Clinical trial NCT03991494
Conditions: Advanced Solid Tumors
Sponsor: BeiGene
Start date: 2019-05-29; Completion date: 2020-08-05
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label study, in participants with advanced and/or metastatic solid tumors, which consists of 2 parts: a research phase (inpatient) and a treatment phase. The research phase (Part 1) of the study will assess the disposition of a single oral dose of \[14C\]-pamiparib. In the treatment phase (Part 2) participants will be allowed to have continued access to pamiparib.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: [14C]-pamiparib
Intervention descriptions: intervention 1: During the treatment phase, pamiparib 60 mg administered orally twice daily

Protocol documents:
Prot_000.pdf: 
Protocol Amendment Version 3.0 
CONFIDENTIAL 
Covance Study: 8381180 
Protocol Reference: BGB-290-106 
12 December 2018 
Page 1 of 72 
 
 
Protocol 
A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of 
[14C]-Pamiparib following Single Oral Dose Administration in Patients with 
Advanced and/or Metastatic Solid Tumors 
 
Protocol Version 1.0 Date: 25 June 2018 
Protocol Amendment Version 3.0 Date: 12 December 2018 
Investigational Medicinal Product: [14C]-Pamiparib and Pamiparib 
 
Protocol Reference Number: BGB-290-106 
Covance Study Number: 8381180 
EudraCT Number: 2018-001156-36 
 
 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc.  
2929 Campus Drive, Suite 300 
San Mateo, CA, 94403, USA 
Study Sites: 
Royal Liverpool University Hospital Clinical 
Research Unit 
2nd Floor, UCD 
Prescot Street 
Liverpool, L7 8XP, UK 
The Clatterbridge Cancer Centre NHS 
Foundation Trust 
Clatterbridge Road 
Bebington, Wirral, CH63 4JY, UK 
Medical Monitor: 
 
 
 
Principal Investigator: 
 
 
 
Information described herein is confidential and may be disclosed only with the express 
written permission of the Sponsor. 


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SPONSOR APPROVAL 
Protocol Number: BGB-290-106 
A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Pamiparib 
following Single Oral Dose Administration in Patients with Advanced and/or Metastatic Solid 
Tumors 
 
 
 
 
 
 
 
 
Date 
Sponsor Medical Monitor 


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INVESTIGATOR AGREEMENT 
Protocol Identifier: 
BGB-290-106  
Protocol Title:  
A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion 
of [14C]-Pamiparib following Single Oral Dose Administration in Patients with Advanced and/or 
Metastatic Solid Tumors 
This protocol is a confidential communication of BeiGene, Ltd and its subsidiaries.  I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol.  I will 
also work consistently with the ethical principles that have their origin in the Declaration of 
Helsinki and that are consistent with good clinical practices and the applicable laws and 
regulations.  Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval from 
BeiGene, Ltd or one of its subsidiaries.  
Instructions for Investigator: Please SIGN and DATE this signature page. PRINT your name, 
title, and the name of the center in which the study will be conducted.  Return the signed copy to 
BeiGene or its designee.  
 I have read this protocol in its entirety and agree to conduct the study accordingly:  
 
 
 
 
 
Date 
 
Principal Investigator 


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PROTOCOL AMENDMENT VERSION 3.0 (12 DECEMBER 2018) 
The Protocol Amendment Version 2.0 (Covance Study 8381180), dated 31 October 2018, is revised as 
Protocol Amendment Version 3.0, dated 12 December 2018 based on Health Authority.  Additions are in 
bold text.  Key changes are summarized by protocol section as shown below:  
Section 
Key Change 
Appendix 8 
Added text to Appendix 8: 
All male patients with partners of childbearing potential who take part in 
this study, must use condoms during sexual intercourse in addition to one 
of the highly effective methods of contraception listed below, from the time 
of taking the first dose of pamiparib until 6 months after taking the last 
dose of pamiparib. If a female partner of a male patient is already 
pregnant, the male patient must use condoms during sexual intercourse 
for the duration of the study and for at least 6 months after the last dose 
of pamiparib. 
Female patients of childbearing potential must use one of the highly 
effective forms of birth control below (preferably those with low user 
dependency) for the duration of the study and for at least 6 months after 
the last dose of pamiparib. 
Appendix 8 
Added asterisks to birth control methods intrauterine device, intrauterine 
hormone-releasing system, bilateral tubal occlusion, and vasectomized male 
partner to indicate that:  *Contraception methods that in the context of this 
protocol are considered to have low user dependency. 


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STUDY IDENTIFICATION 
Sponsor 
BeiGene, Ltd. 
c/o BeiGene USA, Inc.  
2929 Campus Drive, Suite 300 
San Mateo, CA, 94403, USA 
Sponsor’s Study Contact 
Sponsor’s Medical Contact and 
Medical Monitor 
Study Sites 
Royal Liverpool University Hospital Clinical Research 
Unit 
2nd Floor, UCD 
Prescot Street 
Liverpool, L7 8XP, UK 
 
The Clatterbridge Cancer Centre NHS Foundation Trust 
Clatterbridge Road 
Bebington, Wirral, CH63 4JY, UK 
Principal Investigator 


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Bioanalytical Analysis 
Covance Inc. 
1121 East 3900 South 
Building C, Suite 210 
Salt Lake City, UT 84124, USA 
Radioanalytical Laboratory, 
Metabolite Profiling and 
Identification 
Covance Laboratories Ltd. 
Otley Road 
Harrogate, HG3 1PY, UK 
Statistician 


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SYNOPSIS 
Title of study: A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of 
[14C]-Pamiparib following Single Oral Dose Administration in Patients with Advanced and/or 
Metastatic Solid Tumors 
Objectives: 
The primary objectives of the study are: 
 
To assess the disposition of [14C]-pamiparib following oral administration of a single 60 mg 
(~100 µCi) dose in patients with advanced and/or metastatic solid tumors 
 
To assess the plasma pharmacokinetics (PK) of total radioactivity and pamiparib following 
a single oral dose of [14C]-pamiparib 
 
To determine the whole blood and plasma concentrations of total radioactivity 
 
To determine the urinary and fecal recovery of total radioactivity 
The secondary objectives of this study are: 
 
To characterize and identify metabolites of [14C]-pamiparib in plasma, urine, and feces 
 
To determine plasma and urine concentrations of pamiparib and/or its major metabolites 
 
To assess the safety and tolerability of pamiparib during the treatment phase 
 
Study design: 
This is an open-label study, in patients with advanced and/or metastatic solid tumors, which 
consists of 2 parts: a research phase (inpatient) and a treatment phase.  
Part 1 - Research Phase 
The research phase of the study will assess the disposition of [14C]-pamiparib following oral 
administration of a single dose of 60 mg. Patients will be resident at the Clinical Research Unit 
(CRU) from Day -1 until completion of all assessments on Day 7 but may be discharged earlier at 
the Principal Investigator’s (PI’s) discretion if they meet the following discharge criteria: 
 
 Approximately 90% of the radioactive dose is recovered 
or 
 
< 1% of the radioactive dose is recovered in urine and feces for 2 consecutive 24-hour 
collection intervals.  
If the discharge criteria have not been met on Day 7, patients may be asked to collect 24-hour 
excreta samples for up to 7 days on a non-residential basis. Patients may remain resident at the 
CRU if deemed necessary by the PI for safety reasons. A Follow-up visit will occur within 7 days 
of discharge from the CRU (if discharged on Day 7 or before), or within 7 days of the patients’ final 
non-residential visit (if additional non-residential visits are required). At the Follow-up visit, 
patients’ ability to continue into the treatment phase will be determined by the PI. 
Part 2 - Treatment Phase 
The treatment phase of the study will allow patients to have continued access to pamiparib. Safety 
assessments will be conducted ≤ 7 days prior to the start of pamiparib treatment at either the 
Follow-up visit for Part 1 or at a separate visit. Patients will undergo 28-day cycles of pamiparib 
60 mg twice daily dosing. Pamiparib treatment will be continued unless any of the following occur:  
progressive disease (PD), unacceptable toxicity, pregnancy, death, withdrawal of consent, lost to 
follow-up, major protocol violation which in the opinion of the Sponsor would have significant 
impact on the study or its outcome, start of new anticancer therapy, withdrawal by the PI, or study 
termination by Sponsor. There will be a Follow-up visit approximately 30 days following the final 
administration of pamiparib. 


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Number of patients: 
Approximately 10 patients will be enrolled so that 4 patients complete Part 1 of the study. 
Diagnosis and main criteria for inclusion: 
Patients will be male or female, ≥ 18 years of age, who have histologically or cytologically 
confirmed malignancy that has progressed to the advanced or metastatic stage. Patients must have 
an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. 
Investigational products, dose, and mode of administration: 
Part 1: A single oral dose of [14C]-pamiparib 60 mg containing approximately 100 μCi (3.7 MBq). 
Part 2: Oral doses of pamiparib 60 mg twice daily.  
Duration of patient participation in the study: 
Planned Screening duration: approximately 27 days. 
Planned study duration: Part 1 – up to 22 days (Day -1 to Day 21); Part 2 - variable based on time 
required for study drug discontinuation to occur (see previous section). 
Endpoints: 
Pharmacokinetics: 
Part 1 
Plasma, urine, and feces will be collected for the analysis of pamiparib concentrations and total 
radioactivity. The PK parameters of pamiparib and total radioactivity will be calculated using 
standard noncompartmental methods. The following PK parameter endpoints for pamiparib in 
plasma and total radioactivity in whole blood and plasma will be calculated whenever possible: area 
under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞), AUC from time 
zero to the last quantifiable concentration (AUC0-t), maximum observed concentration (Cmax), time 
of Cmax (tmax), and apparent terminal elimination half-life (t1/2). The apparent total clearance (CL/F) 
and apparent volume of distribution (Vz/F) will also be determined. 
The AUC0-∞ of plasma pamiparib relative to AUC0-∞ of plasma total radioactivity (AUC0-∞ Plasma 
pamiparib/Total Radioactivity Ratio) and AUC0-∞ of whole blood total radioactivity to AUC0-∞ of 
plasma total radioactivity (AUC0-∞ Blood/Plasma Ratio) will be calculated. 
The following PK parameter endpoints for pamiparib and total radioactivity in urine will be 
calculated whenever possible: amount excreted in urine (Aeu), cumulative Aeu, percentage excreted 
in urine (feu), and cumulative feu. The renal clearance (CLR) will also be determined for pamiparib. 
The following PK parameter endpoints for total radioactivity in feces will be calculated whenever 
possible: amount excreted in feces (Aef), cumulative Aef, percentage excreted in feces (fef), and 
cumulative fef. 
Plasma, urine, and fecal samples will also be used to establish the metabolic profile of pamiparib 
and to identify its metabolites.  
Part 2 
No analysis of pamiparib PK will be conducted during the treatment phase. 
Safety: 
Safety endpoints for this study include AEs, vital sign measurements, 12-lead electrocardiograms, 
clinical laboratory evaluations, and physical examinations. Tumor assessments will be conducted 
using a computerized tomography or magnetic resonance imaging scan at Screening and every 12 
weeks following the baseline scan. The ECOG performance status will be assessed during Part 1 
and Part 2. 
Statistical methods: 
Pharmacokinetic parameters will be summarized using descriptive methodology. Efficacy and 
safety assessments will be summarized using descriptive methodology and/or listed. No formal 
statistical analysis will be performed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................5 
SYNOPSIS .................................................................................................................................7 
TABLE OF CONTENTS ...........................................................................................................9 
LIST OF ABBREVIATIONS ..................................................................................................13 
1. 
INTRODUCTION ...........................................................................................................16 
1.1. 
Poly (ADP-ribose) Polymerase Inhibitors .............................................................16 
1.2. 
PARP Inhibitor Pamiparib .....................................................................................16 
1.2.1. 
Nonclinical Data for Pamiparib ...................................................................16 
1.2.2. 
Nonclinical Safety Data ...............................................................................16 
1.2.3. 
Nonclinical Activity Data ............................................................................17 
1.3. 
Clinical Data for Pamiparib ...................................................................................21 
1.3.1. 
Clinical Safety and Preliminary Efficacy for Pamiparib .............................21 
1.3.2. 
Pharmacokinetics and Pharmacodynamics ..................................................22 
1.4. 
Study Rationale ......................................................................................................22 
1.5. 
Benefit-Risk Assessment .......................................................................................23 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................23 
2.1. 
Objectives ..............................................................................................................23 
2.1.1. 
Primary Objectives.......................................................................................23 
2.1.2. 
Secondary Objectives...................................................................................23 
2.2. 
Endpoints ...............................................................................................................24 
2.2.1. 
Primary Endpoints .......................................................................................24 
2.2.2. 
Secondary Endpoints ...................................................................................25 
3. 
INVESTIGATIONAL PLAN ..........................................................................................25 
3.1. 
Overall Study Design and Plan ..............................................................................25 
3.1.1. 
Study Part 1 (Research Phase) .....................................................................26 
3.1.2. 
Study Part 2 (Treatment Phase) ...................................................................27 
3.2. 
Discussion of Study Design ...................................................................................28 
3.3. 
Selection of Doses in the Study .............................................................................28 
4. 
SELECTION OF STUDY POPULATION .....................................................................29 
4.1. 
Inclusion Criteria ...................................................................................................29 
4.2. 
Exclusion Criteria ..................................................................................................30 
4.3. 
Patient Number and Identification .........................................................................31 


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4.4. 
Patient Withdrawal and Replacement ....................................................................31 
4.5. 
Study Termination .................................................................................................32 
5. 
STUDY TREATMENTS .................................................................................................33 
5.1. 
Description, Storage, Packaging, and Labelling ....................................................33 
5.2. 
Study Treatment Administration............................................................................33 
5.2.1. 
Part 1 ............................................................................................................33 
5.2.2. 
Part 2 ............................................................................................................33 
5.3. 
Treatment Compliance ...........................................................................................34 
5.4. 
Drug Accountability...............................................................................................34 
5.5. 
Dose Hold and Modification ..................................................................................34 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................38 
6.1. 
Concomitant Therapies ..........................................................................................38 
6.1.1. 
Permitted Concomitant Treatment ...............................................................38 
6.1.2. 
Prohibited Concomitant Treatment ..............................................................38 
6.2. 
Diet .........................................................................................................................38 
6.3. 
Smoking .................................................................................................................39 
6.4. 
Contraception .........................................................................................................39 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................39 
7.1. 
Pharmacokinetic Assessments (Part 1 Only) .........................................................39 
7.1.1. 
Pharmacokinetic and Metabolite Blood Sample Collection and Processing
......................................................................................................................39 
7.1.2. 
Pharmacokinetic, Total Radioactivity, and Metabolite Urine and Fecal 
Collection and Processing ............................................................................40 
7.1.3. 
Emesis Sample Collection ...........................................................................40 
7.1.4. 
Analytical Methodology ..............................................................................40 
7.2. 
Safety and Tolerability Assessments (Parts 1 and 2) .............................................40 
7.2.1. 
Adverse Events ............................................................................................40 
7.2.2. 
Clinical Laboratory Evaluations ..................................................................41 
7.2.3. 
Vital Signs ....................................................................................................41 
7.2.4. 
12-Lead Electrocardiogram .........................................................................41 
7.2.5. 
Physical Examination...................................................................................42 
7.2.6. 
Eastern Cooperative Oncology Group .........................................................42 
7.2.7. 
Tumor Assessments .....................................................................................42 
7.3. 
End-of-Treatment Visit ..........................................................................................42 
7.4. 
Follow-up Assessments .........................................................................................43 
7.4.1. 
Safety Follow-up ..........................................................................................43 
8. 
SAFETY MONITORING AND REPORTING...............................................................43 


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8.1. 
Adverse Events ......................................................................................................43 
8.1.1. 
Definition and Reporting of an Adverse Event ............................................43 
8.1.2. 
Assessment of Severity ................................................................................44 
8.1.3. 
Assessment of Causality ..............................................................................44 
8.1.4. 
Follow-up of Adverse Events ......................................................................45 
8.2. 
Laboratory Test Abnormalities ..............................................................................46 
8.3. 
Definition of a Serious Adverse Event ..................................................................46 
8.4. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ......................................................................................................47 
8.4.1. 
Adverse Event Reporting Period .................................................................47 
8.4.2. 
Eliciting Adverse Events..............................................................................47 
8.5. 
Disease Progression ...............................................................................................47 
8.6. 
Death ......................................................................................................................47 
8.7. 
Myelodysplastic Syndrome and Acute Myeloid Leukemia ...................................48 
8.8. 
Reporting Serious Adverse Events ........................................................................48 
8.8.1. 
Prompt Reporting of Serious Adverse Events .............................................48 
8.8.2. 
Completion and Transmission of the Serious Adverse Event Report ..........48 
8.9. 
Regulatory Reporting Requirements for Serious Adverse Events .........................48 
8.10. Suspected Unexpected Serious Adverse Reactions ...............................................49 
8.11. Pregnancy Reporting ..............................................................................................49 
8.12. Post Study Adverse Events ....................................................................................49 
8.13. Expedited Reporting to Health Authorities, Ethics Committees, and the Principal 
Investigator ............................................................................................................49 
8.14. Regulatory, Ethical, and Study Oversight Considerations.....................................50 
8.14.1. 
Regulatory and Ethical Considerations ........................................................50 
8.14.2. 
Finances and Insurance ................................................................................50 
8.14.3. 
Informed Consent.........................................................................................51 
8.14.4. 
Patient Data Protection ................................................................................51 
8.14.5. 
Disclosure ....................................................................................................51 
8.14.6. 
Data Quality Assurance ...............................................................................51 
8.14.7. 
Principal Investigator Documentation Responsibilities ...............................52 
8.14.8. 
Publications and Data Sharing .....................................................................53 
9. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................53 
9.1. 
Determination of Sample Size ...............................................................................53 
9.2. 
Analysis Populations ..............................................................................................54 
9.2.1. 
Pharmacokinetic Population ........................................................................54 
9.2.2. 
Safety Population .........................................................................................54 


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9.3. 
Pharmacokinetic Analyses .....................................................................................54 
9.4. 
Safety Analysis ......................................................................................................54 
9.5. 
Interim Analysis .....................................................................................................54 
10. REFERENCES ................................................................................................................55 
11. APPENDICES .................................................................................................................56 
Appendix 1: Clinical Laboratory Evaluations ...................................................................57 
Appendix 2: Total Blood Volume......................................................................................58 
Appendix 3: Eastern Cooperative Oncology Group (ECOG) Performance Status ...........61 
Appendix 4: Schedule of Assessment ................................................................................62 
Appendix 5: New York Heart Association Functional Classification ...............................67 
Appendix 6: Prohibited Medications and Medications to Be Used with Caution .............68 
Appendix 7: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation
................................................................................................................................70 
Appendix 8: Contraception Guidelines and Definitions of “Women of Childbearing 
Potential”, “No Childbearing Potential” ................................................................71 
 
LIST OF FIGURES 
Figure 1: 
Pamiparib Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-053 Small Cell Lung Cancer Xenograft Model ..19 
Figure 2: 
Pamiparib Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-080 Small Cell Lung Cancer Xenograft Model ..20 
Figure 3: 
Study Schematic: Part 1 .............................................................................26 
Figure 4: 
Study Schematic: Part 2 .............................................................................27 
  
LIST OF TABLES 
Table 1: 
PARP Enzyme Inhibition and PARP Trapping Activity of PARP 
Inhibitors ....................................................................................................18 
Table 2: 
Dose Levels for Pamiparib.........................................................................35 
Table 3: 
Criteria for Modification of Pamiparib Dosing for Related Adverse Events
....................................................................................................................35 
Table 4: 
Timeframes for Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee ............................................................48 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
Aef 
amount excreted in feces 
Aeu 
amount excreted in urine 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC0- 
area under the concentration-time curve from time zero to infinity 
AUC0-∞ Blood/ 
Plasma Ratio 
area under the concentration-time curve from time zero to infinity of 
whole blood total radioactivity to area under the concentration-time 
curve from time zero to infinity of plasma total radioactivity 
AUC0-∞ Plasma 
pamiparib /Total 
Radioactivity Ratio 
area under the concentration-time curve from time zero to infinity of 
plasma pamiparib relative to area under the concentration-time curve 
from time zero to infinity of plasma total radioactivity 
AUC0-t 
area under the concentration-time curve from time zero to the last 
quantifiable concentration 
BID 
twice daily 
BRCA 
breast cancer susceptibility gene 
14C 
carbon-14 
CFR 
Code of Federal Regulations 
CHO 
Chinese hamster ovary 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL/F 
apparent total clearance 
CLR 
renal clearance 
Cmax 
maximum observed concentration 
CNS 
central nervous system 
CR 
complete response 
CRO 
Contract Research Organization 
CRU 
Clinical Research Unit 
CSR 
Clinical Study Report 
CT 
computed tomography 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicity 
ECOG 
Eastern Cooperative Oncology Group 


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EDC 
electronic data capture 
E/C 
etoposide and carboplatin 
EC 
Ethics Committee 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EOT 
end-of-treatment 
FDG-PET 
fluorodeoxyglucose-positron emission tomography 
fef 
percentage excreted in feces 
feu 
percentage excreted in urine 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
hERG 
human ether-à-go-go related gene 
IB 
Investigator’s Brochure 
IC50 
half-maximal inhibition concentration 
ICF 
Informed Consent Form 
ICH 
International Council for/Conference on Harmonisation 
ICRP 
International Commission on Radiological Protection 
IMP 
investigational medicinal product 
MDRD 
Modification of Diet in Renal Disease 
MDS 
myelodysplastic syndrome 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
PAR 
poly (ADP-ribose) 
PARP 
poly (ADP-ribose) polymerase 
PD 
progressive disease  
PI 
principal investigator 
PK 
pharmacokinetic(s) 
PR 
partial response 
QWBA 
quantitative whole-body autoradiography 
QTc(F) 
QT interval corrected for heart rate using Fridericia’s formula 
SAE 
serious adverse event 
SCLC 
small cell lung cancer 
SD 
stable disease 
SEM 
standard error of the mean 
SOP 
standard operating procedure 


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SSBs 
single-strand DNA breaks 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
apparent terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time of maximum observed concentration 
ULN 
upper limit of normal 
VZ/F 
apparent volume of distribution 
 
 
 


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1. INTRODUCTION 
1.1. 
Poly (ADP-ribose) Polymerase Inhibitors 
Poly (ADP-ribose) polymerase (PARP) proteins are involved in DNA replication, transcriptional 
regulation, and DNA damage repair. DNA-bound PARP1/2 catalyzes the synthesis of poly 
(ADP-ribose) (PAR) onto a range of DNA-associated proteins that mediate DNA repair. PARP1 
also undergoes auto-PARylation, a molecular change that ultimately leads to its release from 
DNA. Inhibition of PARP converts common single-strand DNA breaks (SSBs) into 
double-strand breaks during DNA replication. Small-molecule inhibitors of PARP1/2 represent a 
class of anticancer agents that exert their cytotoxic effects by interfering with DNA repair 
mechanisms. Since the discovery of synthetic lethality of PARP inhibitors in breast cancer 
susceptibility gene (BRCA)-deficient cells and, more broadly, cells with homologous 
recombination deficiency, accumulation of unrepaired SSBs resulting from catalytic PARP 
inhibition has been considered central to the mechanism of action of PARP inhibitors. More 
recently, it has been demonstrated that PARP inhibitors also trap PARP1- and PARP2-DNA 
complexes at DNA damage sites and that PARP trapping can be more cytotoxic than unrepaired 
SSBs.1–3 
In the clinic, PARP inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, have 
demonstrated sustained antitumor responses as a single agent in patients with BRCA1- or 
BRCA2-mutated tumors, while achieving a favorable safety profile. Olaparib has been approved 
in the US as a single agent for advanced ovarian cancer patients with a deleterious germline 
BRCA mutation whereas rucaparib has been approved for patients with a deleterious germline or 
somatic BRCA mutation.4,5 Niraparib was approved by the US Food and Drug Administration in 
2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian 
tube, or primary peritoneal cancer who are in complete response (CR) or partial response (PR) to 
platinum-based chemotherapy. 
1.2. 
PARP Inhibitor Pamiparib 
1.2.1. 
Nonclinical Data for Pamiparib 
 
 
 
1.2.2. 
Nonclinical Safety Data 
 
 
 
 
 
 
 




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Figure 1: 
Pamiparib Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-053 Small Cell Lung Cancer Xenograft Model 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.3. 
Clinical Data for Pamiparib 
Pamiparib monotherapy has been administered in 2 Phase 1 studies. This includes 81 patients 
across Phase 1A and Phase 1B in Study BGB-290-AU-002 (01 Dec 2017), and 15 patients in 
Study BGB-290-102 (25 Sept 2017).  Data are also available for pamiparib in combination 
regimens. This includes 10 patients in Study BGB-290-103 (combination with temozolomide; 
01 Dec 2017),  4 patients in Study BGB-290-104 (combination with radiation therapy and/or 
temozolomide; 01 Dec 2017) and 82 patients  in BGB-A317/BGB-290_Study_ 001(combination 
with the antibody tislelizumab [also known as BGB-A317, an immune checkpoint inhibitor 
targeting programmed cell death-1];05 February 2018). 
Three additional studies are in study start-up:  monotherapy study BGB-290-201 and placebo-
controlled studies BGB-290-302 and BGB-290-303. 
The study data from BGB-290-AU-002 are the most mature and key interim results are 
summarized below. 
1.3.1. 
 Clinical Safety and Preliminary Efficacy for Pamiparib 
BGB-290-AU-002 is a first-in-human study evaluating pamiparib to characterize the safety, the 
MTD, preliminary antitumor activity, and the PK of pamiparib given as a monotherapy in a 3+3 
dose escalation scheme. Pamiparib was administered in doses ranging from 2.5 to 120 mg orally 
twice daily. 
Dose-limiting toxicities (DLTs) were observed in 4 patients during Cycle 1 at the following dose 
levels: 40 mg PO twice daily (n = 1); 80 mg PO twice daily (n = 1); and 120 mg PO twice daily 
(n = 2). Two patients, one treated with 40 mg PO twice daily and one treated with 80 mg PO 
twice daily, had two separate events of Grade 2 nausea lasting between 2 and 9 days that resulted 
in dose interruption. One patient treated with 120 mg PO twice daily had two separate Grade 2 
events of nausea and anorexia events each that resulted in dose interruption and dose reduction. 
A second patient treated with 120 mg PO twice daily experienced Grade 2 nausea starting on 
Day 3 lasting for 13 days, Grade 3 fatigue and Grade 2 paresthesia starting on Day 4 and lasting 
for 12 and 6 days respectively, followed by Grade 3 paresthesia starting on Day 11 and lasting 
for 17 days, all resulting in dose interruption. Dose-limiting toxicities were not reported beyond 
Cycle 1 or in any additional patients.   
The MTD was determined to be 80 mg PO twice daily based on 2 of 5 patients (40%) who 
experienced a DLT at 120 mg PO twice daily. 
In Phase 1A, Part 1 of the study (twice daily dosing), 100.0% of patients experienced a 
treatment-emergent adverse event (TEAE), while 75.6% of patients experienced a drug-related 
TEAE. A total of 10 patients (22.2%) experienced a severe (≥ Grade 3) pamiparib-related TEAE. 
Serious TEAEs were reported in 25 patients (55.6%), while 6.7% experienced a serious 
pamiparib-related TEAE. Four patients (8.9%) died as a result of a TEAE in Phase 1A, Part 1 of 
Study BGB-290-AU-002 (1 adverse event [AE] of pleural effusion in a breast cancer patient who 
died of disease progression complicated by respiratory failure; 1 AE of intestinal obstruction in 


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an ovarian cancer patient; 1 AE of intestinal perforation in an ovarian cancer patient; and 1 AE 
of gastric obstruction in a fallopian tube cancer patient). All 4 fatal events were assessed by the 
investigator as not related to the study treatment. 
In Phase 1A, Part 2 (once daily dosing), 2 patients (66.7%) experienced a TEAE; both were 
assessed as pamiparib-related TEAEs.  One patient (33.3%) experienced a severe (≥ Grade 3) 
TEAE, which was assessed as related to pamiparib. No serious AEs (SAEs) were reported and 
no patients discontinued treatment due to a TEAE in Phase 1A, Part 2 of 
Study BGB-290-AU-002. 
In Phase 1B of the study (dose expansion), 100.0% of patients experienced a TEAE, while 
87.9% of patients experienced a drug-related TEAE. A total of 10 patients (30.3%) experienced a 
severe (≥ Grade 3) pamiparib-related TEAE. Serious TEAEs were reported in 9 patients (27.3%), 
while 1 patient (3.0%) experienced a serious pamiparib-related TEAE. No patients discontinued 
treatment due to a TEAE or died in Phase 1B of Study BGB-290-AU-002. 
Ten patients achieved either CR (n = 2) or PR (n = 8); all responses were observed in patients 
with gynecological cancers. 
Please refer to the Investigator’s Brochure (IB) for additional information regarding clinical 
studies being conducted with pamiparib.6 
1.3.2. 
Pharmacokinetics and Pharmacodynamics 
1.4. 
Study Rationale 
The purpose of this study is to determine the absorption, metabolism, and excretion of 
[14C]-pamiparib and to characterize and identify metabolites present in plasma, urine, and, where 
possible, feces, in male and female patients with advanced and/or metastatic solid tumors 
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Pamiparib was not mutagenic in the in vitro Ames (bacterial reverse mutation) assay, but, 
consistent with its mechanism of action, was clastogenic in the in vitro chromosomal aberration 
assay in mammalian CHO cells and in the in vivo rat bone marrow micronucleus assay. 
Consequently, pamiparib cannot be given to healthy volunteers and will be administered to 
cancer patients in this study. The results from this study may guide future study designs 
evaluating the potential for drug-drug interactions. 
1.5. 
Benefit-Risk Assessment 
Pamiparib has been studied in nonclinical toxicity and Phase 1 clinical studies. Pamiparib 
toxicities are largely consistent with the safety profile shared by other PARP inhibitors with the 
possible exception that pamiparib may cause less myelosuppression. 
The radiation dose is an acceptable dose to give to both male and female patients with advanced 
cancer (Section 3.3).  
More information about the known and expected benefits, risks, and reasonably anticipated AEs 
associated with pamiparib may be found in the IB.6 For the most comprehensive nonclinical and 
clinical information regarding pamiparib background, safety, efficacy, and in vitro and in vivo 
nonclinical activity and toxicology of pamiparib, refer to the latest version of the pamiparib IB.6 
Based on the nonclinical and clinical data to date, pamiparib warrants further exploration in 
patients with advanced solid tumors and the overall risk-benefit ratio appears favorable. 
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
2.1.1. 
Primary Objectives 
The primary objectives of the study are: 
 To assess the disposition of [14C]-pamiparib following oral administration of a single 
60 mg (~100 µCi) dose in patients with advanced and/or metastatic solid tumors 
 To assess the plasma PK of total radioactivity and pamiparib following a single oral dose 
of [14C]-pamiparib 
 To determine the whole blood and plasma concentrations of total radioactivity 
 To determine the urinary and fecal recovery of total radioactivity 
2.1.2. 
Secondary Objectives 
The secondary objectives of the study are: 
 To characterize and identify metabolites of [14C]-pamiparib in plasma, urine, and feces 


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 To determine plasma and urine concentrations of pamiparib and/or its major metabolites 
 To assess the safety and tolerability of pamiparib during the treatment phase 
2.2. 
Endpoints 
2.2.1. 
Primary Endpoints 
The following PK outcome endpoints of pamiparib (plasma), and total radioactivity (whole 
blood and plasma) derived from the concentration-time profiles following a single oral dose of 
[14C]-pamiparib are as follows: 
 AUC from time zero to infinity (AUC0-∞) 
 AUC from time zero to the last quantifiable concentration (AUC0-t) 
 Cmax 
 Time of Cmax (tmax) 
 t1/2 
 Apparent total clearance (CL/F) 
 Apparent volume of distribution (Vz/F) 
 AUC0-∞ of plasma pamiparib relative to AUC0-∞ of plasma total radioactivity (AUC0-∞ 
Plasma Pamiparib Total Radioactivity Ratio) 
 AUC0-∞ of whole blood total radioactivity to AUC0-∞ of plasma total radioactivity 
(AUC0-∞ Blood/Plasma Ratio). 
The primary PK outcome endpoints of pamiparib and total radioactivity derived from urine 
collections are as follows: 
 Amount excreted in urine (Aeu) 
 Cumulative Aeu 
 Percentage excreted in urine (feu) 
 Cumulative feu 
 Renal clearance (CLR; pamiparib only). 
The primary PK outcome endpoints of total radioactivity derived from fecal collections are as 
follows: 
 Amount excreted in feces (Aef) 
 Cumulative Aef 
 Percentage excreted in feces (fef) 


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 Cumulative fef. 
2.2.2. 
Secondary Endpoints 
The metabolite outcome endpoints will be derived: 
 Metabolic profile of pamiparib 
 Identification of pamiparib metabolites. 
The secondary safety outcome measures are as follows: 
 Incidence and severity of AEs 
 Incidence of laboratory abnormalities, based on hematology and clinical chemistry test 
results 
 12-lead ECG parameters 
 Vital sign measurements 
 Physical examinations. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This is an open-label, inpatient study in patients with advanced and/or metastatic solid tumors, 
which consists of 2 parts: a research phase and a treatment phase.  
An overview of the study design for Part 1 and Part 2 is shown in Figure 3 and Figure 4, 
respectively. 
Potential patients will be screened to assess their eligibility to enter the study within 28 days 
prior to the first dose administration. Re-screening of patients will be allowed per the Principal 
Investigator’s (PI’s) discretion. Up to approximately 10 patients will be enrolled to ensure 
4 patients complete Part 1 of the study.  
The start of the study is defined as the date the first enrolled patient signs an Informed Consent 
Form (ICF). The point of enrollment occurs at the time of patient number allocation. The end of 
the study is defined as the date of the last patient’s last assessment (scheduled or unscheduled) or 
follow-up. 
A Schedule of Assessments is presented in Appendix 4.  
 


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3.1.1. 
Study Part 1 (Research Phase) 
Figure 3: 
Study Schematic: Part 1 
 
-28
-2
-1
1
2
7
14
Screening
Study day
Admission to 
the CRU
Discharge from 
the CRU1
Part 1: Research Phase
[14C]-pamiparib 
administration
Part 2: Treatment 
Phase
Follow-up2
 
Abbreviation: CRU = Clinical Research Unit. 
1  Discharge may occur earlier than Day 7 if discharge criteria have been met (approximately 90% mass balance 
recovery, or < 1% of total dose recovered in urine and feces for 2 consecutive 24-hour collection intervals). 
2  Patients will attend a Follow-up visit within 7 days of Discharge (if discharged on Day 7 or before), or within 
7 days of their final non-residential visit (if additional non-residential visits are required). 
Patients will be admitted into the Clinical Research Unit (CRU) on Day -1. On the morning of 
Day 1, patients will receive a single oral dose of 60 mg containing approximately 100 μCi 
(3.7 MBq) of [14C]-pamiparib.  
Patients will be resident at the CRU until completion of all assessments on Day 7, but may be 
discharged earlier at the PI’s discretion if they meet the following discharge criteria: 
 Approximately 90% of the radioactive dose is recovered 
or 
 < 1% of the radioactive dose is recovered in urine and feces for 2 consecutive 24-hour 
collection intervals.  
If the discharge criteria have not been met on Day 7, patients may be asked to collect 24-hour 
excreta samples for up to a further 7 days (up to Day 14) on a non-residential basis. Patients may 
be required to remain resident at the CRU for longer than 7 days if deemed necessary by the PI 
to ensure patient safety. If the discharge criteria have not been met by Day 14, the need for 
additional sample collection will be at the discretion of the PI.  
Patients experiencing emesis during the first 4 hours postdose may not be evaluable and 
therefore may be discharged on the same day from the clinical site, provided there are no safety 
concerns, and after discharge study procedures are performed. These patients will attend a 


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Follow-up visit within 7 days of Discharge and may be enrolled to Part 2 of the study at the 
discretion of the PI. Patients may be prescribed anti-emetics if required.  
A Follow-up visit will occur within 7 days of Discharge from the CRU (if discharged on Day 7 
or before), or within 7 days of the patients’ final non-residential visit (if additional 
non-residential visits are required). During the Follow-up visit, the patients may be entered into 
Part 2 of the study if deemed appropriate by the PI.  
3.1.2. 
Study Part 2 (Treatment Phase) 
Figure 4: 
Study Schematic: Part 2 
28
Cycle
 day
Safety Follow-up 
visit (approximately 
30 days post last 
dose)
1
Part 2: Treatment Phase – pamiparib (60 mg BID) administration
Cycle 1 & 2
15
28
1
Cycles 3+
CRU visits (+/- 2 days)
CRU visit 
(+/- 2 days)
Safety 
assessments
≤7 days
End of Treatment 
visit (7 days post 
last dose)
 
Abbreviations: BID = twice daily; CRU = Clinical Research Unit. 
Patients will undergo safety assessments ≤ 7 days prior to the start of pamiparib treatment in 
Part 2. These assessments may be conducted at the Follow-up visit for Part 1 if it occurs within 
this time window, or at a separate site visit. If there are greater than 8 weeks between tumor 
assessments at study Screening and the planned start of pamiparib treatment in Part 2, patients 
should undergo a computed tomography (CT) scan prior to the start of treatment in Part 2.  
During Part 2, patients will attend 2 site visits per cycle during Cycles 1 and 2, and 1 site visit 
per cycle during each subsequent cycle. Patients will continue receiving treatment until 
occurrence of progressive disease (PD), unacceptable toxicity, pregnancy, death, withdrawal of 
consent, lost to follow-up, major protocol violation which in the opinion of the Sponsor would 
have significant impact on the study or its outcome, start of new anticancer therapy, withdrawal 
by the PI, or study termination by Sponsor. Patients will attend an End-of-treatment (EOT) visit 
within 7 days following their last dose and a safety Follow-up visit approximately 30 days after 
the last dose of pamiparib.  
The reason for treatment discontinuation will be recorded on the electronic Case Report Form 
(eCRF). An EOT visit should occur within 7 days after the final pamiparib dose. The visit should 
be scheduled as soon as possible, but the EOT visit may occur later after discussion with the 


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Medical Monitor for specific circumstances, such as prolonged hospitalization. Every effort must 
be made to encourage the patient to complete their EOT visit and appropriate safety follow-ups. 
3.2. 
Discussion of Study Design 
This study is an open-label study with the objectives and endpoints described in Section 2. The 
study will be conducted in patients with advanced and/or metastatic solid tumors. The dose, 
patient population, study duration, and sample collection timing are considered adequate to 
achieve the study objectives. 
Oral administration was chosen since this is the intended clinical route of administration. Based 
on the nonclinical data and the known PK of pamiparib, the sample collection timing and 
duration of this study are considered adequate to achieve the study objectives. 
Part 2 of the study is to allow patients participating in Part 1 of the study continued access to 
pamiparib. Patients will be allowed to continue on the study as detailed in Section 3.1.2.  
3.3. 
Selection of Doses in the Study 
A dose of oral pamiparib 60 mg twice daily was chosen based upon the overall safety, efficacy, 
and PK profile of pamiparib using available clinical data from Study BGB-290-AU-002 
(Section 1.3.1). Study BGB-290-AU-002 determined the MTD of pamiparib to be 80 mg 
administered orally twice daily (160 mg/day). The dose of 60 mg twice daily was selected for 
further evaluation based on the following findings (refer to the pamiparib IB6): 
 A linear PK profile observed up to 80 mg twice daily 
 Similar toxicity profiles at 60 mg and 80 mg twice daily with the following exceptions: 
o Fewer patients at 60 mg twice daily experienced treatment-related TEAEs of 
anemia and neutropenia than those receiving higher doses 
o There was a slightly higher rate of dose interruptions at 80 mg versus 60 mg twice 
daily for anemia and nausea 
 Responses were observed across the dose range evaluated. 
In Part 1, the radioactive dose of approximately 3.7 MBq (~100 μCi) of [14C]-pamiparib was 
chosen to provide sufficient radioactive signal for total radioactivity counting and quantitative 
radio-profiling of [14C]-pamiparib in blood, plasma, and excreta (primary objectives of the 
study), with minimal radiation risk to patients. 
Dosimetry calculations were based on QWBA studies in male and female Long Evans rats 
receiving an oral dose of [14C]-pamiparib. An administration of approximately 3.7 MBq will 
result in an overall human effective dose of 0.98 to 1.08 mSv. This falls well within the 
International Commission on Radiological Protection (ICRP) 629,10 risk category IIb (1 to 
10 mSv, minor to intermediate risk) and World Health Organization11 category IIb (0.5 to 5 mSv, 
within dose limits for members of the public). 


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The effective radiation dose is defined as being within dose limits for members of the public 
(Category II study, World Health Organization) with a minor associated risk (risk Category IIb, 
ICRP).10 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Patients must satisfy all of the following criteria at the Screening visit unless otherwise stated: 
1. Able to comprehend and willing to sign an ICF and to abide by the study restrictions 
2. Male or female of any race, ≥ 18 years of age at Screening 
3. A total body weight between 50 and 100 kg, inclusive, at Screening 
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (see 
Appendix 3) 
5. Ability to swallow whole capsules 
6. Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has 
progressed after treatment with approved therapies or for which there are no standard 
therapies available 
7. Adequate organ functions as indicated by the following Screening laboratory values 
(obtained ≤ 2 weeks prior to Day 1): 
 Absolute neutrophil count ≥ 1.5 x 109/L 
 Platelets ≥ 100 x 109/L 
 Hemoglobin ≥ 9 g/dL (≥ 14 days after growth factor support or transfusion) 
 Estimated glomerular filtration rate  30 mL/min/1.73 m2 by the Modification of Diet 
in Renal Disease study equation 
 Total serum bilirubin ≤ 1.5 x ULN (total bilirubin must be ≤ 4 x ULN for patients 
with Gilbert’s syndrome) 
 Aspartate and alanine aminotransferase  3 x ULN OR ≤ 5 x ULN for patients with 
liver metastases 
 Serum albumin ≥ 3 g/dL 
8. Patients must agree to use contraception as detailed in Section 6.4.  Nonsterile males 
must avoid sperm donation for the duration of the study and for at least 6 months after the 
last dose of study drug. 
9. Have regular bowel movements (minimum of 1 bowel movement per day or every other 
day; no more than 3 bowel movements per day) for 2 weeks without diarrhea prior to 
Screening (laxatives will be allowed in the study per the PI’s discretion) 
10. Have the ability to provide regular urine samples. 


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4.2. 
Exclusion Criteria 
Patients will be excluded from the study if they satisfy any of the following criteria at the 
Screening visit unless otherwise stated: 
1. Chemotherapy, biologic therapy, immunotherapy, investigational agents, or herbal 
remedies  14 days (or  5 half-lives, whichever is shorter) prior to Day 1 
 Bisphosphonate and denosumab use is allowed on study as appropriate, if 
administered at a stable dose > 28 days before enrollment 
 Patients who have participated in any clinical trial involving a radiolabeled 
investigational product within 12 months prior to Check-in are excluded 
2. Patients who have received local radiotherapy of non-target lesions for local symptom 
control within the last 4 weeks must have recovered from any adverse effects of 
radiotherapy before commencing this study 
3. Unresolved acute effects of any prior therapy of Grade 2 or higher, except for AEs not 
constituting a safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities) 
4. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 2 weeks prior to 
Day 1, or anticipation of need for major surgical procedure during the course of the study  
 Placement of a vascular access device is not considered major surgery 
5. Leptomeningeal disease or uncontrolled, untreated brain metastases. Patients with a 
history of treated and, at the time of screening, asymptomatic brain metastases are eligible, 
provided they meet all of the following: 
 Only supratentorial metastases 
 Brain imaging at Screening without evidence of interim progression 
 No ongoing requirement for corticosteroids as therapy for brain metastases 
o Anticonvulsants at a stable dose allowed 
 No stereotactic radiation or whole-brain radiation ≤ 14 days prior to Day 1 
6. Active infection requiring systemic treatment, active viral hepatitis, or active tuberculosis 
7. Any of the following cardiovascular criteria: 
 Cardiac chest pain, defined as moderate pain that limits instrumental activities of 
daily living,  28 days before first dose 
 Symptomatic pulmonary embolism  28 days before first dose 
 Any history of acute myocardial infarction  6 months before first dose 
 Any history of heart failure meeting New York Heart Association Classification III or 
IV  6 months before first dose (see Appendix 5) 


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 Any event of ventricular arrhythmia  Grade 2 in severity  6 months before 
enrollment 
 Any history of cerebral vascular accident  6 months before enrollment. 
8. Have a previous complete gastric resection, chronic diarrhea, active inflammatory 
gastrointestinal disease, or any other disease causing malabsorption syndrome. 
Gastro-esophageal reflux disease under treatment with proton pump inhibitors is allowed 
9. Use or have anticipated need for food or drugs known to be strong or moderate CYP3A 
inhibitors or strong CYP3A inducers ≤ 10 days or ≤ 5 half-lives, whichever is shorter, 
prior to Day 1 (see Appendix 6) 
10. Are pregnant or nursing (females of childbearing potential require a negative serum 
pregnancy test at Screening and a negative urine pregnancy test on Day -1) 
11. Significant intercurrent illness that may result in the patient’s death before death from 
cancer 
12. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, including known history of intolerance to the excipients of the 
pamiparib capsule 
13. Poor peripheral venous access. Venous access via a port will be permitted. 
4.3. 
Patient Number and Identification 
At Screening, all patients will be assigned a unique screening identification number. If enrolled 
into the study, patients will be assigned a patient number prior to the first dosing occasion. 
Assignment of patient numbers will be in ascending order based on time of enrollment, and no 
numbers will be omitted (eg, Patients 101, 102, 103). 
Enrolled patients will be identified by patient number only on all study documentation. A list 
identifying the patients by patient number will be kept in the Site Master File. 
4.4. 
Patient Withdrawal and Replacement 
A patient is free to withdraw from the study at any time. A patient may be withdrawn for any of 
the following reasons: 
 PD 
 AEs 
 Pregnancy 
 Major protocol violation  
 Patient withdrew consent for study treatment 
o Patients may voluntarily withdraw consent from study treatment at any time 


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o Patients should be requested to participate in the follow-up phase, if patient 
withdraws consent from the treatment phase only 
 Investigator’s discretion 
 Start of new anticancer therapy 
If a patient is withdrawn from dosing, the Sponsor will be notified and the date and reason(s) for 
the withdrawal will be documented in the patient’s eCRF. If a patient is withdrawn, efforts will 
be made to perform all discharge assessments, if possible (Appendix 4). Other procedures may 
be performed at the PI’s (or designee’s) and/or Sponsor’s discretion. If the patient is in-house, 
these procedures should be performed before the patient is discharged from the clinic. The PI (or 
designee) may also request that the patient return for an additional Follow-up visit. All 
withdrawn patients will be followed until resolution of all their AEs or until the unresolved AEs 
are judged by the PI (or designee) to have stabilized. 
Patients withdrawn prior to first investigational medicinal product (IMP) administration and/or 
during Part 1 of the study may be replaced following discussion between the PI and Sponsor. 
4.5. 
Study Termination 
The Sponsor has the right to terminate this study at any time. Reasons for terminating the study 
early may 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  
 Overall patient enrollment is unsatisfactory 
 Poor protocol adherence  
 Inaccurate or incomplete data recording  
 Good Clinical Practice (GCP) noncompliance 
 Study activity is completed (ie, all patients have completed and all obligations have been 
fulfilled). 
The Sponsor will notify the PI if a decision is made to terminate the study. Should this be 
necessary, prematurely discontinued patients should be seen as soon as possible for an EOT visit 
and safety Follow-up visit. 
The PI may be informed of additional procedures to be followed in order to ensure that adequate 
consideration is given to the protection of the patient’s interests. The PI will be responsible for 
informing the EC of the early termination of the study. 


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5. STUDY TREATMENTS 
5.1. 
Description, Storage, Packaging, and Labelling 
 
 
 
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
 
5.2. 
Study Treatment Administration 
5.2.1. 
Part 1 
Patients should be fasted 1 hour before and 2 hours after the dose. [14C]-pamiparib will be 
administered orally with approximately 240 mL of room temperature water. 
 
 
 At all times during the study, patients may consume water ad libitum. 
Patients will be dosed while seated and will not be permitted to lie supine for 2 hours after 
administration of [14C]-pamiparib except as necessitated by the occurrence of an AE(s) and/or 
study procedures. 
5.2.2. 
Part 2 
Pamiparib capsules will be dispensed to patients by qualified site personnel at scheduled site 
visits throughout Part 2 to ensure that patients have an adequate drug supply for administration at 
home. The patient will be instructed to take the study drug exactly as prescribed, once in the 
morning and once in the evening at approximately the same time each day. 


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Patients will be requested to bring their unused medication to the CRU at each visit. All dosages 
prescribed and dispensed to the patient and all dose changes including reason for dose changes 
during the study must be recorded in the eCRF. 
5.3. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance in Part 1: 
 The dose will be administered under the supervision of suitably qualified study site staff. 
 Immediately after oral administration, visual inspection of the mouth will be performed 
on each patient. 
In Part 2, patients will self-administer all doses of pamiparib at home. Patients will be asked to 
record daily timing and dose in a dosing diary, and the dosing diary will be reviewed at site visits 
to check treatment compliance. 
5.4. 
Drug Accountability 
The PI (or designee) will maintain an accurate record of the receipt of the study supplies 
received. In addition, an accurate drug disposition record will be kept, specifying the amount 
dispensed to each patient and the date of dispensing. This drug accountability record will be 
available for inspection at any time. At the completion of the study, the original drug 
accountability record will be available for review by the Sponsor upon request. 
In Part 1, empty, used unit dose containers will undergo radioanalysis to determine the amount of 
any residual radioactivity remaining after dose administration and will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused assembled 
unit doses will be retained until completion of Part 1 of the study before being returned to the 
Sponsor or disposed of by the study site, per the Sponsor’s written instructions or site standard 
operating procedures (SOPs). 
In Part 2, all unused pamiparib will be returned to the study site. 
At the completion of the study, all unused supplies will be returned to the Sponsor or disposed of 
by the study site, per the Sponsor’s written instructions or site SOPs. 
5.5. 
Dose Hold and Modification 
The relationship between AEs and pamiparib will be assessed by the PI (or designee). Dosing of 
pamiparib in Part 2 can be withheld for up to 28 days consecutively. 
Criteria for treatment modifications and suggested guidelines for the management of some 
toxicity related to pamiparib are summarized below. These general guidelines may be modified 
at the discretion of the PI based on discussions with the Medical Monitor and the best clinical 
judgment at that time; any decisions should be documented. Any toxicity related to pamiparib 
should be managed according to standard medical practice. 


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A maximum of 2 dose reductions is allowed before the patient must be permanently withdrawn 
from study drug. Dose levels for pamiparib are summarized in Table 2. Pamiparib should be 
dose-modified as outlined in Table 3. 
Table 2: 
Dose Levels for Pamiparib 
Dose Level 
Pamiparib 
1 
60 mg orally, twice daily 
-1 
40 mg orally, twice daily 
-2 
20 mg orally, twice daily 
Pamiparib may be dose-reduced for a maximum of 2 dose reductions. 
 
Table 3: 
Criteria for Modification of Pamiparib Dosing for Related Adverse Events 
 
Toxicity 
Recommended Dose Modificationa 
Hematologic 
Anemia (hemoglobin, Hgb) 
Grade 2 (Hgb < 10 - 8 g/dL) 
 
First occurrence: continue dosing at current dose level 
Second and subsequent occurrences: hold pamiparib until resolved to 
≤ Grade 1 or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  pamiparib by 1 dose level 
Grade 3 (Hgb < 8 g/dL) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  pamiparib by 1 dose level 
Grade 4 (life-threatening 
consequences; urgent intervention 
indicated) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Neutropenia (absolute neutrophil count, ANC) 
Grade 3 (ANC < 1.0 - 0.5  109/L) 
Hold pamiparib until resolved to ≤ Grade 2 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (ANC < 0.5  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Febrile neutropenia (ANC < 1.0 
109/L with single temperature of 
> 38.3°C or sustained temperature of 
≥ 38°C for > 1 hour) 
Hold pamiparib until resolved and 
 pamiparib by 1 dose level 


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Toxicity 
Recommended Dose Modificationa 
Thrombocytopenia (platelet count, PLT) 
Grade 3 (PLT < 50 - 25  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (PLT < 25  109/L) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Renal 
Estimated glomerular filtration rate (MDRD STUDY EQ; www mdrd.com or Appendix 7) 
If ≥ 60 mL/min/1.73 m2 at baseline: 
< 30 to 15 mL/min/1.73 m2 or 
If < 60 mL/min/1.73 m2 at baseline: 
≥ 50% reduction from baseline 
Hold pamiparib until resolved to ≥ 60 mL/min/1.73 m2 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Regardless of baseline: 
< 15 mL/min/1.73 m2 
Permanently discontinue pamiparib 
Hepatic 
Bilirubin 
Grade 2 (> 1.5 - 3.0  ULN) 
Only applies to patients with 
normal bilirubin at baseline 
Hold pamiparib until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 3 (> 3.0 - 10.0  ULN) 
Hold pamiparib until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  pamiparib by 1 dose level 
Grade 4 (> 10.0  ULN) 
Permanently discontinue pamiparib 
Note: If Grade 3 or 4 hyperbilirubinemia is due to the indirect 
(unconjugated) component only, and hemolysis as the etiology has been 
ruled out as per institutional guidelines (eg, review of peripheral blood 
smear and haptoglobin determination), then  pamiparib by 1 dose level 
and continue treatment at the discretion of the Investigator in discussion 
with the Medical Monitor 
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
Grade 3 (> 5 and ≤ 20  ULN) 
Hold pamiparib until AST and/or ALT resolved to ≤ 5  ULN or 
baseline 
 If ≤ 5  ULN within 14 days, then  pamiparib by 1 dose level 
 If second episode, permanently discontinue pamiparib 
 If persistent for > 14 days, permanently discontinue pamiparib 
Grade 4 (> 20  ULN) 
Permanently discontinue pamiparib 
Pancreatic 
Pancreatitis 
Grade 3 or 4 
Permanently discontinue pamiparib 


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Toxicity 
Recommended Dose Modificationa 
Cardiac 
Cardiac - Prolonged QTc interval 
QTcF > 500 ms or > 60 ms from the 
higher of the baseline or predose value 
 Obtain triplicate ECGs (2 to 3 minutes apart) ~ 1 hour after initial 
ECG 
 If mean QTcF > 500 ms, or > 60 ms from baseline value, 
hold pamiparib until evaluation of ECGs by cardiologist 
o Cardiology evaluation as soon as practical but within 7 days of 
initial abnormal ECG 
 If mean QTcF > 500 ms confirmed by cardiologist, 
permanently discontinue pamiparib 
Cardiac - General 
Grade 3 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and 
 pamiparib by 1 dose level 
Grade 4 
Permanently discontinue pamiparib  
Other adverse events 
 
Grade 3 
Hold pamiparib until resolved to ≤ Grade 1 or baseline and  pamiparib 
by 1 dose level 
No dose reduction required for asymptomatic laboratory abnormalities 
Grade 4 
Permanently discontinue pamiparib 
Abbreviations: ECG = electrocardiogram; MDRD = Modification of Diet in Renal Disease; QTcF = QT interval 
corrected for heart rate using Fridericia’s formula; ULN = upper limit of normal. 
a. Dosing of pamiparib can be withheld for up to 28 days consecutively. 
 
 


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6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
The PI will instruct the patient to notify the study site about any new medical treatment that 
she/he takes during the study period. All concomitant medications, both permitted and non-
permitted, and significant non-drug therapies (eg, surgery, blood transfusions, and physical 
therapy) administered/conducted after the patient is enrolled in this study will be recorded in the 
source documents and eCRF. All concomitant medications, including all prescription and 
over-the-counter drugs, supplements, and intravenous medications and fluids, taken by or 
administered to the patient within 28 days before Day 1 should be recorded as well. 
6.1.1. 
Permitted Concomitant Treatment 
Supportive therapy considered necessary for the patients’ welfare may be given at the discretion 
of the PI. This includes, but is not limited to, analgesics, anticonvulsants, anti-emetics, 
antidiarrheal treatment, laxatives, opiates, and transfusion of blood products. 
6.1.2. 
Prohibited Concomitant Treatment 
Patients are not allowed to receive other anticancer therapy, including surgery; chemotherapy; 
radiation therapy; immunotherapy; investigational agents; cytotoxic, biologic, or hormone 
therapy; anticancer Chinese medicine; or herbal remedies ≤ 14 days (or ≤ 5 half-lives, if 
applicable, whichever is shorter) prior to first dose and during the study. Hormone replacement 
therapy is allowed. Bisphosphonate and denosumab use is permitted if the patient had already 
been receiving it at a stable dose > 28 days before enrollment. 
The primary metabolic pathway for pamiparib involves the CYP3A isoform. Administration of 
strong/moderate inhibitors of CYP3A or strong CYP3A inducers is not allowed ≤ 10 days or ≤ 5 
half-lives, whichever is shorter, prior to Day 1 until the EOT visit. Refer to the drugs/substances 
listed in Appendix 6 for a more complete list of medications that are not allowed or that need to 
be taken with caution. 
6.2. 
Diet 
While confined at the study site, patients will receive a standardized diet at scheduled times that 
do not conflict with other study-related activities. 
 
 
 
 
 
 
Caffeine-containing foods and beverages will not be allowed from 36 hours before Check-in 
until discharge from the CRU (Part 1). 


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Consumption of alcohol will not be permitted from 36 hours prior to Check-in until the end of 
Part 1. 
6.3. 
Smoking 
Patients will not be permitted to use tobacco-containing products while admitted to the CRU. 
Nicotine replacement therapy will be available on request to be used per the package insert. 
6.4. 
Contraception 
Females of childbearing potential, nonsterile males, and female partners of nonsterile male study 
patients must agree to practice highly effective methods of birth control for the duration of the 
study and for at least 6 months after the last dose of study drug. Nonsterile males must avoid 
sperm donation for the duration of the study and for at least 6 months after the last dose of study 
drug.  See Appendix 8 for contraception guidelines. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving consideration to appropriate posture conditions, practical restrictions, and 
the other procedures to be performed at the same timepoint. 
In Part 1, the recommended order of priority for scheduling procedures around a timepoint is (in 
descending order of priority): 
 Physical examinations 
 ECOG 
 Vital sign measurements 
 ECGs 
 Blood and urine samples for clinical laboratory evaluations 
 Dosing 
 Blood samples for PK assessments of pamiparib, total radioactivity, and metabolites 
 Start and end of urine and fecal collections for PK assessments. 
In Part 2, assessments will be conducted at study visits as in the Schedule of Assessments in 
Appendix 4.  
7.1. 
Pharmacokinetic Assessments (Part 1 Only) 
7.1.1. 
Pharmacokinetic and Metabolite Blood Sample Collection and Processing 
Blood samples will be collected by venipuncture or cannulation at the times indicated in the 
Schedule of Assessments in Appendix 4 for determination of pamiparib concentration, total 


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radioactivity, and metabolite profiling and identification. Procedures for collection, processing, 
and shipping of blood samples will be detailed in a separate document. 
Approximately 1 × 2 mL blood sample will be collected for total radioactivity in whole blood 
and approximately 1 × 6 mL blood sample will be collected for total radioactivity in plasma. 
Approximately 1 × 4 mL blood sample will be collected for pamiparib concentration in plasma. 
Approximately 1 × 10 mL blood sample will be collected for metabolite profiling and 
identification in plasma. 
7.1.2. 
Pharmacokinetic, Total Radioactivity, and Metabolite Urine and Fecal 
Collection and Processing 
Urine will be collected over the time intervals indicated in the Schedule of Assessments in 
Appendix 4 for determination of pamiparib concentration, total radioactivity, and metabolite 
profiling and identification. Procedures for collection, processing, and shipping of urine 
collections will be detailed in a separate document. 
Feces will be collected over the time intervals indicated in the Schedule of Assessments in 
Appendix 4 for determination of total radioactivity, and, where possible, metabolite profiling and 
identification. If possible, a single baseline fecal sample will be collected between Check-in on 
Day -1 and dose administration on Day 1. Procedures for collection, processing, and shipping of 
fecal collections will be detailed in a separate document. 
7.1.3. 
Emesis Sample Collection 
For patients experiencing emesis within 4 hours following oral dosing, vomitus will be collected. 
If possible, vomitus from patients experiencing emesis after 4 hours postdose will be collected. 
All vomitus collected will be stored for possible analysis as deemed appropriate. 
7.1.4. 
Analytical Methodology 
Plasma and urine concentrations of pamiparib will be determined using a validated analytical 
procedure. Whole blood, plasma, urine, and feces total radioactivity will be determined with 
liquid scintillation counting. Profiling and identification of metabolites in plasma, urine, and, 
where possible, feces will be conducted using standard laboratory procedures. Specifics of the 
analytical methods will be provided in separate documents. 
7.2. 
Safety and Tolerability Assessments (Parts 1 and 2) 
7.2.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Section 8. 
The condition of each patient will be monitored from the time of signing the ICF to final 
discharge from the study. Patients will be observed for any signs or symptoms and asked about 


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their condition by open questioning, such as “How have you been feeling since you were last 
asked?,” at least once each day while resident at the study site and at each study visit. Patients 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
Any AEs and remedial action required will be recorded in the patient’s source data. The nature, 
time of onset, duration, and severity will be documented, together with a PI’s (or designee’s) 
opinion of the relationship to study drug. 
Adverse events recorded during the course of the study will be followed up, where possible, until 
resolution. This will be completed at the PI’s (or designee’s) discretion. 
7.2.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations (including clinical 
chemistry, hematology, serology, and urinalysis) at the times indicated in the Schedule of 
Assessments in Appendix 4. Clinical laboratory evaluations are listed in Appendix 1. 
For all female patients of childbearing potential, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments (Part 1 and Part 2) in Appendix 4.  An FSH test will be 
performed at Screening to confirm postmenopausal status. 
The PI (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.2.3. 
Vital Signs 
Supine blood pressure, supine heart rate, and oral body temperature will be assessed at the times 
indicated in the Schedule of Assessments in Appendix 4. Vital signs will be performed at other 
times if judged to be clinically appropriate, if the ongoing review of the data suggests a more 
detailed assessment of vital signs is required. These data will be captured in the eCRF. In line 
with local CRU policies, vital signs will also be assessed at other timepoints but will not be 
documented unless determined to be of clinical relevance. 
All measurements will be performed singly and repeated once if outside the relevant clinical 
reference range. 
Patients must be supine for at least 5 minutes before blood pressure, heart rate, and temperature 
measurements. During the in-house period in Part 1, blood pressure, heart rate, and temperature 
measurements should be conducted in the morning. 
7.2.4. 
12-Lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the patient has been supine and at rest for at least 
5 minutes at the times indicated in the Schedule of Assessments in Appendix 4. 
Single 12-lead ECGs will be repeated once if outside the clinical reference range. 


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In the case of an abnormality such as prolonged QT interval corrected for heart rate using 
Fridericia’s formula > 500 msec or > 60 msec from the highest baseline or predose value, new 
arrhythmia, or other clinically significant finding, ECGs will be recorded in triplicate at least 2 
minutes apart. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically appropriate 
or if the ongoing review of the data suggests that a more detailed assessment of ECGs is 
required. The PI (or designee) will perform a clinical assessment of each 12-lead ECG. 
7.2.5. 
Physical Examination 
Complete and limited physical examinations will be performed at the timepoints specified in the 
Schedule of Assessments in Appendix 4. A complete physical examination includes a review of 
the following systems: head/neck/thyroid; eyes/ears/nose/throat; respiratory; cardiovascular; 
lymph nodes; abdomen; skin; musculoskeletal; and neurological. A limited physical examination 
includes an assessment of the patient’s general appearance, skin, thorax/lungs, cardiovascular, 
and abdomen. 
7.2.6. 
Eastern Cooperative Oncology Group 
The ECOG performance status will be evaluated at the times indicated in the Schedule of 
Assessments in Appendix 4. 
7.2.7. 
Tumor Assessments 
Tumor imaging (CT or magnetic resonance imaging [MRI], with preference for CT) will be 
performed at Screening or Part 2 Pre-dose Visit and every 12 weeks (± 7 days) from the time of 
the Part 2 C1D1. At the PI’s discretion, CT or MRI scans may be repeated at any time if PD is 
suspected. 
A CT scan or MRI of the thorax, abdomen, and pelvis plus other relevant evaluations as 
appropriate will be performed to assess all known disease.  
The same imaging technique should be used for each patient throughout the study.  
7.3. 
End-of-Treatment Visit 
The EOT visit should occur within 7 days after pamiparib has been permanently discontinued. 
Required assessments are listed in Appendix 4. A visit should be scheduled as soon as possible, 
but the EOT visit may occur later after discussion with the Medical Monitor for specific 
circumstances, such as prolonged hospitalization. The visit at which tumor assessments showed 
PD may be used as the EOT visit provided that all required assessments were performed. Tumor 
assessments do not have to be repeated if they were performed within 14 days of the EOT visit or 
at a prior response evaluation that documented PD. An ECG does not have to be repeated if it 
was performed within 14 days of the EOT visit.  


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7.4. 
Follow-up Assessments 
7.4.1. 
Safety Follow-up 
All patients who discontinue pamiparib will have a safety follow-up approximately 30 days after 
the last day of study drug or before initiation of new anticancer therapy, whichever comes first. 
The purpose of this visit is to collect AEs and SAEs that may have occurred after the patient 
discontinued from the study drug, as well as to record any additional concomitant medications 
and to conduct a limited physical examination. For patients who complete Part 2, clinical 
laboratory evaluations are only required if the patient had an ongoing clinical laboratory 
abnormality at the previous visit that the PI considered to be related to study drug. 
8. SAFETY MONITORING AND REPORTING 
The PI is responsible for the monitoring and documentation of events that meet the criteria and 
definition of an AE or SAE as provided in this protocol. 
8.1. 
Adverse Events 
8.1.1. 
Definition and Reporting of an Adverse Event 
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study 
drug, whether considered related to pamiparib or not.  
Examples of an AE include: 
 Worsening of a chronic or intermittent pre-existing condition including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome 
 New conditions detected or diagnosed after study drug administration even though it may 
have been present before the start of the study 
 Signs, symptoms, or the clinical sequelae of a suspected interaction 
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or 
a concurrent medication (overdose per se should not be reported as an AE or SAE). 
When an AE or SAE occurs, it is the responsibility of the PI to review all documentation (eg, 
hospital progress notes, laboratory results, and diagnostics reports) relative to the AE or SAE. 
The PI will then record all relevant information regarding an AE or SAE in the eCRF. However, 
there may be instances when copies of medical records for certain cases are requested by the 
Sponsor. In this instance, all patient identifiers will be blinded on the copies of the medical 
records before submission to the Sponsor. 


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8.1.2. 
Assessment of Severity 
The PI will make an assessment of severity for each AE and SAE reported during the study. 
Adverse events and SAEs should be assessed and graded based upon the National Cancer 
Institute Common Terminology Criteria for Adverse Events Version 4.03 or higher. 
Toxicities that are not specified in the National Cancer Institute Common Terminology Criteria 
for Adverse Events will be defined as follows: 
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
 Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
 Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
 Grade 5: Death related to AE 
Note: The terms “severe” and “serious” are not synonymous. Severity is a measure of intensity 
(eg, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe [Grade 3], or 
life-threatening [Grade 4]); whereas, seriousness is classified by the criteria based on the 
regulatory definitions. Seriousness serves as the guide for defining regulatory reporting 
obligations from the Sponsor to applicable regulatory authorities as described below in 
Section 8.8. 
8.1.3. 
Assessment of Causality 
The PI is obligated to assess the relationship between the study drug and the occurrence of each 
AE or SAE. The PI will use clinical judgment to determine the relationship. Alternative causes, 
such as natural history of the underlying diseases, concomitant therapy, and other risk factors, 
and the temporal relationship of the AE or SAE to the study drug will be considered and 
investigated. The PI will also consult the IB6 in the determination of his assessment.  
There may be situations when an SAE has occurred and the PI has minimal information to 
include in the initial report to the Sponsor. However, it is very important that the PI always make 
an assessment of causality for every SAE before transmission of the SAE report/eCRF to the 
Sponsor since the causality assessment is one of the criteria used when determining regulatory 
reporting requirements. The PI may change his opinion of causality in light of follow up 
information, amending the SAE report accordingly.  
The causality of each AE should be assessed and classified by the PI as “related” or “not 
related.” An AE is considered related if there is “a reasonable possibility” that the AE may have 


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been caused by the study drug (ie, there are facts, evidence, or arguments to suggest possible 
causation). A number of factors should be considered in making this assessment, including: 
 Temporal relationship of the AE to the administration of study drug/study procedure 
 Whether an alternative etiology has been identified 
 Mechanism of action of the study drug 
 Biological plausibility. 
An AE should be considered “related” to study drug if any of the following criteria are met, 
otherwise the event should be recorded as not related: 
 There is clear evidence to suggest a causal relationship, and other possible contributing 
factors can be ruled out 
 There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely 
 There is some evidence to suggest a causal relationship (eg, the AE occurred within a 
reasonable time after administration of the study drug). However, the influence of other 
factors may have contributed to the AE (eg, the patient’s clinical condition or other 
concomitant AEs). 
8.1.4. 
Follow-up of Adverse Events 
After the initial AE or SAE report, the PI is required to proactively follow each patient and 
provide further information to the Sponsor on the patient’s condition.  
All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts. 
All AEs and SAEs will be followed until resolution, the condition stabilizes or is considered 
chronic, the AE or SAE is otherwise explained, the patient is lost to follow-up, or the patient 
withdraws consent. Once resolved, the appropriate AE or SAE eCRF page(s) will be updated. 
The PI will ensure that follow-up includes any supplemental investigations as may be indicated 
to elucidate the nature and/or causality of the AE or SAE. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
The Sponsor may request that the PI perform or arrange for the conduct of supplemental 
measurements and/or evaluations to elucidate as fully as possible the nature and/or causality of 
the AE or SAE. The PI is obligated to assist. If a patient dies during participation in the study or 
during a recognized follow-up period, the Sponsor will be provided with a copy of any 
postmortem findings, including histopathology. 


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New or updated information will be recorded on the originally completed SAE report, with all 
changes signed and dated by the PI. The updated SAE report should be re-sent to the Sponsor 
within the timeframes outlined in Table 4. 
8.2. 
Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, hematology or chemistry) or other abnormal assessments (eg, 
ECGs or vital signs) that are judged by the PI as clinically significant will be recorded as AEs or 
SAEs. This includes clinically significant abnormal laboratory findings or other abnormal 
assessments that are detected during the study or are present at baseline and significantly worsen 
following the start of the study. The definition of clinically significant is left to the judgment of 
the PI. In general, these are the laboratory test abnormalities that are associated with clinical 
signs or symptoms, require active medical intervention, or lead to dose interruption, 
discontinuation, or further diagnostic investigation.  
8.3. 
Definition of a Serious Adverse Event 
An SAE is defined as any untoward medical occurrence that at any dose: 
 Results in death 
 Is life-threatening. 
Note: The term “life-threatening” in the definition of “serious” refers to an AE in which the 
patient was at risk of death at the time of the AE. It does not refer to an AE which hypothetically 
might have caused death if it were more severe. 
 Requires hospitalization or prolongation of existing hospitalization. 
Note: In general, hospitalization signifies that the patient was admitted (usually involving at least 
an overnight stay) to the hospital or emergency ward for observation and/or treatment that would 
not have been appropriate in the physician’s office or outpatient setting.  
 Results in disability/incapacity.  
Note: The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle), which may interfere with or prevent everyday life 
functions, but do not constitute a substantial disruption. 
 Is a congenital anomaly/birth defect 
 Is considered a significant medical AE by the PI based on medical judgment (eg, may 
jeopardize the patient or may require medical/surgical intervention to prevent one of the 
outcomes listed above) 
 The following are NOT considered SAEs: 
o Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an SAE 


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o Hospitalization for social/convenience considerations is not considered an SAE 
o Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience, is not considered an SAE. 
8.4. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious Adverse 
Events 
8.4.1. 
Adverse Event Reporting Period 
After the ICF has been signed, but prior to administration of study drug, only SAEs should be 
reported. After initiation of study drug, all AEs and SAEs, regardless of relationship to study 
drug, will be reported until 30 days after the last dose of study drug or initiation of new 
anticancer therapy, whichever occurs first. After this period, the PI should report any SAEs that 
are believed to be related to study drug. 
8.4.2. 
Eliciting Adverse Events 
The PI or designee will inquire about AEs by asking the following standard questions: 
 How are you feeling? 
 Have you had any medical problems since your last visit? 
 Have you taken any new medicines since your last visit? 
8.5. 
Disease Progression 
Disease progression (including fatal disease progression), which is expected in this study 
population, should not be reported as an AE term. Instead, the symptoms, signs, or clinical 
sequelae that result from disease progression should be reported as the AE term(s).  
For instance, a patient with pleural effusion presents with shortness of breath. The cause of the 
shortness of breath is a pleural effusion resulting from disease progression. The AE term should 
be reported as “pleural effusion” instead of disease progression. If a patient has a seizure that is 
determined to be associated with a brain metastasis, the term “seizure” should be recorded as the 
AE instead of disease progression or brain metastasis. If a patient experienced multi-organ 
failure due to disease progression, the term “multi-organ failure” should be reported as the SAE 
with death as the outcome instead of reporting “fatal disease progression” or “death due to 
disease progression.”  
8.6. 
Death 
Death is an outcome and usually not considered an event. If the only information available is 
death and the cause of death is unknown, then the death is reported as an event (eg, “death,” 
“death of unknown cause” or “death unexplained”).  


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8.7. 
Myelodysplastic Syndrome and Acute Myeloid Leukemia  
Events of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) should be treated 
as medically serious, even if the patient is not admitted to a hospital. These events should be 
reported to the Sponsor irrespective of the time elapsed since the end of study treatment. 
8.8. 
Reporting Serious Adverse Events 
8.8.1. 
Prompt Reporting of Serious Adverse Events 
As soon as the PI determines that an AE meets the protocol definition of an SAE, the event must 
be reported promptly (within 24 hours) to the Sponsor or designee as described in Table 4. 
 
Table 4: 
Timeframes for Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
Type of 
SAE 
Timeframe for 
Making Initial 
Report 
Documentation 
Method 
Timeframe for 
Making Follow-
up Report 
Documentation 
Method 
Reporting 
Method 
All SAEs 
Within 24 hours of 
first knowledge of 
the AE 
SAE form 
As expeditiously 
as possible 
Updated SAE 
form 
Email or 
fax SAE 
form or 
Pregnancy 
form 
Abbreviations: AE = adverse event; SAE = serious adverse event. 
8.8.2. 
Completion and Transmission of the Serious Adverse Event Report 
Once the PI becomes aware that an SAE has occurred in a patient, he will report the information 
to the Sponsor within 24 hours as detailed above in Table 4. The SAE Report will always be 
completed as thoroughly as possible with all available details of the SAE and forwarded to the 
Sponsor or designee within the designated timeframes.  
If the PI does not have all information regarding an SAE, he will not wait to receive additional 
information before notifying the Sponsor or designee of the SAE and completing the form. The 
form will be updated when additional information is received.  
The PI must always provide an assessment of causality for each SAE as described in 
Section 8.1.3. 
8.9. 
Regulatory Reporting Requirements for Serious Adverse Events 
The PI will promptly report all SAEs to the Sponsor in accordance with the procedures detailed 
above. The Sponsor has a legal responsibility to notify, as appropriate, both the local regulatory 
authority and other regulatory agencies about the safety of a product under clinical investigation. 


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The PI, or responsible person according to local requirements, will comply with the applicable 
local regulatory requirements related to the reporting of SAEs to regulatory authorities and the 
Ethics Committee (EC). 
All suspected unexpected serious adverse reactions (SUSARs; as defined in Section 8.10) will be 
submitted to all applicable regulatory authorities and Investigators for pamiparib studies. 
When a study site receives an initial or follow-up report or other safety information (eg, revised 
IB) from the Sponsor, the PI or designate responsible is required to promptly notify his/her EC. 
The PI should place copies of Safety Reports from the Sponsor in the Investigator Site File. 
8.10. Suspected Unexpected Serious Adverse Reactions 
A SUSAR is a serious adverse reaction that is both unexpected (ie, not present in the product’s 
Reference Safety Information) and meets the definition of a serious adverse drug reaction, the 
specificity or severity of which is not consistent with those noted in the IB.  
8.11. Pregnancy Reporting 
If a female patient or the partner of a male patient becomes pregnant while receiving study drug 
or within 6 months after the completion of the last dose of study drug, a pregnancy report form 
should be completed and expeditiously submitted to the Sponsor to facilitate outcome follow-up. 
Information on the status of the mother and child will be forwarded to the Sponsor.   
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or SAE.  
An abortion, whether accidental, therapeutic, or spontaneous, should always be reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study drug should be recorded and reported as an SAE. 
8.12. Post Study Adverse Events 
A post study AE or SAE is defined as any AE that occurs outside of the AE/SAE reporting 
period. 
The PI should follow up patients for post study period cases of MDS and AML. If the PI learns 
of any study drug-related SAE, including a death, at any time after a patient has been discharged 
from the study, he/she should notify the Sponsor using the SAE procedure. 
8.13. Expedited Reporting to Health Authorities, Ethics Committees, and the Principal 
Investigator 
The Sponsor will promptly assess all SAEs against cumulative study drug experience to identify 
and expeditiously communicate new safety findings to regulatory authorities, the PI, and ECs 
based on applicable legislation. To determine the reporting requirements for individual SAEs, the 


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Sponsor will assess the expectedness of the SAEs using the following reference safety 
information document: 
  Pamiparib (BGB-290) IB6. 
8.14. Regulatory, Ethical, and Study Oversight Considerations 
8.14.1. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines 
 Applicable ICH Good Clinical Practice (GCP) Guidelines 
 Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents must be submitted to 
an EC by the PI and reviewed and approved by the EC, and also approved by the regulatory 
authority (as applicable by local law and regulation), before the study is initiated. 
Any substantial protocol amendments, likely to affect the safety of the patients or the conduct of 
the study, will require EC and regulatory authority (as locally required) approval before 
implementation of changes made to the study design, except for changes necessary to eliminate 
an immediate hazard to study patients or any nonsubstantial changes, as defined by regulatory 
requirements. 
The PI will be responsible for the following: 
 Providing written summaries of the status of the study to the EC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the EC 
 Notifying the EC of SAEs or other significant safety findings as required by EC 
procedures 
 Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the EC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local regulations. 
The study will additionally be approved by the Administration of Radioactive Substances 
Advisory Committee. 
8.14.2. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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8.14.3. 
Informed Consent 
Prior to starting participation in the study, each patient will be provided with a study-specific ICF 
giving details of the study drugs, procedures, and potential risks of the study. Patients will be 
instructed that they are free to obtain further information from the PI (or designee) and that their 
participation is voluntary, and they are free to withdraw from the study at any time. Patients will 
be given an opportunity to ask questions about the study prior to providing consent for 
participation. 
Following discussion of the study with CRU personnel, patients will sign 3 copies of the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. One copy will be given to the patient, one placed in the site file, and the other 
will be maintained in the patient’s records. 
Patients must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
8.14.4. 
Patient Data Protection 
Patients will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Patient and PI personal data will 
be treated in compliance with all applicable laws and regulations. In the event the study protocol, 
study report, or study data are included in a public registry, all identifiable information from 
individual patients or PI will be redacted according to applicable laws and regulations. 
The patient must be informed that their personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the patient. The patient must also be informed that their study-related data may be examined by 
Sponsor or Contract Research Organization (CRO) auditors or other authorized personnel 
appointed by the Sponsor, by appropriate EC members, and by inspectors from regulatory 
authorities. 
8.14.5. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The PI (or designee) 
agrees not to disclose such information in any way without prior written permission from the 
Sponsor. 
8.14.6. 
Data Quality Assurance 
The following data quality steps will be implemented: 
 All patient data relating to the study will be recorded on eCRFs unless directly 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The PI is 


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responsible for verifying that data entries are accurate and correct by electronically 
signing the eCRF. 
 The PI must maintain accurate documentation (source data) that supports the information 
entered in the eCRF. 
 The PI must permit study-related monitoring, audits, EC review, and regulatory agency 
inspections and provide direct access to source data documents. 
 Covance is responsible for the data management of this study, including quality checking 
of the data. Predefined, agreed risks, monitoring thresholds, quality tolerance thresholds, 
controls, and mitigation plans will be documented in a risk management register. 
Additional details of quality checking to be performed on the data may be included in a 
Data Management Plan.  
 A Study Monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of patients are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
 Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the PI in the study site archive for at least 5 years after the end of the 
study unless local regulations or institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of 
the Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
8.14.7. 
Principal Investigator Documentation Responsibilities 
All individual, patient-specific study data will also be entered into a 21 CFR Part 11-compliant 
electronic data capture (EDC) system on an eCRF in a timely fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and transmitted 
electronically to the Sponsor or designee, will be integrated with the patient’s eCRF data in 
accordance with the Data Management Plan. EDC data will be transmitted to the Sponsor at the 
end of the study as well. 
An eCRF must be completed for each patient who signs an ICF, undergoes Screening 
procedures, and is not a screen failure, in accordance with the eCRF completion instructions. The 
Sponsor, or CRO, will review the supporting source documentation against the data entered into 
the eCRFs to verify the accuracy of the electronic data. The PI will ensure that corrections are 
made to the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The PI will sign and date the eCRF via the EDC system’s electronic signature procedure. These 
signatures will indicate that the PI reviewed and approved the data on the eCRF, data queries, 
and site notifications. 


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8.14.8. 
Publications and Data Sharing 
A Clinical Study Report (CSR) will be prepared and provided to the regulatory 
agency(ies). BeiGene Ltd. (the Sponsor) will ensure that the report meets the standards set out in 
the ICH Guideline for Structure and Content of Clinical Study Reports (ICH E3). Note that an 
abbreviated report may be prepared in certain cases. 
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulatory guidance, and the need to protect the intellectual property of the Sponsor, regardless 
of the outcome of the study. The data generated in this clinical study are the exclusive property 
of the Sponsor and are confidential.  Authorship will be determined by mutual agreement and all 
authors must meet the criteria for authorship established by the International Committee of 
Medical Journal Editors Uniform Requirements for Manuscripts or stricter local criteria.12 
After conclusion of the study and without prior written approval from the Sponsor, the PI may 
communicate, orally present, or publish in scientific journals or other scholarly media only after 
the following conditions have been met: 
 The results of the study in their entirety have been publicly disclosed by or with the 
consent of the Sponsor in an abstract, manuscript, or presentation form; or 
 The study has been completed for at least 2 years. 
No such communication, presentation, or publication will include the Sponsor’s confidential 
information.  
The PI agrees to submit all manuscripts or congress abstracts and posters/presentations to the 
Sponsor prior to submission. This allows the Sponsors to protect proprietary information, 
provide comments based on information from other studies that may not yet be available to the 
PI, and ensure scientific and clinical accuracy. The details of the processes of producing and 
reviewing reports, manuscripts, and presentations based on the data from this trial will be 
presented in the PI’s clinical study agreement. 
9. SAMPLE SIZE AND DATA ANALYSIS 
9.1. 
Determination of Sample Size 
No formal statistical assessment of sample size has been conducted. The sample size chosen for 
this study is common in human radiolabeled studies and is considered sufficient to achieve the 
objectives of the study. Up to approximately 10 patients will be enrolled and studied in order that 
4 patients complete Part 1 of the study. 


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9.2. 
Analysis Populations 
9.2.1. 
Pharmacokinetic Population 
The PK population will include all patients who received [14C]-pamiparib and have evaluable PK 
data. Patients will be excluded from the PK summary statistics and statistical analysis if a patient 
has an AE of vomiting that occurs at or before 2 times median tmax. 
9.2.2. 
Safety Population 
The safety population will include all patients who received [14C]-pamiparib. 
9.3. 
Pharmacokinetic Analyses 
Plasma and urine PK parameters of pamiparib and whole blood and plasma parameters of total 
radioactivity will be calculated using standard noncompartmental methods.  
Additional noncompartmental PK parameters may be determined where appropriate. 
Pharmacokinetic parameters will be summarized using descriptive methodology. No formal 
statistical analysis will be performed. 
Descriptive statistics (mean, median, minimum, maximum, standard deviation, geometric mean, 
and geometric coefficient of variation) will be calculated for all PK parameters and PK 
concentration data where applicable. 
Specification of PK parameters to be presented in the CSR; procedures for accounting for 
missing, unused, or spurious data; procedures for reporting deviations from the original statistical 
plan; and selection of patients to be included in the analyses population(s) will be presented in 
the CSR and/or the Statistical Analysis Plan as appropriate. 
All statistical summary calculations will be performed using SAS Version 9.4 or greater. 
9.4. 
Safety Analysis 
All AEs will be listed and summarized using descriptive methodology. No formal statistical 
analysis will be performed. The incidence of AEs will be presented by severity and by 
relationship with the study drug as determined by the PI (or designee). Each AE will be coded 
using the Medical Dictionary for Regulatory Activities.  
Patient ECOG performance will be reported for the Safety population and will be listed.  
 
9.5. 
Interim Analysis 
No interim analyses are planned for this study. 


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10. REFERENCES 
1.  
Pommier Y, O’Connor MJ, Bono J de. Laying a trap to kill cancer cells: PARP inhibitors 
and their mechanisms of action. Sci Transl Med. 2016 Oct 26;8(362):362ps17-362ps17.  
2.  
O’Connor MJ. Targeting the DNA Damage Response in Cancer. Mol Cell. 2015 Nov 
19;60(4):547–60.  
3.  
Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science. 2017 
17;355(6330):1152–8.  
4.  
LYNPARZA Full Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, 
DE.  
5.  
Rubraca (rucaparib) [package insert]. Boulder, CO: Clovis Oncology, Inc.; 2017.  
6.  
BeiGene USA Inc. BGB-290 Investigator’s Brochure. Current Version.  
7.  
Murai J, Huang SN, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 
and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588–99.  
8.  
BeiGene Co. Ltd. Study No. BCLU-053-1302. Efficacy study of BGB-290 in BCLU-053 
xenograph model. 2014 Feb;  
9.  
International Commission on Radiological Protection (ICRP). Radiological Protection in 
Biomedical Research. ICRP Publication 60. 1991;21(1–3).  
10.  International Commission on Radiological Protection (ICRP). Radiological Protection in 
Biomedical Research. ICRP Publication 62. Ann ICRP. 1992;22(3).  
11.  World Health Organisation. Use of ionising radiation and radionuclides on human beings 
for medical research, training and nonmedical purposes. Tech Rep Ser No 611 Geneva. 
1977;  
12.  International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly work in Medical Journals. [Internet]. 2017 
[cited 2018 May 14]. Available from: http://www.icmje.org/recommendations/ 
 
 


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11. APPENDICES 


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Appendix 1: Clinical Laboratory Evaluations 
Clinical Chemistry: 
Hematology: 
Urinalysis: 
Serologya: 
Alkaline 
phosphatase 
Alanine 
aminotransferase 
Aspartate 
aminotransferase 
Albumin 
Total bilirubin 
Direct bilirubin 
Blood urea 
nitrogen or urea 
Potassium 
Sodium 
Corrected calcium  
Creatinine 
Glucose 
Lactate 
dehydrogenase 
Total protein 
 
Hematocrit  
Hemoglobin 
Platelet count 
Red blood cell (RBC) count 
White blood cell (WBC) count 
WBC differential: 
   Lymphocytes 
   Neutrophils 
 
Blood 
Glucose 
Ketones 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic 
examination  
Hepatitis B surface 
antigen 
Hepatitis C antibody 
 
Hormone Panel – 
females only 
Follicle-stimulating 
hormone (FSH)b 
Serum pregnancy test 
(human chorionic 
gonadotropin)c 
Urine pregnancy testd 
a. 
Only analyzed at Screening. 
b. 
Performed at Screening on postmenopausal females only. 
c. 
Performed at Screening on female patients of childbearing potential. 
d. 
Performed on females of childbearing potential at Day -1 (Part 1) and on Day 1 of each treatment cycle (Part 2).  A positive 
urine pregnancy test will be confirmed with a serum pregnancy test. 
 


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Appendix 2: Total Blood Volume 
The following blood volumes are the maximum planned to be withdrawn for each patient. 


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Part 1: 
 
Volume per blood 
sample (mL) 
Maximum 
estimated number 
of blood samples 
Total amount of 
blood (mL) 
Clinical chemistry 
4.7 
4 
18.8 
Hematology 
2.7 
4 
10.8 
Serology 
7.5  
1 
7.5 
Glucose 
2.7  
4 
10.8 
Plasma for pamiparib 
concentration 
4  
16 
64 
Whole blood for total 
radioactivity 
2 
16 
32 
Plasma for total radioactivity 
6 
16 
96 
Plasma for metabolite 
profiling and identification 
10 
11 
110 
Total: 
349.9 
Part 2: 
 
Volume per blood 
sample (mL) 
Maximum estimated number 
of blood samples per visit 
Total amount of 
blood (mL) per visit 
Predose, End-of-
treatment, and 
Follow-up visits 
 
 
 
Clinical chemistry 
4.7 
1 
4.7 
Hematology 
2.7 
1 
2.7 
Glucose 
2.7 
1 
2.7 
 
Volume per blood 
sample (mL) 
Maximum estimated number 
of blood samples per cycle 
Total amount of 
blood (mL) per 
cycle 
Cycle 1 and Cycle 2 
 
 
 
Clinical chemistry 
4.7 
2 
9.4 
Hematology 
2.7 
2 
5.4 
Glucose 
2.7 
2 
5.4 
Cycles 3+ 
 
 
 
Clinical chemistry 
4.7 
1 
4.7 
Hematology 
2.7 
1 
2.7 
Glucose 
2.7 
1 
2.7 
 


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If extra blood samples are required in Part 1, the maximum blood volume to be withdrawn per 
patient will not exceed 400 mL. If extra blood samples are required in Part 2, the maximum 
blood volume to be withdrawn per patient will not exceed 40 mL per cycle. 
 
 


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Appendix 3: Eastern Cooperative Oncology Group (ECOG) Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all pre-diseases performance without restriction. 
(Karnofsky 90-100) 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature (eg, light housework, office work). 
(Karnofsky 70-80) 
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. 
(Karnofsky 50-60) 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
(Karnofsky 30-40) 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
(Karnofsky 10-20) 
5 
Dead 
As published by Oken et al, 1982. Eastern Cooperative Oncology Group, Robert Comis MD, Group Chair. 
 
 






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after discussion with the Medical Monitor for specific circumstances, such as prolonged hospitalization. An ECG does not need to occur at the End-of-Treatment 
visit if one was performed within 14 days prior to the visit. This visit will count as the patient’s End-of-Treatment visit. 
d. 
Demographics: Date of birth, gender, ethnicity, and race must be recorded.   
e. 
Medical History/Current Medical Conditions:  General and disease-specific medical history including a history of past and current medical conditions must be 
recorded at Screening.   
f. 
Follicle-stimulating hormone: conduced in postmenopausal females only. 
g. 
Pregnancy test (in female patients of childbearing potential): Performed in serum at Screening and in urine at all other times. A positive urine pregnancy test 
will be confirmed with a serum pregnancy test. 
h. 
PK sample timepoints: 
1  
Blood sampling for pamiparib concentration (plasma): Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours postdose. If 
patient does not meet discharge criteria by Day 7, additional samples may be collected every 24 hours after Day 7. 
2  
Blood sampling for total radioactivity (plasma and whole blood): Predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 6, 12, 24, 48, 72, 96, 120, and 144 hours 
postdose. If patient does not meet discharge criteria by Day 7, additional samples may be collected every 24 hours after Day 7. 
3  
Blood sampling for metabolite analysis (plasma): 0.5, 1, 2, 6, 12, 24, 48, 72, 96, 120, and 144 hours postdose. 
4  
Urine collection: Predose (within 1 hour prior to dosing [patients will be asked to empty their bladder immediately prior to administration of 
[14C]-pamiparib on Day 1]) and 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, and 120 to144 hours postdose. Complete daily 
urine output may be collected at home if ≥ 90% of the radioactivity dose is not recovered while the patient is in the CRU. 
5  
Fecal collection: Predose (-12 to 0 hours) and 0 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, and 120 to 144 hours postdose. Complete daily fecal 
output may be collected at home if ≥ 90% of the radioactivity dose is not recovered while the patient is in the Clinical Research Unit. 
For subjects who meet Discharge criteria and are discharged from the CRU prior to Day 7, blood, urine, and feces sampling for PK will cease. 
i. 
Vital signs:  Blood pressure, heart rate, and temperature must be measured after the patient has been supine for at least 5 minutes at Screening and in the morning 
during the in-house period 
j. 
ECG: Single 12-lead ECGs will be repeated once if outside the clinical reference range. A single ECG will be recorded unless there is an abnormality such as 
prolonged QTc(F) > 500 msec or > 60 msec from the highest baseline or predose value, new arrhythmia, or other clinically significant finding, then ECGs will be 
recorded in triplicate at least 2 minutes apart. ECGs will be recorded after the patient has been supine for at least 5 minutes. 
k. 
Complete physical examination: A complete physical examination includes a review of the following systems: head/neck/thyroid; eyes/ears/nose/throat; 
respiratory; cardiovascular; lymph nodes; abdomen; skin; musculoskeletal; and neurological. 
l. 
Limited physical examination: A limited physical examination includes assessment of general appearance and additional examination of symptomatic systems or 
those affected by the patient’s disease. 
 
 




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e. 
Safety Follow-up visit: Approximately 30 days after the last day of study drug administration or before initiation of new anticancer therapy, whichever occurs 
first; a safety follow-up will occur with the outlined safety assessments. If new anticancer therapy is initiated before this safety follow-up, a safety follow-up 
should be scheduled as soon as possible. Clinical laboratory evaluations are only required if the patient had an ongoing clinical laboratory abnormality at the 
previous visit that the Principal Investigator considered to be related to study drug. For patients who do not want to or cannot return to the clinic for the safety 
follow-up, the patient should be contacted by telephone for a review of adverse events. 
f. 
Pregnancy test (in female patients of childbearing potential): Urine pregnancy test conducted as indicated. A positive urine pregnancy test will be confirmed 
with a serum pregnancy test. 
g. 
Dosing: Pamiparib capsules should be administered continuously from Cycle 1 Day 1 (60 mg twice daily), until patients are discontinued from treatment.      
h. 
CT or MRI scan: Scan to be done every 12 weeks ± 7 days from the time of Part 2 C1D1. 
i. 
Vital Signs: Blood pressure, heart rate, and temperature must be measured after the patient has been supine for 5 minutes at Screening. 
j. 
ECG Single 12-lead ECGs will be repeated once if outside the clinical reference range, or there is other clinically significant finding.  Repeat ECGs will be 
recorded in triplicate at least 2 minutes apart. ECGs will be recorded after the patient has been supine for 5 minutes. 
k. 
Limited physical examination: A limited physical examination includes assessment of general appearance and additional examination of symptomatic systems or 
those affected by the patient’s disease.  For the follow-up visit, the limited physical examination is only to be done if this visit is conducted whilst the patient is 
attending the clinic. 
l. 
Follow-up assessments: only to be conducted if the patient has an ongoing laboratory abnormality at the previous visit that the PI considers to be related to the 
study drug. 


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Appendix 5: New York Heart Association Functional Classification 
 
Class 
Symptoms 
I 
Cardiac disease, but no symptoms and no limitation in ordinary physical activity, eg, no shortness 
of breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary 
activity. 
III 
Marked limitation in activity due to symptoms, even during less-than-ordinary activity, eg, 
walking short distances (20-100 m). Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. 
Adapted from Dolgin M, Association NYH, Fox AC, Gorlin R, Levin RI, New York Heart Association. Criteria Committee. 
Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Lippincott Williams and 
Wilkins; March 1, 1994. 
Original source: Criteria Committee, New York Heart Association, Inc. Diseases of the Heart and Blood Vessels. Nomenclature 
and Criteria for diagnosis, 6th edition. Boston: Little, Brown and Co. 1964, p 114. 


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Appendix 6: Prohibited Medications and Medications to Be Used with Caution 
 
Strong and Moderate Cytochrome P450 (CYP)3A Inhibitors and Strong CYP3A Inducers 
Strong CYP3A Inhibitors 
Antibiotics: clarithromycin, telithromycin, troleandomycin 
Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole 
Antivirals: boceprevir, telaprevir 
Other: cobicistat, conivaptan, elvitegravir, mibefradil, nefazodone 
Protease inhibitors: indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir 
Strong CYP3A Inducers 
Avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin 
(rifampicin), St. John’s wort (Hypericum perforatum) 
Moderate CYP3A Inhibitors 
Antibiotics: ciprofloxacin, erythromycin 
Antifungals: fluconazole 
Protease inhibitors: amprenavir, atazanavir, darunavir, fosamprenavir 
Calcium channel blockers: diltiazem, verapamil 
Tyrosine kinase inhibitors (anticancer): imatinib 
Food products: grapefruit and juice (Citrus paradisi), Seville orange and juice (Citrus 
aurantium) 
Herbal medications: Schisandra sphenanthera 
Others: aprepitant, casopitant, cimetidine, cyclosporine, dronedarone, tofisopam 
 
Medications to Be Used with Caution 
Sensitive CYP2C9 Substrates or CYP2C9 Substrates with Narrow Therapeutic Index: 
 Celecoxiba 
 Phenytoinb 
 Warfarinb 
a. Sensitive substrates: Drugs that exhibit an area under the concentration-time curve (AUC) ratio (AUCi/AUC) of 
5-fold or more when coadministered with a known potent inhibitor, where AUCi is the AUC of the substrate when 
coadministered with a known potent inhibitor and AUC is the AUC of substrate alone. 


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b. Substrates with narrow therapeutic index: Drugs whose exposure-response indicates that increases in their 
exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (eg, Torsade de 
Pointes). 
Strong CYP2C8 Inhibitors: 
 Gemfibrozil 
Data compiled from the FDA’s “Guidance for Industry, Drug Interaction Studies” 
(http://www fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664 htm); from 
the Indiana University School of Medicine’s “Clinically Relevant” Table (http://medicine.iupui.edu/flockhart/table htm); from 
the University of Washington’s Drug Interaction Database (www.druginteractioninfo.org) 


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Appendix 7: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation 
In adults, the most widely-used equations for estimating glomerular filtration rate (GFR) from 
serum creatinine are the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 
equation and the Modification of Diet in Renal Disease Study equation. The National Kidney 
Disease Education Program calculators rely on creatinine determinations which are isotope 
dilution mass spectrometry traceable. All laboratories should be using creatinine methods 
calibrated to be isotope dilution mass spectrometry traceable. Read more about creatinine 
standardization. This CKD-EPI equation calculator should be used when Scr is reported 
in mg/dL. This equation is recommended when estimated GFR values above 60 mL/min/1.73 m2 
are desired. 
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 
[if black] 
where: 
Scr is serum creatinine in mg/dL, 
κ is 0.7 for females and 0.9 for males, 
α is -0.329 for females and -0.411 for males, 
min indicates the minimum of Scr /κ or 1, and 
max indicates the maximum of Scr /κ or 1. 
The equation does not require weight because the results are reported normalized to 1.73 m2 
body surface area, which is an accepted average adult surface area. 
The online calculator for CKD-EPI can be found here: 
https://www.niddk.nih.gov/healthinformation/health-communication-programs/nkdep/lab-
evaluation/gfr-calculators/Pages/gfrcalculators.aspx. 
 


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Appendix 8: Contraception Guidelines and Definitions of “Women of Childbearing 
Potential”, “No Childbearing Potential” 
Contraception Guidelines 
All male patients with partners of childbearing potential who take part in this study, must use 
condoms during sexual intercourse in addition to one of the highly effective methods of 
contraception listed below, from the time of taking the first dose of pamiparib until 6 months after 
taking the last dose of pamiparib. If a female partner of a male patient is already pregnant, the male 
patient must use condoms during sexual intercourse for the duration of the study and for at 
least 6 months after the last dose of pamiparib. 
Female patients of childbearing potential must use one of the highly effective forms of birth control 
below (preferably those with low user dependency) for the duration of the study and for at 
least 6 months after the last dose of pamiparib. 
The Clinical Trials Facilitation Group’s recommendations related to contraception and pregnancy 
testing in clinical trials include the use of highly effective forms of birth control. These methods 
include the following: 
 Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation (oral, intravaginal, or transdermal) 
 Progestogen-only hormonal contraception associated with the inhibition of ovulation:  
o Oral 
o Injectable 
o Implantable* 
 Intrauterine device (IUD)* 
 Intrauterine hormone-releasing system (IUS)* 
 Bilateral tubal occlusion* 
 Vasectomized male partner*, provided that the vasectomized partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the vasectomized 
partner has received medical assessment of surgical success 
 Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of exposure associated with the study treatment) 
NOTE: Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the patient’s usual and preferred lifestyle.  
Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), 
declaration of abstinence for the duration of exposure to study drug, and withdrawal are 
not acceptable methods of contraception. 


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Of note, barrier contraception (including male and female condoms with or without spermicide) is 
not considered a highly effective method of contraception and if used, this method must be 
combined with another acceptable method listed above. 
*Contraception methods that in the context of this protocol are considered to have low user 
dependency. 
Definitions of “Women of Childbearing Potential”, “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are females who are physiologically 
capable of becoming pregnant. 
Conversely, “women of no childbearing potential” are defined as females meeting any of the 
following criteria: 
 Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) 
 Postmenopausal, defined as: 
o ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR 
o < 55 years of age with no spontaneous menses for ≥ 12 months AND with a 
postmenopausal follicle-stimulating hormone concentration > 30 IU/mL and all 
alternative medical causes for the lack of spontaneous menses for ≥ 12 months have 
been ruled out, such as polycystic ovarian syndrome, hyperprolactinemia, etc. 
If an FSH measurement is required to confirm postmenopausal state, concomitant use of hormonal 
contraception or hormonal replacement therapy should be excluded. 
 
Adapted from Clinical Trials Facilitation Group (CTFG). Recommendations related to contraception and pregnancy 
testing in clinical trials. September 15, 2014. http://www hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
 


Signature Page for VV-CLIN-007674 v1.0
Signature Page for VV-CLIN-007674 v1.0
Approval
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SAP_001.pdf: 
Final Version 2: 14th November 2019 
 
Page 1 of 20 
 
STATISTICAL ANALYSIS PLAN 
A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of 
[14C]-Pamiparib following Single Oral Dose Administration in Patients with Advanced 
and/or Metastatic Solid Tumors 
Statistical Analysis Plan Status: Final Version 2 
Statistical Analysis Plan Date:  14th November 2019 
 
Study Drug: [14C]-Pamiparib and Pamiparib 
 
Sponsor Reference Number: BGB-290-106 
Covance Study Number: 8381180 
Clinical Phase 1 
 
 
Sponsor: 
 
BeiGene, Ltd. 
c/o BeiGene USA, Inc.  
2929 Campus Drive, Suite 300 
San Mateo, CA, 94403, USA 
Study Sites: 
Royal Liverpool University Hospital 
Clinical Research Unit 
2nd Floor, UCD 
Prescot Street 
Liverpool, L7 8XP, UK 
 
The Clatterbridge Cancer Centre NHS 
Foundation Trust 
Clatterbridge Road  
Bebington, Wirral, CH63 4JY, UK 
 
 
Sponsor Signatory: 
 
Principal Investigator: 
 
 
 
 


Statistical Analysis Plan  
 
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Sponsor Reference: BGB-290-106 
 
Final Version 2: 14th November 2019 
 
Page 2 of 20 
 
1  STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES 
By signing this page when the Statistical Analysis Plan (SAP) is considered final, the signatories 
agree to the statistical and pharmacokinetic (PK) analyses to be performed for this study, and to 
the basic format of the tables, figures, and listings (TFLs). Once the SAP has been signed, 
programming of the TFLs based upon this document can proceed. Any modifications to the SAP 
and TFLs made after signing may result in a work-scope change. 
 
Covance approval: 
 
 
 
 
Statistician 
 
 
 
 
 
 
Pharmacokineticist 
 
Date 
 
 
Sponsor approval: 
 
 
 
 
Statistician  
 
Date 
 
 
 
 
 
Clinical Pharmacologist 
 
 
Date 
 


Statistical Analysis Plan  
 
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Final Version 2: 14th November 2019 
 
Page 3 of 20 
 
2  TABLE OF CONTENTS 
1 
STATISTICAL ANALYSIS PLAN APPROVAL SIGNATURES ................................... 2 
2 
TABLE OF CONTENTS ................................................................................................... 3 
3 
ABBREVIATIONS ............................................................................................................ 5 
4 
INTRODUCTION .............................................................................................................. 7 
5 
STUDY OBJECTIVES ...................................................................................................... 7 
5.1 
Primary Objectives ...................................................................................................... 7 
5.2 
Secondary Objectives .................................................................................................. 7 
6 
STUDY DESIGN ............................................................................................................... 8 
6.1 
Study Part 1 (Research Phase) ..................................................................................... 8 
6.2 
Study Part 2 (Treatment Phase) ................................................................................... 9 
7 
TREATMENTS ................................................................................................................ 10 
8 
SAMPLE SIZE JUSTIFICATION ................................................................................... 10 
9 
DEFINITION OF ANALYSIS POPULATIONS ............................................................ 10 
10 STATISTICAL METHODOLOGY ................................................................................. 11 
10.1 General ....................................................................................................................... 11 
10.1.1 Definition of Baseline and Change from Baseline ........................................... 11 
10.1.2 Repeat and Unscheduled Readings .................................................................. 12 
10.2 Demographics and Patient Disposition ...................................................................... 12 
10.3 Pharmacokinetic Assessment ..................................................................................... 12 
10.3.1 Pharmacokinetic Analysis ................................................................................ 12 
10.3.2 Criteria for handling concentrations below the limit of quantification in 
Pharmacokinetic analysis ................................................................................. 15 
10.3.3 Criteria for the Calculation of an Apparent Terminal Elimination Half-Life .. 15 
10.3.4 Calculation of AUC .......................................................................................... 16 
10.3.5 Anomalous Values ........................................................................................... 16 
10.4 Presentation of Pharmacokinetic Data ....................................................................... 16 
10.4.1 Presentation of Pharmacokinetic Plasma Drug Concentrations and Total 
Radioactivity in Whole Blood and Plasma Data .............................................. 16 
10.4.2 Presentation of Pharmacokinetic Parameters ................................................... 17 
10.4.3 Pharmacokinetic Statistical Methodology ........................................................ 17 
10.5 Safety and Tolerability Assessments ......................................................................... 17 
10.5.1 Adverse Events ................................................................................................. 17 
10.5.2 Concomitant Medications ................................................................................. 18 
10.5.3 Clinical Laboratory Parameters ........................................................................ 18 
10.5.4 Vital Signs ........................................................................................................ 18 
10.5.5 Electrocardiogram ............................................................................................ 18 


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10.5.6 Eastern Cooperative Oncology Group (ECOG) Performance Status ............... 19 
10.5.7 Tumor Assessment ........................................................................................... 19 
10.5.8 Other Assessments ........................................................................................... 19 
10.5.9 Safety and Tolerability Statistical Methodology .............................................. 19 
11 INTERIM ANALYSES .................................................................................................... 19 
12 CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ....... 19 
13 DATA PRESENTATION ................................................................................................ 19 
13.1 Insufficient Data for Presentation ............................................................................... 19 
14 REFERENCES ................................................................................................................. 19 


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Final Version 2: 14th November 2019 
 
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3  ABBREVIATIONS 
Abbreviations pertain to the SAP only (not the TFLs). 
ADaM 
analysis data model 
AE 
adverse event 
 Aef 
Amount excreted in the feces per sampling interval 
Aeu 
Amount excreted in urine per sampling interval 
AUC 
area under the concentration-time curve 
AUC0-t 
AUC from time 0 to the time of last quantifiable concentration, 
calculated using the linear trapezoidal rule for increasing 
concentrations and the logarithmic rule for decreasing 
concentrations 
AUC0- 
AUC from time zero to infinity 
AUC0-∞ 
Blood/Plasma 
Ratio 
Ratio of AUC0- of whole blood total radioactivity relative to 
AUC0- of plasma total radioactivity 
AUC0-∞ Plasma 
Pamiparib / Total 
Radioactivity 
Ratio 
Ratio of AUC0- of plasma pamiparib relative to AUC0- of 
plasma total radioactivity 
BLQ 
below the limit of quantification 
CDISC 
Clinical Data Interchange Standards Consortium 
BID 
twice daily 
CL/F 
Apparent total plasma clearance (pamiparib only) 
CLR 
Renal clearance (pamiparib only) 
Cmax 
maximum observed concentration 
CSR 
Clinical Study Report 
CRU 
Clinical Research Unit  
CT 
computed tomography 
 Cum Aef 
Cumulative amount excreted in feces 
Cum Aeu 
Cumulative amount excreted in urine  
 Cum %fef 
Cumulative percentage of radioactive dose excreted in feces 
Cum %feu 
Cumulative percentage of drug or radioactive dose excreted in 
urine 
CV% 
coefficient of variation 
EC 
Early Clinical 
ECG 
electrocardiogram 


Statistical Analysis Plan  
 
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ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EOT 
End-of-treatment 
%fef 
Percentage of radioactive dose excreted in feces per sampling 
interval 
%feu 
Percentage of drug or radioactive dose excreted in urine per 
sampling interval 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
λz 
Apparent terminal elimination rate constant 
LLOQ 
lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
NR 
no result 
NC 
not calculated 
NDA 
New Drug Application 
PI 
Principal Investigator 
PK 
pharmacokinetic 
QTc 
QT correction; QT interval corrected for heart rate 
QTcF 
QTc calculated using the Fridericia correction  
SAP 
Statistical Analysis Plan 
t1/2 
Apparent terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
tmax 
Time of Cmax 
Vz/F 
Apparent volume of distribution during the terminal elimination 
phase (pamiparib only) 
WHO 
World Health Organization 


Statistical Analysis Plan  
 
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Covance Study: 8381180 
 
Sponsor Reference: BGB-290-106 
 
Final Version 2: 14th November 2019 
 
Page 7 of 20 
 
4  INTRODUCTION 
This SAP has been developed after review of the clinical study protocol (Final Version 1.0 dated 
25 June 2018) and protocol amendment Version 3 dated 12 December 2018. 
This SAP describes the planned analysis of the safety, tolerability and PK data from this study. A 
detailed description of the planned TFLs to be presented in the Clinical Study Report (CSR) is 
provided in the accompanying TFL shell document. 
The intent of this document is to provide guidance for the statistical analyses of PK data. In 
general, the analyses are based on information from the protocol, unless they have been modified 
by agreement between BeiGene, Ltd. and Covance Early Clinical (EC) Biometrics. A limited 
amount of information concerning this study (eg, objectives, study design) is given to help the 
reader’s interpretation. This SAP must be finalized prior to the lock of the clinical database for 
this study. When the SAP and TFL shells are agreed upon and finalized, they will serve as the 
template for this study’s CSR. 
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon 
between BeiGene, Ltd. and Covance EC Biometrics and identified in the CSR. 
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 guideline entitled, “Guidance for Industry: Statistical 
Principles for Clinical Trials” and the ICH E3 guideline entitled, “Guidance for Industry: 
Structure and Content of Clinical Study Reports.”1,2 
5  STUDY OBJECTIVES 
5.1 Primary Objectives 
 To assess the disposition of [14C]-pamiparib following oral administration of a single 
60 mg (~100 μCi) dose in patients with advanced and/or metastatic solid tumors 
 To assess the plasma PK of total radioactivity and pamiparib following a single oral dose 
of [14C]-pamiparib 
 To determine the whole blood and plasma concentrations of total radioactivity 
 To determine the urinary and faecal recovery of total radioactivity 
 
5.2 Secondary Objectives 
 To characterize and identify metabolites of [14C]-pamiparib in plasma, urine, and feces 
 To determine plasma and urine concentrations of pamiparib and/or its major metabolites 
 To assess the safety and tolerability of pamiparib during the treatment phase 


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Sponsor Reference: BGB-290-106 
 
Final Version 2: 14th November 2019 
 
Page 8 of 20 
 
6  STUDY DESIGN 
This is an open-label, inpatient study in patients with advanced and/or metastatic solid tumors, 
which consists of 2 parts: a research phase and a treatment phase. 
An overview of the study design for Part 1 and Part 2 is shown in Figure 1 and Figure 2, 
respectively. 
Potential patients will be screened to assess their eligibility to enter the study within 28 days 
prior to the first dose administration. Re-screening of patients will be allowed per the Principal 
Investigator’s (PI’s) discretion. Up to approximately 10 patients will be enrolled to ensure 
4 patients complete Part 1 of the study. 
The start of the study is defined as the date the first enrolled patient signs an Informed Consent 
Form (ICF). The point of enrollment occurs at the time of patient number allocation. The end of 
the study is defined as the date of the last patient’s last assessment (scheduled or unscheduled) or 
follow-up. 
6.1 Study Part 1 (Research Phase) 
Figure 1: Study Schematic: Part 1 
 
Patients will be admitted into the Clinical Research Unit (CRU) on Day -1. On the morning of 
Day 1, patients will receive a single oral dose of 60 mg containing approximately 100 μCi 
(3.7 MBq) of [14C]-pamiparib. 


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Patients will be resident at the CRU until completion of all assessments on Day 7, but may be 
discharged earlier at the PI’s discretion if they meet the following discharge criteria: 
Approximately 90% of the radioactive dose is recovered 
or 
< 1% of the radioactive dose is recovered in urine and feces for 2 consecutive 24-hour 
collection intervals 
If the discharge criteria have not been met on Day 7, patients may be asked to collect 24-hour 
excreta samples for up to a further 7 days (up to Day 14) on a non-residential basis. Patients may 
be required to remain resident at the CRU for longer than 7 days if deemed necessary by the PI 
to ensure patient safety. If the discharge criteria have not been met by Day 14, the need for 
additional sample collection will be at the discretion of the PI. 
Patients experiencing emesis during the first 4 hours postdose may not be evaluable and 
therefore may be discharged on the same day from the clinical site, provided there are no safety 
concerns, and after discharge study procedures are performed. These patients will attend a 
Follow-up visit within 7 days of Discharge and may be enrolled to Part 2 of the study at the 
discretion of the PI. Patients may be prescribed anti-emetics if required. 
A Follow-up visit will occur within 7 days of Discharge from the CRU (if discharged on Day 7 
or before), or within 7 days of the patients’ final non-residential visit (if additional non-
residential visits are required). During the Follow-up visit, the patients may be entered into Part 2 
of the study if deemed appropriate by the PI. 
6.2 Study Part 2 (Treatment Phase) 
Figure 2: Study Schematic: Part 2 
 
Patients will undergo safety assessments ≤ 7 days prior to the start of pamiparib treatment in 
Part 2. These assessments may be conducted at the Follow-up visit for Part 1 if it occurs within 


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this time window, or at a separate site visit. If there are greater than 8 weeks between tumor 
assessments at study Screening and the planned start of pamiparib treatment in Part 2, patients 
should undergo a computed tomography (CT) scan prior to the start of treatment in Part 2. 
During Part 2, patients will attend 2 site visits per cycle during Cycles 1 and 2, and 1 site visit 
per cycle during each subsequent cycle. Patients will continue receiving treatment until 
occurrence of progressive disease, unacceptable toxicity, pregnancy, death, withdrawal of 
consent, lost to follow-up, major protocol violation which in the opinion of the Sponsor would 
have significant impact on the study or its outcome, start of new anticancer therapy, withdrawal 
by the PI, or study termination by Sponsor. Patients will attend an end-of-treatment (EOT) visit 
within 7 days following their last dose and a safety Follow-up visit approximately 30 days after 
the last dose of pamiparib. 
The reason for treatment discontinuation will be recorded on the electronic Case Report Form 
(eCRF). An EOT visit should occur within 7 days after the final pamiparib dose. The visit should 
be scheduled as soon as possible, but the EOT visit may occur later after discussion with the 
Medical Monitor for specific circumstances, such as prolonged hospitalization. Every effort must 
be made to encourage the patient to complete their EOT visit and appropriate safety follow-ups. 
7   TREATMENTS 
The following is a list of the study treatment abbreviations and ordering that will be used in the 
TFLs. 
Part 
Study Treatment Name 
1 
60 mg [14C]-pamiparib 
2 
60 mg pamiparib BID 
 
8  SAMPLE SIZE JUSTIFICATION 
No formal statistical assessment of sample size has been conducted. The sample size chosen for 
this study is common in human radiolabeled studies and is considered sufficient to achieve the 
objectives of the study. Up to approximately 10 patients will be enrolled and studied in order that 
4 patients complete Part 1 of the study. 
9  DEFINITION OF ANALYSIS POPULATIONS 
The Safety Population for part 1 will consist of all patients who received at least 1 dose of 
study drug, 60 mg [14C]-pamiparib in Part 1. 
The Safety Population for part 2 will consist of all patients who received at least 1 dose of 60 
mg pamiparib in Part 2. 


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The PK Population will consist of all patients who received at least 1 dose of study drug 
(60 mg [14C]-pamiparib, and have evaluable PK data. A patient will be excluded from the PK 
summary statistics and statistical analysis if the patient has an adverse event (AE) of vomiting 
that occurs at or before 2 times median time to maximum concentration (tmax).  
All protocol deviations that occur during the study will be considered prior to database lock for 
their severity/impact and will be taken into consideration when patients are assigned to analysis 
populations. Details of patient assignment to the analysis populations will be listed. 
10  
STATISTICAL METHODOLOGY 
10.1 General 
Data listings will be provided for the Safety Population. Summary statistics and statistical 
analyses will be performed for patients included in the relevant analysis populations (Safety/PK).  
For continuous data, summary statistics will include the arithmetic mean, arithmetic standard 
deviation, median, minimum, maximum, and number. For log-normal data (eg, the PK 
parameters: areas under the concentration-time curve [AUCs] and maximum observed 
concentration [Cmax]), the geometric mean and geometric coefficient of variation (CV%) will 
also be presented. For categorical data, frequency counts and percentages will be presented. Data 
listings will be provided for all patients up to the point of withdrawal, with any patients excluded 
from the relevant population highlighted. For the calculation of summary statistics and statistical 
analysis, unrounded data will be used. 
Missing values will not be imputed. 
Data analysis will be performed using SAS® Version 9.4 or higher. 
Analysis Data Model (ADaM) datasets will be prepared using Clinical Data Interchange 
Standards Consortium (CDISC) ADaM Version 2.1, and CDISC ADaM Implementation Guide 
Version 1.1. Pinnacle 21 Community Validator Version 2.2.0 will be utilized to ensure 
compliance with CDISC standards. 
10.1.1 Definition of Baseline and Change from Baseline 
Baseline for each parameter is in each part  defined as the last value measured prior to dosing for 
that part i.e. Baseline for Part 1 is to be the last value prior to dosing for Part 1 and for Part 2, last 
value prior to the 1st dose in Part 2, including repeat (vital signs and electrocardiograms [ECGs]) 
and unscheduled (clinical laboratory parameters) readings (see Section 10.1.2 for definitions of 
repeat and unscheduled readings). For ECGs taken in triplicate, baseline will be the mean of the 
last 3 values taken prior to dosing. 
Mean change from baseline is the mean of all individual patient’s change from baseline values. 
Each individual change from baseline will be calculated by subtracting the individual patient’s 
baseline value from the value at the timepoint. The individual patient’s change from baseline 


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Final Version 2: 14th November 2019 
 
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values will be used to calculate the mean change from baseline using a SAS procedure such as 
Proc Univariate. 
10.1.2 Repeat and Unscheduled Readings 
Repeat readings occur when the original vital signs or ECG result requires confirmation. Repeat 
readings are labelled as ‘Repeat’ in the listings and replace the original readings in all summaries 
and changes from baseline presentations and calculations. Prior to dosing, all readings taken in 
addition to the original reading are defined as predose repeats. Postdose repeat readings are 
defined as readings collected within 15 minutes of the actual time of the original reading. Where 
results are taken in triplicate and repeated, the last 3 readings are used in all subsequent 
calculations. 
With the exception of predose results described above, unscheduled readings for vital signs or 
ECGs are defined as readings collected >15 minutes from the actual time of the original reading. 
Where results are taken in triplicate, the original reading is defined as the first reading of the 
triplicate. All results not taken at a scheduled timepoint for other data types (eg, clinical 
laboratory parameters) are unscheduled. Unscheduled readings are labelled as ‘Unscheduled’ in 
the listings. Because unscheduled readings are not associated with any scheduled timepoint, they 
are excluded from all summaries (with the exception that they may be used as baseline, as stated 
in Section 10.1.1). 
10.2 Demographics and Patient Disposition 
The demographic variables age, sex, race, ethnicity, body weight, height, and body mass index 
will be summarized and listed. If only a subset of patient’s progress from part 1 to part 2 then 
demographics will be also presented by part. Patient disposition will be summarized and listed. 
Disease-specific characteristics and surgical history, including previous cancer treatment will be 
summarized and listed.  Medical history data will be listed. 
10.3 Pharmacokinetic Assessment 
10.3.1 Pharmacokinetic Analysis 
The following PK parameters will be determined where possible from the plasma concentrations 
of pamiparib and the whole blood and plasma concentrations of total radioactivity using 
non-compartmental methods performed using Phoenix WinNonlin (Version 8.1 or higher):


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Parameter 
Definition 
AUC0-t 
AUC from time 0 to the time of last quantifiable concentration, 
calculated using the linear trapezoidal rule for increasing 
concentrations and the logarithmic rule for decreasing 
concentrations 
AUC0- 
AUC from time zero to infinity 
AUC0-9 
AUC from time zero to 9 hours postdose 
AUC0-12 
AUC from time zero to 12 hours postdose 
Cmax 
Maximum observed concentration 
tmax 
Time of Cmax 
λz 
Apparent terminal elimination rate constant 
t1/2 
Apparent terminal elimination half-life 
CL/F 
Apparent total plasma clearance (pamiparib only) 
Vz/F 
Apparent volume of distribution during the terminal elimination 
phase (pamiparib only) 
AUC0-∞ Blood/Plasma 
Ratio 
Ratio of AUC0- of whole blood total radioactivity relative to 
AUC0- of plasma total radioactivity 
AUC0-∞ Plasma pamiparib 
/ Total Radioactivity Ratio 
Ratio of AUC0- of plasma pamiparib relative to AUC0- of 
plasma total radioactivity  
 
Additional PK parameters may be determined where appropriate. 
The ratio of AUC total radioactivity in whole blood to AUC total radioactivity in plasma and the 
ratio of AUC of plasma pamiparib to AUC total radioactivity in plasma will be based on AUC0-. 
Where AUC0- cannot be reliably calculated an alternative AUC measure, such as AUC to a 
common time point or AUC0-t, may be used. 
Additionally, blood-to-plasma ratios at each sampling time point will be calculated to determine 
partitioning of total radioactivity into red blood cells. Plasma pamiparib-to-total radioactivity 
ratios at each sampling time point will be calculated to determine the fraction of total 
radioactivity attributed to pamiparib. These ratios will be calculated by the radioanalysis 
laboratory and reported in the radioanalysis report 
The PK analysis will, where possible, be carried out using actual postdose times recorded in the 
raw data.  


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Concentrations are used as supplied by the analytical laboratory for PK analysis. The units of 
concentration and resulting PK parameters, with amount or concentration in the unit, will be 
presented as they are received from the analytical laboratory.  
The Cmax and tmax will be obtained directly from the plasma concentration-time profiles. For 
multiple peaks, the highest postdose concentration will be reported as Cmax. In the case that 
multiple peaks are of equal magnitude, the earliest tmax will be reported.  
The following excretion parameters will be calculated, whenever possible, based on the urine 
concentrations of pamiparib using Phoenix WinNonlin (Version 8.1 or higher): 
Parameter 
Definition 
Aeu 
Amount excreted in urine per sampling interval 
Cum Aeu 
Cumulative amount excreted in urine  
CLR 
Renal clearance, where: 
CLR = Cum Aeu / AUC 
AUC0- may be used, if appropriate (pamiparib only) 
%feu 
Percentage of drug or radioactive dose excreted in urine per sampling interval 
Cum %feu 
Cumulative percentage of drug or radioactive dose excreted in urine 
 
The amount excreted in urine (Aeu) for each collection interval will be calculated as the product 
of urine concentration and urine sample weight (assuming a specific gravity of 1 g/mL); Cum 
Aeu will be calculated by summing the Aeu values for each collection interval over the entire 
collection period.  
The percent of the dose excreted (%feu) will be calculated for each urine collection interval (i) 
according to the following formula:  %feu(i) = [feu (i) / dose] × 100 
Cum %feu will be calculated by summing the %feu values for each collection interval over the 
entire collection period. 
The following PK parameters will be calculated, whenever possible, based on the fecal total 
radioactivity concentrations: 
Parameter 
Definition 
Aef 
Amount excreted in the feces per sampling interval 
Cum Aef 
Cumulative amount excreted in feces 
%fef 
Percentage of radioactive dose excreted in feces per sampling interval 
Cum %fef 
Cumulative percentage of radioactive dose excreted in feces 
 
Excretion parameters for total radioactivity (Aeu, Cum Aeu, %feu, Cum %feu, Aef, Cum Aef, %Fef, 
and Cum %fef) will be calculated by the radioanalysis laboratory and reported in the 
radioanalysis report and therefore not presented within the TFLs. 


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10.3.2 Criteria for handling concentrations below the limit of quantification in 
Pharmacokinetic analysis 
Concentration values that are below the level of quantification (BLQ) will be set to zero, with 
defined exceptions as follows; 
 Any embedded BLQ value (between 2 quantifiable concentrations) and BLQ values 
following the last quantifiable concentration in a profile will be set to missing for the 
purposes of PK analysis. 
 If there are late positive concentration values following 2 BLQ concentration values in the 
apparent terminal phase, these values will be evaluated. If these values are considered to be 
anomalous, they will be set to missing. 
 If an entire concentration-time profile is BLQ, the profile will be excluded from the PK 
analysis. 
 If a predose concentration is missing, it will be set to zero by default within Phoenix 
WinNonlin. 
10.3.3 Criteria for the Calculation of an Apparent Terminal Elimination Half-Life 
10.3.3.1 Number of Data Points 
At least three data points will be included in the regression analysis and preferably should not 
include Cmax. 
10.3.3.2 Goodness of Fit 
When assessing terminal elimination phases, the R2 adjusted value will be used as a measure of 
the goodness of fit of the data points to the determined line.  
Regression-based parameters (AUC0-, λz, t1/2, CL/F, and Vz/F) will only be calculated if the R2 
adjusted value of the regression line is greater than or equal to 0.7. 
10.3.3.3 Period of Estimation 
Time period used for the estimation of apparent terminal elimination half-lives, where possible, 
will be over at least two half-lives.  
Where an elimination half-life is estimated over a time period of less than two half-lives, it will 
be flagged in the data listings at the discretion of the pharmacokineticist, and the robustness of the 
value should be discussed in the study report. 


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10.3.4 Calculation of AUC 
 The minimum requirement for the calculation of AUC will be the inclusion of at least 
three consecutive concentrations above the lower limit of quantification (LLOQ), with 
at least one of these concentrations following Cmax.  
 For any partial AUC determination (eg, AUC from time zero to 24 hours postdose), 
nominal time will generally be used for the end of the interval. Actual times for partial 
AUC intervals may be used at the discretion of the Pharmacokineticist.  
 AUC0- values where the percentage extrapolation is greater than 30% will be listed but 
excluded from descriptive statistics.   
10.3.5 Anomalous Values 
If a value is considered to be anomalous due to being inconsistent with the expected PK profile, 
it may be appropriate to exclude this point from the PK analysis. However, the exclusion of data 
must have strong justification and will be documented in the raw data and study report. 
Embedded BLQ values may be considered anomalous depending on the route of administration 
and the characteristics of the drug. 
Positive predose value(s) greater than 5% of Cmax may be excluded from the summary statistics 
of PK tables and statistical analysis at the discretion of the Pharmacokineticist. 
10.4 Presentation of Pharmacokinetic Data 
10.4.1 Presentation of Pharmacokinetic Plasma Drug Concentrations and Total 
Radioactivity in Whole Blood and Plasma Data 
The following rules will be applied if there are values that are BLQ or if there are missing values 
(eg, no result [NR]) in a concentration data series to be summarized. 
 For the calculation of summary statistics, BLQ values will be set to zero. 
 If an embedded BLQ value is considered anomalous within the concentration-time profile, 
this value will be excluded from the summary statistics. 
 Where there is NR, these will be set to missing. 
 If there are less than three values in the data series, only the min, max and N will be 
presented. The other summary statistics will be denoted as not calculated (NC). BLQ is 
considered a value. 


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 If all the values are BLQ, then the arithmetic mean, arithmetic standard deviation, median, 
min and max will be presented as zero, and the geometric mean and geometric CV% will 
be denoted as NC. 
 If the value of the arithmetic mean or median is below the LLOQ, these values will be 
presented as zero and the geometric mean and geometric CV% will be denoted as NC. 
10.4.2 Presentation of Pharmacokinetic Parameters 
For the calculation of summary statistics of PK parameters, all NR and NC values in a data series 
will be set to missing. 
The AUC values will be set to NC if they have been calculated using fewer than three 
concentrations, and/or three concentrations if the last is Cmax. 
10.4.3 Pharmacokinetic Statistical Methodology 
No formal statistical analysis will be performed. 
Assessment of pamiparib is only occurring in Part 1 of the study.  
The PK parameters of pamiparib (plasma) and total radioactivity (plasma and whole blood) will 
be listed and summarized. The concentrations of plasma pamiparib will be listed and 
summarized. Ratios of plasma pamiparib to plasma total radioactivity concentrations and ratios 
of whole blood total radioactivity to plasma total radioactivity will be summarized and listed.  
Concentrations of pamiparib (plasma) and total radioactivity (plasma and whole blood) will be 
presented graphically on linear and semi-logarithmic scales; this will include individual patient 
profiles, arithmetic mean (± standard deviation) profiles, and individual profiles for all patients 
over time.   
10.5 Safety and Tolerability Assessments 
10.5.1 Adverse Events 
A baseline signs and symptom is defined as an AE that starts after the patient has provided 
written informed consent and that resolves prior to the first dosing occasion, or an AE that starts 
prior to the first dosing occasion and does not increase in toxicity grade after dosing. A treatment 
emergent AE (TEAE) is defined as an AE that occurs postdose or that is present predose and 
becomes more severe postdose. A Part 1 TEAE is defined as an AE that occurs or becomes more 
severe post Part 1 dosing and prior to Part 2 dosing. A Part 2 TEAE is defined as an AE that 
occurs or becomes more severe after dosing in Part 2.  
All TEAEs will be listed. The TEAEs will be summarized by part, toxicity grade, and 
relationship to the study drug. The frequency (the number of TEAEs, the number of patients 
experiencing a TEAE, and the percentage of patients experiencing a TEAE) of TEAEs will be 


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summarized by part and by Medical Dictionary for Regulatory Activities (MedDRA version 21.1 
or higher) system organ class, preferred term and Lowest Level Terms. A frequency summary 
will be presented by day of onset across the multiple-dosing period for Part 2. The summary and 
frequency TEAE tables will be presented for all causalities and for those TEAEs considered 
related to the study drug (those that have a relationship of related). Any severe (CTCAE grade 3, 
4 or 5) or serious TEAEs will be tabulated. For any AEs that change toxicity grade or severity 
the AE within the same Part will be included only once under the maximum toxicity grade in the 
summaries. A TEAE which occurs in Part 1 and becomes more severe in Part 2 will be presented 
in both Parts with the corresponding severity.    
Onset times postdose are calculated from the time of the last dose administered.   
10.5.2 Concomitant Medications  
Prior and concomitant medications will be coded using the World Health Organization (WHO) 
Drug Dictionary (Version September 2018 Dictionary Global B3 format [or higher if version is 
updated during the study]). Prior and concomitant medications will be listed separately.  
10.5.3 Clinical Laboratory Parameters 
Clinical chemistry and hematology data will be summarized by part and parameter. In addition, 
all clinical chemistry, hematology, and urinalysis data outside the clinical reference ranges will 
be listed by part and parameter. 
Values for any clinical chemistry, hematology, and urinalysis values outside the clinical 
reference ranges will be flagged on the individual patient data listings. 
10.5.4 Vital Signs 
The vital signs data (including supine blood pressure, supine pulse rate, and body temperature) 
will be summarized together with changes from baseline by part. Figures of mean change from 
baseline profiles will be presented by part. Vital signs values outside the clinical reference ranges 
will be flagged on the individual patient data listings. Repeat and unscheduled readings will be 
handled as defined in Section 10.1.2. 
10.5.5 Electrocardiogram 
The ECG data will be obtained directly from the 12-lead ECG traces. These data include the QT 
interval calculated using the Fridericia correction (QTcF), the PR and QT intervals, the QRS 
duration, and heart rate.  
Where ECGs are measured in triplicate (at approximately 2-minute intervals), the mean value 
will be used in all subsequent calculations. Changes from baseline will be calculated.    
Values for ECG parameters outside the clinical reference ranges will be flagged on the individual 
patient data listings. 


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The ECG data will be summarized by part. Change from baseline will also be summarized for 
Part 1.  
10.5.6 Eastern Cooperative Oncology Group (ECOG) Performance Status 
The frequency of patients with each grade will be presented for ECOG performance status data 
by part and listed for individual patients. 
10.5.7 Tumor Assessment 
Tumor imaging (CT or magnetic resonance imaging [MRI], with preference for CT) will be 
performed.  
Data will be listed for individual patients and overall tumor assessment data for each tumor 
assessment (response rates) will be presented in a frequency table. 
10.5.8 Other Assessments 
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed. 
10.5.9 Safety and Tolerability Statistical Methodology 
No inferential statistical analyses are planned. 
 
11  
INTERIM ANALYSES 
No formal interim statistical analyses are planned.  
12  
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES 
There were no changes from the protocol-specified statistical analyses. 
13  
DATA PRESENTATION 
13.1 Insufficient Data for Presentation 
Some of the TFLs may not have sufficient numbers of patients or data for presentation. If this 
occurs, the blank TFL shell will be presented with a message printed in the center of the table, 
such as, “No serious adverse events occurred for this study.” 
14  
REFERENCES 
1. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998. 


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2. International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonised Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995.