Clinical trial NCT04672460
Conditions: Advanced Solid Tumors Solid Tumors Ovarian Cancer Breast Cancer Prostate Cancer NSCLC Pancreatic Cancer Colorectal Cancer
Keywords: PARP inhibitor Talazoparib Talzenna BRCA mutation ATM mutation Pharmacokinetics Bioequivalence Bioavailability Food effect
Sponsor: Pfizer
Start date: 2020-12-21; Completion date: 2022-07-22
Enrollment: 73 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple dosing under fasting conditions in participants with advanced solid tumors. In addition, the effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be evaluated in fixed sequence after the 2 BE assessment periods.

Detailed description:

Arms: arm 1: Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days. arm 2: Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.
Interventions: intervention 1: TALZENNA capsule intervention 2: Talazoparib soft gel capsule intervention 3: Talazoparib soft gel capsule
Intervention descriptions: intervention 1: Current commercial talazoparib formulation 1 mg once daily given under fasting condition intervention 2: Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition intervention 3: Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

Protocol documents:
Prot_000.pdf: 
Talazoparib
Protocol C3441037
Final Protocol Amendment 1, 22 June 2021
PFIZER CONFIDENTIAL
Page 1
A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO ESTABLISH 
BIOEQUIVALENCE BETWEEN THE PROPOSED SOFT GEL TALAZOPARIB 
CAPSULE FORMULATION AND THE CURRENT TALAZOPARIB 
COMMERCIAL FORMULATION AND TO ESTIMATE THE FOOD EFFECT ON 
PHARMACOKINETICS OF THE PROPOSED TALAZOPARIB SOFT GEL
CAPSULE FORMULATION IN PARTICIPANTS WITH ADVANCED SOLID 
TUMORS
Study Intervention Number:
PF-06944076
Study Intervention Name:
Talazoparib
US IND Number:
EudraCT Number:
2020-006101-35
Protocol Number:
C3441037
Phase:
1
Short Title: A Phase 1 bioequivalence study between the current commercial 
formulation and the proposed soft gel capsule formulation of talazoparib, and food 
effect study for the proposed talazoparib soft gel capsule formulation in 
participants with advanced solid tumors
This document and accompanying materials contain confidential information belonging to Pfizer. Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
Document History
Document
Version Date
Summary and Rationale for Changes
Amendment 1
22 June 2021
The primary purpose of the amendment is 
to incorporate initial design assumptions
reassessment during the trial. The
previous estimation of power/sample size
was based on the AUC24 variance of the 
current commercial formulation as no
clinical data was available for the 
proposed soft gel capsule formulation and 
assumed ratio 1.07. In addition, previously 
issued Protocol Administrative Change
Letters and clarifications were
incorporated in this amendment. All 
modifications are summarized below.

The cover page is updated with the 
EudraCT number due to the inclusion 
of sites in European Union.

Synopsis, Sections 4.1, 9.2 and 9.4.2
are updated to include the 
reassessment of initial design 
assumptions and potential sample 
size revision.

Section 4.1 is updated to clarify the 
definition of unstable renal function.

Section 5.1, #2b is updated to clarify 
criteria for participants with ovarian 
cancer, #2c is updated to clarify
criteria for participants with NSCLC 
with EGFR mutations.

Section 5.2, #18 and 21 are updated 
to clarify the washout periods for 
compounds with long half-lives.

Section 6.2, #8 is updated to clarify 
the number of units required for 
sample retention to align with the 
FDA guidance.

Section 10.9 Appendix 9 is added to 
list the drugs with long half-lives and 
no potential for DDI with talazoparib.
Original protocol
29 July 2020
N/A


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This amendment incorporates all revisions to date, including amendments made at the 
request of country healthy authorities and IRBs/ECs and any protocol administrative 
clarification letter.


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
LIST OF FIGURES ...................................................................................................................9
1. PROTOCOL SUMMARY...................................................................................................10
1.1. Synopsis ..................................................................................................................10
1.2. Schema ....................................................................................................................14
1.3. Schedule of Activities .............................................................................................15
2. INTRODUCTION ...............................................................................................................21
2.1. Study Rationale .......................................................................................................21
2.2. Background .............................................................................................................21
2.2.1. Clinical Overview.......................................................................................23
2.3. Benefit/Risk Assessment.........................................................................................24
2.3.1. Risk Assessment.........................................................................................24
2.3.2. Benefit Assessment.....................................................................................25
2.3.3. Overall Benefit/Risk Conclusion................................................................25
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................26
4. STUDY DESIGN.................................................................................................................26
4.1. Overall Design.........................................................................................................26
4.2. Scientific Rationale for Study Design.....................................................................27
4.2.1. Participant Input Into Design......................................................................31
4.3. Justification for Dose ..............................................................................................32
4.4. End of Study Definition ..........................................................................................32
5. STUDY POPULATION......................................................................................................32
5.1. Inclusion Criteria.....................................................................................................32
5.2. Exclusion Criteria....................................................................................................34
5.3. Lifestyle Considerations..........................................................................................37
5.3.1. Contraception..............................................................................................37
5.3.2. Meals and Dietary Restriction ....................................................................37
5.3.3. Caffeine, Alcohol and Tobacco ..................................................................37
5.4. Screen Failures ........................................................................................................38
6. STUDY INTERVENTION..................................................................................................38
6.1. Study Intervention(s) Administered........................................................................38


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6.1.1. Administration............................................................................................39
6.2. Preparation/Handling/Storage/Accountability ........................................................41
6.2.1. Preparation and Dispensing........................................................................43
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................43
6.3.1. Allocation to Study Intervention ................................................................44
6.4. Study Intervention Compliance...............................................................................44
6.5. Concomitant Therapy..............................................................................................45
6.6. Dose Modification...................................................................................................46
6.7. Intervention After the End of the Study..................................................................48
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................48
7.1. Discontinuation of Study Intervention ....................................................................48
7.2. Participant Discontinuation/Withdrawal from the Study........................................49
7.2.1. Withdrawal of Consent...............................................................................49
7.3. Lost to Follow-up....................................................................................................50
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................50
8.1. Efficacy Assessments..............................................................................................52
8.1.1. Imaging Assessments..................................................................................52
8.2. Safety Assessments .................................................................................................52
8.2.1. Physical Examinations................................................................................52
8.2.2. Vital Signs ..................................................................................................52
8.2.3. Electrocardiograms.....................................................................................53
8.2.4. Clinical Safety Laboratory Assessments ....................................................53
8.2.5. Pregnancy Testing ......................................................................................54
8.3. Adverse Events and Serious Adverse Events..........................................................54
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......54
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................55
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................55
8.3.2. Method of Detecting AEs and SAEs ..........................................................56
8.3.3. Follow-up of AEs and SAEs.......................................................................56
8.3.4. Regulatory Reporting Requirements for SAEs...........................................56
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................56


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8.3.5.1. Exposure During Pregnancy......................................................57
8.3.5.2. Exposure During Breastfeeding ................................................58
8.3.5.3. Occupational Exposure .............................................................59
8.3.6. Cardiovascular and Death Events...............................................................59
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................59
8.3.8. Adverse Events of Special Interest.............................................................59
8.3.8.1. Lack of Efficacy........................................................................59
8.3.9. Medical Device Deficiencies......................................................................59
8.3.9.1. Prompt Reporting of Device Deficiencies to Sponsor ..............59
8.3.10. Medication Errors.....................................................................................59
8.4. Treatment of Overdose............................................................................................60
8.5. Pharmacokinetics ....................................................................................................61
8.6. Pharmacodynamics..................................................................................................62
8.7. Genetics...................................................................................................................62
8.7.1. Specified Genetics ......................................................................................62
8.9. Immunogenicity Assessments.................................................................................62
8.10. Health Economics .................................................................................................62
9. STATISTICAL CONSIDERATIONS ................................................................................62
9.1. Estimands and Statistical Hypotheses.....................................................................63
9.1.1. Statistical Hypothesis..................................................................................63
9.2. Sample Size Determination.....................................................................................63
9.3. Analysis Sets ...........................................................................................................64
9.4. Statistical Analyses .................................................................................................64
9.4.1. General Considerations...............................................................................64
9.4.2. Primary Endpoint(s)....................................................................................64
9.4.3. Secondary Endpoint(s)................................................................................65
9.4.3.1. Pharmacokinetic Analyses ........................................................65
9.4.3.2. Safety Analyses.........................................................................66
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9.5. Interim Analyses .....................................................................................................66
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............66
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................67
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............67
10.1.1. Regulatory and Ethical Considerations ....................................................67
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................67
10.1.2. Financial Disclosure .................................................................................68
10.1.3. Informed Consent Process ........................................................................68
10.1.4. Data Protection .........................................................................................69
10.1.5. Dissemination of Clinical Study Data ......................................................69
10.1.6. Data Quality Assurance ............................................................................71
10.1.7. Source Documents....................................................................................72
10.1.8. Study and Site Start and Closure ..............................................................72
10.1.9. Publication Policy.....................................................................................73
10.1.10. Sponsor’s Qualified Medical Personnel .................................................74
10.2. Appendix 2: Clinical Laboratory Tests .................................................................75
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................76
10.3.1. Definition of AE .......................................................................................76
10.3.2. Definition of SAE.....................................................................................77
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................79
10.3.4. Reporting of SAEs....................................................................................82
10.4. Appendix 4: Contraceptive Guidance ...................................................................83
10.4.1. Male Participant Reproductive Inclusion Criteria....................................83
10.4.2. Female Participant Reproductive Inclusion Criteria.................................83
10.4.3. Woman of Childbearing Potential ............................................................84
10.4.4. Contraception Methods.............................................................................85
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........88
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................90
10.8. Appendix 8: Alternative Measures During Public Emergencies ..........................92
10.8.1. Eligibility..................................................................................................92
10.8.2. Telehealth Visits.......................................................................................92
10.8.3. Alternative Facilities for Safety Assessments ..........................................93
10.8.3.1. Laboratory Testing ..................................................................93
10.8.3.2. Imaging....................................................................................93
10.8.3.3. Electrocardiograms..................................................................93
10.8.4. Study Intervention ....................................................................................93
10.8.5. Home Health Visits...................................................................................94
10.8.6. Adverse Events and Serious Adverse Events...........................................94
10.9. Appendix 9: List of Long Half-Life Drugs with No Potential for Drug 
Interaction with Talazoparib......................................................................................94
10.10. Appendix 10: Abbreviations ...............................................................................95
11. REFERENCES ..................................................................................................................99


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LIST OF TABLES
Table 1.
Treatment Sequences................................................................................27
Table 2.
Evaluation of Pharmacokinetic Sample Collection Days on the 
Determination of Steady state AUC24.......................................................31
Table 3.
High-Fat Meal Example ...........................................................................40
Table 4.
Dose Reduction Levels for Adverse Reactions ........................................46
Table 5.
Dose Modification and Management Due to Adverse Reactions.............46
Table 6.
Protocol-Required Safety Laboratory Assessments .................................75
LIST OF FIGURES
Figure 1.
Simulated PK and Pharmacodynamics (Hemoglobin) Profiles After 
1 mg QD Talazoparib ...............................................................................29


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A Phase 1 bioequivalence study between the current commercial 
formulation and the proposed soft gel capsule formulation of talazoparib, and food 
effect study for the proposed talazoparib soft gel capsule formulation in participants 
with advanced solid tumors
Rationale
In order to facilitate greater flexibility in batch size production, a proposed talazoparib 
liquid-filled soft gelatin capsule (hereafter referred as “soft gel capsule”) formulation is 
currently being developed. The drug substance will be dissolved into a fill consisting of 
polyethylene glycol, glycerol and tocopherol. The fill will be encapsulated into a shell 
consisting of gelatin, sorbitol, glycerol and pigments. This study will be conducted to support 
the bridging of the current commercial capsule with the proposed talazoparib soft gel capsule
formulation, and to explore the potential food effect on the pharmacokinetics of the proposed 
talazoparib soft gel capsule formulation.
Objectives, Estimands, and Endpoints
Objectives
Endpoints
Primary: 
Primary: 

To establish the BE of the proposed talazoparib soft 
gel capsule formulation to the current commercial 
formulation (Gen 3.1 talazoparib capsules) after 
multiple dosing under fasting condition.

To estimate the effect of food on the PK of the 
proposed talazoparib soft gel capsule formulation 
after multiple dosing.

Plasma AUC24 and Cmax of talazoparib after 
multiple dosing under fasted conditions.

Plasma AUC24 and Cmax of talazoparib after 
multiple dosing under fed condition.
Secondary: 
Secondary: 

To characterize the relevant talazoparib plasma PK 
parameters for all treatments.

To evaluate the safety and tolerability of the 
proposed talazoparib soft gel capsule formulation.

Plasma CL/F, Tmax, AUClast, and Ctrough of 
talazoparib after multiple dosing for all treatments.

Incidence of AEs characterized by type, severity 
(graded by NCI CTCAE version 5.0), timing, 
seriousness and relationship to study treatment. 
Overall Design
This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the 
current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed 
talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple 
dosing under fasting conditions in participants with advanced solid tumors. In addition, the 


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effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be 
evaluated in fixed sequence after the 2 BE assessment periods.
Number of Participants
Approximately 46 participants will be enrolled into the study intervention to ensure at least 
22 PK-evaluable participants for the BE phase and at least 12 after the food effect evaluation 
phase. Initial number of 46 participants is estimated based on 52% non-evaluable rate and 
might be adjusted during enrollment if non-evaluable rate changes.
When approximately 12 evaluable participants complete both Periods 1 and 2, initial 
assumptions (AUC24 variability and point estimate) for power/sample size calculation may be 
reassessed. Sample size may be increased; however the total number of participants to be 
enrolled in the study may not exceed approximately 88 participants.  
Intervention Groups and Duration
Participants will be randomly assigned to 1 of 2 sequences to receive Treatment A, B and C 
in different order as shown below. The first 2 periods will be for BE assessment, with the 
first period being 28 days and the following periods being 21 days. Period 3 will be a 21 day 
period to evaluate the food effect on the PK of the proposed talazoparib soft gel capsule
formulation that will be included in the fixed sequence after the 2 BE assessment periods (for 
participants who can tolerate one high-fat/high-calorie meal). Participants must have received 
21 consecutive days of continuous 1mg QD drug administration to be considered as 
completers of a treatment period, before moving on to the next scheduled treatment. When 
dose interruptions or missed doses occur, participants may repeat a treatment period for 21 
days up to 2 additional times in order to qualify as completers. Participants who have 
repeated a period 2 times but still cannot meet PK evaluable criteria, need a dose reduction, 
have unstable renal function, have experienced renal function worsening to moderate/severe 
renal impairment during the study, or have completed the food effect assessment, will be 
rolled over to the maintenance phase which will consist of repeating 28 day cycles of 
treatment with the current commercial formulation.
Treatment Sequence
Period 1
Period 2
Period 3
1 (n=23 in total)
B
A
C
2 (n=23 in total)
A
B
C
Treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition 
(reference for BE evaluation)
Treatment B: the proposed talazoparib soft gel capsule formulation 1 mg once daily given under fasting 
condition (test for BE evaluation, reference for food effect evaluation)
Treatment C: the proposed talazoparib soft gel capsule formulation 1 mg once daily given with food (on the 
PK sampling day, high-fat/high-calorie meal will be administered in the clinical sites prior to the 
administration of the proposed talazoparib soft gel capsule formulation; test for food effect evaluation)


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Data Monitoring Committee or Other Independent Oversight Committee: No
This study will not use a DMC.
Statistical Methods
Sample Size Estimation
It is estimated that 22 participants will be required to provide 90% power that the 90% CI for 
the Test/Reference ratio of talazoparib AUC24 falls within the 80‑125% acceptance interval 
for bioequivalence. Additionally, with 22 participants the probability that Test/Reference 
ratio for Cmax will fall within 80%-125% is estimated to be 86%. These estimates are based 
on the assumption that the true ratio between Test and Reference treatments for AUC24 and 
Cmax is 1.07 and 1.1 and also assumes within subject standard deviations of 0.407 and 0.17 
for loge Cmax and loge AUC24 respectively, as obtained from rifampin and itraconazole 
cohorts from study MDV3800-04.
Participants who withdraw from the study or fail to provide evaluable samples may be 
replaced at the discretion of the sponsor.
Primary Endpoints
To assess BE, natural log transformed AUC24 and Cmax after multiple dosing on the last day 
of treatment Period 1 and 2 will be analyzed using a mixed-effect model with sequence, 
period, and treatment as fixed effects and participant within sequence as a random effect.
Estimates of the adjusted mean differences (Test-Reference) and corresponding 90% CIs will 
be obtained from the model. The adjusted mean differences and 90% CIs for the differences 
will be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. Treatment A (commercial formulation given 
under fasting condition) will be the Reference treatment while Treatment B (the proposed 
talazoparib soft gel capsule formulation under fasting condition) will be Test treatment.
To assess food effect, natural log transformed AUC24 and Cmax after multiple dosing on the 
last day of treatment B and C will be analyzed using a mixed effect model with sequence and 
treatment as fixed effects and participant within sequence as a random effect. Estimates of 
the adjusted mean differences (Test‑Reference) and corresponding 90% CIs will be obtained 
from the model. The adjusted mean differences and 90% CIs for the differences will be 
exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) 
and 90% CIs for the ratios. Treatment B (the proposed talazoparib soft gel capsule 
formulation under fasting condition) will be the Reference treatment while Treatment C (the 
proposed talazoparib soft gel capsule formulation given with high fat/high-calorie meal) will 
be the Test treatment. 
If initial design assumptions are reassessed during the trial, additional sensitivity analysis of 
BE will be performed by combining estimators from 2 stages using Cui, Hung, Wang 1999.1
The 90% CI will be constructed using combined weighted estimate and standard error from 
2 stages1.


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Secondary Endpoints
Safety analyses will be performed on the safety population using AE data. The number and 
percentage of participants with AEs will be presented by MedDRA system organ class and 
preferred term, relationship to IP, and severity. Treatment-emergent safety data will be 
defined as events from the first dose of study treatment through approximately 28 days after 
the last dose of study drug, or upon initiation of new antineoplastic therapy, whichever 
occurs first. Descriptive statistics will be used.


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1.2. Schema 










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PK Sampling Schedule on PK Visits
Visit Days
Time Points
Window of Acceptability
Period 1 Day 27*
Period 2 Day 20*
Predose PK Collection
24 ± 2 hours from dose on prior day and before the dosing time on the PK sampling day
Period 1 Day 28**
Period 2 Day 21**
Period 3 Day 21**
Predose PK Collection
24 ± 2 hours from dose on prior day and before the dosing time on the PK sampling day
Talazoparib Dose
Within 10 minutes after the predose PK sample collection
0.5 hours PK Collection
±3 minutes
0.75 hours PK Collection
±5 minutes
1 hours PK Collection
±6 minutes
1.5 hours PK Collection
±9 minutes
2 hours PK Collection
±12 minutes
4 hours PK Collection
±24 minutes
6 hours PK Collection
±36 minutes
8 hours PK Collection
±48 minutes
24 hours PK Collection***
±60 minutes and before the dosing time on the same day, ie, Day 1 in the following period
*PK sampling visits can occur between Day 25 to Day 29 for period 1, and can occur between Day 18 and Day 27 for period 2 while continuing daily drug 
administration to accommodate scheduling convenience and compliance as described in the footnotes of the SoA. 
**PK sampling on Period 1 Day 28 and Period 2 Day 21 occur on the days immediately after Period 1 Day 27 visit and Period 2 Day 20 visit, respectively; 
PK sampling on Period 3 Day 21 can occur between Day 19 and Day 28 while coninuitng daily drug administration to accommodate scheduling 
convenience and compliance as described in the footnotes of the SoA.
***24 hours PK on Day 28 for Period 1 and Day 21 on Periods 2 and 3 is the same PK sample as predose PK on Day 1 in the following period. 






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mutations, for example in the maintenance setting in ovarian cancer. The major indications 
for which PARP inhibitors have been approved are described below.2,3,4,5
The most recent indication was approved for olaparib on December 2019 by the FDA for the 
maintenance treatment of adult patients with deleterious or suspected deleterious germline 
BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-
approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-
based chemotherapy regimen.2
Indications for maintenance therapy in patients with ovarian, fallopian tube, and peritoneal 
adenocarcinoma for patients with recurrent disease, BRCA-associated mutations, and with ≥2 
lines of chemotherapy were approved initially in 2014 (olaparib, 2017,2018), and for other 
PARP inhibitors in 2016 (rucaparib, 2018) and 2017 (niraparib, 2019). 2,3,4,5
Olaparib is indicated for the following indications in ovarian, fallopian tube, and primary 
peritoneal cancer: maintenance treatment of recurrent ovarian cancer and advanced gBRCA 
mutated ovarian cancer after 3 or more lines of chemotherapy.2
Other PARP inhibitors such as rucaparib and niraparib are also indicated in the maintenance 
and advanced setting in patients with platinum sensitive, relapsed or progressive advanced 
high grade epithelial ovarian, fallopian tube or primary peritoneal cancer based on data from 
the large ARIEL and NOVA trials respectively. 3,4
PARP inhibitors were approved for patients with gBRCA positive, advanced or metastatic 
HER2-negative breast cancer in 2018 (olaparib), and 2018 (talazoparib).2,5
Talazoparib is highly potent at inducing single agent synthetic lethality of BRCA1 and 
BRCA2 deficient tumor cells in vitro . Consistent with its cytotoxic effects in tissue culture 
studies, talazoparib demonstrated antitumor activity in xenograft tumor models. Potent tumor 
activity was observed at an oral daily dose 1 mg/kg/day. Complete suppression of growth of 
BRCA1-deficient tumors (ie, MX1 model) was achiveved in a 3-month study when 
talazoparib was dosed at 0.165 mg/kg. These in vitro and in vivo activities suggest that 
talazoparib may have clinical activity in patients with BRCA mutated breast cancer.
In Study PRP001, a Phase 1, first in human, single-arm, open-label dose escalation study of 
once daily talazoparib (BMN 673) in patients with advanced or recurrent solid tumors with 
DNA repair deficiencies, a total of 110 patients were treated with talazoparib at doses 
ranging from 0.025 to 1.1 mg/day. During the dose escalation phase of the study, 2 of the 
6 patients enrolled in the talazoparib 1.1 mg/day dose level experienced a dose limiting 
toxicity: one was Grade 4 thrombocytopenia, the other was Grade 3 thrombocytopenia 
requiring >5 days off study treatment. Therefore, 1 mg/day was considered the maximum 
tolerated dose and recommended Phase 2 dose. Between the dose escalation and dose 
expansion portions of the study, a total of 77 patients were treated with talazoparib at the 1 
mg/day dose level in Study PRP001 which was generally well tolerated and warranted 
further evaluation in patients with solid tumors with DNA repair deficiencies. As a result, 
talazoparib has been dosed at 1 mg/day in subsequent studies in patients with solid tumors, 


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including the phase 2 and 3 breast cancer studies ABRAZO, EMBRACA, and currently 
ongoing investigator-initiated research trials.
The class of PARP inhibitors has demonstrated a risk for dose-dependent reversible 
myelosuppression and gastrointestinal toxicity, and these events were observed in studies 
where patients received 1mg/day talazopirib monotherapy. Study drug-related TEAEs 
occurring in ≥20% of patients in the talazoparib 1 mg/day population were anemia (45.8%), 
fatigue (36.1%), nausea (32.5%), neutropenia (21.9%), and alopecia (20.1%). Grade 3 or 4 
drug-related TEAEs occurring in ≥5% of patients were anemia (34.1%), neutropenia 
(13.9%), thrombocytopenia (10.6%), and platelet count decreased (5.4%). 
2.2.1. Clinical Overview
Talazoparib is currently approved and in development for the treatment of a variety of 
cancers. Approximately 1212 patients have received talazoparib in company-sponsored 
studies as of the data cutoff date of the most recent investigator’s brochure (30 September
2019).
The single dose PK of talazoparib have been evaluated in a total of 7 clinical studies, of 
which 6 were conducted in cancer patients (Studies PRP-001, PRP-002, MDV3800-01,
MDV3800-03, MDV3800-04, and MDV3800-14) and 1 in healthy subjects (Study 673-103).
After administration of a single 1 mg dose of talazoparib capsules to cancer patients, the 
median Tmax ranged from 1.0 to 2.0 hours across studies. The geometric mean Cmax ranged 
from 4.35 to 8.79 ng/mL and the geometric mean AUCinf ranged from 116 to 220 ng•hr/mL.
Talazoparib was eliminated slowly with the geometric mean CL/F values ranging from 4.55 
to 7.71 L/hr and the mean t½ ranging from 62.4 to 98.1 hours, while the t½ of 62.4 hours 
might be an underestimate as the PK sampling time was only up to 168 hours postdose in the
corresponding study. The talazoparib geometric mean Vz/F values estimated ranged from 447 
to 847 L, which is significantly greater than total body water (42 L), indicating that 
talazoparib extensively distributes to peripheral tissues.
The PK of talazoparib following multiple oral daily doses was evaluated in a total of 
6 studies in patients with cancer (Studies PRP-001, PRP-002, 673-201, 673-301, 
MDV3800-01, and MDV3800-14), and Studies 673-201 and 673-301 only included sparse 
sampling. Following repeated 1 mg QD dosing of talazoparib capsules in cancer patients, 
talazoparib was rapidly absorbed with a median Tmax ranging from approximately 1.0 to 2.0 
hours. The geometric mean Cmax values ranged from 11.4 to 19.1 ng/mL and the geometric 
mean AUC24 values ranged from 126 to 208 ng•hr/mL. The talazoparib geometric mean 
Ctrough values ranged from 2.99 to 4.95 ng/mL. The geometric mean CL/F ranged from 4.80 
to 5.53 L/hr, with a mean plasma t½ of 57.8 hours (Study PRP-001), which may be an 
underestimate as the last PK sampling time was at 168 hours postdose.
Based on the multiple dosing data from Studies PRP-001 and PRP-002 and consistent with 
its observed t½ of 89.8 hours (Study MDV3800-03), talazoparib plasma concentrations 
reached steady state around 3 weeks after repeated daily dosing. The median accumulation 
ratio ranged from 2.33 to 5.15 following repeated oral administration of 1 mg dose.


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The talazoparib plasma exposure (AUC24) and Cmax increased in a dose-proportional manner 
over the dose range of 0.025 to 2 mg QD.
2.3. Benefit/Risk Assessment
The doses of talazoparib in this protocol are supported by nonclinical studies and clinical 
studies in patients with advanced malignancies. Talazoparib has shown anti-tumor activity in 
patients with breast, ovarian, peritoneal and pancreatic cancers, as described in the 
background and talazoparib Investigator’s Brochure. Talazoparib is currently approved for 
use in patients with metastatic breast cancer with germline BRCA mutations.
The expected AEs with talazoparib include myelosuppression, gastrointestinal toxicity, 
fatigue, and alopecia. Hepatotoxicity, febrile neutropenia, and neutropenic sepsis are 
potential risks per the Investigator’s Brochure, Section 7. The activity of talazoparib as 
monotherapy and in combination with other agents is being evaluated in multiple indications.
Based on the available safety and efficacy data, the overall benefit risk profile of talazoparib 
remains favorable.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of talazoparib may be found in the Investigator’s Brochure, which is the SRSD 
for this study.
2.3.1. Risk Assessment
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for 
Risk
Mitigation Strategy
Study Intervention(s) talazoparib
Potential risks associated with 
talazoparib include the 
following: MDS, AML and 
myelosuppresion. 
The potential risks are based 
on safety data summarized in 
product label and the 
investigator’s brochure for 
talazoparib. 
Eligibility criteria have been 
selected to ensure that only 
appropriate participants are 
included in the study (see 
Section 5).
Conduct safety assessment 
(eg, hematology) according to 
the SoA. 
Investigator can provide 
unplanned assessment  as 
clinically indicated.


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2.3.2. Benefit Assessment
Talazoparib has shown anti-tumor activity in patients with breast, ovarian, peritoneal and 
pancreatic cancers, as described in the background and talazoparib Investigator’s Brochure.
The benefit of talazopairb for individual pariticipants with solid tumors may include:

Potential clinical benefit of receiving talazoparib during study. 

Participants in this study will contribute to the process of developing a new 
formulation for talazoparib.

Medical assessment (eg, physical exams, ECGs, labs, etc.) associated with study 
procedures and health care provider visits will be more frequent compared to standard 
of care.
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with talazoparib are justified by the 
anticipated benefits that may be afforded to participants with solid cancer tumors.


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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Endpoints
Primary: 
Primary: 

To establish the BE of the proposed talazoparib soft gel
capsule formulation to the current commercial 
formulation (Gen 3.1 talazoparib capsules) after 
multiple dosing under fasting condition.

To estimate the effect of food on the PK of the 
proposed talazoparib soft gel capsule formulation after 
multiple dosing.

Plasma AUC24 and Cmax of talazoparib after multiple 
dosing under fasted conditions.

Plasma AUC24 and Cmax of talazoparib after multiple 
dosing under fed condition.
Secondary: 
Secondary: 

To characterize the talazoparib plasma PK parameters 
for all treatments.

To evaluate the safety and tolerability of the proposed 
talazoparib soft gel capsule formulation.

Plasma CL/F, Tmax, AUClast, and Ctrough of talazoparib 
after multiple dosing for all treatments.

Incidence of AEs characterized by type, severity 
(graded by NCI CTCAE version 5.0), timing, 
seriousness and relationship to study treatment.
4. STUDY DESIGN
4.1. Overall Design
This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the 
current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed 
talazoparib soft gel capsule formulation after multiple dosing under fasting conditions in 
participants with advanced solid tumors, and to explore the potential food effect on the 
pharmacokinetics of the proposed talazoparib soft gel capsule formulation. The first 2 
periods will be for BE assessment, with the first period being 28 days and the following 
periods being 21 days. Period 3 will be a 21-day period to evaluate the food effect on the PK 
of the proposed talazoparib soft gel capsule formulation that will be included in the fixed 
sequence after the 2 BE assessment periods (for participants who can tolerate one 
high-fat/high-calorie meal). Participants must have received 21 consecutive days of 
continuous 1 mg QD drug administration to be considered as completers of a treatment 
period, before moving on to the next scheduled period. When dose interruptions or missed 
doses occur, participants may repeat a treatment period for 21 days up to 2 additional times 
in order to qualify as completers. Participants who have repeated a period 2 times but still 
cannot meet PK evaluable criteria, need a dose reduction, have unstable renal function 
(>25% change in CLCR between 2 visits which is considered clinically significant by the 
investigator and will require a dose reduction), have experienced renal function worsening to 
moderate/severe renal impairment (CLCR dropped to <60 mL/min) during the study, or have 
completed the food effect assessment, will be allowed to roll over to the maintenance phase
which will consist of repeating 28 day cycles of treatment with the current commercial 
formulation. The maintenance phase consists of repeating 28 day cycles of treatment with the 
current commercial formulation.
Participants will be randomly assigned to 1 of the 2 sequences shown in Table 1.


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Table 1.
Treatment Sequences
Treatment 
Sequence
Period 1
Period 2
Period 3
1 (n= 23 in total)
B
A
C
2 (n= 23 in total)
A
B
C
Treatment A: current commercial talazoparib formulation 1 mg once daily given under fasting condition 
(reference for BE evaluation)
Treatment B: the proposed talazoparib soft gel capsule formulation 1 mg once daily given under fasting 
condition (test for BE evaluation, reference for food effect evaluation)
Treatment C: the proposed talazoparib soft gel capsule formulation 1 mg once daily given with food (on the 
PK sampling day, high-fat/high-calorie meal will be administered in the clinical sites prior to the 
administration of the proposed talazoparib soft gel capsule formulation; test for food effect evaluation)
Approximately 46 participants (23 per sequence) will be enrolled into the study intervention
to ensure at least 22 PK-evaluable participants for the BE phase and at least 12 after the food 
effect evaluation phase. Initial number of 46 participants is estimated based on 52% 
non-evaluable rate and might be adjusted during enrollment if non-evaluable rate changes.
When approximately 12 evaluable participants complete both Periods 1 and 2, assumptions 
(AUC24 variability and point estimate) for power/sample size calculation may be reassessed.
Sample size may be increased; however, the total number of participants to be enrolled in the 
study may not exceed approximately 88 participants.
Participants will be randomized 1:1 to receive treatments in sequence 1 or 2. Participants 
who are still on 1 mg daily after the completion of the first 2 periods and can tolerate one 
high-fat/high-calorie meal will receive treatment C in period 3 to evaluate the food effect on 
the PK of the proposed talazoparib soft gel capsule formulation. On the day before the last 
treatment day of each period, a pre-dose PK sample will be collected. On the last treatment 
day of each period, participants will undergo serial PK sampling for 24 hours. Participants 
who have had less than 21 consecutive days of continuous QD dosing of IP (regardless of 
formulation) on the last day of a treatment period will be considered non-completers of that 
treatment period (Period X). PK assessment will not be performed for non-completers of a 
treatment periods, but other scheduled activities will be performed per the SoA. After 
completion of Period X, instead of moving on to the next treatment, the same treatment in 
Period X will be repeated until participants have received at least 21 consecutive daily doses 
of IP on the last day of the treatment period (ie, considered as completers).
4.2. Scientific Rationale for Study Design
Talazoparib is clastogenic and therefore it is unacceptable to enroll healthy participants for 
this study. All clinical studies administering talazoparib should be conducted in cancer 
patients for whom there is potential benefit to offset this risk. Cancer patients who will likely 
benefit from talazoparib treatment and have good disease control will be recruited to 
minimize dropouts through progression of disease because of the long duration of treatment
(at least 70 days). The selected participant population will include patients with advanced 
solid tumors that are not amenable for treatment with curative intent who may benefit from 
treatment with talazoparib.


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Due to the selected participant population, a single-dose study is not feasible as the long 
elimination half-life (t½, 89.9±57.6 hours) of talazoparib would require too long a washout 
duration with no treatment to be ethical in a cancer patient population setting. Due to high 
PK variability of talazoparib in cancer patients, (total variability of 47-62% for Cmax and 
32%-42% for AUC [PRP-002 and MDV3800-04 with N>18], single dose studies), a parallel 
study design would require a large sample size (>100 participants per arm) and therefore 
would not be feasible. Collectively, inherent properties of talazoparib limit the acceptable 
BA/BE assessment options to a multiple-dose crossover design in cancer patients. In order to
achieve 90% power that the 90% CI for the Test/Reference ratio of talazoparib Cmax fall 
within the 80‑125%, a full replicate design (TRTR, RTRT) with 40 evaluable participants 
would be required. Due to the treatment length of this design (at least 84 days), the non-
evaluable rate was estimated to be ~65% and approximately 114 participants need to be 
enrolled, rendering the implementation of this design non-feasible. In addition, Cmax is not 
considered a main driver for the efficacy and safety events of talazoparib as illustrated below. 
If the Cmax of the proposed formulation is lower than that of the current commercial 
formulation, it is not expected to have an impact on efficacy. In the preclinical studies, in 
MX1 tumors xenograft model, dosing talazoparib at 0.166 mg/kg BID schedule showed a 
better anti-tumor effect profile compared to dosing talazoparib at 0.33 mg/kg QD schedule.
This suggests Cmax is not the driver for efficacy. This study result led to the registrational 
Phase 3 study (Study C3441009; EMBRACA) being conducted with talazoparib taken 
without regard to food intake, as food had no effect on the AUC even though it reduced 
talazoparib Cmax by 46%. Consistently, in the USPI talazoparib is recommended to be given 
with or without of food. 
The lack of impact of higher Cmax on safety was evaluated using ER modeling.
Myelosuppression-related AEs are the main side effects of talazoparib treatment and Anemia 
was reported for 49.2% of patients (Module 2.7.4 NDA 211651 seq 001). Thus, Anemia was 
selected as a representative safety endpoint for ER modeling to evaluate the impact of Cmax
increase on the safety profile of talazoparib. Simulations were conducted to compare the 
projected PK profile based on the assumed ratio between the two formulations (10% higher
Cmax for the proposed formulation) and the time course of Anemia (Figure 1). Patient ID 1 
represented the population typical talazoparib PK profile; Patients ID 2 had 10% higher Cmax
and same AUC24 compared to Patient ID1. As shown in Figure 1, limited increase of Cmax
would not have significant impact on the safety profile of talazoparib (Anemia) when AUC 
remains the same.


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Figure 1.
Simulated PK and Pharmacodynamics (Hemoglobin) Profiles After 1 mg 
QD Talazoparib
Therefore, since Cmax is not considered a driver for efficacy and safety, and to ensure 
operational feasibility, a two-way crossover study powered to show 90% CI for the 
Test/Reference ratio of talazoparib AUC24 within the 80‑125% acceptance interval for BE
was selected.
In order to assess the steady state PK of talazoparib to demonstrate BE, lengthy continuous 
treatment with talazoparib at 1 mg QD before PK sampling is required. Participants who 
undergo a dose reduction before the PK sampling will not be included in the PK evaluable 
population, and participants with dosing interruptions before the PK sampling need to 
continue talazoparib treatment until the steady state is reached for PK sampling. In addition, 
disease progression necessitating coming off the study before completing all PK evaluation 
days may also preclude participants from completing the BE assessment period. With this
longer study duration, there could be higher rates of disease progression and dose reduction
leading to a higher non-evaluable rate. In addition, the longer the study duration, the higher 
the likelihood of drug administration non-compliance, leading to higher PK non-evaluable 
rate. Therefore, to minimize the treatment duration, the study was designed to be 28 days for 
Period 1 to ensure attainment of steady state, and 21 days for Periods 2 and 3, which is 
shown to be adequate for steady-state BE and food effect evaluation based on the simulation 
results below. In addition, three pre-dose PK samples will be collected on consecutive days 
in period 1 and 2 to show attainment of steady state for BE assessment.


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To investigate the shortest adequate treatment durations prior to PK assessment for steady 
state BE evaluation, simulations were conducted using the final popPK model submitted in 
the original NDA 211651 (PMAR-EQDD-C344a-DP4-840). Using the proposed treatment 
duration for each period, simulations were performed for fixed sequence with the second 
administered formulation having known bioavailability (F1) changes (10% or 5% increase or 
10% or 5% decrease in F1 relative to the first administered formulation). Population typical 
CL and lower 5 percentile CL were used to represent typical participants and participants 
with lower CL (slower elimination and longer half-life). In the simulation, formulation 1 was 
administered from Day 1 to Day 28, and formulation 2 was administered from Day 29 to Day 
56. PK parameters obtained on Day 14 of Period 2 (ie, Day 42) for the second formulation 
were compared to those obtained on Day 28 of Period 1 and the AUC ratio obtained was 
compared to the true difference in F1 used for simulation to illustrate the accuracy of the 
determination of true formulation effect on bioavailability. In addition, the second 
formulation had extended dosing to Day 28 for Period 2 (ie, Day 56) in the simulation to 
further demonstrate whether the steady state for the second formulation was achieved on Day 
14 of Period 2 by comparing the results for Day 14 and Day 28 of Period 2 respectively.
Table 2 exhibits the simulation results. When the formulation with 10% higher F1 was 
administered in Period 3, the ratio of AUC24 obtained on Day 14 in Period 2 (Day 42) vs 
AUC24 obtained on Day 28 of Period 1 (Day 28) exhibited 9.9% and 9.8% increase when 
population typical CL and the lower 5 percentile CL were used in the simulation, 
respectively. AUC24 ratio was similar between Day 42 and Day 56, which indicates that no 
meaningful improvement in accuracy is achieved with additional 14 days of treatment in 
Period 2. The same results were observed for the simulated formulation with 5% higher or 
5% lower or 10% lower F1 case scenarios. These simulation results suggest that following 
28-day treatment of the first formulation, a minimum of 14-day treatment duration for the 
following periods is needed for steady state BE and food effect evaluation, and therefore 
21-day treatment for period 2 and 3 is adequate for steady-state BE and food effect 
evaluation. 




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4.3. Justification for Dose
According to FDA guidance, when several doses of a drug that exhibit linear PK will be 
marketed, the highest clinically recommended dose should be used unless safety concerns 
necessitate a lower dose.6 The highest clinically recommended dose strength of talazoparib is 
1 mg taken as a single oral daily dose in the approved indication (deleterious or suspected 
deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer). 
Therefore, the highest approved dose strength, 1 mg QD, was chosen for this study.
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study, including the End of Study visit.
The end of the study is defined as the date of the last scheduled procedure shown in the SoA
for the last participant in the trial globally after collection of the final data point for primary 
and secondary study objectives.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, are not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Male or female participants between the ages of 18 (or the minimum country specific age 
of consent if >18) and 70 years, inclusive, at Visit 1 (Screen 1).
Type of Participant and Disease Characteristics:
2. Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that is not 
amenable for treatment with curative intent. 
a.
Solid tumors with known or likely pathogenic germline or somatic tumor gene defect (eg, 
one or more BRCA1 or BRCA2 gene defect except for ovarian cancer) that would benefit 
from PARPi therapy per current approvals for the tumor indication or supported by 
strong scientific evidence. Gene mutation determined by local assessment and 
classification using a test of either germline or tumor DNA which was performed in a 
CAP/CLIA certified (or comparable local or regional certified) laboratory.


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b. Received at least 1 prior SOC regimen, if it exists, as appropriate for the respective tumor 
type unless deemed unsuitable or declined these therapies; ovarian cancer participants 
must have at least 1 prior cytotoxic chemotherapy regimen, including at least 1 line of 
platinum-based therapy. Participants (except for those with ovarian cancer) must not have 
had disease progression within 6 months of initiation of platinum containing regimen;

Participants with ovarian cancer must not have progressed during or within 1 month 
after the last dose of the most recent platinum-based chemotherapy;

Participants with ovarian cancer previously treated with ≤2 prior cytotoxic 
chemotherapy regimens, participants must have had disease progression within 6 
months after the last dose of platinum-based chemotherapy, also termed “platinum-
resistant recurrent disease”

Participants with ovarian cancer previously treated with >2 prior cytotoxic 
chemotherapy regimens, ie, platinum sensitive recurrent disease is allowed;

Any treatment regimen that began with cytotoxic chemotherapy and continued with 
another regimen for maintenance therapy following best response to initial cytotoxic 
regimen will count as one line of prior therapy.
c.
Participants with NSCLC harboring B-Raf proto-oncogene (BRAF) v600 mutations,
ALK and c-ros oncogene 1 (ROS1) translocation/rearrangements, or epidermal growth 
factor receptor (EGFR) mutations must have received the appropriate targeted therapy as 
approved by the relevant health authority.
3. ECOG performance score of 0-1.
4. Adequate bone marrow function, as defined as:

ANC ≥1500 cells/mm3

Platelets ≥100,000 cells/mm3 

Hemoglobin ≥10.0 g/dL 
5. Adequate renal function, as defined as:

A CLCR ≥60 mL/min by Cockcroft-Gault formula or as: CLCR={[(140–age) × 
weight)]/(72 × SCR)} × 0.85 (if female), where CLCR is measured in mL/min, age is 
expressed in years, weight in kilograms, and SCR in mg/dL; Other methods for 
calculating CLCR can be used as long as the same method is used for the entire study;

No documented CLCR <60 mL/min and no change in CLCR >25% in the past 4 weeks.


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6. Adequate hepatic function, as defined as:

AST and ALT ≤2.5 × ULN; if liver function abnormalities are due to hepatic metastasis, 
then AST and ALT ≤5 × ULN; 

Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert’s syndrome); 
7. Life expectancy of at least 12 weeks.
8. Able to swallow capsules whole without breaking apart or crushing.
9. Participants who are willing and able to comply with all scheduled visits, treatment plan, 
laboratory tests, lifestyle considerations, and other study procedures.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which includes 
compliance with the requirements and restrictions listed in the ICD and in this protocol. 
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant 
potential (ie, borderline tumors) or mucinous tumors.
2. Toxicities from previous anti-cancer therapies must be resolved to NCI CTCAE Grade 
2, except for alopecia, sensory neuropathies ≤Grade 2, or other Grade ≤2 AEs not 
constituting a safety risk, based on investigator’s judgment, are acceptable.
3. Diagnosed with MDS or AML.
4. Active infection requiring systemic therapy within 2 weeks of enrollment.
5. Transfusions or hematopoietic growth factors within 2 weeks of enrollment.
6. Any major surgery within 4 weeks of enrollment.
7. Any condition in which active bleeding or pathological conditions may carry a high risk 
of bleeding (eg, known bleeding disorder, coagulopathy or tumor involvement with major 
vessels). 
8. Known or suspected brain metastasis or active leptomeningeal disease undergoing or 
requiring treatment. Asymptomatic brain metastases currently not undergoing treatment 
are allowed.


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9. Spinal cord compression is allowed if definitive treatment was provided and participant 
has stable disease 4 weeks prior to randomization.
10. In the opinion of the investigator, any clinically significant gastrointestinal disorder 
affecting absorption (eg, malabsorption syndrome, uncontrolled inflammatory bowel 
disease, PUD, requires hyperalimentation, or prior surgical procedures effecting 
absorption.
11. Inability to swallow capsules or any known hypersensitivity to Talzenna™(talazoparib) 
or any of the product components.
12. Clinically significant cardiovascular disease:

Myocardial infarction or symptomatic cardiac ischemia within 6 months of 
randomization;

New York Heart Association Class III or IV congestive heart failure;

History of clinically significant ventricular arrhythmias (history of sustained ventricular 
tachycardia, ventricular fibrillation, Torsades de Pointes) within 1 year prior to 
randomization.

History of Mobitz II second degree or third degree heart block unless a permanent 
pacemaker is present.

Hypotension: systolic blood pressure <80 mm Hg at screening;

Bradycardia: HR of <45 beats per minute at screening on electrocardiogram;

Uncontrolled hypertension: systolic blood pressure >170 mm Hg or diastolic >105 mm 
Hg at screening; rescreening is allowed after adequate blood pressure control is achieved.
13. Women of childbearing potential who are pregnant, breast-feeding or plan to conceive 
during study participation.
14. Women of childbearing potential who are unwilling or unable to use highly effective 
methods of contraception as appropriate as outlined in this protocol for the duration of the 
study and for 7 months after the last dose of IP.
15. Fertile male participants with female partners of reproductive potential or pregnant 
partners, unwilling to use a condom (even after vasectomy) during treatment and for at 
least 4 months after the last dose of IP.
16. Known history of testing positive for HIV, AIDS, positive HBV surface antigen, positive 
HCV RNA, or positive COVID-19 viral test. Asymptomatic patients with no active 
COVID-19 infection detected but positive antibody tests, indicating past infection, are 
allowed.


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17. Other medical or psychiatric condition including recent (within the past year) or active 
suicidal ideation/behavior or laboratory abnormality that may increase the risk of study 
participation or, in the investigator’s judgment, make the participant inappropriate for the 
study.
Prior/Concomitant Therapy:
18. Prior anti-cancer therapy within 2 weeks or 5 half-lives prior to randomization 
(whichever is longer). Prior anti-cancer treatments with 5 half-lives longer than 30 days 
and no evidence of drug-drug interaction (DDI) with talazoparib require a 30-day 
washout period. See Section 10.9 Appendix 9 for more details on DDI potential.
19. Current or anticipated use of P-gp inhibitors, BCRP inhibitors, and P-gp inducers within 
2 weeks or 5 half-lives prior to randomization (whichever is longer). See Section 6.5 for 
more details.
20. Prior radiation within 2 weeks of randomization. Prior palliative radiotherapy to 
metastatic lesions(s) is permitted, provided it has been completed at least 2 days prior to 
enrollment and no clinically significant toxicities are expected (eg, mucositis, 
esophagitis).
Prior/Concurrent Clinical Study Experience:
21. Previous administration with an investigational drug within 30 days (or as determined by 
the local requirement) or 5 half-lives prior to randomization (whichever is longer). Prior 
treatments with 5 half-lives longer than 30 days and no evidence of DDI with talazoparib
require a 30-day washout period.
Diagnostic Assessments:
22. QTc interval >470 msec. If the baseline uncorrected QT interval is >470 msec, this 
interval should be rate corrected using the Fridericia method and the resulting QTcF 
should be used for decision making and reporting. If QTc exceeds 470 msec, or QRS 
exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 
QTc or QRS values should be used to determine the participant’s eligibility. Computer 
interpreted ECGs should be overread by a physician experienced in reading ECGs before 
excluding participants.
Other Exclusions:
23. Investigator site staff or Pfizer employees directly involved in the conduct of the study, 
site staff otherwise supervised by the investigator, and their respective family members. 


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5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use highly effective contraception consistently and 
correctly and document the conversation and the participant’s affirmation in the participant’s 
chart (participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception). In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.3.2. Meals and Dietary Restriction
Bioequivalence and Food-effect Phase
On non-site visit days, in the first 2 periods, participants must abstain from all food and drink 
(except water) at least 2 hours prior to drug administration and remain fasting after drug 
administration for at least 2 hours. In period 3, participants will start a formal breakfast 
within 30 minutes prior to drug administration.
High fat meal will be started within 30 minutes prior to dosing and finish before drug 
administration. On non-site visit days of Period 3, IP will be taken after a proper breakfast. 
Participants who cannot tolerate a high fat meal can be excluded from the food effect phase 
and roll over to the maintenance phase.
On site visit day, the requirement for food intake is described in detail in Section 6.1.1. 
Maintenance Phase
No meal or dietary restrictions.
5.3.3. Caffeine, Alcohol and Tobacco
Bioequivalence and Food-effect Phase
Participants will abstain from caffeine containing products for 48 hours prior to and for the 
duration of the PK sampling days.
Participants will abstain from alcohol for 72 hours prior to and after drug administration on 
PK sampling days. Participants may undergo an alcohol breath test or blood alcohol test at 
the discretion of the investigator.






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Water is permitted until 1 hour prior to investigational product administration. Water may be 
consumed without restriction beginning 1 hour after dosing.
Table 3.
High-Fat Meal Example
Total Calories
800-1000
Calories from Protein
150
Calories from Carbohydrates
250
Calories from Fat
500-600
Example of a High-Fat Breakfast
2 eggs fried in butter, 2 strips of bacon, 2 slices of 
toast with butter, 4 ounces of hash brown potatoes, 
8 ounces of whole milk.
2 slices of buttered toast, cottage cheese (90 g), 
buffalo milk (8 oz), an apple. (avocado and nuts 
can be substitutes)
50% of calories are derived from fat. Substitutions can be made to this meal, if the content, volume, and 
viscosity are maintained.
Safety assessments should be reviewed prior to starting the next period of IP treatment. On 
Period 1 Day 1 (treatment sequence 2) or Period 2 Day 1 (treatment sequence 1), participants 
should be observed after dosing for any events over the first 2 hours.
Guidance on missed doses and IP administered outside of the allowed window:

If vomiting occurs within 2 hours after drug administration, it will be considered as a 
missed dose. Participants should not make up vomited doses; dosing should resume 
on the next calendar day unless otherwise instructed.

If participants have had less than 21 consecutive days of continuous QD dosing of IP 
(regardless of formulation) on the last day of a treatment period, they will be 
considered non-completers of that treatment period (Period X). Otherwise the 
treatment needs to be extended within the allowed window or repeated for 21 days 
(-2/+7). PK assessment will not be performed for non-completers of a treatment 
period, but other scheduled activities for D28 visit (period 1) or Day 21 visit (period 2 
and 3) will be performed per the SoA and new bottles of IP (same treatment as Period 
X) will be dispensed on D28 or D21 visit instead of Day 1. After the completion of 
Period X, instead of moving on to the next treatment, the same treatment in Period X 
will be repeated for 21 days (-2/+7 days). In this situation, where Period X gets 
repeated to ensure 21 continuous days of dosing prior to PK assessment, the repeated 
period will get noted as Period Xa, and then if repeated a second time as Period Xb.
Please note the visit windows shown in the SoA (-2/+2 days for period 1 and -2/+7 
days for period 2 and 3) allow the treatment to be extended to meet 21 (-2/+7)
continuous days instead of repeating a period.

Participants must complete a given treatment period before they can enter the next 
scheduled period.

If the participant has repeated a period twice due to a missed dose (original plus 2 
repeat periods, a total of 3 for the same period), the participant should discontinue the 


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BE/food effect Phase and roll over to the Maintenance Cycle Phase schedule (SoA).
The sponsor reserves the right for taking participants off treatment due to compliance 
issue.

On the visit days with PK assessment, participants will take IP at the site 
approximately 24 hours after the previous dose (ie, nominal time). Drug 
administration outside of ±2 hours of nominal time will be recorded as a protocol 
deviation. If drug administration occurs >28 hours from the previous dose (ie, >4 
hours after nominal time) or <20 hours from the previous dose (ie, <4 hours before 
nominal time), PK assessment will not be performed on that day and the participant 
will need to take at least 2 more daily doses at the nominal time before performing the 
scheduled activities; as long as the visit occurs within (+4 day) window of the 
original schedule.

If a participant forgets his daily dose of IP at the time he/she typically takes it, but 
remembers it later on the same day, the dose may be taken on that day. As long as the 
delayed dosing occurs at least 2 days before PK sampling day, the treatment schedule 
will remain unchanged. If this occurs within 2 days before PK sampling day, the 
treatment will need to be extended by at least 2 days before the PK sampling visit.
Any dose that is missed (not taken on the same day of the intended time) should be 
skipped and should not be made up on the following day.
In order to standardize the conditions on PK sampling days, all participants will be required 
to refrain from lying down (except when required for BP, pulse rate, and ECG 
measurements) during the first 2 hours after dosing.
Participants who have repeated a period 2 times but still cannot meet PK evaluable criteria, 
need a dose reduction, have unstable renal function, or have experienced renal function 
reduction to moderate/severe renal impairment during the study, or have completed the food 
effect assessment will roll over to the maintenance phase which will consist of repeating 28
day cycles of treatment with the current commercial formulation.
Maintenance Phase
Participants will continue the same dosage as the last dose from the BE and/or Food Effect 
Phase, whichever is later, with the commercial formulation. There are no specific dosing 
restrictions during the maintenance phase. IP may be taken with or without food.
During BE, food-effect, and maintenance phase of the study, participants will be instructed to 
self-administer their IP according to the provided administration instructions, store the IP at 
home at 20°C to 25°C (68°F to 77°F), return all unused IP/bottles to the site, and record 
study-specific details and any deviations from instructions in a diary provided for the study.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 


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2. Talazoparib is considered a cytotoxic and clastogenic agent; precautions regarding 
appropriate secure storage and handling must be used by healthcare professionals, 
including personal protective clothing, disposable gloves, and equipment. Participants 
should be advised that oral anticancer agents (ie, talazoparib) are toxic substances and 
that other caregivers should always use gloves when handling the capsules.
3. Only participants enrolled in the study may receive IP and only authorized site staff 
may supply or administer study intervention. All IP must be stored in a secure, 
environmentally controlled, and monitored (manual or automated recording) area in 
accordance with the labeled storage conditions with access limited to the investigator 
and authorized site staff. At a minimum, daily minimum and maximum temperatures 
for all site storage locations must be documented and available upon request. Data for 
nonworking days must indicate the minimum and maximum temperatures since 
previously documented for all site storage locations upon return to business.
4. Any excursions from the IP label storage conditions should be reported to Pfizer upon 
discovery along with any actions taken. The site should actively pursue options for 
returning the IP to the storage conditions described in the labeling, as soon as 
possible. Once an excursion is identified, the IP must be quarantined and not used 
until Pfizer provides permission to use the IP. Specific details regarding the definition 
of an excursion and information the site should report for each excursion will be 
provided to the site in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
6. IP should be stored in their original containers.
7. Site staff will instruct participants on the proper storage requirements for take-home 
IP.
8. The following are the BA/BE retain requirements:

Stored by the investigator site

Stored under conditions consistent with product labeling

Stored in an area segregated from the area where testing is conducted 

Stored with access limited to authorized personnel

Minimum of 4 (30 count bottles), per lot of the test article and reference standard

The subject dosing and retention sample containers must be identical in 
formulation, manufactured lot, and packaging and labeling presentation.
For non-US sites, there may be local country regulations (eg, import license 
restrictions of subject dosing containers only) which prevent distribution of the 
retention sample containers; they may be stored at a 3rd party vendor location 
contracted by test site.
Each reserve sample shall be retained at the investigator site for a period of at 
least 5 years following the date on which the application or supplemental 
application is approved, or, if such application or supplemental application is not 


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approved, at least 5 years following the date of completion of the bioavailability 
study in which the sample from which the reserve sample was used.
9. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for IP accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records), such as the IPAL or sponsor
approved equivalent. All IP will be accounted for using a IP accountability 
form/record. All IP that is taken home by the participant, both used and unused, must 
be returned to the investigator by the participant. Returned IP must not be redispensed 
to the participants. to the participants.
10. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP Manual.
6.2.1. Preparation and Dispensing
The IP will be dispensed using an IRT drug management system at each visit. A qualified 
staff member will dispense the IP via unique container numbers in the bottles provided, in 
quantities appropriate for the study visit schedule. The participant/caregiver should be 
instructed to maintain the IP in the bottle provided throughout the course of dosing and return 
the bottle to the site at the next study visit.
See the IP manual for instructions on how to prepare the IP for administration. IP should be 
prepared and dispensed by an appropriately qualified and experienced member of the study 
staff (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacy 
assistant/technician, or pharmacist) as allowed by local, state, and institutional guidance.
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
themselves and to the environment should undertake the preparation, handling, and safe 
disposal of PARP inhibitor agents.
6.3. Measures to Minimize Bias: Randomization and Blinding
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
Participant numbers will be assigned as participants are screened for the study. Investigative 
sites will utilize IRT to assign randomization numbers and in accordance with the 
randomization numbers, the participant will receive the study treatment regimen.


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6.3.1. Allocation to Study Intervention
Allocation of participants to treatment groups will proceed through the use of an IRT/IWR 
system. The site personnel (study coordinator or specified designee) will be required to enter 
or select information including but not limited to the user’s ID and password, the protocol 
number, and the participant number. The site personnel will then be provided with a 
treatment assignment, randomization number, and DU or container number when study 
intervention is being supplied via the IRT system. The IRT system will provide a 
confirmation report containing the participant number, randomization number, and DU or 
container number assigned. The confirmation report must be stored in the site’s files. 
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be redispensed to the participants.
The study specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
This will be an open label study; however, the specific study intervention dispensed to the 
participant will be assigned using an IRT. The site will contact the IRT prior to the start of 
study intervention administration for each participant. The site will record the study 
intervention assignment on the applicable CRF, if required. Potential bias will be reduced by 
the following steps: central randomization, competitive enrollment.
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
IP will be dispensed at the study visits summarized in the SoA. 
Returned IP must not be re-dispensed to the participants.
The study specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
Intervention compliance will be assessed at each visit. Compliance will be assessed by 
counting returned capsules. For home IP self-administration, a diary will be provided to the 
participant to aid in compliance with the dosing instructions. Participants should be 
instructed by the site to enter data in the diary in real-time. The site should review 
participants’ eDiary IP compliance on add and 1 day before the site visit day to check for 
missed doses/out of window dosing and follow the guidance on missed doses and IP 
administered outside of the allowed window. Data entered in the diary by the participant will 
be compared with drug accountability done by the site prior to performing serial PK 
samplings/prior to dispensing additional IP. Deviation(s) from the prescribed dosage regimen 
should be recorded in the CRF.


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Bottles will be returned and compliance checked with eDiary dosing compliance from the 
web portal prior to PKs to ensure required daily 1 mg dosing.
Dosing compliance is critical to obtaining quality PK results for the BE and food effect phase 
of this study.
During the Maintenance Phase, compliance is defined as 80% of the total doses for each 
cycle. See Section 8.3.10 for Medication Errors.
6.5. Concomitant Therapy
The following concomitant medications are prohibited during the study:

P-gp inhibitors: amiodarone, carvedilol, clarithromycin, cobicistat, dronedarone, 
erythromycin, glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, 
lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, 
sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tipranavir, valspodar, and verapamil, 
atorvastatin, azithromycin, conivaptan, curcumin, cyclosporine, diltiazem, diosmin, 
eliglustat, elacridar, eltrombopag, felodipine, flibanserin, fluvoxamine, piperine, 
quercetin, and schisandra chinensis extract.

P-gp inducers: avasimibe, carbamazepine, phenytoin, rifampin, and St. John’s Wort.

BCRP inhibitors: curcumin, cyclosporine, elacridar, and eltrombopag. 
Alternative therapies should be considered whenever possible. If usage of any of the above 
treatment is deemed medically necessary, consultation and agreement with the sponsor is 
required prior to treatment initiation as appropriate dose modification of IP may be needed.
Please refer to FDA website:
(https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInte
ractionsLabeling/ucm093664.htm#table5-2 ) and University of Washington Drug-Drug 
Interaction database (https://www.druginteractioninfo.org/) for DDI potential with P-gp and 
BCRP and contact the sponsor when new concomitant medications are used.
Concomitant use of any systemic anti-cancer therapy for disease under study is not allowed 
during study participation.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, unit and frequency, and start and stop dates of administration. All participants will be 
questioned about concomitant treatment at each clinic visit.
Treatments taken within 28 days before the first dose of study intervention will be 
documented as a prior treatment. Treatments taken after the first dose of study intervention 
will be documented as concomitant treatments. 


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6.6. Dose Modification 
This protocol allows for dose modifications from the currently outlined dosing schedule, but 
the maximum daily dose will not exceed 1 mg. Dose modifications for talazoparib due to 
adverse events are described in Table 6.
Dose Modifications for Adverse Reactions 
To manage adverse reactions, consider interruption of treatment with or without dose 
reduction based on severity and clinical presentation. Recommended dose reductions are 
indicated in Table 4 and Table 5. 
If a participant requires a dose reduction, the talazoparib commercial formulation will be 
utilized and dispensed. Reduction may necessitate an additional entry into IRT to request a 
formulation change. Dose reductions will be in increments of 0.25 mg/dose, therefore, 
participant may need to self-administer more than 1 capsule for the reduced dose which will 
be supplied as 0.25 mg capsules (eg, 0.75 mg = 3 capsules daily, 0.50 mg = 2 capsules daily, 
0.25 mg = 1 capsule daily) with 30 capsules per bottle. Treatment with IP should be 
discontinued if more than three dose reductions are required. 
Table 4.
Dose Reduction Levels for Adverse Reactions
Dose Level
Dose
Recommended starting dose 
1 mg (one 1 mg commercial formulation or the 
proposed talazoparib soft gel capsule formulation 
once daily
First dose reduction 
0.75 mg (three 0.25 mg commercial formulation 
capsules) once daily
Second dose reduction 
0.50 mg (two 0.25 mg commercial formulation 
capsules) once daily
Third dose reduction 
0.25 mg (one 0.25 mg commercial formulation 
capsule) once daily
After dose reduction, re-escalation is not allowed. Treatment-emergent hematological and 
non-hematological events will be managed by the following dose modifications.
Table 5.
Dose Modification and Management Due to Adverse Reactions
Toxicity
Management of Adverse Events 
Grade 1 or 2
Selected 
hematologic and 
nonhematologic 
grade 3 or 4 events
No requirement for dose interruption or dose reduction.


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Table 5.
Dose Modification and Management Due to Adverse Reactions
Toxicity
Management of Adverse Events 
Anemia 
(hemoglobin <8.0 
g/dL)
Hold talazoparib and monitor weekly until hemoglobin returns to baseline (day 1) 
grade or better. Implement supportive care per local guidelines.
Talazoparib may be reduced by 1 dose level per Table 4.
If anemia persists for >4 weeks without recovery to baseline grade, discontinue 
talazoparib and refer to a hematologist for evaluation, including assessment for 
possible MDS/AML.
Neutropenia 
(ANC <1000/µL)
Hold talazoparib and monitor weekly until ANC ≥1500/µL. Implement supportive 
care per local guidelines. Reduce talazoparib by 1 dose level per Table 4.
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 ≥50,000/µL. Implement supportive care per local 
guidelines. Reduce talazoparib by 1 dose level per Table 4.
If thrombocytopenia persists for >4 weeks without recovery to ≥50,000/µL, 
discontinue talazoparib and refer to a hematologist for evaluation, including 
assessment for possible MDS/AML.
Nonhematologic 
laboratory grade 
≥3 events except 
abnormal liver 
tests 
Hold talazoparib as follows: 

For clinically significant grade 3 laboratory abnormalities talazoparib may be 
held. Resume talazoparib at the same dose or reduce by 1 dose level per 
Table 4 when the laboratory abnormality resolves to grade ≤2(baseline grade 
for creatinine increases). 

For grade 4 laboratory abnormalities, hold talazoparib. Resume talazoparib 
when the laboratory abnormality resolves to grade ≤2(baseline grade for 
creatinine increases) at a 1 dose level reduction per Table 4.
Implement supportive care per local guidelines. Contact medical monitor to discuss
potential dose modification. Talazoparib must be permanently discontinued for 
unresolved grade 3 toxicity lasting longer than 4 weeks or for grade 4 toxicity 
lasting longer than 1 week. Treatment may be resumed at a 1 dose level reduction if 
clear clinical benefit is observed, after discussion with the medical monitor.
Talazoparib must be discontinued if a grade 4 AE recurs after talazoparib resumes.
Grade ≥3 
abnormal liver 
tests
If baseline Grade 1 AST or ALT, temporary hold if elevation >5 × ULN (ALT or 
AST ≥3 × ULN with the presence of signs and symptoms consistent with acute 
hepatitis and/or eosinophilia 
[≥500 eosinophils/μL]) until resolves to grade ≤1 or baseline. Resume talazoparib 
at the same dose or reduce by 1 dose level per Table 4.
If baseline Grade 2 ALT or AST, temporary hold if elevation >8 × ULN until 
resolves to grade ≤1 or baseline. Resume talazoparib at the same dose or reduce by 
1 dose level per Table 4.
If baseline Grade 1 bilirubin, temporary hold if elevation >3 × ULN until resolves to 
grade ≤1 or baseline. Resume talazoparib at the same dose or reduce by 1 dose 
level per Table 4.
If baseline Grade 2 bilirubin, temporary hold if elevation > 5 × ULN until resolves 
to grade ≤1 or baseline. Resume talazoparib at the same dose or reduce by 1 dose 
level per Table 4.


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Table 5.
Dose Modification and Management Due to Adverse Reactions
Toxicity
Management of Adverse Events 
Nonlaboratory 
grade ≥3 events 
Hold talazoparib as follows: 

For clinically significant grade 3 AEs, hold talazoparib until the AEs resolves 
to grade ≤1 or baseline. Resume talazoparib at the same dose or reduce by 1 
dose level per Table 4.

For grade 4 AEs, hold talazoparib until the AE resolves to grade ≤1 or 
baseline. Resume talazoparib at a 1 dose level reduction per Table 4. 
Implement supportive care per local guidelines.
Contact medical monitor to discuss potential dose modification. 
Talazoparib must be permanently discontinued for unresolved grade 3 toxicity 
lasting longer than 4 weeks or for grade 4 toxicity lasting longer than 1 week.
Treatment may be resumed at a 1 dose level reduction if clear clinical benefit is 
observed, after discussion with the medical monitor. Talazoparib must be 
discontinued if a grade 4 AE recurs after treatment resumes.
6.7. Intervention After the End of the Study
No study intervention will be provided to study participants at the end of the study unless 
otherwise required by local laws or regulations.
Preparations for study closure will occur at the collection of the final data point for primary 
and secondary study objectives. During study closure preparations, the sponsor may work 
with sites to explore options for alternative source of treatment for remaining patients in the 
maintenance phase.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention include the following 

Objective disease progression.

Global deterioration of health status;

Unacceptable toxicity;

Pregnancy;

Significant protocol violation;

Lost to follow-up;

Patient refused further treatment;


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
Study terminated by sponsor; or

Death.
Note that discontinuation of study intervention does not represent withdrawal from the study.
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for safety follow-up until 28 days after the last dose. See the SoA for data to be 
collected at the time of discontinuation of study intervention and follow-up for any further 
evaluations that need to be completed.
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, post treatment study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and withdraws consent (see Section 7.2.1) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of IP will remain in the study and must 
continue to be followed for protocol-specified follow-up procedures. The only exception to 
this is when a participant specifically withdraws consent for any further contact with him or 
her or persons previously authorized by the participant to provide this information.
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible. The withdrawal of consent should be explained in 


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detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of study intervention or also from study procedures and/or posttreatment study 
follow-up, and entered on the appropriate CRF page. In the event that vital status (whether 
the participant is alive or dead) is being measured, publicly available information should be 
used to determine vital status only as appropriately directed in accordance with local law.
7.3. Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study specific procedures. Signing of the informed consent 
by the participant is the start of the study.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.


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Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline 
purposes provided the procedures met the protocol specified criteria and were performed 
within the time frame defined in the SoA, except:

The imaging window for eligibility at screening will be allowed to precede the Period 1 
Day 1 visit by 60 days to allow for utilization of standard of care imaging. 

Any historical diagnostic testing may be utilized to document mutations, no diagnostic 
testing will be performed in this study.

Participants will be required to maintain a diary to capture daily dosing in real-time, 
date and time of each dose (or missing doses).

PK shipment requirements will be documented in a Study Laboratory Manual.
The total blood sampling volume for individual participants in this study is approximately 
270 mL for the BE phase (57 days) plus 260 mL for completion of 21 cycles. The actual 
collection times of blood sampling may change. Additional blood samples may be taken for 
safety assessments at times specified by Pfizer, provided the total volume taken during the 
study does not exceed 550 mL during any period of 60 consecutive days.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. Unplanned procedures or visits per investigator’s discretion 
for safety management will be reported on the Unscheduled CRFs.
Every effort should be made to ensure that protocol required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
wellbeing of the participant. When a protocol required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.


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8.1. Efficacy Assessments
Efficacy will not be evaluated in this study. Participants will be evaluated for disease 
progression per standard of care and investigators will confirm disease progression has not 
occurred for the participant’s continuation in the study.
8.1.1. Imaging Assessments
Participants will provide consent for use of their imaging data for participation in this study. 
Standard of care assessments will be utilized for respective tumor diagnosis (but no later than 
every 6-12 months or as clinically indicated) to monitor for continued benefit on treatment.
SOC imaging will be utilized for eligibility and RECIST criteria will not be reported during 
the study.
8.2. Safety Assessments
Safety assessments will include collection of AEs, SAEs, vital signs, 12-lead ECG and 
laboratory assessments, including pregnancy tests. AEs and SAEs will be assessed per NCI 
CTCAE version 5.0.
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Physical Examinations
A complete physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal, and neurological systems.
A brief physical examination will include, at a minimum, assessments of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen).
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. Vital Signs
Oral temperature, pulse/heart rate, weight, and blood pressure will be assessed. Height will 
be reported at screening.
Blood pressure and pulse rate measurements will be assessed in supine position during the
BE/BA Phases and sitting position during the Maintenance Phase with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available.
Blood pressure and pulse rate measurements should be preceded by at least 5 minutes of rest 
for the participant in a quiet setting without distractions (eg, television, cell phones).
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse 
rate and 3 blood pressure measurements (3 consecutive blood pressure readings will be 


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recorded at intervals of at least 1 minute). The average of the 3 blood pressure readings will 
be recorded on the CRF.
8.2.3. Electrocardiograms
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) should be 
collected at times specified in the SoA section of this protocol using an ECG machine that 
automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS 
complex. Alternative lead placement methodology using torso leads (eg, Mason-Likar) is not 
recommended given the potential risk of discrepancies with ECGs acquired using standard 
limb lead placement. All scheduled ECGs should be performed after the participant has 
rested quietly for at least 10 minutes in a supine position. 
If a) a post dose QTc interval remains ≥60 msec from the baseline and is >470 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator); or c) QTc intervals get progressively longer, the 
participant should undergo continuous ECG monitoring. A cardiologist should be consulted 
if QTc intervals do not return to less than the criterion listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator). 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.4. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA.
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically abnormal during participation in the 
study or within 28 (+7) days after the last dose of study intervention should be repeated until 
the values return to normal or baseline or are no longer considered clinically significant by 
the investigator or medical monitor.


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If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.5. Pregnancy Testing
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA.
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the IP. Pregnancy tests will also be done whenever 1 
menstrual cycle is missed during the active treatment period (or when potential pregnancy is 
otherwise suspected) and at the end of the study. Pregnancy tests may also be repeated if 
requested by IRBs/ ECs or if required by local regulations. If a urine test cannot be 
confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such 
cases, the participant must be excluded if the serum pregnancy result is positive.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
Each participant will be questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving IP), through and including a minimum of 28 
calendar days, except as indicated below, after the last administration of the study 
intervention. 


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Follow-up by the investigator continues throughout and after the active collection period and
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and Pfizer concurs with that assessment.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant definitively discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek AEs or SAEs after the participant has 
concluded study participation. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has completed the study, and he/she considers the event 
to be reasonably related to the study intervention, the investigator must promptly report the 
SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
If a participant begins a new anticancer therapy, SAEs occurring during the above-indicated 
active collection period must still be reported to Pfizer Safety irrespective of any intervening 
treatment. Note that a switch to a commercially available version of the study intervention is 
considered as a new anticancer therapy for the purposes of SAE reporting.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
If a participant begins a new anticancer therapy, the recording period for nonserious AEs 
ends at the time the new treatment is started; however, SAEs must continue to be recorded on 
the CRF during the above-indicated active collection period. Note that a switch to a 
commercially available version of the study intervention is considered as a new anticancer 
therapy for the purposes of SAE reporting.


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8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to followup (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of an
IP under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.


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8.3.5.1. Exposure During Pregnancy
An EDP occurs if:

A female participant is found to be pregnant while receiving or after discontinuing IP.

A male participant who is receiving or has discontinued IP exposes a female partner 
prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to IP 
due to environmental exposure. Below are examples of environmental exposure 
during pregnancy:

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the IP by inhalation or skin contact.

A male family member or healthcare provider who has been exposed to the IP by 
inhalation or skin contact then exposes his female partner prior to or around the 
time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of IP and up to 7 months for females and up 
to 4 months for males after the last dose of IP.

If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).


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Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly (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 including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. 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.
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing IP.

A female is found to be breastfeeding while being exposed or having been exposed to 
IP (ie, environmental exposure). An example of environmental exposure during 
breastfeeding is a female family member or healthcare provider who reports that she 
is breastfeeding after having been exposed to the IP by inhalation or skin contact.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 


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CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
IP, which may or may not lead to the occurrence of an AE. Such persons may include 
healthcare providers, family members, and other roles that are involved in the trial 
participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE. The information 
must be reported using the CT SAE Report Form. Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events 
Not applicable.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable.
8.3.8. Adverse Events of Special Interest 
Not applicable.
8.3.8.1. Lack of Efficacy
This section is not applicable because efficacy will not be analyzed in the study population.
8.3.9. Medical Device Deficiencies 
Not applicable.
8.3.9.1. Prompt Reporting of Device Deficiencies to Sponsor
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the IP by the wrong 
participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the IP under study may occur in clinical trial settings, such as medication 
errors.


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Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 24 
Hours of Awareness
Medication errors All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Lack of dose reduction as specified by the protocol;

Continuation of treatment although participant met discontinuation criteria;

Incorrect IP dose by participant;

Participant did not take IP for 6 or more days (approximately <80%) within 4 weeks, 
unless dose was withheld due to an AE;

Participant did not receive treatment as assigned by IRT;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of talazoparib greater than 1 mg within a 24-hour time period will be 
considered an overdose.
Pfizer does not recommend specific treatment for an overdose. All overdose events are to be 
reported per requirements in Section 8.3.10.






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9.1. Estimands and Statistical Hypotheses
9.1.1. Statistical Hypothesis
The alternative hypothesis of BE (H1: L <=T - R <=U), and the null hypothesis of 
inequivalence (Ho: T - R <L or T - R >U) can be expressed as the following 2 separate 
one-sided hypotheses:
HoA: T - R <L
H1A: L <=T - R
HoB: T - R >U
H1B: T - R <=U
where T and R represent the average bioavailability on a log scale for the Test and 
Reference products respectively and [L, U] defines the BE range.
The 2 one-sided hypotheses will be tested at the = 0.05 levels of significance for log 
transformed AUC24 and Cmax by constructing the 90% CI for the ratio between the test and 
reference geometric means.
9.2. Sample Size Determination
It is estimated that 22 participants will be required to provide 90% power that the 90% CI for 
the Test/Reference ratio of talazoparib AUC24 falls within the 80‑125% acceptance interval 
for bioequivalence. Additionally, with 22 participants, probability that Test/Reference ratio 
for Cmax will fall within 80%-125% is estimated to be 86%. These estimates are based on the 
assumption that the true ratio between Test and Reference treatments for AUC24 and Cmax is 
1.07 and 1.1 and also assumes within subject standard deviations of 0.407 and 0.17 for loge
Cmax and loge AUC24 respectively, as obtained from rifampin and itraconazole cohorts from 
study MDV3800-04.
Participants who withdraw from the study or fail to provide evaluable samples may be 
replaced at the discretion of the sponsor. Approximately 46 participants will be enrolled into 
the study to ensure at least 22 evaluable participants for the BE phase and 12 evaluable 
participants for the food effect evaluation phase. The initial number of 46 participants is 
estimated based on 52% non-evaluable rate and might be adjusted during enrollment if non-
evaluable rate changes. The criteria for PK-evaluability will be described in detail in the 
SAP.
When approximately 12 evaluable participants complete both Periods 1 and 2, initial 
assumptions (AUC24 variability and point estimate) for power/sample size calculation may be 
reassessed. Sample size may be increased; however, the total number of participants to be 
enrolled in the study may not exceed approximately 88 participants.


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9.3. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
PK Concentration
The PK concentration population is defined as all 
participants randomized and treated who have at least 1 
concentration in at least 1 treatment period.
PK Parameter
The PK parameter population is defined as all participants 
randomized and treated who have meaningful primary PK 
parameter of AUC24 or Cmax in at least 1 treatment period.
Safety
All participants randomly assigned to IP and who take at 
least 1 dose of IP. Participants will be analyzed according 
to the product they actually received.
9.4. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data.
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. General Considerations
Methodology for summary and statistical analyses of the data collected in this study is 
outlined here and further detailed in a SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
9.4.2. Primary Endpoint(s)
To assess BE, natural log transformed AUC24 and Cmax after multiple dosing on the last day 
of Period 1 and 2 will be analyzed using a mixed-effect model with sequence, period, and 
treatment as fixed effects and participant within sequence as a random effect. Estimates of 
the adjusted mean differences (Test‑Reference) and corresponding 90% CIs will be obtained 
from the model. The adjusted mean differences and 90% CIs for the differences will be 
exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) 
and 90% CIs for the ratios. Treatment A (commercial formulation given under fasting 
condition) will be the Reference treatment while Treatment B (the proposed talazoparib soft 
gel capsule formulation under fasting condition) will be the Test treatment.  
To assess food effect, natural log transformed AUC24 and Cmax after multiple dosing on the 
last day of Treatment B and C will be analyzed using a mixed effect model with sequence 
and treatment as fixed effects and participant within sequence as a random effect. Estimates 


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of the adjusted mean differences (Test‑Reference) and corresponding 90% CIs will be 
obtained from the model. The adjusted mean differences and 90% CIs for the differences will 
be exponentiated to provide estimates of the ratio of adjusted geometric means 
(Test/Reference) and 90% CIs for the ratios. Treatments B (the proposed talazoparib soft gel 
capsule formulation under fasting condition) is the Reference treatment while Treatments C 
(the proposed talazoparib soft gel capsule formulation given with high-fat/high-calorie meal) 
is Test treatment.
If initial design assumptions are reassessed during the trial, additional sensitivity analysis of 
BE will be performed by combining estimators from 2 stages using Cui, Hung, Wang 19991. 
The 90% CI will be constructed using combined weighted estimate and standard error from 
2 stages.1
9.4.3. Secondary Endpoint(s)
The PK parameters AUC24, AUClast,Cmax, Ctrough, CL/F, and Tmax on the last day of Period 1 
to 3 will be summarized descriptively by treatment. Concentrations will be listed and 
summarized descriptively by treatment, and PK sampling time. Individual participant and 
median profiles of the concentration‑time data will be plotted by treatment. For summary 
statistics and median plots by sampling time, the nominal PK sampling time will be used. For 
individual participant plots by time, the actual PK sampling time will be used. Ctrough on 3
consecutive days will be compared to assure steady state is reached. 
9.4.3.1. Pharmacokinetic Analyses
Derivation of Pharmacokinetic Parameters
Parameter
Definition
Method of Determination
AUC24
Area under the plasma 
concentration-time curve from 
time 0 to 24 hours on the last day 
of treatment period 1 to 3
Linear/Log trapezoidal method
AUClasta
Area under the plasma 
concentration-time profile from 
time zero to the time of the last 
quantifiable
concentration (Clast) on the last 
day of treatment period 1 to 3
Linear/Log trapezoidal method
Cmax
Maximum plasma concentration 
on the last day of treatment period 
1 to 3
Observed directly from data
Tmax
Time for Cmax on the last day of 
treatment period 1 to 3
Observed directly from data as 
time of first occurrence
Ctroughb
Predose plasma drug 
concentration 
Observed directly from data
CL/F
Apparent clearance after oral dose 
on the last day of treatment period 
1 to 3
Dose/ AUC24 
a.
Calculated when the last measurable PK sample is not taken at 24 hours postdose.
b.
Predose sample from a PK-evaluable participant




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


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


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A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 30 days from the previous ICD signature date.
Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research. The optional 
additional research does not require the collection of any further samples. The investigator or 
authorized designee will explain to each participant the objectives of the additional research.
Participants will be told that they are free to refuse to participate and may withdraw their 
consent at any time and for any reason during the storage period.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper 
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record identification. In 
case of data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.


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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.


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Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the study 
monitoring plan and respective monitoring vendor contract.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 


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being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in Study Manual and/or CRF 
Guidelines.
Description of the use of computerized system is documented in the Data Management Plan.
10.1.8. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.


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The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the CRO if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.


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The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in study team on demand (SToD) 
system.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent. The contact card contains, at a minimum, protocol and study intervention identifiers, 
participant numbers, contact information for the investigator site, and contact details for a 
contact center in the event that the investigator site staff cannot be reached to provide advice 
on a medical question or problem originating from another healthcare professional not 
involved in the participant’s participation in the study. The contact number can also be used 
by investigator staff if they are seeking advice on medical questions or problems; however, it 
should be used only in the event that the established communication pathways between the 
investigator site and the study team are not available. It is therefore intended to augment, but 
not replace, the established communication pathways between the investigator site and the 
study team for advice on medical questions or problems that may arise during the study. The 
contact number is not intended for use by the participant directly, and if a participant calls 
that number, he or she will be directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Table 6.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count
Total neutrophils (Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN and creatinine
Glucose 
Calcium
Sodium
Potassium
Magnesium
Chloride
Total CO2 (bicarbonate)
AST, ALTd
Total bilirubin
Alkaline phosphatase
Uric acid
Albumind
Phosphorus or phosphate
Total protein
Direct/Indirect Bilirubin
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya

Pregnancy test (β-hCG)c
At screening only:

Coagulation (INR PT, 
aPTT) or as clinically 
indicated

FSHb
a.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
b.
For confirmation of postmenopausal status only.
c.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/EC. Serum or urine -hCG for female participants of childbearing potential with sensitivity of at 
least 25 IU/mL.
d.
For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma glutamyl transferase, INR 
international normalized ratio, alkaline phosphatase.
Investigators must document their review of each laboratory safety report.
















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10.4. Appendix 4: Contraceptive Guidance
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 4 months after the last dose of study intervention, 
which corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent. 
OR

Must agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), as described below, during the intervention period 
and for at least 7 months after the last dose of study intervention, which 
corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s). If a highly effective method that is user dependent is 
chosen, a second effective method of contraception, as described below, must also
be used. The investigator should evaluate the effectiveness of the contraceptive 
method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 


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10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. In addition, a

high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

Female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.


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10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;

Injectable.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.


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In addition, one of the following effective barrier methods must also be used when 
option 6 or 7 are chosen above:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).




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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI.
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations (>2 ×
ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT is/are 
still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same 
laboratory sample). In rare instances, by the time TBili elevations are detected, AST/ALT 
values might have decreased. This occurrence is still regarded as a potential DILI. Therefore, 
abnormal elevations in either AST OR ALT in addition to TBili that meet the criteria 
outlined below are considered potential DILI (assessed per Hy’s law criteria) cases and 
should always be considered important medical events, even before all other possible causes 
of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
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.


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






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10.8. Appendix 8: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic at specific location(s) and will become effective for other public 
emergencies only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories).
10.8.1. Eligibility
While SARS-CoV2 testing is not mandated for this study, local clinical practice standards for 
testing should be followed. A patient could be excluded if he/she has a positive test result for 
SARS-CoV2 infection, is known to have asymptomatic infection, or is suspected of having 
SARS-CoV2. Patients with active infections are excluded from study participation as per 
exclusion criteria 4 (active infection requiring therapy) and exclusion 16 (positive CoVID-19 
viral test). 
10.8.2. Telehealth Visits
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare 
information and services via telecommunication technologies (eg, audio, video, 
video-conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit:

Review and record study intervention(s), including compliance and missed doses.

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4 and Section 10.8.3.1 of this appendix regarding 
pregnancy tests.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.


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10.8.3. Alternative Facilities for Safety Assessments
10.8.3.1. Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local regulations.
The local laboratory may be a standalone institution or within a hospital. The following 
safety laboratory evaluations may be performed at a local laboratory:

Blood draw for hematology and blood chemistry

Urine sample collection

Pregnancy test
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible. Study participants should be instructed to collect their laboratory test 
results and bring them to the next in-clinic visit. The local laboratory reports should 
be filed in the participant’s source documents/medical records. Relevant data from the local
laboratory report should be recorded on the CRF. 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 IU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol.
10.8.3.2. Imaging
Not Applicable
10.8.3.3. Electrocardiograms
If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must order, 
receive, and review results. 
10.8.4. Study Intervention
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered.
Talazoparib may be shipped by courier to study participants if permitted by local regulations 
and in accordance with storage and transportation requirements for talazoparib. Pfizer does 
not permit the shipment of talazoparib by mail. The tracking record of shipments and the 
chain of custody of talazoparib must be kept in the participant’s source documents/medical 
records.


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The following is recommended for the administration of talazoparib for participants who 
have active confirmed (positive by regulatory authority-approved test) or presumed (test 
pending/clinical suspicion) SARS-CoV2 infection:

For symptomatic participants with active SARS-CoV2 infection, talazoparib should be 
delayed for at least 14 days from the start of symptoms. This delay is intended to allow 
the resolution of symptoms of SARS-CoV2 infection.

Prior to restarting treatment, the participant should be afebrile for 72 hours, and SARS-
CoV2-related symptoms should have recovered to ≤ Grade 1 for a minimum of 72 
hours. Notify the study team when treatment is restarted.

Continue to consider potential drug-drug interactions as described in Section 6.5 for 
any concomitant medication administered for treatment of SARS-CoV2 infection.
10.8.5. Home Health Visits
A home health care service may be utilized to facilitate scheduled visits per the Schedule of 
Activities. Home health visits include a healthcare provider conducting an in-person study 
visit at the participant’s location, rather than an in-person study visit at the site. The 
following may be performed during a home health visit:

Physical exam

Blood pressure, heart rate, temperature, and weight assessments

Blood draw for hematology and blood chemistry

Urine sample collection

Pregnancy test

Contraception check

IP compliance check, accountability, and dispensation

Adverse event monitoring

Concomitant medication monitoring
10.8.6. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided. Study treatment should continue unless the 
investigator/treating physician is concerned about the safety of the participant, in which case 
temporary or permanent discontinuation may be required.
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor.
10.9. Appendix 9: List of Long Half-Life Drugs with No Potential for Drug Interaction 
with Talazoparib
The following treatments with half-lives greater than 6 days and no potential for DDI with 
talazoparib will require at least a 30-day washout period prior to randomization: 
bevacizumab, fulvestrant, ipilumab, nivolumab, pembrolizumab, ramucirumab, and 
trastuzumab. For drugs with long half-lives (>6 days) not included in the list above, consult 
with the sponsor regarding DDI potential.


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10.10. Appendix 10: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALK
anaplastic lymphoma kinase
ALT
alanine aminotransferase
AML
acute myeloid leukemia
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under concentration-time curve
AUC24
AUC from time 0 to 24 hours
AUCinf
AUC from time 0 to infinity
AUClast
AUC from time 0 to last quantifiable concentration
AV
atrioventricular
BA
bioavailability
BCRP
breast cancer resistance protein
BE
bioequivalence
-hCG
-human chorionic gonadotropin
BID
twice daily
bpm
beats per minute
BRAF
B-Raf proto-oncogene
BRCA
BReast CAncer gene
BUN
blood urea nitrogen
CAP
College of American Pathologists
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CL
clearance
CLCR
creatine clearance
CL/F
apparent clearance of drug from plasma
CLIA
Clinical Laboratory Improvement Amendments
Cmax
maximum plasma concentration
CO2
carbon dioxide (bicarbonate)
CoVID-19
coronavirus disease of 2019
CRF
case report form
CRO
contract research organization
CSR
clinical study report
CT
clinical trial
CTCAE
Common Terminology Criteria for Adverse Events


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Abbreviation
Term
Ctrough
steady-state predose plasma concentration
D
day
DDI
drug-drug interaction
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
eDiary
electronic diary
EGFR
epidermal growth factor receptor
EOS
end of study
EOT
end of treatment
ER
exposure-response
EDP
exposure during pregnancy
EMA
European Medicines Agency
EU
European Union
EudraCT
European Clinical Trials Database
F1
bioavailability
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
gBRCAm
germline BRCA-mutated
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBV
hepatitis B virus
HCV
hepatitis C virus
HER2
human epidermal growth factor receptor 2
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HPMC
hydroxypropyl methyl cellulose
HR
heart rate
HRT
hormone replacement therapy
IB
investigator’s brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IMP
investigational medicinal product
IND
Investigational New Drug
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IPAL
Investigational Product Accountability Log


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Abbreviation
Term
IRB
Institutional Review Board
IRT
Interactive Response Technology
IWR
interactive Web-based response
LFT
liver function test
loge
base-e logarithm
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
msec
millisecond
MX1
myxovirus resistance 1
n
number of participants
N/A
not applicable
NDA
New Drug Application
NIMP
noninvestigational medicinal product
NSCLC
non-small cell lung cancer
PARP
poly ADP-ribose polymerase
PARPi
PARP inhibitor
PD
progressive disease
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PO
taken by mouth
PT
prothrombin time
PUD
peptic ulcer disease
P#D#
Period # Day #
PVC
premature ventricular contraction/complex
QD
once daily
QTc
corrected QT interval
QTcF
QTc corrected using Fridericia’s formula
qual
qualitative
RBC
red blood cell
RECIST
Response Evaluation Criteria in Solid Tumor
ROS1
c-ros oncogene 1
RTRT
reference-test-reference-test
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV2
Severe acute respiratory syndrome coronavirus 2 of the genus 
Betacoronavirus
SCR
serum creatinine
SMCC
succimidyl-4-N-maleimidomethyl cyclohexane-1-carboxylate
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
single-reference safety document
SToD
study team on demand


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Abbreviation
Term
SUSAR
Suspected Unexpected Serious Adverse Reaction
t1/2
terminal half life
TBili
total bilirubin
TEAE
treatment-emergent adverse event
Tmax
time to reach maximum plasma concentration
TRTR
test-reference-test-reference
ULN
upper limit of normal
US
United States
USPI
United States package insert
Vz/F
apparent volume of distribution during the terminal phase
WBC
white blood cell
WOCBP
woman of childbearing potential


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11. REFERENCES
1.
Cui L, Hung HM, Wang SJ, et al. Modification of sample size in group sequential 
clinical trials. Biometrics. 1999, 55:853-7. 
2.
LYNPARZA® prescribing information. Wilmington, DE: AstraZeneca; 2020. 
Available from: www.lynparza.com/. Accessed: 09 March 2020
3.
Rubraca® (rucaparib) prescribing information. Doulder, CO: Clovis Oncology, Inc, 
2020. Available from: www.rubraca.com/. Accessed: 09 March 2020
4.
Zejula® (niraparib) prescribing information. Research Triangle Park, NC: 
GlaxoSmithKline; 2020. Available from: www.zejula.com/. Accessed: 09 March 2020
5.
Talazoparib prescribing information. New York, NY: Pfizer, Inc, 2020. Available from: 
www.talzenna.com/. Accessed: 09 March 2020
6.
US Food and Drug Administration. Guidance for industry: Assessing the Effects of 
Food on Drugs in INDs and NDAs - Clinical Pharmacology Considerations Guidance 
for Industry. Available from: www.fda.gov/media/121313/download. Accessed: 10 June 
2020

SAP_001.pdf: