Conditions: Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 120
Healthy volunteers: no

Brief summary:
This is a single-arm, open-label, extended treatment, safety study in patients treated with talazoparib in qualifying studies.

Detailed description:

Arms:
arm 1: None

Interventions: intervention 1: Talazoparib
Intervention descriptions: intervention 1: Maximum starting dose: 1mg/day or last tolerated dose in the originating protocol

Protocol document:
Prot_000.pdf: 
C3441010 (MDV3800-13) 
Final Amendment 4, 14 November 2018
PFIZER CONFIDENTIAL
Page 1
Pfizer, Inc.
CLINICAL RESEARCH PROTOCOL
Study Title:
A Single-Arm, Open-Label, Multicenter, Extended Treatment, 
Safety Study in Patients Treated With Talazoparib
Protocol Identifier:
MDV3800-13 (C3441010)
Phase:
2
Investigational 
Product:
Talazoparib (also known as MDV3800, BMN 673, PF-06944076)
Indication:
Advanced solid tumors (from multiple originating studies)
Sponsor:
Pfizer, Inc. 
235 East 42nd St. New York, NY 10017
Telephone: 
+1 (212) 733-7900
Fax:
+1 (415) 543-3411
Reference Numbers:
United States IND 
 EudraCT 2016-001972-31
Sponsor Medical 
Monitor:
MD 
Telephone: 
Mobile:
Email:
 
Original Protocol:
v1.0 – 06 Jun 2016
Amendment 1:
Amendment 2: 
Amendment 3:
Amendment 4:
v2.0 – 29 Jul 2016
v.3.0 – 15 May 2017 (Poland)
v4.0 – 24 Aug 2018
v5.0 – 14 Nov 2018 (Investigational sites US0002, US0117, 
US0121, US0839, US230)
This study will be conducted according to the principles of Good Clinical Practice as described in
International Conference on Harmonisation guidelines, including the archiving of essential documents.
Confidentiality Statement
The information contained in this document and all information provided to you related to talazoparib are the 
confidential and proprietary information of Pfizer, Inc. (“Pfizer”) and except as may be required by federal, 
state, or local laws or regulations, may not be disclosed to others without prior written permission of Pfizer. 
However, the investigator may disclose such information to supervised individuals working on talazoparib, 
provided such individuals agree to be bound to maintain the confidentiality of such information.
PPD
PPD
PPD
PPD
CCI


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PFIZER CONFIDENTIAL
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SYNOPSIS
Title of Study: A Single-Arm, Open-Label, Multicenter, Extended Treatment, Safety Study in Patients
Treated With Talazoparib
Protocol Identifier: MDV3800-13 (C3441010)
Phase of Development: 2
Number of Patients: Approximately 150
Study Centers: Approximately 50 (international)
Study Objective:
To obtain additional safety data on long-term talazoparib use
Methods:
This is a single-arm, open-label, extended treatment, safety study in patients treated with talazoparib (also 
known as MDV3800, BMN 673, PF-06944076,) as a single agent or in combination with another agent in 
qualifying originating clinical studies sponsored by Medivation/Pfizer. The safety and tolerability of long-term 
talazoparib use will be evaluated, and the data collected will be limited to safety assessments. The study 
provides access to single-agent talazoparib for qualifying patients who may benefit from continuing therapy 
with talazoparib.
Eligible patients must have received talazoparib in a qualifying study and have no ongoing grade 3 or 
4 talazoparib-related toxicities.  Patients must receive their first dose of talazoparib in this protocol within 
2 months after their last dose of talazoparib in the originating study and may not receive any intervening 
antineoplastic therapies before starting this study. Patients will have clinic visits approximately every 4 weeks 
for the first 24 weeks and then approximately every 8 weeks thereafter (additional visits for laboratory testing 
every 2 weeks through week 9 and every 4 weeks thereafter) or as clinically indicated (patients enrolling from 
study PRP-001 may continue the last visit schedule they tolerated in that study eg, if a PRP-001 patient is on an 
every 4 week schedule in the originating study, the patient is required to complete the week 5 and week 9 visits 
but not the Complete Blood Count (CBC) assessments at week 3 and week 7; afterwards, these patients would 
follow the schedule of activities in Appendix 1). Additional clinic visits and laboratory testing may be 
necessary to monitor safety (eg, for dose modification, hematologic toxicity, pregnancy testing).
The maximum starting dose of talazoparib will be 1 mg/day or the last tolerated dose administered in the 
originating study. Talazoparib capsules will be administered by mouth once daily with or without food at 
approximately the same time of day.  Patients receiving talazoparib as combination treatment in the originating 
study will receive talazoparib as a single agent in this extended treatment study.  Talazoparib administration 
may continue as long as the investigator considers treatment to be providing clinical benefit or until other study 
discontinuation criteria are met (Section 5.3).  The addition of any other antineoplastic therapy and the 
concurrent use of investigational agents during the study are prohibited.
Study assessments will include adverse events, local clinical laboratory tests, concomitant medications, 
physical examinations, and vital signs (and weight).  Clinical laboratory tests (hematology, serum chemistry) 
will be performed every 4 weeks through week 25 and every 8 weeks thereafter during the study. Complete 
blood count (CBC) tests will be completed every 2 weeks through week 9 and every 4 weeks thereafter.  
Women of childbearing potential must have a pregnancy test every 4 weeks.  Safety follow-up will be through 
and including 30 days after the last dose of talazoparib.


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Study Schematic:
Key assessments: laboratory tests, physical examinations, adverse events.
Patients enrolling from study PRP-001 may continue the last visit schedule they tolerated in that study.
Open-Label
Treatment
Informed 
consent 
Key Eligibility Criteria:
Eligible patients must have received talazoparib as a single agent or in combination with another agent in a 
qualifying Medivation/Pfizer-sponsored study in advanced solid tumors and have no ongoing National Cancer 
Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 talazoparib-related 
toxicities. All patients must provide signed informed consent. Eastern Cooperative Oncology Group (ECOG) 
must be ≤2.  Patients must have tolerated ≥0.25 mg/day talazoparib during the originating study. Women of 
childbearing potential must have a negative pregnancy test before entering the study, be willing to have 
additional pregnancy tests while receiving talazoparib, and agree to avoid pregnancy by using a highly 
effective birth control method from the first dose of talazoparib through 7 months after the last dose. Male 
patients must use a condom when having sex with a pregnant woman or with a woman of childbearing 
potential from the first dose of talazoparib through 4 months after the last dose. Patients who permanently 
discontinued from any Medivation/Pfizer-sponsored study with talazoparib alone or in combination with 
another agent or who received an antineoplastic therapy after treatment with talazoparib in the originating 
study are excluded.
Test Product, Dose, and Mode of Administration:
Talazoparib is provided as the 4-methylbenzenesulfonate (tosylate) salt and has the chemical name (8S,9R) 
5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3H-
pyrido[4,3,2-de]phthalazin-3-one.
The drug product is a capsule containing talazoparib tosylate and silicified microcrystalline cellulose. The 
capsules for each dose strength will be provided in dose-specific colors.
Talazoparib (maximum starting dose of 1 mg/day or last tolerated dose administered in the originating study) 
will be self-administered orally once daily at approximately the same time each day. Talazoparib will be 
swallowed whole with a glass of water and may be taken with or without food.
Reference Therapy, Dose, and Mode of Administration:
Not applicable.
Duration of Treatment (End of Study):
Patients will continue receiving talazoparib as long as the investigator considers treatment to be providing 
clinical benefit or until other study discontinuation criteria (Section 5.3) are met.
The study may continue until the last patient has stopped deriving clinical benefit as assessed by the 
investigator or until the last patient meets other study discontinuation criteria (anticipated to be approximately
4 years).
Patients treated 
with 
talazoparib 
(single agent or 
in combination) 
in selected 
clinical studies 
sponsored by 
Medivation/
Pfizer
Talazoparib
Daily
Maximum 
starting dose: 
1 mg/day or 
last tolerated 
dose in the 
originating 
study
Visits 
every 4 
weeks for 
24 weeks, 
every 8 
weeks 
thereafter
End of 
Treatment
Patient no 
longer 
receiving 
clinical benefit 
(investigator 
decision) or 
meets other 
discontinuation 
Safety 
Follow-Up
Through 
and 
including 
30 days 
after last 
dose


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Statistical Methods:
All safety analyses will be conducted using the safety population defined as all patients who receive any 
amount of talazoparib.
Safety will be evaluated using summaries of adverse events, vital signs, and clinical laboratory tests. 
Treatment-emergent safety data will be collected from the first dose of talazoparib through through and 
including 30 days after the last dose. Drug exposure will be summarized using descriptive statistics.  
All adverse events will be coded to preferred term and system organ class using the Medical Dictionary for 
Regulatory Activities (MedDRA) and classified by severity using CTCAE.  The number and percentage of 
patients with adverse events will be presented by MedDRA system organ class and preferred term, 
relationship to study treatment, severity, seriousness, and outcome (eg, leading to permanent treatment 
discontinuation). Descriptive statistics will be used.
Laboratory values will be classified for severity using the CTCAE. Laboratory shift tables of baseline results 
versus postbaseline results will be produced as appropriate.


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TABLE OF CONTENTS
SYNOPSIS.................................................................................................................................2
LIST OF TABLES.....................................................................................................................8
LIST OF FIGURES ...................................................................................................................8
APPENDICES ...........................................................................................................................8
1. INTRODUCTION ...............................................................................................................10
1.1. Background .............................................................................................................10
1.2. Summary of Relevant Clinical Experience With Talazoparib................................10
1.2.1. Efficacy.......................................................................................................10
1.2.2. Safety..........................................................................................................11
1.2.3. Pharmacokinetics........................................................................................11
1.3. Summary of Relevant Nonclinical Experience With Talazoparib..........................12
1.3.1. Nonclinical Pharmacology of Talazoparib Monotherapy...........................12
1.3.2. Nonclinical PK and Metabolism.................................................................13
1.3.3. Nonclinical Toxicology ..............................................................................14
1.4. Talazoparib Benefits and Risks Assessment...........................................................15
2. STUDY OBJECTIVE..........................................................................................................15
3. INVESTIGATIONAL PLAN..............................................................................................15
3.1. Overall Study Design and Plan: Description..........................................................15
3.2. Study Schematic......................................................................................................16
3.3. Blinding...................................................................................................................17
3.4. Duration of Study....................................................................................................17
3.5. Discussion of Study Design ....................................................................................17
3.5.1. Rationale for Dose and Schedule................................................................17
4. SELECTION OF STUDY POPULATION .........................................................................18
4.1. Inclusion Criteria.....................................................................................................18
4.2. Exclusion Criteria....................................................................................................18
4.3. Reproductive Considerations ..................................................................................20
5. ENROLLMENT AND STUDY PROCEDURES ...............................................................21
5.1. Informed Consent and Eligibility............................................................................21
5.2. Treatment Period.....................................................................................................22
5.2.1. Treatment Period Visit Windows ...............................................................22
5.2.2. Treatment Period Study Visit Procedures...................................................22


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5.2.3. Unscheduled Visit Procedures....................................................................23
5.3. Permanent Treatment Discontinuation....................................................................23
5.4. Safety Follow-Up ....................................................................................................24
5.5. Loss to Follow-Up...................................................................................................24
6. INVESTIGATIONAL PRODUCT INFORMATION.........................................................24
6.1. General Information ................................................................................................24
6.2. Talazoparib Product Characteristics........................................................................25
6.2.1. Packaging of Talazoparib ...........................................................................25
6.2.2. Storage and Handling of Talazoparib.........................................................25
6.2.3. Directions for Administration of Talazoparib ............................................25
6.2.3.1. Dose Modifications ...................................................................26
6.2.3.2. Overdose Management..............................................................27
6.3. Treatment Compliance ............................................................................................27
7. PRIOR AND CONCOMITANT THERAPY......................................................................27
7.1. Prior Medications ....................................................................................................27
7.2. Concomitant Therapy..............................................................................................27
7.3. Potential Interactions Between Talazoparib and Concomitant Medications ..........28
8. ADVERSE EVENT REPORTING......................................................................................29
8.1. Requirements...........................................................................................................29
8.1.1. Additional Details on Recording Adverse Events on the CRF...................30
8.1.2. Eliciting Adverse Event Information..........................................................30
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Permanent Treatment Discontinuation section)...............................................30
8.1.4. Time Period for Collecting AE/SAE Information......................................30
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................31
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF .................31
8.1.5. Causality Assessment .................................................................................31
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................32
8.2. Definitions...............................................................................................................32
8.2.1. Adverse Events ...........................................................................................32
8.2.2. Abnormal Test Findings .............................................................................33
8.2.3. Serious Adverse Events ..............................................................................33
8.2.4. Hospitalization............................................................................................34


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8.3. Severity Assessment................................................................................................35
8.4. Special Situations ....................................................................................................36
8.4.1. Protocol-Specified Serious Adverse Events...............................................36
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................36
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................38
8.4.3.1. Exposure During Pregnancy......................................................38
8.4.3.2. Exposure During Breastfeeding ................................................39
8.4.3.3. Occupational Exposure .............................................................39
8.4.4. Medication Errors .......................................................................................40
8.4.4.1. Medication Errors......................................................................40
9. ASSESSMENT OF SAFETY ENDPOINTS ......................................................................40
9.1. Clinical Laboratory Tests........................................................................................41
9.1.1. Dose Modifications Due to Adverse Events...............................................42
9.1.2. Assessment of Abnormal Liver Tests.........................................................43
9.1.2.1. Criteria for Permanent Discontinuation of Talazoparib in 
Association with Liver Test Abnormalities .....................................44
9.2. Physical Examinations and Vital Signs...................................................................46
10. STATISTICAL METHODS..............................................................................................46
10.1. Statistical and Analytical Plans.............................................................................46
10.2. Analysis Populations.............................................................................................46
10.3. Safety Analyses.....................................................................................................47
11. STUDY COMMITTEES AND COMMUNICATIONS ...................................................47
12. LABORATORY REQUIREMENTS ................................................................................47
13. INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS .................................47
13.1. Ethics.....................................................................................................................48
13.1.1. Ethics Committee......................................................................................48
13.1.2. Ethical Conduct of the Study....................................................................48
13.1.3. Patient Information and Informed Consent ..............................................49
13.1.4. Maintaining Patient Confidentiality .........................................................50
13.2. Data Quality Assurance.........................................................................................50
13.2.1. Data Management.....................................................................................50
13.2.2. Case Report Forms ...................................................................................50


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13.2.3. Study Monitoring......................................................................................51
13.2.4. Study Audits .............................................................................................51
13.3. Investigational Product Accountability.................................................................51
13.4. Compensation, Insurance, and Indemnity.............................................................52
13.5. Record Retention...................................................................................................53
13.6. Study Termination.................................................................................................53
14. USE OF STUDY INFORMATION AND PUBLICATION .............................................54
15. REFERENCES ..................................................................................................................56
16. INVESTIGATOR SIGNATURE.......................................................................................57
LIST OF TABLES
Table 1.
Primary Reasons For Permanent Treatment Discontinuation ..............................23
Table 2.
Prohibited Concomitant Therapies .......................................................................28
Table 3.
Clinical Laboratory Tests .....................................................................................41
Table 4.
Talazoparib Dose Modifications Due To Adverse Events ...................................42
Table 5.
Talazoparib Dose Reduction for Toxicity ............................................................43
Table 6.
Criteria for Temporary Withholding of Talazoparib in Association with 
Liver Test Abnormalities......................................................................................43
Table 7.
Criteria for Temporary Withholding of Talazoparib in Association with 
Liver Test Abnormalities......................................................................................44
Table 8.
Monitoring of Liver Tests for Potential Drug Induced Liver Injury ....................46
LIST OF FIGURES
Figure 1.
Study Schematic ...................................................................................................17
APPENDICES
Appendix 1. Study Schedule of Activities...............................................................................58
Appendix 2. France Appendix.................................................................................................60


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LIST OF ABBREVIATIONS AND TERMS
Abbreviation
Definition
AE
Adverse event
ALT
Alanine aminotransferase
AML
Acute myeloid leukemia
AST
Aspartate aminotransferase
AUC
Area under the plasma concentration-time curve
BCRP
Breast cancer resistance protein
BRCA
Breast cancer susceptibility gene
CBC
Complete blood count
CFR
Code of Federal Regulations
CL/F
Apparent oral clearance
Cmax
Maximum plasma concentration
Cmin
Plasma trough concentration
CR
Complete response
CRF
Case Report Form
CSA
Clinical study agreement
CT
Clinical trial
CTCAE
Common Terminology Criteria for Adverse Events
DILI
Drug-induced liver injury
EC
Ethics committee (global term including institutional
ECOG
Eastern Cooperative Oncology Group
EDP
Exposure during pregnancy
eGFR
Estimated glomerular filtration rate
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
ICH
International Conference on Harmonisation
ID
Identification
IP
Investigational product
INR
International normalized ratio
IRT
Interactive Response Technology
MDS
Myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
NASH
Nonalcoholic fatty liver disease
PARP
Poly(ADP-ribose) polymerase
P-gp
P-glycoprotein
PK
Pharmacokinetics
PR
Partial response
SAE
Serious adverse event
SRSD
Single reference safety document
TBili
Total bilirubin
ULN
Upper limit of normal
US
United States


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1. INTRODUCTION
MDV3800-13 is designed to evaluate the safety and tolerability of long-term talazoparib use 
for patients who were treated with talazoparib as a single agent or in combination with 
another agent in a qualifying talazoparib clinical study who may benefit from continuing 
therapy with talazoparib.
1.1. Background
Talazoparib (also known as MDV3800, BMN 673, PF-06944076) is a potent, orally 
bioavailable, small molecule poly(ADP-ribose) polymerase (PARP) inhibitor in development 
for the treatment of a variety of human cancers.  PARP inhibitors including talazoparib exert 
cytotoxic effects via 2 mechanisms, inhibition of PARP1 and PARP2 catalytic activity, and 
PARP trapping, a process in which PARP protein bound to a PARP inhibitor does not readily 
dissociate from DNA, preventing DNA repair, replication, and transcription (Murai et al, 
2012).5 Inhibition of PARP catalytic activity contributes to the process of synthetic lethality, 
as it results in persistent single-strand breaks that require homologous recombination DNA 
repair for survival.  Stabilized PARP-DNA complexes (ie, trapped) inhibit DNA repair, 
replication, and transcription, and are more cytotoxic than unrepaired single-strand breaks 
because they do not readily dissociate.  Although other PARP inhibitors possess both 
activities, in vitro studies demonstrated that talazoparib has greater PARP trapping activity 
than other PARP inhibitors in clinical development (Hopkins et al, 2015; Murai et al, 
2014).3,6
1.2. Summary of Relevant Clinical Experience With Talazoparib
Approximately 319 patients have received talazoparib in company-sponsored studies as of
30 Nov 2015, including 3 studies in solid tumors and 1 in hematologic malignancies. Studies 
include a phase 1 study (PRP-001) in advanced solid tumors, a phase 2 study (673-201) in 
locally advanced and/or metastatic breast cancer, and a phase 3 study (673-301) in locally 
advanced and/or metastatic breast cancer.
1.2.1. Efficacy
PRP-001 is a phase 1, open-label, safety, pharmacokinetic (PK), and dose-escalation 
(0.025-1.1 mg/day) and expansion (1 mg/day) study of talazoparib monotherapy in 
110 patients with advanced or recurrent solid tumors with DNA repair deficiencies. As of 
the data cutoff date of 30 Nov 2015, objective responses (complete response [CR] or partial 
response [PR]) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) 
were observed in 8 of 18 patients (44%) with breast cancer and 12 of 25 patients (48%) with 
ovarian/primary peritoneal cancer with deleterious germline breast cancer susceptibility gene 
(BRCA) mutations; clinical benefit (CR, PR, or stable disease ≥24 weeks) was observed 
in 13 of 18 patients (72%) and 19 of 25 patients (76%), respectively.  Seven of 12 patients 
with confirmed objective responses were treated with talazoparib at 0.1 to 0.9 mg/day, and
5 patients were treated at the recommended dose of 1 mg/day.
Additional information on the clinical efficacy of talazoparib is provided in the talazoparib 
investigator brochure.


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1.2.2. Safety
The safety of talazoparib as monotherapy is based on phase 1 and 2 studies in patients with 
advanced cancer.
Aggregate safety data from 3 of the 5 company-sponsored clinical studies (phase 1 studies 
PRP-001 and PRP-002, and phase 2 study 673-201; N = 214 patients; data as of
30 Nov 2015) provide the basis for the most common treatment-emergent adverse events.
The most common adverse events associated with talazoparib (>20%) were 
myelosuppression (anemia, thrombocytopenia, neutropenia), gastrointestinal toxicity (nausea, 
diarrhea, vomiting), and fatigue.  The most common grade 3 or higher adverse events and 
serious adverse events were associated with myelosuppression.  A total of 25 of 214 patients 
had an adverse event that led to death (12 associated with underlying malignancies, 3 disease 
progression, 2 each lung infection and pneumonia, and 1 each cardiorespiratory arrest, 
neutropenic sepsis, renal impairment, dyspnea, hypoxia, and respiratory failure).  Of these 
events, none was assessed as related to study drug.  Eight of 214 patients discontinued study 
drug due to an adverse event.
In the ongoing phase 3 study 673-301, an adverse event of veno-occlusive disease of the liver 
leading to death was assessed as related to talazoparib by the investigator.
Additional information on the clinical safety of talazoparib is provided in the talazoparib 
investigator brochure.
1.2.3. Pharmacokinetics
The PK of talazoparib as a single agent was evaluated in 142 adult patients with cancer, 
including 109 patients with solid tumors (PRP-001) and 33 with hematologic malignancies 
(PRP-002).  Doses of 0.025 mg to 2 mg were administered orally as a single dose or as 
once-daily doses.  This dose range bracketed the 1 mg/day dose used in ongoing safety and 
efficacy studies, and provided a framework for assessing dose linearity. As the PK of 
talazoparib was similar in patients with solid tumors and hematologic malignancies, and no 
differences were apparent between males and females, the results are summarized 
collectively.
Oral absorption of talazoparib was rapid and independent of dose after administration of 
single or once-daily doses.  Peak talazoparib concentrations were generally reached 
approximately 1 to 8 hours postdose. Exposure increased approximately dose-proportionally 
with increasing doses. At 1 mg/day, the mean half-life was approximately 2 days; the mean 
apparent volume of distribution (V/F) was 415 L, indicating extensive extravascular 
distribution. Steady state was reached in approximately 2 to 3 weeks with daily 
administration.
Apparent oral clearance (CL/F) of talazoparib appeared to be dose linear, with a mean CL/F 
across doses of approximately 5 L/h.  Renal excretion was a major elimination pathway for 
unchanged parent talazoparib.  Following oral administration, 44% to 90.6% of the dose was 
recovered in urine as unchanged parent drug over 24 hours at steady state for doses up to
1 mg/day.  Mean renal clearance ranged from 1.38 L/h to 4.96 L/h independent of dose, 
suggesting linear urinary elimination kinetics.


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Following repeated administration at 1 mg/day, talazoparib accumulated approximately
2.4-fold relative to a single dose.  At steady state, the mean maximum plasma concentration 
(Cmax) was 21.0 ng/mL, the mean plasma trough concentration (Cmin) was 3.72 ng/mL, and 
the mean area under the plasma concentration-time curve (AUC) was 202 ng•h/mL.
PK data from a food-effect study showed that food had no effect on the extent of absorption 
of talazoparib (AUC) but decreased the rate of absorption (Cmax was 46% lower and time to 
Cmax [Tmax] was 2.63 hours later); however this reduction in the rate of absorption following a 
single dose is not clinically relevant because talazoparib accumulates 2.4-fold at steady state 
after 1 mg once-daily dosing.  Furthermore, AUC or Cmin is thought to drive efficacy, not 
Cmax; therefore, talazoparib can be taken with or without food. Talazoparib is being 
administered without regard to food in ongoing safety and efficacy studies.
A preliminary population PK analysis was performed with data from patients in studies 
PRP-001 and PRP-002 to assess the effects of renal function on PK parameters of 
talazoparib. Talazoparib CL/F in patients with mild renal impairment (creatinine clearance 
[CLCR] 60-89 mL/min) was similar compared with patients with normal renal function
(CLCR 90 mL/min). In patients with moderate renal impairment (CLCR 30-59 mL/min), 
the talazoparib CL/F was decreased by 44% from normal, resulting in higher talazoparib 
exposure. Therefore, patients with moderate or severe renal impairment
(CLCR <60 mL/min) may be at risk of elevated exposure (≥50%) to talazoparib. The effects 
of hepatic impairment on talazoparib PK have not been studied.
The potential for talazoparib to affect the PK of other drugs was assessed through in vitro 
experiments and is described in Section 1.3.2.
Additional information on the PK of talazoparib is provided in the investigator brochure.
1.3. Summary of Relevant Nonclinical Experience With Talazoparib
1.3.1. Nonclinical Pharmacology of Talazoparib Monotherapy
The cytotoxic activity of talazoparib was demonstrated in cell culture, and antitumor effects 
were demonstrated in mouse xenograft models.
In cell-free enzyme assays, talazoparib inhibited PARP1 and PARP2 catalytic activity (Wang 
et al, 2016).10  In vitro experiments showed that talazoparib was approximately 3- to 8-fold 
more potent at blocking PARP1 catalytic activity and up to 100-fold more potent at PARP 
trapping than other PARP inhibitors in clinical development (Murai et al, 2014; Shen et al, 
2013).6,8
In tissue culture studies, talazoparib was cytotoxic to cancer cell lines harboring gene 
mutations that compromise DNA repair pathways, including MX-1 (BRCA1-mutant) and 
MDA-MB-468 (PTEN-mutant) mammary cancer cells, LNCaP (PTEN- and ATM-mutant) 
and PC-3 (PTEN-mutant) prostate cancer cells, and HCT-116 (MLH-1-mutant) colorectal 
tumor cells. The half-maximal inhibitory concentration (IC50) values of talazoparib in these 
cancer cell lines were in the single-digit nanomolar or subnanomolar range.  The talazoparib 
IC50 for growth inhibition of Capan-1 pancreatic adenocarcinoma cells (BRCA2-deficient) 
was 50- to over 2000-fold lower than the other PARP inhibitors tested (Shen et al, 2013).8


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The higher potency of talazoparib relative to the other PARP inhibitors is thought to be due 
to the more potent PARP trapping activity seen with talazoparib as opposed to inhibition of 
PARP catalytic activity (Shen et al, 2015).9
Talazoparib demonstrated potent antitumor activity in mouse xenograft models of small cell 
lung cancer (SCLC) (Cardnell et al, 2013)1 and a mammary cancer xenograft (Shen et al, 
2013).8
Additional information on the nonclinical pharmacology of talazoparib is provided in the 
talazoparib investigator brochure.
1.3.2. Nonclinical PK and Metabolism
PK studies in rats and dogs show that talazoparib oral bioavailability was >43% in rats and
>51% in dogs.  A Good Laboratory Practice (GLP) study in dogs demonstrated that the 
capsule formulation used in clinical studies is approximately 2-fold more bioavailable than 
the suspension formulation used in nonclinical studies. In general, talazoparib displays 
greater than or approximately dose-proportional increases in exposure in rats and dogs with 
no evidence of sex differences.
Studies of [14C]-talazoparib in rats and dogs indicate rapid absorption, wide distribution
(greater than total body water), and nearly complete elimination of drug substance (>90%)
by 7 days.  Fecal elimination was the main route of elimination in both species, and renal
excretion was moderate (21-26%).  In a study in rats, [14C]-talazoparib was widely
distributed, reaching maximum levels 1 to 4 hours postdose.
Excluding the gastrointestinal
tract, the highest radioactivity levels were observed in liver and kidney (and the eye uveal
tract in albino rats).  Tissue radioactivity levels were greater than blood levels in the target
organs of talazoparib toxicity (bone marrow, spleen, and thymus) through 7 days. Metabolic
profiling of plasma, urine, and feces samples indicated that [14C]-talazoparib is largely
cleared via excretion of unchanged parent drug and metabolized to a minor extent via
oxidation and dehydrogenation.
In vitro metabolism studies in rat, dog, and human hepatic microsomes demonstrated that 
[14C]-talazoparib has high metabolic stability (>90%) over 2 hours.  A minimal extent or a 
lack of metabolism for [14C]-talazoparib was observed in the presence of freshly isolated 
mouse, rat, dog, and human hepatocytes or cryopreserved human hepatocytes. Talazoparib 
does not appear to be a substrate of any major cytochrome P450 (CYP450) metabolizing 
enzyme.
Mean binding to human plasma proteins is 78.7%; therefore, it is unlikely that talazoparib
will demonstrate clinically significant drug-drug interactions related to displacement from
plasma protein binding sites.  At therapeutic exposures, talazoparib does not markedly induce
or inhibit CYP450 enzymes.  Therefore, it is unlikely that talazoparib will demonstrate
clinically significant CYP450 inhibition- or induction-based drug-drug interactions when
coadministered with corresponding substrates.  At therapeutic exposures, talazoparib does
not markedly induce or inhibit any transporters.
Therefore, it is unlikely that talazoparib 
will demonstrate clinically significant drug transporter inhibition-based drug–drug 
interactions when coadministered with corresponding substrates.


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Because talazoparib is a substrate for P-glycoprotein (P-gp) and breast cancer resistance 
protein (BCRP), plasma talazoparib concentrations may increase or decrease when 
coadministered with P-gp or BCRP inhibitors or inducers, respectively. Guidelines for 
concomitant use of talazoparib inhibitors or inducers of P-gp or inhibitors of BCRP are 
provided in Section 7.3.
Additional information on the nonclinical PK and drug metabolism of talazoparib is provided 
in the investigator brochure.
1.3.3. Nonclinical Toxicology
Safety pharmacology, single- and repeat-dose toxicity, genotoxicity, embryo-fetal 
development, and in vitro phototoxicity studies were conducted to evaluate the nonclinical 
toxicology profile of talazoparib.  Repeat-dose toxicity/toxicokinetic studies were conducted 
with talazoparib utilizing the intended oral route of administration in mice, rats, and dogs. A 
repeat-dose study with talazoparib was conducted in BALB/c nude mice to select doses and 
exposures for the mouse xenograft studies.
Five-day, 28-day, and 13-week repeat-dose GLP toxicity and toxicokinetic studies with
28-day recovery periods were conducted in the rat and dog. The major findings are as 
follows:

Dose-dependent pancytopenia with bone marrow hypocellularity and depletion of 
lymphoid tissue in multiple organs was observed and considered possibly due to 
exaggerated pharmacology of talazoparib based on the higher (relative to baseline) 
poly(ADP-ribose) (index of PARP1/2 activity) tissue levels in these organs. The 
hematologic findings were partially reversible and may be readily monitored in the 
clinic.  The toxicities that resulted in mortality in dogs (0.1 mg/kg/day) and some rats 
(1 mg/kg/day) occurred at AUC0-24 exposures that were >0.8- and 4-fold higher, 
respectively, than the exposure at the recommended human dose of 1 mg/day. The 
toxicities were mainly due to septicemia that resulted from the severe bone marrow 
and lymphoid depletion;

A dose-dependent increased incidence of gastrointestinal tract findings of 
apoptosis/necrosis in the stomach and duodenum was observed. Additional findings 
at higher doses included reversible villous atrophy and increased apoptosis 
throughout the gastrointestinal tract, most notably in the small intestine. 
Gastrointestinal tract toxicities of enteropathy and villous atrophy caused mortality in 
rats at 3.0 mg/kg/day.  Exposures at 3.0 mg/kg/day are significantly higher than the 
exposures at the recommended human dose;

Additional findings at the high dose (≥1 mg/kg/day) in the 5-day GLP study in rats 
included focal necrotic changes in the ovarian follicular atresia and hepatocyte 
necrosis of the liver.  These findings were not observed in the 28-day or 13-week 
repeat-dose studies in rats;


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
Atrophy and/or degenerative changes in testes and epididymis and effects on the 
seminiferous tubules were observed in rats and dogs; the severity correlated with both 
dose and duration of treatment.
There were no talazoparib-related effects on respiratory or central nervous system parameters 
after a single oral administration to rats (safety pharmacology studies), or on cardiovascular 
parameters and electrocardiogram evaluations after a repeat-dose oral administration in dogs 
(repeat-dose toxicity studies).  Talazoparib had no effect on ophthalmologic end points in rats 
or dogs in repeat-dose toxicity studies.  Talazoparib was not mutagenic in a bacterial reverse 
mutation assay, but consistent with the genomic instability of its primary pharmacology, was 
clastogenic in an in vitro chromosomal aberration assay and an in vivo micronucleus assay, 
indicating the potential for genotoxicity in humans.  Talazoparib caused fetal malformations, 
structural variations, and death in an embryo-fetal development study in rats.  Based on an in 
vitro 3T3 neutral red uptake assay, which results in a high incidence of false positives, 
talazoparib is potentially phototoxic in humans.  In conclusion, the main nonclinical 
toxicologic findings were early hematologic changes and subsequent bone marrow and 
lymphoid organ depletion; focal atrophy and degeneration of testes, epididymis, and 
seminiferous tubules; and dose-dependent apoptosis/necrosis in the gastrointestinal tract and 
liver after repeat-dose talazoparib.  These findings are consistent with the exaggerated 
pharmacology of talazoparib and its tissue exposure pattern.
Additional information on the toxicology of talazoparib is provided in the talazoparib 
investigator brochure.
1.4. Talazoparib Benefits and Risks Assessment
The doses of talazoparib in this protocol are supported by nonclinical studies and phase 1 
studies in patients with advanced malignancies. Antitumor activity has been observed in 
these studies and is being further evaluated in a larger patient population. Common adverse 
events with talazoparib as monotherapy include myelosuppression, gastrointestinal toxicity, 
fatigue, and alopecia.  Myelodysplastic syndrome/Acute Myeloid Leukemia, hepatotoxicity, 
second primary malignancies (other than hematologic), and pneumonitis are additional rare 
and serious adverse events of special interest per the investigator’s brochure, Section 7.  
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, 
which is the single reference safety document (SRSD) for this study.
2. STUDY OBJECTIVE

To obtain additional safety data on long-term talazoparib use.
3. INVESTIGATIONAL PLAN
3.1. Overall Study Design and Plan: Description
This is a single-arm, open-label, extended treatment, safety study in patients treated with 
talazoparib (also known as MDV3800, BMN 673, PF-06944076) as a single agent or in 
combination with another agent in qualifying originating clinical studies sponsored by 
Medivation/Pfizer. The safety and tolerability of long-term talazoparib use will be evaluated, 


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and the data collected will be limited to safety assessments.  The study provides access to 
single-agent talazoparib for qualifying patients who may benefit from continuing therapy 
with talazoparib.
Eligible patients must have received talazoparib in a qualifying study and have no ongoing 
grade 3 or 4 talazoparib-related toxicities.  Patients must receive their first dose of 
talazoparib in this protocol within 2 months after their last dose of talazoparib in the
originating study and may not receive any intervening antineoplastic therapies before starting 
this study. Patients will have clinic visits approximately every 4 weeks for the first 24 weeks 
and then approximately every 8 weeks thereafter (additional visits for laboratory testing 
every 2 weeks through week 9 and every 4 weeks thereafter) or as clinically indicated.  
Patients enrolling from study PRP-001 may continue the last visit schedule they tolerated in 
that study (eg, if a PRP-001 patient is on an every 4 week schedule in the originating study, 
the patient is required to complete the week 5 and week 9 visits but not the CBC assessments 
at week 3 and week 7; afterwards, these patients would follow the schedule of activities in 
Appendix 1). Additional clinic visits and laboratory testing may be necessary to monitor 
safety (eg, for dose modification, hematologic toxicity, pregnancy testing).
The maximum starting dose of talazoparib will be 1 mg/day or the last tolerated dose 
administered in the originating study. Talazoparib capsules will be administered by mouth 
once daily with or without food at approximately the same time of day. Patients receiving 
talazoparib as combination treatment in the originating study will receive talazoparib as a 
single agent in this extended treatment study.  Talazoparib administration may continue as 
long as the investigator considers treatment to be providing clinical benefit or until other 
study discontinuation criteria are met (Section 5.3).  The addition of any other antineoplastic 
therapy and the concurrent use of investigational agents during the study are prohibited.
Study assessments will include adverse events, local clinical laboratory tests, concomitant 
medications, physical examinations, and vital signs (and weight). Clinical laboratory tests 
(hematology, serum chemistry) will be performed every 4 weeks through week 25 and every 
8 weeks thereafter during the study. Complete blood count (CBC) tests will be completed 
every 2 weeks through week 9 and every 4 weeks thereafter. Women of childbearing 
potential must have a pregnancy test every 4 weeks. Safety follow-up will be through and 
including 30 days after the last dose of talazoparib.
3.2. Study Schematic
The study schematic is provided in Figure 1.


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Figure 1.
Study Schematic
Treatment
Informed 
consent 
Key assessments: laboratory tests, physical examinations, adverse events.
Patients enrolling from study PRP-001 may continue the last visit schedule they tolerated in that study.
3.3. Blinding
All talazoparib treatment will be open label.  All patients, study site personnel (including
investigators), and sponsor staff and its representatives will be unblinded to treatment
identity.
3.4. Duration of Study
Talazoparib administration will continue until the last patient has stopped deriving clinical
benefit as assessed by the investigator or meets other study discontinuation criteria
(Section 5.3).  The total duration of this study is anticipated to be approximately 4 years.
3.5. Discussion of Study Design
This study is designed to evaluate the safety and tolerability of long-term talazoparib use for
patients who were treated with talazoparib as a single agent or in combination with another
agent in a qualifying talazoparib clinical study who may benefit from continuing therapy
with talazoparib.  Talazoparib is considered a cytotoxic and clastogenic agent and therefore,
cannot be administered to healthy volunteers.  Only patients with cancer may be enrolled in
talazoparib studies, including phase 1 and clinical pharmacology studies, which generally
include only a single dose or very short dosing periods.
3.5.1. Rationale for Dose and Schedule
Patients will receive talazoparib at a maximum starting dose of 1 mg/day or the last tolerated
dose administered in the originating study.  The maximum tolerated dose of talazoparib is
1 mg/day and is the recommended phase 2 monotherapy dose based on the results of the
phase 1, dose-escalation study in patients with solid tumors (PRP-001).  However, patients
whose last tolerated dose of talazoparib was reduced from 1 mg/day in the originating study
will continue to receive the reduced dose in this study.  The maximum dose of talazoparib 
allowed for patients with moderate renal impairment (defined as estimated Glomerular 
Filtration Rate (eGFR) ≥30 and ≤59 mL/min/1.73m2) is 0.75 mg/day. The maximum dose of 
talazoparib allowed for patients with severe renal impairment (defined as eGFR ≥15 and 
≤29 mL/min/1.73m2, not on dialysis) is the last tolerated dose on the originating study up to a 
maximum dose of 0.5 mg/day.  
Patients treated 
with 
talazoparib 
(single agent or 
in combination) 
in selected 
clinical studies 
sponsored by 
Medivation/
Pfizer
Talazoparib
Daily
Maximum 
starting dose: 
1 mg/day or 
last tolerated 
dose in the 
originating 
study
Visits 
every 4 
weeks for 
24 weeks, 
every 8 
weeks 
thereafter
End of 
Treatment
Patient no 
longer 
receiving 
clinical benefit 
(investigator 
decision) or 
meets other 
discontinuation 
Safety 
Follow-Up
Through 
and 
including 
30 days 
after last 
dose


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4. SELECTION OF STUDY POPULATION
The specific eligibility criteria for selection of patients are provided in Section 4.1 and
Section 4.2. The sponsor will not grant any eligibility waivers.
4.1. Inclusion Criteria
Each patient eligible to participate in this study must meet all of the following criteria:
1. Treated with talazoparib as a single agent or in combination with another agent in a
qualifying talazoparib clinical study in advanced solid tumors sponsored by 
Medivation/Pfizer and has no ongoing National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 talazoparib-related
toxicities.
2. Willing and able to provide informed consent for extended open-label treatment.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
4. Able to swallow capsules whole, have no known intolerance to talazoparib or 
excipients, and able to comply with study requirements throughout the study.
5. Able to tolerate ≥0.25 mg/day talazoparib during the originating study.
6. Female patients of childbearing potential (defined in Section 4.3) must have a 
negative pregnancy test before the first dose of talazoparib and must agree to use a 
highly effective birth control method (defined in Section 4.3) from the time of the 
first dose of talazoparib through 7 months after the last dose.
7. Male patients must use a condom when having sex with a pregnant woman or with a 
woman of childbearing potential from the time of the first dose of talazoparib through 
4 months after the last dose.  Contraception should be considered for a nonpregnant 
female partner of childbearing potential.
8. Female patients may not be breastfeeding at the first dose of talazoparib and must not
breastfeed during study participation through 7 months after the last dose of 
talazoparib.
9. Male and female patients must agree not to donate sperm or eggs, respectively, from
the first dose of talazoparib through 4 and 7 months, respectively, after the last dose.
4.2. Exclusion Criteria
Each patient eligible to participate in this study must NOT meet any of the following 
exclusion criteria:
1. Permanently discontinued from any Medivation/Pfizer-sponsored study with 
talazoparib alone or in combination with another agent.


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2. Received an antineoplastic therapy or investigational agent after treatment with 
talazoparib in the originating study.
3. Has a clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, 
hematologic, infectious, metabolic, neurologic, psychologic, or pulmonary disorder or
any other condition, including excessive alcohol or drug abuse, or secondary 
malignancy, that may interfere with study participation in the opinion of the 
investigator.
4. Diagnosis of myelodysplastic syndrome (MDS).
5. For patients entering from studies MDV3800-01 (renal impairment) or MDV3800-02 
(hepatic impairment), clinically significant deterioration of renal or hepatic function, 
respectively, after dosing in the originating study.
6. Serious accompanying disorder or impaired organ function, including the following:

Renal: Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 by the 
MDRD equation (Modification of Diet in Renal Disease [available via
www.mdrd.com]), except for patients from study MDV3800-01 (renal 
impairment) with severe renal impairment (eGFR 15-29 mL/min/1.73 m2).

Hepatic:

For patients entering from all other qualifying studies excluding 
MDV3800-02 (hepatic impairment): Total serum bilirubin >1.5 times the 
upper limit of normal (ULN) (>3 × ULN for patients with Gilbert syndrome or 
for whom indirect bilirubin concentrations suggest an extrahepatic source of 
elevation). Aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) ≥2.5 times ULN (if liver test abnormalities are due to hepatic 
metastases, AST or ALT ≥5 × ULN).

For patients entering from study MDV3800-02 (hepatic impairment): Inability 
to tolerate talazoparib 0.25 mg/day or had liver tests (bilirubin, AST, or ALT) 
that worsened to clinically significant values during the study.

Bone marrow reserve (Blood samples collected after at least 14 days without 
growth factor support or transfusion. Dose modification in the originating study 
is permitted to improve bone marrow reserve for eligibility):

For patients entering from all qualifying studies excluding patients with 
moderate or severe hepatic dysfunction (Groups C and D) of study 
MDV3800-02 (hepatic impairment): Absolute neutrophil count <1500/µL,
platelets <100,000/µL, or hemoglobin <9 g/dL.


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
For patients with moderate or severe hepatic dysfunction (Groups C and D) 
entering from study MDV3800-02 (hepatic impairment): Absolute neutrophil 
count <1500/µL, platelets <50,000/µL, or hemoglobin <8 g/dL.
4.3. Reproductive Considerations
Female patients of childbearing potential must have a negative serum pregnancy test before
the first dose of talazoparib and a negative urine or serum test every 4 weeks thereafter
during the treatment period and must avoid pregnancy during the study.  Urine pregnancy
tests must have a limit of detection of 25 IU/L (or equivalent units) for human chorionic
gonadotropin.  If a pregnancy test is positive, talazoparib will be discontinued.
Female patients of childbearing potential must use a highly effective form of birth control
from the first dose of talazoparib through 7 months after the last dose, defined as follows:

Established use of an oral, intravaginal, or transdermal combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition of
ovulation;

Established use of an oral, injectable, or implantable progestogen-only hormonal
contraception associated with inhibition of ovulation;

Placement of an intrauterine device or intrauterine hormone-releasing system;

Bilateral tubal ligation for ≥6 months before the first dose of talazoparib in the
current study;

Partner vasectomized for ≥6 months before the first dose of talazoparib in the current
study;

Sexual abstinence when in relation to the preferred and usual lifestyle of the patient.
Female patients who meet 1 of the following criteria are considered not of childbearing
potential:
1. Surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy);
OR
2. Postmenopausal, defined as follows:

≥55 years of age with no spontaneous menses for ≥12 months before the first dose
of talazoparib in the current study;

<55 years of age with no spontaneous menses for ≥12 months before the first dose
of talazoparib in the current study and with a postmenopausal follicle-stimulating
hormone (FSH) concentration >30 IU/L.


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Male patients must use a condom when having sex with a pregnant woman or with a woman
of childbearing potential from the first dose of talazoparib through 4 months after the last
dose.  Contraception should be considered for a nonpregnant female partner of childbearing
potential.
Details regarding the reporting procedures to follow in the event of pregnancy are provided 
in Section 8.4.3.1 Instructions regarding egg donation and breastfeeding are provided in 
Section 4.1.
5. ENROLLMENT AND STUDY PROCEDURES
Study enrollment and procedures are summarized in the following subsections. The study 
periods will include treatment and safety follow-up.  The timing of all study procedures is 
provided in the schedules of activities (Appendix 1). Signed informed consent must be 
obtained before performing any study-specific procedures.
The informed consent may be signed and eligibility may be evaluated while the patient is 
participating in the originating study and may be completed greater than 28 days prior to the 
week 1 visit.  The Interactive Response Technology (IRT) system user manual contains the 
information needed for registering patient status.
5.1. Informed Consent and Eligibility
Study site personnel must explain to potential study participants all aspects of the study,
including all scheduled visits and activities.  Study site personnel must obtain signed
informed consent before any study-specific procedures are conducted unless the procedures
were part of the originating study or routine standard of care, and must document the
informed consent process in the patient’s source documents.  The informed consent form
must be signed before any study-specific procedures and eligibility testing must be completed 
within 28 days before the week 1 visit.  Any eligibility testing procedures completed for the 
originating study within 28 days prior to the week 1 visit in this study may be used to assess 
eligibility for this study as applicable.
Patients will be identified with the patient number used in the originating study. After 
obtaining signed informed consent, study site personnel will evaluate potential study 
participants for eligibility.
The investigator will assess the eligibility of each patient. All relevant information must be 
available before eligibility can be determined. Eligibility assessments include ECOG status, 
adverse events, physical examination, pregnancy test (female patients of childbearing 
potential only), and hematology and serum chemistry tests. All inclusion criteria must be 
met and none of the exclusion criteria may apply.  No eligibility waivers will be granted.
After the investigator determines the patient is eligible for the study, study site personnel will 
complete an Enrollment Authorization Form and email it to the medical monitor or designee 
ideally 2 business days before the anticipated week 1 visit to approve the enrollment in 
writing. Study site personnel should ensure that an approved Enrollment Authorization Form 
is in the patient’s file before proceeding with week 1 procedures.


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5.2. Treatment Period
5.2.1. Treatment Period Visit Windows
All treatment period visits have a visit window of ±7 days (ie, 7 days before or after the
given day), except the week 1 visit (assessment of eligibility and start of study treatment),
which has a visit window of -28 days.
Talazoparib supplies (and the relative total number of capsules provided each time) must be 
taken into account when scheduling visits during visit windows to ensure patients do not run 
out of study drug between visits.  Procedures for a given visit may be split across the window 
to allow for drug resupply and completion of study procedures.
5.2.2. Treatment Period Study Visit Procedures
For the purpose of this study, there will be no day 0.
During the week 1 visit, the investigator will determine whether the patient is eligible for the
study (Section 5.1) and the patient will start study treatment.  Day 1 is the day of the first
dose of talazoparib in this study, which will occur within 2 months after the last dose in the
originating study.
All patients will have visits approximately every 4 weeks for the first 24 weeks and then 
approximately every 8 weeks thereafter or as clinically indicated (additional visits for 
laboratory testing every 2 weeks through week 9 and every 4 weeks thereafter). Patients 
enrolling from study PRP-001 may continue the last visit schedule they tolerated in that study
(eg, if a PRP-001 patient is on an every 4 week schedule in the originating study, the patient 
is required to complete the week 5 and week 9 visits but not the CBC assessments at week 3 
and week 7; afterwards, these patients would follow the schedule of activities in 
Appendix 1).
Specified study procedures will be performed at each clinic visit according to the schedule of 
activities (Appendix 1).
Clinical laboratory assessments will be conducted and reviewed before dosing at each visit.
Any clinically significant abnormalities must be reported as adverse events per CTCAE, 
version 4 criteria.  Dose modifications will be made as necessary Section 9.1.1).
Potential hematologic toxicities will be monitored by completing CBC tests every 2 weeks 
through week 9 and every 4 weeks thereafter (if abnormal, refer to Section 9.1.1).
Female patients of childbearing potential must have a negative serum pregnancy test before 
the first dose of talazoparib and a negative urine or serum test every 4 weeks thereafter 
before dosing.
Study visits and talazoparib treatment will continue as long as the investigator considers 
treatment to be providing clinical benefit or until other study discontinuation criteria are met 
(Section 5.3).


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5.2.3. Unscheduled Visit Procedures
Unscheduled visits may be performed anytime to assess or follow up adverse events, for dose 
modification, or at the request of the patient or investigator. The date and reason for the 
unscheduled visit must be recorded in the source documentation.
A review of adverse events and changes to concomitant medications or treatments (including 
herbal therapies) occurring since the previous visit should be performed at unscheduled 
visits.  If an unscheduled visit is necessary to assess toxicity, diagnostic tests may be 
performed based on investigator assessment as appropriate.
Unscheduled visit procedures are listed in Appendix 1. Other study procedures may be 
performed as clinically appropriate.
5.3. Permanent Treatment Discontinuation
Permanent treatment discontinuation is defined as cessation of talazoparib administration.
After permanent discontinuation, safety follow-up will be per Section 5.4, unless the patient
withdraws consent for further follow-up.
Temporary treatment interruption (eg, due to an adverse event) is not considered permanent
discontinuation.
The primary reasons for which patients permanently discontinue study treatment are listed in
Table 1.
Table 1.
Primary Reasons For Permanent Treatment Discontinuation
Reason
Comment
Disease progression
Talazoparib treatment will be discontinued if the investigator
believes that talazoparib is no longer providing clinical benefit.
Adverse event or intercurrent illness
Any intolerable adverse event that cannot be ameliorated by the 
use of adequate medical intervention or that in the opinion of the 
investigator or sponsor would lead to undue risk if study 
treatment were continued (eg, severe drug induced liver injury 
Section 9.1.2.1 or myelodysplastic syndrome [MDS]/acute 
myeloid leukemia [AML] [Table 4]).  Refer to Section 8.2.1.
May or may not be related to disease progression.
Administration of prohibited concomitant 
therapy
Refer to Section 7.2.
Patient decision
Patients may permanently discontinue treatment anytime for any 
reason.
Investigator decision
The investigator may elect to discontinue talazoparib if in their 
opinion it is in the patient’s best interest.  This category should 
be selected if adverse event or administration of prohibited 
concomitant therapy do not apply and the patient preferred to 
continue treatment.


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Major noncompliance with protocol
The medical monitor or investigator may request permanent 
treatment discontinuation in the event of a major protocol 
deviation, lack of cooperation, or noncompliance.
Loss to follow-up
Refer to Section 5.5.
Sponsor discontinuation of study
The sponsor reserves the right to terminate the study anytime for 
any reason as described in Section 13.6. The sponsor will 
terminate this study following completion of the study 
objectives, or earlier if deemed necessary.
5.4. Safety Follow-Up
Patients will have safety follow-up after permanent discontinuation of talazoparib. Safety 
follow-up should occur through and including 30 days after the last dose of talazoparib.
Safety follow-up procedures are listed in Appendix 1.
If treatment is discontinued due to an adverse event or serious adverse event, the event(s)
must be followed up as described in Section 8.1.4.1.
For patients who refuse to come to the clinic for safety follow-up, telephone contact must be
attempted and documented to review for adverse events through approximately 30 days after
the last dose of talazoparib. If the patient does not respond to telephone calls, the procedures
for loss to follow-up in Section 5.5 should be followed.
5.5. Loss to Follow-Up
Every reasonable effort must be made to contact any patient apparently lost to follow-up
during the course of the study to complete study-related assessments and record outstanding
data.  Following unsuccessful telephone contact, the following should occur:

An effort to contact the patient by mail using a method that provides proof of receipt
should be attempted.

Alternate contacts are permissible if the patient is not reachable (eg, primary care
providers, referring physician, relatives).

Such efforts should be documented in the patient’s source documents.
If all efforts fail to establish contact, the patient will be considered lost to follow-up. Patients 
who withdraw consent will be considered lost to follow-up for analysis purposes.
6. INVESTIGATIONAL PRODUCT INFORMATION
6.1. General Information
The study drug is talazoparib.  The sponsor will provide talazoparib capsules.


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6.2. Talazoparib Product Characteristics
Talazoparib is provided as the 4-methylbenzenesulfonate (tosylate) salt and has the chemical 
name (8S,9R) 5-fluoro-8-(4-fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-
yl)-3H-pyrido[4,3,2-de]phthalazin-3-one.  The drug product is a capsule containing 
talazoparib tosylate and silicified microcrystalline cellulose. The capsules for each dose 
strength will be provided in dose-specific colors. Additional details will be provided in the
Investigational Product (IP) Manual.
6.2.1. Packaging of Talazoparib
Talazoparib study drug is packaged in induction sealed, high-density polyethylene bottles
with child-resistant caps.
The label will vary depending on individual country requirements.  At minimum, each label
typically provides the study protocol number, contents, directions for use, storage directions,
clinical trial statement, sponsor name, batch/lot number, and product retest or expiration date.
6.2.2. Storage and Handling of Talazoparib
The drug product should be stored safely and properly in accordance with the study drug
label.
Talazoparib is considered a cytotoxic and clastogenic agent; precautions regarding appropriate
secure storage and handling must be used by healthcare professionals, including disposable 
gloves, and equipment (Goodin et al, 2011).2  Patients should be advised that oral anticancer 
agents are toxic substances and that other caregivers should always use gloves when
handling the capsules.
6.2.3. Directions for Administration of Talazoparib
The maximum daily dose of talazoparib is 1 mg/day given orally at approximately the same
time each day.  For patients who last tolerated a reduced dose in the originating study, the
last tolerated dose will be given as the daily dose in this study. The maximum dose of 
talazoparib allowed for patients with moderate renal impairment (defined as eGFR ≥30 and 
≤59 mL/min/1.73m2) is 0.75 mg/day.  The maximum dose of talazoparib allowed for patients 
with severe renal impairment (defined as eGFR ≥15 and ≤29 mL/min/1.73m2, not on 
dialysis) is the last tolerated dose on the originating study up to a maximum dose of 
0.5 mg/day.
Patients should self-administer talazoparib orally once daily, with or without food. The 
capsules should be swallowed whole with a glass of water without chewing, dissolving, or 
opening them.
Patients should not make up missed or vomited doses; dosing should resume on the next
calendar day unless otherwise instructed.


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Medication errors for this study include: 

Medication errors involving patient exposure to the investigational product:

Lack of dose reduction as specified by the protocol;

Continuation of treatment although patient met discontinuation criteria;

Incorrect study drug dose taken by patient;

Patient did not take study medication for 6 or more days (approximately 
<80% compliance) within 4 weeks, unless dose withheld due to an AE;

Patient did not receive treatment as assigned by IRT.

Potential medication errors or used outside of what is foreseen in the protocol that do 
or do not involve the participating patient.
Refer to Section 8.4.4 for instructions on how to report a medication error.
6.2.3.1. Dose Modifications
Dose modifications for talazoparib due to adverse events are described in Section 9.1.1.
Talazoparib dose escalation at 0.25 mg increments up to the maximum protocol specified 
dose of 1.0 mg/day may be allowed at the next visit if the following conditions are all met:

The reduced dose is tolerated and any toxicities are resolved;

Dose re-escalation has been agreed with the medical monitor prior to implementation 
of the dose escalation;

Dose escalation for patients with moderate renal impairment (defined as eGFR 
≥30 and ≤59 mL/min/1.73 m2) may be allowed up to a maximum dose of 
0.75 mg/day;

Dose escalation for patients with severe renal impairment (defined as eGFR ≥15 and 
≤29 mL/min/1.73m2, not on dialysis) may be allowed up to the last dose tolerated in 
the originating study up to a maximum dose of 0.5 mg/day;

Dose escalation for patients that are coadministered a strong P-gp inhibitor, may be 
allowed up to a maximum dose of 0.75 mg/day.
Dose modifications due to adverse events are described in Section 8.2.1.


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6.2.3.2. Overdose Management
An overdose is defined as any dose greater than the protocol-specified maximum starting 
dose. 
There is no specific treatment in the event of talazoparib overdose, and symptoms of 
overdose are not established. In the event of overdose, treatment with talazoparib should be 
stopped, and physicians should consider gastric decontamination, follow general supportive 
measures and treat symptomatically taking into consideration the mean half-life is 
89.9 hours.  All overdose events are to be reported within 24 hours of awareness by the study 
site according to Section 8.4.4 whether or not the overdose is associated with an adverse 
event and the sponsor/medical monitor must be contacted.
6.3. Treatment Compliance
Accountability for the talazoparib capsules will be performed to document compliance with
the dosing regimens.  Patients will be asked to bring all used and unused talazoparib bottles
to study visits.  Study site personnel must make reasonable efforts to obtain used and unused
talazoparib bottles from patients who do not routinely return them at study site visits.
Unreturned capsules will be considered to have been taken.
7. PRIOR AND CONCOMITANT THERAPY
Prior and concomitant medications include all vitamins, herbal remedies, and
over-the-counter and prescription medications.
7.1. Prior Medications
Medications taken after the last dose of talazoparib in the originating study and before the 
first dose of talazoparib in the current study, and any medications prescribed for chronic or 
intermittent use during the study, or dose adjustments of these medications, must be recorded 
on the case report form and in the patient’s source documents.
Per the study eligibility criteria (Section 4), patients who received an antineoplastic therapy 
or investigational agent after treatment with talazoparib in the originating study are excluded 
from study participation.
7.2. Concomitant Therapy
Concomitant therapy (noninvestigational products) includes any concomitant medications,
blood transfusions, or radiotherapy used between day 1 and safety follow-up.
Palliative radiation is allowed during the study, but the combination of radiation therapy and 
talazoparib as monotherapy has not been studied.


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Concomitant medications will be assessed at all clinic visits (excluding weeks 3 and 7 and 
every 4 weeks after week 25 when only CBC testing is scheduled). All concomitant 
medications, including over-the-counter and prescription medications, must be recorded on
the appropriate case report form.  If the use of any medication during the study is due to an 
adverse event, the adverse event must be recorded on the adverse event case report form and 
in the patient’s source documents.
Prohibited medications are described in Table 2. Deviation from these guidelines should 
occur only if absolutely necessary for the well-being of the patient, and the medical monitor 
is to be notified to determine whether continued treatment with talazoparib is permitted.
Talazoparib must be permanently discontinued upon initiation of a new antineoplastic
therapy.  Patients who discontinue treatment due to initiation of such therapy will complete
safety follow-up per Section 5.4.
Table 2.
Prohibited Concomitant Therapies
Medication or Treatment
Comment on Use
Any antineoplastic therapy (including biologic, 
radionuclide)
Any time after treatment in the originating study through 
safety follow-up.
Other investigational agent (eg, biologic, 
vaccine, or other agents not approved for 
marketing)
Any time after treatment in the originating study through 
safety follow-up.
Live bacterial and virus vaccines
7.3. Potential Interactions Between Talazoparib and Concomitant Medications
Talazoparib is a substrate for drug transporters P-gp and BCRP and mainly eliminated by 
renal clearance as unchanged compound.  P-gp inhibitors, P-gp inducers, and BCRP 
inhibitors may affect talazoparib plasma concentrations.
Guidelines for concomitant use of talazoparib with inhibitors or inducers of P-gp or
inhibitors of BCRP are as follows:

Use of strong P-gp inhibitors (including but not limited to amiodarone, carvedilol, 
clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, 
itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, 
ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil) is not 
recommended. If patients must be coadministered a strong P-gp inhibitor, the 
maximum dose of talazoparib should be 0.75 mg/day.

Use of P-gp inducers (including but not limited to carbamazepine, rifampin, and 
St. John’s wort) and BCRP inhibitors (including but not limited to curcumin, 
cyclosporine, and elacridar,[GF120918]) should be avoided.  Refer to the following 
website for a complete list:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Dr
ugInteractionsLabeling/ucm093664.htm.
The sponsor/medical monitor should be consulted prior to a patient taking strong a P-gp 
inhibitor, a P-gp inducer, or a BCRP inhibitor.


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8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the Case Report 
Form (CRF) and for reporting safety events on the Clinical Trial (CT) Serious Adverse Event 
(SAE) Report Form to Pfizer Safety.  These requirements are delineated for 3 types of 
events: (1) SAEs; (2) non-serious adverse events (AEs); and (3) exposure to the 
investigational product under study during pregnancy or breastfeeding, and occupational 
exposure.  
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All for all enrolled patients*
All
Non-serious AE
All for all enrolled patients*
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
* Please note that AEs including SAEs for all enrolled patients that occur between consent for this study and 
first dose in this study are to be recorded on the Medical History CRF and not as AEs. AEs are recorded in the 
qualifying originating study as AEs, if occurring during the active collection period of the qualifying originating 
study.
All observed or volunteered events regardless of suspected causal relationship to the 
investigational product will be reported as described in the following paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 


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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 
patient death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded in the CRF.  It should be noted that the 
CT SAE Report Form for reporting of SAE information is not the same as the AE page of the
CRF.  When the same data are collected, the forms must be completed in a consistent 
manner.  AEs should be recorded using concise medical terminology and the same AE term 
should be used on both the CRF and the CT SAE Report Form for reporting of SAE 
information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study patient/parent(s)/legal guardian/legally acceptable representative.  In 
addition, each study patient/parent(s)/legal guardian/legally acceptable representative will be 
questioned about the occurrence of AEs in a non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Permanent 
Treatment Discontinuation section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.  
When a patient withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each patient begins from the time the patient takes the first dose of study drug 
(investigational product) through and including a minimum of 30 calendar days after the last 
administration of the investigational product.  Adverse events including SAEs for all enrolled 
patients that occur between when patient provides informed consent for this study, which is 
obtained before the patient’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product) and first dose in this study 
are to be collected on the Medical History CRF for this study and not as AEs and 
collected/reported in the qualifying originating study as AEs.


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For patients who are screen failures, the active collection period ends when screen failure 
status is determined. No data is to be entered in the CRF for screen failures for this study; 
however, SAEs must still be reported to Pfizer safety within 24 hours for screen failures.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a patient during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a patient after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
If a patient 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.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs for all enrolled patients 
are recorded on the CRF.  As noted above, AEs including SAEs for all enrolled patients that 
occur between consent for this study and first dose in this study are to be recorded on the 
Medical History CRF and not as AEs. AEs are recorded in the qualifying originating study 
as AEs, if occurring during the active collection period of the qualifying originating study.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious) occurring after the first dose of study drug in this study; the investigator must 
record the causal relationship on the CRF, and report such an assessment in accordance with 
the SAE reporting requirements, if applicable.  An investigator’s causality assessment is the 
determination of whether there exists a reasonable possibility that the investigational product 
caused or contributed to an AE; generally the facts (evidence) or arguments to suggest a 
causal relationship should be provided.  If the investigator does not know whether or not the 
investigational product caused the event, then the event will be handled as “related to 
investigational product” for reporting purposes, as defined by the sponsor.  If the 
investigator's causality assessment is “unknown but not related” to investigational product, 
this should be clearly documented on study records.  


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In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study patient administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to:

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.


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Worsening of signs and symptoms of the malignancy under study should be recorded as AEs 
in the appropriate section of the CRF.  Disease progression assessed by measurement of 
malignant lesions on radiographs or other methods should not be reported as AEs.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.


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Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Additionally, for this study important medical events include:

A diagnosis of MDS or acute myeloid leukemia (AML). Tissue samples and any 
other supporting data used to enable the diagnosis of MDS or AML should be 
submitted for central review if requested.

Second primary malignancy

Abnormal liver test results (in addition to the requirement for Potential Cases of 
Drug-Induced Liver Injury, Section 8.4.2), as described below: 

AST or ALT ≥3 times ULN (>5 × ULN if baseline ALT/AST is >3 × ULN) and 
total bilirubin >2 times ULN or INR >1.5;

AST or ALT ≥3 times ULN with signs and symptoms consistent with hepatitis 
and/or eosinophilia (≥500 eosinophils/µL).
Important medical events occurring during the safety reporting period must be reported 
within 24 hours of awareness by the study site using a CT SAE report form.
Progression of the malignancy under study (including signs and symptoms of progression) 
should not be reported as an SAE unless the outcome is fatal within the active collection 
period.  Hospitalization due to signs and symptoms of disease progression should not be 
reported as an SAE.  If the malignancy has a fatal outcome during the study or within the 
active collection period, then the event leading to death must be recorded as an AE on the 
CRF, and as an SAE with Common Terminology Criteria for Adverse Events (CTCAE) 
Grade 5 (see the Severity Assessment section).
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);


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
Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the following definitions of 
severity in accordance with the current CTCAE version to describe the maximum intensity of 
the adverse event.  


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GRADE
Clinical Description of Severity
0 
No change from normal or reference range (This grade is not included in the 
Version 4.03 CTCAE document but may be used in certain circumstances.)
1
MILD adverse event
2
MODERATE adverse event
3
SEVERE adverse event
4
LIFE-THREATENING consequences; urgent intervention indicated
5
DEATH RELATED TO adverse event
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the patient's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.2. 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 patients, transaminase elevations are a harbinger of a more 
serious potential outcome.  These patients fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Patients who experience a transaminase elevation above 3 times the upper limit of 
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (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 lab 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.


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The threshold of laboratory abnormalities for a potential DILI case depends on the patient’s 
individual baseline values and underlying conditions.  Patients 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:

Patients 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 patients 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).
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 patient 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.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered.  
In addition to repeating measurements of AST and ALT and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
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 (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) may be warranted. 


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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.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy. 
If a patient or patient’s partner becomes or is found to be pregnant during the patient’s 
treatment with the investigational product, 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.  In addition, the investigator must submit information 
regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a patient 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) to Pfizer Safety using the EDP supplemental form.  This must be done irrespective 
of whether an AE has occurred and within 24 hours of awareness of the exposure.  The 
information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).


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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 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
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 [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), 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 includes 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 investigational product.
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 patient with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
patient was given the Pregnant Partner Release of Information Form to provide to his partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  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’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.


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An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a patient 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.
8.4.4. Medication Errors 
Other exposures to the investigational product 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
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong patient, or at the wrong time, or at the wrong dosage strength. 
Medication errors include:

Medication errors involving patient exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating patient.
Such medication errors occurring to a study patient 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 immediately.
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 non-serious, are recorded on an 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.
9. ASSESSMENT OF SAFETY ENDPOINTS
Study assessments will include adverse events, physical examinations, vital signs (and
weight), and clinical laboratory tests.  The procedures for the investigator assessment of
adverse events are presented in detail in Section 8.  The procedures for clinical laboratory
safety tests are presented in Section 9.1, and for physical examinations and vital signs in
Section 9.2.


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9.1. Clinical Laboratory Tests
Routine clinical laboratory tests (hematology, serum chemistry) will be performed according 
to the schedules of activities (Appendix 1). Samples will be stored until the specified 
analyses are completed and then will be destroyed in accordance with standard laboratory 
practice and applicable local regulations.
A list of the required routine clinical laboratory tests and other evaluations is provided in 
Table 3. All samples for laboratory analysis must be collected, prepared, and labeled 
according to laboratory requirements.
All clinical laboratory tests will be performed by the local laboratory.  The local laboratory 
reference ranges will be used.
Table 3.
Clinical Laboratory Tests
Hematology
Chemistry
Additional Tests
Hematocrit 
Hemoglobin
Mean corpuscular volume 
Red blood cell count 
Platelet count
White blood cell count with 
differential

Total neutrophils

Lymphocytes

Monocytes

Eosinophils

Basophils
Albumin 
Total protein
Alkaline phosphatase
ALT (alanine aminotransferase) 
AST (aspartate aminotransferase) 
Total bilirubin
Blood urea nitrogen 
Creatinine
Glucose (nonfasting) 
Bicarbonate
Calcium
Chloride 
Magnesium 
Phosphate 
Potassium 
Sodium
LDH (lactate dehydrogenase)
Serum and urine pregnancy tests for 
women of childbearing potential


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9.1.1. Dose Modifications Due to Adverse Events
Table 4.
Talazoparib Dose Modifications Due To Adverse Events
Toxicity
Management of Adverse Events (Except Liver Abnormalities1)
Grade 1 or 2
No requirement for dose interruption or dose reduction.
Selected hematologic grade 3 or 4 events
Anemia (hemoglobin
<8.0 g/dL)
Hold talazoparib and monitor weekly until hemoglobin returns to 9 g/dL (for patients 
originating from Groups C or D of study MDV3800-02: hold talazoparib and monitor at 
least twice weekly until hemoglobin returns to 8 g/dL).  Implement supportive care 
per local guidelines.

Talazoparib may be reduced by 1 dose level as described in Table 5. If 
anemia persists for >4 weeks without recovery to 9g/dL (to 8 g/dL for 
patients originating from Groups C or D of study MDV3800-02), discontinue 
talazoparib and refer to a hematologist for evaluation, including assessment 
for possible MDS/AML.
Toxicity
Management of Adverse Events (Except Liver Abnormalities1
Neutropenia (ANC <1000/µL)Hold talazoparib and monitor weekly until ANC ≥1500/µL.  Implement supportive care 
per local guidelines.  Resume talazoparib based on the following recovery times:

≤1 week: No change.

>1 week: Reduce talazoparib by 1 dose level as described in Table 5.  If 
neutropenia persists for >4 weeks without recovery to ≥1500/µL, discontinue 
talazoparib and refer to a hematologist for evaluation, including assessment 
for possible MDS/AML.
Thrombocytopenia (platelets 
<50,000/µL)
Hold talazoparib until platelets ≥75,000/µL (for patients originating from Groups C or 
D of study MDV3800-02: hold talazoparib and monitor at least twice weekly until 
platelets return to 50,000/ µL).  Implement supportive care per local guidelines.  
Resume talazoparib based on the following recovery times:

≤1 week: No change.

>1 week: Reduce talazoparib by 1 dose level as described in Table 5.
If thrombocytopenia persists for >4 weeks without recovery to ≥75,000/µL (to 50,000/ 
µL for patients originating from Groups C or D of study MDV3800-02), discontinue 
talazoparib and refer to a hematologist for evaluation, including assessment for possible 
MDS/AML.
Other grade 3 or 4 events, 
except abnormal liver tests1
Hold talazoparib as follows:

For clinically significant grade 3 or 4 laboratory abnormalities, talazoparib 
may be held.  Resume talazoparib when the laboratory abnormality resolves to 
grade ≤2 (baseline grade for creatinine increases).

For clinically significant grade 3 or 4 adverse events, hold talazoparib until 
the adverse event resolves to grade ≤2.  Resume talazoparib at the same dose 
or reduce by 1 dose level as described in Table 5 if the event resolves or 
improves within 4 weeks of holding talazoparib, and can be monitored if it 
recurs.
Implement supportive care per local guidelines. Contact medical monitor to discuss 
potential dose modification.
Talazoparib should be permanently discontinued for unresolved grade 3 or 4 toxicity 
per investigator decision that continued talazoparib treatment is not in the patient’s best 
interest.
1.
Dose modifications for liver abnormalities are discussed in Table 6.
AML, acute myeloid leukemia; ANC, absolute neutrophil count; MDS, myelodysplastic syndrome.


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NOTE: Patients originating from Groups C or D of study MDV3800-02 with hemoglobin 
≥8 and <9 g/dL and/or platelet count ≥50,000 and <100,000/L at study entry, need to be
able to maintain values at ≥8 g/dL and ≥50.000/L, respectively, during the study. Upon 
second dose interruption due to drop in hemoglobin and/or platelet count below 8 g/dL and 
below 50.000/L, respectively, they need to permanently discontinue study treatment.  
The dose of talazoparib may be reduced incrementally as shown in Table 5.
Table 5.
Talazoparib Dose Reduction for Toxicity
Talazoparib Dose Level
Talazoparib Dose (mg/day)
Initial maximum dose [1]
1.0
First dose reduction
0.75
Second dose reduction
0.50
Third dose reduction
0.25
1.
If the starting dose is less than 1.0 mg/day, dose reductions will be in 0.25 mg/day increments.
9.1.2. Assessment of Abnormal Liver Tests
Patients who develop abnormal liver tests (AST, ALT, total bilirubin), abnormal international 
normalized ratio (INR) values, or signs or symptoms of hepatitis during the study treatment 
period may meet the criteria for temporarily withholding or permanently discontinuing 
talazoparib as specified in United States (US) Food and Drug Administration (FDA)
Guidance for Industry - Drug-Induced Liver Injury: Premarketing Clinical Evaluation (2009).  
Patients who meet criteria for permanent discontinuation or temporary withholding of 
talazoparib or who do not meet the criteria but who have abnormal liver tests are to be 
followed up according to the recommendations in this section.
Talazoparib should be withheld for any liver test abnormality listed in Table 6.
Table 6.
Criteria for Temporary Withholding of Talazoparib in Association with 
Liver Test Abnormalities
Baseline AST or ALT Value
Elevation
≤3 × ULN
>5 × ULN (ALT or AST ≥3 × ULN with the presence of signs and 
symptoms consistent with acute hepatitis and/or eosinophilia
[≥500 eosinophils/µL])
>3 × ULN
>8 × ULN
Baseline Total Bilirubin Value
Elevation
≤1.5 × ULN
>3 × ULN (>5 × ULN in patients with a baseline total bilirubin
value of >1.5 × ULN and ≤3 × ULN [patients with Gilbert
syndrome or for whom indirect bilirubin concentrations suggest an
extrahepatic source of elevation])
For rechallenge, dose modification may be required per Table 3.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.


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Talazoparib should be withheld pending investigation of alternative causes of liver injury 
(Table 7). When withholding talazoparib, follow-up should continue for possible
drug-induced liver injury until the liver test abnormalities resolve to baseline grade. 
Rechallenge may be considered if an alternative cause for the abnormal liver tests (ALT, 
AST, total bilirubin) is discovered and the laboratory abnormalities resolve to normal or 
baseline values.
Table 7.
Criteria for Temporary Withholding of Talazoparib in Association with 
Liver Test Abnormalities
Recommended tests:
Complete blood count with differential to assess for eosinophilia;
Serum total immunoglobulin G (IgG), antinuclear antibody (ANA), antismooth muscle antibody,
liver kidney microsomal antibody 1 (LKM1), and liver cytosol type 1 antibodies (L-C-1) to assess for
autoimmune hepatitis;
Serum acetaminophen (paracetamol) concentration.
Obtain a more detailed history:
Prior and concurrent diseases or illness;
Exposure to environmental and/or industrial chemical agents;
Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-type reactions,
fatigue, nausea, vomiting, and fever;
Prior and concurrent use of alcohol, recreational drugs, and special diets;
Concomitant use of medications (including nonprescription medicines and herbal and dietary
supplements), plants, and mushrooms;
Obtain viral serologies for hepatitis A, B, C, and E (D if positive for hepatitis B), cytomegalovirus,
Epstein-Barr virus, herpes simplex virus.
Recommended tests as clinically indicated:
Echocardiogram (ECHO);
Serum and urine copper and serum ceruloplasmin;
Iron studies (serum iron and ferritin) and transferrin saturation Serology for celiac disease;
Serum alpha-1 antitrypsin;
Creatine phosphokinase (CPK), haptoglobin, lactate dehydrogenase (LDH), and peripheral blood
smear;
Appropriate liver imaging;
Hepatology consult (liver biopsy may be considered in consultation with a hepatologist).
The investigator and sponsor should discuss and agree with any decision to rechallenge. 
Following rechallenge, patients should be closely monitored for signs and symptoms of 
hepatitis and/or abnormal liver test results. If signs or symptoms recur with rechallenge, 
talazoparib should be permanently discontinued. Rechallenge should never occur if the 
criteria for permanent discontinuation are clearly met.
9.1.2.1. Criteria for Permanent Discontinuation of Talazoparib in Association with
Liver Test Abnormalities
Talazoparib should be discontinued permanently if all of the following 4 criteria are met (ie, 
potential severe drug-induced liver injury/Hy’s law case):
1. AST or ALT increases to ≥3 times ULN (>5 ×ULN if baseline ALT/AST is 
>3 ×ULN).


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2. Total bilirubin increases to >2 times ULN or INR >1.5.
3. Alkaline phosphatase value does not reach 2 times ULN (note: in the presence of 
elevated alkaline phosphatase associated with bone metastases, gamma glutamyl 
transferase should be tested and the results should be within the reference range).
4. No alternative cause explains the combination of the above laboratory abnormalities;
important alternative causes include, but are not limited to the following:

Hepatobiliary tract disease;

Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr virus, cytomegalovirus, 
herpes simplex virus, varicella, toxoplasmosis, and parvovirus);

Congestive heart failure, hypotension, or any cause of hypoxia to the liver causing
ischemia;

Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and 
dietary supplements, plants, and mushrooms;

Alcoholic hepatitis;

Nonalcoholic steatohepatitis (NASH);

Autoimmune hepatitis;

Wilson disease and hemochromatosis;

Alpha-1 antitrypsin deficiency.
If an alternative cause for hepatotoxicity is identified or less stringent conditions developed 
than those noted above, then it should be determined (based on the patient population as 
determined by the originating protocol and/or severity of the hepatotoxicity or event) whether 
talazoparib should be withheld or permanently discontinued as appropriate for the safety of 
the patient. When talazoparib is temporarily withheld or permanently discontinued due to a 
potential drug-induced liver injury, a period of close observation is to commence until the 
liver test abnormalities return to baseline or normal values.  The evaluations listed in Table 8
should be performed.


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Table 8.
Monitoring of Liver Tests for Potential Drug Induced Liver Injury
Results
Frequency for Repeating Liver (AST, ALT, Bilirubin 
[Total and Direct]) and INR Tests
After the initial liver test abnormality
Within 24 hours
If AST or ALT ≥3 × ULN (>5 × ULN if baseline 
ALT/AST is >3 × ULN), and total bilirubin
>2 × ULN or INR >1.5
Every 24 hours until laboratory abnormalities improve
If ALT or AST ≥3 × ULN (>5 × ULN if baseline 
ALT/AST is >3 × ULN) and total bilirubin or 
INR are normal
Every 48 to 72 hours until laboratory abnormalities
improve
If the liver test abnormalities improve AND the
patient is asymptomatic
Frequency may decrease
ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, international normalized ratio;
ULN, upper limit of normal.
As drug-induced liver injury is a diagnosis of exclusion, it is important to initiate 
investigation of alternative causes for abnormal liver tests, which may include consultation 
with a hepatologist.  The medical monitor should be contacted for questions regarding 
adequate follow-up tests.
9.2. Physical Examinations and Vital Signs
The investigator will perform brief physical examinations and vital sign measurements 
according to the schedule of activities (Appendix 1).  Interval medical history will be 
reviewed as a part of physical examinations.
Brief physical examinations will be symptom-directed, including investigating any new 
abnormalities, and may include an assessment of systems (eg, general appearance, head, 
eyes, ears, nose, mouth, skin, heart, lungs, lymph nodes, gastrointestinal, genitourinary, 
neurologic, and skeletal) per standard of care at the study site or as clinically indicated by 
symptoms.
Vital sign measurements will include blood pressure, heart rate, and temperature. Weight 
will be measured at the time of the examination.
Clinically significant abnormalities observed after signed informed consent is obtained and 
before the first dose of talazoparib in this study must be documented on the medical history 
case report form; any clinically significant change observed after the first dose of talazoparib 
must be documented as an adverse event.
10. STATISTICAL METHODS
10.1. Statistical and Analytical Plans
10.2. Analysis Populations
The safety population is defined as all patients who receive any amount of talazoparib. The 
safety population will be used for all safety analyses.


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10.3. Safety Analyses
All safety analyses will be performed using the safety population. Drug exposure will be 
summarized using descriptive statistics. Treatment-emergent safety data will be collected 
from the first dose of talazoparib through approximately 30 days after the last dose (ie, 
permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever 
occurs first as applicable based on the protocol version at the time the patient discontinued.  
For protocol version 4.0 or later, treatment-emergent safety data will be collected from the 
first dose of talazoparib through and including 30 days after the last dose (ie, permanent 
discontinuation) regardless of initiation of a new antineoplastic therapy.
The safety of talazoparib monotherapy will be evaluated by the analysis of incidence of 
serious and nonserious adverse events; severity of adverse events; incidence of dose 
reductions and of permanent treatment discontinuation due to adverse events; and incidence 
of new clinically significant changes in vital signs and clinical laboratory values.
Adverse events will be coded to preferred term and system organ class using the Medical 
Dictionary for Regulatory Activities (MedDRA) and classified by severity using the CTCAE 
version 4.  The number and percentage of patients with adverse events will be presented by 
MedDRA system organ class and preferred term, relationship to study treatment, severity,
seriousness, and outcome (eg, leading to permanent treatment discontinuation). Descriptive 
statistics will be used.
Laboratory values will be classified for severity using the CTCAE, version 4. Laboratory 
shift tables of baseline to maximum or minimum postbaseline results to each subsequent visit 
will be produced as appropriate.
Vital signs will be tabulated descriptively when applicable.
11. STUDY COMMITTEES AND COMMUNICATIONS
No formal study committees are planned for this study.
12. LABORATORY REQUIREMENTS
The local laboratory will analyze the clinical laboratory safety samples for this study as 
described in Section 9.2.
13. INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS
Before initiating the study, the investigator must provide the following documents to the 
sponsor:

Fully executed and signed Form FDA 1572;

Fully executed clinical trial agreement;

Current curriculum vitae (also applies to all subinvestigators listed on the Form FDA 
1572);

Financial disclosure (also applies to all subinvestigators listed on the Form FDA 
1572);


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
Signed protocol signature page;

Signed acknowledgment of receipt of the current investigator brochure;

Ethics committee (EC) approval letter;

EC-approved informed consent form;

Additional documents as necessary per local requirements.
If an investigator changes during the course of the study, the sponsor and any local regulatory 
authorities, as applicable, must first approve the change of investigator and the new 
investigator must provide the sponsor all of the documents listed above.
The sponsor personnel or representatives may visit the study site, if necessary, before 
initiation of the study to review information with study site personnel about protocol 
requirements pertaining to the study drug, case report forms, monitoring, serious adverse 
event reporting, and other relevant information.
13.1. Ethics
13.1.1. Ethics Committee
Before initiating the study, the investigator will obtain confirmation from the EC that the EC 
is properly constituted and compliant with all requirements and local regulations.
The investigator will provide the EC with all appropriate material, such as the protocol, 
current investigator brochure, site-specific informed consent form, and other written 
information provided to the patients. The study will not be initiated until the investigator 
obtains appropriate EC approval in writing for the protocol and informed consent document, 
and copies are received by the sponsor.
EC and health authority approval will be obtained for any substantial protocol amendments 
and informed consent revisions before implementing the changes.  The investigator will 
provide appropriate reports on the progress of the study to the EC, per local requirements, 
and to the sponsor or designee in accordance with applicable local regulations.
13.1.2. Ethical Conduct of the Study
This study will be conducted under the guiding principles of the World Medical Association 
Declaration of Helsinki, including current Good Clinical Practice (GCP) according to 
International Conference on Harmonisation (ICH) guidelines. Specifically, this study is 
based on adequately performed laboratory and animal experimentation; the study will be 
conducted under a protocol reviewed and approved by an EC; the study will be conducted by 
scientifically and medically qualified persons; the anticipated benefits of the study are in 
proportion to the risks; the rights and welfare of the patients will be respected; the physicians 
conducting the study do not find the hazards to outweigh the potential benefits; and each 
patient will provide written informed consent before any protocol-specific tests or 
evaluations are performed.


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13.1.3. Patient Information and Informed Consent
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of patient personal data.  Such 
measures will include omitting patient names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws. 
The 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 shall 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 natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, patient names will be removed and will be replaced by a single, specific, numerical 
code, based on a numbering system defined by Pfizer.  All other identifiable data transferred 
to Pfizer or other authorized parties will be identified by this single, patient-specific code.
The investigator site will maintain a confidential list of patients who participated in the study, 
linking each patient’s numerical code to his or her actual identity.  In case of data transfer, 
Pfizer will maintain high standards of confidentiality and protection of patients’ personal data 
consistent with the Clinical Study Agreement and applicable privacy laws.
The informed consent documents and any patient recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any patient 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC 
before use, and available for inspection.
The investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study, the sharing of data relating to the study and possible risks associated 
with participation, including the risks associated with the processing of the patient’s personal 
data.  The investigator further must ensure that each study patient 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 investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient before any study specific activity is performed.  The investigator 
will retain the original of each patient's signed consent document.


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13.1.4. Maintaining Patient Confidentiality
All reports and patient samples will be identified only by the originating study ID number 
and actual initials (if permitted) or mock initials and date of birth (month/year only if no date 
is permitted) in order to maintain patient confidentiality.  Additional patient confidentiality 
issues are addressed in the clinical trial agreement and in the informed consent form signed 
by each study participant.
13.2. Data Quality Assurance
13.2.1. Data Management
Clinical data management will be performed by the sponsor or designee according to 
procedures described in a comprehensive data management plan.  The data management plan 
will include procedures for processing the data from this study, and will describe the 
responsibilities of the sponsor and designee when clinical data management is provided by an 
external vendor.  In particular, the data management plan will include a list of the standard 
operating procedures that apply to this study.
Adverse events and medications will be coded using MedDRA and the World Health 
Organization Drug Dictionary (WHO-DD), respectively.  The dictionary versions will be 
named in the data management plan.
13.2.2. Case Report Forms
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included patient.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.  The investigator shall ensure that the 
CRFs are securely stored at the study site in encrypted electronic form and will be password 
protected to prevent access by unauthorized third parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases the source documents are the hospital or the physician's chart.  In these cases, 
data collected on the CRFs must match those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document. 


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Page 51
13.2.3. Study Monitoring
The sponsor or designee will monitor this study in accordance with current GCP guidelines. 
By signing this protocol, the investigator grants permission to the sponsor or designee and 
appropriate regulatory authorities to conduct onsite monitoring of all appropriate study 
documentation.  To ensure the accuracy of data collected on the case report forms, it is 
mandatory that sponsor representatives (eg, study monitor) have direct access to original 
source documents (eg, paper or electronic patient records, patient charts, and laboratory 
reports) needed to verify the entries on case report forms. During the review of these 
documents, the anonymity of the patient will be respected with strict adherence to 
professional standards of confidentiality.  A study monitor will contact and visit the site
regularly and will be allowed, on request at a mutually acceptable time, to inspect the various
original medical records (paper or electronic) related to the study.  The study monitor will be
responsible for inspecting the case report forms at regular intervals throughout the study, to 
verify the adherence to the protocol and the completeness and correctness of all case report 
form entries. The investigator agrees to cooperate with the study monitor to ensure that any 
problems detected in the course of these monitoring visits are resolved.
13.2.4. Study Audits
During the course of the study and after study completion, it is likely that one or more quality
assurance audits will be undertaken by authorized sponsor representatives.  The purpose of 
the audit is to ensure that the study is (or was) conducted and monitored in compliance with
the protocol as well as recognized GCP guidelines and regulations. These audits will also 
increase the likelihood that the study data and all other study documentation can withstand a 
regulatory authority inspection. If such audits are to occur, they will be arranged for a 
reasonable and agreed upon time.  By signing this protocol, the investigator grants
permission to the sponsor or designee to conduct onsite audits of all appropriate facilities and 
study documentation.
13.3. Investigational Product Accountability
The investigator must maintain accurate records of all study drug supplies received. All 
records must be made available to the sponsor, authorized representatives, and appropriate 
regulatory agencies, upon request.
Current ICH GCP guidelines require the investigator to ensure that study drug deliveries 
from the sponsor are received by a responsible person (eg, pharmacist), and the following:

That such deliveries are recorded, for example, on the sponsor’s drug accountability 
log or other sponsor-approved pharmacy log;

That study drug is handled and stored safely and properly in accordance with the label 
and the study protocol;

That study drug is only administered or dispensed to study patients in accordance 
with the protocol;

That any used or unused drug is returned by the patient at each required visit;


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PFIZER CONFIDENTIAL
Page 52

That any unused study drug is returned to the sponsor-designated facility or standard 
procedures for the alternative disposition of unused study drug are followed and only 
after approval by the sponsor representative.
Drug inventory and accountability records for the study drug will be kept by the 
investigator/pharmacist. Study drug accountability throughout the study must be 
documented.  The following guidelines are therefore pertinent:

The investigator agrees not to supply study drug to any persons except the patients in 
this study;

The investigator/pharmacist will keep the study drug in a pharmacy or other locked 
and secure storage facility under controlled storage conditions as required by the 
study drug label, accessible only to those authorized by the investigator to dispense 
the study drug;

The investigator/pharmacist will maintain a study drug inventory. The inventory will 
include details of material received and a clear record of when they were dispensed 
and to which patient;

The investigator/pharmacist agrees to conduct a final drug supply inventory and to 
record the results of this inventory on the drug accountability record at the conclusion 
or termination of this study.  It must be possible to reconcile delivery records with 
those of used and returned study drug.  Any discrepancies must be accounted for. 
Appropriate forms of deliveries and returns must be signed by the person responsible;

Used or unused study drug may be destroyed at the study site according to standard 
institutional procedures if the sponsor agrees with the procedure, and after drug 
accountability has been conducted by the sponsor or representative, unless otherwise 
approved. A copy of the standard institutional procedure for destroying 
investigational drugs will be provided to the sponsor or designee upon request for 
review and approval before the first onsite destruction.  Unused study drug not 
destroyed at the site must be returned to the sponsor-designated facility at the end of 
the study or upon expiration.
13.4. Compensation, Insurance, and Indemnity
In the event of a side effect or injury, appropriate medical care as determined by the 
investigator or designated alternate will be provided.
If bodily injury is sustained, resulting directly from the use of the study drug or by required 
study procedures, the sponsor will reimburse for reasonable physician fees and medical 
expenses necessary for treatment of only the bodily injury that is not covered by the patient’s 
medical or hospital insurance, provided that the injury is not due to a negligent or wrongful 
act or omission by the study doctor and study staff.  No other compensation of any type will 
be provided by the sponsor.  Financial compensation for lost wages, disability, or discomfort 
due to the study participation or procedures is not available.


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13.5. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating patients 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to the ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer.  The 
investigator must ensure that the records continue to be stored securely for so long as they are 
retained.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.  The 
investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met.
Investigators must maintain all study documentation for at least 2 years following the 
approval of the drug, or until 2 years after the investigational drug program is discontinued, 
or longer if required by local regulations.  Study documentation includes all essential 
documents as defined in ICH E6 Guidelines for Good Clinical Practice. The sponsor or 
designee will notify the investigator when any records may be discarded, but investigators 
must comply with local regulations.
13.6. Study Termination
The sponsor will terminate this study following completion of the study objectives, or earlier 
if deemed necessary.  Pfizer retains the right to discontinue development of talazoparib at 
any time.
The sponsor reserves the right to terminate the study anytime.  When the sponsor is aware of 
information on matters concerning the quality, efficacy, and safety of the study drug, as well 
as other important information that may affect proper conduct of the clinical study, the 
sponsor may terminate the study and send a written notice of the termination along with the 
reasons to the investigator.
If an investigator or the investigator’s EC intends to terminate participation in the study, the 
investigator must immediately inform the sponsor and provide the reason for it.


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PFIZER CONFIDENTIAL
Page 54
14. USE OF STUDY INFORMATION AND PUBLICATION
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulator guidance, and the need to protect the intellectual property of Pfizer (sponsor), 
regardless of the outcome of the trial. The data generated in this clinical trial are the 
exclusive property of the sponsor and are confidential.  Written approval from the sponsor is 
required before disclosing any information related to this clinical trial, and no publications 
initiated by investigators may be published until all protocol-defined primary and secondary 
endpoints are published in a manuscript. Every attempt will be made to minimize the
interval between the completion of data analysis and publication of the study results.
Recommendations for the timing of presentation of trial endpoint data and the publication 
venues (congresses/journals) will be given by the sponsor’s Publications Subcommittee.
Each investigator agrees to submit all manuscripts or congress abstracts and 
posters/presentations to the sponsor prior to submission. This allows the sponsor to protect 
proprietary information, provide comments based on information from other studies that may 
not yet be available to the investigator, and ensure scientific and clinical accuracy.  The 
details of the processes of producing and reviewing reports, manuscripts, and presentations 
based on the data from this trial will be presented in the investigator’s clinical study 
agreement.
In accord with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter trials only in their entirety and not as individual center data.
In this case, a coordinating investigator and lead author will be designated by mutual 
agreement.
Any formal publication of the study in which input of sponsor personnel exceeded that of 
conventional monitoring will be considered as a joint publication by the investigator and the 
appropriate sponsor personnel.  Authorship will be determined by mutual agreement and all 
authors must meet the criteria for authorship established by the International Committee of 
Medical Journal Editors (ICMJE) Uniform Requirements for Manuscripts or stricter local 
criteria (ICMJE, 2015). The sponsor does not compensate for authorship of a publication and 
all authors will be required to disclose, as part of the publication submission, any potential 
conflicts of interest, including pertinent financial or personal relationships with the sponsor
or related entities, including sponsors of competing products that might be perceived to be a 
source of bias.  Authorship is decided on an individual basis and the sponsor’s Publications 
Steering Committee and sponsor representatives will mutually determine authors and their 
sequence on individual publications based on the relative contribution of each author to the 
study and/or publication.
Investigators in this study agree to have their name listed as an investigator in any 
publication reporting results from this study, whether or not they are an author on the 
publication.


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Page 55
Professional medical writing support is permissible, and any writing support will be 
acknowledged in each applicable publication, explaining the role the professional writer had 
in the drafting of the publication. Medical writing and publications support funded by the 
sponsor on behalf of investigator authors will be considered as a transfer of value under the 
reporting requirements of Section 6002 of the Patient Protection Affordable Care Act 
(PPACA, 2010).  Transfer of value will be allocated to authors following sponsor guidelines.


C3441010 (MDV3800-13) 
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Page 56
15. REFERENCES
1.
Cardnell RJ, Feng Y, Diao L, Fan YH, Masrorpour F, Wang J, et al. Proteomic markers
of DNA repair and PI3K pathway activation predict response to the PARP inhibitor 
BMN 673 in small cell lung cancer. Clin Cancer Res. 2013 Nov 15;19(22);6322-8.
2.
Goodin S, Griffith N, Chen B, Chuk K, Daouphars M, Doreau C, et al. Safe handling of 
oral chemotherapeutic agents in clinical practice: recommendations from an
international pharmacy panel. J Oncol Pract. 2011 Jan;7(1):7-12.
3.
Hopkins TA, Shi Y, Rodriguez LE, Solomon LR, Donawho CK, DiGiammarino EL, et 
al. Mechanistic dissection of PARP1 trapping and the impact on in vivo tolerability and 
efficacy of PARP inhibitors. Mol Cancer Res. 2015 Nov;13(11):1465-77.
4.
International Committee of Medical Journal Editors (ICMJE). Recommendations for the
conduct, reporting, editing, and publication of scholarly work in medical journals 
[Internet]. 2015 Dec [cited 2016 May 25]. Available from: http://www.icmje.org.
5.
Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of 
PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012 Nov 
1;72(21):5588-99.
6.
Murai J, Huang SY, Renaud A, Zhang Y, Ji J, Takeda S, et al. Stereospecific PARP 
trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther.
2014 Feb;13(2):433-43.
7.
Patient Protection and Affordable Care Act of 2010 [PPACA]. Section 6002: 
Transparency reports and reporting of physician ownership or investment interests. 
Pub. L. 111-148, 124 Stat. 119 (Mar. 23, 2010) [cited 2016 May 25]. In: gpo.gov 
[Internet]. Available from: http://www.gpo.gov/fdsys/pkg/PLAW-
111publ148/pdf/PLAW-111publ148.pdf.
8.
Shen Y, Aoyagi-Scharber M, Wang B. Trapping poly(ADP-ribose) polymerase. J 
Pharmacol Exp Ther. 2015 Jun;353(3):446-57.
9.
Shen Y, Rehman FL, Feng Y, Boshuizen J, Bajrami I, Elliott R, et al. BMN 673, a novel 
and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA 
repair deficiency. Clin Cancer Res. 2013 Sep 15;19(18):5003-15.
10.
Wang B, Chu D, Feng Y, Shen Y, Aoyagi-Scharber M, Post LE. Discovery and
characterization of (8S, 9R)-5-
Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyr
ido[4,3,2- de]phthalazin-3-one (BMN 673, talazoparib), a novel, highly potent, and
orally efficacious poly(ADP-ribose) polymerase-1/2 inhibitor as an anticancer agent. J 
Med Chem. 2016 Jan 14;59(1):335-57.


C3441010 (MDV3800-13) 
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PFIZER CONFIDENTIAL
Page 57
16. INVESTIGATOR SIGNATURE
PFIZER, INC.
A Single-Arm, Open-Label, Multicenter, Extended Treatment, Safety Study in Patients
Treated With Talazoparib
Signature of Agreement for Protocol MDV3800-13 (C3441010) Amendment 4 –14 Nov
2018
I have read this protocol and agree to conduct the study as outlined herein, in accordance 
with Good Clinical Practice and the Declaration of Helsinki, and complying with the 
obligations and requirements of clinical investigators and all other requirements listed in 
21 CFR Part 312.
Print Study Site Name
Study Site Number
Print Investigator Name
Investigator Signature
Date


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Page 58
Appendix 1. Study Schedule of Activities
Study Period or Visit1 Study 
Week Interval
Study Week
Window (Days)6
Treatment
Unsched2
Safety FU3
14
3
5
7
9
Through Week 25 After Week 255
Varies
Varies
1
3
5
7
9
13, 17, 21, 25
Every 8 Weeks
Varies
Varies
-28
±7
±7
±7
±7
±7
±7
Not Applicable -3 to +10
Informed consent7
X
Eligibility criteria7
X
Brief physical examination8 X
X
X
X
X
X
X
Vital signs9
X
X
X
X
X
X
X
Adverse events review10
X
X
X
X
X
X
X
Con medications review
X
X
X
X
X
X
X
Dispense talazoparib11
X (day 1)
X
X
X
X
Talazoparib accountability
X
X
X
X
X (optional)
X
Local clinical lab eval12
X
X
X
X
X
X (optional)
X
CBC only13
X
X
X (q4 weeks)
Pregnancy test14
X
X
X
X
X (q4 weeks)
X (optional)
X
Blood sample for storage15
X
1.
Patients enrolling from study PRP-001 may continue the last visit schedule they tolerated in that study eg, if a PRP-001 patient is on an every 4 week schedule in the 
originating study, the patient is required to complete the week 5 and week 9 visits but not the CBC assessments at week 3 and week 7; afterwards, these patients would follow 
the schedule of activities as above.  
2.
Anytime necessary to assess or follow up adverse events, for dose modification, or as requested by patient or investigator.
3.
Approximately 30 days after the last dose of talazoparib. Phone patients for adverse event follow up if they do not come to the clinic.
4.
First dose will occur within 2 months after the last dose in the originating study.
5.
Adjust schedule as clinically indicated.
6.
Drug supply must be taken into account if a window is used to schedule the next visit.  Visit procedures may be split across the window to allow for
drug resupply and 
completion of study procedures.
7.
Obtain informed consent before performing any study-specific procedures. Ensure consent is on the current version of form approved by the ethics committee. May be 
completed while the patient is participating in the originating study and may be completed greater than 28 days prior to the week 1 visit.
8.
Symptom-directed, including investigating any new abnormalities, and may include an assessment of systems (eg, general appearance, head, eyes, ears, nose, mouth, skin, 
heart, lungs, lymph nodes, gastrointestinal, genitourinary, neurologic, and skeletal) per standard of care at the study site or as clinically indicated by symptoms.
9.
Vital signs include blood pressure, heart rate, and temperature. Measure in the supine position. Measure weight.


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Page 59
10. Collect serious adverse event information from the time of signed informed consent through through and including 30 days after the last dose of talazoparib. As noted above, 
AEs including SAEs for all enrolled patients that occur between consent for this study and first dose in the study are to be recorded on the Medical History CRF and not as 
AEs.  AEs are recorded in the qualifying originating study as AEs, if occurring during the active collection period of the qualifying originating study.
11. Dispense 4- or 8-week supply after completing all other activities/assessments for the visit. First dose is taken in clinic on day 1; record time of dose.
12. Hematology (including CBC testing), serum chemistry per Table 3. Review clinical laboratory results before dosing at each visit. Investigators must
report any clinically 
significant abnormalities as adverse events per CTCAE v4 criteria. If abnormal, refer to Section 9.1.1.
13. Perform CBC testing only every 2 weeks through week 9 and every 4 weeks thereafter ; if abnormal, refer to Section 9.1.1.
14. For women of childbearing potential. Perform a serum pregnancy test before the first dose and a urine or serum test every 4 weeks thereafter before dosing. Discontinue 
talazoparib if a pregnancy test is positive.
15. For patients who did not have a sample collected prior to dosing in the originating study for possible reflex testing for HBV (HBsAg, anti-HBc) and HCV (HCV antibody, 
reflex testing for HCV RNA if positive) or who were not tested for hepatitis: collect blood sample to be stored locally. May be completed while the patient is participating
in the originating study.
Anti-HBc, hepatitis B core antibody; CBC, complete blood count; con, concomitant; CTCAE v4, Common Terminology Criteria for Adverse Events, version 4; eval, evaluation; 
FU, follow-up; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; lab, laboratory; q, every; unsched, unscheduled.


C3441010 (MDV3800-13) 
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Page 60
Appendix 2. France Appendix
This appendix applies to study sites located in France.
1. GCP Training.
Prior to enrollment of any subjects, the investigator and any sub-investigators will complete 
the Pfizer-provided Good Clinical Practice training course (“Pfizer GCP Training”) or 
training deemed equivalent by Pfizer.  Any investigators who later join the study will 
complete the Pfizer GCP Training or equivalent before performing study-related duties.  For 
studies of applicable duration, the investigator and sub-investigators will complete Pfizer 
GCP Training or equivalent every three years during the term of the study, or more often if 
there are significant changes to the ICH GCP guidelines or course materials.
2. Investigational Product.
No subjects or third-party payers will be charged for investigational product.
3. Inspections.
The investigator(s) will notify Pfizer or its service provider immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with Pfizer or its service provider to prepare the study site for the inspection and will allow 
Pfizer or its service provider (if not prohibited by law) to be present during the inspection. 
The study site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the subject's medical records.  The investigator will promptly 
provide copies of the inspection findings to Pfizer or its service provider.  Before response 
submission to the regulatory authorities, the investigator will provide Pfizer or its service 
provider with an opportunity to review and comment on responses to any such findings.
4. Urgent Safety Measures.
The investigator will inform Pfizer immediately of any urgent safety measures taken by the 
investigator to protect the study subjects against any immediate hazard, and of any serious 
breaches of this protocol or of ICH GCP that the investigator becomes aware of.
5. SUSARs.
Pursuant to a sponsor’s safety reporting obligations under 21 CFR 312.32(c)(1), Pfizer will 
report to the Investigator all Serious Unexpected Suspected Adverse Reactions (“SUSARs”).  
Investigator will receive and review SUSAR reports and report SUSARs to the responsible 
IRB/IEC according to institution’s guidelines.  Institution will retain SUSAR reports.

SAP_001.pdf: 
Protocol MDV3800-13 (C3441010) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
Protocol MDV3800-13 (C3441010) 
 
 
A Single-Arm, Open-Label, Multicenter, Extended Treatment, Safety Study in Patients 
Treated With Talazoparib 
 
 
 
Statistical Analysis Plan 
 
 
 
Version: 
Final 1.0 
Authors: 
 PhD 
Date:  
15-JUN-2017 
 
 
 
 
PPD


Protocol MDV3800-13 (C3441010) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
Page 2 
 
TABLE OF CONTENTS 
1. VERSION HISTORY ..................................................................................................................4 
2. INTRODUCTION .......................................................................................................................4 
2.1. Study Objective ...............................................................................................................4 
2.2. Study Design ...................................................................................................................4 
3. ENDPOINT AND BASELINE VARIABLES ............................................................................5 
3.1. Baseline Variables ...........................................................................................................5 
3.2. Safety Endpoints .............................................................................................................6 
3.2.1. Adverse Events ...................................................................................................6 
3.2.2. Laboratory Data ..................................................................................................6 
3.2.3. Vital Signs and Weight .......................................................................................6 
4. ANALYSIS POPULATIONS .....................................................................................................6 
4.1. Screened Population ........................................................................................................6 
4.2. Safety Population ............................................................................................................6 
5. GENERAL METHODOLOGY AND CONVENTIONS ............................................................6 
5.1. Definitions .......................................................................................................................6 
5.1.1. Study Drug ..........................................................................................................6 
5.1.2. Date of First Dose ...............................................................................................6 
5.1.3. Study Day ...........................................................................................................6 
5.1.4. Treatment-Emergent Period ................................................................................7 
5.1.5. Baseline and Post-baseline Values .....................................................................7 
5.1.6. Initial and Durable Dose Levels .........................................................................7 
5.1.7. Study Visits .........................................................................................................7 
5.2. Standard Derivations and Reporting Conventions ..........................................................8 
5.3. Handling of Missing Data ...............................................................................................9 
6. ANALYSES AND SUMMARIES ............................................................................................10 
6.1. Baseline Summaries and Other Analyses ......................................................................10 
6.1.1. Demographics and Baseline Characteristics .....................................................10 
6.1.2. Medical History ................................................................................................10 
6.1.3. Enrollment Status ..............................................................................................10 
6.1.4. Patient Disposition ............................................................................................11 
6.1.5. Protocol Deviations ..........................................................................................11 


Protocol MDV3800-13 (C3441010) Statistical Analysis Plan 
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6.1.6. Study Treatment Exposure and Compliance ....................................................11 
6.1.7. Prior and Concomitant Medications .................................................................11 
6.2. Safety Summaries and Analyses ...................................................................................12 
6.2.1. Adverse Events .................................................................................................12 
6.2.2. Laboratory Data ................................................................................................12 
6.2.3. Vital Signs and Weight .....................................................................................13 
7. INTERIM ANALYSES .............................................................................................................13 
8. REFERENCES ..........................................................................................................................13 
 
 
 


Protocol MDV3800-13 (C3441010) Statistical Analysis Plan 
PFIZER CONFIDENTIAL 
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1. VERSION HISTORY 
This Statistical Analysis Plan (SAP) for study MDV3800-13 (C3441010) is based on the 
Protocol Amendment 1 dated 29JUL2016. 
Table 1 Summary of Major Changes in SAP Amendments 
SAP Version 
Change 
Rationale 
Final 1.0 
 
 
2. INTRODUCTION 
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study PF-06944076, MDV3800-13 (C3441010). 
The data will be analyzed by Medivation (a wholly owned subsidiary of Pfizer Inc.). 
All analyses stated in this Statistical Analysis Plan will be performed using SAS® software 
version 9.4 or later. 
2.1. Study Objective 
 To obtain additional safety data on long-term talazoparib use. 
2.2. Study Design 
This is a single-arm, open-label, extended treatment, safety study in patients treated with 
talazoparib (also known as MDV3800, BMN 673) as a single agent or in combination with 
another agent in qualifying originating clinical studies sponsored by Medivation.  The safety 
and tolerability of long-term talazoparib use will be evaluated, and the data collected will be 
limited to safety assessments.  The study provides access to single-agent talazoparib for 
qualifying patients who may benefit from continuing therapy with talazoparib. 
Eligible patients must have received talazoparib in a qualifying study and have no ongoing 
grade 3 or 4 talazoparib-related toxicities. Patients must receive their first dose of talazoparib 
in this protocol within 2 months after their last dose of talazoparib in the originating study 
and may not receive any intervening antineoplastic therapies before starting this study. 
Patients will have clinic visits approximately every 4 weeks for the first 24 weeks and then 
approximately every 8 weeks thereafter or as clinically indicated (patients enrolling from 
study PRP-001 may continue the last visit schedule they tolerated in that study). Additional 
clinic visits and laboratory testing may be necessary to monitor safety (i.e., for dose 
modification, hematologic toxicity, pregnancy testing). 
The maximum starting dose of talazoparib will be 1 mg/day or the last tolerated dose 
administered in the originating study. Talazoparib capsules will be administered by mouth 
once daily with or without food at approximately the same time of day. Patients receiving 
talazoparib as combination treatment in the originating study will receive talazoparib as a 
single agent in this extended treatment study. Talazoparib administration may continue as 
long as the investigator considers treatment to be beneficial or until other study 


Protocol MDV3800-13 (C3441010) Statistical Analysis Plan 
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discontinuation criteria are met. The addition of any other antineoplastic therapy and the 
concurrent use of investigational agents during the study are prohibited. 
The study design is summarized graphically in Figure 1. 
Figure 1. Overall Study Design 
 
Key assessments:  laboratory tests, physical examinations, adverse events. 
Patients enrolling from study PRP-001 may continue the last visit schedule they tolerated in that study. 
Approximately 150 patients who may benefit from continuing therapy with talazoparib will 
be enrolled in this extended treatment study from qualifying talazoparib clinical studies in 
advanced solid tumors sponsored by Medivation (a wholly owned subsidiary of Pfizer Inc.). 
Studies include a phase 1 dose-escalation study (PRP-001) and 5 short-duration clinical 
pharmacology studies. 
3. ENDPOINT AND BASELINE VARIABLES 
3.1. Baseline Variables 
The baseline characteristics include: 
 Age 
 Sex 
 Race 
 Height 
 Weight 
 Eastern Cooperative Oncology Group (ECOG) performance status 
 Primary diagnosis 
 Prior surgeries 
 Prior systemic anti-cancer therapies 
 Prior radiotherapy 


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3.2. Safety Endpoints 
3.2.1. Adverse Events 
All adverse events will be graded by the Investigator according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4 and coded by system organ class (SOC) and 
preferred term (PT) based on Medical Dictionary for Regulatory Activities (MedDRA). The 
latest version of MedDRA available at the time of the final analyses will be used for 
reporting the results of the study and the version number will be specified in the clinical 
study report (CSR). 
3.2.2. Laboratory Data 
Laboratory data in this study consist of hematology and blood chemistry values. All clinical  
laboratory tests will be performed by the local laboratory. Laboratory values will be 
classified by severity using the CTCAE version 4, as appropriate. 
3.2.3. Vital Signs and Weight 
Temperature, blood pressure (systolic and diastolic), weight, and heart rate will be collected 
at baseline and each subsequent scheduled assessment. 
4. ANALYSIS POPULATIONS 
4.1. Screened Population 
Screened population includes all patients who have signed the informed consent form (ICF) 
and completed the screening phase. 
4.2. Safety Population 
Safety population includes all patients who receive any amount of talazoparib. 
5. GENERAL METHODOLOGY AND CONVENTIONS 
5.1. Definitions 
5.1.1. Study Drug 
The study drug is talazoparib (ie, PF-06944076, MDV3800), which is self-administered daily 
for as long as the investigator considers treatment to be beneficial or until other study 
discontinuation criteria are met. 
5.1.2. Date of First Dose 
Date of first dose is the first date when a non-zero dose of talazoparib is administered in the 
treatment phase. 
5.1.3. Study Day 
Study day will be calculated in reference to the date of first dose. 


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For assessments conducted on or after the first dose, study day is calculated as (assessment 
date – first dose date + 1). 
For assessments conducted before the first dose date, study day is calculated as (assessment 
date – first dose date). 
The study day will be displayed in all relevant data listings. 
5.1.4. Treatment-Emergent Period 
The treatment emergent period is defined as the duration of time from the first dose of 
talazoparib through approximately 30 days after the last dose (ie, permanent discontinuation) 
or before initiation of a new antineoplastic therapy, whichever occurs first. 
5.1.5. Baseline and Post-baseline Values 
Baseline is the non-missing measurement of an investigation obtained during the period from 
the date of signing an ICF to the start date of study treatment or an assessment to be collected 
post-dose on Week 1, whichever occurs first. If patients have no result as defined above, the 
baseline value will be missing. 
Post-baseline values are defined as any measurements after the start date of study treatment, 
if applicable, but to exclude any baseline result taken on Week 1 as defined above. 
Change from baseline is defined as (post-baseline value – baseline value).  
5.1.6. Initial and Durable Dose Levels 
The initial dose level is defined as the last tolerated dose given as the daily dose in the 
originating study. 
The durable dose level is defined as the daily dose taken for the longest duration during the 
extended treatment period in this study. 
5.1.7. Study Visits 
Study visits will be determined from the scheduled times as reported on the electronic case 
report form (eCRF) for the summarization and analysis of data that are shown by study visits 
unless otherwise specified. 
Study assessments including clinical laboratory tests, physical examinations, and vital signs 
will be performed every 4 weeks through week 25 and every 8 weeks thereafter during the 
study. Complete blood count (CBC) tests will be completed every 2 weeks through week 9 
and every 4 weeks thereafter. Women of childbearing potential must have a pregnancy test 
every 4 weeks. Patients enrolling from study PRP-001 may continue the last visit schedule 
they tolerated in that study. 
All treatment period visits have a visit window of ± 7 days (ie, 7 days before or after the 
given day), except the week 1 visit (assessment of eligibility and start of study treatment), 
which has a visit window of -28 days. 


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5.2. Standard Derivations and Reporting Conventions 
Descriptive statistics (the number of patients [n], mean, standard deviation [SD], median, 
minimum, and maximum) will be used to summarize continuous variables. Means will be 
presented to 1 more decimal place than the recorded data. Medians will be presented using 
the same number of decimal places as the recorded data unless the calculated median results 
in an additional decimal place ending in ‘5’ (i.e., 5 and 7 = 6, 5 and 8 = 6.5, etc.). Standard 
deviations will be presented to 2 more decimal places than the recorded data. Minimum and 
maximum values will be presented using the same number of decimal places as the recorded 
data. 
Frequency distributions (number [n] and percentage of patients [%]) will be used to 
summarize categorical or qualitative variables. In general, the denominator for the percentage 
calculation will be based upon the total number of patients in the study population for that 
particular time point assessment. Records that are missing or not done will not be factored 
into the percentage calculation, unless otherwise specified. 
Percentages will be presented to a maximum of 1 decimal place. 
Unless otherwise specified, the following conventions will be applied to all analyses: 
 1 year = 365.25 days. Year is calculated as (days/365.25) rounded up to 1 significant 
digit 
 1 month = 30.4375 days. Month is calculated as (days/30.4375) rounded up to 1 
significant digit 
 Age will be calculated as the integer relative to the patient’s signed informed consent 
date and Date of Birth. 
 1 pound = 0.454 kg 
 1 inch = 2.54 cm 
 Missing data will not be imputed unless otherwise specified 
 For laboratory results collected as < or > for a numeric value, 0.0000000001 will be 
subtracted or added, respectively, to the value 
 For safety analyses, percentages will be calculated based on the number of patients in 
the safety population  
 For by-visit observed data analyses, percentages will be calculated based on the 
number of patients with non-missing data as the denominator unless otherwise 
specified 
 Medical history and adverse events will be coded using the MedDRA. 
Prior therapies and concomitant medications will be coded using the World Health 
Organization Drug Dictionary (WHO-DD). 


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5.3. Handling of Missing Data 
Unless otherwise specified, all data will be evaluated as observed, and no imputation method 
for missing values will be used. 
The imputed dates for adverse events will be used to determine the treatment-emergent 
period. For adverse events with a partial date, available date parts (year, month, and day) of 
the partial date will be compared with the corresponding date components of the start date 
and end date of the treatment-emergent period to determine if the event is treatment 
emergent. When in doubt, the adverse event will be considered treatment emergent by 
default. 
The following rules will be applied to impute partial dates for adverse events: 
 If start date of an adverse event is partially missing, impute as follows: 
- 
If both month and day are missing and year = year of treatment start date, then set 
to treatment start date 
- 
If both month and day are missing and year ≠ year of treatment start date, then set 
to January 1 
- 
If day is missing and month and year = month and year of treatment start date, 
then set to treatment start date 
- 
If day is missing and month and year ≠ month and year of treatment start date, 
then set to first of the month 
- 
If start date is completely missing, set to treatment start date as long as adverse 
event end date is not prior to treatment start date 
 If end date of an adverse event is partially missing, impute as follows: 
- 
If both month and day are missing, then set to December 31 
- 
If only day is missing, then set to last day of the month 
- 
If end date is completely missing, do not impute 
When the start date or end date of a medication is partially missing, the date will be imputed 
to determine whether the medication is prior or concomitant (or both). The following rules 
will be applied to impute partial dates for medications: 
 If start date of a medication is partially missing, impute as follows: 
- 
If both month and day are missing, then set to January 1 
- 
If only day is missing, then set to the first of the month 
 If end date of a medication is partially missing, impute as follows: 


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- 
If both month and day are missing, then set to December 31 
- 
If only day is missing, then set to last day of the month 
 If start date or end date of a medication is completely missing, do not impute 
Listings will show the original date information without imputation, but derived parameters 
(treatment-emergent adverse event indicator and duration of adverse events) will be flagged. 
6. ANALYSES AND SUMMARIES 
6.1. Baseline Summaries and Other Analyses 
6.1.1. Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized and tabulated by qualifying 
originating clinical study for the safety population. The variables to be included in the 
summary are age, sex, race, ethnicity, baseline body weight, height, and body mass index 
(BMI). Age in years will be calculated as the whole number of years between the date of 
birth and the date of informed consent. 
Cancer diagnosis, disease characteristics and ECOG performance status will be summarized 
using frequency counts and percentages.  
Note: Demographics and baseline disease characteristics can be obtained from the 
corresponding eCRF page collected in the originating clinical studies (ie, PRP-001, 
MDV3800-01 [C3441001], MDV3800-2 [C3441002], MDV3800-03 [C3441003], 
MDV3800-04 [C3441004], and MDV3800-14 [C3441005]). 
6.1.2. Medical History 
Verbatim medical history terms collected will be coded by SOC and PT based on MedDRA 
coding dictionary. The latest version of MedDRA available at the time of the final analyses 
will be used for reporting the results of the study and the version number will be specified in 
the clinical study report (CSR). 
The number and percentage of patients with at least one medical history will be summarized 
by SOC and PT and tabulated by qualifying originating clinical study for the safety 
population. 
All medical history data will be provided in a listing. 
6.1.3. Enrollment Status 
All inclusion/exclusion criteria met, not met, or not done will be provided in listings. These 
listings will also provide any eCRF data collected detailing the allowance of patients into a 
study if at least one inclusion/exclusion criterion is not met. 
Additional patient informed consent and eligibility information collected on the eCRF will be 
also provided in a listing. 


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6.1.4. Patient Disposition 
Patients included in the safety populations, who completed the study, discontinued with 
reasons for treatment discontinuation will be summarized and listed as well. 
6.1.5. Protocol Deviations 
Patients with major protocol deviations will be listed and categories of major deviations 
include at least one of the following: 
 Eligibility criteria not met 
 Excluded concomitant medication taken 
 Informed consent not signed before study-specific procedures were performed 
A detailed list of all major protocol deviations will be determined before the database lock 
and a listing of all major deviations will be provided. 
6.1.6. Study Treatment Exposure and Compliance 
The initial dose level from qualifying originating studies and the durable dose level given 
during extended treatment period in this study will be summarized for the safety population. 
Patient exposure and compliance to study drug will be presented by durable dose level, and 
the variables include duration of exposure in months, number of capsules taken and percent 
compliance. 
Treatment compliance will be assessed based on patients’ used and unused study drug 
containers and their completed study drug diary. Dose administration and treatment 
compliance will be listed for all patients. 
6.1.7. Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the WHO-DD, and will be classified 
according to the default Anatomical Therapeutic Chemical (ATC) classification system code, 
WHO-DD Drug Name, and PT. 
Depending on the start and stop dates of the medication, it is possible for a medication to be 
both prior and concomitant. 
Prior and concomitant medications will be summarized by the highest ATC class level and 
PT by treatment group for the safety population. Patients may have more than one 
medication per ATC category and PT. At each level of patient summarization, a patient will 
be counted once if he/she reports one or more medications at that specific level. 
All medications will be presented in a data listing. 


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6.2. Safety Summaries and Analyses 
6.2.1. Adverse Events 
An adverse event will be considered treatment-emergent adverse event (TEAE) if the onset 
date occurred on or after the administration of first dose of study drug through approximately 
30 days after the last dose. A study drug-related TEAE is defined as any TEAE with at least a 
possible relationship to the study drug as assessed by the investigator or that is missing the 
assessment of causal relationship whose relationship to the study drug could not be ruled out. 
Summaries including the number of patients and percentages of the following adverse events 
will be provided: 
 Overview of TEAE 
 TEAE by SOC and PT 
 TEAE by decreasing frequency of PT 
 TEAE related to study drug by SOC and PT 
 TEAE related to study drug by decreasing frequency of PT 
 TEAE by SOC, PT, and maximum severity 
 Serious TEAE by SOC and PT 
 Serious TEAE related to study drug by SOC and PT 
 TEAE leading to study drug discontinuation by SOC and PT 
 TEAE leading to death by SOC and PT 
All AEs will be listed with its relationship to study drug and severity, flagging those which 
are not events during treatment-emergent period. 
A listing of all deaths with date, cause and its relationship to study drug will be also listed. 
6.2.2. Laboratory Data 
Quantitative laboratory test results and their change from baseline will be summarized by 
scheduled visit. Shift tables using CTCAE grades will be provided to compare the baseline 
with the worst post-baseline toxicity. The latest non-missing measurement taken on or before 
Week 1 will be used as baseline. 
Liver tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), 
alkaline Phosphatase (ALP), and total bilirubin (TBL) are used to assess possible drug 
induced liver toxicity. The ratios of test result over the upper limit of normal (ULN) will be 
calculated and classified for these parameters. The number and percentage of patients with 
each of the following categories will be summarized: 


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 ALT ≥ 3xULN 
 AST ≥ 3xULN 
 ALT or AST ≥ 3xULN 
 ALT or AST > 5xULN 
 ALT or AST > 10xULN 
 ALT or AST > 20xULN 
 TBL > 2xULN 
 ALT or AST ≥ 3xULN and TBL > 2xULN 
 ALT or AST ≥ 3xULN and TBL > 2xULN and ALP < 2xULN 
 Concurrent or within 14 days ALT or AST ≥ 3xULN and TBL > 2xULN 
 Concurrent or within 14 days ALT or AST ≥ 3xULN and TBL > 2xULN and ALP < 
2xULN 
Concurrent measurements are those occurring on the same date. 
All laboratory data will be provided in data listings. 
6.2.3. Vital Signs and Weight 
Change from baseline will be calculated and presented at scheduled postbaseline assessments 
for each vital sign parameter (ie, temperature, systolic and diastolic blood pressure, heart 
rate, weight). The latest non-missing measurement taken on or before Week 1 will be used as 
baseline. 
Clinically notable changes in vital signs results will be summarized using frequency counts 
and percentages. 
Vital sign data will be provided in a listing. 
7. INTERIM ANALYSES 
N/A 
8. REFERENCES 
No literature reference is cited.