Conditions: Advanced Breast Cancer HER2/Neu Negative Triple-Negative Breast Cancer
Keywords: PALB2 mutation BRIP1 mutation BARD1 mutation Rad51c mutation PTEN mutation CHEK2 mutation ATM mutation NBN mutation Rad51d mutation Rad50 mutation MRE11 mutation FANC mutation HRD assay score ATR mutation
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 21
Healthy volunteers: no

Brief summary:
The aim of this single-arm phase 2 clinical trial is to evaluate the anti-cancer activity of Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative breast cancer are eligible.

Detailed description:
Talazoparib (BMN 673) is a novel, dual-mechanism PARP inhibitor that potently inhibits the PARP enzyme and effectively traps PARP on DNA. Talazoparib has shown promising single-agent anti-tumor efficacy in several BRCA1/2 mutation-associated advanced cancers. The efficacy of PARP inhibition in BRCA1/2 wild-type TNBC with homologous recombination (HR) defects and in breast tumors with mutations in other non-BRCA1/2 HR pathway genes is currently unknown.

This phase 2 trial explores the activity of single agent talazoparib in BRCA1/2 wild-type BC patients using an optimal Simon two-stage design. Eligible subjects will be assigned to one of two parallel cohorts: 1) Cohort A: Subjects (n=29) with advanced TNBC with underlying HR defects as assessed by the HRD assay and, 2) Cohort B: Subjects (n=29) with advanced HER2-negative BC with a somatic or germline mutation in a non-BRCA1/2 HR pathway gene. Gene mutations of interest are: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes (FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL).

Arms:
arm 1: Participants with advanced triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD) based on the Myriad HRD Assay.

Participants receive talazoparib 1 mg by mouth daily. arm 2: Participants with advanced HER2-negative solid tumor with a deleterious hereditary or cancer somatic mutation in one of the following genes:

PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, Fanconi anemia complementation group of genes.

Participants receive talazoparib 1 mg by mouth daily.

Interventions: intervention 1: Talazoparib Tosylate
Intervention descriptions: intervention 1: Participants receive Talazoparib tosylate at 1 mg by mouth daily.

Protocol document:
Prot_SAP_000.pdf: 
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A P h ase  2 cli nic al tri al of t he P A R P i n hi bit or t al az o p ari b i n B R C A 1 a n d B R C A 2 wil d -t y pe 
p atie nts wit h a d v a nce d tri ple -ne g ati ve bre ast c a ncer a n d h o m ol o g o us rec o m bi n ati o n 
deficie nc y or a d v a nce d H E R 2 -ne g ati ve bre ast c a ncer or ot her s oli d t u m o rs wit h a m ut ati o n 
i n h o m ol o g o us rec o m bi n ati o n p at h w a y ge nes 
C o or di n ati n g Ce nter  
Sta nf or d Ca ncer I nstit ute  
8 7 5 Bla ke Wil b ur Dri ve  
Sta nf or d, C A 9 4 3 0 5  
I n vesti g at ors 
Meli n d a  L  Telli,  M D  
Assista nt Pr ofess or of M e dici ne  
Di visi o n of O nc ol o g y  
Sta nf or d U ni versit y Sc h o ol of Me dic i ne 
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J os h u a  Gr u ber,  M D,  P h D  
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Bi ost atistici a n  
Ale x Mc Milla n, P h D  
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Bi o me dical D ata Scie nce  
Sta nf or d  U ni versit y Sc h o ol of Me dici ne  
H R P Re d w o o d B uil di n g, R o o m T 1 6 0 A  
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St u d y C o or di n at or  
W yatt  F orrest  Gr oss , B S  
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T A B L E:  S U M M A R Y O F C H A N G E S  
Re visi o n D ate  
C h a n ges  
Pri or 
a me n d me nts  
 Title c orrecte d o n pa ge 1 a n d t hr o u g h o ut  
 Clarifie d S A E re p orti n g g ui da nce f or Pfizer, t he n e w st u d y s p o ns or.  A d de d S CI 
S A E re p orti n g g ui deli nes f or i n vesti gat or -i nitiate d trials i n A p pe n di x B.  
 Clarifie d st u d y  cale n dar –  c ha n ge d st u d y wee ks t o st u d y c ycl es.  
 Clarifie d defi niti o n of c hil d beari n g p ot e ntial o n eli gi bilit y c hec klist a n d i n 
eli gi bilit y criteria secti o n i n pr ot oc ol  
 Clarifie d nee d e d i ma gi n g at baseli ne o n eli gi bilit y c hec klist  
 A d de d t he f oll o wi n g t o e li gi bilit y c hec klist 
o  A vaila bilit y of arc hi val t u m or tiss ue fr o m pri mar y breast/t u m or site  
o  A de q uate fres h or arc hi v al t u m or tiss ue fr o m metastatic bi o ps y site, if bi o ps y 
is tec h nicall y feasi ble 
o  S u bjects of c hil d beari n g p ote ntial m ust be willi n g t o ha ve a d d iti o nal uri ne 
pre g na nc y t ests d uri n g t h e st u d y.  
o  Clarifie d t hat le pt o me ni n geal disease is e xcl u de d  
T he a b o ve c ha n ges were pre vi o usl y re p orte d t o t h e I R B, b ut are retai ne d f or 
ali g n me nt wit h t his versi o n of t he pr ot oc ol, as s u b mitte d t o t he I N D.  
 Eli gi bilit y  Criteria har m o nize d wit h Eli gi bilit y  C h ec klist, a n d prese nt e d as a 
si n gle i nsta nce at Secti o n 3. 1.  
o  U p date d t he refere nce t o N CI 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 t o versi o n  5 . . 
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I N V E S TI G A T O R S ....................................................................................................................... 1  
P R O T O C O L S Y N O P SI S  ............................................................................................................. 5  
S T U D Y S C H E M A  ........................................................................................................................ 8  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  .............................................. 9  
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P RI M A R Y O BJ E C TI V E  ..................................................................................................... 1 0  
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B A C K G R O U N D  ................................................................................................................. 1 0  
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B R C A 1/ 2 -M U T A TI O N A S S O CI A T E D B R E A S T C A N C E R  ................................................... 1 0  
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S P O R A DI C T RI P L E -N E G A TI V E B R E A S T C A N C E R  ............................................................. 1 1  
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C A N C E R S WI T H G E R M LI N E  O R S O M A TI C D E FI CI E N C Y I N D N A  D O U B L E -S T R A N D R E P AI R
  
1 1  
2. 4  
T H E M Y RI A D H O M O L O G O U S R E C O M B I N A TI O N D E FI CI E N C Y (H R D ) A S S A Y  .................. 1 3  
2. 5  
O V E R VI E W O F T H E S T U D Y  A G E N T T A L A Z O P A RI B  ............................................................ 1 4  
2. 6  
R A TI O N A L E  .................................................................................................................... 1 8  
2. 7  
S T U D Y D E SI G N  .............................................................................................................. 2 0  
3.  
P A R TI CI P A N T S E L E C TI O N A N D E N R O L L M E N T P R O C E D U R E S  ...................... 2 1  
3. 1  
E LI GI BI LI Y C RI T E RI A  A N D P A R TI CI P A N T E LI GI BI LI T Y C H E C K LI S T  ... E R R O R ! B O O K M A R K 
N O T D E FI N E D . 
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IN F O R M E D C O N S E N T P R O C E S S  ....................................................................................... 2 1  
3. 3  
R A N D O MI Z A TI O N P R O C E D U R E S  ..................................................................................... 2 6  
3. 4  
S T U D Y T I M E LI N E ........................................................................................................... 2 6  
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T R E A T M E N T P L A N  ......................................................................................................... 2 6  
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S C R E E NI N G P R O C E D U R E S  .............................................................................................. 2 6  
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D O SI N G A N D A D MI NI S T R A TI O N S C H E D U L E  .................................................................... 2 7  
4. 3  
P R E -T R E A T M E N T E V A L U A TI O N S  .................................................................................... 2 8  
4. 4  
E N D O F T R E A T M E N T P R O C E D U R E S  ................................................................................ 2 8  
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G E N E R A L C O N C O MI T A N T M E DI C A TI O N A N D S U P P O R TI V E C A R E G UI D E LI N E S  ............... 2 9  
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D U R A TI O N O F T H E R A P Y A N D F O L L O W -U P  ..................................................................... 2 9  
4. 7  
C RI T E RI A F O R R E M O V A L F R O M S T U D Y  .......................................................................... 2 9  
4. 8  
A L T E R N A TI V E S  .............................................................................................................. 2 9  
4. 9  
C O M P E N S A TI O N  ............................................................................................................. 3 0  
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I N V E S TI G A TI O N A L A G E NT/ D E VI C E/ P R O C E D U R E I N F O R M A TI O N  ............... 3 0  
5. 1  
IN V E S TI G A TI O N A L A G E N T  ............................................................................................. 3 0  
5. 2  
P H A R M A C O D Y N A MI C P R O P E R TI E S  ................................................................................. 3 0  
5. 3  
P H A R M A C O KI N E TI C P R O P E R TI E S  .................................................................................... 3 1  
5. 4  
S U P P LI E R  ....................................................................................................................... 3 1  
5. 5  
D O S A G E F O R M  ............................................................................................................... 3 1  
5. 6  
A G E N T O R D E RI N G A N D P A C K A GI N G  .............................................................................. 3 1  
5. 7  
S T O R A G E A N D S H E L F LI F E  .............................................................................................. 3 2  


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N A T U R E A N D C O N T E N T S O F C O N T AI N E R  ....................................................................... 3 2  
5. 9  
S P E CI A L P R E C A U TI O N S F O R D I S P OS A L A N D O T H E R H A N D LI N G  ..................................... 3 2  
6.  
D O S E M O DI FI C A TI O N S  ................................................................................................. 3 2  
7.  
A D V E R S E E V E N T S A N D R E P O R TI N G P R O C E D U R E S  ........................................... 3 3  
7. 1  
P O T E N TI A L A D V E R S E E V E N T S  ....................................................................................... 3 3  
7. 2  
A D V E R S E E V E N T A N D P R E G N A N C Y R E P O R TI N G  ............................................................ 3 5  
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P R O D U C T C O M P L A I N T S R E P O R TI N G  ............................................................................... 3 6  
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C O R R E L A TI V E  S T U DI E S  .............................................................................................. 3 6  
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S T U D Y C A L E N D A R  ......................................................................................................... 3 8  
1 0.  
M E A S U R E M E N T S  ........................................................................................................ 3 9  
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P RI M A R Y E N D P OI N T  ...................................................................................................... 3 9  
1 0. 2     S E C O N D A R Y E N D P OI N T S  .................................................................................................. 3 9  
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C O R R E L A TI V E E N D P OI N T S  ............................................................................................. 4 0  
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R E G U L A T O R Y C O N SI D E R A TI O N S  ........................................................................ 4 0  
1 1. 1  
IN S TI T U TI O N A L R E VI E W O F P R O T O C O L  .......................................................................... 4 0  
1 1. 2  
D A T A A N D S A F E T Y M O NI T O RI N G P L A N  ......................................................................... 4 0  
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D A T A M A N A G E M E N T P L A N  ........................................................................................... 4 1  
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S T A TI S TI C A L C O N SI D E R A TI O N S  .......................................................................... 4 1  
1 2. 1  
A N A L Y TI C P L A N F O R S T U D Y O BJ E C TI V E S  ..................................................................... 4 1  
1 2. 2  
A N A L Y SI S P O P U L A TI O N  .................................................................................................. 4 2  
1 2. 3  
S A M P L E S I Z E C A L C U L A TI O N S  ........................................................................................ 4 2  
1 2. 4   A C C R U A L E S TI M A T E S A N D F E A SI BI LI T Y  ........................................................................ 4 2  
R E F E R E N C E S  ............................................................................................................................ 4 3  
A P P E N DI X A :  
S A E R E P O R TI N G G UI D E L I N E S; S CI S O P 1 0-1 6 -2 0 1 4  ...................... 4 6  
 


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P R O T O C O L S Y N O P SI S  
Title of St u d y:   A p hase  2  cli nical trial of t he P A R P i n hi bit or talaz o parib  i n B R CA 1 a n d B R C A 2 
wil d -t y pe patie nts wit h a d va nce d tri ple-ne gati ve breast ca ncer a n d h o m ol o g o us rec o m bi nati o n 
deficie nc y or  a d va nce d H E R 2 -ne gati ve breast  ca ncer  or ot her s oli d t u m ors  wit h a m utati o n i n 
h o m ol o g o us rec o m bi nati o n pat h wa y ge nes  
C o nce pt a n d R ati o n a le:  I n t his p hase 2  pr o of -of -c o nce pt cli nical trial, we pr o p ose t o test t he 
efficac y of  talaz o pari b, a p ote nt, orall y-bi oa vaila ble P A R P i n hi bit or, wit h a n esta blis he d P hase  2  
rec o m me n de d d ose, i n t he treat me nt of a d va nce d B R C A wil dt y pe ( W T ), H E R 2-n e gati ve  breast 
ca ncer a n d ot her s oli d t u m ors  wit h h o m ol o g o us rec o m bi nati o n ( H R ) deficie nc y.  T he trial is 
c o m p ose d of t w o patie nt c o h orts .  C o h ort  A  c o nsists of patie nts wit h a d va nce d tri ple-ne gati ve 
breast ca ncer ( T N B C ) a n d a hi g h h o m ol o g o us rec o m bi nati o n defici e nc y ( H R D ) sc ore as assesse d 
b y t he M yria d  H R D  assa y.  C o h ort  B  c o nsists of patie nts wit h a d va nce d H E R 2 -ne gati ve breast 
ca ncer or ot her s oli d t u m ors  wit h a ger mli ne  or s o matic m utati o n i n a ge ne li n ke d t o t he  H R 
pat h wa y .  Patie nts alrea d y i de ntifie d as har b ori n g a deleteri o us or s us pecte d deleteri o us ger mli ne  
or s o matic m utati o n i n t he  H R pat h wa y will be i m me diatel y eli gi ble f or treat me nt i n C o h ort  B.  
      T he 
M yria d  H R D  assa y is a t u m or tiss ue -base d assa y t hat has bee n de vel o pe d usi n g a n 
i n direct a p pr oach t hat all o ws f or t he detecti o n of  H R D  as assesse d b y q ua ntif yi n g le vels of 
ge n o mic i nsta bilit y .  T he Sta nf or d Breast Ca ncer gr o u p has pre vi o usl y assesse d t his assa y i n a 
plati n u m -base d ne oa dj u va nt p hase  2  trial a n d s h o we d t hat a hi g h H R D  sc ore si g nifica ntl y 
c orrelates wit h a fa v ora ble pat h ol o gic res p o nse i n earl y -sta ge T N B C wit h a n d wit h o ut a ger mli ne  
B R C A 1/ 2 m utati o n .  Li ke wise, Isa k off a n d c ollea g ues rece ntl y re p orte d t he c orrelati ve e n d p oi nts 
of t he T B C R C 0 0 9 st u d y, a si n gle -ar m p hase  2  trial of plati n u m t hera p y i n metastatic T N B C.  
W hile esta blis he d bi o mar kers, i ncl u di n g p 6 3/ p 7 3 rati o a n d p 5 3 a n d PI K 3 C A m utati o ns faile d t o 
pre dict f or plati n u m res p o nse,  H R D  assa ys di d i de ntif y s p ora dic T N B C t u m ors t hat were m ore 
res p o nsi ve t o plati n u m t hera p y.  
      A s e parate a p pr oac h t o detecti n g  H R D  ma y be t he use of  m ulti ple x ge ne pa nels t hat e val uate  
n o n -B R C A 1/ 2  ger mli ne  m utati o ns i m plicate d i n h o m ol o g o us rec o m bi nati o n .  M utati o ns i n ge nes 
li n ke d t o t he H R pat h wa y, s uc h as A T M, P A L B 2 a n d R A D 5 1  a m o n g ot hers , are h y p ot hesize d t o 
ha ve si milar c he m ose nsiti vit y t o D N A -da ma gi n g t hera pies as m utati o ns i n B R C A 1 a n d B R C A 2 
gi ve n a si milar s y nt heticall y let hal effect .  I de ntificati o n of s o m atic m utati o ns i n  H R -relate d 
ge nes t hr o u g h c o m merciall y a vaila ble ne xt -ge nerati o n D N A se q ue nci n g of t u m or tiss ues als o has 
p ote ntial t o i de ntif y patie nts w h o ma y deri ve be nefit fr o m D N A re pair defect -tar gete d t hera p y.  
H o we ver, n o st u dies t o -date ha ve directl y e val uate d t he r ole of D N A -da ma gi n g t hera pies i n s uc h 
patie nt p o p ulati o ns.  
Pri m ar y O bjecti ve(s):   
T o deter mi ne w het her si n gle a ge nt talaz o pari b ca n res ult i n a 3 0 % or greater o bjecti ve res p o nse 
i n patie nts wit h a d va nce d s p or a dic tri ple-ne gati ve breast ca ncer wit h h o m ol o g o us rec o m bi nati o n 
deficie nc y as assesse d b y t he  H R D  assa y ( C o h ort  A)  or a d va nce d H E R 2 ne gati ve (ie , T N or 
E R/ P R p ositi ve) breast ca ncer or  ot her  s oli d t u m ors wit h a ger mli ne  or s o m atic m utati o n i n 
t he H R pat h wa y, e xcl u di n g B R C A 1/ 2 ( C o h ort  B).  
Sec o n d ar y O bjecti ve(s):  
1. T o deter mi ne t he cli nical be nefit rate (c o m plete res p o nse, partial res p o nse or sta ble diseas e 
≥ 2 4  wee ks)  
2 . T o deter mi ne pr o gressi o n-free s ur vi val 
3 . T o e val uate t he safet y of talaz o pari b i n t his patie nt p o p ulati o n 
C orrel ati ve O bjecti ve(s):  
1. T o c o m pare t he rate of res p o nse i n s u bjects wit h T N B C wit h or wit h o ut a n u n derl yi n g 


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ger mli ne  H R pat h wa y m utati o n (C o h ort  A).  
2. T o c o m pare t he  H R D  sc ores i n res p o n ders vers us n o n-res p o n ders wit h u n derl yi n g deleteri o us 
or s us pecte d deleteri o us ger mli ne  or s o matic  H R ge ne m utati o ns ( C o h ort  B).  
3. T o assess t he c o nc or da nce of t he  H R D  sc ores i n t he pri mar y t u m or tiss ue wit h t hat i n t he 
metastatic t u m or tiss ue.  
4. T o assess i n metastatic t u m or bi o ps y sa m ples, t he R A D 5 1 stat us of t he t u m or at baseli ne 
(a bse nt or prese nt) as a f u ncti o nal rea d o ut of H R ca pacit y a n d c orrelate t his wit h  H R D  a n d 
m utati o nal stat us  
Pri m ar y E n d p oi nt(s):  
T he o bjecti ve res p o nse rate of  talaz o pari b usi n g R E CI S T 1. 1 criteria  
Sec o n d ar y E n d p oi nt(s):   
1. Cli nical be nefit rate  
2 . Pr o gressi o n-free s ur vi val 
3 . Safet y 
C orrel ati ve E n d p oi nt(s):  
1. O bj ecti ve res p o nse rate i n s u bjects wit h T N B C wit h or  wit h o ut a n u n derl yi n g ger mli ne  H R 
pat h wa y m utati o n i n C o h ort  A  
2. C orrelati o n of  H R D  sc ores wit h res p o nse i n s u bj ects  wit h u n derl yi n g  ger mli ne  or s o matic  H R 
ge ne m utati o ns i n C o h ort  B  
3. C orrelati o n of  H R D  sc ores i n t he pri mar y t u m or tiss ue a n d t he metastatic t u m or tiss ue. 
4. C orrelati o n of R A D 5 1 stat us i n t he metastatic t u m or wit h H R D  a n d m utati o nal stat us. 
St u d y Desi g n:  A si n gle -ar m, p hase  2  cli nical trial c o nsisti n g of 2 patie nt c o h orts 
( parallel desi g n), usi n g a n o pti mal t w o -sta ge desi g n.  T he t w o pa tie nt c o h orts are t he f oll o wi n g: 
C o h ort  A:   T N B C patie nts wit h  H R deficie nc y as meas ure d b y t he M yria d  H R D  assa y 
C o h ort  B:   H E R 2 -ne gati ve (ie , tri ple-ne gati ve or estr o ge n/ pr o gester o ne rece pt or -p ositi ve) breast 
ca ncer or ot her s oli d t u m or  patie nts wit h a ge r mli ne or s o m atic m utati o n i n a  H R pat h wa y ge ne .  
Ge ne m utati o ns of i nterest are:  P T E N ;  P A L B 2 ;  C H E K 2 ;  A T M ;  N B N ;  B A R D 1 ;  B RI P 1 ;  
R A D 5 0 ;  R A D 5 1 C ;  R A D 5 1 D ;  M R E 1 1 ;  A T R ;  Fa nc o ni a ne mia c o m ple me ntati o n gr o u p of 
ge nes ( F A N C A ;  F A N C C ;  F A N C D 2 ;  F A N C E ;  F A N C F ;  F A N C G ;  F A N C L).  
N u m ber of P atie nts:  We will accr ue 1 0 patie nts, if we o bser ve a res p o nse i n at least 2 patie nts, 
t he n we will accr ue 10  a d diti o nal patie nts f or a t otal of 2 0  patie nts i n eac h c o h ort , a n d re q uire a 
res p o nse i n at least 3 patie nts o ut of 2 0 t o declare statistical si g nifica nce at a o ne si de d 
si g nifica nce le vel of 5 %, i n or der t o ass ure 8 0 % p o wer.   It is e x pecte d t hat at least 
1 0  H E R 2 -ne gati ve breast ca ncer patie nts will be e nr olle d i n C o h ort  B.  
S u m m ar y of Eli gi bilit y :  
 A d ults wit h a s ol i d t u m or meas ura ble per R E CI S T v 1. 1,  wit h o ut s us pecte d deleteri o us 
ger mli ne B R C A 1 or B R C A 2 ge ne m utati o n i n t he ger mli ne, a n d ha vi n g recei ve d at least 1 
pri or s yste mic t h era p e utic re gi me n.  Eli gi ble s u bjects will ha ve E C O G perf or ma nce 
stat us of 0 t o 2 a n d a de q uate or ga n f u ncti o n, wit h a de q uate birt h c o ntr ol preca uti o ns.  Please 
see c o m plete Eli gi bilit y Criteria at Secti o n 3 . 1.  
I nter ve nti o n a n d M o de of Deli ver y:   T alaz o pari b , 1 m g  P O dail y (c o nti n u o us d osi n g) o n a 
2 8 -da y c ycle.  Patie nts will be e val uate d  pri or t o eac h c ycle.  T his will i ncl u de a cli nical 
e val uati o n, i ncl u di n g safet y assess me nt a n d p h ysical e xa m, as well as la b orat or y assess me nt.  
D ur ati o n of I nter ve nti o n a n d E v al u ati o n:   T he n o mi nal d urati o n of treat me nt is 3 6  c ycles 


I R B-3 1 9 1 3 versi o n 8  
P a ge 7  of 4 6   
2  Se pte m ber  2 0 2 0  
( 2 8 da ys per c ycle),  b ut C R, P R, or S D patie nts ma y  c o nti n ue t hera p y u ntil e vi de nce of 
pr o gressi ve disease or u nacce pta ble t o xicit y occ urs.  Pr ot oc ol t hera p y will be disc o nti n ue d f or 
pr o gressi ve disease at a n y ti me .  Patie nts are free t o halt t hera p y at t heir re q uest .  Treat m e nt ma y 
be disc o nti n ue d if i nterc urre nt c o -m or bi dities occ ur, w hic h, i n t he o pi ni o n of t he treati n g 
p h ysicia n, w o ul d precl u de safe a d mi nistrati o n of st u d y dr u gs.  
F u n di n g, Re g ul at or y, a n d F e asi bilit y Iss ues:   T his i n vesti gat or -i nitiate d P hase 2  cli nical t rial 
will be f u n de d b y  Pfizer P har mace utical, I nc.  T his p har mace utical c o m pa n y has c o m mitte d t o 
pr o vi di n g t he st u d y dr u g, talaz o pari b.  
P atie nt Acce pt a bilit y/ Et hics a n d C o nse nt Iss ues:   Gi ve n t he lac k of tar gete d t hera p y o pti o ns 
f or T N B C patie nts, we belie ve t his trial will be a welc o me d alter nati ve c o m pare d t o sta n dar d 
c yt ot o xic c he m ot hera p y i n t his patie nt p o p ulati o n.  Of p ossi ble c o ncer n t o t he patie nt or a d v ocate 
c o m m u nit y ma y be t hat we will re q uire t u m or tiss ue of a metastatic site f or trial partici pati o n .  
T his bi o ps y is critical f or t he s uccessf ul c o n d uct of t his st u d y .  F urt her m ore, as patie nts will 
re q uire ge netic testi n g, we will offer ge netic c o u nseli n g t o all patie nts e nr olle d i n t his trial.  
 


I R B-3 1 9 1 3 versi o n 8  
P a ge 8  of 4 6   
2  Se pte m ber  2 0 2 0  
S T U D Y S C H E M A  
 
 


I R B-3 1 9 1 3 versi o n 8  
P a ge 9  of 4 6   
2  Se pte m ber  2 0 2 0  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI T I O N O F T E R M S 
A E  
A d verse e ve nt  
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 S T  
As partate a mi n otra nsferase  
BI D  
T wice dail y  
B S A  
B o d y s urface area  
C B C  
C o m plete bl o o d c o u nt  
CI  
C o nfi de nce i nter val  
C M A X  
Ma xi m u m c o nce ntrati o n of dr u g  
C N S  
Ce ntral ner v o us s yste m  
C R F  
Case re p ort/ Rec or d f or m  
C R  
C o m plete res p o nse  
C T C A E  
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts  
D L T  
D ose Li miti n g T o xicit y  
D S M C  
Data Safet y M o nit ori n g C o m mittee  
E C G  
Electr ocar di o gra m  
E C O G  
Easter n c o o perati ve o nc ol o g y gr o u p  
E R  
Estr o ge n rece pt or  
F D A  
U S f o o d a n d dr u g a d mi nistrati o n  
F F P E  
F or mali n -fi xe d paraffi n e m be d de d 
G C P  
G o o d cli nical practice  
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 N S T D  
Hi g hest n o n -se verel y t o xic d ose 
H R  
H o m ol o g o us Rec o m bi nati o n  
H R D  
H o m ol o g o us Rec o m bi nati o n Deficie nc y  
I B 
I n vesti gat or's br oc h ure 
I P 
I n vesti gati o nal pr o d uct 
I R B 
I nstit uti o nal Re vie w B oar d 
I V 
I ntra ve n o us 
L F T  
Li ver f u ncti o n test  
L O H  
L o ss of heter oz yg osit y  
M T D  
Ma xi m u m t olerate d d ose  
O S  
O verall s ur vi val  
P A R P  
P ol y -A D P ri b o se p ol y merase 
p C R  
P at h ol o gic c o m plete res p o nse  
P D  
Pr o gressi ve disease d  or P har mac o d y na mic s 
P F S  
Pr o gressi o n -free s ur vi val  
P K  
P har mac o ki netic  
Plt  
Platelet c o u nt  
P R  
P artial res p o nse  or Pr o gester o ne rece pt or  
Q D  
O nce dail y  
R E CI S T  
Res p o nse e val uati o n cr iteria i n s oli d t u m ors 
R R  
Res p o nse rate  
S A E  
Seri o us a d verse e ve nt  
S D  
Sta ble disease  
S R C  
Scie ntific Re vie w C o m mittee  
T N  
Tri ple -ne gati ve  
T K  
T o xic o ki netic  
T N B C  
Tri ple -ne gati ve breast ca ncer  
U L N  
U p per li mit of n or mal  
W B C  
W hite bl o o d cell  


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 0  of 4 6   
2  Se pte m ber  2 0 2 0  
1.   
O B J E C TI V E S  
1. 1   
Pri m ar y O bjecti ve  
  
T o deter mi ne w het her si n gle a ge nt talaz o pari b pr o d uces better t ha n e x pecte d res p o nses  i n 
patie nts 
wit h a d va nce d  s p or a dic tri ple-ne gati ve breast ca ncer 
wit h h o m ol o g o us 
rec o m bi nati o n deficie nc y as assess e d b y t he  H R D  assa y (C o h ort  A)  a n d/or  a d va n ce d 
H E R 2 -ne gati ve ( ie, T N - or E R/ P R -p ositi ve) breast  ca n cer or ot her n o n -breast s oli d 
t u m ors wit h  a ger mli ne  or s o m atic m utati o n i n t he H R pat h wa y , e x cl u di n g B R C A 1 or 
B R C A 2 (C o h ort  B).   
1. 2   
Sec o n d ar y O bjecti ves  
1. 2. 1  T o deter mi ne cli nical b e ne fit rate (c o m plete res p o nse, partial res p o ns e or sta ble 
disease ≥ 2 4  wee ks)  
1. 2. 2   T o deter mi ne pr o gressi o n -free s ur vi val i n b ot h c o h orts 
1. 2. 3  T o e val uate t he s afet y of talaz o pari b i n b ot h patie nt p o p ulati o n s 
1. 3   
C orrel ati v e O bjecti v es  
1. 3. 1  T o c o m pare t h e rate of res p o nse i n s u bjects wit h T N B C wit h or wit h o ut a n 
u n de rl yi n g ger mli ne  H R pat h wa y m utati o n ( C o h ort  A).  
1. 3. 2  T o c o m pare t h e  H R D  sc ores i n res p o n ders vers us n o n-res p o n ders wit h u n derl yi n g 
deleteri o us or s us pecte d deleteri o us ger mli ne  or s o matic  H R ge n e m utati o ns 
(C o h ort  B).  
1. 3. 3  T o assess t he c o n c or da n ce of t he  H R D  sc ores i n t h e pri mar y t u m or tiss ue wit h 
t hat i n t he metastatic t u m or tiss ue. 
1. 3. 4  T o assess i n metastatic t u m or bi o ps y sa m ples, t he R A D 5 1 stat us of t he t u m or at 
baseli ne (a bs e nt or pres e nt) as a f u ncti o nal rea d o ut of  H R ca pacit y a n d c orrelate 
t his wit h  H R D  a n d m utati o nal stat us 
2.   
B A C K G R O U N D  
2. 1  
B R C A 1/ 2 -M ut ati o n Ass oci ate d Bre ast C a ncer  
Ca ncer is a ge netic dise ase ca use d b y a n acc u m ulati o n of c ha n ges i n t he D N A s e q ue nce o ver 
ti me, ge n erall y i n v ol vi n g t u m or s u p pressor ge nes or pr ot o -o nc o ge n es .1 Cells c o nti n uall y ac q uire 
D N A da ma ge a n d ha v e r o b ust a n d re d u n d a nt D N A da ma ge re pair mec h a nis ms t hat f u ncti o n t o 
mai n tai n ge n o mic sta bilit y.  D o u ble -stra n d D N A brea ks are e xtre mel y c yt ot o xic a n d t heir re pair 
via  n o n -h o m ol o g o us e n d j oi ni n g a n d h o m ol o g o us rec o m bi nati o n are criticall y i m p orta nt .  
E x cisi o n re pair pat h wa ys, i ncl u di n g base e x cisi o n re pair, n ucle oti de e x cisi o n re pair a n d 
mis matc h re pair, als o pla y i m p orta nt r oles i n rest ori n g t he n or mal D N A s e q ue nce.  
Breast ca ncers t hat arise i n B R C A 1 a n d B R C A 2 
m utati o n carriers are c haract erize d b y 
h o m ol o g o us rec o m bi nati o n D N A re pair defici e n c y d ue t o l oss of t he f u ncti o ni n g w il d-t y p e 
B R C A 1 or B R C A 2 allele .  T he B R C A 1 a n d B R C A 2 ge n e pr o d ucts are critical f or D N A 
d o u ble -stra n d brea k re p air via h o m ol o g o us rec o m bi nati o n.1  P ol y ( A D P -ri b ose) p ol y merase-1 
( P A R P 1) a n d P A R P 2 are n uclear e nz y mes cr ucial f or recr uit me nt of a cell's base e x cisi o n re pair 
mac hi ner y t o sites of D N A da ma ge .  It h as b ee n esta blis he d t hat P A R P 1/ 2 i n hi bit ors ca n ca use 
selecti ve c yt ot o xicit y i n cell li nes m uta nt f or B R C A 1 or B R C A 2, d ue t o stalli n g of re plicati o n 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 1  of 4 6   
2  Se pte m ber  2 0 2 0  
f or ks i n d uce d b y a bse n ce of P A R P e nz y me a n d s u bse q ue nt s h utti n g of t he D N A da ma ge t o 
d o u blestra n d brea ks .  Wit h 
c o nc urre nt l oss of h o m ol o g o us rec o m bi nati o n -de pe n de n t D N A 
d o u ble -stra n d brea k re pair, t his lea ds t o a s y nt h eticall y let hal i nteracti o n .2 -7   
2. 2   
S p or a dic Tri ple -Ne g ati ve Bre ast C a ncer   
F or s o me ti me, it has bee n a p preciate d t hat t he maj orit y of i n vasi ve breast ca nce rs t hat de v el o p 
i n 
w o me n 
wit h deleteri o us 
B R C A 1 ger mli ne  m utati o ns are tri ple -ne gati ve, 8, 9 defi ne d 
pat h ol o gicall y as lac ki n g e x pressi o n of t he estr o ge n a n d pr o gester o ne rece pt ors ( E R/ P R) wit h n o 
a m plificati o n of t h e H E R 2/ ne u o nc o ge ne ,1 0 a n d t his has pr o vi de d fasci nati n g mec h a nistic cl ues 
t o u n derl yi n g t u m or bi ol o g y a n d p ossi ble t hera pe utic tar gets.  Base d o n si milarities bet wee n 
s p ora dic tri ple-n e gati ve breast ca ncer a n d B R C A 1 -deficie nt breast ca n cer a n d t he k n o w n r ole of 
B R C A 1 i n D N A re pair, t he h y p ot hesis h as e mer ge d t hat s p ora d ic tri ple-ne gati ve  breast t u m ors 
ma y p ossess si milar D N A re p air d efects a n d de m o nstrate si milar c h e m ose nsiti vit y as B R C A 1 
m utati o n -ass ociate d breast  t u m ors.  Pre -cli nicall y, tri ple-ne gati ve  breast ca ncer cell li nes, li k e 
B R C A 1 -defi cie nt ca ncer cell li nes, de m o nstrat e i ncrea se d se nsiti vit y t o P A R P i n hi bito rs, 
cis plati n a n d ge mcita bi n e. 1 1  A d diti o nall y, t hese ce ll li nes are m ore se nsiti ve t o o xi dati ve D N A 
da ma ge c o m pare d t o l u mi nal breast t u m or cells or n or mal breast e pit heli al cells a n d h a ve b ee n 
s h o w n t o be deficie nt i n base e x cisi o n re pair. 1 2  
T he acti vit y of ola pari b,  a b o na fi de P A R P i n hi bit or, was i n vesti gate d i n a s mall c o h ort of 
u nselecte d s p ora dic tri pl e -ne gati ve breast ca n cer patie nts, h o we ver, n o o bjecti ve res p o ns es were 
n ote d a n d f u rt her de vel o p me nt was halte d.1 3  U nf or t u natel y, t his e x perie n ce t h warte d t he cli nical 
pr o gress of P A R P i n hi bit ors i n s p ora dic tri ple -n e gati ve breast ca n cer.  T he i na bilit y t o select 
B R C A 1/ 2 wil d -t y p e t u m ors wit h u n derl yi n g D N A re pair defects f urt her c o m p o u n de d t he 
pr o ble m .  D ue t o t hese earl y c halle n ges, t he r ole of P A R P i n hi biti o n i n t he treat me nt of s p ora di c 
tri ple-ne gati ve breast c a n cer has re mai ne d u n d efi ne d.  
2. 3   
C a ncers wit h Ger mli ne  or S o m atic Deficie nc y i n D N A D o u ble -Str a n d Re p air  
I n t he past year, tar get e d ge n e p a nels h a ve arise n t hat e val u ate ger mli ne  m utati o ns i n D N A re p air 
pat h wa ys i m plicate d i n ca ncer de vel o p me nt a n d pr o gressi o n .  M utati o ns i n ge nes li n ke d t o 
c hec k p oi nt c o ntr ol a n d re g ulati o n of t he D N A -d o u ble stra n d brea k re p air pat h wa y, s uc h as 
A T M, P A L B 2 a n d R A D 5 1 are h y p ot hesiz e d t o h a ve si milar c he m os e nsiti vit y t o D N A -da ma gi n g 
t hera pies, s uc h as P A R P i n hi bit ors, as m utati o ns i n B R C A 1 a n d B R C A 2 gi ve n a si milar 
s y nt heticall y l et hal effect.  H o we ver, n o st u dies t o date h a ve directl y e val uate d t h e r ole of 
D N A -da m a gi n g t hera pies i n s uc h patie nt p o p ulati o ns, i n part d ue t o a lac k of c o m merciall y 
a vaila ble m ulti ple x ge ne pa nels usi n g n e xt ge nerati o n D N A se q ue nci n g u ntil rece ntl y as well as 
t he l o w pre vale nce of s uc h m utati o ns i n t he ge neral p o p ulati o n. 
I n a Fre nc h st u d y p u blis he d t his year, ne xt -ge nerati o n -seq ue n ci n g -base d s cree ni n g i n 
7 0 8  patie nts wit h eit her a pers o nal hist or y of breast or o varia n ca n cer at a y o u n g a ge, male breast 
ca ncer, or str o n g fa mil y hist or y d e m o nstrate d a n o verall m utati o nal rate of B R C A 1 a n d B R C A 2 
of 1 0. 8 % .  In a d diti o n, 1 0 i nacti vati n g m utati o ns were f o u n d i n P A L B 2 a n d R A D 5 1 C a n d 
1 0  i nacti vati n g m utati o ns f o u n d i n C H E K 2 a n d A T M, wit h a c ollecti ve c o ntri b uti o n esti mate d t o 
be at least 3 % (s ee fi g ure). 1 4 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 2  of 4 6   
2  Se pte m ber  2 0 2 0  
 
Fi g ure 1.  Cas tera L, et al .  E ur o pea n J o ur nal of H u ma n Ge netics, J a n uar y 2 0 1 4. 
T he m y Ris k ge ne p a nel de vel o pe d b y M yria d Ge netics similarl y e val u ates a set of 2 5 ca ncer 
s usce pti bilit y ge nes i m plicate d i n here ditar y breast a n d o varia n ca n cer b y ne xt ge n erati o n 
se q ue nci ng .  In  an  a bstract pres e nte d at t he 2 0 1 3 Sa n A nt o ni o Breast Ca n cer S y m p osi u m , 1 9 5 5 
pr os pecti vel y accr ue d patie nt cases (e x cl u di n g p atie nts of 
As h ke n azi J e wis h herita ge t o 
deter mi ne rel ati ve pre vale nce i n t he ge neral p o p ulati o n) were teste d, a n d de m o nstrate d t hat 
2 7 5  ( 1 4. 0 7 %) were m utati o n carriers i n at least o ne of t he 2 5 ge nes .  I nteresti n gl y, 1 8 2 ( 9. 3 %) of 
patie nts ha d a m utati o n i n B R C A 1 or B R C A 2, w hile 9 6  ( 4. 9 1 %) of patie nts ha d a m utati o n i n 
ot her ge nes, i n cl u di n g A T M, C H E K 2, N B N, a n d P A L B 2 .  1 7 3 8 o ut  of t he 1 9 5 5 patie nts i n t he 
st u d y ha d a pers o nal hist or y of breast ca ncer, wit h 6 3 % dia g n ose d pri or t o t he a ge of 5 0, a n d 
3 7 % at or after t he a ge 5 0.  N ota bl y 1 9 0 2 ( 9 7. 2 9 %) patie nts ha d a varia nt of u ncertai n 
si g nifica n ce i n at least o ne of t he ge n es teste d a n d a n a vera ge of t hree v aria nts was f o u n d per 
patie nt. 1 5  
I n a d diti o n t o breast ca ncer, h o m ol o g o us rec o m bi nati o n pat h wa y m utati o ns ha ve bee n i m plicate d 
i n m ulti ple ot her s oli d t u m ors i ncl u di n g o varia n, pr ostate, pa n creas, a n d gastri c ca n cers a m o n g 
ot hers a n d are p ost ulate d t o res ult i n a ‘ B R C A ness’ p he n ot y p e .  F or e x a m ple, a rece nt st u d y has 
s h o w n t hat ger mli ne  m utati o ns i n D N A -re pair ge nes ca n be detecte d i n a p pr o xi matel y 1 0 % of 
patie nts wit h 
metastatic pr ostate ca ncer. 2 8  Of patie nts wit h i de ntifie d 
m utati o ns, B R C A 2  
m utati o ns c o m prise d 4 4 % of t otal m utati o ns.  Ot her m utati o ns i de ntifie d i ncl u de d A T M  i n 1 3 %, 
C H E K 2  i n 1 2 %, B R C A 1  i n 7 %, R A D 5 1 D  i n 4 %, a n d P A L B 2  i n 4 %.  T hese data pr o vi de str o n g 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 3  of 4 6   
2  Se pte m ber  2 0 2 0  
rati o nale f or t he use of P A R P i n hi bit ors i n s oli d t u m ors wit h h o m ol o g o us re pair deficie nc y 
o utsi de of B R C A 1/ 2  m utati o ns i n t u m ors ot her t ha n breast ca ncer.  
F urt her m ore, i de ntificati o n of s o matic m utati o ns i n  H R -relate d ge nes t hr o u g h c o m merciall y 
a vaila ble ne xt ge nerati o n se q ue nci n g of t u m or tiss ues als o has p ote ntial t o i de ntif y p atie nts wit h 
s o matic D N A re pair alterati o n w h o ma y d eri ve p ote ntial be nefit fr o m D N A defect -t ar gete d 
t hera p y, s uc h as a P A R P i n hi bit or.  St u dies t o assess t he efficac y of t his a p pr oac h are c urre ntl y 
n ot a vaila ble.   
2 . 4  
T he M yri a d H o m ol o g o us Rec o m bi n ati o n Deficie nc y ( H R D ) Ass a y  
T he M yria d H o m ol o g o us Rec o m bi nati o n Defici e n c y ( H R D ) Assa y is a n o v el assa y t hat h as bee n 
de vel o pe d usi n g a n i n direct a p pr oac h t hat all o ws f or t he d etecti o n of  H R D  re gar dless of its 
eti ol o g y or  mec ha nis m as meas ure d b y le vels of ge n o mic i nsta bilit y .  T he assa y is c o m pati ble 
wit h f or mali n -fi x e d paraffi n-e m be d de d ( F F P E) t u m or tiss ue a n d B R C A 1 a n d B R C A 2 t u m or 
se q ue nce d ata is si m ulta ne o usl y ge nerate d.  Earl y i n assa y d e vel o p me nt, ge n o mic re gi o ns of  l oss 
of heter oz y g osit y ( L O H) of i nter me diate le n gt h ( >  1 5  M b a n d <  1  c hr o m os o me) were s h o w n t o 
be hi g hl y ass o ciate d wit h  H R deficie nc y a n d t he  H R D -L O H sc ore was deri ve d as a c o u nt of 
L O H re gi o ns of t his le n gt h acr oss t he t u m or ge n o me .1 6  
O ur gr o u p has pre vi o usl y ass esse d t he  H R D -L O H  assa y i n Pr E C O G 0 1 0 5,  a ne oa dj u v a nt trial 
t hat e x pl ore d a n o n-a nt hrac ycli ne, n o n -t a x a ne, plati n u m-base d re gi me n i n patie nts 
wit h 
tri ple-ne gati ve or B R C A 1/ 2 m utati o n -ass ociate d breast ca ncer .  We  s h o we d t hat a hi g h H R D  
sc ore si g nifica ntl y c orrel ates wit h fa v ora ble pat h ol o gic res p o nse t o a plati n u m -base d re gi me n i n 
earl y-sta ge tri ple-n e gati v e  a n d B R C A 1 or B R C A 2 m utati o n -ass ociate d breast ca ncer 1 7 I n t his 
st u d y, patie nts recei ve d car b o plati n A U C 2 a n d ge m cita bi ne 1 0 0 0  m g / m2 o n da ys 1 a n d 8 e ver y 
2 1  da ys i n a d diti o n t o i ni pari b o n da ys 1, 4, 8, a n d 1 1. 1 8, 1 9 T he o verall p C R rate i n t he 
i nte nt-t o-treat p o p ulati o n was 3 6 % ( 9 0 % CI:  2 7 -4 6 %) .  N ota bl y, B R C A 1 a n d B R C A 2 m utati o n 
stat us was c o m pre he nsi v el y ass esse d a n d T N B C patie nts wit h a ger mli ne  B R C A 1 or B R C A 2 
m utati o n ac hie ve d a hi g her rate of p C R ( 5 6 %)  c o m pare d t o patie nts w h o were B R C A 1 a n d 
B R C A 2 wil d -t y pe ( 3 3 %).1 8, 1 9  A maj or ai m of Pr E C O G 0 1 0 5 was t o e val uate bi o mar kers of 
res p o nse t o t his ne o a dj u v a nt t hera p y i n patie nts wit h s p ora dic T N B C.  T he  H R D  assa y s c ore was 
assesse d i n a c o h ort of 7 7 t u m ors i n Pr E C O G 0 1 0 5 w here p at h ol o gic res p o nse was ass esse d 
usi n g t he resi d ual ca ncer b ur de n ( R C B) i n de x. 1 7, 2 0  T he a vera ge  H R D  assa y sc ore f or res p o n ders 
was 1 6. 2 a n d t he a vera ge sc ore f or n o n -res p o n ders 1 1. 2 ( p =  0. 0 0 0 3)  usi n g t he  H R D -L O H assa y .  
I nteresti n gl y, n o differen ce i n me dia n  H R D  sc ores was  n ote d bet wee n B R C A 1/ 2 -deficie nt vers us 
B R C A 1/ 2 -pr oficie nt res p o n ders .  F urt her m or e, if B R C A 1/ 2 -deficie nt sa m ples were e x cl u de d 
( n =  5 8), t he ass ociati o n bet wee n res p o ns e t o treat me nt a n d  H R D  assa y sc ore re mai n e d 
si g nifica nt ( p =  0. 0 0 0 6) .  O verall, 7 0 % of pati e nts wit h a n  H R D  assa y sc ore of  1 0 or a 
deleteri o us B R C A 1/ 2 m utati o n res p o n d e d c o m pare d wit h 1 2 % of p atie nts wit h a n  H R D  assa y 
sc ore of <  1 0 a n d i ntact B R C A 1/ 2 stat us ( p  =  0. 0 0 0 0 2). 1 7 T hese data s u g gest t hat t u m or 
meas ures of L O H ma y be i m p orta nt bi o mar kers i n t he i de ntificati o n of ger mli ne  B R C A 1 a n d 
B R C A 2 wil d -t y pe p atie nts w h o ma y be n efit fr o m D N A defect-tar get e d t hera p y, s uc h as plati n u m 
or a P A R P i n hi bit or.  
A d diti o nall y, t he  H R D -L O H  assa y h as bee n vali d ate d i n t w o pr os pecti ve b reast ca n cer c o h orts.  
T he Cis plati n -1 c o h ort i ncl u de d 2 8, mai nl y s p ora dic, tri ple -n e gati ve breast ca ncer patie nts 
treate d wit h ne oa dj u va nt cis plati n, 7 5 m g / m2 e ver y 2 1 da ys f or 4 c ycles .  T he Cis plati n -2 c o h ort 
i ncl u de d 5 1 tri ple-n e gati ve breast ca ncer pa tie nts treate d wit h ne o a dj u va nt cis plati n 7 5 m g / m2 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 4  of 4 6   
2  Se pte m ber  2 0 2 0  
e ver y 2 1 da ys f or 4 c ycl es pl us be vaciz u ma b 1 5  m g / k g f or 3 c ycl es.  T he pat h ol o gic res p o nse i n 
t hese st u dies was assesse d b y t he Miller-Pa y n e ( M P) sc ore, wit h res p o n ders ha vi n g a M P sc ore 
of 4 or 5, a n d n o n -res p o n ders M P sc ores of 1 t o 3 .  A nal yses were als o perf or me d i n patie nts 
ac hie vi n g a p C R vers us n o p C R .  T he a nal ysis of  H R D  sc ore vers us pat h ol o gic res p o ns e was 
perf or me d o n t he c o m bi ne d dataset .  T he mea n  H R D  sc ore a m o n g res p o n ders ( M P 4-5) vers us 
n o n -res p o n ders ( M P 1-3) was 1 8. 0 vers us 1 2. 9 wit h a n o d ds rati o of 3. 6 ( 3. 2 -4. 0) a n d p -v al ue of 
0. 0 1 3 .  Mea n  H R D  sc ores a m o n g patie nts wit h a p C R vers us n o n-p C R was 2 0. 6 vers us 1 3. 4 wit h 
a n o d ds rati o of 7. 4 ( 6. 3 -8. 6) a n d a p -v al ue of 0. 0 0 4 8 .  I m p orta ntl y, a mo n g patie nts wit h a n  H R D  
sc ore <  1 0, n o patie nts ac hie ve d a p C R w hile 2 4 % of patie nts wit h a n  H R D  ≥ 1 0 ac hie ve d a p C R 
res ulti n g i n 1 0 0 % se nsiti vit y a n d 1 0 0 % ne gati ve pre dicti ve v al ue f or p C R.  I n t his c o m bi ne d 
c o h ort, 7 2 % of patie nts ha d a n  H R D  sc ore of 1 0 or great er. 
Rece ntl y, t he  H R D  ass a y h as bee n f urt her o pti mize d a n d c urre ntl y i n c or p orat es a d diti o nal 
meas ures of ge n o mic i nsta bilit y, i ncl u di n g tel o meric allelic i m bala nce ( T AI; t he n u m ber of 
re gi o ns wit h allelic i m bala nce t hat e xte n d t o t he s u btel o mere, b ut d o n ot cr oss t he ce ntr o mere) 
a n d lar ge-scale state tra nsiti o ns ( L S T; t he n u m ber of c hr o m os o mal  brea ks bet wee n a djace nt 
ge n o mic re gi o ns l o n ger t ha n 1 0 M b after filteri n g o ut re gi o ns s h orter t ha n 3 M b). 2 1, 2 2 T he  H R D  
sc ore is c urre ntl y calc ul ate d b y a d di n g t he L O H, T AI a n d L S T s c ores a n d is re p orte d as a 
c o ntin u o us sc ore fr o m 0 -1 0 0 .  A n  H R D  sc ore of <  4 1 ( pre vi o usl y <  1 0) is defi ne d as  H R 
pr oficie nt a n d  H R D  s c ore of ≥ 4 2 ( pre vi o usl y ≥ 1 0) as  H R -deficie nt .  Usi n g t his c ut off, ~ 4 8 % of 
T N B C patie nts are classifie d as  H R -deficie nt.  
2. 5   
O ver vie w of t he st u d y a ge nt t al az o p ari b 
2. 5 . 1 N o ncli nic al St u dies of t al az o p ari b 
Talaz o pari b  is a hi g hl y p ote nt a n d s pecific i n hi bit or of P A R P 1 a n d 2 wit h acti vit y i n t u m or cell 
li nes beari n g D N A re p air deficie ncies.2 3, 2 4 talaz o pari b i n hi bits P A R P i n vitr o at a l o wer 
c o nce ntr ati o n (I C 5 0  =  0. 5 7  n M ) t ha n A B T 8 8 8 (I C 5 0 =  4. 7 3  n M ), A G 1 4 4 4 7 (I C 5 0 =  1. 9 8  n M ), 
or ola pari b (I C 5 0  =  1. 9 4  n M ).  Talaz o pari b  als o e x ert s si n gle-a ge nt s y nt hetic let halit y of B R C A 
1 a n d 2 a n d P T E N deficie nt cell li nes .  I n B R CA 2 ne gati ve Ca pa n 1 -cells, talaz o pari b was m ore 
p ote nt as si n gle a ge nt t ha n A B T -8 8 8 ( 1 0, 0 0 0 ti mes), A G 1 4 4 4 7 ( 6 0 9 ti mes) a n d ola pari b 
( 2 5 9 ti mes) i n i n hi biti n g P A R P acti vit y.  I n a ni mal m o dels, p ote nt a nti-t u m or acti vit y was 
o bser ve d at oral dail y d oses <  1  m g / k g/ da y.  C o m plete s u p pressi o n of B R C A 1 -deficie nt t u m or 
gr o wt h i n t he M X 1 m o d el was ac hie ve d i n a 3 -m o nt h st u d y w he n d os e d at 0. 1 6 5  m g / k g BI D .2 4 
Si milarl y, s u p pressi o n of P T E N -deficie nt t u m or gr o w t h was ac hie ve d i n x e n otra ns pla nt 
e x peri me nts wit h talaz o pari b d ose d at 0. 3 3  m g / k g o nce dail y f or 2 8 c o nsec uti ve da ys.2 4  
T he oral bi oa vaila bilit y, calc ulate d fr o m t he rati o of t he area u n d er t he c o n ce ntrati o n -ti me c ur ve 
( A U C) f oll o wi n g oral a d mi nistrati o n relati v e t o t he 
A U C f ollo wi n g i ntra v e n o us (I V) 
a d mi nistrati o n ( A U C oral/ A U CI V), was >  4 2. 7 % i n rats a n d >  5 0. 5 % i n d o gs base d o n si n gle d ose 
c o m paris o ns .  T he c o m p o u n d was meta b oli call y sta ble.  T he ter mi nal half -life of talaz o pari b at 
vari o us d oses i n rats a n d d o gs ra n ges fr o m 2 8 . 5 t o 3 2. 0 hr  a n d 6 9. 7 t o 9 1. 2  hr , res pecti vel y, 
w hic h all o ws f or o nce dail y d osi n g.  
P har mac o ki netic st u dies ha ve b ee n p erf or me d i n rats a n d d o gs .  Stea d y st ate c o n ce ntrati o ns were 
reac h e d o n Da y  1 5 i n rats a n d o n Da y  2 0 i n d o gs usi n g dail y a d mi nistrati o n  of talaz o pari b.  
C o m pari n g Da y  1 5 a n d 2 8 wit h Da y  1 f or all d ose le vels i n d o gs, A U C a n d C ma x  i ncrease d fr o m 
Da y  1 t o Da y  1 5 t o Da y  2 8.  


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 5  of 4 6   
2  Se pte m ber  2 0 2 0  
Fi ve -da y re peat d ose t o xicit y a n d t o xic o ki netic ( T K) st u dies wit h 2 8 -da y rec o ver y were 
c o n d ucte d i n rats a n d d o gs .  I n d o gs (t he m ost se nsiti ve s pecies), talaz o pari b was a d mi nistere d at 
d ose l e vels of 0. 0 0 3, 0. 0 1, 0. 0 3, 0. 1  m g / k g/ da y o ver 5 c o nsec uti ve da ys.  Se vere pa n c yt o p e nia 
was o bser ve d i n d o gs tr eate d wit h t he t w o hi g h est d ose gr o u ps ( 0. 0 3 a n d 0. 1  m g / k g/ da y).  At 
t hese d oses, t he m ea n ( or me dia n) retic ul oc yte na dir occ urre d o n Da y  6 a n d t he platel et a n d 
W B C na dirs o n Da y  1 1.  T hese c h a n ges were re v erse d i n t he gr o u p treate d at 0. 0 3  m g / k g/ da y o n 
da ys  1 7  t o 1 8 ( ie, 1 2  t o 1 3 da ys after t he last d ose of t he dr u g) .  M ortal ities occ urre d i n a ni mals 
gi ve n 0. 1  m g / k g/ da y d ue t o bact erial s e ptice mia s ec o n dar y t o b o n e marr o w h y p ocell ularit y a n d 
l y m p h oi d or ga n de pleti o n o n Da y  1 2  t o 1 3 .  C oa g ul ati o n para meters were u naffecte d .  After 
re peat-d ose a d mi nistrati o n of dail y oral tal az opari b  i n d o gs f or 5-da ys, t he hi g h est n o n -se v erel y 
t o xic d ose ( H N S T D) was 0. 0 3 m g / k g/ da y.  T we nt y -ei g ht d a y re p eat d ose t o xicit y a n d T K st u dies 
wit h 2 8 -da y rec o v er y were als o c o n d u cte d i n rats a n d d o gs .  I n d o gs, talaz o pari b was 
a d mi nistere d at d osa ge le ve ls of 0. 0 0 0 5, 0. 0 0 1 5, 0. 0 0 5, 0. 0 1 m g / k g/ da y o ver 2 8 c o nsec uti ve 
da ys .  Tal az o pari b -rel ate d si g ns i ncl u de d he mat ol o g y fi n di n gs i n males a n d fe males gi ve n 0. 0 0 5 
or 0. 0 1  m g / k g/ da y s uc h as mil dl y l o w er re d cell mass, mil dl y t o m o derat el y l o wer platelet a n d 
a bsol ute retic ul oc yte c o u nts, a n d mi ni mall y t o mil dl y l o wer w hite bl o o d cell c o u nts wit h a 
ge n eralize d d ecrease i n all le u k oc yt es .  All of t hese si g ns re verse d or were re versi n g b y t he e n d 
of t he rec o v er y p h ase .  After re peat -d ose a d mi nistrati o n of dail y oral  talaz o pari b i n d o g f or 2 8 
da ys, t he H N S T D was 0. 0 1  m g / k g/ da y. 
I n c o n cl usi o n, t he mai n n o ncli nical fi n di n gs of earl y he m at ol o gical c ha n ges, a n d s u bse q ue nt 
b o ne marr o w a n d l y m p h oi d or ga n d e pleti o n as well as f ocal n ecr osis after re p eat a d mi nistrati o n 
of talaz o pari b are i n acc or da nce wit h t he mec ha nis m of acti o n a n d t he e x p os ure/ distri b uti o n 
patter n .  T hese fi n di n gs were re versi ble a n d t he decrease d retic ul oc yte, platelet, re d bl o o d cell 
( R B C) a n d W B C c o u nts were s e nsiti ve a n d earl y mar kers of tar get or ga n t oxicit y .  Decreases i n 
he mat ol o g y p ara meters were us e d t o cli nicall y m o nit or safet y .  A starti n g cli nical d ose was 
esti mate d usi n g t h e d o g H N S T D as t he d o g was m ore se nsiti ve t o tal az o pari b-rel ate d pri mar y 
t o xicities t ha n t he rat.  Base d o n a 6 ti mes safet y  fact or relati ve t o t he 2 8-da y t o xicit y st u d y i n 
d o g H N S T D, t he esti mat e d safe cli nical starti n g d ose is 1  μ g / k g/ da y.  T he differe n ce i n relati ve 
bi oa vaila bilit y after a d mi nistrati o n of t he ca ps ule a n d oral ga va ge s us pe nsi o n of talaz o pari b was 
a p pr o xi matel y t w o -f ol d.  Ta ki n g i nt o acc o u nt t he relati ve c ha n ge i n e x p os ure wit h t he ca ps ul e 
vers us t he oral ga v a ge s us pe nsi o n, t he esti mate d safe cli nical starti n g d os e was recalc ulate d a n d 
is 0. 5 μ g / k g/ da y t alaz o pari b.  T heref ore, t he sta rti n g fi xe d cli nical d os e of 2 5 μ g  talaz o pari b i n a 
ca ps ule f or m c orres p o n ds t o 0. 4 2  μ g / k g/da y f or a 6 0 -k g a d ult.  
2. 5 . 2 Cli nic al St u dies of T al az o p ari b   
T hree st u dies o n g oi n g  at t he ti me of t his u p date : 
 P R P -0 0 1, i nitiate d o n J a n uar y 3r d 2 0 1 1, is a si n gl e -ar m, o pe n -la bel st u d y t o assess t h e safet y, 
p har mac o ki netics ( P K), p har mac o d y n a mics ( P D), a n d preli mi nar y efficac y of talaz o pari b i n 
patie nts wit h a d va nce d t u m ors wit h D N A -re pair pat h wa y a b n or malities, partic ularl y t h ose 
ass ociate d wit h B R C A - a n d P T E N-d ysf u ncti o n .  T he i nitial c o h or t of patie nts was treate d 
wit h 2 5  µ g talaz o pari b o nce dail y .  T his t w o -sta ge p h ase  1  st u d y was u p date d at t he 2 0 1 4 
A S C O A n n ual Meeti n g .  At t his ti me e x pa nsi o n p hase e nr oll me nt i n s mall cell l u n g ca ncer, 
ger mli ne  B R C A breast a n d o varia n ca n cer a n d E wi n g's sarc o ma is c o m plete.  T he M T D a n d 
Rec o m me n de d P has e 2 D ose ( R P 2 D) was esta blis he d at 1  m g / d i n 3 9 pts ( 3 3 F/ 6 M) treate d at 
d oses ra n gi n g fr o m 2 5 t o 1 1 0 0  μ g / d.  D ose -li miti n g t hr o m b oc yt o p e nia occ urre d i n 1/ 6 a n d 
2/ 5 pts at 9 0 0 a n d 1 1 0 0  μ g / d, res p ecti vel y2 5. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 6  of 4 6   
2  Se pte m ber  2 0 2 0  
 6 7 3 -3 0 1, i nitiate d o n Oct o ber 3 0,  2 0 1 3 is a n o pe n -la bel, ra n d o mize d, parallel, 2-ar m st u d y of 
talaz o parib  vers us pr ot oc ol -s pecific p h ysicia n's c h oice t hera p y i n s u bjects wit h ger mli ne  
B R C A m utati o n  wit h  l ocall y a d v a nce d a n d/ or met astatic breast ca ncer.  
 6 7 3 -2 0 1: 2 -sta ge, 2-c o h ort p hase  2 trial is t o e val uate t he safet y a n d efficac y of talaz o pari b i n 
s u bjects wit h l ocall y a d v a nce d or m etastatic breast ca ncer wit h a deleteri o us ger mli ne  B R C A 
1 or B R C A 2 m utati o n .  S u bjects will be assi g ne d t o eit her C o h ort  1 or 2 base d o n pri or 
c he m ot hera p y f or metast atic disease:  
 C o h ort  1) S u bjects w h o ha ve pre vi o usl y res p o n d e d t o plati n u m -c o ntai ni n g re gi me n f or 
metastatic diseas e wit h disease pr o gressi o n 
>  8 wee ks f oll o wi n g t he last d ose of 
plati n u m; or  
 C o h ort  2) S u bjects w h o ha ve recei ve d >  2 c h e m ot hera p y re gi me ns a n d w h o ha ve ha d n o 
pri or plati n u m t hera p y f or metastatic dise as e  
I n a d diti o n, a f o o d effect st u d y ( 6 7 3-1 0 3) i n 1 8 healt h y v ol u nteers has bee n c o m plete d .  T he f o o d 
effect st u d y s h o w e d t hat, w hile a hi g h -fat, hi g h-cal orie meal del a ye d t he a bs or pti o n of orall y 
a d mi nistere d talaz o pari b, it di d n ot affect t he o v erall e xte nt of a bs or pti o n .  Si n gle 5 0 0 µ g d os es 
were s afe a n d well t olerate d i n healt h y m ale v ol u nteers.  
Preli mi nar y P K data fr o m Part 1 of P R P -0 0 1, t hr o u g h C ycle 1, was a v aila ble at t he ti me of t his 
re p ort.  O verall, plas ma c o nce ntrati o ns of t alaz o pari b i ncrease d i n a d ose-de pe n d e nt ma n ner, 
wit h m ost patie nts o btai ni n g ste a d y -state plas ma c o nce ntrati o ns b y t he e n d of t he s ec o n d wee k of 
dail y d osi n g ( Da y  2 2) .  As i n dicate d b y l o g -li near c o n ce ntrati o n-ti me pr ofiles o n Da y  1 a n d 
Da y  3 5, talaz o pari b eli mi nati o n a p pear e d t o f oll o w bi p hasic ki netics.  
C u m ulati vel y, t here h a v e bee n 1 1 1 S A Es re p orte d i n cli nical st u dies wit h talaz o pari b as of 
N o ve m ber 3 0 t h 2 0 1 3.  T he m ost c o m m o n reas o ns f or S A Es ha ve bee n i nfecti o us ( 3 3 e ve nts), 
gastr oi ntesti nal dis or d ers ( 1 6 e v e nts), bl o o d  a n d l y m p hatic dis or ders ( 1 3 e ve nts), a n d res pir at or y 
dis or ders ( 1 2 e ve nts) .  T he m ost c o m m o nl y re p orte d S A Es b y preferre d ter m i ncl u de fe brile 
ne utr o pe nia ( 9 e ve nts), ne utr o pe nic s e psis ( 7 e ve nts), as cites  ( 5 e ve nts), a n d bactere mia ( 5 
e ve nts).  All b ut 9  of t hese 1 1 1 S A Es were assesse d b y t he i n vesti gat ors as n ot relate d t o 
treat me nt wit h talaz o pari b. 
A d verse e v e nts occ urri n g i n at least 1 0 % of patie nts i n t he p o ole d st u d y p o p ulati o n of P R P -0 0 1, 
P R P -0 0 2, 6 7 3 -1 0 3 a n d 6 7 3 -3 0 1 ha ve i ncl u de d: fati g ue, na usea,  a n e mia, c o nsti pati o n, diarr hea, 
v o miti n g, t hr o m b oc yt o p e nia, c o u g h, p yre xia, hea dac he, n e utr o pe nia, al o peci a, decrease d 
a p petite, a b d o mi nal pai n, bac k pai n, d ys p nea, pai n i n e xtre mities, h y p o kal e mia, a n xiet y, 
art hral gia, a n d dizzi ness .  A d verse reacti o ns h a v e n ot w orse n e d wit h c o nti n ue d t hera p y at t he 
sa me or re d u ce d d os e.  
Base d o n its mec ha nis m of acti o n, precli nical acti vit y a n d p har mac o ki netic ( P K) a n d t o xicit y 
pr ofile , talaz o pari b was selecte d f or cli nical e val u ati o n i n t u m ors wit h de m o nstrate d or p ote ntial 
defects i n D N A re pair pat h wa ys, s uc h as B R C A m utati o ns, P T E N d ysf u ncti o n or a b n or mal 
R A D 5 1 f oci f or mati o n .  Talaz o pari b  has b ee n s h o w n t o be hi g hl y selecti ve a n d p ote nt c yt ot o xic 
a ge nt i n h u ma n ca n cer cell li nes a n d i n a ni mal m o dels of t u m ors h ar b ori n g m utati o ns t hat 
c o m pr o mise 
D N A re p air pat h wa ys .  P har mac o ki netic para meters de m o nstrate d a hi g h 
bi oa vaila bilit y wit h a distri b uti o n pr ofile i n dicati n g e xte nsi ve tiss ue distri b uti o n, a n d a d urati o n 
of e x p os ure s ufficie nt t o s u p p ort o nce dail y d osi n g .  C ha n ges i n he mat ol o g y para meters were 
earl y mar kers of t o xic ol o g y fi n di n gs .  A ne mia, t hr o m b oc yt o pe ni a, a n d n e utr o pe nia ha v e all b ee n 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 7  of 4 6   
2  Se pte m ber  2 0 2 0  
o bser ve d, i ncl u di n g Gra de  3 -4 e ve nts .  T he e v e nts of fati g ue, n a usea, c o nsti pati o n, diarr hea, 
v o miti n g, c o u g h, p yre xia, hea dac h e, al o p ecia, d ecrease d a p petite, a b d o mi nal pai n, bac k pai n, 
d ys p nea, pai n i n t he e xtre mities, h y p o k ale mia, a n xiet y, art hral gia, a n d diz zi ness ha ve als o b ee n 
o bser ve d i n s u bjects recei vi n g 
talaz o pari b.  All 
patie nts are 
bei n g 
m o nit ore d f or 
m yel o -s u p pressi on i n t he o n g oi n g st u dies.  
T he  ta ble b el o w s u m marize s t he safet y d ata of  t alaz o pari b as ass esse d b y t he p hase  1  tri al i n 
patie n ts wit h a d va nce d s oli d t u m ors.2 5 
T a ble 1 .  Safet y dat a f or p hase  1  d ose es calati o n/e x pa nsi o n trial f or patie nts wit h s oli d ca ncers 2 5 
 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 8  of 4 6   
2  Se pte m ber  2 0 2 0  
 
Fi g ure 2 .  B R C A 1/ B R C A 2  breast c a ncer R E CI S T waterfall pl ot i n p hase  1  trial of talaz o pari b2 5 
2. 6   
R ati o n ale   
P ol y ( A D P -ri b ose) p ol y merase-1 ( P A R P 1) a n d P A R P 2 pla y i m p orta nt r oles i n D N A re pair .7 T he 
cli nical de v el o p me nt of P A R P 1/ 2 i n hi bit ors a d va nce d w he n t he pri n ci ple of c h e mical s y nt hetic 
let halit y was esta blis he d i n B R C A 1/ 2-deficie nt cells .2 S y nt hetic let halit y st e ms fr o m t he i na bilit y 
of B R C A -defi cie nt cells t o u n der g o h o m ol o g o us rec o m bi nati o n -me diate d d o u ble -stra n d D N A 
brea k re pair, ma ki n g t he m s usce pti ble t o D N A da ma ge ca us e d b y a P A R P i n hi bit or .3, 5, 6 T w o 
p hase  2  pr o of -of -c o n ce pt st u dies d oc u me nte d o bjecti ve res p o nses t o si n gle a ge nt ola pari b, a n 
oral P A R P i n hi bit or, i n B R C A 1/ 2  m utati o n carri ers wit h a d v a n ce d o v aria n a n d breast ca n cer .1 3, 2 6  
Gi ve n t hat s p ora dic tri ple -ne gati ve breast ca n cers s h are ma n y p at h ol o gical a n d m olec ular 
feat ur es wit h breast ca ncers arisi n g i n t he setti n g of a here ditar y B R C A m utati o n, it was 
s u g geste d t hat t hese s p ora dic t u m ors mi g ht s hare si milar D N A re p air defects a n d s h o w si milar 
c he m ose nsiti vit y t o B R C A m utati o n -ass ociate d t u m ors .  T he acti vit y of si n gle -a ge nt ol a pari b, a 
b o na fi de P A R P i n hi bit or, 
was i n vesti gate d i n a s mall c o h ort of u nselecte d s p ora dic 
tri ple-ne gati ve breast ca ncer patie nts, h o we ver, n o o bjecti ve res p o nses were n ote d a n d f urt h er 
i n vesti gati o n was h alte d.1 3 T hese e x perie nces t h warte d t h e cli nical d e ve l o p me nt of P A R P 
i n hi bit ors i n s p ora dic tri ple-ne gati ve breast ca ncer .  T he i na bilit y t o select B R C A 1/ 2 wil d -t y p e 
t u m ors wit h u n derl yi n g D N A re p air defects f urt her c o m p o u n de d t he pr o ble m. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 1 9  of 4 6   
2  Se pte m ber  2 0 2 0  
D ue t o t hes e earl y c halle n ges, t he r ole of P A R P i n hi biti o n i n t he tre at me nt of s p ora di c 
tri ple-ne gati ve breast ca n cer h as re mai n e d u n defi ne d .  T he c halle n ge at h a n d is t o a p pr o priat el y 
select patie nts lac ki n g a ger mli ne  B R C A 1/ 2 m utati o n f or t he ne xt ge nerati o n of cli nical trials .  
Patie nt C o h ort  A of o ur pr o p ose d st u d y wit h  t h e P A R P i n hi bit or talaz o pari b ai ms t o a d dress t his 
i m p orta nt q uesti o n b y selecti n g a s u b p o p ulati o n of s p ora dic, tri ple-ne gati ve breast ca ncer 
patie nts e nric he d f or h o m ol o g o us rec o m bi nati o n deficie nc y (H R D ) as assesse d b y a n o vel 
tiss ue-base d assa y d e vel o p e d b y M yri a d Ge netics .  T he  H R D  assa y has bee n de vel o pe d usi n g a n 
i n direct a p pr oac h t hat all o ws f or t he detecti o n of H R D  re gar dless of its eti ol o g y or mec ha nis m as 
assesse d b y l e vels of ge n o mic i nsta bilit y.1 6 O ur gr o u p has pre vi o usl y e val u ate d t he  H R D  assa y i n 
a ne o a dj u va nt p has e  2  tri al of ge mcita bi ne, car b o plati n a n d i ni pari b a n d s h o we d t hat a hi g h H R D  
sc ore si g nifi ca ntl y c orrel ate d wit h fa v ora ble pat h ol o gic res p o nse t o t his plati n u m -base d re gi me n 
i n earl y-sta ge tri ple-ne gati ve breast ca n cer p atie nts wit h a n d wit h o ut a ger mli ne  B R C A 1/ 2 
m utati o n .1 7, 1 9  
Gi ve n o ur fi n di n gs, we h y p ot hesize t hat t he  H R D  assa y ca n be use d t o select tri ple -ne gati ve 
breast ca n cer patie nts m ost li k el y t o deri ve be nefit fr o m a si n gle -a ge nt P A R P i n hi bit or treat me nt 
strate g y.  Talaz o pari b  is a n o vel oral P A R P 1/ 2 i n hi bit or s h o w n i n precli ni cal m o dels t o be m ore 
p ote nt t ha n ot her a ge nts i n its class a n d a rec o m m e n de d phas e  2  d ose has b ee n deter mi ne d .2 4, 2 5, 2 7 
As s uc h, it is a n i deal dr u g t o e val uat e i n a pr o of -of -c o nce pt st u d y of si n gle -a ge nt P A R P 
i n hi bit or t hera p y i n patie nts wit h a d va nce d tri ple-ne gati ve breast ca ncer, w h o lac k a ger mli ne  
B R C A 1 or B R C A 2 m utati o n,  b ut are  H R -deficie nt b y t he  H R D  assa y.  
O ur sec o n d p atie nt c o h ort ( C o h ort  B) ai ms t o e val uate t he efficac y a n d s afet y of tal az o pari b i n a n 
e mer gi n g s u b -gr o u p of breast ca ncer patie nts , or ot her n o n -breast metastatic s oli d t u m ors  wit h 
hi g h li keli h o o d of  H R  d eficie nc y st e m mi n g fr o m ger mli ne  or s o matic m utati o ns i n ge nes ot h er 
t ha n B R C A 1 a n d B R C A 2 i m plicate d i n t he d o u bl e-stra n de d D N A brea k re pair pat h w a y.  Bas e d 
o n t he li mite d c urre nt data, t he pre vale nce of s uc h here ditar y breast a n d o varia n ca ncer 
s y n dr o mes is esti mate d t o be as hi g h as 5 % of t he ge neral breast ca ncer p atie nt p o p ulati o n. 1 4, 1 5 
Gi ve n t he i n crease d utilizati o n of c o m mercial m ulti ple x ger mli ne  ge ne pa nels  as well as t h e 
i ncreas e d a v aila bilit y of ne xt generati o n t u m or se q ue nci n g , we will li kel y  ca pt ure m ore of t hese 
pati e nts i n c o m m u nit y a n d aca de mic  o nc ol o g y  practices  i n c o mi n g years; h o we ver, d ue t o t he 
c urre nt lac k of  cli nical trials assessi n g t he utilit y of P A R P i n hi bit ors i n t his heter o ge ne o us gr o u p 
of breast ca ncer patie nts, we d o n ot yet k n o w t he efficac y of s uc h a strate g y .  T h us, t his 
pr o of -of -c o nce pt st u d y will assess t he r ole of P A R P i n hi biti o n i n a d va nce d H E R 2 -ne gati v e 
breast ca ncer a n d ot h er n o n -breast s oli d t u m ors wit h pres u me d u n derl yi n g  H R -deficie nc y d ue t o 
a ger mli ne  or s o matic m utati o n i n t he  H R pat h wa y .  


I R B-3 1 9 1 3 versi o n 8  
P a ge 2 0  of 4 6   
2  Se pte m ber  2 0 2 0  
2. 7   
St u d y Desi g n  
T his is a si n gle -ar m, o pe n -la bel treat me nt pr ot oc ol desi g ne d t o e val uate t he efficac y a n d s afet y 
of talaz o pari b i n 2  patie nt c o h orts:  
 C o h ort  A : A d v a nce d s p ora dic, tri ple -n e gati ve breast ca n cer wit h h o m ol o g o us rec o m bi nati o n 
deficie nc y b ase d o n a hi g h  H R D  assa y sc ore (H R D  sc ore ≥ 4 2 ) 
 C o h ort  B : A d va n ce d H E R 2 -ne gati ve ( ie, E R a n d/ or P R p ositi ve or T N) breast ca n cer or 
ot her n o n -breast metastatic  ca ncer wit h  a d eleteri o us  or s us pecte d del eteri o us ger mli ne  or 
s o matic ge n e m utati o n i n t he h o m ol o g o us rec o m bi nati o n pat h wa y, e x cl u di n g B R C A 1 a n d 
B R C A 2 .  M utati o ns of i nterest are:  
o  P T E N ;  P A L B 2 ;  C H E K 2 ;  A T M ;  N B N ;  B A R D 1 ;  B RI P 1 ;  R A D 5 0 ;  R A D 5 1 C ;  
R A D 5 1 D ;  M R E 1 1 ;  A T R ;  Fa nc o ni a ne mia c o m ple me ntati o n gr o u p of ge nes ( F A N C A ;  
F A N C C ;  F A N C D 2 ;  F A N C E ;  F A N C F ;  F A N C G ;  F A N C L) ;  pl us ot her  H R -relate d 
ge n es a t t he discreti o n of t he pri mar y i n vesti gat ors . 
T his st u d y 
will pr ocee d 
wit h 2  p hases: scree ni n g a n d treat me nt .  D uri n g scree ni n g, 
all 
partici pa nts will be as ke d t o pr o vi de a metastatic t u m or  bi o ps y sa m ple t o assess t he H R D  sc ore 
base d o n t he  H R D  assa y.  T his res ult is re q uire d f or eli gi bilit y deter mi nati o n i n C o h ort  A .  If t he 
patie nt d oes n ot ha ve a n a de q uate  t u m or bi o ps y sa m ple fr o m a metastatic site, bi o ps y will be 
perf or me d d uri n g scree ni n g .  If t his is n ot feasi ble, we will use t he pri mar y  t u m or f or H R D  sc ore 
assess me nt .  At t his ti me, we will n ot be offeri n g s cree ni n g ger mli ne  testi n g t o assess t he 
prese nce of a delet eri o us B R C A 1 or B R C A 2 m utati o n n or t he ot her  H R pat h wa y ge n es of 
i nterest i n t his trial.  Patie nts w h o ha ve alrea d y bee n i de ntifie d as h ar b ori n g a  deleteri o us  or 
s us pecte d d eleteri o us  ger mli ne  m utati o n i n t h e  H R pat h w a y o n m ulti ple x ger mli ne  p a nels 
(M y Ris k, A m br y, I n Vitae, B R O C A, or ot her C LI A a p pr o ve d assa y ) or t h ose patie nts w h o ha d an  
deleteri o us or s us p ecte d deleteri o us  H R pat h wa y s o matic m utati o n i de ntifie d t hr o u g h ne xt 
ge n erati o n s e q ue n ci n g  of t heir t u m or ( F o u n dati o n O ne or ot her C LI A a p pr o ve d assa y) will be 
eli gi ble f or tr eat me nt i n C o h ort  B .  All p atie nts will be as ke d t o pr o vi de a bl o o d s a m ple t o r u n 
t he m y Ris k here ditar y 2 5-ge ne pa n el f or researc h p ur p oses o nl y. 
Patie nts w h o are eli gi ble f or treat me nt i n C o h ort  A  i ncl u de t h os e w h o are B R C A 1 a n d B R C A 2 
wil d -t y pe, h a ve a d v a nce d  T N B C a n d a t u m or H R D  sc ore of ≥ 4 2 .  
Patie nts w h o are eli gi ble f or treat me nt i n C o h ort  B  i ncl u de t h ose w h o are B R C A 1 a n d B R C A 2 
wil d -t y pe wit h H E R 2-n e gati ve a d va n ce d breast ca ncer or ot her n o n -breast s oli d t u m ors a n d 
eit her a d eleteri o us or s us pecte d del eteri o us ger mli ne  or  s o matic m utati o n i n H R pat h wa y -relate d 
ge n es be y o n d B R C A 1 a n d B R C A 2 .  T hese ge nes i ncl u de:  
P T E N ;  P A L B 2 ;  C H E K 2 ;  A T M ;  N B N ;  B A R D 1 ;  B RI P 1 ;  R A D 5 0 ;  R A D 5 1 C ;  R A D 5 1 D ;  
M R E 1 1 ;  A T R ;  Fa n c o ni a ne mia c o m ple m e ntati o n gr o u p of ge n es ( F A N C A ;  F A N C C ;  
F A N C D 2 ;  F A N C E ;  F A N C F ;  F A N C G ;  F A N C L) ;  pl us ot her  H R -relate d ge nes at t he 
discreti o n of t he pri mar y i n vesti gat ors .  
T he n o mi nal d urati o n of treat me nt is 3 6  c ycl es ( 2 8  da ys per c ycle), b ut C R, P R, or S D patie nts 
ma y c o nti n ue t hera p y u ntil e vi de nce of pr o gressi ve disease or u nacce pta ble t o xicit y occ urs .  
Pr ot oc ol t hera p y will be disc o nti n ue d  f or pr o gressi ve disease at a n y ti me.  Patie nts are free t o 
halt t hera p y at t heir re q u est.  Treat me nt ma y b e disc o nti n ue d if i nterc urre nt c o -m or bi dities occ ur, 
w hic h, i n t he o pi ni o n of t he treati n g p h ysicia n, w o ul d precl u de safe a d mi nistrati o n of st u d y dr u gs  


I R B-3 1 9 1 3 versi o n 8  
P a ge 2 1  of 4 6   
2  Se pte m ber  2 0 2 0  
P ati e nts will be sc he d ule d f or f oll o w-u p  ge netic c o u nseli n g if acti o n a ble m ut ati o ns are 
f o u nd.   
3.   
P A R TI CI P A N T S E L E C TI O N A N D E N R O L L M E N T P R O C E D U R E S  
3. 1  Eli gi bilit y Criteri a a n d P artici p a nt Eli gi bilit y C hec klist  
I n cl usi o n a n d E x cl usi o n Criteria are pr o vide d o n t he Eli gi bilit y  C hec klist f oll o wi n g, w hic h is t o 
be e xtracte d fr o m t his d o c u me nt f or use i n scree ni n g p ote ntial s u bjects.  F or eac h pr os pecti ve 
st u d y partici p a nt t hat is scree n e d, t his c hec klist will be pri nte d, c o m plete d i n its e ntiret y a n d t h e 
results rec or de d, a n d t he c hec klist will be file d i n t he res pecti ve s u bject  bi n der or file.  It is 
a ntici pate d t hat n ot all pr os pecti ve st u d y p artici pa nts t hat are scree n e d will be e nr olle d.   
P urs ua nt t o Sta nf or d Me dici ne S O P “ C o nfir mati o n of Partici pa nt Eli gi bilit y i n Cli nical Trials,” 
t he treati n g P h ysici a n (i n vesti gat or);  t he St u d y C o or di nat or;  a n d a n I n d e p e n de nt  Re vie wer will  
verif y t hat t he s u bject’s eli gi bilit y is acc urate;  c o m plete;  a n d le gi ble i n s o urce rec or ds.  
A  descri pti o n of t he eli gi bilit y v erificati o n pr o cess will be i ncl u de d i n t he E PI C or ot her 
Electr o nic Me dical Rec or d pr o gress n ote.  
  










I R B-3 1 9 1 3 versi o n 8  
P a ge 2 6  of 4 6   
2  Se pte m ber  2 0 2 0  
3. 2   
I nf or me d C o nse nt Pr ocess 
All pa tie nts m ust be pr o vi de d a c o nse nt f or m descri bi n g t he st u d y wit h s ufficie nt i nf or mati o n f or 
parti ci pa nts t o ma ke a n i nf or me d decisi o n re gar di n g t heir partici pati o n.  Partici pa nts m ust si g n 
t he I R B a p pr o ve d i nf or me d c o nse nt pri or t o partici pati o n i n a n y st u d y s pecific pr oce d ure.  T he 
partici pa nt m ust recei v e a c o p y of t he si g ne d a n d date d c o nse nt d o c u m e nt.  T he ori gi nal si g ne d 
c o p y of t he c o ns e nt d oc u me nt m ust be retai ne d i n t he me dical rec or d or res earc h file.  
3. 3   
R a n d o miz ati o n Pr o ce d ures  
Patie nts will n ot be ra n d o mize d i n t his st u d y, as it is a n o pe n-la bel si n gle ar m trial c o nsisti n g of 
2  c o h orts, b o t h of w hic h will recei ve t he st u d y dr u g.  At least 1 0 H E R 2 -ne gati ve breast ca ncer 
patie nts will be e nr olle d i n C o h ort  B.  
3. 4   
St u d y Ti meli ne  
Pri m ar y C o m pleti o n:   T he st u d y will reac h  pri mar y c o m pleti o n 3 6  m o nt hs fr o m t he ti me t he 
st u d y o pe ns t o accr ual.  T his is t he esti mate d ti me of accr ual of t he last patie nt ( n u m ber  2 0 ) i n 
eac h c o h ort . 
St u d y C o m pleti o n:  T he st u d y will reac h st u d y c o m pleti o n 3 6  m o nt hs fr o m t he ti me t he st u d y 
o pe ns t o accr ual.   
4.   
T R E A T M E N T P L A N  
4. 1   
Scree ni n g Pr oce d ures  
I nf or me d c o nse nt m ust be d oc u me nte d bef ore a n y trial-s pecific pr oce d ures or treat me nts are 
c o n d ucte d.  T his st u d y will ha ve a m olec ular pre -scree n c o ns e nt f or C o h ort  A  t o assess t he H R D  
sc ore usi n g F F P E t u m or tiss ue e val uate d b y t he M yria d H R D  assa y.  All patie nts w h o m eet 
eli gi bilit y criteria base d o n t he pre-s cree n c o nse nt will be pr o vi de d  a writte n m ai n st u d y 
i nf or me d c o nse nt  d o c u me nt .  At t his ti me we will n ot be offeri n g s cree ni n g f or ger mli ne  or 
s o matic m utati o ns i n t he H R pat h wa ys ge nes of i nterest .  All patie nts e nr ol le d i n C o h ort  B of t his 
trial will ha ve a k n o w n deleteri o us or s us pecte d deleteri o us ger mli ne  or s o matic m utati o n i n a 
ge n e of i nterest pri or t o st u d y e nr oll me nt.  
T he f oll o wi n g s cree ni n g pr oce d ures will be perf or me d o n s u bjects c o nse nti n g f or m olec ular 
pre -scree ni n g f or C o h ort  A : 
 Deter mi nati o n of  H R D  s c ore bas e d o n f or mali n fi xe d paraffi n e m be d d e d ( F F P E) 
metastatic t u m or site c ore bi o ps y .  If t he patie nt d oes n ot ha ve a n a de q uat e t u m or bi o ps y 
sa m ple fr o m a metast atic site, bi o ps y will be perf or me d d uri n g scree ni n g.  If t his is n ot 
feasi ble, we will use t he pri mar y t u m or f or H R D  s c ore ass ess me nt. 
T he f oll o wi n g scree ni n g pr oce d ures will be perf or me d o n c o nse nt e d a n d eli gi ble s u bjects after 
t he mai n st u d y c o ns e nt is si g ne d wit hi n 2 8 da ys  of i nitiati n g st u d y tre at me nt:  
 Me dical hist or y  
 C o m plete p h ysical e x a mi nati o n, i ncl u di n g hei g ht a n d wei g ht  
 Vital si g n assess me nt, i n cl u di n g bl o o d press ure a n d p ulse  
 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 assess me nt  


I R B-3 1 9 1 3 versi o n 8  
P a ge 2 7  of 4 6   
2  Se pte m ber  2 0 2 0  
 La b orat or y e val uati o n, i n cl u di n g C B C wit h d iffere ntial, c o m pre he nsi ve met a b olic pa nel, 
a n d uri ne pre g na nc y t est  
 Pat h ol o g y re vie w (i ncl u di n g re vi e w of E R/ P R/ H E R 2  f or breast ca ncers) of t u m or fr o m 
metastatic site or a bi o ps y of met astatic site, if n ot d o ne pre vi o usl y .  
 C T sca n wit h I V c o ntr ast of c he st, a b d o me n, a n d pel vis or P E T/ C T sca n wit h I V c o ntrast 
f or c o m plete disease e v al uati o n.  C o ntin ue t o use t he sa me e v al uati o n met h o d d uri n g t he 
st u d y as use d f or i nitial e val uati o n 
 M RI brai n  or C T h ea d, if pri or hist or y of brai n metastases 
 F or patie nts eli gi ble f or C o h ort  B, deter mi nati o n of  H R D  sc ore b ase d o n f or mali n fi xe d 
paraffi n e m be d de d ( F F P E) metastatic t u m or site c ore bi o ps y is r e q uire d, b ut is n ot nee de d 
f or eli gi bilit y a n d d oes n ot nee d t o be re p orte d pri or t o treat me nt i nitiati o n.  If t he patie nt 
d oes n ot ha ve a n a de q uat e t u m or bi o ps y sa m ple fr o m a metastatic site, bi o ps y will be 
perf or me d d uri n g scree ni n g .  If t his is n ot feasi ble, we will use t he pri mar y t u m or 
f or H R D  sc ore assess me nt. 
 Researc h ger mli ne  bl o o d c ollecti o n  
 Researc h M y Ris k ger mli ne  bl o o d c ollecti o n  
 Researc h pl as ma c ollecti o n  
 S u b missi o n of arc hi val t u m or tiss ue fr o m t he pri mar y breast t u m or  
4. 2   
D osi n g a n d A d mi nistr ati o n Sc he d ule  
N O T E:     1  c ycle =  2 8  d a ys  
Talaz o pari b  will be a d mi nistere d at 1 milli gra m orall y dail y .  Talaz o pari b  s h o ul d be ta ke n at 
a p pr o xi matel y t he sa me ti me eac h d a y .  Talaz o pari b  will be ta ke n orall y a n d s wall o we d w h ole.  
All d osa ges prescri be d a n d dis pe nse d t o t he patie nt a n d all d ose c ha n ges d uri n g t h e st u d y m ust 
be rec or de d .  Me dicati o n la bels will c o m pl y wit h U S 
le gal re q uire m e nts a n d be pri nte d i n 
E n glis h .  T he y will s u p pl y n o i nf or m ati o n a b o ut t he patie nt.  
T he I P is talaz o pari b, a w hite t o off-w hite cr ystalli ne p o w der .  T he dr u g s u bsta n ce is a 
4 -met h yl be nze n es ulf o nat e (t os ylate) salt of talaz o pari b free base, the acti ve m oiet y .  T he dr u g 
pr o d uct c o nsists of t he dr u g s u bsta n ce f or m ulate d wit h a p har mace uticall y -s uita ble e x ci pie nt 
fille d i nt o h y dr o x y met h yl pr o p ylcell ul ose ca ps ul es.  Ca ps ules will be pr o vi de d t o t he site i n 3 
d ose stre n gt hs of 0. 1 0  m g , 0. 2 5 m g , a n d 1. 0  m g  ca ps ules .  T he d ose str e n gt hs are base d o n t he 
acti ve m oiet y ( t alaz o pari b free bas e).  T he ca ps ules are pr o vi de d i n d ose -s pecifi c c ol ors t o 
pr o vi de a vis ual met h o d of disti n g uis hi n g d ose stre n gt hs .  St u d y dr u g s h o ul d be st ore d at r o o m 
te m perat ur e ( 15  t o 3 0° C;  5 9  t o 8 6° F) .  T he ca ps ules are s u p plie d i n 3 0 -c o u nt i n d ucti o n -seale d 
hi g h -de nsit y p ol yet h yle ne ( H D P E) b ottles.  
T he i n vesti gat or s h o ul d pr o m ote c o m plia nce b y i nstr ucti n g t he p atie nt t o ta ke t he st u d y dr u g 
e x actl y as pres cri be d a n d b y st ati n g t ha t c o m plia nce is necessar y f or t he p atie nt’s safet y a n d t he 
vali dit y of t he st u d y .  T he patie nt s h o ul d be i nstr ucte d t o c o ntact t he i n vesti gat or if he/s he is 
u na ble f or a n y reas o n t o ta ke t he st u d y dr u g as prescri be d.  


I R B-3 1 9 1 3 versi o n 8  
P a ge 2 8  of 4 6   
2  Se pte m ber  2 0 2 0  
C a ps ules  
T he ca ps ules  s h o ul d be s wall o we d w h ole wit h a glass of water a n d s h o ul d n ot be c he we d or 
cr us he d.  If v o miti n g occ urs, n o atte m pt s h o ul d be ma de t o re place t he v o mite d d ose.  Patie nts 
s h o ul d be i nstr ucte d t hat if t he y miss a d ose o n o ne da y, t he y m ust n ot ta ke a n y e xtra d ose t he 
ne xt d a y, b ut i nstea d t o i m me diatel y c o ntact t he st u d y ce nter as s o o n as p ossi ble t o as k f or 
a d vice.  
Patie nts 
ma y c o nti n ue c o nc o mita nt 
me dicati o ns  f or ot her c o n diti o ns a n d a n y a d diti o nal 
a p pr o priate s u p p orti ve care me dicati o ns or treat me nts.   
4. 3   
Pre -T re at me nt E v al u ati o ns  
Patie nts will be e val uate d i n cli nic o n Da y  1 of eac h c ycle .  F or t he first c ycle, we will als o 
re q uire a mi d-c ycle p h ysi cia n's visit .  F urt her m ore,  wee kl y C B C wit h diff will be re q uire d f or t he 
first c ycle ( q 7 d a ys +/- 3  da ys) a n d bi wee kl y  ( q 14 da ys +/ - 3  da ys)  C B C wit h diff will be 
re q uire d f or t he sec o n d c ycl e.  S u bse q ue nt t o t his, we will o nl y re q uire a C B C wit h diff per c ycle 
( q 4 wee ks +/- 3  da ys) .  La b orat or y tests ca n be p er f or me d e xter nall y a n d fa x e d t o t he PI/researc h 
tea m.  T he f oll o wi n g ass ess me nts will be perf or me d at eac h p h ysicia n's visit : 
 P h ysical e xa mi nati o n, i ncl u di n g wei g ht  
 Vital si g ns, i ncl u di n g bl o o d press ure, p ulse, a n d te m perat ure  
 E C O G Perf or ma nce Stat us assess me nt  
 Cli nical la b orat or y tests:  C B C wit h differe ntial a n d c o m pre he nsi ve m eta b olic pa nel  
 Uri ne pre g n a nc y test  (fe male s u bjects of c hil d beari n g p ote ntial) 
 Assess me nt of c o nc o mita nt me dicati o ns  
 Assess me nt of a d verse e ve nts a n d d ose m o dificati o ns as necessar y.  A d verse e ve nts 
s h o ul d be m o nit ore d c o nti n u o usl y 
 T u m or e val uat i o n wit h i ma gi n g e v er y 2 c ycles ( 8 wee ks +/- 1 wee k)  
4. 4   
E n d of Tre at me nt Pr o ce d ures  
If patie nts are n o l o n ger recei vi n g treat me nt, t he assess me nts s h o ul d be c o m plete d wit hi n 
3 0  da ys of t he last d ose of talaz o pari b.   
 P h ysical e xa mi nati o n, i ncl u di n g wei g ht  
 Vital si g ns, i ncl u di n g bl o o d press ure, p ulse, a n d te m perat ure  
 E C O G Perf or ma nce Stat us assess me nt  
 Cli nical la b orat or y tests: C B C wit h differe ntial, c o m pre he nsi ve meta b olic pa nel  
 Uri ne pre g n a nc y test  (fe male s u bjects of c hil d beari n g p ote ntial) 
 Assess me nt of  a d verse e ve nts  
 St u d y dr u g c o m plia nce ( pill diar y)  


I R B-3 1 9 1 3 versi o n 8  
P a ge 2 9  of 4 6   
2  Se pte m ber  2 0 2 0  
4. 5   
Ge ner al C o nc o mit a nt Me dic ati o n a n d S u p p orti ve C are G ui deli nes  
C o nc o mita nt treat me nt is per mitte d if t he me dicati o n is n ot e x pecte d t o i nterfere wit h t he 
e val uati o n of safet y or efficac y of t he st u d y dr u g .  D uri n g t he st u d y, if t he use of a n y 
c o nc o mita nt treat me nt bec o mes necessar y ( e g, f or treat me nt of a n a d verse e ve nt), t he treat me nt 
m ust be d oc u me nte d, i ncl u di n g t he reas o n f or treat me nt, ge neric na me of t he dr u g, d osa ge, r o ute, 
a n d start a n d st o p da tes of a d mi nistrati o n. 
A ll s u p p orti ve meas ures c o nsiste nt wit h o pti mal patie nt care will be gi ve n t hr o u g h o ut t he st u d y.  
T he cli nical t olera nce of t he patie nt, t he o verall t u m or res p o nse, a n d t he me dical j u d g me nt of t he 
i n vesti gat or will deter mi ne if it is i n t he patie nt’s best i nterest t o c o nti n ue or disc o nti n ue 
treat me nt.  If treat me nt is disc o nti n ue d d ue t o a n y t o xicit y, t he p atie nt m ust be f oll o we d t o 
m o nit or d urati o n of t o xicit y, res p o nse a n d ti me t o pr o gressi o n or s ur vi val a n d i nitiati o n of a n y 
ne w s y st e mic t hera p y.  
4. 6   
D ur ati o n of T her a p y a n d F oll o w -U p  
T he n o mi nal d urati o n of treat me nt is 3 6  c ycl es ( 2 8  da ys per c ycle), b ut C R, P R, or S D patie nts 
will c o nti n ue t hera p y u ntil e vi de nce of pr o gressi ve disease or  u n acce pta ble t o xicit y occ urs.  
Pr ot oc ol t he ra p y will be disc o nti n ue d f or pr o gressi ve disease at a n y ti me.  Patie nts are free t o 
halt t hera p y at t heir re q u est.  Treat me nt ma y b e disc o nti n ue d if i nterc urre nt c o -m or bi dities occ ur, 
w hic h, i n t he o pi ni o n of t he treati n g p h ysicia n, w o ul d precl u de safe a d mi nistrati o n of st u d y 
dr u gs.  
4. 7   
Criteri a f or Re m o v al f r o m St u d y  
Patie nts M U S T be disc o nti n ue d fr o m st u d y t hera p y A N D be wit h dra w n fr o m t he st u d y f or t he 
f oll o wi n g reas o ns:  
 Wit h dra wal of t he patie nt’s c o nse nt ( patie nt’s d ecisi o n t o wit h dra w f or a n y reas o n)  
 A n y cli nical a d verse e v e nt, la b orat or y a b n or malit y or i nterc urre nt ill ness w hic h, i n 
t he o pi ni o n of t he i n vesti gat or, i n dicates t hat c o nti n ue d partici pati o n i n t he st u d y is 
n ot i n t he best i nterest of t he s u bject  
 I n a bilit y t o c o m pl y wit h pr ot oc ol  
 Dis creti o n of t he i n vesti gat or  
 Disease pr o gressi o n ( pati e nt c o nti n ue t o be f oll o we d f or s ur vi val) 
 Deat h  
If a s u bject is wit h dra w n bef ore c o m pleti n g t h e st u d y, t he reas o n f or wit h dra wal m ust be e ntere d 
o n t he a p pr o priat e cas e re p ort f or m.   
4. 8   
Alter n ati ves  
Alt er nati ves t o partici pati o n i n t his cli nical trial i ncl u de use of c he m ot hera pe utic a ge nts f or t h e 
treat me nt of metastatic tri ple-ne gati ve breast ca ncer .  Alter n ati ves f or metastatic E R a n d/ or 
P R -p ositi ve, H E R 2 -ne gati ve breast c a ncer i ncl u de a nti-estr o ge n t hera p y a n d c he m ot hera p e utic 
a ge nts.  


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 0  of 4 6   
2  Se pte m ber  2 0 2 0  
4. 9   
C o m pe ns ati o n  
Patie nts ma y be eli gi ble f or tra vel a n d m eal rei m b urse me nt if t he y li ve m ore t ha n 5 0 miles fr o m 
st u d y site.   
5.   
I N V E S TI G A TI O N A L A G E N T/ D E VI C E/ P R O C E D U R E I N F O R M A TI O N  
5. 1   
I n vesti g ati o n al A ge nt   
Please n ote t hat more c o m plete i nf or mati o n ca n b e o btai ne d fr o m t he I n vesti gat or’s Br oc h ure 
(I B). 
Talaz o pari b  is a n o vel p ol y( A D P-ri b ose) p ol y merase ( P A R P) i n hi bit or.  T he acti ve i n gre die nt is 
talaz o pari b; t he c he mical na me is 3H -P yri d o[ 4, 3, 2 -de] p ht halazi n -3 -o ne, 
5 -flu or o -8 -( 4-fl u or o p he n yl)-2, 7, 8, 9 -tetra h y dr o-9 -( 1-met h yl -1 H -1, 2, 4 -triaz ol-5 -yl) -, ( 8S , 9R )-, 
4 -met h yl be nze nes ulf o nate ( 1: 1).  
C he mical str uct ure of talaz o pari b: 
 
M olec ular F or m ula ( tal az o pari b): C 2 6 H 2 2 F 2 N 6 O 4 S 
M olec ular Wei g ht ( talaz o pari b): 5 5 2. 5 6 2 4 
Talaz o par i b is 
ma n ufact ure d b y c he mical s y nt hesis i n acc or da nce 
wit h c urre nt 
G o o d 
Ma n ufact uri n g Practices (c G M P) .  T he dr u g pr o d uct is a ca ps ule f or m ulati o n c o m prise d of a 
ble n d of talaz o pari b dr u g s u bsta nce a n d silicifie d 
micr ocr ystalli ne cell ul ose fille d i nt o a 
h y pr o mell ose ca ps ule .  T he ca ps ule is prese nte d i n f o ur stre n gt hs –  2 5 -μ g ;  5 0 -μ g ;  2 5 0 -μ g ;  or 
1 -m g talaz o pari b free bas e e q ui vale nt –  t hat are disti n g uis he d eit her b y ca ps ule c ol or or size. 
Talaz o pari b is c o nsi dere d a c yt ot o xic a ge nt; preca uti o ns re gar di n g a p pr o priate sec ure st ora ge 
a n d ha n dli n g m ust b e us e d b y h ealt hcare pr ofessi o nals, i ncl u di n g pers o nal pr otecti ve cl ot hi n g, 
dis p osa ble gl o ves a n d e q ui p me nt .  S u bjects s h o ul d be a d vise d t hat oral a ntica n cer a ge nts are 
t o xic s u bsta nces a n d t h at ( ot her t h a n the s u bject) care gi vers s h o ul d al wa ys use gl o v es w he n 
ha n dli n g t he ca ps ules.  
5. 2   
P h ar m a c o d y n a mi c Pr o perties   
Pri mar y P D st u dies ass esse d talaz o pari b a n d relate d c o m p o u n ds f or i n vitr o a n d i n viv o 
p har mac ol o gical acti vities .  Assess me nt of tal az o pari b effect s i n t u m or cell i nc u bati o ns re veale d 
selecti ve a n d p ote nt c yt ot o xicit y i n h u ma n ca ncer cell li nes har b ori n g m utati o ns t hat c o m pr o mise 
D N A re pair p at h wa ys .  Ge ne m utati o ns t hat c o nfer sel ecti ve t u m or cell c yt ot o xicit y i ncl u de d 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 1  of 4 6   
2  Se pte m ber  2 0 2 0  
B R C A 1 ( M X -1 ma m mar y t u m or cell s);  B R C A 2 ( Ca pa n -1 pa n creatic t u m or cells) ;  P T E N 
( M D A-M B -4 6 8 ma m mar y ;  L N Ca p a n d P C -3 pr ostate t u m or cells) ;  a n d M L H -1 m utati o ns 
( H C T-1 1 6 c ol or ectal t u m or cells) .  T he I C 5 0 val ues of tal az o pari b i n t hese t u m or cell li nes were 
i n t he si n gl e di git na n o m olar or s u b -na n o m olar ra n ge .  I n c o ntrast, t he I C 5 0 of talaz o pari b a gai nst 
n or mal h u ma n pri mar y cell M R C -5 a n d se veral t u m or cell li nes t hat d o n ot ha ve re p orte d D N A 
re pair-relat e d m utati o ns are si g nifica ntl y greater ( 2 5 0 n M  t o >  1 0 0 0  n M ). 
5. 3   
P h ar m a c o ki neti c Pr o perties   
T he p har mac o ki n etic ( P K) res ults f or t he d ose escalati o n p hase of P R P -0 0 1 ha ve bee n assess e d 
wit h preli mi nar y c o nce ntrati o n data fr o m 2 5  μ g / da y t hr o u g h 1 1 0 0 μ g / d a y.  I n c ycl e 1, sa m ples 
were c ollecte d f or a wee k after t he first si n gle d ose ( Da y  1) of a c o h ort, pre -d ose sa m ples were 
c ollecte d d uri n g dail y d osi n g (tr o u g hs), a n d sa m ples were c ollect e d f or a wee k after t he last d ose 
i n c ycle 1 (Da y  3 5) .  F oll o wi n g a si n gle d ose ( Da y  1), mea n plas ma C ma x  a n d A U C 0 -2 4 hr  ra n ge d 
fr o m 
6 0. 0 t o 1 3, 2 0 0  p g /m L  a n d fr o m 
9 5 3  t o 9 2, 1 0 0  p g -hr/ m L , res pecti vel y, 
o ver t he 
2 5  t o 1 1 0 0  μ g  d ose ra n ge .  F oll o wi n g m ulti ple dail y d osi n g ( Da y  3 5), mea n plas ma C ma x  a n d 
A U C 0 -2 4 hr ra n ge d fr o m 3 0 0 t o 2 3, 4 0 0  p g/ m L  a n d fr o m 3 9 6 0  t o 2 0 3, 0 0 0  p g -hr/ m L , res pecti vel y, 
o ver t he 2 5 t o 1 1 0 0  μ g / da y d os e ra n ge.  At t he defi ne d ma xi m u m t olerate d d ose ( M T D) of 
1 0 0 0  μ g / da y, 
mea n ( S D) 
Cma x  a n d A U C 0 -2 4 hr  were 2 1, 0 0 0 ( 7, 9 9 0)  p g /m L  a n d 2 0 3, 0 0 0 
( 5 4, 8 0 0) p g -hr/ m L , res p ecti vel y, o n Da y  3 5 .  T he plas ma pr ofiles i n dicate e nter o he p atic c ycli n g 
of talaz o pari b beca us e of t he a d diti o nal c o n ce ntrati o n pea ks be y o n d T ma x .  Eli mi nati o n a p pears t o 
be 
bi -e x p o ne ntial .  Mea n  
talaz o pari b t1/ 2 
ra n ge d fr o m 
5 3. 5 t o 2 3 4  h o urs  a n d fr o m 
4 0. 4  t o 1 1 5  h o urs  o n Da y  1 a n d Da y  3 5, res p ecti vel y .  At t he u p per e n d of t he d ose ra n ge 
e val uate d ( 9 0 0  t o 1 1 0 0  μ g ), t1/ 2 ra n ge d fr o m 5 3. 5 t o 6 6. 1  h o urs  a n d fr o m 4 0. 4  t o 5 1. 8  h o urs  o n 
Da y  1 a n d Da y  3 5, res pecti vel y .  Stea d y state was a p pare nt i n m ost patie nts b y t w o wee ks wit h 
dail y d osi n g .  Acc u m ulati o n base d o n A U C 0 -2 4 hr  was o bser ve d f or all pati e nts c o m pari n g Da y  3 5 
wit h Da y  1 a n d 
mea n val ues ra n ge d fr o m 2. 4 2  t o 9. 9 2 a n d fr o m 2. 4 2  t o 3. 6 9 acr oss t he 
2 5  t o 1 1 0 0  μ g  d ose ra n ge a n d t h e 9 0 0  t o 1 1 0 0  μ g  d os e ra n ge, res pecti vel y .  F oll o wi n g si n gle 
d oses, talaz o pari b C ma x  a n d A U C 0 -2 4 hr  were li near bet wee n 4 0 0 a n d 1 1 0 0  μ g .  F oll o wi n g 
m ulti ple d oses, talaz o pari b C ma x  a n d A U C 0 -2 4 hr  were li near bet w ee n 2 5 a n d 1 1 0 0  μ g / da y.  
A f o o d effect st u d y ( 6 7 3 -1 0 3) i n 1 8 healt h y v ol u nteers has bee n c o m plete d .  T his st u d y s h o we d 
t hat w hile a hi g h-fat, hi g h cal orie m eal dela ye d t h e a bs or pti o n of orall y a d mi nistere d talaz o pari b, 
it di d n ot affect t he o verall e xte nt of t he a bs or pti o n.  Base d o n t hese fi n di n gs, talaz o pari b ca n be 
a d mi nistere d wit h o ut re gar d t o f o o d.  
5. 4   
S u p plier  
T he i n vesti gati o nal a ge nt, talaz o pari b, will be pr o vi de d b y Pfizer P har mace utical, I nc.   
5. 5   
D os a ge F or m  
Talaz o pari b  will be s u p plie d as ca ps ules f or oral a d mi nistrati o n.  
5. 6   
A ge nt Or deri n g  a n d P a c k a gi n g  
Re q uests f or s hi p me nts of t he i n vesti gati o nal a ge nt will be c o or di nate d b y t he st u d y c o or di nat or 
directl y wit h  Pfizer  P har mace utical, I nc.  B ottles will c o ntai n a s uffici e nt n u m ber of ca ps ules f or 
o ne c ycle of d osi n g.   


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 2  of 4 6   
2  Se pte m ber  2 0 2 0  
5. 7   
St or a ge a n d s helf life  
Sta bilit y d ata o btai n e d f or b ot h pr ot ot y pe a n d cli nical dr u g pr o d uct bat c hes c urre n tl y s u p p ort 
retest dati n g of 3 6 m o nt hs f or dr u g pr o d uct .  B ot h dr u g pr o d uct a n d dr u g s u bsta nce e x hi bit 
e x celle nt sta bilit y tr e n ds .  T he dr u g pr o d uct is st ore d at r o o m te m perat ure ( 1 5  t o 3 0  de g  C; 
5 9  t o 8 6  de g  F) a n d s h o ul d be pr otecte d fr o m li g ht.  
5. 8   
N at ure a n d C o nte nts of C o nt ai ner  
T he ca ps ules a re pac k a ge d i n perf orate d u nit-d ose blister car ds c o m p ose d of c ol d f or m 
al u mi n u m f oil a n d p us h t hr o u g h al u mi n u m li d di n g .  T he 4  ca ps ule stre n gt hs are pac k a ge d i nt o 
t he sa me blister car d desi g n.  A d diti o nall y, 2 5 0 -μ g ca ps ules ( o pa q ue w hite, size 4) are pac k a ge d 
i n 3 0-c o u nt H D P E b ottles wit h a n i n d ucti o n seal a n d c hil d -resista nt ca p.  
5. 9   
S peci al Prec a uti o ns f or Dis p os al a n d Ot her H a n dli n g  
A n y u n us e d pr o d uct or waste material is t o be dis p ose d of i n acc or da n ce wit h l ocal re q uire me nts.   
6.   
D O S E M O DI FI C A TI O N S  
Dail y d osi n g of talaz o pari b ca n be i nterr u pte d f or rec o ver y fr o m t o xicit y f or u p t o 2 8  da ys .  
T hereafter,  tr eat me nt at t he sa me or a re d u ce d d ose ca n be c o nsi dere d bas e d o n t he discreti o n of 
t he pri mar y i n vesti gat or if t he s u bject has n ot de vel o pe d pr o gressi ve disease.  D ose 
m o dificati o ns  s h o ul d be ma de base d o n o bs er ve d t o xicit y as f oll o ws: 
 Gra de  1 or 2 t o xicit y:  N o re q uire me nt f or d ose i nterr u pti o n or d ose re d ucti o n .  If t he 
t o xicit y persists at Gra de  2, a d ose re d u cti o n t o t he ne xt l o wer d ose le vel (e g,  fr o m 
1. 0  m g / da y t o 0. 7 5  m g/ da y) ma y be i m ple me nte d at t he discreti o n of t he I n vesti gat or  
 Gra de  3 t o xicit y:  Dail y d osi n g s h o ul d be st o p pe d .  Talaz o pari b  d osi n g ma y res u me at  t he 
ne xt l o wer d ose le vel (e g,  fr o m 1. 0 m g / da y t o 0. 7 5  m g / da y; 0. 7 5  m g / da y t o 0. 5  m g / da y;  
0. 2 5  m g / da y t o 0. 1 0  m g / da y) w he n t o xicit y res ol ves t o Gra de  1 or ret ur ns t o baseli ne  
 Gra de  4 t o xicit y:  Dail y d osi n g s h o ul d be st o p pe d .  Talaz o pari b  ma y res u m e at a l o wer 
d ose le vel ( 1  t o 2 d ose le vel decrease) wit h t he a p pr o val of t he PI  w he n t o xicit y res ol v es 
t o Gra de  1 or ret ur ns t o b aseli ne  
T a ble 3 .  D ose m o dificati o ns f or t o xicities  
  
D ose Le vel  
I nitial d ose le vel  
1. 0  m g / da y 
First d ose le vel r e d ucti o n  
0. 7 5  m g / da y 
Sec o n d d ose le vel r e d ucti o n  
0. 5  m g / da y 
T hir d d ose le vel r e d ucti o n  
0. 2 5  m g / da y 
F o urt h d ose le vel re d ucti o n  
0. 1 0  m g / da y 
Talaz o pari b  will be per m a ne ntl y disc o nti n ue d f or i n di vi d ual s u bjects as a res ult of a n y  
u nres ol ve d Gra de  3 or Gra de  4 t o xicit y or base d o n a decisi o n b y t he s u bject or I n vesti gat or t hat 
c o nti n ue d talaz o pari b treat me nt is n ot i n t he s u bject’s best i nterest. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 3  of 4 6   
2  Se pte m ber  2 0 2 0  
7 .  
A D V E R S E E V E N T S A N D R E P O R TI N G P R O C E D U R E S  
7. 1   
P ote nti al A d verse E ve nts  
Acc or di n g t o t he I C H defi niti o n, a n a d verse e ve nt ( A E) is a n y u nt o w ar d m e dical occ urre nce i n a 
patie nt or cli nical i n vesti gati o n s u bjec t a d mi nistere d a p har mace utical pr o d uct, a n d t hat d oes n ot 
necessaril y h a ve a ca us al relati o ns hi p wit h t his treat me nt.  A n A E ca n t heref ore be a n y 
u nfa v ora bl e a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal la b orat or y fi n di n g), s y m pt o m, or 
disease te m p orall y as s ociate d wit h t he use of a me dici nal (i n vesti gati o nal) pr o d uct, w het her or 
n ot c o nsi dere d relate d t o t he i n vesti gati o nal pr o d uct.  
T his defi niti o n i ncl u des i nterc urre nt ill nesses or i nj uries t hat re pres e nt a n e x acer bati o n (i ncreas e 
i n fre q ue nc y, s e verit y, or s pecificit y) of pre-e xisti n g c o n diti o ns.  
W he ne ver p ossi ble, it is 
prefera ble t o rec or d a dia g n osis as t he A E t er m rat her t ha n a s eries of ter ms relati n g t o a 
dia g n osis .  A d verse e ve nt i nf or mati o n will be c ollecte d i n a n o n g oi n g fas hi o n t hr o u g h p atie nt 
re p orti n g A Es t o t heir p h ysicia n or healt h care pr o vi der.  Seri o us n ess a n d relate d n ess will be 
assesse d b y t he treati n g p h ysicia n, wit h a p pr o priat e re p orti n g.  
A desi g nate d pri mar y c o ntact pers o n base d at t he treat me nt ce nter will be res p o nsi ble f or t he 
c ollecti o n a n d re p orti n g of A Es f or patie nts partici pati n g i n t he pr o gra m.   
A d verse e ve nts t hat be gi n or w orse n after i nf or m e d c o ns e nt s h o ul d be rec or de d i n t h e A d verse 
E ve nts C R F .  C o n diti o ns t hat were alrea d y pres e nt at t he ti me of i nf or me d c o nse nt s h o ul d b e 
rec or de d i n t he Me dical Hist or y pa ge of t he patie nt’s C R F.  A d verse e ve nt m o nit ori n g s h o ul d be 
c o nti n ue d f or at least 3 0  da ys ( or 5  half -li ves, w hic he ver is l o n ger) f oll o wi n g t he last d ose of 
st u d y tr eat me nt.  A d verse e v e nts (i ncl u di n g la b a b n or malities t hat c o nstit ute A Es) s h o ul d be 
descri be d usi n g a dia g n osis w he ne ver p ossi ble, rat her t ha n i n di vi d ual u n derl yi n g si g ns a n d 
s y m pt o ms.  W he n a cl ear dia g n osis ca n n ot be i de ntifie d, eac h si g n or s y m pt o m s h o ul d be 
re p orte d as a se p arate A d verse E ve nt. 
T he occ ur re nce of a d v erse e v e nts s h o ul d be s o u g ht b y n o n-directi ve q u esti o ni n g of t he patie nt at 
eac h visit d uri n g t he st u d y.  A d verse e ve nts als o ma y be det ecte d w he n t he y are v ol u nteere d b y 
t he patie nt d uri n g or bet wee n visits or t hr o u g h p h ysical e x a mi nati o n, la borat or y test, or ot her 
assess me nts .  As far as p ossi ble, eac h a d v erse e ve nt s h o ul d be e val uate d t o deter mi ne:  
 T he se verit y gra de ( C T C A E Gra d e  1  t o 4)  
 Its d ur ati o n (start a n d e n d dates or if c o nti n ui n g at t he Safet y F oll o w-u p Visit)  
 Its r elati o ns hi p t o t he st u d y treat me nt ( Reas o n a ble p ossi bilit y t hat A E is rel ate d: N o, Yes)  
 Acti o n ta ke n wit h res p ect t o st u d y or i n vesti gati o nal treat me nt ( n o ne, d ose a dj uste d, 
te m p oraril y i nterr u pte d, per ma ne ntl y disc o nti n ue d, h os pitalize d, u n k n o w n, n ot 
a p plica ble)  
 W het her me dicati o n or t hera p y was gi ve n ( n o c o nc o mita nt me dicati o n/ n o n -dr u g t hera p y, 
c o nc o mita nt me dicati o n/ n o n -dr u g t hera p y)  
 O utc o me ( n ot  rec o vere d/ n ot res ol ve d;  rec o v ere d/res ol ve d;  rec o veri n g/res ol vi n g;  
rec o vere d/r es ol ve d wit h se q ualae;  fatal;  u n k n o w n)  
 W het he r it is seri o us, w here a s eri o us a d v erse e ve nt ( S A E) is defi ne d as i n Secti o n  7. 1. 2  


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 4  of 4 6   
2  Se pte m ber  2 0 2 0  
All a d verse e ve nts s h o ul d be treate d a p pr o priatel y .  S uc h treat me nt ma y i ncl u de c ha n ges i n st u d y 
dr u g tr eat me nt i ncl u di n g p ossi ble i nterr u pti o n or disc o nti n uati o n, starti n g  or st o p pi n g 
c o nc o mita nt treat me nts, c ha n ges i n t h e fre q ue n c y or nat ure of assess me nts, h os pitalizati o n, or 
a n y ot her me dicall y re q uire d i nter ve nti o n .  O nce a n a d v erse e ve nt is d etecte d, it s h o ul d be 
f oll o we d u ntil its res ol uti o n, a n d assess me nt s h o ul d be ma de at eac h visit ( or m ore fre q ue ntl y, if 
necessar y) of a n y c ha n ges i n se v erit y, t h e s us pecte d rel ati o ns hi p t o t he st u d y dr u g, t he 
i nter ve nti o ns re q uire d t o treat it, a n d t he o utc o me. 
I nf or mati o n a b o ut c o m m o n si de effects alrea d y k n o w n a b o ut t he i n vesti gati o nal dr u g ca n b e 
f o u n d i n t he I n v esti gat ors’ Br oc h ure.  T his i nf or mati o n s h o ul d be i n cl u de d i n t he p atie nt 
i nf or me d c o nse nt a n d s h o ul d be disc usse d wit h t he patie nt d uri n g t he st u d y as nee de d.  A d verse 
e ve nt m o nit ori n g s h o u l d be c o nti n ue d f or at least 3 0 da ys f oll o wi n g t he last d ose of st u d y 
treat me nt. 
Gi ve n ot her dr u gs i n t his class ha ve bee n ass oci ate d wit h he mat ol o gic mali g na n cies, s uc h as 
m yel o d ys plastic s y n dr o me ( M D S) a n d ac ute le u ke mias, a n y pr ol o n ge d c yt o p e nias, defi ne d as 
greater t ha n 6  wee ks, wil l be t h or o u g hl y e v al uate d i ncl u di n g referral t o he mat ol o g y cli nic, w here 
r o uti ne pr oce d ures i ncl u di n g b o ne marr o w bi o ps y, if dee me d a p pr o priate, will be c o n d ucte d.  
7. 1. 1  L a b or at or y test a b n or m alities  
La b orat or y a b n or malit ies t hat c o nstit ute a n A d verse Eve nt i n t heir o w n ri g ht (are c o nsi dere d 
cli nicall y si g nifica nt, i n d uce cli nical si g ns or s y m pt o ms, re q uire c o nc o mit a nt t hera p y or re q uire 
c ha n ges i n st u d y treat me nt), s h o ul d be rec or de d o n t he A d verse E ve nts C R F .  W he ne ver 
p ossi ble, a dia g n osis, rat her t ha n a s y m pt o m s h o ul d be pr o vi de d ( e g, a ne mia i nstea d of l o w 
he m o gl o bi n) .  La b orat or y a b n or malities t hat meet t he criteria f or A d verse E ve nts s h o ul d b e 
f oll o we d u ntil t he y h a ve ret ur n e d t o n or mal or a n a de q u ate e x pla nati o n of t he a b n or malit y is 
f o u n d.  W he n a n a b n or mal la b orat or y or test res ult c orres p o n ds t o a si g n/s y m pt o m of a n alrea d y 
re p orte d a d v erse e ve nt, it is n ot necessar y t o se p aratel y rec or d t he la b/test res ult as a n a d diti o nal 
e ve nt.  
La b orat or y a b n or malities, t hat d o n ot meet t he defi niti o n of a n a d v e rse e ve nt, s h o ul d n ot be 
re p orte d as a d verse e ve nts.  A Gra de  3 or 4 e ve nt (se vere) as per C T C A E d oes n ot a ut o maticall y 
i n dicate a S A E u nless it meets t he defi niti o n of seri o us as defi ne d bel o w a n d/ or as p er 
i n vesti gat or’s discreti o n.  A d ose h ol d or me dic ati o n f or t he la b a b n or malit y ma y be re q uire d b y 
t he pr ot oc ol a n d is still, b y defi niti o n, a n a d verse e ve nt. 
7. 1. 2   Seri o us A d verse E ve nts  ( S A E)  
A seri o us a d verse e v e nt is a n u n desira ble si g n, s y m pt o m or me dical c o n diti o n w hic h:  
 is fatal or life-t hr eate ni n g 
 res ults i n persiste nt or si g nifica nt disa bilit y/i n ca pacit y 
 c o nstit utes a c o n ge nital a n o mal y/ birt h defect  
 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, u nless 
h os pitalizati o n is f or:  
o  electi ve or pre-pla n ne d treat me nt f o r a pre-e xisti n g c o n diti o n t hat is u nrelat e d t o 
t he i n dicati o n u n der st u d y a n d h as n ot w orse n e d si nce t he start of st u d y dr u g 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 5  of 4 6   
2  Se pte m ber  2 0 2 0  
o  treat me nt o n a n e m er ge n c y o ut p atie nt basis f or a n e ve nt n ot f ulfilli n g a n y of t he 
defi niti o ns of a S A E gi v e n a b o ve a n d n ot res ulti n g i n h os pital a d missi o n  
o  s ocial reas o ns a n d res pite care i n t he a bse n ce of a n y det eri orati o n i n t he pati e nt’s 
ge n eral c o n diti o n  
o  is me dicall y si g nifica nt, i e, defi ne d as a n e v e nt t hat je o par dizes t he patie nt or ma y 
re q uire me di cal or s ur gical i nter ve nti o n to pre ve nt o ne of t he o utc o mes liste d 
a b o ve  
7. 1. 3  Pre g n a nc y  
If a patie nt bec o mes pre g na nt d uri n g t he st u d y, st u d y dr u g a d mi nistrati o n m ust be disc o nti n ue d 
a n d t he p re g na n c y m ust  be re p orte d i m me diatel y ( wit hi n 2 4  h o urs  of b ec o mi n g a ware of t h e 
pre g na nc y) t o  Pfizer Safet y p ortal s yste m b y usi n g t h e F D A 3 5 0 0 A ( Me d Watc h F or m).  E ver y 
eff ort s h o ul d be ma de t o f oll o w t he patie nt t hr o u g h res ol uti o n of t he pre g na nc y (ter mi nati o n or 
deli ver y) a n d re p ort t he res ol uti o n of t he F D A 3 5 0 0 A ( Me d Watc h F or m) t o Pfizer Safet y p ortal 
s yste m (
). 
7. 2   
A d verse E ve nt a n d Pre g n a nc y Re p orti n g  
A d verse e v e nts will be gra de d acc or di n g t o C T C A E v 5 .  B ot h Seri o us a n d N o n -Seri o us A d verse 
E ve nts will be clearl y  n ote d i n s o urce d o c u me nt ati o n a n d liste d o n st u d y s pecific Case Re p ort 
F or ms ( C R Fs).  T he Pr ot oc ol Direct or ( P D) or d esi g nee will ass ess eac h A d verse E ve nt ( A E) t o 
deter mi ne w het her it is u ne x pecte d acc or di n g t o t he I nf or me d C o nse nt, Pr ot oc ol D oc u me nt, or  
I n v esti gat or’s Br oc h ure, a n d relate d t o t he i n vesti gati o n.  All Seri o us A d verse E ve nts ( S A Es) 
will be trac ke d u ntil res ol uti o n, or u ntil 3 0 da ys after t he last d ose of t h e st u d y treat me nt.  
S A Es C T C A E Gra de  3 a n d a b o ve, a n d all s u bse q ue nt f oll o w -u p re p ort s will be re p orte d t o t he 
Sta nf or d Ca ncer I nstit ute Data a n d Safet y 
M o nit ori n g C o m mittee ( D S M C) usi n g t he st u d y 
s pecific C R F wit hi n 2 4  h o urs of n otificati o n of e v e nt re gar dless of t he e v e nt’s relate d n ess t o t he 
i n vesti gati o n.  Please f oll o w ste ps i n A p pe n d i x B: Sta nf or d Ca n cer I nstit ute S A E re p orti n g 
g ui deli nes f or i n vesti gat or-i nitiate d trials.  
I n i n vesti gat or I N D st u dies, talaz o pari b seri o us, relate d, u nla bele d, ( u ne x pecte d) a d v erse e ve nts 
will be re p orte d t o t he F D A as re q uire d b y 2 1 C F R § 3 1 2. 3 2 b y t he I n v esti gat or  wit hi n 2 4  h o urs of 
n otificati o n of t he e v e nt.  T he  Me d Watc h  F or m ( F or m  3 5 0 0 A 
Ma n d at or y Re p orti n g) a n d 
F D A  F or m  1 5 7 1 m ust be c o m plete d a n d se nt t o t h e F D A.  
All S A Es (e x pecte d or u ne x pecte d, ca usall y rel ate d or n ot) a n d pre g n a nc y re p orts m ust al s o be 
re p orte d t o Pfizer Safet y p ortal s yste m, 
, a n d fa x e d t o Pfizer 
 wit hi n 2 4  h o urs  of t he I n vesti gat or’s a ware ness.   Pfizer will re vie w t h e A E d ata as 
d oc u me nte d i n t he site’s fi nal st u d y re p ort.  
F or C o m parat or Dr u gs/ Sec o n dar y S us pects ( C o nc o mita nt 
Me dicati o ns), all seri o us a d verse 
e x perie nces will be f or war de d t o t he pr o d u ct ma n ufact urer.  
T he peri o d d uri n g w hic h all n o n -seri o us A Es a n d S A Es will be re p orte d be gins after i nf or me d 
c o nse nt is o btai ne d a n d will c o nti n ue t hr o u g h 3 0  da ys after t he last st u d y visit or 3 0 da ys after 
t he last d ose of st u d y m e dicati o n, w hic he ver c o m es first. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 6  of 4 6   
2  Se pte m ber  2 0 2 0  
7. 3   
Pr o d uct C o m pl ai nts Re p orti n g  
A pr o d uct c o m plai nt (“ C o m plai nt”) is a n y direct, writte n, electr o ni c, or oral c o m m u nicati o n of 
dissatisfacti o n t hat alle ges deficie ncies rel ate d t o t he i de ntit y, q ualit y, d ura bilit y, la beli n g, p urit y, 
sta bilit y, a p p eara nce, effecti ve ness, s afet y, a n d/ or desi g n of a dr u g pr o d uct after it is release d f or 
d istri b uti o n.  
C o m plai nts t hat si m ulta ne o usl y fall u n der A d verse E ve nt defi niti o ns u n der t his Pr ot oc ol nee d 
o nl y be re p orte d vi a t he A d verse E v e nt re p orti n g pr oce d ure set f ort h i n t his Pr ot oc ol.   
I n v esti gat or or desi g nee ( Re p orter) s h all ca pt ure t he f oll o wi n g C o m plai nt i nf or mati o n as relates 
t o talaz o pari b ( B M R N 6 7 3 ) use d u n der t his Pr ot oc ol:  
• 
Date c o m plai nt recei ve d  
• 
Pr o d uct Na me a n d L ot N u m ber  
• 
I n dicate if t he pr o d uct is a vaila ble f or ret ur n t o Pfizer f or i n vesti gati o n  
• 
Q ua ntit y Affecte d  
• 
Detaile d Des cri pti o n  of c o m plai nt  
• 
St u d y Pr ot o c ol N u m ber  
• 
I n v esti gat or Na me 
• 
Site C o ntact  
• 
Site N u m ber  
• 
S u bject N u m ber  
• 
Na me a n d c o ntact i nf or mati o n of t he pers o n w h o is re p orti n g t he c o m plai nt as well as 
na me a n d c o ntact i nf or mati o n of t he c o m plai n a nt.  T he re p orter will be c o nta cte d b y 
Pfizer Pr o d uct C o m plai nt Q ualit y Ass ura nce De p art me nt.  
I n v esti gat or or desi g nee ( Re p orter) will use his or her b est eff orts t o re p ort C o m plai nts t o Pfizer 
wit hi n fi ve da ys of l ear ni n g of t he C o m plai nt .  I n v esti gat or or desi g nee will s u b mit t he c o mplai nt 
i nf or mati o n b y e mail.  
8 .  
C O R R E L A TI V E   S T U DI E S  
T his st u d y is d esi g n e d t o assess h ere ditar y a n d s o matic defects i n ge nes t hat s u p p ort  
h o m ol o g o us rec o m bi nati o n d o u ble -stra n d brea k re pair defects be y o n d 
B R C A a n d t heir 
i m plicati o n i n t u m ori ge n esis.  T he g oal is t o use s uc h i de n tifia ble defects as bi o mar kers t o tail or 
dr u g t hera p y  utilizi n g t he pri nci ple of s y nt hetic let halit y ; i n t his case wit h talaz o pari b, a p ote nt 
P A R P i n hi bit or .  C orrelati ve st u dies will be c o n d ucte d t o assess u n d erl yi n g ger mli ne  m u tati o ns, 
ge n o mic i nsta bilit y  as assesse d b y t h e t u m or  H R D  sc ore, a n d res p o nse t o dr u g .  All partici p a nts 
will be as ke d t o pr o vi de a bl o o d sa m ple t o r u n t he m y Ris k here ditar y 2 5 -ge ne pa n el  o n a 
researc h basis.  T he m y Ris k here ditar y 2 5 -ge n e pa nel  e val uat es a br oa d n u m ber of here ditar y 
ca ncer s y n dr o mes i ncl u di n g se v eral ge n es i m plicate d i n  H R d o u ble -stra n de d D N A re pair .  A 
se parat e res earc h ger mli ne  bl o o d sa m ple  a n d plas ma sa m ple  will als o be c ollecte d .  F urt her m ore , 
all partici pa nts will be as ke d t o pr o vi de an a de q u ate  metastatic t u m or  bi o ps y t o assess t he  H R D  
sc ore base d o n t he H R D  assa y a n d R A D 5 1 stat us .  O nl y i n cases w here a metastatic bi o ps y is n ot 
tec h nicall y feasi ble will t he H R D  sc ore or R A D 5 1 stat us  be assesse d o n t he pri mar y t u m or .  All 
s u bjects will be as ke d t o s u b mit a n arc hi val s a m ple of t heir pri mar y breast t u m or.  T he R A D 5 1 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 7  of 4 6   
2  Se pte m ber  2 0 2 0  
stat us of t he t u m or will be assesse d usi n g i m m u n o hist oc he mistr y at baseli ne (a bse nt or prese nt) 
as a f u ncti o nal r ea d o ut of  H R ca pacit y a n d t his will be c orrelate d wit h  H R D  stat us.  
All c orrelati ve e n d p oi nts will be meas ure d usi n g u ni variate a n d m ulti variate l o gisti c re gressi o n 
m o dels , rec o g nizi n g t hat t hese are e x pl orat or y a n al yses a n d t h us ma y be i ns ufficie ntl y p o were d 
f or statistical p ur p oses.  F or s pecifi c c orrelati ve e n d p oi nts  a nd t he statistical met h o ds use d f or 
e val uati o n, please refer t o Secti o n  1 2 . 3. 
Tiss ue bi o psies, w h ole bl o o d a n d plas ma will be s a m ple d i n t his st u d y .  T he y will be st ore d a n d 
ma y b e use d f or f ut ure researc h p ur p os es pr o vi de d t he patie nt has gi ve n his/ h er c o nse nt .  All 
s uc h sa m ples will be la bele d wit h a u ni q ue n u meric i de ntifier t hat will be c o de d f or patie nt 
pri vac y .  O nl y a ut h orize d st u d y pers o n nel will ha ve access t o t hese tiss ues.  If t he patie nt 
decli nes t his o pti o n, re mai ni n g tiss ue a n d bl o o d will  be discar de d after s pecifie d c orrelati ve 
st u d y pr oce d ures ha ve b ee n perf or me d. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 8  of 4 6   
2  Se pte m ber  2 0 2 0  
9.   
S T U D Y C A L E N D A R  
 
Pre -St u d y 
Scree ni n g  
C ycle 1  
( 1 c ycle = 2 8 d a ys) 
+/ - 3 d a ys  
C ycle 2  
( 1 c ycle = 2 8 d a ys) 
+/ - 3 d a ys  
C ycle 3  t o 3 6  
( 1 c ycle = 2 8 
d a ys)  
+/ - 3 d a ys  
E n d of  
St u d y  b  
 
D a ys -2 8 t o 0  
D 1   D 8   D 1 5   D 2 2   
D 1   
D 1 5   
D 1   
 
I nf or me d c o nse nt 
X  
  
  
  
  
  
 
 
 
De m o gra p hics  
X  
  
  
  
  
  
 
 
 
Me dical hist or y  
X  
   
  
  
  
 
 
 
Fa mil y hist or y  
X  
  
  
  
  
  
 
 
 
C o nc urre nt me ds  
X  
  
  
  
  
  
 
 
 
Tala z o pari b dis pe nsi n g a n d dail y d osi n g 
f or 2 8 da ys st arti n g c ycle Da y  1  
  
X   
  
  
  
X   
 
X  
 
P h ysical e xa m  
X   
X   
  
X   
  
X   
 
X   
X  
Vital si g ns  
X   
X   
  
X   
  
X   
 
X   
X  
Hei g ht  
X   
  
  
  
  
  
 
 
 
Wei g ht  
X   
X   
  
X   
  
X   
 
X   
X  
P erf or ma nce stat us  
X   
X   
  
X   
  
X   
 
X   
X  
C B C w/ diff  ( +/ - 3 da ys)  
X   
X   
X   
X   
X   
X   
X   
X   
X  
Ser u m c he mistr y  a ( +/- 3 da ys)  
X   
X   
  
X   
  
X   
 
X   
X  
A d verse e ve nt e val u ati o n   
  
X   
  
X   
  
X   
 
X   
X  
Uri ne pre g na nc y ( w o me n of 
c hil d beari n g p ote ntial)  
X   
X  
  
  
  
X  
 
X   
X  
Assess me nt of  H R D  sc ore usi n g H R D  
assa y fr o m c ore bi o ps y of metastatic 
site.  If a n a de q uate metastatic bi o ps y 
is n ot a vaila ble, a fres h bi o ps y will be 
perf or me d.  Res ults ar e re q uire d pri or 
t o treat me nt i nitiati o n f or C o h ort A 
o nl y.  
X  
  
  
  
  
  
 
 
 
S u b missi o n of arc hi val t u m or sa m ple of 
pri mar y t u m or  
X  
  
  
  
  
  
 
 
 
M yria d M y Ris k bl o o d c ollecti o n  
X  
  
  
  
  
  
 
 
 
W h ole bl o o d c ollecti o n  
X  
  
  
  
  
  
 
 
 
Plas ma c ollecti o n  
X  
  
  
  
  
  
 
 
X  
T u m or meas ure me nts  
X  
T u m or meas ure me nts are re peate d e ver y 8 we e ks t hr o u g h 
c ycle 8 ( o pti o n t o re peat e ver y 1 2 we e ks after c ycle 8).  
D oc u me ntati o n m ust b e pr o vi d e d f or patie nts re m o ve d fr o m 
st u d y f or pr o gressi ve diseas e. 
X  
Ra di ol o gic e val uati o n ( C T wit h I V 
c o ntrast a nd b o ne sca n or  P E T C T 
wit h I V c o ntrast, pl us M RI brai n or 
C T h ea d if hist or y of brai n 
metastases).  
X  
Ra di ol o gic meas ure me nts s h o ul d be perf or me d e ver y 8  wee ks 
±  1  wee ks.  T here is t he o pti o n t o decrease ra di ol o gic e val u ati o n 
t o e ver y 1 2 wee ks after c ycle 8.  
X  
a. Al b u mi n, al kali ne p h os p hatase, t otal bilir u bi n, bicar b o nate, B U N, calci u m, c hl ori d e, creati ni ne, gl u c ose, p otassi u m, t otal pr otei n, 
S G O T[ A S T], S G P T[ A L T], s o di u m.  
b .  T o be c ollecte d at first cli nic visit after e vi d e nce of disease pr o gressi o n ( ±  7  da ys).  


I R B-3 1 9 1 3 versi o n 8  
P a ge 3 9  of 4 6   
2  Se pte m ber  2 0 2 0  
1 0 .  
M E A S U R E M E N T S  
1 0 . 1 
Pri m ar y E n d p oi nt  
T he o bjecti ve res p o nse r ate of t al az o p ari b defi ne d as c o m plete res p o nse or p arti al res p o nse 
per  R E CI S T v 1. 1  
O bjecti ve res p o nse rate is defi ne d as c o m plete res p o nse or partial res p o nse a n d deter mi ne d b y 
R E CI S T  v 1. 1 criteri a.  All st u d y p artici pa nts will ha ve meas ura ble disease at st u d y i nitiati o n.  
O bjecti ve res p o ns es are defi ne d usi n g R E CI S T v. 1. 1 criteria:  
 C o m plete Res p o nse ( C R): Disa p peara nce of all tar get lesi o ns .  A n y p at h ol o gical l y m p h 
n o des ( w het her tar get or n o n -tar get) m ust ha v e re d ucti o n i n s h ort a xis t o <  1 0 m m.  
 Partial Res p o nse ( P R):  At least a 3 0 % decrease i n t he s u m of dia meters of tar get lesi o ns, 
ta ki n g as refere n ce t he baseli ne s u m dia meters.  
 Pr o gressi ve Diseas e ( P D): At least a 2 0 % i ncrease i n t he s u m of dia meters of tar get lesi o ns, 
ta ki n g as refere n ce t he s mallest s u m o n st u d y (t his i ncl u des t he baseli ne s u m if t hat is t he 
s mallest o n st u d y).  I n a d diti o n t o t he relati ve i ncrease of 2 0 %, t he s u m m ust als o 
de m o nstrate a n a bs ol ute i ncreas e of a t least 5 m m.  ( N ote: t he a p peara nce of o ne or m ore n e w 
lesi o ns is als o c o nsi dere d pr o gressi o n)  
C o nfir mati o n of a res p o nse re q uires a re p eat o bser vati o n at least 4 wee ks a part.  
F or t he p ur p oses of t his st u d y, patie nts s h o ul d be e val uate d f or res p o nse at 8  wee ks  +/ - 1  wee k, 
t he n re-e val u ate d f or res p o nse e ver y 8  wee ks  +/ - 1  wee k, or s o o n er if t here is a cli nical or 
la b orat or y fi n di n g t hat is c o ncer ni n g f or disease pr o gressi o n.  T he t y pe of i ma gi n g m o dalit y is 
de pe n de nt o n sites of metastases b ut will mai nl y  c o nsist of C T c hest, a b d o me n a n d pel vis wit h 
c o ntrast a n d b o n e sca n or P E T C T wit h I V c o ntrast .  All baseli ne e val uati o ns s h o ul d be 
perf or me d as cl os el y as p ossi ble t o t he be gi n ni n g of treat me nt a n d ne v er m ore t h a n 4  wee ks 
bef ore i nitiati o n.  
Res p o nse a n d pr o gressi o n will be e val uat e d i n t his st u d y usi n g t he i nter nati o nal criteria pr o p ose d 
b y t h e re vise d 
Res p o nse 
E val uati o n 
Criteria i n 
S oli d 
T u m ors ( R E CI S T) 
g ui deli ne 
(v ersi o n 1. 1).  2 9  C ha n ges i n t he lar gest dia meter ( u ni -di me nsi o nal meas ure me nt) of t he t u m or 
lesi o ns a n d t he s h ortest dia meter i n t he cas e of mali g na nt l y m p h n o d es are us e d i n t he R E CI S T 
criteria.  T he Eise n ha uer 2 0 0 9 E ur o pea n J o ur nal of Ca ncer ma n uscri pt details t he c o m plete 
descri pti o n of R E CI S T  v 1. 1 criteria f or res p o ns e assess me nt a n d will be f oll o we d f or t his st u d y.  
1 0. 2  
Sec o n d ar y E n d p oi nts  
1 0. 2. 1  Cli nic al be nefit r ate ≥ 2 4  wee ks  
T his is defi ne d as c o m plete res p o nse, partial res p o nse or sta ble diseas e as assesse d after at least 
2 4  wee ks o n t he i n vesti gati o nal dr u g .  R es p o nse a n d pr o gressi o n will be e v al uate d usi n g 
R E CI S T  g ui deli ne v 1. 1 .  I ma gi n g will be perf or me d e ver y 8  wee ks .  
1 0 . 2.2  P r o g ressi o n -free s ur vi v al 
Pr o gressi o n -free s ur vi val is defi ne d as t he ti me fr o m ra n d o mizati o n t o d oc u me nte d diseas e 
pr o gressi o n or deat h.   Patie nts wit h o ut pr o gressi o n at t he e n d of t he st u d y will be ce ns ore d at t he 
date of t heir last ra di o gra p hic e val uati o n.  


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 0  of 4 6   
2  Se pte m ber  2 0 2 0  
1 0 . 2.3  S afet y of t al az o p ari b i n t his st u d y p o p ul ati o n 
All a d verse e ve nts will be gra de d acc or di n g t o C T C A E  v 5 . 
1 0. 3  
C orrel ati v e E n d p oi nts  
1 0. 3. 1  O bjecti ve res p o nse r ate i n s u bjects wit h T N B C wit h or wit h o ut a n  u n derl yi n g 
ger mli ne  H R p at h w a y m ut ati o n i n C o h ort  A  
T he 2 5 -ge n e M y Ris k ger mli ne  m utati o n pa nel will be perf or me d o n all s u bjects o n a res earc h 
basis i n C o h ort  A .  O bjecti ve res p o nse rates b y R E CI S T v 1. 1 will be c o m pare d i n s u bjects wit h 
a n d wit h o ut a n i de ntifie d  H R pat h wa y ge n e m ut ati o n of i nterest.  
1 0. 3. 2  C orrel ati o n of  H R D  sc o res wit h res p o nse i n s u bjects wit h u n derl yi n g deleteri o us  or 
s us pecte d deleteri o us  ger mli ne  or s o m atic  H R g e ne m ut ati o ns i n C o h ort  B  
T he  H R D  sc ore is a c o nti n u o us meas ure me nt ( 0 t o 1 0 0) t hat will be assesse d fr o m metastatic 
F F P E t u m or tiss ue usi n g t he M yri a d  H R D  assa y o n a researc h b asis i n s u bjects e nr olle d o n 
C o h ort  B .  Base d o n pri or st u dies, a n  H R D  c ut off sc ore of 4 2  or hi g h er will be use d t o defi ne  
H R -deficie nt breast c a ncer .  We will c orrel ate t he mea n  H R D  sc ores a n d di c h ot o m o us H R D  
sc ores (H R D  d eficie n t v ers us H R D  i ntact) wit h t hera p y res p o nse. 
1 0. 3. 3  C orrel ati o n of  H R D  sc o res i n t he pri m ar y t u m o r tiss ue a n d t he met ast atic t u m or 
tiss ue. 
All s u bjects will ha ve b ot h metastatic a n d arc hi val pri mar y breas t t u m or sa m ples assesse d 
f or H R D .  We will assess t he c orrelati o n of sc ores ( mea n a n d dic h ot o m o us sc ores) f or t hese t w o 
t u m or sa m ple t y pes wit hi n eac h p atie nt.  Patie nts i n w h o m a metastatic bi o ps y was dee me d n ot 
feasi ble will be e x cl u de d. 
1 0. 3. 4  C orrel ati o n of R A D 5 1 st at us i n t he met ast atic t u m or wit h  H R D  a n d m ut ati o n al 
st at us. 
R A D 5 1 b y i m m u n o hist oc he mistr y as a f u ncti o nal rea d o ut of  H R ca pacit y will be assesse d i n 
baseli ne F F P E metastatic t u m or bi o ps y sa m ples .  R A D 5 1 stat us, a bse nt or prese nt, will be 
c orrel ate d wit h H R D  a n d m utati o nal stat us.  
1 1 .  
R E G U L A T O R Y C O N SI D E R A TI O N S  
1 1 . 1 
I nstit uti o n al Re vie w of Pr ot oc ol 
T he pr ot oc ol, t he pr o p os e d i nf or me d c o ns e nt a n d all f or ms of partici pa nt i nf or mati o n relate d t o 
t he st u d y (e g, a d vertise m e nts use d t o recr uit p arti ci pa nts) will be re vie we d a n d a p pr o ve d b y t h e 
Sta nf or d I R B a n d Sta nf or d Ca ncer I nstit ute Scie ntific Re vie w C o m mittee ( S R C).  A n y c ha n ges 
ma de t o t he pr ot oc ol will be s u b mitte d as a m o dificati o n a n d will be a p pr o ve d b y t he I R B pri or 
t o i m ple me ntati o n.  T he Pr ot oc ol Direct or will disse mi nate t he pr ot oc ol a me n d me nt i nf or mati o n 
t o all partici pati n g i n vesti gat ors. 
1 1 . 2 
D at a a n d S afet y M o nit ori n g Pl a n  
T he Sta nf or d Ca n cer I nstit ute Data a n d Safet y 
M o nit ori n g C o m mittee ( D S M C) will be t he 
m o nit ori n g e ntit y f or t his st u d y.  T he D S M C will a u dit st u d y -relate d acti vities t o deter mi ne 
w het her t he st u d y has bee n c o n d ucte d i n acc or da nce wit h t he pr ot oc ol, l ocal sta n dar d o perati n g 
pr oce d ures, F D A re g ulati o ns, a n d  G o o d Cli nical Practice  ( G C P).  T his ma y i ncl u de re vie w of t he 
f oll o wi n g t y pes of d oc u me nts partici pati n g i n t he st u d y: re g ulat or y bi n d ers, case re p ort f or ms, 


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 1  of 4 6   
2  Se pte m ber  2 0 2 0  
eli gi bilit y c h ec klists, a n d s o urce d oc u me nts.  I n a d diti o n, t he D S M C will re g ularl y re vie w 
seri o us a d verse e ve nts a n d pr ot oc ol de vi ati o ns ass ociate d wit h t he re searc h t o e ns ure t he 
pr otecti o n of h u ma n s u bjects.  Res ults of t he D S M C a u dit will be c o m m u nicate d t o t he I R B a n d 
t he a p pr o pri ate re g ulat or y a ut h orities at t he ti me of c o nti n ui n g re vi e w, or i n a n e x pe dite d 
fas hi o n, as nee de d. 
1 1 . 3 
D at a M a n a ge me nt Pl a n  
Elec tr o nic Cas e Re p ort F or ms ( C R Fs) will be us e d t o rec or d all pr ot oc ol -relate d i nf or mati o n o n 
eac h trial partici pa nt .  C R Fs will s u m marize t he cli nical fi n di n gs a n d o bser vati o ns necessar y t o 
e ns ure safet y of partici pa nts o n t he st u d y, a n d t o d oc u me nt t he st u d y o utc o mes.  
Re d Ca p Electr o nic Cas e Re p ort F or ms (e C R F) will be us e d t o rec or d all pr ot oc ol -relate d 
i nf or mati o n o n eac h tri al partici pa nt.  A C R F will be c o m plete d f or eac h e nr olle d st u d y 
partici pa nt .  It is t he i n vesti gat or's res p o nsi bilit y t o e ns ure t he acc urac y, c o m plete ness, clarit y, 
a n d ti meli ness of t h e dat a re p orte d i n t h e partici pa nt's C R F .  S o urce d o c u me ntati o n s u p p orti n g 
t he C R F dat a s h o ul d i n dicate t he patie nt's p arti ci pati o n i n t he st u d y a n d s h o ul d d oc u me nt t h e 
date a n d det ails of st u d y pr oce d ur es, A Es, ot her o bser vati o ns a n d patie nt st at us.  
T he i n vesti gat or is re q uire d t o pre pare a n d mai ntai n a de q uate a n d acc urate case hist ories 
desi g ne d t o rec or d all o bser vati o ns a n d ot h er data perti ne nt t o t he st u d y f or eac h st u d y 
partici pa nt .  T he st u d y data f or eac h e nr olle d partici pa nt will be e ntere d i nt o a C R F b y site 
pers o n nel usi n g a sec ure, vali date d, we b -bas e d electr o nic data ca pt ure a p plicati o n .  A n y c ha n ges 
t o st u d y d ata will be ma de t o t he C R F a n d d oc u me nte d i n a n a u dit trail t hat will be mai ntai ne d 
wit hi n t he cli nical data base.  
1 2 .  
S T A TI S TI C A L C O N SI D E R A TI O N S  
1 2 . 1 
A n al ytic Pl a n f or St u d y O bjecti ves  
1 2. 1. 1  Pri m ar y O bjecti ve  
T o deter mi ne t he o bjecti ve res p o nse rate, defi ne d as c o m plete res p o nse or  partial  res p o nse per 
R E CI S T 1. 1 , t he o bjecti ve res p o ns e rate a n d 9 5 % c o nfi de nce i nter val will be calc ul ate d usi n g t he 
e x act bi n o mial m o del.   
1 2. 1. 2  Sec o n d ar y O bjecti ves  
T o deter mi ne t he cli nical be nefit rate, defi ne d as c o m plete res p o nse, partial res p o nse or sta ble 
disease ≥ 2 4  wee ks per R E CI S T  v 1. 1 , t he clinical be nefit rate a n d 9 5 % c o nfi de nce i nter val will 
be calc ul ate d usi n g t h e e x act bi n o mial m o del.   
T o deter mi ne pr o gressi o n -free s ur vi val, Ka pla n -Meier  c ur ves will be calc ulate d , al o n g wit h a 
9 5 % c o nfi de n ce i nter val f or P F S at o ne year, calc ulate d usi n g G ree n w o o d’s f or m ula.   
T o assess safet y of t alaz o pari b i n t his st u d y p o p ulati o n, ad verse e v e nts will be gra d e d usi n g 
C T C A E v 5  a n d s u m marize d descri pti vel y as descri be d i n Secti o n  7. 1.  
1 2. 1. 3  C orrel ati v e O bjecti v es  
I n c orrelati n g H R D  sc ore (ra n gi n g o ver 0 t o 1 0 0) wit h a bi nar y varia ble s uc h o bjecti ve res p o nse 
stat us, R A D 5 1 stat us a n d s o o n, we will calc ulate t he mea n a n d sta n d ar d de viati o n of  H R D  sc ore 
i n t he t w o s u bsets a n d e v al uate t he stre n gt h of t h e ass ociati o n usi n g t he Wilc o x o n ra n k s u m 
statistic.  


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 2  of 4 6   
2  Se pte m ber  2 0 2 0  
I n eval uati n g t he c o n c or da nce of  H R D  sc ore i n t he pri mar y t u m or a n d H R D  i n t he metastatic 
t u m or, t he Wilc o x o n si g ne d ra n k test will be use d. 
All re mai ni n g c o m paris o n i n v ol ve c orrel ati n g t w o bi nar y v aria bl es, w hic h will be d o n e b y 
prese nti n g pr o p orti o ns wit h 9 5 % e x act c o nfi de nce i nter vals .  T he si g nifica n ce of t he c orrelati o n 
will be assesse d usi n g Fis her’s e x act test.   A t w o -si de d P val ue of 5 % or less will be c o nsi dere d 
statisticall y si g nifica nce. 
T he p r o p orti o n of s pecific mutati o ns wit h its 9 5 % c o nfi de nce i nter val will be calc ulate d usi n g 
t he e x act bi n o mial m o del. 
1 2 . 2 
A n al ysis p o p ul ati o n   
Safet y a n al ysis will be c o n d ucte d o n all patie nts w h o recei ve d at l east o n e d ose of tri al t hera p y .  
Efficac y a n al ysis will be perf or me d o n all patie nts w h o recei ve at least 1 c ycl e of t hera p y u nl ess 
t he reas o n f or c o m pleti n g less t ha n 1 c ycle of t h era p y was attri b uta ble t o disease pr o gressi o n.  
Patie nts w h o c o me off trial bef ore c o m pleti n g 1 c ycle of t hera p y f or reas o ns ot her t ha n disease 
p r o gressi o n will be c o nsi dere d n o n-e val ua bl e f or res p o nse a n d will be re place d.  
1 2 . 3 
S a m ple Size C alc ul ati o ns  
T his 
p hase  2  pr o of -of -c o nce pt trial is a n o pe n -la bel st u d y i n patie nts 
wit h a d va nce d, 
H E R 2 -ne gati ve breast ca ncer or n o n -breast metastatic ca ncer .  A t w o -sta ge desi g n will be use d 
f or e nr oll me nt of st u d y partici pa nts se paratel y i n C o h ort  A a n d  i n C o h ort  B wit h a set 
n ull  h y p ot hesis of  5 % o bjecti ve res p o nse rate a n d alter nati ve res p o ns e rate of  3 0 % base d o n 
sta n dar d R E CI S T v 1. 1 criteria.  
I nteri m anal ysis will be perf or me d, se paratel y i n eac h c o h ort, after accr ual of 1 0  patie nts a n d 
ha ve ha d at least o ne res p o nse assess me nt i n t hat c o h ort.  P atie nts will be o bser ve d f or res p o ns es 
e ver y 8  wee ks +/ - 1  wee k .  If at least t w o o ut of t he 1 0  patie nts r es po n ds, t he n we will accr ue 
1 0  a d ditio nal patie nts f or a t otal of 2 0  patie nts i n eac h c o h ort (t otal n u m ber of patie nts f or t he 
trial =  4 0) .  Bas e d o n o ur statistical c o nstrai nts, at least 3  patie nts o ut of t he 2 0 res p o n d i n eac h 
c o h ort t o declare statistical  si g nifica nce at a o ne-si de d 5 % le vel wit h 8 0 % p o wer or b etter 
1 2 . 4  Accr u al Esti m ates a n d Fe asi bilit y    
 
We see >  7 5 ne w patie nts wit h a d va nce d, tri ple -ne gati ve breast ca n cer at t he Sta nf or d W o me n’s 
Ca ncer Ce nter eac h year a n d fr o m 2 0 0 9  t o 2 0 1 3 h a ve c o nsis te ntl y e nr olle d >  2 5 patie nts p er year 
t o tri ple-ne gati ve s pecifi c cli nical trials.  Base d o n o ur pre vi o us ne oa dj u va nt st u d y utilizi n g 
t he H R D  assa y, a p pr o xi matel y half of s p ora dic, tri ple -ne gati ve breast ca ncer patie nts ha ve 
a n H R D  sc ore t hat is greater tha n or e q u al t o 4 2 .  As s uc h we are c o nfi de nt t hat we ca n accr ue 
o ur  patie nts i n t he pr oject e d ti meli ne pr o vi de d.  
Gi ve n t h at t he  utilizati o n of m ulti ple x  ge n e p a nels t o assess ger mli ne  m ut ati o ns i n t he H R re pair 
pat h wa y h as rece ntl y e mer ge d  a n d b eca us e t he  use of t u m or N G S is j ust rece ntl y o n t h e rise , we 
ha ve n o hist orical meas ures t o h el p esti mate t he n u m ber of patie nts we will be accr ue i n 
C o h ort  B wit hi n  o ur  si n gle i nstit uti o n.  T hat b ei n g sai d, we are e nc o u nteri n g a n i ncreasi n g 
n u m ber of t h ese p atie nts  t hr o u g h o ur Ca ncer Ge n o mics Pr o gra m.  We will w or k cl os el y wit h t he 
here ditar y ca n cer n o n -pr ofit or ga nizati o n F O R C E t o p u blicize t his trial .  S h o ul d accr ual be 
li mite d, we will c o nsi der a d di n g a d diti o nal st u d y sites t o c o m plete t his c o h ort accr ual. 


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 3  of 4 6   
2  Se pte m ber  2 0 2 0  
R E F E R E N C E S  
1.  F or d J M, Kasta n M B. D N A da ma ge res p o nse pat h wa ys a n d ca ncer. 4t h e d: C h urc hill 
Li vi n gst o n; 2 0 0 8.  
2.  As h w ort h A. A s y nt hetic let hal t hera pe utic a p pr oac h: p ol y( A D P) ri b ose p ol y m erase 
i n hi bit ors f or t he treat me nt of ca ncers deficient i n D N A d o u ble -str a n d brea k re pair. J o ur nal 
of cli nical o nc ol o g y : offi cial j o ur nal of t he A m erica n S ociet y of Cli nical O nc ol o g y 
2 0 0 8; 2 6: 3 7 8 5 -9 0.  
3.  Br ya nt H E, Sc h ultz N, T h o mas H D, et al . S pecifi c killi n g of B R C A 2-deficie nt t u m o urs wit h 
i n hi bit ors of p ol y( A D P-ri b ose) p ol y m eras e. Nat ure 2 0 0 5; 4 3 4: 9 1 3-7.  
4.  Cleat or S, Heller W, C o o m bes R C. Tri ple -ne gati v e breast ca ncer: t hera pe utic o pti o ns. T he 
la ncet o nc ol o g y 2 0 0 7; 8: 2 3 5-4 4.  
5.  Far mer H, Mc Ca b e N, L or d CJ, et al . Tar geti n g t he D N A re pair defect i n B R C A m utant cells 
as a t hera pe utic strate g y. Nat ure 2 0 0 5; 4 3 4: 9 1 7 -2 1.  
6.  L or d CJ, As h w ort h A. T he D N A da m a ge res p o ns e a n d ca ncer t hera p y. Nat ure 
2 0 1 2; 4 8 1: 2 8 7 -9 4.  
7.  R o ulea u M, Patel A, He n dzel MJ, Ka uf ma n n S H, P oirier G G. P A R P i n hi biti o n: P A R P 1 a n d 
be y o n d. Nat ur e re vie ws Ca ncer 2 0 1 0; 1 0: 2 9 3 -3 0 1.  
8.  F o ul kes W D, Stefa nss o n I M, C ha p p uis P O, et al . Ger mli ne  B R C A 1 m utati o ns a n d a basal 
e pit helial p he n ot y p e i n breast c a ncer. J o ur nal of t he Nati o nal Ca ncer I nstit ute 
2 0 0 3; 9 5: 1 4 8 2 -5.  
9.  S orlie T, Ti bs hira ni R, Par ker J, et al . Re peate d o bser vati o n of breast t u m or s u bt y pes i n 
i n de pe n de nt ge n e e x pressi o n data sets. Pr ocee di n gs of t he Nati o nal Aca de m y of Scie n ces of 
t he U nite d States of A merica 2 0 0 3; 1 0 0: 8 4 1 8-2 3.  
1 0.  Nielse n T O, Hs u F D, J e nse n K, et al . I m m u n o hist oc he mical a n d cli nical c haract erizati o n of 
t he basal-li ke s u bt y pe of i n vasi ve breast carci n o ma. Cli nical Ca ncer Res earc h 
2 0 0 4; 1 0: 5 3 6 7 -7 4.  
1 1.  Hasta k K, Alli E, F or d J M. S y ner gistic c h e m ose nsiti vit y of tri ple -ne gati ve breast ca ncer cell 
li nes t o p ol y( A D P-Ri b os e) p ol y m eras e i n hi biti o n, ge m cita bi ne, a n d cis plati n. Ca ncer 
researc h 2 0 1 0; 7 0: 7 9 7 0-8 0.  
1 2.  Alli E, S har ma V B, S u n d eresa k u m ar P, F or d J M. Defecti ve re p air of o xi dati ve d na da ma ge 
i n tri ple-ne gati ve breast c a ncer c o nfers se nsiti vit y t o i n hi biti o n of p ol y( A D P -ri b ose) 
p ol y me rase. Ca ncer researc h 2 0 0 9; 6 9: 3 5 8 9-9 6.  
1 3.  Gel m o n K A, Tisc h k o wit z M, Mac ka y H, et al . Ol a pari b i n patie nts wit h rec urre nt hi g h-gra de 
ser o us or p o orl y differe ntiate d o varia n carci n o ma or tri ple-ne gati ve breast ca ncer: a p has e 2, 
m ultice ntre, o pe n -la bel, n o n-ra n d o mise d st u d y. T he la ncet o n c ol o g y 2 0 1 1; 1 2: 8 5 2-6 1.  
1 4.  Castera L, Kri e ger S, R o usseli n A, et al . Ne xt-ge n erati o n se q ue n ci n g f or t h e dia g n osis of 
here ditar y breast a n d o varia n ca n cer usi n g ge n o mi c ca pt ure tar geti n g m ulti ple ca n di date 
ge n es. E ur o pea n j o u r nal of h u ma n ge netics : EJ H G 2 0 1 4. 
1 5.  T u n g N, Bat elli C, Alle n B, et al . Pre val e nce of ge ne m utati o ns a m o n g here ditar y breast a n d 
o varia n ca ncer patie nts usi n g a 2 5 ge ne pa n el ( A bstract P D 4 -8).  Sa n A nt o ni o Breast Ca ncer 
S y m p osi u m; 2 0 1 3; Sa n A nt o ni o, T X.  
1 6.  A b ke vic h V, Ti m ms K M, He n ness y B T, et al . Patter ns of ge n o mic l oss of heter oz y g osit y 
pre dict h o m ol o g o us rec o m bi nati o n re pair defects i n e pit helial o varia n ca ncer. Britis h j o ur nal 
of ca ncer 2 0 1 2; 1 0 7: 1 7 7 6 -8 2.  
1 7.  Telli M, J e nse n K, A b ke vic h V, et al . H om ol o g o us Rec o m bi nati o n Deficie nc y ( H R D ) sc ore 
pre dicts pat h ol o gic res p o nse f oll o wi n g n e oa dj u va nt plati n u m -base d t hera p y i n tri ple -n e gati ve 


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 4  of 4 6   
2  Se pte m ber  2 0 2 0  
a n d B R C A 1/ 2 m utati o n -ass ociate d breast ca ncer ( B C).  Sa n A nt o ni o Breast Ca ncer 
S y m p osi u m; 2 0 1 2; Sa n A nt o ni o, T X.  
1 8.  Telli M L , J e nse n K C, K uria n A W. Pr E C O G 0 1 0 5: Fi nal efficac y res ults fr o m a p hase II 
st u d y of ge m cita bi ne ( G) a n d car b o plati n ( C) pl us i ni pari b ( B SI-2 0 1) as ne o a dj u va nt t hera p y 
f or tri ple-ne gati ve ( T N) a n d B R C A 1/ 2 m utati o n -ass ociate d breast ca n cer.  3 1. J o u r nal of 
cli nical o nc ol o g y : offici al j o ur nal of t he A merica n S ociet y of Cli nical O n c ol o g y 
2 0 1 3; 3 1: A bstract 1 0 0 3.  
1 9.  Telli M L , J e nse n K C, K uria n A W, et al . Pr E C O G 0 1 0 5: Fi nal effi cac y res ults fr o m a p hase II 
st u d y of ge m cita bi ne ( G) a n d car b o plati n ( C) pl us i ni pari b ( B SI-2 0 1) as ne o a dj u va nt t hera p y 
f or tri ple-ne gati ve ( T N) a n d B R C A 1/ 2 m utati o n -ass ociate d breast ca n cer.  A S C O A n n ual 
Meeti n g; 2 0 1 3; C hica g o, U S A: J Cli n O nc ol 3 1, 2 0 1 3 (s u p pl; a bstr 1 0 0 3).  
2 0.  S y m m a ns W F, Pei nti n ger F, Hatzis C, et al . Meas ure me nt of resi d ual breast ca ncer b ur de n t o 
pre dict s ur vi val after ne o a dj u va nt c he m ot hera p y. J o ur nal of cli nical o nc ol o g y : offi cial 
j o ur nal of t he A meri ca n S ociet y of Cli nical O n c ol o g y 2 0 0 7; 2 5: 4 4 1 4-2 2.  
2 1.  P o p o va T, Ma nie E, Rie u nier G, et al . Pl oi d y a n d l ar ge-s cale ge n o mic i nsta bilit y c o nsiste ntl y 
i de ntif y bas al-li ke breast carci n o mas wit h B R C A 1/ 2 i nacti vati o n. Ca ncer researc h 
2 0 1 2; 7 2: 5 4 5 4 -6 2.  
2 2.  Bir k ba k NJ, Wa n g Z C, Ki m J Y, et al . Tel o meric allelic i m bala nce i n dicates defecti ve D N A 
re pair a n d se nsiti vit y t o D N A -da m a gi n g a ge nts. Ca ncer disc o v er y 2 0 1 2; 2: 3 6 6 -7 5.  
2 3.  S he n Y, Re h ma n F L, Fe n g Y, et al . B M N 6 7 3, a n o vel a n d hi g hl y p ote nt P A R P 1/ 2 i n hi bit or 
f or t he treat me nt of h u ma n ca ncers wit h D N A re pair deficie nc y. Cli nical ca ncer researc h : a n 
official j o ur nal o f t h e A merica n Ass o ciati o n f or Ca ncer Res earc h 2 0 1 3; 1 9: 5 0 0 3-1 5.  
2 4.  S he n YJ, Fe n g Y, Wa n g B, C h u D, M yers P, P ost L. A bstract 3 5 1 4: L T -0 0 6 7 3, a hi g hl y 
p ote nt P A R P i n hi bit or, s h o ws a ntit u m or acti vit y a gai nst cells wit h D N A re pair defici e ncies.  
A A C R 1 0 1st  A n n ual Meeti n g: Ca ncer Researc h; 2 0 1 0; Was hi n gt o n D C.  
2 5.  Wai n ber g Z A, Rafi S, Ra ma nat ha n R K, et al . Safet y a n d a ntit u m or acti vit y of t he P A R P 
i n hi bit or B M N 6 7 3 i n a P hase I trial recr uiti n g m etastatic s mall-cell l u n g ca ncer ( S C L C) a n d 
B R C A m utati o n carrie r ca ncer patie nts.  A S C O A n n ual Meeti n g; 2 0 1 4; C hica g o. 
2 6.  T utt A, R o bs o n M, Gar ber J E, et al . Oral p ol y( A D P-ri b ose) p ol y m erase i n hi bit or ola pari b i n 
patie nts wit h B R C A 1 or B R C A 2 m utati o ns a n d a d va nce d breast ca ncer: a pr o of -of -c o nce pt 
trial. La ncet 2 0 1 0;3 7 6: 2 3 5 -4 4.  
2 7.  de B o n o J S, Mi na L A, G o nzalez M, et al . A bstract 2 5 8 0: First-i n-h u ma n trial of n o vel oral 
P A R P i n hi bit or B M N 6 7 3 i n patie nts wit h s oli d t u m ors. A S C O A n n ual Meeti n g; 2 0 1 3; 
C hica g o, I L.  
2 8. Pritc har d C C, Mate o J,  Wals h M F et al . I n h erite d D N A-Re p air Ge n e M utati o ns i n Me n wit h 
Metastatic Pr ostate Ca ncer. N EJ M 2 0 1 6; 3 7 5: 4 4 3 -4 5 3.  
2 9. Eise n ha uer E A, T herasse P, B o gaerts J, et al. Ne w res p o nse e v al uati o n criteria i n s oli d 
t u m o urs: re vise d R E CI S T g ui deli ne ( versi o n 1. 1). E ur J Ca ncer 2 0 0 9; 4 5( 2): 2 2 8-4 7  
 


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 5  of 4 6   
2  Se pte m ber  2 0 2 0  
A P P E N DI C E S  


I R B-3 1 9 1 3 versi o n 8  
P a ge 4 6  of 4 6   
2  Se pte m ber  2 0 2 0  
A P P E N DI X A :   
S A E Re p orti n g G ui deli nes; S CI S O P 1 0 -1 6 -2 0 1 4  
H O W T O R E P O R T S E RI O U S A D V E R S E E V E N T S ( S A E s)  
I N I N V E S TI G A T O R-I NI TI A T E D T RI A L S 
 1. D et er mi n e if t h e e v e nt m e et s crit eri a f or S A E i n St u d y pr ot o c ol a n d St a nf or d S O P  
( all S A E s Gr a d e  3 a n d a b o v e, m u st b e s u b mitt e d t o C C T O/ St a nf or d).  
 2. C o m pl et e A L L fi el d s of C C T O S A E C a s e R e p ort F or m  ( C R F) a n d v erif y wit h 
i n v e sti g at or.  
 3. C o nfir m wit h i n v e sti g at or S A E gr a d e, E x p e ct e d or U n e x p e ct e d a n d Attri b uti o n.  
 4.  O bt ai n i n v e sti g at or si g n at ur e o n t h e f or m aft er  filli n g o ut all t h e i nf or m ati o n. 
 5. S e n d si g n e d C C T O S A E f or m t o 
 vi a S E C U R E e m ail 
wit hi n 2 4  h o ur s of n otifi c ati o n o f t h e e v e nt. C C T O S af et y will e nt er it i nt o O n C or e. 
 6. V erif y wit h i n v e sti g at or if t h e S A E i s U n a nti ci p at e d Pr o bl e m  ( U P: u n e x p e cte d, 
r el at e d t o r e s e ar c h a n d h ar mf ul) a n d r e p ort it t o I R B, wit hi n 2 4  h o ur s of n otifi c ati o n 
of t h e e v e nt . 
 Cli c k o n r e p ort i n e Pr ot o c ol.  
 U pl o a d t h e c o m pl et e S A E r e p ort.  
 Fill o ut e Pr ot o c ol r e p ort f or m.  
 Cli c k o n “ S u b mit pr ot o c ol” b utt o n o n t h e l eft.  
 7. If S A E i s n ot U P, t h e n r e p ort d uri n g n e xt I R B r e n e w al.  
F or I n v e sti g at or -i niti at e d st u d y wit h a n I N D a n d If S A E i s U n a nti ci p at e d Pr o bl e m  
( U P) t h e n r e p ort t o F D A wit hi n 2 4 h o ur s of n otifi c ati o n of t h e e v e nt  
 8. C o m pl et e M e d W at c h F or m ( F or m 3 5 0 0 A) .  T h e f or m M U S T b e t y p e d!  F or 
a s si st a n c e c o nt a ct 
. A ct u al li n k f or t h e f or m:  
htt p s:// w w w. p dffill er. c o m/ e n/ pr oj e ct/ 1 5 0 7 0 0 5 2 0. ht m ?f
h a s h = 7 a 4 e 5 d &r el o a d =tr u e   
 9. Wit h a s si st a n c e fr o m t h e r e g ul at or y f a cilit at or, s e n d t h e c o m pl et e d M e d W at c h 
f or m a n d F D A F or m  1 5 7 1 t o t h e F D A f oll o wi n g t h e w e b sit e i n str u cti o n s.  
 1 0. If r e q uir e d, n otif y m a n uf a ct ur er.  D e -i d e ntif y a p pli c a bl e s o ur c e d o c u m e nt s:  
M D  n ot e s ( a d mi s si o n, pr o gr e s s n ot e, di s c h ar g e n ot e, a n d d at e of d e at h 
if a v ail a bl e), l a b or at or y r e p ort s, r a di ol o g y r e p ort s, m e di c al a d mi ni str ati o n r e c or d s.  
 1 1. S e n d si g n e d C C T O S A E f or m  a n d d e -i d e ntifi e d s o ur c e d o c u m e nt s. 
 1 2. Fil e S A E r e p ort  i n p ati e nt r e s e ar c h c h art. 
 1 3. F oll o w S A E a n d s u b mit u p d at e d r e p ort s t o St a nf or d a n d/ or S p o n s or u ntil:  
 R e s ol uti o n of e v e nt.  
 R e s ol uti o n of e v e nt wit h s e q u el a e.  
 D e at h of p ati e nt.  
U nl e s s ot h er wi s e s p e cifi e d b y s p o n s or  

ICF_001.pdf: 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
Page 1 of 20 
IRB-31913  29 October 2018 
IRB Use Only 
   Approval Date:   September 20, 2022 
  Expiration Date:  September 20, 2023 
Participant ID: 
STANFORD CONSENT FORM 
*************** 
 
Are you participating in any other research studies? _____ Yes _____No 
 
PURPOSE OF RESEARCH 
 
You are invited to participate in this clinical trial (a type of research study) because you have 
HER2 negative breast cancer or a non-breast metastatic solid tumor that has spread outside of the 
breast or other part of body (metastasized) and which may be sensitive to a class of drugs called 
PARP inhibitors. This study is a single-arm clinical trial, which means all participants will receive 
the study drug. 
The information in this form is part of a process called informed consent, which will allow you 
to make a decision about whether you want to volunteer for this clinical trial. Your study doctor 
will also explain the clinical trial to you. Clinical trials include only those people who choose to 
take part. Please take your time to make your decision and discuss it with your friends and 
family. 
Once all of your questions have been answered, if you still wish to take part, you will be asked to 
sign this form. Your study doctor and/or a member of the study team will also sign the form. You 
will receive a copy of the form to keep. If you have any questions at any time during the research 
study, you should feel free to ask them. You will receive answers to your questions in a way that 
you will be able to understand. You are not giving up any of your legal rights by volunteering for 
this research study or signing this consent form. 
This is an investigator-initiated led by Dr. Melinda Telli.  
 
This research study contains two patient cohorts. Each cohort is looking for a total of 20 patients. 
Cohort A consists of patients with sporadic (i.e. lacking an inherited form of the BRCA1 or 
BRCA2 gene mutation), advanced triple-negative (estrogen receptor-/progesterone receptor-
negative, and HER2-negative) breast cancer with faulty DNA repair mechanisms based on a new 
tumor tissue assay produced by Myriad Genetics. Cohort B consists of patients with HER2-
negative breast cancer or non-breast metastatic solid tumors with either evidence of a hereditary 
breast cancer syndrome, excluding BRCA1 or BRCA2, or with evidence of genetic changes in the 
tumor tissue, making the tumor sensitive to the study agent. Enrollment will only occur at the 
Stanford Women's Cancer Center.  
 
If you decide to terminate your participation in this study at any time, you should notify Dr. 
Melinda Telli at 
.  
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
Page 2 of 20 
IRB-31913  29 October 2018 
IRB Use Only 
   Approval Date:   September 20, 2022 
  Expiration Date:  September 20, 2023 
Participant ID: 
WHY IS THIS STUDY BEING DONE?  
 Studies have documented tumor shrinkage when using this class of study agents called PARP 
inhibitors in advanced breast cancer patients who carry an inherited BRCA1 or BRCA2 
mutation.  
 It has been suggested that PARP inhibitors may also have a role in the treatment of triple-
negative breast cancer patients, who do not have an inherited risk, but whose tumors have 
similar DNA repair defects. 
 Likewise this study agent may have a role in the treatment of breast cancer patients with 
different inherited mutations affecting the same DNA repair pathway, or similar types of 
mutations arising in the tumor tissue itself. 
 
The purpose of this study is to evaluate if treatment with the study drug, talazoparib, causes 
tumor shrinkage in breast cancer and non-breast cancer patients whose tumor cell’s have 
impaired ability to repair DNA. 
 
VOLUNTARY PARTICIPATION  
 
Your participation in this study is entirely voluntary.  Your decision not to participate will not 
have any negative effect on you or your medical care.  You can decide to participate now, but 
withdraw your consent later and stop being in the study without any loss of benefits or medical 
care to which you are entitled. 
 
DURATION OF STUDY INVOLVEMENT  
HOW LONG WILL YOU BE IN THE STUDY? 
Following the Pre-Study visit you will be required to visit Stanford every 28 days. Each visit will 
last a few hours depending on the examinations to be performed. The study doctor and research 
coordinator will inform you of the length of each visit.   
You will receive study treatment for 12 cycles with talazoparib (first stage of treatment called the 
Induction Phase). Each cycle is 28 days long. The Induction Phase will be given for up to 12 
cycles (or up to about 12 months), unless your disease progresses or side effects of therapy 
would make it unsafe for you to continue. 
If after 12 cycles your disease has not progressed and you remain on treatment, you will proceed 
to the second stage of treatment called the Continuation Phase. You will continue to receive 
treatment every 28 days. 
You will continue treatment until your disease progresses or side effects of therapy would make 
it unsafe for you to continue. 
Your study doctor will keep track of your medical condition for up to 3 years from the time you 
enrolled on this study to look at the long-term effects of the treatment. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
Page 3 of 20 
IRB-31913  29 October 2018 
IRB Use Only 
   Approval Date:   September 20, 2022 
  Expiration Date:  September 20, 2023 
Participant ID: 
Your study doctor may decide to take you off this study if your disease does not improve or if 
side effects of treatment would make it unsafe to continue. You will be informed of new 
developments that may become available that might affect your participation in the study. 
 
PROCEDURES 
WHAT IS INVOLVED IN THIS STUDY? 
BEFORE YOU BEGIN THE STUDY 
You will need to have the following exams, tests and procedures done in order to find out if you 
can safely be in the study. Many of these are part of your regular care and would be done even if 
you were not to take part in this study. If you have had some of these recently, they may not need 
to be repeated. You will need to sign this consent form before any study related procedures are 
performed.   
Within 4 weeks prior to treatment initiation, the following will be performed: 
 Review of your medical history, including any medications you are currently taking. The 
review will also include an assessment of any history of or risk factors you may have for 
hepatitis B or hepatitis C. 
 Complete physical examination, including an assessment of your heart rate, blood pressure, 
temperature, height and weight 
 Evaluation of how active you are and your ability to perform every day activities 
(performance status) 
 Radiology or Imaging scans to measure the size and location of the cancer (such as a CT or 
“CAT” Scan) 
 Serum pregnancy test for women of childbearing potential  
 Blood tests including complete blood count and metabolic chemistry panel 
 Hepatitis B and/or Hepatitis C tests may be done if you have any known risk factors. If you 
have a positive hepatitis B or hepatitis C result, you may be required to take an antiviral 
medication for 1-2 weeks prior to the first dose of study drug. 
The results of these tests will be reviewed by your study doctor to see if you have met all of the 
requirements for the study. 
DURING THE INDUCTION PHASE OF THE STUDY  
If the exams, tests and procedures show that you can be in the study and you choose to take part, 
then you will need the following exams, tests and procedures during the study: 
Day 1 of Each Cycle- At least once every 28 days, the following will be performed: 
 Physical examination including heart rate, blood pressure, temperature, and weight 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
Page 4 of 20 
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 Review of any medications you are currently taking 
 Evaluation of how active you are and your ability to perform every day activities 
(performance status) 
 Blood tests including complete blood count and liver and kidney function tests. Additional 
blood may be required to perform tests for hepatitis B and/or hepatitis C if you had a 
positive result prior to the start of the study. Please note: You will have a complete blood 
count measured once every two weeks for the first two cycles. 
 Check to see how you are taking the study medication at home. You will be asked to 
complete a Patient Pill Diary. Please bring your study medication and Patient Pill Diary to 
each visit. 
 Monitoring of side effects – you should tell your study doctor if you have new problems at 
any time when they occur. Your study doctor or nurse will also ask you about new 
problems before the start of a new study cycle. You should also tell your study doctor if 
you are taking any other medications. 
Once every 8 weeks (every 2 treatment cycles) the following will be performed: 
 Radiology or Imaging scans to measure the size and location of the cancer (such as a CT or 
“CAT” Scan). You may have additional radiology tests during the study if your study 
doctor feels it is necessary. 
DURING THE CONTINUATION PHASE (AFTER COMPLETION OF 12 CYCLES OF 
THERAPY IN THE INDUCTION PHASE) 
You will continue to receive single-agent talazoparib.  At each clinic visit, we will evaluate the 
following:  
 Complete blood count and kidney and liver function tests. 
 You will continue to complete a Patient Pill Diary. Please bring your study medication and 
Patient Pill Diary to each visit. 
 Monitoring of any unresolved side effects – you should tell your study doctor if you have 
new problems at any time when they occur. Your study doctor or nurse will also ask you 
about any ongoing problems after you have stopped taking the study medication. You 
should also tell your study doctor if you are taking any other medications. 
Once every 12 weeks (every 3 treatment cycles) the following will be performed: 
 Radiology or Imaging scans to measure the size and location of the cancer (such as a CT or 
“CAT” Scan). You may have additional radiology tests during the study if your study 
doctor feels it is necessary. 
You can discuss the details of the study calendar with your study doctor or the study staff. 
AFTER END OF FIRST STAGE OR END OF ALL TREATMENT 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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When you go off the study you will be asked to return for a follow-up exam within 30 days after 
receiving your last dose of talazoparib. The following tests and procedures will be done at the 
off-study visit: 
 Physical examination including heart rate, blood pressure, temperature, and weight 
 Review of any medications you are currently taking 
 Evaluation of how active you are and your ability to perform every day activities 
(performance status) 
 Blood tests including complete blood count and kidney and liver function tests. 
 Final check to see how you took the study medication at home. Please bring your study 
medication and completed Patient Pill Diary. 
 Monitoring of side effects – you should tell your study doctor if you have new problems at 
any time when they occur. Your study doctor or nurse will also ask you about any ongoing 
problems after you have stopped talking the study medication. You should also tell your 
study doctor if you are taking any other medications. 
 Radiology or Imaging scans to measure the size and location of the cancer (such as a CT or 
“CAT” Scan), if due. 
Once you have come off study, you will be followed for 3 years from the date you were 
randomized to the study. Your doctor will ask you about problems that were ongoing at the time 
you came off the study. The following tests and procedures may be done approximately every 3 
months: 
 Complete blood count – only if there are any ongoing side effects. 
 Radiology or Imaging scans to measure the size and location of the cancer (such as a CT or 
“CAT” Scan), if your cancer had not previously progressed (gotten worse). 
WHAT IS THE STUDY TREATMENT PLAN? 
After you have agreed to be in the study by signing this consent form and you have met all of the 
conditions for the study, you will receive the study drug, talazoparib. All study participants will 
receive a pill bottle containing 28 capsules of equal concentration of talazoparib to take daily. 
We will provide a refill every 28 days after our clinic visit with you.  
You will continue to take the study drug as prescribed during the Induction Phase, for 
approximately 12 cycles (each cycle is 28 days long) or until the disease gets worse or the side 
effects are not acceptable. If your tumor grows, or if you develop new tumors, the study 
treatment will be stopped. Your study doctor may stop treatment if you have side effects that 
would make it unsafe for you to continue, or you may decide to stop participating in the study at 
any time for any reason. Even if you stop treatment, you will be followed by your study doctor 
for up to three years. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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If you forget to take a pill and remember by 10 PM, you may take the dose. Otherwise just skip 
that dose and begin as usual the next day. Please mark dates of any missed pills on your Patient 
Pill Diary. Your study doctor or nurse will give you the Patient Pill Diary to write down the pills 
that you take. 
If your disease has not progressed (gotten worse) after 12 cycles of treatment (Induction Phase), 
you may continue to receive treatment (Continuation Phase). You may continue to receive 
treatment as long as your disease is not getting worse. You will continue be followed by your 
study doctor on a monthly basis. 
If you have serious side effects during your treatment, the dose of talazoparib may be lowered. If 
the serious side effects do not improve with the lowering of the dose or if the side effects are life 
threatening, the drug may be stopped by your study doctor.  
Women of Childbearing Potential 
If you are a woman who is able to become pregnant, it is expected that you will use an effective 
method of birth control such as an intrauterine device (IUD) or double barrier contraception during 
treatment and for 30 days after the last dose of study drug to prevent exposing a fetus to a 
potentially dangerous agent with unknown risk.  If you are pregnant or currently breast feeding, 
you may not participate in this study.  You understand that if you are pregnant, if you become 
pregnant, or if you are breast-feeding during this study, you or your child may be exposed to an 
unknown risk. 
 
To confirm to the extent medically possible that you are not pregnant, you agree to have a 
pregnancy test done before beginning this research study.   
 
You must agree to avoid sexual intercourse or use a birth control method judged to be effective by 
the investigator and which will not interfere with the proposed investigation.  You must accept the 
risk that pregnancy could still result despite the responsible use of reliable method of birth control.  
You agree to notify the investigator as soon as possible of any failure of proper use of your birth 
control method, or if you become pregnant, either of which may result in your being withdrawn 
from the study. 
 
Blood and Tissue Sampling for Research  
Research using blood and tissue is an important way to try to understand human disease.  You 
have been given this information because the investigators want to include results from your 
blood and tumor tissue in this research project and because they want to save the samples for 
future research.  If you do not already have an adequate tumor tissue biopsy from a 
metastatic site (i.e. a site that your cancer has spread to), you are required to undergo a 
repeat tissue biopsy to be considered eligible for this study. There are several things you 
should know before allowing your blood and tumor tissue to be studied.   
Your blood and tissues will be stored using a unique identifier and not linked to your medical 
record number. Tissues will be sent outside of Stanford University for analysis.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Because your samples will not be linked to your name after they are stored, you cannot withdraw 
your consent to the use of the samples after they are taken.  Following completion of all research 
the samples will be destroyed.  
You will be told the results of tests that are part of your clinical care, but you will not be told the 
results of the research tests, including any future research tests.  
 
_____ I consent to my samples being analyzed for this research study and being saved for 
 
 
future research 
 
_____ I consent to my samples being analyzed for this research study only; I do not  
 
 
consent to my samples being saved for future research 
 
_____ I do not consent to my samples being used for this research study or saved for  
 
 
future  research (please note: you will not be eligible for the study if you select  
 
 
this option) 
 
Tissue Sampling for Genetic Testing 
 
Genetic research is research that studies genes, including gene characteristics and gene versions 
that are transmitted by parents to children.  Genetic research may include looking at information, 
such as personal appearance and biochemistry, gene sequences, genetic landmarks, individual 
and family medical histories, reactions to medications and responses to treatment.  Genetic 
research raises certain questions about informing you of any results.  Possible risks of knowing 
results include:  anxiety; other psychological distress; and the possibility of insurance and job 
discrimination.  A possible risk of not knowing includes being unaware of the need for treatment.  
These risks can change depending on the results of the research and whether there is a treatment 
or cure for a particular disease.  
 
Sometimes patients have been required to provide information from genetic testing for health 
insurance, life insurance, and/or a job.  A Federal law, the Genetic Information 
Nondiscrimination Act of 2008 (GINA), generally makes it illegal for health insurance 
companies, group health plans, and employers with 15 or more employees to discriminate 
against you based on your genetic information.  
 
Any tissues you have donated which are used in research may result in new products, tests or 
discoveries. In some instances, these may have potential commercial value and may be 
developed and owned by the researchers, Stanford University and/or others. However, donors of 
tissues do not retain any property rights to the materials. Therefore, you would not share in any 
financial benefits from these products, tests or discoveries. 
 
Regarding informing you of the test results, you should understand the following:  
 The information may be too limited to give you particular details or consequences;  
 You may be determined to carry a gene for a particular disease that can be treated; 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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 You may be determined to carry a gene for a particular disease for which there is no 
current treatment;  
 You may carry a gene for a disease and might consider informing relatives that they, too, 
might carry the gene.   
Please circle [ yes or no ] as to whether you wish to be told the test results. 
Please circle [ yes or no ] as to whether you wish your family members to be told the test results. 
Birth Control  
If you and your sex partner are able to have a baby, you must agree to avoid pregnancy by using 
highly effective birth control methods such as an intrauterine device (“IUD”), oral (birth control 
pills), intravaginal, transdermal (patch) or injectable contraception methods or use abstinence 
(not having sexual intercourse).   
 
A woman receiving talazoparib must use the birth control from the time she signs the informed 
consent and for 45 days after the last dose of treatment.   
Men receiving talazoparib must use a condom when having sex with a pregnant woman and 
when having sex with a woman who could have a baby, from the time of the first dose of study 
drug through 105 days after the last dose of study drug. Men should talk about the use of highly 
effective birth control methods with a woman partner who could have a baby.   
 
This is important in research studies when the drugs have not been tested on pregnant women or 
the fetus. The only sure way to keep from getting pregnant or to make sure you do not make your 
partner pregnant is to not have sex. If you choose to have sex while you are in this study, you 
must talk about birth control and make an agreement with the study doctor. There is a risk that 
you could still get pregnant, even if you are using birth control. The treatment could make you 
lose the pregnancy (miscarry) or it might hurt the fetus. Ask your study doctor if you have 
questions about pregnancy or birth control during this study. 
 
Risks associated with pregnancy and nursing: 
Like any other experimental drug, talazoparib may have unknown and serious risks that could 
lead to death. If you are pregnant or breast feeding (nursing) a child, you cannot be in this study. 
Talazoparib was shown to harm the fetus of pregnant rats. Although the risk in humans of 
harming the fetus, nursing a baby, or losing a pregnancy (miscarriage) while taking talazoparib is 
unknown, you must use highly effective birth control during the study.  If you think you could be 
pregnant you must tell your study doctor. 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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For male patients, if your partner becomes pregnant or for female patients, if you become 
pregnant, you must immediately notify the study doctor of the pregnancy. The sponsor will ask 
the study doctor to provide medical information on the pregnancy and the health of the baby. 
 
PARTICIPANT RESPONSIBILITIES           
 
As a participant, your responsibilities include:  
 
 Follow the instructions of the Protocol Director and study staff. 
 Take the study drug as instructed  
 Keep your study appointments.  If it is necessary to miss an appointment, please contact 
the Protocol Director or research study staff to reschedule as soon as you know you will 
miss the appointment. 
 Tell the Protocol Director or research study staff about any side effects, doctor visits, or 
hospitalizations that you may have. 
 Tell the Protocol Director or research staff if you believe you might be pregnant or gotten 
your partner pregnant. 
 Keep the study drug in a safe place, away from children and for your use only. 
 Keep your diaries as instructed. 
 Complete your questionnaires as instructed. 
 Ask questions as you think of them. 
 Tell the Protocol Director or research staff if you change your mind about staying in the 
study. 
 
WITHDRAWAL FROM STUDY 
WHAT WILL HAPPEN IF I DO NOT WISH TO PARTICIPATE OR DECIDE NOT TO 
CONTINUE IN THE STUDY? 
Taking part in this study is your choice (voluntary). You may choose not to take part or may 
leave the study at any time. Leaving the study, or choosing not to take part, will not affect further 
treatment options or your relationship with your doctor. If you do not wish to participate in this 
trial, your doctor will discuss your other treatment options with you. You can change your mind 
at any time and withdraw your permission to allow your personal health information to be used 
in the research. Beginning on the date you withdraw your permission, no new personal health 
information will be used for research. However, researchers may continue to use the health 
information that was provided before you withdrew your permission. 
If you decide to withdraw your consent to participate in this study, you should notify Dr. Telli at 
. 
 
If you withdraw from the study, or the study medication is stopped for any reason, we will ask 
you to return all study-related supplies, including unused study drug. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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The Protocol Director may also withdraw you from the study and the study medication may be 
stopped, without your consent for one or more of the following reasons:  
 Failure to follow the instructions of the Protocol Director and study staff. 
 The Protocol Director decides that continuing your participation could be harmful 
to you. 
 Pregnancy  
 You need treatment not allowed in the study. 
 The study is cancelled.  
 Other administrative reasons. 
 Unanticipated circumstances. 
 
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
WHAT ARE THE RISKS OF THE MEDICATION OR TREATMENTS IN THE STUDY? 
While you are participating in this study, you should tell your study doctor about all medications 
that you are currently taking and before starting any new medications (including all herbal and 
over-the-counter medications). You should also tell your study doctor about any allergies to 
medications which you currently have or have had in the past. Severe allergic reactions, which 
may be life threatening, are possible with the medication prescribed in this study. For your 
safety, you will be monitored throughout the study for any changes that may occur because of 
the treatment that you receive. 
There are risks, discomforts, and inconveniences associated with any research study.  These 
deserve careful thought.  You should talk with the Protocol Director if you have any questions. 
 
Risks that have been associated with talazoparib are: 
 Low red blood cell counts (anemia), low platelet counts (thrombocytopenia), and low 
neutrophil counts (neutropenia) 
 Low neutrophil count (falls within subgroup of white blood cells) can weaken the 
immune system and increase the risk of infection, including severe infection or sepsis 
requiring hospitalization and IV antibiotics 
 Other side effects associated with this drug include: nausea, vomiting, diarrhea, muscle 
cramps, fatigue, dizziness, hair loss, cough, swelling or irritation of the mucus 
membranes (mucus membranes form a moist lining for body parts like your mouth, 
lungs, and digestive tract) and flatulence  
 
Talazoparib is considered a cytotoxic agent, subjects should be advised that oral anticancer 
agents are toxic substances and that (other than the subject) caregivers should always use gloves 
when handling the capsules. 
Furthermore, this class of drugs has been associated with a small risk of secondary hematological 
malignancies, such as acute leukemia. As such, if you decide to enroll in this study, we will pay 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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very close attention to your laboratory results and will refer you to a hematologist (blood 
specialist) if your blood counts remain low for more than six weeks. 
 
As this is an investigational therapy it may involves risk to the study participant that is currently 
be unforeseeable.  
All problems need to be reported to the study doctors or study nurses looking after you either by 
phone or at the next visit. 
For more information about risks and side effects, you should feel free to ask your study doctor. 
If you are concerned about your health between visits due to participating in this trial, please call 
your study doctor using the telephone numbers provided at the end of this document. 
In rare instances where a nurse, a doctor, or a laboratory technician sustains an exposure to your 
blood by needle stick, cut or splash to mucosa or damaged skin, it may be necessary to test your 
blood for certain viral infections including Hepatitis B, Hepatitis C, and HIV on the blood 
sample already available. This is to enable that person to receive appropriate counseling, 
monitoring and treatment, if necessary. In this instance the study doctor will offer you the 
information relevant to your health and advise you on the next steps. Confidentiality of your data 
will be respected at all times. 
OTHER RISKS AND DISCOMFORTS 
Other Medications 
Other drugs may be given to make side effects less serious and less uncomfortable including 
drugs for nausea, such as ondansetron or prochlorperazine. Other medications may be given to 
address symptoms of cancer. Please discuss the potential side effects of any new medications 
with your study doctor. 
Blood Collection 
The risks from having blood drawn and or inserting the needle in your vein when giving study 
drug include fainting, bleeding, bruising at the place on your arm where the blood was drawn or 
needle inserted, as well as pain, swelling and rarely, infection or nerve damage. 
 
Tumor Assessments 
Imaging scans such as CT, MRI, and bone scans will expose you to low doses of radiation and 
some may be performed with contrasting agents (dyes), which have additional side effects. If you 
need an MRI scans, there is a risk of heating from radiofrequency imaging coils and their cables, 
button response boxes and their cables, and the cables from monitoring devices that record 
physiologic processes such as heart beats per minute or electrical activity of the brain. Please 
report any heating sensation immediately. You may have the scan stopped at any time if this 
occurs. The risks of these procedures should be discussed with your study doctor and the person 
performing the exam.  This research study involves exposure to radiation from a screening CT 
scan. This radiation exposure is not necessary for your medical care and is for research purposes 
only. The additional amount of radiation exposure is about 20 mSv, which is approximately 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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equal to 40% of the limit that radiation workers (for example, a hospital x-ray technician) are 
allowed to receive in one year. This amount of radiation involves minimal risk and is necessary 
to obtain the research information desired. 
 
Tumor Biopsy 
In general, having a biopsy can cause pain, swelling, bleeding and/or infection at the site where 
the biopsy needle penetrates through your skin. If your doctor decides to use anesthetic, an 
allergic reaction may occur.  With a tumor biopsy, there is a rare possibility of tumor cells 
spreading from the tumor into the nearby area. 
 
POTENTIAL BENEFITS                              
If you agree to take part in this study, there may or may not be any direct medical benefit to you. 
The possible benefits to you from taking part in this study are that the drug may slow the growth 
or shrink your tumor. However, this cannot be guaranteed. We hope the information learned 
from this study will benefit other patients with cancer in the future. 
WE CANNOT AND DO NOT GUARANTEE OR PROMISE THAT YOU WILL RECEIVE 
ANY BENEFITS FROM THIS STUDY. 
 
ALTERNATIVES 
 
 Standard chemotherapy if you have triple-negative breast cancer 
 Standard chemotherapy or anti-estrogen therapy if you have estrogen receptor and/or 
progesterone receptor-positive breast cancer 
 Stanford chemotherapy if you have a non-breast metastatic cancer  
 Enrollment in a different clinical trial, if you meet the eligibility criteria 
 No therapy at this time, with care to help you feel more comfortable 
 
Please talk to your doctor about these and other options available to you for your treatment. 
 
PARTICIPANT’S RIGHTS 
 
You should not feel obligated to agree to participate.  Your questions should be answered clearly 
and to your satisfaction.  If you decide not to participate, tell the Protocol Director.   
 
You will be told of any important new information that is learned during the course of this 
research study, which might affect your condition or your willingness to continue participation in 
this study. 
 
If new information is learned that may affect you after the study has been completed, you will be 
contacted by the study doctor. 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Participant ID: 
ClinicalTrials.gov 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
CONFIDENTIALITY 
 
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
except as authorized by you or as required by law.  However, there is always some risk that even 
de-identified information might be re-identified.  
 
Patient information may be provided to Federal and other regulatory agencies as required.  The 
Food and Drug Administration (FDA), for example, may inspect research records and learn your 
identity if this study falls within its jurisdiction. 
 
The purpose of this study is to find out what effect single agent talazoparib will have on your 
cancer. This study will also look at the side effects associated with this drug.  The results will be 
provided to the drug manufacturer, the Food and Drug Administration and other federal and 
regulatory agencies as required. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Authorization To Use Your Health Information For 
Research Purposes 
 
Because information about you and your health is personal and private, it generally 
cannot be used in this research study without your written authorization.  If you 
sign this form, it will provide that authorization.  The form is intended to inform 
you about how your health information will be used or disclosed in the study.  
Your information will only be used in accordance with this authorization form and 
the informed consent form and as required or allowed by law.  Please read it 
carefully before signing it.   
 
What is the purpose of this research study and how will my health 
information be utilized in the study? 
The purpose of this study is to find out what effect single agent talazoparib will 
have on your cancer. This study will also look at the side effects associated with 
this drug. 
 
Do I have to sign this authorization form? 
You do not have to sign this authorization form.  But if you do not, you will not be 
able to participate in this research study, including receiving any research-related 
treatment.  Signing the form is not a condition for receiving any medical care 
outside the study. 
 
If I sign, can I revoke it or withdraw from the research later? 
If you decide to participate, you are free to withdraw your authorization regarding 
the use and disclosure of your health information (and to discontinue any other 
participation in the study) at any time.  After any revocation, your health 
information will no longer be used or disclosed in the study, except to the extent 
that the law allows us to continue using your information (e.g., necessary to 
maintain integrity of research).  If you wish to revoke your authorization for the 
research use or disclosure of your health information in this study, you must write 
to: Dr. Melinda Telli, 
.  
 
 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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What Personal Information Will Be Obtained, Used or Disclosed? 
Your health information related to this study, may be used or disclosed in 
connection with this research study, including, but not limited to, 
 The history and diagnosis of your disease; 
 Specific information about the treatments you received, including previous 
and future treatment(s); 
 Information about other medical conditions that may affect your treatment; 
 Medical data including laboratory test results, health status (blood pressure, 
activity status, smoking status, etc.) tumor measurements, imaging scans 
(CT or Cat scan, MRI), x-rays, and pathology results; 
 Information on side effects (adverse events) you may experience, and how 
these were treated; 
 Long-term information about your general health status and the status of 
your disease; 
 Information that will identify you for the study, such as your date of birth, 
sex, age, and other medical history 
You may request a blank copy of the forms that will be used to collect your study 
data, from the study doctor or his/her research staff to learn what information will 
be shared. 
 
Who May Use or Disclose the Information? 
The following parties are authorized to use and/or disclose your health information 
in connection with this research study: 
 The Protocol Director, Dr. Melinda Telli 
 The Stanford University Administrative Panel on Human Subjects in 
Medical Research and any other unit of Stanford University as necessary 
 Research Staff 
 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your health information 
to the following persons and organizations for their use in connection with this 
research study:  
 The Office for Human Research Protections in the U.S. Department of 
Health and Human Services 
  The Food and Drug Administration 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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 The drug supplier, Pfizer, Inc. 
 Government agencies as authorized or required by law; 
 Other auditors sent for review of research at the site by any of the persons 
listed above. 
 
Your information may be re-disclosed by the recipients described above, if they are 
not required by law to protect the privacy of the information. 
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health information will 
end on December 31, 2025 or when the research project ends, whichever is earlier.  
 
Will access to my medical record be limited during the study? 
To maintain the integrity of this research study, you may not have access to any 
health information developed as part of this study until it is completed.  At that 
point, you would have access to such health information if it was used to make a 
medical or billing decision about you (e.g., if included in your official medical 
record).  
 
 
 
________________________________           
______________ 
Signature of Adult Participant                                    Date 
 
 
________________________________ 
Print name of Adult Participant  
 
 
________________________________ 
 
 
 
____________ 
Signature of Legally Authorized Representative (LAR) 
 
Date 
(e.g., parent, guardian or conservator) 
 
________________________________ 
______________________________ 
Print Name of LAR 
 
 
 
Authority to Act for Participant 
 
 
 
 
 
 
 
(e.g., parent, guardian or conservator)  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Participant ID: 
FINANCIAL CONSIDERATIONS 
 
Payment 
You may be eligible for travel and meal reimbursement if you live more than 50 miles from 
study site.  Payments may only be made to U.S. citizens, legal resident aliens, and those who 
have a work eligible visa.  
 
 
Costs 
If you participate in this study, there may be additional costs to you.  These include the personal 
time it will take to come to all of the study visits.   
 
The study will pay for those services, supplies, procedures, and care associated with this study 
that are not a part of your routine medical care.  If you would like to review the list of such 
covered services, supplies, procedures and care, please tell us now or at any time during the 
study.   
 
Participation in this study is not a substitute for health insurance.  You and/or your health 
insurance must pay for those services, supplies, procedures, and care that you require during this 
study for routine medical care.  You will be responsible for any co-payments and/or 
deductibles as required by your insurance.   
 
The drug company, Pfizer, Inc., which supplies the study drug, will provide the study drug free 
of charge to all study participants. All other drugs will not be supplied and will be billed to your 
insurance company. Your doctor will answer any questions you may have. 
 
Sponsor 
This is an investigator-initiated clinical trial led by Dr. Melinda Telli. The study will be 
conducted at the Stanford Women's Cancer Center. The study is financially supported by Pfizer, 
Inc., which is providing the study drug, talazoparib. The National Institutes of Health are 
providing some financial support for the facility and staff where part or all of the study is taking 
place. 
 
Consultative or Financial Relationships 
Dr Melinda Telli is a paid advisor to Pfizer, the company sponsoring this study.  
 
COMPENSATION for Research-Related Injury 
 
All forms of medical diagnosis and treatment – whether routine or experimental – involve some 
risk of injury.  In spite of all precautions, you might develop medical complications from 
participating in this study.  If such complications arise, the Protocol Director and the research 
study staff will assist you in obtaining appropriate medical treatment.  In the event that you have 
an injury or illness that is directly caused by your participation in this study, reimbursement for 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Participant ID: 
all related costs of care first will be sought from your insurer, managed care plan, or other 
benefits program.  You will be responsible for any associated co-payments or deductibles as 
required by your insurance. 
 
If costs of care related to such an injury are not covered by your insurer, managed care plan or 
other benefits program, you may be responsible for these costs.  If you are unable to pay for such 
costs, the Protocol Director will assist you in applying for supplemental benefits and explain how 
to apply for patient financial assistance from the hospital. 
 
You do not waive any liability rights for personal injury by signing this form. 
 
CONTACT INFORMATION  
 
Questions, Concerns, or Complaints:  If you have any questions, concerns or complaints about 
this research study, its procedures, risks and benefits, or alternative courses of treatment, you 
should ask the Protocol Director, Dr. Melinda Telli. You may contact her now or later at  
.   
 
Injury Notification: You should also contact her at any time if you feel you have been hurt by 
being a part of this study. 
 
Independent Contact:  If you are not satisfied with how this study is being conducted, or if you 
have any concerns, complaints, or general questions about the research or your rights as a 
participant, please contact the Stanford Institutional Review Board (IRB) to speak to someone 
independent of the research team at (650)-723-5244 or toll free at 1-866-680-2906.  You can also 
write to the Stanford IRB, Stanford University, 1705 El Camino Real, Palo Alto, CA 94306. 
WHERE CAN I GET MORE INFORMATION? 
You will get a copy of this form. You may talk to your study doctor at any time regarding your 
participation in the study or your treatment. More information on cancer clinical trials may be 
available from your study doctor, and can be found through resources like the National Cancer 
Institute (1-800-4-CANCER) or http://www.cancer.gov/clinicaltrials. 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
 
As a research participant you have the following rights.  These rights include but are not limited 
to the participant's right to: 
 
be informed of the nature and purpose of the experiment;  
 
be given an explanation of the procedures to be followed in the medical experiment, and 
any drug or device to be utilized;  
 
be given a description of any attendant discomforts and risks reasonably to be expected;  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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 
be given an explanation of any benefits to the subject reasonably to be expected, if 
applicable;  
 
be given a disclosure of any appropriate alternatives, drugs or devices that might be 
advantageous to the subject, their relative risks and benefits; 
 
be informed of the avenues of medical treatment, if any available to the subject after the 
experiment if complications should arise;  
 
be given an opportunity to ask questions concerning the experiment or the procedures 
involved;  
 
be instructed that consent to participate in the medical experiment may be withdrawn at 
any time and the subject may discontinue participation without prejudice;  
 
be given a copy of the signed and dated consent form; and  
 
be given the opportunity to decide to consent or not to consent to a medical experiment 
without the intervention of any element of force, fraud, deceit, duress, coercion or undue 
influence on the subject's decision. 
 
May we contact you about future studies that may be of interest to you?   ____ Yes  ____ No 
 
Signing your name means you agree to be in this study and that you were given a copy of this 
signed and dated consent form.  
 
 
_____________________________________ 
               ____________ 
Signature of Adult Participant 
 
 
 
   Date 
 
 
_____________________________________            
Print Name of Adult Participant                                         
 
 
_____________________________________ 
                
____________         
Signature of Legally Authorized Representative (LAR) 
 
 Date  
(e.g., parent, guardian or conservator)    
 
 
_____________________________________             
 
Print Name of LAR                                         
                             
  
 
_____________________________________ 
LAR’s Authority to Act for Participant  
 
 
(e.g., parent, guardian or conservator) 
 
 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: 
Melinda Telli, M.D. 
Protocol Title:   
A Phase II clinical trial of the PARP inhibitor talazoparib in BRCA1 and BRCA2 wild-type 
patients with advanced triple-negative breast cancer and homologous recombination deficiency 
or advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous 
recombination pathway genes 
 
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Participant ID: 
 
 
 
 
 
____________________________________             
 _____________ 
Signature of Person Obtaining Consent 
 
 
 Date 
 
 
_____________________________________             
 
Print Name of Person Obtaining Consent 
 
 
 
The following witness line is to be signed only if the consent is provided as a summary form and 
accompanied by a short form foreign language consent. 
 
 
 
_____________________________________                      
____________ 
Signature of Witness                                                               Date 
 
__________________________________              
Print Name of Witness                                         
 
(e.g., staff, translator/interpreter, family member) 
 
 Translated short form must be signed and dated by both the participant (or their LAR) AND 
the witness. 
 The English consent form (referred to as the "Summary Form" in the regulations): 
o Must be signed by the witness AND the Person Obtaining Consent (POC). 
o The non-English speaking participant/LAR does not sign the English consent. 
o The non-English speaking participant/LAR should not sign the HIPAA participant line 
o If the participant or the LAR is non-English speaking, the Person Obtaining Consent (POC) 
must ensure that 1) the LAR's Description of Authority is completed and 2) that any 
questions or options presented by the consent form are documented and initialed by the 
POC on the Summary Form, per the participant's wishes, as they are understood during the 
consent process.