A Phase 2b Study of ZEN003694 in Combination With Talazoparib in Patients With Triple-Negative Breast Cancer
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Sponsor: Zenith Epigenetics

Document Type 
Clinical Study Protocol 
Official Protocol Title 
A Phase 2b Study of ZEN003694 in Combination With Talazoparib in 
Patients With Triple-Negative Breast Cancer 
NCT Number 
NCT03901469 
Document Date 
26 May 2022 
 

 
ZEN003694-004 Clinical Study Protocol 
 
Version:  Final 
Amendment 6 
 
26 May 2022 
Zenith Epigenetics Ltd./Newsoara Biopharma Co. Ltd. 
Confidential 
Page 1 of 116 
 CLINICAL STUDY PROTOCOL 
TITLE 
A Phase 2 Study of ZEN003694 in Combination with Talazoparib in 
Patients with Triple-Negative Breast Cancer 
INVESTIGATIONAL 
NEW DRUG NUMBER 
USA:  141108 
China (for Expansion phase only):  JXHL2000118, JXHL2000119 
EUDRACT NUMBER 
2018-003906-26 
STUDY DRUGS 
ZEN003694, Talazoparib 
PROTOCOL NUMBER ZEN003694-004 
SPONSOR 
Zenith Epigenetics Ltd. 
SPONSOR’S HEAD 
OFFICE 
Suite 300, 4820 Richard Road SW 
Calgary, Alberta 
Canada  T3E 6L1 
SPONSOR’S 
REPRESENTATIVE  
US OFFICE 
 
 
 
 
 
 
 
 
SPONSOR’S  
MEDICAL MONITOR  
US OFFICE 
 
 
 
 
 
 
 
 
CO-SPONSOR 
(Expansion phase, China 
only) 
Newsoara Biopharma Co. Ltd. 
Room 809, 999 West Zhongshan Road 
Shanghai 200051,  China 
PROTOCOL  
DATE 
Amendment 6 
26 May 2022 
Confidentiality Statement 
This document contains proprietary and confidential information of the Sponsors Acceptance of 
this document constitutes agreement by the recipient that no previously unpublished information 
contained herein will be published or disclosed without the prior written approval of the Sponsors 
with the exception that this document may be disclosed to study personnel under your supervision 
who need to know the contents for conducting the study and appropriate Ethics 
Committees/Institutional Review Boards under the condition that the personnel have agreed to 
keep this information confidential.  The foregoing shall not apply to disclosure required by 
governmental regulations or laws; however, the Sponsors shall be promptly notified of any such 
disclosure. 

ZEN003694-004 Clinical Study Protocol 
 
Version:  Final 
Amendment 6 
 
26 May 2022 
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Page 2 of 116 
LIST OF ABBREVIATIONS AND ACRONYMS 
5-HT3 
5-hydroxytryptamine type 3 
ABC 
ATP-binding cassette 
ADC 
Antibody drug conjugate 
ADL 
Activities of daily living 
ADT 
Androgen deprivation therapy 
AE 
Adverse event 
AML 
Acute myeloid leukemia 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AR 
Androgen receptor 
ASCO 
American Society of Oncology 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
AUC 
Area under the curve 
AUC0-∞ 
Area under the curve, from time zero to infinity 
AUC0-24 
Area under the curve, from time zero to 24 hours 
AUC0-last 
Area under the curve, from time zero to last time point with a 
quantifiable level of drug 
BCL2 
B-cell lymphoma 2 
BCL2L1 
B-cell lymphoma 2-like 1 
BCRP 
Breast cancer resistance protein 
BET 
Bromodomain and extra-terminal motif 
BETi 
BET bromodomain inhibitor 
BICR 
blinded independent central review 
BID 
Twice Daily 
BM 
bone marrow 
BRCA1 
Breast cancer 1 gene 
BRCA2 
Breast cancer 2 gene 
BRCA1/2 wt 
BRCA1 and BRCA2, wild-type 
BRD2 
Bromodomain-containing protein 2 
BRD3 
Bromodomain-containing protein 3 
BRD4 
Bromodomain-containing protein 4 
BRDT 
Bromodomain-testis-specific containing protein T 
BUN 
Blood urea nitrogen 
Cmax 
Maximum or peak concentration 
Cmin 
Minimum or trough concentration 
Css 
Concentration steady-state 
CAP 
CBC 
College of American Pathologists 
Complete blood count 
CCR1 
Chemokine (C-C motif) receptor 1 
CDMS 
Clinical data management system 
CI 
Confidence interval 
 
 
CNS 
Central nervous system 

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CR 
Complete response 
CRF 
Case report form 
CRPC 
Castration-resistant prostate cancer 
CT 
Computed tomography 
CTC(s) 
Circulating tumor cell(s) 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
CYP1A2 
Cytochrome P450, family 1, subfamily A, polypeptide 2 
CYP2C8 
Cytochrome P450, family 2, subfamily C, polypeptide 8 
CYP2C9 
Cytochrome P450, family 2, subfamily C, polypeptide 9 
CYP2C19 
Cytochrome P450, family 2, subfamily C polypeptide 19 
CYP3A4 
Cytochrome P450, family 3, subfamily A, polypeptide 4 
CYP17A1 
Cytochrome P450, family 17, subfamily A, polypeptide 1, or 
steroid 17-alpha-hydroxylase/17,20 lyase 
DC 
Dose confirmation 
DDI 
Drug-drug interaction 
DDR 
DE 
DNA damage response/repair 
Dose escalation 
dL 
Decilitre 
DLT 
Dose-limiting toxicity 
DMP 
Data management plan 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double-stranded DNA 
DOR 
Duration of response 
 
 
 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EFD 
embryo-fetal development 
ER 
Estrogen receptor 
ERG 
V-Ets avian erythroblastosis virus E26 oncogene 
ETS 
E26 transformation-specific 
ETV1 
ETS translocation variant 1 
FDA 
Food and Drug Administration 
 
 
GCP 
Good Clinical Practice 
gBRCA1/2m 
Germline BRCA1 or BRCA2 mutation 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
GPR183 
G Protein-Coupled Receptor 183 
GR 
Glucocorticoid receptor 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HED 
Human equivalent dose 

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HER2 
Human epidermal growth factor receptor 2 
hERG 
Human ether-à-go-go related gene (an ion channel found in 
cardiac cell membranes ) 
HIST2H2BE 
Histone gene cluster 1, H2BE histone family member E 
HIV 
Human immunodeficiency virus 
HNSTD 
Highest non-severely toxic dose 
HPBL 
human peripheral blood lymphocytes 
HR 
Homologous recombination 
HRD 
Homologous recombination deficiency 
 
 
IB 
Investigator’s Brochure 
IC50 
Half maximal inhibitory concentration 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IL1RN 
Interleukin 1 receptor antagonist 
INR 
International normalized ratio 
IQR 
interquartile range 
IRB 
Institutional Review Board 
IV 
Intravenous  
kg 
Kilogram(s) 
L 
Litre 
LC-MS/MS 
Liquid chromatography-tandem mass spectrometry  
LD 
Longest diameter 
LDH 
Lactate dehydrogenase 
mCRPC 
Metastatic castration-resistant prostate cancer 
mg 
Milligram(s) 
min 
Minute(s) 
mm3 
Cubic milimeter 
MMS 
methyl methane sulfonate 
MRI 
Magnetic resonance imaging 
mRNA 
Messenger ribonucleic acid 
msec 
Millisecond(s) 
MTD 
Maximum tolerated dose 
MUGA 
Multigated acquisition (scan) 
MYC 
V-Myc avian myelocytomatosis viral oncogene homolog 
NCI 
National Cancer Institute 
NF-kB 
Nuclear factor kappa-light-chain-enhancer of activated B cells  
ng 
Nanogram(s) 
NHEJ 
Non-homologous end joining 
NUT 
NUT gene that codes for a protein in germ cells 
 
 
ORR 
Objective response rate 
PARPi 
Poly adenosine diphosphate ribose polymerase inhibitor 
PBMC 
Peripheral blood mononuclear cell 
PCT 
physician’s choice treatment 

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PD 
Pharmacodynamics 
PD 
Progressive disease 
PDX 
Patient derived xenograft 
PFS 
progression-free survival 
P-gp 
P-glycoprotein 
PK 
Pharmacokinetics 
PR 
Partial response 
PR 
Progesterone receptor  
PRES 
Posterior reversible encephalopathy syndrome 
PRN 
Pro re nata (when necessary) 
PSA 
Prostate-specific antigen 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QD 
Once daily 
qPCR 
Quantitative polymerase chain reaction  
QTcF 
QT interval corrected by the Fridericia correction formula 
Rac 
Accumulation ratio 
RAD51 
Gene involved in homologous recombination and repair of DNA 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors 1.1 
RNA 
Ribonucleic acid 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCLC 
Small-cell lung cancer 
SD 
Stable disease 
SLC 
Solute carrier 
SRSD 
single reference safety document  
STD10 
Severely toxic dose in approximately 10% of animals  
SUSAR 
Suspected unexpected serious adverse event 
t1/2 
Half-life 
TEAE 
Treatment emergent adverse event 
Tmax 
Time to maximum concentration 
TFS 
tumor-free survival  
TGI 
Tumor growth inhibition 
TNBC 
Triple negative breast cancer 
TROP-2 
Tumor-associated calcium signal transducer 2 
UGT 
uridine 5'-diphospho-glucuronosyltransferase 
ULN 
Upper limit of normal 
 

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Table of Contents 
2. 
SYNOPSIS ................................................................................................................. 11 
3. 
BACKGROUND ....................................................................................................... 30 
3.1 
BET Inhibitors in Cancer ............................................................................................ 30 
3.2 
PARP inhibitors in Cancer .......................................................................................... 30 
3.3 
Rationale and Mechanism for BET Inhibitors in BRCA1/2 wt TNBC ...................... 31 
3.4 
ZEN003694 ................................................................................................................. 32 
3.5 
Talazoparib ................................................................................................................. 32 
3.6 
ZEN003694 Preclinical Data in TNBC Models ......................................................... 34 
3.7 
ZEN003694 Clinical Data........................................................................................... 37 
3.8 
Talazoparib Clinical Data ........................................................................................... 42 
3.8.1 
Pharmacokinetics ........................................................................................................ 42 
3.8.2 
Safety .......................................................................................................................... 42 
3.8.3 
Efficacy ....................................................................................................................... 43 
3.9 
Study Rationale ........................................................................................................... 44 
3.10 
Dosing Rationale ......................................................................................................... 44 
3.11 
Rationale for Expanding Phase 2 Study and Patient Pre-Selection ............................ 45 
4. 
OBJECTIVES ........................................................................................................... 48 
4.1 
Primary ........................................................................................................................ 48 
4.2 
Secondary .................................................................................................................... 48 
4.3 
Exploratory ................................................................................................................. 49 
5. 
STUDY DESIGN ....................................................................................................... 50 
5.1 
Part 1:  Dose escalation ............................................................................................... 50 
5.1.1 
Dose Escalation Safety Reviews ................................................................................. 51 
5.1.2 
Definition of Dose-limiting Toxicity .......................................................................... 51 
5.1.3 
Definition of the Maximum Tolerated Dose ............................................................... 52 
5.1.4 
Definition of the Recommended Phase 2 Dose .......................................................... 52 
5.2 
Expansion .................................................................................................................... 53 
5.3 
Number Patients and Sites .......................................................................................... 54 
5.4 
Study Duration ............................................................................................................ 54 
5.5 
Premature Study Termination or Suspension of Enrollment ...................................... 54 
6. 
PATIENT SELECTION .......................................................................................... 55 
6.1 
Inclusion Criteria ........................................................................................................ 55 
6.2 
Exclusion Criteria ....................................................................................................... 56 
7. 
STUDY DRUG AND MATERIALS ....................................................................... 59 
7.1 
ZEN003694 Administration........................................................................................ 59 
7.1.1 
Precautions .................................................................................................................. 59 
7.1.2 
ZEN003694 Formulation ............................................................................................ 59 
7.1.3 
Storage Conditions ...................................................................................................... 59 
7.2 
Talazoparib Administration ........................................................................................ 59 
7.2.1 
Talazoparib Formulation ............................................................................................. 60 
7.2.2 
Talazoparib Handling and Storage Conditions ........................................................... 60 
7.3 
Study Drug Dispensation ............................................................................................ 60 
7.4 
Study Drug Accountability ......................................................................................... 60 
7.5 
Treatment Compliance ................................................................................................ 61 
8. 
STUDY TREATMENT GUIDELINES .................................................................. 62 

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8.1 
Guidelines for Management of Treatment-Related Toxicity ...................................... 62 
8.2 
Management of Selected Talazoparib-Related Toxicities .......................................... 62 
8.3 
Management Guidelines for All Other Toxicities (not listed in Section 8.2, Table 6) 65 
8.4 
Intra-Patient Dose Escalation in Part 2, Simon 2-Stage ............................................. 66 
8.5 
Concomitant Medications and Therapies .................................................................... 67 
8.5.1 
Prohibited Concomitant Medications and Therapies .................................................. 67 
8.5.2 
Permitted Concomitant Medications and Therapies ................................................... 69 
9. 
STUDY VISIT PROCEDURES AND ASSESSMENTS ....................................... 70 
9.1 
Study Procedures by Visit ........................................................................................... 70 
9.1.1 
Screening Visit ............................................................................................................ 70 
9.1.2 
Cycle 1 ........................................................................................................................ 71 
9.1.3 
Cycle 2 ........................................................................................................................ 74 
9.1.4 
Cycles 3 and onward ................................................................................................... 77 
9.1.5 
Unscheduled Visit ....................................................................................................... 78 
9.1.6 
End of Treatment Visit................................................................................................ 78 
9.1.7 
Safety Follow-up Visit ................................................................................................ 79 
9.1.8 
Cross-Over of Expansion Cohort B ZEN003694 Monotherapy Patients ................... 80 
9.2 
Study Assessments ...................................................................................................... 80 
9.2.1 
Informed Consent........................................................................................................ 80 
9.2.2 
Inclusion/Exclusion Criteria ....................................................................................... 81 
9.2.3 
Medical History and Demographics ........................................................................... 81 
9.2.4 
Physical Examination/Symptom-directed Physical Examination ............................... 81 
9.2.5 
Height and Weight ...................................................................................................... 81 
9.2.6 
ECOG Performance Status ......................................................................................... 81 
9.2.7 
Vital Signs ................................................................................................................... 81 
9.2.8 
Laboratory Parameters ................................................................................................ 81 
9.2.9 
12-lead ECG ................................................................................................................ 82 
9.2.10 
Pharmacokinetic (PK) Sampling ................................................................................. 82 
9.2.11 
Germline BRCA1/2 Mutation Status and Sampling ................................................... 82 
9.2.12 
Pharmacodynamic Sampling ...................................................................................... 83 
9.2.13 
Adverse Events ........................................................................................................... 83 
9.2.14 
Concomitant Medications ........................................................................................... 83 
9.2.15 
Tumor Assessment – Imaging/Radiologic Evaluation ............................................... 84 
 
 
9.2.17 
EORTC Quality of Life .............................................................................................. 84 
10. 
WITHDRAWAL OR EARLY TERMINATION OF PATIENTS ....................... 85 
11. 
SAFETY ASSESSMENTS ....................................................................................... 86 
11.1 
Adverse Event and Suspected Unexpected Serious Adverse Reaction Definitions ... 86 
11.1.1 
Adverse Event ............................................................................................................. 86 
11.1.2 
Serious Adverse Event ................................................................................................ 86 
11.1.3 
Suspected Unexpected Serious Adverse Reaction ...................................................... 87 
11.2 
Reporting Serious Adverse Events and Suspected Unexpected Serious Adverse 
Reactions ..................................................................................................................... 87 
11.2.1 
Disease-related Events That Are Endpoints ............................................................... 87 
11.3 
Adverse Events ........................................................................................................... 88 
11.3.1 
Commonly reported Study Drug Related Adverse Events ......................................... 89 

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11.3.2 
Classification of Adverse Events by Severity ............................................................. 89 
11.3.3 
Classification of Adverse Events by Relationship to Study Drug .............................. 89 
11.4 
Abnormal Laboratory Results ..................................................................................... 90 
11.5 
Overdose ..................................................................................................................... 90 
11.6 
Pregnancy .................................................................................................................... 90 
11.7 
Study Safety Monitoring and Dose Escalation or Modification ................................. 91 
11.8 
Reporting Safety Information to the Institutional Review Board ............................... 91 
12. 
STUDY ENDPOINTS ............................................................................................... 92 
12.1 
Primary Endpoints ...................................................................................................... 92 
12.2 
Secondary Endpoints .................................................................................................. 92 
12.3 
Exploratory Endpoints ................................................................................................ 93 
13. 
STATISTICS ............................................................................................................. 94 
13.1 
General Considerations ............................................................................................... 94 
13.2 
Sample Size Determination ......................................................................................... 94 
13.3 
Analysis Populations ................................................................................................... 95 
13.4 
Data Handling ............................................................................................................. 95 
13.5 
Statistical Analyses ..................................................................................................... 96 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE ...................................... 97 
14.1 
Study Monitoring ........................................................................................................ 97 
14.2 
Audit and Inspection ................................................................................................... 98 
14.3 
Regulatory Authority Correspondence ....................................................................... 98 
15. 
ETHICAL AND LEGAL ISSUES ........................................................................... 99 
15.1 
Statement of Compliance ............................................................................................ 99 
15.2 
Ethics Committee or Institutional Review Board Approval ....................................... 99 
15.3 
Patient Informed Consent/Assent ............................................................................... 99 
15.4 
Patient Compensation for Adverse Effects on Health .............................................. 100 
15.5 
Changes to the Conduct of the Study, Protocol and Study Termination .................. 100 
15.5.1 
Protocol Amendments ............................................................................................... 100 
15.5.2 
Study Termination .................................................................................................... 100 
16. 
INVESTIGATOR RESPONSIBILITIES ............................................................. 101 
16.1 
Staff Training ............................................................................................................ 101 
16.2 
Study Conduct ........................................................................................................... 101 
16.3 
Recordkeeping .......................................................................................................... 102 
17. 
PUBLICATIONS .................................................................................................... 103 
18. 
CONFIDENTIALITY ............................................................................................ 104 
19. 
REFERENCES ........................................................................................................ 105 
 
 
 

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LIST OF TABLES 
Table 1:  Schedule of Assessments ................................................................................................25 
Table 2:  Grade 1-4 adverse events in mCRPC single agent study (only shown for AEs in ≥ 2 
patients) ........................................................................................................................40 
Table 3:  Grade 1-4 adverse events in mCRPC combination study (only shown for AEs in   ≥ 2 
patients) ........................................................................................................................41 
Table 4.  Grade 3/4 related adverse events in both single agent and combination Phase 1 mCRPC 
trials..............................................................................................................................41 
Table 5:  Dose Escalation Scheme .................................................................................................51 
Table 6:  Management of Selected Grade 3/4 Talazoparib-related Toxicities ..............................62 
Table 7:  Guidelines for Dose Holds and Dose Reductions of both Talazoparib and ZEN003694
......................................................................................................................................66 
Table 8:  Inhibitors and Inducers of Relevant Drug-metabolizing Enzymes .................................68 
 
 
 

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LIST OF APPENDICES 
Appendix 1:  ECOG Performance Status .....................................................................................110 
Appendix 2:  NCI CTCAE Version 5.0 Adverse Event Severity Grading ..................................111 
Appendix 3:  RECIST 1.1 Criteria ...............................................................................................112 
Appendix 4:  Investigator Agreement Page .................................................................................115 
Appendix 5:  Sponsor Signature Page (China only) ....................................................................116 
 
 
 
 
 
 

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2. 
SYNOPSIS 
A Phase 2 Study of ZEN003694 in Combination with Talazoparib in Patients with Triple-Negative 
Breast Cancer 
PROTOCOL NUMBER:  ZEN003694-004  
STUDY PHASE:  Phase 2 
 
INVESTIGATIONAL DRUG:  ZEN003694 
OBJECTIVES: 
Primary 
Part 1 
• 
To determine the safety, tolerability, maximum tolerated dose (MTD) and recommended 
Phase 2 dose (RP2D) of ZEN003694 in combination with talazoparib in patients with locally 
advanced or metastatic triple-negative breast cancer (TNBC)  
Part 2  
• 
To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with 
locally advanced or metastatic TNBC  
Expansion 
• 
To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with  
locally advanced or metastatic TNBC whose cancer was hormone receptor negative (<5%) 
at the time of initial breast cancer diagnosis and who have received TROP2-ADC therapy in 
the unresectable locally advanced or metastatic disease setting. 
Secondary 
Part 1 
• 
To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791, and 
talazoparib  
• 
To evaluate the effects of ZEN003694 and talazoparib on mRNA expression of 
pharmacodynamic markers 
• 
To evaluate the clinical activity of ZEN003694 in combination with talazoparib by 
radiographic response rate and progression-free survival 
• 
To determine the effect of ZEN003694 and talazoparib on patient reported health status and 
quality of life  
 
Part 2  
• 
To further evaluate the safety and tolerability of ZEN003694 in combination with talazoparib 

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• 
To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791, and 
talazoparib 
• 
To determine the effect of ZEN003694 and talazoparib on patient reported health status and 
quality of life 
Expansion 
• 
To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with 
locally advanced or metastatic TNBC whose cancer was hormone receptor negative at the 
time of initial breast cancer diagnosis and who have not received TROP2-ADC in the 
unresectable locally advanced or metastatic disease setting 
• 
To evaluate the ZEN003694 monotherapy in patients with locally advanced  or metastatic 
TNBC whose cancer was hormone receptor negative at the time of initial breast cancer 
diagnosis and who may or may not have received prior TROP2-ADC. 
• 
To further evaluate the safety and tolerability of ZEN003694 in combination with talazoparib 
• 
To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791, and 
talazoparib 
• 
To determine the effect of ZEN003694 and talazoparib patient reported health status and 
quality of life 
 
Exploratory 
Parts 1 and 2; and Expansion 
• 
 
 
 
 
STUDY DESIGN:  
 
Part 1  
 
Part 1 is an open label, non-randomized, dose escalation of ZEN003694 in combination with 
talazoparib in patients with TNBC. A standard 3+3 cohort design will be utilized. Cohorts of 3 
patients and up to 6 patients will be enrolled at each dose level, and each patient will participate in 
only one cohort. Each cycle will be 28 days in duration. Patients at each dose level will be treated and 
observed through the end of the first 28-day cycle before treatment of patients at the next higher dose 
level can begin. 
  
Dose escalation will continue after all patients enrolled within a cohort have completed the 28-day 
Cycle 1 DLT observation period with either 0 of 3 patients, or no more than 1 out of 6 patients in a 
cohort experiencing a DLT. Dose escalation decisions will be made based on clinical safety and (when 
available) PK data (maximum or peak concentration [Cmax] and area under the curve [AUC]) after 
review by the Investigators and Zenith. If a DLT is observed in 1 of 3 patients in a cohort, 3 additional 
patients will be enrolled into that cohort. If 1 of 6 patients in a cohort experiences a DLT, then dose 
escalation may continue in the next cohort or the MTD of the combination can be declared. If ≥ 2 of 
3 – 6 patients experience DLTs within a cohort, then the MTD will be considered to have been 

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exceeded and further dose escalation will cease. In this case, if fewer than 6 patients have been 
enrolled at the previous dose level, that cohort will be expanded to 6 patients to confirm the MTD. 
Should the MTD of the combination be exceeded at Dose Level 1, a cohort may be explored with a 
reduced dose of ZEN003694 or talazoparib. Cohort management is summarized below.  
Number of Patients with 
Dose-limiting Toxicity 
Action 
0 of 3 or 1 of 6 
Dose escalate to next cohort 
1 of 3 
Add 3 more patients 
1 of 6 
Proceed to next dose level 
≥ 2 of 3 or ≥ 2 of 6 
Add 3 more patients in the next lower dose level if only 
3 patients were treated in the next lower dose.  If 6 patients 
were treated at the next lower dose level and no more than 
one patient had DLT, then the next lower dose is the 
MTD. 
 
Enrollment in the dose escalation part of the study will commence with a 48 mg oral once daily dose 
as the starting dose for ZEN003694 in combination with a 1 mg oral once daily dose of talazoparib.  
The dose of ZEN003694 will be held constant throughout Cycle 1, however doses may be held for 
the management of toxicity.  The dose of talazoparib may be held and reduced from the initial 1.0 mg 
dose in 0.25 mg increments in accordance with the talazoparib label and by agreement with Zenith.  
Dose escalation/de-escalation of ZEN003694 will proceed per the schema below unless intervening 
toxicity is observed.  Alternative dosing schedules may be evaluated based on the evaluation of 
clinical safety and upon agreement of the Investigators and Zenith.  Alternative dosing schedules may 
include intermittent dosing that could necessitate a change in the cycle duration from 28 days to 21 
days. 
Dose Level 
ZEN003694 (mg)** 
Fold Increase from 
Prior Dose Level 
-1 
36 
0.75 
1 
48 
-- 
2 
72 
1.50 
** Dose de-escalation from 48 mg is allowed and additional dose levels may be 
explored based on safety and at the discretion of the Sponsor.    
 
No intra-patient dose escalation is allowed during the first two cycles of therapy.  If a patient has not 
experienced any Grade 2 or higher drug-related AEs after three cycles, dose escalation up to the 
highest ZEN003694 dose currently declared tolerable will be allowed and further intra-patient dose 
escalation(s) will be determined on a cycle-by-cycle basis at the discretion of the Investigators and 
with approval by the Sponsor.   
Investigator/Sponsor teleconferences will be held during the dose escalation phase to discuss any 
suspected DLTs that have occurred in patients within each cohort.  The frequency of the 
teleconference calls will be determined by the rate of enrollment, data review, frequency of DLT 
notifications, discussions with investigational sites and other factors.  Approximately one week after 
the last patient in a dose cohort completes Cycle 1 and prior to enrolling in the next dose level, the 

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Investigators and Sponsor will review toxicities and available PK (e.g., Cmax and AUC) from the 
current cohort of the study during a teleconference call.  
Definition of Dose-limiting Toxicity 
Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose 
escalation phase.  Toxicity will be graded and recorded according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.  A DLT is defined 
as a clinically significant AE or laboratory abnormality that is considered possibly, probably or 
definitely related to study drug and which meets any of the following criteria: 
• 
Grade 3 or greater non-hematologic clinical toxicity with the exception of a) Grade 3 nausea 
or Grade 3/4 vomiting or diarrhea unless persisting more than 72 hours despite maximal 
medical therapy and b) Grade 3 or 4 amylase or lipase elevations that are not associated with 
symptoms or clinical manifestations of pancreatitis  
• 
Grade 3 or greater fatigue for at least 1 week  
• 
Grade 4 anemia  
• 
Grade 4 neutropenia lasting more than 5 days 
• 
Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC) 
• 
Grade 4 thrombocytopenia; or Grade 3 thrombocytopenia with clinically significant bleeding; 
or any requirement for platelet transfusion 
• 
Grade 3 or 4 electrolyte abnormality lasting more than 72 hours, unless the patient has clinical 
symptoms, in which case all Grade 3 or 4 electrolyte abnormalities regardless of duration will 
be considered a DLT 
• 
Any other Grade 3 or 4 laboratory abnormality that requires hospitalization 
• 
An ALT or AST  ≥ 3x ULN with concomitant total bilirubin > 2x ULN, and serum alkaline 
phosphatase ≤ 2x ULN (Hy’s Law).  For patients with hepatic metastases, AST or ALT 
>8xULN or AST or ALT >5x ULN for ≥14 days 
• 
Any Grade 3 or 4 visual symptoms   
• 
Any toxicity that results in more than 25% of missed doses during Cycle 1 of the 28-days of 
treatment, with the exception of a dose hold for Grade 3  thrombocytopenia, in which case a 
dose hold of both talazoparib and ZEN003694 for 10 consecutive days in Cycle 1 will be 
allowed and not considered a DLT .  For an intermittent schedule of 2-weeks on/1-week off, 
if any toxicity results in more than 2 missed doses during the 2-week treatment period the 
toxicity would be considered a DLT.   
• 
In the situation where toxicity requires withholding study drugs following the receipt of at 
least 75% of scheduled dosing during Cycle 1: Failure to begin Cycle 2 within 1 week of the 
scheduled start date due to ongoing toxicity. 
All patients experiencing a DLT must discontinue dosing with ZEN003694 and talazoparib, except 
in the event that the DLT is thrombocytopenia, in which case patients may be re-challenged with 
ZEN003694 and talazoparib at doses agreed upon with the  Sponsor if platelets recover to at least 

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75,000/µL within a 10-day dose hold.  All patients who discontinue treatment must complete the 
Safety Follow-up visit prior to discontinuation from the study.   
Determination of evaluability will be made during the first 28 days of study treatment (i.e., Cycle 1) 
in the dose escalation phase.  Patients who miss more than 25% of ZEN003694 and talazoparib doses 
(except in the case of a dose hold for thrombocytopenia where 10 consecutive days of missed doses 
are allowed) or fail to begin Cycle 2 within 1 week of the scheduled start date for reasons other than 
drug-related toxicity will be considered unevaluable and will be replaced. 
 
Definition of the Maximum Tolerated Dose 
 
 
The MTD is defined as the highest dose level of ZEN003694 in combination with talazoparib 
at which no more than 1 of 6 patients experiences a DLT during the first cycle of therapy.  
 
Definition of the Recommended Phase 2 Dose 
The RP2D as determined in Part 1 of the study is defined as the dose level of ZEN003694 in 
combination with talazoparib recommended for further clinical study.  The RP2D may be the same 
as the MTD or modified from the MTD based on assessment of overall exposure, safety experience 
in Cycle 2 and beyond, PD and clinical benefit data in this study.   
Part 2:  Simon 2-Stage 
Stage 1: 
Once an RP2D of ZEN003694 in combination with talazoparib has been determined in the dose 
escalation part of the study, 17 patients will be enrolled in Stage 1 of a Simon 2-Stage design (Simon, 
1989) for evaluation of objective response (complete response (CR), partial response (PR), or stable 
disease (SD) for ≥ 4 cycles) by RECIST 1.1 (Eisenhauer, et al., 2009).  If there are ≥4 objective 
responses the study will proceed to Stage 2.  If there are <4 responses, the study will be stopped. 
Stage 2: 
If at least 4 patients in Stage 1 have an objective response (CR, PR or SD for ≥ 4 cycles) by RECIST 
1.1, 20 patients will be enrolled in Stage 2 of the Simon 2-Stage design.  Patients will receive daily 
RP2D doses of ZEN003694 (48mg) in combination with 0.75 mg talazoparib.  Patients may continue 
receiving ZEN003694 in combination with talazoparib until radiographic or clinical progression, 
unacceptable toxicity, requirement for non-protocol therapy or patient withdrawal from study. 
Expansion 
The expansion of the study will be implemented under amendment following the determination of 
the RP2D of ZEN003694 in Part 1 and after meeting the primary endpoint of clinical benefit rate of 
35% in Part 2.  The study will be expanded to enroll an additional 120 patients with locally advanced 
or metastatic TNBC that is without germline BRCA1/BRCA2 mutations and was hormone receptor 
negative (<5%) at the time of initial breast cancer diagnosis.    
Expansion Cohort A:  Combination Treatment in post-TROP2-ADC patients:  Eighty (80) 
patients will receive daily RP2D doses of ZEN003694 (48mg QD) in combination with talazoparib 
(0.75mg QD).  Patients may continue receiving ZEN003694 in combination with talazoparib until 

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radiographic or clinical progression, unacceptable toxicity, requirement for non-protocol therapy or 
patient withdrawal from the study. 
Expansion Cohort B:  ZEN003694 Monotherapy:  As mandated by the FDA to assess any potential 
single agent ZEN003694 activity, ten (10) patients will initially receive daily doses of 48mg 
ZEN003694 as monotherapy with the option to cross-over to combination treatment of 48mg 
ZEN003694 plus 0.75mg talazoparib at the time of disease progression (but no sooner than after 6 
weeks of monotherapy).  Patients in the cross-over group may continue receiving ZEN003694 in 
combination with talazoparib until radiographic or clinical progression, unacceptable toxicity, 
requirement for non-protocol therapy or patient withdrawal from study. 
Expansion Cohort C:  Combination Treatment in TROP2-ADC naïve patients:  Thirty (30) 
patients who have not received prior TROP2-ADC will receive daily RP2D doses of ZEN003694 
(48mg QD) in combination with talazoparib (0.75mg QD).  Patients may continue receiving 
ZEN003694 in combination with talazoparib until radiographic or clinical progression, unacceptable 
toxicity, requirement for non-protocol therapy or patient withdrawal from the study. 
NUMBER OF SITES:  
Approximately 9 sites in the United States; 4 sites in Western Europe; and 5 sites in China (Expansion 
only).    
NUMBER OF PATIENTS: 
In Parts 1 and 2, up to approximately 52 evaluable subjects will be enrolled in the study with up to 
approximately 16 patients in Part 1 dose escalation and up to 37 patients in Part 2, a Simon 2-Stage 
evaluation of objective response. 
In the Expansion part of the study, approximately 80 evaluable patients (in US and EU) will be 
enrolled in Cohort A (combination treatment in post-TROP2-ADC patients) and approximately 10 
evaluable patients (in US and EU) will be enrolled in Cohort B (ZEN003694 monotherapy).  
Approximately 30 evaluable patients (in China only) will be enrolled in Cohort C (combination 
treatment in TROP2-ADC-naïve patients). 
ESTIMATED STUDY DURATION: 
The estimated study duration for Part 1 dose escalation is approximately 6 months.  The estimated 
duration for Part 2 Simon 2-Stage is approximately 12 months.  The estimated duration of the 
Expansion phase will be approximately 18 months. 
ELIGIBILITY CRITERIA: 
Inclusion Criteria 
Patients must meet the following inclusion criteria to be eligible for the study. 
1. Females or males age ≥ 18 years (at time of signing informed consent) 
2. Parts 1 and 2:  Histologically confirmed metastatic or recurrent, or locally advanced triple-
negative breast cancer (estrogen receptor (ER) ≤10%; progesterone receptor (PR) ≤10%; 
HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) 
Expansion:  Histologically confirmed metastatic or recurrent, or locally advanced triple-
negative breast cancer as defined by the most recent American Society of Clinical 
Oncology/College of American Pathologists (ASCO/CAP) guidelines.  

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3. Patient is not a candidate for endocrine based therapy, based on Investigator judgement 
4. Have a history of progressive disease despite prior therapy 
5. Part 1:  Have had at least 1 prior cytotoxic chemotherapy. 
Part 2:  Have had no more than 2 prior chemotherapy-inclusive regimens for locally 
advanced or metastatic disease, unless approved by the Sponsor (no limit on prior targeted 
anticancer therapies such as mechanistic target or rapamycin (mTOR) or CDK4/6 inhibitors, 
immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against 
CTL4 or VEGF.)  
Expansion Cohort A (combination treatment in post-TROP2-ADC patients):  Have 
received TROP2-ADC therapy for unresectable locally advanced or metastatic disease. 
Expansion Cohort B (ZEN003694 monotherapy):  Have had at least 1 prior systemic 
therapy for locally advanced or metastatic disease which may or may not have included 
TROP2-ADC therapy. 
Expansion Cohort C (combination treatment in TROP2-ADC-naive patients):  Have 
had at least 1 prior systemic therapy for locally advanced or metastatic disease and who have 
not received prior TROP2-ADC therapy. 
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
7. Part 2 and Expansion only:  Measurable disease per RECIST version 1.1 
8. Adequate laboratory parameters at Screening including: 
a. Parts 1 and 2:  Hemoglobin ≥ 10.0 gm/dL without transfusions during the 4 weeks 
prior to Screening.  Expansion:  Hemoglobin ≥ 9.0 gm/dL  
b. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 
c. Platelet count ≥ 150,000/mm3 
d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.0 x ULN 
or if liver function abnormalities due to liver metastases AST and ALT ≤ 5.0 x ULN   
e. Total bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN for subjects with known Gilbert’s 
syndrome) 
f. Calculated (Cockcroft-Gault formula) or measured creatinine clearance ≥ 60 
mL/min 
g. Prothrombin time (PT), international normalized ratio (INR) and partial 
thromboplastin time (PTT) < 1.5 x ULN 
9. Female subjects may be enrolled if they are not of childbearing potential, permanently sterile 
or who are post-menopausal, defined as no menses for at least 1 year without an alternative 
medical cause and FSH levels in the post-menopausal range.  Female subjects of 
childbearing potential may be enrolled if they consistently and correctly use a highly 
effective form of contraception from the time point of study drug administration until at 
least 7 months thereafter.  Highly effective forms of contraception include: combined 
(estrogen and progestogen hormonal contraceptives (oral, intravaginal, transdermal) 

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associated with inhibition of ovulation; progestogen-only hormonal contraception (oral, 
injectable, implantable) associated with inhibition of ovulation; intrauterine device (IUD); 
intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized 
partner; sexual abstinence.   Female subjects should not donate eggs from the time point of 
study drug administration until at least 7 months thereafter.  
        
10. Males with partners of childbearing potential may be enrolled if they use a condom when 
having sex with a pregnant woman or with a non-pregnant female of childbearing potential  
from 21 days before the first dose of study drug through 4 months after the last dose of study 
drug, and males should not donate sperm from the time point of study drug administration 
until at least 4 months thereafter.  Contraception should be considered for a non-pregnant 
female partner of childbearing potential.  
11. Females of childbearing potential must have a negative serum or urine pregnancy test before 
the first dose of study drug and must agree to pregnancy tests during the study. 
12. Females may not be breast-feeding at the first dose of study drug, during study participation 
or through 7 months after the last dose of study drug.     
13. Ability to swallow capsules and comply with study procedures 
14. Ability to understand and willingness to sign informed consent form prior to initiation of 
any study procedures 
Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the 
study. 
1. Documented germline mutations of BRCA1 or BRCA2 
2. Parts 1 and 2 only:  Evidence of disease progression during platinum treatment either in 
the neoadjuvant or in the metastatic setting. For patients receiving platinum in 
the neoadjuvant setting, at least 6 months must have elapsed between the last dose of 
platinum-based treatment and enrollment.  
3. Part 2 only:  Patients with inflammatory breast cancer  
4. Current or anticipated use of medications known to be strong inhibitors or inducers of 
CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows.  Strong inhibitors, 
inducers or substrates must be discontinued at least 7 days prior to the first administration of 
study drug. 
5. Current or anticipated use within 7 days prior to the first administration of study drug, or 
during the study, of strong P-gp inhibitors.  
6. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban 
otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran).  Low 
molecular weight heparin is allowed. 
7. Prior anticancer therapy (chemotherapy, radiation, hormone therapy, immunotherapy or 
investigational agent) within 3 weeks from the start of study drug (except for nitrosoureas 

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and mitomycin C within 6 weeks from start of study drug).   
8. Parts 1 and 2 only:  Radiation to >25% of the bone marrow  
9. Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug. 
10. Have previously received an investigational BET inhibitor (including previous participation 
in studies with the Sponsor’s drug, ZEN003694); except for patients in Expansion Cohort B 
who received ZEN003694 monotherapy and are eligible to cross-over to combination 
treatment 
11. Prior treatment with a PARP inhibitor. 
12. QTcF interval > 470 msec. 
13. Insufficient recovery (i.e., has not recovered to at least Grade 1) from prior treatment-related 
toxicities except for alopecia, fatigue and Grade 2 neuropathy. 
14. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture caused 
by a pre-existing pathological bone lesion). 
15. Parts 1 and 2 only: Brain metastases not adequately treated and clinically stable (at the 
discretion of the Investigator) for at least 3 months prior to the start of study treatment, unless 
a shorter interval is approved by the Sponsor’s Medical Monitor  
Expansion only:  Progressive, symptomatic, or untreated brain metastases. CNS metastases 
treated definitively with surgery and/or radiation must be radiographically stable based on 
imaging at least 3 months after definitive treatment.  CNS metastases requiring steroid doses 
equivalent to prednisone doses >10 mg daily or an increase in steroid doses due to CNS 
disease prior to consent are not eligible 
16. Expansion only: Disease initially diagnosed with expression of estrogen receptor (ER) or 
progesterone receptor (PR) as ≥5% 
17. Expansion only: Patients treated with prior endocrine therapy 
18. Known impaired cardiac function or clinically significant cardiac disease such as 
uncontrolled supraventricular arrhythmia, ventricular arrhythmia requiring therapy, or 
congestive heart failure (New York Heart Association functional class III or IV).  
19. Myocardial infarction or unstable angina within 6 months prior to the first administration of 
study drug. 
20. Known myelodysplastic syndrome. 
21. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active 
central nervous system disease, active, uncontrolled bacterial, viral, or fungal infection(s) 
requiring systemic therapy, or any other condition that could compromise safety or the 
patient’s participation in the study, 
22. Impairment of gastrointestinal function (i.e., diagnosis of malabsorption syndrome) that 
may significantly alter the absorption of ZEN003694 or talazoparib. 

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23. Other known active cancer requiring therapy at time of study entry or that progressed or 
required treatment within 3 years prior to starting study drug (except for skin basal cell 
carcinoma or squamous cell carcinoma or in situ cervical cancer). 
24. Historically positive (screening tests not required) for human immunodeficiency virus (HIV); 
or hepatitis B virus (HBV) with currently active disease defined as hepatitis B surface antigen 
(HBsAg) positivity; or hepatitis C virus (HCV) unless previously treated and viral load is 
undetectable.   
25. Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior 
to the first administration of study drug. 
26. Concurrent participation in another clinical investigational treatment trial with a systemic 
therapy 
27. Any other reason that in the opinion of the Investigator would prevent the patient from 
completing participation or following the study schedule. 
DOSE, REGIMEN AND ROUTE OF ADMINISTRATION: 
ZEN003694 
ZEN003694 will be supplied in capsules of two different dosage strengths:  12 mg and 48 mg.   
The ZEN003694 starting dose for this study is 48 mg, administered orally once daily. Doses 
will be administered in 28-day cycles and should be administered with a full (8-ounce) glass 
of water at least 1 hour before eating or 2 hours after eating (fasting).  The RP2D of 48 mg 
once daily will be administered in Part 2 and Expansion. 
 
Talazoparib 
Talazoparib will be supplied as oral capsules in strengths of 1.0 mg and 0.25 mg.  
Talazoparib will be administered as a starting dose of 1 mg once daily in Part 1 to be taken at the 
same time as ZEN003694.   The talazoparib dose of 0.75 mg once daily will be administered in Part 
2 and Expansion. 
STUDY ASSESSMENTS: 
Safety 
Safety will be assessed by periodic physical examinations, weight, ECOG performance status, vital 
signs, clinical laboratory assessments (hematology, serum chemistries, coagulation tests and 
urinalysis), 12-lead electrocardiogram (ECG) and monitoring of AEs (see Schedule of Assessments).  
Pharmacokinetics 
Plasma samples will be collected to assess the PK properties of ZEN003694 and its active metabolite, 
ZEN003791, and talazoparib. Plasma concentrations of ZEN003694, its active metabolite 
ZEN003791, talazoparib will be determined by a validated liquid chromatography-tandem mass 
spectrometry (LC-MS/MS) bioanalytical method.  Samples will be collected as indicated in the 
Schedule of Assessments. 

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Pharmacodynamics 
Blood samples will be analysed for the effects of ZEN003694 and talazoparib on five PD mRNA 
markers.  Samples for exploratory prognostic and/or predictive biomarkers in whole blood by ctDNA 
analyses and in tumor tissue by RNA-sequencing, DNA-sequencing and immunohistochemical 
staining will be collected for banking and possible future analyses in Simon 2-Stage and in the 
Expansion phase of the study.  Tumor tissue will be obtained as indicated in the Schedule of 
Assessments. 
Objective Responses 
Tumor assessments and measurable disease is to be assessed per RECIST 1.1 guidance.  Measurable 
disease must be accurately measured in at least one dimension (longest diameter in the plane of 
measurement is to be recorded) with a minimum size of: 
• 
10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
• 
10 mm by caliper measurement by clinical exam (lesions cannot be accurately measured with 
calipers should be recorded as non-measurable).  
• 
20 mm by chest X-ray 
• 
Baseline measurements should be performed as close as possible to the treatment start and 
not more than 4 weeks before the start of treatment. 
CT is the best and most reproducible method to measure lesions selected for response assessment.  
CT slice thickness should be 5 mm or less per RECIST 1.1.  CT scans having slice thickness greater 
than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness.  Chest CT 
is preferred over Chest X-ray. 
MRI is also acceptable in certain situations (e.g. for body scans).  
Disease status should be assessed according to RECIST 1.1 at visits as indicated in the Schedule of 
Assessments. 
STATISTICAL METHODS:  
Sample Size Determination 
Part 1: Dose escalation 
A conventional algorithm (3+3 patients per dose level) will be used to identify the MTD, 
escalating on 0 of 3 or 1 of 6 DLTs, and de-escalating if 2 DLTs are encountered.  The MTD 
will be the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, with the 
next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.  With this 
design, there is a 71% chance of escalation if the true but unknown rate of DLT is 20%, and 
less than 50% chance of escalation if the true but unknown rate of DLT is higher than 30%. 
Approximately 12 patients may be enrolled in the dose escalation phase of the study.   
Part 2:  Simon 2-Stage 
Stage 1:  17 patients are planned to be enrolled at the MTD or RP2D in Stage 1 based on a 
null hypothesis that TNBC patients will have an overall response rate (ORR) of 20% and the 
study will target an ORR of 40%. For purposes of this study, the overall response rate (ORR) 
is more accurately defined as clinical benefit rate (CBR).  CBR is defined as percentage of 

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patients with a confirmed RECIST 1.1 response or stable disease ≥4 cycles. Ho = 20 % will 
be tested against a one-sided alternative. (A CBR of 20% is not of clinical interest whereas a 
CBR of 40% warrants further investigation.)  If there are less than 4 responses in the 17 
patients enrolled, the study will be stopped.  
 
Stage 2:  20 patients are planned to be enrolled if there are at least 4 responders in Stage 1.  
Ho will be rejected if there are > 11 patients with a CBR in 37 patients. Type I error rate of 
0.1 when the true response rate is 20% and power of 90% when the true CBR is 40% (target 
error rates 0.10 and 0.10); the probability of early termination is 0.55. 
Expansion Cohort A:  Combination Treatment (post-TROP2-ADC patients):   
 
Expansion Cohort A will enroll patients with locally advanced or metastatic TNBC without 
germline BRCA1/BRCA2 mutations who have had prior treatment with TROP2-ADC for 
unresectable locally advanced or metastatic disease. Approximately 80 evaluable patients 
are planned to establish the ORR and further define the safety profile of the combination 
ZEN003694 and talazoparib.  An observed ORR (by blinded independent central review) 
of at least 30% represents a significant improvement over current available therapies in 
this patient population. With 80 patients, 24 or more responders will provide an observed 
ORR of at least 30% and a lower limit of the 95% confidence interval above 20%. The 
RECIST v1.1 assessment of response will be assessed by an independent review 
committee. 
 
Expansion Cohort B:  ZEN003694 Monotherapy: 
 
Expansion Cohort B will enroll patients with locally advanced or metastatic TNBC without 
germline BRCA1/BRCA2 mutations who have had two prior systemic treatments for locally 
advanced or metastatic disease. Approximately 10 evaluable patients are planned to assess 
the preliminary anti-tumor activity and provide additional information for the safety profile 
of ZEN003694. 
 
Expansion Cohort C:  Combination Treatment (TROP2-ADC-naïve patients): 
 
Expansion Cohort C will enroll patients with locally advanced or metastatic TNBC without 
germline BRCA1/BRCA2 mutations who have not previously received TROP2-ADC and 
have had at least two additional prior systemic therapies for locally advanced or metastatic 
disease. Approximately 30 evaluable patients are planned to establish the ORR and further 
define the safety profile of the combination ZEN003694 and talazoparib. 
 
Statistical Analyses 
Part 1:  Dose escalation 
The primary statistical analysis of the data will be descriptive in nature.  For continuous 
variables this means calculation of the number of observations, mean, standard deviation, 
median, minimum, and maximum.  Categorical variables will be summarized by patient 
counts and related percentages.  For ordinal-scaled variables, a combination of the above may 
be employed as appropriate:  frequency and percentage of observations within a category and 

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means and standard deviations of the scores of the categories.  For categorical and ordinal 
variables, percentages will be calculated based on non-missing data. 
Based on the characteristics of the study design and lack of a concurrent control arm, formal 
testing of treatment effects (i.e., inferential statistics) will not be performed.  However, some 
measures will be summarized by both point estimates and the associated 95% confidence 
intervals. 
Part 2:  Simon 2-Stage  
The primary outcome measures in the Simon 2-Stage phase of the study will be clinical 
benefit rate (CBR) defined as a complete response, partial response or stable disease ( ≥ 4 
cycles) by RECIST v1.1.  CBR and 95% confidence interval will be calculated using the 
exact binomial model. 
Secondary outcome measures will include: 
• 
Progression-free survival (PFS):  defined from randomization to documented disease 
progression or death 
• 
Duration of response (DOR):  for confirmed responses, defined as the duration from 
the time of first response (CR or PR) until radiographic disease progression or death. 
• 
Pharmacokinetics (PK):  AUC0-last and AUC0-inf,, Cmax, Cmin, Tmax, and T½ of 
ZEN003694, ZEN003791, and talazoparib during the first 2 treatment cycles 
• 
Incidence of Adverse Events:  from time of signing informed consent 
• 
Quality of Life (EORTC Quality of Life Questionnaires, QLQ-C30 and QLQ-BR23)  
 
Expansion Cohort A:  Combination Treatment (post-TROP2-ADC patients) 
 
The primary outcome measure in Expansion Cohort A (Combination Treatment) will be 
objective response rate (ORR) per RECIST v1.1 as measured by independent central review.  
Secondary outcome measures will include: 
• 
Duration of response (DOR) 
• 
Clinical benefit rate (CBR) 
• 
Progression free survival (PFS) 
• 
Safety analyses will include, but are not limited to, AEs, laboratory abnormalities, 
ECG evaluations, and vital signs 
• 
Pharmacokinetics:  AUC0-last and AUC0-inf,, Cmax, Cmin, Tmax, and T½ of 
ZEN003694, ZEN003791, and talazoparib during the first 2 treatment cycles 
• 
Quality of Life (EORTC Quality of Life Questionnaires, QLQ-C30 and QLQ-BR23) 
Expansion Cohort B:  ZEN003694 Monotherapy 
 
In discussions with the FDA, if no more than 1 patient (out of the 10 evaluable patients 
enrolled) have a confirmed objective response to ZEN003694 monotherapy, it can be 
concluded that ZEN003694 as a monotherapy has no clinical benefit.  
 
Expansion Cohort C:  Combination Treatment (TROP2-ADC-naïve patients)  
Outcome measures for Cohort C will include: 

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• 
Objective response rate (ORR) per RECIST v1.1 as measured by investigator 
• 
Duration of response (DOR) 
• 
Clinical benefit rate (CBR) 
• 
Progression free survival (PFS) 
• 
Safety analyses will include, but are not limited to, AEs, laboratory abnormalities, 
ECG evaluations, and vital signs 
• 
Pharmacokinetics:  AUC0-last and AUC0-inf,, Cmax, Cmin, Tmax, and T½ of 
ZEN003694, ZEN003791, and talazoparib during the first 2 treatment cycles 
• 
Quality of Life (EORTC Quality of Life Questionnaires, QLQ-C30 and QLQ-BR23) 

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Table 1:  Schedule of Assessments  
 
Screening 
(28 Days 
prior to  
C1D1)^ 
Cycle 1** 
(Days 1 – 28) 
Cycle 2** 
(Days 1 – 28) 
Cycle 3 Onward 
(Days 1 – 28) 
Unscheduled 
Visit 
 
p 
End of 
Treatment 
q 
Safety  
Follow-up 
r 
Informed Consent 
X 
 
 
 
 
 
 
Medical, Surgical, Cancer History, Prior 
Cancer Treatments and Demographics 
X 
 
 
 
 
 
 
Physical Examination, Vital Signs, 
Weight, Height, ECOG Status a 
X 
Days 1*, 8, 15, 
22** 
Days 1, 15 
Day 1 
X 
X 
X 
Hematology and Serum Chemistry b 
X 
Days 1*, 8, 15, 
22** 
Days 1, 8, 15, 22** 
Days 1, 15 
X 
X 
X 
Creatinine clearance, calculated b 
X 
 
 
 
 
 
 
Coagulation Tests c 
X 
Days 1*, 15 
Day 1 
Day 1 
X 
 
 
Urinalysis d 
X 
Day 1* 
Day 1 
Day 1 
X 
X 
X 
Quantitative Urinary Analysis d 
X 
Day 1* 
Day 1 
Day 1 
X 
X 
X 
Pregnancy test e 
X 
Day 1 
Day 1 
Day 1 
 
X 
 
12-Lead Electrocardiogram f 
X 
Days 1* 
Day 1 
Day 1 (at C3 and 
every 2 cycles) 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor Assessments (RECIST) h 
X 
 
EXPANSION 
(Cohorts A, B, C):  
Cycle 2, Day 15  
and every 6 weeks 
PARTS 1 & 2 
(every 8 weeks):  
Day 1 (at C3 and 
every 2 cycles) 
EXPANSION: 
(every 6 weeks) 
Day 1 (at C4, C7, 
C10, C13, C16, 
C19, etc.); and  
Day 15 (at C5, C8, 
C11, C14, C17, 
C20, etc.) 
 
X 
 
BRCA1/2 mutation status i  
X 
 
 
 
 
 
 
Pharmacokinetics j  
 
Part 1 only 
Days 1, 15 
Days 1, 15 
 
 
 
 

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Screening 
(28 Days 
prior to  
C1D1)^ 
Cycle 1** 
(Days 1 – 28) 
Cycle 2** 
(Days 1 – 28) 
Cycle 3 Onward 
(Days 1 – 28) 
Unscheduled 
Visit 
 
p 
End of 
Treatment 
q 
Safety  
Follow-up 
r 
BETi and PARPi PD marker mRNA k  
(in Part 1 only)  
 
Day 1 
 
 
 
 
 
ctDNA l (for possible future analysis) 
 
Day 1 
 
Day 1 (at C3 only)  
 
X 
 
Archival Tumor Tissue Collection m  
X 
 
 
 
 
 
 
Tumor Biopsy Collection m 
X 
Parts 1 & 2:  
Days 8-10 
Expansion:   
Days 8-14 m 
 
Day 1 (at C3 only) 
(if not obtained in 
cycle 1)  
 
X m 
 
ZEN003694 Administration n 
 
Days 1 through 28 of each cycle 
 
 
 
Talazoparib Administration n 
 
Days 1 through 28 of each cycle  (except for patients taking 
ZEN003694 monotherapy in Expansion Cohort B) 
 
 
 
Global Health Status / Quality of Life o 
X 
Day 1 
Day 1 
Day 1 
 
X 
 
Adverse Events 
 
Days 1, 8, 15, 22** 
Days 1, 15 
Day 1 
X 
X 
X 
Prior/Concomitant Medications 
X 
Days 1, 8, 15, 22** 
Days 1, 15 
Day 1 
X 
X 
X 
 
TABLE 1 Footnotes: 
All clinic visits should occur within ± 3 days of the scheduled visits listed in Table 1 and tests/samples should be obtained pre-dose unless specified 
otherwise.   
General Notes:   
• 
The visits in Cycle 2 (Days 8 and 22) and in Cycle 3 and onward (Day 15):  will only include blood draws for safety laboratory testing.  The tests  
on C2D8, C2D22 and the Day 15 visit of Cycle 3 and onwards may optionally be drawn at a laboratory local to the patient’s home and may be 
drawn in the morning before or after the patient has taken his/her dose. 
• 
During the COVID-19 pandemic: 
o 
Telephone visits may be performed at the following visits:  Cycle 1, Days 8 and 22; and Cycle 2, Day 15. 
o 
The following prospective deviations are allowed for the non-assessment of the following only if a patient is unable to attend an in-clinic 
visit:  physical examinations, vital signs, weight, ECOG, PK blood draws, PD blood draws, and biopsies. 
o 
In-clinic visits are mandatory at Cycle 1, Days 1 and 15; and on Day 1 of all Cycles.    
 
* Perform laboratory tests at Cycle 1 Day 1 (C1D1) only if Screening tests were performed more than 7 days prior to C1D1 visit 

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**  If intermittent dosing is implemented and/or if there is a need to change the cycle duration from 28 days to 21 days, the Day 22 assessments will not 
be required. 
 
^  Cross-over Expansion Cohort B:  Patients enrolled in the Expansion Cohort B (ZEN003694 monotherapy) are allowed to cross-over to the combination 
treatment within 14 days after radiographic progression on ZEN003694 monotherapy has been established.  Patients may cross-over to the combination treatment 
at the time of disease progression but no sooner than after 6 weeks of receiving ZEN003694 monotherapy. Patients choosing to cross-over treatment must sign a 
new informed consent form and complete all screening assessments as those originally required for enrollment in Expansion Cohort B of the study.  The schedule 
of study assessments for the cross-over patients will be identical to those for Expansion patients starting at C1D1 and throughout the study.   
 
a Complete physical examination to be performed at the Screening visit and a symptom-directed physical examination thereafter.  Height to be measured at the 
Screening Visit only. Vital signs: body temperature, blood pressure and heart rate.  
b Hematology: complete blood count (CBC) with differential and absolute neutrophil count (ANC).  Serum chemistry:  albumin, alanine aminotransferase (ALT), 
aspartate transaminase (AST), alkaline phosphatase, bicarbonate, total bilirubin, blood urea nitrogen (BUN or Urea), total calcium, chloride, creatinine, glucose, 
lactate dehydrogenase (LDH), sodium, potassium, phosphorus and magnesium. Creatinine clearance:  At screening only, to be calculated by Cockcroft-Gault 
formula.  Note:  The Day 8 and Day 22 hematology and chemistry tests in Cycle 2 do not need to occur prior to dosing.  In Cycle 6 and onward, the Day 15 
hematology and serum chemistry tests may be waived at the discretion of the Investigator if platelet counts are stable and there are no other laboratory concerns. 
c Coagulation tests:  prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT, APTT acceptable) 
d Urinalysis: dipstick with micro-analysis if clinically indicated.  From the urine sample collected for standard urinalysis assessment, quantitative biochemical 
analyses of urinary protein, albumin and creatinine is also required along with the reporting of the protein:creatinine ratio and the albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by the local laboratory. 
e  Pregnancy test: At screening a serum or urine pregnancy test is required of all women of child-bearing potential only.  A urine pregnancy test is to be performed 
on Day 1 of each cycle prior to administration of study treatment.  If a urine pregnancy test is positive, study treatment must be interrupted and a serum pregnancy 
test performed. 
f  12-lead electrocardiogram (ECG) to be performed.  To be collected pre-ZEN003694 and talazoparib doses on C1D1, C2D1 and C3D1 and every 2 cycles onward.  
Triplicate ECGs are to be collected if QTc>500msec.  QTc is to be measured using Fridericia’s formula. 
 
 
 
 
 
   
h Tumor assessment (preferably by CT scan) to include whole body imaging with cross-sectional imaging of the chest/abdomen/pelvis.  Use of IV contrast is 
required unless contra-indicated.  Magnetic resonance imaging (MRI) may be substituted for computed tomography (CT) per Investigator’s discretion.  Imaging 
may be scheduled up to 7 days prior to the scheduled clinic visit day.  The EOT tumor assessment is to be performed only if the EOT visit is > 6 weeks from the 
time of the prior tumor assessment.  Tumor Assessments in EXPANSION phase:  In the Expansion phase of the study, tumor assessments will be performed 
every 6 weeks.  Thus, as a cycle is every 28 days, tumor assessments are to occur at Day 15 in Cycles 2, 5, 8, 11, 14, 17, 20, etc.; and at Day 1 in Cycles 4, 7, 10, 
13, 16, 19, etc.  

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i Germline BRCA1/2 mutation status:  Parts 1 and 2: For patients who have prior documentation of gBRCA mutation status, a blood sample for gBRCA testing is 
not required to be collected nor shipped to Myriad Genetics (for US and EU samples). If prior testing of gBRCA status has not been performed, either a blood 
sample can be collected and shipped to Myriad Genetics (for US and EU samples) or if your Institution has a qualified NGS testing panel a blood sample may be 
tested using your platform. Samples collected in China will have gBRCA1/2 testing performed at a laboratory approved by the Sponsor.  Reports showing the panel 
of genes tested to establish BRCA1/2 mutation status are to be provided to the Sponsor. In Cohort A EXPANSION phase only: Germline BRCA1/2 mutation 
status: If prior testing of gBRCA has not been performed, a blood sample will be collected and shipped to Myriad Genetics at ambient temperature. If prior 
documentation of BRCA1/2 mutation status by BRACAnalysis CDx performed by Myriad Genetics is not available, a screening blood sample will be collected 
and frozen for retrospective analysis in batches. For patients who have prior documentation of BRCA mutation status by BRACAnalysis CDx, a blood sample for 
possible retrospective BRCA germline testing should NOT be collected. In cohort B and C EXPANSION phase, BRCA1/2 mutation status may be determined by 
Myriad Genetics or other Sponsor approved laboratory. 
j Blood (plasma) for pharmacokinetic (PK) profile of ZEN003694, ZEN003791 and talazoparib will be collected as specified below:  The pre-dose PK sample 
collections should be collected at least 20 hours after the previous day of dosing talazoparib. 
Part 1 (Dose escalation) PK for ZEN003694 and ZEN003791: 
C1D1:  pre-ZEN003694 and talazoparib doses 
C1D1:  15 min (±5 min), 30 min (±5 min), 1 hour (±5 min), 2 hours (±10 min), 4 hours (±15 min), 6 hours (±15 min) and 8 hours (±30 min) post-
ZEN003694 and talazoparib doses 
C1D15:  pre-ZEN003694 and talazoparib doses 
C2D1:  pre-ZEN003694 and talazoparib doses 
C2D1:  1 hour (±5 min), 2 hours (±10 min), and 4 hours (±15 min) post-ZEN003694 and talazoparib doses 
C2D15:  pre-ZEN003694 and talazoparib doses 
Part 1 (Dose escalation) PK for talazoparib: 
C1D15:  pre-ZEN003694 and talazoparib doses 
C2D1:  pre-ZEN003694 and talazoparib doses 
C2D15:  pre-ZEN003694 and talazoparib doses 
Part 2 (Simon 2-stage) and Expansion Cohorts A, B, C:  PK for ZEN003694 and ZEN003791: 
C2D1:  pre-ZEN003694 and talazoparib doses 
C2D1:  1 hour (±5 min), 2 hours (±10 min), and 4 hours (±15 min) post-ZEN003694 and talazoparib doses 
C2D15:  pre-ZEN003694 and talazoparib doses 
Part 2 (Simon 2-stage) and Expansion Cohorts A and C:  PK for talazoparib: 
C2D1:  pre-ZEN003694 and talazoparib doses 
C2D15:  pre-ZEN003694 and talazoparib doses 
k Blood samples for BET inhibitor and PARP inhibitor PD marker mRNA expression will be collected in Part 1 only: 
• 
C1D1:  pre-ZEN003694 and talazoparib doses 
• 
C1D1:  2 hours (±15 min), 4 hours (±15 min), 6 hour (±15 min) and 8 hour (±15 min) post-ZEN003694 and talazoparib doses 
l Blood samples (whole blood) for ctDNA assessments, US and EU sites only.  (Samples are to be collected for possible future analysis) 
• 
C1D1 pre-ZEN003694 and talazoparib doses 
• 
C3D1 pre-ZEN003694 and talazoparib doses 
• 
End of Treatment Visit 

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m Fresh tumor biopsy collections are mandatory in US and EU only, if the tumor is accessible.  During each biopsy procedure, 2-4 tumor tissue cores (optimally 4 
cores should be collected:  2 frozen cores, 2 formalin fixed cores) should be obtained.  Biopsy procedures are to be scheduled at Screening and at the on-treatment 
visit occurring either at C1D8 or C3D1 (if biopsy was not obtained in Cycle 1).  If possible, an End of Treatment (EOT) biopsy is to be optionally collected at the 
time of progression.  The on-treatment biopsy is at either a) In Parts 1 and 2: C1D8, C1D9, or C1D10, if the biopsy is collected from a palpable lesion (or from 
other lesions, at the Investigator’s discretion); In Expansion phase, biopsies are to be collected for patients in the US and EU between C1D8 and C1D14; or b)  
within ±14 days of the C3D1 visit (if biopsy was not obtained in Cycle 1). Please note: biopsies will NOT be collected for patients in China.  The screening biopsy 
may be performed up to 6 weeks prior to the first dose of study drug.  The on-treatment biopsy should be collected 2-4 hours after ZEN003694 dosing, if possible, 
and should be collected from the same tissue location as the screening biopsy.  Biopsies taken at screening or at the on-treatment visit should not be taken from a 
recent prior irradiated site.  Archival tumor tissue slides (either at least 10 slides preferably from a recent metastatic biopsy or a tissue block), if available and with 
the patient’s consent, will be collected in Parts 1 and 2, and in the Expansion phase, in Cohort A only.  The pathology and molecular report for the archival tissue 
sample is to also be collected. 
n ZEN003694 and talazoparib are to be taken orally on a daily basis and at the same time during the course of treatment.  Patients will be asked to maintain a dosing 
diary. 
o Global Health Status and Quality of Life to be measured by EORTC QLQ-C30; EORTC QLQ BR23 
p During any Unscheduled visit; the physical examination, vital signs, weight, hematology, coagulation tests, serum chemistry, urinalysis, concomitant 
medications and AEs are to be performed.  Any other clinically indicated assessments are also to be performed.   
q  At the End of Treatment visit if a subject’s dose was held and treatment was not resumed after a two week period, the scheduling of the EOT visit from the date 
of last study drug is extended from 7 days to 14 days (±3 days). 
r The Safety Follow-Up Visit should be completed 30 days (±3 days) after the End of Treatment visit or prior to the subject beginning a new anti-cancer 
treatment, whichever occurs first.  If the subject begins a new anti-cancer treatment within 7 days following the End of Treatment visit, the Safety Follow-Up 
visit is not required 

 
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3. 
BACKGROUND 
3.1  
BET Inhibitors in Cancer 
The bromodomain and extra terminal domain (BET) proteins comprise four closely related 
bromodomain-containing proteins (BRD2, BRD3, BRD4, and BRDT) that are a subset of the 
larger family of 46 bromodomain-containing proteins.  The BET proteins are epigenetic readers 
that regulate transcription in part by binding acetylated lysines on histones and transcription 
factors.  BET proteins have generated a lot of interest due to their potential to target the expression 
of oncogenes including V-Myc avian myelocytomatosis viral oncogene homolog (MYC), B-cell 
lymphoma 2 (BCL-2) and B-cell lymphoma 2-like 1 (BCL2L1) as well as for their involvement in 
mediating drug resistance (Dawson, et al., 2012; Dawson, et al., 2011; Goodell & Godley, 2013; 
Neff & Armstrong, 2013; Shi & Vakoc, 2014; Zuber, et al., 2011).  Expression of multiple 
oncogenes is also driven by BRD4 recruitment at super-enhancers, providing a rationale for the 
activity of BET inhibitors (BETi) beyond the MYC family (Hnisz, 2013; Loven, et al., 2013).  All 
of the BETi currently in clinical trials target all members of the BET family, although the anti-
proliferative activity of BETi in cancer cells may be mediated, in large part, through inhibition of 
BRD4 (Filippakopoulos & Knapp, 2014). 
In vitro cell line analyses have shown that targeting BET proteins leads to inhibition of tumor 
growth in multiple cancer types, including both solid tumors and hematological malignancies 
through cell cycle arrest, and induction of senescence and apoptosis. 
3.2  
PARP inhibitors in Cancer 
Poly-ADP ribose polymerases (PARP) are a family of enzymes that catalyze the addition of poly-
ADP ribose moieties to histones and other proteins to regulate various cellular processes, including 
gene transcription and DNA repair.  PARP1 and PARP2 play important roles in DNA repair 
(Schrieber, et al., 2006; Curtin, et al., 2005).  Following DNA damage, PARP1 and PARP2 bind 
to single stranded DNA breaks, cleave nicotinamide adenine dinucleotide, and attach multiple 
ADP ribose units to the target protein, including itself (Gibson & Kraus, 2012; Schreiber, et al., 
2002; Amé, et al., 1999; Johansson, 1999).  The outcome is a highly negatively charged protein, 
which leads to the unwinding of the DNA strands and recruitment of proteins to repair the damaged 
DNA through the base excision repair process.  When PARP1 and PARP2 are inhibited, single 
strand DNA breaks persist, resulting in stalled replication forks and conversion of single strand 
breaks into double strand breaks.  These breaks must be repaired by homologous recombination 
or nonhomologous end joining or they may become lethal.  Thus, inhibition of PARP catalytic 
activity results in synthetic lethality as defects in homologous recombination DNA repair prevent 
double strand breaks from being repaired, thereby killing the cell, including cancer cells.  In 
addition, PARP inhibitors bind to PARP DNA complexes (i.e., become trapped); thereby 
inhibiting DNA repair, replication, and transcription, which may also be is cytotoxic to cancer 
cells. Although other PARP inhibitors possess both activities (i.e., inhibition of PARP catalytic 
activity and PARP trapping), in vitro studies demonstrated that talazoparib is a more potent PARP 
trapper than other PARP inhibitors in clinical development, a property that has been associated 
with significant cytotoxicity in preclinical models (Johansson, 1999; Hopkins, et al., 2015; Lord 

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& Ashworth, 2017).  Cancer cells with deficiencies in homologous recombination (HR) DNA 
repair, namely with mutations in either BRCA1 or BRCA2, are sensitive to inhibition of PARP, 
owing to their inefficacy to repair DNA damage at DNA replication forks (McCabe, et al., 2006; 
Farmer, et al., 2005; Bryant, et al., 2005).  PARP inhibitors have been shown to have clinical 
efficacy in germline BRCA1/2 mutant (gBRCA1/2m) ovarian cancers and triple-negative breast 
cancers (TNBC) (reviewed in Lord & Ashworth, 2017). 
Triple-negative breast cancer (TNBC), defined by the lack of expression of ER and PR, and the 
absence of HER2 overexpression and amplification, represents about 10-20% of all breast cancers. 
TNBC patients have overall worse prognosis compared with other types of breast cancer with 
increased likelihood of early distance recurrences and death (Bauer, et al., 2007).  Metastatic 
disease is marked by a high rate of visceral and central nervous metastases with a median survival 
of approximately 1 year (Kassam, et al., 2009). Novel therapeutic strategies are therefore highly 
needed.   
Recent advances in the biology of the disease might offer opportunities with the classification of 
this heterogeneous entity into molecular subtypes with distinct drivers (Bareche, et al., 2018), 
including patients with gBRCA1/2m.  Indeed, two phase 3 trials that enrolled metastatic breast 
cancer patients with germline BRCA1 or BRCA2 mutations have reported positive results with 
PARP inhibitors olaparib (Robson, et al., 2017) and talazoparib (Litton, et al., 2018) versus 
standard chemotherapy.  Following these results, the US FDA approved olaparib (Lynparza®) and 
talazoparib (Talzenna®) for the treatment of germline BRCA-mutated locally advanced or 
metastatic breast cancer. 
Even though the prevalence of BRCA1 and BRCA2 mutations is higher in TNBC (up to 24% in 
some cohorts) (Copson, et al., 2018), the vast majority of patients with TNBC do not carry 
germline BRCA1 or BRCA2 mutations and would therefore not derive benefit from treatment with 
single agent PARP inhibitor therapy (O’Shaughnessy, et al., 2014). 
 
3.3  
Rationale and Mechanism for BET Inhibitors in BRCA1/2 wt TNBC  
Although several patients with HR deficiency (HRD) benefited from treatment with PARP 
inhibitors, the majority of HR proficient patients did not.  Therefore, strategies to induce a 
“BRCAness” phenotype, namely through inhibition of HR in cancer cells are actively being 
pursued. Recently, significant pre-clinical evidence has shown that BETi synergize with PARPi. 
Among 20 well-characterized epigenetic drugs targeting 7 classes of epigenetic regulators, only 
BET inhibitors sensitized the response of cancer cells to a PARP inhibitor (PARPi) by inducing 
strong synergistic effects with olaparib (Yang, et al., 2017) through downregulation of the 
transcription of several HR genes. Additional recent reports show concordant data on the 
synergism of PARP inhibitors and BET inhibitors in homologous recombination HR-proficient 
tumors, including breast cancer (Yang, et al., 2017; Karakashev, et al., 2017; Sun, et al., 2018; 
Wilson, et al., 2018). We and others hypothesize that BETi may suppress HR and enhance non-
homologous end joining (NHEJ), thereby sensitizing HR-proficient cancer cells to PARP 
inhibition (Wilson, et al., 2018).   
Early clinical trials with BETi showed limited single-agent activity in patients with hematologic 
malignancies (Berthon, et al., 2016), NUT carcinoma (Stathis, et al., 2016) and very recently in 
solid tumors (Aftimos, et al., 2017). However, there is promise for a BETi in combination with 

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other agents as they modulate resistance mechanisms and confer sensitivity to various agents. 
Several combination clinical trials are ongoing with BETi, including combination with checkpoint 
monoclonal antibodies, androgen receptor antagonists, estrogen modulators,  BCL2 inhibitors, and 
others. 
3.4  
ZEN003694 
ZEN003694 is a structurally novel, orally bioavailable small molecule that epigenetically regulates 
gene expression through bromodomain and extra-terminal domain (BET) inhibition.  ZEN003694 
is a small molecule with an empirical formula of 
 and a molecular weight of 
.  ZEN003694 was discovered and developed by Zenith Epigenetics Ltd. and has 
broad potential as an anti-proliferative agent in solid tumors and hematologic malignancies.  
ZEN003694 and its major active metabolite, ZEN003791, bind BET bromodomains and 
selectively inhibit the BET family member BRD4 binding to  super-enhancers in chromatin, in 
turn inhibiting expression of BRD4-dependent genes MYC and BCL-2 family members that drive 
proliferation and inhibit apoptosis of cancer cells.  ZEN003694 and ZEN003791 were equipotent 
biochemically and in cell assays.  
 
 
 
 
 
 
  Based on extensive in vitro binding studies, 
ZEN003694 and ZEN003791 are considered to have low potential for off-target pharmacologic 
effects. 
3.5  
Talazoparib 
Talazoparib is a potent, orally available small molecule PARP inhibitor in development for the 
treatment of a variety of human cancers.  Talazoparib exerts cytotoxic effects via 2 mechanisms: 
(1) inhibition of PARP1 and PARP2 catalytic activity, and (2) PARP trapping, a process in which 
PARP protein bound to a PARP inhibitor does not readily dissociate from DNA, thereby 
preventing DNA repair replication, and transcription (Murai, et al., 2012) through alternative 
mechanisms, resulting in higher potencies than other PARP inhibitors.  
In vitro pharmacology studies with talazoparib demonstrated potent and selective inhibition of 
PARP1 (50% inhibitive concentration [IC50] = 0.7 nM) and PARP2 (IC50 = 0.3 nM) catalytic 
activity in a biochemical assay. Robust cytotoxicity following talazoparib treatment was observed 
in a panel of breast, prostate, pancreatic, and colorectal cancer cell lines with defects in 
deoxyribonucleic acid (DNA) damage repair pathways. Evaluation of PARP trapping in breast and 
prostate cancer cell lines treated with talazoparib resulted in increased trapping in the presence of 
single-strand break inducing agent methyl methane sulfonate (MMS). The reduced population 
growth and cytotoxicity observed in the DNA damage repair (DDR) assays are consistent with the 
proposed mechanisms of action for talazoparib: catalytic activity inhibition and PARP trapping.  
In vivo, antitumor efficacy of single agent talazoparib was better than carboplatin in a breast cancer 
patient-derived xenograft (PDX) model when dosed orally once daily (QD) at 0.3 mg/kg. Breast 

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cancer PDX models (one each with mutated BRCA1 and mutated BRCA2, and 3 models with wild 
type BRCA1/2) evaluated with talazoparib dosed twice a day (BID) at 0.07 mg/kg or 0.15 mg/kg 
showed that talazoparib elicited the strongest, statistically significant (compared to vehicle), dose 
dependent tumor growth inhibition (TGI) response (100% tumor-free survival [TFS]) in the 
BRCA1-mutated PDX model, but also elicited statistically significant TGI responses in the 
BRCA2-mutated model and BRCA1/2 wild type models. While activity was most robust in the 
BRCA1 mutated model, talazoparib was also active in the BRCA2 mutant and in the presence of 
wild type BRCA1/2, possibly due to other unknown DDR-related mutations.  
The absorption, distribution, metabolism and elimination of talazoparib have been characterized 
in mice, rats and dogs, as well as human tissues. Talazoparib was orally bioavailable with low 
plasma clearance and moderate volume of distribution in rats and dogs. Talazoparib was highly 
bound to plasma proteins in rodent and moderately bound in dog, monkey, and human plasma. 
Following oral administration of [14C]talazoparib to pigmented rats, drug-derived 
radioequivalents were widespread in most tissues including the bone marrow (BM) and were 
completely eliminated from all tissues by 168 h, including melanin containing tissues. In several 
studies, talazoparib showed negligible brain distribution in mice and rats. In vitro, talazoparib is 
metabolically stable in liver microsomes and hepatocytes of nonclinical species and humans. In 
vivo, talazoparib mainly circulates as unchanged drug in rats, dogs and humans. In rats and dogs, 
the majority of the [14C]talazoparib-derived radioactivity was eliminated as unchanged drug in 
the feces with excretion in the urine as a minor route, however, in humans [14C]talazoparib-
derived radioactivity was mainly eliminated as unchanged drug in the urine, with excretion in the 
feces as a minor route of elimination. The nonclinical toxicologic profile of talazoparib has been 
characterized through the conduct of studies including repeat dose toxicity in rat and dog of ≤13-
week duration, genetic toxicity (in vitro and in vivo), embryo-fetal development in rat, and 
phototoxicity, in accordance with the International Council for Harmonisation (ICH) S9 
guidelines. Based on the cumulative evaluation of the toxicology profile of talazoparib, the primary 
talazoparib-related target organ findings include effects on the hematolymphopoietic system, the 
male reproductive system and the gastrointestinal (GI) system in both rat and dog. Additional 
target organ findings observed in rat only include findings in the female reproductive system and 
liver. Talazoparib is clastogenic in vitro in human peripheral blood lymphocytes (HPBLs), in 
cancer cell lines and in vivo in rat. Talazoparib caused frank fetotoxicity in an embryo-fetal 
development study in rat.  
The primary nonclinical toxicology profile of talazoparib following oral administration can be 
largely explained by the pharmacological effects of talazoparib on rapidly dividing cells 
(talazoparib-induced PARP inhibition). Talazoparib mechanism of action (cytotoxicity) is 
dependent on the inhibition of PARP1/2 enzyme activity (inhibition of catalytic activity) and its 
robust PARP trapping ability at the site of damaged DNA (causing S-phase induced double-
stranded DNA [dsDNA] break leading to apoptosis and/or necrosis). Evaluation of the cumulative 
toxicological profile of talazoparib suggests that the hematolymphopoietic and testes toxicities 
occur at subtherapeutic clinical exposure margins, while the GI, liver and ovary findings occur in 
rat at higher clinical exposure margins and are potentially mediated by a combination of the 
catalytic activity inhibition and PARP trapping activity. However, the clastogenic potential is 
considered to be mainly a result of talazoparib-induced inhibition of the PARP catalytic activity. 
The frank embryo-fetal toxicity observed in pregnant female rat in the embryo-fetal development 

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(EFD) study is considered to be a result of both the clastogenic and cytotoxic activities of 
talazoparib.  
The nonclinical pharmacologic, PK and toxicologic properties of talazoparib have been thoroughly 
evaluated and support the use of talazoparib in advanced cancer patients. 
Talazoparib has also been shown to enhance the cytotoxic effects of DNA damaging 
chemotherapy, including temozolomide and irinotecan, in both in vitro and in vivo preclinical 
models. 
 
3.6  
ZEN003694 Preclinical Data in TNBC Models  
Zenith’s  preclinical data show 
 
 
 
 ZEN003694 synergizes with talazoparib in patient-derived 
TNBC models that are insensitive to talazoparib alone (Figure 2). Among 9 TNBC models tested, 
2 models demonstrated synergy with talazoparib (one model had a BRCA1 mutation and the 
second model was BRCA1/2 wild-type); whereas the remaining 7 showed additivity (Figure 2; 
synergistic data shown only). All models were sensitive to ZEN003694, but resistant to 
talazoparib. 
 
  
 
 
 
  
 

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Figure 5:  Target modulation by ZEN003694 
 
Dose-dependent modulation of IL1RN, CCR1, and IL-8 in the whole blood of CRPC patients in the 
ZEN003694-001 and ZEN003694-002 clinical trials. 
 
Clinical data from both mCRPC studies have identified the following adverse drug reactions (drug 
related and occurring in > 2 patients) (Table 2 and Table 3); visual disturbance (typically a 
transitory perception of brighter lights and/or light flashes, with or without visual color tinges, and 
with no functional consequences), nausea, fatigue, decreased appetite, vomiting, creatinine 
increase, platelet decrease, diarrhea, dehydration, decreased weight, dizziness, dysgeusia, and 
thrombocytopenia. These ZEN003694-related adverse events (AEs) were generally Grade 1 or 2 
in severity, were managed clinically, did not result in long-term sequelae, and resolved in the 
absence of drug exposure.  
The most frequent and/or clinically important AEs (GI symptoms such as nausea, vomiting, 
diarrhea, and constipation in 59% of patients, visual disturbance in 61% of patients, and 
thrombocytopenia in 7% of patients) can be related to the mechanism of action and molecular 
pharmacology of ZEN003694, and thus appear to be dose-related and readily reversible; they may 
also be managed through modulation of exposure (e.g., changing the dosing regimen or 
withdrawing the drug).  GI symptoms have also been managed through the use of anti-emetics and 
proactive attention to nutrition and hydration; constitutional symptoms generally respond to dose 
reduction or short-term dose holds. Adverse events to date have been transitory, reversible, and 
manageable with symptomatic therapy. 

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3.8  
Talazoparib Clinical Data 
 
A summary of talazoparib clinical data is presented below.  A comprehensive review of talazoparib 
may be found in the single reference safety document (SRSD), which for this study is the 
Investigator’s Brochure (IB).  Investigators are to review this document prior to initiating this 
study. 
 
Investigations of talazoparib are currently on-going with talazoparib being evaluated, both as 
single agent or in combination, in mCRPC, early triple-negative breast cancer, ovarian cancer, and 
small cell lung cancer. 
 
3.8.1 Pharmacokinetics 
The PK of talazoparib as a single agent has been evaluated in a total of 7 clinical studies. The PK 
of talazoparib was similar in patients with hematological malignancies and patients with solid 
tumors, and no differences were apparent between males and females. Oral absorption of 
talazoparib was rapid and independent of dose after administration of single or multiple doses. A 
food-effect study showed that food had no clinically meaningful effect on the extent of absorption; 
talazoparib can be administered without regard to food. The plasma exposure of talazoparib is dose 
proportional in the dose range of 0.025 mg to 2 mg QD, suggesting linear PK. The mean terminal 
half-life (t½) was approximately 4 days. Talazoparib accumulated after 1 mg QD dosing with a 
median accumulation ratio (Rac) ranging from 2.33 to 5.15, consistent with its t½. Steady state 
was reached around 3 weeks after the start of talazoparib dosing. Talazoparib undergoes minimal 
hepatic metabolism in humans. Renal excretion of unchanged talazoparib was the major 
elimination pathway of talazoparib. Talazoparib is moderately bound to human plasma proteins 
(74%, in vitro) and is evenly distributed across human blood cells and plasma compartments. In 
vitro, talazoparib did not significantly interact with any of the major cytochrome P450 (CYP) or 
uridine 5'-diphospho-glucuronosyltransferase (UGT) drug metabolizing enzymes, nor was it an 
inhibitor of any ATP-binding cassette (ABC) or solute carrier (SLC) drug. Talazoparib is a 
substrate for P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and plasma 
talazoparib concentrations may increase or decrease when coadministered with P-gp or BCRP 
inhibitors or inducers, respectively. Based on the high oral bioavailability observed in rats, dogs, 
and humans, absorption of talazoparib is not limited by these efflux transporters.  
 
Additional ongoing Phase 1 company-sponsored clinical studies are evaluating the PK of 
talazoparib in patients with renal impairment or hepatic impairment, and DDIs of talazoparib with 
itraconazole and rifampin. 
 
3.8.2 Safety 
A total of 502 patients with solid tumors received 1 mg/day talazoparib through 31 January 2018  
in 5 Sponsor-initiated studies, namely Study 673-301 (phase 3 EMBRACA  pivotal, open-label 
randomized 2-Arm, Multicenter Study of Talazoparib [BMN 673] Versus Physician’s Choice in 
Patients With Germline BRCA Mutations and Locally Advanced and/or Metastatic Breast Cancer 
Who Had Prior Chemotherapy for Metastatic Disease study), Study 673-201 (phase 2 ABRAZO 
open-label non randomized study in Patients With Germline BRCA Mutations and Locally 

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Advanced and/or Metastatic Breast Cancer), Study MDV3800-13 (open label extension study), 
Study PRP-001 (Phase 1 dose escalation study in patients with advanced or recurrent solid tumors), 
and Study MDV3800-14 (Phase 1 Study MDV3800-14: cardiac repolarization study in patients 
with advanced solid tumors).  
 
The most common adverse events (≥20%) related to talazoparib 1 mg/day, mostly with grade 1 or 
2 severity, were anemia (45.8%), fatigue (36.1%), nausea (32.5%), neutropenia (21.9%), and 
alopecia (20.1%). Grade 3 or 4 drug-related adverse events occurring in ≥5% of patients were 
related to myelosuppression, namely anemia (34.1%), neutropenia (13.9%), thrombocytopenia 
(10.6%), and platelet count decreased (5.4%). Most common serious adverse events (≥3 patients) 
considered related to talazoparib were anemia (4.6%), thrombocytopenia/platelet count decreased 
(2.4%), and neutropenia (0.6%). 
 
A total of 23 of 502 patients had an adverse event that led to death, of these, only veno-occlusive 
liver disease occurred in a patient was assessed as related to study drug by the investigator. 
Adverse events leading to treatment discontinuation occurred in 4% of patients receiving 
talazoparib 1 mg/day, the most common being anemia (in 3 patients) and increased alanine 
aminotransferase (ALT, in 2 patients). Among the 502 patients in the talazoparib 1 mg/day patient 
population, 63.9% had adverse events that led to dose reduction and 61.2% had a TEAE that led 
to dosing interruption, most commonly associated with myelosuppression. 
 
In general, the adverse events associated with talazoparib are detectable through routine laboratory 
and clinical monitoring and may be managed with supportive care or dose reductions or 
interruptions. 
 
3.8.3 Efficacy 
Efficacy data have been obtained from 3 Sponsor-initiated studies (PRP-001, Studies 673-201, and 
673-301) evaluating talazoparib in patients with advanced or metastatic breast cancer.  
 
In the Phase 1 first-in-human study (Study PRP-001 [C3441007]) in patients with advanced or 
recurrent solid tumors, a total of 110 patients were treated at a range of talazoparib doses (0.025-
1.1 mg/day). Data from this study demonstrated objective responses and/or clinical benefit in 
patients with breast, ovarian/peritoneal, and pancreatic cancer; small-cell lung cancer (SCLC); and 
Ewing sarcoma.  
 
In an open-label Phase 2 study (Study 673-201, [C3441008, ABRAZO]) of talazoparib in patients 
with germline BRCA-mutated locally advanced or metastatic breast cancer, 83 patients were 
treated with talazoparib 1 mg/day across 2 cohorts. Cohort 1 enrolled 49 patients (48 treated) who 
had a partial response (PR) or complete response (CR) to a prior platinum-containing regimen for 
metastatic disease with disease progression >8 weeks following the last dose of platinum. Cohort 
2 enrolled 35 patients who received 3 or more prior chemotherapy regimens and no prior platinum 
therapy for metastatic disease. Cohort 1 had an objective response rate (ORR) of 20.8% (95% CI: 
10.5, 35.0) including 2 CRs (4.2%). Cohort 2 had an ORR of 37.1% (95% CI: 21.5, 55.1). Median 
duration of response (DOR) was 4.9 months (interquartile range [IQR]: 2.8, 7.1) in Cohort 1 and 
4.2 months (IQR: 3.2, 5.6) in Cohort 2 (Turner, et al., 2017). 

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In the pivotal randomized Phase 3 study (Study 673-301, [C3441009, EMBRACA]) of talazoparib 
versus physician’s choice treatment (PCT) in patients with germline BRCA-mutated human 
epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, 
431 patients overall were randomized in a 2:1 ratio to receive talazoparib 1 mg/day (n = 287) or 1 
of 4 PCTs (n = 144). In this study, talazoparib demonstrated significantly prolonged progression-
free survival (PFS) by blinded independent central review (BICR) assessment when compared to 
PCT. Median PFS by BICR in the talazoparib arm was 8.6 months (95% CI: 7.2, 9.3) compared 
to 5.6 months (95% CI: 4.2, 6.7) in the PCT arm (Litton, et al., 2018).  
 
3.9  
Study Rationale  
The vast majority of patients with TNBC do not carry germline BRCA1 or BRCA2 mutations and 
would therefore not derive benefit from treatment with single agent PARP inhibitor therapy 
Therefore, strategies to induce a “BRCAness” phenotype, namely through inhibition of HR in 
cancer cells is needed.  Recently, significant pre-clinical evidence has shown that BETi synergize 
with PARPi through downregulation of the transcription of several HR genes. We and others 
hypothesize that BETi may suppress HR and enhance non-homologous end joining (NHEJ), 
thereby sensitizing HR-proficient cancer cells to PARP inhibition (Wilson, et al., 2018). 
To test this hypothesis, we propose this Phase 2 trial with the combination of talazoparib and 
ZEN003694 in previously treated metastatic/advanced BRCA1/2 -proficient TNBC. Talazoparib 
is a potent and selective inhibitor of PARP. In addition to inhibiting PARP catalytic activity, 
talazoparib traps PARP-DNA at sites of single-agent DNA breaks (Murai, et al., 2014). 
ZEN003694 is s a potent and selective inhibitor of the BET family of proteins and is currently 
being tested in a Phase1b/2a mCRPC clinical trial. Clinical data to date show that ZEN003694 has 
dose proportional pharmacokinetics, minimal CYP liabilities, and modulates the target at safe 
doses. Based on ZEN003694 safety profile as described in Section 3.7,  ZEN003694 is expected 
to  combine well with talazoparib.   
The first part of this study is dose escalation using a 3x3 design to determine a safe and optimal 
dose of ZEN003694 when given in combination with talazoparib.  The second part of the study is 
a Simon two-stage design to determine overall response rate to the combination of ZEN003694 
and talazoparib. 
3.10 
Dosing Rationale  
Based on the safety and PK/PD data from the ZEN003694 mCRPC trials, a reasonable ZEN003694 
dose to initiate in this combination trial of ZEN003694 plus talazoparib is 48 mg  QD for 
ZEN003694 in combination with 1 mg QD talazoparib.  The MTD of ZEN003694 was 60 mg QD 
in the single agent study but the dose of 96 mg QD in the mCRPC combination study was tolerated 
with one DLT out of six patients.  Dosing at 120 mg QD has also been tolerated by a cohort of 
three patients in this ongoing combination study of ZEN003694 plus enzalutamide in mCRPC 
patients.  The reason for the higher MTD in the this mCRPC combination study is not definitively 
known but may relate to one or more factors, including:  proactive management of GI toxicities 
with the implementation of PRN use of antiemetics upon onset of nausea and the recommendation 
of oral hydration in the combination study;  outlier high exposures of the two patients who 
experienced a DLT in the single agent study; and/or the higher ratio of active metabolite to parent 

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in the mCRPC combination study with enzalutamide. Although talazoparib is not a CYP3A4 
inducer and is not expected to induce a higher ratio of the ZEN003694 active metabolite to parent 
in this TNBC combination study, it is expected that 48 mg of ZEN003694 will be tolerated in 
combination with 1 mg talazoparib.  In case of clinically significant AEs, a dose reduction and 
dose hold schema is described in Section 8.  Proactive management of nutrition, hydration, and 
anti-emetics will also be implemented in this trial, and pharmacokinetic monitoring will allow 
management of systemic exposure within known tolerated levels. 
3.11 
Rationale for Expanding Phase 2 Study and Patient Pre-Selection 
 
Data from Dose Escalation and Simon 2-Stage  
 
The study enrollment for the dose escalation and Simon 2-stage parts of the study has been 
completed and 57 patients have been dosed. Dosing was started at 48 mg oral daily (QD) for 
ZEN003694 plus 1 mg QD talazoparib. Dose limiting toxicity (DLT) of grade 4 thrombocytopenia 
was seen in 2 patients. Two additional dosing cohorts were tested (48 mg QD ZEN003694 plus 
0.75 mg QD talazoparib and 36 mg QD ZEN003694 plus 1 mg QD talazoparib). Based on 
additional data and no reported DLTs, 48 mg QD ZEN003694 plus 0.75 mg QD talazoparib was 
selected as the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) for the phase 2 
portion of the study due to higher exposure and pharmacodynamic activity (low target engagement 
at 36 mg ZEN003694). Of the 50 evaluable patients receiving the RP2D of the combination, 11 
(22%) had a confirmed objective response rate (ORR) with a median duration of response rate 
(DOR) of 24 weeks and this was driven by the population whose tumors were triple negative at 
diagnosis and did not convert from hormone receptor positive to triple negative. The most 
commonly reported ZEN003694-related AEs (occurring in ≥15% of patients) were 
thrombocytopenia, visual symptoms, fatigue, nausea, vomiting, dysgeusia, increased AST/ALT, 
anorexia and anemia. All AEs were reversible upon dose hold. 
 
A development and registration plan was discussed with the FDA for extending the current study 
by adding additional post TROP2-ADC patients to generate statistically significant ORR and DOR 
data for potential accelerated approval with a commitment for a Phase 3 confirmatory trial. FDA 
agreed that an ORR that is significantly superior to available therapies could be used as a basis for 
approval. Currently, only available therapies for third line mTNBC patients who have received 
prior Sacituzumab-govitecan is chemotherapy which has an ORR of ~ 5-12%. The expansion with 
an additional 80 evaluable patients is powered to show and ORR with a lower 95% confidence 
interval that excludes an ORR of 20%. FDA also asked for a cohort of 10 patients to evaluate the 
efficacy of single agent ZEN003694. This cohort of patients will be crossed over to the 
combination of ZEN003694 plus talazoparib upon progression. 
 
 
 
 
 
 
 

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4.  
OBJECTIVES 
4.1  
Primary 
Part 1 
• 
To determine the safety, tolerability, maximum tolerated dose (MTD) and recommended 
Phase 2 dose (RP2D) of ZEN003694 in combination with talazoparib in patients with 
locally advanced or metastatic triple-negative breast cancer (TNBC)  
Part 2  
• 
To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with 
locally advanced or metastatic TNBC  
Expansion 
• To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with  
locally advanced or metastatic TNBC whose cancer was hormone receptor negative at the 
time of initial breast cancer diagnosis and who have received TROP2-ADC in the 
unresectable locally advanced or metastatic disease setting. 
 
4.2  
Secondary 
Part 1 
• To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791 and 
talazoparib  
• To evaluate the effects of ZEN003694 and talazoparib on mRNA expression of 
pharmacodynamic markers 
• To evaluate the clinical activity of ZEN003694 in combination with talazoparib by 
radiographic response rate and progression-free survival 
 
• To determine the effect of ZEN003694 and talazoparib on patient reported health status 
and quality of life  
Part 2 
• To further evaluate the safety and tolerability of ZEN003694 in combination with 
talazoparib 
• To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791, and 
talazoparib 
• To determine the effect of ZEN003694 and talazoparib on patient reported health status 
and quality of life 

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Expansion 
• To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with 
locally advanced or metastatic TNBC whose cancer was hormone receptor negative (<5%) 
at the time of initial breast cancer diagnosis and who have not received TROP2-ADC in 
the locally advanced or metastatic disease setting 
• To evaluate the ZEN003694 monotherapy in patients with locally advanced or metastatic 
TNBC whose cancer was hormone receptor negative at the time of initial breast cancer 
diagnosis and who may or may not have received prior TROP2-ADC. 
• To further evaluate the safety and tolerability of ZEN003694 in combination with 
talazoparib 
• To determine the pharmacokinetics (PK) of ZEN003694, its metabolite, ZEN003791, and 
talazoparib 
• To determine the effect of ZEN003694 and talazoparib on patient reported health status 
and quality of life 
 
4.3  
Exploratory 
Parts 1 and 2, Expansion 
• 
 
 
 
  

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5.  
STUDY DESIGN 
5.1  
Part 1:  Dose escalation 
Part 1 is an open label, non-randomized, dose escalation of ZEN003694 in combination with 
talazoparib in patients with TNBC.  A standard 3+3 cohort design will be utilized.  Cohorts of 3 
patients and up to 6 patients will be enrolled at each dose level, and each patient will participate in 
only one cohort.  Each cycle will be 28 days in duration. Patients at each dose level will be treated 
and observed through the end of the first 28-day cycle before treatment of patients at the next 
higher dose level can begin. 
Dose escalation will continue after all patients enrolled within a cohort have completed the 28-day 
Cycle 1 DLT observation period with either 0 of 3 patients, or no more than 1 out of 6 patients in 
a cohort experiencing a DLT.  Dose escalation decisions will be made based on clinical safety and 
(when available) PK data (maximum or peak concentration [Cmax] and area under the curve [AUC]) 
after review by the Investigators and the Zenith Medical Monitor.  If a DLT is observed in 1 of 
3 patients in a cohort, 3 additional patients will be enrolled into that cohort.  If 1 of 6 patients in a 
cohort experiences a DLT, then dose escalation may continue in the next cohort or the MTD of the 
combination can be declared.  If ≥ 2 of 3 – 6 patients experience DLTs within a cohort, then the 
MTD will be considered to have been exceeded and further dose escalation will cease.  In this 
case, if fewer than 6 patients have been enrolled at the previous dose level, that cohort will be 
expanded to 6 patients to confirm the MTD.  Should the MTD of the combination be exceeded at 
Dose Level 1, a cohort may be explored with a reduced dose of ZEN003694 or talazoparib. Cohort 
management is summarized below. 
 
Number of Patients with 
Dose-limiting Toxicity 
Action 
0 of 3 or 1 of 6 
Dose escalate to next cohort 
1 of 3 
Add 3 more patients 
1 of 6 
Proceed to next dose level 
≥ 2 of 3 or ≥ 2 of 6 
Add 3 more patients in the next lower dose level if 
only 3 patients were treated in the next lower dose.  If 
6 patients were treated at the next lower dose level 
and no more than one patient had DLT, then the next 
lower dose is the MTD. 
 
Enrollment in the dose escalation part of the study will commence with a 48 mg oral once daily 
dose as the starting dose for ZEN003694 in combination with a 1 mg oral once daily dose of 
talazoparib.  The dose of ZEN003694 will be held constant throughout Cycle 1, however doses 
may be held for the management of toxicity.  The dose of talazoparib may be held and reduced 
from the initial 1.0 mg dose in 0.25 mg increments in accordance with the talazoparib label and by 
agreement with Zenith.  Dose escalation/de-escalation of ZEN003694 will proceed per the schema 
in Table 5 unless intervening toxicity is observed.  Alternative dosing schedules may be evaluated 
based on the evaluation of clinical safety and upon agreement of the Investigators and Zenith.  

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Alternative dosing schedules may include intermittent dosing that could necessitate a change in 
the cycle duration from 28 days to 21 days. 
Table 5:  Dose Escalation Scheme 
 Dose Level 
ZEN003694 (mg) * 
Fold Increase from 
Prior Dose Level 
-1 
36 
0.75 
1 
48 
-- 
2 
72 
1.50 
* Dose de-escalation from 48 mg is allowed and additional dose levels may be explored 
based on safety and at the discretion of the Sponsor with agreement from the Investigators 
 
No intra-patient dose escalation is allowed during the first two cycles of therapy.  If a patient has 
not experienced any Grade 2 or higher drug-related AEs after three cycles, dose escalation up to 
the highest ZEN003694 dose currently declared tolerable will be allowed and further intra-patient 
dose escalation(s) will be determined on a cycle-by-cycle basis at the discretion of the Investigators 
and with approval by the Sponsor.  
5.1.1 Dose Escalation Safety Reviews 
ZEN003694-related adverse events (AEs) for determination of DLTs will be assessed for each 
patient during the 28 days of Cycle 1. Teleconferences between the Sponsor and the Investigators 
will be held during the dose escalation phase to discuss any suspected DLTs that have occurred in 
patients within each cohort.  The frequency of the teleconference calls will be determined by the 
rate of enrollment, data review, frequency of DLT notifications, discussions with investigational 
sites and other factors.  Approximately one week after the last patient in a dose cohort completes 
Cycle 1 and prior to enrolling patients in the next dose, the Sponsor and Investigators will review 
toxicities and available PK (e.g., Cmax and AUC) from the current cohort of the study during a 
teleconference call. 
5.1.2 Definition of Dose-limiting Toxicity 
Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose 
escalation phase.  Toxicity will be graded and recorded according to National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 (see Appendix 2).  
A DLT is defined as a clinically significant AE or laboratory abnormality that is considered 
possibly, probably or definitely related to study drug and which meets any of the following criteria: 
• Grade 3 or greater non-hematologic clinical toxicity with the exception of a) Grade 3 
nausea or Grade 3/4 vomiting and diarrhea unless persisting more than 72 hours despite 
maximal medical therapy and b) Grade 3 or 4 amylase or lipase elevation that is not 
associated with symptoms or clinical manifestations of pancreatitis  
• Grade 3 or greater fatigue for at least 1 week 
• Grade 4 anemia  
• Grade 4 neutropenia lasting more than 5 days 

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• Grade 3 or greater febrile neutropenia (temperature ≥ 38.5ºC) 
• Grade 4 thrombocytopenia; or Grade 3 thrombocytopenia with clinically significant 
bleeding; or any requirement for platelet transfusion 
• Grade 3 or 4 electrolyte abnormality lasting more than 72 hours, unless the patient has 
clinical symptoms, in which case all Grade 3 or 4 electrolyte abnormalities regardless of 
duration will be considered a DLT 
• Any other Grade 3 or 4 laboratory abnormality that requires hospitalization 
• An ALT or AST ≥3x ULN with concomitant total bilirubin > 2x ULN, and serum alkaline 
phosphatase ≤ 2x ULN (Hy’s Law)  For patients with hepatic metastases, AST or ALT 
>8x ULN or AST or ALT >5x ULN for ≥14 days 
• Any Grade 3 or 4 visual symptoms 
• Any toxicity that results in more than 25% of missed doses during Cycle 1 of the 28 days 
of treatment, with the exception of a dose hold for Grade 3 thrombocytopenia, in which 
case a dose hold of both talazoparib and ZEN003694 for 10 consecutive days in Cycle 1 
will be allowed and not considered a DLT.  For an intermittent schedule of 2-weeks on/1-
week off, if any toxicity results in more than 2 missed doses during the 2-week treatment 
period the toxicity would be considered a DLT.   
• In the situation where toxicity requires withholding study drug following the receipt of 
at least 75% of scheduled dosing during Cycle 1: Failure to begin Cycle 2 within 1 week 
of the scheduled start date due to ongoing toxicity 
All patients experiencing a DLT must discontinue dosing with ZEN003694 and talazoparib, except 
in the event that the DLT is thrombocytopenia, in which case patients may be re-challenged with 
ZEN003694 and talazoparib at doses agreed upon with the Sponsor if platelets recover to at least 
75,000/µL within a 10-day dose hold.  All patients who discontinue treatment must complete the 
Safety Follow-up visit prior to discontinuation from the study.   
Determination of evaluability will be made during the first 28 days of study treatment (i.e., Cycle 
1) in the dose escalation phase.  Patients who miss more than 25% of ZEN003694 or talazoparib 
doses (except in the case of a dose hold for thrombocytopenia where 10 consecutive days of missed 
doses are allowed); or fail to begin Cycle 2 within 1 week of the scheduled start date for reasons 
other than drug-related toxicity will be considered unevaluable and will be replaced. 
5.1.3 Definition of the Maximum Tolerated Dose 
The MTD is defined as the highest dose level of ZEN003694 in combination with talazoparib at 
which no more than 1 of 6 patients experiences a DLT during the first cycle of therapy.  
5.1.4 Definition of the Recommended Phase 2 Dose 
The RP2D as determined in Part 1 of the study is defined as the dose level of ZEN003694 in 
combination with talazoparib recommended for further clinical study.  The RP2D may be the 

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same as the MTD or modified from the MTD based on assessments of overall exposure, safety 
experience in Cycle 2 and beyond, PD and clinical benefit data in this study.  Part 2:  Simon 2-
Stage  
 
Once an RP2D of ZEN003694 in combination with talazoparib has been determined in the dose 
escalation part of the study, 17 patients will be enrolled in Stage 1 of a Simon 2-Stage design 
(Simon, 1989) for evaluation of objective response (complete response (CR), partial response 
(PR), or stable disease (SD) for ≥ 4 cycles) by RECIST 1.1 (Eisenhauer, 2009).  If there are ≥4 
objective responses the study will proceed to Stage 2.  If there are <4 responses, the study will be 
stopped.   
If at least 4 patients in Stage 1 have an objective response (CR, PR or SD for ≥ 4 cycles) by 
RECIST 1.1, 20 patients will be enrolled in Stage 2 of the Simon 2-Stage design.  Patients will 
receive daily RP2D doses of ZEN003694 in combination with 1 mg talazoparib.  Patients may 
continue receiving ZEN003694 in combination with talazoparib until radiographic or clinical 
progression, unacceptable toxicity, requirement for non-protocol therapy or patient withdrawal 
from study. 
5.2  
Expansion 
The expansion of the study will be implemented under amendment following the determination of 
the RP2D of ZEN003694 in Part 1 and after meeting the primary endpoint of clinical benefit rate 
of 35% in Part 2.  The study will be expanded to enroll an additional 120 patients with  locally 
advanced or metastatic TNBC that is without germline BRCA1/BRCA2 mutations and was 
hormone receptor negative (<5%) at the time of initial breast cancer diagnosis.    
Expansion Cohort A:  Combination Treatment in post-TROP2-ADC patients:  Eighty (80) 
patients who have received prior TROP2-ADC treatment will receive daily RP2D doses of 
ZEN003694 (48mg QD) in combination with talazoparib (0.75mg QD).  Patients may continue 
receiving ZEN003694 in combination with talazoparib until radiographic or clinical progression, 
unacceptable toxicity, requirement for non-protocol therapy or patient withdrawal from the study. 
Expansion Cohort B:  ZEN003694 Monotherapy:  As mandated by the FDA to assess any 
potential single agent ZEN003694 activity, ten (10) patients will initially receive daily doses of 
48mg ZEN003694 as monotherapy with the option to cross-over to combination treatment of 48mg 
ZEN003694 plus 0.75mg talazoparib at the time of disease progression (but no sooner than after 
6 weeks of monotherapy). Patients in the cross-over group may continue receiving ZEN003694 in 
combination with talazoparib until radiographic or clinical progression, unacceptable toxicity, 
requirement for non-protocol therapy or patient withdrawal from study. 
Expansion Cohort C:  Combination Treatment in TROP2-ADC-naïve patients:  Thirty (30) 
patients who have not received prior TROP2-ADC will receive daily RP2D doses of ZEN003694 
(48mg QD) in combination with talazoparib (0.75mg QD).  Patients may continue receiving 
ZEN003694 in combination with talazoparib until radiographic or clinical progression, 
unacceptable toxicity, requirement for non-protocol therapy or patient withdrawal from the study. 
 

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5.3  
Number Patients and Sites 
In Parts 1 and 2, up to 52 evaluable patients will be enrolled in the study at approximately 10 sites 
(in the US and Western Europe).  Approximately 15 patients will be enrolled in Part 1 (dose 
escalation) and approximately 37 patients will be enrolled in the Part 2 of the study with 17 patients 
enrolled in Stage 1 of the Simon 2-Stage design and 20 patients enrolled in Stage 2. 
 
In the Expansion phase, approximately 120 evaluable patients will be enrolled in the study (80 
patients in Cohort A; 10 patients in Cohort B; and 30 patients in Cohort C) at approximately 18 
sites (approximately 9 sites in the US; 4 sites in Western Europe; and 5 sites in China). Cohort A 
and B will enroll at all US and EU sites.  Cohort C will be enrolled at sites in China only. 
5.4  
Study Duration 
The duration of Stage 1 is approximately 6 months to enroll 17 patients who are treated through 5 
cycles (2 post baseline scans). The duration for Stage 2 is approximately 12 months to enroll 20 
patients who are treated through 5 cycles (2 post baseline scans).  
The duration of the Expansion phase is approximately 24 months. 
5.5  
Premature Study Termination or Suspension of Enrollment 
The Sponsors have the right to terminate the participation of an individual study site or the entire 
study, at any time, for any reason.  Reasons for terminating the study include, but are not limited 
to, the following: 
• The incidence or severity of AEs in this or other studies indicates a potential health hazard 
to patients 
• Patient enrollment is unsatisfactory 
• Data records are inaccurate or incomplete 
• The Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation or 
development of ZEN003694 
In addition, the Sponsor may suspend enrollment in the study at any time for any reason. 
All Investigators and appropriate Regulatory Authorities will be promptly notified upon early 
termination of the study.  In addition, Investigators and Regulatory Authorities will be promptly 
notified if enrollment is terminated or suspended for any reason. 
 

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6. 
 PATIENT SELECTION 
6.1  
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for the study: 
1. Females or males age ≥ 18 years (at time of signing informed consent) 
2. Parts 1 and 2 only:  Histologically confirmed metastatic or recurrent or locally advanced 
triple-negative breast cancer (estrogen receptor (ER) ≤10%; progesterone receptor (PR) 
≤10%; and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ 
hybridization (FISH) 
Expansion only:  Histologically confirmed metastatic or recurrent, or locally advanced 
triple-negative breast cancer as defined by the most recent American Society of Clinical 
Oncology/College of American Pathologists (ASCO/CAP) guidelines.  
3. Patient is not a candidate for endocrine based therapy, based on Investigator judgement 
4. Have a history of progressive disease despite prior therapy 
5. Part 1: Have had at least 1 prior cytotoxic chemotherapy  
Part 2:  Have had no more than 2 prior chemotherapy-inclusive regimens for locally 
advanced or metastatic disease, unless approved by the Sponsor (no limit on prior targeted 
anticancer therapies such as mechanistic target or rapamycin (mTOR) or CDK4/6 
inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies 
against CTL4 or VEGF.) 
Expansion Cohort A (combination treatment in post-TROP2-ADC patients):  Have 
received TROP2-ADC therapy for unresectable locally advanced or metastatic disease. 
Expansion Cohort B (ZEN003694 monotherapy):  Have had at least 1 prior systemic 
therapy for locally advanced or metastatic disease which may or may not have included a 
TROP2-ADC. 
Expansion Cohort C (combination treatment in TROP2-ADC-naive patients):  Have 
had at least 1 prior systemic therapy for locally advanced or metastatic disease and who 
have not received prior TROP2-ADC therapy. 
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
7. Part 2 and Expansion only:  Measurable disease per RECIST version 1.1 
8. Adequate laboratory parameters at Screening including: 
a. Parts 1 and 2:  Hemoglobin ≥ 10.0 g/dL without transfusions during the 4 weeks 
prior to Screening.  Expansion:  Hemoglobin ≥ 9.0 g/dL 
b. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 
c. Platelet count ≥ 150,00/mm3 

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d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.0 x 
ULN or if liver function abnormalities due to liver metastases AST and ALT ≤ 5.0 
x ULN   
e. Total bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN for subjects with known Gilbert’s 
syndrome)  
f. Calculated (Cockcroft-Gault formula) or measured creatinine clearance ≥ 60 
mL/min 
g. Prothrombin time (PT), international normalized ratio (INR) and partial 
thromboplastin time (PTT) < 1.5 x ULN 
9. Female subjects may be enrolled if they are not of childbearing potential, permanently 
sterile or who are post-menopausal defined as no menses for at least 1 year without an 
alternative medical cause and FSH levels in the post-menopausal range.   Female subjects 
of childbearing potential may be enrolled if they consistently and correctly use a highly 
effective form of contraception from the time point of study drug administration until at 
least 7 months thereafter.  Highly effective forms of contraception include: combined 
(estrogen and progestogen hormonal contraceptives (oral, intravaginal, transdermal) 
associated with inhibition of ovulation; progestogen-only hormonal contraception (oral, 
injectable, implantable) associated with inhibition of ovulation; intrauterine device (IUD); 
intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized 
partner; sexual abstinence.  Female subjects should not donate eggs from the time point 
of study drug administration until at least 7 months thereafter.  
 
10. Males with partners of childbearing potential may be enrolled if they use a condom when 
having sex with a pregnant woman or with a non-pregnant female of childbearing 
potential from 21 days before the first dose of study drug through 4 months after the last 
dose of study drug, and males should not donate sperm from the time point of study drug 
administration until at least 4 months thereafter.  Contraception should be considered for 
a non-pregnant female partner of childbearing potential.  
11. Females of childbearing potential must have a negative serum or urine pregnancy test 
before the first dose of study drugs and must agree to pregnancy tests during the study.  
12. Females may not be breast-feeding at the first dose of study drugs, during study 
participation or through 7 months after the last dose of study drugs  
13. Ability to swallow capsules and comply with study procedures  
 
14. Ability to understand and willingness to sign informed consent form prior to initiation of 
any study procedures 
6.2  
Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the 
study: 

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1. Documented germline mutations of BRCA1 or BRCA2  
2. Parts 1 and 2 only:  Evidence of disease progression during platinum treatment either in 
the neoadjuvant or in the metastatic setting. For patients receiving platinum in 
the neoadjuvant setting, at least 6 months must have elapsed between the last dose of 
platinum-based treatment and enrollment 
3. Part 2 only:  Patients with inflammatory breast cancer   
4. Current or anticipated use of medications known to be strong inhibitors or inducers of 
CYP3A4 or  substrates of CYP1A2 with narrow therapeutic windows.  Strong inhibitors, 
inducers or  substrates must be discontinued at least 7 days prior to the first administration 
of study drug.  
5. Current or anticipated use within 7 days prior to the first administration of study drug, or 
during the study, of strong P-gp inhibitors.  
6. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban 
otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran).  Low 
molecular weight heparin is allowed 
7. Prior anticancer therapy (chemotherapy, radiation, hormone therapy, immunotherapy or 
investigational agent) within 3 weeks from the start of study drug (except for nitrosoureas 
and mitomycin C within 6 weeks from start of study drug) 
8. Parts 1 and 2 only:  Radiation to >25% of the bone marrow  
9. Treatment with a bone-targeted radionuclide within 6 weeks of first dose of study drug 
10. Have previously received an investigational BET inhibitor (including previous 
participation in studies with the Sponsor’s drug, ZEN003694); except for patients in 
Expansion Cohort B who received ZEN003694 monotherapy and are eligible to cross-over 
to combination treatment 
11. Prior treatment with a PARP inhibitor 
12. QTcF interval > 470 msec 
13. Insufficient recovery (i.e., has not recovered to at least Grade 1) from prior treatment-
related toxicities except for alopecia, fatigue and Grade 2 neuropathy 
14. Non-healing wound, ulcer or bone fracture (not including a pathological bone fracture 
caused by a pre-existing pathological bone lesion) 
15. Parts 1 and 2 only:  Brain metastases not adequately treated and clinically stable (at the 
discretion of the Investigator) for at least 3 months prior to the start of study treatment, 
unless a shorter interval is approved by the Sponsor’s Medical Monitor 
Expansion only:  Progressive, symptomatic, or untreated brain metastases.  CNS 
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stable based on imaging at least 3 months after definitive treatment.  CNS metastases 
requiring steroid doses equivalent to prednisone doses  >10 mg daily or an increase in 
steroid doses due to CNS disease prior to consent are not eligible 
16. Expansion only: Disease initially diagnosed with expression of estrogen receptor (ER) or 
progesterone receptor (PR) as ≥5% 
17. Expansion only: Patients treated with prior endocrine therapy 
18. Known impaired cardiac function or clinically significant cardiac disease such as 
uncontrolled supraventricular arrhythmia, ventricular arrhythmia requiring therapy, or 
congestive heart failure (New York Heart Association functional class III or IV) 
19. Myocardial infarction or unstable angina within 6 months prior to first dose of study drug 
20. Known myelodysplastic syndrome 
21. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active 
central nervous system disease, active, uncontrolled bacterial, viral, or fungal infection(s) 
requiring systemic therapy, or any other condition that could compromise safety or the 
patient’s participation in the study 
22. Impairment of gastrointestinal function (i.e., diagnosis of malabsorption syndrome) that 
may significantly alter the absorption of ZEN003694 or talazoparib 
23. Other known active cancer requiring therapy at time of study entry or that progressed or 
required treatment within 3 years prior to starting study drug (except for skin basal cell 
carcinoma or squamous cell carcinoma or in situ cervical cancer) 
24. Historically positive (screening tests not required) for human immunodeficiency virus 
(HIV); or hepatitis B virus (HBV) with currently active disease defined as hepatitis B surface 
antigen (HBsAg) positivity; or hepatitis C virus (HCV) unless  previously treated and viral load 
is undetectable.   
25. Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior 
to the first administration of study drug 
26. Concurrent participation in another clinical investigational treatment trial with a systemic 
therapy 
27. Any other reason that in the opinion of the Investigator would prevent the patient from 
completing participation or following the study schedule 
 

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7. 
STUDY DRUG AND MATERIALS  
7.1  
ZEN003694 Administration 
For this study ZEN003694 is to be ingested with a full (8-ounce) glass of water at least 1 hour 
before eating or 2 hours after eating (fasting).  Each capsule should be swallowed whole.  Patients 
should be advised not to chew, dissolve, or open the capsules. 
In Part 1 (dose escalation), the RP2D of ZEN003694 was established as 48 mg once daily.   
In Part 2 and Expansion, ZEN003694 will be administered as 48 mg once daily.  
7.1.1 Precautions 
Patients should also be advised to minimize their exposure to sunlight. 
 
 
 
 
   
Patients should be provided ‘filled’ prescriptions for an anti-emetic, if possible, or ensure patients 
fill their prescriptions of an anti-emetic on the first day of dosing (C1D1).  Patients are to be 
instructed to take the anti-emetic at first signs of nausea.     
7.1.2 ZEN003694 Formulation 
ZEN003694 capsules for oral administration are supplied as 12 mg and 48 mg capsules containing 
ZEN003694 as the active substance with no additional excipients filled in the capsule.  The 12 mg 
ZEN003694 capsules are size 3, Swedish orange, hard gelatin capsules and the 48 mg ZEN003694 
capsules are size 0, white opaque, hard gelatin capsules.   
The drug substance is manufactured under Good Manufacturing Practice conditions 
 
  The drug product is manufactured, packaged 
and labeled 
  Capsules are 
packaged in high density polyethylene opaque, white resin bottles with screw-cap, child-resistant 
closures.  
7.1.3 Storage Conditions 
ZEN003694 should be securely stored at room temperature 20 – 25°C (68 – 77°F) (excursions 
from 15° – 30C [59 – 86F] are permitted).  Protect from light and do not freeze.  
7.2  
Talazoparib Administration 
Talazoparib will be administered as a 1 mg once daily dose (as a starting dose in dose escalation, 
Part 1) and will be taken at the same time as ZEN003694, at approximately the same time each 
day.  In Part 2 and Expansion, talazoparib will be administered at a starting dose of 0.75mg once 
daily.  As with ZEN003694, talazoparib is to be self-administered at least 1 hour before eating or 

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2 hours after eating (fasting).  Talazoparib capsules should be swallowed whole with a glass of 
water without chewing, dissolving, or opening them. Subjects should not make up missed or 
vomited doses; dosing should resume on the next calendar day unless otherwise instructed.    
7.2.1 Talazoparib Formulation 
Talazoparib (also known as MDV3800, BMN 673) has the chemical name (8S,9R) 5-fluoro-8-(4-
fluorophenyl)-2,7,8,9-tetrahydro-9-(1-methyl-1H-1,2,4-triazol-5-yl)-3H-pyrido[4,3,2-
de]phthalazin-3-one (provided as the 4 methylbenzenesulfonate [tosylate] salt). The drug 
substance is formulated with silicified microcrystalline cellulose.  The product will be provided as 
powder filled, hard gelatin capsules containing talazoparib in strengths of 1.0 mg and 0.25 mg. 
The capsules for each dose strength will be provided in dose specific colors. Additional details 
will be provided in a pharmacy binder.   
7.2.2 Talazoparib Handling and Storage Conditions 
Talazoparib should be securely stored at room temperature.  Protect from light and do not freeze.  
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 (Goodin, et al., 2011). Subjects should be 
advised that oral anticancer agents are toxic substances and that other caregivers should always 
use gloves when handling the capsules. 
7.3   
Study Drug Dispensation 
Study drugs are to be dispensed in the study clinic on a cycle-by-cycle basis, at Day 1 of each 28 
day cycle.  Additional drug supplies may be dispensed mid-cycle to cover the needs due to any 
dose modifications.  Quantities dispensed on Day 1 of each cycle should cover the needs for 28 
days of daily dosing, plus supplies for an extra 1-3 days of dosing should a patient need to delay 
their visit to start the next cycle.   
 
NOTE:  During the COVID-19 pandemic, drug supplies may be dispensed (shipped by courier) 
by the study clinic’s pharmacy directly to the study patient’s home. Upon deliver, a signature of 
receipt by the patient is required.  A copy of the signed receipt is to retained and returned to the 
study clinic (by either scan/email or held and returned at the time the patient returns for their  next 
visit).  In addition, at the time of receipt, the patient is to complete a form acknowledging the 
number of bottles received and the condition in which they were received.  The acknowledgement 
form should also be scanned/emailed to the clinic or returned by the patient at their next visit.  The 
pharmacy/clinic staff are to follow-up by phone call within 2 days of the drug shipment to ensure 
the patient received drug supplies.   
   
7.4    
Study Drug Accountability 
The Investigator, pharmacist or qualified designee is responsible for making an inventory of study 
drug (both ZEN003694 and talazoparib) upon receipt.  All used and unused study drug must be 
retained until final reconciliation or as indicated by the Sponsor.  The study drug is to be 
administered/dispensed by the Investigator or appropriately qualified site personnel named on the 
delegation of authority log.  Under no circumstances will the Investigator allow the study drug to 
be used other than as directed by this protocol.  Although appropriate personnel may be designated 

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to administer/dispense drug and maintain drug accountability records, the Investigator is ultimately 
responsible for all drug accountability. 
The Investigator or designee must maintain accurate records of the receipt, disposition and return 
of study drug (ZEN003694 and talazoparib).  Documentation of drug disposition/return should 
identify the patient receiving the study drug, the quantities (by dosage strength) of study drug 
dispensed/returned and dates study drug were dispensed/returned/destroyed.  This documentation 
is required in addition to drug accountability information recorded on case report forms (CRFs).  
A copy of the reconciled drug inventory record will be provided to the Sponsor or its designee, 
and the study site will retain the original record.  A written explanation must be provided for any 
discrepancies. 
The Sponsor’s representatives will authorize the return or destruction of all used, partially used, 
and unused bottles of study drug.  If the study site is capable of destroying study drug it may do 
so upon authorization by the Sponsor.  Records will include date of destruction or return, and 
quantities destroyed or returned to the Sponsor or its designee.  Detailed instructions on study drug 
accountability will be provided in a study reference manual. 
7.5  
Treatment Compliance 
Trained study personnel will dispense ZEN003694 and talazoparib and will instruct patients to 
take their study medication at least 1 hour before eating or 2 hours after eating (fasting).  Treatment 
compliance will be monitored by the review of the patient’s dosing diary and drug accountability 
records.  Study treatment administration data will be recorded in the patient’s medical record and 
on the Drug Administration CRFs. 
 

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8. 
STUDY TREATMENT GUIDELINES 
8.1  
Guidelines for Management of Treatment-Related Toxicity  
In Part 1 (dose escalation), dose holds of ZEN003694 and talazoparib are  allowed in Cycle 1.  If 
a dose hold is indicated for the management of a treatment related toxicity to ZEN003694 and/or 
talazoparib, both ZEN003694 and talazoparib doses are to be held.  In Cycle 1 of the dose 
escalation phase, dose reduction of ZEN003694 is not allowed; however the dose of talazoparib 
may be  reduced from the initial 1.0 mg dose in 0.25 mg increments in accordance with the 
talazoparib label and by agreement with Zenith.  For guidance regarding drug-related toxicities 
that qualify as a DLT in Cycle 1 of the dose escalation phase of the study, refer to Section 5.1.2.   
In Part 1, beyond Cycle 1 and at any time in Part 2 (Simon 2-stage) or in the Expansion phase, 
dose holds or dose reductions are allowed for both ZEN003694 and talazoparib.  Intra-patient dose 
reductions of talazoparib are allowed in 0.25mg increments.  Intra-patient dose reductions of 
ZEN003694 are allowed in 12mg to 24mg increments.  All dose reductions should be based on 
prior approval by the Sponsor.  Dose holds and reductions are to be managed by the guidelines set 
forth in Sections 8.2 and 8.3.   
8.2  
Management of Selected Talazoparib-Related Toxicities  
For toxicities of anemia, neutropenia and abnormal liver tests (regardless of severity), the dose of 
talazoparib should be held and/or reduced prior to holding or making any changes in the dosing of 
ZEN003694.  If these toxicities are not managed by a talazoparib dose hold or reduction, the dosing 
of ZEN003694 can be held and/or modified with Zenith’s approval.   
 
For Grade 3/4 anemia, neutropenia, abnormal liver tests, thrombocytopenia and clinically 
significant laboratory events, the dosing of talazoparib and ZEN003694 should follow the 
guidelines outlined in Table 6.  Prior to making any changes in dosing, the Investigator is to obtain 
agreement by the Sponsor.  For Grade 1/2 anemia, neutropenia and abnormal liver tests, no dose 
reductions are required however, should the Investigator elect to hold dosing, the dose of 
talazoparib should be held first prior to holding ZEN003694 dosing.   
     
For the management of all other treatment related toxicities (except Grade3/4 anemia, neutropenia 
and abnormal liver tests), the guidelines outlined in Table 7 should be followed.  If a dose hold is 
indicated, the doses of both talazoparib and ZEN003694 are to be held.  If a dose modification is 
indicated, doses of talazoparib and/or ZEN003694 may be modified (except in Cycle 1 of dose 
escalation) based upon the Sponsor’s approval.   
 
Table 6:  Management of Selected Grade 3/4 Talazoparib-related Toxicities 
 
Selected Toxicity 
Talazoparib and ZEN003694 management 
Grade 3 or 4 Anemia (hemoglobin < 8.0 g/dL)  
Hold talazoparib only and implement supportive 
care per local guidelines. Monitor weekly until 
hemoglobin returns to 9 g/dL or better, then 
resume talazoparib at a reduced dose.  

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• 
If anemia with hemaglobin < 8.0 g/dL 
recurs after dose reduction, hold 
talazoparib and implement supportive care 
per local guidelines.  ZEN003694 may 
also be held with agreement by the 
Sponsor.  Monitor weekly until 
hemoglobin returns to 9.0 g/dL (Day 1), 
then resume talazoparib at a further 
reduced dose.  The dose of ZEN003694 
may also be modified with agreement by 
the Sponsor. 
• 
If anemia persists for >4 weeks without 
recovery of hemoglobin to at least 9.0 
g/dL despite supportive care measures at 
any dose level, discontinue talazoparib 
and ZEN003694 and consider referral to a 
hematologist. 
Transfusions and other supportive measures are 
permitted to support management of 
hematological toxicities at any occurrence. 
Grade 3 or 4 Neutropenia (ANC < 1000/μL)  
Hold talazoparib only and implement supportive 
care per local guidelines.  Monitor weekly until 
ANC ≥1500/µL, then resume talazoparib at a 
reduced dose.  
• 
If neutropenia recurs after the dose 
reduction, hold talazoparib and implement 
supportive care per local 
guidelines.  ZEN003694 may also be held 
with agreement by the Sponsor.  Monitor 
weekly until ANC ≥1500/µL, then resume 
talazoparib at a further reduced dose.  The 
dose of ZEN003694 may also be modified 
with agreement by the Sponsor.   
• 
If neutropenia persists for >4 weeks 
without recovery to ≥1500/μL at any dose 
level despite supportive care measures, 
discontinue talazoparib and ZEN003694 
and consider a referral to a hematologist. 
G-CSF and GM-CSF may be used at investigators 
discretion for the supportive treatment of 
neutropenia at any occurrence. 
 
Grade 3 or 4 Thrombocytopenia  
(platelets < 50,000/μL)  
Hold talazoparib and ZEN003694 and implement 
supportive care per local guidelines.  Monitor 
weekly until platelets ≥75,000/μL, then resume 
talazoparib at a reduced dose.  Resume 
ZEN003694 at the same or reduced dose with 
agreement by the Sponsor.  Note:  If platelet 

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counts are increasing but have not fully recovered 
to at least 75,000/μL, dosing may be restarted 
based on discussion and approval by the Sponsor. 
• 
If thrombocytopenia (<50,000/μL) recurs 
after one dose reduction, hold talazoparib 
and ZEN003694 and implement 
supportive care per local 
guidelines.  Monitor weekly until platelets 
≥75,000/µL, then resume talazoparib and 
ZEN003694 at the same dose or, with 
agreement by Zenith, at a reduced dose. 
• 
If thrombocytopenia persists for >4 weeks 
without recovery to ≥ 50,000/μL despite 
supportive care measures, discontinue 
talazoparib and ZEN003694 and consider 
a referral to a hematologist. 
Thrombopoietin 
analogues 
and/or 
platelet 
transfusions may be used at investigators discretion 
for the supportive treatment of thrombocytopenia 
at any occurrence. 
Grade 3 or 4 Laboratory events determined to 
be clinically significant, except for: 
a)  Grade 3/4 Liver, Anemia, Neutropenia, or 
Thrombocytopenia (as listed in this table); and 
b)  Grade 3/4 amylase or lipase elevations that are 
not associated with manifestations of pancreatitis 
Hold talazoparib and ZEN003694 for any Grade ≥ 
3 laboratory events. If after a 14 day hold the 
toxicity has resolved to a Grade ≤ 1 (or to a 
baseline grade level) resume talazoparib at a 
reduced level per the talazoparib dosing label and 
at a reduced level of ZEN003694 with agreement 
by the Sponsor.    
 
If laboratory abnormality does not resolve to 
Grade ≤ 1 after 14 days, both talazoparib and 
ZEN003694 are to be permanently discontinued 
 
All Grade 3/4 amylase or lipase elevations should 
be discussed with the Sponsor’s Medical Monitor. 
  
 
Grade 3 or 4 Abnormal Liver tests 
Hold talazoparib alone if any of the following 
occur: 
• 
Subjects who develop AST or ALT > 5 x 
ULN (without TBili >2 x ULN) OR 
• 
Subjects with baseline total bilirubin ≤1.5 
x ULN who subsequently present with > 3 
x ULN OR 
• 
Subjects with baseline total bilirubin > 1.5 
x ULN and ≤ 3 x ULN (e.g., Gilberts) 
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If abnormalities resolve to baseline values within 
2 weeks, there are no signs of drug-induced liver 
injury, and none of the permanent discontinuation 
criteria are met (listed below), then upon 
discussion with the Sponsor, the investigator may 
resume talazoparib at a reduced dose level.   
 
Criteria for Permanent Discontinuation of 
Both Study Drugs in Association with Liver 
Test Abnormalities if any of the following 
occur: 
 
• 
Subjects who develop with AST OR ALT 
values >3 × ULN AND a Tbili value >2 × 
ULN  
• 
Subjects with AST/ALT >5 × ULN that 
persists for more than 7 days (AST/ALT 
>8 × ULN for subjects with hepatic 
involvement). 
• 
Subjects with AST/ALT >20 × ULN that 
persists for longer than 3 days 
• 
Subjects with Tbili >3 × ULN that persists 
for longer than 7 days (>5 × ULN for 
subjects with Gilbert’s disease). 
 
 
8.3  
Management Guidelines for All Other Toxicities (not listed in Section 8.2, 
Table 6) 
 
For all other treatment related toxicities not listed in Table 6, dose holds and reductions of both 
talazoparib and ZEN003694 should be managed according the guidelines in Table 7. If a toxicity 
requires a dose hold, the doses of both talazoparib and ZEN003694 are to be held.  If a dose change 
is required, the next lower dose of both or either talazoparib and ZEN003694 should be discussed 
and approved by the Sponsor. 

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Table 7:  Guidelines for Dose Holds and Dose Reductions of both Talazoparib and 
ZEN003694 
Event 
Other Toxicities (not listed in Section 8.2, Table 6)* 
 
Grade 1  
No change 
Grade 2 
No change required; but a dose hold of both ZEN003694 and talazoparib for Grade 
2 laboratory toxicity or a laboratory trend of concern is allowed based on 
Investigator discretion. 
 
For dose holds due to Grade 2 anemia, neutropenia or abnormal liver tests:  hold 
talazoparib dosing first prior to holding ZEN003694 dosing. 
 
In cases where doses are held, if toxicity or trend is reduced to a Grade 1 within 14 
days*, treatments will resume at the original dose level for the first event, and at 
the next lower dose level for a subsequent event, with mutual agreement between 
the Investigator and the Sponsor.   
Grade 3 
Hold both ZEN003694 and talazoparib treatments.   
 
If toxicity (except for those noted in Table 6) resolves to baseline or Grade 1 
within 14 days*, resume treatments and reduce the dose of both ZEN003694 and 
talazoparib by one dose level (except in Cycle 1 of dose escalation).  If toxicity has 
not resolved to at least a Grade 1 toxicity within 14 days of a dose hold, 
permanently discontinue talazoparib and ZEN003694.   
 
 
Grade 4 
Hold both ZEN003694 and talazoparib treatments.   
 
Except for toxicities noted in Table 6; if toxicity is resolved to Grade ≤ 1 within 
14 days*, resume treatments at one dose level below (except in Cycle 1 of dose 
escalation ) with mutual agreement between the Investigator and Sponsor. 
 
If toxicity has not resolved to a Grade ≤ 1 within 14 days of a dose hold 
permanently discontinue talazoparib and ZEN003694. 
* Dose interruption caused by any toxicities lasting longer than 14 days (hematologic or non-
hematologic toxicity) will result in study drug discontinuation of both ZEN003694 and talazoparib.   
8.4  
Intra-Patient Dose Escalation in Part 2, Simon 2-Stage 
For patients enrolled in Part 2 of the study (Simon 2-Stage), intra-patient dose escalations are 
allowed based upon agreement between the Investigator and the Sponsor.  Dose escalation up to 
a maximum of 48mg ZEN003694 and/or 1.0mg Talazoparib will be allowed only after 
tolerability and laboratory results have been shown to be stable for 2 cycles.   
 

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8.5  
Concomitant Medications and Therapies 
8.5.1 Prohibited Concomitant Medications and Therapies  
ZEN003694 is primarily metabolized by CYP3A4.  Therefore, strong inhibitors and inducers of 
CYP3A4 must be excluded during ZEN003694 administration.  
 
  
 
substrates of CYP1A2 with narrow therapeutic ranges must be avoided.  
If use of a strong CYP3A4 inhibitor or inducer, or CYP1A2 substrate with a narrow therapeutic 
range cannot be avoided, then the patient must discontinue the study. 
Use of moderate CYP3A4 inhibitors and inducers or significant CYP1A2 substrates will be 
determined on a case-by-case basis at the discretion of the Investigator and with approval from the 
Sponsor.  
A list of CYP3A4 inhibitors and inducers and CYP1A2 substrates that should be avoided are listed 
in Table 8.  This list is not comprehensive; when considering use of a medication that could be a 
potential CYP3A4 inhibitor or inducer or CYP1A2 substrate, the Investigator should consult with 
the Sponsor. 
 
In addition, Table 8 contains a list of strong P-gp inhibitors that should be avoided during 
concomitant treatment with talazoparib.  Strong P-gp inhibitors are defined as the P-gp inhibitors 
that result in ≥ 2-fold increase in the exposure of an in vivo probe P-gp substrate according to the 
University of Washington Drug-Drug Interaction database (https://www.druginteractioninfo.org) 
 

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Table 8:  Inhibitors and Inducers of Relevant Drug-metabolizing Enzymes 
Category 
Inhibitors 
of CYP3A4 
(May increase 
ZEN003694 
exposure) 
Inducers 
of CYP3A4 
(May decrease 
ZEN003694 
exposure) 
Substrates 
of CYP1A2* 
 
 
 
 
Inhibitors  
of P-gp 
AVOID 
boceprevir 
clarithromycin 
conivaptan 
grapefruit juice 
indinavir 
itraconazole 
ketoconazole  
lopinavir/ 
ritonavir 
mibefradil 
nefazodone 
nelfinavir 
posaconazole 
ritonavir  
saquinavir 
telaprevir 
telithromycin 
voriconazole 
avasimibe 
rifampin 
St. John’s wort 
 
ramelteon 
tizanidine 
theophylline 
amiodarone 
carvedilol 
clarithromycin 
cobicistat 
dronedarone 
erythromycin 
glecaprevir/ 
pibrentasvir 
 indinavir 
itraconazole 
ketoconazole 
lapatinib  
lopinavir 
propafenone 
quinidine 
ranolazine 
ritonavir 
saquinavir 
sofosbuvir/ 
velpatasvir/voxi-
laprevir 
telaprevir 
tipranavir 
valspodar 
verapamil 
Source:   http://www fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/  
ucm093664.htm  
*NOTE:  Exposure to the following substrates of CYP1A2 
 
associated toxicity should be closely monitored:  alosetron, duloxetine, melatonin, tacrine  
 
Caution should be used for coadministration of other P-gp inhibitors: (e.g., atorvastatin, 
azithromycin, conivaptan, diltiazem, diosmin, eliglustat, felodipine, flibanserin, fluvoxamine, 
piperine, quercetin, and schisandra chinensis extract) and BCRP inhibitors (curcumin, 
cyclosporine, elacridar [GF120918]). 
Any CYP3A4 inhibitors or inducers; CYP1A2 substrates; P-gp inhibitors or inducers; or BCRP 
inhibitors taken by the patient during the study period must be documented in the patient’s chart 
and on the Concomitant Medications CRF.  If the Sponsor’s approval is not obtained prior to 
administration of these medications, the patient may be withdrawn from the study by the Sponsor. 
Because of the known risk of QT/QTc prolongation from 5-hydroxytryptamine type 3 (5-HT3) 

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receptor anti-emetics, 5-HT3 receptor antagonist antiemetic drugs should be used with Investigator 
discretion, if alternative drugs are not available.  Dolasetron should be avoided, as the prolongation 
of QTc may be greater with this drug based upon American Society of Clinical Oncology (ASCO) 
guidelines (Basch, et al., 2011). To date, ZEN003694 has shown no evidence of QT prolongation, 
suggesting that drugs such as 5-HT3 antagonists may be safely used concomitantly where indicated 
by the Investigator's clinical judgment. 
Concomitant endocrine-based therapies for breast cancer are prohibited in this study.  
Therapeutic anticoagulation with warfarin, apixaban, or other anti-factor agents (Factor Xa 
inhibitors and Factor IIa inhibitors) are not permitted (i.e., rivaroxaban, apixaban, betrixaban, 
edoxaban otamixaban, letaxaban, eribaxaban, dabigaran).  Low-dose warfarin for maintenance of 
port patency or prophylactic anti-platelet agents are allowed. 
During the study, other chemotherapy, immunotherapy, radiation (except, if ≤ 5 fractions for 
palliative care of solitary lesions), bone-targeting radionuclides, or surgery are also prohibited.   
8.5.2 Permitted Concomitant Medications and Therapies 
Use of corticosteroids is allowed up to a daily dose of 10 mg prednisone or equivalent provided 
that the dose has been stable for at least 2 weeks prior to the start of ZEN003694 dosing and will 
remain stable during ZEN003694 treatment. 
Treatment with anti-emetic therapy will be permitted, if clinically indicated.  Based on experience 
in previous ZEN003694 trials, Investigators are instructed to prescribe prophylactic use of anti-
emetics for any possible GI intolerance and instruct patients to maintain adequate hydration during 
the course of treatment.  Patients should be provided ‘filled’ prescriptions for an anti-emetic, if 
possible, or ensure patients fill their prescriptions of an anti-emetic on the first day of dosing 
(C1D1).   
Treatment with filgrastim or other colony stimulating factors will be permitted for Grade 3 or 
higher hematologic toxicity as per Package Insert, but may not be used prophylactically.  Patients 
should receive full supportive care, including hematopoietic growth factors based upon ASCO 
guidelines (Smith, et al., 2015), if clinically indicated.  
Treatment required for care of complications/adverse events arising from the cancer and/or 
treatment will be permitted. All concomitant medications must be recorded on the Concomitant 
Medications CRF. 
 

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9.  
STUDY VISIT PROCEDURES AND ASSESSMENTS 
The Schedule of Assessments (Table 1) provides an overview of the timeline when clinic visits 
and assessments are to be performed during the course of the study.  This section provides a 
detailed description of required evaluations and assessments during each scheduled study visit.     
9.1  
Study Procedures by Visit 
All scheduled study visits are to occur within ± 3 days of the specified dates outlined in Table 1.  
All visits are to be scheduled relative to Cycle 1 Day 1 regardless if a intervening scheduled visit 
is missed or rescheduled, or if doses were held or missed.  All assessments and sample collections 
required during a specific study visit are to be performed prior to study drug administration to be 
given in the clinic, unless otherwise specified. 
NOTE:  During the COVID-19 pandemic, the following prospective deviations are allowed for 
the non-assessment of the following, only if a patient is unable to attend an in-clinic visit:  physical 
examinations, vital signs, weight, ECOG, PK blood draws, PD blood draws, and biopsies.  In-
clinic visits are mandatory at Cycle 1, Days 1 and 15; and on Day 1 of all Cycles.   
 
9.1.1 Screening Visit  
All screening tests must be performed within 28 days before the first day of treatment (Cycle 1, 
Day 1).  The informed consent form (ICF) must be signed before screening procedures are 
performed (see Section 9.2.1).  
Screening will include: 
• Collection of information on status of inclusion and exclusion criteria (see Section 9.2.2) 
• Complete medical history, including cancer history, prior cancer-related surgery and 
treatments, and demographic history (see Section 9.2.3) 
• Listing of all medications taken within 21 days of enrollment and any ongoing medications 
• Physical examination including height (cm) and weight (kg) (see Sections 9.2.4 and 9.2.5) 
• ECOG performance status (see Section 9.2.6 and Appendix 1) 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate) (see Section 9.2.7) 
• Hematology (see Section 9.2.8)  
• Coagulation tests (see Section 9.2.8)   
• Serum chemistries (see Section 9.2.8) 
• Calculated creatinine clearance (see Section 9.2.8) 
• Serum or urine pregnancy test (see Section 9.2.8) 

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• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory. (see Section 9.2.8)  
• HIV/HBV/HCV test (China only) 
• 12-lead ECG:  triplicate ECGs if QTc > 500msec (see Section 9.2.9) 
 
 
 
 
• Quality of Life: QLQ-C30 and QLQ-BR23 completion by patient  
• Fresh tumor biopsy samples (US and EU only), archival tumor slides (US and EU only) 
(see Section 9.2.11). The screening biopsy may be performed up to 6 weeks prior to the 
first dose of study drug.   
• Tumor assessment (see Section 9.2.15)  Imaging for tumor assessments must be performed 
within 4 weeks of the first dose of study drug (C1D1) 
• Parts 1 and 2 Germline BRCA1/2 mutation assessment:  For patients who have prior 
documentation of gBRCA mutation status, a blood sample for gBRCA testing is not 
required to be collected nor shipped to Myriad Genetics. If prior testing of gBRCA status 
has not been performed, either a blood sample can be collected and shipped to Myriad 
Genetics or if your Institution has a qualified NGS testing panel a blood sample may be 
tested using your platform.  Reports showing the panel of genes tested to establish 
BRCA1/2 mutation status are to be provided to the Sponsor.   
• In EXPANSION Cohort A only:  Germline BRCA1/2 mutation status: If no prior 
documentation of BRCA1/2 mutation status is known, a sample will be collected and sent 
by ambient shipping to Myriad genetics for BRACAnalysis CDx. If prior documentation 
of BRCA1/2 mutation status by BRACAnalysis CDx performed by Myriad Genetics is not 
available, a screening blood sample will be collected and frozen and stored for 
retrospective analysis at Myriad Genetics. For patients who have prior documentation of 
BRCA mutation status by BRACAnalysis CDx, a blood sample for possible retrospective 
BRCA germline testing should NOT be collected.  
• In EXPANSION Cohort B and C: Germline BRCA1/2 mutation assessment:  For 
patients who have prior documentation of gBRCA mutation status, a blood sample for 
gBRCA testing is not required to be collected. If prior testing of gBRCA status has not 
been performed, either a blood sample can be collected and shipped to Myriad Genetics or 
another equivalent test may be performed.  Reports showing the panel of genes tested to 
establish BRCA1/2 mutation status are to be provided to the Sponsor.    
•  
9.1.2 Cycle 1  
Day 1 (Pre-dose) 
• Symptom-directed physical examination and weight 

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• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Coagulation tests 
• Serum chemistries 
• Urine pregnancy test (see Section 9.2.8) 
• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory.  (see Section 9.2.8) 
• 12-lead ECG:  triplicate ECGs if QTc > 500msec 
• PK sample for ZEN003694/ZEN003791 (see Section 9.2.10) (in Part 1 only)   
• PD samples for whole blood BET inhibitor and PARP inhibitor PD marker expression (in 
Part 1 only) (see Section 9.2.11) 
• PD samples: in whole blood for ctDNA (US and EU sites only):  samples will be banked 
for possible future analysis (see Section 9.2.11) 
• AEs 
 
 
• Quality of Life: QLQ-C30 and QLQ-BR23 completion by patient 
• Concomitant medications  
Day 1 (Dosing) 
• ZEN003694 and talazoparib at least 1 hour before eating or 2 hours after eating 
Day 1 (Post-dose) 
• PK samples for ZEN003694/ZEN003791: (in Part 1 only)  
o 15 minutes (±5 min), 30 minutes (±5 min), 1 hour (±5 min), 2 hours (±10 min), 4 hours 
(±15 min), 6 hours (±15 min) and 8 hours (±30 min) post-ZEN003694 and talazoparib 
doses  
• PD samples:  whole blood for BET inhibitor and PARP inhibitor PD marker expression 
(Part 1 only) at 2 hours (±15 min), 4 hours (±15 min), and 6 hours (±15 min) and 8 hours 
(±15 min) post- ZEN003694 and talazoparib doses (Part 1 only)  
 

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• AEs 
• Concomitant medications 
Days 2 – 28 (Dosing) 
• ZEN003694 and talazoparib daily at least 1 hour before eating or 2 hours after eating 
Note:  Instruct patients not to take study drug and talazoparib before their clinic visits on 
Days 8, 15 and 22. 
Day 8 (Pre-dose):  During the COVID-19 pandemic, this visit may be performed as a 
telephone visit 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Serum chemistries 
• Fresh tumor biopsy:  In Parts 1 and 2, to be collected on C1D8, C1D9 or C1D10 if the 
biopsy is from a palpable lesion (or from other lesions, at the Investigator’s discretion). In 
the Expansion phase, biopsies are to be collected between C1D8 and C1D14, or within 
±14 days of the C3D1 visit (if biopsy was not collected in Cycle 1).  If tumor is accessible, 
biopsies are mandatory in the US and EU. The biopsy should be collected 2-4 hours after 
ZEN003694 dosing, if possible (see Section 9.2.11); and should be collected from the same 
tissue location as the screening biopsy, if possible.  The dosing date and time of the dose 
taken just prior to the biopsy is to be recorded. 
• AEs 
• Concomitant medications  
Day 15 (Pre-dose) 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology  
• Coagulation tests 
• Serum chemistries 

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• PK sample for ZEN003694/ZEN003791 (Part 1 only) 
• PK sample for talazoparib (Part 1 only):  (Pre-dose sample collection should be at least 20 
hours after the previous dose of talazoparib.  Instruct patients to not take their study drugs 
in the morning before their clinic visit.) 
o The PK collection date, exact collection time, study drug doses taken and dosing 
time for both study drugs are to be recorded in source documents and in the eCRF. 
o On the day prior to the C1D15 PK collections, the date, dosing time and study drug 
doses taken and dosing time for both study drugs are to be recorded in source 
documents and in the eCRF. 
o In the event the C1D15 pre-dose PK samples cannot be collected (or is not 
collected), ‘makeup samples’ should be collected on a later date using the same 
criteria 
• AEs 
• Concomitant medications  
Day 22 (Pre-dose):  If intermittent dosing is implemented and/or if there is a need to change the 
cycle duration from 28 days to 21 days, the Day 22 assessments will not be required.  During the 
COVID-19 pandemic, this visit may be performed as a telephone visit 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Serum chemistries 
• AEs 
• Concomitant medications  
9.1.3 Cycle 2  
Day 1 (Pre-dose) 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 

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• Coagulation tests 
• Serum chemistries 
• Urine pregnancy test: serum pregnancy test will be required if the urine pregnancy test is 
positive (see Section 9.2.8) 
• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory.  (see Section 9.2.8) 
• 12-lead ECG:  triplicate ECGs if QTc > 500msec 
• PK sample for ZEN003694/ZEN003791 
• PK sample for talazoparib (Parts 1 and 2, and Expansion Cohorts A and C):  (Pre-dose 
sample collection should be at least 20 hours after the previous dose of talazoparib.  Instruct 
patients to not take their study drugs in the morning before their clinic visit.) 
o The PK collection date, exact collection time, study drug doses taken and dosing 
time for both study drugs are to be recorded in source documents and in the eCRF. 
o On the day prior to the C2D1 PK collections, the date, dosing time and study drug 
doses taken and dosing time for both study drugs are to be recorded in source 
documents and in the eCRF. 
o In the event the C2D1 pre-dose PK samples cannot be collected (or is not collected), 
‘makeup samples’ should be collected on a later date using the same criteria 
• AEs 
 
 
• Quality of Life:  QLQ-C30 and QLQ-BR23 completion by patient 
• Concomitant medications 
Day 1 (Post-dose) 
• PK samples for ZEN003694/ZEN003791:   
o 1 hour (±5 min), 2 hours (±10 min) and 4 hours (±15 min) post-ZEN003694 and 
talazoparib doses   
Days 1 – 28 (Dosing) 
• ZEN003694 dosing and talazoparib daily at least 1 hour before eating or 2 hours after 
eating 
Note:  Instruct patients to not take study drug and talazoparib before their clinic visit on 
Day 15. 

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Day 8 (The Cycle 2, Day 8 visit will only include blood draws for safety laboratory testing 
and may be drawn in the morning after the patient has taken his/her dose.  Testing may be  
drawn at a laboratory local to the patient’s home) 
• Hematology 
• Serum chemistries 
Day 15 (Pre-dose): During the COVID-19 pandemic, this visit may be performed as a 
telephone visit 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Serum chemistries 
• PK sample for ZEN003694/ZEN003791 
• PK sample for talazoparib (Parts 1 and 2, and Expansion Cohorts A and C): (Pre-dose 
sample collection should be at least 20 hours after the previous dose of talazoparib.  Instruct 
patients to not take their study drugs in the morning before their clinic visit.) 
o The PK collection date, exact collection time, study drug doses taken and dosing 
time for both study drugs are to be recorded in source documents and in the eCRF. 
o On the day prior to the C2D15 PK collections, the date, dosing time and study drug 
doses taken and dosing time for both study drugs are to be recorded in source 
documents and in the eCRF. 
o In the event the C2D15 pre-dose PK samples cannot be collected (or is not 
collected), ‘makeup samples’ should be collected on a later date using the same 
criteria. 
• Tumor assessments (RECIST):  Expansion only:  at Cycle 2 Day 15 (± 7 days) 
• AEs 
• Concomitant medications  
 
 

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Day 22 (The Cycle 2, Day 22 visit will only include blood draws for safety laboratory testing 
and may be drawn in the morning after the patient has taken his/her dose.  Testing may be  
drawn at a laboratory local to the patient’s home).  If intermittent dosing is implemented 
and/or if there is a need to change the cycle duration from 28 days to 21 days, the Day 22 
assessments will not be required. 
• Hematology 
• Serum chemistries 
9.1.4 Cycles 3 and onward  
Day 1 (Pre-dose, ± 3 days unless otherwise stated) 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Coagulation tests 
• Serum chemistries 
• Urine pregnancy test:  serum pregnancy test will be required if the urine pregnancy test is 
positive (see Section 9.2.8)  
• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory.  (see Section 9.2.8) 
• 12-lead ECG:  (at Cycle 3 and every 2 cycles)  triplicate ECGs if QTc > 500msec 
• Tumor assessments (RECIST v1.1):  Parts 1 and 2 only: (at Cycle 3 Day 1 and every 2 
cycles; ± 7 days) 
• Tumor assessments (RECIST v1.1):  Expansion only:  Every 6 weeks (± 7 days):  at Day 
15 in Cycles 2, 5, 8, 11, 14, 17, 20, etc.; and at Day 1 in Cycles 4, 7, 10, 13, 16, 19, etc. 
• PD samples:  whole blood for ctDNA (at Cycle 3 only for possible future analysis)  (US 
and EU sites only) 
• Fresh tumor biopsy samples from US and EU patients only(at Cycle 3 only; ± 14 days; if 
not collected at Cycle 1, Days 8-14) should be collected 2-4 hours after ZEN003694 dosing, 
if possible (see Section 9.2.11), and should be collected from the same tissue location as 
the screening biopsy, if possible. 
• AEs 

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• Quality of Life:  QLQ-C30 and QLQ-BR23 completion by patient 
• Concomitant medications  
Days 1 – 28 (Dosing) 
• ZEN003694 and talazoparib at least 1 hour before eating or 2 hours after eating 
Note:  Instruct patients not to take ZEN003694 and talazoparib before their clinic visit on 
Day 1 of each cycle. 
Day 15 (For Cycles 3 and onwards, the Day 15 visit blood draws for safety laboratory testing 
may be drawn in the morning after the patient has taken their dose.  Testing may be  drawn 
at a laboratory local to the patient’s home).  In Cycle 6 and onward, the Day 15 hematology 
and serum chemistry tests may be waived at the discretion of the Investigator if platelet counts are 
stable and there are no other laboratory concerns. 
• Hematology 
• Serum chemistries 
9.1.5 Unscheduled Visit 
The following assessments and tests are to be performed during an unscheduled visit along with 
any others as clinically indicated:  Other protocol specific tests may be requested and performed 
per Sponsor requirement: 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Serum chemistries 
• Coagulation 
• Urinalysis 
• Quantitative urinary analysis 
• AEs 
• Concomitant medications  
9.1.6 End of Treatment Visit  
The following assessments are to be performed within one week (± 3 days) of discontinuation of 
ZEN003694 treatment:  If a subject’s dose was held and treatment was not resumed after a two 

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week period, the scheduling of the EOT visit from the date of last study drug is extended to 14 
days ±3 days. 
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 
• Serum chemistries 
• Urine pregnancy test:  serum pregnancy test will be required if the urine pregnancy test is 
positive (see Section 9.2.8)  
• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio.  The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory.  (see Section 9.2.8) 
• Tumor assessments (RECIST v1.1): (Only if the EOT visit is > 6 weeks from the time of 
the prior tumor assessment) 
• PD sample:  whole blood for ctCNA (for possible future analysis) (US and EU only) 
 
 
 
• Quality of Life:  QLQ-C30 and QLQ-BR23 completion by patient  
• Fresh tumor biopsy sample (only if possible, at the time of progression) (US and EU only) 
• AEs 
• Concomitant medications  
9.1.7 Safety Follow-up Visit 
The Safety Follow-up visit is to occur 30 days (±3 days) after the End of Treatment visit, or prior 
to beginning a new anti-cancer treatment, whichever occurs first.  If a new cancer therapy is started 
within 7 days following the End of Treatment visit, the Safety Follow-up visit is not required.   
The Safety Follow-up visit is to include the following assessments:  
• Symptom-directed physical examination and weight 
• ECOG performance status 
• Vital signs (temperature [ºF/ºC], blood pressure and heart rate)  
• Hematology 

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• Serum chemistries 
• Urinalysis with quantitative biochemical analyses of urinary protein, albumin and 
creatinine and calculated protein:creatinine ratio and albumin:creatinine ratio. The 
quantitative analysis of glucose will also be required if quantification can be performed by 
the local laboratory.  (see Section 9.2.8) 
• AEs 
• Concomitant medications  
9.1.8 Cross-Over of Expansion Cohort B ZEN003694 Monotherapy Patients 
Patients enrolled in Expansion Cohort B on single agent ZEN003694 who have confirmed 
radiographic progression by RECIST v1.1 criteria will have the choice to cross-over to treatment 
with ZEN003694 in combination with talazoparib.  Patients may cross-over to the combination 
treatment at the time of disease progression but no sooner than after 6 weeks of receiving 
ZEN003694 monotherapy.  Participation in the cross-over phase is optional for these patients. 
To participate in the cross-over phase, patients are required to complete an End of Treatment visit 
for Cohort B monotherapy and sign the cross-over informed consent form.  Once signed, patients 
will be evaluated for eligibility to receive ZEN003694 in combination with talazoparib.  The 
inclusion/exclusion criteria and screening assessments for the cross-over combination treatment 
will be same as those criteria and assessments for patients enrolled in Expansion Cohort B 
(monotherapy).      
The ZEN003694 monotherapy End of Treatment (EOT) visit, the signing of the cross-over 
consent, and the subsequent evaluation of the screening assessments may all be performed on the 
same day.  The EOT visit assessments may be used as the screening assessments for the cross-over 
study.  All screening assessments must be performed and eligibility criteria met within 14 days 
from the date of the EOT visit and the start of cross-over combination treatment at C1D1.  Cross-
over patients will be evaluated for safety and efficacy by protocol assessments as required for all 
patients enrolled in the Expansion cohorts as detailed in Table 1.   
Blinded independent central review of tumor assessments is not required in the cross-over phase 
of the study. Upon discontinuation from the cross-over phase of the study, subjects are required 
to complete End of Treatment and Safety Follow-up visits as set forth in  Table 1. 
 
 
9.2  
Study Assessments 
9.2.1 Informed Consent 
The Investigator or designee must present and explain the study protocol to prospective study 
patients before any study-specific screening procedures are performed.  The ICF presented to the 
patient must be in a language that the patient can read and understand.  Once the patient has had 
an opportunity to read the ICF, the Investigator or designee must be available to answer any 
questions the patient may have regarding the study protocol and procedures.  The Investigator or 
designee must explain that the patient is not obliged to enter the study, and is free to withdraw 

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from it at any time for any reason.  If new safety information becomes available and results in 
significant changes in risk/benefit assessment, the ICF should be reviewed and updated if 
necessary.  Under this circumstance, all patients, including those already being treated, should be 
given the new information, given a copy of the revised ICF, and allowed to re-evaluate their 
consent to continue in the study. 
A copy of the signed and dated ICF will be provided to the patient.  The Investigator will retain 
the original signed ICF. 
9.2.2 Inclusion/Exclusion Criteria 
Review the inclusion/exclusion criteria (Section 6) at the Screening visit to ensure that the patient 
qualifies for the study.  The patient may be enrolled into the study if inclusion criteria are met and 
none of the exclusion criteria are met. 
9.2.3 Medical History and Demographics 
Obtain a complete medical history (significant past and ongoing conditions) including cancer 
history, prior cancer treatments and surgeries, and demographic information at the Screening visit.  
Previous history of allergies/ allergic reactions should also be captured on the Medical History 
eCRF. 
9.2.4 Physical Examination/Symptom-directed Physical Examination 
Physical 
examination 
including 
ears/eyes/nose/throat/neck, 
respiratory, 
cardiovascular, 
gastrointestinal, musculoskeletal, central and peripheral nervous system, and dermatologic 
assessments will be performed at the Screening visit.  A symptom-directed physical examination, 
including evaluation of new symptoms and follow-up findings from previous physical 
examinations, should be performed at each study visit prior to study drug dosing per the Schedule 
of Assessments.  
9.2.5 Height and Weight 
Height (cm) should be recorded only at the Screening visit and weight (kg) measurements should 
be measured per the Schedule of Assessments.  
9.2.6 ECOG Performance Status 
ECOG performance status will be assessed using the criteria described in Appendix 1.  
9.2.7 Vital Signs 
Vital signs include temperature (ºF/ºC), blood pressure and heart rate. 
9.2.8 Laboratory Parameters 
The following laboratory parameters will be performed at the indicated time points in the Schedule 
of Assessments.  The Investigator must evaluate all results outside the reference range and 
determine the clinical significance (clinically significant or not clinically significant) of each 
result.   

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• Hematology:  hemoglobin, hematocrit, red blood cell count, while blood cell count, 
neutrophils (absolute), lymphocytes (absolute), monocytes (absolute), eosinophils 
(absolute), basophil (absolute), mean corpuscular volume and platelet count  
• Coagulation tests: INR or PT and PTT (APTT acceptable). 
• Serum chemistries:  albumin, ALT, AST, alkaline phosphatase, bicarbonate, total bilirubin, 
blood urea nitrogen, urea, calcium, chloride, creatinine, glucose, lactate dehydrogenase 
(LDH), sodium, potassium, phosphorus and magnesium. 
• Urinalysis:  dipstick with micro-analysis if clinically indicated.  From the urine sample 
collected for standard urinalysis assessment, quantitative biochemical analyses of urinary 
protein, albumin and creatinine is required along with the reporting of the protein:creatinine 
ratio and the albumin:creatinine ratio.  The quantitative analysis of glucose will also be 
required if quantification can be performed by the local laboratory. 
• Calculated creatinine:  To be calculated using the Cockcroft-Gault formula. 
• Pregnancy test:  A serum or urine pregnancy test is required at screening in all women of 
child-bearing potential.  A urine pregnancy test is required at timepoints during the study 
as indicated in the Schedule of Assessments.  A serum pregnancy test will be required if 
the urine pregnancy test is positive. 
9.2.9 12-lead ECG 
Twelve-lead ECGs will be obtained at the indicated time points in the protocol and Schedule of 
Assessments.  Triplicate ECGs are to be collected if QTc > 500 msec.  QTc is to be measured 
using the Fridericia correction formula. 
9.2.10 Pharmacokinetic (PK) Sampling 
Plasma samples will be collected to assess the PK properties of ZEN003694, the metabolite 
ZEN003791, and talazoparib at the indicated time points in the protocol (Table 1 and Section 9.1). 
Plasma concentrations will be determined by a validated liquid chromatography-tandem mass 
spectrometry (LC-MS/MS) bioanalytical method.  Samples will be collected as indicated in the 
Schedule of Assessments and the laboratory manual.  Pharmacokinetic sampling details (date, 
dose, dosing time, sample collection times) will be recorded in the eCRF. 
9.2.11 Germline BRCA1/2 Mutation Status and Sampling 
Blood samples may be collected at screening to determine germline BRCA1/2 (gBRCA) mutation 
status at the indicated time points in the protocol, Section 9.1, and the Table 1. The test performed 
prospectively for patients without gBRCA status will be BRACAnalysis CDx performed by 
Myriad Genetics.  If prior testing of gBRCA status has been performed, reports showing the panel 
of genes tested to establish BRCA1/2 mutation status are to be deidentified and provided to the 
Sponsor.    
 

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9.2.12 Pharmacodynamic Sampling  
• Whole blood BETi and PARPi PD marker mRNA expression analysis (Part 1 only):  
Whole blood will be collected in Cycle 1 to measure the effect of talazoparib on PD marker 
mRNA expression of BETi responsive genes.  RNA will be extracted and mRNA 
expression of 5 BETi responsive genes, along with a housekeeping control gene 
(cyclophilin), will be measured using quantitative polymerase chain reaction (qPCR).  
Possible genes to be analyzed are:  
.  Additional 
genes of interest might be individually tested to correlate with ZEN003694 exposure. 
• Whole Blood ctDNA:  Whole blood will be collected from patients to isolate plasma and 
the buffy coat for possible future analysis of ctDNA fraction as well as targeted sequencing 
of the ctDNA for possible correlations with patient’s response and tumor biopsies.   
• Tumor Biopsy:   Metastatic tumor biopsies will be taken with core needle or excisional 
biopsy.  Fine needle aspiration is not allowed.  It is encouraged that 4 core samples be 
collected from a single site with a minimum of 2 core samples collected.  Biopsies should 
not be taken from a recent, prior irradiated site.  The biopsy samples will be either fixed in 
formalin and/or frozen for histological and immunohistochemical (IHC) analyses, and 
RNA and/or DNA sequencing.  Samples collected in Part 1 (dose escalation), Part 2 (Simon 
2-Stage), and Expansion phase will be banked for possible future analyses of exploratory 
biomarkers and DDR genes.  Possible future analyses of  target engagement, changes in 
gene expression and mutation spectrum that correlate with response of patients to identify 
potential biomarkers of response to ZEN003694 and talazoparib.  IHC will be used to 
assess candidate markers of DNA damage response to evaluate the impact of ZEN003694 
to inhibit homologous recombination and induce DNA damage in combination with 
talazoparib. 
 
9.2.13 Adverse Events 
Adverse events will be collected as defined in Sections 11.1, 11.2 and 11.3. 
9.2.14 Concomitant Medications 
All prior cancer-related treatment and procedures will be captured on the CRFs.  All concomitant 
medications (dose and regimen) taken during the course of the study must be recorded on the 
Concomitant Medications CRF.  In addition, any medications taken 21 days prior to enrollment in 
the study should be recorded on the Concomitant Medications CRF. 

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9.2.15 Tumor Assessment – Imaging/Radiologic Evaluation 
Tumor assessments are to be performed according to RECIST Version 1.1 guidelines.  Whole body 
imaging (preferably (and if appropriate) by computed tomography (CT)) with cross-sectional 
imaging of the chest/abdomen/pelvis should be performed in accordance with institutional 
standards.  Use of intravenous contrast is required unless contraindicated.  Magnetic resonance 
imaging (MRI) may be substituted for computed tomography (CT) per the Investigator’s 
discretion. 
Bone scans are to be performed if bone metastases are present at time of entry into the study.   
Note:  To be assigned a status of PR or CR, changes in tumor measurements must be 
confirmed by repeat assessments no less than 4 weeks after the criteria for response are first 
met. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
9.2.17 EORTC Quality of Life 
A validated quality of life questionnaire (EORTC QLQ-C30, Version 3.0) will be used to evaluate 
patient reported outcomes to assess the quality of life of cancer patients.  An additional 
supplemental quality of life questionnaire specific to breast cancer (EORTC QLQ-BR23) will also 
be used to assess specific symptoms related to breast cancer.   
 
 
 

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10. 
WITHDRAWAL OR EARLY TERMINATION OF PATIENTS 
Patients are free to withdraw from study participation at any time for any reason.  Patients may 
discontinue treatment with ZEN003694 and talazoparib either at their request, at the discretion of 
the Investigator for medically indicated reasons or for protocol noncompliance.  Discontinuation 
of one drug (either ZEN003694 or talazoparib) requires the discontinuation of both ZEN003694 
and talazoparib.    
In the event of early termination, the patient should be instructed to report to the clinic as early as 
possible but within 1 week after the decision to terminate from the study has been made or for the 
next scheduled clinic visit.  All End of Treatment visit procedures (see Section 9.1.6) and all Safety 
Follow-up visit procedures (see Section 9.1.7) are to be conducted.  The Investigator shall make 
his or her best efforts to perform these procedures.  The Investigator should make all attempts to 
accurately identify the reason a patient withdrew from the study, while respecting the patient’s 
privacy.  The primary reason for the patient discontinuation should be documented as one of the 
following: 
• Radiographic progression 
• Clinical progression   
• DLT 
• Adverse event  
• Treatment with or need for prohibited concomitant medication 
• Withdrawal by patient 
• Withdrawal by physician 
• Non-compliance 
• Lost to follow-up 
• Death 
 

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11. 
SAFETY ASSESSMENTS 
Safety parameters monitored and recorded during this study include, physical examination 
findings, weight, vital signs, ECOG performance status, ECGs, AEs, laboratory variables 
(hematology, serum chemistries, coagulation tests and urinalysis).    
11.1 
Adverse Event and Suspected Unexpected Serious Adverse Reaction 
Definitions 
11.1.1 Adverse Event 
An AE is any unfavorable or unintended sign, symptom, or disease temporally associated with the 
use of a pharmaceutical product (i.e., study drug), whether or not considered related to the 
pharmaceutical product.   
The recording of AEs will begin at the start of the administration of the first dose of ZEN003694 
and talazoparib.  AEs should record the development of an undesirable medical condition, 
worsening of a pre-existing medical condition and any change in severity (increase or decrease) of 
a previously recorded AE, during or following exposure to study drug, regardless of relationship 
to study drug.  See Section 11.3 for additional information. 
11.1.2 Serious Adverse Event 
A serious adverse event (SAE) is any AE that: 
• Results in death 
• Is life-threatening 
o A life-threatening SAE is any AE that places the patient at immediate risk of death 
from the reaction as it occurred, as assessed by the Investigator.  This definition does 
not include a reaction that might have caused death if it occurred in a more severe form. 
• Requires in-patient hospitalization or prolongs existing hospitalization 
o For the purposes of this protocol, any hospital admission will be considered an in-
patient hospitalization, regardless of duration.  An emergency room visit without 
hospital admission will not be recorded as a SAE under this criterion, nor will 
hospitalizations for a procedure scheduled before study enrollment (first dose of study 
drug) or elective procedures scheduled during the study.  However, unexpected 
complications that occur during elective surgery should be recorded as AEs and 
assessed for seriousness. 
• Results in persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Results in a congenital anomaly or birth defect 
• Is any other important medical event 

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• Other medical events may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention 
to prevent one of the other outcomes in the SAE definition.  Examples include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in hospitalization of the patient, or the 
development of drug dependency or drug abuse.   
11.1.3 Suspected Unexpected Serious Adverse Reaction   
A suspected unexpected serious adverse reaction (SUSAR) is any AE for which there is evidence 
to suggest a causal relationship between the study drug and the AE (e.g., assessed as possibly or 
probably related), and which is both unexpected and serious.  An unexpected adverse reaction (i.e., 
any untoward and unintended response to the study drug) is one for which the nature and severity 
is inconsistent with the applicable reference safety information (e.g., Investigator’s Brochure). 
11.2 
Reporting Serious Adverse Events and Suspected Unexpected Serious 
Adverse Reactions 
Report all SAEs (regardless of drug relatedness) and SUSARs to Drug Safety WITHIN 24 
HOURS of discovery or notification.  Reporting to Drug Safety can be performed by one of two 
methods:  Either complete the SAE eCRF form (preferable method) or record event information 
on the SAE Report Form, and submit the completed form with any other available pertinent 
information (e.g., hospital records, laboratory results, etc.) to Drug Safety (contact information are 
provided in the study reference manual).   
The minimum required information for an initial report is:  
• Reporter’s name and contact information 
• Protocol number 
• Site and patient identification information 
• Event term(s) (with a brief summary of the event[s] and causality assessment) 
If additional follow-up information is required or becomes available for a previously reported SAE 
or SUSAR, the additional information should be entered into the database.  Additional new 
information may also be recorded on a follow-up SAE Report Form and submitted WITHIN 24 
HOURS from the time the additional information was obtained.  
For hospitalizations, all attempts to obtain the hospital record should be documented in the study 
file.  Complete an SAE Report Form with any known information on the hospitalization, however 
minimal, and submit it to Drug Safety (detailed contact information is provided in the study 
reference manual). 
11.2.1 Disease-related Events That Are Endpoints 
For the purposes of this study, progression of the patient’s underlying disease (“disease 
progression”) should generally not be reported as an AE or SAE.  Any ‘symptoms’ of disease 

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progression however should be reported as AEs/SAEs.  If however the Investigator determines 
that there is evidence suggesting a causal relationship between the event and the study medication, 
the event should be immediately reported to Drug Safety and recorded as an AE or SAE. 
Any event that results in death is to be reported as an SAE. Death is an outcome of an adverse 
event and not an adverse event in itself.  The underlying event leading to death is reported as the 
SAE. 
11.3 
Adverse Events 
Events that occur before the first administration of study drug are not considered AEs, by definition 
(Section 11.1.1); record these events on the Medical History CRF.   
The Investigator or a qualified designee will question and examine patients for evidence of AEs.  
Patients should not be asked about specific AEs.  Instead, they should be asked general questions 
(e.g. “How have you been feeling since your last visit?”).  Record all AEs on the AE CRF.  If a 
previously reported AE changes in severity, record the change in the AE severity on the AE CRF. 
For an event to be recorded as an AE, the onset must occur during or after the patient’s first 
exposure to study drug and no later than 30 days after the last study drug dose.  However, there is 
no limit on reporting SAEs considered reasonably related to ZEN003694.  Immediately report all 
SAEs and deaths to Drug Safety (Section 11.2).  This requirement includes deaths within 30 days 
of the last dose of study drug, or before the last formal follow-up contact, whichever occurs later.  
The Investigator should follow all AEs that are considered reasonably related to study drug until 
resolution or stabilization.  All other AEs should be followed until resolution or stabilization or 
until the final visit, whichever occurs first. 
Record syndromes rather than individual signs or symptoms in order to avoid double reporting of 
events and facilitate meaningful interpretation of data.  For example, a patient presenting with 
rhinitis, fever, and headache should be reported as having “flu-like symptoms,” without 
independently recording each accompanying sign.  When no clearly recognizable clinical 
syndrome can be described, record individual clinical signs and symptoms. 
All AEs that occur during the study should be treated appropriately to protect and ensure the 
patient’s well-being.  If such treatment constitutes a deviation from this protocol, Drug Safety must 
be notified and the Investigator should comply with applicable Ethics Committee (EC) or 
Institutional Review Board (IRB) reporting requirements. 
The Investigator is responsible for determining whether or not an AE is severe enough to require 
the patient’s removal from treatment.  A patient may also voluntarily withdraw from treatment 
because of an AE.  If either occurs, the patient must receive appropriate medical care, and the 
Investigator must strongly encourage the patient to return to the study site for the final protocol-
specified visits and assessments, and to continue returning to the study site for follow-up 
evaluations until the AE resolves or stabilizes.  All AEs, serious or not, that result in permanent 
withdrawal from the study treatment should be immediately reported to Drug Safety. 
The Sponsor will conduct reviews of all available AEs approximately once every 3 months.  
During dose escalation, these review timelines may be modified to coincide with enrollment and 

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dose-escalation safety data.  The study sites are to ensure timely entry of AEs on the CRFs to 
facilitate these reviews. 
11.3.1 Commonly reported Study Drug Related Adverse Events 
The most common AEs related to ZEN003694 are visual impairment (typically a transitory 
perception of brighter lights and/or light flashes, with or without visual color tinges, and with no 
functional consequences), nausea, fatigue, decreased appetite, vomiting, creatinine increase, 
platelet decrease, diarrhea, dehydration, decreased weight, dizziness, dysgeusia, and 
thrombocytopenia.  AEs most commonly observed with talazoparib are fatigue, nausea, anemia 
thrombocytopenia, neutropenia, leukopenia, diarrhea, vomiting, headache, alopecia, decreased 
appetite, abdominal pain, dizziness, and weakness.  As the two drugs have overlapping AEs, the 
assessment of relatedness as attributed to either talazoparib alone or ZEN003694 alone may not 
be not be possible and for such cases should be reported as attributable to the combination of 
talazoparib and ZEN003694. 
11.3.2 Classification of Adverse Events by Severity 
The Investigator must categorize the severity of each AE using the NCI CTCAE Version 5.0 (see 
Appendix 2).   
It is important to distinguish between AE seriousness and severity; these terms are not 
interchangeable.  Severity is a measure of intensity whereas seriousness is defined by the criteria 
in Section 11.1.2. 
11.3.3 Classification of Adverse Events by Relationship to Study Drug 
For each AE, the Investigator must decide whether there is a reasonable possibility that the event 
was caused by administration of ZEN003694 (i.e., that the event was a suspected adverse reaction).  
The Investigator should make this decision after careful consideration of the following questions: 
• Does the AE follow a reasonable temporal sequence from administration of study drug? 
• Can the AE be reasonably explained by the known characteristics of the patient’s clinical 
state, environmental or toxic factors, or other therapy? 
• Do the AE symptoms disappear or decrease on cessation of study drug or reduction in study 
drug dose?  (There are exceptions when an AE does not disappear on discontinuation of 
the drug, yet drug relatedness clearly exists [e.g., bone marrow depression, fixed drug 
eruptions, tardive dyskinesia, etc.]). 
• Does the AE reappear or worsen when the study drug is re-administered? 
• Does the AE follow an expected response pattern based on the established pharmacologic 
and toxicologic effects of the study drug? 
• Does the AE follow an expected response pattern based on the known effects of other 
products in the same class? 
For this assessment, the Investigator will classify each AE as one of the following: 

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• Yes, Related: The AE is definitely related or even considered possibly or probably related 
to study drug administration.  
• Not Related: The AE is clearly due to other causes (e.g. concurrent medication, underlying 
disease, etc.). 
11.4 
Abnormal Laboratory Results 
Abnormal laboratory results may occur in the context of an AE that is a clinical syndrome 
(e.g., elevated BUN and creatinine in the setting of an AE of renal failure, or elevated AST/ALT 
in the setting of an AE of hepatitis).  In these cases, do not record the abnormality itself as an AE. 
However, in the absence of an AE that encompasses an observed abnormal laboratory result, report 
the abnormality as an AE if the Investigator judges it to be clinically significant for the patient.  
For the purposes of this study, the criteria for a "clinically significant" abnormal laboratory result 
are any of the following: 
• It leads to DLT 
• It results in any therapeutic intervention 
• It is judged by the Investigator to be of other particular clinical relevance 
11.5 
Overdose 
All study drugs will be administered orally.   
There is no data regarding ZEN003694 or talazoparib overdose in humans.  An overdose and AEs 
should be treated as per standard medical practice. 
Dosing details should be captured on the Study Drug CRF.  If the patient receives a dose of a study 
drug that exceeds protocol specifications and the patient is symptomatic, then the symptom(s) 
should be documented on the AE CRF and on a SAE form as appropriate.  Do not capture the 
event on the AE CRF or SAE form if the patient is not symptomatic. 
Should an overdose occur, the Investigator should also monitor the patient with appropriate blood 
counts and serum chemistry tests and should also provide supportive therapies as necessary. 
11.6 
Pregnancy 
All female patients of childbearing potential are required to consistently and correctly use a highly 
effective form of contraception.  Highly effective forms of contraception include: combined 
(estrogen and progestogen hormonal contraceptives (oral, intravaginal, transdermal) associated 
with inhibition of ovulation; progestogen-only hormonal contraception (oral, injectable, 
implantable) associated with inhibition of ovulation; intrauterine device (IUD); intrauterine 
hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual 
abstinence).  Males with partners of childbearing potential may be enrolled if they use a condom 
when having sex with a pregnant woman or with a non-pregnant female of childbearing potential 
from 21 days before the first dose of study drug through 4 months after the last dose of study drug. 

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Any female patient who becomes pregnant while on study treatment must be withdrawn from the 
study.  If a female partner of a male patient becomes pregnant, the male patient must immediately 
notify the Investigator, and the Investigator must then immediately notify the Sponsor, or designee.  
The female partner must sign an ICF for disclosure of information on the pregnant partner’s and 
baby’s health status.  Information about the pregnancy of any female patient or female partner of 
a male patient will be collected on a pregnancy form for a period of 3 months after the date of 
delivery and will include: demographic data, general health condition, abnormalities and safety 
events. 
11.7 
Study Safety Monitoring and Dose Escalation or Modification 
The Investigator(s) and Sponsor will review safety and available PK data (e.g., Cmax and AUC) for 
each cohort in the dose escalation phase to decide when it is permissible to open a new cohort per 
the study design described in the protocol.  Safety data will include but are not limited to SAEs, 
AEs and laboratory (protocol specified or ad hoc) data, as well as additional information provided 
by the treating Investigators.  Additionally, the accruing safety data for all patients to date will be 
included in the decision making process for dose escalation or modification.  Dose escalation or 
modifications will be allowed in the absence of an unreasonable and significant risk of illness or 
injury to patients.  In addition, the Sponsor will review the study safety data on an ongoing basis.  
An independent specialist may participate in the safety review, if appropriate. 
11.8 
Reporting Safety Information to the Institutional Review Board 
The Sponsor or its designee will provide written safety reports or other safety-related 
communications to the Investigator.  The Investigator will ensure that these reports are reviewed 
and processed in accordance with regulatory and EC/IRB requirements and archived in the site’s 
study file.   
At the completion or early termination of the study, the Investigator will submit a final report to 
the EC/IRB in accordance with local requirements. 
 

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12. 
STUDY ENDPOINTS  
12.1 
Primary Endpoints 
Part 1: 
• Safety profile of ZEN003694 in combination with talazoparib  
• DLT characteristics and MTD determination for ZEN003694 in combination with 
talazoparib  
• RP2D of ZEN003694 in combination with talazoparib for further clinical 
investigation 
Part 2: 
• Clinical benefit rate (CBR) defined as a complete response (CR), partial response 
(PR) or stable disease (SD  ≥ 4 cycles) by RECIST v1.1 
Expansion Cohort A (Combination Treatment in post-TROP2-ADC patients): 
• Objective response rate (ORR) by RECIST v1.1 (CR or PR) by investigator and by 
independent review 
 
12.2 
Secondary Endpoints 
Part 1: 
• Plasma concentrations of ZEN003694, the active metabolite ZEN003791 and 
talazoparib.  The following PK parameters, at a minimum, will be calculated as 
appropriate: AUC0-last and AUC0-inf, Cmax and minimum or trough concentration 
(Cmin), dosing interval, and Tmax and half-life (t1/2) 
• Clinical benefit rate (CBR)  
• Overall response rate (ORR)   
• Progression-free survival (PFS) 
• Quality of Life 
Part 2: 
• Progression-free survival (PFS) 
• Objective response rate (ORR) 
• Duration of response (DOR) 
• Plasma concentrations of ZEN003694, the active metabolite ZEN003791 and 
talazoparib.  The following PK parameters, at a minimum, will be calculated as 
appropriate: AUC0-last and AUC0-inf, Cmax and minimum or trough concentration 
(Cmin), dosing interval, and Tmax and half-life (t1/2) 
• Quality of Life 
• Safety  

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Expansion Cohort A:  Combination Treatment (post-TROP2-ADC patients) 
• Duration of response (DOR) 
• Clinical benefit rate (CBR) 
• Progression free survival (PFS) 
• Safety analyses will include, but are not limited to, AEs, laboratory abnormalities, 
ECG evaluations, and vital signs 
• Pharmacokinetics:  AUC0-last and AUC0-inf,, Cmax, Cmin, Tmax, and T½ of 
ZEN003694, ZEN003791, and talazoparib during the first 2 treatment cycles 
• Quality of Life 
Expansion Cohort B:  ZEN003694 Monotherapy 
In discussions with the FDA, if there are 1 or 0 patients (out of the 10 evaluable patients 
enrolled) who show an objective response to ZEN003694 monotherapy, it could be 
concluded that ZEN003694 as a monotherapy has no clinical benefit.  
 
Expansion Cohort C:  Combination Treatment (TROP2-ADC-naïve patients) 
• Objective response rate (ORR) by RECIST v1.1 (CR or PR) by investigator  
• Duration of response (DOR) 
• Clinical benefit rate (CBR) 
• Progression free survival (PFS) 
• Safety analyses will include, but are not limited to, AEs, laboratory 
abnormalities, ECG evaluations, and vital signs 
• Pharmacokinetics:  AUC0-last and AUC0-inf,, Cmax, Cmin, Tmax, and T½ of 
ZEN003694, ZEN003791, and talazoparib during the first 2 treatment cycles 
• Quality of Life 
 
12.3 
Exploratory Endpoints 
Part 1 only: 
• Modulation of PD marker mRNA expression by BETi and PARPi  
 
Parts 1 and 2, and Expansion Cohorts:  
Possible analysis of: 
• RNA-sequencing, and/or DNA-sequencing and candidate protein markers by IHC 
in tumor tissue 
• Targeted DNA sequencing of ctDNA and determination of ctDNA fraction. 

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13. 
STATISTICS 
13.1 
General Considerations  
The primary statistical analysis of the data will be descriptive in nature.  For continuous variables 
this means calculation of the number of observations, mean, standard deviation, median, minimum, 
and maximum.  Categorical variables will be summarized by patient counts and related 
percentages.  For ordinal-scaled variables, a combination of the above may be employed as 
appropriate:  frequency and percentage of observations within a category and means and standard 
deviations of the scores of the categories.  For categorical and ordinal variables, percentages will 
be calculated based on non-missing data. 
Based on the characteristics of the study design and lack of a concurrent control arm, formal testing 
of treatment effects (i.e., inferential statistics) will not be performed.  However, some measures 
will be summarized by both point estimates and the associated 95% confidence intervals. 
Retrospective analysis of pharmacodynamic assessments for somatic BRCA1/2 mutations and 
analysis of outcomes for patients with prior platinum therapies may be performed.   
13.2 
Sample Size Determination 
Part 1: Dose escalation 
A conventional algorithm (3+3 patients per dose level) will be used to identify the MTD, 
escalating on 0 of 3 or 1 of 6 DLTs, and de-escalating if 2 DLTs are encountered.  The 
MTD will be the highest dose level at which 0 of 3 or 1 of 6 patients experience a DLT, 
with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.  With 
this design, there is a 71% chance of escalation if the true but unknown rate of DLT is 20%, 
and less than 50% chance of escalation if the true but unknown rate of DLT is higher than 
30%. 
Approximately 12 patients will be enrolled in the dose escalation phase of the study.   
Part 2:  Simon 2-Stage 
• The null hypothesis that the true clinical benefit rate (CBR) is 20 % will be tested 
against a one-sided alternative. (CBR of 20% is not of clinical interest whereas CBR 
40% warrants further investigation) 
• In the first stage, 17 patients will be accrued. If there are < 4 patients with clinical 
benefit in these 17 patients, the study will be stopped.  
• Otherwise, 20  additional patients will be accrued for a total of 37. The null hypothesis 
will be rejected if 11 or more patients show clinical benefit out of 37 patients.  
• This design yields a type I error rate of 0.1 when the true CBR is 20% and power of 
90% when the true CBR is 40% (target error rates 0.10 and 0.10); the probability of 
early termination is 0.55. 
• A minimum of 17 and a maximum of 37 evaluable patients will be accrued. 

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• ORR will be reported with 90% CI. AEs will be summarized. PFS and duration of 
response will be summarized with Kaplan-Meier curves.  Clinical benefit rate will be 
reported with 90% CI. 
Expansion Cohort A:  Combination Treatment (post-TROP2-ADC patients): 
The expansion combination treatment cohort will enroll patients with locally advanced or 
metastatic TNBC without germline BRCA1/BRCA2 mutations who have had  prior 
treatment with sacituzumab govitecan and have had at least one additional prior systemic 
therapy for locally advanced or metastatic disease. Approximately 80 evaluable patients 
are planned to establish the ORR and further define the safety profile of the combination 
ZEN003694 + talazoparib.  An observed ORR (by blinded independent central review) of 
at least 30% represents a significant improvement over current available therapies in this 
patient population. With 80 patients, 24 or more responders will provide an observed 
ORR of at least 30% and a lower limit of the 95% confidence interval above 20%. The 
RECIST v1.1 assessment of response will be assessed by an independent central review 
committee. 
 
Expansion Cohort B:  ZEN003694 Monotherapy: 
Expansion Cohort B will enroll patients with locally advanced or metastatic TNBC 
without germline BRCA1/BRCA2 mutations who have had two prior systemic treatments 
for locally advanced or metastatic disease. Approximately 10 evaluable patients are 
planned to assess the anti-tumor activity of ZEN003694 monotherapy.  According to 
FDA discussions, if no more than 1 patient has a confirmed objective response (complete 
response or partial response), it can be concluded that ZEN003694 monotherapy does not 
have anti-tumor activity (clinical benefit) when given as a single drug treatment.    
 
Expansion Cohort C:  Combination Treatment (TROP2-ADC-naive patients) 
 
Expansion Cohort C will enroll patients with locally advanced or metastatic TNBC 
without germline BRCA1/BRCA2 mutations who have not previously received 
sacituzumab govitecan and have had at least two additional prior systemic therapies for 
locally advanced or metastatic disease. Approximately 30 evaluable patients are planned 
to establish the ORR and further define the safety profile of the combination ZEN003694 
and talazoparib.   
 
13.3 
Analysis Populations  
Safety population:  Patients who receive at least one dose of ZEN003694. 
Efficacy population:  Patients enrolled in Part 2 and Expansion who receive at least one dose of 
ZEN003694 and talazoparib. 
13.4 
Data Handling 
Clinical data will be entered into a secure clinical database that it is Part 11 compliant. The 
handling of data, including data quality assurance, will comply with regulatory guidelines, and 

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will be defined in a study-specific data management plan (DMP).  The DMP will define roles and 
responsibilities in regard to data management, data quality processes and expectations, from study 
start-up to final database lock.    
13.5 
Statistical Analyses 
Prior to the analysis of the final study data, a detailed statistical analysis plan (SAP) will be written.  
Detailed information regarding analysis datasets, summarization of the data and analyses will be 
provided in the SAP.  The SAP will contain any modifications to the analyses described in this 
section. 
 

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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Prior to participation in this study, investigational sites and Investigators will be evaluated for 
appropriate qualifications and ability to properly execute the study.  Each investigational site must 
undergo proper training on the study protocol and ancillary study procedures/documents through 
participation in an initiation visit or Investigator meeting.  Such training must take place before 
any patients are enrolled at that site.  Initiation visits and Investigator meetings will include but 
may not be limited to review of Good Clinical Practice (GCP) guidelines, study drug procedures, 
data collection requirements and patient eligibility requirements. 
The Sponsor or designee will make periodic visits to the investigational site to assess compliance 
with study procedures and regulatory requirements; to ensure that the safety, welfare and privacy 
of patients are being protected; and to verify the accuracy and integrity of the study data.   
In addition, the Sponsor will periodically review the study data to ensure that data are being 
appropriately collected and reported.  Logic checks will be also programmed and run to identify 
errors and data discrepancies.  Discrepancies will be reviewed with investigational site personnel, 
corrections will be made to the database, and a validated audit trail will be maintained.  The 
database will be locked and audited before it is released for analysis. 
14.1 
Study Monitoring 
Before the initiation of the study, a representative from the Sponsor will visit the investigational 
site to: 
• Determine the adequacy of the facilities 
• Discuss the responsibilities of the Investigator(s) and other personnel involved with the 
study with regard to protocol adherence and the responsibilities of the Sponsor and their 
representatives 
During the study, the Study Monitor will have regular contact with the investigational site, 
including visits to: 
• Provide information and support to the Investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded on the CRFs, and that the investigational product accountability is 
being performed. 
• Perform source data verification (a comparison of the data on the CRFs with the patient’s 
records at the hospital or practice, and other records relevant to the study). This will require 
direct access to all original records for each patient e.g., clinic charts.  Incorrect or missing 
entries on to the CRFs will be queried and must be corrected immediately. 

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14.2 
Audit and Inspection 
During or after the study is completed, the Sponsor, its representatives or a Regulatory Authority 
may wish to carry out an audit or inspection.  These representatives must have the same access to 
study data and patient source data as the Study Monitor. 
14.3 
Regulatory Authority Correspondence 
The Investigator will notify the Sponsor or designee immediately following any regulatory contact 
with the investigational site.  The Investigator will provide requested copies of all correspondence 
with the Regulatory Authority that may affect the review of the current study (e.g., Form 483, 
Inspectional Observations).  The Sponsor or their designee reserves the right to be at the 
investigational site during any regulatory inspection that involves this protocol. 

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15. 
ETHICAL AND LEGAL ISSUES 
15.1 
Statement of Compliance 
This study will be conducted in accordance with the following: 
• Protocol-related and study-related documents 
• GCP as outlined in the International Conference on Harmonization (ICH) E6 guideline and 
regional regulations 
• Regional required patient data protection laws and regulations 
• Applicable regional regulations 
15.2 
Ethics Committee or Institutional Review Board Approval 
The Principal Investigator at each site is responsible for obtaining regional EC or IRB approval 
for the final protocol, the Sponsor-approved ICF/assent, patient information sheet, if applicable, 
and any advertisements to recruit patients.  Written approval of these documents must be obtained 
from the EC/IRB and a copy submitted to the Sponsor before any patient is enrolled at an 
investigational site. 
The Principal Investigator is also responsible for the following interactions with the regional 
EC/IRB. 
• Obtaining EC/IRB approval for any protocol amendments and ICF/assent revisions before 
implementing the changes 
• Providing the EC/IRB with any required information before or during the study 
• Submitting progress reports to the EC/IRB as required during the conduct of the study, 
requesting re-review and approval of the study as needed, and providing copies of all 
EC/IRB renewal of approvals and relevant communication to the Sponsor and/or its 
representative 
• Notifying the EC/IRB of all serious and unexpected AEs related to the study medication 
reported by the Sponsor and/or its representative, as required 
• Notifying the EC/IRB at the end of the study, in accordance with regional guidelines and 
regulations 
15.3 
Patient Informed Consent/Assent 
The Investigator’s draft ICF/assent must be reviewed by the Sponsor and/or its representative prior 
to submission to a regional EC/IRB for approval.  A copy of the ICF/assent approved by the 
EC/IRB must be forwarded to the Sponsor and/or its representative. 
The consent of the patient to participate in the study has to be given in writing prior to enrollment.  
It must be signed and personally dated by the patient, parent, legal guardian or caretaker and by 

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the Investigator, Sub-investigator or study coordinator designated by the Investigator to conduct 
the informed consent discussion.  The signed and dated declaration of informed consent will 
remain at the Investigators’ site and must be safely archived by the Investigator so that the forms 
can be retrieved at any time for monitoring, auditing and inspection purposes.  A copy of the signed 
and dated ICF should be provided to the patient prior to participation and the original maintained 
in the patient’s source documents or in a separate archive file for the informed consent documents 
for the study. 
15.4 
Patient Compensation for Adverse Effects on Health 
The Sponsor and/or its representative will adhere to regional regulations regarding clinical trial 
compensation to patients whose health is adversely affected by participation in the study. 
15.5 
Changes to the Conduct of the Study, Protocol and Study Termination 
15.5.1 Protocol Amendments 
Changes in the study protocol shall be in the form of written study protocol amendments.  These 
will require the approval of all signatories of the final protocol.  Any substantial amendments to 
the protocol that affect the patient, e.g., changes in procedures/assessments or matters relating to 
patient safety, require a favorable opinion from the EC/IRB for the study sites prior to 
implementation.  Changes of a purely administrative nature should be notified to the committee(s) 
as applicable, but do not require formal approval.  However, a change to the protocol to eliminate 
an apparent immediate hazard to the patient may be implemented immediately provided the 
EC/IRB and applicable Regulatory Authorities are subsequently notified by protocol amendment.  
Any amendment affecting the patient requires further informed consent from each patient before 
implementation.  
15.5.2 Study Termination 
The Sponsor reserves the right to terminate the study at any time for any reason.  The Investigator 
should notify the EC/IRB in writing of the completion or early termination of the study.  The 
Sponsor will promptly notify US FDA and other Regulatory Authorities if enrollment is terminated 
or suspended for any reason.  Upon study completion or termination, applicable regulatory 
reporting requirements will be followed. 
 
 

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16. 
INVESTIGATOR RESPONSIBILITIES 
The Investigators shall be responsible for ensuring that the study is performed in accordance with 
the protocol, Food and Drug Administration (FDA)/ICH GCP regulations and applicable regional 
regulatory requirements.  
16.1 
Staff Training  
The Investigator will maintain a record of all individuals involved in the study.  He or she will 
ensure that appropriate training relevant to the study is given to all staff members involved in this 
study, and that they will receive any new information of relevance to the performance of this study.  
The Investigator should maintain a list of appropriately trained persons to whom the Investigator 
has delegated trial-related duties. 
16.2 
Study Conduct 
In signing this protocol, the Investigator agrees to: 
• Conduct the study in accordance with the relevant, current protocol and make changes only 
after notifying the Sponsor or its representative, except where necessary to eliminate 
apparent immediate hazards to human patients 
• Comply with the ICH guidelines on GCPs plus appropriate regional regulatory laws and 
requirements 
• Personally conduct or supervise the described investigation 
• Inform any patients or persons used as controls that the study drugs are being used for 
investigational purposes 
• Ensure requirements relating to obtaining informed consent and EC or IRB approval have 
been met 
• Report to the Sponsor or its representative any AEs that occur in the course of the 
investigations, as specified in Section 11  
• Read and understand the Investigator’s Brochure, including potential risks and side effects 
of the drug 
• Ensure all associates, colleagues, and employees assisting in the conduct of the study are 
informed of their obligations in meeting their commitments 
• Maintain adequate and accurate records and make these available for inspection by the 
Sponsor and/or its representative, or any regulatory agency authorized by law 
• Promptly report to the EC or IRB all changes in research activity and all unanticipated 
problems involving risks to human patients or others 
• Comply with all other requirements regarding the obligations of clinical Investigators and 
all other pertinent requirements 

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• Administer study drug only to patients who meet study entry criteria and are enrolled in 
the study, and only according to the guidelines set forth in this protocol 
16.3 
Recordkeeping 
The Investigator is responsible for maintaining adequate records to fully document the conduct of 
the study, including but not limited to the following: 
• All versions of the Investigator’s Brochure and the signed protocol and amendments in 
effect during the conduct of the study 
• Signed ICFs/assents 
• Source documents including adequate case histories 
• Signed, dated and completed CRFs or data collection forms and documentation of data 
corrections 
• Notification of SAEs and related reports 
• Investigational product accountability logs and documentation of return of unused and used 
investigational product, if applicable 
• Dated and documented EC/IRB approvals 
• Normal laboratory test values and laboratory certifications, if applicable 
• Curricula vitae of all clinical Investigators 
• Completed Forms US FDA 1572 
• Trial initiation documentation 
• Delegation of Authority Log 
• Signed Signature of Agreement for Protocol and Amendment and agreements between 
involved parties 
• Relevant communication, including that related to the Study Monitor’s site visits 
(e.g., letters, meeting notes, notes from telephone calls) 
• Interim, annual or final reports to ECs/IRBs 
• Patient screening log, patient identification code list and patient enrollment log 
• Audit certificate if applicable 
 

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17. 
PUBLICATIONS 
The data and information generated in this study are the exclusive property of the Sponsor and 
Pfizer and are confidential.   
To avoid disclosures that could jeopardize proprietary rights, the investigator agrees to give the 
Sponsor and Pfizer the right to review all manuscripts, abstracts, and presentations related to this 
study at least 30 days prior to their submission for publication or presentation.  Authorship among 
Investigators generally will be based on the extent of significant contribution, including scientific 
and clinical, to the publication.  
 
 
 

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18. 
CONFIDENTIALITY 
The Investigators as well as their staff, and all its representatives must agree to maintain the 
confidentiality of the study at all times and must not reveal information relating to the 
Investigator’s Brochure, protocol, CRFs or associated documents to unauthorized third parties. 
 
 

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Appendix 1:  ECOG Performance Status  
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature (e.g., light housework, office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  
Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or 
chair. 
5 
Dead. 
Source:  Oken, et al., 1982  
 
 
 

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Appendix 2:  NCI CTCAE Version 5.0 Adverse Event Severity Grading 
Grade refers to the severity of the AE.  The NCI CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline as shown in the table 
below. 
Adverse Event Severity Grading — NCI CTCAE 
  
Description 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADLa 
3 
Severe or medically significant but not immediately life threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL.b 
4 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
A semicolon (;) indicates “or” within the description of the grade.  A single dash (–) indicates a grade is not available.  Not all 
grades are appropriate for all AEs; therefore, some AEs are listed with fewer than 5 options for grade selection. 
Grade 5 (Death) is not appropriate for some AEs and therefore is not an option. 
Activities of Daily Living (ADL) 
a  Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden 
 
 
 
 

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Appendix 3:  RECIST 1.1 Criteria  
MEASUREMENT OF RESPONSE 
Measurement of response in patients with measurable disease 
Response and progression will be evaluated in this study using the international criteria proposed 
by the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria (Eisenhauer et 
al., 2009).  Changes in the sum of the diameters of target lesions of the tumor lesions are used in 
the RECIST criteria. 
Note: lesions are either measurable or non-measurable using the criteria provided 
below. The term “evaluable” in reference to measurability will not be used because 
it does not provide additional meaning or accuracy.  All measurements should be 
taken and recorded in metric notation using a ruler or calipers.  All baseline 
evaluations should be performed as closely as possible to the beginning of treatment 
and never more than 30 days before the beginning of the treatment.  The same 
method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up.  Imaging-based 
evaluation is preferred to evaluation by clinical examination when both methods 
have been used to assess the antitumor effect of a treatment. 
Clinical lesions.  Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes).  In the case of skin lesions, documentation by color 
photography, including a ruler to estimate the size of the lesion, is recommended. 
Chest x-ray.  Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung.  However, CT is preferable. 
Conventional CT and MRI.  These techniques should be performed with cuts of 10 mm or less 
in slice thickness contiguously.  Spiral CT should be performed using a 5 mm contiguous 
reconstruction algorithm.  This applies to tumors of the chest, abdomen, and pelvis.  Head and 
neck tumors and those of extremities usually require specific protocols. 
Measurable disease/ Target lesions 
All measurable lesions (lesions that can be accurately measured in at least one dimension 
[longest diameter to be recorded except for target lymph nodes with are measured on the 
short axis] as ≥ 10mm with spiral CT) up to a maximum of 2 lesions per organ and 5 lesions 
total, representative of all involved organs, should be identified as target lesions and 
recorded and measured at baseline.  Target lesions should be selected on the basis of their 
size (lesions with the longest diameter) and the suitability for accurate repeated 
measurements (either by imaging techniques or clinically).  A sum of the LD for all target 
lesions will be calculated and reported as the baseline sum LD.  The baseline sum LD will 
be used as a reference by which to characterize the objective tumor response. 
Lymph node metastases must measure 1.5 cm or greater in short axis diameter to be 
considered target lesions, while other target lesions must measure 1 cm or greater (with 
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Complete Response (CR): 
Disappearance of all target lesions 
Partial Response (PR): 
At least a 30% decrease in the sum of the longest 
diameter (LD) of target lesions, taking as 
reference the baseline sum LD 
Progressive Disease (PD): 
At least a 20% increase in the sum of the LD of 
target lesions, taking as reference the smallest 
sum LD recorded since the treatment started 
(including baseline LD), or the appearance of one 
or more new lesions 
Evaluation of non-target lesions 
Complete Response (CR): 
Disappearance of all non-target lesions and 
normalization of tumor marker level 
Incomplete Response/ 
Stable Disease (SD): 
Persistence of one or more non-target lesion(s), 
and/or maintenance of tumor marker level above 
the normal limits 
Progressive Disease (PD): 
Appearance of one or more new lesions, and/or 
unequivocal progression of existing non-target 
lesions 
Although a clear progression of non-target lesions only is exceptional, in such 
circumstances, the opinion of the treating physician should prevail and the progression 
status should be confirmed later on by the study chair. 
Evaluation of best overall response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started, including baseline; see table below).  
The patient's best response assignment will depend on the achievement of both 
measurement and confirmation criteria. 
Confirmation 
To be assigned a status of PR or CR, changes in tumor measurements must be confirmed 
by repeat studies no less than 4 weeks after the criteria for response are first met.  In the 
case of SD, follow-up measurements must have met the SD criteria at least once after study 
entry at a minimum of 12 weeks after study entry. 
Duration of overall response 
The duration of overall response is measured from the time measurement criteria are met 
for CR/PR (whichever is first recorded) until the first date that recurrent or progressive 
disease is objectively documented (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The duration of overall complete 

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response is measured from the time measurement criteria are first met for CR until the first 
date that recurrent disease is objectively documented. 
Target Lesions 
Non-Target Lesions 
New Lesions 
Response 
CR 
CR 
No 
CR 
CR 
Incomplete 
response/SD 
No 
PR 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Evaluation of non-measurable bone disease  
Bone scans obtained after the baseline evaluation will be used to evaluate post-treatment changes.  
Bone scans obtained will be evaluated as either “no new lesions” or “new lesions” on the tumor 
measurement forms. 
a. For the first scheduled reassessment:  New lesions at the first scheduled evaluation will 
require a confirmatory bone scan 6 or more weeks later.  If no new lesions are observed on 
the confirmatory bone scan, study therapy is continued.  If additional new lesions are 
observed, then the patient has experienced progression.  Progression in this situation is 
dated as the time of the first reassessment scan. 
b. For subsequent scheduled reassessments:  If no new lesions are observed, study therapy 
will continue. If new lesions are observed, this is evidence of disease progression.  Date of 
progression is the date at which the scan was obtained. 
Progressive disease (PD) 
Progressive disease will be defined by any one of the following: 
a. Appearance of new metastatic lesions outside the bone 
b. New metastatic lesions on bone scan confirmed as described above 
c. Development of an indication for radiotherapy while on treatment 
d. Unequivocal progression of non-target lesions 
e. Global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression 
 
 
 

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Appendix 4:  Investigator Agreement Page 
 
A Phase 2 Study of ZEN003694 in Combination with Talazoparib in Patients  
with Triple-Negative Breast Cancer 
 
Protocol ZEN003694-004 
Protocol Amendment 6:  26 May 2022 
 
I have read the protocol, including all appendices, and I agree that it contains all necessary details 
for me and my staff to conduct this study as described.  I will conduct this study as outlined herein 
and will make a reasonable effort to complete the study within the time designated.  Further, I 
agree to conduct this study in accordance with ICH Guidelines, all applicable United States (US) 
Regulations (21 CFR parts 50, 54, 56 and 312) and Good Clinical Practice and applicable 
regulatory requirements. 
The information contained in this protocol is proprietary and provided to me in confidence, and 
may not be disclosed to any other party, in any form, without prior authorization from the 
Sponsors, except to the extent necessary for the conduct of the study at this study site. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by the Sponsors.  I will discuss this material with them to ensure that they 
are fully informed about the drugs and the study. 
 
Principal Investigator’s Signature 
 
Date 
Principal Investigator’s Name: 
(Print) 
 
Institution’s Name, City, State: