic A n al ysis of P h a r m ac o ki netics 
( P K)/ P h ar m ac o d y n a mic M o deli n g
P K a n d p har mac o d y na mic data fr o m t his st u d y  ma y be a nalyz e d usi n g m o deli n g a p pr oac hes 
a n d ma y als o be p o ole d wit h data fr o m ot her st u dies t o i n vesti gate a n y ass ociati o n bet wee n 
P F -0 6 8 6 3 1 3 5 e x p os ure a n d bi o mar kers or si g nifica nt safet y a n d/ or efficac y e n d p oi nts.  T he 
res ults of t hese a nal yses, if perf or me d, ma y be re p orte d se parately fr o m t he cli nical st u d y 
re p ort.
9. 5. 4. A n al ysis of I m m u n o ge nicit y
F or t he i m m u n o ge nicit y data, t he perce nta ge of patie nts wit h A D A will be s u m marize d.   
Listi n gs a n d s u m mar y  ta b ulati o ns of t he A D A data at baseli ne a n d p ost-ra n d o mizati o n will 
be ge nerate d.   Sa m ples ma y  als o be a nalyz e d f or t he prese nce of N A b, a n d a n y  data will be 
si milarl y s u m marize d.  F or patie nts wit h p ositi ve A D A or N A b, t he ma g nit u de (titer), ti me of 
o nset, a n d d urati o n of A D A or N A b res p o nse will als o be descri be d, if data per mit.   T he 
p o te ntial i m pact of i m m u n o ge nicit y o n P K a n d cli nical res p o nse i ncl u di n g p har mac o dy n a mic 
mar kers, safet y/ t olera bilit y a n d efficac y of A D A will be e x pl ore d, if warra nte d b y t he data.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 6
9. 5. 5. A n al ysis of P h ar m ac o d y n a mics
P har mac o d y na mic e n d p oi nts bei n g meas ure d i ncl u de cell ular B C M A e x pressi o n, plas ma
s ol u ble B C M A, e n d o ge n o us patie nt i m m u ne cell p o p ulati o ns, peri p heral bl o o d ge ne 
e x pressi o n pr ofiles a n d T- cell rece pt or ( T C R) cl o nalit y.  T hese e n d p oi nts will be s u bject t o 
a nal ys is b y s u m mar y statistics of val ues at baseli ne as well as c ha n ge fr o m baseli ne o n st u d y.  
Ge ne e x pressi o n pr ofili n g a n d T C R cl o nal a nal ys is will als o be s u bject t o s pecialize d, 
fit-f or-p ur p ose a nal y sis al g orit h ms use d t o i nterr o gate hi g h di me nsi o nal data sets.
9. 5. 6. A n al ysis of Bi o m ar ker E n d p oi nts
Data fr o m bi o mar ker assa y s ma y be a nal yze d usi n g gra p hical met h o ds a n d descri pti ve 
statistics s uc h as li near re gressi o n, t-test, a n d a nalysis o f varia nce.  T he statistical a p pr oac h 
will e xa mi ne c orrelati o ns of bi o mar ker res ults wit h P K para meters a n d meas ures of 
a nti-ca ncer efficac y.
Res ults fr o m tertiar y /e x pl orat or y a nalys es will be re p orte d i n t he C S R w here p ossi ble.  
H o we ver, gi ve n t he e x pl ora t or y nat ure of e x pl orat or y o bjecti ves a n d e n d p oi nts, t he a nal yses 
ma y  n ot be c o m plete at t he ti me of t he C S R.  Res ults fr o m e x pl orat or y a nal yses t hat are n ot 
i ncl u de d i n t he C S R will be s hare d wit h t he scie ntific c o m m u nit y t hr o u g h p u blicati o n at a 
scie ntific c o nfere nce a n d/ or i n a peer-re vie we d scie ntific j o ur nal. Detaile d a nal ys is f or t he 
tertiar y a n d e x pl orat or y e n d p oi nts will be s pecifie d i n a se parate tec h nical d oc u me nt o utsi de 
of t he S A P.
9. 6. S afet y A n al ysis
S u m maries a n d a nal ys es of safet y para meters will i ncl u de all patie nts i n t he Safet y  A nalys is 
Set.  F or patie nts w h o u n der g o i ntra -patie nt d ose escalati o n, safet y a nal ys is of t heir i nitial 
assi g ne d d ose will be ce ns ore d at ti me of i ntra -patie nt d ose escalati o n ( or mai nte na nce d ose 
escalati o n f or Part 1. 1 ).  T his will all o w at least 6 0 da y s of safet y a nalys is f or all patie nts at 
t heir i nitial assi g ne d d ose le vels.
9. 6. 1. A n al ysis of t he Pri m ar y E n d p oi nt f or P art 1
D L T is t he pri mar y  e n d p oi nt of t he d ose escalati o n c o m p o ne nt of t he st u d y.  T he occ urre nce 
of D L Ts o bser ve d i n t he d osi n g c o h orts is use d t o esti mate t he M T D / M A D as descri be d i n 
t he St u d y Desi g n Secti o n 3 .  A d verse E ve nts c o nstit uti n g D L Ts will be liste d per d ose le vel.
9. 6. 2. A n al ysis of Sec o n d ar y S afet y E n d p oi nts
9. 6. 2. 1. A d verse E ve nts
A Es (e xce pt C R S) will be gra de d b y t he i n vesti gat or acc or di n g t o t he C T C A E versi o n 4. 0 3 
a n d c o de d 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).  C R S will be 
assesse d acc or di n g t o t he gra di n g descri be d b y Lee et al. ( 2 0 1 4 a n d 2 0 1 9 ,2 ,3 See 
A p pe n di x 5 )a n d c o de d usi n g Me d D R A.  T he se verit y  of I C A N S s h o ul d be gra de d acc or di n g 
t o t he A S T C T c o nse ns us criteria3 (A p pe n di x 5 ).  T he f oc us of A E s u m maries will be o n 
Treat me nt E mer ge nt A d verse E ve nts, t h ose wit h i nitial o nset or i ncreasi n g i n se verit y  after 
t he first d ose of st u dy treat me nt.  T he n u m ber a n d perce nta ge of patie nts w h o e x perie nce d 
a n y A E, S A E, treat me nt relate d A E, a nd treat me nt relate d S A E will be s u m marize d 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 7
acc or di n g t o w orst t o xicit y  gra des.  T he s u m maries will prese nt A Es b ot h o n t he e ntire st u d y 
peri o d a n d b y c ycl e ( C yc le 1 a n d C y cles be yo n d 1). 
9. 6. 2. 2. L a b or at or y Test A b n or m alities
T he n u m ber a n d perce nta ge of patie nts w h o e x perie nce d la b orat or y  test a b n or malities will be 
s u m marize d acc or di n g t o w orst t o xicit y gra de o bser ve d f or eac h la b orat or y assa y.  T he 
a nal ys es will s u m marize la b orat or y  tests b ot h o n t he e ntire st u d y peri o d a n d b y c ycle 
( C ycle 1 a n d C ycles be y o n d 1).   S hift ta bles will be pr o vi de d t o e xa mi ne t he distri b uti o n of 
la b orat or y t o xicities.
F or la b orat or y  tests wit h o ut C T C A E gra de defi niti o ns, res ults will be cate g orize d as n or mal, 
a b n or mal, or n ot d o ne. 
9. 6. 2. 3. Electr oc ar di o gr a m
T he a nal ys is of E C G res ults will be base d o n patie nts i n t he safet y a nal ysis set wit h baseli ne 
(sa m ple ta ke n pri or t o first d osi n g) a n d o n-treat me nt E C G data.  E C G meas ure me nts (a n 
a vera ge of t he tri plicate meas ure me nts) will be use d f or t he statistical a nal ysis a n d all data 
prese ntati o ns. A n y data o btai ne d fr o m E C Gs re peate d f or safet y reas o ns after t he n o mi nal 
ti me-p oi nts will n ot be a vera ge d al o n g wit h t he prece di n g tri plicates.  I nter val meas ure me nts 
fr o m re peate d E C Gs will be i ncl u de d i n t he o utlier a nalys is (cate g orical a nal ysis) as 
in di vi d ual val ues o btai ne d at u nsc he d ule d ti me p oi nts.
Q T ( ti me bet wee n t he start of t he Q wa ve a n d t he e n d of t he T wa ve) i nter vals will be 
c orrecte d f or heart rate ( H R , Q Tc) usi n g sta n dar d c orrec ti o n fact ors (ie, Fri dericia’s [defa ult 
c orrecti o n], Bazett’s, a n d p ossi bl y a st u d y -s pecific fact or, as a p pr o priate).  Data will be 
s u m marize d a n d liste d f or Q T, H R, res p o nse rate ( R R), partial res p o nse ( P R), Q R S, Q Tc F 
(a n d ot her c orrecti o n fact ors, e g, c orrecte d Q T i nter val b y  Bazett (Q Tc B ) as a p pr o priate), a n d 
b y  st u d y ar m a n d d ose.  I n di vi d ual Q T (all e val uate d c orrecti o ns) i nter vals will be liste d b y 
st u d y ar m, ti me a n d d ose.  T he m ost a p pr o priate c orrecti o n fact or will be selecte d a n d use d 
f or t he f oll o wi n g a nalys es of ce ntral te n de nc y an d o utliers a n d use d f or t he st u d y  
c o ncl usi o ns.  Descri pti ve statistics ( n, mea n, me dia n, sta n dar d de viati o n, mi ni m u m, a n d 
ma xi m u m) will be use d t o s u m marize t he a bs ol ute c orrecte d Q T i nter val a n d c ha n ges fr o m 
baseli ne i n c orrecte d Q T after treat me nt b y st u d y  ar m, d ose a n d ti me p oi nt.  F or eac h patie nt 
a n d b y treat me nt, t he ma xi m u m c ha n ge fr o m baseli ne will be calc ulate d as well as t he 
ma xi m u m p ost -baseli ne i nter val acr oss ti me -p oi nts.  Cate g orical a nal y sis will be c o n d ucte d 
f or t he ma xi m u m c ha n ge fr o m baseli ne i n c orrecte d Q T a n d t he ma xi m u m p ost-baseli ne Q T 
i nter val. 
S hift ta bles will be pr o vi de d f or baseli ne vs w orst o n treat me nt c orrecte d Q T ( o ne or m ore 
c orrecti o n met h o ds will be use d) usi n g ma xi m u m C T C A E Gra de.  S hift ta bles will als o be 
pr o vi de d f or E C G a b n or malit y  at baseli ne vs. o n treat me nt ( yes, n o, n ot d o ne: ( n, %)).  
Patie nts e x perie nci n g cli nicall y  rele va nt m or p h ol o gical E C G c ha n ges will be s u m marize d 
(i ncl u di n g fre q ue nc y a n d perce nta ge).
T he effect of dr u g c o nce ntrati o ns o n c orrecte d Q T c ha n ge fr o m baseli ne will be e x pl ore d 
gra p hicall y.  A d diti o nal c o nce ntrati o n -c orrecte d Q T a nal ys es ma y be perf or me d.  Data ma y 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 8
be p o ole d wit h ot her st u d y res ults a n d/ or e x pl ore d f urt her wit h P K/ p har mac o d y na mic
m o dels.
9. 7. I nteri m A n al ysis
N o f or mal i nteri m a nal ys is will be perf or me d.  Patie nts’ safety a n d disease pr o gressi o n will 
be m o nit ore d c o nti n u o usl y. 
T he criteria bel o w g ui di n g i nterr u pti o n of st u d y treat me nt are base d o n Ba yesia n p osteri or 
pr o ba bilities usi n g a n o n -i nf or mati ve Beta ( 0. 5, 0. 5) pri or distri b uti o n. T he pr o ba bilities will 
be calc ulate d f or t otal n u m ber of  partici pa nts assi g ne d or tra nsiti o ne d t o m o n ot hera p y wit h 
elra nata ma b acr oss its efficaci o us d ose ra n ge, i ncl u di n g Part 1 S C d oses ≥2 1 5 u g/ k g, Part 
1. 1, Part 2 A, a n d a n y patie nt fr o m Part 1 D tra nsiti o ne d t o m o n ot hera p y. 
If t he n u m ber of e val ua ble partici pa nts o bser ve d t o ha ve treat me nt-relate d Gra de 3-4 G B S
(i ncl u di n g v aria nts) res ults i n a p osteri or pr o ba bilit y t hat t he tr ue rate of s uc h e ve nts 
e xcee di n g 3 % is ≥0. 8 0, st u d y  treat me nt will be i nterr u pte d f or all acti ve partici pa nts pe n di n g 
re vie w of all safety i nf or mati o n . F or e xa m ple, if t he t otal n u m ber of  par tici pa nts e nr olle d i n 
t he c o h orts descri be d a b o ve is 6 2, o bser vi n g 3 or m ore partici pa nts wit h treat me nt -relate d 
Gra de 3 -4 G B S (incl u di n g v aria nts) will res ult i n t he i nterr u pti o n of st u d y  treat me nt f or all 
acti ve partici pa nts . 
If t he n u m ber of e val ua ble partici pa nts o bser ve d t o ha ve treat me nt-relate d Gra de 4 se ns or y 
ne ur o pat h y, Gra de 4 i m m u ne -relate d ne ur ol o gic A Es (excl u di n g I C A N S), or Gra de 3 - 4 
peri p heral m ot or n e ur o pat h y res ults i n a p osteri or pr o ba bilit y t hat t he tr ue rate of s uc h e ve nts 
e xcee di n g 1 0 % is ≥0. 8 0, st u d y  treat me nt will be i nterr u pte d f or all acti ve partici pa nts
pe n di n g re vie w of all safet y i nf or mati o n.  F or e xa m ple, if t he t otal n u m ber of  partici pa nts
e nr olle d i n t he c o h orts descri be d a b o ve is 6 2, o bser vi n g 9 or m ore partici pa nts wit h 
treat me nt-relate d Gra de 4 se ns or y ne ur o pat h y, Gra de 4 i m m u ne-relate d ne ur ol o gic A Es
(excl u di n g I C A N S), or Gra de 3 - 4 peri p heral m ot or n e ur o pat h y will res ult i n t he i nterr u pti o n 
of st u d y  treat me nt f or all acti ve partici pa nts . 
If a partici pa nt e nr olle d o n t he c o m bi nati o n wit h le n ali do mi de ar m de vel o ps ≥Gra de 3 
peri p heral m ot or ne ur o pat h y  (i ncl u di n g G B S), t hat partici pa nt will be ma na ge d acc or di n g t o 
Ta ble 5 a n d the re mai ni n g partici pa nts o n t he c o m bi nati o n ar m will be tra nsiti o ne d t o 
m o n ot hera p y wit h si n gle a ge nt P F - 0 6 8 6 3 1 3 5.
I n a d diti o n, if a ny of t he f oll o wi n g a d verse e ve nts occ ur, st u d y treat me nt will be i nterr u pte d 
f or all acti ve partici pa nts:

1 Gra de 5 e ve nt of C R S

1 Gra de 5 e ve nt of I CA N S

1 Gra de 5 treat me nt -relate d peri p heral ne ur o pat hy or I R ne ur ol o gic e ve nt
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 9

A n y  2 treat me nt-relate d Gra de 5 e ve nts (e xcl u di n g C R S a n d IC A N S a n d peri p heral 
ne ur o pat h y/ I R ne ur ol o gic e ve nt).
9. 8. D at a M o nit ori n g C o m mittee
T his st u d y  will n ot use a data m o nit ori n g c o m mittee ( D M C).
1 0. 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
Pfizer or its a ge nt will c o n d uct peri o dic m o nit ori n g visits d uri n g st u d y c o n d uct t o e ns ure t hat 
t he pr ot oc ol a n d G o o d Cli nical Practices ( G C Ps ) are bei n g f oll o we d.  T he m o nit ors m a y 
re vie w s o urce d oc u me nts t o c o nfir m t hat t he data rec or de d o n C R Fs are acc urate.  T he 
i n vesti gat or a n d i nstit uti o n will all o w Pfizer m o nit ors/a u dit ors or its a ge nts a n d a p pr o priate 
re g ulat or y a ut h orities direct access t o s o urce d oc u me nts t o perf or m t his verificati o n.  T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n.
D uri n g st u d y c o n d uct a n d/ or after st u d y c o m pleti o n, t he i n vesti gat or site ma y be s u bject t o 
re vie w by t he I RB/ E C, a n d/ or t o q ualit y  ass ura nce a u dits perf or me d b y Pfizer, or c o m pa nies 
w or ki n g wit h or o n be half of Pfizer, a n d/ or t o i ns pecti o n b y  a p pr o priate re g ulat or y 
a ut h orities.
T he i n vesti gat or(s) will n otif y  Pfizer or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otificati o n i n relati o n t o t he st u d y . F urt her m ore, t he i n vesti ga t or will c o o perate wit h Pfizer 
or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w Pfizer or its 
a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n.  T he i n vesti gat or site a n d 
i n vesti gat or will pr o m ptl y res ol ve a ny d iscre pa ncies t hat are i de ntifie d bet wee n t he st u d y 
data a n d t he patie nt's me dical rec or ds.  T he i n vesti gat or will pr o m ptl y pr o vi de c o pies of t he 
i ns pecti o n fi n di n gs t o Pfizer or its a ge nt.  Bef ore res p o nse s u b missi o n t o t he re g ulat or y 
a ut h orities, t he i n vesti gat or will pr o vi de Pfizer or its a ge nts wit h a n o p p ort u nit y t o re vie w 
a n d c o m me nt o n res p o nses t o a n y  s uc h fi n di n gs.
It is i m p orta nt t hat t he i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he 
m o nit ori n g visits a n d p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he 
pr ocess.
1 1. 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 1. 1. C ase Re p ort F or ms/ Electr o nic D at a Rec or d
As use d i n t his pr ot oc ol, t he ter m C R F s h o ul d be u n derst o o d t o refer t o eit her a pa per f or m or 
a n electr o nic data rec o r d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d use d i n t his st u d y.
A C R F is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d patie nt .  T he c o m plete d 
ori gi nal C R Fs are t he s ole pr o pert y of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y f or m t o 
t hir d parties, e xce pt f or a ut h orize d re prese ntati ves of Pfizer or a p pr o priate re g ulat or y  
a ut h orities, wit h o ut writte n per missi o n fr o m Pfizer.
T he i n vesti gat or has ulti mate res p o nsi bilit y  f or t he c ollecti o n a n d re p orti n g of all cli nical, 
safety, a n d la b orat or y data e ntere d o n t he C R Fs a n d a n y ot her data c ollecti o n f or ms (s o urce 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 0
d oc u me nts) a n d e ns uri n g t hat t he y are acc urate, a ut he ntic/ ori gi nal, attri b uta ble, c o m plete, 
c o nsiste nt, le gi ble, ti mel y (c o nte m p ora ne o us), e n d uri n g, a n d a vaila ble w he n re q uire d.  T he 
C R Fs m ust be si g ne d b y t he i n vesti gat or or by a n a ut h orize d staff me m ber t o attest t hat t he 
data c o ntai ne d o n t he C R Fs are tr ue. A n y c orrecti o ns t o e ntries ma de i n t he C R Fs or s o urce 
d oc u me nts m ust be date d, i nitiale d , a n d e x plai ne d (if necess ar y) a n d s h o ul d n ot o bsc ure t he 
ori gi nal e ntr y .
I n m ost cases, t he s o urce d oc u me nts are t he h os pital or t he p hys icia n's c hart.  In t hese cases ,
data c ollecte d o n t he C R Fs m ust matc h t he data i n t h ose c harts. 
I n s o me cases, t he C R F ma y als o ser ve as t he s ource d oc u me nt.  I n t hese cases, a d oc u me nt 
s h o ul d be a vaila ble at t he i n vesti gator site a n d at Pfizer t hat clearl y i de ntifies t h ose data t hat 
will be rec or de d o n t he C R F, a n d f or w hic h t he C R F will sta n d as t he s o urce d oc u me nt.
W he n partici pa nt data are t o
be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms .
1 1. 2. Rec or d Rete nti o n
T o e na ble e val uati o ns a n d/ or i ns pecti o ns/a u dits fr o m re g ulat or y a ut h orities or Pfizer, t he 
i n vesti gat or a grees t o kee p rec or ds, i ncl u di n g t he i de ntit y  of all partici pati n g patie nts
(s ufficie nt i nf or mati o n t o li n k rec or ds, e g, C R Fs a n d h os pital rec or ds), all ori gi nal si g ne d 
i nf or me d c o nse nt d oc u me nts , c o pies of all C R Fs, safet y re p orti n g f or ms, s o urce d oc u me nts, 
a n d detaile d rec or ds of treat me nt dis p ositi o n, a n d a de q uate d oc u me ntati o n of rele va nt 
c orres p o n de nce (e g, letters, meeti n g mi n utes, a n d tele p h o ne call re p orts).  T he rec or ds s h o ul d 
be retai ne d b y t he i n vesti gat or acc or di n g t o IC H g ui deli nes , acc or di n g t o l ocal re g ulati o ns, or 
as s pecifie d i n t he cli nical st u d y agree me nt ( C S A), w hic he ver is l o n ger.
If t he i n vesti gat or bec o mes u na ble f or a ny reas o n t o c o nti n ue t o retai n st u d y rec or ds f or t he 
re q uire d peri o d (e g, retire me nt, rel ocati o n), Pfizer s h o ul d be pr os pecti vely n otifie d.  T he 
st u d y rec or ds m ust be tra nsferre d t o a desi g nee acce pta ble t o Pfizer, s uc h as a n ot her 
i n vesti gat or, a n ot her i nstit uti o n, or t o a n i n de pe n de nt t hir d party arra n ge d b y Pfizer. 
I n vesti gat or rec or ds m ust be ke pt f or a mi ni m u m of 1 5 ye ars after c o m pleti o n or 
disc o nti n uati o n of t he st u d y or f or l o n ger if re q uire d b y  a p plica ble l ocal re g ulati o ns. 
T he i n vesti gat or m ust o btai n Pfizer's writte n per missi o n bef ore dis p osi n g of a n y rec or ds, 
e ve n if rete nti o n re q uire me nts ha ve bee n met.
1 1. 3. D at a Pr otecti o n
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of partici pa nt data.
Partici pa nts’ pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte d electr o nic a n d/ or pa per 
f or m a n d will be pass w or d-pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y  
a ut h orize d st u d y staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 1
disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site will be res p o nsi ble f or 
deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g breac h 
n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, partici pa nts will be assi g ne d a si n gle, partici pa nt -s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt-s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nts w h o partici pate d i n t he st u d y , li n ki n g eac h 
partici pa nt’s n u merical c o de t o t heir act ual i de ntit y  a n d me dical rec or d I D. I n case of data 
tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he cli nical st u d y a gree me nt a n d a p plica ble pri vac y  la ws.
I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are 
sec ure d by t ec h nical a n d or ga nizati o nal sec urit y meas ures desi g ne d t o pr ot ect s uc h data 
a gai nst acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access. 
T he s p o ns or mai ntai ns S O Ps o n h o w t o res p o n d i n t he e ve nt of u na ut h orize d access, use, or 
discl os ure of s p o ns or i nf or mati o n or s y ste ms.
1 2. E T HI C S
1 2. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes, i ncl u di n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui del i nes;

A p plica ble I C H G C P g ui deli nes;

A p plica ble la ws a n d re g ulati o ns, i ncl u di n g a p plica ble pri vac y  la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, S R S D(s), a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or, s u b mitte d t o a n IR B/ E C 
b y  t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y t he I R B/ E C bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o n e xce pt f or c ha n ges necessar y t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 2

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n uall y or 
m ore fre q ue ntl y  i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/ E C.

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures.

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H G C P g ui deli nes, t he I R B/ E C, E ur o pea n re g ulati o n 
5 3 6/ 2 0 1 4 f or cl i nical st u dies, E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h, a n d all ot her a p plica ble l ocal re g ulati o ns.
1 2. 2. P atie nt I nf or m ati o n a n d C o nse nt
All parties will e ns ure pr otecti o n of patie nt pers o nal data a n d will n ot i ncl u de patie nt na mes 
or ot her i de ntifia ble data i n a n y re p orts, p u blicati o ns, or ot her discl os ures, e xce pt w here 
re q uire d by la w.
W he n st u d y  data are c o m pile d f or tra nsfer t o Pfizer a n d ot her a ut h orize d parties, patie nt
na mes, a d dress es, a n d ot her i de ntifia ble data will be re place d b y n u merical c o de s base d o n a 
n u m beri n g s ys te m pr o vi de d b y Pfizer i n or der t o de-i de ntif y st u d y patie nt s. T he i n vesti gat or
site will mai ntai n a c o nfi de ntial list of patie nts w h o partici pate d i n t he st u d y, li n ki n g eac h 
patie nt’s n u merical c o de t o his or her act ual i de ntit y. I n case of data tra nsfer, Pfizer will 
mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of patie nt s’ pers o nal data c o nsiste nt 
wit h a p plica ble pri vac y  la ws.
T he i nf or me d c o nse nt d oc u me nt s a n d a n y patie nt recr uit me nt materials m ust be i n 
c o m plia nce wit h I C H G C P, l ocal re g ulat or y re q uire me nts, a n d le gal re q uire me nts, i ncl u di n g 
a p plica ble pri vac y la ws.  P ote ntial be nefit a n d ris ks of alter nati ve pr oce d ures will n ot be 
o utli ne d i n t he c o nse nt f or patie nts o n t his st u d y  per I C H G C P Secti o n 4. 8. 1 0 (i), if t he 
o utli ne of t his i nf or mati o n is n ot i n ali g n me nt wit h i nstit ute’s p olicies.
T he i nf or me d c o nse nt d oc u me nts use d d uri n g t he i nf or me d c o nse nt pr ocess a n d a n y patie nt
recr uit me nt materials m ust be re vie we d an d a p pr o ve d b y  Pfizer , a p pr o ve d b y t he I R B/ E C 
bef ore use, a n d a vaila ble f or i ns pecti o n.
T he i n vesti gat or m ust e ns ure t hat eac h st u d y  patie nt is f ull y i nf or me d a b o ut t he nat ure a n d 
o bjecti ves of t he st u d y a n d p ossi ble ris ks ass ociate d wit h partici pati o n. 
T he i n vesti gat or, or a pers o n desi g nate d b y t he i n vesti gat or, will o btai n writte n i nf or me d 
c o nse nt fr o m eac h patie nt bef ore a n y st u d y -s pecific acti vit y is perf or me d. T he i n vesti gat or 
will retai n t he ori gi nal of eac h patie nt's si g ne d c o nse nt d oc u me nt.
1 2. 3. Re p or ti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y aut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y  ne w 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 3
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he i n vesti gati o nal 
pr o d uct, Pfizer s h o ul d be i nf or me d i m me diatel y. 
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y  patie nts a gai nst a n y i m me diate hazar d, a n d of 
a n y seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o mes a ware of.
1 3. D E FI NI TI O N O F E N D O F T RI A L
1 3. 1. E n d of Tri al i n All P artici p ati n g C o u ntries
E n d of trial i n all partici pati n g c o u ntries is defi ne d as last s u bject last visit ( L S L V).  F or m ore 
i nf or mati o n o n h o w e n d of st u d y is deter mi ne d, please see Secti o n 6. 5 .
1 4. S P O N S O R DI S C O N TI N U A T I O N C RI T E RI A
Pre mat ure ter mi nati o n of t his st u d y  ma y occ ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or i n vesti gati o nal pr o d uct safet y pr o ble ms, or at t he 
discreti o n of Pfizer.  I n a d diti o n, Pfizer retai ns t he ri g ht t o disc o nti n ue de vel o p me nt of 
P F -0 6 8 6 3 1 3 5 at a n y ti me.
If a st u dy is pre mat urel y ter mi nate d, Pfizer will pr om ptl y  n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n vesti gat o r m ust c o ntact all partici pati n g patie nts a n d t he h os pital p har mac y 
(if a p plica ble) wit hi n 2 b usi ness da y s.  As directe d b y Pfizer, all st u d y materials m ust be 
c ollecte d a n d all C R Fs c o m plete d t o t he greatest e xte nt p ossi ble.
1 5. P U B LI C A TI O N O F S T U D Y R E S U L T S
1 5. 1. D isse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E u dra C T/ C TIS, a n d/ or 
w w w. pfizer.c o m, a n d ot her p u blic re gistries a n d we bsites i n acc or da nce wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bj ecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
w w w.cli nicaltrials. g o v
Pfizer p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or Pfizer s p o ns or e d i nter ve nti o nal 
st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safet y a n d/ or efficac y of a pr o d uct, 
re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. T hese res ults are 
s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 4
E u dra C T/ C TI S
Pfizer p osts cli nical trial res ults o n E u dra C T/ C TI S f or Pfizer s p o ns ore d i nter ve nti o nal st u dies 
i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y E U re q uire me nts.  
w w w. pfizer.c o m
Pfizer p osts C S R s y n o pses a n d plai n -la n g ua ge st u d y res ults s u m maries o n w w w. pfizer.c o m 
f or Pfizer s p o ns ore d i nter ve nti o nal st u dies at t he sa me ti me t he c orres p o n di n g st u dy res ults 
are p oste d t o w w w.cli nicaltrials. g o v. C S R s y n o pses will ha ve pers o nall y  i de ntifia ble 
i nf or mati o n a n o ny m ize d.
D oc u me nts wit hi n mar keti n g a p plicati o ns 
Pfizer c o m plies wit h a p plica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts i ncl u de d 
i n mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y d oc u me nts a n d C S Rs 
i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A Ps. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
Data s hari n g
Pfizer pr o vi des researc hers sec ure access t o partici pa nt le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na fi de scie ntific researc h ” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. Pfizer will ma ke data fr o m t hese trials a vala ble 1 8 
m o nt hs after st u d y  c o m pleti o n. Partici pa nt le vel data will be a n o n ymize d i n acc or da nce wit h 
a p plica ble pri vac y la ws a n d re g ulati o ns. C S Rs will ha ve pers o nall y i de ntifia ble i nf or mati o n 
a n o n ymize d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal y ses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses..
1 5. 2. P u blic ati o n P olic y
F or m ultice nter trials, t he pri mar y  p u blicati o n will be a j oi nt p u blicati o n de vel o pe d by t he 
i n vesti gat or a n d Pfizer re p orti n g t he pri mar y e n d p oi nt(s) of the st u d y  c o veri n g all st u d y sites. 
T he i n vesti gat or a grees t o refer t o t he pri mar y  p u blicati o n i n a n y s u bse q ue nt p u blicati o ns. 
Pfizer will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he i n vesti gat or’s partici pati o n i n t he 
pre parati o n of t he pri mar y c o n gres s a bstract, p oster, prese ntati o n, or pri mar y ma n uscri pt f or 
t he st u d y. 
I n vesti gat ors are free t o p u blis h i n di vi d ual ce nter res ults t hat t he y dee m t o be cli nicall y 
mea ni n gf ul after p u blicati o n of t he o verall res ults of t he st u d y  or 1 2 m o nt hs after pri mar y 
c o m pleti o n date or st u d y c o m pleti o n at all sites, w hic he ver occ urs first, s u bject t o t he ot her 
re q uire me nts descri be d i n t his secti o n.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 5
T he i n vesti gat or will pr o vi de Pfizer a n o p p ort u nit y  t o re vie w a n y pr o p ose d p u blicati o n or 
a n y ot her ty pe of discl os ure of t he st u d y res ults (c ollecti vel y, “ p u blicati o n”) bef ore it is 
s u b mitte d or ot her wise discl ose d a n d will s u b mit all p u blicati o ns t o Pfizer 3 0 da ys bef ore 
s u b missi o n. If a ny pate nt acti o n is re q uire d t o pr otect i ntellect ual pr o pert y ri g hts, t he 
i n vesti gat or a grees t o dela y t he discl os ure f or a peri o d n ot t o e xcee d a n a d diti o nal 6 0 da ys 
u p o n re q uest fr o m Pfizer. T his all o ws Pfizer t o pr otect pr o prietar y  i nf or mati o n a n d t o pr o vi de 
c o m me nts, a n d t he i n vesti gat or will, o n re q uest, re m o ve a n y pre vi o usl y u n discl ose d 
c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y i nter ve nti o n or  Pfizer 
relate d i nf or mati o n necessar y f or t he a p pr o priate scie ntific prese ntati o n or u n dersta n di n g of 
t he st u d y res ults. F or j oi nt p u blicati o ns, s h o ul d t here be disa gree me nt re gar di n g 
i nter pretati o n a n d/ or prese ntati o n of s pecific a nalysis res ults, res ol uti o n of, a n d res p o nsi bilit y 
f or, s uc h disa gree me nts will be t he c ollecti ve res p o nsi bilit y of all a ut h ors of t he p u blicati o n.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or a n d Pfizer will c o m pl y wit h 
rec o g nize d et hical sta n dar ds c o ncer ni n g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose 
esta blis he d b y  t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. T he i n vesti gat or will 
discl ose a n y relati o ns hi p wit h Pfizer a n d a n y rele va nt p ote ntial c o nflicts of i nterest, i ncl u di n g 
a n y fi na ncial or pers o nal relati o ns hi p wit h Pfizer, i n a n y p u blicati o ns. All a ut h ors will ha ve 
access t o t he rele va nt statistical ta bles, fi g ures, a n d re p orts (i n t heir ori gi nal f or mat) re q uire d 
to de vel o p t he p u blicati o n. T he res ults of t his st u d y ma y be p u blis he d or prese nte d at 
scie ntific meeti n gs by t he i n vesti gat or after p u blicati o n of t he o verall st u d y res ults or 1 year 
after t he e n d of t he st u d y ( or st u d y ter mi nati o n), w hic he ver c o mes first.  
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 6
1 6. R E F E R E N C E S
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m y el o ma rela psi n g after t hera p y wit h I Mi Ds a n d b ortez o mi b: a m ultice nter 
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Lee D W, Gar d ner R, P orter D L, et al. C urre nt c o nce pts i n t he dia g n osis a n d 
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Lee D W, Sa nt o mass o B D, L oc ke F L, et al. A S T C T C o nse ns us Gra di n g f or C y t o ki ne 
Release S y n dr o me a n d Ne ur ol o gic T o xicit y  Ass ociate d wit h I m m u ne Effect or Cells. 
Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 9; 2 5( 4): 6 2 5- 3 8.
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g ui deli nes f or ser u m -free li g ht c hai n a nalys is i n m ulti ple m yel o ma an d relate d 
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K u mar S, Pai va B, A n ders o n K C, et al. I nter nati o nal M y el o ma W or ki n g Gr o u p 
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Pal u m b o A, A n ders o n K. M ulti ple m y el o ma. N E n gl J Me d. 2 0 1 1; 3 6 4( 1 1): 1 0 4 6 - 6 0.
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1 0.
G a y  F, Ma gar ott o V, Cri p pa C, et al. B ortez o mi b i n d ucti o n, re d uce d-i nte nsit y 
tra ns pla ntati o n, a n d le nali d o mi de c o ns oli dati o n-mai nte na nce f or m yel o ma: u p date d 
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1 1.
D ha kal B, Ves ole D H, Hari P N. All o ge neic ste m cell tra ns pla ntati o n f or m ulti ple 
m y el o ma: is t here a f ut ure? B o ne Marr o w Tra ns pla nt. 2 0 1 6; 5 1( 4): 4 9 2 - 5 0 0.
1 2.  
D urie B, H oeri n g A, Raj k u mar S V, et al. B ortez o mi b, le nali d o mi de a n d 
de xa met has o ne vs. le nali d o mi de a n d de xa met has o ne i n patie nts ( Pts) wit h pre vi o usl y  
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 7
u ntreate d m ulti ple m y el o ma wit h o ut a n i nte nt f or i m me diate a ut ol o g o us ste m cell 
tra ns pla nt ( A S C T): res ults of t he ra n d o mize d p hase III trial S W O G S 0 7 7 7. 2 0 1 5.
1 3.
Ji me nez-Ze pe da V H, Reece D E, Tr u del S, et al. Earl y rela pse after si n gle a ut o-S C T 
f or m ulti ple m yel o ma is a maj or pre dict or of s ur vi val i n t he era of n o vel a ge nts. B o ne 
Marr o w Tra ns pla nt. 2 0 1 5; 5 0( 2): 2 0 4- 8.
1 4.
L o pez A, Mate os M V, Ori ol A, et al. Patter ns of rela pse a n d o utc o me of el derl y  
m ulti ple m y el o ma patie nts treate d as fr o nt- li ne t hera p y wit h n o vel a ge nts 
c o m bi nati o ns. Le u k Res Re p. 2 0 1 5; 4( 2): 6 4 - 9.
1 5.  
K u mar S K, T her nea u T M, Gertz M A, et al. Cli nical c o urse of patie nts wit h rela pse d 
m ulti ple m y el o ma. Ma yo Cli n Pr oc. 2 0 0 4; 7 9( 7): 8 6 7 - 7 4.
1 6.
S o n ne vel d P, Br oijl A. Treat me nt of rela pse d a n d refract or y  m ulti ple m yel o ma. 
Hae mat ol o gica. 2 0 1 6; 1 0 1( 8): 9 9 5.
1 7.
Tric ot G, Ves ole D H, Ja ga n nat h S, et al. Graft -vers us -m y el o ma effect: pr o of of 
pri nci ple. Bl o o d. 1 9 9 6; 8 7( 3): 1 1 9 6- 8.
1 8. 
T o p p M S, G o k b u get N, Stei n A S, et al. Safet y a n d acti vit y of bli nat u m o ma b f or a d ult 
patie nts wit h rela pse d or refract or y  B-prec urs or ac ute l y m p h o blastic le u kae mia: a 
m ultice ntre, si n gle -ar m, p hase 2 st u d y. La ncet O nc ol. 2 0 1 5; 1 6( 1): 5 7 - 6 6.
1 9. 
Lee L, B o u n ds D, Paters o n J, et al. E val uati o n of B cell mat urati o n a nti ge n as a tar get 
f or a nti b o dy dr u g c o nj u gate me diate d c yt ot o xicit y i n m ulti ple m y el o ma. Br J 
Hae mat ol. 2 0 1 6; 1 7 4( 6): 9 1 1- 2 2.
2 0.
Car pe nter R O, E v b u o m wa n M O, Pittal u ga S, et al. B- cell mat urati o n a nti ge n is a 
pr o misi n g tar get f or a d o pti ve T -cell t hera p y of m ulti ple m y el o ma. Cli n Ca ncer Res. 
2 0 1 3; 1 9( 8): 2 0 4 8 -6 0.
2 1.
X u S, L a m K P. B-cell mat urati o n pr otei n, w hic h bi n ds t he t u m or necr osis fact or 
fa mil y me m bers B A F F a n d A P RI L, is dis pe nsa ble f or h u m oral i m m u ne res p o nses. 
M ol Cell Bi ol. 2 0 0 1; 2 1( 1 2): 4 0 6 7 - 7 4.
2 2.
O' C o n n or B P, Ra ma n V S, Eric ks o n L D, et al. B C M A is esse ntial f or t he s ur vi val of 
l o n g-li ve d b o ne marr o w plas ma cells. J E x p Me d. 2 0 0 4; 1 9 9( 1): 9 1- 8.
2 3. 
Ra ma d oss N S, Sc h ul ma n A D, C h oi S H, et al. A n a nti- B cell mat urati o n a nti ge n 
bis pecific a nti b o d y f or m ulti ple m yel o ma. J A m C he m S oc. 2 0 1 5; 1 3 7( 1 6): 5 2 8 8- 9 1.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 8
2 4.
Hi p p S, Tai Y T, Bla nset D, et al. A n o vel B C M A/ C D 3 bis pecific T -cell e n ga ger f or 
t he treat me nt of m ulti ple m yel o ma i n d uces selecti ve l ysis i n vitr o a n d i n vi v o. 
Le u ke mia. 2 0 1 7; 3 1( 8): 1 7 4 3 - 5 1.
2 5.
Pa n o ws ki S H, K u o T C, Z ha n g Y, et al. Precli nical Efficac y  a n d Safet y C o m paris o n 
of C D 3 Bis pecific a n d A D C M o dalities Tar geti n g B C M A f or t he Treat me nt of 
M ulti ple M y el o ma. M ol Ca ncer T her. 2 0 1 9; 1 8( 1 1): 2 0 0 8- 2 0.
2 6.
T o p p M S, Attal M, L a n ger C, et al. P hase 1 d ose -escalati o n st u d y of BI 8 3 6 9 0 9, a n 
a nti-B C M A bi -s pecific T-cell e n ga ger, i n rela pse d a n d/ or refract or y  m ulti ple 
m y el o ma ( R R M M). J o ur nal of Cli nical O nc ol o g y . 2 0 1 6; 3 4( 1 5 _s u p pl): T P S 8 0 6 7-
T P S 6 7.
2 7.
D urie B G, Mi g uel J F, Bla de J, et al. Clarific ati o n of t he defi niti o n of c o m plete 
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2 8.
Mc C u d de n C R, V o or hees P M, Hai ns w ort h S A, et al. I nterfere nce of m o n ocl o nal 
a nti b o d y t hera pies wit h ser u m pr otei n electr o p h oresis tests. Cli n C he m. 
2 0 1 0; 5 6( 1 2): 1 8 9 7 - 9.
2 9.  
K otla V, G oel S, Nisc hal S, et al. Mec ha nis m of acti o n of le nali d o mi de i n 
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3 0.
R E V LI M I D (le nali d o mi de ca ps ule). U S Prescri pti o n Inf or mati o n ( U S PI); 1 0 J u n 
2 0 1 9, S u m mit, NJ, U S A: Cel ge ne C or p. A vaila ble fr o m: 
htt ps:// dail y me d. nl m. ni h. g o v/ dail y m e d/ dr u gI nf o.cf m?seti d = 5fa 9 7 bf 5- 2 8a 2 -4 8f 1 -
8 9 5 5- f 5 6 0 1 2 d 2 9 6 be. Accesse d o n: 0 7 J ul 2 0 2 0.
3 1.
Re vli mi d. E P A R Pr o d uct I nf or mati o n; 0 1 Ja n 2 0 2 0: E M A. A vaila ble fr o m: 
htt ps:// w w w.e ma.e ur o pa.e u/e n/ me dici nes/ h u ma n/ E P A R/re vli mi d #a ut h orisati o n -
details -secti o n. Accesse d o n: 0 7 J ul 2 0 2 0.
3 2.
R E V LI M I D (le nali d o mi de ca ps ule). Healt h Ca na da Pr o d uct M o n o gra p h; 2 0 A u g 
2 0 1 9, Mississa u ga, O ntari o: Cel ge ne C or p. A vaila ble fr o m: 
htt ps:// p df. hres.ca/ d p d _ p m/ 0 0 0 5 2 7 4 9. P D F . Accesse d o n: 0 7 J ul 2 0 2 0.
3 3.
Ric har ds o n P G, Mar k T M, L a c y M Q. P o mali d o mi de: ne w i m m u n o m o d ulat or y a ge nt 
wit h p ote nt a nti pr oliferati ve effects. Crit Re v O nc ol He mat ol. 2 0 1 3; 8 8 S u p pl 1: S 3 6 -
4 4.
3 4.
P O M A L Y S T ( p o mali d o mi de ca ps ule). U S Prescri pti o n I nf or mati o n ( U S PI ); 2 9 Ma y 
2 0 2 0, S u m mit, NJ, U S A: Cel ge ne C or p. A vaila ble fr o m: 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9 9
htt ps:// dail y me d. nl m. ni h. g o v/ dail y m e d/ dr u gI nf o.cf m?seti d = 2 b 2 5ef 0 1- 5c 9e -1 1e 1 -
b 8 6c -0 8 0 0 2 0 0c 9a 6 6 . Accesse d o n: 0 7 J ul 2 0 2 0.
3 5.
I m n o vi d ( pre vi o usl y P o mali d o mi de Cel ge ne). E P A R Pr o d uct I nf or mati on; 1 8 J u n 
2 0 1 9: E M A. A vaila ble fr o m: 
htt ps:// w w w.e ma.e ur o pa.e u/e n/ me dici nes/ h u ma n/ E P A R/re vli mi d #a ut h orisati o n -
details -secti o n. Accesse d o n: 0 7 J ul 2 0 2 0.
3 6.
P o mal y st ( p o mali d o mi de). Healt h Ca na da Pr o d uct M o n o gra p h; 2 Fe b 2 0 2 1 2 0 1 9, 
Sai nt -La u re nt, Q C: Cele ge ne. A vaila ble fr o m: 
htt ps:// w w w.e ma.e ur o pa.e u/e n/ me dici nes/ h u ma n/ E P A R/i m n o vi d . Accesse d o n: 0 7 J ul 
2 0 2 0.
3 7.
N CI .  Nati o nal Ca ncer I nstit ute: Da xa met has o ne. A vaila ble fr o m: 
htt ps:// w w w.ca ncer. g o v/a b o ut -
ca ncer/treat me nt/ dr u gs/ de xa met has o ne #: ~:te xt = De xa met h as o ne % 2 0is % 2 0a p pr o ve d
% 2 0t o % 2 0 be % 2 0 use d % 2 0t o % 2 0re d uce,t he % 2 0f oll o wi n g % 2 0t y pes % 2 0 of % 2 0ca ncer
% 2 0: % 2 0 Le u ke mia % 2 0 . Accesse d o n: 1 6 Ja n 2 0 2 1.
3 8.
Neela p u S S. Ma na gi n g t he t o xicities of C A R T -cell t hera p y. He mat ol O nc ol. 2 0 1 9; 3 7 
S u p pl 1: 4 8 - 5 2.
3 9.
Neela p u S S, T u m mala S, Ke briaei P, et al. C hi meric a nti ge n rece pt or T -cell t hera p y -
assess me nt a n d ma na ge me nt of t o xicities. Nat Re v Cli n O nc ol. 2 0 1 8; 1 5( 1): 4 7 - 6 2.
4 0.  
D urie B G M, H oeri n g A, A bi di M H, et al. B ortez o mi b wit h le nali d o mi de a n d 
de xa met has o ne vers us le nali d o mi de a n d de xa met has o ne al o ne i n patie nts wit h ne wl y  
dia g n ose d m y el o ma wit h o ut i nte nt f or i m me diate a ut ol o g o us ste m- cell tra ns pla nt 
( S W O G S 0 7 7 7): a ra n d o mise d, o pe n-la bel, p hase 3 trial. La ncet. 
2 0 1 7; 3 8 9( 1 0 0 6 8): 5 1 9 -2 7.
4 1.
Fac o n T, K u mar S, Ples ner T, et a l. Darat u m u ma b pl us Le nali d o mi de a n d 
De xa met has o ne f or U ntreate d M yel o ma. N E n gl J Me d. 2 0 1 9; 3 8 0( 2 2): 2 1 0 4 - 1 5.
4 2.  
Wa n g D D, Z ha n g S, Z ha o H, et al. Fi xe d d osi n g vers us b o d y size -base d d osi n g of 
m o n ocl o nal a nti b o dies i n a d ult cli nical trials. J Cli n P har mac o l. 2 0 0 9; 4 9( 9): 1 0 1 2- 2 4.
4 3.
Z ha n g S, S hi R, L i C, et al. Fi xe d d osi n g vers us b o d y size- base d d osi n g of t hera pe utic 
pe pti des a n d pr otei ns i n a d ults. J Cli n P har mac ol. 2 0 1 2; 5 2( 1): 1 8 - 2 8.
4 4. 
T o p p M S, G o k b u get N, Z u g maier G, et al. P hase II trial of t he a nti- C D 1 9 bis pecific T 
cell-e n ga ger bli nat u m o ma b s h o ws he mat ol o gic a n d m olec ular re missi o ns i n patie nts 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 0
wit h rela pse d or refract or y B -prec urs or ac ute l y m p h o blastic le u ke mia. J Cli n O nc ol. 
2 0 1 4; 3 2( 3 6): 4 1 3 4 - 4 0.
4 5.
Raj k u mar S V, Di m o p o ul os M A, Pal u m b o A, et al. I nte r nati o nal Myel o ma W or ki n g 
Gr o u p u p date d criteria f or t he dia g n osis of m ulti ple m y el o ma. La ncet O nc ol. 
2 0 1 4; 1 5( 1 2):e 5 3 8 - 4 8.
4 6.
S mit h TJ, K hatc heressia n J, L y ma n G H, et al. 2 0 0 6 u p date of rec o m me n dati o ns f or 
t he use of w hite bl o o d cell gr o wt h fact ors: a n e vi de nce-base d cli nical practice 
g ui deli ne. J Cli n O nc ol. 2 0 0 6; 2 4( 1 9): 3 1 8 7- 2 0 5.
4 7.
Cars o n J L , G u yatt G, He d dle N M, et al. Cli nical Practice G ui deli nes Fr o m t he 
A A B B: Re d Bl o o d Cell Tra nsf usi o n T hres h ol ds a n d St ora ge. J A M A. 
2 0 1 6; 3 1 6( 1 9): 2 0 2 5 -3 5.
4 8.
Sc hiffer C A, B o hl ke K, Dela ne y  M, et al. Platelet Tra nsf usi o n f or Patie nts Wit h 
Ca ncer: A merica n S ociet y of Cli nical O nc ol o g y  Cli nical Practice G ui deli ne U p date. J 
Cli n O nc ol. 2 0 1 8; 3 6( 3): 2 8 3- 9 9.
4 9. 
Ric har ds o n P G, Delf or ge M, Be ksac M, et al. Ma na ge me nt of treat me nt-e mer ge nt 
peri p heral ne ur o pat h y i n m ulti ple m y el o ma. Le u ke mia. 2 0 1 2; 2 6( 4): 5 9 5 -6 0 8.
5 0. 
T o p p M S, D uell J, Z u g maier G, et al. A nti- B- Cell Mat urati o n A nti ge n Bi T E 
M olec ule A M G 4 2 0 I n d uces Res p o nses i n M ulti ple M y el o ma. J Cli n O nc ol. 
2 0 2 0; 3 8( 8): 7 7 5 - 8 3.
5 1. 
F a nale M, Fa ya d L, Pr o B, et al. P hase I st u d y of b ortez o mi b pl us IC E ( BI C E) f or t he 
treat me nt of rela pse d/refract or y H o d g ki n ly m p h o ma. Br J Hae mat ol. 
2 0 1 1; 1 5 4( 2): 2 8 4 - 6.
5 2.
Ji Y, Li u P, Li Y, et al. A m o difie d t o xicit y pr o ba bilit y i nter val met h o d f or d ose-
fi n di n g trials. Cli n Trials. 2 0 1 0; 7( 6): 6 5 3- 6 3.
5 3.
O ke n M M, Creec h R H, T or me y  D C, et al. T o xicit y a n d res p o nse criteria of t he 
Easter n C o o perati ve O nc ol o g y  Gr o u p. A m J Cli n O nc ol. 1 9 8 2; 5( 6): 6 4 9-5 5.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 1
A p pe n di x 1. A B B R E VI A TI O N S
T he f oll o wi n g is a list of a b bre viati o ns t hat ma y be use d i n t he pr ot oc ol.  
A b bre vi ati o n
Ter m
A A B B
A merica n Ass ociati o n of Bl o o d Ba n ks
A C RI N
A merica n C olle ge of Ra di ol o g y  Ima gi n g Net w or k
A C T H
a dre n oc ortic otr o pic h or m o ne
A D A
a nti-dr u g a nti b o dies
A D L
acti vities of dail y li vi n g
A E
a d verse e ve nt
A H A
A merica n Heart Ass ociati o n
AI D S
ac q uire d i m m u n o deficie nc y  sy n dr o me
A L K
a na plastic l y m p h o ma ki nase
A L L
ac ute l y m p h o blastic le u ke mia
A L T
ala ni ne a mi n otra nsferase
A N C
a bs ol ute ne utr o p hil c o u nt
A N O V A
a nal ys is of varia nce
A P Cs
a nti ge n prese nti n g cells
A P RI L
a pr oliferati o n-i n d uci n g li ga n d
A S C O
A merica n S ociet y of Cli nical O nc ol o g y
A S C T
a ut ol o g o us ste m cell tra ns pla nt 
A S T
as partate a mi n otra nsferase
A S T C T
A merica n S ociet y f or Tra ns pla ntati o n a n d Cell ular T hera py
A U C
area u n der t he c ur ve
A U C 1 6 8
area u n der t he c ur ve meas ure d t o 1 6 8 h o urs
A U C i nf
area u n der t he c o nce ntrati o n vers us ti me c ur ve t o i nfi nit y
A U C last
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 
zer o t o ti me of last meas ura ble c o nce ntrati o n 
A U C s d,
area u n der t he si n gle d ose c o nce ntrati o n -ti me c ur ve o ver 
d osi n g i nter val 
A U C 
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 
zer o t o ti me t
a ut o-H S C T
a ut ol o g o us he mat o p oietic ste m cell tra ns pla ntati o n
A V
A tri o ve ntric ular
B B S
bi os peci me n ba n ki n g s yste m
B C M A
B -cell mat urati o n a nti ge n
BI D
t wice daily
B M
b o ne marr o w
B MI
b o d y  mass i n de x
B N P
B -t ype natri uretic pe pti de
B O R
best o verall res p o nse
B P
bl o o d press ure
B U N
bl o o d urea nitr o ge n
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 2
A b bre vi ati o n
Ter m
C
C y cle
C B C
c o m plete bl o o d c o u nt
C 0 D 1
C y cle 0 Da y 1
C 1 D 1
C y cle 1 Da y 1
C A R
c hi meric a nti ge n rece pt ors
C a v
a vera ge c o nce ntrati o n
C B
cli nical be nefit
C B R
cli nical be nefit rate
C D
cl uster of differe ntiati o n 
C E A
carci n oe m br yo nic a nti ge n
Ceff
efficaci o us c o nce ntrati o n
C H F
c o n gesti ve heart fail ure
CI
c o nfi de nce i nter val
C K
creati ne ki nase
C K -M B
creati ne ki nase M B
C L
cleara nce
C L / F
cleara nce after n o n -i ntra ve n o us a d mi nistrati o n
C ma x
ma xi m u m ( or pea k) c o nce ntrati o n
C mi n
mi ni m u m c o nce ntrati o n
C M V
c yt o me gal o vir us
C N S
ce ntral ner v o us s ys te m
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C R
c o m plete res p o nse
C R A B
calci u m ele vati o n, re nal fail ure, a ne mia, l yt ic b o ne lesi o ns; 
Cra nial ner ve VI
a b d uce ns ner ve
Cr Cl
creati ni ne cleara nce
C R F
case re p ort f or m
C R h
c o m plete re missi o n wit h partial he mat ol o gical rec o ver y
C R P
C -reacti ve pr otei n
C R R
c o m plete res p o nse rate
C R S
c yt o ki ne release sy n dr o me
C S A
cli nical st u d y a gree me nt
C S F
cere br os pi nal fl ui d
C S R
cli nical st u d y re p ort
C T
c o m p ute d t o m o gra p h y
C T S A E
cli nical trial seri o us a d verse e ve nt
C T A
cli nical trial a p plicati o n
C T C A E
C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts
C X D 1
C y cle X Da y 1
C Y P 3 A 4
C y t oc hr o me P 4 5 0 3 A 4
C V
c oefficie nt of variati o n
D C R
disease c o ntr ol rate 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 3
A b bre vi ati o n
Ter m
D DI 
dr u g -dr u g i nteracti o n
D F S
disease free s ur vi val
DI LI
dr u g -i n d uce d li ver i nj ur y
D LI
D o n or L y m p h oc y te I nf usi o n
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
D N A
de o x yri b o n ucleic aci d
D o C R
d urati o n of c o m plete res p o nse
D O R
d urati o n of res p o nse
D O S D
d urati o n of sta ble disease
D U
dis pe nsa ble u nit
E B V
e pstei n-barr vir us
E C
et hics c o m mittee
E C 2 0
effecti ve c o nce ntrati o n 2 0
E C 5 0
effecti ve c o nce ntrati o n 5 0
E C G
Electr ocar di o gra m
ec h o
Ec h ocar di o gra m
E C O G
Easter n C o o perati ve O nc ol o g y  Gr o u p
e C R F
electr o nic case re p ort f or m
E -D M C
e xter nal data m o nit ori n g c o m mittee
E D P
e x p os ure d uri n g pre g na nc y
E D V
e n d-diast olic v ol u me
E E G
E lectr oe nce p hal o gra m
e g
f or e xa m ple
E G F R
e pi der mal gr o wt h fact or rece pt or 
EI
e q ui vale nce i nter val
E M G
electr o m y o gra p h y
E O S
e n d of st u d y
E O T
e n d of treat me nt
E S C
E ur o pea n S ociet y of Car di ol o g y
E S V
e n d-s yst olic v ol u me
Etc
‘a n d ot her t hi n gs’ or ‘a n d s o f ort h’
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n Cli nical Trials Data base
F A P
fi nal a p pr o ve d pr ot oc ol
Fc
fra g me nt cr ystalliza ble
F D A
F o o d a n d Dr u g A d mi nistrati o n ( U nite d States)
F D G -P E T/ C T
fl u or o de o xy gl uc ose p ositr o n e missi o n t o m o gra p h y/c o m p ute d 
t o m o gra p hy
FI P
first i n patie nt
FI S H
fl u oresce nce i n sit u h y bri dizati o n
F L C
free li g ht c hai n a nalys is
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 4
A b bre vi ati o n
Ter m
F S H
f ollicle-sti m ulati n g h or m o ne
G B S
G uillai n -Barré S y n dr o me
G C P
G o o d Cli nical Practice
G G T
ga m ma -gl uta m y l tra nsferase
G H
gr o wt h h or m o ne
GI
gastr oi ntesti nal tract
G L P
G o o d La b orat or y  Practice
G M -C S F
gra n ul oc y te- macr o p ha ge c ol o n y  sti m ulati n g fact or
G n R H
g o na d otr o pi n -releasi n g h or m o ne a g o nist
G v H D
graft -vers us -h ost disease
H b A 1c
he m o gl o bi n A 1c
H Bc
he patitis B c ore
H Bc A b
he patitis B c ore a nti b o d y
H Bs
he patitis B s urface
H Bs A g
he patitis B s urface a nti ge n
H B V
he patitis B vir us
H C V
he patitis C vir us
H g b
He m o gl o bi n
HI V
h u ma n i m m u n o deficie nc y vir us
H L A
h u ma n le u k oc y te a nti ge n
H L H
L y m p h o histi oc y t osis
H R
heart rate
hrs
H o urs
H T L V
h u ma n T -cell l y m p h otr o pic vir us
I B
i n vesti gat or’s br oc h ure
I C A N S
I m m u ne Effect or Cell-Ass ociate d Ne ur ot o xicit y  S yn dr o me
I C D
I nf or me d c o nse nt d oc u me nt
I C E
I m m u ne Effect or Cell -Ass ociate d E nce p hal o pat h y
I C H
I nter nati o nal C o nfere nce o n Har m o nizati o n
I C P
I ntracra nial press ure
I C U
i nte nsi ve care u nit
I D
I de ntificati o n
ie
t hat is
I F N
i nterfer o n ga m ma
I g
I m m u n o gl o b uli n
I GF -1
I ns uli n-li ke gr o wt h fact or 1
I g G 2 Δa
i m m u n o gl o b uli n G 2 Δa
I g Gk
i m m u n o gl o b uli n G ka p pa
I H C
I m m u n o hist oc he mistr y
I L-
I nterle u ki n
I Mi D
i m m u n o m o d ulat or y dr u g
I M W G
i nter nati o nal m yel o ma w or ki n g gr o u p
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 5
A b bre vi ati o n
Ter m
I ND
i n vesti gati o nal ne w dr u g a p plicati o n
I N R
i nter nati o nal n or malize d rati o
I P ma n ual
I n vesti gati o nal Pr o d uct ma n ual
I R
I m m u ne-relate d
I RB
i nstit uti o nal re vie w b oar d
I R C
i nter nal re vie w c o m mittee
I R R
i nf usi o n relate d reacti o n
I S R
i njecti o n site reacti o n 
I T T
i nte nt t o treat
I UD
i ntra uteri ne de vice
I V
I ntra ve n o us
K 2E D T A
di p otassi u m e detic aci d et h yle ne dia mi netetraacetic aci d
K D
e q uili bri u m diss ociati o n c o nsta nt
L B B B
left b u n dle bra nc h bl oc k
L D H
lactate de hy d r o ge nase
L F T
li ver f u ncti o n test
L H
l utei nizi n g h or m o ne
L P F V
last patie nt first visit
L S L V
last s u bject last visit
L T F U
l o n g-ter m f oll o w-u p
L V E F
left ve ntric ular ejecti o n fracti o n
M
M o n ocl o nal
m A b
m o n ocl o nal a nti b o d y
M A B E L
mi ni m u m a ntici pate d bi ol o gical effect le vel
M A D
ma xi m u m a d mi nistere d d ose
M A D -1
1 d ose le vel bel o w t he M A D
M A S
macr o p ha ge acti vati o n s y n dr o me
M D
m ulti ple d ose
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
M F C
m ulti para metric fl o w c y t o metr y
M F D
ma xi m u m feasi ble d ose
M G U S
m o n ocl o nal ga m m o pat h y of u n deter mi ne d cli nical 
si g nifica nce
M H C
maj or hist oc o m pati bilit y  c o m ple x 
M M
m ulti ple m y el o ma
M M 1. S
a gl uc oc ortic oi d se nsiti ve m ulti ple m y el o ma cell li ne
M O L P- 8
a m ulti ple m yel o ma cell li ne wit h t( 1 1; 1 4)( q 1 3; q 3 2) 
c hr o m os o mal a b n or malit y a n d ne gati ve f or C D 2 8
M -Pr otei n
m y el o ma pr otei n
M R
mi ni mal res p o nse
M R D
mi ni mal resi d ual disease
M RI
ma g netic res o na nce i ma gi n g
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 6
A b bre vi ati o n
Ter m
M -s pi ke
m o n ocl o nal s pi ke
M T D
ma xi m u m t olerate d d ose
M T D- 1
1 d ose bel o w t he M T D
m T PI
m o difie d t o xicit y  pr o ba bilit y i nter val
M U G A
m ulti gate d ac q uisiti o n sca n
N 
n u m ber
N/ A
n ot a p plica ble
N A b
ne utralizi n g a nti b o d y
N CI  
Nati o nal Ca ncer I nstit ute 
N C T
Nati o nal Cli nical Trial
N C V
Ner ve c o n d ucti o n vel ocit y
N G F
ne xt ge nerati o n fl o w c y t o metr y
N G S
ne xt ge nerati o n se q ue nci n g
N K
nat ural killer
N O A E L
n o o bser ve d a d verse effect le vel
N S AI D S
n o nster oi dal a nti -i nfla m mat or y dr u gs
N S C L C
n o n -cell s mall cell l u n g ca ncer
N S G
N O D sci d ga m ma 
O B D
o pti mal bi ol o gical d ose
O P M -2
a t ype of m ulti ple m y el o ma cell li ne
O R
o bjecti ve res p o nse or o verall res p o nse
O R R
o bjecti ve res p o nse rate
O S
o verall s ur vi val
P A C L
Pr ot oc ol A d mi nistrati ve C ha n ge Letter
Pa O 2
partial press ure of o x y ge n
P C D
pri mar y  c o m pleti o n date
P D
p har mac o d y n a mic, pr o gressi ve disease
P E T
p ositr o n e missi o n t o m o gra p h y
P F S
pr o gressi o n -Free S ur vi val
P G x
p har mac o ge n o mics
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic
P M L
p r o gressi ve m ultif ocal le u k oe nce p hal o pat hy
P O
b y  m o ut h
P O E M S
p ol y ne ur o pat h y , or ga n o me gal y, e n d ocri n o pat h y, m yel o ma 
pr otei n, a n d s ki n c ha n ges
P P
p osteri or pr o ba bilit y
P P P
pre g na nc y  pre ve nti o n pr o gra m
P R
partial res p o nse
P R L
P r olacti n
P S
perf or ma nce stat us
P T
pr ot hr o m bi n ti me
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 7
A b bre vi ati o n
Ter m
P T T
partial t hr o m b o plasti n ti me
Q 1 W
e ver y wee k
Q 2 W
ever y  2 wee ks 
Q 3 W
e ver y t hree wee ks
Q 4 W
e ver y f o ur wee ks
Q D
e ver y da y
q P C R
q ua ntitati ve p ol y merase c hai n reacti o n 
Q T
ti me bet wee n t he start of t he Q wa ve a n d t he e n d of t he 
T wa ve
Q Tc
c orrecte d Q T i nter val
Q Tc B
c orrecte d Q T i nter val b y Bazett
Q Tc F
C orrecte d Q T i nter val b y Fri dericia
R ac
acc u m ulati o n rati o
R C L
re plicati o n c o m pete nt le nti vir us
R D
res p o nse/re missi o n d urati o n 
R E M S
ris k e val uati o n a n d miti gati o n strate g y 
R N A
ri b o n ucleic aci d
R O
rece pt or occ u pa nc y
R P 2 D
rec o m me n de d P hase 2 d ose
R R
res p o nse rate
R T -P C R
re verse tra nscri pti o n p ol y merase c hai n reacti o n
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S A R S -C o V -2
se vere ac ute res pirat or y s yn dr o me c or o na vir us -2
S B P
s yst olic bl o o d press ure
S C
S u bc uta ne o us
S C C H N
s q ua m o us cell ca ncer of hea d a n d nec k
sc F v
si n gle-c hai n varia ble fra g me nt
S C L C
s mall cell l u n g ca ncer
s C R
stri n ge nt c o m plete res p o nse
S C T
ste m cell tra ns pla nt
S D
sta ble disease
SI F E
ser u m i m m u n ofi xati o n electr o p h oresis 
sIL 2 R 
s ol u ble i nterle u ki n- 2 rece pt or al p ha 
S L A M F 7
Si g nali n g l y m p h oc y tic acti vati o n m olec ule F 7
S o A
Sc he d ule of Acti vities
S O C
sta n dar d of care
S O P
sta n dar d o perati n g pr oce d ure
S P C
S u m mar y  of Pr o d uct C haracteristics
S P D
s u m of t he pr o d ucts of t he ma xi mal per pe n dic ular dia meters 
of meas ure d lesi o ns
S P E P
ser u m pr otei n electr o p h oresis
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 8
A b bre vi ati o n
Ter m
S R S D
si n gle refere nce safety d oc u me nt
S T R
s h ort ta n de m re peat
S U V
sta n dar d u pta ke val ue
S W O G
s o ut h west o nc ol o g y gr o u p
T 1/ 2
ter mi nal eli mi nati o n half-life
T A L E N
tra nscri pti o n acti vat or-li ke effect or n ucleases
T B D
t o be deter mi ne d
T Bili
t otal bilir u bi n
T B N K
T -, B-, a n d nat ural killer l ym p h oc y tes
T B R
t u m or bac k gr o u n d rati o
T C R
T -cell rece pt or 
T E A E
treat me nt-e mer ge nt a d verse e ve nt
T L S
t u m or l ysis s yn dr o me
T ma x
ti me t o ma xi m u m c o nce ntrati o n
T N F
t u m or necr osis fact or
T N F 
t u m or necr osis fact or – al p ha
T N F R S F 1 7
t u m or necr osis fact or rece pt or s u perfa mil y Me m ber 1 7
T R A C
T -cell rece pt or al p ha c o nsta nt 
T R A Es
Treat me nt -e mer ge nt treat me nt -relate d a d verse e ve nts
Tre gs
T re g ulat or y  cells
T ss, ma x
ti me t o ma xi m u m c o nce ntrati o n
T T P
ti me t o pr o gressi o n
T T R
ti me t o res p o nse
U C
ur ot helial carci n o ma
U K
U nite d Ki n g d o m
UI F E
uri ne i m m u n ofi xati o n electr o p h oresis
U L N
u p per li mit of n or mal
U P E P
uri ne pr otei n electr o p h oresis
U P M
u nit pr o ba bilit y  mass
U S
U nite d States
U S PI
U nite d States pac ka ge i nsert
U V B
ultra vi olet B 
V C N
vect or c o p y n u m ber
V G P R
ver y  g o o d partial res p o nse
V ss
v ol u me of distri b uti o n at stea d y  state
V ss/ F
a p pare nt v ol u me of distri b uti o n after n o n -i ntra ve n o us 
a d mi nistrati o n
W B C
w hite bl o o d cell 
w ks
Wee ks
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0 9
A p pe n di x 2. T H E I N T E R N A TI O N A L M Y E L O M A W O R KI N G G R O U P (I M W G) 
R E S P O N S E C RI T E RI A F O R M U L TI P L E M Y E L O M A 
All res p o nse cate g ories re q uire t w o c o nsec uti ve assess me nts ma de a n y ti me bef ore starti n g 
a n y ne w t hera p y.  Patie nts m ust ha ve meas ura ble disease at e nr oll me nt (st u d y e ntr y).  
Meas ura ble disease is defi ne d as: 

Ser u m M -pr otei n 0. 5 g/ d L ( 5 g/ L); ( See i ncl usi o n criteria f or m o dificati o ns);

Uri ne M -pr otei n 2 0 0 m g / 2 4 h;

Ser u m F L C assa y : i n v ol ve d F L C le vel 1 0 m g / d L pr o vi de d ser u m F LC rati o is 
a b n or mal.
W he ne ver m ore t ha n o ne para meter is use d t o assess res p o nse, t he o verall assi g ne d le vel of 
res p o nse is deter mi ne d b y t he l o wer or l o west le vel of res p o nse.  Patie nts will c o nti n ue i n t he 
last c o nfir me d res p o nse cate g or y u ntil t here is c o nfir mati o n of pr o gressi o n or i m pr o ve me nt 
t o a hi g her res p o nse stat us; patie nts ca n n ot m o ve t o a l o wer res p o nse cate g or y.
Res p o nse
I M W G Criteri a
Stri n ge nt 
C o m plete 
Res p o nse (s C R) 

C o m plete res p o nse as defi ne d bel o w pl us n or mal free li g ht c hai n 
( F L C) rati o a n d a bse nce of cl o nal cells i n b o ne marr o w bi o psy b y 
i m m u n o hist oc he mistr y ( κ/rati o ≤4: 1 or ≥1: 2 f or κ a n d patie nts, 
res pecti vely, after c o u nti n g ≥1 0 0 plas ma cells) .2

I n patie nts w here by t he o nl y  meas ura ble disease is b y ser u m F L C 
le vels, s C R is defi ne d as n or mal F L C rati o of 0. 2 6 t o 1. 6 5 pl us 
a bse nce of cl o nal cells i n b o ne marr o w as defi ne d a b o ve.
C o m plete 
R es p o nse ( C R)

Ne gati ve i m m u n ofi xati o n o n t he ser u m a n d uri ne a n d 
disa p peara nce of a n y s oft tiss ue plas mac yt o mas a n d < 5 % plas ma 
cells i n b o ne marr o w as pirates .1

In patie nts w here b y  t he o nl y meas ura ble disease is b y ser u m F L C 
le vels, C R is defi ne d as n or mal F L C rati o of 0. 2 6 t o 1. 6 5 pl us 
criteria liste d a b o ve.
V er y G o o d 
P artial R es p o nse 
( V G P R) 

Ser u m a n d uri ne M -pr otei n detecta ble b y  i m m u n ofi xati o n b ut n ot 
o n elect r o p h oresis.
or

9 0 % re d ucti o n i n ser u m M- pr otei n pl us uri ne M -pr otei n le vel 
< 1 0 0 m g/ 2 4 hr.

I n patie nts w here by t he o nl y  meas ura ble disease is b y ser u m F L C 
le vels, V G P R is defi ne d as a > 9 0 % decrease i n t he differe nce 
bet wee n i n v ol ve d (t u m or) a n d u ni n v ol ve d ( n o n-t u m or) ser u m F LC 
le vels.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 0
Res p o nse
I M W G Criteri a
Partial Res p o nse 
( P R)

5 0 % re d ucti o n of ser u m M -pr otei n a n d re d ucti o n i n 2 4 h o urs 
uri nar y  M-pr otei n b y  9 0 % or t o < 2 0 0 m g / 2 4 hr.

If t he ser u m a n d uri ne M-pr otei n are u n meas ura ble, 4 a 
≥5 0 % decrease i n t he differe nce bet wee n i n v ol ve d a n d u ni n v ol ve d 
F L C le vels is re q uire d i n place of t he M- pr otei n criteria.

I n patie nts w here by t he o nl y  meas ura ble disease is b y ser u m F L C 
le vels, P R is defi ne d as 5 0 % re d ucti o n i n differe nce bet wee n 
i n v ol ve d a n d u ni n v ol ve d F LC.

I n a d diti o n t o t hese criteria, if prese nt at baseli ne, a 5 0 % 
re d ucti o n i n t he size ( S P D)2 of s oft tiss ue plas mac y t o mas is als o 
re q uire d.  
Mi ni mal 
Res p o nse ( M R)
≥2 5 % b ut ≤4 9 % re d ucti o n of ser u m M -pr otei n a n d re d ucti o n i n 2 4 - h 
uri ne M -pr otei n b y 5 0 – 8 9 %.  I n a d diti o n t o t he a b o ve liste d criteria, if 
prese nt at baseli ne, a 5 0 % re d ucti o n i n t he size (s u m of t he pr o d ucts 
of t he ma xi mal per pe n dic ular dia meters of meas ure d lesi o ns [ S P D]) 3
of s oft tiss ue plas ma c yt o mas is als o re q uire d.
N o 
C ha n ge/ Sta ble 
D isease ( S D)
N ot meeti n g criteria f or C R, V G P R, P R, M R or pr o gressi ve disease .
Pr o gressi ve 
D isease ( P D)5
A n y  o ne or m ore of t he f oll o wi n g criteria:

I ncrease of 2 5 % fr o m l o west res p o nse val ue i n a n y  o ne or m ore 
of t he f oll o wi n g:

Ser u m M -c o m p o ne nt a n d/ or (t he a bs ol ute i ncrease m ust be 
0. 5 g/ d L); 4

Ser u m M -pr otei n i ncrease 1 g/ d L, if t he l o west M c o m p o ne nt 
was 5 g/ d L;

Uri ne M -c o m p o ne nt a n d/ or (t he a bs ol ute i ncrease m ust be 
2 0 0 m g/ 2 4 hr.

I n patie nts wit h o ut meas ura ble ser u m a n d uri ne M-pr otei n 
le vels, t he differe nce bet wee n i n v ol ve d a n d u ni n v ol ve d F L C 
le vels (a bs ol ute i ncrease m ust be > 1 0 m g/ d L);

A p peara nce of a ne w lesi o n(s), 5 0 % i ncrease fr o m na dir i n S P D 1
of > 1 lesi o n, or 5 0 % i ncrease i n t he l o n gest dia meter of a 
pre vi o us lesi o n > 1 c m i n s h ort a xis .
Cli nical Rela pse
Cli nical rela pse re q uires o ne or m ore of t he f oll o wi n g criteria:
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 1
Res p o nse
I M W G Criteri a

Direct i n dicat ors of i ncreasi n g disease a n d/ or e n d or ga n 
d y sf u ncti o n ( C R A B feat ures) relate d t o t he u n derl yi n g cl o nal 
plas ma -cell pr oliferati ve dis or der; 

De vel o p me nt of ne w s oft tiss ue plas mac y t o mas or b o ne 
lesi o ns ( oste o p or otic fract ures d o n ot c o nstit ute pr o gressi o n);

Defi nite i ncrease i n t he size of e xisti n g plas mac yt o mas or 
b o ne lesi o ns.  A defi nite i ncrease is defi ne d as a 5 0 % (a n d 
≥1 c m) i ncrease as meas ure d seriall y b y t he S P D 3 of t he 
meas ura ble lesi o n;

H y percalce mia ( > 1 1 m g / d L);

Decrease i n he m o gl o bi n of ≥2 g/ d L n ot relate d t o t hera p y or 
ot her n o n -m y el o ma-relate d c o n diti o ns;

Rise i n ser u m creati ni ne b y  2 m g / d L or m ore fr o m t he start of 
t he t hera py a n d attri b uta ble t o m y el o ma;

H y per visc osit y relate d t o ser u m para pr otei n.
C R A B feat ures =calci u m ele vati o n, re nal fail ure, a ne mia, l ytic b o ne lesi o ns; I M W G =I nter nati o nal M yel o ma 
W or ki n g Gr o u p; F L C =free li g ht c hai n; M -pr otei n = m yel o ma pr otei n; S P D =s u m of t he pr o d ucts of t he 
ma xi mal per pe n dic ular dia meters of meas ure d lesi o ns.
F o ot n otes:
1.
C o nfir mati o n wit h re peat b o ne marr o w  bi o ps y n ot re q uire d.  Caref ul atte nti o n s h o ul d be gi ve n t o ne w 
p ositi ve i m m u n ofi xati o n res ults a p peari n g i n patie nts w h o ha ve ac hie ve d a c o m plete res p o nse, w he n
t he is ot y pe is differe nt.  T his pr o ba bl y re prese nts oli g ocl o nal i m m u ne rec o nstit uti o n a n d s h o ul d n ot be 
c o nf use d wit h rela pse; t hese ba n ds t y picall y disa p pear o ver ti me.
2.
Prese nce/a bse nce of cl o nal cells o n i m m u n o hist oc he mistr y is base d u p o n t he κ/ / L rati o.  A n a b n or mal 
κ/ rati o b y i m m u n o hist oc he mistr y re q uires a mi ni m u m of 1 0 0 plas ma cells f or a nal ysis.  A n a b n or mal 
rati o reflecti n g prese nce of a n a b n or mal cl o ne is κ/of > 4: 1 or < 1: 2.
3.
Plas mac yt o ma meas ure me nts s h o ul d be ta ke n fr o m t he C T p orti o n of t he P E T/ C T, or de dicate d C T 
sca ns w here a p plica ble.  Meas ure me nt of t u m or size will be deter mi ne d b y t he S P D.
4.
All rela pse cate g ories re q uire t w o c o nsec uti ve assess me nts ma de at a n y ti me bef ore classificati o n as 
rela pse or disease pr o gressi o n a n d/ or t he i nstit uti o n of a n y ne w t hera p y.  T o c o nfir m res p o nse or 
pr o gressi ve disease, t w o discrete sa m ples are re q uire d a n d testi n g ca n n ot be base d u p o n t he s plitti n g of 
a si n gle sa m ple.   I n t he I M W G criteria, C R patie nts m ust als o meet t he criteria f or pr o gressi ve disease 
s h o w n here t o be classifie d as pr o gressi ve disease f or t he p ur p oses of calc ulati n g ti me t o pr o gressi o n 
a n d pr o gressi o n -free s ur vi val.  T he defi niti o ns of rela pse, cli nical rela pse a n d rela pse fr o m C R are n ot 
t o be use d i n calc ulati o n of ti me t o pr o gressi o n or pr o gressi o n free s ur vi val.   Patie nts will be 
c o nsi dere d t o ha ve pr o gressi ve disease if t he y meet t he criteria f or pr o gressi o n b y a varia ble t hat was 
n ot c o nsi dere d meas ura ble at baseli ne; h o we ver, f or patie nts w h o ha d a meas ura ble ser u m or uri ne 
M -s pi ke at baseli ne, pr o gressi o n ca n n ot be defi ne d b y i ncreases i n ser u m F L C al o ne.
5.
F or pr o gressi ve disease, ser u m M -c o mp o ne nt i ncreases of ≥1 m g/ d L are s ufficie nt t o defi ne rela pse if 
starti n g M-c o mp o ne nt is ≥5 g/ d L.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 2
A p pe n di x 3. I M W G MI NI M A L R E SI D U A L DI S E A S E
( M R D) Criteri a
Assess f or M R D (at least b y  ce ntrall y c ollecte d fl o w c yt o metr y a n d se q ue nci n g) f or all b o ne 
marr o w as pirates o btai ne d w hile a patie nt is i n s us pecte d or act ual C R . C o nfir mati o n wit h 
t w o c o nsec uti ve assess me nts is n ot re q uire d.
Res p o nse
I M W G Criteri a
S ustai ne d 
M R D - ne gati ve 1
M R D ne gati vit y  i n t he marr o w (N G S ) a n d by i ma gi n g as defi ne d 
bel o w, c o nfir me d mi ni m u m of 1 y ear a part.  S u bse q ue nt e val uati o ns 
ca n be use d t o f urt her s pecif y  t he d urati o n of ne gati vit y 
(e g, M R D -ne gati ve at 5 y ears).
Fl o w 
M R D -ne gati ve 2
A bse nce of p he n ot y picall y a berra nt cl o nal plas ma cells b y N G F ‡ o n 
b o ne marr o w as pirates usi n g t he E ur o Fl o w sta n dar d o perati o n 
pr oce d ure f or M R D detecti o n i n m ulti ple m y el o ma ( or vali date d 
e q ui vale nt met h o d) wit h a mi ni m u m se nsiti vit y  of 1 i n 1 0 5 n ucleate d 
cells or hi g her.
Se q ue nci n g
M R D -ne gati ve
A bse nce of cl o nal plas ma cells b y N G S o n b o ne marr o w as pirate i n 
w hic h prese nce of a cl o ne is defi ne d as less t ha n t w o i de ntical 
se q ue nci n g rea ds o btai ne d after D N A se q ue nci n g of b o ne marr o w 
as pirates usi n g t he L ym p h o SI G H T platf or m ( or vali date d e q ui vale nt 
met h o d) wit h a mi ni m u m se nsiti vit y  of 1 i n 1 05 n ucleate d cells or 
hi g her .
I ma gi n g-p ositi ve
M R D -ne gati ve
M R D ne gati vit y  as defi ne d b y N G S pl us disa p peara nce of e ver y area 
of i ncrease d tracer u p ta ke f o u n d at baseli ne or a prece di n g P E T/ C T or 
decrease t o less me diasti nal bl o o d p o ol S U V or decrease t o less t ha n 
t hat of s urr o u n di n g n or mal tiss ue.
C T = c o m p ute d t o m o gra p h y; I M W G =I nter nati o nal M yel o ma W or ki n g Gr o u p; M R D = m i ni mal resi d ual 
disease; N G F = ne xt -ge nerati o n fl o w c yt o metr y; N G S = ne xt ge nerati o n se q ue nci n g; p ositr o n e missi o n 
t o mo gra p h y = P E T; S U V = sta n dar dize d u pta ke val ue.
F o ot n otes
1.
S ustai ne d M R D ne gati vit y, w he n re p orte d, s h o ul d als o a n n otate t he met h o d use d (e g, s ustai ne d 
se q ue nci n g M R D- ne gati ve).
2.
B o ne marr o w  m ulti para metric fl o w  c yt o metr y M F C s h o ul d f oll o w  N G F g ui deli nes.  T he refere nce 
N G F met h o d is a n ei g ht -c ol or t wo- t u be a p pr oac h, w hic h has bee n e xte nsi vel y vali date d.  T he t w o -t u be 
a p pr oac h i m pr o ves relia bilit y, c o nsiste nc y, a n d se nsiti vit y beca use of t he ac q uisiti o n of a greater 
n u m ber of cells.  T he c o m plete ei g ht -c ol or met h o d s h o ul d use a l y o p hilize d mi xt ure of a nti b o dies.  
5 mi lli o n cells s h o ul d be assesse d.  T he met h o d e m pl o ye d s h o ul d ha ve a se nsiti vit y of detecti o n of at 
least 1 i n 1 0 5 plas ma cells.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 4
A p pe n di x 5. C R S A N D I C A N S MI TI G A TI O N A N D M A N A G E M E N T
C R S is a n o n -a nti ge n-s pecific c yt o ki ne-ass ociate d t o xicit y t hat occ urs as a res ult of 
hi g h -le vel i m m u ne acti vati o n.  C R S is a p ote ntiall y life-t hreate ni n g t o xicit y t hat has bee n 
o bser ve d f oll o wi n g a d mi nistrati o n of i m m u ne -base t hera pies f or ca ncer (a nti b o dies a n d 
a d o pti ve T-cell t hera pies).  C R S is li kel y t o be a c o m m o n t o xicit y t hat ca n be ma na ge d 
t hr o u g h s u p p orti ve care a n d a nti-c yt o ki ne i nter ve nti o ns. 
I n cases of s us pecte d c yt o ki ne release sy n dr o me, a ser u m sa m ple s h o ul d be pr o vi de d f or 
c yt o ki ne release assa y  a nal ysis b y t he l ocal la b (see Secti o n 7. 1. 3 ) s o as l o n g as t he sa m pli n g 
d oes n ot i nterfere w it h t he me dical treat me nt of t he patie nt.
Earl y i nter ve nti o n s h o ul d be u n derta ke n at t he first si g n of C R S; si g ns ma y  i ncl u de pyre xia, 
tac hycar dia, tac h y p nea a n d/ or h y p ote nsi o n a n d are te m p orall y relate d t o P F -0 6 8 6 3 1 3 5 i n t he 
a bse nce of alter nati ve eti ol o gies.  
T he ori gi nal C R S gra di n g s ys te m pr o p ose d by Lee et al i n 2 0 1 4 2 (Ta ble 1 3) s h o ul d be use d
o nl y  f or t he p ur p oses of gra di n g of C R S o n t he a d verse e ve nt case re p ort f or m ( C R F) , b ut n ot 
f or ma na ge me nt of C R S. Gra di n g b y  t he m ore rece nt A S T C T C R S criteria 3 (Ta ble 1 5 ) will 
be ca pt ure d al o n g wit h t he Lee et al 2 0 1 4 criteria o n t he C R S C R F , a n d ma na ge me nt 
g ui deli nes will f oll o w A S T C T C R S gra di n g. T hese treat me nt g ui deli nes3 9 ma y  be m o difie d 
as nee de d b y t he res p o nsi ble I n vesti gat or acc or di n g t o t he best practices at t heir i nstit ute .
T a ble 1 3.
Lee et al 2 0 1 4 C R S re vise d gr a di n g s yste m 2
T o xicit y 
Gr a de
C h ar acteristics
1
S y m pt o ms are n ot life t hreate ni n g a n d re q uire s y m pt o matic treat me nt 
o nl y , e g, Fe ver, na usea, fati g ue, hea dac he, m y al gia, malaise .
2
Gra de 2 h y p o xia * [ decrease d o x y ge n sat urati o n wit h acti vit y  (e g, p ulse 
o xi meter < 8 8 %); i nter mitte nt s u p ple me ntal o x yge n] ; or
H y p ote nsi o n res p o nsi ve t o fl ui ds or l o w - d ose of o ne vas o press or 
(Ta ble 1 4 ) or Gra de 2 or ga n t o xicit y .
3
Gra de 3 h y p o xia * [ decrease d o x y ge n sat urati o n at rest (e g, p ulse 
o xi meter < 8 8 % or partial press ure of o x y ge n ( Pa O 2) < = 5 5 m m H g)] ; or 
H y p ote nsi o n re q uiri n g hi g h -d ose vas o press ors or m ulti ple vas o press ors 
(Ta ble 1 4 ); or 
Gra de 3 or ga n t o xicit y  (e xce pt tra nsa mi nitis); or 
Gra de 4 tra nsa mi nitis .
4
Life -t hreate ni n g sy m pt o ms ;
Gra de 3 h y p o xia * [ decrease d o x y ge n sat urati o n at rest (e g, p ulse 
o xi meter < 8 8 % or partial press ure of o x y ge n ( Pa O 2) < = 5 5 m m H g)] or 
Gra de 4 or ga n t o xicit y  (e xcl u di n g tra nsa mi nitis).
5
D eat h.
* M o dificati o n t o t he Lee et al C R S Re vise d Gra di n g S yste m acc or di n g t o t he C T C A E v 4. 0 3.  Tra nsie nt 
decreases i n o x y ge n le vels bel o w  8 8 % will n ot be c o nsi dere d t o ha ve met t he criteria.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 5
T he defi niti o ns f or hi g h -d ose vas o press ors are s h o w n i n Ta ble 1 4.
T a ble 1 4.
Defi niti o n of Hi g h D ose V as o press or
Press or
Hi g h D ose
( d oses less t ha n t hese w o ul d be c o nsi dere d l o w)
N ore pi ne p hri ne m o n ot hera p y
2 0 g/ mi n
D o pa mi ne m o n ot hera p y
1 0 g/ k g/ mi n
P he n y le p hri ne m o n ot hera p y
2 0 0 g/ mi n
E pi ne p hri ne m o n ot hera p y
1 0 g/ mi n
If o n vas o pressi n
Vas o pressi n + n ore pi ne p hri ne
e q ui vale nt of 1 0 g/ mi n *
If o n c o m bi nati o n vas o press ors
( n ot vas o pressi n)
N ore pi ne p hri ne e q ui vale nt of
2 0 g/ mi n *
* V A S S T Tri al v as o press or e q uiv ale nt e q u ati o n: n ore pi ne p hri ne e q uiv ale nt d ose = [ n ore pi ne p hri ne
(g/ mi n) ]
+ [ d o p a mi ne ( g/k g/ mi n) ÷ 2] + [e pi ne p hri ne ( g/ mi n) ] + [ p he nyle p hri ne ( g/ mi n) ÷ 1 0
T a ble 1 5 . A S T C T C R S re vise d gr a di n g s yste m 3
C R S p ar a meter:
Fe ver *
Wit h H y p ote nsi o n
A n d/ or † H y p o xi a
Gra de 1
T e m p. ≥3 8 °C
N o ne
N o ne
Gra de 2
T e m p. ≥3 8 ° C
N ot re q uiri n g vas o press ors
Re q uiri n g l o w -fl o w‡ nasal 
ca n n ula, l o w-fl o w‡ face mas k or 
bl o w -b y
Gra de 3
T e m p. ≥3 8 ° C
Re q uiri n g a vas o press or wit h or 
wit h o ut vas o pressi n
Re q uiri n g hi g h -fl o w‡ nasal 
ca n n ula, hi g h -fl o w‡ face mas k, 
n o nre breat her mas k, or Ve nt uri 
mas k
Gra de 4
T e m p. ≥3 8 ° C
Re q uiri n g m ulti ple vas o press ors 
(e xcl u di n g vas o pressi n)
Re q uiri n g p ositi ve press ure (e g, 
C P A P, Bi P A P, i nt u bati o n a n d 
mec ha nical ve ntilati o n)
Or ga n t o xicities ass ociate d wit h C R S s h o ul d still be gra de d acc or di n g t o C T C A E v 4. 0 3 a n d d o n ot 
i nfl ue nce C R S gra di n g.
* Fe ver is defi ne d as t e mperat ure ≥3 8 °C a n d n ot attri b uta ble t o a n y ot her ca use. I n patie nts w h o ha ve 
C R S t he n recei ve a nti p yretic or a ntic yt o ki ne t hera p y s uc h as t ociliz u ma b or ster oi ds, fe ver is n o l o n ger 
re q uire d t o gra de s u bse q ue nt C R S se verit y. I n t his case, C R S gra di n g is dri ve n b y h y p ote nsi o n a n d/ or 
h y p o xia.
† C R S gra de is deter mi ne d b y t he m ore se vere e ve nt: h y p ote nsi o n or h y p o xia n ot attri b uta ble t o a n y ot her 
ca use. F or e xa m ple, a patie nt wit h te m perat ure of 3 9. 5 °C h y p ote nsi o n re q uiri n g 1 vas o press or, a n d 
h y p o xia re q uiri n g l o w -fl o w nasal ca n n ula is classifie d as gra de 3 C R S.
‡ L o w -fl o w nasal ca n n ula or face mas k is defi ne d as o x y ge n deli vere d at ≤6 L/ mi n.  L o w fl o w  als o 
i ncl u des bl o w-b y  o x y ge n deli ver y, s o meti mes use d i n pe diatrics.  Hi g h-fl o w nasal ca n n ula or face mas k
is defi ne d as o x y ge n deli vere d at > 6 L/ mi n.  T his is m o difie d fr o m ori gi nal A S T C T criteria t o 
differe ntiate bet wee n l o w -fl o w a n d hi g h-fl o w face mas k.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 6
C R S m a n a ge me nt g ui deli nes
3 8 ,3 9
A S T C T Gr a de 1 C R S:

M o nit or vital si g ns f or w orse ni n g of c o n diti o n .
Fe ver

Aceta mi n o p he n/ paraceta m ol a n d h y p ot her mia bla n ket f or t he treat me nt of fe ver .

N o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds) s uc h as i b u pr ofe n ca n be use d 
as sec o n d treat me nt o pti o n f or fe ver if n ot c o ntrai n dicate d.

Assess f or i nfecti o n usi n g bl o o d a n d uri ne c ult ures, a n d c hest ra di o gra p h y.

E m piric br oa d -s pectr u m a nti bi otics a n d filgrasti m if ne utr o pe nic .

Mai nte na nce I V fl ui ds f or h ydrati o n .

S y m pt o matic ma na ge me nt of c o nstit uti o nal s y m pt o ms or or ga n t o xicit y .

C o nsi der t ociliz u ma b 8 m g/ k g * I V or silt u xi ma b 1 1 m g/ k g I V f or persiste nt 
(lasti n g > 3 da ys) a n d refract or y fe ver.
A S T C T Gr a de 2 C R S:

M o nit or vital si g ns e ver y 4
h o urs f or w orse ni n g of c o n diti o n.
Fe ver

Ma na ge as i n Gra de 1 C R S .
H y p ote nsi o n

I V fl ui d b ol us of 5 0 0-1 0 0 0 ml of n or mal sali ne . Ca n gi ve sec o n d I V fl ui d b ol us if 
s yst olic bl o o d press ure re mai ns < 9 0 m m H g.

C o nsi der t ociliz u ma b 8 m g/ k g ( ma xi m u m d ose 8 0 0 m g) I V or silt u xi ma b 
1 1 m g/ k g I V f or treat me nt of h y p ote nsi o n refract or y  t o fl ui d b ol uses; t ocilizu ma b 
ca n be re p eate d after 6 h if nee de d .

If hy p ote nsi o n persists after 2 fl ui d b ol uses a n d a nti -I L-6 t hera p y, start 
vas o press ors, c o nsi der tra nsfer t o i nte nsi ve care u nit (I C U), o btai n 
ec h ocar di o gra m ( E C H O), a n d i nitiate ot her met h o ds of he m o d yna mic m o nit ori n g .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 7

I n patie nts at hi g h-ris k ( b ul k y disease, ol der a ge or c o m or bi dities) or if 
h y p ote nsi o n persists after 1 -2 d oses o f a nti-I L-6 t hera p y , de xa met has o ne ca n be 
use d at 1 0 m g I V e ver y 6 hrs.
H y p o xi a

S u p ple me ntal o x y ge n .
T ociliz u ma b or silt u xi ma b ± c ortic oster oi ds a n d s u p p orti ve care, as i n dicate d f or 
h y p ote nsi o n .
A S T C T Gr a de 3 C R S:

M o nit or patie nt (i ncl u di n g c o nti n u o us E C G
m o nit ori n g) i n a n I C U a n d o btai n E C H O 
if n ot d o ne alrea dy.
Fe ver

Ma na ge as i n Gra de 1 C R S.
H y p ote nsi o n

I V b ol uses, as nee de d, as rec o m me n de d f or Gra de 2 C R S.

T ociliz u ma b a n d silt u xi ma b as rec o m me n de d f or Gra de 2 C R S if n ot 
a d mi nistere d pre vi o usl y.

Vas o pr ess ors as nee de d.

De xa met has o ne 1 0 m g I V e ver y 6 hrs; if refract or y, i ncrease t o 2 0 m g I V e ver y 
6 hrs .
H y p o xi a

S u p ple me ntal o x y ge n i ncl u di n g hi g h -fl o w o xy ge n deli ver y.

T ociliz u ma b or silt u xi ma b pl us c ortic oster oi ds a n d s u p p orti ve care, as descri be d 
a b o ve.
A S T C T Gr a de 4 C R S:

M o nit or patie nt (i ncl u di n g c o nti n u o us E C G m o nit ori n g) i n a n I C U a n d o btai n E C H O 
if n ot d o ne alrea dy.
Fe ver

Ma na ge as i n Gra de 1 C R S.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 8
H y p ote nsi o n

I V b ol uses, a nti-I L-6 t hera p y , vas o press ors, a n d he m o d yna mic m o nit ori n g as 
rec o m me n de d f or gra de 3 C R S .

Met h y l pre d nis ol o ne 1 g/ da y IV .
H y p o xi a

S u p ple me ntal o x y ge n via p ositi ve press ure/ mec ha nical ve ntilati o n .

T ociliz u ma b or silt u xi ma b pl us c ortic oster oi ds a n d s u p p orti ve care, as descri be d 
a b o ve.
I m m u ne effect or cell- ass oci ate d ne ur ot o xicit y s y n dr o me (I C A N S)
Alt h o u g h less c o m m o nl y see n t ha n C R S, I CA N S has bee n o bser ve d wit h s o me T- cell 
directe d t hera pies a n d ma y  ma nifest as deliri u m, e nce p hal o pat h y, a p hasia, let har g y, diffic ulty 
c o nce ntrati n g, a gitati o n, tre m or, seiz ures, a n d cere bral e de ma. 3 If I CA N S is o bser ve d i n 
relati o n t o P F-0 6 8 6 3 1 3 5, t he A S T C T criteria 3 s h o ul d be f oll o we d f or its gra di n g a n d 
ma na ge me nt .3 8 ,3 9 T hese treat me nt g ui deli nes ma y be m o difie d as nee de d b y t he res p o nsi ble 
I n vesti gat or acc or di n g t o t he best practices at t heir i nstit ute.
T a ble 1 6.
I m m u ne Effect or Cell-Ass oci ate d E nce p h al o p at h y (I C E) Sc ore
C ate g or y
T as k
P oi nts
Orie ntati o n
Orie ntati o n t o y ear, m o nt h, cit y, h os pital
4
Na mi n g
A bilit y  t o na me 3 o bjects
3
F oll o wi n g c o m ma n ds
A bilit y  t o f oll o w si m ple c o m ma n ds
1
Writi n g
A bilit y  t o write a sta n dar d se nte nce
1
Atte nti o n
A bilit y  t o c o u nt bac k war ds fr o m 1 0 0 b y 1 0
1
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1 9
T a ble 1 7.
A S T C T I C A N S Gr a di n g
Ne ur ot o xicit y 
D o m ai n
Gr a de 1
Gr a de 2  
Gr a de 3
Gr a de 4
I C E sc ore*
7 - 9
3- 6 
0- 2
0 ( u nar o usa ble a n d 
u na ble t o perf or m 
I C E)
De presse d le vel 
of 
c o nsci o us ness †
A wa ke ns 
s p o nta ne o usl y
A wa ke ns 
t o v oice
A wa ke ns o nl y t o 
tactile sti m ul us
U nar o usa ble or 
re q uires vi g or o us or 
re petiti ve tactile 
sti m uli t o ar o use. 
St u p or or c o ma
Seiz ure
N/ A  
N/ A
A n y  cli nical 
seiz ure t hat 
res ol ves ra pi dly
or n o n -
c o n v ulsi ve 
seiz ures o n E E G 
t hat res ol ve wit h 
i nter ve nti o n
Life -t hreate ni n g 
pr ol o n ge d seiz ure 
( > 5 mi n); or re petiti ve
cli nical or electrical 
seiz ures wit h o ut ret ur n 
t o baseli ne i n bet wee n
M ot or fi n di n gs ‡
N/ A  
N/ A  
N/ A
Dee p f ocal m ot or 
wea k ness s uc h as 
he mi paresis or 
para paresis
Ele v ate d 
I C P/cere br al 
e de m a
N/ A  
N/ A
F ocal/l ocal 
e de ma o n 
ne ur oi ma gi n g ⁂
Diff use cere bral 
e de ma o n 
ne ur oi ma gi n g; 
decere brate or 
dec orticate p ost uri n g; 
or cra nial ner ve VI
(a b d uce ns ner ve )
pals y ; or pa pille de ma; 
or C us hi n g’s tria d
I C A N S gra de is deter mi ne d b y t he m ost se vere e ve nt (I C E sc ore, le vel of c o nsci o us ness, seiz ure, m ot or 
fi n di n gs, raise d i ntracra nial press ure[I C P]/cere bral e de ma) n ot attri b uta ble t o a n y ot her ca use; f or e xa m ple, a 
patie nt wit h a n I C E sc ore of 3 w h o has a g e neralize d seiz ure is classifie d as gra de 3 I C A N S.
* A patie nt wit h a n I C E sc ore of 0 ma y be classifie d as gra de 3 I C A N S if a wa ke wit h gl o bal a p hasia, b ut a 
patie nt wit h a n I C E sc ore of 0 ma y be classifie d as gra de 4 I C A N S if u nar o usa ble.
† De presse d le vel of  c o nsci o us ness s h o ul d be attri b uta ble t o n o ot her ca use (e g, n o se dati n g me dicati o n).
‡ Tre m ors a n d m y ocl o n us ass ociate d w it h i m m u ne effect or cell t hera pies ma y be gra de d acc or di n g t o 
C T C A E v 4. 0 3, b ut t he y d o n ot i nfl ue nce I C A N S gra di n g.
⁂
I ntracra nial he m orr ha ge wit h or wit h o ut ass ociate d e de ma is n ot c o nsi dere d a ne ur ot o xicit y feat ure a n d is 
e xcl u de d fr o m I C A N S gra di n g. It ma y be gra de d acc or di n g t o C T C A E v 4. 0 3.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 0
I C A N S M a n a ge me nt g ui deli nes
3 8 ,3 9
A S T C T I C A N S Gr a de 1 :

Vi gila nt s u p p orti ve care; as pirati o n preca uti o ns; i ntra ve n o us (I V) h y drati o n .

Wit h h ol d oral i nta ke of f o o d, me dici nes, a n d fl ui ds, a n d assess s wall o wi n g .

C o n vert all oral me dicati o ns a n d/ or n utriti o n t o I V if s wall o wi n g is i m paire d .

A v oi d me dicati o ns t hat ca use ce ntral ner v o us s ys te m de pressi o n.

Ne ur ol o g y  c o ns ultati o n.

E val uate ele vate d i ntracra nial press ure (I C P), if s us pecte d, wit h f u n d osc o pic e xa m f or 
pa pille de ma a n d l u m bar p u nct ure f or cere br os pi nal fl ui d o pe ni n g press ure.

M a g netic res o na nce i ma gi n g (M RI )M RI of t he brai n wit h a n d wit h o ut c o ntrast; C T 
sca n of t he brai n ca n be perf or me d if M RI of t he brai n is n ot feasi ble.

Dail y  3 0 mi n electr oe nce p hal o gra m ( E E G) u ntil to xicit y  sy m pt o ms res ol ve; if n o 
seiz ures are detecte d o n E E G, c o nti n ue le vetiraceta m 7 5 0 m g e ver y 1 2 hrs.

C o nsi der a nti -I L-6 t hera p y  wit h t ociliz u ma b 8 m g/ k g ( ma xi m u m 8 0 0 m g) I V or 
silt u xi ma b 1 1 m g/ k g I V, if t here is c o nc urre nt C R S .
A S T C T I C A N S Gr a de 2 :

S u p p orti ve care a n d ne ur ol o gical w or k -u p as descri be d f or gra de 1 I C A N S .

A nti- I L-6 t hera p y  if ass ociate d wit h c o nc urre nt C R S, as descri be d f or gra de 1 IC A N S 
a n d if n ot a d mi nistere d pre vi o usl y .

De xa met has o ne 1 0 m g I V e ver y 6 h or met h yl pre d nis ol o ne 1 m g/ k g I V e ver y 1 2 h if 
refract or y t o a nti-I L-6 t hera p y , or f or I C A N S wit h o ut c o nc urre nt C R S.

C o nsi der tra nsferri n g patie nt t o i nte nsi ve -care u nit (IC U) if I C A N S ass ociate d wit h 
gra de ≥2 C R S .
A S T C T I C A N S Gr a de 3 :

S u p p orti ve care a n d ne ur ol o gical w or k -u p as i n dica te d f or gra de 1 I CA N S .

I C U tra nsfer is rec o m me n de d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 1

If E E G s h o ws n o n-c o n v ulsi ve stat us e pile ptic us :

Assess air wa y , breat hi n g, a n d circ ulati o n; c hec k bl o o d gl uc ose.

L oraze pa m 0. 5 m g i ntra ve n o usl y  (IV), wit h a d diti o nal 0. 5 m g I V e ver y  5 mi n, as 
nee de d, u p t o a t otal of 2 m g t o c o ntr ol electr o gra p hical seiz ures .

Le vetiraceta m 5 0 0 m g I V b ol us, as well as mai nte na nce d oses .

If seiz ures persist, tra nsfer t o i nte nsi ve-care u nit (I C U) a n d treat wit h 
p he n o bar bital l oa di n g d ose of 6 0 m g I V.

Mai nte na nce d oses after re s ol uti o n of n o n-c o n v ulsi ve stat us e pile ptic us are as 
f oll o ws: l oraze pa m 0. 5 m g I V e ver y 8 h f or t hree d oses; le vetiraceta m 1, 0 0 0 m g 
I V e ver y 1 2 hr; p he n o bar bital 3 0 m g I V e ver y 1 2 hr.

Lac osa mi de ma y  als o be c o nsi dere d f or treat me nt of seiz ures s h o ul d t he seiz ures 
persist b ut s h o ul d n ot be use d i n patie nts wit h c o nc urre nt C R S i n or der t o a v oi d 
arr h yt h mias a n d h y p ote nsi o n .

F or c o n v ulsi ve stat us e pile ptic us :

C o n v ulsi ve stat us e pile ptic us .

Assess air wa y , breat hi n g, a n d circ ulati o n; c hec k bl o o d gl uc ose.

Tra nsfer t o IC U .

L oraze pa m 2 m g I V, wit h a d diti o nal 2 m g I V t o a t otal of 4 m g t o c o ntr ol 
seiz ures.

Le vetiraceta m 5 0 0 m g I V b ol us, as well as mai nte na nce d oses .

If seiz ures persist, a d d p he n o bar bital treat me nt at a l oa di n g d ose of 1 5 m g/ k g I V.

Mai nte na nce d oses after res ol uti o n of c o n v ulsi ve stat us e pile ptic us are: l oraze pa m 
0. 5 m g I V e ver y  8 h f or t hree d oses; le vetiraceta m 1, 0 0 0 m g I V e ver y 1 2 h; 
p he n o bar bital 1 – 3 m g/ k g I V e ver y  1 2 h.

Lac osa mi de ma y  als o be c o nsi dere d f or treat me nt of seiz ures s h o ul d t he seiz ures 
persist b ut s h o ul d n ot be use d i n patie nts wit h c o nc urre nt C R S i n or der t o a v oi d 
arr h yt h mias a n d h y p ote nsi o n .

C o nti n u o us electr oe nce p hal o gra m m o nit ori n g s h o ul d be perf or me d, if seiz ures are 
refract or y t o treat me nt.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 2

Hi g h -d ose met h y l pre d nis ol o ne I V 1 g/ da y  f or f ocal/l ocal e de ma.

A nti- I L-6 t hera p y  if ass ociate d wit h c o nc urrent C R S, as descri be d f or gra de 1 I CA N S 
a n d if n ot a d mi nistere d pre vi o usl y .

C ortic oster oi ds as o utli ne d f or gra de 2 I C A N S if s y m pt o ms w orse n des pite a nti-I L- 6 
t hera py, or f or I C A N S wit h o ut c o nc urre nt C R S; c o nti n ue c ortic oster oi ds u ntil 
i m pr o ve me nt t o gra de 1 I C A N S a n d t he n ta per.
A S T C T I C A N S Gr a de 4 :

S u p p orti ve care a n d ne ur ol o gical w or k -u p as o utli ne d f or gra de 1 I C A N S .

I C U m o nit ori n g; c o nsi der mec ha nical ve ntilati o n f or air wa y pr otecti o n.

A nti- I L-6 t hera p y  a n d re peat ne ur oi ma gi n g as descri be d f or gra de 3 I C A N S.

Hi g h -d ose met h y l pre d nis ol o ne I V 1 g/ da y c o nti n ue d u ntil i m pr o ve me nt t o 
gra de 1 I C A N S a n d t he n ta per; f or e xa m ple, met h yl pre d nis ol o ne I V 1 g/ day f or 
3 da y s, f oll o we d b y ra pi d ta per at 2 5 0 m g e ver y 1 2 h f or 2 da ys, 1 2 5 m g e ver y 1 2 h 
f or 2 da ys, a n d 6 0 m g e ver y 1 2 h f or 2 da ys.

F or seiz ures, treat as descri be d f or gra de 3 I C A N S.

M RI  of t he s pi ne s h o ul d be o btai ne d f or f ocal m ot or wea k ness.

T o ma na g e ele vate d I C P:

Ele vate hea d e n d of t he patie nt's be d t o a n a n gle of 3 0 de gre es.

H y per ve ntilati o n t o ac hie ve tar get partial press ure of arterial car b o n di o xi de 
( Pa C O 2) of 2 8– 3 0 m m H g, b ut mai ntai ne d f or n o l o n ger t ha n 2 4 h rs t o l o wer.

H y per os m olar t hera p y  wit h eit her ma n nit ol ( 2 0 g/ dl s ol uti o n) or h y pert o nic sali ne 
( 3 % or 2 3. 4 %, as detailed bel o w) :

Ma n nit ol: i nitial d ose 0. 5 – 1 g/ k g; mai nte na nce at 0. 2 5 – 1 g/ k g e ver y  6 hrs
w hile m o nit ori n g meta b olic pr ofile a n d ser u m os m olalit y  e ver y 6 hrs, a n d 
wit h h ol d ma n ni t ol if ser u m os m olalit y is ≥3 2 0 m Os m/ k g, or t he os m olalit y  
ga p is ≥4 0 .

H y pert o nic sali ne: i nitial 2 5 0 ml of 3 % h y pert o nic sali ne; mai nte na nce at 
5 0- 7 5 ml/ h w hile m o nit ori n g electr ol yt es e ver y 4 hrs, a n d wit h h ol d i nf usi o n if 
ser u m Na le vels reac h ≥1 5 5 m E q/l .

F or patie nts wit h i m mi ne nt her niati o n: i nitial 3 0 ml of 2 3. 4 % h y pert o nic 
sali ne; re peat after 1 5 mi n, if nee de d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 3

C o nsi der ne ur os ur ger y  c o ns ultati o n f or ve ntric ul o perit o neal s h u nt i n patie nts wit h 
cere bral e de ma a n d I V a nest hetics f or b urst-s u p pressi o n patter n o n E E G.

Meta b olic pr ofili n g e ver y  6 h a n d dail y C T sca n of hea d, wit h a dj ust me nts i n usa ge of 
t he af ore me nti o ne d me dicati o ns t o pre ve nt re b o u n d cere bral oe de ma, re nal fail ure, 
electr ol yt e a b n or malities, h yp o v ole mia, a n d h y p ote nsi o n .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 4
A p pe n di x 6. I N T E R N A TI O N A L M Y E L O M A W O R KI N G G R O U P (I M W G) 
M U L TI P L E M Y E L O M A DI A G N O SI S C RI T E RI A 4 5
Cl o nal b o ne marr o w plas ma cells 1 0 % or bi o ps y -pr o ve n b o n y or e xtra me d ullar y 
plas mac y t o ma a n d a n y o ne or m ore of t he f oll o wi n g myel o ma defi ni n g e ve nts:
1.
E vi de nce of e n d or ga n da ma ge t hat ca n be attri b ute d t o t he u n derl yi n g plas ma cell 
pr oliferati ve dis or der, s pecificall y:
a.
H y percalce mia: ser u m calci u m > 0· 2 5 m m ol/ L  ( > 1 m g/ d L) hi g her t ha n t he u p per 
li mit of n or mal or > 2· 7 5 m m ol/ L  ( > 1 1 m g / d L).
b.
Re nal i ns ufficie nc y : creati ni ne cleara nce < 4 0 m L  per mi n † or ser u m creati ni ne 
> 1 7 7 µ m ol/ L  ( > 2 m g / d L).
c.
A ne mia: he m o gl o bi n val ue of > 2 0 g/ L bel o w t he l o wer li mit of n or mal, or a 
he m o gl o bi n val ue < 1 0 0 g/ L.
d.
B o ne lesi o ns: o ne or m ore oste ol y tic lesi o ns o n s keletal ra di o gra p h y, C T, or 
P E T -C T .‡
2.
A n y  o ne or m ore of t he f oll o wi n g bi o mar kers of mali g na nc y:
e.
Cl o nal b o ne marr o w plas ma cell perce nta ge * 6 0 %.
f.
I n v ol ve d: u ni n v ol ve d ser u m free li g ht c hai n rati o § 1 0 0 > 1 f ocal lesi o ns o n M RI 
st u dies.
P E T -C T = 1 8F -fl u or o de o x y gl uc ose P E T wit h C T. 
* Cl o nalit y s h o ul d be esta blis he d b y s h o wi n g κ /-li g ht-c hai n restricti o n o n fl o w c yt o metr y, 
i m m u n o hist oc he mistr y, or i m m u n ofl u oresce nce.  B o ne marr o w plas ma cell perce nta ge s h o ul d prefera bl y be 
esti mate d fr o m a c ore bi o ps y s peci me n; i n case of a dis parit y bet w ee n t he as pirate a n d c ore bi o ps y, t he 
hi g hest val ue s h o ul d be use d.
† Meas ure d or esti mate d b y vali date d e q uati o ns. 
‡ If b o ne marr o w  has less t ha n 1 0 % cl o nal plas ma cells, m ore t ha n o ne b o ne lesi o n is re q uire d t o disti n g uis h 
fr o m s olitar y plas mac yt o ma wit h mi ni mal marr o w i n v ol ve me nt. 
§ T hese val ues are base d o n t he ser u m freelite assa y ( T he Bi n di n g Site Gr o u p, Bir mi n g ha m, U K).  T he i n v ol ve d 
free li g ht c hai n m ust be 1 0 0 m g/ L.  Eac h f ocal lesi o n m ust be 5 m m or m ore i n size.
Rela pse is defi ne d as pr o gressi o n of disease after a n i nitial res p o nse t o pre vi o us treat me nt, 
m ore t ha n si x m o nt hs after cessati o n of treat me nt.
Refract or y  is defi ne d as resista nce t o treat me nt d ue t o lac k of res p o nse or pr o gressi o n of 
disease d uri n g treat me nt or wit hi n si x m o nt hs after cessati o n of treat me nt. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 5
A p pe n di x 7. M A N A G E M E N T O F I N F U SI O N R E L A T E D R E A C TI O N S, I N C L U DI N G 
A L L E R GI C R E A C TI O N S O R A N A P H Y L A XI S
I n t he e ve nt of i nf usi o n relate d reacti o ns, I n vesti gat ors s h o ul d i nstit ute treat me nt meas ures 
acc or di n g t o best me dical a n d n ursi n g practice.
T he f oll o wi n g treat me nt g ui deli nes s h o ul d be e m pl o y e d:
If c hills a n d fe ver ( > 1 0 0.4 F / 3 8.0 C ) occ ur, t he i nf usi o n s h o ul d be i nterr u pte d.  Patie nts ma y 
be trea te d sy m pt o maticall y  (as descri be d i n Secti o n 5. 5. 2 D ose Dela y ) a n d t he i nf usi o n 
s h o ul d be restarte d at 5 0 % of t he ori gi nal rate. 
H y perse nsiti vit y  reacti o ns:
1.
N CI -C T C A E Gra de 1 aller gic reacti o n :

M o nit or f or w orse ni n g c o n diti o n.  I f t he reacti o n w orse ns, st o p t he i nf usi o n.  
I nstit ute pre me dicati o n f or s u bse q ue nt i nf usi o ns as per Secti o n 5. 5. 2 D ose Dela y . 
2.
N CI -C T C A E Gra de 2 aller gic reacti o n :

St o p P F -0 6 8 6 3 1 3 5 i nf usi o n.

A d mi nister br o nc h o dilat ors, o x y ge n, aceta mi n o p he n, etc. as me dicall y i n dicate d.

Res u me i nf usi o n at 5 0 % of pre vi o us rate o nce reacti o n has decrease d t o Gra de 1 
i n se verit y.  M o nit or cl osel y f or a n y w orse ni n g.  If t he reacti o n rec urs, st o p 
i nf usi o n.  Instit ute pre me dicati o n f or s u bse q ue nt i nf usi o ns as per Secti o n 5. 5. 2
D ose Dela y .
3.
N CI -C T C A E Gra de 3 or Gra de 4 aller gic reacti o n or a na p hyl a xis:

A Gra de 3 a na p h yl a xis ( h yperse nsiti vit y  reacti o n) c o nsists of s ym pt o matic 
br o nc h os pas m re q uiri n g pare nteral me dicati o ns wit h or wit h o ut urticaria, 
aller g y-relate d e de ma/a n gi oe de ma, or hy p ote nsi o n.

A Gra de 4 a na p h yl a xis ( h yperse nsit i vit y reacti o n) is a life-t hreate ni n g e ve nt 
re q uiri n g ur ge nt i nter ve nti o n.
4.
Treat me nt of Gra de 3 or Gra de 4 aller gic reacti o n or a na p h y la xis:

St o p t he P F -0 6 8 6 3 1 3 5 i nf usi o n i m me diatel y  a n d disc o n nect i nf usi o n t u bi n g fr o m 
t he patie nt.

A d mi nister e pi ne p hri ne, br o nc h o dilat ors, a nti hista mi nes, gl uc oc ortic oi ds, 
i ntra ve n o us fl ui ds, vas o press or a ge nts, o x yge n, etc. as me dicall y i n dicate d.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 6

Tele p h o ne S p o ns or or desi g nate d re prese ntati ve t o re p ort a n S A E as per Secti o n 8
A d verse E ve nt Re p orti n g.

F or a N CI -C T C A E Gra de 3 or 4 h y perse nsiti vit y  reacti o n, st u d y treat me nt will be 
disc o nti n ue d.
5.
Re -treat me nt f oll o wi n g Gra de 1 or Gra de 2 a ller gic reacti o ns:

O nce t he P F -0 6 8 6 3 1 3 5 i nf usi o n rate has bee n decrease d d ue t o a n aller gic 
reacti o n or c yt o ki ne release s yn dr o me, it will re mai n decrease d f or all s u bse q ue nt 
i nf usi o ns.

If t he patie nt has a sec o n d reacti o n at t he l o wer i nf usi o n rate, t he i nf usi o n s h o ul d 
be st o p pe d a n d t he patie nt s h o ul d recei ve n o f urt her P F- 0 6 8 6 3 1 3 5.

If t he patie nt e x perie nces a Gra de 3 or 4 aller gic reacti o n or a na p hyl a xis at a n y 
ti me, t he patie nt s h o uld recei ve n o f urt her P F -0 6 8 6 3 1 3 5.

If t here are q uesti o ns c o ncer ni n g w het her a n o bser ve d reacti o n is c o nsiste nt wit h 
a n aller gic reacti o n, c yt o ki ne release sy n dr o me, or a na p h yl a xis, t he me dical 
m o nit or s h o ul d be c o ntacte d i m me diatel y  t o assist wit h gra di n g t he reacti o n.
P K, p har mac o d y n a mic a n d A D A sa m pli n g s h o ul d c o nti n ue as l o n g as t he sa m pli n g d oes n ot 
i nterfere wit h t he me dical treat me nt of t he patie nt.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 8

3 D L Ts - > de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 4 patie nts treate d at c urre nt d ose le vel :

0 D L T -> escalate;

1 D L Ts - > re mai n at t he sa me d ose;

2 D L Ts - > de -escalate;

3- 4 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 5 patie nts treate d at c urre nt d ose le vel :

0 or 1 D L T -> escalate;

2 D L Ts - > re mai n at t he sa me d ose;

3 -5 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 6 patie nts treate d at c urre nt d ose le vel :

0- 1 D L T -> escalate;

2 D L Ts - > re mai n at t he sa me d ose;

3 D L Ts - > de -escalate;

4- 6 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 7 patie nts treate d at
c urre nt d ose le vel :

0- 1 D L T -> escalate;

2- 3 D L Ts - > re mai n at t he sa me d ose;

4 -7 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 8 patie nts treate d at c urre nt d ose le vel :

0 -1 D L T -> escalate;

2 -3 D L Ts - > re mai n at t he sa me d ose;

4 D L Ts -> de -escalate;

5- 8 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2 9

Wit h 9 patie nts treate d at c urre nt d ose le vel :

0- 1 D L T -> escalate;

2 - 4 D L Ts - > re mai n at t he sa me d ose;

5- 9 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wi t h 1 0 patie nts treate d at c urre nt d ose le vel:

0- 1 D L T -> escalate;

2 - 4 D L Ts - > re mai n at t he sa me d ose;

5- 1 0 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 1 1 patie nts treate d at c urre nt d ose le vel :

0 - 1 D L T -> escalate;

2- 4 D L Ts - > re mai n at t he sa me d ose;

5 D L Ts - > de -escalate ( m T PI s u g gests “re mai n at t he sa me d ose”);

6- 1 1 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.

Wit h 1 2 patie nts treate d at c urre nt d ose le vel :

0 -2 D L Ts -> escalate;

3- 5 D L Ts -> re mai n at t he s a me d ose;

6- 1 2 D L Ts -> de -escalate a n d c o nsi der c urre nt d ose as i nt olera ble.
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3 0
A p pe n di x 9. S U B C U T A N E O U S I N J E C TI O N SI T E L O C A TI O N S
I njecti o n site l ocati o ns i ncl u de a ma xi m u m of 8 u ni q ue a d mi nistrati o n sites distri b ute d acr oss 
4 a b d o mi nal q ua dra nts wit h a p ossi bilit y  of u p t o 2 i njecti o n l ocati o ns per q ua dra nt.  
L ocati o n 1 is pr o xi mal t o t he u m bilic us a n d L ocati o n 2 is distal t o t he u m bilic us.
A d mi nister t he re q uire d n u m ber of i njecti o ns i n t he f oll o wi n g or der:
1.
L o wer Left Q ua dra nt L ocati o n 1 ;
2.
L o wer Ri g ht Q ua dra nt L ocati o n 1;
3.
L o wer Left Q ua dra nt L ocati o n 2 ;
4.
L o wer Ri g ht Q ua dra nt L ocati o n 2 ;
5.
U p per Ri g ht Q ua dra nt L ocati o n 1 ;
6.
U p per Left Q ua dra nt L ocati o n 1 ;
7.
U p per Ri g ht Q ua dra nt L ocati o n 2 ;
8.
U p per Left Q ua dra nt L ocati o n 2 .
I njecti o ns t o t he a b d o me n are preferre d.  If S C i njecti o ns i n t he a b d o mi nal l ocati o n are n ot 
p ossi ble, S C i njecti o ns ca n be a d mi nistere d i n a distri b ute d ma n ner i n t he t hi g hs.  S C 
i njecti o ns i n t he u p per e xtre mities (e g, delt oi d, u p per a n d l o wer ar m) are n ot per mitte d.
Trac k t he patie nt’s i njecti o n site (s) se q ue ntiall y o n t his dia gra m wit h a re d pe n a n d mar k t he 
i njecti o n sites o n t he patie nt’s a b d o me n acc or di n g t o yo ur cli nic’s sta n dar d practice.
Rec or d t he l ocati o n, ti me of eac h i njecti o n a n d a n y i njecti o n site reacti o ns i n t he patie nt’s 
s o urce rec or ds a n d st u d y C R F. C o m plete o ne C R F per i njecti o n
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3 1
A p pe n di x 1 0. Alter n ati ve Me as ures D uri n g P u blic E mer ge ncies
T he alter nati ve st u d y meas ures descri be d i n t his secti o n are t o be f oll o we d d uri n g p u blic 
e mer ge ncies, i ncl u di n g t he C O VI D -1 9 pa n de mic. T his a p pe n di x a p plies f or t he d urati o n of 
t he C O VI D-1 9 pa n de mic i n partici pati n g c o u ntries a n d will bec o me effecti ve f or ot her p u blic 
e mer ge ncies o nl y u p o n writte n n otifica ti o n fr o m Pfizer. 
Use of t hese alter nati ve st u d y  meas ures are e x pecte d t o cease u p o n t he ret ur n of b usi ness as 
us ual circ u msta nces (i ncl u di n g t he lifti n g of a n y q uara nti nes a n d tra vel ba ns/a d vis ories). 
Eli gi bilit y
Re gar di n g eli gi bilit y , w hile S A R S-C o V 2 t esti n g is n ot ma n date d f or t his st u d y y o u s h o ul d 
f oll o w l ocal cli nical practice sta n dar ds f or testi n g.  If a partici pa nt has a p ositi ve test res ult 
f or acti ve S A R S -C o V 2 i nfecti o n, is k n o w n t o ha ve as y m pt o matic i nfecti o n or is s us pecte d of 
ha vi n g S A R S -C o V 2, he/s he s h o ul d be e xcl u de d at t his ti me.  Please n ote t he pr ot oc ol
e xcl u des patie nts wit h acti ve i nfecti o ns:
E xcl usi o n Criteria:
4.
Patie nts wit h acti ve u nc o ntr olle d bacterial, f u n gal or viral i nfecti o n, i ncl u di n g k n o w n 
h u ma n i m m u n o deficie nc y vir us ( HI V) i nfecti o n or ac q uire d i m m u n o deficie nc y  
s yn dr o me ( AI D S) relate d ill ness.
W he n t he i nfecti o n res ol ves, t he patie nt c o ul d be c o nsi dere d f or re -scree ni n g, if all o we d b y 
st u d y pr ot oc ol.
Tel e he alt h Visits
I n t he e ve nt t hat i n-cli nic f oll o w- u p st u d y visits ca n n ot be c o n d ucte d w here sa m ple c ollecti o n 
is n ot perf or me d or treat me nt n ot gi ve n, e ver y eff ort s h o ul d be ma de t o f oll o w u p o n t he 
safety of st u d y patie nts at sc he d ule d visits per t he Sc he d ule of Acti vities or u nsc he d ule d 
visits. Tele healt h visits ma y be use d t o c o nti n ue t o assess patie nt safety a n d c ollect data 
p oi nts. Tele healt h i ncl u des t he e xc ha n ge of healt hcare i nf or mati o n a n d ser vices via 
telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, vi de o -c o nfere nci n g s oft ware) re m otel y, 
all o wi n g t he partici pa nt a n d t he i n vesti gat or t o c o m m u nicate o n as pects of cli nical care, 
i ncl u di n g me dical a d vice, re mi n ders, e d ucati o n, a n d safety m o nit ori n g. T he f oll o wi n g 
assess me nts m ust be perf or me d d uri n g a tele healt h visit 

Re vie w a n d rec or d st u d y i nter ve nti o n(s), i ncl u di n g c o m plia nce a n d misse d d oses.

Re vie w a n d rec or d a n y   A Es a n d S A Es si nce t he last c o ntact.  Refer t o Secti o n 8. 1. 4. 2 .

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact .
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3 2

Re vie w a n d rec or d c o ntrace p ti ve met h o d a n d res ults of pre g na nc y testi n g. C o nfir m 
t hat t he patie nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he pr ot oc ol. 
St u d y  p a rtici pa nts m ust be re mi n de d t o pr o m ptl y n otif y site staff a b o ut a ny c ha n ge i n t heir 
healt h stat us.
Alter n ati ve F acilities f or S afet y Assess me nts 
L a b or at or y Testi n g
If a st u dy partici pa nt is u na ble t o visit t he site f or pr ot oc ol -s pecifie d safet y la b orat or y 
e val uati o ns, testi n g m a y  be c o n d ucte d at a l ocal la b orat or y  if per mitte d b y l ocal re g ulati o ns.  
T h e l ocal la b orat or y ma y be a sta n dal o ne i nstit uti o n or wit hi n a h os pital. T he f oll o wi n g 
safety la b orat or y  e val uati o ns as liste d i n Ta ble 1 1 ma y  be perf or me d at a l ocal la b orat or y if 
necessar y : 

He mat ol o g y ;

Bl o o d c he mistr y ;

C oa g ulati o n ;

Uri nal y sis;

Pre g na nc y  test.
If a l ocal la b orat or y is use d, q ualifie d st u d y site pers o n nel m ust or der, recei ve, a n d re vie w 
res ults. Site staff m ust c ollect t he l ocal la b orat or y refere nce ra n ges a n d 
certificati o ns/accre ditati o ns f or fili n g at t he site.   La b orat or y  test res ults are t o be pr o vi de d t o 
t he site staff as s o o n as p ossi ble.   T he l ocal la b orat or y  re p orts s h o ul d be file d i n t he 
partici pa nt’s s o urce d oc u me nts/ me dical rec or ds. Rele v a nt data fr o m t he l ocal la b orat or y  
re p ort s h o ul d be rec or de d o n t he C R F.
If a partici pa nt re q uiri n g pre g na nc y testi n g ca n n ot visit a l ocal la b orat or y f or pre g na nc y 
testi n g, a h o me uri ne pre g na nc y testi n g kit wit h a se nsiti vit y of at least 2 5 I U/ m L ma y be 
use d b y  t he partici pa nt t o perf or m t he test at h o me, if c o m plia nt wit h l ocal re g ulat or y 
re q uire me nts. T he pre g na nc y  test o utc o me s h o ul d be d oc u me nte d i n t he partici pa nt’s s o urce 
d oc u me nts/ me dical rec or ds a n d rele va nt data rec or de d o n t he C R F. C o nfir m t hat t he 
partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he pr ot oc ol.
Electr oc ar di o gr a ms
If t he partici pa nt is u na ble t o visit t he st u d y site f or E C Gs, t he partici pa nt ma y visit an 
alter nati ve facilit y t o ha ve t he E C Gs perf orme d.
Q ualifie d st u d y  site pers o n nel m ust or der, 
recei ve, a n d re vie w res ults. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M

P F -0 6 8 6 3 1 3 5 
C 1 0 7 1 0 0 1 
Fi nal Pr ot oc ol A me n d me nt 9 , 2 8 Marc h
2 0 2 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3 3
St u d y I nter ve nti o n
If t he safety of a trial partici pa nt is at ris k beca use t he y ca n n ot c o m plete re q uire d e val uati o ns 
or a d here t o critical miti gati o n ste ps, t he n disc o nti n ui n g t hat partici pa nt fr o m st u d y 
i nter ve nti o n m ust be c o nsi dere d.
D ose Del a ys
T he f oll o wi n g is rec o m me n de d f or t he a d mi nistrati o n of P F -0 6 8 6 3 1 3 5 f or partici pa nts w h o 
ha ve acti ve [c o nfir me d ( p ositi ve b y  re g ulat or y a ut h orit y-a p pr o ve d test) or pres u me d (test 
pe n di n g/cli nical s us pici o n)] S A R S -C o V 2 i nfecti o n:

F or s y m pt o matic partici pa nts wit h acti ve S A R S- C o V 2 i nfecti o n, i n vesti gati o nal 
treat me nt s h o ul d be dela ye d f or at least 1 4 da ys fr o m t he start of s ym pt o ms. T his 
dela y  is i nte n de d t o all o w t he res ol uti o n of sy m pt o ms of S A R S -C o V 2 i nfecti o n .

Pri or t o restarti n g treat me nt, t he partici pa nt s h o ul d be afe brile f or 7 2 h o urs , a n d 
S A R S -C o V 2 -relate d sy m pt o ms s h o ul d ha ve rec o vere d t o ≤Gra de 1 f or a mi ni m u m of 
7 2 h o urs.  N otif y  t he st u d y tea m w he n treat me nt is restarte d.

C o nti n ue t o co nsi der p ote ntial dr u g -dr u g i nteracti o ns as descri be d Secti o n 5. 9 a n d 
A p pe n di x 1 1 f or a n y c o nc o mita nt me dicati o n a d mi nistere d f or treat me nt of 
S A R S -C o V 2 i nfecti o n.
A d verse E ve nts a n d Seri o us A d verse E ve nts
If a partici pa nt has C O VI D-1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n a d verse e ve nt 
( A E) or seri o us a d verse e ve nts ( S A E) a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. 
Te m p orar y  disc o nti n uati o n of t he st u d y i nter ve nti o n ma y be me dically a p pr o priate u ntil t he 
partici pa nt has rec o vere d fr o m C O VI D - 1 9. 
It is rec o m me nde d t hat t he i n vesti gat or disc uss te m p orar y  or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or. 
0 9 0 1 7 7 e 1 9 d 0 b e 7 c a\ A p pr o v e d\ A p pr o v e d O n: 2 9- M ar- 2 0 2 3 1 9: 5 1 ( G M T)
E T M F C o py of:
 
  1 6 4. 0 1| C 1 0 7 1 0 0 1| 2 8- M ar- 2 0 2 3 | A cti v e | 1 0- A pr- 2 0 2 3 1 0: 1 0: 2 2 A M