Clinical trial NCT04635631
Conditions: Neoplasms
Sponsor: Pfizer
Start date: 2020-11-30; Completion date: 2021-12-14
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A phase1 study to evaluate the PK (single dose and multiple doses) and safety of talazoparib 1 mg Once Daily in Chinese adult participants with advanced solid tumors. A maximum of approximately 15 participants will be enrolled such that approximately 12 evaluable participants complete the study.

Detailed description:

Arms: arm 1: 1 mg QD
Interventions: intervention 1: talazoparib
Intervention descriptions: intervention 1: Talazoparib will be administered orally on a continuous basis. Each cycle will consist of 28 days.

Protocol documents:
Prot_000.pdf: 
Talazoparib 
Protocol C3441049
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AN OPEN-LABEL, SINGLE-ARM, PHASE 1 STUDY OF PHARMACOKINETICS, 
SAFETY AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB MONOTHERAPY IN
CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS 
Study Intervention Number:
PF-06944076
Study Intervention Name:
Talazoparib
US IND Number:
N/A
EudraCT Number:
N/A
Protocol Number:
C3441049
Phase:
1
Short Title: A PHASE 1 STUDY OF TALAZOPARIB MONOTHERAPY IN 
CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS  
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.


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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
27 January 2020
N/A
Amendment 01
26 May 2020

Updated the requirement of keeping 
fasted after dosing on Cycle 1 Day -9, 
Cycle 1 Day 22: reduced the duration
time of fasting to 2 hours after dosing.

Added FSH sample volume in table 3 
to keep consistent with protocol text.

“Leukocytes esterase” is updated to 
“leukocytes esterase/leukocytes” to 
add leukocytes as an alternative 
analyte to accommodate standard 
laboratory testing capabilities.

Update the protocol based on the new 
protocol template (15 May 2020).
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ECs.


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................7
1. PROTOCOL SUMMARY.....................................................................................................8
1.1. Synopsis ....................................................................................................................8
1.2. Schema ....................................................................................................................10
1.3. Schedule of Activities .............................................................................................11
2. INTRODUCTION ...............................................................................................................16
2.1. Study Rationale .......................................................................................................16
2.2. Background .............................................................................................................16
2.2.1. Clinical Overview.......................................................................................16
2.3. Benefit/Risk Assessment.........................................................................................20
2.3.1. Risk Assessment.........................................................................................20
2.3.2. Benefit Assessment.....................................................................................20
2.3.3. Overall Benefit/Risk Conclusion................................................................21
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................22
4. STUDY DESIGN.................................................................................................................22
4.1. Overall Design.........................................................................................................22
4.2. Scientific Rationale for Study Design.....................................................................23
4.3. Justification for Dose ..............................................................................................25
4.4. End of Study Definition ..........................................................................................26
5. STUDY POPULATION......................................................................................................26
5.1. Inclusion Criteria.....................................................................................................26
5.2. Exclusion Criteria....................................................................................................27
5.3. Lifestyle Considerations..........................................................................................29
5.3.1. Contraception..............................................................................................29
5.4. Screen Failures ........................................................................................................29
6. STUDY INTERVENTION..................................................................................................29
6.1. Study Intervention(s) Administered........................................................................30
6.1.1. Administration............................................................................................30
6.2. Preparation/Handling/Storage/Accountability ........................................................31
6.2.1. Preparation and Dispensing........................................................................32


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6.3. Measures to Minimize Bias: Randomization and Blinding.....................................32
6.3.1. Allocation to Study Intervention ................................................................32
6.4. Study Intervention Compliance...............................................................................32
6.5. Concomitant Therapy..............................................................................................33
6.5.1. P-gp Inhibitors and Inducers.......................................................................33
6.5.2. Supportive Care ..........................................................................................35
6.5.3. Other Anti-tumor/Anti-cancer or Experimental Drugs...............................35
6.5.4. Surgery........................................................................................................35
6.6. Dose Modification...................................................................................................35
6.7. Intervention After the End of the Study..................................................................38
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................38
7.1. Discontinuation of Study Intervention ....................................................................38
7.1.1. Temporary Discontinuation........................................................................39
7.2. Participant Discontinuation/Withdrawal From the Study.......................................40
7.2.1. Withdrawal of Consent...............................................................................40
7.3. Lost to Follow-up....................................................................................................41
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................41
8.1. Efficacy Assessments..............................................................................................42
8.1.1. Imaging Assessments..................................................................................42
8.2. Safety Assessments .................................................................................................43
8.2.1. Physical Examinations................................................................................43
8.2.2. Vital Signs ..................................................................................................43
8.2.3. Electrocardiograms.....................................................................................44
8.2.4. Clinical Safety Laboratory Assessments ....................................................44
8.2.5. Pregnancy Testing ......................................................................................45
8.3. Adverse Events and Serious Adverse Events..........................................................45
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......46
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................46
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................47
8.3.2. Method of Detecting AEs and SAEs ..........................................................47
8.3.3. Follow-up of AEs and SAEs.......................................................................47


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8.3.4. Regulatory Reporting Requirements for SAEs...........................................48
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................48
8.3.5.1. Exposure During Pregnancy......................................................48
8.3.5.2. Exposure During Breastfeeding ................................................50
8.3.5.3. Occupational Exposure .............................................................50
8.3.6. Cardiovascular and Death Events...............................................................50
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................50
8.3.8. Adverse Events of Special Interest.............................................................51
8.3.9. Medication Errors .......................................................................................52
8.4. Treatment of Overdose............................................................................................52
8.5. Pharmacokinetics ....................................................................................................53
8.6. Pharmacodynamics..................................................................................................54
8.7. Genetics...................................................................................................................54
8.7.1. Specified Genetics ......................................................................................54
8.8. Biomarkers ..............................................................................................................54
8.8.1. Specified Gene Expression (RNA) Research .............................................54
8.8.2. Specified Protein Research.........................................................................54
8.8.3. Specified Metabolomic Research ...............................................................54
8.9. Immunogenicity Assessments.................................................................................54
8.10. Health Economics .................................................................................................54
9. STATISTICAL CONSIDERATIONS ................................................................................54
9.1. Estimands and Statistical Hypotheses.....................................................................55
9.2. Sample Size Determination.....................................................................................55
9.3. Analysis Sets ...........................................................................................................55
9.4. Statistical Analyses .................................................................................................55
9.4.1. Primary Endpoint(s)....................................................................................56
9.4.2. Secondary Endpoint(s)................................................................................57
9.4.2.1. Safety.........................................................................................57
9.4.2.2. Efficacy .....................................................................................59
9.5. Interim Analyses .....................................................................................................59


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9.6. Data Monitoring Committee or Other Independent Oversight Committee.............59
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................60
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............60
10.1.1. Regulatory and Ethical Considerations ....................................................60
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................60
10.1.2. Financial Disclosure .................................................................................61
10.1.3. Informed Consent Process ........................................................................61
10.1.4. Data Protection .........................................................................................62
10.1.5. Dissemination of Clinical Study Data ......................................................62
10.1.6. Data Quality Assurance ............................................................................63
10.1.7. Source Documents....................................................................................65
10.1.8. Study and Site Start and Closure ..............................................................65
10.1.9. Publication Policy.....................................................................................66
10.1.10. Sponsor’s Qualified Medical Personnel .................................................66
10.2. Appendix 2: Clinical Laboratory Tests .................................................................67
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................68
10.3.1. Definition of AE .......................................................................................68
10.3.2. Definition of SAE.....................................................................................69
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................71
10.3.4. Reporting of SAEs....................................................................................74
10.4. Appendix 4: Contraceptive Guidance ...................................................................76
10.4.1. Male Participant Reproductive Inclusion Criteria....................................76
10.4.2. Female Participant Reproductive Inclusion Criteria.................................76
10.4.3. Woman of Childbearing Potential ............................................................77
10.4.4. Contraception Methods.............................................................................78
10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments ........80
10.6. Appendix 6: ECG Findings of Potential Clinical Concern ...................................82
10.7. Appendix 7: RECIST (Response Evaluation Criteria In Solid Tumors) 
version 1.1 Guidelines...............................................................................................84
10.8. Appendix 8: ECOG Performance Status*.............................................................90


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10.9. Appendix 9: Bone Marrow Reserve in Adults......................................................91
10.10. Appendix 10: Cockcroft-Gault Formula .............................................................93
10.11. Appendix 11: Abbreviations ...............................................................................94
11. REFERENCES ..................................................................................................................98
LIST OF TABLES
Table 1.
Dose Modification of Talazoparib Due to Adverse Events......................36
Table 2.
Dose Modifications for Toxicities............................................................38
Table 3.
Blood Sampling Volume for Each Test....................................................42
Table 4.
Protocol-Required Safety Laboratory Assessments .................................67
Table 5.
Objective Response Status at Each Evaluation ........................................88
Table 6.
Objective Response Status at each Evaluation for Patients with 
Non-Target Disease Only .........................................................................88


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A PHASE 1 STUDY OF TALAZOPARIB MONOTHERAPY IN 
CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS  
Rationale
The purpose of the study is to obtain the pharmacokinetic (PK) profile of talazoparib after 
both single-dose and multiple dose administration as monotherapy in Chinese participants 
with advanced solid tumors to support potential registration of indications in China.  Safety 
and activity of talazoparib will also be assessed as the secondary objectives in this study.


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Objectives, Estimands, and Endpoints
Objectives
Estimands
Endpoints
Primary: 
Primary:
Primary: 

To characterize the single and 
steady-state pharmacokinetics 
(PK) of single-agent talazoparib.
Not applicable.

Single Dose (SD) - Cmax, Tmax, 
AUClast, AUC, CL/F, and Vz/F 
and t½, and AUCinf as data permit.  

Multiple Dose (MD) - Cmax, Tmax, 
C min, AUC, CL/F, Rac 
(AUC/AUCsd,) and Rss 
(AUC/AUCsd,inf) as data permit.
Secondary: 
Secondary:
Secondary: 

To evaluate the overall safety 
profile.

To assess preliminary evidence of 
anti-tumor activity of single-agent 
talazoparib.
Not applicable.
Safety:

Adverse Events as characterized 
by type, frequency, severity (as 
graded by NCI CTCAE 
version 4.03), timing, seriousness, 
and relationship to talazoparib.

Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI 
CTCAE version 4.03), and 
timing.

Vital signs and ECG.

Concomitant medication use. 
Efficacy:

Unconfirmed objective response 
rate (ORR).

Duration of response (DOR).
Overall Design
This study is a Phase 1 study to evaluate the PK and safety of single agent talazoparib 1 mg
Once Daily (QD) in Chinese adult participants with advanced solid tumors who are resistant 
to standard therapy or for whom no standard therapy is available.
Study treatment will be given once daily in 28-day cycles. To understand the single-dose 
safety and single-dose PK assessments of talazoparib, a lead-in period preceding the 
continuous daily doses will be included. In the 9-day lead-in period, a single lead-in dose 
will be given on Day -9 and PK samples will be collected at pre-dose and 0.50, 1, 2, 4, 8, 24, 


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48, 96, 168 and 216 hours post dose. No talazoparib will be administered during the interval 
between the lead-in single dose and Day 1 of the first cycle. Additionally, to characterize the 
steady state PK profile, serial PK samples after multiple doses will be collected on Day 22 of 
the first cycle at pre-dose, 0.50, 1, 2, 4, 8, 24 hours post dose.  
An End of Treatment visit will be performed for participants if the specified assessments are 
not completed in the last week (last 6 weeks for tumor assessments).
Number of Participants
A maximum of approximately 15 participants will be enrolled to study intervention such that 
approximately 12 evaluable participants complete the study. 
Note: "Enrolled" means a participant's, or his or her legally authorized representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process. Potential participants who are screened for the purpose of determining eligibility for 
the study, but do not participate in the study, are not considered enrolled, unless otherwise 
specified by the protocol.
Intervention Groups and Duration
A single dose of talazoparib 1 mg is administered on Day -9, then continuous dosing will 
begin from C1D1.  Participants will be given talazoparib 1 mg orally QD until disease 
progression, death, unacceptable toxicity or withdrawal of consent. Dose modifications and 
reductions for talazoparib are to occur according to the Section 6.6.
Data Monitoring Committee or Other Independent Oversight Committee
No.
Statistical Methods
A maximum of approximately15 patients are needed. Pharmacokinetic parameters and 
plasma concentration data will be summarized as the primary analysis for this study. In 
addition, safety data including adverse events (AE), laboratory abnormalities and 
electrocardiogram measurements (ECG), as well as efficacy information reflected by 
objective response (OR) and duration of response (DOR) will also be summarized and 
estimated.  
1.2. Schema
Not applicable.






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f.
Early Termination/Discontinuation: Applies only to participants who are enrolled and then are prematurely withdrawn from the study.  Obtain these 
assessments if not completed in the last week (last 6 weeks for tumor assessments).
g.
Informed Consent: Must be obtained prior to undergoing any study-specific procedures.  Procedures performed as standard of care prior to signed and dated 
informed consent document (ICD), and within the 28 day screening window may be used for study eligibility.  
h.
Baseline Signs & Symptoms: Patients will be asked about any signs and symptoms experienced within the 14 days prior to PK lead-in dose.  Clinically 
significant baseline signs and symptoms will be recorded as part of the Medical History.
i.
Vital Signs: Systolic and diastolic blood pressure (BP), pulse rate, respiratory rate and temperature at scheduled time points; BP and pulse rate to be recorded 
in sitting position.
j.
Performance Status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 8.
k.
Hematology: No need to repeat on C1D-9 if baseline assessment performed within 7 days prior to that date.  Additional hematology may be performed as 
clinically indicated.  Frequency should be increased as clinically indicated to monitor neutropenia, thrombocytopenia, and anemia.  See Assessments section 
for Laboratory Tests list.
l.
Blood Chemistry: No need to repeat on C1D-9 if baseline assessment performed within 7 days prior to that date.  Additional chemistries may be performed 
as clinically indicated.  See Assessments section for Laboratory Tests list.
m. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  No need to repeat on C1D-9 if baseline assessment performed within 7 days 
prior to that date.  Additional urinalysis may be performed as clinically indicated.  See Assessments section for Laboratory Tests list.
n.
Pregnancy Test: For Woman of Childbearing Potential (WOCBP) only, see protocol Section 10.4 for details.  
o.
FSH: For confirmation of postmenopausal status only.
p.
Virus (HBV/HCV/HIV) test: Perform within 28 days prior to the first study treatment, including HBV (HBsAg and HBcAb), HCV antibody, and HIV 
antibody.
q.
The contraception check is an opportunity to confirm that contraception, if assigned, is used consistently and correctly.  Also, it is the opportunity to assess 
changing potential to father/bear children and allows for altering contraception if new disease contraindicates a selected method of contraception or if 
nonchildbearing status is achieved.
r.
12-Lead ECG: Predose on Day -9 will be used as baseline, three consecutive 12-lead ECG will be performed approximately 2 minutes apart to determine PR 
interval and the mean QTc interval.  At screening as well as each scheduled ECG evaluation on treatment, a single 12-lead ECG will be performed. If there 
is a potential significant change, the investigator can provide additional measurements as appropriate. All ECGs scheduled on treatment should be 
performed pre-dose. When coinciding with blood sample draws for PK or other safety lab tests, ECG assessment should be performed prior to blood sample 
collection.  Additional ECGs may be performed as clinically indicated.  See protocol Section 8.2.3 for details and additional requirement for special case.
s.
Registration: Assign patient number.  
t.
Study Treatment: Described in the Study Treatments section.  A single dose of talazoparib is administered on Day -9, then continuous dosing will begin from 
C1D1.


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u.
Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Imaging may include chest, abdomen, and pelvis CT or MRI 
scans. A brain MRI or CT is to be performed at Screening/baseline to evaluate participants for presence/absence of brain metastases. Bone scans will be 
performed at baseline if disease is suspected and on study as appropriate to follow disease.  CT or MRI scans to be done on D29 (±7 days window) and every 
8 weeks (±7 days window) thereafter for the initial 12 cycles regardless of any dose interruptions or dose delays.  After completion of Cycle 12 (at the 
beginning of Week 45), tumor assessment will be done per local standard practice.  Tumor assessments should be repeated at the end of study visit if more 
than 6 weeks have passed since the last evaluation.  Given the exploratory nature of the efficacy endpoint, confirmation of response (complete response 
[CR]/partial response [PR]) is not required.  As clinically indicated, CT/MRI will be repeated by investigator’s discretion. Assessment of response will be 
made using RECIST version 1.1.
v.
Adverse Event (AE) Assessments: AEs should be documented and recorded at each visit using the NCI CTCAE version 4.03.  The time period for actively 
eliciting and collecting AEs and SAEs (“active collection period”) for each patient begins from the time the patient provides informed consent through and 
including a minimum of 28 calendar days after the last investigational product administration.  If the participant begins a new anti-cancer therapy, the period 
for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active collection period 
must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment.
w.
Concomitant Treatments: all concomitant medications and NonDrug Supportive Interventions should be recorded on the CRF.  All concomitant treatments
and nondrug interventions received by participants from 28 days before first dose are considered as Prior/Concomitant Therapy.
x.
PK Sampling: Refer to Pharmacokinetics Sampling Schema.




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2. INTRODUCTION
Talazoparib tosylate (PF-06944076, formerly BMN 673 or MDV3800), which is cytotoxic to 
human cancer cell lines harboring gene mutations that compromise DNA repair, an effect 
referred to as synthetic lethality, by inhibiting Poly(Adenosine Diphosphate-Ribose) 
Polymerase (PARP) catalytic activity and trapping PARP protein on DNA, thereby 
preventing DNA repair, replication, and transcription.1,2,3
Talazoparib has been approved in United States, European Union and other countries for the 
treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated 
(gBRCAm) HER2-negative locally advanced or metastatic breast cancer.  Other potential 
indications, such as metastatic castration resistant prostate cancer (mCRPC), are currently 
being investigated.
2.1. Study Rationale 
The purpose of the study is to obtain the pharmacokinetic (PK) profile of talazoparib after 
both single-dose and multiple dose administration as monotherapy in Chinese participants
with advanced solid tumors to support potential registration of indications in China.  Safety 
and activity of talazoparib will also be assessed as the secondary objectives in this study.
2.2. Background 
Cancer incidence and mortality are rapidly growing worldwide. GLOBOCAN 2018 
estimated that there will be 18.1 million new cases (17.0 million excluding nonmelanoma
skin cancer (NMSC) ) and 9.6 million cancer deaths (9.5 million excluding NMSC) 
worldwide in 2018. With the world’s largest population, about a fifth of all global cancer 
cases occur in China,4 and cancer has become the leading cause of death in the country in 
recent years.5  Despite a marked increase in 5-year survival from all cancers combined and 
several major cancers over the last decade in China, survival for many major cancers in the 
most recent period studied remained lower than in many developed countries.6 Cancer 
represents a disease are with high unmet medical need in China and the discovery and 
development of new anti-cancer therapies effective is urgently needed.
2.2.1. Clinical Overview
Clinical Pharmacology Overview
Talazoparib plasma exposure is dose proportional in the dose range of 0.025 mg to 2 mg QD 
suggesting linear PK. Talazoparib absolute bioavailability is at least 54.6% based on 
excretion of unchanged talazoparib in urine. After administration of a single 1 mg dose of 
talazoparib to cancer patients, the median Time to Reach Maximum Plasma Concentration 
(Tmax) ranged from 0.5 to 2.0 hours across studies.  Administration of talazoparib with food 
(a high-fat, high-calorie meal) had no impact on the total exposure (AUCinf) while the 
maximum plasma concentration (Cmax) was reduced by 46%. The reduction in the rate of 
absorption with food is not expected to be clinically relevant as efficacy is generally driven 
by total exposure. Therefore, talazoparib can be taken with or without food.


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Talazoparib undergoes minimal hepatic metabolism. Based on population PK analysis, there 
is no effect of mild hepatic impairment (total bilirubin ≤ULN and AST > ULN, or total 
bilirubin >1.0 to 1.5 ULN and any AST) on talazoparib exposure. No dose adjustment is 
necessary for patients with mild hepatic impairment.
Talazoparib is eliminated slowly with a mean terminal plasma half-life of 89.8 hours.  
Talazoparib accumulates after 1 mg QD dosing with a median accumulation ratio ranging 
from 2.33 to 5.15, consistent with its terminal half-life. Population PK analysis showed that 
talazoparib CL/F was 6.45 L/h.  
Excretion of unchanged talazoparib in urine is the major route of elimination accounting for 
54.6% of the administered dose. Study MDV3800-01 was conducted to investigate the effect 
of mild, moderate, and severe renal impairment on the PK of talazoparib following daily oral 
dosing of 0.5 mg talazoparib for 22 days in patients with advanced solid tumors.  No trend 
was observed in the geometric mean fu in plasma with worsening renal function.  The 
adjusted geometric means for total talazoparib exposure (AUC0-24) increased by 
12.2%, 43.0%, and 163.3% after multiple doses with mild (eGFR ≥60 and 
≤89 mL/min/1.73 m2), moderate (eGFR ≥30 and ≤59 mL/min/1.73 m2), and severe renal 
impairment (eGFR ≥15 and ≤29 mL/min/1.73 m2), respectively, relative to patients with 
normal renal function (eGFR ≥90 mL/min/1.73 m2) as assessed by Analysis of Variance
(ANOVA) analyses comparing the categorical renal function groups defined by 
BSA-normalized Estimated Glomerular Filtration Rate (eGFR).  Peak talazoparib exposure 
based on Cmax increased by 11.1%, 31.6%, and 89.3% after multiple doses with mild, 
moderate, and severe renal impairment, respectively, relative to patients with normal renal 
function as assessed by ANOVA analyses comparing the categorical renal function groups 
defined by BSA-normalized eGFR.  Population PK analysis showed that talazoparib CL/F is 
reduced by 14.4% and 37.1% in patients with mild renal impairment (CLcr 60 to 89 mL/min) 
and moderate renal impairment (30 mL/min ≥CLcr <60 mL/min), corresponding to 17% and 
59% increases in AUC respectively, compared to that of patients with normal renal function 
(CLcr ≥90 mL/min), which was consistent with the results in the renal impairment study. No 
dose adjustment is recommended for patients with mild renal impairment. For patients with 
moderate renal impairment, the talazoparib dose in the monotherapy setting should be 
reduced from 1 mg QD to 0.75 mg QD. For patients with severe renal impairment 
(15 mL/min ≤CLcr <30 mL/min), the talazoparib dose should be reduced to 0.5 mg QD.  
Based on in vitro studies, talazoparib is a substrate for the efflux transporters P-gp and Breast 
Cancer Resistance Protein (BCRP).  Data from the recently completed Drug-Drug Interaction 
(DDI) Study C3441004 (MDV3800-04) in patients with advanced solid tumors indicated that 
coadministration of multiple daily doses of strong P-gp inhibitor itraconazole 100 mg twice 
daily with a single 0.5 mg talazoparib dose increased talazoparib AUCinf and Cmax by 
approximately 56% and 40%, respectively, relative to a single 0.5 mg talazoparib dose 
administered alone. The increase in the talazoparib mean terminal half-life when talazoparib 
was administered with itraconazole compared to when talazoparib was administered alone 
(118.5 hours vs 101.3 hours) was minor, suggesting that the increase in talazoparib exposure 
when coadministered with itraconazole is predominantly due to an increase in talazoparib 


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bioavailability with minor effect on elimination. Consistent with findings from Study 
C3441004, population PK analysis indicated that concomitant administration of strong P-gp 
inhibitors with talazoparib increased talazoparib exposure by 44.7% relative to talazoparib 
administered alone. If concomitant use of strong P-gp inhibitors during treatment with 
talazoparib is unavoidable, the talazoparib dose should be reduced from 1 mg QD to 
0.75 mg QD. Data from Study C3441004 indicated that coadministration of multiple daily 
doses of a strong P-gp inducer, rifampin 600 mg, with a single 1 mg talazoparib dose, 
increased talazoparib Cmax by approximately 37% whereas AUCinf was not affected relative 
to a single dose of talazoparib 1 mg administered alone.  
Exposure-efficacy analysis showed that higher talazoparib exposure in the Phase 3 
EMBRACA study (Study 673-301; C3441009) is associated with longer PFS in patients with 
germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.  
Exposure-safety analyses based on pooled data from the Phase 2 ABRAZO study (Study 
673-201; C3441008) and EMBRACA showed that higher talazoparib exposure is also 
associated with a higher risk for Grade 3 or higher anemia and thrombocytopenia, and a trend
for association between higher talazoparib exposure and Grade 3 or higher neutropenia 
although this relationship was not statistically significant. These findings support using the 
Maximum Tolerated Dose (MTD) of 1 mg QD in the monotherapy setting in advanced breast 
cancer patients as the recommended dose for talazoparib treatment and the proposed dose 
modification guidelines as an effective approach for management of AEs.
Clinical Safety and Efficacy
As of 30 September 2019, approximately 1212 participants and 18 healthy volunteers have 
received talazoparib at doses up to 2 mg QD in company-sponsored clinical studies in 
hematologic malignancies and solid tumors.  The majority of available efficacy and safety 
data was obtained from studies in solid tumors.  A phase 1 study in participants with 
advanced or recurrent solid tumors defined the MTD of talazoparib as 1 mg QD.  Data from 
this study demonstrated objective responses and/or clinical benefit in participants with breast, 
ovarian/peritoneal, and pancreatic cancer; SCLC; and Ewing sarcoma.  
Aggregate safety data from 5 open-label, including 1 randomized, company-sponsored 
clinical studies (PRP-001, 673-201, EMBRACA, MDV3800-13, and MDV3800-14; 
N = 502 patients) evaluating talazoparib monotherapy in solid tumors at the proposed dose of 
1 mg QD as of 30 September 2019, provide the basis for the reported treatment-emergent 
adverse events (TEAEs). TEAEs of all causality reported in ≥20% of participants
administered single-agent talazoparib 1 mg QD are related to myelosuppression (anemia, 
neutropenia), GI toxicity (nausea, diarrhea, vomiting, constipation, and decreased appetite), 
fatigue, headache, and alopecia. TEAEs of National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) grade ≥3 severity in ≥5% of participants
were related to myelosuppression. Twenty (20) of 502 participants (4.0%) in the Talazoparib 
1 mg QD Population permanently discontinued study drug due to a TEAE. The events that 
led to study drug permanent discontinuation were anemia (3 participants), increased alanine 
aminotransferase (ALT, 2 participants), and accidental overdose, increased aspartate 


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aminotransferase (AST), bradycardia, metastatic breast cancer, cerebral hemorrhage, 
dyspnea, glioblastoma multiforme, headache, metastases to meninges, muscular weakness, 
neutropenia, obstructive airways disorder, thrombocytopenia, transient ischemic attack, and 
vomiting (1 participant each). Among the 502 participants in the Talazoparib 1 mg QD
Population, 63.9% had a TEAE that led to dose reduction and 61.2% had a TEAE that led to 
dosing interruption. The most common TEAEs that led to dose reduction or interruption 
were associated with myelosuppression.
Efficacy data from 3 Sponsor-initiated studies (PRP-001, Studies 673-201, and 673-301) 
evaluating talazoparib in participants with advanced or metastatic breast cancer are included
in this investigator brochure.  In the Phase 1 first-in-human study (Study PRP-001 
[C3441007]) in participants with advanced or recurrent solid tumors, a total of 
110 participants were treated at a range of talazoparib doses (0.025-1.1 mg QD). Data from
this study demonstrated objective responses and/or clinical benefit in participants with breast,
ovarian/peritoneal, and pancreatic cancer; small-cell lung cancer (SCLC); and Ewing 
sarcoma. 
In an open-label Phase 2 study (Study 673-201, [C3441008, ABRAZO]) of talazoparib in 
participants with germline BRCA-mutated locally advanced or metastatic breast cancer, 
83 participants were treated with talazoparib 1 mg QD across 2 cohorts. Cohort 1 enrolled 
49 participants (48 treated) who had a partial response (PR) or complete response (CR) to a 
prior platinum- containing regimen for metastatic disease with disease progression >8 weeks 
following the last dose of platinum.  Cohort 2 enrolled 35 participants who received 3 or 
more prior chemotherapy regimens and no prior platinum therapy for metastatic disease. 
Cohort 1 had an objective response rate (ORR) of 20.8% (95% CI: 10.5, 35.0) including 
2 CRs (4.2%). Cohort 2 had an ORR of 37.1% (95% CI: 21.5, 55.1). Median duration of 
response (DOR) was 4.9 months (interquartile range [IQR]: 2.8, 7.1) in Cohort 1 and 
4.2 months (IQR: 3.2, 5.6) in Cohort 2.
In the pivotal randomized Phase 3 study (Study 673-301, [C3441009, EMBRACA]) of
talazoparib versus physician’s choice treatment (PCT) in participants with germline 
BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative locally 
advanced or metastatic breast cancer, 431 participants overall were randomized in a 2:1 ratio 
to receive talazoparib 1 mg QD (n = 287) or 1 of 4 PCTs (n = 144) reflecting the standard of 
care in this disease setting (capecitabine, eribulin, gemcitabine, or vinorelbine).  In this study,
talazoparib demonstrated significantly prolonged progression-free survival (PFS) by blinded
independent central review (BICR) assessment when compared to PCT.  Median PFS by
BICR in the talazoparib arm was 8.6 months (95% CI: 7.2, 9.3) compared to 5.6 months
(95% CI: 4.2, 6.7) in the PCT arm.
Talazoparib is currently being evaluated in mCRPC. An ongoing Phase 2 study [C3441006, 
TALAPRO-1] is evaluating talazoparib in men with DNA repair defects and mCRPC who
previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal 
agent (enzalutamide and/or abiraterone acetate/prednisone). In addition, an ongoing Phase 3, 
randomized, double-blind, placebo-controlled study [C3441021, TALAPRO-2] is evaluating 


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talazoparib in combination with enzalutamide in mCRPC participants with and without DNA
damage repair deficiency mutations. The effectiveness of talazoparib is also under 
investigation for the neoadjuvant treatment of germline BRCA 1/2 mutation participants with 
early triple-negative breast cancer, and in combination with the anti-programmed death 
ligand 1(PD-L1) checkpoint inhibitor, avelumab, for the treatment of selected solid tumors.
2.3. Benefit/Risk Assessment
Talazoparib has been approved in multiple countries for the treatment of adult patients with 
deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic 
breast cancer. Preclinical studies shown that talazoparib is a highly selective and potent 
cytotoxic agent in human cancer cell lines and in animal models of tumors harboring 
mutations that compromise DNA repair pathways. Risk assessment, benefit assessment, as 
well as overall risk/benefit analysis are provided separately as below.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of talazoparib may be found in the investigator’s brochure, which is the single 
reference safety document (SRSD) for this study. 
2.3.1. Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale 
for Risk
Mitigation Strategy
Study Intervention(s) talazoparib
Potential risks associated with 
talazoparib include the following: 
Myelodysplastic Syndrome (MDS) 
and Acute Myeloid Leukemia 
(AML), and second primary 
malignancies. These risks 
represent adverse events of special 
interest for talazoparib (see 
Section 8.3.8).
The potential risks are based on 
the investigator’s brochure for
talazoparib.
Eligibility criteria have been 
selected to ensure that only 
appropriate participants are included 
in the study (see Section 5).
Conduct safety assessment 
(eg, hematology) according to the 
SoA. Second primary malignancies
may be identified with imaging 
provided for tumor assessment. 
Investigator can provide unplanned 
assessment as clinically indicated.
2.3.2. Benefit Assessment
The activity of talazoparib as monotherapy and in combination with other agents is being 
evaluated in multiple indications.  The benefit of talazoparib for individual participants with 
solid tumors may include:

Participants in this study will contribute to the process of developing a new therapy in 
an area of unmet need in China.

Potential benefit of receiving talazoparib during study duration that may have clinical 
utility.


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
Medical assessment (eg, imaging, physical exams, ECGs, Labs, etc.) associated with 
study procedures will be provided to explore the benefit/risk profile of the Chinese 
population in this study.
2.3.3. Overall Benefit/Risk Conclusion
According to the aggregate safety data from 5 clinical studies (PRP-001, 673-201, 673-301, 
MDV3800-13, and MDV3800-14; N = 502 participants), treatment-emergent adverse events 
(TEAEs) associated with talazoparib monotherapy in solid tumors at the proposed dose of 
1 mg QD are detectable through routine laboratory and clinical monitoring and may be 
managed with supportive care or dose reductions or interruptions as described in each study 
protocol.
In PRP-001 [C3441007]) study, a total of 110 participants with advanced or recurrent solid 
tumors were treated at a range of talazoparib doses (0.025-1.1 mg QD). Data from this study 
demonstrated objective responses and/or clinical benefit in participants with breast, 
ovarian/peritoneal, and pancreatic cancer; small-cell lung cancer (SCLC); and Ewing 
sarcoma. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of talazoparib may be found in the investigator’s brochure.
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with talazoparib are justified by the 
anticipated benefits that may be afforded to participants with solid tumors.


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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Estimands
Endpoints
Primary: 
Primary:
Primary: 

To characterize the single and 
steady-state pharmacokinetics 
(PK) of single-agent talazoparib.
Not applicable.

Single Dose (SD) - Cmax, Tmax, AUClast, 
AUC, CL/F, and Vz/F and t½, and 
AUCinf as data permit.  

Multiple Dose (MD) - Cmax, Tmax, C min, 
AUC, CL/F, Rac (AUC/AUCsd,) and 
Rss (AUCAUCsd,inf) as data permit.
Secondary: 
Secondary:
Secondary: 

To evaluate the overall safety 
profile.

To assess preliminary evidence of 
anti-tumor activity of single agent 
talazoparib.
Not applicable.
Safety:

Adverse Events as characterized by type, 
frequency, severity (as graded by NCI 
CTCAE version 4.03), timing, 
seriousness, and relationship to 
talazoparib.

Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI CTCAE 
version 4.03), and timing.

Vital signs and ECG.

Concomitant medication use.
Efficacy:

Unconfirmed ORR.

DOR.
4. STUDY DESIGN
4.1. Overall Design
This study is a Phase 1 study to evaluate the PK and safety of single agent talazoparib 
1 mg QD in Chinese adult participants with advanced solid tumors who are resistant to 
standard therapy or for whom no standard therapy is available. 
Approximately 15 participants will be enrolled to obtain about 12 evaluable participants to 
support mCRPC and other future potential indications registration in China. A single dose of 
talazoparib 1 mg is administered on Day -9, then continuous dosing will begin from C1D1.
Participants will be given talazoparib 1.0 mg orally once daily until disease progression, 
death, unacceptable toxicity or withdrawal of consent. Dose modifications and reductions for 
talazoparib are to occur according to the Section 6.6.


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Note: "Enrolled" means a participant's, or his or her legally authorized representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process.  Potential participants who are screened for the purpose of determining eligibility for 
the study, but do not participate in the study, are not considered enrolled, unless otherwise 
specified by the protocol.
Study treatment will be given once daily in 28-day cycles. To understand the single-dose 
safety and single-dose PK assessments of talazoparib, a lead-in period preceding the 
continuous daily doses will be included. In the 9-day lead-in period, a single lead-in dose 
will be given on Day -9 and PK samples will be collected at pre-dose and 0.50, 1, 2, 4, 8, 24, 
48, 96, 168 and 216 hours post dose. No talazoparib will be administered during the interval 
between the lead-in single dose and Day 1 of the first cycle. Additionally, to characterize the
steady state PK profile, serial PK samples after multiple doses will be collected on Day 22 of 
the first cycle at pre-dose, 0.50, 1, 2, 4, 8, 24 hours post dose.  Pre-dose samples will be 
collected on C1D21, C1D23.
Tumor assessments are to be done on D29 (±7 days window) and every 8 weeks (±7 days 
window) thereafter for the initial 12 cycles regardless of any dose interruptions or dose 
delays.  After completion of Cycle 12 (at the beginning of Week 45), tumor assessment will 
be done per local standard practice.  Tumor assessments should be repeated at the end of 
study visit if more than 6 weeks have passed since the last evaluation.  
An End of Treatment visit will be performed for participants if the specified assessments are 
not completed in the last week (last 6 weeks for tumor assessments). 
4.2. Scientific Rationale for Study Design
Talazoparib has a well-established safety, efficacy, and PK profile based on global clinical 
trial experience. As there was not clinical PK data with talazoparib in Chinese participants, 
the current Phase 1 study was initially designed to evaluate the PK profile of talazoparib as a 
single agent in Chinese participants with advanced solid tumors.
Clinical Pharmacology Consideration
The pharmacokinetics (PK) of talazoparib as a single agent was evaluated in participants
with hematologic malignancies and solid tumors at doses of 0.025 to 2 mg QD administered 
orally, as a single dose and/or as multiple doses.  The PK was similar in participants of each 
cancer type and no differences were apparent between males and females. Thus, unselected 
solid tumor patients are considered to be the target population of this study to support future 
potential registration of talazoparib in China.
As mentioned in Section 2.2.1, talazoparib was eliminated slowly with a mean t½ of 
89.8 hours based on absorption, distribution, metabolism, and excretion (ADME) study 
MDV3800-03. It should be noted that the t½ value obtained from Study PRP-001 
(62.4 hours) and Japan C3441030 study (50.73 hours) might be underestimated as the PK 
sampling time was only up to 168 hours versus 504 hours in Study MDV3800-03, thus to 


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fully characterize the single dose PK profile of talazoparib administration in Chinese solid 
tumor patients, 9 days (216 hours) sampling duration is proposed to characterize related PK 
parameter as precise as possible while considering solid tumor patients overall benefit/risk 
assessment.
Specifically, patients are required to be fasted for at least 8 hours prior to dosing and 
continue to be fasted 2 hours after dosing to control the variability due to food effect on Cmax.
Similarly, co-med with P-gp inhibitor and inducer are prohibited for Cycle 1 when intensive 
PK is scheduled after both single dose and multiple dose talazoparib administration to 
minimize the DDI effect to talazoparib exposure and potential alteration to efficacy. 
Notably, only potent P-gp inhibitor are prohibited to accommodate more co-med options for 
solid tumor patient as only sparse PK is schedule for post Cycle 1 PK assessment.
Study population consideration
Several Phase 1 Sponsor-initiated studies of talazoparib in solid tumor have been conducted 
globally. The first-in-human study (Study PRP-001 [C3441007]) in participants with 
advanced or recurrent solid tumors, a total of 110 participants were treated at a range of 
talazoparib doses (0.025-1.1 mg QD). Data from this study demonstrated objective 
responses and/or clinical benefit in participants with breast, ovarian/peritoneal, and 
pancreatic cancer; small-cell lung cancer (SCLC); and Ewing sarcoma. C3441030 study is 
an ongoing, Phase 1, open-label, dose escalation study is evaluating the safety, tolerability, 
PK and anti-tumor activity of talazoparib (0.75 mg and/or 1.0 mg QD) in Japanese patients 
with advanced solid tumors. As of the data cutoff date of 30 September 2019, efficacy data 
for this study was not available. In order to keep this study in historical context, PRP-001 
and C3441030 study were reviewed and key features were incorporated. Chinese locally 
advanced or metastatic solid tumor that is resistant to standard therapy or for which no 
standard therapy is available will be enrolled in this study. 
The results of PK analysis indicated that talazoparib CL/F was reduced in patients with renal 
impairment. Per talazoparib IB (Dec 2019), the recommended dose of talazoparib for 
patients with moderate renal impairment (30 mL/min ≤CLcr <60 mL/min) should be 
reduced to 0.75 mg QD. No dose adjustment is recommended for patients with mild renal 
impairment (60 mL/min ≤CLcr <90 mL/min). In C3441049 study, participants with 
calculated creatinine clearance <60 mL/min should be excluded as the starting dose is 
1 mg QD.
Contraception consideration
There are no data from the use of talazoparib in pregnant women. Studies in animals have 
shown embryo-fetal toxicity and talazoparib was clastogenic in in vitro and in in vivo assays. 
Talazoparib may cause fetal harm when administered to a pregnant woman.


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Talazoparib should not be given to pregnant participants or those who plan to become 
pregnant during treatment. Women of childbearing potential should be advised to avoid 
becoming pregnant while receiving talazoparib. Talazoparib may cause fetal harm when 
administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus.
A highly effective method of contraception is required for female participants during 
treatment with talazoparib, and for at least 7 months after completing therapy. Advise male 
participants with female partners of reproductive potential and pregnant partners to use a 
condom (even after vasectomy), during treatment with talazoparib and for at least 4 months 
after the final dose (see Appendix 4).
4.3. Justification for Dose
In the first-in-human Phase 1 study (PRP-001, C3441007), the MTD and recommended 
Phase 2 dose (RP2D) for talazoparib as a single-agent was investigated using dose escalation 
scheme starting from 0.025 mg QD up to 1.1 mg QD. Two of 6 patients in Part 1 
experienced a DLT (thrombocytopenia) at talazoparib 1.1 mg/day; therefore, 1.0 mg/day was 
considered the MTD and recommended Phase 2 dose. In global pivotal Phase 3 study
673-301 (EMBRACA, C34421009), 1 mg QD is given to the locally advance or metastatic 
breast cancer participants, which has been approved by US Food and Drug Administration 
(FDA), EU EMA and multiple other global health authorities. 
In addition, Japan conducted a Phase 1 study (C3441030) to evaluate the safety, tolerability, 
preliminary efficacy, and PK profile of talazoparib as a single agent in Japanese participants
with advanced solid tumors. The dose was escalated to the next dose level (1 mg QD) 
according to the pre-defined dose escalation scheme and based on the incidence of Dose 
limiting toxicities (DLTs) at the initial dose level (0.75 mg QD). As of 24 January 2019, a 
total of 9 participants were enrolled in the dose escalation part of the C3441030 study. DLT 
were not reported in any participants receiving 0.75 mg QD (n=3) or 1 mg QD (n=6). 
Therefore, the RP2D of single-agent talazoparib was determined to be 1 mg QD in Japanese 
participants with advanced solid tumors. Overall the safety profile in the dose escalation part 
was similar to the adverse events (AEs) observed in global studies of talazoparib. Most 
common AEs of single-agent talazoparib in Japanese participants were hematological 
toxicities and hepatotoxicities. Based on the preliminary PK analysis results (n=3 each in 
0.75 mg QD and 1 mg QD), the PK profile of single-agent talazoparib in Japanese 
participants was comparable with that in Western population. These data also supported 
RP2D in Japanese participants.
A bridging study evaluation (BSE) consists of a summary and analysis of the efficacy, safety, 
and PK data that support the use of talazoparib 1 mg taken orally QD for the treatment of 
adult patients in Asian countries with gBRCA-mutated human epidermal HER2-negative 
locally advanced or metastatic breast. Conclusions from the data in this BSE shown that 
talazoparib exhibited similar PK in Asian Patients compared to non-Asian Patients. While 
population PK analysis showed that talazoparib exposure was 19.2% lower in Asian Patients 
compared with non-Asian Patients, this effect was not considered clinically relevant given 
that a) the within-subject talazoparib pre dose plasma concentration (Ctrough)in Asian Patients 


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are within the range of those in non-Asian Patients and b) the relatively small magnitude of 
lower average exposure in Asian Patients.
Based on the safety data of talazoparib and prior clinical experience as described above, 
talazoparib will be administered orally daily at 1 mg with provision for dose modifications as 
described in Section 6.6 in this protocol.
4.4. End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants age ≥18 years, inclusive, at Visit 1 (Screen 1).

Male participants are eligible to participate if they agree to the requirements 
described in protocol Section 10.4.1 during the intervention period and for at least 
4 months after the last dose of study intervention.

A female participant is eligible to participate if she is not pregnant or 
breastfeeding. Women of childbearing potential (See details in protocol 
Section 10.4.2) must be willing to use a contraceptive method that is highly 
effective (as described in protocol Section 10.4.4) during the intervention period 
and for at least 7 months after the last dose of study intervention.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Histological or cytological diagnosis of locally advanced or metastatic solid tumor 
that is resistant to standard therapy or for which no standard therapy is available.  


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4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.  
5. Adequate bone marrow function, including:

ANC ≥1,500/mm3 or ≥1.5×109/L without the use of growth factor within 14 days 
before obtaining the hematology laboratory tests;

Platelets ≥100,000/mm3 or ≥100×109/L without the use of platelet transfusions or 
growth factors within 14 days before obtaining the hematology laboratory tests;

Hemoglobin ≥9 g/dL, with last transfusion at least 14 days prior to the 
hematology laboratory tests.
6. Adequate renal function.

Estimated creatinine clearance (CLcr) ≥60 mL/min as calculated using the 
Cockcroft-Gault Formula (See Appendix 10).
7. Adequate Liver Function, including:

Serum TBili ≤1.5×ULN unless the patient has documented Gilbert syndrome 
(≤3×ULN for Gilbert syndrome);

AST and ALT ≤2.5×ULN (≤5.0×ULN if there is liver involvement by the tumor);

Alkaline phosphatase ≤2.5×ULN (≤5×ULN in case of bone metastasis).
8. Able to take oral medications.
9. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1, 
except for AEs not constituting a safety risk by investigator judgment.
10. Anticipate life expectancy ≥12 weeks.
Informed Consent:
11. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Participants with brain metastases.


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2. Previous high-dose chemotherapy requiring stem cell rescue.
3. Myocardial infarction within 6 months before starting therapy, symptomatic
congestive heart failure (New York Heart Association class III or IV), unstable
angina, or unstable cardiac arrhythmia requiring medication. Stable cardiac
arrhythmia (eg, chronic atrial fibrillation controlled by medication) can be eligible.
4. Hypertension that cannot be controlled by medications (>150/100 mmHg despite
optimal medical therapy).
5. Known or suspected hypersensitivity to active ingredient/excipients.
6. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
Prior/Concomitant Therapy:
7. Major surgery within 4 weeks prior to the first dose of study treatment.
8. Radiation therapy within 4 weeks prior to the first dose of study treatment. Palliative
radiotherapy for the treatment of painful bony lesions within 2 weeks prior to the first
dose of study treatment.
9. Any anti-tumor systemic cytotoxic therapies within 4 weeks prior to the first dose of
study treatment (6 weeks for nitrosoureas or mitomycin-C), treatment with immune
modulators (including, but not limited to, corticosteroids (at a prednisone-equivalent
dose of >10 mg/day), cyclosporine and tacrolimus; locally active treatments such as
Beconase are allowed) within 4 weeks prior to the first dose of study treatment.
10. Prior irradiation to >25% of the bone marrow (see protocol Appendix 9 Bone Marrow 
Reserve in Adults).
11. Current or anticipated use of P-gp inhibitor and/or inducer within 7 days prior to 
study intervention from lead-in to end of Cycle 1; concomitant use of potent P-gp 
inhibitor after Cycle 1 until the end of treatment. For a list of P-gp inhibitors and 
inducers, refer to protocol Section 6.5.
12. Prior treatment with a PARP inhibitor.
Prior/Concurrent Clinical Study Experience:
13. Participation in other studies involving investigational drug(s) within 4 weeks prior to
the first dose of study treatment.


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Diagnostic Assessments:
14. Active and clinically significant bacterial, fungal, or viral infection, including
hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency
virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
Other Exclusions:
15. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members.
5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use.  At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use highly effective contraception consistently and 
correctly and document the conversation and the participant’s affirmation in the participant’s 
chart (participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened after discussion with the Sponsor’s medical monitor. 
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.


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6.1. Study Intervention(s) Administered
Intervention Name
Talazoparib 
Type
Intervention Type: Drug
Dose Formulation
Capsules
Unit Dose Strength(s)
1 mg; 0.25 mg
1 mg capsule will also be supplied as a starting dose; 
0.25 mg capsule should only be used for participants who 
require dose reduction.
Dosage Level(s)
1 mg QD
Route of Administration
Oral
Use
Experimental
IMP or NIMP
IMP 
Sourcing
Provided centrally by the sponsor 
Packaging and Labeling
Study intervention will be provided in bottles.  Each bottle
will be labeled as required per country requirement.
[Current/Former Name(s) or 
Alias(es)]
Current Names: Talazoparib (PF-06944076)
Former Name or Alias: MDV3800 or BMN 673
6.1.1. Administration
Talazoparib will be administered on a continuous basis. In the food effect study 673-103, 
food intake (a high-fat, high-calorie meal) had no impact on the AUCinf while reduced the 
Cmax by 46%. Consistent with findings from the food effect study, population PK analysis 
using data from Studies 673-301, 673-201, PRP-001, and PRP-002 showed food intake 
decreased absorption rate but had no impact on the extent of the absorption. To reduce the 
variability in Cmax to better characterize the PK profile in Chinese after both single-dose and 
multiple dose, before serial PK sampling (Cycle 1 Day -9, Cycle 1 Day 22), talazoparib will 
be administered with approximately 240 ml water on an empty stomach ie, participants
should refrain from food and beverages (except for water)should keep fasted for 
approximately 8 hours predose and 2 hour postdose. For the rest of PK sampling point, 
talazoparib may be taken with or without food. 
A cycle is defined as the time from Day 1 dose to the next Day 1 dose. If there are no 
treatment delays, a cycle will be 28 days.
Participants will swallow the talazoparib whole, and will not manipulate or chew the 
talazoparib capsule prior to swallowing.  Talazoparib should be taken orally once daily 
(ie, continuous daily dosing) at approximately the same time each day (preferably in the 
morning). If a patient misses a day of treatment or vomits any time after taking a dose, 
he/she must be instructed not to “make it up” but to resume subsequent doses the next day as 
prescribed. If a patient inadvertently takes 1 extra dose during a day, the patient should not 
take the next dose of talazoparib (see details in Section 8.4).


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On days of clinic visits, talazoparib should be taken at the clinic after completion of pre-dose 
sampling and assessments; on these PK sample dates, the clinic visit should be scheduled for 
approximately the same time of day that the dose is typically taken.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention.
7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record.  All talazoparib that is taken 
home by the participant, both used and unused, must be returned to the investigator 
by the participant.  Returned study intervention must not be redispensed to the 
participants.


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8. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP Manual.
6.2.1. Preparation and Dispensing
A qualified staff member will dispense the study intervention using the IRT system via 
unique container numbers in the bottles provided, in quantities appropriate according to the 
SoA.  A second staff member will verify the dispensing.  The participant should be instructed 
to maintain the product in the bottle provided throughout the course of dosing and return the 
bottle to the site at the next study visit.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Allocation of participants to treatment groups will proceed through the use of an IRT system 
(IWR).  The site personnel (study coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when study intervention is being supplied via the IRT system.  The IRT system will provide 
a confirmation report containing the participant number, randomization number, and DU or 
container number assigned.  The confirmation report must be stored in the site’s files. 
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be redispensed to the participants.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
6.4. Study Intervention Compliance
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF.  
The dose of talazoparib and study participant identification will be confirmed at the time of 
dosing by a member of the study site staff other than the person administering talazoparib. 


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When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by counting returned 
capsules during the site visits and documented in the source documents and CRF. A patient 
diary will be provided to the participants to aid in patient compliance with the dosing 
instructions. The diary will be maintained by the patient to include missed or changed 
talazoparib doses. The patient diary may also be used to support this part of the talazoparib 
accountability process. Deviation(s) from the prescribed dosage regimen should be recorded 
in the CRF.
A record of the number of talazoparib capsules dispensed to and taken by each participant 
must be maintained and reconciled with study intervention and compliance records.  
Intervention start and stop dates, including dates for intervention delays and/or dose 
reductions, will also be recorded in the CRF. Participants will be considered out of 
compliance if ≥20% of required doses are missed.
6.5. Concomitant Therapy
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
Concomitant treatment considered necessary for the patient’s well-being may be given at 
discretion of the treating physician.
All concomitant treatments, blood products, as well as nondrug interventions received by 
participants from 28 days before first dose until 28 days after the last dose will be recorded 
on the CRF.
6.5.1. P-gp Inhibitors and Inducers
Data from Study C3441004 indicated that coadministration of multiple daily doses of potent 
P-gp inhibitor itraconazole 100 mg twice daily with a single 0.5 mg talazoparib dose 
increased talazoparib total exposure (AUCinf) and peak concentration (Cmax) by 
approximately 56% and 40%, respectively, relative to a single 0.5 mg talazoparib dose 
administered alone; coadministration of multiple daily doses of a strong P-gp inducer, 
rifampin 600 mg, with a single 1 mg talazoparib dose, increased talazoparib Cmax by 
approximately 37% whereas AUCinf was not affected relative to a single dose of talazoparib 
1 mg administered alone. 
Considering the purpose and endpoint of this study, guidelines for concomitant use of 
talazoparib with P-gp inhibitors and inducers are as follows: 
7 days prior to lead-in to end of Cycle 1:
To adequately evaluate the PK of talazoparib, P-gp inhibitors that result in ≥50% increase in 
the exposure of an in vivo probe P-gp substrate according to the FDA website 
(https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInte
ractionsLabeling/ucm093664.htm#table5-2) and University of Washington Drug-Drug 


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Interaction database (https://www.druginteractioninfo.org/) should not be allowed: 
amiodarone, azithromycin, carvedilol, clarithromycin, cobicistat, curcumin, diosmin, 
dronedarone, erythromycin, flibanserin, fluvoxamine, glecaprevir/pibrentasvir, indinavir, 
itraconazole, ketoconazole, lapatinib, lopinavir, osimertinib, piperine, propafenone, 
quercetin, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, 
telaprevir, tipranavir, valspodar, vemurafenib, and verapamil. 
Similarly, P-gp inducers that result in ≥20% reduction in the exposure of an in vivo probe 
P-gp substrate according to the FDA website 
(https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInte
ractionsLabeling/ucm093664.htm#table5-2) and University of Washington Drug-Drug 
Interaction database (https://www.druginteractioninfo.org/) should not be allowed:
apalutamide, avasimibe, carbamazepine, danshen (salvia miltiorrhiza), efavirenz, phenytoin, 
rifabutin, rifampin, ritonavir, St. John’s wort extract and tivantinib.
Beyond Cycle 1 onwards:
Potent P-gp inhibitors that result in ≥2-fold increase in the exposure of an in vivo probe P-gp 
substrate according to the FDA website 
(https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInte
ractionsLabeling/ucm093664.htm#table5-2) and University of Washington Drug-Drug 
Interaction database (https://www.druginteractioninfo.org/) should not be allowed: 
amiodarone, carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin, 
glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, 
propafenone, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, 
telaprevir, tipranavir, valspodar, and verapamil.
Alternative therapies should be considered whenever possible.  If usage of any of the above 
treatment is deemed medically necessary, consultation and agreement with the Sponsor is 
required prior to treatment initiation as appropriate dose modification of talazoparib may be 
needed.
Caution and monitoring for potential increased adverse reactions should be used upon 
concomitant use of the following transporter inhibitors with talazoparib throughout the study 
course: atorvastatin, azithromycin, conivaptan, curcumin, cyclosporine, diltiazem, diosmin, 
eliglustat, elacridar [GF120918], eltrombopag, felodipine, flibanserin, fluvoxamine, 
osimertinib, piperine, quercetin, schisandra chinensis extract and vemurafenib. 
The list of potent P-gp inhibitors and transporter inhibitors to be used with caution will be 
updated annually and reflected in the Investigator Brochure.


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6.5.2. Supportive Care 
Supportive medications may be provided at the investigator’s discretion. Hematopoietic growth 
factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony 
stimulating factor [GM-CSF]): Primary prophylactic use of granulocyte colony stimulating 
factors is not permitted but they may be used to treat treatment emergent neutropenia as 
indicated by the current American Society of Clinical Oncology (ASCO) guideline.7  If 
neutropenic complications are observed in a cycle in which primary prophylaxis with colony 
stimulating factors (CSFs) was not received, secondary prophylaxis may be given at the 
discretion of the investigator, but only if dose reduction or delay are not considered a 
reasonable alternative.
Allowed medications include (but are not limited to) anti-emetics, such as dexamethasone, 
metoclopramide, ondansetron, or aprepitant; anti-diarrheals, such as loperamide 
hydrochloride; and appetite stimulants such as megestrol acetate. Participants are not 
permitted to initiate treatment with bisphosphonates or denosumab during the study, but are 
permitted to continue on either of these treatments at the same dose as at randomization.
6.5.3. Other Anti-tumor/Anti-cancer or Experimental Drugs
No additional anti-tumor treatment will be permitted while participants are receiving study 
treatment.  The concurrent use of herbal medicines with anti-cancer indication is not 
permitted.
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
provided that the lesions were known at the time of study entry and the investigator clearly 
indicates that the need for palliative radiotherapy is not indicative of disease progression,
after discussion with the Sponsor’s medical monitor.  
6.5.4. Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and talazoparib required to minimize the risk of 
impaired wound healing and bleeding has not been determined.  Stopping talazoparib is 
recommended at least 10 days prior to surgery.  Postoperatively, the decision to reinitiate 
talazoparib treatment should be based on a clinical assessment of satisfactory wound healing 
and recovery from surgery.  Surgical resection of target/non-target lesion is prohibited 
throughout the study period.
6.6. Dose Modification
Daily dosing of talazoparib can be interrupted for recovery from toxicity for up to 28 days. 
For interruptions longer than 28 days, treatment at the same or a reduced dose can be 
considered based on a discussion between the Sponsor or designee and Investigator if 
evidence of response or clinical benefit to talazoparib is noted.
Dose modifications should be made based on the observed toxicity, as summarized in
Table 1 and Table 2.


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Table 1.
Dose Modification of Talazoparib Due to Adverse Events
Toxicity
Management of Adverse Events
Grade 1 or 2
No requirement for dose interruption or dose reduction.  
If the toxicity persists at Grade 2 (for ≥7 days), a dose reduction to the 
next lower dose level (eg, from 1 mg QD to 0.75 mg QD) may be 
implemented at the discretion of the Investigator.
Grade 3 or 4 Anemia 
(hemoglobin <8.0 g/dL)
Hold Talazoparib and implement supportive care per local guidelines. 
Monitor weekly until hemoglobin returns to 9 g/dL or better, then resume 
talazoparib at a reduced dose.  

If anemia with hgb <8.0 g/dL recurs after dose reduction, hold 
talazoparib and implement supportive care per local guidelines.  
Monitor weekly until hemoglobin returns to 9.0 g/dL then 
resume talazoparib at a further reduced dose.

If anemia persists for >4 weeks without recovery of hemoglobin 
to at least 9.0 g/dL despite supportive care measures at any dose 
level, discontinue talazoparib and consider referral to a 
hematologist.
Transfusions and other supportive measures are permitted to support 
management of hematological toxicities at any occurrence.
Grade 3 or 4 Neutropenia 
(ANC <1000/µL)
Hold talazoparib and implement supportive care per local guidelines.  
Monitor weekly until ANC ≥1500/µL, then resume talazoparib at a 
reduced dose.
If neutropenia recurs after the dose reduction, hold talazoparib and 
implement supportive care per local guidelines.  Monitor weekly until 
ANC ≥1500/µL, then resume talazoparib at a further reduced dose.
If neutropenia persists for >4 weeks without recovery to ≥1500/μL at any 
dose level despite supportive care measures, discontinue talazoparib and 
consider a referral to a hematologist.
G-CSF and GM-CSF may be used at investigators discretion for the 
supportive treatment of neutropenia at any occurence.
Grade 3 or 4 
Thrombocytopenia (platelets 
<50,000/µL)
Hold talazoparib and implement supportive care per local guidelines.  
Monitor weekly until platelets ≥50,000/μL, then then resume talazoparib 
at a reduced dose.
If thrombocytopenia (<50,000/μL) recurs after one dose reduction, hold 
talazoparib and implement supportive care per local guidelines. Monitor 
weekly until platelets ≥75,000/µL, then resume talazoparib at a further 
reduced dose.
If thrombocytopenia persists for >4 weeks without recovery to 
≥50,000/μL despite supportive care measures, discontinue talazoparib 
and consider a referral to a hematologist.
Thrombopoietin analogues and/or platelet transfusions may be used at 
investigators discretion for the supportive treatment of thrombocytopenia 
at any occurrence.
Nonhematologic laboratory 
Grade ≥3 events determined 
Hold talazoparib as follows:

For Grade 3 laboratory abnormalities, hold talazoparib until the 
laboratory abnormality resolves to Grade ≤2 (to baseline grade 


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Table 1.
Dose Modification of Talazoparib Due to Adverse Events
Toxicity
Management of Adverse Events
to be clinically significant, 
except abnormal liver tests
for creatinine increases). Resume talazoparib at the same dose 
or reduce to one dose level.  

If Grade 3 laboratory abnormality recurs, hold talazoparib 
until the laboratory abnormality resolves to Grade ≤2 (to 
baseline grade for creatinine increases).  Reduce talazoparib 
one dose level.

For Grade 4 laboratory abnormalities, hold talazoparib until the 
laboratory abnormality resolves to Grade ≤2 (to baseline grade 
for creatinine increases).  Reduce talazoparib one dose level.

Talazoparib must be discontinued if a Grade 4 adverse 
event recurs after treatment resumes.
Implement supportive care per local guidelines.
Contact medical monitor to discuss potential dose modification.
Talazoparib must be permanently discontinued for unresolved Grade 3 
toxicity lasting longer than 14 days or for Grade 4 toxicity lasting longer 
than 3 days. 
Talazoparib may be resumed at a reduced dose level if clear clinical 
benefit is observed, after discussion with the Sponsor.
Grade ≥3 abnormal liver tests
Subjects who develop abnormal liver tests ([AST, ALT, total bilirubin 
[TBili]), signs or symptoms consistent with hepatitis during study 
treatment may meet the criteria for temporarily withholding or 
permanently discontinuing study drug talazoparib.
Criteria for Temporary Withholding of Study Drug in Association with 
Liver Test Abnormalities if any of the following occur:

Subjects who develop AST or ALT >5 x ULN (AST/ALT 
>8 × ULN for subjects with hepatic involvement) without TBili 
>2 x ULN; OR

Subjects with baseline total bilirubin <1.5 x ULN who 
subsequently present with >3 x ULN; OR

Subjects with baseline total bilirubin >1.5 x ULN and <3 x ULN 
(eg, Gilberts) who subsequently present with bilirubin 
>5 x ULN. 
If abnormalities resolve to baseline values within 2 weeks, there are no 
signs of DILI, and none of the permanent discontinuation criteria are met, 
then upon discussion with the Sponsor, the investigator may re-challenge 
at a reduced dose level.
Criteria for Permanent Discontinuation of Study Drug in Association 
with Liver Test Abnormalities if any of the following occur:

Subjects who develop with AST OR ALT values >3 × ULN 
(AST/ALT >8 × ULN for subjects with hepatic involvement) 
AND a Tbili value >2 × ULN.

Subjects with AST/ALT >5 × ULN that persists for more than 
7 days (AST/ALT >8 × ULN for subjects with hepatic 
involvement).


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Table 1.
Dose Modification of Talazoparib Due to Adverse Events
Toxicity
Management of Adverse Events

Subjects with AST/ALT >20 × ULN that persists for longer than 
3 days.
Subjects with Tbili >3 × ULN that persists for longer than 7 days 
(>5 × ULN for subjects with Gilbert’s disease).
Guidelines for follow-up for possible drug-induced liver injury after the 
liver test abnormalities resolve to baseline grade are provided in 
Section 10.5. 
Nonlaboratory Grade ≥3 
events
Hold talazoparib as follows:
For Grade 3 adverse events, hold talazoparib until the adverse event 
resolves to Grade ≤1 or baseline. Resume talazoparib at the same dose or 
reduce by 1 dose level.
For Grade 4 adverse events, hold talazoparib until the adverse event 
resolves to Grade <1 or baseline.  Resume talazoparib at a reduced dose 
level.
Refer to Table 2 for additional information. Dose reduction of talazoparib by 1 and, if 
needed, 2 dose levels (Table 1) will be allowed depending on the type and severity of toxicity 
encountered. Patients requiring more than 3 dose reductions will be discontinued from the 
treatment and entered into the follow-up phase, unless otherwise agreed between the 
investigator and the sponsor. All dose modifications/adjustments must be clearly 
documented in the patient's source notes and case report form (CRF).
Table 2.
Dose Modifications for Toxicities
Dose Level
Initial dose level
1 mg QD
First dose level reduction 
0.75 mg QD
Second dose level reduction 
0.5 mg QD
Third dose level reduction 
0.25 mg QD
Once a dose has been reduced for a given patient, all subsequent cycles should be 
administered at that dose level, unless further dose reduction is required.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants after the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following list reasons for discontinuation of study intervention.


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
Pregnancy (see follow up requirement in Section 8.3.5.1); 

Unacceptable toxicity (see details in Table 1);

Disease-State Criteria (eg, objective disease progression; global deterioration of 
health status requiring discontinuation);

Death;

Patient refused further treatment;

Study terminated by sponsor;

Lost to follow-up;

Significant protocol deviation. 
Note that discontinuation of study intervention does not represent withdrawal from the study.
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for safety at least 28 calendar days after last dose of talazoparib. See the SoA
for data to be collected at the time of discontinuation of study intervention and follow-up for 
any further evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
7.1.1. Temporary Discontinuation
Appropriate follow-up assessments should be done until adequate recovery occurs as 
assessed by the investigator.  Criteria required before treatment can resume are described in 
the Section 6.6.
Doses may be held as needed until toxicity resolution.  Depending on when the adverse event 
resolved, a treatment interruption may lead to the patient missing all subsequent planned 
doses within that same cycle or even to delay the initiation of the subsequent cycle. If the 
adverse event that led to the treatment interruption recovers within the same cycle, then 
re-dosing in that cycle is allowed.  Doses omitted for toxicity are not replaced within the 
same cycle.  The need for a dose reduction at the time of treatment resumption should be 
based on the criteria defined in the Section 6.6, unless expressly agreed otherwise following 
discussion between the investigator and the sponsor.  If a dose reduction is applied in the 
same cycle, the patient will need to return to the clinic to receive new drug supply.
In the event of a treatment interruption for reasons other than treatment-related toxicity 
(eg, elective surgery) lasting >2 weeks, treatment resumption will be decided in consultation 
with the sponsor.


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7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled/randomized and 
then are prematurely withdrawn from the study.  Participants should be questioned regarding 
their reason for withdrawal.  
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further evaluations should be performed and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of study intervention or also from study procedures 
and/or posttreatment study follow-up, and entered on the appropriate CRF page.  In the event 
that vital status (whether the participant is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed 
in accordance with local law.


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7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count, blood chemistry and imaging) and obtained before signing of the ICD may be utilized 
for screening or baseline purposes provided the procedures met the protocol-specified criteria 
and were performed within the time frame defined in the SoA.


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Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study will depend upon 
the actual duration of treatment.  Additional blood samples may be taken for safety 
assessments at times specified by Pfizer, provided the total volume taken during the study 
does not exceed 550 mL during any period of 60 consecutive days.
Volume of blood collected for each test refer to Table 3.
Table 3.
Blood Sampling Volume for Each Test
Testing
Blood sampling volume
Hematology
3 mL
Chemistry 
5 mL
HCV, HBV test 
5 mL
HIV test
5 mL
PK
3 mL
Pregnancy (blood)
3 mL
FSH
3 mL
The actual blood sampling volume may be less, please refer to the site operational manual.
8.1. Efficacy Assessments
Tumor assessment will be conducted in this study to explore the preliminary efficacy profile 
of talazoparib monotherapy in Chinese Participants with advanced solid tumor.
8.1.1. Imaging Assessments
Tumor assessments will include all known or suspected disease sites.  Imaging may include 
chest, abdomen, and pelvis computed tomography (CT) or magnetic resonance imaging 
(MRI) scans. The same imaging technique used to characterize each identified and reported 
lesion at baseline will be employed in the following tumor assessments.


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A brain MRI or CT is to be performed at screening/baseline to evaluate participants for 
presence/absence of brain metastases. Bone scans will be performed at baseline if disease is 
suspected and on study as appropriate to follow disease.  CT or MRI scans to be done on 
D29 (±7 days window) and every 8 weeks (±7 days window) thereafter for the initial 
12 cycles regardless of any dose interruptions or dose delays.
CT or MRI scans to be done on D29 (±7 days window) and every 8 weeks (±7 days window) 
thereafter for the initial 12 cycles regardless of any dose interruptions or dose delays.  After 
completion of Cycle 12 (at the beginning of Week 45), tumor assessment will be done per
local standard practice.  Tumor assessments should be repeated at the end of treatment visit if 
more than 6 weeks have passed since the last evaluation.  
Given the exploratory nature of the efficacy endpoint, confirmation of response (complete 
response [CR]/partial response [PR]) is not required.  As clinically indicated, CT/MRI will 
be repeated by investigator’s discretion.
Assessment for anti-tumor activity
Anti-tumor activity will be assessed through radiological tumor assessments conducted as 
specified in the SoA. Assessment of response will be made using RECIST version 1.1 (see
Section 10.7).
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include general appearance, head, oropharynx, eyes, 
ears, nose, neck, thyroid, lung, heart, breast, abdomen, musculoskeletal, skin. Height and 
weight will also be measured and recorded. Height will be recorded at screening only. 
Weight will be measured according to the SoA.
A brief physical examination will be focused on physical examinations at the discretion of 
the investigator based on the patient's clinical condition. At a minimum, assessments of the 
skin, lungs, heart, and abdomen (liver and spleen).
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.2.2. Vital Signs
Temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure will be 
assessed.


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Blood pressure and pulse rate measurements will be assessed in the sitting position after the 
participant has been resting quietly for at least 5 minutes and prior to dosing on dosing days
with a completely automated device.  Manual techniques will be used only if an automated 
device is not available.
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse 
rate and 3 blood pressure measurements (3 consecutive blood pressure readings will be 
recorded at intervals of at least 1 minute).  The average of the 3 blood pressure readings will 
be recorded on the CRF.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, RR, QT intervals, QTc, QTcF and 
QRS complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) 
is not recommended given the potential risk of discrepancies with ECGs acquired using 
standard limb lead placement.  All scheduled ECGs should be performed after the participant
has rested quietly for at least 10 minutes. 
If a) a postdose QTc interval remains ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator); or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring.  A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator).
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 6.
8.2.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.  


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The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 5 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.5. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the study intervention.  Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study.  Pregnancy tests may also be 
repeated if requested by IRBs/ECs or if required by local regulations.  If a urine test cannot 
be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required.  In 
such cases, the participant must be excluded if the serum pregnancy result is positive.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant/legally authorized representative will be questioned about the occurrence of 
AEs in a nonleading manner.


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In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 28 calendar days, except as indicated below, after the last administration of the 
study intervention.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation.  However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
MDS, AML and second primary malignancies are adverse events of special interest in this 
study. Any diagnosis of MDS, AML or second primary malignancies for any participant
enrolled will be reported as an SAE.


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If a participant begins a new anticancer therapy, SAEs occurring during the above-indicated 
active collection period must still be reported to Pfizer Safety irrespective of any intervening 
treatment.  Note that a switch to a commercially available version of the study intervention is 
considered as a new anticancer therapy for the purposes of SAE reporting.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
If a participant begins a new anticancer therapy, the recording period for nonserious AEs 
ends at the time the new treatment is started; however, SAEs must continue to be recorded on 
the CRF during the above-indicated active collection period.  Note that a switch to a 
commercially available version of the study intervention is considered as a new anticancer 
therapy for the purposes of SAE reporting.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.


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8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental exposure during pregnancy:  

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation or skin 
contact.

A male family member or healthcare provider who has been exposed to the study 
intervention by ingestion, inhalation or skin contact then exposes his female 
partner prior to or around the time of conception.


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The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected in female participants after the start of study intervention 
and until 7 months after the last dose. And female partners of male participants will 
be collected after the start of study intervention and until 4 months after the last dose.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 


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the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by inhalation or skin contact.  
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the CT SAE Report Form.  Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
Death events should be reported as SAEs if meet the criteria.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
The following DREs are common in participants with condition under study and can be 
serious/life threatening:


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
Non-fatal progression of the malignancy under study (including signs and symptoms 
of progression).
Because these events are typically associated with the disease under study, they will not be 
reported according to the standard process for expedited reporting of SAEs even though the 
event may meet the definition of an SAE. These events will be recorded on the efficacy CRF
page in the participant’s CRF within the appropriate time frame.
NOTE: However, if either of the following conditions applies, then the event must be 
recorded and reported as an SAE (instead of a DRE):

The event is, in the investigator’s opinion, of greater intensity, frequency, or duration 
than expected for the individual participant.
OR

The investigator considers that there is a reasonable possibility that the event was 
related to study intervention.
8.3.8. Adverse Events of Special Interest
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), and second 
primary malignancies are the AEs of special interest in this study.  

MDS/AML
Complete blood counts should be obtained at baseline and monitored for signs of 
hematologic toxicity during treatment. If MDS/AML is confirmed, talazoparib should be 
discontinued. Any diagnosis of myelodysplastic syndrome (MDS) or AML for any 
participant enrolled will be reported as an SAE.
MDS and AML, and second primary malignancies.

Second primary malignancies
Due to talazoparib’s mechanism of action, and demonstration of clastogenicity in pre-clinical
studies, second primary malignancies are considered a potential risk for talazoparib.  In the 
talazoparib 1 mg QD Population, 7 AEs of second primary malignancies were reported in 
6 participants (squamous cell carcinoma of skin [2 participants], and basal cell carcinoma, 
glioblastoma multiforme, intraductal proliferative breast lesion, neoplasm skin, and ovarian 
neoplasm [1 participant each].  These second primary malignancies were mostly skin 
malignancies.  In general, latency to diagnosis of the malignancy was relatively short, making
a relationship with talazoparib unlikely, and in some cases, other risk factors were reported.  
None of the events were considered related to talazoparib by the investigator.


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All AESIs must be reported as an AE or SAE following the procedures described in 
Sections 8.3.1 through 8.3.4. An AESI is to be recorded as an AE or SAE on the CRF. In 
addition, an AESI that is also an SAE must be reported using the CT SAE Report Form.
8.3.9. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of talazoparib greater than protocol-specified dose of 1 mg within a 
day will be considered an overdose.
There is no specific treatment in the event of talazoparib overdose, and symptoms of 
overdose are not established. 


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In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of talazoparib (whichever is 
longer). 
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 1 day from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis).  
6. Treatment with talazoparib should be stopped, and physicians should consider gastric 
decontamination, follow general supportive measures and treat symptomatically.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.  
8.5. Pharmacokinetics 
Blood samples of approximately 3 mL, to provide a minimum of 1.5 mL, will be collected 
for measurement of plasma concentrations of talazoparib as specified in the SoA.  
Instructions for the collection and handling of biological samples will be provided in the 
laboratory manual or by the sponsor.  The actual date and time (24-hour clock time) of each 
sample will be recorded.
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from patients experiencing unexpected and/or serious AEs. In case of QTc values 
>500 msec, a blood sample for PK analysis should be collected. The date and time of blood 
sample collection and of last dosing prior to PK collection documented on the CRF. 
The actual times may change, but the number of samples will remain the same.  All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing.  Collection of
samples up to and including 10 hours after dose administration that are obtained within 
10% of the nominal time relative to dosing (eg, within 6 minutes of a 60-minute sample) will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. Collection of samples more than 10 hours after dose
administration that are obtained ≤1 hour away from the nominal time relative to dosing will 
not be captured as a protocol deviation, as long as the exact time of the collection is noted on 
the source document and the CRF. This protocol deviation window does not apply to 
samples to be collected more than 10 hours after dose administration at outpatient/follow-up 
visits with visit windows. In the event of any dose interruption or reduction before Cycle 1 


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Day 22, the intensive PK sampling shall be postponed to Day 1 or 15 of next cycle but no 
later than Cycle 4 if consecutive 20 days dosing prior to PK sampling is achieved. 
PK samples will be assayed for talazoparib using a validated analytical method in 
compliance with Pfizer standard operating procedures (SOPs). 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity.  Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor.  
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
8.6. Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7. Genetics
8.7.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.8. Biomarkers
Biomarkers are not evaluated in this study.
8.8.1. Specified Gene Expression (RNA) Research 
Specified gene expression (RNA) research is not included in this study.
8.8.2. Specified Protein Research
Specified protein research is not included in this study.
8.8.3. Specified Metabolomic Research
Specified metabolomic research is not included in this study.
8.9. Immunogenicity Assessments
Immunogenicity assessments are not included in this study.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor.  The 


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SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.1. Estimands and Statistical Hypotheses
Do not apply.
9.2. Sample Size Determination
To support registration of mCRPC and other future potential indications in China, 
12 evaluable participants will be needed to characterize Chinese PK profile based on 
available talazoparib PK data globalwise and with the intention to satisfy regulatory 
requirement by China National Medical Products Administration (NMPA) in terms of PK 
evaluation in Chinese population. Considering non-evaluable participants, it is estimated that 
approximately 15 patients are needed.
9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
PK concentration 
population
Defined as all participants enrolled and treated who have at 
least 1 PK concentration in the single-dose and/or 
multiple-dose PK part.
PK parameter analysis 
population
Defined as all participants enrolled and treated who have at 
least 1 of the PK parameters of primary interest in the 
single-dose and/or multiple-dose PK part.
PK evaluable analysis set
Defined as all participants in the PK parameter analysis set 
who complete both the single dose PK and multiple dose PK 
parts without major protocol deviations.
Safety/Efficacy
Includes all enrolled participants who receive at least one 
dose of study medication.
9.4. Statistical Analyses
Pharmacokinetic parameters and plasma concentration data will be summarized as the 
primary analysis for this study. In addition, safety data including adverse events (AE), 
laboratory abnormalities and electrocardiogram measurements (ECG), as well as efficacy 
information reflected by objective response (OR) and duration of response (DOR) will also 
be summarized and estimated.  


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9.4.1. Primary Endpoint(s)
PK parameters of talazoparib following single dose administration will be derived from the 
concentration-time profiles as shown in the table below.
Parameter
Definition
Method of determination
Cmax
Maximum plasma 
concentration
Observe directly from data
Tmax
Time for Cmax
Observe directly from data as time of first 
occurrence
AUClast
Area under the plasma 
concentration versus time 
curve from time zero to 
the time of the last 
quantifiable concentration 
(Clast)
Linear/Log trapezoidal method
AUC
Area under the plasma 
concentration versus time 
curve from time zero to 
the time
Linear/Log trapezoidal method
AUCinf
Area under the plasma 
concentration versus time 
curve from time zero 
extrapolated to infinite 
time
AUClast + (Clast/kel), where Clast is the predicted 
plasma concentration at the last quantifiable 
time point estimated from the log-linear 
regression analysis; kel is the terminal phase 
rate constant calculated by a linear regression 
of the log-linear concentration-time curve
CL/F
Apparent oral clearance
Dose/AUCinf
Vz/F
Apparent volume of 
distribution
Dose/(AUCinf * kel), where kel is the terminal 
phase rate constant calculated by a linear 
regression of the log-linear concentration-time 
curve
t1/2
Terminal plasma half-life
Loge(2)/kel
PK parameters of talazoparib following multiple dose administration will be derived from the 
concentration-time profiles as shown in the table below.


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Parameter
Definition
Method of determination
Cmax
Maximum plasma concentration
Observe directly from data
Tmax
Time for Cmax
Observe directly from data as time of 
first occurrence within at steady 
state
Cmin
Minimum plasma concentration
Observe directly from data
AUC
Area under the plasma concentration 
versus time curve within a dosing 
interval of (=24 hr) 
Linear/Log trapezoidal method
CL/F
Apparent clearance
Dose/AUC
Rac
Observed accumulation ratio
Rac=AUC/AUCsd,, where AUCsd,is 
AUC24
Rss
Steady-state accumulation ratio
Rss=AUC/AUCinf, where AUCinf is 
from single dose
Actual PK sampling times will be used in the derivation of PK parameters.
Summary of pharmacokinetic parameters will be for PK parameter analysis set and PK 
evaluable analysis set. The PK parameters AUC10, AUC24, AUClast, AUCinf, Cmax, Tmax, 
CL/F, t1/2, Vz/F and kel of talazoparib following single dose administration of talazoparib 
will be listed and summarized descriptively for Lead-in phase. The PK parameters AUC,
Cmax, Cmin, Tmax, CL/F, Vz/F, t1/2, Rac, and Rss of talazoparib following multiple dose oral 
administration of talazoparib will be listed and summarized descriptively. 
The plasma concentration data for talazoparib will be listed and summarized descriptively by 
day and nominal PK sampling time for subjects in the PK concentration analysis set. 
Overlay multiple patient profiles of the plasma concentration-time data for talazoparib will 
be plotted using actual PK sampling time (separate plots for single and multiple dose PK). 
For mean and median plots of talazoparib plasma concentration-time, the nominal PK 
sampling time will be used. Mean and median profiles will be presented on both linear-linear 
and log-linear scales. For individual patient plots of talazoparib, the actual PK sampling time 
will be used, while the predose time will be set to zero.
The trough plasma concentration of talazoparib on Days 19-21 in Cycle 1 will also be plotted 
for visual inspection of steady-state condition.
9.4.2. Secondary Endpoint(s)
9.4.2.1. Safety
Safety analysis will be based on safety set that was defined in Section 9.3.


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Adverse events and laboratory abnormalities
Adverse events (AEs) will be coded to preferred term (PT) and system organ class (SOC) 
using the Medical Dictionary for Regulatory Activities (MedDRA) and classified by severity 
using the National Cancer Institutes (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE), version 4.03.
The focus of AE summaries will be on Treatment-Emergent Adverse Events (TEAEs), those 
with initial onset after the first dose of study treatment.
An event will be considered treatment related if the investigator considered the event related 
to the study drug. The number and percentage of participants who experienced any AE, 
serious AE (SAE), treatment-related AE, and treatment-related SAE will be summarized 
according to worst toxicity grades. The summaries will present AEs on the entire study 
period as well as by relatedness to study treatment. 
The number and percentage of participants who experienced laboratory test abnormalities 
will be summarized according to worst toxicity grade observed for each laboratory assay 
based on the NCI CTCAE v4.03 severity grade. Shift tables will be provided to examine the 
distribution of laboratory toxicities. The analyses will summarize laboratory tests on the 
entire study period. For laboratory tests without CTCAE grade definitions, results will be 
categorized as normal, abnormal or not done.
Electrocardiogram measurements
All ECGs obtained during the study will be evaluated for safety. The average of the 
triplicate ECG measurements will be used for the statistical analysis and all data 
presentations. Any data obtained from ECGs repeated for safety reasons after the nominal 
time-points will not be averaged along with the preceding triplicates.
Changes from baseline will be defined as the change of QTc post dose from the average of 
the pre-dose triplicate values.
QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie, 
Bazett’s, Fridericia’s and possibly a study specific factor). Data will be summarized and 
listed for QT, HR, RR, PR, QRS and QTc by time. Descriptive statistics (n, mean, median, 
standard deviation, minimum, and maximum) will be used to summarize the absolute QTc 
value and changes from baseline in QTc after treatment by day and time point. For each 
patient, the maximum change from baseline will be calculated as well as the maximum 
post-baseline value across time points. Categorical analysis of the QTc data will be 
conducted and summarized as follows: 
The number of participants with maximum change from baseline in QTc (<30, 30-59, and 
≥60 msec).


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The number of participants with maximum post-dose (post-baseline) QTc (<450, 450-<480, 
480-≤500, and >500 msec).
9.4.2.2. Efficacy
Objective response (OR)
Objective response by investigator assessment is defined as a complete response (CR) or 
partial response (PR) according to the RECIST version 1.1 recorded from Cycle 1 Day 1 
(C1D1) until disease progression, start of subsequent anti-cancer therapy or death due to any 
cause. 
A participant will be considered to have achieved an OR if the participant has a complete 
response (CR) or partial response (PR) according to RECIST v.1.1 definitions. Otherwise, 
the participant will be considered a non-responder in the OR rate analysis. Additionally, 
participants with inadequate data for tumor assessment (eg, no baseline assessment or no 
follow-up assessments) will be considered as non-responders in the OR rate analysis. If 
participants with non-measurable disease are enrolled, they are included in the 
aforementioned calculation of OR rate as well, however, a subgroup calculation of OR rate 
should be conducted among participants who are with measurable disease at baseline.
The OR rate (ORR) will be estimated by dividing the number of participants with objective 
response (CR or PR) by the number of participants in the safety analysis set (response rate). 
An exact 95% confidence interval (CI) by Clopper–Pearson will be provided for the ORR.
Duration of response (DOR)
For participants with an objective response (CR or PR), duration of response (DOR) is the 
time from first documentation of CR or PR to date of first documentation of objective 
progression or death. Date of first documentation of PD and date of first documentation of 
CR or PR will be based on investigator assessment of response. DOR data will be censored 
on the date of the last tumor assessment on study for participants who do not have objective 
tumor progression and who do not die due to any cause while on study. DOR will only be 
calculated for the subgroup of participants with an objective response. 
DOR will be summarized in the efficacy analysis set using the Kaplan-Meier method and 
displayed graphically. Median event time and 95% confidence interval for the median will 
be provided.
9.5. Interim Analyses
No formal interim analysis will be conducted for this study.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
This study will not use a DMC.


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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor and submitted to an 
IRB/EC by the investigator and reviewed and approved by the IRB/EC before the study is 
initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.


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10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study.  The participant or his/her legally authorized representative should be given sufficient 
time and opportunity to ask questions and to decide whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, HIPAA 
requirements, where applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant or his or her legally authorized 
representative is fully informed about the nature and objectives of the study, the sharing of 
data related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant or his or her legally 
authorized representative is fully informed about his or her right to access and correct his or 
her personal data and to withdraw consent for the processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.


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Participants who are rescreened are required to sign a new ICD.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site will be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations.  In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted.  These results are 
submitted for posting in accordance with the format and timelines set forth by US law.


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EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website.  Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods.  Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data.  Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.


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The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic form and are password protected to prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.


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10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the clinical monitoring plan.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.


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Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
Publication will be addressed in the clinical study agreement.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study portal. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant directly, 
and if a participant calls that number, he or she will be directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values.  These additional tests would not require additional collection of 
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety issues.
Table 4.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count
Neutrophils %
Eosinophils %
Monocytes %
Basophils %
Lymphocytes %
BUN or urea
Creatinine
Glucose (fasting)
Calcium
Sodium
Potassium
Magnesium
Chloride
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
CLcra
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte 
esterase/leukocytes
Urobilinogen
Urine bilirubin
Microscopyb
At screening only:

FSHc

Virus test (HBV, 
HCV, HIV)d
For WOCBP only

Pregnancy test (beta 
human chorionic 
gonadotropin 
(-hCG)e
a.
Calculated with serum creatinine, age, weight collected at baseline.
b.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase/leukocytes.
c.
For confirmation of postmenopausal status only.
d.
Perform within 28 days prior to first study treatment, including HBV (HBsAg and HBcAb), 
HCV antibody, and HIV antibody.
e.
Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or IRB/EC.  Serum or urine -hCG for female participants of childbearing potential.
Investigators must document their review of each laboratory safety report.


















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10.4. Appendix 4: Contraceptive Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 4 months after the last dose of study intervention,
which corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s) plus an additional 90 days (a spermatogenesis cycle): 

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual or homosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR

Must agree to use contraception/barrier as detailed below.

Agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

Male participants should be advised of the benefit for a female partner to use a highly 
effective method of contraception, as a condom may break or leak when having 
sexual intercourse with a WOCBP who is not currently pregnant.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below
during the intervention period and for at least 7 months after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention(s). The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.


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
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with high user dependency, as described below during the 
intervention period and for at least 7 months after the last dose of study intervention,
which corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s).  In addition, a second effective method of contraception, as 
described below, must be used.  The investigator should evaluate the effectiveness of 
the contraceptive method in relationship to the first dose of study intervention.

A WOCBP agrees not to donate eggs (ova, oocytes) for the purpose of reproduction 
during this period. The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenarchal.
2. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview.  The method of documentation should be recorded in the participant’s medical 
record for the study.


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3. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition, a

High FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

Female on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study.  Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
Highly Effective Methods That Have Low User Dependency
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed.  If not, an additional highly effective method of contraception 
should be used.  The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent
1. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;


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
Injectable.
2. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
3. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).


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10.5. Appendix 5: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.  
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks.  The increase in TBili typically occurs while 
AST/ALT is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be 
elevated within the same laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased.  This occurrence is still regarded as a 
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  In addition, the possibility 
of hepatic neoplasia (primary or secondary) should be considered.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, CK, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase.  Consideration should 
also be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood 
for further testing, as needed, for further contemporaneous analyses at the time of the 
recognized initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen/paracetamol (either by itself or as a 
coformulated product in prescription or over-the-counter medications), recreational drug, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) and collection of serum samples for acetaminophen/paracetamol drug and/or protein 
adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.






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10.7. Appendix 7: RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 
Guidelines
Adapted from E.A.  Eisenhauer, et al: New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1).  European Journal of Cancer 45 (2009) 228–247.  
CATEGORIZING LESION AT BASELINE
MEASURABLE LESIONS

Lesions that can be accurately measured in at least one dimension.

Lesions with longest diameter twice the slice thickness and at least 10 mm or greater 
when assessed by CT or MRI (slice thickness 5-8 mm).

Lesions with longest diameter at least 20 mm when assessed by Chest X-ray.  

Superficial lesions with longest diameter 10 mm or greater when assessed by caliper.  

Malignant lymph nodes with the short axis 15 mm or greater when assessed by CT.
NOTE: THE SHORTEST AXIS IS USED AS THE DIAMETER FOR MALIGNANT 
LYMPH NODES, LONGEST AXIS FOR ALL OTHER MEASURABLE LESIONS.  
NON-MEASURABLE DISEASE 
Non-measurable disease includes lesions too small to be considered measurable (including 
nodes with short axis between 10 and 14.9 mm) and truly non-measurable disease such as
pleural or pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, 
lymphangitic involvement of skin or lung, clinical lesions that cannot be accurately measured 
with calipers, abdominal masses identified by physical exam that are not measurable by 
reproducible imaging techniques.

Bone disease: Bone disease is non-measurable with the exception of soft tissue 
components that can be evaluated by CT or MRI and meet the definition of 
measurability at baseline.  

Previous local treatment: A previously irradiated lesion (or lesion patiented to other 
local treatment) is non-measurable unless it has progressed since completion of 
treatment.


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NORMAL SITES

Cystic lesions: Simple cysts should not be considered as malignant lesions and should 
not be recorded either as target or non-target disease.  Cystic lesions thought to 
represent cystic metastases can be measurable lesions, if they meet the specific 
definition above.  If non-cystic lesions are also present, these are preferred as target 
lesions.

Normal nodes: Nodes with short axis <10 mm are considered normal and should not 
be recorded or followed either as measurable or non-measurable disease.
RECORDING TUMOR ASSESSMENTS 
All sites of disease must be assessed at baseline.  Baseline assessments should be done as 
close as possible prior to study start.  For an adequate baseline assessment, all required scans 
must be done within 28 days prior to treatment and all disease must be documented 
appropriately.  If baseline assessment is inadequate, subsequent statuses generally should be 
indeterminate.  
TARGET LESIONS
All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total, 
representative of all involved organs, should be identified as target lesions at baseline.  
Target lesions should be selected on the basis of size (longest lesions) and suitability for 
accurate repeated measurements.  Record the longest diameter for each lesion, except in the 
case of pathological lymph nodes for which the short axis should be recorded.  The sum of 
the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions 
at baseline will be the basis for comparison to assessments performed on study.  

If two target lesions coalesce, the measurement of the coalesced mass is used.  If a 
large target lesion splits, the sum of the parts is used.

Measurements for target lesions that become small should continue to be recorded.  If 
a target lesion becomes too small to measure, 0 mm should be recorded if the lesion is 
considered to have disappeared; otherwise a default value of 5 mm should be 
recorded.
NOTE: WHEN NODAL LESIONS DECREASE TO <10 MM (NORMAL), THE 
ACTUAL MEASUREMENT SHOULD STILL BE RECORDED.


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NON-TARGET DISEASE 
All non-measurable disease is non-target.  All measurable lesions not identified as target 
lesions are also included as non-target disease.  Measurements are not required but rather 
assessments will be expressed as ABSENT, INDETERMINATE, PRESENT/NOT 
INCREASED, INCREASED.  Multiple non-target lesions in one organ may be recorded as a 
single item on the case report form (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple 
liver metastases’).
OBJECTIVE RESPONSE STATUS AT EACH EVALUATION
Disease sites must be assessed using the same technique as baseline, including consistent 
administration of contrast and timing of scanning.  If a change needs to be made, the case 
must be discussed with the radiologist to determine if substitution is possible.  If not, 
subsequent objective statuses are indeterminate.  
TARGET DISEASE

Complete Response (CR): Complete disappearance of all target lesions with the 
exception of nodal disease.  All target nodes must decrease to normal size (short axis 
<10 mm).  All target lesions must be assessed.

Partial Response (PR): Greater than or equal to 30% decrease under baseline of the 
sum of diameters of all target measurable lesions.  The short diameter is used in the 
sum for target nodes, while the longest diameter is used in the sum for all other target 
lesions.  All target lesions must be assessed.  

Stable: Does not qualify for CR, PR or Progression.  All target lesions must be 
assessed.  Stable can follow PR only in the rare case that the sum increases by less 
than 20% from the nadir, but enough that a previously documented 30% decrease no 
longer holds.  

Objective Progression (PD): At least a 20% increase in the sum of diameters of target 
measurable lesions above the smallest sum observed (over baseline if no decrease in 
the sum is observed during therapy), with a minimum absolute increase of 5 mm.  

Indeterminate.  Progression has not been documented, and 

one or more target measurable lesions have not been assessed; 

or assessment methods used were inconsistent with those used at baseline;

or one or more target lesions cannot be measured accurately (eg, poorly visible 
unless due to being too small to measure);


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
or one or more target lesions were excised or irradiated and have not reappeared 
or increased.  
NON-TARGET DISEASE

CR: Disappearance of all non-target lesions and normalization of tumor marker 
levels.  All lymph nodes must be ‘normal’ in size (<10 mm short axis).

Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level 
above the normal limits.  

PD: Unequivocal progression of pre-existing lesions.  Generally the overall tumor 
burden must increase sufficiently to merit discontinuation of therapy.  In the presence 
of SD or PR in target disease, progression due to unequivocal increase in non-target 
disease should be rare.  

Indeterminate: Progression has not been determined and one or more non-target sites 
were not assessed or assessment methods were inconsistent with those used at 
baseline.
NEW LESIONS 
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example due to its small size, continued assessment will clarify the etiology.  
If repeat assessments confirm the lesion, then progression should be recorded on the date of 
the initial assessment.  A lesion identified in an area not previously scanned will be 
considered a new lesion.
SUPPLEMENTAL INVESTIGATIONS

If CR determination depends on a residual lesion that decreased in size but did not 
disappear completely, it is recommended the residual lesion be investigated with 
biopsy or fine needle aspirate.  If no disease is identified, objective status is CR.

If progression determination depends on a lesion with an increase possibly due to 
necrosis, the lesion may be investigated with biopsy or fine needle aspirate to clarify 
status.  
SUBJECTIVE PROGRESSION
Patients requiring discontinuation of treatment without objective evidence of disease 
progression should not be reported as PD on tumor assessment CRFs.  This should be 
indicated on the end of treatment CRF as off treatment due to Global Deterioration of Health 
Status.  Every effort should be made to document objective progression even after 
discontinuation of treatment.  


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The objective response status is to be determined by evaluation of target and non-target 
disease as shown in Table 5 and Table 6.
Table 5.
Objective Response Status at Each Evaluation
Target Lesions
Non-target Disease
New Lesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD
No
PR
CR
Indeterminate or 
Missing 
No
PR
PR
Non-CR/Non-PD, 
Indeterminate, or 
Missing
No
PR
SD
Non-CR/Non-PD, 
Indeterminate, or 
Missing
No
Stable
Indeterminate or 
Missing
Non-PD
No
Indeterminate
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Table 6.
Objective Response Status at each Evaluation for Patients with 
Non-Target Disease Only
Non-target Disease
New Lesions
Objective Status
CR
No
CR
Non-CR/Non-PD
No
Non-CR/Non-PD
Indeterminate
No
Indeterminate
Unequivocal progression
Yes or No
PD
Any
Yes
PD


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Determination of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest sum 
on study).




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10.9. Appendix 9: Bone Marrow Reserve in Adults 
Adapted from R.E. ELLIS: The Distribution of Active Bone Marrow in the Adult, Phy. Med. 
Biol. 5, 255-258, 1961
Marrow Distribution of the Adult
SITE
MARROW
wt. (g)
FRACTION 
RED 
MARROW
AGE 40
RED 
MARROW
wt. (g)
AGE 40
% TOTAL
RED MARROW
CRANIUM
Head :
136.6
AND
Cranium
165.8
0.75
124.3
13.1
13.1
MANDIBLE
Mandible
16.4
0.75
12.3
Upper Limb Girdle :
86.7
HUMERI,
SCAPULAE,
2 Humerus, 
head & neck
26.5
0.75
20.0
8.3
8.3
CLAVICLES
2 Scapulae 
67.4
0.75
50.5
2 Clavicles
21.6
0.75
16.2
Sternum
39.0
0.6
23.4
2.3
Ribs : 
82.6
1 pair
10.2
All 0.4
4.1
2 
12.6
5.0
3
16.0
6.4
STERNUM
4
18.6
7.4
AND
5
23.8
9.5
7.9
10.2
RIBS
6
23.6
9.4
7
25.0
10.0
8
24.0
9.6
9
21.2
8.5
10
16.0
6.4
11
11.2
4.5
12
4.6
1.8
Sacrum 
194.0
0.75
145.6
13.9
PELVIC 
BONES
2 os coxae
310.6
0.75
233.0
22.3
36.2
FEMUR
2 Femoral head 
and neck
53.0
0.75
40.0
3.8
3.8


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Marrow Distribution of the Adult (cont’d)
SITE
MARROW
wt. (g)
FRACTION RED 
MARROW
AGE 40
RED 
MARROW
wt. (g)
AGE 40
% TOTAL
RED MARROW
Vertebrae
(Cervical):
35.8
1
6.6
All 0.75
5.0
2
8.4
6.3
3
5.4
4.1
3.4
4
5.7
4.3
5
5.8
4.4
6
7.0
5.3
7
8.5
6.4
Vertebrae
(Thoracic):
147.9
1 pair
10.8
All 0.75
8.1
2
11.7
8.8
3
11.4
8.5
4
12.2
9.1
VERTEBRAE
5
13.4
10.1
14.1
28.4
6
15.3
11.5
7
16.1
12.1
8
18.5
13.9
9
19.7
14.8
10
21.2
15.9
11
21.7
16.3
12
25.0
18.8
Vertebrae
(Lumbar) :
114.1
1 pair
27.8
All 0.75
20.8
2
29.1
21.8
10.9
3
31.8
23.8
4
32.1
24.1
5
31.4
23.6
TOTAL
1497.7
1045.7
100.0
100.0


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10.10. Appendix 10: Cockcroft-Gault Formula
CLcr={((l40–age) x weight)/(72xSCr)}x 0.85 (if female)
Abbreviations/ Units
CLCr (creatinine clearance) = mL/minute
Age = years
Weight = kg
SCr (serum creatinine) = mg/dL


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10.11. Appendix 11: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
AESI
adverse events of special interest
AIDS
acquired immunodeficiency syndrome
ALT
alanine aminotransferase
AML
Acute Myeloid Leukemia
ANC
absolute neutrophil count
ANOVA
Analysis of Variance
AST
aspartate aminotransferase
AUC
Area Under the Concentration-Time Curve
AUC(0-24)
Area Under the Concentration-Time Curve From Time 0 to 
24 Hours
AUCinf
area under concentration-time curve from time 0 to infinity
AUClast
Area under the plasma concentration versus time curve from time 
zero to the time of Clast
AUCsd,inf
Area under the plasma concentration versus time curve from time 
zero to infinity at steady state
AUCsd,τ
Area under the plasma concentration versus time curve within a 
dosing interval of τ (=24 hr) at steady state
AUCτ
Area under the plasma concentration versus time curve from time 
zero to the time τ
AV
atrioventricular
-hCG
beta-human chorionic gonadotropin
BCRP
Breast Cancer Resistance Protein
BICR
blinded independent central review
bpm
beats per minute
BP
blood pressure
BRCA
Breast Cancer gene
BSA
bovine serum albumin
BSE
bridging study evaluation
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CLcr
creatinine clearance 
CL/F
apparent oral clearance
Cmax
maximum plasma concentration
Cmin
Minimum Plasma Concentration


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Abbreviation
Term
ADME
absorption, distribution, metabolism, and excretion
CONSORT
Consolidated Standards of Reporting Trials
CR
complete response
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
computed tomography 
CT
clinical trial
Ctrough
pre dose plasma concentration
CTCAE
Common Terminology Criteria for Adverse Events
DDI
Drug-Drug Interaction
DILI
drug-induced liver injury
DOR
Duration of response
DLT
dose limiting toxicity
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DRE
disease-related event
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDP
exposure during pregnancy
eGFR
Estimated Glomerular Filtration Rate
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
fu
Fraction of Unbound
gBRCAm
germline BRCA-mutated
GCP
Good Clinical Practice
GI
Gastrointestinal
G-CSF
granulocyte colony-stimulating factor
GGT
gamma-glutamyl transferase
GM-CSF
granulocyte-macrophage colony-stimulating factor
HBcAb
hepatitis B core antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus


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Abbreviation
Term
ADME
absorption, distribution, metabolism, and excretion
HIPAA
Health Insurance Portability and Accountability Act
HR
heart rate
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IMP
investigational medicinal product
IND
investigational new drug
INR
international normalized ratio
IQR
interquartile range
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log
IRB
institutional review board
IRT
interactive response technology
IWR
interactive Web-based response
kel
Constant of elimination rate
LFT
liver function test
mCRPC
metastatic castration resistant prostate cancer
MedDRA
Medical Dictionary for Regulatory Activities
MD
multiple dose
MDS
Myelodysplastic Syndrome
MRI
magnetic resonance imaging
MTD
Maximum Tolerated Dose
N/A
not applicable
NCI
National Cancer Institute
NIMP
noninvestigational medicinal product
NMPA
National Medical Products Administration
NMSC
nonmelanoma skin cancer
ORR
objective response rate
PARP
Poly(Adenosine Diphosphate-Ribose) Polymerase
PD
disease progression
PD-L1
programmed death ligand 1
PFS
progression-free survival
P-gp
P-Glycoprotein
PK
pharmacokinetic(s)
PR
partial response
PS
Performance Status
PT
preferred term 
PVC
premature ventricular contraction/complex
QD
Once Daily


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Abbreviation
Term
ADME
absorption, distribution, metabolism, and excretion
OR
objective response
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
Rac
observed accumulation ratio
RBC
red blood cell
Rss
steady-state accumulation ratio
PCT
physician’s choice treatment
RECIST
Response Evaluation Criteria in Solid Tumors
RP2D
recommended Phase 2 dose
SAE
serious adverse event
SAP
statistical analysis plan
SCLC
small-cell lung cancer
SCr 
serum creatinine
SD
single dose
SD
stable disease
SoA
schedule of activities
SOC
system organ class 
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
t1/2
Terminal Half-Life
TBili
total bilirubin
TEAEs
treatment-emergent adverse events
Tmax
Time to Reach Maximum Plasma Concentration
ULN
upper limit of normal
US
United States
Vz/F
Apparent volume of distribution
WBC
white blood cell
WOCBP
woman of childbearing potential

ongoing/continuous event


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11. REFERENCES
1
Shen Y, Aoyagi-Scharber M, Wang B. Trapping poly (ADP-ribose) polymerase. 
J Pharmacol Exp Ther 2015 Jun; 353(3):446-57.
2
Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by clinical PARP 
inhibitors. Cancer Res 2012 Nov 1; 72(21):5588-99.
3
Murai J, Huang SY, Renaud A, et al. Stereospecific PARP trapping by BMN 673 and 
comparison with olaparib and rucaparib. Mol Cancer Ther 2014 Feb; 13(2):433-43.
4
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: 
sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: 
E359–86.
5
Zhou M, Wang H, Zhu J, et al. Cause-specific mortality for 240 causes in China during 
1990–2013: a systematic subnational analysis for the Global Burden of Disease Study 
2013. Lancet 2016; 387: 251–72.
6
Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 
1995-2009: analysis of individual data for 25 676 887 patients from 279 
population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385: 
977-1010.
7
Recommendations for the Use of WBC Growth Factors: American Society of Clinical 
Oncology Clinical Practice Guideline Update JCO Oct 1, 2015:3199-212.

SAP_001.pdf: 
Talazoparib 
Protocol C3441049
Statistical Analysis Plan, 18 March 2020
PFIZER CONFIDENTIAL 
Page 1
Protocol C3441049
AN OPEN-LABEL, SINGLE-ARM, PHASE 1 STUDY OF PHARMACOKINETICS, 
SAFETY AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB MONOTHERAPY IN 
CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS
Statistical Analysis Plan 
(SAP)
Version:
1
Date:
18-Mar-2020


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Statistical Analysis Plan, 18 March 2020
PFIZER CONFIDENTIAL 
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Objectives, Endpoints, and Estimands............................................................6
2.2. Study Design .............................................................................................................6
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ..................................................................................................................7
3.1. Primary Endpoint(s) ..................................................................................................7
3.2. Secondary Endpoint(s) ..............................................................................................9
3.2.1. Efficacy.........................................................................................................9
3.3. Exploratory Endpoint(s)............................................................................................9
3.4. Baseline Variables.....................................................................................................9
3.5. Safety Endpoints .....................................................................................................10
3.5.1. Adverse Events...........................................................................................10
3.5.2. Laboratory Data..........................................................................................11
3.5.3. Electrocardiogram measurements...............................................................11
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................11
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................12
5.1. Hypotheses and Decision Rules ..............................................................................12
5.1.1. Hypotheses and Sample Size......................................................................12
5.2. General Methods .....................................................................................................12
5.2.1. Data Handling after the Cutoff Date...........................................................12
5.2.2. Pooling of Centers ......................................................................................12
5.2.3. Definition of Study Day..............................................................................12
5.2.4. Definition of Cycle and Cycle Day ............................................................12
5.2.5. Definition of Start of New Anti-cancer Drug Therapy...............................13
5.2.6. Definition of Start of New Anti-cancer therapy .........................................13
5.2.7. Date of Last Contact ...................................................................................14
5.2.8. Tumor Assessment Date.............................................................................15
5.2.9. Adequate Baseline Tumor Assessment ......................................................15


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5.2.10. Adequate Post-baseline Tumor Assessment.............................................15
5.2.11. Nominal and Unscheduled Visits .............................................................15
5.2.12. Standard Deviations and Reporting Conventions.....................................15
5.2.13. Analyses for Continuous and Qualitative Variables.................................16
5.2.14. Analyses for Time-to-Event Endpoints ....................................................16
5.3. Methods to Manage Missing Data ..........................................................................16
5.3.1. Missing Pharmacokinetic Data...................................................................16
5.3.2. Missing ECG Data......................................................................................17
5.3.3. Handling of Incomplete or Missing Dates..................................................17
5.3.3.1. Adverse Events..........................................................................17
5.3.3.2. Exposure....................................................................................18
5.3.3.3. Date of Death ............................................................................18
5.3.3.4. Date of Start of New Anti-cancer Therapy ...............................19
5.3.3.5. Other Dates................................................................................20
6. ANALYSES AND SUMMARIES ......................................................................................21
6.1. Primary Endpoint(s) ................................................................................................21
6.1.1. Pharmacokinetic parameters.......................................................................21
6.1.2. PK concentrations.......................................................................................21
6.2. Secondary Endpoint(s) ............................................................................................22
6.2.1. Objective response (OR).............................................................................22
6.2.2. Duration of Response (DOR) .....................................................................23
6.3. Other Endpoint(s)....................................................................................................23
6.4. Subset Analyses.......................................................................................................23
6.5. Baseline and Other Summaries and Analyses.........................................................23
6.5.1. Baseline Summaries....................................................................................23
6.5.1.1. Demographic Characteristics ....................................................23
6.5.1.2. Medical History.........................................................................23
6.5.1.3. Disease Characteristics..............................................................24
6.5.1.4. Prior Anti-cancer Therapy.........................................................24
6.5.2. Study Conduct and Participant Disposition................................................25
6.5.2.1. Disposition ................................................................................25
6.5.2.2. Protocol Deviations...................................................................25


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6.5.3. Study Treatment Exposure .........................................................................25
6.5.3.1. Exposure to talazoparib.............................................................26
6.5.3.2. Dose Reductions, Interruptions.................................................26
6.5.4. Concomitant Medications and Nondrug Treatments..................................27
6.5.5. Subsequent anti-cancer therapies................................................................27
6.6. Safety Summaries and Analyses .............................................................................27
6.6.1. Adverse Events ...........................................................................................27
6.6.1.1. Adverse Events of Special Interest............................................29
6.6.2. Deaths .........................................................................................................29
6.6.3. Laboratory Data..........................................................................................29
6.6.4. Vital Signs ..................................................................................................32
6.6.5. Electrocardiograms.....................................................................................33
6.6.6. Performance Status.....................................................................................34
6.6.7. Physical Examination .................................................................................34
6.6.8. Medication errors........................................................................................34
7. INTERIM ANALYSES.......................................................................................................34
8. APPENDICES .....................................................................................................................35
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................5
APPENDICES
Appendix 1. List of Abbreviations...........................................................................................35


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Statistical Analysis Plan, 18 March 2020
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1. VERSION HISTORY
This Statistical Analysis Plan (SAP) for study C3441049 is based on the protocol dated 
27January2020.  
Table 1.
Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
1
14 Feb 2020
Original 27 
Jan 2020
N/A
N/A
2. INTRODUCTION
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in Study C3441049.  This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment.
Any deviations from this analysis plan will be described in the Clinical Study Report.
The primary analysis will include all data up to a data cutoff date which will be determined 
by the completion of the first cycle, i.e., cycle 1 for the last patient dosed (37 days since last 
patient first dosed ). All summaries and analyses will include all data pertaining to 
visits/assessments performed up to and including the data cutoff date.


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2.1. Study Objectives, Endpoints, and Estimands
Objectives
Estimands
Endpoints
Primary: 
Primary:
Primary: 

To characterize the single and 
steady-state pharmacokinetics 
(PK) of single-agent talazoparib.
Not applicable

Single Dose (SD) - Cmax, Tmax, AUClast, 
AUC, CL/F, and Vz/F and t½, and 
AUCinf as data permit.  

Multiple Dose (MD) - Cmax, Tmax, C min, 
AUC, CL/F, Rac (AUC/AUCsd,) and 
Rss (AUC/AUCsd,inf) as data permit.
Secondary: 
Secondary:
Secondary: 

To evaluate the overall safety 
profile.

To assess preliminary evidence of 
anti-tumor activity of single agent 
talazoparib.
Not applicable
Safety 

Adverse Events as characterized by type, 
frequency, severity (as graded by NCI 
CTCAE version 4.03), timing, 
seriousness, and relationship to 
talazoparib.

Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI CTCAE 
version 4.03), and timing.

Vital signs and ECG

Concomitant medication use
Efficacy

Unconfirmed ORR 

DOR 
2.2. Study Design
This is an open-label, single arm, Phase 1 study of talazoparib monotherapy to primarily 
evaluate the PK and safety of single agent talazoparib 1 mg Once Daily (QD) in chinese 
participants with advanced solid tumors who are resistant to standard therapy or for whom no 
standard therapy is available.
Approximately 15 participants will be enrolled to obtain about 12 evaluable participants to 
support metastatic castration resistant prostate cancer (mCRPC) and other future potential 
indication registrations in China.  
Study treatment will be given once daily in 28-day cycles. To understand the single-dose 
safety and single-dose PK assessments of talazoparib, a lead-in period preceeding the 
continuous daily doses will be included. In the 9-day lead-in period, a single lead-in dose will 
be given on Day -9 and PK samples will be collected at pre-dose and 0.50, 1, 2, 4, 8, 24, 48, 
96, 168 and 216 hours post dose. No talazoparib will be administered during the interval 
between the lead-in single dose and Day 1 of the first cycle. Additionally, to characterize the 
steady state PK profile, serial PK samples after multiple doses will be collected on Day 22 of 


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Statistical Analysis Plan, 18 March 2020
PFIZER CONFIDENTIAL 
Page 7
the first cycle at pre-dose, 0.50, 1, 2, 4, 8, 24 hours post dose. Pre-dose samples will be 
collected on C1D21, C1D23.
Tumor assessments are to be done on D29 (±7 days window) and every 8 weeks (±7 days 
window) thereafter for the initial 12 cycles regardless of any dose interruptions or dose 
delays.  After completion of Cycle 12 (at the beginning of week 45), tumor assessment will 
be done per local standard practice.  Tumor assessments should be repeated at the end of 
study visit if more than 6 weeks have passed since the last evaluation.  
Pharmacokinetic parameters and plasma concentration data will be summarized as the 
primary analysis for this study. In addition, safety data including adverse events (AE), 
laboratory abnormalities and electrocardiogram measurements (ECG), as well as efficacy 
information reflected by objective response (OR) and duration of response (DOR) will also 
be summarized and estimated.
This study will not use a data monitoring committee (DMC).
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND
CONVENTIONS
3.1. Primary Endpoint(s)
PK parameters of talazoparib following single dose administration will be derived from the 
concentration-time profiles as shown in the table below.
Parameter
Definition
Method of determination
Cmax
Maximum plasma 
concentration
Observe directly from data
Tmax
First time at which Cmax is 
observed
Observe directly from data as time of first 
occurrence
AUClast
Area under the plasma 
concentration versus time 
curve from time zero to the 
time of the last quantifiable 
concentration (Clast)
Linear/Log trapezoidal method
AUCτ
Area under the plasma 
concentration versus time 
curve from time zero to the 
time τ(=24 hr) 
Linear/Log trapezoidal method
AUCinf
Area under the plasma 
concentration versus time 
AUClast + (Clast/kel), where Clast is the predicted 
plasma concentration at the last quantifiable 
time point estimated from the log-linear 
regression analysis; kel is the terminal phase 


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curve from time zero 
extrapolated to infinite time
rate constant calculated by a linear regression 
of the log-linear concentration-time curve.
CL/F
Apparent oral clearance
Dose/AUCinf
Vz/F
Apparent volume of 
distribution
Dose/(AUCinf * kel) 
t1/2
Terminal plasma half-life
Loge(2)/kel
PK parameters of talazoparib following multiple dose administration will be derived from the 
concentration-time profiles as shown in the table below.
Parameter
Definition
Method of determination
Cmax
Maximum plasma concentration 
observed during the dosing interval
Observe directly from data
Tmax
First time at which Cmax is observed
Observe directly from data as 
time of first occurrence within τ 
at steady state
Cmin
Minimum plasma concentration observed 
during the dosing interval
Observe directly from data
AUCτ
Area under the plasma concentration 
versus time curve within a dosing 
interval of τ (=24 hr) at steady state
Linear/Log trapezoidal method
CL/F
Apparent clearance
Dose/AUCτ
Rac
Observed accumulation ratio
Rac=AUCτ /AUCsd,τ, where 
AUCsd,τ is AUC24
Rss
Steady-state accumulation ratio
Rss=AUCτ /AUCinf, where 
AUCinf is from single dose.
Actual PK sampling times will be used in the derivation of PK parameters.


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3.2. Secondary Endpoint(s)
3.2.1. Efficacy 
Objective response (OR)
Objective response by investigator assessment is defined as a complete response (CR) or 
partial response (PR) according to the RECIST version 1.1 recorded from Cycle 1 Day 1 
(C1D1) until disease progression, start of subsequent anti-cancer therapy or death due to any 
cause. 
Given the exploratory nature of the efficacy endpoint, confirmation of response is not 
required.  A participant will be considered to have achieved an OR if the participant has a 
complete response (CR) or partial response (PR) according to RECIST v.1.1 definitions. 
Otherwise, the participant will be considered a non-responder in the OR rate analysis. 
Additionally, participants with inadequate data for tumor assessment (eg, no baseline 
assessment or no follow-up assessments) will be considered as non-responders in the OR rate 
analysis. If participants with non-measurable disease are enrolled, they are included in the 
aforementioned calculation of OR rate as well, however, a subgroup calculation of OR rate 
will be conducted among participants who are with measurable disease at baseline.
Duration of response (DOR)
For participants with a objective response (CR or PR), duration of response (DOR) is the 
time from first documentation of CR or PR to date of first documentation of objective 
progression or death. Date of first documentation of PD and date of first documentation of 
CR or PR will be based on investigator assessment of response. DOR data will be censored 
on the date of the last tumor assessment on study for participants who do not have objective 
tumor progression and who do not die due to any cause while on study. DOR will only be 
calculated for the subgroup of participants with an objective response. 
3.3. Exploratory Endpoint(s)
Not applicable.
3.4. Baseline Variables
Start and end dates of study treatment:
The date of first dose (start date) of study treatment is the earliest date of non-zero dosing of 
the study drug, which is in the lead-in period.
The date of last dose of study treatment is the latest date of non-zero dosing of the study 
drug.
Definition of baseline: 
No windowing will be applied when defining baseline.  


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For efficacy analyses and baseline characteristics associated with tumor assessments (e.g. 
number of sites of disease at baseline), the last assessment prior to the first dose will serve as 
the baseline assessment.  
For safety (including Eastern Cooperative Oncology Group (ECOG) performance status)
analysis the last assessment performed on or prior to date of the first dose of study treatment 
will serve as the baseline assessment.  If there are no observations meeting these criteria, then 
baseline is considered missing.  
Participants who start treatment and discontinue from the study on the same day may have 
two different sets of data collected on the start date (one during study and one in the End of 
Treatment (EOT) visit. Data reported at the EOT visit are not eligible for baseline selection.
Triplicate ECGs will be collected on lead in visit and a single ECG will be collected at all 
other scheduled visits; therefore the baseline for each ECG measurement is the average of the 
pre-dose measurements on the start date.  If the triplicate ECG are incomplete (only 2 or 
single), the average of the 2 or the single will be used as baseline. Unscheduled assessment
on the start date will not be included in the calculation of the average.  If the triplicate ECGs 
were not collected, the single ECG closest but prior to the start date will be used. 
3.5. Safety Endpoints
Safety endpoints will be summarized based on the on-treatment period unless otherwise 
specified.
On-treatment is defined as the time from the first dose date of study treatment through
minimum (28 days after last dose/start day of new anti-cancer drug therapy – 1 day).  The 
start of new anti-cancer drug therapy after the first dose of study treatemtn is derived as 
outlined in Section 5.2.5. Adverse events occurring on the same day as the first dose of study 
treatment will be considered to have occurred during the on-treatment period. All other 
assessments which occur on the same day as the first dose of study treatment will be 
considered baseline assessments (see Section 3.4 for the definition of baseline).
Safety data collected outside the on-treatment period as described above will be listed but not 
summarized.
3.5.1. Adverse Events
Adverse events (AEs) will be coded to preferred term (PT) and system organ class (SOC) 
using the Medical Dictionary for Regulatory Activities (MedDRA) and classified by severity 
using the National Cancer Institutes (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE), version 4.03.  An adverse event is considered treatment emergent relative 
to a given treatment, i.e., Treatment-Emergent Adverse Events (TEAEs), if the event start 
date is during the on-treatment period (including on the date of first dose). The focus of AE 
summaries will be on TEAEs.


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An event will be considered treatment related if the investigator considered the event related 
to the study drug.The number and percentage of participants who experienced any AE, 
serious AE (SAE), treatment-related AE, and treatment-related SAE will be summarized 
according to worst toxicity grades. The summaries will present AEs on the entire study 
period as well as by relatedness to study treatment. 
Adverse Events of Special Interest (AESI)
AESIs include Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), and 
second primary malignancies events.
3.5.2. Laboratory Data
Hematology and chemistry result will be programmatically graded according to the NCI 
CTCAE version 4.03 for relevant parameters. Additional details are provided in Section 
6.6.3.
3.5.3. Electrocardiogram measurements
All ECGs obtained during the study will be evaluated for safety. Except for Day -9, single  
ECG measurement is taken for all other visits.The average of the triplicate ECG 
measurements at baseline if not single measurement will be used for the statistical analysis 
and all data presentations. 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
Only participants who signed informed consent will be included in the analysis sets below.
Population
Description
PK concentration 
population
Defined as all participants enrolled and treated who have at 
least 1 PK concentration in the single-dose and/or multiple-dose 
PK part.
PK parameter analysis 
population
Defined as all participants enrolled and treated who have at 
least 1 of the PK parameters of primary interest in the single-
dose and/or multiple-dose PK part.
PK evaluable analysis set
Defined as all participants in the PK parameter analysis set who 
complete both the single dose PK and multiple dose PK parts 
without major protocol deviations.
Safety
Includes all enrolled participants who receive at least one dose 
of study medication.


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5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
5.1.1. Hypotheses and Sample Size 
To support registration of mCRPC and other future potential indications in China, 12  
evaluable participants will be needed to characterize Chinese PK profile based on available 
talazoparib PK data globalwise and with the intention to satisfy regulatory requirement by 
China National Medical Products Administration (NMPA) in terms of PK evaluation in 
Chinese population. Considering non-evaluable participants, it is estimated that 
approximately 15 patients are needed.
All analyses will be descriptive and no hypothesis testing will be conducted. 
5.2. General Methods
5.2.1. Data Handling after the Cutoff Date
Data after the cutoff date may not undergo the cleaning process and will not be displayed in 
any listings or used for summary statistics, statistical analyses or imputations.
5.2.2. Pooling of Centers
In order to provide overall estimates of treatment effects, data will be pooled across centers.  
The ‘center’ factor will not be considered in statistical models or for subgroup analyses due 
to the limited sample size in this study and the relatively high number of participating centers 
in contrast to the anticipated small number of participants enrolled at each center.
5.2.3. Definition of Study Day
The study day for assessments occurring on or after the first dose of study treatment (e.g., 
adverse event onset, tumor measurement) will be calculated as:
Study day = Date of the assessment/event - start date of study treatment + 1. 
The study day for assessments occurring prior to the first dose of study treatment (e.g., 
baseline characteristics, medical history) will be negative and calculated as:
Study day = Date of the assessment/event –start date of study treatment.
The study day will be displayed in all relevant data listings.
5.2.4. Definition of Cycle and Cycle Day
Cycle start and end dates are derived per participant and not per study treatment. 
Study treatment will be given once daily in 28-day cycles; therefore the nominal cycle length 
is 28 days.


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
For Cycle X, the actual cycle start date for each participant is:

the earliest start date of dosing in the Cycle X day 1 visit CRF exposure page, if 
the participant received study treatment on that visit (i.e., any study drug with 
dose>0 at that visit).

the first day of assessments in the Cycle X day 1 visit, if the participant did not 
receive study treatment on that visit (i.e., all study drugs had dose=0 at that visit).  
Use start date in the exposure page if available; if start date is not available then 
use date of collection of vital signs on Cycle X day 1 visit.

For all but the last cycle:

actual cycle stop date is calculated as the start date of the next cycle minus one 
day. 

actual cycle duration is calculated from Day 1 of a cycle to the day prior to Day 1 
of the next cycle, as follows: 
Actual Cycle Duration (weeks) = (cycle stop date – cycle start date + 1) / 7

For the last cycle, actual cycle duration is the planned cycle duration and actual cycle 
stop date is calculated as actual cycle start date + 28 – 1 day.
The cycle day will be calculated as:
Cycle day = Date of the assessment/event – cycle start date + 1.
5.2.5. Definition of Start of New Anti-cancer Drug Therapy
Start date of new anti-cancer drug therapy is used to determine the end of the on-treatment 
period (see Section 3.5) in safety analysis.
The start date of new anti-cancer drug therapy is the earliest start date of anti-cancer drug 
therapy recorded in the ‘Follow-up Cancer Therapy’, ‘Follow-up Radiation Therapy ’and 
‘Follow-up Surgery’ eCRF pages that is after the first dose of study treatment. When start 
date of anti-cancer drug therapy is missing or partially missing, the imputation rules 
described in Section 5.3.3.4 should be applied using only data from the ‘Follow-up Cancer 
Therapy’, ‘Follow-up Radiation Therapy ’and ‘Follow-up Surgery’ eCRF pages.
5.2.6. Definition of Start of New Anti-cancer therapy
Start date of new anti-cancer therapy (drug, radiation, surgery) is used for efficacy analyses 
(see Section 6.1).
The start date of new anti-cancer therapy is the earliest date after first dose of talazoparib
amongst the following:


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
Start date of anti-cancer drug therapy recorded in the ‘Follow-up Cancer Therapy’ 
eCRF pages.

Start date of radiation therapy recorded in ‘Concomitant Radiation Therapy’, and 
‘Follow-up Radiation Therapy’ eCRF pages with ‘Treatment Intent’ = ‘Curative in 
intent’.

Surgery date recorded in ‘Concomitant Surgery’, and ‘Follow-up Surgery’ eCRF 
pages when ‘Surgery Outcome’ = ‘Resected’ or ‘Partially Resected’.  
When start date of anti-cancer therapy is missing or partially missing, the imputation rules 
described in Section 5.3.3.4 should be applied using ‘Follow-up Cancer Therapy’, 
‘Concomitant Radiation Therapy’, ‘Follow-up Radiation Therapy’, ‘Concomitant Surgery’, 
and ‘Follow-up Surgery’ eCRF pages.
5.2.7. Date of Last Contact
The date of last contact will be derived for participants not known to have died at the data 
cutoff date using the latest complete date (i.e. imputed dates will not be used in the 
derivation) among the following:

All assessment dates (e.g. blood draws (laboratory, Pharmacokinetics (PK)), vital 
signs, physical exam, performance status, ECG, tumor assessments);

Start and stop dates of concomitant therapies including non-drug treatments or 
procedures;

Start and end dates of anti-cancer therapies administered after study treatment 
discontinuation including systemic therapy, radiation, and surgeries;

AE start and end dates;

Last date of contact collected on the ‘Survival Follow-up’ CRF (do not use date of 
survival follow-up assessment unless status is ‘alive’);

Study treatment start and end dates;

Date of discontinuation on disposition CRF pages (do not use if reason for 
discontinuation is lost to follow-up or death).
Only dates associated with actual examinations of the participant will be used in the 
derivation.  Dates associated with a technical operation unrelated to participant status such as 
the date a blood sample was processed or dates data were entered into the CRF will not be 
used. Assessment dates after the data cutoff date will not be applied to derive the last contact 
date.


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5.2.8. Tumor Assessment Date
The Date of Tumor Assessment at each nominal timepoint as provided by the investigator on 
the IOTA CRF will be utilized for the respective analyses.  
5.2.9. Adequate Baseline Tumor Assessment
Adequate baseline is defined using the following criteria:

All baseline assessments must be within 28 days prior to and including the date of
first dosing date.

All documented lesions must have non-missing assessments (i.e. non missing 
measurements for target lesions and non missing lesions status at baseline for non-
target lesions).
5.2.10. Adequate Post-baseline Tumor Assessment
An adequate assessment is defined as an assessment where a response of CR, PR, Stable 
Disease (SD), non-CR/non-PD, or PD has been provided by the investigator.  Timepoints 
where the response is not evaluable or no assessment was performed will not be used for 
determining the censoring date.
5.2.11. Nominal and Unscheduled Visits
For all algorithms and analyses, visit labels as specified on the CRF will be used as the 
nominal timepoint (i.e. assessment will not be slotted).
Unless otherwise specified, unscheduled assessments will not be displayed in summary tables 
by nominal visit/timepoint. Unscheduled assessments will be used when deriving baseline 
and worst case on-treatment for safety (except where noted for baseline ECGs). Additionally, 
unscheduled assessments will be used for efficacy analyses (e.g. defining date of 
progression/censoring, best overall response, date of last contact).
5.2.12. Standard Deviations and Reporting Conventions
The following conversion factors will be used to convert days into weeks, months or years:   
1 week = 7 days, 1 month = 30.4375 days, 1 year = 365.25 days.
Demographics and physical measurements:

Age [years]: year of given informed consent - year of birth;

Body Mass Index (BMI, kg/m2) = weight (kg) / [height (m)]2.
For reporting conventions, mean and median should generally be displayed one more 
decimal place than the raw data and standard deviation should be displayed to two more 
decimal places than the raw data. Percentages will be reported to one decimal place. The 
rounding will be performed to closest integer / first decimal using the common mid-point 


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between the two consecutive values. Eg, 5.1 to 5.4 will be rounded to an integer of 5, and 5.5 
to 5.9 will be rounded to an integer of 6.
5.2.13. Analyses for Continuous and Qualitative Variables
Continuous variables will be summarized using descriptive statistics ie, number of non-
missing values and number of missing values [ie, n (missing)], mean, median, standard 
deviation (SD), minimum, maximum and first and third quartile (Q1 and Q3). 
Qualitative variables will be summarized by frequency counts and percentages. Unless 
otherwise specified, the calculation of proportions will include the missing category. 
Therefore counts of missing observations will be included in the denominator and presented 
as a separate category.
In case the analysis refers only to certain visits, percentages will be based on the number of 
participants still present in the study at that visit, unless otherwise specified
5.2.14. Analyses for Time-to-Event Endpoints
If data permits, Kaplan-Meier estimates (product-limit estimates) will be presented together 
with a summary of associated statistics including the median time with two-sided 95% CIs. 
Probabilities of an event at particular timepoints will be estimated with corresponding two-
sided 95% CIs.  The CIs for the median will be calculated according to Brookmeyer and 
Crowley and the CIs for the survival function estimates at particular timepoints will be 
derived using the log(-log) method .  
5.3. Methods to Manage Missing Data
Unless otherwise specified, all data will be evaluated as observed, and no imputation method 
for missing values will be used.
Any imputations will occur at the analysis dataset level. Additionally, in all data listings 
imputed values will be presented and flagged as imputed.
Missing statistics, e.g. when they cannot be calculated, should be presented as ‘ND’ for not 
done, ‘NR’ for not reached or ‘NA’ for not applicable.  For example, if N=1, the measure of 
variability cannot be computed and should be presented as ‘ND’ or ‘NA’. 
5.3.1. Missing Pharmacokinetic Data
Concentrations below the limit of quantification
For all calculations, figures, and estimation of individual pharmacokinetic parameters, all 
concentrations assayed as below the level of quantification (BLQ) will be set to zero. In log-
linear plots these values will not be represented.  The BLQ values will be excluded from 
calculations of geometric means and their confidence intervals. A statement similar to ‘All 
values reported as BLQ have been replaced with zero’ should be included as a footnote to the 
appropriate tables and figures.  In listings BLQ values will be reported as below lower limit 


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of quantification (“<LLOQ”), where LLOQ will be replaced with the corresponding value 
from the analytical assay used.
Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of median profiles, concentrations will be set to missing if one 
of the following cases is true:

A concentration has been reported as ND (i.e., not done) or NS (i.e., no sample);

A deviation in sampling time is of sufficient concern or a concentration has been 
flagged as anomalous by the clinical pharmacologist.
Summary statistics will not be presented at a particular timepoint if more than 50% of the 
data are missing.  For analysis of pharmacokinetic concentrations, no values will be imputed 
for missing data.
Actual PK sampling times will be used in the derivation of PK parameters.  If a PK 
parameter cannot be derived from a patient’s concentration data due to insufficient sampling, 
the parameter will be coded as NC (ie, not calculated). If PK parameter cannot be derived 
from a patient’s concentration data due to discontinuation of treatment, the parameter will be 
coded as NS (ie, no sample).
In summary tables of concentration-time profiles or PK parameters, statistics will be 
calculated by setting NC values to missing; and statistics will not be presented for a 
particular treatment if more than 50% of the data are not collected, not calculated, or below 
LLOQ.  For statistical analyses (i.e. analysis of variance), PK parameters coded as NC will 
also be set to missing.
If an individual participant has a known biased estimate of a PK parameter (due for example 
to a deviation for the assigned dose level), this will be footnoted in summary tables and will 
not be included in the calculation of summary statistics or statistical analyses.
5.3.2. Missing ECG Data
For QTc analyses, no values will be imputed for missing data. For triplicate measurements 
taken at baseline, if one or two of the triplicate measurements for an ECG parameter are 
missed, the average of the remaining two measurements or the single measurement can be 
used in the analyses. If all triplicate measurements are missing  for an ECG parameter, no 
values will be imputed.  
5.3.3. Handling of Incomplete or Missing Dates
5.3.3.1. Adverse Events
AE Onset Date:
The following imputation rules apply if the event is unique for a participant or it is the first of 
a series of similar events; otherwise, the AE Onset Date will not be imputed:


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If the AE start date is missing, and if the date of first dose is less than AE end date, then the 
start date will be assigned as the date of first dose. Otherwise if the date of first dose is after
the AE end date then the AE start date will be imputed as the earliest of non-missing AE end 
date or informed consent date.
AE Stop Date:
Ongoing events will have the AE Stop Date set to one of the following values: if the AE end 
date is missing then the end date will be imputed as the latest of the Subject 
Withdrawal/Completion date, death date, last dose of study treatment, or AE start date.
Imputation will only occur if event is unique for the participant, or it is the last of a series of 
similar events; otherwise the Stop Date will not be imputed.  Adverse Events are deemed 
similar if they have the same verbatim term.
5.3.3.2. Exposure
No imputation will be done for first dose date.  Date of last dose of study treatment, if 
unknown or partially unknown, will be imputed as follows:

If the last date of study treatment is completely missing and there is no End of 
Treatment (EOT) CRF page and no death date, the participant should be considered to 
be ongoing and use the data cutoff date for the analysis as the last dosing date; or

If the last date of study treatment is completely or partially missing and there is 
EITHER an EOT CRF page OR a death date available (on or prior to the data cutoff 
date), then impute this date as the last dose date:
= 31DECYYYY, if only Year is available and Year < Year of min (EOT date, death 
date),
= Last day of the month, if both Year and Month are available and Year = Year of 
min (EOT date, death date) and Month < the month of min (EOT date, death date), or
= min (EOT date, death date), for all other cases.
5.3.3.3. Date of Death
Missing or partial death dates will be imputed based on the last contact date:

If the date is missing it will be imputed as the day after the date of last contact 

If the day or both day and month is missing, death will be imputed to the maximum of 
the full (non-imputed) day after the date of last contact and the following:

Missing day:
1st day of the month and year of death

Missing day and month:
January 1st of the year of death


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5.3.3.4. Date of Start of New Anti-cancer Therapy
Incomplete dates for start date of new anti-cancer therapy (drug therapy, radiation, surgery) 
will be imputed as follows and will be used for determining censoring dates for efficacy 
analyses and in the derivation of the end of on-treatment period.  PD date below refers to PD 
date by investigator assessment.

The end date of new anti-cancer therapy will be included in the imputations for start 
date of new anti-cancer therapy.  If the end date of new anti-cancer therapy is:

completely missing then it will be ignored in the imputations below;

partially missing with only year (YYYY) available then the imputations below 
will consider 31DECYYYY as the end date of the new anti-cancer therapy;

partially missing with only month and year available then the imputations below 
will consider the last day of the month for MMMYYYY as the end date of the 
new anti-cancer therapy

For participants who have not discontinued study treatment at the analysis cutoff date, 
last dose of study treatment is set to the analysis cutoff date in the imputations below. 

If the start date of new anti-cancer therapy is completely or partially missing then the 
imputed start date of new anti-cancer therapy is derived as follows:

Start date of new anti-cancer therapy is completely missing
Imputed start date = min [max(PD date + 1, last dose of study treatment + 1), end 
date of new anti-cancer therapy]

Only year (YYYY) for start of anti-cancer therapy is available
IF YYYY < Year of min [max(PD date + 1, last dose of study treatment + 1), end 
date of new anti-cancer therapy]  THEN imputed start date = 31DECYYYY; 
ELSE IF YYYY = Year of min [max(PD date + 1, last dose of study treatment + 
1), end date of new anti-cancer therapy] 
THEN imputed start date = min [max(PD date + 1, last dose of study treatment + 
1), end date of new anti-cancer therapy]
ELSE IF YYYY > Year of min [max(PD date + 1, last dose of study treatment + 
1), end date of new anti-cancer therapy] 
THEN imputed start date = 01JANYYYY

Both Year (YYYY) and Month (MMM) for start of anti-cancer therapy are 
available
IF


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YYYY = Year of min [max(PD date + 1, last dose of study treatment + 1), 
end date of new anti-cancer therapy], AND
MMM < Month of min [max(PD date + 1 day, last dose of study treatment + 1 
day), end date of new anti-cancer therapy] 
THEN 
imputed start date = DAY (Last day of MMM) MMM YYYY ;
ELSE IF
YYYY = Year of min [max(PD date + 1, last dose of study treatment + 1), 
end date of new anti-cancer therapy], AND
MMM = Month of min [max(PD date + 1 day, last dose of study treatment + 1 
day), end date of new anti-cancer therapy] 
THEN 
imputed start date = min [max(PD date + 1 day, last dose of study treatment + 
1 day), end date of new anti-cancer therapy]);
ELSE IF
YYYY = Year of min [max(PD date + 1, last dose of study treatment + 1), 
end date of new anti-cancer therapy], AND
MMM > Month of min [max(PD date + 1 day, last dose of study treatment + 1 
day), end date of new anti-cancer therapy] 
THEN 
imputed start date = 01 MMM YYYY;
ELSE IF
YYYY < Year of min [max(PD date + 1, last dose of study treatment + 1), 
end date of new anti-cancer therapy]
THEN 
imputed start date = DAY (Last day of MMM) MMM YYYY;
ELSE IF
YYYY > Year of min [max(PD date + 1, last dose of study treatment + 1), 
end date of new anti-cancer therapy]
THEN 
imputed start date = 01 MMM YYYY.
5.3.3.5. Other Dates
Imputation methods for other partial dates as follows: 

If the day of the month is missing for a start date used in a calculation, the first day of 
the month will be used to replace the missing date. 


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
If both the day and month are missing, the first day of the year is used. 

For stop dates, the last day of the month, or last day of the year is used if the day or 
day and month are missing, respectively. 

If the date is completely missing, no imputation will be performed.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
6.1.1. Pharmacokinetic parameters
Summary of pharmacokinetic parameters will be conducted in PK parameter analysis 
population and PK evaluable analysis set. Actual PK sampling times will be used in the 
derivation of PK parameters.
The following PK parameters following single dose administration of talazoparib for lead-in 
phase will be listed and summarized descriptively.
PK parameters
Summary statistics
AUC24, AUClast, AUCinf, 
Cmax, CL/F, Vz/F
N, arithmetic mean, median, CV%, standard deviation, 
minimum, maximum, geometric mean and geometric CV%
Tmax
N, median, minimum, maximum
t1/2
N, arithmetic mean, median, CV%, standard deviation, 
minimum, maximum
The following PK parameters following multiple dose administration of talazoparib will be 
listed and summarized descriptively.
PK parameters
Summary statistics
AUC24, Cmax, Cmin, 
CL/F, Rac, Rss
N, arithmetic mean, median, CV%, standard deviation, minimum, 
maximum, geometric mean and geometric CV%
Tmax
N, median, minimum, maximum
6.1.2. PK concentrations
To assess the single dose and multiple dose PK profiles of talazoparib mono therapy, PK 
concentrations will be listed, summarized and plotted for subjects in the PK concentration 
population, where missing and BLQ values will be handled as detailed in Section 5.3.1.


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Presentations for talazoparib will include:

A listing of all concentrations sorted by subject ID, cycle, study day, and nominal 
time postdose for single dose and multiple dose PK, respectively. The listing of 
concentrations will include the actual times. Deviations from the nominal time will be
also listed.

A summary of concentrations by nominal postdose time points for single dose and 
multiple dose PK, respectively, where the set of statistics will include n, mean, 
median, standard deviation, coefficient of variation (CV), minimum, maximum and 
the number of concentrations above the lower limit of quantification.

Median concentrations time plots (on both linear and semi-log scales) against 
nominal time postdose (based on the summary of concentrations by time postdose) 
for single dose and multiple dose PK, respectively

Mean concentrations time plots (on both linear and semi-log scales) against nominal 
time postdose (based on the summary of concentrations by time postdose) for single 
dose PK and multiple dose PK, respectively..

Overlay individual concentration time plots on both linear and semi-log scales against 
actual time postdose (there will be separate spaghetti plots per scale) for single dose 
PK and multiple dose PK, respectively.

Individual concentration time plots by patient on linear and semi-log scales against 
actual time postdose (there will be separate plots for each patient per scale) for single 
dose PK and multiple dose PK, respectively.

Individual and descriptive summary of talazoparib trough concentrations versus study 
day will also be plotted.
6.2. Secondary Endpoint(s)
6.2.1. Objective response (OR)
The number of patients, with measurable or non-measurable disease at baseline, achieving 
OR (CR or PR) will be summarized. The OR rate (ORR) will be estimated by dividing the 
number of patients with OR by the number of patients in the efficacy analysis set. An exact 
95% confidence interval calculated using Clopper-Pearson method will be provided for ORR.
Confirmed OR rate based on confirmed CR/PR a minimum of four weeks apart will also be 
calculated within efficacy analysis set, associated 95% CI from Clopper-Pearson will be
provided as well.
In addition, the best overall response for each patient will be summarized


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6.2.2. Duration of Response (DOR)
DOR will only be calculated for the subgroup of patients with an objective response. If data 
permits, DOR will be summarized in the efficacy analysis set using the Kaplan-Meier 
method and displayed graphically. Median event time and the 95% CI for the median 
calculated using Brookmeyer and Crowley method will be provided. If otherwise only a few 
responses are observed, the participants with responses and their associated information 
including the BOR, date of response, date of progression/death/censoring will be listed. 
6.3. Other Endpoint(s)
Not applicable.
6.4. Subset Analyses
A subgroup calculation of OR rate would be conducted among participants who are with 
measurable disease at baseline.
6.5. Baseline and Other Summaries and Analyses
6.5.1. Baseline Summaries
Analyses of baseline data will be based on the Safety Set.
6.5.1.1. Demographic Characteristics
The following demographic and baseline characteristics will be summarized by number and 
percentage:

Gender (male, female);

Age (18-<45; 45- <65; ≥65);

Race;

Ethnicity;

Eastern Cooperative Oncology Group (ECOG) Performance status:
will be summarized by category (number and percent).
Age (continuous), height (cm), weight (kg), Body Mass Index (BMI) (kg/m2) will be 
summarized with descriptive statistics (mean, median, standard deviation, minimum, and 
maximum).      
6.5.1.2. Medical History
Medical history will be coded using the most current version of MedDRA and summarized 
by MedDRA’s System Organ Class (SOC) and PT from the ‘Medical History’ eCRF page.  
Each participant will be counted only once within each PT or SOC.  Summaries will be 


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ordered by primary SOC and PT in descending order of frequency by the experimental 
treatment arm.  Separate summaries will be provided for past and present conditions.
6.5.1.3. Disease Characteristics
The following baseline disease characteristics will be summarized by number and 
percentage:

primary diagnosis (coded by MedDRA preferred term. if all participants have the 
same diagnosis this may be omitted);

Measurable disease at baseline (yes/no);

Involved tumor sites at baseline;

Number of target tumor sites at baseline (1, 2,3, ≥4);

Number of non-target tumor sites at baseline (1, 2,3, ≥4).
Time since diagnosis (months), defined as (date of first dose – date of diagnosis)/30.4375, 
will be summarized by descriptive statistics (mean, median, standard deviation, minimum, 
and maximum).  
Involved tumor sites at baseline will be derived from target and non target lesions at baseline.  
Each participant will be counted once per organ.  Similarly, number of sites of disease at 
baseline will be derived by counting the number of unique organ sites from target and non 
target lesions at baseline.  “Other” will be counted as one organ site.
6.5.1.4. Prior Anti-cancer Therapy
The prior anti-cancer therapies are collected under the ‘Prior Cancer Therapy’, ‘Prior 
Radiation Therapy’ and ‘Prior Surgery’ eCRF pages.
The number and percentage of participants in each of the following anti-cancer therapy 
categories will be tabulated:

Participants with at least one type of prior anti-cancer treatment;

Participants with at least one prior anti-cancer drug therapy;

Participants with at least one prior anti-cancer radiotherapy;

Participants with at least one prior anti-cancer surgery.
Prior anti-cancer drug therapy will be summarized as follows based on the number and 
percentage of participants:

Number of prior anti-cancer therapy regimens: missing / 1 / 2 / 3 / ≥4;


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
Type of prior anti-cancer therapy;

Intent of Therapy: Neo-Adjuvant / Adjuvant / Advanced – Metastatic.
The prior anti-cancer drugs will be coded in the WHO Drug coding dictionary and will be 
summarized based on the number and percentage of participants by preferred term. A 
participant will be counted only once within a given preferred term, even if he/she received 
the same medication at different times. The summary will be sorted on decreasing frequency. 
In case of equal frequency, alphabetical order will be used.
Specific details on surgeries and radiotherapy will be listed.
6.5.2. Study Conduct and Participant Disposition
6.5.2.1. Disposition
The percentages below will be calculated based on the overall number of participants.

Number of participants enrolled overall and by site;

Number of participants who discontinued from the study prior to first dose overall 
and by the main reason for discontinuation;

Number and percentage of participants in each of the analysis sets defined in Section 
4;

Number and percentage of participants with study drug ongoing;

Number and percentage of participants who discontinued study drug overall and by 
the main reason for discontinuation of study drug;

Number and percentage of participants who entered follow-up;

Number and percentage of participants who discontinued follow-up overall and by 
the main reason for discontinuation.
6.5.2.2. Protocol Deviations
Protocol deviations will be compiled prior to database closure and will be summarized by 
category (n(%)) for the safety set for treatment arm.  Categories will be assigned by the study 
Clinician.
6.5.3. Study Treatment Exposure
Exposure will be summarized for the safety analysis set.


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6.5.3.1. Exposure to talazoparib
The summary of treatment exposure for talazoparib will include the following information 
(by dose level for safety population):

Treatment duration (months): For each patient, treatment duration is defined as (date 
of last dose – date of first dose + 1) / 30.4375. Treatment duration will be summarized 
both as a continuous measure and a categorical measure (≤ 3 months, 3 to < 6 months, 
6 to < 12 months, ≥ 12 months).

Average daily dose (mg/day): The average daily dose is defined as the cumulative 
dose divided by acutal number of days on treatment, where cumulative dose is the 
sum of the actual dose levels that patient received.

Dose intensity (DI, mg /week)

Relative dose intensity (RDI, %). 
The dose intensity (DI, mg /week) of talazoparib during the study will be defined as follows:

Overall DI (mg /week) = [overall cumulative dose (mg)] / [treatment duration in 
weeks]. 
The RDI of talazoparib will be defined as the ratio of the DI and planned dose intensity and 
expressed in percentage as follows:

Overall RDI (%) = 100 × [overall DI] / [planned dose intensity per week, i.e., 7 
mg/week].
6.5.3.2. Dose Reductions, Interruptions
A dose reduction is defined as a non-zero dose that is less than the prior dose.
The number and percentage of participants with at least one dose reduction as well as a 
breakdown of dose reductions (1 / 2 / 3) will be summarized for safety set.  
Reasons for dose reductions will also be summarized.  Participants can contribute to more 
than one reason if multiple dose reductions occurred for different reasons, but will only be 
counted once per reason.  Percentages will be calculated based on the total number of 
participants in safety analysis set.
An interruption is defined a 0 mg dose administered on one or more days for continuously 
dose medications, in this case talazoparib.  (Note: A dose interruption is not considered a 
dose reduction). The number and percentage of participants with dose interruptions and the 
corresponding reasons will be summarized for safety set. Participants can contribute to more 
than one reason if multiple dose interruptions occurred for different reasons, but will only be 


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counted once per reason.  Percentages will be calculated based on the total number of 
participants in safety analysis set.
6.5.4. Concomitant Medications and Nondrug Treatments
The following analyses will be based on the safety analysis set.
Concomitant medications are medications, other than study medications, which started 
prior to first dose date of study treatment and continued on on-treatment period as well as 
those started during the on-treatment period. 
Summary of concomitant medications will include the number and percentage of participants
by Anatomical Therapeutic Chemical (ATC) Classification level 2 and preferred term. A 
participant will be counted only once within a given drug class and within a given drug 
name, even if he/she received the same medication at different times. If any concomitant 
medication is classified into multiple ATC classes, the medication will be summarized 
separately under each of these ATC classes. The summary tables will be sorted on decreasing 
frequency of drug class and decreasing frequency of drug name in a given drug class. In case 
of equal frequency regarding drug class (respectively drug name), alphabetical order will be 
used. In case any specific medication does not have ATC classification level 2 coded term, it 
will be summarized under ‘Unavailable ATC classification’ category. 
A listing of concomitant medications will be created with the relevant information collected 
on the corresponding eCRF page.  
All concurrent procedures, which were undertaken any time during the on-treatment period, 
will be listed according to the eCRF page ‘General Non-drug Treatments’. 
A listing of concurrent procedures will be created with the relevant information collected on 
the ‘General Non-drug Treatments’ eCRF page.
6.5.5. Subsequent anti-cancer therapies
The following analyses will be based on the safety Set.
Anti-cancer treatment will be provided in a data listing with data retrieved from related eCRF 
pages. 
6.6. Safety Summaries and Analyses
Summaries of AEs and other safety parameters will be based on the safety analysis set. 
6.6.1. Adverse Events
All analyses will be based on treatment emergent events unless otherwise specified.  
Treatment emergent is defined in Section 3.5.1.  AEs not considered treatment emergent will 
be flagged in data listings.
A high level summary of adverse events will include the number and percent of participants
with:


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
Any Adverse Event;

Serious AE;

Adverse Events with CTCAE Grade 3-4;

Grade 5 events;

AEs leading to dose interruptions of talazoparib;

AEs leading to dose reductions of talazoparib;

AEs leading to discontinuation of talazoparib.
Additionally, the number of events reported for each of the categories above will be 
provided.  Each unique adverse event at the PT level for a participant is included in the 
count. 
Seriousness, toxicity grade, action taken (interruption, reduction, and withdraw) are as 
reported by the investigator on the adverse event CRF.
Summaries, SOC and PT in decreasing frequency based on the frequencies observed will be 
provided for:

Treatment Emergent Events by Maximum Toxicity Grade (All Causality);

Treatment Emergent Events by Maximum Toxicity Grade (Treatment Related);

Serious Treatment Emergent Events by Maximum Toxicity (All Causality);

Serious Treatment Emergent Events by Maximum Toxicity (Treatment Related); 
An event will be considered treatment related if the investigator considered the event related 
to study drug.
The following summaries will be provided by PT only (i.e. summaries will not include SOC) 
in decreasing frequency based on the frequencies observed in the treatment arm for:

Treatment Emergent Events (All Causality) by Preferred Term and Maximum 
Toxicity Grade;

Treatment Emergent Grade 3-5 Events (All Causality) by Preferred Term and 
Maximum Toxicity Grade;

Treatment Emergent Adverse Events Leading to Dose Interruptions of Study Drug 
talazoparib (All Causality);


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
Treatment Emergent Adverse Events Leading to Dose Reductions of Study Drug 
talazoparib (All Causality);

Treatment Emergent Adverse Events Leading to Permanent Withdraw of Study Drug 
talazoparib (All Causality);

Serious Treatment Emergent Events (All Causality).
Each participant will be counted only once within each SOC and PT.  
In case a participant has events with missing and non missing toxicity grades, the maximum 
of the non-missing grade will be displayed.  Missing grade will only be displayed in the 
event that only one event has been reported for a participant and the grade is missing.
6.6.1.1. Adverse Events of Special Interest
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML), and second 
primary malignancies are the AEs of special interest in this study.
Complete blood counts should be obtained at baseline and monitored for signs of 
hematologic toxicity during treatment.  If MDS/AML is confirmed, talazoparib should be 
discontinued.  
Any diagnosis of MDS or AML for any participant enrolled will be reported as an SAE.
6.6.2. Deaths
The frequency (number and percentage) of participants in the safety analysis set who died 
and who died within 28 days after last dose of study treatment as well as the primary reason 
for death, will be tabulated based on information from the ‘Notice of Death’ CRFs.  
The frequency (number and percentage) of participants in the safety analysis set who died 
within 42 days of first dose of study treatment will also be provided.
The frequency (number and percentage) of participants in the safety analysis set who died 
due to TEAE will be provided as well.
Date and cause of death will be provided in individual participant data listing together with 
selected dosing information (date of first / last administration, the latest dose).
6.6.3. Laboratory Data
Laboratory results will be converted to International System of Units (Système International 
d'unités, SI) units which will be used for applying toxicity grades and for all summaries. 
A shift summary of baseline grade by maximum post-baseline grade will be presented.  


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Quantitative data will be summarized using simple descriptive statistics (mean, standard 
deviation, median, quartiles, minimum, and maximum) of actual values and change from 
baseline for each nominal visit over time (i.e. unscheduled assessments will be excluded). 
Summary will only include data from central laboratories. The total number of participants
for change from baseline will include all participants in the treatment arm who have both a 
baseline and a value at the nominal visit.  
As described in section 3.4, baseline will defined as the last assessment performed on or prior 
to date of the first dose of study treatment.  If there are multiple assessments that meet the 
baseline definition on the same day without the ability to determine which was truly last, then 
the worst grade will be assigned as the baseline grade.  Several of the CTCAE terms 
(including Hypo/Hypercalcemia, Chronic Kidney Disease, and Activated Partial 
Thromboplastin) can be derived using several laboratory tests (analytes).  
Results collected as strict inequalities (e.g., >10, <10) will be converted to numeric values by 
adding or subtracting a factor of <0.001>, for example ‘<10’ will be converted to 9.999.  
Expressions of the form” ≥” or “≤” will be converted to the end point.  These numeric values 
will be evaluated for clinically significant abnormalities, but will not be included in 
calculations of summary statistics. 
Additionally, laboratory results will be programmatically classified according to NCI-
CTCAE version 4.03 grade.  Non-numerical qualifiers will not be taken into consideration in 
the derivation of grade (e.g. hypokalemia Grade 1 and Grade 2 are only distinguished by a 
non-numerical qualifier and therefore Grade 2 will not be derived). In summary statistics the 
number and percentage of participants corresponding to grades that only include non-
quantitative criteria will be displayed as a blank or NA (not assessed) rather than 0.  If there 
is any overlap between grade criteria (e.g. CTCAE grading criteria for Creatinine Increased –
a value can fall into one range based on comparison to ULN and another range based on 
comparison to baseline), the highest (worst) grade would be assigned to that record. Grade 5 
is defined in the CTCAE criteria guidance as an event with an outcome of death. Since 
laboratory data does not collect an outcome, Grade 5 is not used when programmatically 
grading laboratory data.
Grade 0 or Outside Toxicity Reference (OTR) is not defined specifically by in the CTCAE 
guidance. However, programmatically this is used as a category to represent those 
participants who did not meet any of the Grades 1 to 4 criteria.  If the laboratory value is 
evaluable for CTCAE criteria grading (numeric value is present, valid units and ranges are 
present as required to allow conversion to standard units and grading), and does not qualify 
for any of the Grade 1-4 criteria for a given lab test, then the value is assigned as Grade 0 or 
OTR.
Several of the CTCAE terms (including Hypo/Hypercalcemia, Chronic Kidney Disease, and 
Activated Partial Thromboplastin) can be derived using several laboratory tests (analytes).  
Abnormalities will be described using the worst grade overall.   Worst case overall will be 
determined using  local laboratory results from scheduled and unscheduled visits.  Several 


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laboratory tests have bi-directional grading criteria defined so that both low (hypo) and high 
(hyper) values can be graded separately.  Each criterion will be summarized separately.  In 
the cases where a value is graded as a Grade 1, 2, 3, or 4 for one of the directions, that value 
will also be assigned as a Grade 0 for the opposite direction for that test.  For example, a 
value meeting the criteria for Grade 3 Hypercalcemia will be classified as a Grade 0 
Hypocalcemia. For CTCAE terms that can be derived using one of several laboratory tests, 
the maximum post-baseline grade for a given participant and CTCAE term will be the 
maximum across all possible laboratory tests.
Additional laboratory results that are not part of NCI-CTCAE will be presented according to 
the following categories  overall:  below normal limit, within normal limits, and above 
normal limits. In the unlikely event that for a given participant, clinically significant 
abnormalities are noted in both directions (e.g., > Upper Limit of Normal (ULN)  and < 
Lower Limit of Normal (LLN)), then both abnormalities are counted. Summaries at schedule 
timepoints will consider only central laboratory data; however summaries overall will 
consider both central and local laboratory data.
Liver function tests: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
Alkaline Phosphatase (ALP), and total bilirubin (TBILI) are used to assess possible drug 
induced liver toxicity. The ratios of test result over the ULN will be calculated and classified 
for these three parameters during the on-treatment period.   
Summary of liver function tests will include the following categories.  The number and 
percentage of participants with each of the following during the on-treatment period will be 
summarized:

ALT ≥3×ULN, ALT ≥ 5xULN, ALT ≥ 10×ULN, ALT ≥ 20×ULN;

AST ≥ 3×ULN, AST ≥ 5xULN, AST ≥ 10×ULN, AST ≥ 20×ULN;

(ALT or AST) ≥ 3×ULN, (ALT or AST) ≥ 5×ULN, (ALT or AST) ≥ 10×ULN, (ALT 
or AST) ≥ 20×ULN;

TBILI ≥ 2×ULN;

Concurrent ALT ≥ 3×ULN and TBILI ≥ 2×ULN;

Concurrent AST ≥ 3×ULN and TBILI ≥ 2×ULN;

Concurrent (ALT or AST) ≥ 3×ULN and TBILI ≥ 2×ULN;

Concurrent (ALT or AST) ≥ 3×ULN and TBILI ≥ 2×ULN and ALP > 2×ULN;

Concurrent (ALT or AST) ≥ 3×ULN and TBILI ≥ 2×ULN and ALP ≤ 2×ULN or 
missing.
Concurrent measurements are those occurring on the same date.


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Categories will be cumulative, i.e., a participant with an elevation of AST ≥10×ULN will 
also appear in the categories ≥5×ULN and ≥3×ULN. Liver function elevation and possible 
Hy’s Law cases will be summarized using frequency counts and percentages. 
An evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) plot will also be created, 
with different symbols for different treatment arms, by graphically displaying

peak serum ALT(/ULN) vs peak total bilirubin (/ULN) including reference lines at 
ALT=3×ULN and total bilirubin=2×ULN. 

peak serum AST(/ULN) vs peak total bilirubin (/ULN) including reference lines at  
AST=3×ULN and total bilirubin=2×ULN. 
In addition, a listing of all TBILI, ALT, AST and ALP values for participants with a post-
baseline TBILI ≥ 2×ULN, ALT≥ 3×ULN or AST ≥ 3×ULN will be provided.
6.6.4. Vital Signs
Vital sign summaries will include all vital sign assessments from the on-treatment period.  
All vital sign assessments will be listed, and those collected outside the on-treatment period 
will be flagged in the listing. 
The number and perentage of participants with the following potentially clinically significant 
vital sign changes at any point while on treatment will be presented. The definitions of 
potentially clinically significant abnormalities  are shown as:
Parameter
Criteria for potentially clinically significant abnormalities
Systolic blood pressur
Absolute result > 180 mmHg and increase from baseline ≥ 40 
mmHg
Absolute result < 90 mmHg and decrease from baseline >30 
mmHg
Diastolic blood 
pressure
Absolute result > 110mm Hg and increase from baseline ≥ 30 
mmHg
Absolute result < 50 mmHg and decrease from baseline > 20 
mmHg
≥ 20 mmHG increase from baseline
Pulse rate
Absolute result > 120 bpm and increase from baseline > 30 bpm


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Absolute result < 50 bpm and decrease from baseline > 20 bpm
Weight
>10% decrease from baseline
All assessments, including unscheduled assessments will be considered.  A participant can be 
included in multiple categories if different criteria are met at different timepoints.   
6.6.5. Electrocardiograms
Triplicate ECGs is required for baseline assessment, and a single ECG is required at 
screening and each scheduled ECG evaluation on treatment. A mean score is calculated for 
any replicate measurements having the same nominal visit. The mean measurement is 
reported. 
ECG summaries will include all ECG assessments from the on-treatment period.  All ECG 
assessments will be listed, and those collected outside the on-treatment period will be flagged 
in the listing.  
The analysis of QT data is complicated by the fact that the QT interval is highly correlated 
with heart rate.  Because of this correlation, formulas are routinely used to obtain a corrected 
value, denoted QTc, which is independent of heart rate. This QTc interval is intended to 
represent the QT interval at a standardized heart rate. 
Fridericia’s correction (QTcF) will be programmatically derived using the following formula:
3
(sec)
/
sec)
(
sec)
(
RR
m
QT
m
QTcF

and Bazett’s correction (QTcB) will be programmatically derived using the following 
formula:
(sec)
sec)
(
sec)
(
RR
m
QT
m
QTcB

,
where RR represents the RR interval of the ECG, in seconds.  
Use an ECG machine that automatically calculates the heart rate and measures PR, RR, QT 
intervals, QTc, QTcF (if available) and QRS complex. If HR are not collected,Baseline heart 
rate (HR) will be derived from RR measured in seconds as 60/RR if RR is collected, and 
QT/QTc interval assessments will be derived from the visit where both HR and QT are not 
missing.  QTcF (Fridericia’s correction) and QTcB (Bazett’s correction) will be derived 
based on RR and QT as aforementioned.
Data will be summarized using QTcB and QTcF. 


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Additionally QTcB and QTcF will be summarized by maximum on-treatment values using 
the following categories  

≤ 450 msec;

> 450 msec but ≤ 480 msec; 

> 480 msec but ≤ 500 msec; 

> 500 msec.
List participants with maximum on-treatment QTc values 500 msec including the time that 
value is observed. 
Unscheduled assessments will be utilized in addition to planned assessments.  
Shift tables will be provided for baseline value versus worst on-treatment value.  
Additionally maximum increases from baseline (including scheduled and unscheduled 
assessments) will be summarized based on the following categories:

Change > 60 msec;

Change >30 msec but ≤ 60 msec;

Change ≤ 30 msec.
6.6.6. Performance Status
The ECOG shift from baseline to the highest score during the on-treatment period will be 
summarized. The paticipants with baseline ECOG=0 or 1 but shift to ECOG 2 or higher post 
treatment will also be presented in a data listing.
6.6.7. Physical Examination
Number and percentage of participants with abnormal findings in physical examination will 
be summarized by body system. 
6.6.8. Medication errors
Medication errors for study treatment include lack of dose reduction, continuation of 
treatment after discontinuation criteria met, and incorrect dosage taken.  Medication errors 
will be listed.
7. INTERIM ANALYSES
No formal interim analysis will be conducted for this study.


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8. APPENDICES
Appendix 1. List of Abbreviations


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Abbreviation
Term
AE
adverse event
AESI
adverse events of special interest
ALP
Alkaline Phosphatase
ALT
alanine aminotransferase
AML
Acute Myeloid Leukemia
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
AUC
Area Under the Concentration-Time Curve
AUCinf
area under concentration-time curve from time 0 to infinity
AUClast
Area under the plasma concentration versus time curve from time 
zero to the time of Clast
AUCsd,inf
Area under the plasma concentration versus time curve from time 
zero to infinity at steady state
AUCsd,τ
Area under the plasma concentration versus time curve within a 
dosing interval of τ (=24 hr) at steady state
AUCτ
Area under the plasma concentration versus time curve from time 
zero to the time τ 
BLQ
below the level of quantification
BMI
Body mass index
C1D1
Cycle 1 Day 1
CI
confidence interval
CL/F
apparent oral clearance
Cmax
maximum plasma concentration
Cmin
Minimum Plasma Concentration
CR
complete response
CRF
case report form
CTCAE
Common Terminology Criteria for Adverse Events
CV
Coefficient of variation
DI
Dose intensity
DOR
Duration of response
DMC
data monitoring committee
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
eDISH
evaluation of Drug-Induced Serious Hepatotoxicity
EOT
End of treatment
HR
heart rate
IOTA
Investigator Overall Tumor Assessment
kel
Constant of elimination rate
LLN
Lower limit of normal
LLOQ
Lower limit of quantification
mCRPC
metastatic castration resistant prostate cancer


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MedDRA
Medical Dictionary for Regulatory Activities
MD
multiple dose
MDS
Myelodysplastic Syndrome
N/A
not applicable
NC
Not calculated
NCI
National Cancer Institute
ND
Not done
NMPA
National Medical Products Administration
NS
No sample
OR
Objective response
ORR
objective response rate
OTR
outside toxicity reference
PD
disease progression
PK
pharmacokinetic(s)
PR
partial response
PT
preferred term 
QD
Once Daily
OR
objective response
QTc
corrected QT
QTcB
Bazett’s correction
QTcF
corrected QT (Fridericia method)
Rac
observed accumulation ratio
RDI
Relative dose intensity
Rss
steady-state accumulation ratio
RECIST
Response Evaluation Criteria in Solid Tumors
SAE
serious adverse event
SAP
statistical analysis plan
SD
single dose
SD
stable disease
SD
Standard deviation
SOC
system organ class 
t1/2
Terminal Half-Life
TBili
total bilirubin
TEAEs
treatment-emergent adverse events
Tmax
Time to Reach Maximum Plasma Concentration
ULN
upper limit of normal
Vz/F
Apparent volume of distribution
WHO
World health organization