Conditions: Advanced or Inoperable Gastric Cancer
Keywords: BGB-290 PARP inhibitor Phase 2 maintenance therapy gastric cancer oral treatment PARALLEL 303 PARALLEL BGB290303 BGB-290-303
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 136
Healthy volunteers: no

Brief summary:
This study enrolled participants with previously-treated advanced or inoperable gastric cancer who have responded to first line platinum therapy into two treatment arms. In Arm A participants received BGB-290; in Arm B participants received placebo. The purpose of this study is to show that BGB-290 (pamiparib) (versus placebo) will improve progression-free survival (PFS) in participants with advanced or inoperable gastric cancer.

Detailed description:
This is a double-blind, placebo controlled, randomized multicenter global phase 2 study comparing the efficacy and safety of single agent poly (ADP-ribose) polymerase (PARP) inhibitor BGB-290 to placebo as maintenance therapy in participants with advanced gastric cancer who have responded to first line platinum based chemotherapy. Participants are randomized 1:1 to BGB-290 (Arm A) or placebo (Arm B). Randomization will be stratified by geography, biomarker status, and ECOG performance status.

Participants will undergo tumor assessments at screening and then every 8 weeks, or as clinically indicated. Administration of BGB-290 or placebo will continue until disease progression, unacceptable toxicity, death, or another discontinuation criterion is met.

After end of treatment, long-term follow-up assessments include tumor imaging every 8 weeks for those participants without disease progression, survival status, and new anticancer therapy.

Arms:
arm 1: Participants received pamiparib orally. arm 2: Participants received placebo orally.

Interventions: intervention 1: Pamiparib intervention 2: Placebo
Intervention descriptions: intervention 1: 60 mg orally twice daily intervention 2: 60 mg orally twice daily

Protocol document:
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CLINICAL STUDY PROTOCOL 
 
Protocol Title:  
A Phase 2, Double-blind, Randomized Study of BGB-290 versus 
Placebo as Maintenance Therapy in Patients with Inoperable Locally 
Advanced or Metastatic Gastric Cancer that Responded to Platinum-
based First-line Chemotherapy 
Protocol Identifier: 
BGB-290-303 
EudraCT Number: 
2017-003493-13 
Phase: 
2 
Date of Original Protocol: 
25 October 2017 
Date of Protocol Amendment 13 February 2020, Version 1.0 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc. 
1900 Powell Street, 5th Fl., Suite 500 
Emeryville, CA 94608 
USA 
Sponsor Medical Monitor: 
 
Confidentiality Statement 
This confidential information in this document is provided to you as an investigator or consultant for review 
by you, your staff, and the applicable Institutional Review Board/Independent Ethics Committee. Your 
acceptance of this document constitutes agreement that you will not disclose the information contained 
herein to others without written authorization from the sponsor. 
 
 
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SYNOPSIS 
Name of 
Sponsor/Company: 
BeiGene, Ltd. 
Name of Finished 
Product: 
BGB-290 capsule 
Name of Active 
Ingredient: 
BGB-290 
Title of Study: 
A Phase 2, Double-blind, Randomized Study of BGB-290 versus Placebo as 
Maintenance Therapy in Patients with Inoperable Locally Advanced or 
Metastatic Gastric Cancer that Responded to Platinum-based First-line 
Chemotherapy 
Protocol No: 
BGB-290-303 
Number of Patients: 
Approximately 128 patients will be enrolled 
Study Centers: 
Approximately 110 centers 
Study Phase: 
2 
Treatment Duration: 
Patients will receive daily treatment during the study until occurrence of 
progressive disease (PD), unacceptable toxicity, death, withdrawal of 
consent, lost to follow-up, or study termination by sponsor. 
Objectives: 
Primary: 
 
To evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in patients 
with inoperable locally advanced or metastatic gastric cancer with a complete response (CR) 
or confirmed partial response (PR) after first-line platinum-based chemotherapy, as measured 
by: 
o Progression-free survival (PFS) by investigator assessment 
Secondary: 
 
To further evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in 
patients with inoperable locally advanced or metastatic gastric cancer with a CR or confirmed 
PR after first-line platinum-based chemotherapy, as measured by: 
o Overall survival (OS) 
o Time to second subsequent treatment (TSST) by investigator assessment 
o Objective response rate (ORR; CR or PR) by investigator assessment 
o Duration of response by investigator assessment 
o Time to response by investigator assessment 
 
To evaluate safety and tolerability of BGB-290 versus placebo, as measured by: 
o Incidence, timing, and severity of treatment-emergent adverse events (TEAEs), graded 
according to National Cancer Institute-Common Terminology Criteria for Adverse 
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Events (NCI-CTCAE) Version 4.03 
Exploratory: 
 
To confirm the pharmacokinetics (PK) of BGB-290, as measured by: 
o Lowest observed plasma concentrations (Ctrough) at steady-state and other PK 
parameters for patients who received BGB-290 
 
To assess patient-reported outcomes on health-related quality of life, as measured by: 
o European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) 
o European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire (EORTC QLQ-C30) 
o EORTC QLQ gastric cancer module (EORTC QLQ-STO22) 
 
To explore potential biomarkers associated with the pharmacodynamics, response, and 
resistance to BGB-290: 
o Including, but not limited to, expression and mutations of genes in the DNA damage 
response pathway, genomic loss of heterozygosity (LOH), and relationship to efficacy 
and resistance to BGB-290 
Study Design: 
This is a double-blind, placebo-controlled, randomized, multicenter, global Phase 2 study comparing 
the efficacy and safety of single-agent poly (ADP-ribose) polymerase (PARP) inhibitor BGB-290 to 
placebo as maintenance therapy in patients with advanced gastric cancer who have completed first-line 
platinum-based chemotherapy. 
To be eligible for participation in the study, patients must have histologically confirmed 
adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or 
metastatic disease. Patients must have achieved a PR that is maintained for ≥ 4 weeks or a CR as 
determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) 
Version 1.1 with platinum-based first-line chemotherapy. The primary endpoint of the study is PFS by 
investigator assessment. Sufficient tumor tissue (archival biopsy) must be provided for central 
laboratory determination of homologous recombination deficiency (HRD) status for randomization 
and exploratory biomarker analyses. 
Patients will be randomized  8 weeks after the last platinum dose of first-line chemotherapy. Central 
interactive response technology will be used to randomize patients in a 1:1 ratio and assign eligible 
patients to 1 of 2 arms: Arm A – BGB-290 or Arm B – Placebo. Patient randomization will be 
stratified by HRD status (LOHhigh versus LOHlow versus unknown), region (China/Hong Kong/Taiwan 
versus Australia/Europe/North America versus Japan/South Korea versus rest of world [ROW]), and 
Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1). 
Cycles will be 28 days in length.  
Safety assessments will occur on Day 1 of each cycle, on Day 15 of Cycles 1 and 2, and as needed. 
Dose modifications will be made if appropriate. Adverse events (AEs) will be followed and 
documented during the treatment period and for approximately 30 days after the last dose of study 
drug or until initiation of new anticancer therapy, whichever occurs first. AEs will be graded according 
to NCI-CTCAE Version 4.03. An external independent data monitoring committee will periodically 
review safety data. 
To confirm PK properties of BGB-290, blood samples will be taken at various time points. 
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Additionally, tumor tissue and blood samples will be obtained to explore biomarkers of 
pharmacodynamics, response, and resistance to BGB-290 in gastric cancer. 
Disease status will be assessed by the investigator using RECIST Version 1.1. Patients will undergo 
tumor assessments at screening and then every 8 weeks (±7 days), or as clinically indicated.  
Administration of BGB-290 or placebo will continue until PD, unacceptable toxicity, death, or another 
discontinuation criterion is met. Once the treatment phase has been completed, an end of treatment 
visit should occur within 7 days of stopping BGB-290 or placebo with subsequent phases of safety and 
long-term follow-up. 
Long-term follow-up will include tumor assessments every 8 weeks (±7 days) for those patients 
without PD, survival status, new anticancer therapy, and diagnosis of myelodysplastic syndrome 
(MDS) or acute myeloid leukemia. Long-term follow-up will continue until the patient dies or another 
criterion for discontinuation from study is met. 
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Study Schema 
Abbreviations: AML, acute myeloid leukemia; BID, twice daily; CR, complete response; ECOG, Eastern 
Cooperative Oncology Group; LOH, loss of heterozygosity; HRD, homologous recombination deficiency; 
MDS, myelodysplastic syndrome; PD, progressive disease; PO, oral; PR, partial response; q8w, every 8 weeks; 
ROW, rest of world; vs, versus. 
Note: Key assessments during treatment phase: tumor assessments and patient-reported outcomes every 8 weeks, 
adverse events, hematology, and chemistry every 4 weeks. BGB-290 and placebo are to be administered 
continuously. 
Key Eligibility Criteria: 
The population under study is adult patients (>18 years of age) with histologically proven adenocarcinoma 
of the stomach or gastroesophageal junction, inoperable locally advanced or with metastatic disease. 
Patients with gastric cancer overexpressing HER2 or who received irradiation as part of prior first-line 
treatment are not allowed. All patients are required to have a PR that is maintained for ≥ 4 weeks or CR to 
platinum-based first-line chemotherapy; archival tumor tissue for central laboratory determination of HRD 
status for stratification and exploratory biomarker analyses is also required. 
Test product, dose 
and mode of 
BGB-290: 60 mg will be administered orally (PO) twice daily (BID) 
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administration: 
Reference therapy, 
dose, and mode of 
administration: 
Placebo: 60 mg will be administered PO BID 
Dose Modifications: 
Dosing of BGB-290 or placebo can be withheld for up to approximately 28 days consecutively. A 
maximum of 2 dose reductions is allowed before the patient must be permanently withdrawn from study 
drug. If drug is planned to be held > 28 days, the medical monitor should be contacted before permanent 
patient discontinuation from the study drug. 
Concomitant Therapy and Clinical Practice: 
All treatments and supportive care, including antiemetic therapy, hematopoietic growth factors, and/or red 
blood cell/platelet transfusions, that the investigator considers necessary for a patient’s welfare may be 
administered at the discretion of the investigator in keeping with the local standards of medical care. 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 
randomization and 30 days after the last day of BGB-290 or placebo will be recorded. 
Patients are not allowed to receive other anticancer therapy, including surgery, 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 
randomization 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 prior to 
randomization. 
The primary metabolic pathway for BGB-290 involves the CYP3A isoform. Administration of 
strong/moderate inhibitors of CYP3A or strong CYP3A inducers is not allowed. In addition, careful 
monitoring should be used when co-prescribing CYP2C9 substrates with a narrow therapeutic index, such 
as phenytoin and warfarin. 
Criteria for Evaluation: 
Efficacy: 
Tumor imaging studies will be reviewed for the purposes of eligibility determination and on-study tumor 
monitoring. Following the screening tumor assessment, tumor assessments will occur at the schedule of 
every 8 weeks (±7 days) after Day 1. Any measurable disease must be documented at screening and 
reassessed at each subsequent tumor evaluation. Patients who do not have PD at the time of BGB-290 or 
placebo permanent discontinuation but meet other discontinuation criteria will continue to have tumor 
assessments per protocol. PFS will be assessed by the investigator. Response and duration of response will 
be assessed by the investigator using RECIST Version 1.1. The same imaging method(s) used at screening 
must be used throughout the study. A documented standard-of-care tumor assessment may be used as the 
screening assessment provided it meets protocol requirements. Survival status of patients will be 
monitored through all phases of the study. 
Safety: 
Safety will be monitored throughout the study. Safety assessments include AE monitoring and reporting, 
physical examinations, vital sign measurements, electrocardiograms (ECGs), and clinical laboratory tests. 
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Statistical Methods: 
Analysis Set: 
 
Intent-to-Treat (ITT) Analysis Set includes all randomized patients who are assigned to study drug 
(BGB-290 or placebo). The ITT Analysis Set will be used for all efficacy analyses unless otherwise 
specified in the statistical analysis plan.  
 
Safety Analysis Set includes all patients in the ITT Analysis Set who receive any dose of study drug 
(BGB-290 or placebo). The Safety Analysis Set will be used for all safety analyses. 
 
Per-Protocol (PP) Analysis Set includes all patients in the ITT Analysis Set without major protocol 
deviations that impact assessment of efficacy. Criteria for exclusion from the PP Analysis Set will be 
determined and documented before the final analysis of PFS. The PP Analysis Set will be used to 
perform sensitivity analysis for the PFS and OS endpoints.  
 
PK Analysis Set includes all patients who receive BGB-290 and for whom valid BGB-290 PK 
parameters can be estimated. 
Efficacy Analyses: 
All efficacy analyses will be conducted using the ITT Analysis Set unless otherwise specified. Primary 
efficacy analysis of PFS will use the investigator assessment of PD according to RECIST Version 1.1. 
Secondary efficacy analyses of ORR, time to response, and duration of response will use the investigator 
assessments of response and PD according to RECIST Version 1.1. All stratified efficacy analyses will 
incorporate the stratification factors used at randomization (HRD status [LOHhigh versus LOHlow versus 
unknown], ECOG performance status [0 versus 1], and region [China/Hong Kong/Taiwan versus 
Australia/Europe/North America versus Japan/South Korea versus ROW]), unless otherwise specified. 
Primary Efficacy Analysis: 
A stratified 1-sided log-rank test at a 0.1 significance level incorporating the randomized stratification 
factors will be used to compare treatment groups using the ITT Analysis Set for the PFS primary endpoint. 
The hazard ratio [HR] and its 2-sided 95% confidence interval (CI) will be estimated using the stratified 
Cox-proportional hazards model. 
Secondary Efficacy Analyses: 
A stratified log-rank test incorporating the randomized stratification factors will be used to compare 
treatment groups using the ITT Analysis Set for the OS secondary endpoint. The HR and its 2-sided 
95% CI will be estimated using the stratified Cox-proportional hazards model. The median OS for each 
treatment group will be estimated using the Kaplan-Meier method and the 95% CI will be calculated using 
the Brookmeyer-Crowley method.  
A sensitivity analysis of OS will be conducted using the PP Analysis Set. 
Other secondary time-to-event endpoints, such as TSST and DOR will be analyzed in a similar manner. 
The ORR and its exact 2-sided 95% CI will be reported for each treatment group of the ITT Analysis Set. 
A Cochran-Mantel-Haenszel score test will be used to compare treatment groups. 
Only patients with a response of CR or PR during the study will be included in time to response and 
duration of response analyses. 
Pharmacokinetic Analyses: 
BGB-290 Ctrough at steady-state will be summarized. Descriptive statistics will include means, medians, 
ranges, and standard deviations, as appropriate. 
Population PK analysis may be carried out to include plasma concentrations from this study in an existing 
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model. Additional PK parameters such as apparent clearance (CL/F) of the drug from plasma and area 
under the plasma concentration-time curve from 0 to 12 hours post-dose (AUC0-12) may be derived from 
the population PK analysis if supported by data. 
Exposure-response (efficacy or safety endpoints) analysis may be carried out if supported by data. 
Exploratory Efficacy Analyses: 
Patient-reported outcomes will be assessed using the EORTC QLQ-C30 and QLQ-STO22 questionnaires 
and the EQ-5D-5L health questionnaire. The scores from these questionnaires will be summarized by 
study visit using descriptive statistics. 
Correlative biomarker analyses in tumor tissues and blood will be performed. A separate statistical 
analysis plan will outline details of the biomarker analyses. 
Safety Analysis: 
All TEAEs including, serious AEs (SAEs), deaths,  Grade 3 TEAEs, study drug-related TEAEs, and 
TEAEs that led to study drug withholding or permanent discontinuation, will be summarized. Study drug 
exposure, vital sign measurements, ECG results, and clinical laboratory results will also be summarized. 
Sample Size: 
This study is designed to provide 80% power for PFS. The following assumptions are used in determining 
the sample size for this study: 
 
Overall type I error rate: 0.1 (1-sided) 
 
Randomization: 1:1 
 
Median PFS for placebo group: 6.0 months 
 
PFS HR (BGB-290/placebo): 0.63 
A sample size of approximately 128 patients (64 per treatment group) is required to achieve 85 PFS events 
within the planned study duration of approximately 26 months after the first patient is randomized to 
study, assuming an estimated accrual period of 20 months. 
 
 
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TABLE OF CONTENTS 
PROTOCOL APPROVAL SHEET .......................................................................................2 
SYNOPSIS ................................................................................................................................3 
TABLE OF CONTENTS ......................................................................................................10 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................17 
1. 
INTRODUCTION......................................................................................................20 
1.1. 
Inoperable Locally Advanced and Metastatic Gastric Cancer .........................20 
1.2. 
Poly (ADP-ribose) Polymerase Inhibitors .......................................................21 
1.3. 
Biology of Gastric Cancer and PARP Inhibitors .............................................22 
1.4. 
PARP Inhibitor BGB-290 ................................................................................24 
1.4.1. 
Nonclinical Data for BGB-290 .........................................................24 
1.4.1.1. 
Nonclinical Safety Data ..................................................24 
1.4.1.2. 
Nonclinical Activity Data ...............................................25 
1.4.2. 
Clinical Data for BGB-290 ...............................................................29 
1.4.2.1. 
Pharmacokinetics Data for BGB-290-AU-002 ...............29 
1.4.2.2. 
Exploratory Biomarker Data ...........................................29 
1.4.2.3. 
Clinical Safety and Preliminary Efficacy for BGB-290-
AU-002 ...........................................................................30 
1.5. 
Rationale for Selection of BGB-290 Dose.......................................................31 
1.6. 
Study Rationale ................................................................................................31 
1.7. 
Risk-Benefit Assessment .................................................................................32 
1.8. 
Study Conduct ..................................................................................................32 
2. 
STUDY OBJECTIVES ..............................................................................................33 
2.1. 
Primary Objective ............................................................................................33 
2.2. 
Secondary Objectives.......................................................................................33 
2.3. 
Exploratory Objectives ....................................................................................33 
3. 
STUDY DESIGN ........................................................................................................34 
3.1. 
Summary of Study Design ...............................................................................34 
3.2. 
Independent Data Monitoring Committee .......................................................36 
3.3. 
Blinding............................................................................................................37 
3.4. 
Duration of the Study .......................................................................................37 
4. 
STUDY POPULATION ............................................................................................37 
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4.1. 
Inclusion Criteria .............................................................................................37 
4.2. 
Exclusion Criteria ............................................................................................39 
5. 
STUDY PHASES FROM SCREENING TO END OF STUDY ............................40 
5.1. 
Screening..........................................................................................................40 
5.2. 
Enrollment........................................................................................................41 
5.3. 
Treatment .........................................................................................................41 
5.4. 
Unscheduled Visit ............................................................................................41 
5.5. 
Permanent Discontinuation of Study Drug ......................................................41 
5.5.1. 
Reasons for Permanent Discontinuation of BGB-290 or Placebo ....41 
5.5.2. 
End of Treatment Visit......................................................................42 
5.6. 
Follow-Up Phase ..............................................................................................42 
5.6.1. 
Safety Follow-up ...............................................................................42 
5.6.2. 
Long-term Follow-up ........................................................................43 
5.6.3. 
Lost to Follow-up ..............................................................................43 
5.7. 
End of Study ....................................................................................................43 
6. 
STUDY TREATMENT .............................................................................................44 
6.1. 
Study Drug .......................................................................................................44 
6.1.1. 
Packaging and Labeling ....................................................................44 
6.1.2. 
Handling and Storage ........................................................................44 
6.1.3. 
Dosage and Administration...............................................................44 
6.1.4. 
Dose Hold and Modification .............................................................44 
6.1.5. 
Compliance and Accountability ........................................................48 
6.1.6. 
Disposal and Destruction ..................................................................48 
6.2. 
Concomitant Medications and Nondrug Therapies .........................................48 
6.2.1. 
Permitted Medications and Supportive Care ....................................48 
6.2.2. 
Prohibited Medications .....................................................................49 
6.2.3. 
Medications to Be Used with Caution ..............................................49 
7. 
STUDY ASSESSMENTS ..........................................................................................49 
7.1. 
Study Flow and Visit Schedule ........................................................................49 
7.2. 
Patient Demographics and Other Baseline Characteristics ..............................50 
7.2.1. 
Demographics ...................................................................................50 
7.2.2. 
Medical History ................................................................................50 
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7.2.3. 
Other Baseline Characteristics ..........................................................50 
7.3. 
Efficacy ............................................................................................................50 
7.3.1. 
Tumor Assessments ..........................................................................50 
7.3.1.1. 
Determination of Eligibility ............................................50 
7.3.1.2. 
Screening Tumor Assessment .........................................51 
7.3.1.3. 
On-study Tumor Assessments ........................................52 
7.3.2. 
Survival Assessments........................................................................52 
7.3.3. 
Quality of Life Assessments .............................................................52 
7.4. 
Safety ...............................................................................................................52 
7.4.1. 
Adverse Events .................................................................................52 
7.4.2. 
Physical Examination, Vital Signs, ECOG Performance Status, 
Weight, and Height ...........................................................................52 
7.4.3. 
Electrocardiograms ...........................................................................53 
7.5. 
Laboratory Assessments ..................................................................................53 
7.5.1. 
Hematology .......................................................................................53 
7.5.2. 
Chemistry ..........................................................................................54 
7.5.3. 
Urinalysis ..........................................................................................54 
7.5.4. 
Pregnancy Testing .............................................................................54 
7.6. 
Pharmacokinetics .............................................................................................54 
7.7. 
Biomarkers .......................................................................................................54 
7.8. 
Appropriateness of Measurements ...................................................................55 
8. 
DATA HANDLING AND QUALITY ASSURANCE ............................................55 
8.1. 
Data Collection ................................................................................................55 
8.2. 
Data Management/Coding ...............................................................................55 
8.3. 
Quality Assurance ............................................................................................56 
9. 
SAFETY MONITORING AND REPORTING ......................................................56 
9.1. 
Adverse Events ................................................................................................56 
9.1.1. 
Definition and Reporting of an Adverse Event .................................56 
9.1.2. 
Assessment of Severity .....................................................................57 
9.1.3. 
Assessment of Causality ...................................................................57 
9.1.4. 
Follow-Up of Adverse Events ..........................................................58 
9.1.5. 
Laboratory Test Abnormalities .........................................................58 
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9.2. 
Definition of a Serious Adverse Event ............................................................59 
9.3. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ................................................................................................60 
9.3.1. 
Adverse Event Reporting Period ......................................................60 
9.3.2. 
Eliciting Adverse Events...................................................................60 
9.4. 
Specific Instructions for Recording Adverse Events and Serious Adverse 
Events ...............................................................................................................60 
9.4.1. 
Diagnosis versus Signs and Symptoms.............................................60 
9.4.2. 
Adverse Events Occurring Secondary to Other Events ....................60 
9.4.3. 
Persistent or Recurring Adverse Events ...........................................61 
9.4.4. 
Disease Progression ..........................................................................61 
9.4.5. 
Death .................................................................................................61 
9.4.6. 
Myelodysplastic Syndrome and Acute Myeloid Leukemia ..............61 
9.5. 
Prompt Reporting of Serious Adverse Events .................................................62 
9.5.1. 
Timeframes for Submitting Serious Adverse Events........................62 
9.5.2. 
Completion and Transmission of the Serious Adverse Event Report62 
9.5.3. 
Regulatory Reporting Requirements for Serious Adverse Events ....62 
9.6. 
Pregnancy Reporting ........................................................................................63 
9.7. 
Poststudy Adverse Events ................................................................................64 
9.8. 
Expedited Reporting to Health Authorities, Ethics Committees, and 
Investigators .....................................................................................................64 
10. 
STATISTICAL CONSIDERATIONS AND ANALYTICAL PLAN ....................64 
10.1. Analysis Set .....................................................................................................64 
10.2. Covariates ........................................................................................................65 
10.3. Efficacy Analyses ............................................................................................65 
10.3.1. Primary Efficacy Analyses ...............................................................65 
10.3.2. Secondary Efficacy Analyses ...........................................................66 
10.4. Pharmacokinetic Analyses ...............................................................................67 
10.5. Exploratory Analyses .......................................................................................67 
10.5.1. Health-related Quality of Life ...........................................................67 
10.5.2. Biomarkers ........................................................................................67 
10.6. Safety Analyses ................................................................................................67 
10.6.1. Extent of Exposure ............................................................................68 
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10.6.2. Adverse Events .................................................................................68 
10.6.3. Laboratory Analyses .........................................................................68 
10.6.4. Physical Examinations ......................................................................68 
10.6.5. Vital Signs .........................................................................................69 
10.6.6. Electrocardiograms ...........................................................................69 
10.7. Sample Size Consideration ..............................................................................69 
11. 
STUDY ADMINISTRATION AND INVESTIGATOR OBLIGATIONS ...........69 
11.1. Regulatory Authority Approval .......................................................................69 
11.2. Investigator Responsibilities ............................................................................69 
11.2.1. Good Clinical Practice ......................................................................69 
11.2.2. Ethical Conduct of the Study and Ethics Approval ..........................70 
11.2.3. Informed Consent..............................................................................70 
11.2.4. Investigator Reporting Requirements ...............................................70 
11.2.5. Confidentiality ..................................................................................71 
11.2.6. Electronic Case Report Forms ..........................................................71 
11.2.7. Drug Accountability..........................................................................71 
11.2.8. Inspections ........................................................................................72 
11.2.9. Protocol Adherence ...........................................................................72 
11.3. Sponsor Responsibilities ..................................................................................72 
11.3.1. Protocol Modifications......................................................................72 
11.3.2. Use of Information and Publication ..................................................72 
11.4. Study and Study Center Closure ......................................................................73 
11.5. Records Retention and Study Files ..................................................................73 
11.5.1. Study Files and Retention of Records ...............................................73 
11.5.2. Provision of Study Results and Information to Investigators ...........75 
11.6. Information Disclosure and Inventions ............................................................75 
11.7. Joint Investigator/Sponsor Responsibilities .....................................................76 
11.7.1. Access to Information for Monitoring ..............................................76 
11.7.2. Access to Information for Auditing or Inspections...........................76 
12. 
REFERENCES ...........................................................................................................77 
13. 
APPENDICES ............................................................................................................83 
APPENDIX 1. 
SCHEDULE OF ASSESSMENTS ................................................84 
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APPENDIX 2. 
THE RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS (RECIST) GUIDELINES, VERSION 1.1 .............................................88 
APPENDIX 3. 
ECOG PERFORMANCE STATUS ..............................................97 
APPENDIX 4. 
CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL”, “NO CHILDBEARING 
POTENTIAL” 98 
APPENDIX 5. 
NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION ...................................................................................................99 
APPENDIX 6. 
PROHIBITED MEDICATIONS .................................................100 
APPENDIX 7. 
MEDICATIONS TO BE USED WITH CAUTION ..................101 
APPENDIX 8. 
EUROPEAN QUALITY OF LIFE 5-DIMENSIONS 5-LEVELS 
HEALTH QUESTIONNAIRE ...............................................................................102 
APPENDIX 9. 
EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE CANCER 
QUESTIONNAIRE QLQ-C30 ...............................................................................104 
APPENDIX 10. 
EUROPEAN ORGANISATION FOR RESEARCH AND 
TREATMENT OF CANCER QUALITY OF LIFE GASTRIC CANCER 
MODULE QLQ-ST022 ...........................................................................................106 
APPENDIX 11. 
CHRONIC KIDNEY DISEASE EPIDEMIOLOGY 
COLLABORATION  (CKD-EPI) EQUATION ...................................................107 
APPENDIX 12. 
SIGNATURE OF INVESTIGATOR ..........................................108 
 
LIST OF TABLES 
Table 1: PARP Enzyme Inhibition and PARP Trapping Activity of PARP Inhibitors ...........25 
Table 2: Dose Levels for BGB-290 and Placebo .....................................................................45 
Table 3: Criteria for Modification of BGB-290 or Placebo Dosing for Related Adverse Events
................................................................................................................................46 
Table 4: Time Frame for Reporting Serious Adverse Events to the Sponsor or Designee .....62 
 
LIST OF FIGURES 
Figure 1: BGB-290 Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-053 Small Cell Lung Cancer Xenograft Model ..............27 
Figure 2: BGB-290 Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-080 Small Cell Lung Cancer Xenograft Model ..............28 
Figure 3: Correlation of PAR Inhibition in Peripheral Blood Mononuclear Cells with 
BGB-290 Dose .......................................................................................................30 
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Figure 4: Study Schema ...........................................................................................................36 
 
 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
ATMlow 
low or undetectable levels of ATM 
AUC 
area under the plasma concentration-time curve (drug exposure) 
AUC0-12 
area under the plasma concentration-time curve from 0 to 12 hours postdose 
AUC0-last 
area under the plasma concentration-time curve from 0 to the last measurable 
concentration  
BGB-290 
study drug code 
BID 
twice daily 
C 
Cycle 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIN 
chromosomal instability 
CL/F 
apparent clearance 
Cmax 
maximum concentration 
CNS 
central nervous system 
CNV 
copy number variation 
CR 
complete response 
CT 
computed tomography 
Ctrough 
lowest observed plasma concentration 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicity (or toxicities) 
EBV 
Epstein-Barr virus 
E/C 
etoposide and carboplatin 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire 
EORTC QLQ-STO22 
European Organisation for Research and Treatment of Cancer Quality of Life gastric 
cancer module 
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Abbreviation 
Definition 
EOT 
end of treatment 
EQ-5D-5L 
European Quality of Life 5-Dimensions 5-Levels Health Questionnaire 
FDA 
Food and Drug Administration 
FDG 
fluorine-18 [F-18]fluorodeoxyglucose 
GCP 
Good Clinical Practice 
h 
hour(s) 
HCP 
health care provider  
Hgb 
hemoglobin 
hERG 
human ether-à-go-go related gene 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
IB 
investigator brochure 
IC50 
half-maximal inhibition concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent data monitoring committee 
IEC 
Independent Ethics Committee 
IHC 
immunohistochemistry 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
IV 
intravenous 
LOH 
loss of heterozygosity 
MDRD STUDY EQ 
Modification of Diet in Renal Disease study equation 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PAR 
poly (ADP-ribose) 
PARP 
poly (ADP-ribose) polymerase 
PBMCs 
peripheral blood mononuclear cells 
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Abbreviation 
Definition 
PD 
progressive disease 
PET 
positron-emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PLT 
platelet (count) 
PO 
oral (orally) 
PP 
Per-Protocol 
PR 
partial response 
PT 
preferred term 
q8w 
every 8 weeks 
QTc 
QT interval corrected for heart rate 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
ROW 
rest of world 
SAE 
serious adverse event 
SCLC 
small cell lung cancer 
SD 
stable disease 
SEM 
standard error of the mean 
SOC 
system organ class 
SSBs 
single-strand DNA breaks 
SUSAR 
suspected unexpected serious adverse reactions 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
TSST 
time to second subsequent treatment 
ULN 
upper limit of normal 
US 
United States 
vs 
versus 
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1. 
INTRODUCTION 
1.1. 
Inoperable Locally Advanced and Metastatic Gastric Cancer 
There were an estimated 17.5 million cancer cases and 8.7 million cancer deaths in 2015 worldwide. 
Gastric cancer alone contributed about 1.3 million cases with 800,000 deaths. It is the fifth most 
common cancer worldwide and the second leading cause of cancer death together with colorectal 
and liver cancer (Global Burden of Disease Cancer Collaboration, 2017). More than half of gastric 
cancer cases and deaths are estimated to occur in China, with approximately 680,000 cases and 
approximately 500,000 deaths in 2015 (Chen et al, 2016). Predicted gastric cancer deaths for the 
European Union in 2017 are approximately 55,000 (Malvezzi et al, 2017). For the United States 
(US), estimates for gastric cancer in 2017 are approximately 28,000 cases with 11,000 deaths 
(Siegel et al, 2017). 
Adenocarcinoma is the major histologic subtype representing approximately 90% of gastric cancer 
(Smyth et al, 2016). About two-thirds are true gastric cancers (non-cardia) and the remainder are 
gastroesophageal junction cancers (cardia) (Colquhoun et al, 2015). The most common anatomical 
subsites differ in world regions due to differences in risk factors. Distal and antral gastric cancers 
are more common in East Asia and tumors of the proximal stomach or gastroesophageal junction 
are more common in non-Asian countries (Forman and Burley, 2006; World Cancer Research Fund 
International/American Institute for Cancer Research, 2017). Patients with newly diagnosed 
inoperable locally advanced or metastatic disease generally receive chemotherapy regimens 
containing a platinum and a fluoropyrimidine (Smyth et al, 2016; NCCN 2017). Triplet regimens 
may provide additional clinical benefit, as suggested in a meta-analysis for the addition of an 
anthracycline (Okines et al, 2009). Because of their added toxicities, however, they have not been 
uniformly adopted and are recommended only for medically fit patients with good performance 
status and access to frequent toxicity evaluations. In Western countries, approximately two-thirds of 
patients present with advanced disease. Response rates for first-line chemotherapy regimens are 
around 30% to 50% with median progression-free survival (PFS) ranging from 5 to 7 months. 
Median overall survival (OS) is less than 12 months, and less than 10% of patients are still alive 
after 5 years (Chau et al, 2004; Cunningham et al, 2008; Kang et al, 2009; Koizumi et al, 2008; Van 
Cutsem et al, 2006; Wagner et al, 2006). Approximately 12% to 20% of gastric adenocarcinomas 
are HER2-positive (Van Cutsem et al, 2015). For these patients, a unique treatment paradigm has 
been established that combines first-line platinum- and fluoropyrimidine-based chemotherapy with 
the anti-HER2 antibody trastuzumab (Bang et al, 2010).  
The duration of first-line chemotherapy typically does not exceed 6 months, either because of 
progressive disease (PD) or due to the cumulative toxicities of chemotherapy (Cunningham et al, 
2008; Van Cutsem et al, 2006; Hess et al, 2016). Therefore, for patients who have achieved 
maximum tumor reduction with first-line chemotherapy, the concept of further treatment with a 
regimen of good tolerability is appealing. However, there are currently no approved drugs for 
maintenance treatment after first-line therapy. There are few data for monotherapy with a 
fluoropyrimidine, and they do not support that this approach provides clinical benefit compared 
with best supportive care (Li et al, 2017; Qiu et al, 2014). The concept of further therapy with a 
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different regimen (switch maintenance) is currently being explored in several studies. The Phase 3 
JAVELIN Gastric 100 study is comparing the anti-PD-L1 antibody avelumab to continued 
platinum-based chemotherapy after a short induction phase of only 12 weeks with a platinum 
doublet (ClinicalTrials.gov identifier: NCT02625610). Similarly, the ARMANI Phase 3 trial is 
comparing paclitaxel plus ramucirumab to continued platinum doublet after 12 weeks of induction 
chemotherapy (ClinicalTrials.gov identifier: NCT02934464). The Phase 2 trial MANTRA allows up 
to 6 months of platinum-based chemotherapy before randomization to either regorafenib or placebo 
(Aprile et al, 2016).  
In the second-line setting, several single-agent chemotherapy options are available, including 
irinotecan, docetaxel, or paclitaxel, that have been shown to improve OS compared with best 
supportive care (Ford et al, 2014; Hironaka et al, 2013; Kang et al, 2012; Roy et al, 2013; Thuss-
Patience et al, 2011). The anti-VEGFR-2 antibody ramucirumab is another option for second-line 
therapy since it has shown, as monotherapy, a survival benefit comparable with chemotherapy, and, 
when combined with paclitaxel, a survival benefit over paclitaxel alone (Fuchs et al, 2014; Wilke et 
al, 2014). More recently, immunotherapy with anti-PD1 antibodies pembrolizumab and nivolumab 
has resulted in durable remissions for a subset of patients (Le et al, 2016; Muro et al, 2016). 
ONO-12 (ATTRACTION 2), a randomized Phase 3 study comparing nivolumab with placebo in 
patients with advanced gastric cancer who had received at least 2 prior chemotherapy regimens, 
showed that PD1 inhibition can lead to a survival improvement in heavily pretreated gastric cancer 
patients. Median OS was 5.32 months (95% confidence interval [CI], 4.63%-6.41%) with 
nivolumab versus 4.14 months (95% CI, 3.42%-4.86%) with placebo (hazard ratio [HR] 0.63; 95% 
CI, 0.50%-0.78%; P <0.0001), suggesting that a subset of patients may derive longer-term benefit 
from PD1 inhibition (Kang et al, 2017). Phase 3 studies for second- and third-line patients are now 
ongoing to determine the efficacy of anti-PD1 and PD-L1 antibodies compared to single-agent 
chemotherapy (Kelly, 2017). 
1.2. 
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 BRCA-deficient cells and, more broadly, cells 
with homologous recombination deficiency (HRD), 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 (Pommier et al, 2016; O’Connor, 2015; Lord and Ashworth, 2017). 
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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 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 (Lynparza [olaparib] prescribing information 2017; Rubraca [rucaparib] 
prescribing information 2017). 
Aside from BRCA1 or BRCA2 mutations, other alterations can also result in HRD, which is 
characterized by ‘BRCA-like” genomic scarring. HRD does not only make cancer cells sensitive to 
PARP inhibitors but also to platinums, and shared mechanisms of resistance suggest that both 
classes of drugs have similar antitumor effects in cancers with HRD (Edwards et al, 2008; 
Sakai et al, 2008; Sakai et al, 2009). This concept is supported by clinical data for the PARP 
inhibitor olaparib in patients with BRCA-mutated ovarian cancer demonstrating that platinum 
sensitivity correlated with response and platinum refractoriness with an almost complete lack of 
response to olaparib (Fong et al, 2010; Gelmon et al, 2011). In addition, rucaparib has been shown 
to be effective in platinum-sensitive ovarian cancer with BRCA-mutated patients deriving most 
benefit, followed by nonBRCA HRD and non-HRD patients (Swisher et al, 2017). 
The strongest evidence that platinum sensitivity can predict clinical benefit from PARP inhibition is 
provided by 2 studies for ovarian cancer. The NOVA study for the PARP inhibitor niraparib in 
patients with platinum-sensitive ovarian cancer demonstrated that patients had significantly 
improved median PFS with niraparib compared with placebo regardless of BRCA mutation or HRD 
status (Mirza et al, 2016). Median PFS for niraparib in patients with germline BRCA-mutations was 
21.0 versus 5.5 months for placebo (HR 0.27; P < 0.001). An exploratory analysis for patients who 
were biomarker negative (germline BRCA-wild-type and HRD negative) showed a median PFS of 
6.9 versus 3.8 months (HR 0.58, P = 0.02). This led to the approval of niraparib for the maintenance 
treatment of patients who are in a complete response (CR) or partial response (PR) to platinum-
based chemotherapy (Zejula [niraparib] prescribing information 2017). Similar results were recently 
reported for rucaparib in the ARIEL3 study. Median PFS for rucaparib in patients with BRCA-
mutant (germline or somatic) ovarian cancers was 16.6 versus 5.4 months for placebo (HR 0.23; 
P < 0.0001). In an exploratory analysis for patients who were biomarker negative (BRCA-wild-type 
and HRD negative), median PFS was 6.7 versus 5.4 months (HR 0.58, P = 0.0049) (Coleman et al, 
2017). 
1.3. 
Biology of Gastric Cancer and PARP Inhibitors 
Gastric cancers have been classified, using the Lauren system, as intestinal, diffuse, or 
indeterminate — the vast majority of these being adenocarcinomas. The World Health Organization 
has also applied an alternative system dividing gastric cancer into tubular, papillary, mucinous 
(colloid), or poorly cohesive carcinomas (Hu et al, 2012); however, these classification systems 
have provided little clinical utility. Gastric cancer is largely associated with infectious agents such 
as the Helicobacter pylori bacterium and Epstein-Barr virus (EBV), yet the frequencies of 
histological subtypes and distribution of associated H. pylori or EBV infections vary greatly by 
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geographical regions. Recently, The Cancer Genome Atlas group profiled a global population of 
295 primary gastric cancers (Cancer Genome Atlas Research Network, 2014) and identified 
4 different subtypes according to various molecular characteristics. These were EBV-positive 
tumors, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal 
instability (CIN). These subtypes were found in 9%, 22%, 20%, and 50% of gastric cancers, 
respectively. The CIN subgroup is distinguished by a high frequency of p53 defects and copy 
number variation (CNV), characteristic of DNA repair deficiency. While present across all 
histologies, the CIN subtype was most enriched in the intestinal subtype at the gastroesophageal 
junction.  
PARP inhibitors are particularly effective in tumors that have defects in DNA repair, specifically 
those that have HRD. Many genes are involved in homologous recombination repair including 
BRCA1/2, RAD51, PALB2, ATR, and ATM (Lord and Ashworth, 2016). Defects in these genes 
lead to HRD and large scale CNV. Assessment of these “genomic scarring” patterns, including 
genomic loss of heterozygosity (LOH), by using next generation sequencing techniques have 
recently demonstrated the ability to identify ovarian cancer patients who clinically benefit from 
PARP inhibitors. In the ARIEL2 single-arm Phase 2 study, serous ovarian cancer patients with 
platinum-sensitive relapsed disease were treated with rucaparib and in a prespecified analysis it was 
demonstrated that patients with HRD (including non-BRCA tumors) had a significantly improved 
clinical outcome compared with biomarker-negative patients (Swisher et al, 2017). Moreover, in the 
NOVA and ARIEL3 randomized, switch-maintenance Phase 3 trials, platinum-sensitive high-grade 
serous ovarian cancer patients treated with niraparib or rucaparib, respectively, had a significant 
clinical benefit compared with placebo. A further improvement in clinical benefit was also seen in 
the HRD patients treated with the PARP inhibitors compared with placebo (Mirza et al, 2016; 
Coleman et al, 2017).  
Since platinum-based therapy leads to DNA damage, it follows that platinum-sensitive tumors likely 
have a higher level of HRD and, thus, are more likely to respond to PARP inhibitors. This has been 
shown for BRCA-mutant patients where PARP inhibitor benefit is higher for those who are 
platinum sensitive compared with platinum-resistant patients (Fong et al, 2010). Indeed, acquisition 
of secondary mutations that restore the functionality of homologous recombination proteins 
including BRCA1, BRCA2, RAD51C, and RAD51D have been found in both platinum- and PARP 
inhibitor-resistant disease (Norquist et al, 2011; Pennington et al, 2014; Patch et al, 2015; 
Quigley et al, 2017; Kondrashova et al, 2017). 
In gastric cancer, a recent study assessing LOH in platinum-treated patients indicated that patients 
with HRD may have improved clinical outcome (Cafferkey et al, 2016). Whereas this was a small 
study, there was a trend to improved OS in those patients with a high level of LOH. The cutoff 
chosen in this study identified 14% of patients that had LOHhigh tumors. In addition, a BRCA 
mutational signature has been identified in gastric cancer with a frequency of approximately 7% to 
12% (Alexandrov et al, 2015). Loss of ATM expression, as defined by immunohistochemistry 
(IHC), has also been explored as an approach for identifying patients who may be sensitive to PARP 
inhibitors. Preclinically, there is an association with ATM deficiency and PARP inhibitor response 
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(Kubota et al, 2014). Interestingly, this is related to loss of ATM expression but not mutational 
status. ATM expression is lost in approximately 13% to 21% of gastric cancers (Kim et al, 2013). 
Accordingly, Bang et al, 2015 assessed the clinical benefit of olaparib in a gastric cancer population 
enriched for ATM loss. Approximately half of the patients had loss of ATM expression as defined 
by a validated IHC assay. In a randomized Phase 2 study in 123 second-line metastatic gastric 
cancer patients, the combination of olaparib and paclitaxel significantly improved OS versus 
placebo and paclitaxel; whereas, the best improvement in OS was seen in patients with tumors with 
low or undetectable levels of ATM (ATMlow) (HR 0.35; 80% CI, 0.22%-0.56%; P = 0.002; median 
OS, not reached versus 8.2 months, respectively). The subsequent randomized Phase 3 GOLD study 
did not recapitulate these findings as it did not meet its primary endpoint. However, the proportion 
of patients with ATMlow tumors was significantly lower than the Phase 2 study potentially diluting 
the treatment effect (Smyth et al, 2016). Together, these data suggest that a molecular subtype of 
gastric cancer exists that displays HRD and, thus, may be particularly sensitive to PARP inhibitor 
therapy. 
1.4. 
PARP Inhibitor BGB-290 
1.4.1. 
Nonclinical Data for BGB-290 
BGB-290 is a potent and selective inhibitor of PARP1 and PARP2 that sets itself apart from other 
PARP inhibitors by combining potent PARP-trapping activity with significant brain penetrance. 
1.4.1.1. 
Nonclinical Safety Data 
The nonclinical toxicity and toxicokinetic profile of BGB-290 was characterized in single- and up to 
91-day repeat-oral-dose studies in rats and dogs, and in a core battery of genotoxicity tests, 
including in vitro Ames and chromosomal aberration assays, and in vivo bone marrow micronucleus 
assays in rats. Safety pharmacology assessments included in vitro human ether-à-go-go related gene 
(hERG) channel activity assays and in vivo studies of cardiovascular function in dogs, as well as 
central nervous system (CNS) and respiratory system function tests in rats. 
The main toxicity findings were bone marrow inhibition that correlated with clinical pathology 
changes and gastrointestinal toxicity that presented as emesis, decreased food consumption, and 
decreased body weight. The systemic exposure increased dose-proportionally without apparent sex 
differences or accumulation. The maximum tolerated dose (MTD) was considered to be 6 mg/kg in 
rats and 3 mg/kg in dogs for both 28-day and 91-day toxicity studies.  
BGB-290 was not mutagenic in the in vitro Ames (bacterial reverse mutation) assay, but clastogenic 
in the in vitro chromosomal aberration assay in Chinese hamster ovary cells and in the in vivo bone 
marrow micronucleus assay in rats, which is consistent with its mechanism of action. PARP 
enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle 
regulation, and DNA damage repair. BGB-290 interacts with and inhibits the enzymatic repair 
machinery that carries out detection and repair of SSBs. 
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In the general toxicity studies in rats and dogs, no gross lesions or histopathological changes were 
noted in male and female reproductive organs. No embryo-fetal toxicity studies were planned or 
conducted because of the already established genotoxicity and bone marrow inhibition by BGB-290. 
There was no apparent inhibition of BGB-290 on hERG channel as the value of half-maximal 
inhibition concentration (IC50) was 12.4 μM; for comparison, the IC50 of the positive control 
amitriptyline was 1.9 μM. No effects on blood pressure, heart rate, or electrocardiogram (ECG) 
findings were noted in telemetry-instrumented conscious dogs. No effects on CNS or respiratory 
functions were noted in Sprague-Dawley rats. No abnormal changes in the cardiovascular, CNS, or 
respiratory systems were identified in single- or repeat-dose toxicity studies in both rats and dogs. 
No QT interval prolongation was noted in cardiovascular function studies in conscious dogs and in 
28-day and 91-day repeat-dose toxicity studies in dogs.  
In summary, all available toxicological studies and data are adequate to support clinical 
development of BGB-290 for treatment of patients with advanced cancer. Please refer to the 
investigator’s brochure (IB) for additional information (BGB-290 Investigator’s Brochure). 
1.4.1.2. 
Nonclinical Activity Data 
Biochemical and Cellular Inhibition of PARP Activity by BGB-290 
BGB-290 potently inhibits enzyme activity of PARP1 and PARP2, with IC50s of 1.3 and 0.92 nM, 
respectively (Table 1). Most PARP inhibitors are able to trap PARP enzymes at damaged DNA 
sites, and these trapped PARP-DNA complexes appear to be more cytotoxic than unrepaired DNA 
breaks caused by PARP inactivation (Section 1.2). The PARP-trapping activity of BGB-290 was 
measured by a fluorescence polarization binding assay, similar to the method described in the 
literature (Murai et al, 2012). BGB-290 showed potent PARP-trapping activity (with a half-maximal 
effective concentration [EC50] of 13 nM), similar to olaparib (EC50 = 16 nM), and 30-fold more 
potent than veliparib. 
Table 1: PARP Enzyme Inhibition and PARP Trapping Activity of PARP Inhibitors 
Enzyme 
BGB-290 (nM) 
Olaparib (nM) 
Veliparib (nM) 
PARP1 (Full length), IC50 
1.3 ± 0.058 (n=3) 
1.9 ± 0.12 (n=3) 
5.4 ± 0.70 (n=3) 
PARP2 (aa2-583), IC50 
0.92 
0.92 
3.2 
PARP trapping, EC50 
13 
16 
400 
Source:  BGB-290 Investigator’s Brochure 
Abbreviations: EC50, half-maximal effective concentration; IC50, half-maximal inhibitory concentration; 
PARP, poly (ADP-ribose) polymerase. 
 
Cellular assays confirmed that BGB-290 can potently inhibit intracellular PARP activity in 
hydrogen peroxide-treated HeLa cells, with an IC50 of 0.24 nM. BGB-290 was more potent than 
veliparib and olaparib, which had IC50s of 2.66 nM and 0.47 nM, respectively. 
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Single Agent Antitumor Activity of BGB-290 
BGB-290 as a single agent has demonstrated excellent in vitro activity against tumor cell lines with 
defects of the homologous recombination pathway. In vivo, BGB-290 has shown strong antitumor 
activity against a BRCA1 mutant mouse xenograft model (MDA-MB-436 breast cancer) and was 
16-fold more potent than olaparib. In a pharmacokinetic (PK)/pharmacodynamic study, oral (PO) 
administration of BGB-290 resulted in time- and dose-dependent inhibition of PARylation in MDA-
MB-436 breast cancer xenografts in mice. Inhibition of PARylation in the tumor tissues correlated 
well with tumor drug concentrations of BGB-290. 
Antitumor Activity of BGB-290 Monotherapy in the Maintenance Setting 
BCLU-053 is a primary human small cell lung cancer (SCLC) xenograft model derived from a 
patient who experienced a PR with first-line carboplatin and etoposide treatment. In the mouse 
model, the tumor was also sensitive to this combination with 6 PRs and 4 CRs in 10 mice. However, 
7 of 10 mice showed progression after discontinuation of chemotherapy. In contrast, addition of 
BGB-290 (continuously or intermittently) during chemotherapy and as subsequent single-agent 
maintenance therapy resulted in CRs in all mice and no relapses during BGB-290 monotherapy 
(Figure 1). Thirty days after completion of maintenance treatment (Day 72), most animals were still 
tumor-free with mean tumor volumes of 6 and 10 mm3 in the continuous and intermittent dosing 
groups, respectively. 
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Figure 1: BGB-290 Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-053 Small Cell Lung Cancer Xenograft Model 
 
Source:  BGB-290 Investigator’s Brochure 
Abbreviations: BID, twice daily; E/C, etoposide and carboplatin; SEM, standard error of the mean. 
Data are presented as mean tumor volume ± SEM of 10 animals in each group. E/C treatment: etoposide at 
12 mg/kg (Days 1-3) + carboplatin at 60 mg/kg (Day 1) of each 7-day cycle, for 3 cycles; continuous BGB-
290: 1.36 mg/kg BID; intermittent BGB-290: 1.36 mg/kg BID on Days 1-4 of each 7-day cycle, for 3 cycles; 
maintenance BGB-290: 5.45 mg/kg BID from Day 22 to Day 42. 
 
BCLU-080 is another primary human SCLC xenograft model derived from a patient who 
experienced a PR with first-line carboplatin and etoposide treatment. In the mouse model, the tumor 
was also sensitive to this combination with PR rates of 33% to 60%. However, all mice showed 
progression after discontinuation of chemotherapy. In the combination plus maintenance setting, 
addition of intermittent BGB-290 0.68, 1.36, or 2.73 mg/kg twice daily (BID) during chemotherapy 
and as subsequent single-agent maintenance therapy increased objective response rates (ORR; 
PR+CR) in all dose levels and significantly delayed relapses during BGB-290 monotherapy 
(Figure 2A). After completion of maintenance treatment, 6 out of 9 animals were still tumor-free on 
Day 45 in the intermittent BGB-290 2.73 mg/kg BID group. In the maintenance only setting, 
treatment with BGB-290 after completion of chemotherapy significantly delayed relapses, 
demonstrating more sustained tumor growth inhibition compared with no further treatment after 
chemotherapy (Figure 2B). 
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Figure 2: BGB-290 Activity with Etoposide and Carboplatin and as Maintenance 
Monotherapy in BCLU-080 Small Cell Lung Cancer Xenograft Model 
2A 
 
2B 
 
Source:  BeiGene VIVO-123 (Study No.: BCLU-080-1401) 
Abbreviations: BID, twice daily; E/C, etoposide and carboplatin; SEM, standard error of the mean. 
Data are presented as mean tumor volume ± SEM of 9-10 animals in each group. E/C treatment: etoposide at 
12 mg/kg (Days 1-3) + carboplatin at 60 mg/kg (Day 1) of each 7-day cycle, for 3 cycles; intermittent BGB-
290: 0.68, 1.36 or 2.73 mg/kg BID on Days 1-4 of each 7-day cycle, for 3 cycles; maintenance BGB-290: 5.45 
mg/kg BID from Day 22 to Day 45. 
 
 
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1.4.2. 
Clinical Data for BGB-290 
BGB-290 is currently being studied in two Phase 1a studies (BGB-290-AU-002 in Australia, n = 53 
[as of 30 September 2016] and BGB-290-102 in China, n = 8 [as of 13 March 2017]), as well as one 
Phase 1 study, BGB-A317/BGB-290_Study_001, for the combination of BGB-290 with 
BGB-A317, an anti-PD-1 antibody (n = 41 [as of 02 February 2017]). The study data from 
BGB-290-AU-002 are the most mature and key interim results are summarized below. 
1.4.2.1. 
Pharmacokinetics Data for BGB-290-AU-002 
In the first-in-human Phase 1 study, interim PK data of BGB-290 showed that BGB-290 is rapidly 
absorbed and eliminated after PO administration. The maximum serum concentration and the drug 
exposure (AUC) increased in a nearly dose proportional manner from 2.5 to 120 mg BID both after 
the single-dose administration and at steady-state. The terminal half-life was determined to be 
approximately 13 hours, with a range of 5.5 to 34 hours. At steady-state, from 2.5 to 120 mg BID, 
drug exposure was increased in a dose-dependent manner.  
The impact of administration of a high-fat meal on the PK of BGB-290 after a 60 mg dose is being 
assessed. Preliminary data from 6 patients show that after administration with a high-fat meal, the 
rate of absorption was slower, as indicated by a delay in time to maximum concentration (Tmax) and 
lower maximum concentration (Cmax), but overall there was minimum impact on the extent of 
absorption. The mean Fed:Fasted ratios for Cmax and area under the plasma concentration-time from 
time 0 to the last measurable concentration (AUC0-last) were 0.63 (individual ratios ranged from 0.49 
to 0.85) and 0.85 (individual ratios ranged from 0.71 to 0.95), respectively. Based on 
pharmacodynamic data (Section 1.4.2.2) with an apparent flat exposure-response for PAR inhibition 
and objective responses observed at lower dose levels, the decrease in Cmax and the modest decrease 
of 15% in overall exposure with high-fat meal is not considered to be clinically significant. Thus, 
BGB-290 can be administered without regard to food intake, which is expected to increase patient 
convenience with the BID dosing schedule. 
1.4.2.2. 
Exploratory Biomarker Data 
The PAR formation from peripheral blood mononuclear cells (PBMCs) was detected by 
enzyme-linked immunosorbent assay to explore the pharmacodynamic activity in the Phase 1 study 
BGB-290-AU-002. Blood samples for PK and isolation of PBMCs were obtained at baseline on 
Day 1 (predose) and 4 hours postdose on Days 1 and 17 of Cycle 1. The pharmacodynamic activity 
at 4 hours postdose on Days 1 and 17 was reported as percentage of predose PAR inhibition. 
PK/pharmacodynamic correlation analyses were conducted in 30 patients who received doses of 
2.5, 5, 10, 20, 40, 60, 80, and 120 mg BID. Robust PAR inhibition in PBMCs was observed at the 
first dose level of 2.5 mg BID. The pharmacodynamic activity increased in a dose-dependent 
manner from 2.5 to 10 mg BID. Sustained PAR inhibition in PBMCs was observed at steady-state 
for patients treated at 10 mg BID or higher dose levels (Figure 3). 
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Figure 3: Correlation of PAR Inhibition in Peripheral Blood Mononuclear Cells with 
BGB-290 Dose 
 
Abbreviations: BID, twice daily; h, hours. 
1.4.2.3. 
Clinical Safety and Preliminary Efficacy for BGB-290-AU-002 
BGB-290-AU-002 is a first-in-human study evaluating BGB-290 to characterize the safety, the 
MTD, preliminary antitumor activity, and the PK of BGB-290 given as a monotherapy in a 3+3 
dose escalation scheme. BGB-290 was administered in doses ranging from 2.5 to 120 mg PO BID. 
The study is being conducted in 3 Australian study centers, and preliminary data for 45 patients are 
available (cutoff date of 30 September 2016).  
The preliminary safety data indicate that the most frequent nonhematologic adverse events (AEs) 
( 10% of patients) assessed as related to BGB-290 were nausea (51%, n = 23), fatigue (29%, 
n=13), vomiting (18%, n = 8), diarrhea (16%, n = 7), and decreased appetite (11%, n = 5). 
Hematologic AEs are of interest in this study. The most frequent hematologic AEs (10% of 
patients) assessed as related to BGB-290 were anemia (22%, n = 10) and neutropenia (11%, n = 5). 
Hematologic AEs, regardless of relatedness, were reported in 40% of patients (n = 18). Anemia was 
most frequent (33%, n = 15), followed by neutropenia (11%, n = 5) and thrombocytopenia (2%, 
n = 1). 
Twenty-six patients experienced Grade 3 AEs (regardless of relatedness), and no Grade 4 AEs were 
reported. Eleven Grade 3 AEs in 9 patients (20%) were considered related to BGB-290: anemia 
(11%, n = 5), neutropenia (7%, n = 3), hypophosphatemia (2%, n = 1), paresthesia (2%, n = 1), 
nausea (2%, n = 1), and fatigue (2%, n = 1).  
Serious AEs (SAEs) were reported in 25 patients, and for 3 patients they were considered related to 
BGB-290: anemia (n = 2) and nausea (n = 1). Three patients discontinued study drug because of an 
AE: vomiting (n = 1), oral paresthesia (n = 1), and right neck cutaneous metastases (n = 1). 
Four patients experienced a fatal AE  28 days after the last BGB-290 dose. All deaths were due to 
complications of the underlying malignancy, and none was considered related to BGB-290. 
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Four patients experienced AEs that were considered dose-limiting toxicities (DLTs): Grade 2 
nausea that persisted despite optimal standard medical therapy in 2 patients; Grade 2 anorexia and 
Grade 2 nausea in 1 patient, and Grade 2 nausea and Grade 2 paresthesia in 1 patient. Based on the 
encountered DLTs and the overall safety profile of BGB-290, the MTD of BGB-290 was 
determined to be 80 mg PO BID (160 mg/day). 
Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) are recognized AEs in 
patients receiving PARP inhibitors (Ricks et al, 2015). To date, no cases of MDS or AML have 
been observed in any study that includes BGB-290. 
Ten patients achieved either a CR (n = 2) or PR (n = 8); all responses were observed in patients with 
gynecological cancers. 
1.5. 
Rationale for Selection of BGB-290 Dose 
Based upon the overall safety, efficacy, and PK profile of BGB-290, the dose of BGB-290 60 mg 
PO BID was selected using available clinical data from Study BGB-290-AU-002 (Section 1.4.2.3). 
The study determined the MTD of BGB-290 to be 80 mg PO BID (160 mg/day). The dose of 60 mg 
BID was selected for further evaluation based on the following findings (refer to the BGB-290 
Investigator’s Brochure): 
 A linear PK profile observed up to 80 mg BID 
 Similar toxicity profiles at 60 mg and 80 mg BID with the following exceptions: 
o Fewer patients at 60 mg BID experienced treatment-related TEAEs of anemia and 
neutropenia. 
o There was a slightly higher rate of dose interruptions at 80 mg vs 60 mg BID for 
anemia and nausea. 
 Responses were observed across the dose range evaluated 
1.6. 
Study Rationale 
Inoperable locally advanced and metastatic gastric cancer continues to be an incurable disease with 
5-year survival rates below 10% despite various available treatment regimens, necessitating the 
exploration of additional and different therapeutic approaches. First-line platinum-based therapy can 
result in response rates around 30% to 50%. Treatment with a platinum doublet or triplet, however, 
typically does not last longer than 6 months due to accumulating chemotherapy toxicities, and there 
is no evidence that further treatment with a fluoropyrimidine as single agent provides clinical 
benefit. The time point of maximum tumor response to platinum-based therapy provides a unique 
opportunity to further improve on clinical benefit rather than wait for PD and initiation of second-
line therapy. 
PARP inhibitors, in general, have favorable attributes that make them an interesting drug class for 
maintenance therapy as they are oral agents and tolerated well, in particular when compared with 
first- or second-line chemotherapy. BGB-290 is a promising PARP inhibitor to study in the gastric 
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cancer maintenance setting as it is a potent and selective inhibitor of PARP1 and PARP2. It has 
excellent PARP trapping activity that is likely to be more important for antitumor activity than 
catalytic PARP inhibition. In the clinic, BGB-290 has shown favorable PK properties, has been 
tolerated well, and has achieved maximum pharmacodynamic target modulation in PBMCs at a 
dose level well below the recommended Phase 2 dose (10 versus 60 mg BID). 
The rationale for developing the PARP inhibitor BGB-290 in gastric cancer is several fold. The 
biology of gastric cancer indicates that a large subset of these tumors should be sensitive to PARP 
inhibition because of abnormalities that have been linked to PARP inhibitor sensitivity in various 
tumor types. This includes CIN and evidence of HRD, such as loss of ATM expression or BRCA 
mutational signatures. There is a significant overlap between cancers with platinum sensitivity and 
biomarkers for PARP inhibitors. Furthermore, activity of PARP inhibitors is not limited to 
biomarker-positive cancers but also includes biomarker-negative cancers with demonstrated 
platinum sensitivity. Gastric cancer is a cancer type for which platinum sensitivity has been clearly 
established, predicting that PARP inhibitors may have significant activity in patients with a CR or 
PR. Finally, other PARP inhibitors have shown activity in gastric cancer, particularly in cases with 
loss of ATM.  
In summary, BGB-290 is an excellent candidate to determine the effects of PARP inhibition in this 
unmet medical need of patients with platinum-sensitive disease, as demonstrated by a CR or PR, but 
have no further treatment options to consolidate or maintain the clinical benefit derived from 
first-line chemotherapy. 
1.7. 
Risk-Benefit Assessment 
BGB-290 has been studied in nonclinical toxicity and Phase 1 clinical studies. BGB-290 toxicities 
are largely consistent with the safety profile shared by other PARP inhibitors. 
MDS and AML have been reported in a small number (< 1%) of patients treated with PARP 
inhibitors, especially in patients harboring a germline BRCA mutation (Ricks et al, 2015). 
Typically, patients who develop MDS and AML while on therapy with a PARP inhibitor have a 
history of extensive previous chemotherapy and some have a history of previous cancer or bone 
marrow abnormalities. To date, there have been no reports of MDS or AML in patients treated with 
BGB-290. Patients in this study will be monitored monthly for hematological toxicities and events 
of MDS and AML will be reported as SAEs irrespective of time elapsed since end of study 
treatment. 
Given that patients with advanced gastric cancer currently have no treatment options after 
completion of first-line therapy, the risk of BGB-290 toxicities appears acceptable considering the 
strong rationale for exploring PARP inhibition in the maintenance setting. 
1.8. 
Study Conduct 
This study will be conducted in compliance with the protocol approved by the Institutional Review 
Board (IRB) or Independent Ethics Committee (IEC) and Regulatory Authorities and in accordance 
with Good Clinical Practice (GCP) standards. 
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2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
 To evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in patients 
with inoperable locally advanced or metastatic gastric cancer with a CR or confirmed PR 
after first-line platinum-based chemotherapy, as measured by: 
o PFS by investigator assessment 
2.2. 
Secondary Objectives 
 To further evaluate the efficacy of maintenance therapy with BGB-290 versus placebo in 
patients with inoperable locally advanced or metastatic gastric cancer with a CR or 
confirmed PR after first-line platinum-based chemotherapy, as measured by: 
o OS 
o Time to second subsequent treatment (TSST) by investigator assessment 
o ORR (CR or PR) by investigator assessment 
o Duration of response by investigator assessment 
o Time to response by investigator assessment 
 To evaluate safety and tolerability of BGB-290 versus placebo, as measured by: 
o Incidence, timing, and severity of treatment-emergent adverse events (TEAEs), 
graded according to National Cancer Institute-Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) Version 4.03 
2.3. 
Exploratory Objectives  
 To confirm the PK of BGB-290, as measured by: 
o Lowest observed plasma concentrations (Ctrough) at steady-state and other PK 
parameters for patients who received BGB-290 
 To assess patient-reported outcomes on health-related quality of life, as measured by: 
o European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) 
o European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire (EORTC QLQ-C30) 
o EORTC QLQ gastric cancer module (EORTC QLQ-STO22) 
 To explore potential biomarkers associated with the pharmacodynamics, response, and 
resistance to BGB-290: 
o Including, but not limited to, expression and mutations of genes in the DNA damage 
response pathway, LOH, and relationship to efficacy and resistance to BGB-290 
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3. 
STUDY DESIGN 
3.1. 
Summary of Study Design 
This is a double-blind, placebo-controlled, randomized, multicenter, global Phase 2 study 
comparing the efficacy and safety of single-agent poly (ADP-ribose) polymerase (PARP) inhibitor 
BGB-290 to placebo as maintenance therapy in patients with advanced gastric cancer who have 
completed first-line platinum-based chemotherapy. 
To be eligible for participation in the study, patients must have histologically confirmed 
adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced or 
metastatic disease. Patients must have achieved a PR that is maintained for ≥ 4 weeks or a CR as 
determined by the investigator according to Response Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1 with platinum-based first-line chemotherapy. The primary endpoint of the 
study is PFS by investigator assessment. Sufficient tumor tissue (archival biopsy) must be provided 
for central laboratory determination of HRD status for randomization and exploratory biomarker 
analyses. 
Patients will be randomized  8 weeks after the last platinum dose of first-line chemotherapy. 
Cycles will be 28 days in length. Once the treatment phase has been completed, an end of treatment 
(EOT) visit should occur with subsequent phases of safety and long-term follow-up. 
Central randomization (1:1) will be used to assign eligible patients to 1 of the following 2 arms. 
Arm A: 
BGB-290 60 mg PO BID 
Arm B: 
Placebo 60 mg PO BID  
Patient randomization will be stratified by HRD status (LOHhigh versus LOHlow versus unknown), 
region (China/Hong Kong/Taiwan versus Australia/Europe/North America versus Japan/South 
Korea versus rest of world [ROW]), and Eastern Cooperative Oncology Group (ECOG) 
performance status (0 versus 1). 
Safety assessments will occur on Day 1 of each cycle, on Day 15 of Cycles 1 and 2, and as needed. 
Dose modifications will be made as outlined in Section 6.1.4. AEs will be followed and documented 
during the treatment period and for approximately 30 days after last study drug or until initiation of 
new anticancer therapy, whichever occurs first (Section 9 and Appendix 1). AEs will be graded 
according to NCI-CTCAE Version 4.03. An external independent data monitoring committee 
(IDMC) will periodically review safety data. 
To confirm PK properties of BGB-290, blood samples will be taken at various time points as 
outlined in Section 7.6 and Appendix 1. Additionally, tumor tissue and blood samples will be 
obtained (as outlined in Section 7.7 and Appendix 1) to explore biomarkers of pharmacodynamics, 
response, and resistance to BGB-290 in gastric cancer. 
Disease status will be assessed by the investigator using RECIST Version 1.1 (Appendix 2). 
Patients will undergo tumor assessments at screening and then every 8 weeks (±7 days), or as 
clinically indicated.  
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There is no fixed duration of treatment.  
Administration of BGB-290 or placebo will continue until PD, unacceptable toxicity, death, or 
another discontinuation criterion is met (Sections 5.5 and 5.7). Once the treatment phase has been 
completed, an EOT visit should occur within 7 days of stopping BGB-290 or placebo with 
subsequent phases of safety and long-term follow-up.  
Long-term follow-up will include tumor assessments every 8 weeks (±7 days) for those patients 
without PD, survival status, new anticancer therapy, and diagnosis of MDS or AML. Long-term 
follow-up will continue until the patient dies or another criterion for discontinuation from study is 
met (Section 5.7). 
Once the study is completed and the study results are available, this study will be unblinded. For 
patients who have received BGB-290, the sponsor will continue providing the drug either on this 
study or through other options, ie, a roll-over study. Subjects who are on the Placebo arm will 
discontinue the study treatment.  
Study procedures and assessments are detailed in Section 7 and Appendix 1. The study schema is 
provided in Figure 4. 
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Figure 4: Study Schema 
 
Abbreviations: AML, acute myeloid leukemia; BID, twice daily; CR, complete response; ECOG, Eastern 
Cooperative Oncology Group; LOH, loss of heterozygosity; HRD, homologous recombination deficiency; 
MDS, myelodysplastic syndrome; PD, progressive disease; PO, oral; PR, partial response; q8w, every 
8 weeks; ROW, rest of world; vs, versus. 
Note: Key assessments during treatment phase: tumor assessments and patient-reported outcomes every 
8 weeks, adverse events, hematology, and chemistry every 4 weeks. BGB-290 and placebo are to be 
administered continuously. 
3.2. 
Independent Data Monitoring Committee 
Regular safety monitoring (at least every 6 months) and efficacy monitoring will be performed by 
an IDMC. The IDMC will review SAE reports for the first 40 patients enrolled in the study and 
review aggregate safety data approximately 3 months after the 40th patient started on study drug to 
assess the benefit/risk. The IDMC may recommend study modification including termination of the 
study due to safety and/or efficacy concerns. The function and membership of the IDMC will be 
described in the IDMC charter. 
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In addition to the planned IDMC review(s), ad hoc reviews may take place based on new 
information.  
Following IDMC review and discussion, the sponsor will make all final decisions regarding any 
change in study conduct. Please see the details in the IDMC charter. 
3.3. 
Blinding 
Site staff and blinded sponsor team members will be blinded to treatment allocation (BGB-290 or 
placebo).  
Unblinding of a patient’s treatment assignment may be performed at any time and without 
restrictions based on the investigator’s (or other non-study treating physician’s) clinical judgement 
if the knowledge of the treatment arm is essential for the further management of the patient.  
The investigator can access the IRT system using assigned credentials to immediately perform 
unblinding. Following unblinding, the system will notify the sponsor of unblinding of the patient 
without revealing the patient’s treatment assignment. In the event that the investigator is not 
available to perform unblinding, each randomized patient is provided with a patient information 
card that includes a global phone number linked to an after-hours physician-staffed emergency 
medical service. Additionally, the card provides a unique, blinded number that links to the subject’s 
treatment arm. 
Any physician treating a patient that is participating in the study (eg, emergency room physician or 
other health care provider [HCP] unaffiliated with the study) can contact the emergency medical 
service to unblind the patient using the information located on the patient information card. The 
emergency service will perform this unblinding and inform the treating physician/HCP of the 
patient’s treatment assignment. If unblinding occurs, the service will provide notification to the 
sponsor of the patient-specific unblinding without revealing the patient’s treatment assignment. 
3.4. 
Duration of the Study 
The duration of the study from first enrolled patient until final analysis is estimated to be 2.5 years. 
4. 
STUDY POPULATION 
4.1. 
Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for the study: 
1. Signed informed consent form (ICF) 
2. Age  18 year 
3. Histologically proven adenocarcinoma of the stomach or gastroesophageal junction, 
inoperable locally advanced or with metastatic disease 
a. Patients with gastric cancer overexpressing HER2 are not allowed. 
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 Negative result for HER2, as determined by local assessment, must be 
documented in order for a patient to be eligible. 
b. Irradiation as part of prior first-line treatment is not allowed. 
4. Availability of archival tumor tissue for central laboratory determination of HRD status for 
randomization and exploratory biomarker analyses 
 Tumor tissue needs to originate from core or punch biopsy. 
 Tumor tissue from fine-needle aspiration is not acceptable. 
5. Received platinum-based first-line chemotherapy with a total of  8 platinum-containing 14-
day cycles,  5 platinum-containing 21-day cycles, or  4 platinum-containing 28-day cycles 
for  28 weeks 
6. Confirmed PR that is maintained for ≥ 4 weeks or CR as determined by the investigator per 
RECIST Version 1.1 (Appendix 2) 
7. Ability to be randomized  8weeks after last dose of platinum  
8. ECOG performance status  1 (Appendix 3) 
9. Ability to swallow whole capsules 
10. Ability to comply with study requirements and complete study questionnaires independently 
11. Adequate hematologic and end-organ function, as defined by the following laboratory 
results (obtained  14 days before randomization): 
a. Absolute neutrophil count (ANC)  1.5 × 109/L 
b. 
Platelet count  100 × 109/L 
c. 
Hemoglobin  9 g/dL ( 14 days after growth factor support or transfusion) 
d. 
Estimated glomerular filtration rate  30 mL/min/1.73 m2 by the Modification of 
Diet in Renal Disease study equation (MDRD STUDY EQ; www.mdrd.com or 
Appendix 11) 
e. 
Total serum bilirubin  1.5 × upper limit of normal (ULN) 
  4  ULN, if Gilbert’s syndrome or if indirect bilirubin concentrations 
suggestive of extrahepatic source of elevation 
f. Aspartate and alanine aminotransferase (AST and ALT)  3 × ULN 
12. Females of childbearing potential, nonsterile males, and female partners of nonsterile male 
study patients must agree to practice highly effective methods of birth control (Appendix 4) 
for the duration of the study and for at least 6 months after last study drug. Nonsterile males 
must avoid sperm donation for the duration of the study and for at least 6 months after last 
study drug.  
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4.2. 
Exclusion Criteria 
Patients will be excluded from the study for any of the following reasons: 
1. Unresolved acute effects of prior therapy of  Grade 2 
 Except for AEs not considered a likely safety risk (eg, alopecia, neuropathy and 
specific laboratory abnormalities) 
2. Prior treatment with a PARP inhibitor 
 Subtherapeutic exposure to a PARP inhibitor for  28 days is permissible provided it 
was not the most recent prior therapy. 
3. Chemotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese 
medicine, or herbal remedies  14 days (or  5 half-lives, whichever is shorter) before 
randomization 
 Bisphosphonate and denosumab use is allowed on study, if administered at a stable 
dose > 28 days before randomization. 
4. Major surgical procedure, open biopsy, or significant traumatic injury  14 days before 
randomization, or anticipation of need for major surgical procedure during the course of the 
study  
 Placement of vascular access device is not considered major surgery. 
5. Diagnosis of MDS 
6. Other diagnosis of malignancy 
 Except for surgically excised nonmelanoma skin cancer, adequately treated 
carcinoma in situ of the cervix, localized prostate cancer treated with curative intent, 
adequately treated low-stage bladder cancer, ductal carcinoma in situ treated 
surgically with curative intent, or a malignancy diagnosed > 2 years ago with no 
current evidence of disease and no therapy  2 years before randomization 
7. Leptomeningeal disease or brain metastasis 
8. Active infection requiring systemic treatment, active viral hepatitis, or active tuberculosis 
9. Any of the following cardiovascular criteria: 
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of 
daily living,  28 days before randomization 
b. Symptomatic pulmonary embolism  28 days before randomization 
c. Any history of acute myocardial infarction  6 months before randomization 
d. Any history of heart failure meeting New York Heart Association Classification III 
or IV (Appendix 5)  6 months before randomization 
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e. Any event of ventricular arrhythmia  Grade 2 in severity  6 months before 
randomization  
f. Any history of cerebral vascular accident  6 months before randomization 
10. Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal 
disease, or any other disease causing malabsorption syndrome 
 Gastroesophageal reflux disease under treatment with proton pump inhibitors is 
allowed.  
11. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, 
significant hemoptysis, or melena  6 months before randomization 
12. Use  10 days (or  5 half-lives, whichever is shorter) before randomization or anticipated 
need for food or drugs known to be strong or moderate cytochrome P450 (CYP) 3A 
inhibitors or strong CYP3A inducers (Appendix 6) 
13. Pregnancy or nursing 
a. Females of childbearing potential require a negative serum pregnancy test  7 days 
before randomization. 
14. Significant intercurrent illness that may result in the patient’s death before death from gastric 
cancer 
15. Known history of intolerance to the excipients of the BGB-290 capsule 
5. 
STUDY PHASES FROM SCREENING TO END OF STUDY 
5.1. 
Screening 
As part of the screening visit, study center personnel will explain to the potential patient all aspects 
of the study, obtain signed informed consent, and document the informed consent process in the 
patient’s source documents before any study-specific procedures are conducted. 
The signed ICF initiates screening that must occur within 28 days of randomization (Day -28 to 
Day -1). Study center personnel will access the Interactive Response Technology (IRT) system to 
obtain a screening identification number for the potential patient. 
Required screening assessments, some with shorter screening windows, are listed in Appendix 1. 
Assessments obtained within 7 days of Day 1 do not have to be repeated on Day 1. Patient 
registration and randomization may occur as late as Day 1 before any study treatment. Results of 
standard of-care tests or examinations performed before obtaining informed consent and within the 
screening windows may be used and do not have to be repeated as long as they meet protocol 
specifications.  
The investigator and site radiologist will assess the potential patient for eligibility. Repeating 
screening assessments within the original screening window is allowed if the patient did not 
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previously meet certain eligibility criteria. Screen failures and consent withdrawals will be 
documented in the patients’ source documents. 
5.2. 
Enrollment 
After consent has been obtained, each patient will be assigned a unique patient number by the IRT 
system that cannot be reassigned to any other patient. After determination of eligibility, the 
investigator will complete the randomization request form and supporting documentation and 
provide them to the sponsor and/or designee for review and subsequent approval in the IRT system. 
No eligibility waivers will be granted. 
After medical monitor approval, the investigator or delegate will access the IRT system for 
randomization of the patient based on the protocol-specified stratification factors. The 
randomization list will be kept by the IRT vendor in their secure system and will not be accessible 
to the study center, responsible (or designee) monitors, project statisticians, or to the blinded project 
team at BeiGene, Ltd. (hereafter referred to as BeiGene). Blinded team members will not have 
access to unblinded information in IRT; this will be managed by clearly defined roles and 
permissions within the IRT system. 
5.3. 
Treatment 
Day 1 of Cycle 1 is the first day of study drug administration (there is no Day 0 in this protocol). 
Patients must initiate study treatment within 4 days after randomization. 
Study procedures of each clinic visit are outlined in Appendix 1. 
On days with PK assessments, study drug should be administered in the clinic in accordance with 
the schedule for the PK samples. Assessments should be obtained before study drug administration 
unless stated otherwise in Appendix 1 and should be performed in order of least invasive to most 
invasive assessment. All safety-related assessments must be reviewed and dose modifications, if 
necessary, be made by the investigator or subinvestigator before study drug administration. 
Patient-reported outcome questionnaires should be completed before any other study activities 
occur. 
5.4. 
Unscheduled Visit 
Unscheduled visits may occur any time as necessary as per investigator decision or patient’s request 
for reasons such as assessment or follow-up of AEs. Study activities of an unscheduled visit should 
be performed based on the reason for the unscheduled visit and are outlined in Appendix 1. If PD is 
suspected, imaging studies should be performed and blood for biomarkers should be obtained as 
appropriate. 
5.5. 
Permanent Discontinuation of Study Drug  
5.5.1. 
Reasons for Permanent Discontinuation of BGB-290 or Placebo 
Patients may permanently discontinue BGB-290 or placebo for any of the following reasons: 
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 PD 
 AEs 
 Pregnancy 
 Major protocol deviation  
 Patient withdrew consent for study treatment 
o Patients may voluntarily withdraw consent from study treatment at any time 
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 
The reason for permanent discontinuation of BGB-290 or placebo will be recorded on the electronic 
case report form (eCRF). Patients may discontinue study drug for other reasons but these will result 
in premature discontinuation from study (Section 5.7) and, consequently, result in lack of an EOT 
visit. 
5.5.2. 
End of Treatment Visit 
The EOT visit should occur within 7 days after BGB-290 or placebo has been permanently 
discontinued. Required assessments are listed in Appendix 1. 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 providing 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.  
5.6. 
Follow-Up Phase 
5.6.1. 
Safety Follow-up 
All patients who permanently discontinue study drug and have not initiated new anticancer therapy 
will be followed for AEs and serious AEs (SAEs) as outlined in Section 9.3.1. Approximately 30 
days after the last day of study drug or before initiation of new anticancer therapy, whichever occurs 
first, a safety follow-up will occur with the safety assessments outlined in Appendix 1. If new 
anticancer therapy is inadvertently initiated before this safety follow-up (eg, without the knowledge 
of the study center team), a safety follow-up should be scheduled as soon as possible. 
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 AEs. If these attempts of contact are unsuccessful, 
the additional attempts detailed in Section 5.6.3 should be made. 
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5.6.2. 
Long-term Follow-up 
Patients will be followed for survival, further anticancer therapy, and diagnosis of MDS or AML via 
telephone contact or other means (eg, clinic visit) approximately every 12 weeks until death, 
withdrawal of consent, or the end of study, whichever occurs first (Appendix 1). 
Patients who were permanently discontinued from study drug for reasons other than PD and meet 
criteria otherwise (eg, discontinued for AE and no new anticancer therapy) will be followed with 
tumor assessments every 8 weeks (±7 days) until PD or any other reason listed in Section 5.7, 
whichever occurs first. For efficacy assessments as per protocol, refer to Section 7.3.2 and 
Appendix 1. If the patient refuses to return for these tumor assessments or is unable to do so, every 
effort should be made to contact the patient by telephone to determine the patient’s disease status 
and survival. 
5.6.3. 
Lost to Follow-up 
If attempts to contact the patient by telephone are unsuccessful, the following additional attempts 
should be made to obtain protocol-required follow-up information. The patient should be contacted 
by mail in a manner that provides proof of receipt by the patient. If unsuccessful, other contacts 
should be explored, such as referring physicians or relatives. Attempts of contact should be 
documented in the patient’s source documents. If a patient cannot be contacted despite all attempts, 
the patient will be considered lost to follow-up, and death information should be obtained through a 
public record search if local agencies permit. 
5.7. 
End of Study 
Premature discontinuation from the study (without EOT and any follow-up visits) will occur under 
the following circumstances: 
 Patient withdrew consent for study participation 
o Patients may voluntarily withdraw consent from the study at any time 
 Investigator’s discretion 
 Lost to follow-up 
o Lost to follow-up should be recorded as such in the eCRF 
o The investigator should show due diligence by documenting in the source documents 
steps taken to contact the patient (Section 5.6.3) 
 Death 
 Study termination by sponsor 
 Other, as per the discretion of the sponsor or health authority 
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6. 
STUDY TREATMENT 
6.1. 
Study Drug 
6.1.1. 
Packaging and Labeling 
BGB-290 is provided in 20-mg capsules or matching placebo. BGB-290 and placebo capsules will 
be provided in 30-count child-resistant high-density polyethylene bottles with an induction seal and 
bottle label. The contents of the label will be in accordance with all applicable local regulatory 
requirements. The label will include at a minimum: drug name, dose strength, contents, sponsor, 
protocol number, bottle number, directions for use, storage conditions, caution statements, retest or 
expiration date, and space to enter the patient number and name of investigator. 
6.1.2. 
Handling and Storage 
The instructions for drug ordering are in the pharmacy binder. The IRT system will also be used for 
drug supply management. The study drug will be dispatched to a study center only after receipt of 
the required documents in accordance with applicable regulatory requirements and the sponsor’s 
procedures. The investigator or pharmacist/designated personnel is responsible for maintaining the 
drug supply inventory and acknowledging receipt of all study drug shipments. All study drugs must 
be stored in a secure area with access limited to the investigator and authorized study center 
personnel and under physical conditions that are consistent with study drug specific requirements.  
The study drugs must be kept at the condition as specified on the labels. BGB-290 and placebo 
bottles must be stored at 15°C to 30°C (59°F to 86°F) and protected from light.  
6.1.3. 
Dosage and Administration 
Both BGB-290 and placebo capsules will be administered PO BID, once in the morning and once in 
the evening. The time difference between 2 consecutive doses should be approximately 8 to 
12 hours. 
Patients will be instructed to swallow the capsules whole, in rapid succession, with water. BGB-290 
can be administered with or without food. 
A dose of BGB-290 or placebo should be skipped if it is not taken within 2 hours of the scheduled 
time. An extra dose of BGB-290 or placebo should not be taken to make up for a missed dose. If 
vomiting occurs during the course of treatment, no re-dosing of the patient is allowed before the 
next scheduled dose. 
On days with PK assessments, BGB-290 or placebo should be administered in the clinic in 
accordance with the schedule for the PK samples (Appendix 1). 
6.1.4. 
Dose Hold and Modification 
AEs should be assessed as best as possible regarding their relatedness to BGB-290 or placebo. 
Investigators should assess all patients as if they were receiving BGB-290. Regardless of 
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discontinuation of BGB-290 or placebo, patients should continue on study with follow-up as 
outlined in Sections 5.5 and 5.6. 
Investigators should make every effort to maintain dose intensity in patients. Dosing of BGB-290 or 
placebo can be withheld for up to 28 days consecutively. If drug is planned to be held > 28 days, the 
medical monitor should be contacted before permanent patient discontinuation from the study drug. 
Criteria for treatment modifications and suggested guidelines for the management of some toxicities 
related to BGB-290 or placebo are summarized below. These general guidelines may be modified at 
the discretion of the investigator based on discussions with the medical monitor and the best clinical 
judgment at that time; any decisions should be documented. Any toxicities related to BGB-290 or 
placebo should be managed according to standard medical practice. 
A maximum of 2 dose reductions is allowed before the patient must be permanently withdrawn 
from study drug. Dose levels for BGB-290 or placebo are summarized in Table 2. BGB-290 or 
placebo will be dose modified as outlined in Table 3. 
Table 2: Dose Levels for BGB-290 and Placebo 
Dose Level 
BGB-290 
Placebo 
1 
60 mg PO BID 
60 mg PO BID 
-1 
40 mg PO BID 
40 mg PO BID 
-2 
20 mg PO BID 
20 mg PO BID 
Abbreviations: PO, oral; BID, twice daily. 
BGB-290 may be dose-reduced for a maximum of 2 dose reductions. 
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Table 3: Criteria for Modification of BGB-290 or Placebo Dosing for Related Adverse Events 
Toxicity 
Recommended Dose Modificationa 
Hematologic 
Anemia (hemoglobin, Hgb) 
Grade 2 (Hgb < 10 - 8 g/dL) 
 
Only applies to patients with 
normal Hgb at baseline 
First occurrence: continue dosing at current dose level 
Second and subsequent occurrences: hold BGB-290 or placebo until resolved to 
≤ Grade 1 or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  BGB-290 or placebo by 1 dose level 
Grade 3 (Hgb < 8 g/dL) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline 
 If resolved ≤ 14 days, then maintain dose levels 
 If resolved > 14 days, then  BGB-290 or placebo by 1 dose level 
Grade 4 (life-threatening 
consequences; urgent intervention 
indicated) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline and 
 BGB-290 or placebo by 1 dose level 
Neutropenia (absolute neutrophil count, ANC) 
Grade 3 (ANC < 1.0 - 0.5  109/L) 
Hold BGB-290 or placebo until resolved to ≤ Grade 2 or baseline 
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  BGB-290 or placebo by 1 dose level 
Grade 4 (ANC < 0.5  109/L) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline and 
 BGB-290 or placebo 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 BGB-290 or placebo until resolved and 
 BGB-290 or placebo by 1 dose level 
Thrombocytopenia (platelet count, PLT) 
Grade 3 (PLT < 50 - 25  109/L) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  BGB-290 or placebo by 1 dose level 
Grade 4 (PLT < 25  109/L) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline and 
 BGB-290 or placebo by 1 dose level 
Renal 
Estimated glomerular filtration rate (MDRD STUDY EQ; www mdrd.com or Appendix 11) 
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 BGB-290 or placebo until resolved to ≥ 60 mL/min/1.73 m2  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  BGB-290 or placebo by 1 dose level 
Regardless of baseline: 
< 15 mL/min/1.73 m2 
Permanently discontinue BGB-290 or placebo 
 
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Table 3: Criteria for Modification of BGB-290 or Placebo Dosing for Related Adverse 
Events  
Toxicity 
Recommended Dose Modificationa 
Hepatic 
Bilirubin 
 
Grade 2 (> 1.5 - 3.0  ULN) 
Only applies to patients with 
normal bilirubin at baseline 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  BGB-290 or placebo by 1 dose level 
Grade 3 (> 3.0 - 10.0  ULN) 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline  
 If resolved ≤ 7 days, then maintain dose levels 
 If resolved > 7 days, then  BGB-290 or placebo by 1 dose level 
Grade 4 (> 10.0  ULN) 
Permanently discontinue BGB-290 or placebo 
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  BGB-290 or placebo 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 BGB-290 or placebo until AST and/or ALT resolved to ≤5  ULN or 
baseline 
 If ≤5  ULN within 14 days, then  BGB-290 or placebo by 1 dose level 
 If second episode, permanently discontinue BGB-290 or placebo 
 If persistent for >14 days, permanently discontinue BGB-290 or placebo 
Grade 4 (> 20  ULN) 
Permanently discontinue BGB-290 or placebo 
Pancreatic 
Pancreatitis 
Grade 3 or 4 
Permanently discontinue BGB-290 or placebo 
Cardiac 
Cardiac - Prolonged QTc interval 
QTcF > 500 msec 
 Obtain triplicate ECGs (2 to 3 minutes apart) ~1 hour after initial ECG  
 If mean QTcF > 500 ms, hold BGB-290 or placebo 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 BGB-290 or placebo 
Cardiac - General 
Grade 3 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline and 
 BGB-290 or placebo by 1 dose level 
Grade 4 
Permanently discontinue BGB-290 or placebo 
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Table 3: Criteria for Modification of BGB-290 or Placebo Dosing for Related Adverse 
Events  
Toxicity 
Recommended Dose Modificationa 
Other adverse events 
Grade 3 
Hold BGB-290 or placebo until resolved to ≤ Grade 1 or baseline and 
 BGB-290 or placebo by 1 dose level 
No dose reduction required for asymptomatic laboratory abnormalities 
Grade 4 
Permanently discontinue BGB-290 or placebo 
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 BGB-290 or placebo can be withheld for up to 28 days consecutively.  
 
6.1.5. 
Compliance and Accountability 
Compliance will be assessed by the investigator and/or study personnel at each patient visit and 
information provided by the patient. 
The investigator and/or study personnel will keep accurate records of the quantities of capsules 
dispensed and used by each patient. This information must be captured in the source document at 
the end of each cycle. The investigator is responsible for BGB-290 or placebo accountability, 
reconciliation, and record maintenance. In accordance with all applicable regulatory requirements, 
the investigator or designated study center personnel must maintain BGB-290 or placebo 
accountability records throughout the course of the study. This person will document the amount of 
BGB-290 or placebo received from the sponsor, the amount supplied, and/or administered to and 
returned by patients, if applicable. 
6.1.6. 
Disposal and Destruction 
After completion of the study, all unused BGB-290 or placebo will be inventoried and packaged for 
return shipment by the hospital unit pharmacist or other designated study center personnel. The 
inventoried supplies can be destroyed on site or at the depot according to institutional policies, after 
receiving written sponsor approval. 
6.2. 
Concomitant Medications and Nondrug Therapies 
6.2.1. 
Permitted Medications and Supportive Care 
All treatments and supportive care, including antiemetic therapy, hematopoietic growth factors, 
and/or red blood cell/platelet transfusions, that the investigator considers necessary for a patient’s 
welfare may be administered at the discretion of the investigator in keeping with the local standards 
of medical care. 
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All concomitant medications, including all prescription and over-the-counter drugs, supplements, 
and intravenous (IV) medications and fluids, taken by or administered to the patient within 28 days 
before randomization and 30 days after the last day of BGB-290 or placebo will be recorded. 
6.2.2. 
Prohibited Medications 
Patients are not allowed to receive other anticancer therapy, including surgery; 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 randomization 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 randomization. 
The primary metabolic pathway for BGB-290 involves the CYP3A isoform. Administration of 
strong/moderate inhibitors of CYP3A or strong CYP3A inducers is not allowed. Please refer to the 
drugs/substances listed in Appendix 6 and to http://medicine.iupui.edu/clinpharm/ddis/main-table/ 
for a more complete list of medications that are not allowed. Consumption of grapefruit and Seville 
oranges or their juices are not allowed throughout the study. No other dietary restrictions will apply. 
6.2.3. 
Medications to Be Used with Caution 
Based on preliminary in vitro screening assays, BGB-290 is not a strong inhibitor of other human 
CYP isoenzymes tested. It is a moderate inhibitor of CYP2C9 (IC50 = 6.48 M). Investigators need 
to be aware that BGB-290 has the potential to interfere with the appropriate metabolism of 
medications that rely on CYP2C9 and follow the prescribing information recommendations for use 
with CYP2C9 inhibitors. Therefore, careful monitoring should be used when co-prescribing 
CYP2C9 substrates with a narrow therapeutic index, such as phenytoin and warfarin. 
Examples of these medications are listed in Appendix 7 and these should be used cautiously with 
drug concentration monitoring where appropriate. 
In addition to CYP3A, BGB-290 can also be metabolized by CYP2C8 in human liver microsomes, 
but to a lesser extent. See Appendix 7 for medications that should be used with caution for that 
reason. 
7. 
STUDY ASSESSMENTS 
7.1. 
Study Flow and Visit Schedule 
The study-specific assessments and procedures with allowed time windows are outlined in 
Appendix 1. Assessments of efficacy will occur as outlined in Section 7.3. Assessments of safety 
will be based on AE monitoring and reporting (including attribution of AEs and SAEs), physical 
examinations, vital signs, ECGs, and clinical laboratory tests as outlined in Section 7.4. 
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7.2. 
Patient Demographics and Other Baseline Characteristics 
7.2.1. 
Demographics 
Demographic data will include gender, date of birth (or age), and race/ethnicity. 
7.2.2. 
Medical History 
Clinically significant medical history findings (eg, previous diagnoses, diseases, or surgeries) that 
were present before signing the ICF and considered relevant for the patient’s study eligibility will be 
collected and captured, including baseline severity if the finding is ongoing, in the eCRF. Clinically 
significant is defined as any events, diagnoses, or laboratory values that require treatment or 
follow-up, or the presence of signs or symptoms that require medical intervention. Concurrent 
medical signs and symptoms must be documented to establish baseline severities. 
For gastric cancer history, the date of initial diagnosis and current disease status, staging, sites of 
disease, smoking history, prior anticancer therapies and dates administered, responses, and duration 
of response to these treatments will also be recorded. 
7.2.3. 
Other Baseline Characteristics 
Information will also be collected regarding smoking history, prior medications/significant nondrug 
therapies, childbearing potential (Appendix 4), and any other assessments that are performed for the 
purpose of eligibility for inclusion in the study (Section 5), such as physical examination, vital 
signs, hematology, chemistry, pregnancy test, and ECG. 
7.3. 
Efficacy 
7.3.1. 
Tumor Assessments 
Tumor imaging studies will be reviewed for the purposes of eligibility determination and on-study 
tumor monitoring. Following the screening tumor assessment, tumor assessments will occur at the 
schedule of every 8 weeks (±7 days) after Day 1. Any measurable disease must be documented at 
screening and reassessed at each subsequent tumor evaluation. Patients who do not have PD at the 
time of BGB-290 or placebo permanent discontinuation but meet criteria otherwise will continue to 
have tumor assessments per protocol as outlined in Section 5.6.2. PFS, response, and duration of 
response will be assessed by the investigator using RECIST Version 1.1 (Appendix 2). 
The same imaging method(s) used at screening must be used throughout the study. A documented 
standard-of-care tumor assessment may be used as the screening assessment provided it meets the 
requirements (Section 7.3.1.2). 
7.3.1.1. 
Determination of Eligibility 
The investigator and site radiologist will review tumor assessments to determine whether the patient 
achieved PR that is maintained for ≥ 4 weeks or a CR with platinum-based first-line chemotherapy 
as defined in Section 4.1.  
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For a patient at study entry to confirm response, the following tumor assessments must be 
documented: 
 Tumor assessment that determined baseline disease state before initiation of first-line 
chemotherapy 
 Subsequent tumor assessments that demonstrate a CR or a confirmed PR to the first-line 
chemotherapy 
7.3.1.2. 
Screening Tumor Assessment 
The baseline tumor assessment should include the following: 
 Diagnostic-quality, contrast-enhanced CT scans of the chest, abdomen, and pelvis (Day -14 
to -1) 
o To be suitable for RECIST Version 1.1 assessments, CT scans should have a 
maximum thickness of 5 mm and no gaps. 
o CT is the preferred imaging method for tumor assessments of the chest, abdomen, 
and pelvis. 
o If a positron-emission tomography (PET)/CT scan is performed, the CT portion 
should meet the CT scan requirements described above. 
o In patients for whom the preferred CT scans are contraindicated because of, for 
example, a CT IV contrast allergy, a CT of the chest without contrast and magnetic 
resonance imaging (MRI) of the abdomen and pelvis with contrast are recommended. 
o MRI scans may be performed in lieu of CT scans. At screening, tumor assessments 
should include a diagnostic quality, contrast enhanced MRI scan of the chest, 
abdomen, and pelvis. To be suitable for RECIST Version 1.1 assessments, MRI 
scans should ideally have a maximum thickness of 5 mm and minimal gaps. 
 PET or whole-body radionuclide bone scan to evaluate for bone metastases, if clinically 
indicated (Day -14 to -1) 
o Only to be performed at screening if the patient has known bone metastases or has 
symptoms that could be due to bone metastases 
 CT scan of the neck, if clinically indicated (Day -14 to -1) 
o Only to be performed at screening if the patient has known or suspected metastases 
in this area 
o MRI scan of the neck may be substituted for CT scan of the neck. 
 MRI scan of the brain, if clinically indicated (Day -28 to -1) 
o Only to be performed at screening if the patient has symptoms that could be due to 
brain metastases 
o MRI is the preferred imaging method for tumor assessments of the brain. 
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o In patients for whom MRI of the brain is not available or who are claustrophobic, a 
CT scan of the brain with IV contrast may be performed. 
7.3.1.3. 
On-study Tumor Assessments 
All target and nontarget lesions must be assessed with the same imaging method used at baseline.  
 Diagnostic-quality, contrast-enhanced CT scans of the chest, abdomen, and pelvis (every 8 
weeks ±7 days) 
o CT scan with IV contrast is preferred but the imaging method at screening 
determines the imaging method of subsequent tumor assessments and must be used. 
 Imaging of all other known sites of disease (every 8 weeks ±7 days) 
In addition to the protocol-specified tumor assessments, CT scans or other imaging studies may be 
performed at the investigator’s discretion at any time as clinically indicated. 
7.3.2. 
Survival Assessments 
Survival status of patients will be monitored through all phases of the study as outlined in Section 5 
and Appendix 1. The date and cause of death will be recorded. 
7.3.3. 
Quality of Life Assessments 
Patients will complete 3 questionnaires in the clinic on Day 1 of Cycle 1, then on the same schedule 
as tumor assessments, and at the EOT visit before any other study activities occur (Appendix 1). 
Patients should be given sufficient instruction, space, time, and privacy for completion of the 
questionnaires. A study center team member should check for completeness of answers and 
encourage the patient to complete any missing answers. The questionnaires are validated 
instruments to measure the health status of patients (EQ-5D-5L; Appendix 8), the quality of life of 
cancer patients (EORTC QLQ-C30; Appendix 9), and gastric cancer-specific symptoms or 
problems (EORTC QLQ-STO22; Appendix 10). 
7.4. 
Safety 
7.4.1. 
Adverse Events 
Safety assessments should be performed at the study center visits indicated in Appendix 1. 
All AEs and SAEs, regardless of their relationship to study drug, will be collected in the fashion and 
for the time periods outlined in Section 9. The accepted regulatory definition of AEs and important 
additional requirements for SAE reporting are outlined in Section 9. 
7.4.2. 
Physical Examination, Vital Signs, ECOG Performance Status, Weight, and Height 
A complete or limited physical examination, vital signs (systolic and diastolic blood pressure; pulse 
rate; and oral, temporal, or tympanic temperature), weight, height, and ECOG performance status 
will be performed at time points specified in Appendix 1. 
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A complete physical examination should include an evaluation of head, eyes, ears, nose and throat, 
neck, heart, chest (including lungs), abdomen, extremities, skin, lymph nodes, cardiovascular status, 
and neurological status. A limited physical examination should be directed at the evaluation of 
symptoms or specific safety issues. Changes from baseline abnormalities should be recorded at each 
subsequent physical examination. New or worsened abnormalities should be recorded as AEs if 
appropriate. 
ECOG performance status will be determined as outlined in Appendix 3. 
7.4.3. 
Electrocardiograms 
Single 12-lead ECGs with assessment of PR interval, QRS duration, and QT interval corrected for 
heart rate (QTc) will be obtained at the following timepoints: screening; predose and 2 hours 
postdose on Cycle 1 Day 1, Cycle 1 Day 15; and EOT. Additional ECGs will be performed if 
clinically indicated. To minimize postural variability, it is important that patients are resting and in a 
semirecumbant or supine position for  5 minutes before each ECG collection. Blood draws and 
other procedures should be avoided during the period immediately before ECG measurement, and 
activity should be controlled as much as possible to minimize variability because of the effects of 
physiologic stress. Screening ECG must be performed within 14 days of randomization. For the 
scheduled ECG assessment at the EOT visit, ECG does not have to be repeated if it was performed 
within 14 days of the EOT visit. 
7.5. 
Laboratory Assessments 
On-study clinical laboratory evaluations starting from screening shall be performed by a central 
laboratory, as regionally available. An investigator may obtain safety laboratory results from their 
local laboratory as clinically indicated (eg, on the day of a patient’s visit before results are available 
from the central laboratory for dose modifications or AE/SAE monitoring). Results from the central 
laboratory will serve as the official study laboratory result, where available. If required by local 
regulations, clinical laboratory evaluations performed by a local, instead of a central, laboratory are 
acceptable. 
A detailed description of the procedures for sample collection, handling, storage, and shipment of 
the laboratory samples and all material such as test tubes and labels is provided in the study manual. 
Laboratory assessments will be performed at the time points specified in Appendix 1 and may also 
be performed as medically necessary. Laboratory assessments should be performed before 
BGB-290 or placebo administration. Screening blood tests must be performed within 14 days of 
randomization. If tests were performed within 7 days of Day 1, they do not need to be repeated on 
Day 1. 
7.5.1. 
Hematology 
Hematology includes hemoglobin, platelet count, white blood cell count, neutrophil count, and 
lymphocyte count. 
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7.5.2. 
Chemistry 
Chemistry includes albumin, alkaline phosphatase, ALT, AST, blood urea nitrogen, chloride, 
creatinine, glucose, lactate dehydrogenase, phosphate, potassium, sodium, total bilirubin, and total 
protein.  
7.5.3. 
Urinalysis 
Urinalysis includes blood, protein, ketones, glucose, red blood cells, and white blood cell. 
7.5.4. 
Pregnancy Testing 
The Clinical Trials Facilitation Group’s recommendations related to contraception and pregnancy 
testing in clinical studies include for females with childbearing potential the use of highly effective 
forms of birth control (Appendix 4). For women of childbearing potential, a screening serum 
pregnancy test must be obtained within 7 days before randomization and may be performed by a 
local laboratory. For subsequent pregnancy testing, if clinically indicated, urine pregnancy tests are 
allowed and may be performed by a local laboratory. If a urine pregnancy test is positive, a 
confirmatory serum pregnancy test is required. 
7.6. 
Pharmacokinetics 
PK samples will be collected from patients at the following time points (Appendix 1): predose 
(within 30 minutes before dose) and 2 hours (±30 minutes) postdose on Cycle 1 Day 1 and Cycle 1 
Day 15. The time of study drug administration on the day before Day 15 (Cycle 1 Day 14) must be 
recorded on the eCRF. Details concerning collection, handling, and processing of the PK plasma 
samples will be provided in the study manual. PK samples collected from patients assigned to 
placebo treatment will not be analyzed for BGB-290 concentrations. 
7.7. 
Biomarkers 
Blood samples for biomarker testing will be collected from patients at the time points specified in 
Appendix 1. Patients are required to provide tumor tissue for central laboratory determination of 
HRD status for randomization and the analysis of candidate predictive biomarkers. Archival tumor 
tissue shall be sent to the central laboratory for biomarker testing (either a formalin-fixed paraffin 
embedded block with tumor tissue [preferred] or, ideally, up to 15 unstained slides). The most 
recent tumor block is preferred. 
Candidate markers will include, but are not limited to, those related to pharmacodynamics, 
response, or resistance to PARP inhibitors (eg, HRD signatures, ATM expression, LOH). 
Patients will also provide blood samples to be processed into plasma and cell fractions for the 
analysis of genetic defects associated with gastric cancer, such as, but not limited to, HRD 
signatures and DNA repair deficiency. 
Instructions for the processing, storage, and shipping of samples will be provided in the study 
manual. 
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7.8. 
Appropriateness of Measurements 
All efficacy, safety, and PK assessments used in this study are standard and generally recognized as 
reliable, accurate, and relevant. 
8. 
DATA HANDLING AND QUALITY ASSURANCE 
This study will be organized, performed, and reported in compliance with the protocol, standard 
operating procedures, working practice documents, and applicable regulations and guidelines. Study 
center audits may be made periodically by the sponsor’s or the contract research organization’s 
qualified compliance auditing team, which is an independent function from the study team 
responsible for conduct of the study. 
8.1. 
Data Collection 
Data will be entered into the eCRFs in an electronic data capture (EDC) system. 
Data collection on the eCRF must follow the instructions described in the eCRF completion 
guidelines. The investigator has ultimate responsibility for the collection and reporting of all clinical 
data entered on the eCRF. The investigator or designee must sign the completed casebooks to attest 
to its accuracy, authenticity, and completeness. 
Data contained in the eCRFs are the sole property of BeiGene and should not be made available in 
any form to third parties without written permission from BeiGene, except for authorized 
representatives of BeiGene or appropriate regulatory authorities. 
8.2. 
Data Management/Coding 
All final patient data, both eCRF and external data (eg, laboratory data), collected according to the 
protocol, will be stored at BeiGene at the end of the study.  
Standard procedures (including following data review guidelines, computerized validation to 
produce queries, and maintenance of an audit file, which includes all database modifications) will 
be followed to support accurate data collection. Data will be reviewed for outliers, logic, data 
inconsistencies, and completeness. 
During the course of the study, a study monitor will make study center visits to review protocol 
compliance, compare eCRFs against individual patient’s medical records, and ensure that the study 
is being conducted according to pertinent regulatory requirements. 
eCRF entries will be verified with source documentation. The review of medical records will be 
performed in a manner to ensure that patient confidentiality is maintained. Checking the eCRFs for 
completeness, clarity, and cross checking with source documents is required to monitor the progress 
of the study. Direct access to source data is also required for inspections and audits, and will be 
carried out giving due consideration to data protection and medical confidentiality. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®) Version 
22.0 or higher. Concomitant medications will be coded using the World Health Organization Drug 
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Dictionary. Concomitant diseases/medical history will be coded using the MedDRA Version 22.0 or 
higher. 
8.3. 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory inspection of 
this study. Such audits/inspections can occur at any time during or after completion of the study. If 
an audit or inspection occurs, the investigator and institution agree to allow the auditor/inspector 
direct access to all relevant documents and to allocate his/her time and the time of his/her personnel 
to the auditor/inspector to discuss findings and any relevant issues. 
9. 
SAFETY MONITORING AND REPORTING 
The investigator 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. 
9.1. 
Adverse Events 
9.1.1. 
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 study drug or not.  
Examples of an AE include:  
 Worsening of a chronic or intermittent preexisting 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 investigator to review all documentation 
(eg, hospital progress notes, laboratory results, and diagnostics reports) relative to the AE or SAE. 
The investigator 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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9.1.2. 
Assessment of Severity 
The investigator will make an assessment of severity for each AE and SAE reported during the 
study. AEs and SAEs should be assessed and graded based upon the NCI-CTCAE Version 4.03. 
Toxicities that are not specified in the NCI-CTCAE 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 in Section 9.2. 
9.1.3. 
Assessment of Causality 
The investigator is obligated to assess the relationship between the study drug and the occurrence of 
each AE or SAE. The investigator 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 investigator will also consult the IB and/or product information for 
marketed products in the determination of his/her assessment. 
There may be situations when an SAE has occurred and the investigator has minimal information to 
include in the initial report to the sponsor. However, it is very important that the investigator always 
provides 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 investigator may change his/her opinion of causality in light of follow 
up information, amending the SAE report/eCRF accordingly.  
The causality of each AE should be assessed and classified by the investigator as “related” or “not 
related.” An AE is considered related if there is “a reasonable possibility” that the AE may have 
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 
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 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 are met: 
 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). 
9.1.4. 
Follow-Up of Adverse Events 
After the initial AE or SAE report, the investigator 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 
investigator 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 investigator 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 investigator 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. 
New or updated information will be recorded on the originally completed SAE report/eCRF, with 
all changes signed and dated by the investigator. The updated SAE report/eCRF should be resent to 
the sponsor within the time frames outlined in Section 9.5.1. 
9.1.5. 
Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, hematology or chemistry) or other abnormal assessments (eg, 
ECGs, x-rays, or vital signs) that are judged by the investigator as clinically significant will be 
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recorded as AEs or SAEs if they meet the definition of an AE (as defined in Section 9.1.1) or an 
SAE (as defined in Section 9.2). 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 will be reported as AEs or SAEs. However, clinically 
significant abnormal laboratory findings or other abnormal assessments that are associated with the 
disease being studied, unless judged by the investigator as more severe than expected for the 
patient’s condition, or that are present or detected at the start of the study and do not worsen, will 
not be reported as AEs or SAEs. They should be reported as AEs or SAEs if they induce clinical 
signs or symptoms, need active intervention, require a dose hold or permanent discontinuation, or 
are clinically significant in the opinion of the investigator. 
The investigator will exercise his/her medical and scientific judgment in deciding whether an 
abnormal laboratory finding or other abnormal assessment is clinically significant. 
9.2. 
Definition of a Serious Adverse Event 
An SAE is 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. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the AE is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.  
o Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an SAE. 
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. 
 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 
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trauma (eg, sprained ankle), which may interfere 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 investigator based on medical judgment (eg, 
may jeopardize the patient or may require medical/surgical intervention to prevent one of the 
outcomes listed above). 
9.3. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious Adverse 
Events 
9.3.1. 
Adverse Event Reporting Period 
After the ICF has been signed, but before initiation 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 investigator should report any SAEs that are believed 
to be related to prior study drug. 
9.3.2. 
Eliciting Adverse Events 
The investigator or designee will ask 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?  
9.4. 
Specific Instructions for Recording Adverse Events and Serious Adverse Events 
9.4.1. 
Diagnosis versus Signs and Symptoms 
If a diagnosis is known at the time of reporting, this should be recorded in the eCRF (and SAE 
report, as applicable), rather than the individual signs and symptoms (eg, record only hepatitis rather 
than elevated transaminases, bilirubin, or jaundice). However, if a constellation of signs and/or 
symptoms cannot be medically characterized as a single diagnosis or syndrome at the time of 
reporting, each individual AE should be recorded as an SAE or AE on the eCRF (and SAE report, if 
applicable). If a diagnosis is subsequently established, it should replace the individual signs and/or 
symptoms as the AE term on the eCRF (and SAE report, if applicable), unless the signs/symptoms 
are clinically significant. 
9.4.2. 
Adverse Events Occurring Secondary to Other Events 
In general, AEs occurring secondary to other AEs (eg, clinical sequelae or a cascade of AEs) should 
be identified by their primary cause. For example, if severe vomiting is known to result in 
dehydration, it is sufficient to record only vomiting as the SAE or AE on the eCRF (and SAE report, 
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if applicable). However, if a patient initially has a nonserious AE, and it subsequently becomes an 
SAE, both AEs should be reported separately on the eCRF. The onset date of the nonserious AE 
should be recorded as the start date of the nonserious AE. The onset date of the SAE should be 
recorded as the start date when the nonserious AE becomes an SAE.  
9.4.3. 
Persistent or Recurring Adverse Events 
A persistent AE is one that extends continuously, without resolution, between patient evaluation 
time points. Such AEs should only be recorded once on the AE eCRF (and SAE report, if 
applicable). If a persistent AE worsens in grade, the worst grade should be recorded for the entire 
event. 
A recurrent AE is one that occurs and resolves between patient evaluation time points, and 
subsequently recurs. All recurrent AEs should be recorded separately on the eCRF (and SAE report, 
if applicable).  
9.4.4. 
Disease Progression 
PD is measured as an efficacy endpoint and not considered to be an AE. However, if there are 
separate identifiable clinical sequelae that result from PD, those sequelae are reportable as AEs. 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 PD. The AE term should be reported as “pleural 
effusion” instead of PD or metastasis to lungs. 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 PD or 
brain metastasis. If a patient experienced multi-organ failure due to PD, the term “multi-organ 
failure” should be reported as the AE instead of PD. Deaths that are assessed by the investigator as 
solely due to PD should be recorded on study completion or early discontinuation eCRF as efficacy 
data. They should not be reported as an SAE. If deaths are assessed by the investigator as not solely 
due to PD, whether they are assessed as related or not related to the study drug, they should be 
reported as SAE immediately.  
If there is any uncertainty regarding whether an AE is due to PD, it should be reported as an AE. 
9.4.5. 
Death 
When recording a death as an SAE, the AE that caused or contributed to fatal outcome should be 
recorded as the single medical concept. If the cause of death is unknown and cannot be ascertained 
at the time of reporting, record “unexplained death”. 
9.4.6. 
Myelodysplastic Syndrome and Acute Myeloid Leukemia 
Events of MDS or 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 (see Section 9.7). 
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9.5. 
Prompt Reporting of Serious Adverse Events 
9.5.1. 
Timeframes for Submitting Serious Adverse Events 
SAEs will be reported promptly to the sponsor or designee as described in Table 4 once the 
investigator determines that the AE meets the protocol definition of an SAE. 
Table 4: Time Frame for Reporting Serious Adverse Events to the Sponsor or Designee 
Type of SAE 
Initial SAE Report 
Document 
All SAEs 
Within 24 hours of first 
knowledge of the AE 
eCRF 
Abbreviations: AE, adverse event; eCRF, electronic case report form; SAE, serious adverse 
event. 
 
9.5.2. 
Completion and Transmission of the Serious Adverse Event Report 
Once an investigator becomes aware that an SAE has occurred in a patient, he/she will report the 
information to the sponsor within 24 hours as outlined in Section 9.5.1. The SAE eCRF will always 
be completed as thoroughly as possible with all available details of the SAE, e-signed by the 
investigator, and forwarded to the sponsor or designee within the designated time frames. The data 
alert letter will automatically be submitted to sponsor or designee immediately after investigator 
signature. If the investigator does not have all information regarding an SAE, he/she 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 investigator will always provide an assessment of causality at the time of the initial report as 
described in Section 9.1.3. 
In case the EDC is nonoperational, facsimile transmission of the paper SAE form is the preferred 
backup method to transmit this information to the project contact for SAE receipt. In rare 
circumstances and in the absence of facsimile equipment, notification by telephone or email is 
acceptable with a copy of the paper SAE form sent by overnight mail. Initial notification via the 
telephone does not replace the need for the investigator to complete and sign the paper SAE form 
within the time frames outlined in Section 9.5.1. After the EDC becomes operational again, the 
investigator will enter the information in the EDC system. 
The sponsor will provide a list of project contacts for SAE receipt, fax numbers, telephone numbers, 
and mailing addresses. 
9.5.3. 
Regulatory Reporting Requirements for Serious Adverse Events 
The investigator will promptly report all SAEs to the sponsor in accordance with the procedures 
detailed in Section 9.5.2. 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. Prompt notification of SAEs by the investigator to the appropriate project contact for 
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SAE receipt is essential so that legal obligations and ethical responsibilities towards the safety of 
other patients are met. 
The investigator, 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 IRB/IEC. 
This protocol is being filed under an Investigational New Drug (IND) protocol amendment with the 
US Food and Drug Administration (FDA). Once active, a given SAE may qualify as an IND safety 
report if the SAE is both attributable to the study drug and unexpected. In this case, all investigators 
filed to the IND (and associated INDs for the same compound) will receive an expedited 
investigator safety report, identical in content to the IND safety report submitted to the FDA. 
Expedited investigator safety reports are prepared according to the sponsor’s policy and are 
forwarded to investigators as necessary. Reports that have been unblinded to placebo treatment will 
not be expedited. The purpose of the report is to fulfill specific regulatory and GCP requirements 
regarding the product under investigation. 
When a study center receives an initial or follow-up report or other safety information (eg, revised 
IB) from the sponsor, the responsible person according to local requirements is required to promptly 
notify his/her IRB or IEC. 
Expedited Reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) 
BeiGene, as study sponsor, is responsible for reporting suspected, unexpected, serious adverse 
reactions involving the study drug to all regulatory authorities and participating investigators in 
accordance with International Council for Harmonisation (ICH) Guidelines and/or local regulatory 
requirements, as applicable. In addition, BeiGene or authorized designee will be responsible for the 
submission of safety letters to central independent ECs (IECs). 
The sponsor will notify investigators of all reportable SAEs. This notification will be in the form of 
an expedited safety report. Upon receiving such notices, the investigator must review and retain the 
notice with other study-related documentation. 
The investigator and IRB/EC will determine whether the informed consent requires revision. The 
investigator should also comply with the IRB/EC procedures for reporting any other safety 
information. 
Suspected serious adverse reactions and other significant safety issues reported from the 
investigational product development program will be reported by the sponsor or its designated 
representative—either as expedited safety reports and/or in aggregate reports—to the relevant, 
competent health authorities in all concerned countries. 
9.6. 
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. 
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Information on the status of the mother and child will be forwarded to the sponsor. Generally, 
follow-up will be no longer than 8 weeks following the estimated delivery date. Any premature 
termination of the pregnancy will be reported. 
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 be always 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.  
9.7. 
Poststudy Adverse Events 
A poststudy AE or SAE is defined as any AE that occurs outside of the AE/SAE reporting period, as 
defined in Section 9.3.1. 
Investigators should follow-up patients for poststudy period cases of MDS and AML. If the 
investigator 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. 
9.8. 
Expedited Reporting to Health Authorities, Ethics Committees, and Investigators 
The sponsor will promptly assess all SAEs against cumulative study drug experience to identify and 
expeditiously communicate new safety findings to regulatory authorities, investigators, IRBs, and 
IECs based on applicable legislation. 
To determine the reporting requirements for individual SAEs, the sponsor will assess the 
expectedness of the SAEs using the BGB-290 IB. 
10. 
STATISTICAL CONSIDERATIONS AND ANALYTICAL PLAN 
Details of the statistical analyses will be included in the statistical analysis plan (SAP). 
10.1. 
Analysis Set  
 Intent-to-Treat (ITT) Analysis Set includes all randomized patients who are assigned to 
study drug (BGB-290 or placebo). The ITT Analysis Set will be used for all efficacy 
analyses unless otherwise specified in the statistical analysis plan.  
 Safety Analysis Set includes all patients in the ITT Analysis Set who receive any dose of 
study drug (BGB-290 or placebo). The Safety Analysis Set will be used for all safety 
analyses. 
 Per-Protocol (PP) Analysis Set includes all patients in the ITT Analysis Set without major 
protocol deviations that impact assessment of efficacy. Criteria for exclusion from the PP 
Analysis Set will be determined and documented before the final analysis of PFS. The PP 
Analysis Set will be used to perform sensitivity analysis for the OS and PFS endpoints.  
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 PK Analysis Set includes all patients who receive BGB-290 and for whom valid BGB-290 
PK parameters can be estimated. 
10.2. 
Covariates 
The following covariates may be used to examine efficacy and/or safety in subgroups or covariate 
analyses if deemed appropriate: 
 Geographic region (China/Hong Kong/Taiwan vs Australia/Europe/North America vs 
Japan/South Korea vs ROW) 
 EGOG performance status at baseline (0, 1) 
 HRD status (LOHhigh vs LOHlow vs unknown) 
 Age at baseline:  < 65, ≥ 65; < 75, ≥ 75 
 Race: White vs Asian vs others; Chinese vs Japanese vs White vs others 
 Measurable disease at baseline (yes, no) 
 IRT values and CRF values will be used for primary analyses and sensitivity/subgroup 
analyses, respectively 
10.3. 
Efficacy Analyses 
All efficacy analyses will be conducted using the ITT Analysis Set unless otherwise specified. 
Primary efficacy analysis of PFS will use the investigator assessment of PD according to RECIST 
Version 1.1. Secondary efficacy analyses of ORR, time to response, and duration of response will 
use the investigator assessments of response and PD according to RECIST Version 1.1. All 
stratified efficacy analyses will incorporate the stratification factors used at randomization: HRD 
status (LOHhigh versus LOHlow versus unknown), region (China/Hong Kong/Taiwan versus 
Australia/Europe/North America versus Japan/South Korea versus ROW), and ECOG performance 
status (0 versus 1), unless otherwise specified. 
10.3.1. 
Primary Efficacy Analyses 
PFS is defined as the time from randomization to PD per RECIST Version 1.1 by investigator 
assessment or death due to any cause, whichever occurs first. 
The null and alternative hypotheses for the final PFS analysis are as follows: 
H0: HR (BGB-290/placebo) = 1 
Ha: HR (BGB-290/placebo) < 1  
The final PFS analysis will be performed when 85 PFS events have occurred (66% of target sample 
size). A stratified 1-sided log-rank test at a 0.1 significance level incorporating the randomized 
stratification factors will be used to compare treatment groups using the ITT Analysis Set. The HR 
and its 2-sided 95% CI will be estimated using the stratified Cox-proportional hazards model. The 
median PFS for each treatment group will be estimated using the Kaplan-Meier method, and the 
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2-sided 95% CI will be calculated using the Brookmeyer-Crowley method (Brookmeyer and 
Crowley, 1982). 
PFS censoring rule will follow FDA Guidance for Industry, Clinical Trial Endpoints for Approval 
of Cancer Drugs and Biologics (2007). Data for patients without PD per RECIST Version 1.1 or 
death at the time of analysis will be censored at the date of the last tumor assessment. Data for 
patients who started new anticancer therapy will be censored at the last tumor assessment date 
before the introduction of new anticancer therapy. Data for patients who had 2 or more consecutive 
missed scheduled tumor assessments immediately before PD will be censored at the last tumor 
assessment date before the 2 missed tumor assessments. Non-proportionality of hazard ratios 
between the treatment groups will be assessed and additional sensitivity analysis will be performed. 
Further details will be described in the statistical analysis plan.  
10.3.2. 
Secondary Efficacy Analyses 
A secondary analysis of PFS will be conducted using the PP Analysis Set.  
OS is the key secondary efficacy endpoint and is defined as the time from randomization to death 
due to any cause.  
A stratified log-rank test incorporating the randomized stratification factors will be used to compare 
treatment groups using the ITT Analysis Set. The HR and its 2-sided 95% CI will be estimated 
using the stratified Cox-proportional hazards model. The median OS for each treatment group will 
be estimated using the Kaplan-Meier method and the 95% CI will be calculated using the 
Brookmeyer-Crowley method (Brookmeyer and Crowley, 1982). 
A sensitivity analysis of OS will be conducted using the PP Analysis Set. 
TSST is defined as the time from randomization until the second subsequent anti-cancer therapy or 
death after next-line therapy. Subjects alive and without the 2nd anti-cancer therapy will be 
censored at last known alive. 
TSST will be assessed using a stratified log-rank test in ITT Analysis Set. The HR and its 2-sided 
95% CI will be estimated using the stratified Cox-proportional hazards model. The median for each 
treatment group will be estimated using the Kaplan-Meier method and the 95% CI will be calculated 
using the Brookmeyer-Crowley method (Brookmeyer and Crowley, 1982). 
ORR is defined as the proportion of patients with a best overall response of CR or PR per RECIST 
Version 1.1 by investigator assessment for the ITT Analysis Set. The ORR and its exact 2-sided 
95% CI will be reported for each treatment group. A Cochran-Mantel-Haenszel score test will be 
used to compare treatment groups. 
The best overall response will be summarized by the following categories for the ITT Analysis Set, 
patients with measurable disease at baseline and patients with nonmeasurable disease at baseline. 
 CR 
 PR (for the ITT Analysis Set and patients with measurable disease) 
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 Stable disease 
 PD 
 Not evaluable 
DOR is defined as the time from the first documented confirmed response of CR or PR to PD per 
RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first. 
Only patients with response of CR or PR during the study will be included in duration of response 
analysis. The median duration of response and its 2-sided 95% CI for each treatment group will be 
provided.  
Time to response is defined as the time from randomization to the first documented confirmed 
response of CR or PR per RECIST Version 1.1 by investigator assessment. Only patients with 
response of CR or PR during the study will be included in time to response analysis. Descriptive 
statistics will be provided. 
10.4. 
Pharmacokinetic Analyses 
BGB-290 Ctrough at steady-state will be summarized. Descriptive statistics will include means, 
medians, ranges, and standard deviations, as appropriate. 
Population PK analysis may be carried out to include plasma concentrations from this study in an 
existing model. Additional PK parameters such as apparent clearance (CL/F) of the drug from 
plasma and area under the plasma concentration-time curve from 0 to 12 hours post-dose (AUC0-12) 
may be derived from the population PK if supported by data. 
Exposure-response (efficacy or safety endpoints) analysis may be carried out if supported by data. 
The results of the population PK and exposure-response analyses may be reported separately from 
the clinical study report. Details of the PK analyses will be provided in a separate SAP. 
10.5. 
Exploratory Analyses 
10.5.1. 
Health-related Quality of Life 
Patient reported outcomes will be assessed using the EORTC QLQ-C30 and QLQ-STO22 
questionnaires and the EQ-5D-5L health questionnaire. The scores from these questionnaires will be 
summarized descriptively. 
10.5.2. 
Biomarkers 
Correlative biomarker analyses in tumor tissues and blood will be performed. A separate statistical 
analysis plan will outline details of the biomarker analyses. 
10.6. 
Safety Analyses 
Safety will be assessed by monitoring and recording of all AEs. Laboratory values, vital signs, 
physical examinations, and ECG findings will also be used in determining the safety of the study 
treatment. 
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10.6.1. 
Extent of Exposure 
Extent of exposure to each study treatment will be summarized descriptively as the duration of 
exposure (days), cumulative total dose received per patient (mg), dose intensity (mg/day), and 
relative dose intensity. 
The number (percentage) of patients requiring dose reductions, study drug holds, and permanent 
study drug discontinuation due to AEs will be summarized by treatment group. Frequency of dose 
reductions and study drug withholding will be summarized by categories. 
10.6.2. 
Adverse Events 
The AE will be coded using MedDRA Version 22.0 or higher and graded using the current version 
of NCI-CTCAE. 
A TEAE is defined as an AE that had an onset date on or after first study treatment or was 
worsening in severity from baseline (pretreatment) up to 30 days following permanent study drug 
discontinuation or initiation of new anticancer therapy, whichever occurs first. All TEAEs will be 
included in summary tables and in-patient data listings. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
system organ class (SOC) and preferred term (PT). A patient will be counted only once by the 
highest grade according to NCI-CTCAE Version 4.03 within an SOC and PT, even if the patient 
experienced more than one TEAE within a specific SOC and PT. The number (percentage) of 
patients with TEAEs will also be summarized by relationship to the study treatment. 
Treatment-related AEs include those events considered by the investigator to be related to study 
treatment or with missing assessment of the causal relationship. Serious AEs, deaths, TEAE of 
Grade 3, study drug-related TEAEs, and TEAEs that led to study drug withholding or permanent 
discontinuation will also be summarized. 
10.6.3. 
Laboratory Analyses 
Clinical laboratory (eg, hematology and chemistry) values to be evaluated will be specified in the 
statistical analysis plan and collected in the EDC system. Collected values may be a subset of all the 
values obtained in the requested sampling, eg, a complete blood count with differential may be 
requested for the evaluation of neutrophils only. Analyzed laboratory values that are abnormal will 
be flagged and identified as outside (above or below) the normal range. 
Laboratory parameters that are graded in NCI-CTCAE Version 4.03 will be summarized by 
NCI-CTCAE grade. Shift tables will be provided as appropriate. 
10.6.4. 
Physical Examinations 
Physical examination results collected in association with an AE will be listed and summarized. 
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10.6.5. 
Vital Signs 
Specific vital signs, eg, blood pressure and temperature, will be summarized and listed. The change 
from baseline will also be presented. 
10.6.6. 
Electrocardiograms 
The percentage of patients with abnormal and clinically significant ECG findings will be presented.  
10.7. 
Sample Size Consideration 
This study is designed to provide 80% power for PFS. The following assumptions are used in 
determining the sample size for this study: 
 Overall type I error rate: 0.1 (1-sided) 
 Randomization: 1:1 
 Median PFS for placebo group: 6.0 months 
 PFS HR (BGB-290/placebo): 0.63 
A sample size of approximately 128 patients (64 per treatment group) is required to achieve 85 PFS 
events within the planned study duration of approximately 26 months after the first patient is 
randomized to study, assuming an estimated accrual period of 20 months. 
11. 
STUDY ADMINISTRATION AND INVESTIGATOR OBLIGATIONS 
11.1. 
Regulatory Authority Approval 
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency in 
accordance with any applicable country-specific regulatory requirements or file the protocol to 
appropriate regulatory agency before the study is initiated at a study center in that country. 
11.2. 
Investigator Responsibilities 
11.2.1. 
Good Clinical Practice 
The investigator will ensure that this study is conducted in accordance with the principles of the 
“Declaration of Helsinki”, ICH guidelines, and that the basic principles of “Good Clinical Practice,” 
as outlined in 21 Code of Federal Regulations (CFR) 312, Subpart D, “Responsibilities of Sponsors 
and Investigators,” 21 CFR, Part 50, and 21 CFR, Part 56, are adhered to. 
Investigators and all subinvestigators must provide documentation of their financial interest or 
arrangements with BeiGene, or proprietary interests in the drug being studied. This documentation 
must be provided before participation of the investigator and any subinvestigator. The investigator 
and subinvestigator agree to notify BeiGene or its authorized representative of any change in 
reportable interests during the study and for 1 year following completion of the study. Study 
completion is defined as the date that the last patient has completed the protocol-defined activities. 
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11.2.2. 
Ethical Conduct of the Study and Ethics Approval 
This study will be conducted in accordance with GCP and all applicable regulatory requirements, 
including, where applicable, the current version of the Declaration of Helsinki. 
The investigator (or sponsor, where applicable) is responsible for ensuring that this protocol, the 
study center’s ICF, and any other information that will be presented to potential patients (eg, 
advertisements or information that supports or supplements the ICF) are reviewed and approved by 
the appropriate IEC/IRB. 
The IEC/IRB must be constituted in accordance with all applicable regulatory requirements. The 
sponsor will provide the investigator with relevant document(s)/data that are needed for IEC/IRB 
review and approval of the study. 
Before the study drug(s) can be shipped to the study center, the sponsor or its authorized 
representative must receive copies of the IEC/IRB approval, the approved ICF, and any other 
information that the IEC/IRB has approved for presentation to potential patients. 
If the protocol, the ICF, or any other information that the IEC/IRB has approved for presentation to 
potential patients is amended during the study, the investigator is responsible for ensuring the 
IEC/IRB reviews and approves, where applicable, these amended documents. The investigator must 
follow all applicable regulatory requirements pertaining to the use of an amended ICF including 
obtaining IEC/IRB approval of the amended form before new patient consent to take part in the 
study using this version of the form. Copies of the IEC/IRB approval of the amended ICF/other 
information and the approved amended ICF/other information must be forwarded to the sponsor 
promptly. 
11.2.3. 
Informed Consent 
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and potential 
hazards of the study and before undertaking any study-related procedures. The investigator must 
utilize an IRB/IEC-approved ICF for documenting written informed consent. Each ICF will be 
appropriately signed and dated by the patient or the patient’s legally authorized representative and 
the person obtaining consent. 
Informed consent will be obtained before the patient can participate in the study. The contents and 
process of obtaining informed consent will be in accordance with all applicable regulatory 
requirements. 
11.2.4. 
Investigator Reporting Requirements 
As indicated in Section 9.5, the investigator (or sponsor, where applicable) is responsible for 
reporting SAEs to the IEC/IRB, in accordance with all applicable regulations. Furthermore, the 
investigator may be required to provide periodic safety updates on the conduct of the study at 
his/her study center and notification of study closure to the IEC/IRB. Such periodic safety updates 
and notifications are the responsibility of the investigator and not of the sponsor. 
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11.2.5. 
Confidentiality 
Information on maintaining patient confidentiality in accordance to individual local and national 
patient privacy regulations must be provided to each patient as part of the informed consent process, 
either as part of the ICF or as a separate signed document (for example, in the US, a study center 
specific HIPAA consent may be used). The investigator must assure that patients’ anonymity will be 
strictly maintained and that their identities are protected from unauthorized parties. Only patient 
initials, date of birth, and an identification code (ie, not names) should be recorded on any form or 
biological sample submitted to the sponsor, IRB, or laboratory. The investigator must keep a 
screening log showing codes, names, and addresses for all patients screened and for all patients 
enrolled in the study. 
The investigator agrees that all information received from BeiGene, including but not limited to the 
IB, this protocol, eCRFs, the IND, and any other study information, remain the sole and exclusive 
property of BeiGene during the conduct of the study and thereafter. This information is not to be 
disclosed to any third party (except employees or agents directly involved in the conduct of the 
study or as required by law) without prior written consent from BeiGene. The investigator further 
agrees to take all reasonable precautions to prevent the disclosure by any employee or agent of the 
study center to any third party or otherwise into the public domain. 
11.2.6. 
Electronic Case Report Forms 
For each patient enrolled, an eCRF must be completed and signed by the principal investigator or 
subinvestigator within a reasonable time period after data collection. This also applies to records for 
those patients those patients who discontinue the study early. If a patient withdraws from the study, 
the reason must be noted on the eCRF. If a patient is withdrawn from the study because of a 
treatment-limiting AE, thorough efforts should be made to clearly document the outcome. 
The eCRFs exist within an EDC system with controlled access managed by BeiGene or its 
authorized representative for this study. Study staff will be appropriately trained in the use of eCRFs 
and applications of electronic signatures before the study start and before being given access to the 
EDC system. Original data and any changes of data will be recorded using the EDC system, with all 
changes tracked by the system and recorded in an electronic audit trail. The investigator attests that 
the information contained in the eCRFs is true by providing an electronic signature within the EDC 
system. After final database lock, the investigator will receive a copy of the patient data on CD-
ROMs for archiving the data at the study center.  
11.2.7. 
Drug Accountability 
The investigator or designee (ie, pharmacist) is responsible for ensuring adequate accountability of 
all used and unused study drug. This includes acknowledgment of receipt of each shipment of study 
drug (quantity and condition), patient dispensing records, and returned or destroyed study drug. 
Dispensing records will document quantities received from BeiGene and quantities dispensed to 
patients, including lot number, date dispensed, patient identifier number, patient initials, and the 
initials of the person dispensing the medication. 
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At study initiation, the monitor will evaluate the study center’s standard operating procedure for 
study drug disposal/destruction in order to ensure that it complies with BeiGene requirements. At 
the end of the study, following final drug inventory reconciliation by the monitor, the study center 
will dispose of and/or destroy all unused study drug supplies, including empty containers, according 
to these procedures. If the study center cannot meet BeiGene’s requirements for disposal, 
arrangements will be made between the study center and BeiGene or its representative for 
destruction or return of unused study drug supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
11.2.8. 
Inspections 
The investigator should understand that source documents for this study should be made available to 
appropriately qualified personnel from BeiGene or its representatives, to IRBs/IECs, or to 
regulatory authority or health authority inspectors. 
11.2.9. 
Protocol Adherence 
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. Investigators assert they will apply due 
diligence to avoid protocol deviations. 
11.3. 
Sponsor Responsibilities 
11.3.1. 
Protocol Modifications 
Protocol modifications, except those intended to reduce immediate risk to study patients, may be 
initiated only by BeiGene. All protocol modifications must be submitted to regulatory authorities 
and the IRB/IEC together with, if applicable, a revised model ICF in accordance with local 
requirements. As applicable by local requirements, written documentation of regulatory authorities, 
IRB/IEC, and required study center approval must be obtained by the sponsor before changes can be 
implemented. 
Information on any change in risk and/or change in scope must be provided to patients already 
actively participating in the study, and they must read, understand, and sign each revised ICF 
confirming his/her willingness to remain in the study. 
11.3.2. 
Use of Information and Publication 
A clinical study report will be prepared and provided to the regulatory agency(ies) of participating 
countries. 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 sponsor recognizes the importance of communicating medical study data, and therefore, 
encourages their publication in reputable scientific journals and at seminars or conferences. The 
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details of the processes of producing and reviewing reports, manuscripts, and presentations based on 
the data from this study will be described in the clinical study agreement. 
If a written contract for the conduct of the study, which includes publication provisions inconsistent 
with this statement, is executed that contract’s publication provisions shall apply rather than this 
statement. 
11.4. 
Study and Study Center Closure 
Upon completion of the study, the monitor will conduct the following activities in conjunction with 
the investigator or study center personnel, as appropriate: 
 Return of all study data to the sponsor 
 Data queries 
 Accountability, reconciliation, and arrangements for unused study drug(s) 
 Review of study records for completeness 
 Return of treatment codes to the sponsor 
 Shipment of PK samples to assay laboratories 
In addition, the sponsor reserves the right to temporarily suspend or prematurely discontinue this 
study either at a single study center or at all study centers at any time for reasons including, but not 
limited to, safety or ethical issues or severe noncompliance. If the sponsor determines such action is 
needed, the sponsor will discuss this with the investigator (including the reasons for taking such 
action) at that time. When feasible, the sponsor will provide advance notification to the investigator 
of the impending action before it taking effect. 
The sponsor will promptly inform all other investigators and/or institutions conducting the study if 
the study is suspended or terminated for safety reasons, and will also inform the regulatory 
authorities of the suspension or termination of the study and the reason(s) for the action. If required 
by applicable regulations, the investigator must inform the IEC/IRB promptly and provide the 
reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must be returned to the sponsor. In addition, 
arrangements will be made for all unused study drug in accordance with the applicable sponsor 
procedures for the study. 
Financial compensation to investigators and/or institutions will be in accordance with the agreement 
established between the investigator and the sponsor. 
11.5. 
Records Retention and Study Files 
11.5.1. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the study to 
be fully documented and the study data to be subsequently verified. These documents should be 
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classified into at least the following 2 categories: (1) investigator’s study file and (2) patient clinical 
source documents. 
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC, and governmental approval with correspondence, ICF, drug records, staff curriculum vitae 
and authorization forms, and other appropriate documents and correspondence. 
Patient clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the eCRFs) would include (although not be limited to) the 
following: patient hospital/clinic records, physician’s and nurse’s notes, appointment book, original 
laboratory reports, ECG, electroencephalogram, x-ray, pathology and special assessment reports, 
consultant letters, screening and enrollment log, etc. 
Following closure of the study, the investigator must maintain all study records in a safe and secure 
location. The records must be maintained to allow easy and timely retrieval, when needed (eg, audit 
or inspection), and, whenever feasible, to allow any subsequent review of data in conjunction with 
assessment of the facility, supporting systems, and personnel. Where permitted by local 
laws/regulations or institutional policy, some or all of these records can be maintained in a format 
other than hard copy (eg, microfiche, scanned, or electronic); however, caution needs to be 
exercised before such action is taken. The investigator must assure that all reproductions are legible, 
are a true and accurate copy of the original, and meet accessibility and retrieval standards, including 
regenerating a hard copy, if required. Furthermore, the investigator must ensure there is an 
acceptable back up of these reproductions and that an acceptable quality control process exists for 
making these reproductions. 
The sponsor will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study center for the study, as dictated by any institutional requirements or 
local laws or regulations, or the sponsor’s standards/procedures; otherwise, the retention period will 
default to 15 years. 
The investigator must notify the sponsor of any changes in the archival arrangements, including, but 
not limited to, the following: archiving at an off-site facility and transfer of ownership of the records 
in the event the investigator leaves the study center. 
If the investigator cannot guarantee this archiving requirement at the study center for any or all of 
the documents, special arrangements must be made between the investigator and BeiGene to store 
these in sealed containers outside of the study center so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the patient, appropriate copies should be made for storage outside of the study center. 
Biological samples at the conclusion of this study may be retained in storage by the sponsor as 
outlined in the study manual. 
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11.5.2. 
Provision of Study Results and Information to Investigators 
When the clinical study report is completed, the sponsor will provide the major findings of the study 
to the investigator. 
In addition, details of the study drug assignment will be provided to the investigator to enable 
him/her to review the data to determine the outcome of the study for his/her patient(s). 
The sponsor will not routinely inform the investigator or patient the test results because the 
information generated from this study will be preliminary in nature and the significance and 
scientific validity of the results will be undetermined at such an early stage of research. 
11.6. 
Information Disclosure and Inventions 
All information provided by the sponsor and all data and information generated by the study center 
as part of the study (other than a patient’s medical records) is the sole property of the sponsor. 
All rights, title, and interests in any inventions, know-how, or other intellectual or industrial 
property rights that are conceived or reduced to practice by the study center personnel during the 
course of or as a result of the study are the sole property of the sponsor, and are hereby assigned to 
the sponsor. 
If a written contract for the conduct of the study that includes ownership provisions inconsistent 
with this statement is executed between the sponsor and the study center, that contract’s ownership 
provisions shall apply rather than this statement. 
All information provided by the sponsor and all data and information generated by the study center 
as part of the study (other than a patient’s medical records) will be kept confidential by the 
investigator and other study center personnel. This information and data will not be used by the 
investigator or other study center personnel for any purpose other than conducting the study without 
the prior written consent of the sponsor. 
These restrictions do not apply to: 
Information which becomes publicly available through no fault of the investigator or study center 
personnel 
Information which is necessary to disclose in confidence to an IEC/IRB solely for the evaluation of 
the study 
Information which is necessary to disclose in order to provide appropriate medical care to a patient 
Study results that may be published as described in Section 11.3.2. 
If a written contract for the conduct of the study that includes provisions inconsistent with this 
statement is executed, that contract’s provisions shall apply rather than this statement. 
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11.7. 
Joint Investigator/Sponsor Responsibilities 
11.7.1. 
Access to Information for Monitoring 
In accordance with ICH GCP guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the data recorded in the eCRFs for 
consistency. 
The monitor is responsible for routine review of the eCRFs at regular intervals throughout the study 
to verify adherence to the protocol and the completeness, consistency, and accuracy of the data 
being entered on them. The monitor should have access to any patient records needed to verify the 
entries on the eCRFs. The investigator agrees to cooperate with the monitor to ensure that any 
problems detected in the course of these monitoring visits are resolved. 
11.7.2. 
Access to Information for Auditing or Inspections 
Representatives of regulatory authorities or of BeiGene may conduct inspections or audits any time 
during or after completion of this clinical study. If the investigator is notified of an inspection by a 
regulatory authority the investigator agrees to notify the sponsor or its designee immediately. The 
investigator agrees to provide to representatives of a regulatory agency or BeiGene access to 
records, facilities, and personnel for the effective conduct of any inspection or audit. 
 
 
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12. 
REFERENCES 
Alexandrov LB, Nik-Zainal S, Siu HC, Leung SY, Stratton MR. A mutational signature and gastric 
cancer suggests therapeutic strategies. Nat Commun. 2015 Oct 29. doi: 10.1038/ncomms9683. 
Aprile G, Fanotto V, Garattini SK, et al. The concept of maintenance: may we move it to gastric, 
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APPENDICES 
 
 
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APPENDIX 1. 
SCHEDULE OF ASSESSMENTS 
Study Phase 
Screeninga 
Treatmentb 
Un- 
scheduled 
Visitc 
End of 
treatment 
(EOT) 
Visitd 
Safety 
Follow-upe 
Long-term 
Follow-upf 
Day of Phase 
-28 to -1 
Cycle 1 
Cycle 2 
Cycle ≥3 
Day 1 Day 15 Day 1 
Day 15 
Day 1 
Allowed time window 
 
 
± 2 
± 3 
± 3 
± 3 
Study Day 
-28 to -1 
1 
15 
29 
43 
57, 85, etc. 
Varies 
Varies 
Varies 
Varies 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics, medical history, 
smoking status 
X 
 
 
 
 
 
 
 
 
 
Complete physical examination 
X 
 
 
 
 
 
 
X 
 
 
Limited physical examination 
 
X 
X 
X 
X 
X 
X 
 
 
 
EQ-5D-5L, EORTC QLQ-C30 and 
EORTC QLQ-STO22 questionnaires 
 
X 
 
 
 
X  
(q8w ±7d) 
 
X 
 
 
Vital signs and weightg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
ECOG performance status 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECGh 
X (-14 to -1) 
X 
X 
 
 
 
X 
X 
 
 
Hematologyi 
X (-14 to -1) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistryi 
X (-14 to -1) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysisi 
X (-14 to -1) 
X 
 
 
 
 
X 
X 
 
 
Pregnancy testingj 
X (-7 to -1) 
 
 
X 
 
X 
X 
X 
X 
 
 
 
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APPENDIX 1. 
SCHEDULE OF ASSESSMENTS 
Study Phase 
Screeninga 
Treatmentb 
Un- 
scheduled 
Visitc 
End of 
treatment 
(EOT) 
Visitd 
Safety 
Follow-upe 
Long-term 
Follow-upf 
Day of Phase 
-28 to -1 
Cycle 1 
Cycle 2 
Cycle ≥3 
Day 1 Day 15 Day 1 
Day 15 
Day 1 
Allowed time window 
 
 
± 2 
± 3 
± 3 
± 3 
Study Day 
-28 to -1 
1 
15 
29 
43 
57, 85, etc. 
Varies 
Varies 
Varies 
Varies 
CT with IV contrast of chest, 
abdomen and pelvisk 
X (-14 to -1) 
 
 
 
 
X (q8w ±7d) 
X 
X 
 
X (q8w ±7d) 
PET or bone scan, if clinically 
indicatedl 
X (-14 to -1) 
 
 
 
 
X (q8w ±7d)l 
X 
Xn 
 
X 
(q8w ±7d)l 
MRI scan of brain, if clinically 
indicatedm 
X 
 
 
 
 
X (q8w ±7d)m 
X 
Xo 
 
X 
(q8w ±7d)m 
Patient registration and 
randomization via IRT 
Xa 
 
 
 
 
 
 
 
 
 
BGB-290 or placebo 
 
Twice daily dosing continuously 
 
 
 
 
Study drug dispensing/accountability 
 
X 
 
X 
 
X 
X 
X 
 
 
Adverse eventsn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication(s)o 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X (~q12w) 
Pharmacokineticsp 
 
X 
X 
 
 
 
 
 
 
 
Blood for biomarkersq 
 
X 
 
X 
 
Xq (C4 only) 
 
X 
 
 
Tumor tissuer 
X 
 
 
 
 
 
 
 
 
 
Survival follow-ups 
 
 
 
 
 
 
 
 
 
X (~q12w) 
Abbreviations: -7/-14/-28 to -1, Day -7/-14/-28 to Day -1 (day of randomization) of screening; AE, adverse event; BID, twice daily; C, Cycle; CT, computed 
tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; eCRF, electronic case report form; EORTC QLQ-C30, European 
Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire; EORTC QLQ-STO22, European Organisation for Research and 
Treatment of Cancer Quality of Life gastric cancer module; EOT, end of treatment; EQ-5D-5L, European Quality of Life 5-Dimensions 5 Levels Health 
Questionnaire; HRD, homologous recombination deficiency; IRT, interactive response technology; IV, intravenous; MRI, magnetic resonance imaging; 
NCI-CTCAE; National Cancer Institute-Common Toxicity Criteria for Adverse Events; PARP, poly (ADP-ribose) polymerase; PD, progressive disease; 
PET, positron-emission tomography; PK, pharmacokinetic; PO, oral; q8w ±7d, every 8 weeks ±7 days; ~q12w, approximately every 12 weeks; 
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RECIST, Response Evaluation Criteria in Solid Tumors; SAE, serious adverse event. 
a. 
Screening must occur within 28 days of randomization. Some assessments have a narrower screening window as shown in the table. Assessments obtained 
within 7 days of Day 1 do not have to be repeated on Day 1. Patient registration and randomization may occur as late as Day 1 before any study treatment. 
b. Patients must initiate study treatment within 4 days after randomization. Administration of BGB-290 or placebo will continue until PD, as assessed by 
investigator per RECIST Version 1.1, unacceptable toxicity, death, or another discontinuation criterion is met (Sections 5.5 and 5.7). A cycle is 28 days. 
Assessments shown for Cycle 3 apply to all subsequent cycles except for required tumor assessments that occur every 8 weeks ±7 days (every second cycle) 
and blood collection for biomarkers occurs only on Day 1 of Cycle 4 (not any other Day 1 of  Cycle 3). 
c. 
Unscheduled visits may occur any time as necessary as per investigator decision or patient’s request for reasons such as assessment or follow-up of AEs. 
Study activities, as indicated by ‘X,’ should be performed based on the reason for the unscheduled visit. If PD is suspected, imaging studies should be 
performed and blood for biomarkers should be obtained as appropriate. 
d. The EOT visit should occur within 7 days after BGB-290 or placebo has been permanently discontinued. 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 providing 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. 
e. 
Approximately 30 days after the last day of study drug 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. 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 
AEs. If these attempts of contact are unsuccessful, the additional attempts detailed in Section 5.6.3 should be made. 
f. 
Patients will be followed for survival, further anticancer therapy, and diagnosis of myelodysplastic syndrome or acute myeloid leukemia via telephone 
contact or other means (eg, clinic visit) approximately every 12 weeks until death, withdrawal of consent, or the end of study, whichever occurs first. 
Patients who were permanently discontinued from study drug for reasons other than PD and meet criteria otherwise (eg, discontinued for AE and no new 
anticancer therapy) will be followed with tumor assessments every 8 weeks (±7 days) until PD or any other reason listed in Section 5.7, whichever occurs 
first. For efficacy assessments as per protocol, refer to Section 7.3. If the patient refuses to return for these tumor assessments or is unable to do so, every 
effort should be made to contact the patient by telephone to determine the patient’s disease status and survival. 
Should attempts of telephone contact be unsuccessful, the additional attempts detailed in Section 5.6.3 should be made. If a patient cannot be contacted 
despite all attempts, the patient will be considered lost to follow-up. 
g. Vital signs (systolic and diastolic blood pressure; pulse rate; and oral, temporal, or tympanic temperature) will be measured before study drug administration 
and approximately 15 minutes before each collection of PK blood samples, if applicable, during the treatment period. 
h. ECGs will be obtained at the following timepoints: screening; predose and 2 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 15; and EOT. Additional 
ECGs will be performed, if clinically indicated.  
i. 
Hematology includes hemoglobin, platelet count, white blood cell count, neutrophil count, and lymphocyte count. 
Chemistry includes albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, chloride, creatinine, glucose, 
lactate dehydrogenase, phosphate, potassium, sodium, total bilirubin, and total protein. 
Urinalysis includes blood, protein, ketones, glucose, red blood cells, and white blood cells. 
j. 
For females of childbearing potential, a serum pregnancy test must be performed at a central or local laboratory within 7 days before randomization. For 
subsequent pregnancy testing, if clinically indicated, urine pregnancy tests, performed at a central or local laboratory, are allowed. If a urine pregnancy test is 
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positive, a confirmatory serum pregnancy test is required. 
k. Following the screening tumor assessment within 14 days before randomization, tumor assessments will occur at the schedule of every 8 weeks (±7 days) 
after Day 1. Any measurable disease must be documented at screening and reassessed at each subsequent tumor evaluation. The same imaging method(s) 
used at screening must be used throughout the study. A documented standard-of-care tumor assessment may be used as the screening assessment provided it 
meets protocol requirements (Section 7.3.1.2). CT scan with IV contrast is the preferred imaging method for assessment of the chest, abdomen, and pelvis. 
Other imaging methods are allowed as outlined in Section 7.3.1.2. Imaging of other areas of disease should be performed as clinically indicated. Patients 
without PD at the EOT visit should be followed with tumor assessments every 8 weeks (± 7 days) during the long-term follow-up phase.  
l. 
PET scan or whole-body radionuclide bone scan must be performed at screening if the patient has known bone metastases or has symptoms that could be due 
to bone metastases. If bone metastases are present at baseline, they must be followed on study using the same imaging method as at baseline. 
m. MRI scan of the brain to assess for brain metastases must be performed at screening if the patient has symptoms that could be due to brain metastases. CT 
scan with IV contrast is acceptable if MRI is not available or the patient is claustrophobic.  
n. AEs and laboratory safety measurements will be recorded at each study visit, graded per NCI-CTCAE Version 4.03, and assessed as outlined in Section 9. 
After the informed consent form has been signed, but before initiation 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 last dose of study drug or initiation of new anticancer therapy, 
whichever occurs first. After this period, the investigator should report any SAEs that are believed to be related to prior study drug. 
o. All concomitant medications taken by or administered to the patient within 28 days before randomization and 30 days after the last dose of study drug will 
be recorded. Concomitant medications include subsequent anticancer therapy information acquired during the long-term follow-up phase. 
p. PK samples will be collected from patients at the following time points: predose (within 30 minutes before dose) and 2 hours (±30 minutes) postdose on 
Cycle 1 Day 1 and Cycle 1 Day 15. The time of study drug administration on the day before Day 15 must be recorded on the eCRF. Details concerning 
collection, handling, and processing of the PK plasma samples will be provided in the study manual.  
q. One blood sample (8 mL) must be collected before initiation of study drug on Day 1 of Cycle 1 for the assessment of germline mutations. Two blood 
samples (10 mL each) must be collected for the assessment of plasma biomarkers of PARP inhibitor response/resistance before study drug administration on 
Day 1 of Cycles 1, 2, and 4, as well as at the EOT visit (unless they had been collected within 14 days). Instructions for the processing, storage, and shipping 
of samples will be provided in the study manual.  
r. 
Archival tumor tissue shall be sent to the central laboratory for the determination of HRD status for randomization and the assessment of candidate 
predictive biomarkers.  
s. 
Patients will be followed for survival via telephone contact approximately every 12 weeks or as further detailed in Sections 5.6.2 and 5.6.3. 
 
 
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APPENDIX 2. 
THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS (RECIST) 
GUIDELINES, VERSION 1.1 
The text below was obtained from the following reference: Eisenhauer EA, Therasse P, Bogaerts J, et 
al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J 
Cancer. 2009;45:228-247 (Eisenhauer et al, 2009). 
DEFINITIONS 
Response and progression will be evaluated in this study using the international criteria proposed by 
the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (Version 1.1). Changes in 
only the largest diameter (unidimensional measurement) of the tumor lesions are used in the 
RECIST criteria. Note: Lesions are either measurable or nonmeasurable using the criteria provided 
below. The term “evaluable” in reference to measurability will not be used because it does not 
provide additional meaning or accuracy. 
Measurable Disease 
Tumor lesions: Must be accurately measured in at least 1 dimension (longest diameter in the plane 
of measurement is to be recorded) with a minimum size of: 
 10 mm by CT scan (irrespective of scanner type) and MRI (no less than double the slice 
thickness and a minimum of 10 mm). 
 10 mm caliper measurement by clinical exam (when superficial). 
 20 mm by chest x-ray (if clearly defined and surrounded by aerated lung). 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be 15 mm in short axis when assessed by computed tomography (CT) scan (CT scan slice 
thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only the short 
axis will be measured and followed. 
Nonmeasurable Disease 
All other lesions (or sites of disease), including small lesions (longest diameter 10 to <15 mm with 
conventional techniques or <10 mm using spiral CT scan), are considered nonmeasurable disease. 
Leptomeningeal disease, ascites, pleural, or pericardial effusion, inflammatory breast disease, 
lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by 
physical examination that is not measurable by reproducible imaging techniques are all 
nonmeasurable. 
Bone lesions: 
 Bone scan, positron-emission tomography (PET) scan, or plain films are not considered 
adequate imaging techniques to measure bone lesions. However, these techniques can be 
used to confirm the presence or disappearance of bone lesions. 
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 Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, 
that can be evaluated by cross sectional imaging techniques such as CT or magnetic 
resonance imaging (MRI) can be considered as measurable lesions if the soft tissue 
component meets the definition of measurability described above. 
 Blastic bone lesions are nonmeasurable. 
Cystic lesions: 
 Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor nonmeasurable) since they are, by 
definition, simple cysts. 
 Cystic lesions thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if noncystic 
lesions are present in the same patient, these are preferred for selection as target lesions. 
Lesions with prior local treatment: 
 Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
locoregional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. Trial protocols should detail the conditions under 
which such lesions would be considered measurable. 
Target Lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total should be 
identified as target lesions and recorded and measured at baseline. Target lesions should be selected 
on the basis of their size (lesions with the longest diameter), be representative of all involved organ, 
but in addition should be those that lend themselves to reproducible repeated measurements. 
Lymph nodes merit special mention since they are normal anatomical structures that may be visible 
by imaging even if not involved by tumor. Pathological nodes that are defined as measurable and 
may be identified as target lesions must meet the criterion of a short axis of 15 mm by CT scan. 
Only the short axis of these nodes will contribute to the baseline sum. The short axis of the node is 
the diameter normally used by radiologists to judge if a node is involved by solid tumor. Nodal size 
is normally reported as 2 dimensions in the plane in which the image is obtained (for CT scan this is 
almost always the axial plane; for MRI the plane of acquisition may be axial, sagittal, or coronal). 
The smaller of these measures is the short axis. For example, an abdominal node which is reported 
as being 20 mm × 30 mm has a short axis of 20 mm and qualifies as a malignant, measurable node. 
In this example, 20 mm should be recorded as the node measurement. All other pathological nodes 
(those with short axis 10 mm but <15 mm) should be considered nontarget lesions. Nodes that 
have a short axis <10 mm are considered nonpathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
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sum diameters will be used as reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. 
Nontarget Lesions 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
nontarget lesions and should also be recorded at baseline. Measurements are not required and these 
lesions should be followed as “present”, “absent”, or in rare cases “unequivocal progression” (more 
details to follow). In addition, it is possible to record multiple nontarget lesions involving the same 
organ as a single item on the electronic case report form (eCRF) (eg, “multiple enlarged pelvic 
lymph node” or “multiple liver metastases”). 
GUIDELINES FOR EVALUATION OF MEASURABLE DISEASE 
All measurements should be recorded in metric notation, using calipers if clinically assessed. All 
baseline evaluations should be performed as close as possible to the treatment start and never more 
than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical examination. 
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial and 
P10 mm diameter as assessed using calipers (eg, skin nodules). For the case of skin lesions, 
documentation by color photography including a ruler to estimate the size of the lesion is suggested. 
As noted above, when lesions can be evaluated by both clinical examination and imaging, imaging 
evaluation should be undertaken since it is more objective and may also be reviewed at the end of 
the trial. 
Chest x-ray: Chest CT is preferred over chest x-ray, particularly when progression is an important 
endpoint, since CT is more sensitive than x-ray, particularly in identifying new lesions. However, 
lesions on chest x-ray may be considered measurable if they are clearly defined and surrounded by 
aerated lung. 
CT, MRI: CT is the best currently available and reproducible method to measure lesions selected for 
response assessment. This guideline has defined measurability of lesions on CT scan based on the 
assumption that CT slice thickness is 5 mm or less. When CT scans have slice thickness greater than 
5 mm, the minimum size for a measurable lesion should be twice the slice thickness. MRI is also 
acceptable in certain situations (eg, for body scans). 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a method 
of measurement. Ultrasound examinations cannot be reproduced in their entirety for independent 
review at a later date and, because they are operator dependent, it cannot be guaranteed that the 
same technique and measurements will be taken from one assessment to the next. If new lesions are 
identified by ultrasound in the course of the study, confirmation by CT or MRI is advised. If there is 
concern about radiation exposure at CT, MRI may be used instead of CT in selected instances. 
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Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation is not 
advised. However, they can be useful to confirm complete pathological response when biopsies are 
obtained or to determine relapse in trials where recurrence following complete response (CR) or 
surgical resection is an endpoint. 
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. If markers 
are initially above the upper normal limit, they must normalize for a patient to be considered in CR. 
Because tumor markers are disease specific, instructions for their measurement should be 
incorporated into protocols on a disease specific basis. Specific guidelines for both CA-125 
response (in recurrent ovarian cancer) and prostate-specific antigen response (in recurrent prostate 
cancer), have been published. In addition, the Gynecologic Cancer Intergroup has developed CA-
125 progression criteria that are to be integrated with objective tumor assessment for use in first-line 
trials in ovarian cancer. 
Cytology, histology: These techniques can be used to differentiate between partial response (PR) 
and CR in rare cases if required by protocol (for example, residual lesions in tumor types such as 
germ cell tumors, where known residual benign tumors can remain). When effusions are known to 
be a potential adverse effect of treatment (eg, with certain taxane compounds or angiogenesis 
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment can be considered if the measurable tumor has met criteria for response or 
stable disease (SD) in order to differentiate between response (or SD) and progressive disease (PD). 
RESPONSE CRITERIA 
Evaluation of Target Lesions 
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) 
must have reduction in short axis to <10 mm. 
PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the 
baseline sum diameters. 
PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the 
smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to 
the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. 
SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as 
reference the smallest sum diameters while on study. 
Lymph nodes: Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded (measured in the same anatomical plane as the baseline examination), even if 
the nodes regress to below 10 mm on study. This means that when lymph nodes are included as 
target lesions, the “sum” of lesions may not be zero even if CR criteria are met, since a normal 
lymph node is defined as having a short axis of <10 mm. Case report recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis <10 mm. For PR, SD, and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions. 
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Target lesions that become “too small to measure”: While on study, all lesions (nodal and non-
nodal) recorded at baseline should have their actual measurements recorded at each subsequent 
evaluation, even when very small (eg, 2 mm). However, sometimes lesions or lymph nodes which 
are recorded as target lesions at baseline become so faint on CT scan that the radiologist may not 
feel comfortable assigning an exact measure and may report them as being “too small to measure”. 
When this occurs it is important that a value be recorded on the eCRF. If it is the opinion of the 
radiologist that the lesion has likely disappeared, the measurement should be recorded as 0 mm. If 
the lesion is believed to be present and is faintly seen but too small to measure, a default value of 5 
mm should be assigned (Note: It is less likely that this rule will be used for lymph nodes since they 
usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too small 
to measure, a default value of 5 mm should be assigned in this circumstance as well). This default 
value is derived from the 5 mm CT slice thickness (but should not be changed with varying CT slice 
thickness). The measurement of these lesions is potentially nonreproducible; therefore, providing 
this default value will prevent false responses or progressions based upon measurement error. To 
reiterate, however, if the radiologist is able to provide an actual measure, that should be recorded, 
even if it is below 5 mm. 
Lesions that split or coalesce on treatment: When non-nodal lesions “fragment”, the longest 
diameters of the fragmented portions should be added together to calculate the target lesion sum. 
Similarly, as lesions coalesce, a plane between them may be maintained that would aid in obtaining 
maximal diameter measurements of each individual lesion. If the lesions have truly coalesced such 
that they are no longer separable, the vector of the longest diameter in this instance should be the 
maximal longest diameter for the “coalesced lesion”. 
Evaluation of Nontarget Lesions 
While some nontarget lesions may actually be measurable, they need not be measured and instead 
should be assessed only qualitatively at the time points specified in the protocol. 
CR: Disappearance of all nontarget lesions and normalization of tumor marker level. All lymph 
nodes must be nonpathological in size (<10 mm short axis). 
Non-CR/Non-PD: Persistence of one or more nontarget lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
PD: Unequivocal progression (see comments below) of existing nontarget lesions. 
When the patient also has measurable disease: In this setting, to achieve “unequivocal progression” 
on the basis of the nontarget disease, there must be an overall level of substantial worsening in 
nontarget disease such that, even in presence of SD or PR in target disease, the overall tumor burden 
has increased sufficiently to merit discontinuation of therapy. A modest “increase” in the size of one 
or more nontarget lesions is usually not sufficient to qualify for unequivocal progression status. The 
designation of overall progression solely on the basis of change in nontarget disease in the face of 
SD or PR of target disease will therefore be extremely rare. 
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When the patient has only nonmeasurable disease: This circumstance arises in some Phase 3 trials 
when it is not a criterion of trial entry to have measurable disease. The same general concept apply 
here as noted above, however, in this instance there is no measurable disease assessment to factor 
into the interpretation of an increase in nonmeasurable disease burden. Because worsening in 
nontarget disease cannot be easily quantified (by definition: if all lesions are truly nonmeasurable) a 
useful test that can be applied when assessing patients for unequivocal progression is to consider if 
the increase in overall disease burden based on the change in nonmeasurable disease is comparable 
in magnitude to the increase that would be required to declare PD for measurable disease: ie, an 
increase in tumor burden representing an additional 73% increase in “volume” (which is equivalent 
to a 20% increase diameter in a measurable lesion). Examples include an increase in a pleural 
effusion from “trace” to “large”, an increase in lymphangitic disease from localized to widespread, 
or may be described in protocols as “sufficient to require a change in therapy”. If “unequivocal 
progression” is seen, the patient should be considered to have had overall PD at that point. While it 
would be ideal to have objective criteria to apply to nonmeasurable disease, the very nature of that 
disease makes it impossible to do so; therefore, the increase must be substantial. 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of new 
radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought to 
represent something other than tumor (for example, some “new” bone lesions may be simply 
healing or flare of preexisting lesions). This is particularly important when the patient’s baseline 
lesions show PR or CR. For example, necrosis of a liver lesion may be reported on a CT scan report 
as a “new” cystic lesion, which it is not. 
A lesion identified on a follow-up trial in an anatomical location that was not scanned at baseline is 
considered a new lesion and will indicate disease progression. An example of this is the patient who 
has visceral disease at baseline and while on trial has a CT or MRI brain ordered which reveals 
metastases. The patient’s brain metastases are considered to be evidence of PD even if he/she did 
not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and follow-up 
evaluation will clarify if it represents truly new disease. If repeat scans confirm there is definitely a 
new lesion, then progression should be declared using the date of the initial scan. 
While FDG-PET (PET scanning with the tracer fluorine-18 [F-18]fluorodeoxyglucose [FDG]) 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly possible 
“new” disease). New lesions on the basis of FDG-PET imaging can be identified according to the 
following algorithm: 
 Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the 
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positive FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this 
is PD. If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression occurring 
at that site (if so, the date of PD will be the date of the initial abnormal FDG-PET scan). If 
the positive FDG-PET at follow-up corresponds to a preexisting site of disease on CT that is 
not progressing on the basis of the anatomic images, this is not PD. 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the study drug treatment 
until the end of treatment taking into account any requirement for confirmation. On occasion a 
response may not be documented until after the end of therapy so protocols should be clear if post-
treatment assessments are to be considered in determination of best overall response. Protocols must 
specify how any new therapy introduced before progression will affect best response designation. 
The patient’s best overall response assignment will depend on the findings of both target and 
nontarget disease and will also take into consideration the appearance of new lesions. Furthermore, 
depending on the nature of the trial and the protocol requirements, it may also require confirmatory 
measurement. Specifically, in nonrandomized trials where response is the primary endpoint, 
confirmation of PR or CR is needed to deem either one the “best overall response”. 
The best overall response is determined once all the data for the patient is known. Best response 
determination in trials where confirmation of CR or PR IS NOT required: Best response in these 
trials is defined as the best response across all time points (for example, a patient who has SD at 
first assessment, PR at second assessment, and PD on last assessment has a best overall response of 
PR). When SD is believed to be best response, it must also meet the protocol specified minimum 
time from baseline. If the minimum time is not met when SD is otherwise the best time point 
response, the patient’s best response depends on the subsequent assessments. For example, a patient 
who has SD at first assessment, PD at second and does not meet minimum duration for SD, will 
have a best response of PD. The same patient lost to follow-up after the first SD assessment would 
be considered unevaluable. 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial 
response; SD, stable disease. 
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Note: When nodal disease is included in the sum of target lesions and the nodes decrease to 
“normal” size (<10 mm), they may still have a measurement reported on scans. This measurement 
should be recorded even though the nodes are normal in order not to overstate progression should it 
be based on increase in size of the nodes. As noted earlier, this means that patients with CR may not 
have a total sum of “zero” on the eCRF. 
In trials where confirmation of response is required, repeated ‘not evaluable (NE)’ time point 
assessments may complicate best response determination. The analysis plan for the trial must 
address how missing data/assessments will be addressed in determination of response and 
progression. For example, in most trials it is reasonable to consider a patient with time point 
responses of PR-NE-PR as a confirmed response. 
Patients with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration”. Every effort should be made to document objective progression even after 
discontinuation of treatment. Symptomatic deterioration is not a descriptor of an objective response: 
it is a reason for stopping trial therapy. 
Conditions that define “early progression, early death, and inevaluability” are trial specific and 
should be clearly described in each protocol (depending on treatment duration, treatment 
periodicity). 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. When 
the evaluation of CR depends upon this determination, it is recommended that the residual lesion be 
investigated (fine needle aspirate/biopsy) before assigning a status of CR. FDG-PET may be used to 
upgrade a response to a CR in a manner similar to a biopsy in cases where a residual radiographic 
abnormality is thought to represent fibrosis or scarring. The use of FDG-PET in this circumstance 
should be prospectively described in the protocol and supported by disease specific medical 
literature for the indication. However, it must be acknowledged that both approaches may lead to 
false positive CR due to limitations of FDG-PET and biopsy resolution/ sensitivity. 
For equivocal findings of progression (eg, very small and uncertain new lesions, cystic changes, or 
necrosis in existing lesions), treatment may continue until the next scheduled assessment. If at the 
next scheduled assessment, progression is confirmed, the date of progression should be the earlier 
date when progression was suspected. 
CONFIRMATORY MEASUREMENT/DURATION OF RESPONSE 
Confirmation 
In nonrandomized trials where response is the primary endpoint, confirmation of PR and CR is 
required to ensure responses identified are not the result of measurement error. This will also permit 
appropriate interpretation of results in the context of historical data where response has traditionally 
required confirmation in such trials. However, in all other circumstances, ie, in randomized trials 
(Phase 2 or 3) or trials where stable disease or PD are the primary endpoints, confirmation of 
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response is not required since it will not add value to the interpretation of trial results. However, 
elimination of the requirement for response confirmation may increase the importance of central 
review to protect against bias, in particular in trials which are not blinded. 
In the case of SD, measurements must have met the SD criteria at least once after trial entry at a 
minimum interval (in general not less than 6 weeks). 
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are first met for 
CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded on study). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented. 
Duration of Stable Disease 
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum on 
study (if the baseline sum is the smallest, this is the reference for calculation of PD). 
The clinical relevance of the duration of stable disease varies in different studies and diseases. If the 
proportion of patients achieving stable disease for a minimum period of time is an endpoint of 
importance in a particular trial, the protocol should specify the minimal time interval required 
between two measurements for determination of stable disease. 
Note: The duration of response and stable disease as well as the progression-free survival are 
influenced by the frequency of follow-up after baseline evaluation. It is not in the scope of this 
guideline to define a standard follow-up frequency. The frequency should take into account many 
parameters including disease types and stages, treatment periodicity, and standard practice. 
However, these limitations of the precision of the measured endpoint should be taken into account if 
comparisons between trials are to be made. 
 
 
 
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APPENDIX 3. 
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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APPENDIX 4. 
CONTRACEPTION GUIDELINES AND DEFINITIONS OF “WOMEN OF 
CHILDBEARING POTENTIAL”, “NO CHILDBEARING POTENTIAL” 
Contraception Guidelines 
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) 
o Progestogen-only hormonal contraception associated with the inhibition of ovulation 
(oral, injectable, or implantable) 
 Intrauterine device 
 Intrauterine hormone-releasing system 
 Bilateral tubal occlusion 
 Vasectomized male partner 
 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. 
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. 
Definitions of “Women of Childbearing Potential", “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are female patients who are 
physiologically capable of becoming pregnant.  
Conversely, “women of no childbearing potential” are defined as female patients meeting > 1 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 
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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 
 
Strong and Moderate CYP3A 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 
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. 
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 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. 
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 
 
 
 
 
 
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APPENDIX 8. 
EUROPEAN QUALITY OF LIFE 5-DIMENSIONS 5-LEVELS HEALTH 
QUESTIONNAIRE 
 
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APPENDIX 9. 
EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF 
CANCER QUALITY OF LIFE CANCER QUESTIONNAIRE QLQ-C30 
 
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EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF 
CANCER QUALITY OF LIFE GASTRIC CANCER MODULE QLQ-ST022 
 
 
 
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APPENDIX 11. 
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) 
equation1 and the Modification of Diet in Renal Disease (MDRD) Study equation. The National 
Kidney Disease Education Program (NKDEP) calculators rely on creatinine determinations which 
are isotope dilution mass spectrometry (IDMS) traceable. All laboratories should be using creatinine 
methods calibrated to be IDMS traceable. Read more about creatinine standardization. 
This CKD-EPI equation calculator should be used when Scr reported in mg/dL. This equation is 
recommended when eGFR 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/health-
information/health-communication-programs/nkdep/lab-evaluation/gfr-calculators/Pages/gfr-
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APPENDIX 12. 
SIGNATURE OF INVESTIGATOR 
 
Protocol Title: 
A Phase 2, Double-blind, Randomized Study of BGB-290 versus Placebo as 
Maintenance Therapy in Patients with Inoperable Locally Advanced or 
Metastatic Gastric Cancer that Responded to Platinum-based First-line 
Chemotherapy 
 
Protocol Identifier: 
 
BGB-290-303 
 
This protocol is a confidential communication of BeiGene, Ltd. 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. 
 
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 the entire protocol and agree to carry out the study according to this protocol. 
 
Investigator’s Signature:   
_____________________________  
Investigator’s Printed Name:  _____________________________ 
Date (dd mmm yyyy):  
 
_____________________________ 
Name of the center in which  
the study will be conducted:    _____________________________  
 
 
 
 
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STATISTICAL ANALYSIS PLAN 
Study Protocol 
Number: 
BGB-290-303 
Study Protocol 
Title: 
A Phase 2, Double-blind, Randomized Study of BGB-290 versus Placebo 
as Maintenance Therapy in Patients with Inoperable Locally Advanced or 
Metastatic Gastric Cancer that Responded to Platinum-based First-line 
Chemotherapy 
 
Date: 
August 28, 2020 
Version: 
1.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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SIGNATURE PAGE 
Author: 
 
               
 Biometrics 
                
 
 
 
 
 
Signature 
Date:  ______________ 
 
 
 
Approval 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Data Science 
 
 
 
 
 
Signature 
Date: ________________ 
 
  Clinical 
Development 
 
 
 
 
Signature 
Date: ________________ 
 
 Clinical Development 
 
 
 
Signature 
Date: ________________ 
 
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TABLE OF CONTENTS 
1 
INTRODUCTION 
6 
2 
STUDY OVERVIEW 
6 
3 
STUDY OBJECTIVES 
7 
3.1 
Primary Objectives 
7 
3.2 
Secondary Objectives 
7 
3.3 
Exploratory Objectives 
7 
4 
STUDY ENDPOINTS 
8 
4.1 
Primary Endpoints 
8 
4.2 
Secondary Endpoints 
8 
4.3 
Exploratory Endpoints 
8 
5 
SAMPLE SIZE CONSIDERATIONS 
9 
6 
STATISTICAL METHODS 
9 
6.1 
Analysis Sets 
9 
6.2 
Data Analysis General Considerations 
10 
6.2.1 
Definitions and Computations 
10 
6.2.2 
Conventions 
10 
6.2.3 
Handling of Missing Data 
11 
6.2.4 
Adjustment for Covariates 
11 
6.2.5 
Multiplicity Adjustment 
11 
6.2.6 
Data Integrity 
11 
6.3 
Patient Characteristics 
12 
6.3.1 
Patient Disposition 
12 
6.3.2 
Protocol Deviations 
12 
6.3.3 
Demographic and Baseline Characteristics 
12 
6.3.4 
Disease History 
13 
6.3.5 
Prior Anticancer Drug Therapies  and Radiotherapy 
13 
6.3.6 
Medical History 
13 
6.3.7 
Prior and Concomitant Medications 
14 
6.3.8 
Procedure or Surgery 
14 
6.3.9 
Post Treatment Anticancer Drug Therapy 
14 
6.4 
Efficacy Analysis 
14 
6.4.1 
Primary Efficacy Analysis 
14 
6.4.2 
Secondary Efficacy Analysis 
16 
6.4.3 
Subgroup Analyses 
18 
6.4.4 
Exploratory Efficacy Analysis 
19 
6.5 
Safety Analyses 
19 
6.5.1 
Extent of Exposure 
19 
6.5.2 
Adverse Events 
20 
6.5.3 
Death 
21 
6.5.4 
Laboratory Values 
21 
6.5.5 
Vital Signs 
22 
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6.5.6 
Electrocardiograms (ECG) 
22 
6.5.7 
Eastern Cooperative Oncology Group (ECOG) 
23 
6.6 
Pharmacokinetic Analyses 
23 
6.7 
Pharmacodynamic Analyses 
23 
7 
INTERIM ANALYSIS 
24 
8 
CHANGES IN THE PLANNED ANALYSIS 
24 
9 
REFERENCES 
24 
10 
APPENDIX 
26 
10.1 
handling of partially missing dates 
26 
 
 
 
 
 
 
 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Term 
AE 
adverse event 
CI 
confidence interval 
CR 
complete response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer 
Quality of Life Cancer Questionnaire 
EORTC QLQ-STO22 
European Organisation for Research and Treatment of Cancer 
Quality of Life gastric cancer module 
EOT 
end of treatment 
EQ-5D-5L 
European Quality of Life 5-Dimensions 5-Levels Health 
Questionnaire 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
ITT 
Intent-to-Treat 
LOH 
loss of heterozygosity 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for 
Adverse Events 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
preferred term 
QTcB 
QT interval corrected for heart rate using Bazett's formula 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
ROW 
rest of world 
SAE 
serious adverse event 
SD 
stable disease 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TSST 
Time from randomization to second subsequent anticancer therapy 
or death 
ULN 
upper limit of normal 
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1 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the procedures and the statistical 
methods that will be used to analyze and report results for Protocol BGB-290-303: A Phase 2, 
Double-blind, Randomized Study of BGB-290 (pamiparib) versus Placebo as Maintenance 
Therapy in Patients with Inoperable Locally Advanced or Metastatic Gastric Cancer that 
Responded to Platinum-based First-line Chemotherapy. The focus of this SAP is for the planned   
final analysis specified in the study protocol. 
Reference materials for this statistical plan include the protocol BGB-290-303 (version 1.0, 
2020-02-13). If the protocol or case report forms are amended or updated then appropriate 
adjustments to the SAP may be made if they are related to the planned analyses. 
The SAP described hereafter is an a priori plan. The SAP will be finalized and approved before 
database lock for the primary analysis of this study. Statistical programming may occur in a 
blinded manner as study data accumulate to have analysis programs ready at the time of database 
lock. 
2 
STUDY OVERVIEW 
This is a double-blind, placebo-controlled, randomized, multicenter, global Phase 2 study 
comparing the efficacy and safety of single-agent poly (ADP-ribose) polymerase (PARP) 
inhibitor pamiparib to placebo as maintenance therapy in patients with advanced gastric cancer 
who have completed first-line platinum-based chemotherapy.  
To be eligible for participation in the study, patients must have histologically confirmed 
adenocarcinoma of the stomach or gastroesophageal junction with inoperable locally advanced 
or metastatic disease. Patients must have achieved a partial response (PR) that is maintained for 
≥ 4 weeks or complete response (CR) as determined by the investigator according to Response 
Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 with platinum-based first-line 
chemotherapy. 
All patients will be randomized within 8 weeks after the last platinum dose of first-line 
chemotherapy. Central interactive response technology will be used to randomize patients in a 
1:1 ratio and assign eligible patients to 1 of 2 arms: Arm A – pamiparib or Arm B – Placebo. 
Patient randomization will be stratified by: 
• HRD status (LOHhigh versus LOHlow versus unknown) 
• Region (China/Hong Kong/Taiwan versus Australia/Europe/North America versus 
Japan/South Korea versus rest of world [ROW]) 
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• Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1) 
3 
STUDY OBJECTIVES 
3.1 
PRIMARY OBJECTIVES  
• To evaluate the efficacy of maintenance therapy with pamiparib versus placebo in 
patients with inoperable locally advanced or metastatic gastric cancer with a CR or 
confirmed PR after first-line platinum-based chemotherapy, as measured by: 
o Progression-free survival (PFS) by RECIST Version 1.1 by investigator assessment 
3.2 
SECONDARY OBJECTIVES  
• To further evaluate the efficacy of maintenance therapy with pamiparib versus placebo in 
patients with inoperable locally advanced or metastatic gastric cancer with a CR or 
confirmed PR after first-line platinum-based chemotherapy, as measured by: 
o Overall survival (OS) 
o Time to second subsequent treatment (TSST)   
o Objective response rate (ORR; CR or PR) by investigator assessment 
o Duration of response (DOR) by investigator assessment 
o Time to response by investigator assessment 
• To evaluate safety and tolerability of pamiparib versus placebo, as measured by: 
o Incidence, timing, and severity of treatment-emergent adverse events (TEAEs), 
graded according to National Cancer Institute-Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) Version 4.03 or higher 
3.3 
EXPLORATORY OBJECTIVES 
• To confirm the PK of pamiparib, as measured by: 
o Lowest observed plasma concentrations (Ctrough) at steady-state and plasma 
concentration two hours post-dose (C2h) after a single dose and at steady-state for 
patients who received pamiparib 
• To assess patient-reported outcomes on health-related quality of life, as measured by: 
o European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) 
o European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire (EORTC QLQ-C30) 
o EORTC QLQ gastric cancer module (EORTC QLQ-STO22) 
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• To explore potential biomarkers associated with the pharmacodynamics, response, and 
resistance to pamiparib: 
o Including, but not limited to, expression and mutations of genes in the DNA damage 
response pathway, LOH, and relationship to efficacy and resistance to pamiparib 
4 
STUDY ENDPOINTS 
4.1 
PRIMARY ENDPOINTS 
PFS, defined as the time from randomization to progressive disease (PD) per RECIST Version 
1.1 by investigator assessment or death due to any cause, whichever occurs first. 
4.2 
SECONDARY ENDPOINTS 
Efficacy assessment: 
• OS, defined as the time from randomization to death due to any cause  
• Time to second subsequent treatment (TSST), defined as the time from randomization 
until the second subsequent anticancer therapy or death after next-line therapy  
• ORR, defined as the proportion of patients with a best overall response of CR or PR per 
RECIST Version 1.1 by investigator assessment  
• DOR, defined as the time from the first documented confirmed response of CR or PR to 
PD per RECIST Version 1.1 by investigator assessment or death due to any cause, 
whichever occurs first 
• Time to response, defined as the time from randomization to the first documented  
response of CR or PR per RECIST Version 1.1 by investigator assessment 
  Safety assessment: 
• Incidence, timing, and severity of TEAEs, graded according to NCI-CTCAE Version 
4.03 or higher 
• Safety and tolerability assessment of laboratory measurements, vital signs, and ECG 
findings 
4.3 
EXPLORATORY ENDPOINTS 
Pharmacokinetics (PK) assessment: 
• Lowest observed plasma concentrations (Ctrough) at steady-state for patients who received 
pamiparib  
Patient reported outcomes (PRO) assessments: 
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• European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) 
• European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire (EORTC QLQ-C30) 
• EORTC QLQ gastric cancer module (EORTC QLQ-STO22) 
Biomarkers assessment associated with the pharmacodynamics, response, and resistance to 
pamiparib: 
• Including, but not limited to, expression and mutations of genes in the DNA damage 
response pathway, LOH, and relationship to efficacy and resistance to pamiparib 
5 
SAMPLE SIZE CONSIDERATIONS 
This study is designed to provide 80% power for PFS. The following assumptions are used in 
determining the sample size for this study: 
• Overall type I error rate: 0.1 (1-sided) 
• Randomization: 1:1 
• Median PFS for placebo group: 6.0 months 
• PFS hazard ratio (HR; pamiparib/placebo): 0.63 
A sample size of approximately 128 patients (64 per treatment group) is required to achieve 85 
PFS events within the planned study duration of approximately 26 months after the first patient 
is randomized to study, assuming an estimated accrual period of 20 months. 
6 
STATISTICAL METHODS 
6.1 
ANALYSIS SETS 
Intent-to-Treat (ITT) Analysis Set includes all randomized patients who are assigned to study 
treatment (pamiparib or placebo). The ITT Analysis Set will be used for all efficacy analyses, 
except for endpoints ORR, DOR and time to response.   
Safety Analysis Set includes all patients in the ITT Analysis Set who receive at least one dose of 
study treatment (pamiparib or placebo). The Safety Analysis Set will be used for all safety 
analyses. 
Efficacy Evaluable Analysis Set includes all randomized patients who had measurable disease at 
baseline and had at least one post baseline tumor assessment unless discontinued treatment due 
to clinical progression or death prior to tumor assessment. The Efficacy Evaluable Analysis Set 
will be used for all efficacy analyses related to ORR, DOR and time to response by investigator 
assessment. 
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PK Analysis Set includes all patients who received pamiparib and contributed at least one plasma 
concentration. 
6.2 
DATA ANALYSIS GENERAL CONSIDERATIONS 
6.2.1 
Definitions and Computations 
Study day: Study day will be calculated in reference to the randomization date for efficacy 
analysis, and date of the first dose of study treatment for safety analysis. For assessments 
conducted on or after the randomization date or date of the first dose of study treatment, study 
day will be calculated as (assessment date – randomization date or date of first dose of study 
treatment + 1).  For assessments conducted before the randomization date or date of the first dose 
of study treatment, study day is calculated as (assessment date – randomization date or date of 
first dose of study treatment). There is no study day 0.  
In the situation where the event date is partial or missing, the date will appear partial or missing 
in the listings. Study day and any corresponding durations will be presented based on the 
imputations specified in Appendix 10.1. 
Treatment duration: The treatment duration will be calculated as (date of last dose of study 
treatment – date of first dose of study treatment + 1). 
Baseline: Unless otherwise specified, a baseline value is defined as the last non-missing value 
collected before the time of first dose date. The baseline tumor assessment is defined as the 
screening assessment in reference to randomization date. 
All calculations and analyses will be conducted using SAS version 9.4 or higher. 
6.2.2 
Conventions 
Unless otherwise specified, the following conventions will be applied to all analyses: 
• 1 year = 365.25 days. Number of years is calculated as (days / 365.25) rounded up to the 
nearest tenth (.1) unless otherwise specified. 
• 1 month = 30.4375 days. Number of months is calculated as (days / 30.4375) rounded up 
to the nearest tenth (.1) unless otherwise specified. 
• P-values will be rounded to 4 decimal places.  P-values that round to 0.0000 will be 
presented as ‘< 0.0001’ and p-values that round to 1.000 will be presented as ‘> 0.9999’.   
• Duration of imaging-based event endpoints (such as PFS) will be based on the actual date 
the radiograph was obtained rather than the associated visit date. 
• Missing efficacy or safety data will not be imputed unless otherwise specified. 
• For laboratory results collected as < or >, a numeric value, 0.0000000001 will be 
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subtracted or added, respectively, to the value. 
• For by-visit observed data analyses, percentages will be calculated based on the number 
of patients with nonmissing data as the denominator, unless otherwise specified. 
• For continuous endpoints, summary statistics will include n, mean, standard deviation, 
median, Q1 (the median of the lower half of the data), Q3 (the median of the upper half 
of the data) and range (minimum and maximum).  
• For discrete endpoints, summary statistics will include frequencies and percentages. 
6.2.3 
Handling of Missing Data 
Missing data will not be imputed unless otherwise specified elsewhere in the SAP. Missing dates 
or partially missing dates will be imputed conservatively for adverse events, concomitant 
medications, disease history, and prior therapy. Specific rules for handling of missing or partially 
missing dates for adverse events and prior/concomitant medications/procedures are provided in 
Appendix 10.1. 
By-visit endpoints will be analyzed using observed data as captured in electrical data base, 
unless otherwise specified. For observed data analyses, missing data will not be imputed and 
only the observed records will be included.  
At the time of primary analysis, if death or disease progression is not observed from a patient, 
corresponding censoring rules for OS, DOR and PFS will be followed.  
6.2.4 
Adjustment for Covariates 
Adjustments for stratification factors (region, ECOG performance status) as covariates are 
planned for primary and secondary analyses in the study. Baseline characteristics may be used in 
the model as additional covariates as supportive exploratory analyses, if deemed necessary.  
6.2.5 
Multiplicity Adjustment 
No multiplicity adjustment is considered in this study. 
6.2.6 
Data Integrity 
Before final statistical analysis begins, the integrity of the data should be reviewed to assure fit-
for-purpose.  The data set for analysis should be an accurate and complete representation of the 
patients' relevant outcomes from the clinical database.  All data should be complete and reviewed 
up to a pre-specified cutoff date.  Consistency checks and appropriate source data verification 
should be complete. 
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6.3 
PATIENT CHARACTERISTICS 
6.3.1 
Patient Disposition 
The following patient disposition information will be summarized by treatment groups in the ITT 
Analysis Set:  
• Number of randomized patients 
• Number of treated patients  
• Number (percentage) of treated patients who discontinued treatment  
• Reason for treatment discontinuation  
• Number (percentage) of treated patients who discontinued study (including those who 
discontinued study treatment and did not enter survival follow-up, and those discontinued 
from the survival follow-up) 
• Reason for study discontinuation 
• Duration of follow-up 
The primary reason for study treatment and study discontinued will be summarized according to 
the categories in the electronic case report form. 
Survival status (alive, deceased, withdrew consent, lost to follow-up, or unknown) at the data 
cutoff date will be listed using the data from the survival follow-ups. 
6.3.2 
Protocol Deviations 
Major protocol deviation criteria will be established and patients with major protocol deviations 
will be identified and documented before the database lock. Major protocol deviations will be 
summarized for all patients in the ITT Analysis Set. They will also be listed by each category. 
6.3.3 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized using descriptive statistics for 
patients in the ITT Analysis Set:   
• Age (years) and age categorized (years) as < 65, ≥ 65    
• Gender 
• Race 
• Ethnicity 
• Height (cm) and weight (kg) 
• Body mass index (BMI in kg/m2) 
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• Eastern Cooperative Oncology Group (ECOG) performance status   
A listing of demographic and baseline characteristics for patients in the ITT Analysis Set will be 
provided. 
6.3.4 
Disease History 
The number (percentage) of patients reporting a history of disease and characteristic, as recorded 
on the CRF, will be summarized for patients in the ITT Analysis Set. The following will be 
included for disease history and characteristics:  
• Primary location/types of solid tumor 
• Solid tumor staging  
• Time since initial diagnosis, defined as date of first dose of study treatment minus date of 
initial diagnosis 
• Histologic grade 
• Metastatic disease location 
A listing of disease history and characteristics for patients in the ITT Analysis Set will be 
provided. 
6.3.5 
Prior Anticancer Drug Therapies  and Radiotherapy   
The number and percentage of patients with prior anticancer drug therapies, number of prior 
regimen, duration of last therapy, best overall response for last therapy, reason that last therapy 
ended, time from end of last therapy to study entry, treatment setting for last therapy, and name 
and/or type of drug will be summarized for patients treated in the ITT Analysis Set. 
The number and percentage of patients with any prior anticancer radiotherapy, number of all 
prior radiotherapy treatments, intent and setting of therapy, site irradiated, time from end of last 
radiotherapy to study entry, and duration of last therapy will be summarized for patients treated 
in the ITT Analysis Set.  
The therapies with the same sequence/regimen number are counted as one prior therapy. 
Previous anticancer medication will be summarized in WHO DD preferred term. 
A listing of prior anticancer drug therapies and radiotherapy in the ITT Analysis Set will be 
provided. 
6.3.6 
Medical History 
Medical History will be coded using MedDRA Version 22 or higher. The number (percentage) 
of patients reporting a history of any medical condition, as recorded on the CRF, will be 
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summarized by system organ class and preferred term in the ITT Analysis Set. A listing of 
medical history will be provided. 
6.3.7 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the version of World Health Organization 
Drug Dictionary (WHO DD) drug codes currently in effect at BeiGene at the time of database 
lock and will be further classified to the appropriate Anatomical Therapeutic Chemical (ATC) 
code.  
The number (percentage) of patients reporting prior and concomitant medications will be 
summarized by ATC medication class and WHO DD preferred term in the ITT Analysis Set. 
Prior medications are defined as medications that started and ended before the first dose date. 
Concomitant medications will be defined as medications that (1) started before the first dose of 
study treatment and were continuing at the time of the first dose of study treatment, or (2) started 
on or after the date of the first dose of study treatment up to 30 days after the patient’s last dose 
or initiation of a new anticancer therapy. A listing of prior and concomitant medications will be 
provided. 
6.3.8 
Procedure or Surgery 
The number and percentage of patients with any procedure or surgery, name of procedure or 
surgeries, and reason for procedure or surgery will be summarized for patients treated in the ITT 
Analysis Set. 
A listing of procedure or surgery for patients in the ITT Analysis Set will be provided. 
6.3.9 
Post Treatment Anticancer Drug Therapy 
The number and percentage of patients with post-treatment anticancer drug therapies, number of 
post treatment regimen, time to first post treatment therapy, best overall response for therapy, 
name of medication, and duration of post treatment therapy will be summarized for patients 
treated in the ITT Analysis Set. 
The therapies with the same sequence/regimen number are counted as one post-treatment therapy. 
Post treatment anticancer medication will be summarized in WHO DD preferred term. 
A listing of post treatment anticancer therapy for patients in the ITT Analysis Set will be 
provided. 
6.4 
EFFICACY ANALYSIS 
6.4.1 
Primary Efficacy Analysis 
Progression-Free Survival (PFS) 
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PFS is defined as the time from randomization date to disease progression per RECIST Version 
1.1 by investigator assessment or death, whichever occurs first.   
The final PFS analysis will be performed when 85 PFS events have occurred. The final PFS 
analysis will include all PFS events up to the date of data cutoff which is pre-defined based on 
the projected 85 PFS events on the blinded manner. A stratified 1-sided log-rank test at a 0.1 
significance level incorporating the randomized stratification factors will be used to compare the 
distribution of PFS between pamiparib (Arm A) and placebo (Arm B).    
The null and alternative hypotheses for the final PFS analysis are as follows: 
H0: hazard ratio [HR] (pamiparib/placebo) = 1 
Ha: hazard ratio [HR] (pamiparib/placebo) < 1  
The treatment effect will be estimated by fitting a Cox Proportional Hazards model to the PFS 
including treatment arm as a factor and stratification factors (region, ECOG performance status) 
as strata. From this model, the HR will be estimated and presented with a 2-sided 95% CI.  
The median and other quartiles of PFS for each treatment group will be estimated using the 
Kaplan-Meier method, and the 2-sided 95% CI will be calculated using the Brookmeyer-
Crowley method (Brookmeyer and Crowley, 1982). The point estimate of PFS rates and the 
corresponding 95% CIs at selected landmark points (every three months up to 24 months) will be 
provided based on the Greenwood’s estimate of the variance (Greenwood 1926). Kaplan-Meier 
curves for PFS will also be generated and plotted over time to provide a visual description of the 
PFS change over time. Primary efficacy analysis will be conducted by using the ITT Analysis 
Set. 
PFS censoring rule will follow FDA Guidance for Industry, Clinical Trial Endpoints for 
Approval of Cancer Drugs and Biologics (2007). Data for patients without PD per RECIST 
Version 1.1 or death at the time of analysis will be censored at the date of the last tumor 
assessment. Data for patients who are lost to follow-up before documented PD will be censored 
at the last tumor assessment date when the patient is known to be progression-free. Data for 
patients who started new anticancer therapy will be censored at the last tumor assessment date 
before the introduction of new anticancer therapy. Data for patients who had 2 or more 
consecutive missed scheduled tumor assessments immediately before PD or death will be 
censored at the last tumor assessment date before the 2 missed tumor assessments.   
Table 1 shows the primary censoring rules for the derivation of PFS using RECIST 1.1 criteria 
based upon investigator’s tumor assessment.  
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Table 1. Censoring Rules for Analysis of Progression-Free Survival Per RECIST 1.1 
No. Situation 
Date of Progression or Censoring 
Outcome 
1 
No baseline or postbaseline tumor 
assessments 
Randomization date  
Censored 
2 
Progression documented on scheduled 
visit or between scheduled visits 
Date of first radiologic PD 
assessment  
Progressed 
3 
No progression at the time of data cut-off 
or withdrawal from study 
Date of last adequate radiologic 
assessment before or on date of data 
cut-off or withdrawal from study 
Censored 
4 
New anticancer treatment started 
Date of last radiologic assessment 
before or on date of new anticancer 
treatment 
Censored 
5 
Death before first PD assessment 
Date of death 
Progressed 
6 
Death between adequate assessment 
visits* 
Date of death 
Progressed 
7 
Death or progression after immediate more 
than one missed visit** 
Date of last adequate radiologic 
assessment before missed tumor 
assessments 
Censored 
Abbreviations: CR = complete response, PD = progressive disease, PR = partial response, SD = stable disease, 
* Adequate tumor assessment is a radiologic assessment of CR, PR, SD, non-CR/non-PD or PD as determined by 
investigators. 
** More than one missed visit is defined if the duration between the last tumor assessment and death or PD is longer 
than 17 weeks (eg, 16 week + 1 week).  
6.4.2 
Secondary Efficacy Analysis 
Overall Survival (OS) 
OS is the key secondary efficacy endpoint and is defined as the time from randomization to death 
due to any cause.   
A stratified log-rank test incorporating the randomized stratification factors (region, ECOG 
performance status) will be used to compare treatment groups. The HR and its 2-sided 95% CI 
will be estimated using the stratified Cox-proportional hazards model. The median and other 
quartiles of OS for each treatment group will be estimated using the Kaplan-Meier method and 
the 95% CI will be calculated using the Brookmeyer-Crowley method (Brookmeyer and 
Crowley, 1982). Kaplan-Meier curves for OS will also be generated and plotted over time to 
provide a visual description of the OS change over time.  
OS data will be censored at the date that the patient was last known to be alive before the date of 
data cutoff. For patient who died and have last known alive date after the date of data cutoff, OS 
data will be censored at the date of data cutoff. Analysis will be conducted by using the ITT 
Analysis Set.  
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Time to second subsequent treatment (TSST)   
TSST is defined as the time from randomization until the second subsequent anticancer therapy 
or death. The second subsequent anicancer therapy should be conditional on the first anticancer 
therapy and on or after date of PD from the first anticancer therapy. Patients alive and without 
the second anticancer therapy, or alive with the second anticancer therapy but no PD from the 
first anticancer therapy will be censored at last known alive. Details of the censoring rule are 
specified in Table 2. 
If data collected is deemed as suffice, TSST will be assessed using a stratified log-rank test 
incorporating the randomized stratification factors (region, ECOG performance status) in ITT 
Analysis Set. The HR and its 2-sided 95% CI will be estimated using the stratified Cox-
proportional hazards model. The median and other quartiles of TSST for each treatment group 
will be estimated using the Kaplan-Meier method and the 95% CI will be calculated using the 
Brookmeyer-Crowley method (Brookmeyer and Crowley, 1982). Analysis will be conducted by 
using the ITT Analysis Set. 
Table 2. Censoring Rules for Analysis of TSST 
No. Situation 
Date of Progression or 
Censoring 
Outcome 
1 
Death 
Death Date 
Event 
2 
Second subsequent 
anticancer therapy 
Second subsequent anticancer 
therapy start date 
Event 
3 
No event of interest 
when analysis 
Last available date from the 
following for patient with EOT: 
1) EOT date    
2) Last long-term followup 
visit date   
3) Post-treatment anticancer 
treatment date 
Or cutoff date for patient on 
treatment 
Censored 
 
Objective Response Rate (ORR) by investigator assessment 
ORR is defined as the proportion of patients with a best overall response of CR or PR per 
RECIST Version 1.1 by investigator assessment for the Efficacy Evaluable Analysis Set, before 
data cutoff or initiation of the next line of anticancer therapy, whichever comes first. The number 
and proportion of patients who achieve CR or PR according to both RECIST 1.1 will be 
summarized. Patients without postbaseline tumor assessment will be considered as non-
responders. The ORR and its exact 2-sided 95% CI will be reported for each treatment group. A 
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Cochran-Mantel-Haenszel score test will be used to compare treatment groups. Confirmation of 
CR and PR are not required in this randomized study per RECIST v1.1. 
The best overall response (BOR) will be summarized by the following categories for the Efficacy 
Evaluable Analysis Set. Patients without post-baseline disease assessment should be considered 
non-responders. 
• Complete response 
• Partial response   
• Stable disease 
• Progressive disease 
• Not evaluable / Not evaluated 
Duration of Response (DOR) 
DOR is defined as the time from the first documented confirmed response of CR or PR to PD per 
RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs 
first. Only patients with CR or PR during the study will be included in duration of response 
analysis. Censoring rule for DOR will follow PFS censoring rule. 
The median and other quartiles of duration of response and its 2-sided 95% CI for each treatment 
group will be provided. Kaplan-Meier curve will be used to estimate median time and 95% CI 
for duration of response.  
Waterfall plots will be provided for the maximum tumor shrinkage based on target lesion. The 
maximum tumor shrinkage based on target lesion used in the plots will be listed. These analyses 
will be performed based on RECIST 1.1. 
Time to response by investigator assessment 
Time to response is defined as the time from randomization to the first documented confirmed 
response of CR or PR per RECIST Version 1.1 by investigator assessment. Only patients with 
CR or PR during the study will be included in time to response analysis. Descriptive statistics 
will be provided for the Efficacy Evaluable Analysis Set. 
6.4.3 
Subgroup Analyses 
Table and forest plot of subgroup analysis in PFS will be provided based on the following 
subgroups:   
• Geographic region (China/Hong Kong/Taiwan versus Australia/Europe/North America 
versus Japan/South Korea versus ROW) 
• EGOG performance status at baseline (0 versus 1) 
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• Age at baseline:  < 65 years versus ≥ 65 years  
• Race: White versus Asian versus others  
These planned subgroup analyses may not be explored if sufficient number of samples cannot be 
achieved for certain subgroups. 
6.4.4 
Exploratory Efficacy Analysis 
The scores from these following health-related questionnaires will be summarized by each 
assessment and treatment descriptively (n [%] for categorical variables):   
• European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L) 
• European Organisation for Research and Treatment of Cancer Quality of Life Cancer 
Questionnaire (EORTC QLQ-C30) 
• EORTC QLQ gastric cancer module (EORTC QLQ-STO22) 
The actual scale and the change from baseline to each post-baseline visit and to the end of 
treatment on overall health in EQ-5D-5L and overall health and quality of life in EORTC QLQ-
C30 will be summarized by visit using descriptive summary statistics (n, mean, standard 
deviation, median, Q1, Q3, minimum, and maximum for continuous variables). A listing of 
scores from these health-related questionnaires for patients in the ITT Analysis Set will be 
provided. 
6.5 
SAFETY ANALYSES 
All safety analyses will be performed by cohort and by total (combined cohorts) based on the 
Safety Analysis Set. The incidence of treatment-emergent adverse events (TEAEs) and SAEs 
will be summarized. Laboratory test results, vital signs, ECG, ECOG and their changes from 
baseline will be summarized using descriptive statistics (eg, n, mean, standard deviation, median, 
Q1, Q3, minimum, maximum for continuous variables; n [%] for categorical variables).  
Abnormal values will be flagged. 
6.5.1 
Extent of Exposure 
The duration of treatment (months) will be summarized with descriptive statistics.  It will be 
calculated as (Date of last non-zero dose – Date of first dose + 1) / 30.4375. The total dose 
received per patient (mg), which is sum of actual received doses per patient, will also be 
summarized with descriptive statistics.  
Number of patients with dose modification and their reasons, and number of patients with any 
dose missed, reduced, and increased will be summarized by counts and percentages. In addition, 
frequency of dose reductions, dose missed, and dose increased will be summarized by categories.  
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Average dose intensity per patient (in mg/day) and relative dose intensity (total dose received / 
total dose prescribed) per patient will be summarized. Average dose intensity is calculated as the 
total dose (mg) taken by a patient divided by overall duration of exposure (= date of last non-
zero dose – date of first dose + 1) for this patient. Relative dose intensity is calculated as the total 
dose (mg) taken by a patient divided by the total dose prescribed for the patient.   
Patient data listings will be provided for all dosing records, and for the above calculated 
summary statistics. 
6.5.2 
Adverse Events  
AEs will be graded by the investigators using NCI CTCAE v4.03. The AE verbatim descriptions 
(investigator terms from the CRF) will be classified into standardized medical terminology using 
the Medical Dictionary for Regulatory Activities (MedDRA). Adverse events will be coded to 
the MedDRA (Version 22.0 or higher) lower level term closest to the verbatim term.  The linked 
MedDRA preferred term (PT) and primary system organ class (SOC) are also captured in the 
database. 
A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or 
after the date of the first dose of study treatment through 30 days after the last dose (permanent 
discontinuation of study treatment) or initiation of new anticancer therapy. Only those AEs that 
were treatment emergent will be included in summary tables.  All AEs, treatment emergent or 
otherwise, will be presented in patient data listings. 
An overview table of patients with at least one TEAE will be presented, as the number 
(percentage), with the incidence of following: 
• patients with any TEAE 
• patients with any TEAE with Grade 3 or higher  
• patients with any serious TEAE  
• patients with any TEAE leading to death  
• patients with any TEAE leading to treatment discontinuation 
• patients with any TEAE leading to dose modification 
o patients with any TEAE leading to dose interruption 
o patients with any TEAE leading to dose reduction   
• patients with any treatment-related TEAE 
• patients with any treatment-related TEAE with Grade 3 or higher  
• patients with any treatment-related serious TEAE  
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• patients with any treatment-related TEAE leading to death  
• patients with any treatment-related TEAE leading to treatment discontinuation 
• patients with any treatment-related TEAE leading to dose modification 
o patients with any treatment-related TEAE leading to dose interruption 
o patients with any treatment-related TEAE leading to dose reduction  
Summaries of all above TEAEs will also be reported as the number (percentage) of patients by 
SOC and PT.   
Summaries of all TEAEs, SAE, Grade 3 or higher TEAEs, treatment-related TEAEs, and TEAE 
leading to treatment discontinuation will also be provided by PT only in descending order of 
frequency.   
All TEAEs, SAE, Grade 3 or higher TEAEs, treatment-related TEAEs and TEAEs leading to 
treatment discontinuation will also be summarized by SOC, PT, and maximum severity. A 
patient will be counted only once by the highest severity grade according to CTCAE v.4.03 
within an SOC and PT, even if the patient experienced more than 1 TEAE within a specific SOC 
and PT. 
Patient data listings of all AEs, SAEs, treatment-related AEs, Grade 3 or above AEs, AEs that 
led to death, AEs that led to treatment discontinuation, and AEs that led to dose modification will 
be provided. 
6.5.3 
Death 
All deaths and causes of death will be summarized by treatment arm, including those occurred 
during the study treatment period and those reported during the survival follow-up period after 
treatment completion/discontinuation. Patient data listings of death will be provided. 
6.5.4 
Laboratory Values 
Laboratory safety tests of serum chemistry and hematology will be evaluated for selected 
parameters described in Table 3.  The actual value and the change from baseline to each post-
baseline visit and to the end of treatment will be summarized by visit using descriptive summary 
statistics (n, mean, standard deviation, median, minimum, maximum for continuous variables).    
Urinalysis includes blood, protein, ketones, glucose, red blood cells, and white blood cells. 
Urinalysis results will not be summarized descriptively by visit.  
Laboratory parameters that are graded in NCI CTCAE (v.4.03) will be summarized by shifts 
from baseline CTCAE grades to maximum post-baseline grades. In the summary of laboratory 
parameters by CTCAE grade, parameters with CTCAE grading in both high and low directions 
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will be summarized separately. Number (percentage) of patients with abnormal postbaseline 
laboratory values will be summarized. 
Patient data listings of selected hematology and serum chemistry parameters, and urinalysis will 
be provided. 
A summary of the liver function test abnormalities will also be presented based on Hy’s law 
laboratory criteria defined as 1) Alanine aminotransferase (ALT) or Aspartate aminotransferase 
(AST) > 3 x ULN, 2) Total bilirubin (TBL) > 2 x ULN and 3) Alkaline phosphatase (ALP) < 2 x 
ULN and ALP ≥ 2 x ULN for patients with 1) and 2), at any postbaseline visit.   
Table 3. Serum Chemistry, Hematology, and Urinalysis Laboratory Tests 
Serum Chemistry 
Hematology 
Urinalysis  
Alkaline phosphatase (ALP) 
Hemoglobin 
Blood  
Alanine aminotransferase (ALT) 
Platelet counts 
Protein  
Aspartate aminotransferase (AST) 
White blood cell (WBC) count 
Ketones  
Albumin 
Neutrophil   
Glucose  
Total bilirubin 
Lymphocyte   
Red blood cells  
Blood Urea Nitrogen 
  
White blood cells  
Creatinine 
   
 
Chloride 
  
 
Phosphate 
 
 
Glucose 
 
 
Lactate dehydrogenase 
 
 
Total Protein 
 
 
Potassium 
 
 
Sodium 
  
 
 
  
6.5.5 
Vital Signs 
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
temperature, and weight) and changes from baseline will be presented by visit.  Vital signs will 
be listed by patients and visits. 
6.5.6 
Electrocardiograms (ECG) 
ECG will be obtained during screening, predose and 2 hours postdose on Cycle 1 Day 1 and 
Cycle 1 Day 15, and end of treatment (EOT). Additional ECGs may be performed as clinically 
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indicated at other timepoints. ECG findings at baseline and all other predose and postdose 
assessments on the first cycle and EOT will be descriptively summarized.  
The number and percentage of patients satisfying the following QTcF conditions at any time 
post-baseline will be summarized: 
• 450, > 480, or > 500 msec  
• ≤ 30 msec increase from baseline, > 30 and ≤ 60 msec increase from baseline, or > 60 
msec increase from baseline  
Patient listing of ECG will be provided for all ECG recordings with the indicator whether the 
abnormality is clinical significance. For patients without QTcF, all measures in QTcB will be 
transformed into QTcF by standard derivation method in summary tables. 
6.5.7 
Eastern Cooperative Oncology Group (ECOG) 
ECOG scores will be summarized by visit using descriptive statistics for Safety Analysis Set.   
6.6 
PHARMACOKINETIC ANALYSES 
Individual and summary plasma concentration of pamiparib will be presented.   
PLASMA CONCENTRATIONS   
PK samples will be collected from patients at predose (within 30 minutes before dose) and 2 
hours (±30 minutes) postdose on Cycle 1 Day 1 and Cycle 1 Day 15. PK sampling will be 
collected only at sites that have the capability to collect PK samples. Details concerning 
collection, handling, and processing of the PK plasma samples will be provided in the study 
manual. PK samples collected from patients assigned to placebo treatment will not be analyzed 
for pamiparib concentrations. 
Plasma pamiparib concentration-time data will be summarized in tabular form. Pharmacokinetic 
concentration data for pamiparib will be listed including the dose level, relative time to dosing, 
actual sample collection time. The concentration data will also be summarized with descriptive 
statistics for each timepoint. The number of patients with non-missing plasma concentration, 
mean, standard deviation, minimum, median, maximum, geometric coefficient of variation and 
geometric mean will be included in the summary.   
6.7 
PHARMACODYNAMIC ANALYSES 
Correlative biomarker analyses in tumor tissues and blood will be performed. A separate 
statistical analysis plan will outline details of the biomarker analyses. 
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7 
INTERIM ANALYSIS 
No interim analysis is considered in this study. 
8 
CHANGES IN THE PLANNED ANALYSIS 
• The Per-Protocol (PP) analysis set defined in the protocol BGB-290-303 (version 1.0, 
2020-02-13) will not be considered in the analysis. 
• Progression-free survival 2 (PFS2) by investigator assessment as secondary efficacy 
endpoints defined in the protocol BGB-290-303 (version 1.0, 2020-02-13) will not be 
considered in the analysis.   
• Confirmation of response will not be required for ORR in randomized clinical studies per 
RECIST v1.1. No confirmation of response required for the analysis of DOR and Time to 
response to be consistent with analysis of ORR. 
• The stratification factor of HRD status (LOHhigh versus LOHlow versus unknown) will 
not be included as strata for PFS, OS, and TSST nor covariate in primary or secondary 
analyses due to high rate of patients with unknown LOH reported. And the Region will 
have three strata (China/Hong Kong/Taiwan versus Australia/Europe/North America 
versus Japan/South Korea/rest of world [ROW]) for PFS, OS, TSST, and covariate in 
primary or secondary analyses after combining patients in Japan/South Korea with 
patients in ROW as small number of patients were enrolled in Japan and no patients were 
enrolled in South Korea. 
• No PK parameters will be derived and reported in clinical study report. The definition of 
PK analysis set is thus modified as all patients who have at least one plasma 
concentration. 
9 
REFERENCES 
Brookmeyer R, Crowley J. A Confidence interval for the median survival time. Biometrics. 1982; 38: 29-
41. 
Clopper, C. and Pearson, ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial, Biometrika 1934;26: 404-413.  
Collett D. Modelling survival data in medical research. New York: Chapman & Hall; 1994.  
Common Terminology Criteria for Adverse Events (CTCAE).  Version 4.0.  United States Department of 
Health and Human Services, National Institutes of Health, National Cancer Institute, Washington, DC, 
USA, May 28, 2009. 
Greenwood M. “The natural duration of cancer”. Reports on Public Health and Medical Patients (London: 
Her Majesty’s Stationery Office). 1926; 33:1-26. 
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Kaplan E, Meier P.  Nonparametric estimation from incomplete observations.  J Am Stat Assoc. 1958; 
53:457-81. 
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10 
APPENDIX 
10.1 
HANDLING OF PARTIALLY MISSING DATES   
1)      Adverse Events 
The imputation rule for the safety analyses will be used to address the issues with partial 
dates. When the start date or end date of an adverse event is partially missing, the date will 
be imputed to determine whether the adverse event is treatment-emergent. When in doubt, 
the adverse event will be considered treatment emergent by default. The following rules 
will be applied to impute missing or partial dates for adverse events: 
  
Missing 
Impute 
Exception 
Start Date 
Day 
01 
If Month and Year 
= Month and Year 
of treatment start 
date, then set to 
treatment start date 
  
Day/Month 
January 01 
If Year = Year of 
treatment start date, 
then set to 
treatment start date 
  
Day/Month/Year or 
Year only 
Do not impute 
N/A 
End Date 
Day 
Last day of the 
month 
N/A 
  
Day/Month 
December 31 
N/A 
  
Day/Month/Year or 
Year only 
Do not impute 
N/A 
If the imputed AE start date becomes after AE end date, then update AE start date same as 
AE end date. And if the imputed start date or end date becomes after death date, then set 
to death date. 
The following rule will be applied to impute missing toxicity grade of AE:   
1. The highest grade will be used from patient’s AEs with the same preferred term.   
2. If patient has no AEs with the same preferred terms, the highest grade of the AEs 
with the same SOC will be used. 
3. If patient has no same SOC, the highest grade of all AEs from that patient will be 
used.  
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4. If it is the single AE reported for that patient, no imputation for the missing grade 
will be done. 
2)      Prior/Concomitant Medications, Disease and Medical History, Prior Therapy 
(Drug, Surgery/Procedure, Radiotherapy) 
  
Missing 
Impute 
Exception 
Start Date 
Day 
01 
N/A 
  
Day/Month 
January 01 
N/A 
  
Day/Month/Year or 
Year only 
Do not impute 
N/A 
End Date 
Day 
Last day of the 
month 
N/A 
  
Day/Month 
December 31 
N/A 
  
Day/Month/Year or 
Year only 
Do not impute 
N/A 
For concomitant medications; if the imputed start date or end date becomes after death 
date, then set to death date.  
For disease history and prior therapy, including initial diagnosis date, relapse date, 
therapy date (start/end date), or surgery date; if the imputed start date or end date 
becomes after first dose date, then set to first dose date - 15. 
3)      Initial Diagnosis, Metastatic Disease, and Most Recent Progression  
  
Missing 
Impute 
Exception 
Initial Diagnosis 
Date/ Metastatic 
Disease Date/ 
Most Recent 
Progression Date 
Day 
01 
N/A 
  
Day / Month 
January 01 
N/A 
  
  
Day / Month / Year 
or Year only 
  
Do not impute 
  
N/A 
If the imputed initial diagnosis date, metastatic disease date or most recent progression 
date is on or after the treatment start date, then set to treatment start date - 1. 
 
Version
.0
VV-CLIN-052909
1


 
BeiGene USA, Inc 
                       BGB-290-303 
              (Statistical Analysis Plan) 
 
 
Version 1.0:  08/28/2020 
Page 28 of 28  
CONFIDENTIAL 
 
4)      Death  
In case complete death dates are not recorded, impute as follows: 
• If both month and day are missing, then the imputed month and day will be 01Jan or 
the last date of patient known to be alive + 1, whichever is later. 
• If only day is missing, the death will be assumed to be on the first day of the month or 
the last date of patient known to be alive +1, whichever is later. 
5)      New Anticancer Therapy  
If the start day of a subsequent anticancer therapy is incomplete or missing, impute as 
follows:  
• If both month and day are missing,   
1)     impute the date as 31Dec, if the year is earlier than the year of the first PD date + 
1 or the treatment end date + 1, whichever is later. 
2)     impute the date as 01Jan, if the year is later than the year of the first PD date or 
the treatment end date + 1, whichever is later. 
3)     impute the date as the first PD date + 1 or the treatment end date + 1, whichever 
is later, if the year is the same year of first PD date + 1 or the treatment end date 
+ 1, whichever is later. 
• If only day is missing,   
1)     impute the date as the first day of the month if year and month are available and 
partial new anticancer therapy date still could indicate it is at least one month 
later than the first PD date +1 or the treatment end date +1, whichever is later.  
2)     impute the date as the last day of the month if year and month are available and 
partial new anticancer therapy date still could indicate it is at least one month 
earlier than the first PD date +1 or the treatment end date +1, whichever is later. 
3)      impute the date as the first PD date +1 or the treatment end date +1, whichever is 
later, if the year and month are the same year and month of first PD date +1 or 
the treatment end date +1, whichever is later. 
 
Version
.0
VV-CLIN-052909
1


Signature Page for VV-CLIN-033243 v1.0
Signature Page for VV-CLIN-033243 v1.0
Approval
Biometrics
28-Aug-2020 22:30:20 GMT+0000
Approval
Biometrics
31-Aug-2020 03:26:54 GMT+0000
Approval
Clinical Development
02-Sep-2020 14:48:54 GMT+0000
Approval
Clinical Development
08-Sep-2020 17:45:28 GMT+0000
Version
.0
VV-CLIN-052909
1