A Randomised, Double-blind, Parallel Group, Placebo-controlled Multi-centre Phase III Study to Assess the Efficacy and Safety of Olaparib Versus Placebo as Adjuvant Treatment in Patients With gBRCA1/2 Mutations and High Risk HER2 Negative Primary Breast Cancer Who Have Completed Definitive Local Treatment and Neoadjuvant or Adjuvant Chemotherapy
Phase: PHASE3
Conditions: Breast Cancer
Sponsor: AstraZeneca

  
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Clinical Study Protocol 
Drug Substance
Olaparib (AZD2281)
Study Code
D081CC00006
Study Number
BIG 6-13, NSABP B-55
Version
5
Date
18 May 2018
A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase 
III study to assess the efficacy and safety of olaparib versus placebo as adjuvant 
treatment in patients with germline BRCA1/2 mutations and high risk HER2 
negative primary breast cancer who have completed definitive local treatment and 
neoadjuvant or adjuvant chemotherapy
Sponsor: AstraZeneca AB, 151 85 Södertälje, Sweden

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Applicable section 
number(s)/title
Nature of revision
Title page
Inclusion of Merck logo.
List of olympia protocol authors
List of authors updated.
Protocol synopsis
3.2.3 Study Population
12.2.2 Analysis of secondary 
endpoints
12.2.7 Sample size justification
Number of patients planned has been increased from 
1500 to 1800. 
Number of centres increased from 500 to 700.
Protocol synopsis
12.2.7 Sample size justification
The estimation for study recruitment has been 
increased to 5 years (previously 4.5 years) to account 
for the 300 extra patients.
Protocol synopsis
6.2.5 Patient management 
post-primary analysis
12.2.1.1 Primary analysis
12.2.2 Analysis of secondary 
endpoints
12.2.7 Sample size justification
Removed minimum 24 month follow-up from the data 
cut-off from the primary analysis as the expected high 
event rate in the first 2 years has not been seen.
Protocol synopsis
12.1.1 Full analysis set
12.2.6 Interim analysis
Interim analysis will now be triggered by events in the 
first 900 patients (previously 750 patients).
1.1.9.1 Olaparib monotherapy 
studies in breast cancer patients
Addition of efficacy data for Study D0819C00003 
(OlympiAD).
1.4 Benefit/risk and ethical 
assessment
Addition of details (to the potential benefit section) for 
the olaparib tablet formulation approval for patients 
with deleterious or suspected deleterious gBRCAm, 
HER2-negative metastatic breast cancer.
3.1 Overall study design, flow 
chart and study schedules
3.2.1 Rationale for study design
6.2.2 On-treatment assessments
6.2.3 Efficacy follow-up 
assessments
6.3.1 Tumour evaluation
Text regarding mammogram and/or breast MRI scans 
amended to include ipsilateral and/or contralateral 
scanning. Clarification provided regarding the use of 
ultrasound in patients who underwent a bilateral 
mastectomy and for male patients.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Applicable section 
number(s)/title
Nature of revision
3.1 Overall study design, flow 
chart and study schedules
Information added to Table 3 footnote to clarify 
monitoring of all ongoing AEs/SAEs and any new 
AEs/SAEs identified during the 30 calendar days.
Pneumonitis included in the events occurring after the 
30 day follow-up period that should be reported as an 
SAE.
3.1 Overall study design, flow 
chart and study schedules
6.2.1 Screening procedures
6.2.2 On-treatment assessments
6.4.9.1 Serum or urine pregnancy 
test
Timings for pregnancy testing in women of
childbearing potential clarified. Pregnancy tests on 
blood or urine amended to serum or urine.
4.1 Inclusion criteria
Criterion 11B: Methods of contraception text amended.
4.2 Exclusion criteria
Criterion 11: Use of strong and moderate CYP3A 
inhibitors text amended and new criteria included to 
cover the use of concomitant strong and moderate 
CYP3A inducers on study.
Criterion 13: Criteria modified to patients with current 
or past history of haematologic malignancies and any 
clonal non-malignant haematological disorder which 
predisposes the patient to develop a haematological 
malignancy.
5.1.1 Meals and dietary 
restrictions
New section to cover that grapefruit juice consumption 
on study is prohibited.
5.1.2 Contraception 
Appendix E
Text updated to specify two highly effective forms of 
contraception should be used in combination and this 
should be started from the signing of the informed 
consent. Male patient contraception text clarified.
5.4.2 Methods for unblinding 
individual patients
Text revised to include post treatment data verification 
for unblinded patients.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Applicable section 
number(s)/title
Nature of revision
5.5 Treatments
Table 5 and Table 6 updated to include temporary dose 
reductions to 300 and 200 mg due to CYP3A inhibitor 
exposure.
Table 8 and Table 9 added to cover dose reductions for 
management of renal impairment and the use of strong 
or moderate CYP3A inhibitors while on study.
5.5.6.3 Renal impairment
New section to cover management of renal impairment 
while on study.
5.5.6.7 Interruptions for 
intercurrent non-toxicity related 
events
Additional text provided advising caution while 
driving or using machinery in case of AEs of asthenia, 
fatigue and dizziness.
5.6.2 Restricted concomitant 
medications
Section name changed from CYP3A to restricted 
concomitant medications. Table 10 added detailing 
restricted concomitant medications. CYP3A text is 
now summarised in Table 10.
5.6.3 Effect of olaparib on other 
drugs
5.6.4 Interaction of olaparib and 
specific co-medications
5.6.6 Anticoagulant therapy
Sections deleted. Section text is now summarised in 
Table 10.
5.8.1 Procedures for 
discontinuation of a patient from 
study treatment
6.4.4 Reporting of serious adverse 
events
Reporting of SAEs text amended to specify SAEs, 
must be reported to AstraZeneca via both the eCRF 
and paper SAE report to AstraZeneca data entry site 
(DES) within 24 hours.
6.2.1 Screening procedures
The capturing of adverse events during Screening text 
has been revised to reflect current practice.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Applicable section 
number(s)/title
Nature of revision
6.4.3 Recording of adverse events
The recording of adverse events text has been revised 
to reflect current practice. 
A section for recording of adverse events after the 
30 day follow up period has been included.
CTCAE grade and changes in CTCAE grade has been 
included in the list of variables collected for each AE.
New cancers: Text added to say new primary cancers 
are considered as IDFS event and must also be 
reported on the endpoint CRF. Patients with new 
primary cancers which require (neo)adjuvant treatment 
of any kind for appropriate management must be 
discontinued from study treatment.
New section for olaparib adverse events of special 
interest included. These are MDS/AML, new primary 
malignancy (other than MDS/AML) and pneumonitis. 
A questionnaire will be sent to any investigator 
reporting an AESI by AstraZeneca Patient Safety.
6.8 Pharmacokinetics
Text included to clarify samples should be collected 
preferably on visit 4, day 29, however, samples can 
also be taken at a later treatment visit, provided that 
PK consent was obtained beforehand.
11.1.2.1 Overall Survival
5.9 Withdrawal from study
Removed survival sweep from the protocol.
12.2.1.1 Primary analysis
12.2.7 Sample size justification
Updated text for the predicted timing for the primary 
analysis.
Removed text relating to ER+ proportions as the 
revised predictions are based on the current data which 
has approximately 15% ER+.
12.2.1.2 Sensitivity analysis
Details of sensitivity analyses included where the 
results of ER and PgR status from the local and central 
labs differ in >5% of randomised patients. 
12.2.1.3 Subgroup analysis
12.2.2 Analysis of secondary 
endpoints
Text revised for number of events below which it is not 
considered appropriate to present analyses.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Applicable section 
number(s)/title
Nature of revision
12.2.3.2 Statistical considerations 
for patient reported outcomes
Estimates updated based on the sample size increase.
12.2.6 Interim analysis
Updated text for predicted timing for the interim 
analysis.
12.2.7 Sample size justification
Table 12 Estimated accrual pattern, replaced with new 
version based on actual accrual pattern between June 
2014 and February 2018; now numbered Table 15.
Table 13 Estimated annual hazard rates, and text 
related to this table have been deleted.
13.1 Medical emergencies and 
contacts
Addresses and roles corrected.
13.2 Overdose
Additional text concerning what constitutes an 
overdose has been included. 
13.3 Pregnancy
Table 16, Pregnancy reporting and handling according 
to time of diagnosis and Table 17, Reporting outcomes 
of pregnancy according to time of diagnosis added.
14 List of references
Inclusion of additional references to support new data.
Appendix H CYP3A Medications 
to be avoided with olaparib
Appendix deleted as text now contained within Section 
5.6.2 Restricted concomitant medications.
Appendix I CPS & EG score
Typographical error in table footnote corrected from 
4.1.3a to 4.1.4a. Appendix renumbered to Appendix H.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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of peroxidase staining for ER and PgR in their post-neoadjuvant surgical specimen. By 
removing the new sentences that allow receptor status to be determined from ANY
specimen, we revert to the original protocol version, where the receptor status will be 
determined from a specimen obtained from treatment naïve tissue. This is supported by the 
publication describing the CPS+EG score (Mittendorf et al 2011).
!
Section 5.5.6.6. (Interruptions for intercurrent non-toxicity related events) is added 
back in the protocol. 
This section was in the original version of the protocol and deleted in error when 
Amendment 1 was produced.  Adding the section back in to the protocol brings it back in 
line with the guidance in the Investigator Brochure regarding stopping olaparib 3 days prior 
to planned surgery.
The medical rationale for stopping olaparib 3 days prior to planned surgery is purely a 
precautionary measure. Three days was chosen based on the half-life of olaparib, to assume 
that in 3 days most of the drug has been eliminated. There is no data to suggest that olaparib 
has impact on wound healing, nor have any complications been reported perioperatively 
related to olaparib. 
!
Section 13.1 (Medical emergencies and contacts) is updated
!
Appendix C (Pharmacogenetics Research) is revised in line with the new Clinical 
Study Protocol template:
-
Table of contents is removed
-
List of abbreviations and definition of terms is removed
!
Appendix D (Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law) is revised in line with the new Clinical Study Protocol 
template:
-
Title is revised to “Actions Required in Cases of Increases in Liver 
Biochemistry and Evaluation of Hy’s Law” 
-
Table of contents is removed
-
The following sentence is added to the Introduction: This Appendix 
describes the process to be followed in order to identify and appropriately 
report cases of Hy’s Law.  It is not intended to be a comprehensive guide to 
the management of elevated liver biochemistries.
-
Definitions are revised 
-
Section 6 “ACTIONS REQUIRED WHEN POTENTIAL HY’S 
LAWCRITERIA ARE MET BEFORE AND AFTER STARTING STUDY 
TREATMENT (NOT APPLICABLE)” is removed

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LIST OF OLYMPIA PROTOCOL AUTHORS
Medical Oncologist, Institute of Cancer Research and King's 
College London, UK
Medical Oncologist, Alliance, Dana Farber Cancer Institute,
USA
Medical Oncologist, Sheba Breast Collaborative Group
(SBCG), Israel
Medical Oncologist, NRG Oncology, Virginia Commonwealth 
University Massey Cancer Center, USA
Research Operations Director, Breast International Group 
(BIG),
Belgium
Medical Oncologist, Memorial Sloan-Kettering Cancer
Center, USA
Study Statistician, NRG Oncology, USA
Biostatistics Team Lead, Frontier Science (Scotland) Ltd
Medical Research Fellow, Jules Bordet Institute, Belgium
Head of Medical Support Team, Jules Bordet Institute, 
Belgium
Medical Oncologist, IBCSG, Hospital of Prato, Italy
Medical Oncologist, Perelman School of Medicine, USA
Principal Investigator/Senior Biostatistician, Frontier
Science and Technology Research Foundation (FSTRF), 
Boston, MA, USA
Medical Oncologist, National Cancer Institute Canada,
Clinical Trials Group (NCIC CTG), BC Cancer Agency, 
Canada
Senior Medical Director, Oncology Global Medicines 
Development, AstraZeneca Gaithersburg, USA

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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PROTOCOL SYNOPSIS
A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase 
III study to assess the efficacy and safety of olaparib versus placebo as adjuvant 
treatment in patients with germline BRCA1/2 mutations and high risk HER2 
negative primary breast cancer who have completed definitive local treatment and 
neoadjuvant or adjuvant chemotherapy
International Principal Investigator
Study centre(s) and number of patients planned
The study will be conducted in approximately 25 countries worldwide. Approximately 
700 centres (in the US and Rest of the World countries) will be initiated to randomise 
approximately 1800 patients. Additional countries and sites may be added dependent on 
recruitment rates.
Approximately 150 randomised patients* will be analysed for pharmacokinetic (PK) at those 
sites that have confirmed that they are able to collect the PK assessment samples. PK 
sampling will be performed in a subset of patients who sign an optional PK Informed consent.
Study period
Phase of development
Estimated date of first patient enrolled
Q1 2014
III
Estimated date of last patient completed
2028
* No placebo samples will be analysed unless requested.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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The trial will use one randomisation system and report as one single study. The initial 
collection of the patients’ data will be done using two databases (one for the US patients and 
one for all other patients outside of the US). The two databases will be set up using the same 
standards and eCRFs to ensure consistency in the data collection. The data from both 
databases will be combined into a single consolidated database at regular, pre-specified 
intervals. All study endpoints as well as reports for periodic review by the Independent Data 
Monitoring Committee (IDMC) will be analysed and reported from the single combined 
reporting database, held by Frontier Science on behalf of BIG.
Study design
This is a randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III 
study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in 
patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast 
cancer who have completed definitive local treatment and neoadjuvant or adjuvant 
chemotherapy.
Patients will be randomised in a 1:1 ratio to either olaparib or placebo. Randomisation will be 
stratified by hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC), 
by prior neoadjuvant versus adjuvant chemotherapy, and prior platinum use for breast cancer 
(yes versus no).
Eligible patients with deleterious or suspected deleterious gBRCA mutations and high risk 
HER2 negative breast cancer should be randomised in the trial ideally within a maximum of 
8 weeks of completing their last treatment modality (chemotherapy and definitive local or 
locoregional treatment), but in no case longer than 12 weeks. Randomised patients will 
receive study treatment for up to a maximum of 12 months. All patients will have safety 
assessments every 2 weeks during the first month, every 4 weeks for the following 5 months 
(up to week 24) and 3 monthly for the remaining 6 months of study treatment plus 30 days 
after its discontinuation. All randomised patients will have clinical assessment visits for 
approximately 10 years following their randomisation into the study, or until an IDFS 
endpoint due to a breast cancer related distant relapse, whichever comes first. They then enter 
the annual survival follow-up phase of the trial, which will continue until 10 years after the 
last patient is randomised. No clinic visits will be required during the survival follow-up 
phase; information may be collected via telephone, medical records or death registries.
Target patient population
Patients eligible for the trial are those with a deleterious or suspected deleterious germline 
BRCA mutation (defined by local or central Myriad testing) with high risk HER2 negative 
primary breast cancer who have completed definitive local treatment, and neoadjuvant or 
adjuvant chemotherapy. Definitions of high risk HER2 negative patients are provided below.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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1.
For patients who underwent initial surgery and received adjuvant chemotherapy
∀
TNBC patients must have been axillary node-positive (≥pN1, any tumour size) 
or axillary node negative (pN0) with invasive primary tumour pathological size 
> 2 cm (≥pT2) 
∀
ER and/or PgR positive/HER2 negative patients must have had ≥4 
pathologically confirmed positive lymph nodes. 
2.
For patients who underwent neoadjuvant chemotherapy followed by surgery
∀
TNBC patients must have residual invasive breast cancer in the breast and/or 
resected lymph nodes (non pCR)
∀
ER and/or PgR positive/HER 2 negative patients must have residual invasive 
cancer in the breast and/or the resected lymph nodes (non pCR) AND a 
CPS&EG score ≥3 (Clinical stage (CS), estrogen receptor status (E), nuclear 
grade (G), and post-treatment pathologic stage (PS)- a disease scoring system). 
Instructions how to calculate CPS&EG score (Mittendorf et al 2011; Jeruss et 
al 2008) are provided in Appendix H. 
Germline BRCA1 and BRCA2 (gBRCA) testing
Local gBRCA testing results, if available, can be used for establishing eligibility. If local 
gBRCA testing results are not available, central testing will be provided for those patients who 
otherwise appear to be eligible. Irrespective of the availability of local gBRCA testing results, 
all patients must provide a sample for central gBRCA testing. 
Central tumour analyses (e.g. somatic BRCA1/2 functional status, ER/PgR and HER2 
status) 
Archival tumour samples must be provided for all patients. 
For adjuvant patients, this refers to the surgical specimen; for neoadjuvant patients, both the 
pre-treatment core biopsy and the surgical specimen with residual disease are requested but 
only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, 
sites may submit a portion of invasive tumour from the original block, either by taking at least 
one core of at least 3 mm in diameter, or by splitting the original block in two parts, and re-
embedding one in a new block for central submission. If blocks containing pre-neoadjuvant 
treatment core biopsies are available but cannot be submitted, sections mounted on glass 
slides prepared from the block can be provided. If tumour sample can’t be provided as 
requested above or if it’s not available, approval by Study Team for patient’s entry into the 
trial is required.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Study treatment, dosage and mode of administration
AstraZeneca’s Pharmaceutical Development, R&D Supply Chain will supply olaparib and 
matching placebo to the investigator as green film-coated tablets.
Patients will be randomised in a 1:1 ratio to one of the following treatments:
!
12 months treatment with olaparib tablets p.o. 300 mg twice daily (two 150 mg 
tablets in the morning and two 150 mg tablets in the evening)
!
12 months treatment with matching placebo tablets p.o. twice daily (two tablets in 
the morning and two tablets in the evening)
Stratification
Patients will be stratified at randomisation by the following baseline factors:
!
Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC)
NOTE: In cases of multifocal, multicentric or synchronous bilateral invasive 
disease, stratification is based on the status of the lesion considered at highest risk 
(at the investigator’s discretion) that was used to determine eligibility.
!
Neoadjuvant versus adjuvant chemotherapy
!
Platinum therapy for current breast cancer: Yes/No
Within this study, patients will not be provided with olaparib post discontinuation of study 
treatment. Patients and investigators will not be routinely unblinded to study treatment prior to 
the final overall survival (OS) analysis. Unblinding is allowed only in case of compelling 
medical or safety reasons (Section 5.4.2).
Outcome(s): 
!
Primary outcome 
∀
Invasive Disease Free Survival (IDFS)
!
Secondary outcomes 
∀
Overall Survival (OS)
∀
Distant Disease Free Survival (DDFS)
∀
New primary contralateral breast cancers (invasive and non-invasive), new 
primary ovarian cancer, new primary fallopian tube cancer and new primary 
peritoneal cancers in patients at risk for these events

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Patient reported outcomes and health related quality of life (HRQoL) will be assessed through 
the planned correlative study using the FACIT-Fatigue and the EORTC QLQ-C30 
questionnaires.
An analysis of IDFS, DDFS and OS will be conducted based on patients with gBRCA
mutations confirmed by the central test, if this population differs from the primary ITT 
population. Similar sensitivity analyses will be performed based on ER and/or PgR 
positive/HER2 negative and TNBC subsets as defined by the central laboratory testing.
Full details of all the statistical analyses will be documented in the SAP. Version 1.0 of the 
SAP will be prepared prior to first subject in (FSI).
Pharmacokinetic analysis
The plasma concentration-time data will be analysed by non-linear mixed effects modelling in 
order to evaluate the pharmacokinetic characteristics of olaparib, quantify variability in the 
pharmacokinetics, identify demographic or pathophysiological covariates, which may explain 
the observed variability and explore exposure-response relationships.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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TABLE OF CONTENTS
PAGE
TITLE PAGE.......................................................................................................1
VERSION HISTORY..........................................................................................2
LIST OF OLYMPIA PROTOCOL AUTHORS..................................................11
PROTOCOL SYNOPSIS...................................................................................13
TABLE OF CONTENTS...................................................................................21
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS.........................28
1.
INTRODUCTION .............................................................................................33
1.1
Background........................................................................................................33
1.1.1
Breast cancer and its treatment...........................................................................33
1.1.2
Triple Negative Breast Cancer (TNBC)..............................................................34
1.1.3
Adjuvant chemotherapy for TNBC..................................................................... 34
1.1.4
Neoadjuvant chemotherapy for TNBC ............................................................... 34
1.1.5
ER/PgR positive HER2 negative breast cancer with germline BRCA
mutations ........................................................................................................... 35
1.1.6
PARP inhibition as a therapeutic strategy target for BRCA mutated breast 
cancer ................................................................................................................36
1.1.7
Pre-clinical experience .......................................................................................36
1.1.8
Toxicology and safety pharmacology summary..................................................36
1.1.9
Clinical experience.............................................................................................37
1.1.9.1
Olaparib monotherapy studies in breast cancer patients......................................37
1.2
Research hypothesis...........................................................................................39
1.3
Rationale for conducting this study ....................................................................39
1.3.1
Rationale for central BRCA mutation test at Myriad Genetics, Inc......................40
1.4
Benefit/risk and ethical assessment ....................................................................41
2.
STUDY OBJECTIVES......................................................................................46
2.1
Primary objective...............................................................................................46
2.2
Secondary objectives..........................................................................................46
2.3
Safety objective..................................................................................................46
.......................................................................................46
3.
STUDY PLAN AND PROCEDURES ...............................................................47
3.1
Overall study design, flow chart and study schedules .........................................48
3.2
Rationale for study design, doses and control groups..........................................62

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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3.2.1
Rationale for study design.................................................................................. 62
3.2.2
Rationale for patient reported outcomes ............................................................. 63
3.2.3
Study Population................................................................................................64
4.
PATIENT SELECTION CRITERIA.................................................................. 65
4.1
Inclusion criteria ................................................................................................65
4.2
Exclusion criteria ............................................................................................... 70
5.
STUDY CONDUCT..........................................................................................72
5.1
Restrictions during the study..............................................................................72
5.1.1
Meals and dietary restrictions.............................................................................72
5.1.2
Contraception.....................................................................................................72
5.2
Patient enrolment and randomisation and initiation of study treatment ...............73
5.2.1
Procedures for randomisation.............................................................................73
5.3
Procedures for handling patients incorrectly enrolled or randomised or 
initiated on study treatment ................................................................................74
5.4
Blinding and procedures for unblinding the study...............................................75
5.4.1
Methods for ensuring blinding ...........................................................................75
5.4.2
Methods for unblinding individual patients ........................................................75
5.5
Treatments.........................................................................................................76
5.5.1
Identity of study treatment ................................................................................. 76
5.5.2
Doses and treatment regimens............................................................................76
5.5.2.1
Olaparib and matching placebo (study treatment)............................................... 76
5.5.3
Additional study drug - Not applicable...............................................................78
5.5.4
Labelling............................................................................................................78
5.5.5
Storage...............................................................................................................78
5.5.6
Management of toxicity of study treatment ........................................................ 78
5.5.6.1
Study therapy following breast cancer recurrence or second primary cancer....... 79
5.5.6.2
Olaparib/placebo dose levels..............................................................................79
5.5.6.3
Renal impairment...............................................................................................82
5.5.6.4
Management of haematological toxicity.............................................................82
5.5.6.5
Management of new or worsening pulmonary symptoms ...................................83
5.5.6.6
Management of nausea and vomiting .................................................................83
5.5.6.7
Interruptions for intercurrent non-toxicity related events ....................................83
5.6
Concomitant and subsequent treatment(s) .......................................................... 84
5.6.1
Administration of endocrine therapy ..................................................................84
5.6.2
Restricted concomitant medications ...................................................................84
5.6.3
Anti-emetics/Anti-diarrheals ..............................................................................86
5.6.4
Live virus and bacterial vaccines........................................................................86
5.7
Treatment compliance........................................................................................87
5.7.1
Accountability....................................................................................................87

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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5.8
Discontinuation of study treatment..................................................................... 87
5.8.1
Procedures for discontinuation of a patient from study treatment........................88
5.9
Withdrawal from study.......................................................................................89
6.
COLLECTION OF STUDY VARIABLES........................................................90
6.1
Recording of data...............................................................................................90
6.2
Study procedures................................................................................................90
6.2.1
Screening procedures ......................................................................................... 90
6.2.2
On-treatment assessments ..................................................................................93
6.2.3
Efficacy follow-up assessments..........................................................................95
6.2.4
Safety follow-up assessments 30 days after last dose of olaparib/placebo........... 95
6.2.5
Patient management post-primary analysis.........................................................96
6.2.6
Patient management post-final analysis ..............................................................96
6.3
Efficacy .............................................................................................................96
6.3.1
Tumour evaluation............................................................................................. 96
6.4
Safety................................................................................................................. 98
6.4.1
Definition of adverse event (AE)........................................................................98
6.4.2
Definitions of serious adverse event (SAE) ........................................................98
6.4.3
Recording of adverse events...............................................................................99
6.4.4
Reporting of serious adverse events ................................................................. 104
6.4.5
Laboratory safety assessment ........................................................................... 104
6.4.5.1
Full haematology assessments for safety .......................................................... 105
6.4.5.2
Coagulation...................................................................................................... 105
6.4.5.3
Clinical chemistry assessments for safety......................................................... 105
6.4.5.4
Urinalysis......................................................................................................... 106
6.4.5.5
Bone marrow or blood cytogenetic samples ..................................................... 106
6.4.6
Physical examination ....................................................................................... 106
6.4.7
ECG................................................................................................................. 107
6.4.7.1
Resting 12-lead ECG ....................................................................................... 107
6.4.8
Vital signs........................................................................................................ 107
6.4.8.1
Pulse and blood pressure.................................................................................. 107
6.4.8.2
Body temperature............................................................................................. 107
6.4.9
Other safety assessments.................................................................................. 107
6.4.9.1
Serum or urine pregnancy test.......................................................................... 107
6.5
Patient reported outcomes (PRO) ..................................................................... 108
6.5.1
FACIT-Fatigue ................................................................................................ 108
6.5.2
EORTC QLQ-C30 ........................................................................................... 108
6.5.3
Administration of PRO questionnaires ............................................................. 109
6.6
Biomarkers ...................................................................................................... 110
6.6.1
Biomarker samples........................................................................................... 110
6.6.2
Collection of blood sample for Myriad germline BRCA1 and BRCA2
testing .............................................................................................................. 111

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9.3
Monitoring of the study.................................................................................... 123
9.3.1
Source data ...................................................................................................... 124
9.4
Study agreements............................................................................................. 124
9.4.1
Archiving of study documents.......................................................................... 124
9.5
Study timetable and end of study...................................................................... 124
10.
DATA MANAGEMENT................................................................................. 124
11.
EVALUATION AND CALCULATION OF VARIABLES ............................. 125
11.1
Calculation or derivation of efficacy variable(s)............................................... 125
11.1.1
Primary endpoint.............................................................................................. 125
11.1.2
Secondary endpoints ........................................................................................ 127
11.1.2.1
Overall Survival............................................................................................... 127
11.1.2.2
Distant disease free survival (DDFS)................................................................ 127
11.1.2.3
Incidence of contralateral invasive breast cancer, contralateral non-
invasive breast cancer, new primary ovarian cancer, new primary fallopian 
tube cancer and new primary peritoneal cancer ................................................ 128
11.2
Calculation or derivation of safety variable(s) .................................................. 128
11.2.1
Other significant adverse events (OAE)............................................................ 128
11.3
Calculation or derivation of patient reported outcome variables........................ 129
11.4
Calculation or derivation of pharmacokinetic variables .................................... 129
11.5
Calculation or derivation of pharmacodynamic variable(s) - not applicable ...... 129
11.6
Calculation or derivation of 
 variables.................................... 129
11.7
Calculation or derivation of health economic variables –not applicable ............ 129
12.
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ......... 129
12.1
Description of analysis sets .............................................................................. 129
12.1.1
Full analysis set................................................................................................ 129
12.1.2
Safety analysis set............................................................................................ 130
12.1.3
PK analysis set................................................................................................. 130
12.2
Methods of statistical analysis.......................................................................... 131
12.2.1
Analysis of primary endpoint ........................................................................... 131
12.2.1.1
Primary analysis............................................................................................... 131
12.2.1.2
Sensitivity analysis........................................................................................... 131
12.2.1.3
Subgroup analysis............................................................................................ 132
12.2.1.4
Analysis of Interaction ..................................................................................... 134
12.2.2
Analysis of secondary endpoints ...................................................................... 134
12.2.3
Analysis of patient reported outcomes.............................................................. 136
12.2.3.1
Hypotheses and objectives ............................................................................... 136
12.2.3.2
Statistical considerations for patient reported outcomes.................................... 137
12.2.3.3
Pharmacokinetic analysis ................................................................................. 139

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.................................................................... 139
12.2.5
Multiplicity strategy for primary and key secondary endpoints......................... 140
12.2.6
Interim analysis................................................................................................ 141
12.2.7
Sample size justification................................................................................... 144
12.3
Independent Data monitoring committee.......................................................... 145
13.
IMPORTANT MEDICAL PROCEDURES TO BE FOLLOWED BY THE 
INVESTIGATOR ............................................................................................ 147
13.1
Medical emergencies and contacts.................................................................... 147
13.2
Overdose.......................................................................................................... 148
13.3
Pregnancy ........................................................................................................ 148
13.3.1
Maternal exposure............................................................................................ 148
13.3.2
Paternal exposure............................................................................................. 149
14.
LIST OF REFERENCES ................................................................................. 151
LIST OF TABLES
Table 1
Study Schedule - Screening (PART 1 and PART 2) ..............................52
Table 2
Study Schedule – On treatment (Year 1)................................................55
Table 3
Study Schedule - Follow-up Visits (Year 2 onwards) ............................59
Table 4
Identity of study treatment.....................................................................76
Table 5
Study treatment doses and treatment regimens ......................................77
Table 6
Olaparib/placebo dose levels.................................................................79
Table 7
Mandatory Treatment for Hematologic Toxicity and Treatment 
Guidance for other olaparib/placebo Toxicities .....................................80
Table 8
Dose reduction for study treatment to manage moderate renal 
impairment............................................................................................81
Table 9
Dose reduction for study treatment with concurrent use of a strong 
or moderate CYP3A inhibitor................................................................82
Table 10
Restricted concomitant medications ......................................................85
Table 11 
Samples for Biomarker Research.........................................................110
Table 12 
Volume of blood to be drawn from each patient ..................................116
Table 13 
Summary of Outcome Variables and Analysis Populations..................130
Table 14 
Summary of 2-sided significance levels and total alpha spend 
across the endpoints and analyses........................................................143
Table 15
Actual accrual between June 2014 and February 2018......................... 145

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Edition Number 5
Date 18 May 2018
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Table 16
Pregnancy reporting and handling according to time of diagnosis........149
Table 17
Reporting outcomes of pregnancy according to time of diagnosis........150
Table 18
Point assignments for the CPS + EG staging system............................176
LIST OF FIGURES
Figure 1
Study Flow Chart ..................................................................................50
Figure 2
Screening Plan ......................................................................................51
Figure 3
Multiple testing procedure...................................................................141
LIST OF APPENDICES
Appendix A
Additional Safety Information.............................................................159
Appendix B
International Airline Transportation Association (IATA) 6.2 
Guidance Document............................................................................161
................................................................162
Appendix D
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law ......................................................................166
Appendix E
Acceptable Birth Control Methods ......................................................170
Appendix F
ECOG Performance Status..................................................................172
Appendix G
Patient Reported Outcomes (FACIT-Fatigue, EORTC QLQ-C30).......173
Appendix H
CPS & EG score..................................................................................176

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Edition Number 5
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
The following abbreviations and special terms are used in this study Clinical Study Protocol.
Abbreviation or 
special term
Explanation
AE
Adverse event (see definition in Section 6.4.1)
AESI
Adverse event of special interest
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AML
Acute Myeloid Leukaemia
ANC
Absolute neutrophil count
APTT
Activated Partial Thromboblastin Time
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
AUC
Area Under Curve
b.i.d.
Twice daily
BP
Blood Pressure
BRCA
Breast cancer susceptibility gene
BUN
Blood Urea Nitrogen
CA-125
Cancer antigen-125
CfDNA
Circulating free DNA
CHO
Chinese hamster ovary
CI
Confidence Interval
Cmaxss
Maximum concentration at steady state
Cminss
Minimum concentration at steady state
CNS
Central Nervous System
CPS&EG
Clinical stage (CS), estrogen receptor status (E), nuclear grade (G), and post-
treatment pathologic stage (PS)- a disease scoring system
CR
Complete Response
CRF (eCRF)
Case Report Form (electronic/paper)
CRO
Contract Research Organisation
CSA
Clinical Study Agreement
CSR
Clinical Study Report
CT
Computerised Tomography

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Abbreviation or 
special term
Explanation
CTCAE
Common Terminology Criteria for Adverse Event
DAE
Discontinuation of study treatment due to Adverse Event
DCIS
Ductal carcinoma in situ
DCO
Data cut off
DDFS
Distant disease free survival
DES
Data entry site
DFS
Disease free survival
DNA
Deoxyribonucleic acid 
DSB
Double strand break
DUS
Disease under Study
EC
Ethics Committee, synonymous to Institutional Review Board (IRB) and 
Independent Ethics Committee (IEC)
ECG
Electrocardiogram
ECOG performance 
status
Eastern Cooperative Oncology Group performance status using scales and 
criteria to assess how a patient’s disease is progressing
EORTC QLQ-C30
The European Organisation for Research and Treatment of Cancer -Quality of 
Life Questionnaire-Core questions 30
ER
Estrogen receptor
ESMO
European Society for Medical Oncology
ESTRO
European Society for Radiation and Oncology
FACIT-Fatigue
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue 
Measurement questionnaire
FAS
Full Analysis Set
FFPE
Formalin Fixed Paraffin Embedded
FSH
Follicle Stimulating Hormone
gBRCA mutation or 
gBRCAm
The term "gBRCA mutation" is used to refer to a germline BRCA1 or BRCA2 
mutation classified as "deleterious" or "suspected deleterious" in accordance 
with the American College of Medical Genetics and Genomics 
recommendations for standards for interpretation and reporting of sequence 
variants
GCP
Good Clinical Practice
G-CSF
Granulocyte Colony Stimulating Factor
GMP
Good Manufacturing Practice
Hgb
Hemoglobin

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Abbreviation or 
special term
Explanation
HDPE
High Density Polyethylene
HER2
Human Epidermal Growth Factor Receptor 2
HR
Hazard Ratio
HRD
Homologous Recombination Deficiency
HRQoL
Health Related Quality of Life
IB
Investigators Brochure
ICH
International Conference on Harmonisation
International 
Co-ordinating 
investigator
If a study is conducted in several countries the International Co-ordinating 
Investigator is the Investigator co-ordinating the investigators and/or activities 
internationally. 
IDFS
Invasive Disease-free Survival
IDMC
Independent Data Monitoring Committee
IHC
Immunohistochemistry
IIBTR
Ipsilateral invasive breast tumour recurrence
INR
International Normalised Ratio
IPCW
Inverse Probability of Censoring Weighting
ISH
In Situ Hybridisation (includes FISH, DISH, CISH)
ISS
Investigator Sponsored Study
ITT
Intention To Treat
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
KM
Kaplan-Meier
LDH
Lactic Dehydrogenase
LIMS
Laboratory Information Management System
LLOQ
Lower Limit of Quantification
LSI
Last Subject in
LSLV
Last Subject Last Visit
MCH
Mean Cell Haemoglobin
MCHC
Mean Cell Haemoglobin Concentration
MCV
Mean Cell Volume
MDS
Myelodysplastic Syndrome
MMRM
Mixed Model for Repeated Measures

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Abbreviation or 
special term
Explanation
MRI
Magnetic Resonance Image
MTD
Maximum Tolerated Dose
MTP
Multiple testing procedure
NCCN
National Comprehensive Cancer Network
NSABP
National Surgical Adjuvant Breast and Bowel Project 
NSCLC
None Small cell lung cancer
OAE
Other Significant Adverse Event (see definition in Section 11.2.1)
OD
Once Daily
OR
Objective Response
ORR
Objective Response Rate
OS
Overall survival
PARP
Polyadenosine 5’diphosphoribase [poly (ADP ribose)] polymerisation
pCR
Pathological Complete Response
PD
Pharmacodynamics
PFS
Progression Free Survival
PFS2
Time to second progression
PgR
Progesterone receptor
PGx
Pharmacogenetic research
PI
Principal Investigator 
PK
Pharmacokinetics
PO
Per Os (by mouth)
PRO
Patient Reported Outcome
QOL
Quality of Life
QT/QTc
A measure of the time between the start of the Q wave and the end of the T 
wave in the heart's electrical cycle (c indicates the corrected value for this time 
period)
RBC
Red Blood Cells
RECIST
Response Evaluation Criteira in Solid tumours. This study will use modified 
RECIST version 1.1.
REML
Restricted Maximum Likelihood
RPSFT
Rank Preserving Structural Failure Time
SAE
Serious adverse event (see definition in Section 6.4.2).

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Abbreviation or 
special term
Explanation
SAP
Statistical Analysis Plan
SCLC
Small Cell Lung Cancer
SD
Stable Disease
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic-pyruvic transaminase
SNB
Sentinel Node Biopsy
SSB
Single Strand Break
STEEP
Standardised Terms for Efficacy Endpoints
Study treatment
Study treatment is the treatment to which patient was randomised. In this study 
it is either olaparib or placebo
TN1-3
TNM classification. Axillary node positive disease regardless of the tumour 
size
TNBC
Triple negative breast cancer
TPC
Chemotherapy of physician’s choice
ULN
Upper Limit of Normal
WBC
White Blood Cells
WBDC
Web Based Data Capture
Wt
Wildtype (patients without evidence of BRCA1 or BRCA2 deleterious or 
suspected deleterious mutations)

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1.
INTRODUCTION
1.1
Background
1.1.1
Breast cancer and its treatment 
Breast cancer is a life-threatening disease and is the second leading cause of cancer death 
among women. In 2013, an estimated 232,340 new cases of invasive breast cancer were 
expected to be diagnosed among US women, and approximately 39,620 women were 
expected to die from breast cancer (American Cancer Society 2013). In the European 
Community, the estimated age adjusted annual incidence in 2008 was 88.4/ 100 000 and the 
mortality 24.3/100 000 (Aebi et al 2011). 
Approximately 5% of breast cancers are associated with a mutation in the BRCA1 and/or 
BRCA2 gene with approximately 3% associated with the BRCA1 gene (generally presenting 
with TNBC phenotype) and approximately 2% associated with the BRCA2 gene (generally 
ER/PgR positive phenotype). In the general population, BRCA mutation carriers have an 
increased relative risk of breast cancer. The presence of BRCA1 mutations is associated with a 
lifetime risk of breast cancer of 60 to 70% and a lifetime risk of ovarian cancer of 20 to 45% 
(Antoniou et al 2003). BRCA2 mutations are associated with lifetime risk of breast cancer of 
40 to 60% in women and 5 to 10% in men and a lifetime risk of ovarian cancer of 10 to 20%. 
Rare individuals carry deleterious mutations in both BRCA1 and BRCA2 genes.
In breast cancer, there are differences between BRCA1 and BRCA2 mutation carriers. 
Approximately 70% of breast cancer patients with BRCA1 mutations present as triple negative 
breast cancer (TNBC). In contrast, patients carrying mutations in the BRCA2 gene are more 
likely to be positive for expression of the estrogen receptor in their breast cancer while 
approximately 20% will have triple negative cancers (Mavaddat et al 2012).
Although there are phenotypic differences in breast cancers resulting from BRCA1 or BRCA2
mutations, their important commonality is that mutations in either gene result in tumours that 
are deficient in homologous recombination, making both appropriate for treatment with 
polyadenosine 5’diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitors 
whereby the process of synthetic lethality can be exploited. In a previous AstraZeneca 
sponsored Phase II proof of concept study in patients with breast cancer carrying BRCA
mutations (Study D0810C00008), approximately 60% of cases were BRCA1 mutations (the 
other 40% were BRCA2 mutations) with 55% of tumours overall triple negative in phenotype. 
In this study, anti-tumour activity was seen in patients with either BRCA1 or BRCA2
mutations (Tutt et al 2010). 
Given the small size of the BRCA subpopulation in breast cancer, information comparing the 
outcome from this subpopulation with the overall breast cancer population is based on reports 
from a number of small studies (Robson et al 2004, Rennert et al 2007, Bordeleau et al 2011, 
Goodwin et al 2012), and firm conclusions cannot be drawn. The overall body of evidence 
suggests that once baseline prognostic factors (such as hormone receptor and HER2 status) 
and treatment are taken into account, patients with BRCA mutations have a similar outcome to 

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their sporadic counterparts (Huzarski et al 2013). This is in contrast to patients with 
BRCA1/BRCA2-related ovarian cancer who have an improved survival compared with non-
carriers, particularly if they receive platinum-based therapy.
Currently, there are no approved treatments specific for germline BRCA1/2 mutated breast 
cancer patients and these patients are treated according to their hormone receptor and HER2 
status.
1.1.2
Triple Negative Breast Cancer (TNBC)
TNBC is a particular subset of breast cancer defined by lack or low immunohistochemical 
expression of ER, PgR and HER2 (IHC 0, 1+ or 2+ /FISH non-amplified) and represents 
approximately 12-17% of breast cancers overall (Foulkes et al 2010). Although it is a 
heterogeneous group, patients with TNBC have generally poor prognosis (Metzger-Filho et al 
2010). The fundamental clinical characteristic of TNBC is early recurrence with likely early 
visceral metastases, as well as shorter period from time to recurrence to death as compared 
with other breast cancer types (Dent et al 2007). Chemotherapy remains the ultimate treatment 
option for those patients with varied impact on long-term prognosis. No targeted treatment has 
been developed for TNBC, in contrast to endocrine treatment and anti-HER2 treatments, 
which have significantly improved the clinical outcomes in ER/PgR positive and HER2 
positive breast cancer patients, respectively. The standard clinical practice for early stage 
TNBC following completion of definitive local and systemic chemotherapy treatment is 
observation. Therefore, TNBC patients having a poor prognosis and limited treatment options 
present an unmet need for targeted treatment development.
1.1.3
Adjuvant chemotherapy for TNBC
The majority of patients presenting with early TNBC receive adjuvant chemotherapy. The first 
randomised Phase III study specifically conducted in early TNBC is the BEATRICE study- an 
Open Label 2-arm Study to Evaluate the Impact of Adjuvant Bevacizumab on Invasive 
Disease Free Survival in Triple Negative Breast Cancer (Cameron et al 2013). In this study, 
2591 patients with resected early TNBC were randomised to receive adjuvant anthracycline 
and/or taxane chemotherapy with or without bevacizumab, followed by bevacizumab 
monotherapy for 12 months. The trial did not meet its primary objective of prolonging 
invasive disease free survival (IDFS). The 3-year IDFS for both arms of the study was 
approximately 83%. It was commented that this 3-year IDFS was better than anticipated; 
however, it should be noted that 63% of patients in the trial were node negative, and ~36% 
had tumours < 2cm. There are no published robust long-term data for subgroups (e.g. different 
nodal status or BRCA mutated tumours) of TNBC treated with standard of care chemotherapy.
1.1.4
Neoadjuvant chemotherapy for TNBC
It is assumed that approximately a third to half of the patients with TNBC will receive 
chemotherapy in the neoadjuvant setting. The key prognostic information following 
neoadjuvant chemotherapy is whether patients have residual disease or have had a 
pathological complete response (pCR; absence of any residual invasive cancer on hematoxylin 

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and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes). 
Individual patients who achieve pCR following neoadjuvant chemotherapy have significant 
improvement in both disease-free survival (hazard ratio (HR) 0.48, 95% CI: 0.37-0.63) and 
overall survival (HR 0.48, 95% CI: 0.33-0.69) compared with patients with residual invasive 
disease (Mieog et al 2007). An M.D. Anderson, single institution experience reported 46% 
pCR rate achieved in a small number of BRCA1 mutated (n=57) breast cancer patients 
following anthracycline/taxane neoadjuvant chemotherapy (Arun et al 2011). In TNBC, the 
prognosis of patients who experience pCR is very similar to that for patients with other breast 
cancer subtypes with less than 10% developing a distant recurrence at 5 years. However, those 
patients with TNBC who do not experience pCR have a much poorer prognosis (Liedtke et al 
2008,Carey 2011). A recently published meta-analysis of anthracycline and taxane containing 
neoadjuvant chemotherapy trials showed that of 911 patients with TNBC, 282 patients (31%) 
experienced a pCR (Von Minckwitz et al 2012). Compared with these patients, patients who 
did not experience a pCR were at higher risk of earlier recurrence over time (HR 6.02, 95% 
CI: 3.92-9.25) and at higher risk of earlier death over time (HR 12.41, 95% CI: 5.82-26.49). 
These results highlight the need to develop further treatment options to improve the prognosis
of TNBC patients who do not achieve pCR after neoadjuvant chemotherapy.
1.1.5
ER/PgR positive HER2 negative breast cancer with germline BRCA mutations    
While most breast cancers arising in patients with germline BRCA mutations are associated 
histologically with the TNBC phenotype, some - particularly those with underlying germline 
BRCA2 mutations - display a non-TNBC phenotype (Honrado et al 2006; Mavaddat et al 
2012). Atchley et al 2008 found positivity for ER/PgR receptor expression in more than 60% 
of patients with documented germline BRCA2 mutations and in about 30% of patients with 
documented BRCA1 mutations. 
Traditionally, these patients have been treated in the same manner as ER/PgR positive patients 
with either unknown or wildtype BRCA status. However, ER/PgR positive, HER2 negative 
patients with BRCA2 mutations have been shown to have higher risk of recurrence and death 
than similar patients without mutations (Tryggvadottir et al 2013), suggesting that the current 
management of these patients could be suboptimal.
This could be particularly true for high-risk ER/PgR positive, HER2 negative breast cancer 
patients. Results from NSABP B-38, a trial which employed modern anthracycline and taxane 
regimens in the adjuvant setting, showed that hormone receptor positive patients with 4 or 
more positive axillary nodes at surgery had a 3 year DFS of 83%, which is comparable to the 
3-year DFS of node negative TNBC (Swain et al 2013). 
Similar considerations can be applied to the neoadjuvant setting. In a recently published, FDA 
co-sponsored meta-analysis looking into the association between the achievement of pCR and 
long-term clinical benefit, pCR rates in patients with ER and/or PgR positive, HER2 negative 
tumours were between 8% to 16%, as opposed to 34% in TNBC (Cortazar et al 2014). While 
all published subgroups in that analysis indicated clinical benefit (longer recurrence-free 
survival) for those patients achieving a pCR, the associated prognostic value varied 

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quantitatively as evidenced by HRs between 0.24 (TNBC patients) and 0.63 (low grade ER 
and/or PgR positive, HER2 negative tumours with an upper bound of the confidence interval 
[CI] being slightly above 1.0). A robust association between failure to achieve pCR and event-
free survival was demonstrated in patients with ER and/or PgR positive, HER2 negative 
Grade 3 tumours. Specifically, the HR for event-free survival in that patient group was found 
to be almost the same (0.27) as the HR for event-free survival in patients with TNBC (0.24). 
This demonstrates that for carefully selected, high risk ER and/or PgR positive, HER2 
negative patients, failure to achieve pCR can have relatively similar prognostic value as in 
patients with TNBC who have residual disease after neoadjuvant chemotherapy. 
1.1.6
PARP inhibition as a therapeutic strategy target for BRCA mutated breast 
cancer
PARP inhibition is a novel approach to targeting tumours with deficiencies in DNA repair 
mechanisms. PARP enzymes are essential for repairing DNA single strand breaks (SSBs). 
Inhibiting PARPs leads to the persistence of SSBs, which are then converted to the more 
serious DNA double strand breaks (DSBs) during the process of DNA replication. During the 
process of cell division, DSBs can be efficiently repaired in normal cells by homologous 
recombination repair. Tumours with homologous recombination deficiencies (HRD), such as 
ovarian or breast cancers in patients with germline BRCA1/2 mutations, cannot accurately 
repair the DNA damage, which may become lethal to cells as it accumulates. In such tumour 
types, olaparib may offer a potentially efficacious and less toxic cancer treatment compared 
with currently available chemotherapy regimens.
BRCA1 and BRCA2 defective tumours are intrinsically sensitive to PARP inhibitors, both in 
tumour models in vivo (Rottenberg et al 2008, Hay et al 2009) and in the clinic (Fong et al 
2009). The mechanism of action for olaparib results from the trapping of inactive PARP onto 
the single-strand breaks preventing their repair (Helleday 2011, Murai et al 2012). Persistence 
of SSBs during DNA replication results in their conversion into the more serious DNA DSBs 
that would normally be repaired by homologous recombination repair. Olaparib has been 
shown to inhibit selected tumour cell lines in vitro and in xenograft and primary explant 
models as well as in genetic BRCA knockout models, either as a stand-alone treatment or in 
combination with established chemotherapies (data on file at AstraZeneca).
Olaparib is a potent PARP inhibitor (PARP-1, -2 and -3) that is being developed as an oral 
therapy, both as a monotherapy (including maintenance) and for combination with 
chemotherapy and other anti-cancer agents.
1.1.7
Pre-clinical experience
The pre-clinical experience is fully described in the current version of the olaparib IB. 
1.1.8
Toxicology and safety pharmacology summary
Olaparib has been tested in a standard range of safety pharmacology studies e.g., dog 
cardiovascular and respiratory function tests, and the rat Irwin test. There were no noticeable 

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effects on the cardiovascular or respiratory parameters in the anaesthetised dog or any 
behavioural, autonomic or motor effects in the rat at the doses studied.
Rodent and dog toxicology studies have indicated that the primary target organ of toxicity is 
the bone marrow with recovery seen following withdrawal of olaparib. Ex vivo studies have 
confirmed that olaparib is cytotoxic to human bone marrow cells.
Olaparib was not mutagenic in the Ames test but was clastogenic in the Chinese hamster 
ovary (CHO) chromosome aberration test in vitro. When dosed orally, olaparib also induced 
micronuclei in the bone marrow of rats. This profile is consistent with the potential for 
genotoxicity in man.
Reproductive toxicology data indicate that olaparib can have adverse effects on embryofoetal 
survival and development at dose levels that do not induce significant maternal toxicity.
Further information can be found in the current version of the olaparib IB.
1.1.9
Clinical experience
Clinical experience with olaparib is fully described in the current version of the olaparib IB.
1.1.9.1 Olaparib monotherapy studies in breast cancer patients
Study D0819C00003
Olaparib demonstrated a statistically significant improvement in PFS in Study D0819C00003 
(OlympiAD), a randomised Phase III study comparing olaparib to chemotherapy of 
physician’s choice (TPC) in the treatment of gBRCAm HER2 negative metastatic breast 
cancer. At 77% maturity, PFS by blinded independent central review was significantly longer 
in patients treated with olaparib vs. TPC (HR 0.58; 95% CI 0.43-0.80; p=0.0009; 7.0 vs 4.2 
months, respectively). Results in the East Asian and White sub-populations were consistent 
with these findings. PFS2 (time to second progression; investigator-assessed) was also longer 
in the olaparib arm (HR 0.57; 95% CI 0.40-0.83). Objective response rate was 59.9% and 
28.8% in the olaparib and TPC arms, respectively. Final analysis of OS at 64% maturity 
revealed a median OS of 19.3 months for olaparib vs 17.1 months for TPC (HR 0.90; 95% CI 
0.66-1.23) (Robson et al 2017).
Study D0810C00002 
Study D0810C00002 was a Phase I open-label, dose escalation and cohort expansion study in 
98 patients with solid tumours. Patients in the dose-escalation cohort received olaparib at 
doses ranging from 10 mg daily to 600 mg twice daily (b.i.d.); whereas all patients in the 
dose-expansion cohort received olaparib at 200 mg twice daily after the MTD was identified 
as 400 mg b.i.d. The main tumours by type were ovarian (54 [55.1%]), breast, (13 [13.3%]); 
colon (5 [5.1%]), prostate (4 [4.1%]) and skin cancers (4 [4.1%]). Overall 23 patients were 
BRCA mutation carriers; of these, 19 patients had BRCA mutated ovarian, breast, or prostate 
cancer and were evaluable for response. Forty-seven percent (9/19) of the patients had an 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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objective response as defined by Response Evaluation Criteria in Solid Tumors (RECIST), 
and 63% (12/19) had stable disease for at least 4 months (Fong et al 2009). 
Study D0810C00008
Study D0810C00008 was a Phase II proof-of-concept study initiated as an open-label, single-
arm, international, multicenter study to assess the efficacy and safety of olaparib given orally 
b.i.d. in patients with gBRCA1 and gBRCA2 mutations and advanced breast cancer. Patients 
had a median of 3 previous chemotherapy regimens and approximately half of the patients had 
TNBC. The primary objective was to assess the efficacy of the capsule formulation at 
2 different doses of olaparib in terms of ORR (overall response rate) in patients with advanced 
breast cancer. Patients received olaparib at a dose of 400 mg b.i.d. or 100 mg b.i.d. 
continuously in 28-day cycles, for multiple cycles, until no further clinical benefit was 
apparent or the patient was withdrawn from the study. The cohorts were conducted in 
sequence, the 400 mg b.i.d. group first (n=27) followed by the 100 mg b.i.d. group (n=27). In 
the ITT analysis set, the confirmed RECIST ORR overall was 11/27 (41%) at 400 mg b.i.d. 
and 6/27 (22%) at 100 mg b.i.d. Responses were seen in both gBRCA1 and gBRCA2 carriers. 
Median time to progression was 5.3 months for the 400 mg b.i.d. group and 3.7 months for the 
100 mg b.i.d. group (Tutt et al 2010).
Study D0810C00020
Study D0810C00020 was a Phase II open-label, non-randomised study of olaparib in patients 
with known gBRCA or high-grade serous/undifferentiated ovarian cancer and patients with 
known gBRCA or TNBC. All patients received olaparib 400 mg b.i.d. until disease 
progression or until the investigator believed it was in the best interest of the patient to stop 
treatment. Tumour response data was analysed in 64 ovarian (BRCA or serous ovarian) and 
26 breast (BRCA or triple negative) cancer patients who received olaparib 400 mg b.i.d. 
Germline BRCA mutations were present in 11 of the 26 breast cancer patients. Median number 
of prior chemotherapies in the breast cancer group was 3 (range: 1 to 7). Over 70% of the 
breast cancer patients had received 3 or more previous lines of prior chemotherapy, with a 
median of 35.3 months from diagnosis to start of treatment with olaparib. None of the breast 
cancer patients achieved a RECIST response. However, 63% of the patients with BRCA
mutations had an overall best response of SD lasting 8 weeks or more. The median PFS in this 
cohort was 3.6 months in this group (Gelmon et al 2011).
Study D0810C00042
Study D0810C00042 was a Phase II, open label, non-randomised, non-comparative, 
multicenter study in patients with advanced cancers who had confirmed germline BRCA1 
and/or BRCA2 mutations. A total of 62 breast cancer patients were recruited, all of whom 
received at least 3 prior lines of therapy (with a median of 6 prior regimens). Eight (12.9%) of 
the breast cancer patients had an OR and the median duration of response was 204 days. At 16 
= weeks, disease control was observed in 23 (37.1%) patients. The median PFS (progression 
free survival) was 3.68 months. The median OS was 11.01 months; the survival rate at 
6 months was 74.6%, and at 1 year was 44.7% (Kaufman et al 2014).

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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The details on the pivotal phase II data in ovarian cancer patients as well as olaparib 
combination with chemotherapy are presented in the Investigator Brochure.
1.2
Research hypothesis
Following completion of definitive local and systemic neoadjuvant or adjuvant chemotherapy 
treatment, giving olaparib tablets 300 mg b.i.d. (twice daily) in the adjuvant setting for up to 
12 months in patients with germline BRCA mutations and high risk, Stage II-III HER2 
negative primary breast cancer has superior efficacy and acceptable tolerability profile as 
compared with no further treatment. The efficacy in this study will be assessed by the primary 
analysis of IDFS defined as the time from randomisation to the date of first treatment failure 
that is loco-regional, distant recurrence, new invasive cancer or death from any cause. 
Supportive efficacy analyses include assessment of distant disease free survival and overall 
survival.
1.3
Rationale for conducting this study
The aim of the proposed phase III study is to obtain a reliable evaluation of whether olaparib 
monotherapy following completion of definitive local and systemic neoadjuvant or adjuvant
chemotherapy is sufficiently safe and provides clinically meaningful benefit in the proposed 
indication.
The primary endpoint of the trial is IDFS, defined as the time from randomisation to date of 
first treatment failure that is loco-regional or distant recurrence or new cancer or death from 
any cause. IDFS is further detailed according to the standardised STEEP system definition 
(Hudis et al 2007) as one of the following:
!
Ipsilateral invasive breast tumour recurrence (IIBTR): invasive breast cancer 
involving the same breast parenchyma as the original primary.
!
Regional invasive breast cancer recurrence: invasive breast cancer in the axilla, 
regional lymph nodes, chest wall, and skin of the ipsilateral breast.
!
Distant recurrence: metastatic breast cancer that has either been biopsy confirmed 
or clinically diagnosed as recurrent invasive breast cancer.
!
Death attributable to any cause, including breast cancer, non-breast cancer, or 
unknown cause.
!
Contralateral invasive breast cancer.
!
Second primary non-breast invasive malignancies (i.e. excluding new in situ 
carcinomas at any site). Second primary non-breast invasive malignancies include 
hematologic malignancies and MDS. Squamous or basal cell skin cancers will not 
be counted as primary endpoint events.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
40(176)
Considering the tendency of TNBCs to metastasise to viscera more often than other types of 
breast cancer, and knowing the generally incurable nature of those with metastases, a 
secondary endpoint of DDFS will be measured to support the primary endpoint of IDFS and 
help characterise the secondary endpoint of OS.
In addition to TNBC, the study will also allow patients with positive hormone receptor status 
as long as they are HER2 negative, who have a germline BRCA mutation and fulfil additional 
criteria for high recurrence risk (see Section 4.1 Inclusion crit. 3A, 3B, 4b). While events in 
these patients might not accumulate at the same rate as in gBRCAm TNBC, extrapolations 
from the metastatic setting (Tutt et al 2010) support the expectations that these patients will 
also benefit from adjuvant olaparib treatment. 
In addition, PARP and BRCA function has been linked to estrogen and other hormone receptor 
transcriptional function (Zhang et al 2013; Schiewer et al 2013), supporting the expectation 
that additive/synergistic effects could manifest when combining hormonal treatments with 
olaparib in hormone receptor-positive patients with gBRCAm status. Recent preclinical data 
by Nardone et al (2015) indicate that olaparib may enhance endocrine therapy efficacy and 
circumvents resistance; as a consequence, addition of olaparib to hormonal treatment might 
confer additional treatment benefits in patients with high recurrence risk.
Hence, hormone-receptor-positive gBRCAm patients will be allowed to receive hormonal 
treatments at any time during the study. Based on in vitro P450 inhibition and induction data, 
olaparib would not be expected to alter the PK of standard hormonal therapies used in the 
adjuvant setting (tamoxifen, aromatase inhibitors with or without ovarian suppression). Based 
on a preliminary analysis from an ongoing olaparib/hormonal treatment study sponsored by 
AstraZeneca (Study D081CC00001) there was no indication for clinically relevant drug-drug 
interaction between olaparib and the anti-hormonal agents tamoxifen, letrozole or anastrozole.
All patients will be followed for local recurrence, distant recurrence (including subsequent 
sites of recurrence), new cancers and overall survival for a minimum of 10 years, in order to 
fully describe the long-term impact of adjuvant olaparib therapy.
1.3.1
Rationale for central BRCA mutation test at Myriad Genetics, Inc 
The FDA has indicated that the BRCA1 and BRCA2 mutation assay will need to be approved 
as a companion diagnostic in the US.
Myriad Genetics, Inc has been chosen as a partner in developing a companion diagnostic for 
BRCA1 and BRCA2 testing because it has extensive experience in BRCA1 and 2 mutation 
detection. Myriad keeps the most comprehensive database on BRCA1 and 2 gene mutations 
and their clinical relevance. Furthermore, Myriad has an established laboratory infrastructure, 
which supports high volume testing with turnaround times that can meet the needs of a clinical 
trial.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
41(176)
1.4
Benefit/risk and ethical assessment
As of 20 March 2015, approximately 3862 patients with ovarian, breast, gastric, pancreatic, 
and a variety of other solid tumours are estimated to have received treatment with olaparib in 
AstraZeneca-sponsored, investigator-sponsored, and collaborative group studies and a 
Managed Access Programme. Olaparib has been given as either monotherapy (an estimated 
2327 patients) or in combination with other chemotherapy/anticancer agents (an estimated 
1535 patients). Many of these combination studies are ongoing. An estimated 1835 patients to 
date have received the capsule formulation of olaparib, 27 patients have received both the 
capsule and tablet formulation, and 2000 patients have received the tablet formulation. 
Approximately 878 patients have received comparator or placebo across the olaparib 
development programme.
An analysis of monotherapy data across 13 AstraZeneca sponsored monotherapy studies in 
1006 patients with ovarian cancer and other non-ovarian solid tumours who have been given 
olaparib capsules estimated that 16.0% (161/1006) of patients had been exposed to olaparib 
capsules for ≥12 months, 8,3% (84/1006) for >18 months and 4,1% for >24 months at the 
time of database closure for the respective studies. Twenty one patients (2.1%) had received 
≥48 months of olaparib exposure. From the available data to date, there is no evidence of any 
unexpected toxicity following long-term olaparib (capsule) monotherapy exposure.
In a Phase I study in ovarian cancer patients (Study DO810C00024) the 300 mg b.i.d. 
monotherapy tablet regimen was considered to have an acceptable tolerability profile relative 
to the 400 mg b.i.d. capsule and has been determined to be the recommended olaparib 
monotherapy tablet dose for future studies with olaparib using the tablet formulation. Olaparib 
as monotherapy at doses up to 400 mg b.i.d. (capsule formulation) and 300 mg b.i.d. (tablet 
formulation) is generally well tolerated, with most common AEs including nausea, fatigue, 
vomiting, and anaemia. There were mainly mild-to-moderate (CTCAE Grade ≤ 2) in severity. 
In addition, in a small number of patients MDS/AML or pneumonitis have been observed and 
identified as important risks. 
Important Potential Risks 
Myelodysplastic syndrome/acute myeloid leukaemia
There have been 21 reports of myelodysplastic syndrome (MDS) and/or acute myeloid 
leukaemia (AML) in patients treated with olaparib as of 20 March 2015; 14 cases in olaparib 
monotherapy trials and 7 cases in olaparib combination studies with carboplatin and paclitaxel 
(n=4) or cediranib (n=1), irinotecan and cisplatin (n=2). A total of 3862 patients are estimated 
to have received olaparib, giving a cumulative incidence of 0.5% for MDS/AML. Two 
additional reports of MDS have been received from a blinded study (D0816C00002) in which 
the treatment of the 2 patients (olaparib or placebo) is unknown, and if these patients are 
considered to have been on olaparib treatment, the estimated incidence would be 0.6%. MDS 
was also reported for 2 patients who were known to have received placebo or a comparator in 
the olaparib trial programme (1 patient received placebo in Study D0810C00019 and 1 patient 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
42(176)
received liposomal doxorubicin in Study D0810C00012). The 21 olaparib-treated patients and 
two patients on blinded treatment had primary ovarian, peritoneal, fallopian tube cancer 
(n=20), pancreatic cancer (n=2) or breast cancer (n=1) and 18 of them had germline BRCA1/2
mutations (3 cases BRCA status unknown; 2 cases negative). It has been hypothesised that a 
deficiency in the expression of BRCA genes may leave patients more vulnerable to the adverse 
effects of chemotherapy, and therefore, at an increased risk of MDS/AML as a result of cancer 
treatment (Cole and Strair 2010). Eleven patients had received olaparib for ≤ 12 months 
(5 patients had < 6 months exposure, 6 patients had 6 to 12 months exposure) and the other 
12 cases occurred following longer than 12 months olaparib exposure (2 patients following 
12-18 months exposure, 2 patients 18-24 months and 8 patients following > 2 years exposure 
to olaparib). 
The median time to onset of t-AML from ovarian cancer diagnosis is reported as 
approximately 5.5 years (Gupta et al 2007; Vay et al 2011). The overall standardised 
incidence ratio (8.68 overall) varies over time - 12.07 within 1 to 5 years, 10.81 within 5 to 
10 years and 2.30 after 10 years (Morton et al 2013).
Eighteen of the 23 patients died: in 12 of these patients, MDS/AML or myelodysplasia was 
recorded as either a primary or secondary cause of death. The other 6 deaths were reported as 
follows: 1 due to cerebral haemorrhage and disseminated intravascular coagulation, 1 due to 
complication of double umbilical cord blood transplantation and 4 due to disease progression 
(2 ovarian cancer, 1 breast cancer [patient had a prior history of ovarian cancer treated with 
platinum-based chemotherapy] and 1 pancreatic cancer). In 5 patients, the event of 
MDS/AML is reported as ongoing as of the 20th March 2015. All patients had other potential 
features that may be contributing factors for the development of MDS/AML. All patients had 
received previous chemotherapy with DNA damaging agents including platinum, with many 
patients having extensive previous chemotherapy with multiple treatment regimens over 
multiple years including carboplatin, taxanes, anthracyclines, other alkylating and DNA 
damaging agents and radiotherapy.
Since bone marrow is known to be a target organ for olaparib toxicity, increased risk of 
MDS/AML with long-term exposure to olaparib cannot be excluded. However, there is 
insufficient data at present to evaluate this relationship. Moreover, while non-clinical data 
suggest bone marrow progenitor cell populations are reduced temporarily following olaparib 
treatment, there is no evidence to date linking olaparib treatment to the generation of abnormal 
bone marrow precursors. Furthermore, all patients who developed MDS/AML had extensive 
prior chemotherapy and while it is not possible to exclude the contribution of olaparib, it must 
be considered that there were other potential contributing factors in all cases. Preclinical data 
also suggest potential benefit with PARP inhibitors in MDS/AML and clinical trials are now 
underway to assess this effect (Gaymes et al 2008). The risk of developing MDS/AML as a 
long term toxicity in breast cancer patients with stage I-III disease exposed to standard dose 
adjuvant chemotherapy including alkylator and anthracycline with or without taxane, is 
estimated to be around 0.5% varying between 0.37% and 1.16% (Praga et al 2005, Smith et al 
2003, Hershman et al 2007, Burnell et al 2010, Aebi et al 2011). Both alkylators and 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
43(176)
topoisomerase II inhibitors (anthracyclines) have been associated with treatment related 
MDS/AML. The risk is perceived as low and not outweighing the benefit of adjuvant 
chemotherapy in breast cancer patients. To ensure robust safety monitoring, patients in this 
clinical trial will have safety assessments every two weeks during the first month and monthly 
safety assessments for the first 6 months of treatment followed by 3 monthly assessments until 
completion of treatment (maximum 12 months treatment). In addition, an Independent Data 
Monitoring Committee (IDMC) will review the emerging safety data from the trial in an 
unblinded fashion. Long term safety follow-up will be implemented in the trial. Clinical 
guidelines for managing bone marrow toxicity are implemented as part of the safety 
management plan (Section 5.5.6).
Pneumonitis
As of 20 March 2015, 14 patients out of a total of 3862 patients, estimated to have received 
olaparib, have reported pneumonitis, giving a cumulative incidence of 0.36% for pneumonitis. 
Six additional reports of pneumonitis have been received from 4 blinded studies, where the 
treatment of the patients is unknown (3 either olaparib or placebo; 2 either olaparib + 
paclitaxel or placebo + paclitaxel and 1 olaparib + abiraterone or placebo + abiraterone). If 
these patients were considered to have been on olaparib treatment, the estimated cumulative 
incidence would be 20/3862 (0.52%). Pneumonitis was also reported for 2 patients (1%) of 
190 patients that received placebo or comparator in the olaparib trial programme (1 patient on 
placebo in Study 19 and 1 patient on paclitaxel in Study 39). The patients were treated with 
olaparib for breast cancer (n=3), ovarian cancer (n=6), non-small cell lung cancer (NSCLC) 
(n=4), small cell lung cancer (SCLC) (n=1), pancreatic cancer (n=1), gastric cancer (n=3), 
prostate cancer (n=1) and thymic cancer (n=1). The reports of pneumonitis presented with no 
consistent clinical pattern and were heavily confounded by a number of pre-disposing factors 
(including disease under investigation, underlying pulmonary disease, pre-existing medical 
conditions, smoking history and/or previous chemotherapy and radiotherapy). The majority of 
patients had received prior radiotherapy and/or chemotherapy and had other risk factors within 
the medical histories including pneumonitis, interstitial lung fibrosis, dyspnoea, haemoptysis, 
chest infection, allergic asthma, pleural effusion, pleural metastases and smoking. Five 
patients had current SCLC or NSCLC. An independent review of available chest computed 
tomography (CT) scans and radiographs associated with the reports of pneumonitis concluded 
that there appeared to be no clear consistent clinical pattern.
Investigation of any new or worsening pulmonary symptoms has been implemented as part of 
the safety management plan (Section 5.5.6).
New Primary Malignancies other than MDS/AML
Overall, the number of reports of new primary malignancies is low, with 24 events (in 
22 patients) being reported to 20 March 2015 in 3862 olaparib treated patients (0.57%) and 
one event (bladder cancer) reported in the placebo arm of the double-blind Study 19. Three 
additional reports of new primary malignancies have been received from 1 blinded study for 
the maintenance treatment of ovarian cancer (D0818C00001, tablet formulation), where the 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
44(176)
treatment of the patients is unknown (either olaparib or placebo). If these patients are 
considered to have been on olaparib treatment, the estimated cumulative incidence would be 
0.65%. 
The types of new primary malignancies reported in the 22 patients on olaparib treatment were 
breast cancer, colon cancer, lung neoplasm malignant, gastric cancer, plasma cell myeloma, 
basal cell carcinoma, skin cancers, neoplasm skin, squamous cell carcinoma, malignant 
melanoma, malignant muscle neoplasm, precursor T-lymphocytoc lymphoma/leukaemia, 
tongue cancer and papillary thyroid carcinoma. The 3 patients on blinded treatment reported 
new primary breast cancer malignancies.
Of the 25 patients (22 on olaparib, 3 on blinded treatment) subsequently diagnosed with a new 
primary malignancy, the majority were reported whilst receiving study treatment (21 patients). 
In 4 patients the event was reported after olaparib discontinuation (within 60 days after 
olaparib discontinuation in 2 patients, and more than 240 days after olaparib discontinuation 
in 2 patients). 
The duration of treatment for the 25 patients was:
!
<6 months for 5 patients
!
6 to 12 months for 8 patients
!
12 to 18 months for 2 patients
!
18 to 24 months for 3 patients
!
>2 years for 7 patients.
The type of new primary cancers reported were generally in line with secondary cancers 
observed in ovarian and breast cancer populations reported in the literature (Bergfeldt et al 
1995, Fowble et al 2001, Wesolowski et al 2007), or were cancers such as skin cancer, known 
to be the most common cancer in the general population and associated with high cure rates.
Ovarian cancer patients have been reported to have an increased risk of developing second 
primary malignancies. Patients with germline BRCA mutations are at risk of developing other 
primary cancers notably breast cancer. Ginsburg et al 2010 reported higher rates of skin 
cancers in patients with BRCA1 (1.6%) and BRCA2 (3.0%) mutations.
There were other contributing factors/potential alternative explanations for the development of 
the new primary malignancy in all 22 olaparib treated patients and the 3 on blinded treatment. 
All patients had previously received various chemotherapy agents including multiple cycles of 
DNA damaging platinum containing chemotherapies, taxanes, anthracyclines and other 
alkylating and DNA damaging agents. Four patients were reported to have had prior 
radiotherapy. Twenty two patients had a documented breast cancer gene mutation (BRCA 1 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
45(176)
or 2). Seven of the 25 patients had previous medical histories of cancer (ovarian, cervix, 
breast, peritoneal) and 3 patients with skin cancers either had previous basal cell carcinoma 
reported or skin lesions evident prior to study treatment.
There is insufficient evidence for an association between olaparib treatment and the 
development of new primary malignancies in the clinical trial programme to date. The risk is 
perceived as low and not outweighing the benefit of adjuvant chemotherapy in breast cancer 
patients. An IDMC will review the emerging data from the trial in an unblinded fashion.
Potential benefit
A Marketing Authorisation Application was approved in EU/EEA on 16 December 2014 for 
the indication ‘LYNPARZA monotherapy for the maintenance treatment of adult patients with 
platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous 
epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete 
response or partial response) to platinum-based chemotherapy.’
A New Drug Application was approved in the US on 19 December 2014 for the indication 
‘LYNPARZA monotherapy in patients with deleterious or suspected deleterious germline 
BRCA mutated (as detected by an FDA-approved test) advanced ovarian cancer who have 
been treated with three or more prior lines of chemotherapy.’
Olaparib tablet formulation was approved in January 2018 for patients with deleterious or 
suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have previously 
been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients 
with hormone receptor-positive breast cancer should have been treated with a prior endocrine 
therapy or be considered inappropriate for endocrine treatment.
Phase II clinical studies have investigated the effect of olaparib either as monotherapy or in 
combination with other chemotherapy agents in cancer patients. In patients carrying germline 
BRCA mutations, monotherapy studies in patients with heavily pre-treated breast cancer have 
reported an ORR of up to 41%.
In ovarian cancer patients, the pivotal phase II study D0810C00019, a double-blind, 
randomised study assessed the efficacy of olaparib 400 mg b.i.d capsules as a maintenance 
treatment following platinum-based chemotherapy in patients with platinum sensitive relapsed 
high grade serous ovarian cancer. The PFS following olaparib maintenance therapy was 
significantly longer compared with the placebo group (HR 0.35; 95% CI: 0.25, 0.49; 
p<0.00001) in the overall population. In the subgroup of patients with BRCA mutant ovarian 
cancer, the effect was even greater with a PFS HR of 0.18 (95% CI: 0.11, 0.31; p<0.00001; 
median 11.2 versus 4.3 months). An interim analysis of OS was performed at 58% maturity. 
In the overall population, the analysis demonstrated a non-statistically significant numerical 
advantage for olaparib-treated patients (OS HR 0.88; 95% CI 0.64-1.21; p=0.43808) and there 
was again a greater effect in the BRCA-mutated subgroup: the OS HR was 0.74 (95% CI 0.46 
to 1.19; p=0.20813) with a numerical advantage in median OS observed with olaparib (median 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
46(176)
34.9 months versus 31.9 months with placebo). Among the 62 placebo-treated patients with 
BRCA mutations, 14 switched to a PARP inhibitor post progression.
Based on these results and data from the full clinical program to date, it is anticipated that in 
the adjuvant setting, olaparib will have a positive benefit risk profile for the treatment of the 
small well-defined population of high-risk HER2 negative primary breast cancer patients with 
BRCA mutations.
2.
STUDY OBJECTIVES
2.1
Primary objective
The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive 
Disease Free Survival (IDFS).
2.2
Secondary objectives
The secondary objectives of this study are:
1.
To assess the effect of adjuvant treatment with olaparib on overall survival (OS)
2.
To assess the effect of adjuvant treatment with olaparib on Distant Disease Free 
Survival (DDFS)
3.
To assess the effect of adjuvant treatment with olaparib on the incidence of new 
primary contralateral breast cancers (invasive and non-invasive), new primary 
ovarian cancer, new primary fallopian tube cancer and new primary peritoneal 
cancer
4.
To assess the effect of olaparib on patient reported outcomes using the FACIT-
Fatigue and EORTC QLQ-C30 questionnaires
5.
To assess the efficacy of olaparib in patients identified as having a deleterious or 
suspected deleterious variant in either of the BRCA genes using variants identified 
with current and future BRCA mutation assays (gene sequencing and large 
rearrangement analysis)
6.
To determine the exposure to olaparib (in plasma) in patients receiving olaparib as 
adjuvant therapy
2.3
Safety objective
To assess the safety and tolerability of adjuvant treatment with olaparib

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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3.1
Overall study design, flow chart and study schedules
This is a randomised, double-blind placebo controlled multicentre, phase III study to assess 
the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with 
germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have 
completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.
Randomised patients will receive study treatment for up to a maximum of 12 months. All 
patients will have safety assessments every 2 weeks during the first month, every 4 weeks for 
the following 5 months (up to week 24) and 3 monthly for the remaining 6 months of study 
treatment, plus 30 days after its discontinuation. Efficacy assessments (medical history and 
physical examination) will be performed on a 3 monthly basis during the first 2 years 
following end of study treatment, followed by 6 monthly assessments for years 3, 4 and 5 and 
annually thereafter. Radiological tests to exclude a second primary breast cancer (ipsilateral 
and/or contralateral) are mandatory before enrolment (within 12 months prior to Screening 
PART 1) and during study participation (starting at week 24 and yearly thereafter) for patients 
with any remaining intact breast tissue (including male patients). The preferred tests are 
mammogram or magnetic resonance imaging (MRI; MRI preferred for patients below 
50 years of age). For patients who underwent a bilateral mastectomy, with no remaining breast 
tissue, a physical examination is sufficient and radiological tests are not mandatory. For 
patients who underwent a bilateral mastectomy, as well as for male patients, clinical exam 
may be supplemented by ultrasound exams at investigator’s discretion. Evidence of disease 
recurrence or new primary cancer will require histopathological and/or radiological 
confirmation. 
Patients who develop loco-regional recurrence should have cytological/histological 
confirmation. Loco-regional recurrence should be treated with curative intent when possible. 
Appropriate imaging (CT, MRI bone and/or PET scan) of the chest/abdomen/pelvis or any 
other area as clinically indicated (MRI preferred to examine CNS (central nervous system) if 
new neurological symptoms occur) should be performed at the time of local recurrence to 
exclude further spread of the disease.
Distant recurrence should be diagnosed by radiological/imaging examination and every 
attempt should be made for histopathological confirmation when metastatic lesion is 
accessible for biopsy. 
If the patient meets the IDFS endpoint due to a breast cancer related distant relapse, the patient 
will enter the survival follow-up phase of the trial, with annual assessments from the date of 
distant relapse, which will continue until 10 years after the last patient is randomised. No 
clinic visits will be required during the survival follow-up phase; information may be 
collected via telephone, medical records or death registries. During the survival follow-up 
phase, in addition to vital status, the following information will be collected (if available): 
specific cancer therapies (only first line treatment for first breast cancer recurrence and any 
subsequent regimens containing PARP inhibitors or platinum received by the patient at any 
time), sites of metastases and any other new cancers. 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
49(176)
If the IDFS endpoint is met due to events other than distant relapse, the patient will continue 
the efficacy assessment visit study schedule until breast cancer related distant relapse occurs, 
or approximately 10 years following their randomisation into the study, whichever occurs 
first. They will then enter the survival follow-up phase of the trial.
See Section 5.8.1 for guidelines on study visits for any patient discontinuing prior to 
completing 52 weeks of study treatment. 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
51(176)
Figure 2
Screening Plan
Screening PART 1– Patients with Unknown gBRCA Mutation Status:
!
Only those patients who do not know their gBRCA mutation status prior to entry in to the study 
These patients will undergo screening assessments as described for PART 1 in Table 1. Screening PART 1 is 
conducted to determine if the patient is considered eligible to undergo the BRCA status blood test. Once 
PART 1 has been successfully completed and patients have had a BRCA test, these patients will continue to 
PART 2 and have all procedures performed as described for PART 2 (see Table 1) 
Screening – PART 2 – ALL Patients (Patients with Known gBRCA Mutation Status):
!
Those patients who already know their gBRCA mutation status and have a deleterious or suspected 
deleterious mutation to undergo screening assessments as described for PART 2 (see Table 1)
!
Those patients originally with unknown gBRCA status who have completed screening PART 1 and 
now have a confirmed deleterious or suspected deleterious mutation should undergo screening 
assessments as described for PART 2 (see Table 1)

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
52(176)
Table 1
Study Schedule - Screening (PART 1 and PART 2) 
Day
Any time prior, during or 
after neoadjuvant/adjuvant 
chemotherapy or 
radiotherapy   
PART 1 a
(ONLY Patients requiring a 
gBRCA status Myriad test 
before randomisation)
-28 to 0 days
PART 2
(Patients with confirmed 
gBRCA status by Myriad or 
if BRCA status is known 
prior to study entry j)
Informed consent
X bc
X j
Demographics (date of birth)
X
X
Medical and surgical history d
X
Prior cancer therapies including 
radiotherapy
X
Inclusion/exclusion criteria
X (all ** criteria)
X
ECOG Performance Status
X
Physical examination
X
Vital signs
X
ECG f
X g
Haematology / clinical 
chemistry/Coagulation o
X
Urinalysis h
X
Pregnancy test i
X
EORTC QLQ-C30 n
X
FACIT-Fatigue n
X
Blood sample for determination of 
BRCA status via Myriad
X
X e
Blood sample for assessment of 
current and future BRCA mutation 
assay(s) c
X
X e
Concomitant medications
X
Archival tumour sample (FFPE) 
(mandatory) k
X
Surgical tumour sample (FFPE)
(post neoadjuvant chemotherapy 
(mandatory)) k
X

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
53(176)
Table 1
Study Schedule - Screening (PART 1 and PART 2) 
Day
Any time prior, during or 
after neoadjuvant/adjuvant 
chemotherapy or 
radiotherapy   
PART 1 a
(ONLY Patients requiring a 
gBRCA status Myriad test 
before randomisation)
-28 to 0 days
PART 2
(Patients with confirmed 
gBRCA status by Myriad or 
if BRCA status is known 
prior to study entry j)
Radiological assessment to 
exclude metastatic breast cancer 
(where applicable) l
X
Family history of cancer
X
Serious Adverse Events m
X (only SAEs due to study 
procedures)
X (SAEs only)
a
The time period is to allow those patients that require a Myriad gBRCA sample to have the test taken and 
the results returned prior to randomisation.
b
It is recommended that patients that require the Myriad gBRCA sample testing are to be consented for 
BRCA testing and participation in the trial prior or during neoadjuvant/adjuvant chemotherapy prior to 
entering the study.
c
Any patient who consents to study related Myriad gBRCA status testing, must also have a blood sample 
taken at the same time for the purpose of developing and validating a future mutation assay. 
d
Include history of blood transfusion within previous 120 days from start of study treatment and the reasons 
e.g. bleeding. Additionally CPS+EG score components should be collected (Clinical stage (CS), estrogen 
receptor status (E), nuclear grade (G), and post-treatment pathologic stage (PS)) for the non-pCR patients 
who received prior neoadjuvant chemotherapy. Instructions on how to calculate the CPS&EG score 
(Mittendorf et al 2011; Jeruss et al 2008) are provided in Appendix H.   
e
Samples to be taken in screening PART 2 only for patients with known gBRCA mutation who have not 
completed PART 1.
f
ECG recordings should be performed once the patient has been in the supine position for at least 5 minutes
g
ECG assessments to be completed within 28 days before randomisation.   
h
Urinalysis (dipstick) should be performed at screening. After screening, urinalysis will only be required if 
clinically indicated.
i
Women who are not postmenopausal or have not undergone hysterectomy must have a negative urine or 
serum pregnancy test within 28 days prior to randomisation and a confirmatory test on Day 1 before starting 
study treatment. If results are positive the patient is ineligible.
j
Patients for whom their gBRCA status is already known, should be consented to the study within 28 days 
prior to randomisation.
k
Mandatory for all randomised patients i.e. for adjuvant patients this refers to the surgical specimen; for 
neoadjuvant patients, both the pre-treatment core biopsy and the surgical specimen with residual disease are 
requested but only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, 
sites may submit a portion of invasive tumour from the original block, either by taking at least one core of 
at least 3 mm in diameter, or by splitting the original block in two parts, and re-embedding one in a new 
block for central submission. If blocks containing pre-neoadjuvant treatment core biopsies are available but 
cannot be submitted, sections mounted on glass slides prepared from the block can be provided. If tumour 
sample can’t be provided as requested above or if it’s not available, approval by Study Team for patient’s 
entry into the trial is required. Samples will only be sent to the study bio-repository once the patient has 
been randomised. 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
54(176)
l
Patients considered at high risk of having disseminated disease (i.e. those with locally advanced 
disease, clinical N2-3 or pathological N1-3 with the exception of pN1a in adjuvant patients are expected to 
have a CT/MRI scan of the Thorax/Abdomen/Pelvis or any other area as clinically indicated and a bone 
scan at any point between diagnosis of the current breast cancer and randomisation to rule out metastatic 
breast cancer. (Note PET/CT scan may be used as an alternative imaging technique and precludes the need 
for bone scan). Radiological tests to exclude a second primary breast cancer (ipsilateral and/or contralateral) 
are mandatory before enrolment (within 12 months prior to Screening PART 1) for patients with any 
remaining intact breast tissue (including male patients). The preferred tests are mammogram or MRI (MRI 
preferred for patients below 50 years of age). For patients who underwent a bilateral mastectomy, with no 
remaining breast tissue, a physical examination is sufficient and radiological tests are not mandatory. For 
patients who underwent a bilateral mastectomy, as well as for male patients, clinical exam may be 
supplemented by ultrasound exams at investigator’s discretion.
To rule out metastatic breast cancer, patients with screening ALT/AST or ALP above institutional upper 
limit of normal should have liver ultrasound, CT or MRI at any time point between diagnosis of current 
breast cancer and randomisation. Screening bone scan is required if ALP and/or corrected calcium level are 
above the institutional upper limit. (Note PET/CT scan may be used as an alternative imaging technique).
m
Serious adverse events must be captured from time of consent. In Screening PART 1 of the study only 
SAEs related to a study procedure will be collected. In Screening PART 2 all SAEs will be collected.
n
EORTC QLQ-C30 + FACIT-Fatigue will be collected prior to randomisation once eligibility is confirmed.
o
Coagulation analysis only required at baseline.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
55(176)
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 
months (14 
weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 
days after last 
dose of study 
medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Serum or urine pregnancy 
test for women of 
childbearing potential a
X
X
X
X
X
ECOG performance status 
X b
Vital signs 
X b
X
X (weeks 12 
and 24 only)
X
X
X
Haematology / clinical 
chemistry c
X b, c
X
X
X
X
X
X
Recurrent/new cancers 
assessment (includes 
physical exam d, clinical 
signs and symptoms) 
X
X (weeks 12 
and 24 only)
X
X
X
Mammogram and/or breast 
MRI (ipsilateral and/or 
contralateral) (MRI 
preferred for patients 
younger than 50 years) e
X (week 24 
only)
Adverse Events
X
X
X
X
X
X
X

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
56(176)
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 
months (14 
weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 
days after last 
dose of study 
medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Concomitant medications 
including blood 
transfusions
X
X
X
X
X
X
X
Demographics j
X 
EORTC QLQ-C30 
X (week 24 
only)
X (week 52 
only)
FACIT-Fatigue 
X (week 24 
only)
X (week 52 
only)
Biomarker Blood 2 
samples (mandatory)
X i
X
PGx Blood sample 
(optional)
X
Blood sample for PK 
analysis (optional; after 
signing PK Informed 
consent) (subset of 
patients)h
X

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
57(176)
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 
months (14 
weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 
days after last 
dose of study 
medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Blood biomarker samples 
at disease recurrence 
(Mandatory)
X
X
X
X
X
X
X
Tumour sample at disease 
recurrence (Optional) k
X
X
X
X
X
X
X
Olaparib 
dispensed/returnedf
X
X
X
X
X
a
Pregnancy tests on serum or urine samples will be performed for women of childbearing potential within 28 days prior to randomisation, on Day 1 of the 
study prior to commencing treatment, at the time points shown in Table 2 during study treatment and at the 30 day follow up visit. If results are positive 
the patient is ineligible/must be discontinued from study treatment immediately. Details of the pregnancy tests must be recorded in the patient’s medical 
records and in the CRF.
b
If assessed within 7 days before randomisation, it does not need to be repeated on Day 1 of study treatment unless investigator believes that it is likely to 
have changed significantly.
c
Safety blood samples do not need to be repeated on Day 1 of study treatment if they have been assessed within 7 days before randomisation and which 
must have been done at least 3 weeks after the last dose of chemotherapy, unless the investigator believes that they are likely to have changed 
significantly. Safety blood samples are to be collected every 2 weeks during the first 4 weeks, then every 4 weeks until week 24 and then at weeks 38 
and 52 of study treatment.
d
Physical examination both local and general should be performed at day 1 and then at weeks 12, 24 and 38 and 52 post randomisation until study 
treatment is discontinued (data is not required to be captured on an eCRF, however any significant changes from baseline must be reported as an AE).
e
Radiological tests to exclude a second primary breast cancer (ipsilateral and/or contralateral) are mandatory during study participation (starting at week 
24 and yearly thereafter) for patients with any remaining intact breast tissue (including male patients). The preferred tests are mammogram or MRI (MRI 
preferred for patients below 50 years of age). For patients who underwent a bilateral mastectomy, with no remaining breast tissue, a physical 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
58(176)
examination is sufficient and radiological tests are not mandatory. For patients who underwent a bilateral mastectomy, as well as for male patients, 
clinical exam may be supplemented by ultrasound exams at investigator’s discretion.
f
Sufficient study treatment should be dispensed for at least each treatment period plus overage, however additional treatment can be dispensed to patients 
to last longer in accordance with local practice.
g
If a patient discontinues prior to completing 52 weeks of study treatment, the patient should have the study treatment discontinuation visit performed 
followed by the 30 day follow-up visit and site staff completes relevant CRF pages as required. In case of premature treatment discontinuation only the 
visits where efficacy assessments are scheduled should be performed i.e. week 12, 24, 38, 52 (as applicable) in Year 1 and all visits in Year 2 onwards. 
Collection of vital signs, AEs, haematology/clinical chemistry results and concomitant medications is no longer required. Information on endocrine 
therapies should be collected and recorded in the clinical database until IDFS endpoint is met due to breast cancer related distant relapse. The date of 
discontinuation, the reasons, and details of the following specific cancer therapies (first line treatment for first breast cancer recurrence and any 
subsequent regimens containing PARP inhibitors or platinum received by the patient at any time) should also be recorded on the eCRF. If the IDFS 
endpoint is met due to breast cancer related distant relapse, the patient enters the survival follow-up phase and is assessed annually from the date of 
distant relapse and until 10 years after the last patient is randomised. If the IDFS endpoint is met due to other events, the patient will continue the study 
schedule until a breast cancer related distant relapse occurs or approximately 10 years following their randomisation into the study, whichever occurs 
first. They will then enter the survival follow-up phase of the trial. During the annual survival follow-up phase, in addition to vital status, the following 
information will be collected (if available): specific cancer therapies (only first line treatment for first breast cancer recurrence and any subsequent 
regimens containing PARP inhibitors or platinum received by the patient at any time), sites of metastases and any other new cancers. If a recurrent/new 
cancer assessment is scheduled within 4 weeks of the study treatment discontinuation visit it can be performed at the 30-day follow-up visit (for more 
details see Section 5.8.1).
h 
PK sampling (optional) to be performed in a subset of patients. Sampling times: pre-dose (before morning dose) plus one sample in each of the 
following sampling windows: 0 to 0.5 h post dose, >0.5 to 1.5 h post dose, 3 to 6 h post dose and >6 to 12 h post dose (before evening dose) preferably 
on visit 4, day 29. Nevertheless, the samples can also be taken at a later treatment visit, provided that PK consent was obtained beforehand (for details 
see Section 6.8).
i
Blood samples (plasma and serum) for biomarker analysis should be collected on Day 1 prior to first dose of study treatment.
j
Race and ethnicity data to be collected unless not allowed by local regulations.
k
The provision of tumour tissue is encouraged only if clinically appropriate and not considered detrimental to patient care and patient signed the 
appropriate consent form.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
59(176)
Table 3
Study Schedule - Follow-up Visits (Year 2 onwards)
Visit Number
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Survival 
Follow-up  
(Every 12 
months)
Year
2
3
4
5
6
7
8
9
10
11+
Month
15
18
21
24
30
36
42
48
54
60
66
78
90
102
114
126, 138, 
etc.
Visit Window
±1month
±2months
±3months
±3months
Recurrent/new cancers 
assessment (includes physical 
exam, clinical signs and 
symptoms)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Mammogram and/or breast 
MRI (ipsilateral and/or
contralateral) (MRI preferred 
for patients younger than 
50 years) a
X
X
X
X
X
X
X
X
X
Subsequent cancer therapy b
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xd
Overall survival assessment
Xd
EORTC QLQ-C30 
X
X
FACIT-Fatigue 
X
X
Blood biomarker samples at 
disease recurrence 
(Mandatory)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
60(176)
Visit Number
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Survival 
Follow-up  
(Every 12 
months)
Year
2
3
4
5
6
7
8
9
10
11+
Month
15
18
21
24
30
36
42
48
54
60
66
78
90
102
114
126, 138, 
etc.
Visit Window
±1month
±2months
±3months
±3months
Tumour sample at disease 
recurrence (Optional) c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SAEe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Radiological tests to exclude a second primary breast cancer (ipsilateral and/or contralateral) are mandatory during study participation (starting at week 
24 and yearly thereafter) for patients with any remaining intact breast tissue (including male patients). The preferred tests are mammogram or MRI (MRI 
preferred for patients below 50 years of age). For patients who underwent a bilateral mastectomy, with no remaining breast tissue, a physical 
examination is sufficient and radiological tests are not mandatory. For patients who underwent a bilateral mastectomy, as well as for male patients, 
clinical exam may be supplemented by ultrasound exams at investigator’s discretion.
b
First line treatment for first breast cancer recurrence and any subsequent regimens containing PARP inhibitors or platinum received by the patient at any 
time need to be recorded. Information on endocrine therapies should be collected and recorded in the clinical database until IDFS endpoint is met due to 
breast cancer related distant relapse.  
c
The provision of tumour tissue is encouraged only if clinically appropriate and not considered detrimental to patient care and patient signed the 
appropriate consent form.
d
During the survival follow-up phase, information (where available) on further subsequent cancer therapies (see footnote b), sites of metastases and any 
other new cancers will be collected in addition to vital status.
e 
All ongoing AEs/SAEs and any new AEs/SAEs identified during the 30 calendar days follow-up period after last dose of study medication must be 
followed to resolution unless the event is considered by the investigator to be unlikely to resolve, or the patient is lost to follow-up or in survival follow-
up. If an Investigator learns of any SAEs, including death, at any time after a patient has completed the 30 days post treatment follow-up period, and 
he/she considers there is a reasonable possibility that the event is causally related to the study treatment, the investigator should report it according to 
SAE reporting procedures for this study. Any cases of MDS/AML, new primary malignancies or pneumonitis occurring after the 30 day follow-up 
period should be reported as an SAE. Non-melanoma skin cancers need to be reported as a non-serious AE unless at least one of the seriousness criteria 
is met which then requires to be reported as an SAE, see Section 6.4.2. Any of these types of serious or non-serious events need to be reported to 
AstraZeneca Patient Safety according to SAE reporting procedures for this study, regardless of investigator’s assessment of causality or knowledge of 
the treatment arm. If a patient develops MDS/AML full diagnostic details and classification should be provided e.g. bone marrow and cytogenetic 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
61(176)
analysis reports, see Sections 5.5.6.3 and 6.4.5.5. A questionnaire will be sent to any investigators reporting MDS/AML or new primary malignancies as 
an aid to provide detailed information on the case.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
62(176)
3.2
Rationale for study design, doses and control groups
3.2.1
Rationale for study design 
In this placebo-controlled, double-blinded adjuvant study, TNBC patients and ER and/or PgR 
positive HER2 negative patients with germline BRCA mutations at high risk of recurrence will 
be randomised to receive monotherapy olaparib 300 mg tablet b.i.d. (twice daily) or 
corresponding placebo for a maximum of 12 months following completion of their definitive 
loco-regional treatment and chemotherapy in the adjuvant or neoadjuvant setting.
The rationale for allowing patients with ER and/or PgR positive HER2 negative breast cancer 
who carry a gBRCAm (including gene rearrangements) is provided in Section 1.3. 
The use of a placebo comparator to olaparib is considered acceptable in order to objectively 
test the hypothesis of improved efficacy with the addition of olaparib for up to 12 months as 
compared to no further therapy (i.e. placebo) in patients with TNBC and endocrine therapy 
alone in patients with ER and/or PgR positive cancer. By blinding patients and investigators, 
using placebo control and assessing patients for disease recurrence at pre-defined intervals, the 
risk of bias that could affect the interpretation of the IDFS endpoint should be minimised. In 
line with international clinical guidelines evidence of disease recurrence will be assessed 
during the regular follow-ups (3 monthly during the first 2 years, 6 monthly during the 3rd, 
4th and 5th year and annually afterwards) by medical history, physical examination and 
mammogram and/or breast MRI (MRI preferred for patients younger than 50 years)
(ipsilateral and/or contralateral), unless clinical signs and symptoms require further 
investigation (Khatcheressian et al 2012). In addition safety follow-ups are implemented 
during the 12-month study treatment period and 30 days after its discontinuation.
It should be noted that the safety and efficacy of olaparib has been demonstrated in the clinical 
program using the capsule formulation (400 mg - 8 capsules - twice daily); however, an 
improved tablet formulation (2 tablets twice daily) has been developed and will be used in this 
study. The tablet dose of olaparib that will be investigated is 300 mg b.i.d. (twice daily) which 
is considered similar to the capsule 400 mg b.i.d. (twice daily) dose. This tablet dose has been 
chosen based on data from Study D0810C00024. Since it has been shown that the capsule and 
tablet formulations are not bioequivalent, a formulation switch based on bioequivalence has 
not been possible. The tablet dose of 300 mg b.i.d. is considered to have similar efficacy in 
terms of tumour shrinkage in ovarian cancer patients with BRCA mutations to the 400 mg 
b.i.d. capsule. The 300 mg b.i.d. tablet dose matches or exceeds the exposure of the 400 mg 
capsule in terms of AUC, Cmaxss, and Cminss. The tolerability profile of the 300 mg b.i.d. tablet 
dose in Study D0810C00024 was considered similar to the 400 mg b.i.d. capsule formulation. 
The most common AEs were consistent with the known safety profile of olaparib, namely low 
grade nausea, vomiting, fatigue, and anaemia. Further information is provided in the olaparib 
Investigator’s Brochure.

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Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
63(176)
3.2.2
Rationale for patient reported outcomes 
The patient population for this study will have had intensive treatments with chemotherapy 
(neoadjuvant or adjuvant), surgery, and possibly radiation therapy prior to entry and 
randomisation on this study. Prior research by the NSABP and other investigators has 
demonstrated physical disruption and many symptoms at the end of primary treatment (Ganz 
et al 2011B, Ganz et al 2004). Research has shown that it may take a year or more for the 
physical and emotional recovery and that symptoms may persist well beyond improvements in 
health related quality of life (HRQoL) (Ganz et al 2011A, Ganz et al 1998A, Ganz et al 
1998B, Ganz et al 2002, Bower et al 2000, Bower et al 2006). Thus, in any studies that are 
designed to capture patient-reported outcomes (PROs) of treatment, consideration should be 
given to assessment of both HRQoL and symptoms.
In this trial of olaparib versus placebo, there is an important opportunity to determine whether 
or not the use of olaparib delays or retards recovery after primary breast cancer treatment, and 
if so, what aspects of symptoms and HRQoL are impaired. Gelmon et al 2011 reported on a 
Phase II open label study of olaparib in breast and ovarian cancer patients, in which fatigue 
was the most common reported toxicity (50-70% of patients) followed by nausea (62-66%), 
vomiting (35-39%), and decreased appetite (27-36%). In a Phase II study in patients with 
BRCA1 or BRCA2 mutations and advanced breast cancer, fatigue was the most significant 
toxicity (41% grade 1-2, and 15% grade 3-4) in the cohort given olaparib 400 mg twice daily 
(Tutt et al 2010). These trials did not use PROs, and since they were conducted in patients 
with advanced disease, there is uncertainty about how much fatigue patients will have in the 
B-55/6-13 trial. However, since this is the most frequent side effect of olaparib, it is our 
primary patient reported outcome in this placebo-controlled comparison.
The FACIT-Fatigue scale will be used to measure treatment related fatigue. The FACIT-
Fatigue measure that is being used in this study is well-established and available in multiple 
languages.
A standard measure of health-related cancer specific HRQoL, the EORTC QLQ-C30, will be 
used in this study to track recovery in key domains of HRQoL in the year after initial 
treatment, and to measure symptoms, with a heightened focus on fatigue and GI symptoms 
(nausea, vomiting, diarrhea), as these symptoms have been reported with olaparib. The GI 
symptoms items from the EORTC QLQ-C30 will be used to assess their severity, with the 
focus on assessments during the treatment period, and in the year following the end of 
treatment. These self-report instruments have been selected for this study due to the need for 
reliable and valid translations in multiple languages, given the international scope of this trial 
and the need to include a large number of participants.
Refer to Section 12.2.3 for patient reported outcomes hypotheses and objectives.

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Drug Substance Olaparib (AZD2281)
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3.2.3
Study Population
Approximately 1800 patients with germline BRCA mutations (gBRCAm) and HER2 negative 
breast cancer who are at high risk of recurrence will be randomised into the trial.
All patients recruited in the study will be selected based on the following 3 principles: 
!
Genetic selection: Documented germline mutation in BRCA1 or BRCA2 that is 
predicted to be deleterious or suspected deleterious (known or predicted to be 
detrimental/lead to loss of function). Patients with germline BRCA1 and/or germline 
BRCA2 mutations that are considered to be non-detrimental (e.g. “Variants of 
uncertain clinical significance” or “Variant of unknown significance” or “Variant, 
favour polymorphism” or “benign polymorphism,” etc) will not be eligible for the 
study. In terms of BRCA mutation status, the following scenarios are considered: 
∀
Status known: for patients already known to have a gBRCA loss of function 
mutation (known as deleterious or suspected deleterious) the exact sequence 
variant must be recorded on the eCRF and a copy of the genetic diagnosis must 
be available at site. These patients may be randomised into the study based on 
the known status, however, re-confirmation of the loss of function mutation 
from a blood sample will be undertaken soon after randomisation by Myriad 
Genetic Inc.
∀
Status unknown: The gBRCA mutation status must be determined by Myriad 
Genetic Inc. prior to randomisation as a loss of function mutation i.e. a known 
deleterious or suspected deleterious mutation
!
Phenotypic tumour selection: All patients must have either TNBC or ER and/or 
PgR positive HER2 negative breast cancer as defined in the eligibility criteria 
section.
!
Prognostic factor selection: Patients will be selected based on high risk of 
recurrence regardless of whether they received their chemotherapy in the adjuvant 
or neoadjuvant setting. High risk of recurrence will be defined as follows:
1. For patients who underwent initial surgery and received adjuvant chemotherapy
∀
TNBC patients must have been axillary node-positive (≥pN1, any tumour size) 
or axillary node negative (pN0) with invasive primary tumour pathological size 
> 2 cm (≥pT2) 
∀
ER and/or PgR positive/HER 2 negative patients must have had ≥4 
pathologically confirmed positive lymph nodes. 
2. For patients who underwent neoadjuvant chemotherapy followed by surgery

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
65(176)
∀
TNBC patients must have residual invasive breast cancer in the breast and/or 
resected lymph nodes (non pCR)
∀
ER and/or PgR positive/HER 2 negative patients must have residual invasive 
cancer in the breast and/or the resected lymph nodes (non pCR) AND a 
CPS&EG score ≥3. Instructions how to calculate CPS&EG score (Mittendorf et 
al 2011; Jeruss et al 2008) are provided in Appendix H.  
4.
PATIENT SELECTION CRITERIA
Investigator(s) should keep a patient screening log of patients who entered pre-study 
screening.
Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this 
study. Under no circumstances can there be exceptions to this rule.
Criteria relevant to Part 1 BRCA screening (Table 1) are marked with ** (double asterisk)
4.1
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria:
1.
**Provision of informed consent prior to any study specific procedures 
2.
**Female or male patients must be ≥18 years of age
3A.
For patients who underwent initial surgery and received adjuvant chemotherapy
∀
TNBC patients must have been axillary node-positive (≥pN1, any tumour size) 
or axillary node-negative (pN0) with invasive primary tumour pathological size 
> 2 cm (≥pT2)
∀
ER and/or PgR positive/HER 2 negative patients must have had ≥4 
pathologically confirmed positive lymph nodes 
3B.
For patients who underwent neoadjuvant chemotherapy followed by surgery
∀
TNBC patients must have residual invasive breast cancer in the breast and/or 
resected lymph nodes (non pCR)
∀
ER and/or PgR positive/HER 2 negative patients must have residual invasive 
cancer in the breast and/or the resected lymph nodes (non pCR) AND a 
CPS&EG score ≥3. Instructions how to calculate CPS&EG score (Mittendorf et 
al 2011; Jeruss et al 2008) are provided in Appendix H  

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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4.
**Histologically confirmed non-metastatic primary invasive adenocarcinoma of the   
breast that is one of the two following phenotypes:
a) TNBC defined as:
∀
ER and PgR negative defined as IHC nuclear staining <1%. 
AND 
∀
HER2 negative (not eligible for anti-HER2 therapy) defined as:
o
IHC 0, 1+ without ISH OR
o
IHC 2+ and ISH non-amplified with ratio less than 2.0 and if 
reported, average HER2 copy number < 4 signals/cells OR
o
ISH non-amplified with ratio less than 2.0 and if reported, 
average HER2 copy number < 4 signals/cells (without IHC)
b) ER and/or PgR positive, HER2 negative breast cancer defined as:
∀
ER and/or PgR positive defined as IHC nuclear staining ≥1%.
AND
∀
HER2 negative (not eligible for anti-HER2 therapy) defined as:
o
IHC 0, 1+ without ISH OR
o
IHC 2+ and ISH non-amplified with ratio less than 2.0 and if 
reported, average HER2 copy number < 4 signals/cells OR
o
ISH non-amplified with ratio less than 2.0 and if reported, 
average HER2 copy number < 4 signals/cells (without IHC)
Patients with multifocal or multicentric invasive disease are eligible as long as all 
the lesions for which HER2 characterization is available are HER2 negative. 
Patients with synchronous bilateral invasive disease are eligible as long as all the 
lesions assessed for HER2 on both sides are negative. 
In both the above cases the lesion considered at highest risk for recurrence based on 
the investigator’s discretion will be used for eligibility determination.
5. 
Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious 
or suspected deleterious (known or predicted to be detrimental/lead to loss of function) 

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Local gBRCA testing results, if available, will be used for establishing eligibility. If 
local gBRCA testing results are not available, central testing will be provided for those 
patients who otherwise appear to be eligible (see Section 6.2.1).
6A.
Completed adequate breast surgery defined as:
∀
The inked margins of breast conservation surgery or mastectomy must be 
histologically free of invasive breast cancer and ductal carcinoma in situ with 
the exception of the posterior margin if this margin is the pectoralis major 
fascia or the anterior margin if this is the dermis. Patients with resection 
margins positive for lobular carcinoma in situ are eligible. 
∀
Patients with breast conservation must have adjuvant radiotherapy. Patients 
having mastectomy may have adjuvant radiotherapy according to local policy 
and/or international guidelines.
6B.
Completed adequate axilla surgery defined as:
Adjuvant Chemotherapy Patients:
∀
Sentinel lymph node biopsy alone if negative or if lymph node(s) only contain 
micrometastases (≤2.0 mm) OR 
∀
Positive sentinel lymph node biopsy followed by axillary nodal dissection or 
radiotherapy as per local guidelines OR
∀
Axillary dissection
Neoadjuvant Chemotherapy Patients:
∀
Sentinel lymph node biopsy performed before neoadjuvant chemotherapy: 
∀
If negative or if lymph node(s) only contain micrometastases 
(≤2.0 mm) additional axillary surgery is not required 
∀
If positive, axillary node dissection or axillary nodal radiotherapy 
should follow completion of neoadjuvant chemotherapy
∀
Sentinel lymph node biopsy performed after neoadjuvant chemotherapy: 
∀
If negative, additional axillary surgery not mandated 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
68(176)
∀
If positive (micrometastases are regarded as positive), additional 
axillary surgery is required unless the patient is enrolled in a Phase 
III multicenter clinical trial proposing radiotherapy as alternative 
treatment of the axilla. The trial must be pre-approved by the 
OlympiA Executive Committee
∀
Axillary dissection
7.
Completed at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing 
anthracyclines, taxanes or the combination of both. Prior platinum as potentially 
curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant 
treatment for breast cancer is allowed. (For neoadjuvant patients all chemotherapy 
should be delivered prior to surgery. No further cycles of chemotherapy post 
surgery are allowed.) 
8.
Patients must have adequate organ and bone marrow function measured within 
28 days prior to randomisation with no blood transfusions (packed red blood cells 
and/or platelet transfusions) in the past 28 days prior to testing for organ and bone 
marrow function as defined below:
∀
Haemoglobin ≥10.0 g/dL 
∀
Absolute neutrophil count (ANC) ≥1.5 x 109/L
∀
Platelet count ≥100 x 109/L
∀
Total Bilirubin ≤ ULN (institutional upper limit of normal) except elevated 
total bilirubin <1.5 x ULN due to Gilbert’s disease or similar syndrome 
involving slow conjugation of bilirubin
∀
AST (SGOT)/ALT (SGPT) ≤2.5 x ULN
∀
ALP ≤2.5 x ULN
To rule out metastatic breast cancer, patients with screening ALT/AST or ALP 
above institutional upper limit of normal should have liver ultrasound, CT or MRI 
at any time point between diagnosis of current breast cancer and randomisation. 
Screening bone scan is required if ALP and/or corrected calcium level are above the 
institutional upper limit. (Note: PET CT scan may be used as an alternative imaging 
technique). 
9.
Serum or plasma creatinine ≤1.5 x ULN
10.
ECOG performance status 0-1

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
69(176)
11A.
Women who are not postmenopausal or have not undergone hysterectomy must 
have documented negative pregnancy test within 28 days prior to randomisation: 
Postmenopausal is defined as: 
∀
Age ≥60 years
∀
Age <60 years and amenorrheic for 1 year or more in the absence of 
chemotherapy and/or hormonal treatment
∀
Follicle stimulating hormone (FSH) and plasma estradiol levels in the 
postmenopausal range for women under 60 years
∀
Radiation-induced oophorectomy with last menses >1 year ago
∀
Bilateral oophorectomy
11B. 
**Women of child bearing potential and their partners, who are sexually active, 
must agree to the use of two highly effective forms of contraception in combination. 
This should be started from the signing of the informed consent and continue,
throughout the period of taking study treatment and for at least 1 month after last 
dose of study drug, or they must totally/truly abstain from any form of sexual 
intercourse. Male patients must use a condom during treatment and for 3 months 
after last dose of study drug when having sexual intercourse with a pregnant woman 
or with a woman of childbearing potential. Female partners of male patients should 
also use a highly effective form of contraception (see Appendix E for acceptable 
methods) if they are of childbearing potential.
12.
**Patient is willing and able to comply with the protocol for the duration of the 
study including undergoing treatment and scheduled visits and examinations
13.
Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary 
tumour, mandatory*.
*NOTE: For adjuvant patients, this refers to the surgical specimen; for neoadjuvant 
patients, both the pre-treatment core biopsy and the surgical specimen with residual 
disease are requested but only one is mandatory. If the surgery tumour blocks are 
available, but cannot be submitted, sites may submit a portion of invasive tumour 
from the original block, either by taking at least one core of at least 3 mm in 
diameter, or by splitting the original block in two parts, and re-embedding one in a 
new block for central submission. If blocks containing pre-neoadjuvant treatment 
core biopsies are available but cannot be submitted, sections mounted on glass 
slides prepared from the block can be provided. If tumour sample can’t be provided 
as requested above or if it’s not available, approval by Study Team for patient’s 
entry into the trial is required.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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14.
Patient should be randomised in the trial ideally within a maximum of 8 weeks of 
completion of their last treatment (surgery, chemotherapy or radiotherapy), but in 
no case longer than 12 weeks. 
4.2
Exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1.
**Involvement in the planning and/or conduct of the study.
2.
Patients who do not have deleterious or suspected deleterious gBRCA1 and/or 
2 mutations but only have BRCA1 and/or BRCA2 mutations that are considered to 
be non-detrimental (e.g., “Variants of uncertain clinical significance” or “Variant of 
unknown significance” or “Variant, favour polymorphism” or “benign 
polymorphism” etc.).
3.
**Previous randomisation in the present study.
4.
**Evidence of metastatic breast cancer. Patient considered at high risk of having 
disseminated disease (i.e. those with locally advanced disease, clinical N2-3 or 
pathological N1-3 with the exception of pN1a in adjuvant patients) should have a 
CT/MRI scan of the Thorax/Abdomen/Pelvis or any other area as clinically 
indicated and a bone scan at any point between diagnosis of the current breast 
cancer and randomisation to rule out metastatic breast cancer. (Note PET/ CT scan 
may be used as an alternative imaging technique and precludes the need for bone 
scan). Patients with screening ALT/AST or ALP above institutional upper limit of 
normal should have liver ultrasound, CT or MRI at any time point between 
diagnosis of current breast cancer and randomisation. Screening bone scan is 
required if ALP and/or corrected calcium level are above the institutional upper 
limit. (Note PET/ CT scan may be used as an alternative imaging technique).
5.
**Exposure to an investigational product within 30 days or five half-lives
(whichever is the longer) prior to randomisation.
6.
**Any previous treatment with a PARP inhibitor, including olaparib and/or known 
hypersensitivity to any of the excipients of study treatment.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
71(176)
7.
**Patients with second primary malignancy. EXCEPTIONS are: 
o
adequately treated non-melanoma skin cancer, curatively treated in situ cancer 
of the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 
endometrial carcinoma.
o
other solid tumours and lymphomas (without bone marrow involvement) 
diagnosed ≥5 years prior to randomisation and treated with no evidence of 
disease recurrence and for whom no more than one line of chemotherapy was 
applied. 
8.
Resting ECG with QTc >470 msec detected on 2 or more time points within a 
24-hour period or family history of long QT syndrome. If ECG demonstrates QTc 
>470 msec, patient will be eligible only if repeat ECG demonstrates QTc 
≤470 msec.
9.
Patients receiving systemic chemotherapy within 3 weeks prior to randomisation.
10.
Patients receiving adjuvant radiotherapy within 2 weeks prior to randomisation.
11.
Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole,
telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or 
cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate 
CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, 
verapamil). The required washout period prior to starting study treatment is 
2 weeks. Concomitant use of known strong (e.g., phenobarbital, enzalutamide, 
phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St 
John’s Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). 
The required washout period prior to starting study treatment is 5 weeks for 
enzalutamide or phenobarbital and 3 weeks for other agents.
12.
Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy, 
excluding alopecia and CTCAE grade 2 peripheral neuropathy.
13.
**Patients with current or past history of haematologic malignancies and any clonal 
non-malignant haematological disorder which predisposes the patient to develop a 
haematological malignancy. Exception: lymphoma (refer to Exclusion Criterion 7).
14.
Major surgery within 2 weeks prior to randomisation: patients must have recovered 
from any effects of any major surgery.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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15.
Patients considered at poor medical risk due to a serious, uncontrolled medical 
disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent 
(within 3 months) myocardial infarction, uncontrolled major seizure disorder, 
extensive bilateral lung disease on High Resolution Computed Tomography scan or 
any psychiatric disorder that prohibits obtaining informed consent.
16.
**Patients unable to swallow orally administered medication and patients with 
gastrointestinal disorders likely to interfere with absorption of the study medication.
17.
Pregnant or breastfeeding women.
18.
**Patients with known active Hepatitis B or C or HIV 
19.
**Previous allogeneic bone marrow transplant.
20.
**Whole blood transfusions in the last 120 days prior to entry to the study which 
may interfere with gBRCA testing (packed red blood cells and platelet transfusions 
are acceptable, for timing refer to inclusion criteria no. 8)
For procedures for withdrawal of incorrectly enrolled patients see Section 5.3.
5.
STUDY CONDUCT
5.1
Restrictions during the study
5.1.1
Meals and dietary restrictions
It is prohibited to consume grapefruit juice while on study therapy.
5.1.2
Contraception
Women of childbearing potential, who are sexually active, must agree to the use of two highly 
effective forms of contraception in combination (as described in Appendix E). This should be 
started from the signing of the informed consent and continue throughout the period of taking 
study treatment and for at least 1 month after last dose of study drug or they must totally/truly 
abstain from any form of sexual intercourse. Male patients must use a condom during 
treatment and for 3 months after last dose of study drug when having sexual intercourse with a 
pregnant woman or with a woman of childbearing potential. Female partners of male patients 
should also use a highly effective form of contraception if they are of childbearing potential. 
Male patients should not donate sperm throughout the period of taking olaparib and for 3 
months following the last dose of olaparib. For details please refer to Appendix E Acceptable 
Birth Control Methods.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
73(176)
5.2
Patient enrolment and randomisation and initiation of study treatment
The following section outlines procedures for Screening Registration and for Randomisation, 
and for ordering Study Drug at randomisation:
1.
The Investigator must obtain signed informed consent from the potential patient 
before any study specific procedures are performed.
2.
The authorised site staff should register the patient for screening using the Frontier 
Science web-based Registration and Randomisation system. At the time of 
registration, the patient will be assigned a unique patient identifier (E-code) which 
should be used to identify the patient on the central Myriad sample, the eCRFs in 
Medidata Rave and any other trial-related communications.
3.
The Investigator must determine patient eligibility. See Sections 4.1 and 4.2
4.
If the patient meets the eligibility requirements, the authorised site staff should 
randomise the patient using the same Frontier Science web-based Registration and 
Randomisation system answering all questions which are asked by the system 
including questions relative to the stratification factors.
5.
The randomisation system will randomly assign treatment (olaparib or placebo). 
The treatment allocation will be blinded for the Investigator and the patient. 
6.
Randomisation will automatically trigger initial study drug shipment to the site 
(except for countries where the initial drug shipment is sent upon site activation).
7.
Once medication is received and confirmed in IVRS/IWRS, the site personnel can 
dispense the medication pack matching the kit identification number (Kit ID) 
assigned to the patient by the IVRS/IWRS drug ordering system.
8.
Before dispensing, the site personnel should perform Kit verification transaction in 
IVRS/IWRS by matching the drug Kit ID with 2 letter security code printed on the 
medication pack’s label.
9.
Details of drug dispensing procedures can be found in the IVRS/IWRS manual.
5.2.1
Procedures for randomisation
Patient eligibility must be established before randomisation is undertaken. Randomisation can 
be performed for patients who met all eligibility criteria upon completion of all necessary 
Screening PART 2 procedures, either prior to or on Day 1, depending on the drug supply 
strategy for a particular country. This is to ensure that the study drug is available at site and 
can be dispensed to the patient during Visit 2 (Day1).
The randomisation system will use the following stratification factors:

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
74(176)
!
Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC)
!
NOTE: In cases of multifocal, multicentric or synchronous bilateral invasive 
disease, stratification is based on the status of the lesion considered at highest risk 
(at the investigator’s discretion) that was used to determine eligibility.
!
Neoadjuvant versus adjuvant chemotherapy
!
Platinum therapy for current breast cancer: Yes/No
Eligible patients will be randomised in a 1:1 ratio to one of the following treatments:
!
Olaparib tablets p.o. 300 mg twice daily
!
Matching placebo tablets p.o. twice daily 
It is recommended that patients commence study treatment within 7 days of randomisation, 
but no later than 21 days.
If, following randomisation, it is discovered that incorrect information on the stratification 
factors was entered at randomisation, then the correct information should be recorded in the 
eCRF but the randomisation system will retain the information that was provided at the time 
of randomisation.
Further details about the randomisation process can be found in the Randomisation 
Guidelines.
5.3
Procedures for handling patients incorrectly enrolled or randomised or 
initiated on study treatment
Patients who fail to meet the inclusion/exclusion criteria must not, under any circumstances, 
be enrolled or receive study medication. There can be no exceptions to this rule.
Where patients that do not meet the eligibility criteria are randomised in error or incorrectly 
started treatment, or where patients are subsequently found not to meet the pre-study criteria, a 
discussion should occur between the Study Physician or Medical Team (see Section 13.1) and 
the Investigator regarding whether to continue or discontinue the patient from treatment. Once 
a decision is made, Investigators need to ensure they comply with all applicable requirements 
for human patient protection and ethical review. The data on these patients will remain in the 
study database and will be included in appropriate analyses as defined by the Statistical 
Analysis Plan. Data values provided at the time of randomisation will not be changed. Any 
corrected values for stratification fields or other randomisation data fields will be recorded 
elsewhere in the clinical database, leaving the randomisation record to reflect the data actually 
provided at the time of randomisation.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
75(176)
Contact with the Study Physician or Medical Team (see Section 13.1) is to ensure all such 
decisions are appropriately documented. In situations where an agreement cannot be reached, 
the patient should have their study therapy stopped but should continue to have efficacy 
assessments as per the study plan, unless the patient withdraws consent.
5.4
Blinding and procedures for unblinding the study 
5.4.1
Methods for ensuring blinding
Olaparib and placebo treatment will be blinded.
The study medication will be labelled using a unique Kit ID number. The active and placebo 
tablets will be identical and presented in the same packaging to ensure blinding of the study 
medication.
5.4.2
Methods for unblinding individual patients
The treatment code for an individual patient should not be broken except in medical 
emergencies and when the appropriate management of the patient requires knowledge of the 
actual treatment assignment. The study investigator(s) can access unblinded patient 
information (i.e. randomised treatment information) through the IVRS/IWRS. The process for 
unblinding individual patients will be described in the IVRS/IWRS Manual that will be 
provided to each site. Following emergency unblinding the investigator should report the 
unblinding to the relevant Site Monitor, without revealing any treatment information.
Only life threatening situations should be considered as emergency such as in the cases listed 
below: 
!
Study drug was taken by someone else other than the patient by mistake.
!
Patient is in a life threatening condition following intentional or unintentional 
consumption of study drug in higher doses than indicated.
!
Patient admitted to emergency unit with what is regarded as life threatening condition 
irrespective of potential causal relationship with OLYMPIA study drug, and the 
treating team has to know the nature of all medications the patient is receiving.
Most other situations not mentioned above are regarded as non-emergency and hence the non-
emergency unblinding procedure should apply.
Where a non-emergency unblinding is sought for an individual patient the process will require 
a discussion with the Study Physician or Medical Team (see Section 13.1) to understand the 
need for unblinding and help minimise any unnecessary unblinding, before the patient is 
unblinded. However the final decision as to whether or not to unblind the patient will be made 
by the investigator.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
76(176)
Disease progression or medical conditions that are manageable without any compromise to 
patient care in the absence of knowledge of the treatment received by the patient will not be 
considered as valid reasons for unblinding.
In both emergency and non-emergency cases, the information on the assigned treatment (i.e. 
Olaparib or Placebo) should be restricted only to the Principal Investigator and/or personnel 
involved in the clinical care of the patient as deemed appropriate by the Principal Investigator. 
This information should not be revealed to the sponsor or any member of the study team
except for cases when the Monitor is required to access unblinded data to perform data 
verification in the eCRF.
Any patient unblinded by the site personnel will need to be immediately discontinued from the 
study treatment.
The AstraZeneca patient safety team retains the right to break the code for individual SAEs 
that are unexpected and are suspected to be causally related to the study treatment and that 
potentially require expedited reporting to regulatory authorities. Treatment codes will not be 
broken for the planned analyses of data until all decisions on the evaluability of the data from 
each individual patient have been made and documented and the target number of events has 
been reached.
5.5
Treatments
5.5.1
Identity of study treatment
AstraZeneca’s Pharmaceutical Development, R&D Supply Chain will supply olaparib and 
matching placebo to the Investigator as green film-coated tablets as shown in Table 4 below.
Table 4
Identity of study treatment 
Study treatment
Dosage form and strength
Olaparib*
Tablet –100 mg
Olaparib*
Tablet – 150 mg
Placebo to match olaparib
Tablet to match 100 mg olaparib
Placebo to match olaparib
Tablet to match 150 mg olaparib
* Descriptive information for olaparib can be found in the Investigator’s Brochure
5.5.2
Doses and treatment regimens
5.5.2.1
Olaparib and matching placebo (study treatment)
Study treatment is available as a green film-coated tablet containing 150 mg or 100 mg of 
olaparib or matching placebo.
For all centres, olaparib and matching placebo (study treatment) will be packed in high-
density polyethylene (HDPE) bottles with child-resistant closures. The randomised study 

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Drug Substance Olaparib (AZD2281)
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Edition Number 5
Date 18 May 2018
77(176)
treatment will be dispensed to patients. Each dosing container will contain sufficient 
medication for at least each treatment period plus overage. The planned dose of 300 mg b.i.d. 
(twice daily) will be made up of two (2) x 150 mg tablets b.i.d. (twice daily) with 100 mg 
tablets used to manage dose reductions, as explained in Table 5.
Table 5
Study treatment doses and treatment regimens
Total
daily dose
Dose
twice daily 
(b.i.d.)
Morning
Evening
Number of 
tablets
Tablet 
strength
Number of 
tablets
Tablet 
strength
600 mg
300 mg
2 tablets
150 mg
2 tablets
150 mg
Initial dose (300 mg twice daily) can be reduced as follows for AEs (no re-escalation allowed):
500 mg
250 mg
1 tablet
150 mg
1 tablet
150 mg
1 tablet
100 mg
1 tablet
100 mg
400 mg
200 mg
2 tablets
100 mg
2 tablets
100 mg
Temporary dose levels due to CYP3A inhibitor exposure (re-escalation allowed):
300 mg
150 mg
1 tablet
150 mg
1 tablet
150 mg
200 mg
100 mg
1 tablet
100 mg
1 tablet
100 mg
As soon as possible following randomisation, patients will be administered olaparib or 
matching placebo orally twice daily (b.i.d.) at 300 mg for 52 weeks. Two (2) x 150 mg 
olaparib or matching placebo tablets should be taken at the same time each morning and 
evening of each day, approximately 12 hours apart with approximately 240 mL of water. The 
olaparib/placebo tablets should be swallowed whole and not chewed, crushed, dissolved or 
divided. Olaparib/placebo tablets can be taken with a light meal/snack (e.g., two pieces of 
toast or two biscuits).
If vomiting occurs shortly after the study treatment tablets are swallowed, the dose should 
only be replaced if all of the intact tablets can be seen and counted. Should any patient 
enrolled on the study miss a scheduled dose for whatever reason (e.g., as a result of forgetting 
to take the tablets or vomiting), the patient will be allowed to take the scheduled dose up to a 
maximum of 2 hours after that scheduled dose time. If greater than 2 hours after the scheduled 
dose time, the missed dose is not to be taken and the patient should take their next allotted 
dose at the next scheduled time. Patient should not take two doses (4 tablets) at the same time.

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Within this study, patients will not be provided olaparib post discontinuation of study 
treatment. Patients and investigators will not be routinely unblinded to study treatment prior to 
the final overall survival (OS) analysis.
5.5.3
Additional study drug - Not applicable
5.5.4
Labelling
Labels will be prepared in accordance with Good Manufacturing Practice (GMP) and local 
regulatory guidelines. The labels will fulfil GMP Annex 13 requirements for labelling. Label 
text will be translated into local language. 
Specific dosing instructions will not be included on the label; the site must complete the 
“Patient Dispensing Card” with the details of the dosing instructions at the time of dispensing.
The patient emergency contact details will not be on the label, unless it is a country-specific 
regulatory requirement, but can be found in the informed consent and the ‘Patient Dispensing 
Card’. For emergency purposes the patient must be in possession of the emergency contact 
details at all times.
5.5.5
Storage
All study drugs should be kept in a secure place under appropriate storage conditions. The 
study treatment label on the bottle specifies the appropriate storage.
5.5.6
Management of toxicity of study treatment 
General instructions
!
The CTCAE v4.0 must be used to grade the severity of AEs.
!
All dose modifications should be based on the AE requiring the greatest modification.
!
Therapy should be held until the AE returns to ≤ grade 1 unless specified otherwise in the 
dose modification instructions.
!
If study drug must be held for more than 4 weeks due to an AE or for any other 
reasons, permanently discontinue olaparib/placebo.
!
Once a dose has been reduced, dose escalation is not permitted.
!
If olaparib/placebo must be permanently discontinued, patient follow-up continues to be 
required as described in Table 2 and Table 3.
!
If any other investigational treatment is administered, olaparib/placebo must be 
discontinued.

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Drug Substance Olaparib (AZD2281)
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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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5.5.6.1
Study therapy following breast cancer recurrence or second primary cancer
Olaparib/placebo must be discontinued following diagnosis of breast cancer recurrence or 
diagnosis of a second primary malignancy (i.e., excluding new in situ carcinomas of any site 
and squamous or basal cell skin cancers). Further therapy is at the investigator's discretion.
5.5.6.2
Olaparib/placebo dose levels
All olaparib/placebo dose reductions are based on the dose levels listed in Table 6.
Any toxicity observed during the course of the study should be managed by guidelines as 
outlined in Table 7 Table 8 and Table 9. Once a dose has been reduced, dose re-escalation to a 
higher dose is not permitted.
Table 6
Olaparib/placebo dose levels
Dose Level (mg) twice daily
Starting 
dose
Dose levels for AEs (no re-
escalation)
Temporary dose levels due 
to CYP3A inhibitor 
exposure
Olaparib/placebo
300
250
200
150
100

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Table 7
Mandatory Treatment for Hematologic Toxicity and Treatment 
Guidance for other olaparib/placebo Toxicities
Important table instructions:
!
Dose modifications must be based on the AE requiring the greatest modification.
Adverse 
Event
CTCAE 
(v 4.0) 
Grade
Action to be Taken
Hematologic 
Toxicity
Mandatory
Anaemia
2
(8.0-9.5 
g/dL)
Hold study therapy until # 9.5 g/dL: If recovery 
without packed red blood cells transfusion takes:
1-2 weeks – maintain dose; 
3-4 weeks – ∃one dose level
If packed red blood cells transfusion given:
reduce one dose level
3, 4
Hold study therapy until # 9.5 g/dL:
1st appearance – ↓ 1 dose level 
2nd appearance – ↓ 2 dose levels or discontinuation
Neutrophil 
count 
decreased
(incl. febrile 
neutropenia)
3
Hold study therapy until % 1200/mm3 
∃one dose level
4
Hold study therapy until % 1200/mm3 
∃two dose levels
Platelet count 
decreased
2
Hold study therapy until % 75,000//mm3
↓ one dose level
3,4
Hold study therapy until % 75,000//mm3
↓ two dose levels
Other 
toxicity 
deemed to 
be 
attributable 
to study 
treatment
Guidance
Diarrhea (if 
attributable to 
olaparib/place
bo)
2
Maintain dose or ↓ one dose level
3
↓ one dose level
4
Discontinuation
Mucositis –
oral
2
Maintain dose or ↓ one dose level
3
↓ one dose level
4
Discontinuation
Nausea 
(despite 
antiemetics)
2
Maintain dose or ↓ one dose level
3
↓ one dose level
2
Maintain dose or ↓ one dose level

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Drug Substance Olaparib (AZD2281)
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Important table instructions:
!
Dose modifications must be based on the AE requiring the greatest modification.
Adverse 
Event
CTCAE 
(v 4.0) 
Grade
Action to be Taken
Vomiting 
(despite 
antiemetics)
3
↓ one dose level
4
↓ one dose level or discontinuation
Infection
3
Hold study therapy: When resolved:
Maintain dose or ↓ one dose level
Repeat appearance – ↓ one dose level
4
Hold study therapy: When resolved:
↓ two dose levels or discontinuation
Dyspnea
1, 2, 3
Hold study therapy; rule out pneumonitis 
Follow instructions in footnote a
4
Discontinuation
Pneumonitis
2
Follow instructions in footnote a
3, 4
Discontinuation
Other 
clinically 
significant 
AEs deemed 
related to 
study 
treatment 
b
2
Maintain dose or ↓ one dose level
3
↓ one dose level
4
↓ two dose levels or discontinuation
a
Hold olaparib/placebo and determine etiology. Unless prohibited based on instructions for other clinical 
diagnoses (i.e. other AEs), resume olaparib when grade 0 (if the AE requiring olaparib to be held was 
dyspnea) or when ≤ grade 1 (if the AE requiring olaparib to be held was ≥ grade 2).
b
Determination of "clinically significant" AEs is at the investigator's discretion.
Table 8
Dose reduction for study treatment to manage moderate renal 
impairment
Initial dose
Moderate renal impairment (calculated creatinine clearance 
by Cockcroft -Gault equation or based on a 24 hour urine 
test between 31 and 50 ml/min): Dose reduction 
300 mg twice daily
200 mg twice daily

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Table 9
Dose reduction for study treatment with concurrent use of a strong 
or moderate CYP3A inhibitor
Initial dose
Strong CYP3A inhibitor
Moderate CYP3A inhibitor
300 mg twice daily
100 mg twice daily
150 mg twice daily
For guidance on dose reductions for management of renal impairment refer to Section 5.5.6.3.
For guidance on dose reductions when concomitant strong or moderate CYP3A inhibitors 
cannot be avoided see section 5.6.2.
5.5.6.3
Renal impairment
If subsequent to study entry and while still on study therapy, a patient’s estimated creatinine 
clearance falls below the threshold for study inclusion (≥51 ml/min), retesting should be 
performed promptly. 
A dose reduction is recommended for patients who develop moderate renal impairment 
(calculated creatinine clearance by Cockcroft-Gault equation or based on a 24 hour urine test 
of between 31 and 50 ml/min) for any reason during the course of the study: the dose of study 
treatment should be reduced to 200 mg b.i.d.
Because the creatinine clearance determination is only an estimate of renal function, in 
instances where the creatinine clearance falls between 31 and 50 mL/min, the investigator 
should use his or her discretion in determining whether a dose change or discontinuation of 
therapy is warranted.
Olaparib has not been studied in patients with severe renal impairment (creatinine clearance 
≤30 ml/min) or end-stage renal disease; if patients develop severe impairment or end stage 
disease is it recommended that study treatment be discontinued.
5.5.6.4
Management of haematological toxicity 
If blood transfusion support is required to maintain haemoglobin levels above 9.5 mg /dl at 
Dose Level -2 with no alternative explanation for the recurring anaemia, study treatment 
should be permanently discontinued and the patient referred for haematological evaluation.
If a patient develops febrile neutropenia, study treatment should be stopped and appropriate 
management including G-CSF may be given according to local hospital guidelines. If grade 3 
or 4 anaemia, neutropenia or thrombocytopenia occurs, weekly differential blood counts 
including reticulocytes and peripheral blood smear should be performed until Hgb is 
> 9.5 mg/dl, ANC is > 1200/mm3 and platelets are > 75,000/mm3. If persistent haematological 
toxicities lead to discontinuation of study therapy, the patient should be referred to a 
haematologist for further investigations. Differential blood counts including reticulocytes and 

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peripheral blood smear should be performed at least every 2 weeks until resolution or 
stabilization. 
Bone marrow analysis and/or blood cytogenetic analysis should be considered at this stage 
according to standard haematological practice. Clinical notes and results from further testing 
should be submitted. 
Development of a confirmed myelodysplastic syndrome or other clonal blood disorder should 
be reported as an SAE and full reports must be provided by the investigator to AstraZeneca 
Patient Safety. 
Administration of blood cell products and platelet transfusions must be recorded in eCRF.
5.5.6.5
Management of new or worsening pulmonary symptoms 
If new or worsening pulmonary symptoms (e.g., dyspnoea) or radiological abnormality 
occurs, study treatment should be held and a diagnostic workup (including a high resolution 
CT scan) should be performed, to exclude pneumonitis. Following investigation, if no 
evidence of abnormality is observed on CT imaging and symptoms resolve, then study 
treatment can be restarted, if deemed appropriate by the investigator. If significant pulmonary 
abnormalities are identified, these need to be discussed with the Study Physician or Medical 
Team (see Section 13.1). 
5.5.6.6
Management of nausea and vomiting
No routine prophylactic anti-emetic treatment is required at the start of study treatment, 
however, patients should receive appropriate anti-emetic treatment at the first onset of nausea 
or vomiting and as required thereafter, in accordance with local treatment practice guidelines. 
As per international guidance on antiemetic use in cancer patients (ESMO, NCCN), generally 
a single agent antiemetic should be considered. 
5.5.6.7
Interruptions for intercurrent non-toxicity related events
Study treatment dose interruption for conditions other than toxicity resolution should be kept
as short as possible. If a patient cannot restart study treatment within 4 weeks for resolution of 
intercurrent conditions not related to disease recurrence or toxicity, the case should be
discussed with AZ study physician. All dose reductions and interruptions (including any 
missed doses), and the reasons for the reductions/interruptions are to be recorded according to 
the eCRF guidelines. Study treatment should be stopped at least 3 days prior to planned 
surgery. After surgery study treatment can be restarted when the wound has healed. No 
stoppage of study treatment is required for any needle biopsy procedure. Study treatment 
should be discontinued for a minimum of 3 days before a patient undergoes radiation 
treatment. Study treatment should be restarted within 4 weeks as long as any bone marrow 
toxicity has recovered.

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Drug Substance Olaparib (AZD2281)
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Because the AEs related to olaparib may include asthenia, fatigue and dizziness, patients 
should be advised to use caution while driving or using machinery if these symptoms occur.
5.6
Concomitant and subsequent treatment(s)
Any concomitant medications (exceptions described in Table 10) which are considered 
necessary for the patient's welfare, and which will not interfere with the study medication (in 
the opinion of the treating physician), may be given at the discretion of the investigator, 
providing the medications, the doses, dates and reasons for administration are recorded on the 
appropriate eCRF page in Medidata Rave.
Bisphosphonates or denosumab are allowed during study treatment phase and follow-up.
In addition, any relevant unplanned diagnostic, therapeutic or surgical procedure performed 
during the study period must be recorded. This includes any blood transfusions.
The reasons for the use, doses and dates of treatment should be recorded in the patient’s 
medical records and appropriate sections of the eCRF.
All medications (prescriptions or over the counter medications) continued at the start of study 
or started during the study or until 30 days from the end of the last protocol treatment and 
different from the study medication must be documented.
Information on endocrine therapies should be collected and recorded in the clinical database 
until IDFS endpoint is met due to breast cancer related distant relapse.
The receipt of other anti-neoplastic medications (with the exception of hormonal therapies as 
addressed in Section 5.6.1) and other investigational medication is prohibited during study 
treatment and follow-up. 
Subsequent anti-cancer treatment is expected to be initiated following breast cancer 
recurrence; if subsequent anti-cancer treatment needs to be initiated during the 1-year 
treatment phase, study treatment must be stopped. Information on first line treatment for first 
breast cancer recurrence and any subsequent regimens containing PARP inhibitors or platinum 
received by the patient at any time must be recorded in the clinical database. 
5.6.1
Administration of endocrine therapy
Patients should receive adjuvant endocrine therapy per local policy and/or international 
guidelines. Information on endocrine therapies should be collected and recorded in the eCRF 
until IDFS endpoint is met due to breast cancer related distant relapse. 
5.6.2
Restricted concomitant medications
The use of any natural/herbal products or other traditional remedies should be discouraged but 
use of these products, as well as any medication or vaccine including over-the-counter or 

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Drug Substance Olaparib (AZD2281)
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Edition Number 5
Date 18 May 2018
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prescription medicines, vitamins, and/or herbal supplements that the patient is receiving at the 
time of enrolment or receives during the study must be recorded along with:
!
Reason for use
!
Dates of administration including start and end dates
!
Dosage information including dose and frequency
Table 10
Restricted concomitant medications
Medication/class of drug:
Usage (including limits for duration 
permitted and special situations in which it’s 
allowed ):
Strong CYP3A inhibitors:
itraconazole, telithromycin, clarithromycin, 
boosted protease inhibitors, indinavir, 
saquinavir, nelfinavir, boceprevir, telaprevir
Moderate CYP3A inhibitors:
ciprofloxacin, erythromycin, diltiazem, 
fluconazole, verapamil
Strong or moderate CYP3A inhibitors should not 
be taken with study treatment. If there is no 
suitable alternative concomitant medication then 
the dose of study treatment should be reduced 
for the period of concomitant administration. 
The dose reduction of study treatment should be 
recorded in the CRF with the reason documented 
as concomitant CYP3A inhibitor use. 
•
Strong CYP3A inhibitors – reduce the 
dose of study treatment to 100 mg b.i.d 
for the duration of concomitant therapy 
with the strong inhibitor and for 5 half-
lives afterwards.
•
Moderate CYP3A inhibitors - reduce the 
dose of study treatment to 150 mg b.i.d for 
the duration of concomitant therapy with 
the moderate inhibitor and for 3 half-lives 
afterwards.
•
After the washout of the inhibitor is 
complete, the study treatment dose can be 
re-escalated.
Strong CYP3A inducers:
phenobarbital, phenytoin, rifampicin, rifabutin, 
rifapentine, carbamazepine, nevirapine, 
enzalutamide and St John’s Wort
Moderate CYP3A inducers:
bosentan, efavirenz and modafinil
Strong or moderate CYP3A inducers should not 
be taken with study treatment.
If the use of any strong or moderate CYP3A 
inducers are considered necessary for the 
patient’s safety and welfare this could diminish 
the clinical efficacy of olaparib.
If a patient requires use of a strong or moderate 
CYP3A inducer then they must be monitored 
carefully for any change in efficacy of study 
treatment.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
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Edition Number 5
Date 18 May 2018
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Table 10
Restricted concomitant medications
Medication/class of drug:
Usage (including limits for duration 
permitted and special situations in which it’s 
allowed ):
•
CYP3A4 substrates: hormonal 
contraceptive, simvastatin, cisapride, 
cyclosporine, ergot alkaloids, fentanyl, 
pimozide, sirolimus, tacrolimus and 
quetiapine
•
CYP2B6 substrates: bupropion, efavirenz
•
OATP1B1substrates: bosentan, 
glibenclamide, repaglinide, statins and 
valsartan
•
OCT1, MATE1 and MATE2K substrates:  
metformin
•
OCT2 substrates: serum creatinine
•
OAT3 substrates: furosemide, methotrexate
Effect of olaparib on other drugs
Based on limited in vitro data, olaparib may 
increase the exposure to substrates of CYP3A4, 
OATP1B1, OCT1, OCT2, OAT3, MATE1 and 
MATE2K.
Based on limited in vitro data, olaparib may 
reduce the exposure to substrates of 2B6.
Caution should be observed if substrates of these 
isoenzymes or transporter proteins are 
co-administered.
Anticoagulant therapy
Patients who are taking warfarin may participate 
in this trial; however, it is recommended that 
international normalised ratio (INR) be 
monitored carefully at least once per week for 
the first month, then monthly if the INR is 
stable. Subcutaneous heparin and low molecular 
weight heparin are permitted.
Administration of other anti-cancer agents
Patients must not receive any other concurrent 
anti-cancer therapy, including investigational 
agents, while on study treatment. Patients may 
continue the use of bisphosphonates or 
denosumab.
5.6.3
Anti-emetics/Anti-diarrheals
Should a patient develop nausea, vomiting and/or diarrhoea, then these symptoms should be 
reported as AEs (see Section 6.4.3) and appropriate treatment given.
5.6.4
Live virus and bacterial vaccines
Live virus and bacterial vaccines should not be administered whilst the patient is receiving
study treatment and during the 30-day follow-up period. An increased risk of infection by the 
administration of live virus and bacterial vaccines has been observed with conventional
chemotherapy drugs and the effects with olaparib are unknown.

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5.7
Treatment compliance
The administration of all study drugs during the 1-year treatment phase of the study should be 
recorded in the appropriate sections of the eCRF.
Patients should be given clear instructions on how and when to take their study treatment. 
Patients will self-administer study treatment. Study site staff should do a tablet count at 
regular intervals during treatment. Compliance will be assessed by the tablet count and the 
information should be recorded in the appropriate section of the eCRF. After the tablet count 
has been performed, the remaining tablets will not be returned to the patient, but will be 
retained by the investigative site until reconciliation is completed by the study monitor. All 
patients must return their bottle(s) of study treatment at the appropriate scheduled visit, when 
a new bottle will be dispensed. Patients should be instructed to notify study site personnel of 
missed doses. Site staff will then complete the relevant eCRF pages to document the drug 
actually given.
Patients should return all containers at the next scheduled visit and any remaining tablets at 
the End of Treatment visit.
5.7.1
Accountability
The study drug provided for this study will be used only as directed in the study protocol.
The study personnel will account for all study drugs dispensed to and returned from the 
patient.
Study site personnel will account for all study drugs received at the site, unused study drugs 
and for appropriate destruction. Certificates of delivery, destruction and return should be 
signed and retained. Any discrepancies must be accounted for on the appropriate forms.
5.8
Discontinuation of study treatment 
Patients may be discontinued from the study treatment in the following situations:
!
Patient decision. The patient is free at any time to discontinue study treatment, 
without prejudice to further clinical care
!
Adverse Event
!
Completion of 12 months treatment period
!
Confirmed pregnancy during treatment
!
Severe non-compliance with study protocol 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
88(176)
!
Loco-regional breast cancer recurrence (ipsilateral invasive breast cancer 
recurrence, regional invasive breast cancer recurrence)
!
Distant breast cancer recurrence
!
Contralateral invasive breast cancer or second primary non-breast invasive cancer
!
Death
!
Bone marrow findings consistent with myelodysplastic syndrome (MDS)/acute 
myeloid leukaemia (AML)
5.8.1
Procedures for discontinuation of a patient from study treatment
A patient that decides to discontinue study treatment should always be asked about the 
reason(s) and the presence of any adverse events. If possible, he/she will be seen and assessed 
by an investigator(s). Adverse events will be followed up (See Sections 6.4.3 and 6.4.4); 
questionnaires and all study drugs should be returned by the patient.
If a patient is withdrawn from study, see Section 5.9.
If patients discontinue study treatment early, the site monitor must be informed immediately. 
Any patient discontinuing prior to completing 52 weeks of study treatment should attend the 
treatment discontinuation visit, if possible. Thereafter the patient should be seen at 30 days 
post discontinuation for the evaluations outlined in the study schedule. 
After premature discontinuation of study treatment, the principal investigator/sub-investigator 
will continue to provide appropriate clinical care and, as far as possible, follow the study visit 
schedule. Only the visits where efficacy assessments are scheduled should be performed i.e. 
week 12, 24, 38, 52 (as applicable) in Year 1 and all visits in Year 2 onwards. Only the 
following assessments should be done: recurrent/new cancers assessment, mammogram 
and/or breast MRI, and Quality of Life questionnaires. 
Collection of vital signs, AEs, haematology/clinical chemistry results and concomitant 
medications is no longer required. Information on endocrine therapies should be collected and 
recorded in the clinical database until IDFS endpoint is met due to breast cancer related distant 
relapse. The date of discontinuation, the reasons, and details of the following specific cancer 
therapies (first line treatment for first breast cancer recurrence and any subsequent regimens 
containing PARP inhibitors or platinum received by the patient at any time) should also be 
recorded on the eCRF.
Samples should be collected at disease recurrence per protocol: blood biomarker samples 
(mandatory) and tumour sample (optional). If a recurrent/new cancer assessment is scheduled 

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within 4 weeks of the study treatment discontinuation visit, it can be performed at the 30 day 
follow-up visit.
Patients who meet the IDFS endpoint while on study therapy should attend the treatment 
discontinuation visit and follow up visit 30 days after the last dose of study treatment. See 
Section 3 for guidelines on subsequent study visits, which are dependent on which IDFS 
endpoint has been met. 
After discontinuation of study treatment at any points in the study, all ongoing AEs or SAEs 
must be followed until resolution unless, in the investigator’s opinion the condition is unlikely 
to resolve due to the patients underlying disease, or the patient is lost to follow-up (see 
Sections 6.4.3 and 6.4.4). All new AEs and SAEs occurring during the 30 calendar days after 
the last dose of study medication must be reported (if SAEs, they must be reported to 
AstraZeneca via both the eCRF and paper SAE report to AstraZeneca data entry site (DES)
within 24 hours as described in Section 6.4.4) and followed to resolution as above. Patients 
should be seen at least 30 days after discontinuing study medication to collect and / or 
complete AE information.
5.9
Withdrawal from study
Patients are at any time free to withdraw from study (study treatment and assessments), 
without prejudice to further clinical care (withdrawal of consent). Such patients should always 
be asked about the reason(s) and the presence of any adverse events. If possible, they will be 
seen and assessed by an investigator. Adverse events will be followed up (See Sections 6.4.3
and 6.4.4); questionnaires (e.g. for patient reported outcomes) and all study drugs should be 
returned by the patient.
Withdrawn patients will not be replaced. 
Reasons for withdrawal from the study:
!
Voluntary withdrawal by the patient who is at any time free to discontinue their 
participation in the study, without prejudice to further treatment*
!
Incorrectly enrolled patients i.e., the patient does not meet the required 
inclusion/exclusion criteria for the study – this option is only applicable to patients 
not randomised into the study (i.e. screen failures identified prior to randomisation)
!
Patient lost to follow-up
!
Death
* If a patient decides at any point in the trial that they do not wish to continue with the full 
study schedule of assessments but are still willing to provide important study information (e.g. 
disease recurrence information and/or survival status information) then the patient should 

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continue in the study and information should continue to be collected in the eCRF. However if 
a patient does not wish to have any further data collected, only then should they be considered 
as withdrawing consent from the study. To minimise the number of cases of early withdrawal 
the investigator should discuss the options with the patient to see if they would still be willing 
to provide information on the important study endpoints (disease recurrence and overall 
survival), in which case they would remain in the study.
If a patient withdraws consent (i.e. no further assessment or collection of their data) he/she 
should be specifically asked if they are also withdrawing consent to the use of any of their 
samples (tumour and blood) taken during the trial (see Section 6.6, 6.7 and 6.8).
Data obtained prior to withdrawal of consent will be maintained in the clinical database and 
used in the study reporting.
6.
COLLECTION OF STUDY VARIABLES
6.1
Recording of data
A Web Based Data Capture (WBDC) Medidata Rave system will be used for data collection 
and query handling. This system is provided by Frontier Science. The investigator will ensure 
that data are recorded on the eCRFs as specified in the study protocol and in accordance with 
the instructions provided.
The investigator will sign the completed eCRFs when requested by the Frontier Science Data 
Management Team. A copy of the completed eCRFs will be archived at the study site.
6.2
Study procedures
A study initiation visit must be conducted at the centre prior to the commencement of any 
study activities requiring informed consent. A schedule for the tests and evaluations to be 
conducted in this study is contained in this section and in Table 1, Table 2 and Table 3.
6.2.1
Screening procedures
The following assessments, procedures and data collection should be performed during 
screening as per Figure 1 and Table 1:
!
Provision of informed consent
!
Assessment of eligibility against inclusion/exclusion criteria
!
Date of birth 
!
Current and concomitant medications including previous cancer therapies 
!
Medical and surgical history including previous cancer and radiotherapy and history 
of blood transfusions in previous 120 days 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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!
Family history of cancer
!
Physical examination
!
Vital signs (blood pressure and pulse; body temperature), body weight, height
!
ECG (within 28 days prior to randomisation)
!
Haematology/Clinical chemistry/Coagulation (see Section 6.4.5.2)/Urinalysis
!
ECOG Performance Status
!
If a patient with conservative surgery does not have a mammogram or breast MRI 
within 12 months prior to Screening PART 1, then this assessment must be 
performed prior to randomisation. Breast imaging should be performed on any 
remaining intact breast. Radiological tests to exclude a second primary breast 
cancer (either ipsilateral and/or contralateral) are mandatory before enrolment 
(within 12 months prior to Screening PART 1) for patients with any remaining 
intact breast tissue (including male patients). The preferred tests are mammograms 
or MRI (MRI preferred for patients below 50 years of age). For patients who 
underwent a bilateral mastectomy, with no remaining breast tissue, a physical 
examination is sufficient and radiological tests are not mandatory. For patients who 
underwent a bilateral mastectomy, as well as for male patients, clinical exam may 
be supplemented by ultrasound exams at investigator’s discretion.
!
Pregnancy tests on serum or urine samples will be performed for women of 
childbearing potential within 28 days prior to randomisation on Day 1 of the study 
prior to commencing treatment.
!
CPS+EG score (Clinical stage (CS), estrogen receptor status (E), nuclear grade (G), 
and post-treatment pathologic stage (PS)) for the non-pCR patients who received 
prior neoadjuvant chemotherapy (Mittendorf et al 2011; Jeruss et al 2008). 
Instructions on how to calculate the CPS&EG score are provided in Appendix H.  
!
Patient Reported Outcomes and Quality of life questionnaire: FACIT-Fatigue and 
EORTC QLQ-C30 will be collected prior to randomisation once eligibility is 
confirmed.
!
Germline BRCA 1/2 mutation status determination
o
All patients must have a known deleterious or suspected deleterious germline 
BRCA mutation to be randomised; this may have been determined by local 
genetic testing prior to enrolment into the study or may be assessed as part of 
the enrolment procedure for the study which requires a central laboratory test at 
Myriad Genetics Inc.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
92(176)
o
Two blood samples are mandated for all patients, one sample will be used to test 
for BRCA mutations using the current commercial Myriad BRCAnalysis test, 
and the second sample is required for a bridging study to validate the 
companion diagnostic test for olaparib.
o
Patients with unknown BRCA status must have a central test performed by 
Myriad prior to randomisation into the study. Patients will need to have met the 
locally agreed guidelines for BRCA testing with genetic counselling arranged as 
appropriate. When the result from the Myriad test indicates the patient does 
have a deleterious or suspected deleterious BRCA mutation, and the patient 
meets all other eligibility criteria, the patient can be randomised into the study. 
Specimen collection and results disclosure to the potential subject will be 
conducted using local ethical procedures.
o
It is recommended that, where required, the Myriad gBRCA test is undertaken 
during adjuvant or neoadjuvant chemotherapy to allow time for necessary 
counselling and for the return and discussion of the test result.
o
Patients with known deleterious or suspected deleterious BRCA mutation/s prior 
to enrolment into the study can be randomised into the study based on this local 
result provided they meet all other eligibility criteria. The specific BRCA1/2
mutation must be reported in the clinical database by selecting the appropriate 
value from the drop down menu. At screening, reconfirmation of the BRCA
mutation from a blood sample will be undertaken by a central laboratory 
(Myriad Genetic Inc). Should the result from the central Myriad test indicate 
that the patient does not have a deleterious or suspected deleterious BRCA
mutation, this information will be available to the study investigator and the 
decision as to whether or not the patient continues study treatment should be 
made between the patient and study investigator.
o
If the discordance is based on the absence of the alteration identified in the local 
laboratory by the central laboratory, then analysis of a second specimen, 
collected independently from the patient and sent to Myriad Genetics for re-
analysis of the presence or absence of the mutation specified in the original test 
or otherwise as discussed with Myriad laboratory staff, may be performed under 
the protocol, to eliminate sample mislabelling and similar errors. These errors 
are expected to be uncommon. If the discordance is based on interpretation of 
the pathogenicity of an alteration identified by both laboratories (i.e., Myriad 
classifies the alteration as neither deleterious nor suspected deleterious), a repeat 
test will not be indicated. The OlympiA trial Genetic Advisory Committee can 
be consulted if needed.
See Section 6.6.2 for gBRCA Myriad samples collection.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
93(176)
!
Adverse events must be captured from time of main consent. Any medical condition 
(new or worsening of a pre-existing condition) that occurs post Screening PART 2 
and is continuing at randomisation should be recorded in Medical History in the 
eCRF as a medical condition current at randomisation. If the condition worsens post 
randomisation, this should be recorded as an AE/SAE in the eCRF with start date as 
the date the grade worsened and the new grade should be reported on the AE form. 
The AE/SAE would be considered to have resolved when it resolves to the baseline 
grade, not to zero. Any medical condition considered of clinical relevance (new or 
worsening of a pre-existing condition) that occurs post consent for PART 2 and 
resolves prior to randomisation should also be recorded as medical history. In 
Screening PART 1 of the study only SAEs related to study mandated procedures 
(i.e. blood draw) will be collected and reported to AstraZeneca DES via the paper 
SAE report. In Screening PART 2 all SAEs will be collected and reported via the 
paper SAE report to AstraZeneca DES within 24 hours. For the patients who 
experienced an SAE in either Screening PART 1 or PART 2 that were eventually 
randomised, the SAE should be reported in the eCRF retrospectively in addition to 
paper reporting as described in Section 6.4.4.
!
Check availability of an archival paraffin embedded tumour tissue sample (see 
Section 6.6.3). (The sample will only be submitted to the study bio-repository once 
the patient has been randomised)
!
Check availability of an archival paraffin embedded post neoadjuvant tumour tissue 
sample (see Section 6.6.4). (The sample is required from neoadjuvant patients only 
and will only be sent to the study bio-repository once the patient has been 
randomised)
The Principal Investigator/Sub-Investigator should adhere to the study plan, procedures and 
perform tests/observations in accordance with the protocol.
6.2.2
On-treatment assessments 
Patients will attend the clinic on day 1 (1st day of treatment) and, following the 
commencement of 300 mg b.i.d. twice daily dosing, every 2 weeks during the first month, 
every 4 weeks for the following 5 months and 3 monthly for the remaining 6 months of study 
treatment plus 30 days after its discontinuation.
The following assessments will be performed at time points specified in the study schedule 
(see Section 3.1, Table 1 and Table 2):
!
Physical examination (data does not need to be entered in the eCRF, however any 
clinically significant changes from baseline must be reported as an AE or an event) 
– e.g. any signs of recurrence of disease should be reported

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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radiological tests are not mandatory. For patients who underwent a bilateral 
mastectomy, as well as for male patients, clinical exam may be supplemented by 
ultrasound exams at investigator’s discretion.
!
Dispensing of and return of unused study treatment
Within this study, patients will not be provided olaparib post discontinuation of study 
treatment. Patients and investigators will not be unblinded to study treatment prior to the final 
overall survival (OS) analysis.
6.2.3
Efficacy follow-up assessments
Assessments for disease recurrence, new cancers and overall survival will be performed based 
on signs and symptoms, clinical assessment (i.e. physical exam), mammograms and/or breast 
MRI and vital status.
Following randomisation, during the first 2 years patients will be assessed for disease 
recurrence and new cancers every 3 months. During years 3, 4 and 5 patients will be assessed 
every 6 months and then annually until approximately 10 years from randomisation if an IDFS 
endpoint due to a distant breast cancer relapse has not been met.
Mammograms and/or MRI (MRI preferred for patients younger than 50 years) (ipsilateral 
and/or contralateral) will be performed annually in patients with retained breast tissue 
beginning 6 months after first day of treatment for approximately 10 years if an IDFS 
endpoint due to a distant breast cancer relapse has not been met.
Once a patient has received clinical follow-up for efficacy for approximately 10 years, or an 
IDFS endpoint due to a distant breast cancer relapse has been met, the patient will then enter 
the annual survival follow-up phase of the study. During the survival follow-up phase, no 
clinic visits will be required; information may be collected via telephone, medical records or 
death registries. Vital status information, as well as other information specified in footnote g 
of Table 2 will be collected until 10 years after the last patient is randomised.
In addition to disease status and vital status, information on first line treatment for first breast 
cancer recurrence and any subsequent regimens containing PARP inhibitors or platinum 
received by the patient at any time, including those received during the survival follow-up 
phase, will be collected. Information on endocrine therapies should be collected and recorded 
in the eCRF until IDFS endpoint is met due to breast cancer related distant relapse. The 
therapy type and start and stop dates of therapy will be collected.
6.2.4
Safety follow-up assessments 30 days after last dose of olaparib/placebo 
A follow-up visit should be conducted 30 days after the last dose of olaparib/placebo. Any 
serious and/or non-serious AEs ongoing at the time of discontinuation of study treatment or 
which have occurred during the defined 30-day follow-up period must be followed up (in 
accordance with Section 6.4.3). Appropriate safety evaluations should be repeated and/or 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
96(176)
additional tests performed at any time when clinically indicated, or at the discretion of the 
investigator, until resolution, unless, in the investigator’s opinion, the condition is unlikely to 
resolve due to the patient’s underlying disease. If the patient is lost to follow-up, then this 
should be noted in the eCRF. The assessments to be carried out at the 30-day follow-up visit 
are detailed in the study schedule (Table 2). 
See Section 6.4.3 for details of long term safety collection. 
6.2.5
Patient management post-primary analysis
The data cut off (DCO) for the primary analysis for IDFS will occur once 330 IDFS events 
have been reported. Once this data is fully validated the primary analysis will be conducted 
and reported.
At the time of the DCO for the primary analysis patients will continue in the study as per the 
protocol following the outlined study plan assessments. Patients who have completed 
treatment and all relevant safety assessments will continue to have regular efficacy 
assessments as detailed in the study plan. All ongoing patients will continue to be followed for 
recurrence, new cancers and overall survival irrespective of treatment status.
It is anticipated that further analysis of the efficacy data, particularly the secondary endpoints, 
will be conducted with more mature follow-up. Any further available safety data will also be 
reported.
6.2.6
Patient management post-final analysis 
Study follow-up will continue until approximately 10 years after the last patient is 
randomised. After this time no further data collection is anticipated.
Patient management post the final analysis will be according to local clinical practice. All 
patients will have completed study treatment by the time of the final analysis.
6.3
Efficacy 
6.3.1
Tumour evaluation
All treatment decisions and analysis for this study will be based on investigator evaluation of 
assessments. Following randomisation, all patients will be assessed regularly for signs, 
symptoms and evidence of disease recurrence by reviewing medical history, performing 
physical examination and mammogram and/or breast MRI (MRI preferred for patients 
younger than 50 years) see Table 2 and Table 3. Efficacy assessments (medical history and 
physical examination) will be performed on a 3 monthly basis during the first 2 years, 
followed by 6 monthly assessments for years 3, 4 and 5 and annually thereafter. All patients 
will have mammogram and/or breast MRI (ipsilateral and/or contralateral) annually for 
approximately 10 years beginning 6 months after day 1. Evidence of disease recurrence or 
new primary cancer will require histopathological and/or radiological confirmation.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Patients will be regularly assessed, through clinical visits, for recurrence (local and distant) 
and new cancers for approximately 10 years follow-up regardless of whether they have 
discontinued study treatment or started any subsequent anti-cancer therapies. Following 
completion of approximately 10 years’ clinical follow-up assessments, patients will enter a 
survival follow-up phase, which will continue until 10 years after the last patient is 
randomised. During the survival contact period information on any known subsequent sites of 
metastases, new cancers and further subsequent therapies (information on first line treatment 
for first breast cancer recurrence and any subsequent regimens containing PARP inhibitors or 
platinum received by the patient at any time) will be captured as well as vital status. Study 
visits are not required during the survival follow-up phases; contact will be made via 
telephone, medical records or death registries once per year.
Loco-regional recurrence of the disease (ipsilateral or regional invasive breast cancer) should 
be cytologically/histologically confirmed. Imaging to assess for distant metastatic disease or 
any other area as clinically indicated should be performed at the time of local recurrence to 
ensure that any further spread of the disease is detected. Isolated loco-regional recurrence 
should be managed with curative intent when possible. Suspected distant recurrence should be 
confirmed by radiological examination and every attempt be made to obtain histopathological 
confirmation when a metastatic lesion is easily accessible for biopsy. Invasive contralateral 
breast cancer or invasive non-breast secondary primary cancer should be confirmed by 
histopathology.  
Patients who develop loco-regional recurrence should discontinue study treatment (if within 
the study treatment period) but will continue to be followed for distant recurrence (including 
subsequent sites of metastases) and all new cancers (local, regional, second primary 
malignancy or contralateral breast cancer), subsequent therapies and survival as per study 
schedule. The first EVENT (local, regional or distant recurrence, second primary malignancy 
or contralateral breast cancer) should be recorded in the eCRF. The following additional 
information should also be recorded in the eCRF along with results of confirmatory tests:
∀
First distant relapse (if not the first EVENT);
∀
CNS metastases, that should always be reported regardless of any prior recurrences;
∀
Loco-regional relapses, occurring after the first event;
∀
Contralateral breast cancer, at any time;
∀
Any second primary malignancies, at any time. 
Patients who develop distant recurrence should discontinue study treatment (if within the 
study treatment period) but will continue to be followed for development of additional sites of 
metastatic disease, new cancers, subsequent therapies and survival as per the survival follow-
up schedule.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Disease recurrence or new cancers should be reported in the eCRF as soon as possible after 
they are discovered. This includes events diagnosed during study visits but also any event 
diagnosed during non-study visits.
Once known, death information should also be recorded in the eCRF as soon as possible.
6.4
Safety
The Principal Investigator is responsible for ensuring that all staff involved in the study is 
familiar with the content of this section.
6.4.1
Definition of adverse event (AE)
An adverse event is the development of an undesirable medical condition or the deterioration 
of a pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product. An undesirable medical condition 
can be symptoms (e.g. nausea, chest pain), signs (e.g. tachycardia, enlarged liver) or the 
abnormal results of an investigation (e.g. laboratory findings, electrocardiogram).
The term AE is used to include both serious and non-serious AEs.
6.4.2
Definitions of serious adverse event (SAE)
A serious adverse event is an AE occurring during any study phase (i.e. from the time a 
patient signs a study specific consent form, treatment, and follow-up), that fulfils one or more 
of the following criteria:
!
Results in death
!
Is immediately life-threatening
!
Requires in-patient hospitalisation or prolongation of existing hospitalisation 
!
Results in persistent or significant disability/incapacity or substantial disruption of 
the ability to conduct normal life functions
!
Is a congenital abnormality or birth defect
!
Is an important medical event that may jeopardise the patient or may require 
medical intervention to prevent one of the outcomes listed above.
For further guidance on the definition of an SAE, see Appendix A to the Clinical Study 
Protocol.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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6.4.3
Recording of adverse events
Time period for collection of adverse events
Adverse events will be collected from time of signature of main informed consent* throughout 
the treatment period up to and including the 30-day follow-up period. All ongoing and any 
new AEs/SAEs identified during the 30 calendar days follow-up period after the last dose of 
study medication must be followed to resolution unless the event is considered by the 
investigator to be unlikely to resolve, or the patient is lost to follow-up or in survival 
follow-up. AstraZeneca retains the right to request additional information for any patient with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary. Any medical condition 
(new or worsening of a pre-existing condition) that occurs post Screening PART 2 and is 
continuing at randomisation should be recorded in medical history in the eCRF as a medical 
condition current at randomisation. If the condition worsens post randomisation, this should 
be recorded as an AE/SAE in the eCRF with start date as the date the grade worsened and the 
new grade should be reported on the AE form. The AE/SAE would be considered to have 
resolved when it resolves to the baseline grade, not to zero. Any medical condition considered 
of clinical relevance (new or worsening of a pre-existing condition) that occurs post consent 
for PART 2 and resolves prior to randomisation should also be recorded as medical history. 
Any AE happening from randomisation to the 30-day follow-up period should be reported on 
the AE form in the eCRF. If an Investigator learns of any SAEs, including death, at any time 
after a patient has completed 30 days post treatment follow-up period, and he/she considers 
there is a reasonable possibility that the event is causally related to the study treatment, the 
investigator should notify AstraZeneca, Patient Safety by reporting the SAE via both the 
eCRF in Medidata Rave and paper SAE report to AstraZeneca DES.
Any case of MDS/AML or new primary malignancy occurring at any time from signature of 
informed consent for the entire participation of the patient in the study including the follow-up 
period should be reported as an SAE. Non-melanoma skin cancers need to be reported as a 
non-serious AE unless at least one of the seriousness criteria is met and then it must be 
reported as an SAE, see Section 6.4.2. Any of these types of serious or non-serious events 
need to be reported to AstraZeneca Patient Safety according to SAE reporting procedures for 
this study, regardless of investigator’s assessment of causality or knowledge of the treatment 
arm. If a patient develops MDS/AML, full diagnostic details and classification should be 
provided e.g. bone marrow and cytogenetic analysis reports, see Sections 5.5.6.3 and 6.4.5.5. 
A questionnaire will be sent to any investigator reporting MDS/AML or new primary 
malignancy so that relevant details can be reported.
*In Screening PART 1 of the study only SAEs related to study mandated procedures (i.e. 
blood draw) will be collected and reported to AstraZeneca DES via the paper SAE report. In 
Screening PART 2 all SAEs will be collected and reported via the paper SAE report to 
AstraZeneca DES within 24 hours. For the patients who experienced an SAE in either 
Screening PART 1 or PART 2 that were eventually randomised, the SAE should be reported 
in the eCRF retrospectively in addition to paper reporting as described in Section 6.4.4.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
100(176)
Adverse events after the 30 day follow up period 
For pharmacovigilance purposes and characterisation, any SAE of MDS/AML, new primary 
malignancy, or pneumonitis occurring after the 30 day follow up period should be reported to 
AstraZeneca Patient Safety regardless of investigator’s assessment of causality or knowledge 
of the treatment arm. After all follow up visits investigators should report the occurrence of 
any MDS/AML or any new primary malignancies as per protocol.
At any time after a patient has completed the study, if an investigator learns of any SAE 
including sudden death of unknown cause, and he/she considers there is a reasonable 
possibility that the event is causally related to the investigational product, the investigator 
should notify AstraZeneca, Patient Safety.
Otherwise, after study treatment completion (i.e. after any scheduled post treatment follow-up 
period has ended) there is no obligation to actively report information on new AEs or SAEs 
occurring in study patients. This includes new AEs/SAEs in patients still being followed up 
for survival but who have completed the post treatment follow up period (30 days).
Follow-up of unresolved adverse events
Any SAE or non-serious adverse event that is still ongoing during the 30-day follow-up visit 
must be followed up to resolution unless the event is considered by the investigator to be 
unlikely to resolve, or the patient is lost to follow-up. AstraZeneca may request additional 
information for any patient with ongoing AE(s)/SAE(s) at the end of the study, if necessary.
Variables
The following variables will be collected for each AE;
!
AE description (verbatim)
!
The dates when the AE started and stopped
!
CTCAE grade and changes in CTCAE grade
!
Whether the AE is serious or not
!
Investigator causality rating against the study treatment (yes or no)
!
Action taken with regard to study treatment
!
Outcome.
In addition, the following variables will be collected for SAEs:
!
Date that the AE met criteria for serious AE

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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!
Date Investigator became aware of serious AE
!
Reason for AE being considered serious 
!
Date of hospitalisation
!
Date of discharge
!
Probable cause of death
!
Date of death
!
Autopsy performed
!
Causality assessment in relation to Study treatment or procedure(s)
!
Causality assessment in relation to Other medication
!
Description of AE.
Severity of AE
For each episode of an adverse event, all changes to the CTCAE grade attained as well as the 
highest attained CTC grade should be reported.
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Section 6.4.2. An AE of severe 
intensity should not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not an SAE. On the other hand, a stroke 
that results in only a limited degree of disability may be considered a mild stroke but would be 
an SAE.
The grading scales found in the National Cancer Institute (NCI) CTCAE version 4.0 will be 
utilised for all events with an assigned CTCAE grading. For those events which do not fall 
under any of the CTCAE defined categories, the investigator should assess them as mild, 
moderate, severe, or life-threatening, or, if the patient dies, as an event leading to the patient’s 
death.  
A copy of the CTCAE version 4.0 can be downloaded from the NCI Cancer Therapy 
Evaluation Program website http://ctep.cancer.gov/.
Causality collection
The Investigator will assess causal relationship between study treatment and each Adverse 
Event, and answer ‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable 
possibility that the event may have been caused by the study treatment?’

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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For SAEs causal relationship will also be assessed for other medication and study procedures. 
Note that for SAEs that could be associated with any study procedure the causal relationship is 
implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix A to the Clinical 
Study Protocol.
Adverse events based on signs and symptoms
All AEs spontaneously reported by the patient or reported in response to the open question 
from the study personnel: ‘Have you had any health problems since the previous visit/you 
were last asked?’, or revealed by observation will be collected and recorded in the eCRF. 
When collecting AEs, the recording of diagnoses is preferred (when possible) rather than 
recording a list of signs and symptoms. However, if a diagnosis is known and there are other 
signs or symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom will be recorded separately.
Adverse events based on examinations and tests
The reporting of laboratory/vital signs/ECG abnormality as an AE should be avoided unless 
one of the following is met:
!
Any criterion for an SAE is fulfilled
!
Causes study treatment discontinuation
!
Causes study treatment interruption
!
Causes study treatment dose reduction
!
The investigator believes that the abnormality should be reported as an AE
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible the reporting investigator 
uses the clinical, rather than the laboratory term (e.g. anaemia versus low haemoglobin value). 
In the absence of clinical signs or symptoms, clinically relevant deteriorations in non-
mandated parameters should be reported as AE(s).
Deterioration of a laboratory value, which is unequivocally due to disease recurrence, should 
not be reported as an AE/SAE.
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE.

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Edition Number 5
Date 18 May 2018
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NB. Cases where a patient shows an AST or ALT ≥3xULN or total bilirubin ≥2xULN may 
need to be reported as SAEs, please refer to Appendix D ‘Actions Required in Cases of 
Increases in Liver Biochemistry and Evaluation of Hy’s Law’, for further instructions.
Disease recurrence
The development of loco-regional recurrence or distant metastasis to the primary cancer under 
study should be considered as disease progression and not an AE. Events, which are 
unequivocally due to disease recurrence, should not be reported as an AE during the study.
New cancers
The development of a new primary cancer should be reported as an AE (see Section Olaparib 
adverse events of special interest) and would in most cases meet seriousness criteria (with the 
exception of some non-melanoma skin cancers). New primary cancers are those that are not 
the primary reason for the administration of the study treatment and have developed after the 
inclusion of the patient into the study. They do not include metastases of the original cancer. 
Symptoms of metastasis or the metastasis itself should not be reported as an AE/SAE, as they 
are considered to be disease recurrence. New primary cancers are considered as IDFS event
and must also be reported on the endpoint CRF. Patients with new primary cancers that can be 
adequately treated with surgery only and which do not require any additional (neo)adjuvant 
treatment of any kind can continue to receive investigational product and be followed for 
secondary endpoints. Rules regarding temporary interruption due to surgery apply (see 
Section 5.5.6.7). Patients with new primary cancers which require (neo)adjuvant treatment of 
any kind for appropriate management must be discontinued from study treatment.
Deaths
All deaths that occur during the study must be reported as follows:
!
Death that is clearly the result of breast cancer recurrence or progression should be 
reported to the study monitor at the next monitoring visit and should be documented in 
the DEATH eCRF but should not be reported as an SAE.
!
Where death is not due (or not clearly due) to breast cancer recurrence or 
progression of the disease under study, the cause of death must be reported to the 
study monitor as an SAE within 24 hours (see Section 6.4.4 for further details). The 
report should contain a comment regarding the co-involvement of progression of 
disease, if appropriate, and should assign main and contributory causes of death. 
This information should be captured in the relevant eCRF.
Deaths with an unknown cause should always be reported as an SAE. A post mortem maybe 
helpful in the assessment of the cause of death, and if performed a copy of the post-mortem 
results should be forwarded to AstraZeneca Patient Safety within the usual timeframes.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Olaparib adverse events of special interest
Adverse events of special interest (AESI) are events of scientific and medical interest specific 
to the further understanding of olaparib’s safety profile and require close monitoring and rapid 
communication by the investigators to AstraZeneca. Adverse Events of Special Interest for 
olaparib are MDS/AML, new primary malignancy (other than MDS/AML) and pneumonitis.  
A questionnaire will be sent to any investigator reporting an AESI by AstraZeneca Patient 
Safety, as an aid to provide further detailed information on the event. During the study there 
may be other events identified as AESIs that require the use of a questionnaire to help 
characterise the event and gain a better understanding regarding the relationship between the 
event and study treatment.
6.4.4
Reporting of serious adverse events
All SAEs have to be reported, whether or not considered causally related to the study 
treatment, or to the study procedure(s). All SAEs will be recorded in the eCRF and 
AstraZeneca Patient Safety Database.
If any SAE occurs in the course of the study, then investigators or other site personnel should 
inform their site monitor immediately, or no later than 24 hours after being made aware of it.
The designated study representative works with the investigator to ensure that all the 
necessary information is provided to the AstraZeneca Patient Safety data entry site via the 
paper SAE report and is completed in the eCRF within one calendar day of initial receipt for 
fatal and life threatening events and within five calendar days of initial receipt for all other 
SAEs.
For fatal or life-threatening adverse events where important or relevant information is missing, 
active follow-up is undertaken immediately. Investigators or other site personnel inform the 
site monitor of any follow-up information on a previously reported SAE immediately, or no 
later than 24 hours after being made aware of it.
If the WBDC system is not available, then the Investigator or other study site personnel 
reports an SAE to the appropriate AstraZeneca representative via the paper SAE report and 
while eCRF is completed immediately upon its availability.
The AstraZeneca representative will advise the Investigator/study site personnel how to 
proceed.
6.4.5
Laboratory safety assessment
Blood and urine samples for determination of clinical chemistry, haematology, coagulation, 
and urinalysis will be taken at the times indicated in the Study Schedule (see Table 1 and 
Table 2).

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These tests will be performed by the hospital’s local laboratory. Additional analyses may be 
performed if clinically indicated. 
Any clinically significant abnormal laboratory values should be repeated as clinically 
indicated and recorded on the eCRF.
The following laboratory variables will be measured:
6.4.5.1
Full haematology assessments for safety
!
haemoglobin 
!
red blood cells [RBC]
!
platelets
!
mean cell volume [MCV]
!
mean cell haemoglobin concentration [MCHC] 
!
mean cell haemoglobin [MCH]
!
white blood cells [WBC] 
!
absolute differential white cell count 
∀
(neutrophils, lymphocytes, monocytes, eosinophils and basophils) and absolute 
neutrophil count or segmented neutrophil count and Band forms should be 
performed at each visit and when clinically indicated. If absolute differentials 
not available please provide % differentials 
6.4.5.2
Coagulation 
!
activated partial thromboplastin time (APTT) will be performed at baseline and if 
clinically indicated
!
international normalised ratio (INR) will be performed at baseline and if clinically 
indicated unless the patient is receiving warfarin. Patients taking warfarin may 
participate in this study; however, it is recommended that prothrombin time (INR 
and APTT) be monitored carefully at least once per week for the first month, then 
monthly if the INR is stable 
6.4.5.3
Clinical chemistry assessments for safety 
!
sodium
!
potassium

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!
calcium 
!
creatinine
!
total bilirubin
!
alkaline phosphatase [ALP]
!
aspartate transaminase [AST]
!
alanine transaminase [ALT]
!
urea or blood urea nitrogen [BUN]
!
total protein
!
albumin
NB. If a patient has AST or ALT ≥3xULN or total bilirubin ≥2xULN please refer to 
Appendix D ‘‘Actions Required in Cases of Increases in Liver Biochemistry and Evaluation 
of Hy’s Law’, for further instructions.
For blood volume see Section 7.1.
6.4.5.4
Urinalysis
Urinalysis by dipstick should be performed at baseline and then only if clinically indicated. 
Microscopic analysis should be performed by the hospital’s local laboratory if required.
6.4.5.5
Bone marrow or blood cytogenetic samples 
Bone marrow or blood cytogenetic samples may be collected for patients with prolonged 
haematological toxicities as defined in Section 5.5.6.3. 
Bone marrow analysis should include an aspirate for cellular morphology, cytogenetic 
analysis and flow cytometry, and a core biopsy for bone marrow cellularity. If it is not 
possible to conduct cytogenetic analysis or flow cytometry on the bone marrow aspirate, then 
attempts should be made to carry out the tests on a blood sample. Full reports must be 
provided by the investigator for documentation on the Patient Safety database.
6.4.6
Physical examination
For timing of individual measurement refer to study schedule (Table 1, Table 2 and Table 3). 
A physical examination will be performed according to site’s local practice. 
Clinical signs and symptoms of disease recurrence should be further investigated as 
appropriate (please refer to Section 6.3).

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6.4.7
ECG
6.4.7.1
Resting 12-lead ECG
ECGs are required during screening within 28 days prior to randomisation. 
Twelve-lead ECGs will be obtained after the patient has been rested in a supine position for at 
least 5 minutes. The investigator or designated physician will review the paper copies of each 
of the timed 12-lead ECGs. 
ECGs will be recorded at 25 mm/sec. All ECGs should be assessed by the investigator as to 
whether they are clinically significantly abnormal / not clinically significantly abnormal. If 
there is a clinically significant abnormal finding, the investigator will record it as an AE on the 
eCRF. The original ECG traces must be stored in the patient medical record as source data.
6.4.8
Vital signs
Height will be assessed at screening only.
Weight will be assessed at screening and as clinically indicated at any other time. 
Any changes in vital signs should be recorded as an AE, if applicable.
The date of collection and measurement will be recorded on the appropriate eCRF.
6.4.8.1
Pulse and blood pressure
Blood pressure and pulse rate will be measured preferably using a semi-automatic BP 
recording device with an appropriate cuff size. For timings of assessments refer to the Study 
Schedule (see Table 1 and Table 2).
The date of collection and measurement will be recorded on the appropriate eCRF.
6.4.8.2
Body temperature
Body temperature will be measured in degrees Celsius at the times indicated in the Study 
Schedule (see Table 1 and Table 2).
The date of collection and measurement will be recorded on the appropriate eCRF.
6.4.9
Other safety assessments
6.4.9.1
Serum or urine pregnancy test
Pregnancy tests on serum or urine samples will be performed for women of childbearing 
potential within 28 days prior to randomisation (Table 1), on Day 1 of the study prior to 
commencing treatment, at the time points shown in Table 2 during study treatment and at the 
30 day follow up visit. Tests will be performed by the hospital’s local laboratory. If results are 

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positive the patient is ineligible/must be discontinued from study treatment immediately. 
Details of the pregnancy tests must be recorded in the patient’s medical records.
6.5
Patient reported outcomes (PRO)
6.5.1
FACIT-Fatigue
The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F Scale) is a 
13-item questionnaire that assesses patient self-reported fatigue and its impact upon daily 
activities and function (Yellen et al 1997). Response options for each item range from 0 (Not 
at all) to 4 (Very much), where higher scores indicate greater patient-reported fatigue. The 
FACIT-F scale was originally developed to evaluate fatigue associated with anaemia in cancer 
patients and has been used as an endpoint in clinical trials in various cancer populations 
including breast cancer and non-small cell lung cancer. Content validity of the FACIT-F has 
been demonstrated in a large sample of mixed cancer patients (n>300). Reliability (internal 
consistency, test-retest reliability, criterion validity, and responsiveness/sensitivity to change) 
of the FACT-F has also been documented (Yellen et al 1997).
6.5.2
EORTC QLQ-C30
In this study patient-reported disease related symptoms and health-related quality of life 
(HRQoL) will be evaluated using the validated EORTC QLQ-C30 questionnaire (Aaronson et 
al 1993). The EORTC QLQ-C30 questionnaire was developed to assess HRQoL and is the 
most commonly used cancer-specific tool in oncology. It has undergone extensive testing and 
validation as well as detailed cross-cultural testing and validation and has been used in breast 
cancer trials.
The EORTC QLQ-C30 comprises 30 questions designed for all cancer types. Questions can 
be grouped into the following subscales:
!
5 multi-item functional scales (physical, role, emotional, cognitive and social 
functioning) 
!
A 2-item global health status scale
!
Symptom scales/items
∀
3 multi-item symptom scales (fatigue, pain, nausea and vomiting)
∀
Dyspnoea
∀
Insomnia
∀
Appetite loss
∀
Constipation

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∀
Diarrhoea
∀
Financial difficulties
6.5.3
Administration of PRO questionnaires
FACIT-Fatigue and EORTC QLQ-C30 questionnaires will be collected at baseline (within 
screening period after eligibility confirmed but prior to randomisation) and then 6 months, 
(24 weeks), 12 months (52 weeks), 18 months and 24 months following randomisation.
Questionnaires shall be administered to a patient by delegated site personnel (e.g., a research 
nurse, study coordinator) adequately trained and listed on Site's Delegation Log. Site shall 
assign a trained back-up person to cover if that individual is absent. The AZ Study Delivery 
Team (or delegate) will provide relevant training in administration of the questionnaires. The 
significance and relevance of the data need to be explained carefully to participating patients 
so that they are motivated to comply with data collection.
The instructions for completion of the PRO questionnaires are as follows:
!
They must be completed at the clinical visit prior to any other study procedures 
(following informed consent) and before discussion of disease progress to avoid 
biasing the patient’s responses to the questions. They must be completed in private 
by the patient
!
The patient should be given sufficient time to complete at their own speed
!
The patient should not receive help from relatives, friends or clinic staff to answer 
the questionnaire. However, if the patient is unable to read the questionnaires (e.g., 
is blind or illiterate) the questionnaires may be read out by trained clinic staff and 
responses recorded
!
On completion of the questionnaires they should be handed back to the person 
responsible for questionnaires who should check for completeness
!
Only one answer should be recorded for each question.
The site staff should enter the information directly into the eCRF.
After the baseline, questionnaires are to be administered at follow-up visits, so that when a 
follow-up visit is delayed, completion of the questionnaire may also be delayed. Patients who 
experience disease recurrence or diagnosis of a second primary cancer will not be expected to 
continue with the PRO assessments. Patients who discontinue study drug for other reasons 
will be expected to continue the PRO assessments per protocol schedule. Patients who never 
initiate study medication should not continue to complete PRO assessments. If a patient 
declines to complete a scheduled PRO assessment or if the questionnaire is not completed for 

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mandatory. If the surgery tumour blocks are available, but cannot be submitted, sites may submit a 
portion of invasive tumour from the original block, either by taking at least one core of at least 3 mm 
in diameter, or by splitting the original block in two parts, and re-embedding one in a new block for 
central submission. If blocks containing pre-neoadjuvant treatment core biopsies are available but 
cannot be submitted, sections mounted on glass slides prepared from the block can be provided. If 
tumour sample can’t be provided as requested above or if it’s not available, approval by Study Team 
for patient’s entry into the trial is required.
The samples and data from this research will be coded and not identified with any personal 
details. Each sample will be identified with the study and patient enrolment number. In this 
way biomarker data may be correlated with clinical data, samples destroyed in the event of 
withdrawal of consent and regulatory audit enabled. However, only the investigator will be 
able to link the biomarker sample to the individual patient. Research biomarker data may be 
generated in real time during the study or retrospectively and will have unknown clinical 
significance. The study investigative team will not provide research biomarker results to 
patients, their family members, any insurance company, an employer, clinical study 
investigator, general physician or any other third party unless required to do so by law. The 
patient’s samples will not be used for any purpose other than those described in the protocol.
The gBRCA status result from the Myriad assessment for patients with unknown BRCA status 
will be provided to the investigator and will be collected as part of the patient’s demography 
and medical history details.
6.6.2
Collection of blood sample for Myriad germline BRCA1 and BRCA2 testing
Two blood samples are mandated for all patients. One sample will be used to test for BRCA
mutations using the current commercial Myriad BRCAnalysis test. This result will confirm or 
determine subject eligibility. The second sample is required for a bridging study to validate 
the companion diagnostic test for olaparib (see Section 6.6.2.1 below).
All patients must have a known deleterious or suspected deleterious germline BRCA mutation 
to be randomised; this may have been determined by local genetic testing prior to study entry 
or may be assessed as part of the enrolment procedure for the study (via central testing by 
Myriad), see Section 6.2.1. The specific gBRCA alteration on which eligibility is based must 
be entered into the trial database by selecting the appropriate value from the drop down menu. 
If the central laboratory analysis does not confirm a local gBRCA determination, that 
information should also be entered in the eCRF, along with an indication of whether or not the 
patient was enrolled into the trial.  
Residual blood (or its derivatives) may be used to evaluate future BRCA companion 
diagnostic tests and for additional exploratory work, to elucidate the mechanism of response, 
understand the mode of action of study treatment, and improve the understanding of disease 
recurrence (including BRCA mutation status and its role in response).
For blood volume see Section 7.1.

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To ensure that the assessments are carried out in the correct order, and that PK sampling is 
conducted within the required sampling window, it will be necessary to arrange the 
assessment procedures so that the PK assessments fall on/around the correct timing (see 
Section 6.8). The actual time of dosing and collection of all PK samples must be recorded as 
described below:
It is essential that the time of collection of all 5 PK samples is recorded and that the times of 
the morning and evening dose on the day of PK sampling and the time of dose the evening 
before is recorded.
Samples will be collected, labelled, stored and shipped as detailed in the Laboratory Manual. 
For blood volume see Section 7.1.
6.8.3
Determination of drug concentration
Samples for determination of olaparib concentrations in plasma will be analysed by Covance 
on behalf of Clinical Bioanalysis Alliance, AstraZeneca R&D, using an appropriate 
bioanalytical method. Full details of the analytical method used will be described in a separate 
bioanalytical report. Placebo samples will not be analysed unless specified.
Full instructions for collection, labeling, storage and shipment of samples are provided in the 
Laboratory Manual. Results will only be reported for samples shipped within a timeframe for 
which the stability of olaparib in the samples has been validated and shown to be acceptable.
6.9
Health economics
6.9.1
Resource use (serious adverse events)
Resource use for serious adverse events (including hospitalisations) will be captured through 
the adverse reporting procedures described in Section 6.4.
7.
BIOLOGICAL SAMPLING PROCEDURES 
7.1
Volume of blood
The volume of blood that will be drawn from each patient will vary, depending upon the 
length of time that the patient remains in the trial and if the patient is in the subset of patients 
having PK samples taken. However, the total volume of blood to be drawn from each patient 
in the study (including for PK samples), assuming they complete screening, 12 months of 
treatment, a treatment discontinuation visit and the 30-day follow-up visit, should not exceed 
208 mL.
Safety laboratory assessments will be performed locally at each centre’s laboratory by means 
of their established methods. The number of samples/blood volumes is therefore subject to 
site-specific change. 

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7.2
Handling, storage and destruction of biological samples
The samples may be used up, disposed of after analyses or retained for further use as 
described here.
Biological samples for future research will be retained at the study bio-repository for a 
maximum of 15 years following the Last Patient’s Last Visit in the study. The results from 
future analysis will not be reported in the Clinical Study Report but separately in a Scientific 
Report.
Biosamples collected for this study will be stored in study specific bio-repositories that are
under the guardianship of BIG (non-US samples) and NRG Oncology and NCI (US samples) 
on behalf of the study Steering Committee.
7.2.1
Pharmacogenetic samples
The processes adopted for ensuring confidentiality of samples for genetic analysis are 
important. Samples will be stored for a maximum of 15 years, from the date of the Last 
Patient’s Last Visit, after which they will be destroyed. DNA is a finite resource that may be 
used up during analyses. Samples will be stored and used until no further analyses are possible 
or the maximum storage time has been reached after which samples will be destroyed.
DNA will be extracted from the blood sample. The DNA sample will be assigned a unique 
number replacing the information on the sample tube. Thereafter, the DNA sample will be 
identifiable by the unique DNA number only. The DNA number is used to identify the sample 
and corresponding data at the AstraZeneca genetics laboratories, or at the designated contract 
laboratory. No personal details identifying the individual will be available to any person 
(AstraZeneca employee or contract laboratory staff working with the DNA.)
The samples and data for genetic analysis in this study will be single coded. The link between 
the patient enrolment/randomisation code and the DNA number will be maintained and stored 
in a secure environment, with restricted access within the Clinical Genotyping Group 
Laboratory Information Management System (LIMS) at AstraZeneca. The link will be used to 
identify the relevant DNA samples for analysis, facilitate correlation of genotypic results with 
clinical data, allow regulatory audit and to trace samples for destruction in the case of 
withdrawal of consent when the patient has requested disposal/destruction of collected 
samples not yet analysed.
7.2.2
Pharmacokinetic samples
Pharmacokinetic samples will be disposed of after the Bioanalytical Report finalisation or six 
months after issuance of the draft Bioanalytical Report (whichever is earlier), unless required 
for future analyses. Additional analyses may be conducted on the anonymised, pooled 
pharmacokinetic samples to further evaluate and validate the analytical method. Any results 
from such analyses will be reported separately from the Clinical Study Report (CSR). 

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Sample reproducibility analysis, if any, will be performed alongside the bioanalysis of the test 
samples. The results from the evaluation will not be reported in the CSR but separately in a 
Bioanalytical Report. Anonymised samples will be retained for no longer that 12 months after 
the Bioanalytical Report is finalised.
7.3
Labeling and shipment of biohazard samples
The Principal Investigator should ensure that samples are labelled and shipped in accordance 
with the Laboratory Manual and the Biological Substance, Category B Regulations (materials 
containing or suspected to contain infectious substances that do not meet Category A criteria), 
see Appendix B ‘IATA 6.2 Guidance Document’.
Any samples identified as Infectious Category A materials should not be shipped and no 
further samples will be taken from the patient unless agreed with AstraZeneca/BIG or Partners 
and appropriate labelling, shipment and containment provisions are approved.
7.4
Chain of custody of biological samples
A full chain of custody is maintained for all samples throughout their lifecycle.
The Principal Investigator at each centre is responsible for ensuring full traceability of 
collected biological samples from the patients while in storage at the centre until shipment or 
disposal (where appropriate).
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps documentation of receipt of arrival.
AstraZeneca/BIG/NRG Oncology and their Partners keep oversight of the entire life cycle 
through internal procedures, monitoring of study sites and auditing of external laboratory 
providers.
Biosamples collected for this study will be stored in study specific bio-repositories that are 
under the guardianship of BIG (non-US samples) and NRG Oncology and NCI (US samples) 
on behalf of the study Steering Committee. 
Samples retained for further use are registered in the bio-repositories systems during the entire 
sample life cycle.
If required, the remaining biological samples are returned to the site, according to local 
regulations or at the end of the retention period, whichever is the sooner.
7.5
Withdrawal of informed consent for donated biological samples
If a patient withdraws consent to the use of donated biological samples, the samples will be 
disposed of/destroyed, and the action documented. If samples are already analysed,

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AstraZeneca/BIG/NRG Oncology and their Partners are not obliged to destroy the results of 
this research.
BRCA sample: As collection of the biological samples is an integral part of the study, then the 
patient is withdrawn from further study participation.
Archival tumour sample: Although mandatory*, the patient may continue in the study if the 
patient is already randomised.
* For adjuvant patients, this refers to the surgical specimen; for neoadjuvant patients, both the 
pre-treatment core biopsy and the surgical specimen with residual disease are requested but 
only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, 
sites may submit a portion of invasive tumour from the original block, either by taking at least 
one core of at least 3 mm in diameter, or by splitting the original block in two parts, and re-
embedding one in a new block for central submission. If blocks containing pre-neoadjuvant 
treatment core biopsies are available but cannot be submitted, sections mounted on glass 
slides prepared from the block can be provided. If tumour sample can’t be provided as 
requested above or if it’s not available, approval by Study Team for patient’s entry into the 
trial is required.
Tumour samples at relapse: As collection of the biological samples is an optional part of the 
study, then the patient may continue in the study.
Pharmacokinetic samples: As collection of the pharmacokinetic samples is an optional part of 
the study, then the patient may continue in the study.
Blood samples for biomarker analysis (e.g. cfDNA): Collection of the biological samples is a 
mandatory part of the study, however, the patient may continue in the study despite 
withdrawing consent for analysis of the biomarker samples.
Blood sample for pharmacogenetic analysis: As collection of the biological samples is an 
optional part of the study, then the patient may continue in the study.
The Principal Investigator/site staff:
!
Should ensure that the Site Monitor is notified immediately of a patient’s 
withdrawal of informed consent for the use of donated samples  
!
Should ensure that biological samples from that patient, if stored at the study site, 
are immediately identified, disposed of /destroyed, and the action documented
!
Should ensure that the laboratory(ies) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed/destroyed, the action 
documented and the signed document returned to the study site

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!
Should ensure that the patient and Site Monitor are informed about the sample 
disposal.
The Site Monitor ensures that the central laboratory(ies) holding the samples is/are informed 
about the withdrawn consent immediately and that samples are disposed of/destroyed and the 
action documented and returned to the study site.
8.
ETHICAL AND REGULATORY REQUIREMENTS
8.1
Ethical conduct of the study
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, applicable 
regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological 
Samples.
8.2
Patient data protection
The Informed Consent Form will incorporate (or, in some cases, be accompanied by a 
separate document incorporating) wording that complies with relevant data protection and 
privacy legislation.
AstraZeneca will not provide individual genotype results to patients, any insurance company, 
any employer, their family members, general physician or any other third party, unless 
required to do so by law.
Extra precautions are taken to preserve confidentiality and prevent genetic data being linked to 
the identity of the patient. In exceptional circumstances, however, certain individuals might 
see both the genetic data and the personal identifiers of a patient. For example, in the case of a 
medical emergency, a study medical representative or an investigator might know a patient’s 
identity and also have access to his or her genetic data. Also Regulatory authorities may 
require access to the relevant files, though the patient’s medical information and the genetic 
files would remain physically separate.
The exception to the above is the result of the Myriad gBRCA test. This will be made available 
to the Investigator and patient.
8.3
Ethics and regulatory review
An Institutional Review Board (IRB)/Ethics Committee should approve the final study 
protocol, including the final version of the Informed Consent Form and any other written 
information and/or materials to be provided to the patients. The investigator will ensure the 
distribution of these documents to the applicable Ethics Committee, and to the study site staff.
The opinion of the Ethics Committee should be given in writing. The investigator should 
submit the written approval to AstraZeneca/BIG/Partners (and the CTSU for US centres) 
before enrolment of any patient into the study.

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The Ethics Committee should approve all advertising used to recruit patients for the study.
AstraZeneca/BIG/Partners (and NRG Oncology/CTEP for US centres) should approve major 
modifications to the Informed Consent Form that are needed to meet local requirements.
If required by local regulations, the protocol should be re-approved by the Ethics Committee 
annually.
Before enrolment of any patient into the study, the final study protocol, including the final 
version of the Informed Consent Form must be approved by the national regulatory authority 
or a notification to the national regulatory authority must be done, according to local 
regulations.
AstraZeneca/BIG/Partners will handle the distribution of these documents to the national 
regulatory authorities.
AstraZeneca/BIG/Partners will provide Regulatory Authorities, Ethics Committees and 
Principal Investigators with safety updates/reports according to local requirements, including 
SUSARs (Suspected Unexpected Serious Adverse Reactions), where relevant.
Each Principal Investigator is responsible for providing the Ethics Committees/IRB with 
reports of any serious and unexpected adverse drug reactions from any other study conducted 
with the investigational product. AstraZeneca will provide this information to the Principal 
Investigator so that he/she can meet these reporting requirements.
8.4
Informed consent
The Principal Investigator(s) at each centre will:
!
Ensure each patient is given full and adequate oral and written information about 
the nature, purpose, possible risk and benefit of the study
!
Ensure each patient is notified that they are free to discontinue from the study at any 
time
!
Ensure that each patient is given the opportunity to ask questions and allowed time 
to consider the information provided
!
Ensure each patient provides signed and dated informed consent before conducting 
any procedure specifically for the study
!
Ensure the original, signed Informed Consent Form(s) is/are stored in the 
Investigator’s Study File
!
Ensure a copy of the signed Informed Consent Form is given to the patient

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!
Ensure that any incentives for patients who participate in the study as well as any 
provisions for patients harmed as a consequence of study participation are described 
in the informed consent form that is approved by an Ethics Committee.
8.5
Changes to the protocol and informed consent form
Study procedures will not be changed without the mutual agreement of the International co-
ordinating Investigator, National Co-ordinating Investigator, and the Principal Investigator 
and AstraZeneca/BIG/NRG Oncology/Partners and the study Steering Committee.
If there are any substantial changes to the study protocol, then these changes will be 
documented in a study protocol amendment and where required in a new version of the study 
protocol (Revised Clinical Study Protocol).
Any protocol amendment must be approved by the relevant Ethics Committee and if 
applicable, should obtain the national regulatory authority approval, before implementation. 
Local requirements are to be followed for amended protocols.
AstraZeneca will distribute any subsequent amendments and new versions of the protocol to 
each Principal Investigator(s). For distribution to Ethics Committee see Section 8.3.
If a protocol amendment requires a change to a centre’s Informed Consent Form, 
AstraZeneca/BIG/Partners, NRG Oncology/CTEP for US centres, and the centre’s Ethics 
Committee are to approve the revised Informed Consent Form before the revised form is used. 
If required by local regulations, any administrative changes will be communicated to or 
approved by each Ethics Committee.
8.6
Audits and inspections
Authorised representatives of AstraZeneca, a regulatory authority, or an Ethics Committee 
may perform audits or inspections at the centre, including source data verification. The 
purpose of an audit or inspection is to systematically and independently examine all study-
related activities and documents, to determine whether these activities were conducted, and 
data were recorded, analysed, and accurately reported according to the protocol, Good Clinical 
Practice (GCP), guidelines of the International Conference on Harmonisation (ICH), and any 
applicable regulatory requirements. The investigator/ site staff should contact the site monitor 
immediately if contacted by a regulatory agency about an inspection at the centre.
9.
STUDY MANAGEMENT
9.1
Pre-study activities
Before the first patient is entered into the study by a site, a representative of 
AstraZeneca/BIG/Partners may visit the investigational study site to:
!
Determine the adequacy of the facilities

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Edition Number 5
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!
Determine availability of appropriate patients for the study
!
Discuss with the investigator(s) (and other personnel involved with the study) their 
responsibilities with regard to protocol adherence, and the responsibilities of 
AstraZeneca/BIG/Partners or representatives. This will be documented in a Clinical 
Study Agreement or equivalent.
9.2
Training of study site personnel
Before the first patient is entered into the study, AstraZeneca/BIG/Partners will review and 
discuss the requirements of the Clinical Study Protocol and related documents with the 
investigational staff and also train them in any study specific procedures and the WBDC.
The Principal Investigator should ensure that appropriate training relevant to the study is given 
to all site staff, and that any new information relevant to the performance of this study is 
forwarded to the staff involved.
The Principal Investigator will maintain a record of all individuals involved in the study 
(medical, nursing and other staff).
9.3
Monitoring of the study
During the study, a representative of AstraZeneca/BIG/Partners will have regular contacts 
with the study site, including visits to:
!
Provide information and support to the investigator(s)
!
Confirm that facilities remain acceptable
!
Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs in a timely way, that biological samples are 
handled in accordance with the Laboratory Manual and that study drug 
accountability checks are being performed
!
Perform source data verification (a comparison of the data in the eCRFs with the 
patient’s medical records at the hospital or practice, and other records relevant to 
the study) including verification that the appropriate version of the consent form 
was used and that it was signed and dated prior to any study procedures. This will 
require direct access to all original records for each patient (e.g. clinic charts)
!
If relevant, ensure withdrawal of informed consent to the use of the patient’s 
biological samples is reported and biological samples are identified and disposed 
of/destroyed accordingly, and the action is documented, and reported to the patient.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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The AstraZeneca/BIG/Partners representative will be available between visits if the 
investigator(s) or other staff at the centre needs information and advice about the study 
conduct.
9.3.1
Source data
Refer to the Clinical Study Agreement or equivalent for location of source data.
9.4
Study agreements
The Principal Investigator at each centre should comply with all the terms, conditions, and 
obligations of the Clinical Study Agreement, or equivalent, for this study. In the event of any 
inconsistency between this Clinical Study Protocol and the Clinical Study Agreement, or 
equivalent, the terms of Clinical Study Protocol shall prevail with respect to the conduct of the 
study and the treatment of patients and in all other respects, not relating to study conduct or 
treatment of patients, the terms of the Clinical Study Agreement, or equivalent, shall prevail.
Agreements between AstraZeneca/BIG/NRG Oncology/Partners and the Principal Investigator 
should be in place before any study-related procedures can take place, or patients are enrolled.
9.4.1
Archiving of study documents
The Investigator should follow the principles outlined in the Clinical Study Agreement (CSA) 
or equivalent.
9.5
Study timetable and end of study
The end of the study is defined as ‘the last visit of the last patient undergoing the study’.
The study is expected to start in Q1 2014 and to end by 2028.
The study will end approximately 10 years following the randomisation of the last patient. 
Patients will be followed up until 10 years after the randomisation of the last patient. 
The study may be prematurely terminated at individual centres if the study procedures are not 
being performed according to GCP, or if recruitment is slow. AstraZeneca may also terminate 
the entire study prematurely upon recommendations of the study IDMC if concerns for safety 
arise within this study or in any other study with olaparib.
10.
DATA MANAGEMENT 
Data management will be performed by Frontier Science.
The data collected through third party sources will be obtained and reconciled against study 
data by Frontier Science.
Adverse events and medical/surgical history will be classified according to the terminology of 
the latest version of the Medical Dictionary for Regulatory Activities (MedDRA). 

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Medications will be classified according to the AstraZeneca Drug Dictionary. Coding will be 
done by Frontier Science.
Additional details of data management procedures can be found in the Data Management Plan 
for the Study. This document will be continuously updated through the life of the study.
Data queries will be raised for inconsistent, impossible or missing data. All entries to the study 
database will be available in an audit trail.
The data will be validated as defined in the Data Management Plan. Quality control 
procedures will be applied to each stage of data handling to ensure that all data are reliable 
and have been processed correctly. The Data Management Plan will also document the roles 
and responsibilities of the various functions and personnel involved in the data management 
process.
When all data have been coded, validated, and locked, clean file will be declared. Any 
treatment revealing data may thereafter be added and the final database will be locked. 
The results from genetic research may be reported in the CSR for the main study, or in a 
separate report as appropriate. Refer to Appendix C.
11.
EVALUATION AND CALCULATION OF VARIABLES
11.1
Calculation or derivation of efficacy variable(s)
11.1.1
Primary endpoint
The primary endpoint of the trial is invasive disease free survival (IDFS), defined as the time 
from randomisation to date of first recurrence, where recurrence is defined as loco-regional, 
distant recurrence, new cancer or death from any cause. IDFS is further detailed according to 
the standardised STEEP system definition (Hudis et al 2007) as one of the following:
!
Ipsilateral invasive breast tumour recurrence (IIBTR): Invasive breast cancer 
involving the same breast parenchyma as the original primary.
!
Regional invasive breast cancer recurrence: Invasive breast cancer in the axilla, 
regional lymph nodes, chest wall, and skin of the ipsilateral breast.
!
Distant recurrence: Metastatic disease-breast cancer that has either been biopsy 
confirmed or radiologically diagnosed as recurrent invasive breast cancer.
!
Death attributable to any cause, including breast cancer, non-breast cancer, or 
unknown cause.
!
Contralateral invasive breast cancer.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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!
Second primary non-breast invasive malignancies (i.e., excluding new in situ 
carcinomas of any site). Second primary non-breast invasive malignancies include 
hematologic malignancies and MDS. Squamous or basal cell skin cancers will not 
be counted as primary endpoint events.
Loco-regional recurrence of the disease (ipsilateral or regional invasive breast cancer) should 
be cytologically/histologically confirmed. Appropriate imaging (CT, MRI bone and/or PET 
scan) of the chest/abdomen/pelvis or any other area as clinically indicated should be 
performed at the time of local recurrence to exclude further spread of the disease. Distant 
recurrence should be diagnosed by radiological examination and/or histopathological 
confirmation when metastatic lesion is easily accessible for biopsy.
For confirmed local recurrence events, the earliest date of diagnosis based on an objective 
finding (physical exam, radiological/imaging assessment, cytological/histopathological 
assessment) will be used to determine the time to event for the analysis but not the date of the 
first symptoms or blood analysis abnormality. For example if a physical exam results in 
‘suspected’ disease recurrence and disease recurrence is then confirmed by cytology/histology 
then the date of the physical exam will be used to derive the time to event.
For confirmed distant recurrence the date of the earliest radiological/imaging examination or 
cytological/histopathological assessment linked to the diagnosis will be used to determine the 
time to event for the analysis (i.e. physical exam will not be considered within the derivation 
of time to distant recurrence nor will be symptoms or blood analysis).
Invasive contralateral breast cancer or invasive non-breast secondary primary cancer should 
be confirmed by histopathological report. The date of the earliest objective finding related to 
diagnosis of the new cancer will be used as the date of new cancer for the analysis.
If two recurrence events (local and distant) are reported within 2 months of each other then 
this is referred to as a simultaneous event and will be considered as a single event. In this 
situation the worst case will be taken as the event ‘type’ but the date of recurrence will be the 
earliest date of the two events. For example if local and distant recurrence are reported within 
a 2 month period then for the analysis and reporting of IDFS the event type will be distant 
recurrence but the date of recurrence will be the earliest date of the two events. 
If two recurrence events are reported but more than 2 months has elapsed between the events 
then the events will be regarded as two separate recurrence events and the earliest event and 
corresponding date of event will be used in the derivation of IDFS (i.e. IDFS is based on the 
first recurrence event).
If a patient dies during the study with no documented disease recurrence or invasive 
contralateral breast cancer or invasive non-breast secondary primary cancer then death will be 
regarded as an event and the date of death will be used to determine the patients IDFS time.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Patients who have not had a recorded IDFS event at the time of the analysis will be censored 
at the date of their last disease evaluation. Disease evaluation includes mammogram and/or 
breast MRI (MRI preferred for patients younger than 50 years), other radiological/imaging 
examination or clinical examination (e.g. physical exam).
11.1.2
Secondary endpoints 
11.1.2.1
Overall Survival
Overall survival is defined as the time from the date of randomisation until death due to any 
cause. Any patient not known to have died at the time of analysis will be censored based on 
the last recorded date on which the patient was known to be alive.
11.1.2.2
Distant disease free survival (DDFS)
DDFS will be defined as the time from randomisation until documented evidence of first 
distant recurrence of breast cancer. Distant recurrence will include the following events:
!
Distant recurrence: Metastatic disease-breast cancer that has either been biopsy 
confirmed or radiologically diagnosed as recurrent invasive breast cancer.
!
Death attributable to any cause, including breast cancer, non-breast cancer, or 
unknown cause.
!
Second primary non-breast invasive cancer.
Evidence of distant recurrence should be provided by either radiological examination or 
preferably by histopathological examination when metastasis is easily accessible for biopsy. 
Second primary non-breast invasive cancer should be confirmed by histopathological report.
For the analysis of DDFS, the date of the confirmed DDFS event will use the earliest 
assessment date from the radiological and/or histological or cytological assessment. For 
example if a patient has distant recurrence suspected by radiological examination which is 
later confirmed by biopsy then the date of the radiological examination will be used as the 
date of event.
Patients who do not have documented evidence of DDFS at the time of the analysis of DDFS 
will be censored at the date of their last clinical examination (i.e. last physical exam or 
radiological evaluation). 
The first site of distant recurrence will be recorded and used in the analysis. Information on 
subsequent sites of recurrence will also be collected during follow-up assessments to ensure as
complete as possible information on distant recurrence is obtained.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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11.1.2.3
Incidence of contralateral invasive breast cancer, contralateral non-invasive 
breast cancer, new primary ovarian cancer, new primary fallopian tube cancer 
and new primary peritoneal cancer
The incidence of contralateral invasive breast cancer, contralateral non-invasive breast cancer, 
new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal 
cancer will each be considered separately and be defined as the number and percentage of 
patients with documented evidence of contralateral invasive breast cancer, contralateral non-
invasive breast cancer, new primary ovarian cancer, new primary fallopian tube cancer and 
new primary peritoneal cancer regardless of when this occurs (i.e. does not need to be their 
first recurrence event).
All patients should be followed for evidence of new primary breast cancers and all other 
cancers. This includes patients with a first event of local or distant recurrence as they may go 
on to develop new cancers in the future. All new cancers will be collected for all patients not 
just the first new cancer.
Data analyses of new contralateral breast cancer (invasive and non-invasive) will exclude 
patients who have had bilateral mastectomy prior to randomisation.
Data analyses of new ovarian cancers will exclude patients who have had both ovaries 
removed prior to randomisation.
Data analyses of new fallopian tube cancers will exclude patients who have had both fallopian 
tubes removed prior to randomisation.
Data analyses of new peritoneal cancer will include all patients in the ITT populations.
11.2
Calculation or derivation of safety variable(s)
Safety and tolerability will be assessed in terms of AEs, deaths, laboratory data and vital 
signs. These will be collected for all patients. Appropriate summaries of these data will be 
presented as described in Section 12.
11.2.1
Other significant adverse events (OAE)
During the evaluation of the AE data, an AstraZeneca medically qualified expert will review 
the list of AEs that were not reported as SAEs and DAEs. Based on the expert’s judgement, 
significant adverse events of particular clinical importance may, after consultation with the 
Global Patient Safety Physician, be considered OAEs and reported as such in the Clinical 
Study Report. A similar review of laboratory/vital signs/ECG data will be performed for 
identification of OAEs.
Examples of these are marked haematological and other laboratory abnormalities, and certain 
events that lead to intervention (other than those already classified as serious), dose reduction 
or significant additional treatment.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
129(176)
11.3
Calculation or derivation of patient reported outcome variables
Patient reported outcomes will be assessed based on the FACIT-Fatigue symptoms and the 
EORTC QLQ-C30 questionnaires. Further details are given in Section 12.2.3 and full details 
will be provided in the statistical analysis plan.
11.4
Calculation or derivation of pharmacokinetic variables 
The pharmacokinetic (PK) analysis of the plasma concentration data for olaparib will be 
performed at AstraZeneca R&D or by a CRO identified by AstraZeneca R&D. The actual 
sampling times will be used in the PK calculations. For each patient providing a complete set 
of PK samples, non-linear mixed effects modelling (NONMEM) will be used to estimate 
steady state Cmax, AUC and Cmin.
11.5
Calculation or derivation of pharmacodynamic variable(s) - not 
applicable
11.6
Calculation or derivation of 
 variables
Any data summaries that will be reported in the main clinical study report will be detailed 
within the statistical analysis plan. Additional exploratory analyses or data summaries that 
may be produced outside of the main study report will be defined in an exploratory analysis 
plan, if appropriate.
11.7
Calculation or derivation of health economic variables –not applicable
12.
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION 
12.1
Description of analysis sets
A comprehensive statistical analysis plan (SAP) will be prepared before first subject in (FSI).
Table 13 gives a summary of outcome variables and analysis populations.
12.1.1
Full analysis set
Intention to treat (ITT): The primary statistical analysis of the efficacy of olaparib will include 
all randomised patients and will compare the treatment groups on the basis of randomised 
treatment, regardless of the treatment actually received. Patients who were randomised but did 
not subsequently go on to receive study treatment are included in the Full Analysis Set (FAS). 
For the interim analysis two efficacy populations will be defined
1.
ITT population: This will include all randomised patients and will compare the 
treatment groups on the basis of randomised treatment, regardless of the treatment 
actually received. Note: it is anticipated that all patients will be randomised by the 
time of the interim analysis.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
130(176)
2.
Mature cohort ITT population: This will include the first 900 randomised patients 
only and will compare the treatment groups on the basis of randomised treatment, 
regardless of the treatment actually received.
12.1.2
Safety analysis set
All patients who received at least one dose of randomised study treatment, olaparib or 
placebo, will be included in the safety analysis set. If a patient receives at least one dose of 
olaparib he/she will be summarised in the olaparib arm for safety summaries (e.g. olaparib 
arm will include patients randomised to olaparib who receive at least one dose of olaparib or 
placebo patients who receive at least one dose of olaparib in error at any time). If a patient 
randomised to olaparib receives only placebo treatment then he/she will be summarised as part 
of the placebo arm. 
Table 13
Summary of Outcome Variables and Analysis Populations
Outcome Variable
Populations
Efficacy Data - Interim
IDFS 
Other efficacy variables
FAS (ITT), Mature cohort ITT
FAS (ITT)
Efficacy data- Final
IDFS, OS, DDFS, incidence of contralateral 
breast cancers, new primary ovarian, new primary 
fallopian tube cancers and new primary peritoneal 
cancer and symptom/HRQoL endpoints
FAS (ITT)
Demography
FAS (ITT)
Pharmacokinetics data
PK
Safety Data
Exposure
Safety
Adverse Events
Safety
Lab measurements
Safety
Vital Signs
Safety
12.1.3
PK analysis set
PK data will be analysed according to treatment received. This population will comprise all 
randomised to olaparib patients who receive at least one dose of study treatment and have at 
least one PK sample collected.

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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12.2
Methods of statistical analysis
12.2.1
Analysis of primary endpoint
12.2.1.1
Primary analysis
The primary analysis of IDFS will occur when a minimum of 330 IDFS events have been 
observed (to provide at least 90% power to detect a hazard ratio of 0.7). Based on the event 
rate from the 10 November 2017 database, the number of IDFS events required to trigger the 
primary analysis is expected to be accrued by November 2020 (80% CI: March 2020 to
September 2021). The maturity rate will be 18.3%, where maturity is defined as the number of 
events divided by the total number of randomised patients. 
IDFS will be compared across two treatment arms using a log rank test stratified by the 
stratification factors at randomization, and the corresponding p-value will be reported as the 
primary analysis result. In addition, IDFS will be analysed using a stratified Cox proportional 
hazard model stratified by the stratification factors at randomisation and using the Efron 
approach for handling ties. The point estimate of the treatment effect, i.e., the hazard ratio of 
IDFS (olaparib vs. placebo) will be obtained by maximizing the Cox partial likelihood 
function, which is the product of the partial likelihood of each stratum. The 95% confidence 
interval will be estimated using the profile likelihood approach.
A Kaplan-Meier plot of IDFS will be presented by treatment group. Summaries of the number 
and percentage of patients experiencing an IDFS event, and the type of event (recurrence or 
death) will be provided for each treatment.
The estimated 3 year IDFS will be summarised (using estimates from the KM curve) and 
presented by treatment group.
12.2.1.2
Sensitivity analysis
If applicable, an analysis will be performed for IDFS using the same model as described 
above but based on all randomised patients confirmed to have gBRCA mutations by the central 
test. This analysis is only required if the analysis population differs from the primary ITT 
population.
Any patients mis-stratified in the randomisation system (i.e. incorrect details are entered at the 
time of randomisation) will be included in the primary stratified log rank test and Cox 
proportional hazard model using the baseline data collected from the randomisation system 
(Registration and Randomisation System). If >5% of randomised patients are incorrectly 
stratified (i.e., randomization system data does not match baseline data), then a sensitivity 
analysis will be performed for IDFS based on the (correct) baseline data collected in the 
eCRF. If the results of ER and PgR status from the local and central labs differ in >5% of 
randomised patients, a sensitivity analyses will also be performed based on ER and/or PgR 
positive/HER2 negative and TNBC subsets as defined by the central laboratory testing.

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Edition Number 5
Date 18 May 2018
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The assumption of proportionality will be assessed. Proportionality will be tested firstly by 
producing plots of complementary log-log (event times) versus log (time) and, if these raise 
concerns, a time dependent covariate would be fitted to assess the extent to which this 
represents random variation. Note that in the presence of non-proportionality, the HR will be 
interpreted as an average HR over the observed extent of follow-up.
As patients will be randomised, imbalances in demographic factors between the treatment 
groups are not anticipated. However if any imbalances should occur, these additional 
demographic variables may be fitted into the stratified Cox model. The HR and associated 
confidence interval would be presented.
12.2.1.3
Subgroup analysis
Subgroup analyses will be conducted to assess consistency of treatment effect across potential 
or expected prognostic factors, including the baseline stratification factors. 
If there are too few results available for a meaningful analysis of a particular subgroup (it is 
not considered appropriate to present analyses where there are less than 5 events in either 
treatment group), the relationship between that subgroup and IDFS will not be formally 
analysed. In this case, only descriptive summaries will be provided.
The following subgroups are of primary interest:
!
Hormone receptor status (ER and/or PgR positive and HER2 negative; TNBC)
!
Neoadjuvant chemotherapy; adjuvant chemotherapy
!
Prior platinum therapy for current breast cancer (Yes;No)
!
BRCA mutation type (BRCA1; BRCA2; BRCA1/2 both)
!
Hormone receptor status by prior chemotherapy setting (if there are sufficient 
events to split into the four groups)
∀
ER and/or PgR positive with neoadjuvant chemotherapy
∀
ER and/or PgR positive with adjuvant chemotherapy
∀
ER and PgR negative with neoadjuvant chemotherapy
∀
ER and PgR negative with adjuvant chemotherapy
!
BRCA status by prior platinum therapy setting
∀
BRCA1 with prior platinum therapy for current breast cancer

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∀
BRCA1 with no prior platinum therapy for current breast cancer
∀
BRCA2 with prior platinum therapy for current breast cancer
∀
BRCA2 with no prior platinum therapy for current breast cancer
The following additional subgroups will also be analysed to assess consistency in treatment 
effect across a broader set of baseline characteristics known before start of study medication:
!
Type of prior Neo/Adjuvant chemotherapy (anthracycline; taxane; anthracycline 
plus taxane)
!
Type of breast surgery prior to randomisation (breast conservation; unilateral 
mastectomy; bilateral mastectomy)
!
Bilateral Oophorectomy (Yes; No) 
!
Axillary nodal status at surgery prior to randomisation (Positive or negative for the 
post adjuvant patients only)
!
CPS+EG score at baseline (2, 3 or 4; 5 or 6 for the post neoadjuvant group only)
!
Age at randomisation (<50; 50-64; ≥65)
!
Race 
!
Sponsor (AZ; NRG Oncology) 
Other baseline variables may also be assessed if there is clinical justification. These would be 
pre-defined within the SAP.
For each subgroup, the HRs (olaparib: placebo) and associated CIs will be calculated from a 
Cox proportional hazards model (using the Efron approach for handling ties) that contains the 
treatment term, factor and treatment-by-factor interaction term. The treatment effect HRs for 
each treatment comparison along with their confidence intervals will be obtained for each 
level of the subgroup from this single model. The HRs and 95% CIs will be presented on a 
forest plot including the HR and 95% CI from the overall population (using the primary 
analysis).
No adjustment to the significance level for testing subgroups will be made since all these 
subgroup analyses will be considered exploratory. The results would be used as supportive
data for the primary analysis of IDFS based on all randomised patients.

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
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12.2.1.4
Analysis of Interaction
The presence of quantitative interactions will be assessed by means of an overall global 
interaction test. This will be performed in the overall population by comparing the fit of a Cox 
proportional hazards model including treatment, all covariates (including stratification 
factors), and all covariate-by-treatment interaction terms, with one that excludes the 
interaction terms and will be assessed at the 2-sided 10% significance level. If a covariate 
does not have more than 20 events per level (of the covariate) it will be included as a covariate 
in the model, but the covariate-by-treatment interaction term will be omitted. If the fit of the 
model is not significantly improved then it will be concluded that overall the treatment effect 
is consistent across the subgroups.
If the global interaction test is found to be statistically significant, an attempt to determine the 
cause and type of interaction will be made. Stepwise backwards selection will be performed 
on the saturated model, whereby (using a 10% level throughout) the least significant 
interaction terms are removed one-by-one and any newly significant interactions re-included 
until a final model is reached where all included interactions are significant and all excluded 
interactions are non-significant. Throughout this process all main effects will be included in 
the model regardless of whether the corresponding interaction term is still present. This 
approach will identify the factors that independently alter the treatment effect and prevent 
identification of multiple correlated interactions.
Any quantitative interactions identified using this procedure will then be tested to rule out any 
qualitative interaction using the approach of Gail and Simon 1985.
12.2.2
Analysis of secondary endpoints
OS and DDFS
OS and DDFS will be analysed at the time of the IDFS analysis as per the multiple testing 
procedure (MTP) outlined in Section 12.2.5 and will use the same methodology and model as 
described above for the primary analysis of IDFS. 
If applicable, a sensitivity analysis will be performed for DDFS and OS using the same model 
as described above for IDFS but based on all randomised patients confirmed to have gBRCA
mutations by the central test. This analysis is only required if the analysis population differs 
from the primary ITT population. Subgroup analyses will also be conducted for DDFS and OS 
based on the same subgroups described above for IDFS.
DDFS and OS will be analysed at the time of the primary analysis for IDFS (when 330 IDFS 
events are reported).
The final OS analysis will be conducted once the trial follow-up is complete (i.e. 10 years 
from when the last patient is randomised, estimated 14 years from first patient randomised 
assuming recruitment of 5 years). 

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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In addition another analysis will be performed half way between the primary IDFS analysis 
and the final overall survival analysis (estimated around 10 years from first patient 
randomised but timings will be driven by the primary IDFS analysis once known). At this 
time point both DDFS and OS will be analysed and some alpha will be reserved for formal 
hypothesis testing. IDFS may also be updated if more information is available but this would 
be considered a supportive update of the primary analysis and no alpha will be reserved for 
IDFS.
For details on alpha spend and how this will be allocated across the planned analyses see 
Section 12.2.6.
Incidence of contralateral invasive breast cancer, contralateral non-invasive breast 
cancer, new primary ovarian cancer, new primary fallopian tube cancer and new 
primary peritoneal cancer
The actual number and percentage of patients with new contralateral breast cancers (invasive 
and non-invasive), new primary ovarian cancer, new primary fallopian tube cancer and new 
primary peritoneal cancers will be presented. In addition a table summarising all reported new 
cancers (i.e. not just breast, ovarian, fallopian tube or peritoneal cancers) will also be 
produced.
As described in Section 11.1.2.3, patients who have had a bilateral mastectomy prior to 
randomisation will be excluded from the analysis of new contralateral breast cancers (invasive 
and non-invasive) and patients who have had a bilateral oophorectomy prior to randomisation 
will be excluded from the analysis of new ovarian cancers and patients who have had their 
fallopian tubes removed prior to randomisation will be excluded from the analysis of new 
fallopian tube cancers. 
The cumulative incidence of new primary contralateral invasive breast, new primary 
contralateral non-invasive breast, new primary ovarian cancers, new primary fallopian tube
cancers and new primary peritoneal cancers will be compared between treatment groups using 
competing risk analysis (Gray test, Fine and Gray 1999). Death will be considered a 
competing risk for each endpoint. In addition, bilateral mastectomy after randomization will 
be a competing risk for the contralateral breast cancer analyses, bilateral oophorectomy will 
be a competing risk for the new primary ovarian cancers analysis and removal of the fallopian 
tubes will be a competing risk for the new primary fallopian tube cancer analysis. Hazard 
ratios and 95% confidence intervals from competing risks regression analyses (Fine and Gray 
1999) adjusted for treatment and the stratification factors will also be presented – more details 
of these analyses are given in the SAP (Edition 2).
Safety
Safety data will be summarised descriptively in terms of AEs, vital signs, clinical chemistry & 
haematology and physical exam and will include data from the treatment and safety follow-up 
period. Cumulative incidence plots may also be presented for specific adverse events or 

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Edition Number 5
Date 18 May 2018
136(176)
groups events of interest. Further information on the summary of safety data will be provided 
in the SAP.
12.2.3
Analysis of patient reported outcomes
12.2.3.1
Hypotheses and objectives
The hypotheses and measurement strategy focus on the fact that patients in the trial will be 
starting with significant decrements in HRQoL and high rates of symptoms at study entry 
(baseline) due to previous chemotherapy and local treatments (surgery with or without 
radiation therapy). All analyses of Patient Reported Outcomes will be conducted on ITT 
population as listed in Table 13. Therefore, the following hypotheses are proposed, based on 
the expected toxicities of olaparib.
Primary hypothesis
Patients receiving olaparib may experience greater fatigue severity during treatment than those 
receiving placebo as measured by the FACIT-Fatigue scale at 6 and 12 months after 
randomisation.
Secondary hypotheses
Patients receiving olaparib may experience greater GI symptoms (nausea, vomiting and 
diarrhoea) severity during treatment than those receiving placebo as measured at 6 and 
12 months after randomisation but no difference expected by 24 months after randomisation.
There will be no difference in fatigue post discontinuation of study treatment as measured at 
18 and 24 months. 
There will be no difference in QOL between the two treatment arms as measured by the global 
QOL score and other sub scales from the EORTC QLQ-C30 at 6, 12, 18 and 24 months after 
randomisation and patients will demonstrate improvements in functioning over time.
Primary PRO objective 
To determine the effect of olaparib on patient-reported fatigue at 6 and 12 months after 
randomisation as measured by the FACIT-Fatigue symptoms questionnaire.
Secondary PRO objectives 
!
To determine the effect of olaparib on patient-reported GI symptoms (nausea, 
vomiting and diarrhea) over time at 6, 12, 18 and 24 months as measured by the 
EORTC QLQ-C30 scale.
!
To determine the effect of olaparib on patient reported fatigue over time at 6, 12, 
18 and 24 months as measured by the FACIT-Fatigue questionnaire.

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!
To determine if there will be a difference in QOL between the two treatment groups 
over time as measured by the 2 item global QOL score of the EORTC QLQ-C30 
scale at 6, 12, 18 and 24 months and assess if patients demonstrate improvement in 
scores over time.
!
To examine and compare the effect of olaparib over time on different functional sub 
scale scores as measured by the EORTC QLQ-C30 and assess if patients 
demonstrate improvement in functioning over time, with particular interest in the 
physical and emotional sub scales.
12.2.3.2
Statistical considerations for patient reported outcomes
Statistical analyses
Primary endpoint – Fatigue
For the primary hypothesis, the composite fatigue score (FACIT-Fatigue questionnaire) 
measured at 6 and 12 months after randomisation will be compared between the two treatment 
arms using analysis of covariance (ANCOVA) with adjustment for the corresponding baseline 
measurement. Separate analyses will be done for patients who have received prior 
neoadjuvant chemotherapy and patients who have received standard post-surgical adjuvant 
chemotherapy. Separate analyses are preferable because the timing of chemotherapy is 
expected to impact the fatigue outcome directly. Each comparison will be performed at the 
significance level of 0.05. No multiple comparisons adjustment will be employed since these 
outcomes evaluate the toxicity of the study treatment.
To further assess the effect of olaparib on fatigue over time (study treatment period and the 
year following) the composite fatigue score (FACIT-Fatigue questionnaire) measured at 6, 12, 
18 and 24 months after randomisation will be compared between the two treatment arms using 
a mixed model for repeated measures (MMRM) analysis of all of the post baseline scores. The 
model will include treatment, time and treatment by time interaction as explanatory variables 
and baseline score and baseline by time interaction as covariates. The treatment by visit 
interaction will remain in the model regardless of significance. The adjusted mean change 
from baseline estimates for each treatment arm, difference in the adjusted mean change from 
baseline estimates between the arms and corresponding confidence intervals will be presented 
by time point. Plots of the adjusted means changes over time will also be presented. 
Secondary PRO endpoints
A secondary analysis based on GI symptoms (nausea, vomiting and diarrhoea) over time from 
the EORTC QLQ-C30 scale will be performed using the same MMRM model described 
above. The adjusted mean change from baseline estimates for each treatment arm, difference 
in the adjusted mean change from baseline estimates between the arms and corresponding 
confidence intervals will be presented by visit. Plots of the adjusted means changes over time 
will also be presented for nausea, vomiting and diarrhoea.

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To assess if there are any difference in HRQoL, the 2 item global QOL score assessed by 
EORTC QLQ-30 measured at 6, 12, 18 and 24 months after randomisation will be compared 
between the two treatment arms using the same MMRM model described above. Plots over 
time will also be produced for the global QOL score.
In addition, other subscales of the EORTC QLQ-C30 will be analysed using the MMRM 
model described above with particular interest in the emotional and physical subscales. Plots 
over time will also be produced.
All secondary analyses are considered exploratory and therefore no adjustments for 
multiplicity will be made. For each comparison, p-values (along with CIs) will be generated to 
help aid interpretation of the results using a nominal significance level of 0.05 (2-sided).
Because this trial is being conducted internationally, responses to patient reported outcomes 
may be influenced by differences between country/language categories (Bernhard J et al 
2007). Therefore, analyses will be stratified by country/language groups. Further details will 
be provided in the SAP.
Adjustment for previous treatment exposures (radiation, type of chemotherapy, and surgery) 
may also be considered as part of the secondary analyses. Further details will be given in the 
SAP.
Sample size consideration
We assume that half of triple negative patients and a quarter of hormone receptor positive 
patients will have received neoadjuvant chemotherapy and we anticipate that 95% of patients 
enrolled in the trial will complete the HRQoL instrument. In addition, adjusting downward to 
allow for 20% of missing data at the 12 months assessment point, we expect that data from 
633 neoadjuvant and 735 adjuvant patients will be available (assuming that 15% of the total 
1800 enrolled patients are ER and/or PgR positive HER2 negative). These will be sufficient to 
provide statistical power of 93% and 96% correspondingly to detect a difference of 3 points 
on the FACIT-Fatigue scale score between treatment groups assuming a standard deviation of 
10.9 (Cella D et al 2002) (estimated SD of mean baseline score) and controlling α-level at 
0.05. A collection of PROs and QOL from all patients enrolled in the main trial will give us 
sufficient statistical power to detect important differences between two treatment groups.
Missing PRO data
A certain amount of missing data is expected. If data for individual items are missing, 
imputation will be done as follows: if less than 50% of the subscale items were missing (e.g. 
at most 2 out of 5 items, etc), the subscale score based on the non-missing items will be 
divided by the number of non-missing items and multiplied by the total number of items on 
the subscale. If at least 50% of the items are missing, that subscale will be treated as missing 
(not evaluable). If the scale is a single-item measure, a missing value will automatically be 
defined as ‘Non-Evaluable’. The information from patients with missing data will be reviewed 

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
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Figure 3
Multiple testing procedure
IDFS is planned to be analysed at the interim and the final analysis (see Section 12.2.6 for 
further details). If IDFS is significant at the interim based on the ITT population then 
secondary endpoints will be formally tested at the interim based on the MTP outlined above. 
To account for multiple analyses on each endpoint a separate alpha spending function will be 
applied to each endpoint (Glimm et al 2010 ). Further analyses of DDFS and OS with more 
mature follow-up may be required for which some alpha will be reserved for significance 
testing.
12.2.6
Interim analysis
A superiority interim analysis of IDFS will occur when half the events needed for at least 90% 
power (165 events) have been observed from the first 50% of patients recruited (i.e. from first 
900 patients) providing a cohort of patients with a similar level of maturity that is planned for 
the final analysis. Based on the database at time of amendment, the interim analysis is 
predicted to be October 2019 (80% CI: March 2019 to August 2020). The predictions will be 
tracked and monitored as more patients are enrolled in the study and additional data is added 
to the database. Two populations will be analysed at the interim analysis based on the analysis 
methods described in Section 12.2.1 for IDFS
1
Primary: ITT population (all patients randomised, estimated 254 events [80% CI: 
226 to 289])
2
Supportive: Mature cohort population (first 900 patients randomised, 165 events 
anticipated)
The inclusion of a mature cohort population at the interim is to provide confidence that any 
observed treatment effect from the interim ITT population is maintained with longer-term 

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follow-up. It is anticipated, based on the assumed recruitment and event rate that the interim 
analysis will occur approximately 5.3 years after the first patient is randomised and that all 
patients will have been randomised. At the time of the interim analysis, median time at risk 
per patient is expected to be 27 months in the ITT set, and 34 months in the mature cohort. 
The critical HR value at the interim analysis is 0.701.
Evidence of superiority for IDFS would only be determined at the interim if the results from 
both analysis populations provide evidence of a sustainable clinically relevant treatment effect 
for IDFS. More specifically, as a minimum the result in the ITT population would need to 
have met the statistical threshold defined below. Having met the statistical threshold in the 
ITT population, the result in the mature cohort (i.e. HR) would need to be of a similar 
magnitude such that the IDMC would consider it supportive of the ITT result and therefore 
have added confidence in the result in the ITT population. Statistical significance is not 
required for the mature cohort population. This analysis will be regarded as supportive, based 
on a cohort of patients with longer-term follow-up, to aid interpretation of the result in the ITT 
population based on interim data. Other outcome measures such as 3 year IDFS rate will also 
be presented to aid the interpretation of the HRs (particularly in the case where the assumption 
of proportional hazards may not hold). KM plots will also be produced for IDFS.
The test mass alpha for IDFS (1 sided 2.5%) will be split between the final and the interim 
analysis using a bespoke spending function where a fixed significance level will be assigned 
at the interim and the remaining significance level assigned to the final analysis, taking 
account of correlation (Stone 2010 ). A 2-sided significance level of 0.005 will be assigned to 
the interim analysis so that a highly significant and clinically relevant result will need to be 
observed to declare superiority on IDFS. As an illustration, if 70% of the total required 330 
IDFS events have occurred in the ITT population at the interim then the observed HR would 
need to be <0.7 for superiority to be declared. The HR in the mature cohort would need to be 
supportive of the ITT result. More detail around the criteria required for the mature cohort will 
be provided in the IDMC charter or SAP.
If the null hypothesis for IDFS is rejected at the interim for the ITT population then secondary 
endpoints (DDFS and OS) will be tested based on the MTP procedure outlined in Section
12.2.5 using the significance levels provided in Table 14. If IDFS is not significant at the 
interim, DDFS and OS will not be tested at the IDFS interim and the significance level 
allocated to the IDFS interim for DDFS and OS will not be allocated to later timepoints.
Similar to IDFS, a bespoke spending function will be applied to the secondary endpoints OS 
and DDFS where a fixed significance level will be assigned to each analysis time point and 
the remaining significance level assigned to the final analysis time point controlling the 
overall type 1 error at the pre-specified alpha amount (Stone 2010 ). Provided the last analysis 
is known in advance of the penultimate one then the remaining alpha can be split to ensure 
that some alpha is always reserved for the final analysis. This approach allows flexibility in 
the number of analyses while appropriately controlling the overall type 1 error. Three analyses 
are planned for DDFS and four for OS for which some alpha will be reserved for significance 

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testing. If additional analyses are required beyond the planned analyses and some alpha is still 
available for testing then any remaining alpha can be further split to strongly control the type 
1 error (based on process described above). If no alpha remains then the additional analyses 
will be considered supportive updates of the already conducted analyses. 
Given the split in alpha between DDFS and OS, if OS is significant based on the assigned 
significance level then the alpha assigned to OS will be recycled to DDFS and split across the 
planned analyses (and vice versa if DDFS is significant alpha for DDFS will be recycled to 
OS and split across analyses). The recycled alpha will be split based on the ratio of the 
originally assigned alpha split. For example if the original alpha allocation was split 1/3 for 
each analysis time point then the recycled alpha would also be split 1/3 across each analysis 
time point. For example, at the first interim analysis, assume IDFS is statistically significant 
and the secondary endpoint OS is also statistically significant. The significance level for 
testing DDFS is therefore 0.005 + (alpha assigned to OS recycled to DDFS and split across the 
planned analyses), i.e. 0.005 + (1% * 0.005/0.04 = 0.00125) = 0.00625, or alternatively 
thought of as 0.005 * 5/4.
Secondary endpoints will be assessed based on the ITT population. Table 14 shows the 
different 2-sided significance levels that will be applied to the primary and secondary 
endpoints across the planned analyses as well as the total alpha spend for each endpoint. Note 
the significance level for the final analyses of each endpoint will be calculated using the 
relevant correlation based on the actual number of events for each analysis, the previous alpha 
spend and the total allocated alpha for that endpoint. 
Table 14
Summary of 2-sided significance levels and total alpha spend across 
the endpoints and analyses
Endpoints
Estimated 
timings 
from FSI**
Interim 
analysis
5.3 years
Final IDFS 
analysis 
6.5 years 
DDFS and OS 
analysis
10 years 
Final OS 
analysis
14 years
Significance 
level
Significance level
Significance 
level
Significance 
level
Total 
alpha 
spend (2-
sided)
IDFS
0.005
TBC*
N/A
N/A
5%
If IDFS is statistically significant and alpha is not recycled between secondary endpoints at the 
analysis
DDFS
0.005
0.02
TBC*
N/A
4%
OS
0.002
0.003
0.004
TBC*
1%
If IDFS is statistically significant and alpha is recycled between secondary endpoints at the analysis

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Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
144(176)
Table 14
Summary of 2-sided significance levels and total alpha spend across 
the endpoints and analyses
Endpoints
Estimated 
timings 
from FSI**
Interim 
analysis
5.3 years
Final IDFS 
analysis 
6.5 years 
DDFS and OS 
analysis
10 years 
Final OS 
analysis
14 years
DDFS
0.00625 
0.025
TBC*
N/A
5%
OS
0.01
0.015
0.02
TBC*
5%
*TBC: to be calculated; significance level to be calculated once relevant correlation based on the actual number 
of events for each analysis is known taking account of previous alpha spend and total allocated alpha
**FSI: first subject in
The IDMC will review the data from the interim analysis. The boundaries defined by the 
interim p-values for efficacy will be used as guidelines by the IDMC along with all other 
relevant trial information, including the safety data, to decide if it is appropriate to make a 
recommendation other than that to continue the trial as planned.
At the time of the interim analysis for superiority, an assessment of futility will also be 
performed. This futility assessment will be based on the probability of eventually showing 
statistical significance for the primary endpoint when the final number of IDFS events 
(n=330) is reached (Lachin 2005). The determination of this probability will be conditional on 
the observed data in the ITT population at the time of the interim analysis for superiority and 
on the assumed hazard ratio for the alternative hypothesis (IDFS HR=0.7). If the probability is 
less than 0.1, the IDMC will consider the option of declaring futility.
Full details on the process around the interim analysis and the efficacy criteria will be 
documented in the SAP and IDMC charter.
12.2.7
Sample size justification
The primary endpoint of the study is IDFS and patients will be randomised 1:1 to either 
olaparib 300 mg b.i.d. (twice daily) or matching placebo. 
A total of 1800 patients will be randomised into the study to achieve 330 IDFS events. If the 
true HR for the comparison of olaparib versus placebo in terms of IDFS is 0.7 then with 
330 events, the analysis of IDFS will have 90% power to demonstrate a statistically significant 
difference in IDFS, assuming a 2-sided 5% significance level. The critical HR value at the 
primary analysis is 0.805. 
The actual accrual pattern between June 2014 and February 2018 is shown in Table 15. It is 
estimated that 1800 patients will be randomised by April/May 2019 so that the study will take 

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Edition Number 5
Date 18 May 2018
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approximately 5 years to complete recruitment (approximately 230 patients in US and 
approximately 1570 patients in the Rest of the World countries).
Table 15
Actual accrual between June 2014 and February 2018
Interval since start of 
randomisation
(months)
Number of patients 
randomised in interval
Cumulative number of 
patients randomised
Average number of 
patients randomised 
per month in interval
0-6
21
21
3.5
6-12
94
115
15.7
12-18
174
289
29
18-24
180
469
33
24-30
229
698
38.2
30-36
249
947
41.5
36-42
234
1181
39
42-45*
118
1299
39.3
*Note: 3-month interval: December 2017 to February 2018 inclusive.
The primary analysis population will be all patients randomised (ITT). A subgroup analysis 
based on prior chemotherapy (adjuvant or neoadjuvant), prior platinum therapy (yes or no) 
and hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC) will be 
conducted to check for consistency in the treatment effect but this analysis is considered 
supportive of the primary analysis in the overall population. 
During the trial, the Steering Committee will monitor the recruited patient population and
actual event rate whilst remaining blinded to treatment. If the data suggests that the original 
sample size assumptions are incorrect such that achieving the required number of events with 
the current number of patients does not seem feasible then in consultation with the IDMC a 
decision may be made to increase the number of patients recruited into the trial to achieve the 
required 330 events.
12.3
Independent Data monitoring committee 
This study will utilise an Independent Data Monitoring Committee (IDMC) whose members 
include therapeutic area experts and statisticians who are not employed by AstraZeneca and 
do not have any major conflict of interest. Members of the IDMC will be jointly selected by 
BIG, AstraZeneca, CTEP and NRG Oncology and the IDMC will report their 
recommendations to the Steering Committee.
The IDMC will meet approximately every 6 months and will review ongoing study progress 
including safety and, when appropriate, efficacy data. They will also review the data presented 
at the time of the protocol-defined interim analysis. The IDMC will have the ability to 

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recommend suspension of enrolment if safety concerns are identified at any of the 6 monthly 
assessments. At the interim analysis, both efficacy and safety will be reviewed and trial 
recommendations will be based on the totality of the data. The IDMC can recommend changes 
to the trial, including stopping of the trial, if they have concerns over the benefit risk profile 
for olaparib.
Reports for the IDMC will be prepared by an Independent Statistical Centre (ISC) and will be 
presented to the IDMC in closed session. Following review of data, the IDMC will make a 
recommendation regarding the future conduct of the trial to the Steering Committee. The 
IDMC recommendation will not contain any unblinded information or any information related 
to treatment outcomes of the trial.
A separate IDMC Charter will be developed defining the responsibilities and procedures for 
the IDMC.

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13.2
Overdose 
There is currently no specific treatment in the event of overdose with olaparib and possible 
symptoms of overdose are not established. Study treatment must only be used in accordance 
with the dosing recommendations in this protocol. Any dose or frequency of dosing that 
exceeds the dosing regimen specified in this protocol should be reported as an overdose. 
Monitors should report any overdose as a minor protocol deviation. The MTD is 300 mg b.i.d 
(tablet).
Adverse reactions associated with overdose should be treated symptomatically and should be 
managed appropriately.
!
An overdose with associated AEs is recorded as the AE diagnosis/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.
!
An overdose without associated symptoms is only reported on the Overdose eCRF 
module.
If an overdose on an AstraZeneca study drug occurs in the course of the study, then 
Investigators or other site personnel inform appropriate medical representatives immediately, 
or no later than 24 hours of when he or she becomes aware of it.
The designated study representative works with the Investigator to ensure that all relevant 
information is provided to the AstraZeneca Patient Safety data entry site.
For overdoses associated with SAE, standard reporting timelines apply (see Section 6.4.4). 
For other overdoses, reporting should be done within 30 days.
13.3
Pregnancy
All outcomes of pregnancy should be reported to AstraZeneca (see Table 16 and Table 17).
13.3.1
Maternal exposure
If a patient becomes pregnant during the course of the study the investigational product should 
be discontinued immediately.
The outcomes of any conception occurring from the date of the first dose of study medication 
until 3 months after the last dose of study medication must be followed up and documented. 
Pregnancy itself is not regarded as an adverse event unless there is a suspicion that the 
investigational product under study may have interfered with the effectiveness of a 
contraceptive medication. Congenital abnormalities/birth defects and spontaneous 
miscarriages should be reported and handled as SAEs. Elective abortions without 
complications should not be handled as AEs. The outcome of all pregnancies (spontaneous 

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miscarriage, elective termination, ectopic pregnancy, normal birth or congenital abnormality) 
should be followed up and documented even if the patient was discontinued from the study.
If any pregnancy occurs in the course of the study, then Investigators or other site personnel 
inform appropriate medical representatives immediately, or no later than 24 hours of when he 
or she becomes aware of it.
The designated study representative works with the Investigator to ensure that all relevant 
information is provided to the AstraZeneca Patient Safety data entry site within 1 or 5 days for 
SAEs (see Section 6.4.4) and within 30 days for all other pregnancies.
The same timelines apply when outcome information is available.
The relevant module in the eCRF is used to report the pregnancy and the relevant eCRF 
module is used to report the outcome of the pregnancy. 
13.3.2
Paternal exposure 
Male patients should refrain from fathering a child or donating sperm during the study 
treatment period and for 3 months following the last dose. Pregnancy of the patient’s partners 
is not considered to be an adverse event. However, the outcome of all pregnancies 
(spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth or congenital 
abnormality) should if possible be followed up and documented.
The outcome of any conception occurring from the date of the first dose until 3 months after 
the last dose should be followed up and documented.
Table 16
Pregnancy reporting and handling according to time of diagnosis
Time point of diagnosis
Handling and reporting
During screening
Do not randomise, record as reason for screen 
failure by completing the Step 3 Screening 
Failure Confirmation checklist in the FS 
Registration and Randomisation system.
After randomisation but before first dose
Do not start study treatment, continue to follow 
patient for study end-points, report in eCRF and 
AstraZeneca Patient Safety DES via the paper 
Pregnancy form within 24 hours
During study treatment (maternal exposure)a
Discontinue from study treatment immediately, 
continue to follow patient for study end-points, 
report in eCRF, to medical team via email and 
AstraZeneca Patient Safety DES via the paper 
Pregnancy form within 24 hours

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Table 16
Pregnancy reporting and handling according to time of diagnosis
Time point of diagnosis
Handling and reporting
Follow-up: Within 3 months of the end of study 
treatment
Continue to follow patient for study end-points, 
report in eCRF, to medical team via email and 
AstraZeneca Patient Safety DES via the paper 
Pregnancy form within 24 hours
Follow-up: After 3 months of the end of study 
treatment
Report in eCRF and to AstraZeneca Patient 
Safety DES via the paper Pregnancy form within 
30 days
a
This includes pregnancies identified during Follow-up but with a probable date of conception during the 
period in which the patient was still receiving study treatment.
Table 17
Reporting outcomes of pregnancy according to time of diagnosis
Time point of diagnosis
Normal outcome
Abnormal outcomea, b
During screening
No need to report on outcomes
No need to report on 
outcomes
After randomisation but 
before first dose
In eCRF and AstraZeneca Patient Safety 
DES via the paper Pregnancy form Part II 
within 30 days
Treat as an SAE (report 
within 24 hours)
During study treatment 
(maternal exposure)a
In eCRF, to the medical team via email 
and AstraZeneca Patient Safety DES via 
the paper Pregnancy form Part II within 
24 hours
Treat as an SAE (report 
within 24 hours)
Follow-up: Within 3 
months of the end of study 
treatment
In eCRF, to the medical team via email 
and AstraZeneca Patient Safety DES via 
the paper Pregnancy form Part II within 
24 hours
Treat as an SAE (report 
within 24 hours)
Follow-up: After 3 months 
of the end of study 
treatment
In eCRF and AstraZeneca Patient Safety 
DES via the paper Pregnancy form Part II 
within 30 days
Treat as an SAE (report 
within 24 hours)
a
Abnormal outcome means congenital abnormalities/birth defects, ectopic pregnancy and spontaneous 
miscarriages. Elective abortions without complications should not be handled as AEs.
b
If there is a suspicion that the investigational product under study may have interfered with the 
effectiveness of a contraceptive medication, pregnancy should be reported as an AE.

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14.
LIST OF REFERENCES
Aaronson et al 1993
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner 
H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment 
of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in 
oncology.
Aebi et al 2011
S. Aebi, T. Davidson, G. Gruber & F. Cardoso. Primary breast cancer: ESMO Clinical 
Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 22 
(Supplement 6): vi12–vi24, 2011.
American Cancer Society 2013
American Cancer Society. Cancer Facts and Figures 2013. Atlanta, Georgia: American Cancer 
Society, 2013. http://www.cancer.org.
Antoniou et al 2003
Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of 
breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series 
unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 
2003;72(5):1117-30.
Arun et al 2011
Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, et al. Response to 
neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and non-carriers: a 
single-institution experience. J Clin Oncol 2011; 29(28):3739-46.
Atchley et al 2008
Atchley DP, Albarracin CT, Lopez A, Valero V, Amos CI, Gonzalez-Angulo AM, et al. 
Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative 
breast cancer. J Clin Oncol. 2008;26(26):4282-8.
Bergfeldt et al 1995 
Bergfeldt K, Einhorn S, Rosendahl I, Hall P. Increased risk of second primary malignancies in 
patients with gynecological cancer. A Swedish record-linkage study. Acta Oncol. 
1995;34(6):771-7.
Bernhard J et al 2007
Bernhard J, Zahrieh D, Castiglione-Gertsch M, et al. Adjuvant chemotherapy followed by 
goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and 
quality of life in premenopausal patients—the International Breast Cancer Study Group Trial 
VIII. J Clin Oncol 2007; 25:263-270.

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
152(176)
Bordeleau et al 2011
Bordeleau L, Lipscombe L, Lubinski J, et al. Diabetes and breast cancer among women with 
BRCA1 and BRCA2 mutations. Cancer 2011;117:1812-8.
Bower et al 2000
Bower JE, Ganz PA, Desmond KA, et al. Fatigue in breast cancer survivors: occurrence, 
correlates, and impact on quality of life. J Clin Oncol 2000; 18(4):743-753.
Bower et al 2006
Bower JE, Ganz PA, Desmond KA, et al. Fatigue in long-term breast carcinoma survivors: a 
longitudinal investigation. Cancer 2006; 106(4):751-758.
Burnell et al 2010
Burnell M, Levine MN, Chapman JW, Bramwell V, Gelmon K, Walley B, et al. 
Cyclophosphamide, Epirubicin, and Fluorouracil Versus Dose-Dense Epirubicin and 
Cyclophosphamide Followed by Paclitaxel Versus Doxorubicin and Cyclophosphamide 
Followed by Paclitaxel in Node-Positive or High-Risk Node-Negative Breast Cancer. Journal 
of Clinical Oncology;vol28 no 1.
Cameron et al 2013
Cameron D, Brown J, Dent R et al. Adjuvant bevacizumab-containing therapy in triple-
negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet 
Oncol 2013; 14:933-42.
Carey 2011
Carey LA. Directed Therapy of Subtypes of Triple-Negative Breast Cancer. The Oncologist 
2011;16(suppl 1):71–78.
Cella D et al 2002
Cella D, Eton DT, Lai JS, et al. Combining anchor and distribution-based methods to derive 
minimal clinically important differences on the Functional Assessment of Cancer Therapy 
(FACT) anemia and fatigue scales. J Pain Symptom Manage 2002; 24(6):547-561
Cole and Strair 2010
Cole M, Strair R. Acute myelogenous leukemia and myelodysplasia secondary to breast 
cancer treatment: case studies and literature review. Am J Med Sci 2010;339(1):36-40.
Cortazar et al 2014
Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical 
benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384:164-72.
Dent et al 2007
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson 
E, Sun P, Narod SA. Triple-negative breast cancer: clinical features and patterns of 
recurrence. Clin Cancer Res. 2007;13:4429-34.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
153(176)
Fine and Gray 1999
Fine, J. and Gray, R. A Proportional Hazards Model for the Subdistribution of a Competing 
Risk, Journal of the American Statistical Association, 1999: 94, 496–509.
Fong et al 2009
Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of 
poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 
2009;361(2);123-34.
Foulkes et al 2010 
Foulkes, W, Smith, IE, Reis-Filho, JS. Triple Negative Breast Cancer. N Engl J Med 
2010;363;1938-48. 
Fowble et al 2001
Fowble B, Hanlon A, Freedman G, Nocolaou N, Anderson P. Second cancers after 
conservative surgery and radiation for stages I-II breast cancer : identifying a subset of women 
at increased risk. Int J Radiat Oncol, Biol, Phys. 2001; 51 (3);679-690.
Gail and Simon 1985
Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient 
subsets. Biometrics 1985;41:361-72.
Ganz et al 1998A
Ganz PA, Rowland JH, Desmond K, et al. Life after breast cancer: understanding women's 
health-related quality of life and sexual functioning. J Clin Oncol 1998; 16(2):501-514.
Ganz et al 1998B
Ganz PA, Rowland JH, Meyerowitz BE, et al. Impact of different adjuvant therapy strategies 
on quality of life in breast cancer survivors. Recent Results Cancer Res 1998; 152(9):396-411.
Ganz et al 2002
Ganz PA, Desmond KA, Leedham B, et al. Quality of life in long-term, disease-free survivors 
of breast cancer: a follow-up study. J Natl Cancer Inst 2002; 94(1):39-49.
Ganz et al 2004
Ganz PA, Kwan L, Stanton AL, et al. Quality of life at the end of primary treatment of breast 
cancer: first results from the moving beyond cancer randomized trial. J Natl Cancer Inst 2004; 
96(5):376-387.
Ganz et al 2011A
Ganz PA, Land SR, Geyer CE, et al. Menstrual history and quality-of-life outcomes in women 
with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial. J 
Clin Oncol 2011; 29(9):1110-1116.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
154(176)
Ganz et al 2011B
Ganz PA, Kwan L, Stanton AL, et al. Physical and psychosocial recovery in the year after 
primary treatment of breast cancer. J Clin Oncol 2011; 29(9):1101-1109.
Gaymes et al 2008
Gaymes TJ, Shall S, MacPherson LJ, Twine NA, Lea NC, Farzaneh F, and Mufti GJ. 
Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic 
cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes. 
Haematologica 2009; 94:638-646. doi:10.3324/haematol.2008.001933.
Gelmon et al 2011
Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, et al. Olaparib 
in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or 
triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. 
Lancet Oncol 2011; 12: 852–61
Ginsburg et al 2010
Ginsburg OM, Kim-Sing C, Foulkes WD, Ghadirian P, Lynch HT, Sun P, et al. BRCA1 and 
BRCA2 families and the risk of skin cancer. Fam Cancer 2010; 9:489-93.
Glimm et al 2010 
Glimm, E., Maurer, W., and Bretz, F. Hierarchical testing of multiple endpoints in group-
sequential trials. Statistics in Medicine 2010;29, 219–228.
Goodwin et al 2012
Goodwin PJ, Phillips KA, West DW, et al. Breast cancer prognosis in BRCA1 and BRCA2 
mutation carriers: An international perspective breast cancer family registry population-based 
cohort study. J Clin Oncol 2012;30:19-26.
Gupta et al 2007
Gupta B, Sait SN, Block AW, Ford LA, moysich KB, Baer MR. Acute myeloid leukemia 
(AML) and myelodysplastic syndrome (MDS) following treatment for ovarian cancer. J Clin 
Oncol 2007;ASCO Annual Meeting Proceedings Part 1,Vol 25, No 18S:17506.
Hay et al 2009
Hay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, et al. Poly(ADP-ribose) 
polymerase-1 inhibitor treatment regresses autochthonous BRCA 2/p53-mutant mammary 
tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res. 
2009;69(9):3850-5. 
Helleday 2011
Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing 
up the misunderstandings. Molecular Oncology 2011; 5: 387-393.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
155(176)
Hershman et al 2007
Hershman D, Neugut AI, Jacobson JS, Wang J, Tsai W, McBride R, Bennett CL, Grann VR. 
Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte 
Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy. JNCI 2007 Vol. 
99, Issue 3,Febr7.
Honrado et al 2006
Honrado E, Benítez J, Palacios J. Histopathology of BRCA1- and BRCA2-associated breast 
cancer.Crit Rev Oncol Hematol. 2006;59:27-39
Hudis et al 2007
Hudis CA, William E, Barlow JP, Costantino RJ, Gray KI, Pritchard J-AW, et al. Proposal for 
Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials: The 
STEEP System. J Clin Oncol 2007;25(15):2127-32.
Huzarski et al 2013
Huzarski T, Byrski T et al. Ten-Year Survival in Patients With BRCA1-Negative and BRCA1-
Positive Breast Cancer. J Clin Oncol 2013; 31:3191-3196.
Jeruss et al 2008
Jeruss SJ, Mittendorf EA et al. Combined Use of Clinical and Pathologic Staging Variables to 
Define Outcomes for Breast Cancer Patients Treated With Neoadjuvant Therapy. J Clin Oncol 
2008; J Clin Oncol 26:246-252.
Khatcheressian et al 2012
Khatcheressian JL, Hurley P et al. Breast Cancer Follow-Up and Management after primary 
treatment: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin 
Oncol 30, 2012.
Kaufman et al 2014
Kaufman B, Shapira-Frommer R et al. Olaparib monotherapy in patients with advanced 
cancer and a germline BRCA1/2 mutation. J Clin Oncol 2014 Nov 3. pii: JCO.2014.56.2728.
Lachin 2005
Lachin, J. M. (2005). A review of methods for futility stopping based on conditional power. 
Statist. Med., 24: 2747–2764. Statist Med 24:2747-2764
Liedtke et al 2008
Liedtke, C, Mazouni C, Hess K, Andre´ F, Tordai A, Mejia JA, et al. Response to 
Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast 
Cancer. Journal of Clinical Oncology; 2008 vol 26 no 8.
Mavaddat et al 2012
Mavaddat et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation 
carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) 

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
156(176)
Cancer Epidemiol Biomarkers Prev. 2012 January; 21(1): 134–147. doi:10.1158/1055-
9965.EPI-11-0775.
Metzger-Filho et al 2010
Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, et al. Disecting the 
heterogeneity of triple negative breast cancer. J Clin Oncol. 2012 May 20;30 915:1879-87. 
Doi: 10.1200/JCO.2011.38.2010.
Mieog et al 2007
Mieog JS, van der Hage JA, van de Velde CJ. Preoperative chemotherapy for women with 
operable breast cancer. Cochrane Database Syst Rev. 2007;18(2):CD005002.
Mittendorf et al 2011
Mittendorf EA, Jeruss JS, Tucker SL, Kolli A, Newman LA, Gonzalez-Angulo et al. 
Validation of a Novel Staging System for Disease-Specific Survival in Patients With Breast 
Cancer Treated With Neoadjuvant Chemotherapy. Journal of Clinical Oncology 2011 vol 29 
no 15 may.
Morton et al 2013
Morton LM, Dores GM, Tucker MA, Kim CJ, Onel K, Gilbert ES, et al. Evolving risk of 
therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the 
United States, 1975-2008. Blood 2013;121(15):2996-3004.
Murai et al 2012
Murai J, Huang SN, Das BB, Renaud A, et al. Trapping of PARP1 and PARP2 by Clinical 
PARP Inhibitors. AACR 2012; 72(21); 5588–99.
Nardone et al (2015)
Nardone A, Goldstein A, Shea MJ, Mithchell T, Fu X, De C et al. PARP inhibition effects on 
endocrine therapy and resistance in estrogen receptor positive (ER+) breast cancer models. 
AACR 2015, abstract # 15LB8846AACR
Praga et al 2005
Praga C, Bergh J, Bliss J, Bonneterre J, Cesana B, Coombes RC, et al. Risk of Acute Myeloid 
Leukemia and Myelodysplastic Syndrome in Trials of Adjuvant Epirubicin for Early Breast 
Cancer: Correlation With Doses of Epirubicin and Cyclophosphamide. Journal of Clinical 
Oncology 2005 Vol23 no 18 June.
Rennert et al 2007
Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Hedy S. Clinical 
outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 
2007;357:115-23.

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
157(176)
Rottenberg et al 2008
Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, et al. High 
sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and 
in combination with platinum drugs. Proc Natl Acad Sci. 2008;105(44):17079-84.
Robins et al 1991
Robins JM, Tsiatis AA. Correcting for noncompliance in randomized trials using rank 
preserving structural failure time models. Communications in Statistics - Theory and Methods 
1991; 20:2609-2631.
Robson et al 2004
Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, et al. A combined 
analysis of outcome following breast cancer: Differences in survival based on BRCA1/BRCA2 
mutation status and administration of adjuvant treatment. Breast Cancer Res 2004;6(1):R8-17.
Robson et al 2017
Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic 
breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377(6):522-33.
Schiewer et al 2013
Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, et al. Dual roles of 
PARP-1 promote cancer growth and progression. Cancer Discov. 2012;2(12):1134-49
Smith et al 2003
Smith RE, Bryant J, DeCillis A, Anderson S. Acute Myeloid Leukemia and Myelodysplastic 
Syndrome After Doxorubicin-Cyclophosphamide Adjuvant Therapy for Operable Breast 
Cancer: The National Surgical Adjuvant Breast and Bowel Project Experience 2003 J Clin 
Oncol 21:1195-1204.
Stone 2010 
A Stone. The application of bespoke spending functions in group-sequential designs and the 
effect of delayed treatment switching in survival trials. Pharmaceutical statistics 2010; 9, 151-
161.
Swain et al 2013
Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, et al. Definitive results 
of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, 
node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-
204.
Tryggvadottir et al 2013
Tryggvadottir L, Olafsdottir EJ, Olafsdottir GH, Sigurdsson H, Johannsson OT, Bjorgvinsson 
E, et al. Tumour diploidy and survival in breast cancer patients with BRCA2 mutations. Breast 
Cancer Res Treat 2013 Jul;140:375–38

Clinical Study Protocol
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 5
Date 18 May 2018
158(176)
Tutt et al 2010
Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-
ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and 
advanced breast cancer: a proof-of-concept trial. Lancet 2010; 376: 235–44.
Vay et al 2011
Vay A, Kumar S, Seward S, Semaan A, Schiffer CA, Munkarah AR at al. Therapy-related 
myeloid leukemia after treatment for epithelial ovarian carcinoma: an epidemiological 
analysis. Gynecologic Oncology 2011;123:456-60.
Von Minckwitz et al 2012
Von Minckwitz G, Untch M, Blohmer JU et al. Definition and impact of pathologic complete 
response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer 
subtypes. J Clin Oncol 2012; 30: 1796–1804.
Wesolowski et al 2007
Wesolowski R, Choueiri TK, Rybicki L, Shealy AG, Casey G, Weng D, et al. BRCA mutation 
status and risk of secondary malignancy following chemotherapy for breast cancer. J Clin 
Oncol, 2007;ASCO Annual Meeting Proceedings Part I. Vol (25);No. 18S (June 20 
Supplement):11017.
Yellen et al 1997
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other 
anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) 
measurement system. J Pain Symptom Manage 1997; 13(2), 63-74.
Zhang et al 2013
Zhang F, Wang Y, Wang L, Luo X, Huang K, Wang C, Du M, Liu F, Luo T, Huang D, 
Huang K. Poly(ADP-ribose) polymerase 1 is a key regulator of estrogen receptor α-dependent
gene transcription. J Biol Chem. 2013;288(16):11348-57.

Clinical Study Protocol Appendix A
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
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Appendix A
Additional Safety Information
Further Guidance on the Definition of a Serious Adverse Event (SAE)
Life threatening
‘Life-threatening’ means that the subject was at immediate risk of death from the AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
subject’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (e.g., hepatitis that resolved without hepatic failure).
Hospitalisation
Outsubject treatment in an emergency room is not in itself a serious AE, although the reasons 
for it may be (e.g., bronchospasm, laryngeal oedema).Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study.
Important medical event or medical intervention
Medical and scientific judgement should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalisation, disability or incapacity but may jeopardize the subject or may require 
medical intervention to prevent one or more outcomes listed in the definition of serious.  
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgement must be used.
Examples of such events are: 
!
Angioedema not severe enough to require intubation but requiring iv hydrocortisone 
treatment
!
Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment 
with N-acetylcysteine
!
Intensive treatment in an emergency room or at home for allergic bronchospasm
!
Blood dyscrasias (e.g., neutropenia or anaemia requiring blood transfusion, etc.) or 
convulsions that do not result in hospitalisation
!
Development of drug dependency or drug abuse

Clinical Study Protocol Appendix A
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A Guide to Interpreting the Causality Question
The following factors should be considered when deciding if there is a “reasonable 
possibility” that an AE may have been caused by the drug.
!
Time Course.  Exposure to suspect drug.  Has the subject actually received the suspect 
drug?  Did the AE occur in a reasonable temporal relationship to the administration of 
the suspect drug?
!
Consistency with known drug profile.  Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? OR could the AE be anticipated from its pharmacological 
properties?
!
Dechallenge experience.  Did the AE resolve or improve on stopping or reducing the 
dose of the suspect drug?
!
No alternative cause.  The AE cannot be reasonably explained by another aetiology 
such as the underlying disease, other drugs, other host or environmental factors.
!
Rechallenge experience.  Did the AE reoccur if the suspected drug was reintroduced 
after having been stopped? AstraZeneca would not normally recommend or support a 
rechallenge.
!
Laboratory tests.  A specific laboratory investigation (if performed) has confirmed the 
relationship?
A “reasonable possibility” could be considered to exist for an AE where one or more of these 
factors exist.
In contrast, there would not be a “reasonable possibility” of causality if none of the above 
criteria apply or where there is evidence of exposure and a reasonable time course but any 
dechallenge (if performed) is negative or ambiguous or there is another more likely cause of 
the AE.
In difficult cases, other factors could be considered such as:
!
Is this a recognised feature of overdose of the drug?
!
Is there a known mechanism?
Ambiguous cases should be considered as being a “reasonable possibility” of a causal 
relationship unless further evidence becomes available to refute this.  Causal relationship in 
cases where the disease under study has deteriorated due to lack of effect should be classified 
as no reasonable possibility.

Clinical Study Protocol Appendix B
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Appendix B
International Airline Transportation Association (IATA) 6.2 
Guidance Document
Labelling and shipment of biohazard samples 
International Airline Transportation Association (IATA) classifies biohazardous agents into 3 
categories.  For transport purposes the classification of infectious substances according to risk 
groups was removed from the Dangerous Goods Regulations (DGR) in the 46th edition 
(2005).  Infectious substances are now classified either as Category A, Category B or Exempt.  
There is no direct relationship between Risk Groups and categories A and B.
Category A Infectious Substances are infectious substances in a form that, when exposure to 
it occurs, is capable of causing permanent disability, life-threatening or fatal disease in 
otherwise healthy humans or animals.  Category A pathogens are e.g., Ebola, Lassa fever 
virus:
!
are to be packed and shipped in accordance with IATA Instruction 602.
Category B Infectious Substances are infectious Substances that do not meet the criteria for 
inclusion in Category A.  Category B pathogens are e.g., Hepatitis A, B, C, D, and E viruses, 
Human immunodeficiency virus (HIV) types 1 and 2.  They are assigned the following UN 
number and proper shipping name:
!
UN 3373 – Biological Substance, Category B
!
are to be packed in accordance with UN3373 and IATA 650
Exempt - all other materials with minimal risk of containing pathogens
!
Clinical trial samples will fall into Category B or exempt under IATA regulations
!
Clinical trial samples will routinely be packed and transported at ambient temperature 
in IATA 650 compliant packaging 
!
Biological samples transported in dry ice require additional dangerous goods 
specification for the dry-ice content
!
IATA compliant courier and packaging materials should be used for packing and 
transportation and packing should be done by an IATA certified person, as applicable
!
Samples routinely transported by road or rail are subject to local regulations which 
require that they are also packed and transported in a safe and appropriate way to 
contain any risk of infection or contamination by using approved couriers and 
packaging / containment materials at all times.  The IATA 650 biological sample 
containment standards are encouraged wherever possible when road or rail transport is 
used.

Clinical Study Protocol Appendix D
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Appendix D
Actions Required in Cases of Increases in Liver 
Biochemistry and Evaluation of Hy’s Law
Introduction
This Appendix describes the process to be followed in order to identify and appropriately 
report cases of Hy’s Law.  It is not intended to be a comprehensive guide to the management 
of elevated liver biochemistries.
During the course of the study the Investigator will remain vigilant for increases in liver 
biochemistry. The Investigator is responsible for determining whether a subject meets 
potential Hy’s Law (PHL) criteria at any point during the study.
The Investigator participates, together with AstraZeneca clinical project representatives, in 
review and assessment of cases meeting PHL criteria to agree whether Hy’s Law (HL) criteria 
are met.  HL criteria are met if there is no alternative explanation for the elevations in liver 
biochemistry other than Drug Induced Liver Injury (DILI) caused by the Investigational 
Medicinal Product (IP). 
The Investigator is responsible for recording data pertaining to PHL/HL cases and for 
reporting Adverse Events (AE) and Serious Adverse Events (SAE) according to the outcome 
of the review and assessment in line with standard safety reporting processes.
Definitions
Potential Hy’s Law (PHL)
Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 3x Upper Limit of 
Normal (ULN) together with Total Bilirubin (TBL) ≥ 2xULN at any point during the study 
following the start of study medication  irrespective of an increase in Alkaline Phosphatase 
(ALP). 
Hy’s Law (HL)
AST or ALT ≥ 3x ULN  together with TBL ≥ 2xULN, where no other reason, other than the 
IMP, can be found to explain the combination of increases, e.g., elevated ALP indicating 
cholestasis, viral hepatitis, another drug.  
For PHL and HL the elevation in transaminases must precede or be coincident with (i.e. on the 
same day) the elevation in TBL, but there is no specified timeframe within which the 
elevations in transaminases and TBL must occur.
Identification of Potential Hy’s Law Cases
In order to identify cases of PHL it is important to perform a comprehensive review of 
laboratory data for any subject who meets any of the following identification criteria in 
isolation or in combination:

Clinical Study Protocol Appendix D
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!
ALT ≥ 3xULN
!
AST ≥ 3xULN
!
TBL ≥ 2xULN
The Investigator will without delay review each new laboratory report and if the identification 
criteria are met will:
!
Determine whether the subject meets PHL criteria (see Section Definitions within this 
Appendix for definition) by reviewing laboratory reports from all previous visits
!
Promptly enter the laboratory data into the laboratory CRF
Follow-up
Potential Hy’s Law Criteria not met
If the subject does not meet PHL criteria the Investigator will:
!
Perform follow-up on subsequent laboratory results according to the guidance 
provided in the Clinical Study Protocol.
Potential Hy’s Law Criteria met
If the subject does meet PHL criteria the Investigator will:
!
Notify the AstraZeneca representative who will then inform the central Study Team 
The Study Physician contacts the Investigator, to provide guidance, discuss and agree an 
approach for the study subjects’ follow-up and the continuous review of data.  Subsequent to 
this contact the Investigator will:
!
Monitor the subject until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated.
!
Investigate the etiology of the event and perform diagnostic investigations as discussed 
with the Study Physician.
!
Complete the three Liver CRF Modules as information becomes available.
!
If at any time (in consultation with the Study Physician) the PHL case meets serious 
criteria, report it as an SAE using standard reporting procedures.

Clinical Study Protocol Appendix D
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Review and Assessment of Potential Hy’s Law Cases
The instructions in this Section should be followed for all cases where PHL criteria are met.
No later than 3 weeks after the biochemistry abnormality was initially detected, the Study 
Physician contacts the Investigator in order to review available data and agree on whether 
there is an alternative explanation for meeting PHL criteria other than DILI caused by the 
IMP.  The AstraZeneca Medical Science Director and Global Safety Physician will also be 
involved in this review together with other subject matter experts as appropriate.  
According to the outcome of the review and assessment, the Investigator will follow the 
instructions below.
If there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for a SAE:
!
If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF
!
If the alternative explanation is an AE/SAE, record the AE /SAE in the CRF 
accordingly and follow the AZ standard processes
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IMP:
!
Report an SAE (report term ‘Hy’s Law’) according to AstraZeneca standard processes. 
∀
The ‘Medically Important’ serious criterion should be used if no other serious 
criteria apply
∀
As there is no alternative explanation for the HL case, a causality assessment of 
‘related’ should be assigned.
If, there is an unavoidable delay, of over 3 weeks, in obtaining the information necessary to 
assess whether or not the case meets the criteria for HL, then it is assumed that there is no 
alternative explanation until such time as an informed decision can be made:
!
Report an SAE (report term ‘Potential Hy’s Law’) applying serious criteria and 
causality assessment as per above
!
Continue follow-up and review according to agreed plan.  Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are met.  Update the SAE report according to the outcome of the 

Clinical Study Protocol Appendix D
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
169(176)
review amending the reported term if an alternative explanation for the liver 
biochemistry elevations is determined.
Actions Required for Repeat Episodes of Potential Hy’s Law
This section is applicable when a subject meets PHL criteria on study treatment and has 
already met PHL criteria at a previous on study treatment visit.
The requirement to conduct follow-up, review and assessment of a repeat occurrence(s) of 
PHL is based on the nature of the alternative cause identified for the previous occurrence.  
The investigator should determine the cause for the previous occurrence of PHL criteria being 
met and answer the following question:
!
Was the alternative cause for the previous occurrence of PHL criteria being met found 
to be the disease under study e.g. chronic or progressing malignant disease, severe 
infection or liver disease?
If No: follow the process described in Potential Hy’s Law Criteria met of this Appendix
If Yes:
Determine if there has been a significant change in the subject’s condition# compared with 
when PHL criteria were previously met
!
If there is no significant change no action is required
!
If there is a significant change follow the process described in Section Follow-up of 
this Appendix
# A ‘significant’ change in the subject’s condition refers to a clinically relevant change in any 
of the individual liver biochemistry parameters (ALT, AST or total bilirubin) in isolation or in 
combination, or a clinically relevant change in associated symptoms.  The determination of 
whether there has been a significant change will be at the discretion of the Investigator; this 
may be in consultation with the Study Physician if there is any uncertainty.
References
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing 
clinical evaluation’

Clinical Study Protocol Appendix E
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
170(176)
Appendix E
Acceptable Birth Control Methods 
Olaparib is regarded as a compound with medium/high foetal risk.
Women of childbearing potential and their partners, who are sexually active, must agree to the 
use of TWO highly effective forms of contraception in combination (as listed below). This 
should be started from the signing of the informed consent and continue throughout the period 
of taking study treatment and for at least 1 month after last dose of study drug, or they must 
totally/truly abstain from any form of sexual intercourse (see below).
Male patients must use a condom during study treatment and for 3 months after last dose of 
study drug when having sexual intercourse with a pregnant woman or with a woman of 
childbearing potential. Male patients should not donate sperm throughout the period of taking 
study treatment and for 3 months following the last dose of study drug.
Acceptable Non-hormonal birth control methods include 
!
Total/True abstinence: When the patient refrains from any form of sexual 
intercourse and this is in line with their usual and/or preferred lifestyle, this must 
continue for the total duration of the treatment period and for 1 month after the last 
dose of study drug for female patients, for 3 months after last dose for male 
patients. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods, or declaration of abstinence solely for the duration of a trial) 
and withdrawal are not acceptable methods of contraception] 
!
Vasectomised sexual partner plus male condom. With participant assurance that 
partner received post-vasectomy confirmation of azoospermia
!
Tubal occlusion plus male condom 
!
IUD plus male condom. Provided coils are copper-banded
Acceptable hormonal methods
!
Etonogestrel implants (e.g., Implanon, Norplan) PLUS male condom 
!
Normal and low dose combined oral pills PLUS male condom 
!
Norelgestromin / EE transdermal system PLUS male condom 
!
Intravaginal device (e.g., EE and etonogestrel) PLUS male condom  
!
Cerazette (desogestrel) PLUS male condom. Cerazette is currently the only highly 
efficacious progesterone based pill.
!
Hormonal shot or injection (e.g., Depo-Provera) PLUS male condom

Clinical Study Protocol Appendix E
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
171(176)
!
Intrauterine system [IUS] device (e.g., levonorgestrel releasing IUS -Mirena®) 
PLUS male condom 

Clinical Study Protocol Appendix F
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
172(176)
Appendix F
ECOG Performance Status
Example of Performance Status (ECOG SCALE)
DESCRIPTION
ECOG GRADE
Fully active, able to carry on all pre-disease performance without 
restriction.
0
Restricted in physically strenuous activity, but ambulatory and able 
to carry out work of a light or sedentary nature, i.e. light 
housework, office work.
1
Ambulatory and capable of self-care, but unable to carry out any 
work activities. Up and about more than 50% of waking hours.
2
Capable of only limited self care, confined to bed or chair more 
than 50% of waking hours.
3
Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair.
4

Clinical Study Protocol Appendix G
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
173(176)
Appendix G
Patient Reported Outcomes (FACIT-Fatigue, EORTC 
QLQ-C30)

Clinical Study Protocol Appendix G
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
174(176)

Clinical Study Protocol Appendix G
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
175(176)

Clinical Study Protocol Appendix IH
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Version 5
Date 18 May 2018
176(176)
Appendix H
CPS & EG score
Calculation instructions:  Add the points for Clinical Stage + Pathologic Stage + ER status + 
Nuclear grade to derive a sum (CPS&EG score) between 0 and 6.
Table 18
Point assignments for the CPS + EG staging system
Stage/feature
Points
Clinical Stage
(AJCC staging1)
I
0
IIA
0
IIB
1
IIIA
1
IIIB
2
IIIC
2
Pathologic Stage
(AJCC staging1)
0
0
I
0
IIA
1
IIB
1
IIIA
1
IIIB
1
IIIC
2
Receptor status
ER negative2
1
Nuclear grade3
Nuclear grade 3
1
1
AJCC: American Joint Committee on Cancer (https://cancerstaging.org/Pages/default.aspx).
2
ER: Estrogen receptor; definitions for ER negativity see eligibility criteria Section 4.1.4.a.
3
In the unlikely situation nuclear grade cannot be determined, regular histologic grade should be used; if 
only Nottingham overall grade is reported, the Nottingham overall grade must be 9 to be scored as 1 point 
in the CPS&EG score (http://pathology.jhu.edu/breast/grade.php).

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Statistical Analysis Plan
Drug Substance
Olaparib (AZD2281)
Study Code
D081CC00006
Study Number
BIG 6-13, NSABP B-55
Edition Number
3.0
Date
12th  June 2019
A randomised, double-blind, parallel group, placebo-controlled multi-
centre Phase III study to assess the efficacy and safety of olaparib versus 
placebo as adjuvant treatment in patients with germline BRCA1/2
mutations and high risk HER2 negative primary breast cancer who have 
completed definitive local treatment and neoadjuvant or adjuvant 
chemotherapy

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
7
!
Section 4.2.7.3 – CPS+EG score comes directly from the eCRF and data 
management check if the score is correct. Table 8 point assignments for the 
CPS+EG score derivation is obsolete and therefore deleted. 
!
Section 4.2.7.3 – Expanded subgroup analyses methods.
!
Section 4.2.7.3 – pvalue for interaction to be assessed at 10% for purpose of 
hypothesis generation.
!
Section 4.2.7.4 – Added more detail on the global interactions
!
Section 4.2.9 – Expanded details on Fine and Gray models using SAS 9.4
!
Section 4.2.10 – Text on PRO consent included, included NRG updates to the PRO 
section
!
Section 4.2.11 – Specified LOQ is 0.0005 μg/mL
!
Section 4.2.13 – Summary of long term tolerability, analyses originally described 
for AESI are to be done for nausea, vomiting, anaemia, neutropenia, 
thrombocytopenia, and fatigue and asthenia
!
Section 4.2.16 – Central pathology result time point for analysis 
!
Section 4.2.13 – Summary of AESI > 30days included
!
Section 4.2.13 – Updated the Hy’s law section
!
Section 4.2.13– Deaths section revised
!
Section 4.2.14 – Modifications replaced with interruptions and reductions
!
Throughout – Updated text for inadvertent randomisation to be clear that they had 
no follow-up nor treatment
!
Section 4.2.9 – Males excluded from analyses of new primaries that they are not at 
risk for.
!
Section 6.1 – Defence of censoring at 0.5 days.
!
Appendix A – Event prediction (survival model) for protocol amendment (protocol 
version 5.)
!
Appendix D – Contains the GailSimon macro
!
Appendix E –  Included text on central pathology results  
!
Changed b.i.d to be bd throughout in line with AZ Olaparib studies
!
References added for GailSimon macro, R packages for non-proportional hazards 
and for Greenwoods formula.

OlympiA SAP – Summary of Changes from V1 to V2 
In line with the protocol edition 2 the number of subjects was increased, the resulted in updates to 
the following sections;  
x 
1.3 Number of subjects, 
x 
Table 4 Estimated Accrual Pattern 
x 
Added Table 5 Estimated Annual Hazard Rates 
x 
Added Section on Revised Accrual Pattern with Tables 10-20 
x 
1.2 Study design 
x 
4.2.3.1 Primary analysis 
x 
4.2.6.3 Sample size consideration for PRO endpoints 
x 
5. Interim analysis 
x 
Added Section 8 Appendix A 
Other changes not relating to the increase in sample size include; 
2.1 Added Definition of PK dataset 
3.1.4 Added incidence of new primary fallopian tube cancer and new primary peritoneal cancer 
4.2.1 Added section on Demographics and baseline characteristic data (moved from previous 4.2.8) 
Under 4.2.3 Primary Endpoint Invasive Disease Free Survival IDFS, added headers to existing text for: 
x 
4.2.3.2 Sensitivity Analyses 
x 
4.2.3.3 Subgroup Analyses 
x 
4.2.3.4 Analysis of Interactions 
4.2.5 Added Contralateral Invasive breast cancer, contralateral non-invasive breast cancer, new 
primary ovarian cancer, primary fallopian tube cancer and new primary peritoneal cancer 
4.2.7 Added Pharmacokinetic Analysis 
4.2.12 Added Imputation for missing/ partial dates 
Added Section 9 Appendix B 
Added Section 10 Appendix C 
 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
8
TABLE OF CONTENTS
PAGE
TITLE PAGE.......................................................................................................1
SIGNATURE OF STUDY STATISTICIAN........................................................2
SIGNATURE OF GLOBAL PRODUCT STATISTICIAN ..................................3
SIGNATURE OF GLOBAL PRODUCT STATISTICIAN ..................................4
SIGNATURE OF GLOBAL PRODUCT STATISTICIAN ..................................5
TABLE OF CONTENTS.....................................................................................8
1.
STUDY DETAILS.............................................................................................15
1.1
Study Objectives................................................................................................15
1.2
Study Design...................................................................................................... 16
1.3
Number of subjects ............................................................................................29
1.4
DCO Interim analysis......................................................................................... 30
2.
ANALYSIS SETS .............................................................................................30
2.1
Definition of analysis sets .................................................................................. 30
Full Analysis Set................................................................................................30
Safety Analysis Set ............................................................................................31
PRO analysis set ................................................................................................31
PK analysis set...................................................................................................31
2.2
Violations and deviations ................................................................................... 32
3.
PRIMARY AND SECONDARY VARIABLES.................................................34
3.1
Outcome variables ............................................................................................. 34
3.1.1
Invasive Disease Free Survival........................................................................... 34
3.1.2
Overall Survival.................................................................................................36
3.1.3
Distant disease free survival (DDFS)..................................................................36
3.1.4
Incidence of contralateral invasive breast cancer, contralateral non-
invasive breast cancer, new primary ovarian cancer, new primary fallopian 
tube cancer and new primary peritoneal cancer ..................................................38
3.2
Patient reported outcome variables..................................................................... 39
3.2.1
FACIT-Fatigue ..................................................................................................39
3.2.2
EORTC QLQ-C30 ............................................................................................. 39
3.3
Safety................................................................................................................. 40
3.3.1
Adverse events...................................................................................................40
3.3.1.1
Olaparib adverse events of special interest (AESI) .............................................42

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
9
3.3.2
Treatment exposure............................................................................................42
3.3.3
Dose intensity ....................................................................................................44
3.3.4
Laboratory data.................................................................................................. 44
3.3.5
ECGs .................................................................................................................45
3.3.6
Vital signs.......................................................................................................... 45
3.3.7
General consideration for safety assessments .....................................................45
3.3.8
PK variables.......................................................................................................46
3.4
Resource use...................................................................................................... 47
4.
ANALYSIS METHODS....................................................................................47
4.1
General principles.............................................................................................. 48
4.2
Analysis methods...............................................................................................48
4.2.1
Confidence intervals at the interim analysis........................................................49
4.2.2
Median clinical follow-up ..................................................................................49
4.2.3
Kaplan-Meier estimates of IDFS ........................................................................ 49
4.2.4
Percentages of invasive disease free subjects at yearly intervals .........................49
4.2.5
Demographic and baseline characteristics data...................................................51
4.2.6
Multiplicity........................................................................................................ 52
4.2.7
Primary endpoint - Invasive Disease-Free Survival (IDFS) ................................53
4.2.7.1
Primary Analysis................................................................................................53
4.2.7.2
Sensitivity Analyses for IDFS............................................................................55
4.2.7.3
Subgroup analyses .............................................................................................57
4.2.7.4
Analysis of interactions......................................................................................62
4.2.8
Overall survival (OS) and Distant disease free survival (DDFS).........................63
4.2.9
Contralateral invasive breast cancer, contralateral non-invasive breast 
cancer, new primary ovarian cancer, primary fallopian tube cancer and 
new primary peritoneal cancer............................................................................64
4.2.10
Analysis of patient reported outcomes................................................................65
4.2.10.1
Hypotheses and objectives ................................................................................. 65
4.2.10.2
Administration of patient-completed questionnaire.............................................67
4.2.10.3
Statistical considerations for patient reported outcomes......................................67
4.2.11
Pharmacokinetic analysis ...................................................................................70
4.2.11.1
PK level deviations ............................................................................................71
4.2.12
Exploratory analyses..........................................................................................71
4.2.13
Safety.................................................................................................................73
4.2.14
Treatment exposure............................................................................................77
4.2.15
Imputation for Missing/Partial Dates..................................................................78
4.2.16
Central pathology result timepoint for analysis................................................... 80
5.
INTERIM ANALYSES .....................................................................................80
6.
CHANGES OF ANALYSIS FROM PROTOCOL .............................................84
6.1
Censoring of patients not at risk for disease evaluated........................................84
7.
REFERENCES ..................................................................................................86

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
10
8.
APPENDIX A....................................................................................................89
9.
APPENDIX B....................................................................................................90
10.
APPENDIX C....................................................................................................91
11.
APPENDIX D....................................................................................................92
12.
APPENDIX E....................................................................................................94
12.1
Purpose..............................................................................................................94
12.2
Derivation of Central pathology results from the data provided by IEO.............. 94
12.3
Identification of Patient’s central pathology result..............................................95
12.3.1
Considerations ...................................................................................................95
12.3.2
Identifying the central pathology result ..............................................................96
LIST OF TABLES
Table 1
Study Schedule - Screening (PART 1 and PART 2) ..............................20
Table 2
Study Schedule – On treatment (Year 1)................................................23
Table 3
Study Schedule - Follow-up Visits (Year 2 onwards) ............................27
Table 4
Actual accrual between June 2014 and February 2018...........................29
Table 5
Summary of Outcome Variables and Analysis Populations....................31
Table 6
Search strategy to identify AESI...........................................................42
Table 7
Formal Statistical Analyses to be Conducted.........................................50
Table 8
AEs for summary of long term tolerability ............................................75
Table 9
Imputation for missing or partial dates ..................................................78
Table 10
Summary of 2-sided significance levels and total alpha spend 
across the endpoints and analyses..........................................................83
Table 11
Example of patient who permanently discontinued during a dose 
interruption, documented on eCRF page “Administration of 
Olaparib/Placebo”.................................................................................90
Table 12
IEO data HR status (ER & PgR) and HER2 results (See DTS) ..............94
Table 13
Derivations for classifications of HR status and HER2 results for 
CSR ......................................................................................................95

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
11
LIST OF FIGURES
Figure 1
Study Flow Chart ..................................................................................19
Figure 2
Screening Plan ......................................................................................20
Figure 3
Multiple Testing Procedure...................................................................53
Figure 4
Examples of dose intensity for olaparib/placebo dosing.........................91

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
12
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
The following abbreviations and special terms are used in this study Statistical Analysis Plan.
Abbreviation or 
special term
Explanation
AE
Adverse event
AESI
Adverse event of special interest
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AML
Acute Myeloid Leukaemia
AST
Aspartate aminotransferase
bd.
Twice daily
BIG
Breast International Group
BP
Blood pressure
BRCA
Breast cancer susceptibility gene
CI
Confidence Interval
CNS
Central nervous system
CPS+EG
Clinical stage (CS), estrogen receptor status (E), nuclear grade (G), and post-
treatment pathologic stage (PS)- a disease scoring system
CRF (eCRF)
Case Report Form (electronic/paper)
CSP
Clinical Study Protocol
CSR
Clinical Study Report
CT
Computerised Tomography
CTCAE
Common Terminology Criteria for Adverse Event
CTEP
Cancer Therapy Evaluation Program
DBP
Diastolic blood pressure
DCO
Data cut off
DDFS
Distant Disease-Free Survival
DNA
Deoxyribonucleic acid 
ECG
Electrocardiogram
ECOG performance 
status
Eastern Cooperative Oncology Group: a performance status using scales and 
criteria to assess how a patient’s disease is progressing
eCRF
Electronic case report form

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
13
Abbreviation or 
special term
Explanation
EORTC QLQ-C30
The European Organisation for Research and Treatment of Cancer -Quality of 
Life Questionnaire-Core questions 30
ER
Estrogen receptor
FACIT-Fatigue
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue 
Measurement System
FAS
Full Analysis Set
FFPE
Formalin Fixed Paraffin Embedded
FDA
Food and Drug Administration
gBRCA mutation or 
gBRCAm
The term "gBRCA mutation" is used to refer to a germline BRCA1 or BRCA2 
mutation classified as "deleterious" or "suspected deleterious" in accordance 
with the American College of Medical Genetics and Genomics 
recommendations for standards for interpretation and reporting of sequence 
variants
GCP
Good clinical practice
HER2
Human Epidermal Growth Factor Receptor 2
HR
Hazard Ratio
HRQoL
Health Related Quality of Life
ID
Identifier
IDFS
Invasive Disease-Free Survival
IDMC
Independent Data Monitoring Committee
IIBTR
Ipsilateral invasive breast tumour recurrence
IPD
Important protocol deviation
IQR
Inter-quartile range
ITT
Intention To Treat
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
KM
Kaplan-Meier
MDS
Myelodysplastic Syndrome
MMRM
Mixed Model for Repeated Measures
MRI
Magnetic Resonance Image
MTP
Multiple Testing Procedure
NSABP
National Surgical Adjuvant Breast and Bowel Project 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
14
Abbreviation or 
special term
Explanation
NONMEM
NON-linear Mixed Effects Modelling 
OS
Overall Survival
PARP
Polyadenosine 5’diphosphoribase [poly (ADP ribose)] polymerisation
pCR
Pathologic Complete Response
PGx
Pharmacogenetic research
PMG
Precision Medicin and Genomics
PID
Percentage Intended Dose
PK
Pharmacokinetics
PRO
Patient Reported Outcome
PgR
Progesterone receptor
QOL
Quality of Life
RDI
Relative Dose Intensity
REML
Restricted Maximum Likelihood
RPSFT
Rank Preserving Structural Failure Time
SAE
Serious adverse event (see definition in CSP Section 6.4.2).
SBP
Systolic blood pressure
SD
Standard Deviation
STEEP
Standardised Terms for Efficacy Endpoints
Study treatment
Study treatment is the treatment to which patient was randomised. In this study 
it is either olaparib or placebo
TNBC
Triple negative breast cancer
ULN
Upper Limit of Normal

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
15
1.
STUDY DETAILS
1.1
Study Objectives
Primary:
The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive 
Disease Free Survival (IDFS).
Secondary:
The secondary objectives of this study are:
1
To assess the effect of adjuvant treatment with olaparib on Overall Survival (OS).
2
To assess the effect of adjuvant treatment with olaparib on Distant Disease Free Survival 
(DDFS).
3
To assess the effect of adjuvant treatment with olaparib on the incidence of new primary 
contralateral breast cancers (invasive and non-invasive), new primary ovarian cancer, new 
primary fallopian tube cancer and new primary peritoneal cancer.
4
To assess the effect of olaparib on the patient reported outcomes using the FACIT-
Fatigue and EORTC QLQ-C30 questionnaires.
5
To assess the efficacy of olaparib in patients identified as having a deleterious or 
suspected deleterious variant in either of the BRCA genes using variants identified with 
current and future germline BRCA mutation assays (gene sequencing and large 
rearrangement analysis).
6
To determine the exposure to olaparib (in plasma) in patients receiving olaparib as 
adjuvant therapy as part of the PK analysis.
Safety:
To assess the safety and tolerability of adjuvant treatment with olaparib
 
 
 
 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
17
positive/HER2 negative versus TNBC), by prior neoadjuvant versus adjuvant chemotherapy, 
and prior platinum use for breast cancer (yes versus no).
Patients will be randomised to one of the following treatments:
!
12 months treatment with olaparib tablets p.o. 300 mg twice-daily (two 150 mg tablets in 
the morning and two 150 mg tablets in the evening)
!
12 months treatment with matching placebo tablets p.o. twice daily (two tablets in the 
morning and two tablets in the evening)
Randomised patients will receive study treatment for up to a maximum of 12 months. All 
patients will have safety assessments every 2 weeks during the first month, every 4 weeks for 
the following 5 months (up to week 24) and 3 monthly for the remaining 6 months of study 
treatment, plus 30 days after its discontinuation. 
All randomised patients will have clinical assessment visits for approximately 10 years 
following their randomisation into the study, or until an IDFS endpoint due to a breast cancer 
related distant relapse, whichever comes first. Efficacy assessments (medical history and 
physical examination) will be performed on a 3 monthly basis during the first 2 years 
following end of study treatment, followed by 6 monthly assessments for years 3, 4 and 5 and 
annually thereafter. All patients will have a mammogram and/or breast MRI annually for 
approximately 10 years beginning 6 months (24 weeks) after day 1. They then enter the 
survival follow-up phase of the trial, which will continue until 10 years after the last patient is 
randomised. No clinic visits will be required during the survival follow-up phase; information 
may be collected via telephone, medical records and death registries.
This is a collaborative study being coordinated worldwide by the Breast International Group 
(BIG) in partnership with Frontier Science (FS), NRG Oncology (NCI supported National 
Clinical Trials Network Group), AstraZeneca (AZ) and Merck & Co (Merck). Two versions 
of the protocol have been written to cover this global adjuvant breast cancer study. One 
protocol version covers all patients recruited outside of the US (where AZ is the sponsor) and 
one protocol version covers patients recruited within the US (where NRG Oncology is the 
sponsor). The two versions of the protocol are identical in terms of study objectives and 
scientific content and only differ in logistical content appropriate for the country(ies) they 
cover (i.e. drug distribution, mechanisms for SAE reporting during the study, etc.). It is 
expected that approximately 230 patients will be randomised under the US protocol and 
approximately 1570 patients will be randomised under the non-US protocol.
The study will be conducted in approximately 25 countries worldwide. Approximately 700
centres (in the US and rest of the world countries) will be initiated to randomise the total 1800
patients. Additional countries and sites may be added dependent on recruitment rates.
The trial will use one randomisation system and report as one single study. The initial 
collection of the patients’ data will be done using two databases (one for the US patients and 
one for all other patients outside of the US). The two databases will be set up using the same 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
18
standards and eCRFs to ensure consistency in the data collection. The data from both 
databases will be combined into a single consolidated database at regular, pre-specified 
intervals. All study endpoints as well as reports for periodic review by the Independent Data 
Monitoring Committee (IDMC) will be analysed and reported from the single combined 
reporting database, held by Frontier Science on behalf of BIG.
Approximately, 150 randomised patients will be analysed for pharmacokinetic (PK) at those 
sites that have confirmed that they are able to collect the PK assessment samples. PK 
sampling will be performed in a subset of patients who sign an optional PK Informed consent.
The study flow chart is shown in Figure 1 and the screening plan in Figure 2. Screening 
schedules are detailed in Table 1 and the study schedule is detailed in Table 2 and Table 3
below.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
19
Figure 1
Study Flow Chart
Neoadjuvant chemotherapy
Minimum 6 cycles (containing anthracyclines, 
taxanes or the combination of both)
Surgery
HER2-For TNBC: Axillary node positive 
(≥pN1, any tumour size) If axillary node 
negative (pN0): (T > 2cm (≥pT2)m)
For ER+ and/or PgR+, HER2¯: ≥ 4 positive 
lymph nodes    
Surgery
Adjuvant Chemotherapy
Minimum 6 cycles (containing anthracyclines, 
taxanes or the combination of both)
Radiotherapy/additional surgery as required
Path CR
For TNBC: Non-Path CR      
For ER+ and/or PgR+
HER2-: Non-Path CR AND 
CPS+EG score ≥3            
Randomisation
(within ideally within 8 weeks after last treatment (surgery, chemotherapy or radiotherapy) but in no 
case longer than 12 weeks)
Olaparib 300 mg orally twice daily, continuous for 12 months
OR
Placebo orally twice daily, continuous for 12 months
Follow-up for local and distant recurrence and survival status
Patients will continue to be followed clinically on a 3 monthly basis during the first 2 years, followed 
by 6 monthly assessments for the 3rd, 4th and 5th year, and annually thereafter
Yearly breast imaging (mammogram and/or /MRI) for 10 years*
*The study will end 10 years after the last patient has been randomised
Mammogram/ and/or breast MRI 6 months from randomisation day 1
Adjuvant radiotherapy as 
required
ICF for patients with unknown BRCA status to undergo central BRCA testing during, or prior to, 
neoadjuvant/adjuvant chemotherapy
Informed consent for participation in the study for patients with known gBRCA mutation  
status
Not eligible

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
20
Figure 2
Screening Plan
Screening PART 1– Patients with Unknown gBRCA Mutation Status:
!
Only those patients who do not know their gBRCA mutation status prior to entry in to the study 
These patients will undergo screening assessments as described for PART 1 in Table 1. Screening PART 1 is 
conducted to determine if the patient is considered eligible to undergo the BRCA status blood test. Once PART
1 has been successfully completed and patients have had a BRCA test, these patients will continue to PART 2 and 
have all procedures performed as described for PART 2 (see Table 1)
Screening – PART 2 – ALL Patients (Patients with Known gBRCA Mutation Status):
!
Those patients who already know their gBRCA mutation status and have a deleterious or suspected 
deleterious mutation to undergo screening assessments as described for PART 2 (see Table 1)
!
Those patients originally with unknown gBRCA status who have completed screening PART 1 and 
now have a confirmed deleterious or suspected deleterious mutation should undergo screening 
assessments as described for PART 2 (see Table 1)
Table 1
Study Schedule - Screening (PART 1 and PART 2) 
Day
Any time prior, during or 
after neoadjuvant/adjuvant
chemotherapy or 
radiotherapy
PART 1 a
(ONLY Patients requiring 
a gBRCA status Myriad 
test before randomisation)
-28 to 0 days
PART 2
(Patients with confirmed 
gBRCA status by 
 or 
if BRCA status is known 
prior to study entry j)
Informed consent
X bc
X j
Demographics (date of birth)
X
X
Medical and surgical history d
X
Prior cancer therapies including 
radiotherapy
X
Inclusion/exclusion criteria
X (all ** criteria)
X
ECOG Performance Status
X
Physical examination
X
Vital signs
X
ECG f
X g

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
21
Table 1
Study Schedule - Screening (PART 1 and PART 2) 
Day
Any time prior, during or 
after neoadjuvant/adjuvant
chemotherapy or 
radiotherapy
PART 1 a
(ONLY Patients requiring 
a gBRCA status
 
test before randomisation)
-28 to 0 days
PART 2
(Patients with confirmed 
gBRCA status by 
 or 
if BRCA status is known 
prior to study entry j)
Haematology / clinical 
chemistry/Coagulation o
X
Urinalysis h
X
Pregnancy test i
X
EORTC QLQ-C30 n
X
FACIT-Fatigue n
X
Blood sample for determination of 
BRCA status via 
X
X e
Blood sample for assessment of 
current and future BRCA mutation 
assay(s) c
X
X e
Concomitant medications
X
Archival tumour sample (FFPE) 
(mandatory if available) k
X
Surgical tumour sample (FFPE)
(post neoadjuvant chemotherapy 
(mandatory)) k
X
Radiological assessment to exclude 
metastatic breast cancer (where 
applicable) l
X
Family history of cancer
X
Serious Adverse Events m
X (only SAEs due to study 
procedures)
X (SAEs only)
a
The time period is to allow those patients that require a 
 gBRCA sample to have the test taken and 
the results returned prior to randomisation.
b
It is recommended that patients that require the 
 gBRCA sample testing are to be consented for 
BRCA testing and participation in the trial prior or during neoadjuvant/adjuvant chemotherapy prior to 
entering the study.
c
Any patient who consents to study related 
 gBRCA status testing, must also have a blood sample 
taken at the same time for the purpose of developing and validating a future mutation assay.
d
Include history of blood transfusion within previous 120 days from start of study treatment and the reasons 
e.g. bleeding. Additionally CPS+EG score components should be collected (Clinical stage (CS), estrogen 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
22
receptor status (E), nuclear grade (G), and post-treatment pathologic stage (PS)) for the non-pCR patients 
who received prior neoadjuvant chemotherapy. Instructions on how to calculate the CPS+EG score 
(Mittendorf et al 2011; Jeruss et al 2008) are provided in Appendix J of protocol edition 2.
e
Samples to be taken in screening PART 2 only for patients with known gBRCA mutation who have not 
completed PART 1.
f
ECG recordings should be performed once the patient has been in the supine position for at least 5 minutes.
g
ECG assessments to be completed within 28 days before randomisation.
h
Urinalysis (dipstick) should be performed at screening. After screening, urinalysis will only be required if 
clinically indicated.
i
Women who are not postmenopausal or have not undergone hysterectomy must have a negative urine or 
serum pregnancy test within 28 days prior to randomisation and a confirmatory test on Day 1 before starting 
study treatment. In the event of suspected pregnancy during the study, the test should be repeated and, if 
positive, the patient discontinued from study treatment immediately.  
j
Patients for whom their gBRCA status is already known, should be consented to the study within 28 days 
prior to randomisation.
k
Mandatory for all randomised patients, i.e. for adjuvant patients this refers to the surgical specimen; for 
neoadjuvant patients, both the pre-treatment core biopsy and the surgical specimen with residual disease are 
requested but only one is mandatory. If the surgery tumour blocks are available, but cannot be submitted, 
sites may submit a portion of invasive tumour from the original block, either by taking at least one core of 
at least 3mm in diameter, or by splitting the original block in two parts, and re-embedding one in a new 
block for central submission. If blocks containing pre-neoadjuvant treatment core biopsies are available but 
cannot be submitted, sections mounted on glass slides prepared from the block can be provided. If tumour 
sample can’t be provided as requested above or if it’s not available, approval by Study Team for patient’s 
entry into the trial is required. Sample will only be sent to the study bio-repository once the patient has been 
randomised.
l
Patients considered at high risk of having disseminated disease (i.e. those with locally advanced 
disease, clinical N2-3 or pathological N1-3 with the exception of pN1a in adjuvant patients are expected to 
have a CT/MRI scan of the Thorax/Abdomen/Pelvis or any other area as clinically indicated and a bone 
scan at any point between diagnosis of the current breast cancer and randomisation to rule out metastatic 
breast cancer. (Note: PET/CT scan may be used as an alternative imaging technique and precludes the need 
for bone scan). If a patient does not have a mammogram or breast MRI within 12 months prior to screening 
part 1, then this assessment must be repeated prior to randomisation. Breast imaging should be performed 
on any remaining breast tissue.
To rule out metastatic breast cancer, patients with screening ALT/AST or ALP above institutional upper 
limit of normal should have liver ultrasound, CT or MRI at any time point between diagnosis of current 
breast cancer and randomisation. Screening bone scan is required if ALP and/or corrected calcium level are 
above the institutional upper limit. (Note: PET/CT scan may be used as an alternative imaging technique).
m
Serious adverse events must be captured from time of consent. In Screening PART 1 of the study only 
SAEs related to study procedure will be collected. In Screening PART 2 all SAEs will be collected.
n
EORTC QLQ-C30 + FACIT-Fatigue will be collected prior to randomisation once eligibility is confirmed.
o      Coagulation analysis only required at baseline.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
23
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 months 
(14 weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 days 
after last dose of 
study medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Serum or urine pregnancy 
test for women of 
childbearing potential prior 
to 1st dose of study 
treatment
X a
X
X
X
X
ECOG performance status 
X b
Vital signs 
X b
X
X (weeks 12 and 
24 only)
X
X
X
Haematology / clinical 
chemistry c
X b,c
X
X
X
X
X
X
Recurrent/new cancers 
assessment (includes 
physical exam d, clinical 
signs and symptoms) 
X
X (weeks 12 and 
24 only)
X
X
X
Mammogram and/or breast 
MRI (MRI preferred for 
patients younger than 50 
yrs) e
X (week 24 
only)
Adverse Events
X
X
X
X
X
X
X

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
24
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 months 
(14 weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 days 
after last dose of 
study medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Concomitant medications 
including blood 
transfusions
X
X
X
X
X
X
X
Demographics j
X
EORTC QLQ-C30 
X (week 24 
only)
X (week 52 only)
FACIT-Fatigue 
X (week 24 
only)
X (week 52 only)
Biomarker Blood 2 
samples (mandatory)
Xi
X
PGx Blood sample 
(optional)
X
Blood sample for PK 
analysis (optional; after 
signing PK Informed 
consent) (subset of 
patients) h
X
Blood biomarker samples 
at disease recurrence 
(Mandatory)
X
X
X
X
X
X
X

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
25
Table 2
Study Schedule – On treatment (Year 1)
Visit Number
2
3
4
5-9
(Every 4 
weeks)
10-11
(Every 3 months 
(14 weeks))
Premature study 
treatment 
discontinuation g
Follow-up 30 days 
after last dose of 
study medication (all 
patients)
Week
0
2
4
8, 12, 16, 20, 24
38, 52
Day
1
15
29
Visit Window
±3d
±3d
±1 week
±2 week
+2 week
+2 week
Tumour sample at disease 
recurrence (Optional) k
X
X
X
X
X
X
X
Olaparib 
dispensed/returned f
X
X
X
X
X
a
Women who are not postmenopausal or have not undergone hysterectomy must have a negative urine or serum pregnancy test prior to first dose of study 
treatment on Day 1.
b
If assessed within 7 days before randomisation, it does not need to be repeated on Day 1 of study treatment unless investigator believes that it is likely to 
have changed significantly.
c
Safety blood samples do not need to be repeated on Day 1 of study treatment if they have been assessed within 7 days before randomisation and which 
must have been done at least  3 weeks after the last dose of chemotherapy, unless the investigator believes that they are likely to have changed 
significantly.  Safety blood samples are to be collected every 2 weeks during the first 4 weeks, then every 4 weeks until week 24 and then at weeks 38 
and 52 of study treatment.
d
Physical examination both local and general should be performed at day 1 and then at weeks 12, 24 and 38 and 52 post randomisation until study 
treatment is discontinued (data is not required to be captured on an eCRF, however any significant changes from baseline must be reported as an AE).
e
Mammogram and/or breast MRI (MRI is preferred for patients younger than 50 years) to be performed at week 24 (6 months). Breast imaging should be 
performed on any remaining breast tissue.
f
Sufficient study treatment should be dispensed for at least each treatment period plus overage, however additional treatment can be dispensed to patients 
to last longer in accordance with local practice.
g
If a patient discontinues prior to completing 52 weeks of study treatment, the patient should have the study treatment discontinuation visit performed 
followed by the 30 day follow-up visit and site staff completes relevant CRF pages as required. In case of premature treatment discontinuation only the 
visits where efficacy assessments are scheduled should be performed i.e. week 12, 24, 38, 52 (as applicable) in Year 1 and all visits in Year 2 onwards. 
Collection of vital signs, AEs, haematology/clinical chemistry results and concomitant medications is no longer required. Information on endocrine 
therapies should be collected and recorded in the clinical database until IDFS endpoint is met due to breast cancer related distant relapse. The date of 
discontinuation, the reasons, and details of the following specific cancer therapies (first line treatment for first breast cancer recurrence and any 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
26
subsequent regimens containing PARP inhibitors or platinum received by the patient at any time) should also be recorded on the eCRF. In case the IDFS 
endpoint is met due to breast cancer related distant relapse, the patient enters the survival follow-up phase and is assessed annually from the date of 
distant relapse and until 10 years after the last patient is randomised. In the IDFS endpoint is met due to other events, the patient will continue the study 
schedule until a breast cancer related distant relapse occurs or approximately 10 years following their randomisation into the study, whichever occurs 
first. They will then enter the survival follow-up phase of the trial. During the annual survival follow-up phase, in addition to vital status, the following 
information will be collected (if available): specific cancer therapies (only first line treatment for first breast cancer recurrence and any subsequent 
regimens containing PARP inhibitors or platinum received by the patient at any time), sites of metastases and any other new cancers. If a recurrent/new 
cancer assessment is scheduled within 4 weeks of the study treatment discontinuation visit it can be performed at the 30-day follow-up visit.
h       PK sampling (optional) to be performed in a subset of patients. Sampling times: pre-dose (before morning dose) plus one sample in each of the 
following sampling windows: 0 to 0.5 h post dose, 0.5 to 1.5 h post dose, 3 to 6 h post dose and 6 to 12 h post dose (before evening dose).
i
Blood samples (plasma and serum) for biomarker analysis should be collected on Day 1 prior to first dose of study treatment.
j
Race and ethnicity data to be collected unless not allowed by local regulations.
k
The provision of tumour tissue is encouraged only if clinically appropriate and not considered detrimental to patient care and patient signed the 
appropriate consent form.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
27
Table 3
Study Schedule - Follow-up Visits (Year 2 onwards)
Visit Number
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Survival 
Follow-up  
(Every 12 
months)
Year
2
3
4
5
6
7
8
9
10
11+
Month
15
18
21
24
30
36
42
48
54
60
66
78
90
102
114
126, 138, 
etc.
Visit Window
±1month
±2months
±3months
±3months
Recurrent/new cancers 
assessment (includes physical 
exam, clinical signs and 
symptoms)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Mammogram and/or breast 
MRI (MRI preferred for 
patients younger than 50 yrs) a
X
X
X
X
X
X
X
X
X
Subsequent cancer therapy b
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xd
Overall survival assessment
Xd
EORTC QLQ-C30 
X
X
FACIT-Fatigue 
X
X
Blood biomarker samples at 
disease recurrence 
(Mandatory)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tumour sample at disease 
recurrence (Optional) c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 27 May 2019
28
Visit Number
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Survival 
Follow-up  
(Every 12 
months)
Year
2
3
4
5
6
7
8
9
10
11+
Month
15
18
21
24
30
36
42
48
54
60
66
78
90
102
114
126, 138, 
etc.
Visit Window
±1month
±2months
±3months
±3months
SAEe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Mammogram and/or breast MRI (MRI is preferred for patients younger than 50 years) to be performed every 12 months after the 6 months (24 weeks) 
scan, unless indicated otherwise. Breast imaging should be performed on any remaining intact breast.
b
First line treatment for first breast cancer recurrence and any subsequent regimens containing PARP inhibitors or platinum received by the patient at any 
time need to be recorded. Information on endocrine therapies should be collected and recorded in the clinical database until IDFS endpoint is met due to 
breast cancer related distant relapse.
c
The provision of tumour tissue is encouraged only if clinically appropriate and not considered detrimental to patient care and patient signed the 
appropriate consent form.
d
During the survival follow-up phase, information (where available) on further subsequent cancer therapies (see footnote b), sites of metastases and any 
other new cancers will be collected in addition to vital status.
e      After study treatment completion (i.e. after any scheduled post treatment follow-up period has ended) there is no obligation to actively report 
information on new AEs or SAEs occurring to study patients. This includes new AEs/SAEs in patients still being followed up for survival but who have 
completed the post treatment follow-up period (30 days). If an investigator learns of any SAEs, including death, at any time after a patient has completed 
the 30 days post treatment follow-up period, and he/she considers there is a reasonable possibility that the event is causally related to the study treatment, 
the investigator should report it according to SAE reporting procedures for this study. Any cases of MDS/AML or new primary malignancies occurring 
after the 30 day follow-up period should be reported as an SAE. Non-melanoma skin cancers need to be reported as a non-serious AE unless at least one 
of the seriousness criteria is met which then requires to be reported as an SAE, see section 6.4.2 of the protocol edition 2. Any of these type of serious or 
non-serious events need to be reported to AstraZeneca Patient Safety according to SAE reporting procedures for this study, regardless of investigator’s 
assessment of causality or knowledge of the treatment arm. If a patient develops MDS/AML full diagnostic details and classification should be provided 
e.g. bone marrow and cytogenetic analysis reports, see Sections 5.5.6.3 and 6.4.5.5 of protocol edition 2. A questionnaire will be sent to any 
investigators reporting MDS/AML or new primary malignancies as an aid to provide detailed information on the case.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
1.3
Number of subjects
The primary endpoint of the study is invasive disease free survival (IDFS) and patients will be 
randomised 1:1 to either olaparib 300 mg bd or matching placebo. 
Approximately, 1800 patients will be randomised into the study. If the true hazard ratio (HR) 
for the comparison of olaparib versus placebo (in terms of IDFS) is 0.7, then with 330 events 
the analysis of IDFS will have 90% power to demonstrate a statistically significant difference, 
assuming a 2-sided 5% significance level.
The primary analysis will be triggered by 330 IDFS events (required for overall 90% power to 
detect a HR at 0.7). The critical HR value at the primary analysis is 0.805.
The actual accrual pattern between June 2014 and February 2018 is shown in Table 4. It is 
estimated that 1800 patients will be randomised by April/May 2019, hence the study will take 
approximately 5 years to complete recruitment. (Around 230 patients in US and 
approximately 1570 patients in the Rest of World (RoW) countries).
Table 4
Actual accrual between June 2014 and February 2018
Interval since start of 
randomisation
(months)
Number of patients 
randomised in 
interval *
Cumulative 
number of 
patients 
randomised
Average number of
patients randomised 
per month in interval
0 - 6
21
21
3.5
6 - 12
94
115
15.7
12 - 18
174
289
29.0
18 - 24
180
469
33.0
24 - 30
229
698
38.2
30 - 36
249
947
41.5
36 - 42
234
1181
39.0
42 - 45*
118
1299
39.3
* Note: 3-month interval: Dec 2017 to Feb 2018 inclusive
The primary analysis population will include all patients randomised (ITT). Subgroup 
analyses based on prior chemotherapy (adjuvant or neoadjuvant), prior platinum therapy (yes 
or no), and hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC)
will be conducted to check for consistency in the treatment effect, whereby this analysis is 
considered supportive of the primary analysis in the overall population. Stratification factor 
values according to eCRFs will be used to define subgroups for the subgroup analyses.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
30
During the trial, the Steering Committee will monitor the recruited patient population and 
actual event rate whilst remaining blinded to treatment allocation. If the data indicates that the 
original sample size assumptions are incorrect, such that achieving the required number of 
events with the current number of patients is not feasible, then in consultation with the IDMC 
a decision may be made to increase recruitment of patients into the trial to achieve the 
required 330 events.
An interim analysis for superiority will be triggered once 165 IDFS events have been 
observed in the first 900 patients recruited (see Section 5 for details). It is estimated that this 
analysis will occur approximately 5.4 years after the first patient is randomised.
1.4
DCO Interim analysis
The data cut-off (DCO) for the interim analysis is defined as the date that the 165th event 
confirmed by clinical exams, from the first 900 randomised patients, is reported in the 
database. Due to the reporting lag, this date will be later than the date when the 165th event is 
observed and confirmed in the clinic.
A programmatic data-cut will be applied to the OlympiA clinical database prior to the Interim 
and Final Analyses as defined in OlympiA_datacut_specification.docx .
2.
ANALYSIS SETS
2.1
Definition of analysis sets
Only patients that signed the main informed consent form will be analysed, the analysis sets 
are defined as follows:
Full Analysis Set
Intention to treat (ITT): The primary statistical analysis of the efficacy of olaparib will include 
all randomised patients and will compare the treatment groups based on randomised treatment, 
regardless of the treatment actually received. Patients who were randomised but did not 
subsequently go on to receive study treatment are included in the Full Analysis Set (FAS). 
For the interim analysis (see Section 5) two efficacy populations will be defined:
1
ITT population: This will include all randomised patients and will compare the treatment 
groups based on randomised treatment, regardless of the treatment actually received.
Note: it is anticipated that all patients will be randomised by the time of the interim 
analysis.
2
Mature cohort ITT population: This will include the first 900 randomised patients only 
and will compare the treatment groups based on randomised treatment, regardless of the 
treatment actually received. This analysis will be regarded as supportive, to aid 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
31
interpretation of the result in the ITT population based on interim data. Statistical 
significance is not required for the mature cohort population.
Safety Analysis Set 
All safety data will be summarised by actual treatment received. All patients who received at 
least one dose of randomised study treatment, olaparib or placebo, will be included in the 
Safety Analysis Set. If a patient receives at least one dose of olaparib he/she will be included 
in the olaparib arm for safety summaries (e.g. olaparib arm will include patients randomised to 
olaparib who receive at least one dose of olaparib or placebo patients who receive at least one 
dose of olaparib in error at any time). If a patient randomised to olaparib receives only placebo 
treatment then he/she will be summarised as part of the placebo arm.
PRO analysis set 
This population will comprise patients who consent to participate in the PRO assessment 
portion of the study, who start treatment and who provide evaluable baseline FACIT-Fatigue
or EORTC QLQ-C30 data, where evaluable means that at least one sub-scale baseline score 
can be determined. Baseline is defined as the last result on or before the first day of study 
drug. For patients who are randomised but not treated, baseline will not be derived and they 
will be excluded from the PRO analysis set. Two sub-populations will be analysed dependent 
on whether they have evaluable baseline for the questionnaire being analysed. The PRO 
analysis will be summarised by planned treatment group. 
PK analysis set 
Approximately 150 patients randomised to olaparib/placebo will provide pharmacokinetic 
(PK) samples at those sites that have confirmed that they are able to collect the PK assessment 
samples. Placebo samples will not be analysed unless specified. PK sampling will be 
performed in a subset of patients who sign an optional PK informed consent. 
The PK analysis set will comprise of patients who signed the optional PK informed consent 
form, were randomised to the olaparib arm, received at least one dose of study treatment, had 
at least one PK sample collected and did not violate or deviate from the protocol in ways that 
would significantly affect the PK analyses. The population will be defined by the Study Team 
Physician, Pharmacokineticist and Statistician prior to any analyses being performed and 
whilst blinded to treatment allocation. 
Table 5
Summary of Outcome Variables and Analysis Populations
Outcome Variable
Analysis set
Efficacy data Interim
IDFS 
IDFS, OS, DDFS, incidence of contralateral breast cancer, 
new primary ovarian cancer, new primary fallopian tube 
cancer and new primary peritoneal cancer and 
symptom/HRQoL endpoints
FAS (ITT), Mature cohort (ITT)
FAS (ITT)

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
32
Table 5
Summary of Outcome Variables and Analysis Populations
Outcome Variable
Analysis set
Efficacy data Final
IDFS, OS, DDFS, incidence of contralateral breast cancer, 
new primary ovarian cancer, new primary fallopian tube 
cancer and new primary peritoneal cancer and 
symptom/HRQoL endpoints
FAS (ITT)
Demography
FAS (ITT)
PRO data
PRO
Pharmacokinetics data
PK
Safety data
Exposure
Safety
Adverse Events
Safety
Lab measurements
Safety
Vital Signs
Safety
2.2
Violations and deviations
The important protocol deviations will be listed and summarised by randomised treatment 
group for the FAS. None of the deviations will lead to any patients being excluded from any 
of the primary analysis sets described in Section 2.1.  
A per-protocol analysis is not planned, however a ‘deviation bias’ sensitivity analysis will be 
performed if the following criteria are met. Patients with important protocol deviations (IPDs)
that may affect the efficacy of the trial therapy (as listed below) will be excluded if >10% of 
the randomised patients: 
-
Did not have the intended disease or indication or
-
Did not receive any randomised therapy
The trigger for a sensitivity analysis will be determined following review of the protocol 
deviations ahead of database lock or data freeze for the interim analysis and final analysis.  
This will be documented prior to the analysis being conducted.  
The following general categories will be considered as IPDs and be summarised and discussed 
in the CSR. Further detailed criteria are described in a separate Important Protocol Deviations 
Specification V6.0. 
IPDs that may affect efficacy

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
33
!
Not fulfilling criteria for high risk disease
!
No histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
!
No documented germline mutation in BRCA1 or BRCA2
!
Inadequate breast surgery and/or radiotherapy
!
Inadequate axilla surgery
!
Completed less than 6 cycles of neoadjuvant or adjuvant chemotherapy containing 
anthracyclines, taxanes or the combination of both
!
Peri-operative chemotherapy, (patients who had both neoadjuvant and adjuvant therapy; 
'unquantifiable risk of disease relapse')
!
Evidence of metastatic disease (to include only those patients who had suspicion or 
confirmation of recurrence prior to randomisation)
!
No staging or insufficient staging
!
Prior PARP inhibitor use
!
Prior cancer < 5 years ago including MDS/t-AML
!
Randomized but did not receive any study treatment
!
Received no study treatment whatsoever for a period of more than 7 days due to errors in 
dispensing of medication.
!
Received an alternative study treatment to that which they were randomized
!
Received prohibited concomitant medication
!
Lack of confirmatory exams for events that count towards the analysis end points, efficacy 
and safety
IPDs – GCP violations
!
GCP violation relating to informed consent
!
GCP violation relating to serious adverse events
!
GCP violation: other
The final classification will be made prior to database lock and all decisions will be made 
whilst blinded to study treatment allocation. For example, details of disallowed concomitant 
medication use will be reviewed by a physician using blinded data and may be determined as 
key.
Incorrect stratifications (i.e. patients for whom incorrect stratification information was 
provided at the time of randomisation) will be listed and summarised. In addition, any known 
treatment dispensing errors will also be listed and summarised. Dispensing errors, considered 
IPDs are described above.
Patients who receive the wrong treatment at any time will be included in the Safety Analysis 
Set as described in Section 2.1.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
34
3.
PRIMARY AND SECONDARY VARIABLES
3.1
Outcome variables
3.1.1
Invasive Disease Free Survival
The primary endpoint of the trial is invasive disease free survival (IDFS), defined as the time 
from randomisation to date of first recurrence, where recurrence is defined as loco-regional, 
distant recurrence, new cancer or death from any cause. IDFS is further detailed according to 
the standardised terms for efficacy endpoints (STEEP) system definition (Hudis et al 2007) as 
one of the following:
!
Ipsilateral invasive breast tumour recurrence (IIBTR): Invasive breast cancer involving the 
same breast parenchyma as the original primary.
!
Regional invasive breast cancer recurrence: Invasive breast cancer in the axilla, regional 
lymph nodes, chest wall, and skin of the ipsilateral breast.
!
Distant recurrence: Metastatic disease-breast cancer that has either been biopsy confirmed 
or radiologically diagnosed as recurrent invasive breast cancer.
!
Death attributable to any cause, including breast cancer, non-breast cancer, or unknown 
cause.
!
Contralateral invasive breast cancer.
!
Second primary non-breast invasive malignancies (i.e., excluding new in situ carcinomas 
of any site). Second primary non-breast invasive malignancies include hematologic 
malignancies and MDS. Squamous or basal cell skin cancers will not be counted as 
primary endpoint events.
Loco-regional recurrence of the disease (ipsilateral or regional invasive breast cancer) should 
be cytologically/histologically confirmed. Appropriate imaging (CT, MRI bone and/or PET 
scan) of the chest/abdomen/pelvis or any other area as clinically indicated should be 
performed at the time of local recurrence to exclude further spread of the disease. Distant 
recurrence should be diagnosed by radiological examination and/or histopathological 
confirmation when metastatic lesion is easily accessible for biopsy.
For confirmed local recurrence events, the earliest date of diagnosis based on an objective 
finding (physical exam, radiological/imaging assessment, and cytological/histopathological 
assessment) will be used to determine the time to event for the analysis but not the date of the 
first symptoms or blood analysis abnormality. For example, if a physical exam results in 
‘suspected’ disease recurrence and disease recurrence is then confirmed by cytology/histology 
then the date of the physical exam will be used to derive the time to event.  
For confirmed distant recurrence, the date of the earliest radiological/imaging examination or 
cytological/histopathological assessment linked to the diagnosis will be used to determine the 
time to event for the analysis (i.e. neither the symptoms or blood analysis, nor the physical 
exam, will be considered within the derivation of time to distant recurrence).

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
35
Invasive contralateral breast cancer or invasive non-breast secondary primary cancer should 
be confirmed by histopathological report. The date of the earliest objective finding related to 
diagnosis of the new cancer will be used as the date of new cancer for the analysis.
If multiple recurrence events are reported within 2 months of each other this is referred to as a 
simultaneous event and will be considered as a single event. In this situation, the worst case 
will be taken, as the event ‘type’ but the date of recurrence will be the earliest date of the 
multiple events. For example, if local and distant recurrence are reported within a 2-month
period, then for the analysis and reporting of IDFS, the event type will be distant recurrence 
but the date of recurrence will be the earlier date of the two events. 
If 2 recurrence events are reported but more than 2 months has elapsed between the events,
then the events will be regarded as two separate recurrence events and the earlier event and 
corresponding date of event will be used in the derivation of IDFS (i.e. IDFS is based on the 
first recurrence event).
The hierarchy of event categories, from most to least severe (and with death without 
recurrence as last in hierarchy), will be as follows:
!
CNS recurrences
!
Distant visceral recurrence: lung, liver, pleural effusion
!
Distant bone recurrence
!
Other distant recurrence (assumed soft tissue)
!
Regional recurrences
!
Local recurrences
!
Invasive contralateral breast cancer
!
Second (non-breast) primary malignancy
!
Death without recurrence
!
If a patient dies during the study, and while being followed-up for efficacy, i.e. before the 
patient enters the survival follow-up only phase, and has no documented disease 
recurrence or invasive contralateral breast cancer or invasive non-breast secondary 
primary cancer then death will be regarded as an event and the date of death will be used 
to determine the patient’s IDFS time.
Patients who have not had a recorded IDFS event at the time of the analysis will be censored 
at their last disease evaluation if efficacy follow-up is ongoing, or at the date of last contact if 
lost to follow-up, withdrawn from study or consent to survival follow-up only. For the 
purpose of the 10-year update, any patients completing the 10-year follow-up visit without 
recorded IDFS event will be censored at the 10-year follow-up visit. Disease evaluation 
includes mammogram and/or breast MRI (MRI preferred for patients younger than 50 years), 
other radiological/imaging examination or clinical examination (e.g. physical exam).
Patients will be censored at 0.5 days after randomisation under the following three
circumstances:

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
36
!
Patients who have had an event prior to randomisation.
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site noticed afterwards that they should not have been randomised, they have had
no follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.
3.1.2
Overall Survival
Overall survival is defined as the time from the date of randomisation until death due to any 
cause. Any patient not known to have died at the time of analysis will be censored based on 
the last recorded date on which the patient was known to be alive.
!
Date of last contact given that the patient status is alive recorded within the survival 
follow-up module of the eCRF
!
Date of randomisation
!
Date of last contact
!
NRG: “Date of last contact” on the “End of study” form 
!
RoW: “Date of last contact or death” on the “End of study” form 
!
Date of last disease evaluation
!
Date of consent change for patients with “Partial withdrawal of consent, survival follow-
up only”
!
Date of withdrawal.
Patients will be censored at 0.5 days after randomisation under the following two
circumstances:
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site noticed afterwards that they should not have been randomised, they have had 
no follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.
3.1.3
Distant disease free survival (DDFS)
DDFS will be defined as the time from randomisation until documented evidence of first 
distant recurrence of breast cancer or death from any cause. Distant recurrence will include the 
following events (as per STEEP system definition):
!
Distant recurrence: Metastatic disease-breast cancer that has either been biopsy confirmed 
or radiologically diagnosed as recurrent invasive breast cancer.
!
Death attributable to any cause, including breast cancer, non-breast cancer, or unknown 
cause.
!
Second primary non-breast invasive cancer.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
37
Evidence of distant recurrence should be provided by either radiological examination or 
preferably by histopathological examination when metastasis is easily accessible for biopsy.
Second primary non-breast invasive cancer should be confirmed by histopathological report. 
For the analysis of DDFS, the date of the confirmed DDFS event will use the earliest 
assessment date from the radiological and/or histological or cytological assessment. For 
example, if a patient has distant recurrence suspected by radiological examination which is 
later confirmed by biopsy, then the date of the radiological examination will be used as the 
date of event.
The hierarchy of event categories, from most to least severe (and with death without 
recurrence as last in hierarchy), will be as follows:
!
CNS recurrences
!
Distant visceral recurrence: lung, liver, pleural effusion
!
Distant bone recurrence
!
Other distant recurrence (assumed soft tissue)
!
Second (non-breast) primary malignancy
!
Death without recurrence
If multiple recurrence events are reported within 2 months of each other then this is referred to 
as a simultaneous event and will be considered as a single event. In this situation the worst 
case will be taken as the event ‘type’ but the date of recurrence will be the earliest date of the 
multiple events.
If 2 recurrence events are reported but more than 2 months has elapsed between the events,
then the events will be regarded as two separate recurrence events and the earlier event and 
corresponding date of event will be used in the derivation of DDFS (i.e. DDFS is based on the 
first recurrence event).
Patients who do not have documented evidence of DDFS at the time of the analysis of DDFS 
will be censored at:
!
Last disease evaluation if efficacy follow-up is ongoing 
!
Date of last contact if lost to follow-up, withdrawn from study or consent to survival 
follow-up only
!
For the purpose of the 10 year update, any patient completing 10 year follow-up visit 
without recorded DDFS event will be censored at 10 year follow-up.
Disease evaluation includes mammogram and/or breast MRI (MRI preferred for patients 
younger than 50 years), other radiological/imaging examination or clinical examination (e.g. 
physical exam).
Patients will be censored at 0.5 days after randomisation under the following 3 circumstances:

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
38
!
Patients who have had an event prior to randomisation, if the event was distant disease.
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site later realised that they should not have been randomised, they have had no 
follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.
The first site of distant recurrence will be recorded and used in the analysis. Information on 
subsequent sites of recurrence will also be collected during follow up assessments to ensure as 
complete as possible information on distant recurrence is obtained.
3.1.4
Incidence of contralateral invasive breast cancer, contralateral non-invasive 
breast cancer, new primary ovarian cancer, new primary fallopian tube cancer
and new primary peritoneal cancer
All patients should be followed for evidence of new primary breast cancers and all other 
cancers. This includes patients with a first event of local or distant recurrence as they might
develop new cancers in the future. All new cancers will be collected for all patients not just 
the first new cancer.
Evidence of new contralateral breast cancer (invasive and non-invasive), and new ovarian, 
fallopian, or peritoneal cancers should be confirmed by clinical or radiological examination, 
with positive histology or cytology (confirmation of invasive tumour). The date of event will 
be taken as the earliest date from radiological, clinical and, histological or cytological exam
(invasive disease only).
Time to new primary contralateral (invasive and non-invasive) breast cancer is defined as the 
interval between the date of randomisation and the date of the first occurrence of a new 
primary contralateral invasive breast cancer. Data analyses of new contralateral breast cancer 
(invasive and non-invasive) will exclude patients who have had bilateral mastectomy prior to 
randomisation.
Time to new ovarian cancers is defined as the interval between the date of randomisation and 
the date of the first occurrence of a new ovarian cancer, data analyses of new ovarian cancers 
will exclude patients who have had both ovaries removed prior to randomisation. Male 
patients will also be excluded from this analysis.
Time to new fallopian tube cancer is defined as the interval between the date of randomisation
and the date of the first occurrence of a new fallopian tube cancer, data analyses of new 
fallopian tube cancers will exclude patients who have had both fallopian tubes removed prior 
to randomisation. Male patients will also be excluded from this analysis.
Time to new peritoneal cancer is defined as the interval between the date of randomisation and 
the date of the first occurrence of a new peritoneal cancer. Data analyses of new peritoneal 
cancer will include all patients in the ITT population with the exception of male patients, 
males will be excluded from this analysis.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
39
Patients will be censored at 0.5 days after randomisation under the following 3 circumstances:
!
Patients who have had an event prior to randomisation, if the event is the one being 
analysed.
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site later realised that they should not have been randomised, they have had no 
follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.
3.2
Patient reported outcome variables
Patient reported outcomes will be assessed based on the FACIT-Fatigue symptoms scale and 
the EORTC QLQ-C30 scale.
3.2.1
FACIT-Fatigue
The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F Scale) is a 
13-item questionnaire that assesses patient self-reported fatigue and its impact upon daily 
activities and function (Yellen et al 1997).
The FACIT-Fatigue scale is a validated instrument with a set method for scoring (FACIT-
Fatigue Subscale Scoring Guidelines Version 4). The scale includes 13 items asking in 
different ways how the patients feels regarding being energetic, tired, weak or fatigue in the 
past 7 days with the patient selecting one of five categories of feeling levels ranging from “not 
at all” to “very much.”  Items #1 through #6 and items #9 through #13 are scored as follows: 
not at all=4; a little bit=3; somewhat=2; quite a bit=1; very much=0. Items #7 and #8 are 
reversed scored as follows: not at all=0; a little bit=1; somewhat=2; quite a bit=3; very 
much=4. The composite score is found by summing the scores for each of the 13 items. Thus, 
the composite score range is 0-52. The higher the score, the better the quality of life. A score 
of less than 30 indicates severe fatigue.
The FACIT-F scale was originally developed to evaluate fatigue associated with anaemia in 
cancer patients and has been used as an endpoint in clinical trials in various cancer 
populations including breast cancer and non-small cell lung cancer. Content validity of the 
FACIT-F has been demonstrated in a large sample of mixed cancer patients (n>300). 
Reliability (internal consistency, test-retest reliability, criterion validity, and 
responsiveness/sensitivity to change) of the FACIT-F have also been documented (Yellen et al 
1997).
3.2.2
EORTC QLQ-C30
In this study patient-reported disease related symptoms and health-related quality of life 
(HRQoL) will be evaluated using the validated EORTC QLQ-C30 questionnaire (EORTC 
QLQ-C30 Scoring Manual 3rd edition).  The EORTC QLQ-C30 questionnaire was developed 
to assess HRQoL and is the most commonly used cancer-specific tool in oncology. It has 

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Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
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Edition Number 3.0
Date 12th  June 2019
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undergone extensive testing and validation as well as detailed cross-cultural testing and 
validation and has been used in breast cancer trials.
The EORTC QLQ-C30 comprises 30 questions designed for all cancer types.  Questions can 
be grouped into the following scales:
!
5 multi-item functional scales (physical, role, emotional, cognitive and social) 
!
3 multi-item symptom scales (fatigue, pain, nausea vomiting)
!
A 2-item global health status/QoL scale
!
5 single items assessing the following common cancer symptoms:
∀
dyspnoea
∀
loss of appetite
∀
insomnia
∀
constipation
∀
diarrhoea
!
1 item on the financial impact of the disease.
All of the scales and single-item measures range in score from 0 to 100. A high scale score 
represents a higher response level. Thus a high score for a functional scale represents a high 
health/level of functioning, a high score for the global health status/QOL represents a high
QOL, but a high score for a symptom scale /item represents a high level of 
symptomatology/problems.
The global health status/QOL score is based on two items (numbers 29 and 30) from the 
EORTC-QLQ-C30.
3.3
Safety
Safety and tolerability will be assessed for all randomised patients who received at least one 
dose of study treatment in terms of adverse events (AEs), serious adverse events (SAE), 
deaths, laboratory data and vital signs.
3.3.1
Adverse events
Adverse events will be collected from time of signature of main informed consent* throughout 
the treatment period up to and including the 30-day follow-up period. All ongoing and any 
new AEs/SAEs identified during the 30 calendar days follow up period after the last dose of 
study medication must be followed to resolution unless the event is considered by the 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
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investigator to be unlikely to resolve, or the patient is lost to follow-up or in survival follow-
up. Any medical condition (new or worsening of a pre-existing condition) that occurs post 
Screening PART 2 and is continuing at randomisation should be recorded in medical history 
in the eCRF as a medical condition current at randomisation. If the condition worsens post 
randomisation, this should be recorded as an AE/SAE in the eCRF with start date as the date 
the grade worsened and the new grade should be reported on the AE form. The AE/SAE 
would be considered to have resolved when it resolves to the baseline grade, not to zero. Any 
medical condition considered of clinical relevance (new or worsening of a pre-existing 
condition) that occurs post consent for PART 2 and resolves prior to randomisation should 
also be recorded as medical history. Any AE happening from randomisation to the 30-day 
follow-up period should be reported on the AE form in the eCRF. If an investigator learns of 
any SAEs, including death, at any time after a patient has completed 30 days post treatment 
follow-up period, and he/she considers there is a reasonable possibility that the event is 
causally related to the study treatment, the investigator should notify AstraZeneca, Patient 
Safety by reporting the SAE via both the eCRF in Medidata Rave and paper SAE report to 
AstraZeneca DES.
At any time after a patient has completed the study, if an investigator learns of any SAE 
including sudden death of unknown cause, and there is a reasonable possibility that the event 
is causally related to the investigational product, this should be notified to AstraZeneca, 
Patient Safety. Otherwise, after study treatment completion (i.e. after any scheduled post 
treatment follow-up period has ended) there is no obligation to actively report information on 
new AEs or SAEs occurring in study patients.  This includes new AEs/SAEs in patients still 
being followed up for survival but who have completed the post treatment follow up period 
(30 days). 
Any case of MDS/AML or new primary malignancy occurring at any time from signature of 
informed consent for the entire participation of the patient in the study including the follow-up 
period should be reported as an SAE. Any MDS/AML, new primary malignancies or 
pneumonitis occurring after the 30 day follow up period should be reported to AstraZeneca 
Patient Safety regardless of causality, investigator’s assessment or knowledge of treatment 
arm. Non-melanoma skin cancers need to be reported as a non-serious AE unless at least one 
of the seriousness criteria is met and then it must be reported as an SAE, see Section 6.4.2 of 
the CSP. Any of these type of serious or non-serious events need to be reported to 
AstraZeneca Patient Safety according to SAE reporting procedures for this study, regardless 
of investigator’s assessment of causality or knowledge of the treatment arm. If a patient 
develops MDS/AML full diagnostic details and classification should be provided e.g. bone 
marrow and cytogenetic analysis reports, see Sections 5.5.6.3 and 6.4.5.5 of the CSP. A 
questionnaire will be sent to any investigator reporting MDS/AML or new primary 
malignancy so that relevant details can be reported.
*In Screening PART 1 of the study only SAEs related to study mandated procedures (i.e. blood 
draw) will be collected. In Screening PART 2 all SAEs will be collected.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
42
3.3.1.1
Olaparib adverse events of special interest (AESI)
Adverse events of special interest (AESI) are events of scientific and medical interest specific
to the further understanding of olaparib’s safety profile and require close monitoring and rapid
communication by the investigators to AstraZeneca. Adverse events of special interest for
olaparib are MDS/AML, new primary malignancy (other than MDS/AML) and pneumonitis.
The search strategy to identify AESIs as provided by AstraZeneca Patient Safety is shown in 
Table 6. 
Table 6
Search strategy to identify AESI
MDS/AML
Myelodysplastic syndrome (SMQ-Narrow)
+AML PTs: Acute biphenotypic leukaemia, acute leukaemia, acute 
megakaryocytic leukaemia, acute monocytic leukaemia, acute myeloid 
leukaemia, acute myeloid leukaemia recurrent, acute myelomonocytic 
leukaemia, acute promyelocytic leukaemia, acute undifferentiated 
leukaemia, blast cell crisis, blast crisis in myelogenous leukaemia, 
chloroma, eosinophilic leukaemia, erythroleukaemia, leukaemia basophilic, 
leukaemia granulocytic, leukaemia monocytic, myeloid leukaemia, 
transformation to acute myeloid leukaemia
Other NPMs
Malignant or unspecified tumours (SMQ)
Pneumonitis
Interstitial Lung Disease (SMQ-Narrow)
Note: this search strategy could be updated at any point up to database lock.
3.3.2
Treatment exposure
Exposure will be defined as follows:
Total (or intended) exposure of olaparib/placebo
!
Total (or intended) exposure (days) = last dose date  – first dose date + 1
Last dose date is defined as earliest of:
∀
- Last dose date at discontinuation
∀
- Last dose date at treatment completion
∀
- Last dose date at Data cut off (DCO)
Actual exposure of olaparib/placebo
!
Actual exposure (days) = Total exposure – Total duration of dose interruptions, where 
Total exposure will be calculated as above.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
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Number of days on 300 mg olaparib/placebo bd.
!
Number of days on 300 mg olaparib/placebo bd. = actual exposure for the dose assigned.
Cumulative exposure
Cumulative exposure over time is categorized by duration of total intended exposure in 
months of cumulative exposure;>0 months, ≥ 1 month, ≥ 2 months, ≥ 3 months, ≥ 4 months, ≥ 
5 months, ≥ 6 months, ≥ 7 months, ≥ 8 months, ≥ 9 months, ≥ 10 months, ≥ 11 months, 12 
months. Subjects are counted under each category providing their total intended exposure is 
up to and including that duration. 
Exposure by dose
The following summaries are produced for exposure by dose;
!
Range of any dose for any subject = minimum dose for any subject (mg/day) -maximum 
dose for any subject (mg/day)  
!
Mean dose (mg/day) = mean (any dose (mg/day) for any subject)
!
Range of mean doses = minimum (mean dose (mg/day) per subject) - maximum (mean 
dose (mg/day) per subject)
!
Mean total cumulative dose (mg) = mean (cumulative dose (mg) per subject)
!
Range of total cumulative doses (mg) = minimum (cumulative dose (mg) per subject) -
maximum (cumulative dose (mg) per subject)
!
Range of maximum doses = minimum (maximum dose (mg/day) per subject) - maximum 
(maximum dose (mg/day) per subject) 
Olaparib total daily dose
The total daily dose is defined as the mean total daily dose for each subject in each 3 month 
period.
!
>500 to ≤600
!
>400 to ≤500
!
≤400
Over three monthly periods 
!
Up to 3 months
!
>3 to <=6 months
!
>6 to <=9 months
!
>9 to <=12 months

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
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In each time period the total daily dose for each patient is as shown in the categories above, 
the number and % of patients with total daily dose as categorised will be presented, the 
denominator is the number of patients receiving Olaparib in that time period.
Appendix C gives an example of how to consider patients who permanently discontinued 
treatment during a dose interruption.
3.3.3
Dose intensity 
Relative dose intensity (RDI) is the percentage of the actual total dose delivered relative to the 
intended total dose through to treatment discontinuation. Percentage intended dose (PID) is 
the percentage of the actual total dose delivered relative to the intended total dose through to 
invasive disease recurrence. Both will be derived using study treatment data up to one year or 
until the date of invasive disease (whichever is earliest).
Relative dose intensity (RDI) and percent intended dose (PID) will be defined as follows:
!
RDI = 100% * d/D, where d is the total actual dose delivered up to the earlier of a 
censoring event or the actual last day of dosing and D is the total intended dose up to a
censoring event or the actual last day of dosing. The censoring events areTrinvasive 
disease, withdrawal from study and DCO. 
For example: For a patient with a date of invasive disease before the date of last study 
treatment, the date of invasive disease is treated as a censoring event, i.e. the total 
intended dose (D) is calculated until the date of recurrence.
!
PID = 100% * d/D, where d is the total actual dose delivered up to invasive disease or a 
censoring event or the actual last day of dosing and D is the total intended dose up to 
invasive disease or a censoring event. The censoring events are withdrawal from study and 
DCO. D is the total dose that would be delivered, if there were no modification to dose or 
schedule.
Due to the eCRF design, the actual cumulative dose does not capture all missed or forgotten 
doses within an individual day. This will be recorded as if the patient took a full daily dose, 
which could lead to an overestimation of RDI and PID.
Examples of calculating RDI and PID are given in Appendix C.
3.3.4
Laboratory data 
Laboratory data will be collected throughout the study, from screening to follow-up visit as 
described in Table 1 and Table 2 of the CSP. Blood and urine samples for determination of 
haematology, clinical chemistry, and urinalysis will be collected as described in Section 6.4.5 
of the CSP.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
45
3.3.5
ECGs
ECGs are required during screening within 28 days prior to randomisation and when clinically 
indicated afterwards. All ECGs should be assessed by the investigator as to whether they are 
clinically significantly abnormal / not clinically significantly abnormal.
3.3.6
Vital signs
Vital signs data obtained up until the 30 days from date of last dose of olaparib/placebo 
treatment will be used for reporting. For derivation of post baseline visit values considering 
visit window and to handle multiple records, derivation rules as described in Section 3.3.7
below will be used.
3.3.7
General consideration for safety assessments
Time windows will be defined for any presentations that summarise values by visit (see 
below). The following conventions should also apply:
!
The time windows should be exhaustive so that data recorded at any time point has the 
potential to be summarised. Inclusion within the time window should be based on the 
actual date and not the intended date of the visit.
!
All unscheduled visit data should have the potential to be included in the summaries.
!
The window for the visits following baseline will be constructed in a way that the upper 
limit of the interval falls half way between the two visits (the lower limit of the first post-
baseline visit will be Day 2). If an even number of days exists between two consecutive 
visits then the upper limit will be taken as the midpoint value minus 1 day.
For example, the visit windows for laboratory data are:
∀
Week 2, Day 15, visit window 2 – 21
∀
Week 4, Day 29, visit window 22 – 42
∀
Week 8, Day 57, visit window 43 – 70
∀
Week 12, Day 85, visit window 71 – 98
∀
Week 16, Day 113, visit window 99 – 126
∀
Week 20, Day 141, visit window 127 – 154
∀
Week 24, Day 169, visit window 155 – 217
∀
Week 38, Day 267, visit window 218 – 315
∀
Week 52, Day 365, visit window 316 - 379

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
46
!
For summaries showing the maximum or minimum values, the maximum/minimum value 
recorded on treatment will be used (regardless of where it falls in an interval).
!
Listings should display all values contributing to a time point for a patient.
!
For visit based summaries:
∀
If there is more than one value per patient within a time window, then the 
closest value should be summarised, or the earlier in the event the values 
are equidistant from the nominal visit date. The listings should highlight 
the value for that patient that went into the summary table, wherever 
feasible.
∀
To prevent the creation of very large tables or plots that contain many cells 
with meaningless data, the visit data for each treatment group should only 
be summarised if the number of observations is greater than the minimum 
of 20 and > 1/3 of patients dosed.
!
For summaries at a patient level, all values should be included, regardless of whether they 
appear in a corresponding visit based summary, when deriving a patient level statistic e.g.
a maximum. 
!
Baseline will be defined as the last non-missing measurement prior to dosing with study 
treatment (olaparib or placebo). For laboratory data and vital signs data, any assessments 
made on day 1 will be considered pre-dose. Where safety data are summarised over time, 
study day will be calculated in relation to date of first treatment (olaparib or placebo).
Missing safety data will generally not be imputed, although partial/missing start and end dates 
for adverse events and concomitant medications will be imputed (see Section 4.2.15). 
However, safety assessment values of the form of “< x” (i.e., below the lower limit of 
quantification) or > x (i.e., above the upper limit of quantification) will be imputed as “x” in 
the calculation of summary statistics but displayed as “< x” or “> x” in the listings.
3.3.8
PK variables
The PK and PKPD analysis will be described in detail in a separate modelling analysis plan.
Pharmacokinetic (PK) sampling will be performed in a subset of patients. Each patient will be 
asked to contribute 5 blood samples, one from each of the predefined time windows below 
preferably on visit 4, day 29. Nevertheless, the samples can also be taken at a later treatment 
visit, provided that PK consent was obtained beforehand.
!
Pre-dose (before morning dose)
!
Between 0 and 0.5 hour post-dose
!
Between >0.5 and 1.5 hour post-dose
!
Between 3 and 6 hours post-dose
!
Between >6 and 12 hours post-dose (before evening dose).

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
47
The PK analysis of the plasma concentration data for olaparib will be performed by Covance 
on behalf of Clinical Bioanalysis Alliance, AstraZeneca R&D, using an appropriate 
bioanalytical method. The actual sampling times will be used in the PK calculations. For each 
patient providing a complete set of PK samples, non-linear mixed effects modelling 
(NONMEM) will be used to estimate steady state Cmax, AUC and Cmin.
3.4
Resource use
Resource use for serious adverse events (including hospitalisations) will be captured through 
the serious adverse events reporting procedures.
Resource use outcome variables include the following:
!
Length of hospital stay
!
Number of hospital admissions
The length of hospital stay will be calculated as the difference between the date of hospital 
discharge (or death date) and the start date of hospitalisation or start of study drug if the start 
of study drug is after start date of hospitalisation (length of hospital stay = end date of 
hospitalisation – start date of hospitalisation + 1). Patients with missing discharge dates will 
be calculated as the difference between the last day with available data and the start date of 
hospitalisation.
Sum of total duration of hospital stay will be considered for analysis if patient was admitted to 
hospital more than one time during study period. 
4.
ANALYSIS METHODS
The primary analysis of IDFS will occur when 330 IDFS events have occurred (have been 
counted in the clinical database).
An initial analysis of OS and DDFS will be performed at the same time as the primary 
analysis of IDFS and will use the same methodology and model.
The final OS analysis will be conducted once the trial follow up is complete (i.e. 10 years 
from when the last patient is randomised, estimated 15 years from first patient randomised 
assuming recruitment of 5 years). 
In addition, an analysis will be performed half way between the primary IDFS analysis and 
the final overall survival analysis (estimated around 10 years from first patient randomised but 
timings will be driven by the primary IDFS analysis once known). At this time point both 
DDFS and OS will be analysed and some alpha (see Section 5 for full details) will be reserved 
for formal hypothesis testing. IDFS may also be updated if more information is available but 
this would be considered a supportive update of the primary analysis and no alpha will be 
reserved for IDFS.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
Study Number BIG 6-13, NSABP B-55
Edition Number 3.0
Date 12th  June 2019
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For details on alpha spend and how this will be allocated across the planned analyses, see 
Section 5.
Supportive analyses of contralateral invasive breast cancer, new primary ovarian cancer, new 
primary fallopian tube cancer and new primary peritoneal cancer will be provided at the 
interim and at the primary analysis of IDFS, however no multiple adjustment will be applied 
as these are viewed as supportive endpoints.
4.1
General principles
The primary statistical analysis of the efficacy of olaparib will include all randomised patients 
and will compare the treatment groups on the basis of randomised treatment, regardless of the 
treatment actually received. Patients who were randomised but did not subsequently go on to 
receive study treatment are included in the Full Analysis Set. Therefore, all efficacy will be 
summarised and analysed in the FAS on an intention-to-treat basis. All patient reported 
outcome data will be summarised and analysed in a subset of the FAS, the PRO analysis set.
When assessing safety and tolerability, summaries will be produced based on the Safety 
Analysis Set. This will include all patients who receive at least one dose of randomised 
treatment (olaparib or placebo). Patients in the Safety Analysis Set will be analysed by 
whether or not the patient received at least one dose of olaparib. The safety data will be 
summarised descriptively and will not be formally analysed.
If there are any randomised patients not confirmed to have a gBRCA mutation by the central
test, a subset of confirmed 
 gBRCAm patients will be defined for sensitivity 
analyses.  In this case, key efficacy, demographic, patient characteristics and safety outputs 
will be repeated in this subset.
Summary statistics for continuous variables will include the number of subjects, mean, 
standard deviation, median, minimum, and maximum values. Continuous variables will 
generally be presented with the mean and median to 1 decimal more than the individual data, 
and the standard deviation to 2 decimals more than the individual data. Summary statistics for 
categorical variables will include frequencies and percentages. Percentages will be presented 
to one decimal place.
The SAS programming language will be used to produce all outputs except for the test of non-
proportional hazards by Grambsch-Therneau methods. This analysis will use the R package 
survival (Therneau and Grambsch 2000; Therneau 2015), specifically the coxph (Therneau 
and Grambsch 2000) and cox.zph (Grambsch and Therneau 1994) functions.
A SAS macro for the GailSimon method will be used (see appendix D).
4.2
Analysis methods
The treatment comparison is olaparib 300 mg bd. versus placebo.

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
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Edition Number 3.0
Date 12th  June 2019
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If the significance level has been adjusted for an analysis (e.g. interim analysis of IDFS) then 
results will be presented using a confidence interval corresponding to the significance level 
applied and a 95% CI will also be presented for descriptive purposes. Otherwise, results of all 
statistical analysis will be presented using a 95% CI. All p-values presented will be 2-sided.
4.2.1
Confidence intervals at the interim analysis
In the event of stopping for efficacy at the interim analysis the secondary endpoints will be 
analysed according to the rules in Section 5 Interim Analyses: 4% on DDFS and 1% on OS, 
inferential and exploratory CIs will be reported for DDFS and OS.
Inferential confidence intervals will be presented for IDFS, and, if the null is rejected for 
IDFS, they will also be presented for OS and DDFS.
Under the scenario of no alpha recycling (i.e. both OS and DDFS rejected or accepted) the 
following intervals will be presented;
!
IDFS: 99.5%
!
DDFS: 99.5%
!
OS: 99.8%
If the null is rejected for OS and not for DDFS then alpha will be recycled to DDFS from OS. 
In this scenario the following intervals will be presented;
!
IDFS: 99.5%
!
DDFS: 99.375%
!
OS: 99.8%
If the null is rejected for DDFS and not for OS then alpha will be recycled to OS from DDFS. 
In this scenario the following intervals will be presented;
!
IDFS: 99.5%
!
DDFS: 99.5%
!
OS: 99%
4.2.2
Median clinical follow-up 
Median clinical follow-up will be calculated using the reverse censoring method (Schuster, 
1991; Schemper, 1996)
4.2.3
Kaplan-Meier estimates of IDFS 
IDFS times will be summarized using Kaplan-Meier survival curves (Kaplan & Meier, 1958).
4.2.4
Percentages of invasive disease free subjects at yearly intervals
The percentages of surviving subjects who are invasive disease free at yearly intervals from 
the time of randomisation will be estimated from the Kaplan-Meier curves (Kaplan & Meier, 

Statistical Analysis Plan
Drug Substance Olaparib (AZD2281)
Study Code D081CC00006
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Edition Number 3.0
Date 12th  June 2019
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1958). This will include at a minimum the following time points as the data become available 
during the trial: 1 year, 2 years, and 3 years. Approximate 95% confidence limits will be 
calculated, based on Greenwood’s formula (Collett 2003) for the standard error of the Kaplan-
Meier estimate 
The following table details which endpoints are to be subject to formal statistical analysis.
Table 7
Formal Statistical Analyses to be Conducted
Endpoints Analysed
Notes
IDFS (Time from randomisation to invasive 
disease recurrence or death due to any cause)
Primary analysis stratified log-rank test and Cox 
regression
Key sensitivity analysis: Stratified Cox regression
in randomised patients confirmed as gBRCA
mutation positive by central 
 test (if 
different from FAS(ITT))
Overall Survival (Time from randomisation to 
death due to any cause)
Stratified log-rank test and Cox regression
Key sensitivity analysis: Stratified Cox regression
in randomised patients confirmed as gBRCA
mutation positive by central 
 test (if 
different from FAS(ITT))
DDFS (Time from randomisation to distant 
recurrence or death due to any cause)
Stratified log-rank test and Cox regression
Key sensitivity analysis: Stratified Cox regression
in randomised patients confirmed as gBRCA
mutation positive by central 
 test (if 
different from FAS(ITT))
Incidence of contralateral invasive breast cancer, 
contralateral non-invasive breast cancer, new 
primary ovarian cancer, primary fallopian tube 
cancer and new primary peritoneal cancer
Fine and Gray models
FACIT-Fatigue
Primary analysis MMRM at 6 and 12 months
Sensitivity analysis MMRM
EORTC QLQ-C30 GI symptoms
MMRM
EORTC QLQ-C30 HRQoL
MMRM

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4.2.5
Demographic and baseline characteristics data
The following will be summarised by randomised treatment group:
!
Patient disposition
!
Important deviations
!
Inclusion in analysis populations
!
Demographics (age, age group, sex, race and ethnicity)
!
Patient characteristics at baseline (height, weight, weight group, body mass index (BMI) 
and BMI group)
!
Stratification factors recorded on the eCRF
!
Stratification factors according to the randomisation system.
!
Local and central BRCA mutation type (using the central 
 test as reviewed by 
PMG)
!
Breast cancer surgical history (breast conservation; sentinel nodal status; axillary nodal 
status)
The following will be summarised by randomised treatment group:
!
Patient recruitment by country and centre
!
Receptor status  (HER2 status, ER status, PgR status) from local and central 
!
Prior chemotherapy for primary breast cancer and for primary malignancies (including 
anthracycline, taxane, and anthracycline plus taxane)
!
Prior hormone therapy for primary breast cancer and for primary malignancies
!
Prior platinum therapy for primary breast cancer and for primary malignancies
!
Pathological characteristics of primary breast cancer at baseline (bilateral, histological 
grade, clinical stage and pathological stage, CPS+EG score)
!
ECOG performance status at baseline
!
Ovarian surgical history (both ovaries removed: Yes; No) Note: oophorectomy is collected 
on the Procedures eCRF page
!
Fallopian tube surgical history  (Note: salpingectomy is collected on the Procedures eCRF 
page
!
Time from last treatment (surgery, chemotherapy or radiotherapy) to randomisation
!
Time from diagnosis to randomisation
!
Medical History
!
Disallowed concomitant medications
!
Allowed concomitant medications
!
Post-discontinuation disease-related cancer therapy
!
Post-event treatments/radiotherapy/surgery
!
Family history of cancer
For concomitant medication coding the WHO Drug Dictionary Enhanced with Herbal 
Dictionary (release date 1st March 2016)

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Date 12th  June 2019
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Prior chemotherapy, platinum therapy, primary breast cancer surgery and ovarian surgery will 
also be summarised separately for patients who received neo-adjuvant or adjuvant 
chemotherapy, and pathological characteristics will be summarised according to hormone 
receptor status and neo-adjuvant or adjuvant chemotherapy.  In addition, prior and/or 
concurrent hormone therapy will be summarised separately for ER and/or PgR positive /HER2 
negative patients.
The total number of patients unblinded and patients who were unblinded (a) prior to invasive 
disease recurrence and (b) prior to or on the day of treatment discontinuation will be 
summarised by treatment group.
Patient disposition, demographic and patient characteristics, and pathological characteristics 
will also be presented in the confirmed 
 gBRCAm patients if appropriate.
4.2.6
Multiplicity 
The primary endpoint of the study is IDFS. However, key secondary endpoints will be OS and 
DDFS.
In order to describe the nature of the effects of olaparib treatment IDFS, DDFS and OS will be 
tested at a 2-sided significance level of 5%. However, in addition, in order to strongly control 
the overall type I error at 2.5% 1-sided (5% 2 sided), a multiple testing procedure (MTP) will 
be employed across the primary endpoint and all key secondary endpoints intended for label 
claims (DDFS and OS). The MTP will account for any interim analyses on IDFS, DDFS and 
OS and also planned further analyses post the primary 330 IDFS event data cut off.
A hierarchical testing strategy will be employed where IDFS is tested first using the full test 
mass (i.e. full 2.5%, 1-sided alpha), then DDFS and OS will be tested if IDFS is significant 
based on a weighted proportion of the test mass (2% for DDFS and 0.5% for OS, 1-sided) 
which can be recycled to secondary endpoints not yet rejected. Testing stops when the entire 
test mass is allocated to non-rejected endpoints.

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Figure 3
Multiple Testing Procedure 
IDFS is planned to be analysed at the interim and the final analysis (see Section 5 for further 
details). If IDFS is significant at the interim based on the ITT population then secondary 
endpoints will be formally tested at the interim based on the MTP outlined above. To account 
for multiple analyses on each endpoint a separate alpha spending function will be applied to 
each endpoint (Glimm et al 2009). Further analyses of DDFS and OS with more mature 
follow-up may be required for which some alpha will be reserved for significance testing.
All planned analyses will be performed, regardless of the outcome of the MTP. If the full test 
mass has been used on an earlier test in the MTP, no claims regarding the statistical 
significance of a subsequent analysis in the MTP will be made.
4.2.7
Primary endpoint - Invasive Disease-Free Survival (IDFS) 
4.2.7.1
Primary Analysis
As described in Section 3.1.1, patients who have not had a recorded IDFS event at the time of 
the analysis will be censored at the date of last contact if lost to follow-up or withdrawn from 
study or their last disease evaluation if follow-up is ongoing. 
Patients will be censored at 0.5 days after randomisation under the following 3 circumstances:
!
Patients who have had an event prior to randomisation.
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site later realised that they should not have been randomised, they have had no 
follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.

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These randomised patients will be counted in the Full Analysis Set, however they will be 
treated as being censored for the IDFS event just after randomisation. Censoring these patients 
at day 0.5 will not affect the log-rank test, however, they will be counted in the total number at 
risk and in the Kaplan-Meier (KM) plot. The reason for censoring at day 0.5 is to avoid ties 
with other patients censored on day 1.
IDFS will be analysed using a log-rank test stratified by the stratification factors (using the 
information entered into the randomisation system) and the corresponding p-value will be 
reported as the primary analysis result. 
In addition, IDFS will be analysed using a stratified Cox proportional hazard model 
incorporating the Efron approach for handling ties. As with the IDFS analysis, the 
stratification factor categories used in the Cox model will be those identified for each patient 
at the time of randomisation. The point estimate of the treatment effect, i.e., the hazard ratio of 
IDFS (olaparib vs. placebo) will be obtained by maximizing the Cox partial likelihood 
function, which is the product of the partial likelihood of each stratum. The 95% confidence 
interval will be estimated using the profile likelihood approach. Should the conclusion from 
the log-rank test not agree with the score test from the Cox proportional hazards model, the 
log-rank test will dominate.
A KM plot of IDFS, with tick marks to identify censored observations, will be presented by 
treatment group. Summaries of the number and percentage of patients experiencing an IDFS 
event, and the site of first event (see Section 3.1.1 for the hierarchy) will be provided for each 
treatment group.
The estimated 3 year IDFS will be summarised (using estimates from the KM curve) and 
presented by treatment group.
The primary stratified log-rank test of IDFS will be based on the stratification factors 
determined from the following pooling strategy. 
In the event that there are fewer than 5 IDFS events per treatment arm within any individual 
stratum (initially starting with 16 strata ; 16=2x2x2x2 including treatment group), one 
stratification factor will be removed at a time until there are at least 5 IDFS events within each 
individual stratum in the following order:
1
Prior platinum use for breast cancer (yes/no)
2
Prior chemotherapy (neo-adjuvant vs. adjuvant)
3
Hormone receptor status (ER and/or PgR positive/HER2 negative vs. TNBC)
The additional Cox analysis will be based on the same stratification factors. An unadjusted 
analysis will also be done as a sensitivity analysis and compared with the primary results.

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4.2.7.2
Sensitivity Analyses for IDFS
The following sensitivity analyses will be done to compare against the primary IDFS analysis 
result. For each of the analyses specified the HR and CI from the Cox model will be reported 
alongside. The stratification factors for the sensitivity analyses will be the same as for the 
main analysis with the exception of the unadjusted analysis, mis-stratification in the 
randomisation system and the central pathology review, stratification factors for these are 
detailed below.
Confirmed (central 
 test) gBRCA mutation
If applicable, an analysis will be performed for IDFS using the same model as described 
above but based on all randomised patients confirmed to have gBRCA mutations by the central
test. This analysis is only required if the analysis population differs from the primary 
ITT population (i.e. only required if any of the randomised patients are not confirmed to have 
gBRCA mutations by the central 
 test).
Mis-stratification in the randomisation system 
Any patients mis-stratified in the randomisation system (i.e. incorrect details are entered at the 
time of randomisation) will be included in the primary analysis as stratified. Cross-tabulations 
of stratification factors from the randomisation system and the correct baseline data from the 
eCRF will be considered. If >5% of randomised patients are incorrectly stratified (i.e. 
randomisation system data does not match baseline data) then a sensitivity analysis will be 
performed for IDFS using the same model as described above but using the eCRF 
information.
Stratification factors and therefore the stratification errors will be based on the pooling 
strategy identified for the main IDFS analysis. For example, if only HR status is a 
stratification factor following the pooling for the main IDFS analysis then only the 
stratification errors between HR status on the randomisation system and on the eCRF will be 
taken into account when calculating the % of stratification errors. Under this scenario, if the 
sensitivity analysis was triggered then it would only include HR status from the eCRF as a 
stratification factor in the fitted Cox model.
Central pathology review
If the results of ER and PgR status from the local and central labs differ in >5% of randomised 
patients, then a sensitivity analysis will be performed for IDFS using the same model as 
described above, but using the central lab result to determine the HR status stratification factor 
and compared with the primary analysis result. 
Note: central HR status results not available for China.
Important PDs
A ‘deviation bias’ sensitivity analysis may be performed excluding patients with IPD’s that 
may affect the efficacy of the trial therapy. Further details are given in Section 2.2.

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Unadjusted analysis
An unadjusted (unstratified Cox model) analysis will be performed as a sensitivity analysis 
and compared with the primary results.
Assumption of proportional hazards
The assumption of proportional hazards underlying the log-rank test and the Cox model used 
for the primary analysis will be assessed. Proportionality will be assessed using two 
approaches, firstly by inspecting plots of complementary log-log (time) versus log (time) and 
secondly by formally testing using the Grambsch–Therneau test (G-T) based on scaled 
Schoenfeld residuals from a Cox model including treatment group as a factor. If the G-T test 
is significant (p<0.05), and proportionality is rejected, Restricted Mean Survival Time 
(RMST) methods will be used to estimate and test the treatment difference while allowing for 
non-proportional hazards. RMST will be based on the Pseudo-observations method (Anderson 
et al 2004) with covariates included in the model using Generalised estimating equations 
(GEE) with robust standard errors. 
The cut-off time (t∗) for RMST will be the minimum of the largest observed event time over
the two treatment groups. Note: in the presence of non-proportionality, the HR point estimate 
of the treatment difference obtained from the main analysis of the IDFS primary end-point (in 
Section 4.2.3.1) will be interpreted as an average HR over the observed extent of follow-up.
Note: in the presence of non-proportionality, the HR will be interpreted as an average HR over 
the observed extent of follow-up.
As described in Section 3.3.1, patients with events prior to randomisation will be censored at 
0.5 days after randomisation. In addition, the IDFS analysis will be run excluding these 
patients from the Full Analysis Set.
Interval censored Cox regression
A sensitivity analysis will be performed where patients whose visit schedule has not been 
according to the protocol are fitted in the Cox model using interval censoring.
Specifically;
-
For patients experiencing an event, and without follow-up according to the protocol 
(defined as over 18 months between the event and the last visit), the interval from the 
last date at which the subject was known to be IDFS free to the date of recurrence or 
death, will be used.
-
For patients that were previously censored, or had an event and were seen according to 
the protocol defined visit schedule, the lower limit of the interval will be set to the 
censoring/event date, while the upper limit will be set to missing.

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Note: Missed visit will be defined according to the year of study that a patient is in, and 
incorporate the allowed windows.
This analysis will be performed using SAS function PROC ICLIFETEST. The ICLIFETEST 
procedure performs nonparametric survival analysis for interval-censored data. Default weight 
function will be used, this is the generalised log-rank test with constant weights over time.
4.2.7.3
Subgroup analyses
Subgroup analyses will be conducted to assess consistency of treatment effect across potential 
or expected prognostic factors, including the baseline stratification factors determined from 
the eCRF data. 
The interaction between treatment and subgroup will be assessed by fitting an unstratified Cox 
model with the two main effects; treatment and subgroup, with the interaction term for 
treatment by subgroup.
Patients with missing data for subgroups will not be included in the subgroup analysis.
Hazard ratios will not be presented for any subgroup levels with less than 5 events in either 
treatment arm. The HAZARDRATIO statement in the PHREG procedure in SAS will only
include levels with at least 5 events in both treatment arms.
For example: subgroup analysis for BRCA gene name has 3 levels
-
BRCA1
-
BRCA2
-
BRCA1/2
If subgroup levels for BRCA1 and BRCA2 have at least 5 events in both treatment arms, and 
there are less than 5 events in either one of the BRCA1/2 treatment arms then the patients 
associated with subgroup BRCA1/2 will still be included in the analysis as the level provides 
valuable information, however the hazard ratio will not be generated.
The following subgroups are of primary interest:
!
Neoadjuvant chemotherapy; adjuvant chemotherapy
This will be determined from the response to the variable “Intent” (prior neo-/adjuvant 
chemotherapy for primary breast cancer page) on the eCRF at randomisation. 
Note: a patient should only have either prior adjuvant chemotherapy or prior neoadjuvant 
chemotherapy and no patient should have received both. Patients for whom it is not possible 
to determine their chemotherapy “intent” from the CRF, will be categorised according to how 
they were randomised.

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Prior chemotherapy will be coded for the analysis as follows
∀
0= Prior neoadjuvant chemotherapy
∀
1= Prior adjuvant chemotherapy
!
Prior platinum therapy for current breast cancer (Yes; No)
This will be determined from the WHODrug coded term associated with response to the 
variable “Treatment name” (prior neo-/adjuvant chemotherapy for primary breast cancer page) 
on the eCRF at randomisation. If the coded term is ‘Platinum compound, the patients will be 
considered a “Yes”. Otherwise, they will be considered a “No”.
Prior platinum therapy will be coded for the analysis as follows
∀
0= No 
∀
1= Yes
!
Hormone receptor status ( ER and/or PgR positive /HER2 negative ; TNBC)
ER status will be determined from the response to “ER status” and PgR status will be 
determined from the response to “PgR status” (local laboratory page; hormone receptor status 
section) on the eCRF at randomisation.
∀
0= ER and/or PgR positive/HER2 negative
∀
1= TNBC
!
BRCA mutation type (BRCA1, BRCA2 or BRCA1/2 both) 
This will be determined from the BRCA mutation type based on central 
 data.
∀
0=BRCA1
∀
1=BRCA2
∀
2=BRCA1/2 both
!
Hormone receptor status by prior chemotherapy setting 
∀
0= ER and/or PgR positive with neoadjuvant chemotherapy
∀
1= ER and/or PgR positive with adjuvant chemotherapy
∀
2= ER and PgR negative with neoadjuvant chemotherapy

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∀
3= ER and PgR negative with adjuvant chemotherapy
!
BRCA status by prior platinum therapy setting
∀
0=BRCA1 with prior platinum therapy for current breast cancer
∀
1=BRCA1 with no prior platinum therapy for current breast cancer
∀
2=BRCA2 with prior platinum therapy for current breast cancer
∀
3=BRCA2 with no prior platinum therapy for current breast cancer
∀
4=BRCA1/2 both with prior platinum therapy for current breast cancer
∀
5=BRCA1/2 both with no prior platinum therapy for current breast cancer
The following additional subgroups will also be analysed to assess consistency in treatment 
effect across a broader set of baseline characteristics known before start of study medication:
!
Type of prior Neoadjuvant/Adjuvant chemotherapy (anthracycline ; taxane ; 
anthracycline plus taxane)
This will be determined from the WHODrug coded term associated with response to 
“Treatment name” from the prior neo-/adjuvant chemotherapy for primary breast cancer page 
on the eCRF at randomisation. The following therapies will be considered to each category
∀
0= Prior anthracycline alone
∀
1=Prior taxane alone
∀
2= Prior anthracycline and taxane 
!
Type of breast surgery prior to randomisation (breast conservation ; unilateral 
mastectomy ; bilateral mastectomy)
This will be determined from the response to “Type of surgery” (Breast cancer surgery page; 
primary breast cancer surgery section) on the eCRF at randomisation. 
∀
0= Breast conservation defined as Partial mastectomy / Breast Quadrantectomy 
/ Breast Segmentectomy / Breast Lumpectomy and Breast re-excision of 
margins
∀
1= unilateral mastectomy defined as Modified radical mastectomy, Radical 
mastectomy (Halsted) or Simple mastectomy 
∀
2= bilateral mastectomy defined as Bilateral Mastectomy

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!
Have both ovaries been removed? (Yes; No)
This will be determined from the Procedures page on the eCRF and will only include ovarian 
surgeries prior to the first dose of study medication. Note: if the number of patients with local 
mastectomy/ oophorectomy or bilateral mastectomy/ oophorectomy is low then local and 
bilateral may be combined into one category.
∀
0= not bilateral oophorectomy
∀
1= bilateral oophorectomy
!
Axillary nodal status at surgery prior to randomisation: (Positive or negative for the 
TNBC, adjuvant patients only)
This will be determined from the response to “Axillary sentinel node biopsy” (breast cancer 
surgery page; sentinel node sampling section) on the eCRF at randomisation.
∀
0= node negative
∀
1= node positive
!
CPS+EG score at baseline (2, 3 or 4 ; 5 or 6 for the post neoadjuvant group only)
This will be derived from the responses to “CPS &EG Score” on the Breast Cancer History 
Form. These scores are checked by data management.
∀
0= CPS+EG score of 2, 3 or 4
∀
1= CPS+EG score of 5 or 6
!
Age at randomisation (<50; 50-64; ≥ 65)
This will be determined from “AGE at randomisation” which is derived in the database using 
the patient’s date of birth (informed consent and demography page). The following categories
may be revised after consideration of the distribution of ages when recruitment has been 
completed.
∀
0= Age < 50 years
∀
1= Age 50 - 64 years
∀
2= Age ≥65 years
!
Race (White, Black/African-American, Asian and Other [Native Hawaiian/Pacific 
Islander or American Indian/Alaska Native or Others])

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This will be determined from the response to “Race” (informed consent and demography 
page) on the eCRF at Randomisation. Note: from the study schedule (Table 2) that Race data 
will be collected unless not allowed by local regulations.
∀
0= White
∀
1= Black/African-American
∀
3=Asian
∀
4=Other
!
Ethnicity (Hispanic or Latino; Not Hispanic or Latino; Not known, not recorded or 
refused)
This will be determined from the response to “Ethnicity” (informed consent and demography 
page) on the eCRF at Randomisation. Note: from the study schedule (Table 2) that Ethnicity
data will be collected unless not allowed by local regulations.
∀
0= Hispanic or Latino
∀
1= Not Hispanic or Latino
∀
2=Not known, not recorded or refused
!
Jewish descent (Ashkenazi Jewish descent or not of Ashkenazi Jewish descent)
This will be determined from the response to question on Jewish descent (informed consent 
and demography page) on the eCRF at Randomisation.
∀
0= Not of Ashkenazi Jewish descent
∀
1= Yes, of Ashkenazi Jewish descent
!
Sponsor (AZ; NRG)
This will be determined from the centre number.
∀
0 = AstraZeneca (AZ)
∀
1 = NRG
!
Geographic region 
-
0= North America (Canada, United States of America)

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-
1= South America (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala,  
Mexico, Panama, Peru, Philippines, Puerto Rico, Uruguay, Venezuela)
-
2= Europe (Austria, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, 
Estonia, Finland, France, Georgia, Germany, Great Britain, Greece, Hungary, 
Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, 
Poland, Portugal, Romania, Russian Federation, Serbia and Montenegro, 
Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine)
-
3= Asia Pacific and South Africa (Afghanistan, Australia, China, Hong Kong, 
India, Indonesia, Israel, Japan, Malaysia, New Zealand, South Korea, 
Singapore, South Africa, Taiwan, Thailand, Vietnam)
Other baseline variables may also be assessed if there is clinical justification.
To avoid potential problems with non-proportionality in the covariates, the HRs (olaparib: 
placebo) and profile likelihood CIs for the treatment effect will be calculated from a Cox 
proportional hazards model (using the Efron approach for handling ties) for each level of the 
subgroup. The model will include factors for treatment group and subgroup and the treatment-
by-subgroup interaction. All patients with non-missing subgroup data will be included in the 
model. However, HR/CI estimates from the model will only be displayed in categories with 
sufficient number of events available (at least 5 events in both treatment groups). For 
subgroups with too few events we will only display the number of patients and number (%) of 
events. 
For subgroups with sufficient number of events, we will display all stats including the HR/CI 
estimates from the model in a table. In addition, the HRs and 95% CIs will be presented on a 
forest plot including the HR and 95% CI from the overall population (using the primary 
analysis). The p-value for interaction TRT*SUBG will also be presented, to be assessed at a 
10% level for the purpose of hypothesis generation.
No adjustment to the significance level for testing subgroups will be made since all these 
subgroup analyses will be considered exploratory. The results would be used as supportive 
data for the primary analysis of IDFS based on all randomised patients.
For each subgroup, a Kaplan-Meier plot of IDFS, with tick marks to identify censored 
observations, will be presented by treatment group and summaries of the IDFS survival 
probabilities for each treatment will also be produced.
4.2.7.4
Analysis of interactions
The presence of quantitative interactions will be assessed by means of an overall global 
interaction test. This will be performed in the overall population by comparing the fit of a Cox 
proportional hazards model including treatment, all covariates (including stratification factors
as derived from the eCRF data), and all covariate-by-treatment interaction terms, with one that 
excludes the interaction terms and will be assessed at the 2-sided 10% significance level.

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Plausible covariates include only the stratification factors, therefore the full model fitted will 
include the 3 stratification factors and treatment as main effects, and the two way interactions 
between each stratification factor and treatment. 
If a covariate does not have at least 20 events per level (of the covariate) it will be included as 
a covariate in the model, but the covariate-by-treatment interaction term will be omitted. If the 
fit of the model is not significantly improved then it will be concluded that overall the 
treatment effect is consistent across the subgroups.
If the global interaction test is found to be statistically significant, an attempt to determine the 
cause and type of interaction will be made. Stepwise backwards selection will be performed 
on the full model, whereby (using a 10% level throughout) the least significant interaction 
terms are removed one-by-one and any newly significant interactions re-included until a final 
model is reached where all included interactions are significant and all excluded interactions 
are non-significant. Throughout this process all main effects will be included in the model 
regardless of whether the corresponding interaction term is still present. This approach will 
identify the factors that independently alter the treatment effect and prevent identification of 
multiple correlated interactions.
Any quantitative interactions identified using this procedure will then be tested to rule out any 
qualitative interaction using the approach of Gail and Simon 1985. This will be done using 
SAS macro %GailSimon (Appendix D).
4.2.8
Overall survival (OS) and Distant disease free survival (DDFS)
OS and DDFS will be analysed at the time of the IDFS analysis as per the multiple testing 
procedure (MTP) outlined in Section 4.2.6 and will use the same methodology and model as 
described above for the primary analysis of IDFS. The same pooling strategy as defined above 
for the IDFS end-point will be applied separately to the OS and DDFS end-points. Unadjusted 
analyses will also be done as a sensitivity analysis for OS and DDFS.
If applicable, a sensitivity analysis will be performed for DDFS and OS using the same model 
as described above for IDFS but based on all randomised patients confirmed to have gBRCA
mutations by the central test. This analysis is only required if the analysis population differs 
from the primary ITT population (i.e. if any randomised patient is not confirmed to have a 
gBRCA mutation by the central test).
If the results of ER and PgR status from the local and central labs differ in >5% of randomised 
patients, then the stratified log-rank analysis will be performed for DDFS and OS using the 
central lab result to determine the HR status stratification factor and compared with the main 
OS/DDFS analysis result.
Subgroup analyses will also be conducted for DDFS and OS based on the same subgroups 
described above for IDFS. DDFS and OS will be analysed at the time of the primary analysis 
for IDFS.

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The final OS analysis will be conducted once the trial follow up is complete (i.e. 15 years 
from first patient randomised assuming recruitment of 5 years). 
In addition another analysis will be performed half way between the primary IDFS analysis 
and the final overall survival analysis (estimated around 10 years from first patient 
randomised but timings will be driven by the primary IDFS analysis once known). At this 
time point both DDFS and OS will be analysed and some alpha will be reserved for formal 
hypothesis testing. IDFS may also be updated if more information is available but this would 
be considered a supportive update of the primary analysis and no alpha will be reserved for 
IDFS.
For details on alpha spend and how this will be allocated across the planned analyses see 
Section 5.
4.2.9
Contralateral invasive breast cancer, contralateral non-invasive breast cancer,
new primary ovarian cancer, primary fallopian tube cancer and new primary 
peritoneal cancer
The incidence of contralateral invasive breast cancer, contralateral non-invasive breast cancer, 
new primary ovarian cancer, new primary fallopian tube cancer and new primary peritoneal 
cancer will each be considered separately and be defined as the number and percentage of 
patients with documented evidence of contralateral invasive breast cancer, contralateral non-
invasive breast cancer (contralateral DCIS), new primary ovarian cancer, new primary 
fallopian tube cancer and new primary peritoneal cancer regardless of when this occurs (i.e. 
does not need to be their first recurrence event).
The incidence of new contralateral breast cancer (invasive and non-invasive), new primary 
ovarian cancer, new fallopian tube cancer and new primary peritoneal cancer will be presented
by randomised treatment group for the ITT population.
In addition, a table summarising all reported new cancers (i.e. not just breast, ovarian, 
fallopian tube or peritoneal cancers) will also be produced.
As described in Section 3.1.4, patients who have had a bilateral mastectomy prior to 
randomisation will be excluded from the analysis of new contralateral breast cancers (invasive 
and non-invasive) and patients who have had both ovaries removed prior to randomisation 
will be excluded from the analysis of new ovarian cancers and patients who have had their 
fallopian tubes removed prior to randomisation will be excluded from the analysis of new 
fallopian tube cancers. Males will be excluded from analyses of new primary ovarian, new 
primary fallopian and new primary peritoneal cancers.
The cumulative incidence of new primary contralateral invasive breast, new primary 
contralateral non-invasive invasive breast, new primary ovarian cancer, new primary fallopian 
tube cancer and new primary peritoneal cancer will be compared between treatment groups 
using competing risk analysis (Gray test, Fine and Gray 1999). Death will be considered a 
competing risk for each endpoint. In addition, bilateral mastectomy after randomisation will 

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be a competing risk for the contralateral breast cancer analyses, and bilateral oophorectomy 
after randomisation will be a competing risk for the new primary ovarian cancers analysis and 
removal of the fallopian tubes will be a competing risk for the new primary fallopian tube 
cancer analysis. Hazard ratios and 95% confidence intervals from competing risks regression 
analyses (Fine and Gray 1999) adjusted for randomised treatment group and the stratification 
factors will also be presented.
The same pooling strategy as defined above for IDFS, OS and DDFS end-points will be 
applied separately to each of new cancers endpoints. Unadjusted analyses will also be done as 
a sensitivity analysis for new cancers end points.
The Gray test and Fine and Gray models, not previously implemented in SAS, are now
implemented in version 9.4.
-
The data derivation requirements are similar to those of a traditional survival analysis, 
with “survival time” calculated as the time from randomisation to the occurrence of an 
event (or, here one of two or more possible events) or censored at the time of analysis 
if the event has not yet occurred. The key difference is a status variable which labels 
distinct codes for different causes of failure and a distinct code for censored 
observations. 
-
Cumulative incidence estimates will be plotted by treatment arm, for both the cause of 
interest and the competing risk(s). CI estimates are generated using the ODS option 
CIFPLOT in SAS 9.4.
-
Proportional hazards model for the subdistribution of the competing risk, Fine and 
Gray models, will include the treatment arm and stratification factors and will be fitted 
using the ‘/ eventcode = #’ option in the model statement of PHREG function in 
SAS9.4 to represent the event of interest (i.e. the new primary).
-
The model will be stratified according to the pooling strategy.
-
As with the proportional hazards model, tests will be performed to assess whether the 
Fine and Gray model is actually a reasonable fit to the data.
-
The competing risk cumulative estimates will be presented for the 1st, 2nd and 3rd
percentiles. The CIF estimates are generated using the OUTCIF option. 
4.2.10
Analysis of patient reported outcomes
PRO consent
In the US patients must consent specifically to collection of PRO data, the main study 
agreement is considered PRO consent for RoW.
4.2.10.1
Hypotheses and objectives
The hypotheses and measurement strategy focus on the fact that patients in the trial will be 
starting with significant decrements in HRQoL and high rates of symptoms at study entry 
(baseline) due to previous chemotherapy and local treatments (surgery with or without 

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radiation therapy). Therefore, the following hypotheses are proposed based on the expected 
toxicities of olaparib.
Primary PRO hypothesis
Patients receiving olaparib may experience greater fatigue severity during treatment than those 
receiving placebo as measured by the FACIT-Fatigue scale at 6 and 12 months after 
randomisation.
Secondary PRO hypotheses
!
Patients receiving olaparib may experience greater GI symptoms (nausea/vomiting,
diarrhoea and pain) severity during treatment than those receiving placebo as measured at 
6 and 12 months after randomisation but no difference expected by 24 months after 
randomisation.
!
There will be no difference in fatigue post discontinuation of study treatment as measured 
at 18 and 24 months. 
!
There will be no difference in QOL between the two treatment arms as measured by the 
global health status/QOL score and other functional sub-scales from the EORTC QLQ-
C30 at 6, 12, 18 and 24 months after randomisation and patients will demonstrate 
improvements in functioning over time.
Primary PRO objective 
To determine the effect of olaparib on patient-reported fatigue at 6 and 12 months after 
randomisation as measured by the FACIT-Fatigue symptoms questionnaire.
Secondary PRO objectives 
!
To determine the effect of olaparib on patient-reported GI symptoms (nausea, vomiting 
and diarrhoea) over time at 6, 12, 18 and 24 months as measured by the EORTC QLQ-
C30 scale.
!
To determine the effect of olaparib on patient reported fatigue over time at 6, 12, 18 and 
24 months as measured by the FACIT-Fatigue questionnaire.
!
To determine if there will be a difference in QOL between the two treatment groups over 
time as measured by the 2 item global health status/QOL score of the EORTC QLQ-C30 
scale at 6, 12, 18 and 24 months and assess if patients demonstrate improvement in scores 
over time.
!
To examine and compare the effect of olaparib over time on different functional sub scale 
scores as measured by the EORTC QLQ-C30 and assess if patients demonstrate 
improvement in functioning over time, with particular interest in the physical and 
emotional sub scales.

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4.2.10.2
Administration of patient-completed questionnaire
Time points for administration
The QOL questionnaires will be administered at the following time points:
!
Baseline: Prior to randomisation after the consent form has been signed and eligibility 
confirmed.
!
Following randomisation at 6 months, 12 months, 18 months and 24 months.
Administration instructions
After baseline, the QoL form will be administered at follow-up visits, so that when a follow-
up visit is delayed, completion of the questionnaire may also be delayed. Patients who 
experience disease recurrence or diagnosis of a second primary cancer will not be expected to 
continue with the PRO assessments. Patients who discontinue study drug for other reasons 
will be expected to continue the PRO assessments per protocol schedule. Patients who never 
initiate study medication should not continue to complete PRO assessments. If a patient 
declines to complete a scheduled PRO assessment or if the questionnaire is not completed for 
any other reason (and cannot be completed by phone or mail), a Quality of Life Missing Data 
form should be submitted by the institution instead.
4.2.10.3
Statistical considerations for patient reported outcomes
Statistical analyses
Primary PRO endpoint – Fatigue
For the primary hypothesis, the composite fatigue score (FACIT-Fatigue questionnaire) 
measured at 6 and 12 months after randomisation will be compared between the two treatment 
arms using a mixed model for repeated measures analysis (MMRM) with adjustment for the 
corresponding baseline measurement. Separate analyses will be done for patients who have 
received prior neoadjuvant chemotherapy and patients who have received standard post-
surgical adjuvant chemotherapy. Separate analyses are preferable because the timing of 
chemotherapy is expected to impact the fatigue outcome directly. Each comparison will be 
performed at the significance level of 0.05. No multiple comparisons adjustment will be 
employed since these outcomes evaluate the toxicity of the study treatment.
To further assess the effect of olaparib on fatigue over time (study treatment period and the 
year following) the composite fatigue score (FACIT-Fatigue questionnaire) measured at 6, 12, 
18 and 24 months after randomisation will be compared between the two treatment arms using 
a mixed model for repeated measures (MMRM) analysis of all of the post baseline scores.
Separate MMRM analyses will be done for patients who have received prior neoadjuvant 
chemotherapy and patients who have received standard post-surgical adjuvant chemotherapy. 
Further subgroup analysis by geographical region will be done if there are treatment 
differences at the higher level.

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The model response variable will be average change from baseline and will include factors for 
treatment, visit and treatment by visit interaction, as well as covariates for baseline score and 
the baseline score by visit interaction. The treatment by visit interaction will remain in the 
model regardless of significance. Restricted maximum likelihood (REML) estimation will be 
used. The adjusted mean change from baseline estimates for each treatment arm, difference in 
the adjusted mean change from baseline estimates between the arms and corresponding 
confidence intervals will be presented by time point. Plots of the adjusted means changes (and 
corresponding confidence intervals) over time will also be presented. 
An unstructured covariance matrix will be used to model the within-subject error and the 
Kenward-Roger approximation will be used to estimate the degrees of freedom. 
If the fit of the unstructured covariance structure fails to converge, the following covariance 
structures will be tried in order until convergence is reached: toeplitz with heterogeneity, 
autoregressive with heterogeneity, toeplitz, and autoregressive.
Because this trial is being conducted internationally, responses to patient reported outcomes 
may be influenced by differences between country/language categories 
Therefore, a subgroup MMRM analysis will be conducted for fatigue to assess consistency of 
treatment effect across geographic region (same categories as specified in Section 0). Separate 
MMRM analyses will be done for patients who have received prior neoadjuvant 
chemotherapy and patients who have received standard post-surgical adjuvant chemotherapy.
Adjustment for previous treatment exposures may also be considered as part of the secondary 
analyses. The following may be considered (by adding as a factor to the MMRM detailed 
above); previous radiation (yes vs. no), type of previous chemotherapy (anthracycline vs. 
taxane vs. both), previous platinum therapy (yes vs. no) and type of surgery (breast conserving 
vs. mastectomy).
As part of the secondary analyses, presence of treatment by hormone receptor status 
interaction will be investigated. Separate analyses will be performed for patients who have 
received prior neoadjuvant chemotherapy and patients who have received adjuvant 
chemotherapy. Each comparison will be performed at the significance level of 0.05. If the test 
is found to be statistically significant, the results of the treatment comparison will be presented 
by hormone receptor status
Secondary PRO endpoints
A secondary analysis based on GI symptoms (nausea/ vomiting, diarrhoea and pain) from the 
EORTC QLQ-C30 symptom scale will be performed using the same MMRM model described 
above. Separate analyses will be done for patients who have received prior neoadjuvant 
chemotherapy and patients who have received standard post-surgical adjuvant chemotherapy.
The adjusted mean change from baseline estimates for each treatment arm, difference in the 
adjusted mean change from baseline estimates between the arms and corresponding 

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confidence intervals will be presented by visit. Plots of the adjusted means changes (and 
corresponding confidence intervals) over time will also be presented for nausea, vomiting and 
diarrhoea.
To assess if there are any difference in HRQoL, the 2 item global health status/QOL score 
assessed by EORTC QLQ-30 measured at 6, 12, 18 and 24 months after randomisation will be 
compared between the two treatment arms using the same MMRM model described above. 
Separate analyses will be done for patients who have received prior neoadjuvant 
chemotherapy and patients who have received standard post-surgical adjuvant chemotherapy.
Plots of the adjusted means changes (and corresponding confidence intervals) over time will 
also be produced for the global health status/QOL score.
In addition, the 5 multi-item functional scales of the EORTC QLQ-C30 will be analysed using 
the MMRM model described above with particular interest in the emotional and physical 
subscales. Plots of the adjusted means changes (and corresponding confidence intervals) over 
time will also be produced.
All secondary analyses are considered exploratory and therefore no adjustments for 
multiplicity will be made. For each comparison, p-values (along with CIs) will be generated to 
help aid interpretation of the results using a nominal significance level of 0.05 (2-sided).
Sample size consideration for PRO endpoints
We assume that half of triple negative patients and a quarter of hormone receptor positive 
patients will have received neoadjuvant chemotherapy and we anticipate that 95% of patients 
enrolled in the trial will complete the HRQoL instrument. In addition, adjusting downward to 
allow for 20% of missing data at the 12 months assessment point, we expect that data from 
633 neoadjuvant and 735 adjuvant patients will be available (assuming that 15% of the total 
1800 enrolled patients are ER and/or PgR positive/HER2 negative). These will be sufficient to 
provide statistical power of 93% and 96% correspondingly to detect a difference of 3 points 
on the FACIT-Fatigue scale score between treatment groups assuming a standard deviation of 
10.9 (Cella et al 2002) (estimated SD of mean baseline score) and controlling α-level at 0.05.
A collection of PROs and QOL from all patients enrolled in the main trial will give us 
sufficient statistical power to detect important differences between the two treatment groups.
Missing PRO data
If data for individual items are missing, imputation will be done according to the following: if 
less than 50% of the subscale items were missing (e.g. at most 2 of 5 items), the subscale 
score based on the non-missing items will be divided by the number of non-missing items and 
multiplied by the total number of items on the subscale. If at least 50% of the items are 
missing, that subscale will be treated as missing (not evaluable). If the scale is a single-item 
measure, a missing value will automatically be defined as ‘Non-Evaluable’.
A certain amount of missing data is expected. The information from patients with missing data 
will be reviewed in order to determine whether data analytic procedures are likely to be 

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biased. Patients with missing data will be reviewed for imbalances in factors such as trial arm, 
treatment adherence, institution, and reason for non-adherence. When QOL data are missing at 
a particular time point, data from prior time points will be reviewed in order to investigate 
whether missing status was preceded by a significant change in QOL scores. In addition, we 
will investigate whether missing item status is related to other scores on the same 
questionnaire.
If there is no evidence from this review for dependence of the missingness mechanism on 
covariates or prior QoL scores, the data will be analysed assuming the data are missing at 
random (MAR). 
If, on the other hand, the MAR assumption appears implausible, we will undertake to develop 
an appropriate analytic strategy to control for the potential bias and, if possible, to impute the 
missing values taking account of apparent dependencies in the data, for example by multiple 
imputation by chained equations. We will also present sensitivity analyses based on varying 
assumptions about the missing-data mechanism.
4.2.11
Pharmacokinetic analysis
The sample bioanalysis will be performed by 
 and will be the responsibility of the 
clinical pharmacology scientist at AstraZeneca. The creation of a dataset suitable for non-
linear mixed effects modelling (NONMEM) will be the responsibility of the AstraZeneca 
programmer and pharmacometrician. The NONMEM analysis will be the responsibility of the 
pharmacometrician and clinical pharmacology scientist at AstraZeneca. The plasma 
concentration summary and data listings will be the responsibility of Frontier Science.
A modelling analysis plan (MAP) will describe the population PK modelling objectives and 
approach. The plasma concentration-time data will be analysed (by NONMEM) in order to 
evaluate the pharmacokinetic characteristics of olaparib, quantify variability in the PK, 
identify demographic or pathophysiological covariates, which may explain the observed 
variability and explore exposure-response relationships to be reported outside of the CSR.
The olaparib plasma concentration data obtained from the samples collected in this study will 
be summarised and listed for the CSR but these data may be pooled with data from other 
studies in order to perform a population PK analysis. The PK/pharmacodynamic modelling 
methodology, results and conclusions will be reported in a separate PK/pharmacodynamic 
modelling report.
All plasma concentration data received will be presented in data listings based on the Full 
Analysis Set. A plasma concentration summary of the five samples taken on visit 4, Day 29 
will be presented for patients in the PK analysis set, as defined in Section 2.1. Data from 
patients excluded from the PK analysis set and the reasons for exclusion from the PK analysis
will be included in the data listings, but not in the summary. Extra measurements (such as 
unscheduled or repeat assessments) will also be excluded from the summary table but will be 
included in patient listings.

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!
AEs leading to permanent discontinuation of olaparib, causally related to olaparib/placebo
!
SAEs leading to permanent discontinuation
!
AEs leading to dose reductions
!
AEs leading to dose interruptions
!
AEs leading to dose reductions and interruptions
!
AEs of special interest 
An overall summary of the number and percentage of patients in each category will be 
presented, as will an overall summary of the number of episodes in each category. In addition, 
a truncated adverse event table of most common AEs, showing all events that occur in at least 
5% of patients in any treatment arm will be summarised by preferred term, by decreasing 
frequency. This cut-off may be modified after review of the data.
Each AE event rate (per 1000 patient years) will also be summarised by preferred term within 
each system organ class. For each preferred term, the event rate will be presented and will be 
defined as the number of patients with that AE divided by the sum of the duration of therapy 
(for patients without the event) and the time to the AE (for patients with the event) in each 
group multiplied by 1000.
AEs will be assigned CTCAE grades (National cancer institute (NCI) CTCAE version 4.0) 
and summaries of the number and percentage of patients will be provided by maximum 
reported CTCAE grade, system organ class, preferred term and actual treatment group. 
Fluctuations observed in CTCAE grades during study will be listed.
In addition, adverse events with outcome of death, serious adverse events, adverse events 
leading to discontinuation of treatment and adverse events causally related to olaparib/placebo 
will be listed. 
A summary of deaths will be provided with number and percentage of patients by actual 
treatment group, categorised as:
!
Primary cause of death 
!
Time to death from last dose
!
<=30 days
!
>30 days
A corresponding listing will also be produced. 
Summary of long-term tolerability
To assess long-term tolerability, provided that there are a sufficient number of patients with 
events to warrant it, prevalence plots, life table plots and cumulative incidence plots will be 
presented for each of nausea, vomiting, anaemia, neutropenia, thrombocytopenia, and fatigue 
and asthenia, provided there are ≥ 10 events, see table below for preferred terms to identify 
the AE.

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Table 8
AEs for summary of long term tolerability
AE
Preferred terms
Nausea
Nausea
Vomiting
Vomiting
Anaemia
Anaemia, Haemoglobin decreased, Haematocrit decreased, Red 
blood cell count decreased, Erythropenia, Anaemia macrocytic, 
Normochromic anaemia, Normochromic normocytic anaemia, 
Normocytic anaemia
Neutropenia
Febrile neutropenia, Granulocyte count decreased, 
Granulocytopenia, Neutropenia, Neutropenic infection, Neutropenic 
sepsis, Neutrophil count decreased, Idiopathic neutropenia, 
Agranulocytosis
Thrombocytopenia
Platelet count decreased, Platelet production decreased, 
Thrombocytopenia, Plateletcrit decreased
Fatigue & asthenia
fatigue and asthenia
A prevalence plot provides information on the extent to which the events may be an ongoing 
burden to patients. The prevalence at time t after first dose of study treatment is calculated as 
the number of patients experiencing the event divided by the number of patients receiving 
study treatment or in safety follow-up at time t; generally, t is categorised by each day after 
dosing. The prevalence is plotted over time split by treatment arm. Multiple occurrences of the 
same event are considered for each patient but a patient is only counted in the numerator 
whilst they are experiencing one of the occurrences of the event. 
For each AE, median time to first onset of the AE will be presented in patients in the Safety 
Analysis Set by actual treatment group. Patients who did not experience the AE will be 
censored at the end of their safety follow-up. Summary tables of time to first onset for each 
AE will also be produced (e.g. 1-28 days, 29-56 days, 57-84 days, 85-112 days, >112 days).
Median duration of the AE will be presented in patients who experienced each AE.
Median time to first occurrence is calculated using Kaplan-Meier. Patients who do not 
experience the event are censored at the end of the survival at either the end of safety follow-
up or at data cut-off if they are still in follow-up at data cut-off. The ODS options ‘Quartiles’ 
from PROC LIFETEST can be used to identify the median time to first occurrence.
Duration of first adverse event is defined as end date - start date + 1. If there is no end date 
recorded then the end of safety follow-up or (if they are still in follow-up) the data cut-off will 

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replace the end date. The median duration will be calculated including the first occurrence of 
the AE per patient across all the patients that experience the adverse event.
Number of patients with a first event that has a resolution is the count of the patients with first 
event where the adverse event outcome = ‘Resolved’.
Summary statistics for time to first occurrence are calculated only for patients who experience 
the adverse event, summary statistics include; n, mean, median, min, and max. 
A life table plot will be used to describe the time to onset of the event and specifically when 
patients are at most risk of first experiencing the event. The hazard, or in other words, the 
probability of having an AE in a specified time period (e.g. 0-1 months, 1-3 months, 3-6 
months, etc.) given that the patient reaches that time period without having an event will be 
plotted for each time period split by treatment.  
A cumulative incidence plot, which is a plot of the raw cumulative incidence and cumulative 
incidence function over time, will be produced with the treatment arms presented on separate 
plots. The raw cumulative incidence will be the actual probability that a patient will have 
experienced their first occurrence of the event by a given time point. The cumulative 
incidence function will estimate the cumulative incidence if the data cut-off had not been 
imposed and all patients had completed safety follow-up. The raw cumulative incidence is 
derived by calculating the number of subject events occurring up to a given month, divided by 
the number of patients still taking study medication at that month.
A summary of AESI occurring > 30days post treatment will also be included.
Laboratory assessments
Box-plots of absolute values and change from baseline for continuous laboratory assessments 
will be presented, with AZ project defined reference ranges indicated. For all continuous key 
laboratory parameter assessments, absolute value, change from baseline and percentage 
change from baseline will be summarised using descriptive statistics at each scheduled 
assessment time by actual treatment group. For categorical laboratory assessments, shift from 
baseline will be summarised using frequency and proportion at each scheduled assessment 
time by actual treatment group.
Shift tables for laboratory values by worst common toxicity criteria (CTC) grade will be 
produced, and for specific parameters separate shift tables indicating hyper- and hypo-
directionality of change will be created. For parameters with no CTCAE grading, shift tables 
from baseline to worst value on-treatment will be provided (i.e. on-treatment is defined as data 
collected up until the last dose of olaparib/placebo). Shift tables for appropriate urinalysis 
values by worst grade may be also provided as appropriate. 
Summary of Hy’s law
Hy’s law: Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 3x Upper 
Limit of Normal (ULN) together with Total Bilirubin (TBL) ≥ 2xULN.

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Potential Hy’s law: AST or ALT ≥ 3x ULN together with TBL ≥ 2xULN at any point during 
the study following the start of study medication irrespective of an increase in Alkaline 
Phosphatase (ALP).
For Hy’s law and Potential Hy’s law the elevation in transaminases must precede or be 
coincident with (i.e. on the same day) the elevation in TBL, but there is no specified 
timeframe within which the elevations in transaminases and TBL must occur.
Maximum on treatment ALT and AST by maximum total bilirubin for assessing Hy’s Law 
criteria will be summarised.
An eDISH plot of maximum alanine aminotransferase (ALT) versus maximum total bilirubin, 
both expressed as multiples of upper limit of normal (ULN), will be produced. The eDISH
plot will be repeated for maximum aspartate aminotransferase (AST) versus maximum total 
bilirubin.  
Liver biochemistry test results over time for patients meeting Potential Hy’s law criteria with 
elevated ALT or AST, and elevated total bilirubin (at any time) will be plotted.
Individual subject data will be presented for subjects with potential Hy’s Law.
Clinically significant laboratory results will be flagged and listed. Reference ranges will also 
be listed. All laboratory summaries and listings will be presented by actual treatment group.
Vital signs
Box plots for absolute values and change from baseline in systolic blood pressure (SBP), 
diastolic blood pressure (DBP), heart rate and body temperature will be produced. Vital signs 
(SBP, DBP, heart rate and body temperature) will be summarised over time in terms of 
absolute values and changes from baseline at each scheduled measurement by actual treatment 
group. Height, weight and vital signs data at baseline will be summarised in baseline 
characteristics summaries by planned treatment group. 
ECGs
Overall evaluation of ECG at baseline will be summarised by planned treatment. The results 
will be classified as normal or abnormal with abnormal having sub-categories of “clinically 
significant” and “not clinically significant”. Any clinically significant ECG assessments on 
whilst on study treatment will be listed.
4.2.14
Treatment exposure
The following summaries related to study treatment will be produced for the Safety 
Analysis Set by treatment received:
!
Total intended exposure of olaparib/placebo.
!
Actual exposure of olaparib/placebo.

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!
Number of days on 300 mg olaparib/placebo bd. = actual exposure for the dose assigned.
!
Reasons for dose reductions, dose interruptions, and dose reduction & interruption of 
olaparib/placebo. Dose reductions and dose interruptions will be based on investigator 
initiated dosing decisions. Dose interruptions/reductions due to “Subject non-compliance” 
will be omitted from these summaries.
!
Number of dose interruptions of olaparib/placebo that last for a period of three days or 
more.
!
PID and RDI of olaparib/placebo (entire intended treatment period). 
4.2.15
Imputation for Missing/Partial Dates
Data management will query all missing or partial fields in the eCRF, however it is expected 
that some queries will not be resolved. To limit the impact on the analyses and reporting, 
some imputations will be applied if dates relating to adverse events, concomitant medication 
or efficacy events are partial or missing (see Table 9 below). For AE and concomitant 
medications, imputation methods will be used on partially missing or wholly missing start or 
end dates to decide if an observation is treatment emergent.
Imputed dates will not be displayed in listings and duration of AE/Medication will not be 
calculated for imputed dates. The partial date imputation will follow ADaM conventions 
which populates the numeric date variables with the imputed date and adds a flag variable to 
the dataset that indicates the level of imputation. 
Table 9
Imputation for missing or partial dates
Field
Missing 
element(s)
Rule
Start Date for 
AE/Concomitant 
Medication
Any
Ensure that the new imputed date is not after the end 
date* of the AE or Medication or after the data cut-
off date.
*provided there is more information known.
Day
If month and year same as month and year of first 
dose of study drug then impute first dose date, else 
impute first day of the month
Day and 
month
If year same as year of first dose of study drug then 
impute first dose date, else impute 1st January
Day, month 
and year
Impute first dose date unless it is after the end date in 
which case impute the 1st January of the same year as 
the end date

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End Date for 
AE/Concomitant 
Medication
Any
Ensure that the new imputed date is not before the 
start date (including imputed start date) of the AE or 
Medication or after the data cut-off date.
Day
If month and year same as month and year of last 
dose of study drug then impute last dose date, else 
impute the last day of the month
Day and 
month
If year same as year of last dose date then impute last 
dose date, else impute 31st December
Day, month
and year
Check if AE/Medication is still ongoing and when it 
started in relation to study drug. (1) If ongoing flag is 
missing, assume AE/Medication is still being taken 
and do not impute, (2) If AE/Medication has stopped 
and start date is prior to first dose date then impute 
first dose date (3) If AE/Medication has stopped and 
start date is on or after first dose date then impute last 
dose date
Date of death
Day
If month and year same as month and year of date of 
last contact (see Section 3.1.2), then impute date of 
last contact, else impute first day of the month.
Day and 
month
No imputation
Day, month 
and year
No imputation
Recurrences and 
second primary 
malignancies
Day
If month and year same as month and year of date of 
last disease evaluation (see Section 3.1.1), then 
impute date of last disease evaluation, else impute 
first day of the month.
Day and 
month
No imputation
Day, month 
and year
No imputation

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4.2.16
Central pathology result timepoint for analysis
Central pathology review samples are analysed by IEO, the results from these samples are 
used in the summary of patients’ central receptor status (ER, PgR and HER2) and in central 
pathology review sensitivity analysis which is triggered by the difference between local and 
central HR status.
Adjuvant patients are expected to have an archival tumour sample, neoadjuvant patients can 
have both archival and post neoadjuvant, however both are not compulsory (as of protocol 
version 2), thus resulting in some patients having central pathology review results for more 
than one timepoint. For the purpose of the CSR analysis specified in the SAP it is key to have 
a single central pathology review result for ER, PgR and HER2.
The following process was agreed by the study team (reference memorandum) for identifying 
the single central pathology review result to be used in the summary tables and in the 
sensitivity analysis using the central pathology results.
!
When a patient has central pathology review results for more than one timepoint, sites 
were asked which sample was used to determine eligibility. If sites can confirm which of 
the archival or surgical sample was used then this is used as the central pathology result.
!
In the case that the site cannot provide an answer the earliest sample date will be used to 
identify which result should be used for the analyses.
The scenario could also occur where more than one specimen is taken at a single time point, 
resulting in a single accession number and more than one sample result.
!
If the samples provide the same result for HR and HER2 then the central pathology result 
will be the combined result.
!
If the central result samples are not the same then accession number and sample that has 
the same HR result as the eCRF will be identified and used as the central result.
Appendix E contains the specification for identification of a patients central pathology review 
result.
5.
INTERIM ANALYSES
A superiority interim analysis of IDFS will occur when half the events required for the final 
analysis (165 events) have been observed in the first 900 patients (50% of the planned total 
recruitment). This provides a cohort of patients with a similar level of maturity that is planned 
for the final analysis. The interim analysis is predicted to be October 2019 (80% confidence 
interval: March 2019 - August 2020).
If the interim analysis is triggered then all analyses, with the exception of the exploratory 
analyses will be generated. 

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The same pooling strategy as defined above (section 4.2.7.1) for the primary analyses will be 
applied at the interim. Two populations will be analysed at the interim analysis based on the 
analysis methods described in Section 4.2 for IDFS:
1
Primary: ITT population (all patients randomised, estimated 254 events (80% confidence 
interval: 226 - 289).
2
Supportive: Mature cohort population (first 900 patients randomised, 165 events 
anticipated).
The inclusion of a mature cohort population at the interim provides confidence that any 
observed treatment effect from the interim ITT population is maintained with longer-term 
follow up. It is anticipated, based on the data available at the time of the protocol amendment 
(version 5) and on the assumed recruitment and event rate, that the interim analysis will occur 
approx. 5.3 years after the first patient is randomised and that all patients will have been 
randomised. The mean follow-up is expected to be 27 months in the ITT set, and 34 months in 
the mature cohort.
Evidence of superiority for IDFS would only be determined at the interim if the results from 
both analysis populations provide evidence of a sustainable clinically relevant treatment 
effect. More specifically, the result in the ITT population would need to have met the 
statistical threshold defined below. When the statistical threshold is met in the ITT population, 
the result in the mature cohort (i.e. HR) would need to be of a similar magnitude, such that the 
IDMC would consider it supportive of the ITT result. This will have added confidence in the 
result in the ITT population. Statistical significance is not required for the mature cohort 
population. This analysis will be regarded as supportive, based on a cohort of patients with 
longer term follow up. This to aid interpretation of the result in the ITT population based on 
interim data. Other outcome measures such as 3 year IDFS rate will also be presented to aid 
the interpretation of the HRs (particularly in the case where the assumption of proportional 
hazards may not hold). KM plots will also be produced for IDFS.
The test mass alpha for IDFS (1 sided 2.5%) will be split between the final and the interim
analysis using a bespoke spending function where a fixed significance level will be assigned 
at the interim and the remaining significance level assigned to the final analysis, taking 
account of correlation (Stone 2009). A 2-sided significance level of 0.005 will be assigned to 
the interim analysis so that a highly significant and clinically relevant result will need to be 
observed to declare superiority on IDFS. As an illustration, if 70% of the total required 330 
IDFS events have occurred in the ITT population at the interim then the observed HR would 
need to be <0.701 for superiority to be declared based on p<0.005 and the HR in the mature 
cohort would need to be supportive of the ITT result. The significance level for the final IDFS 
analysis would be 0.0493 in this example.
If the null hypothesis for IDFS is rejected at the interim for the ITT population then secondary 
endpoints (DDFS and OS) will be tested based on the MTP procedure outlined in 
Section 4.2.2 using the significance levels provided in Table 10. If IDFS is not significant at 

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the interim, DDFS and OS will not be tested at the IDFS interim and the significance level 
allocated to the IDFS interim for DDFS and OS will not be allocated to later time points.
Similar to IDFS, a bespoke spending function will be applied to the secondary endpoints OS 
and DDFS where a fixed significance level will be assigned to each analysis time point and 
the remaining significance level assigned to the final analysis time point controlling the 
overall type 1 error at the pre-specified alpha amount (Stone 2009). Provided the last analysis 
is known in advance of the penultimate one then the remaining alpha can be split to ensure 
that some alpha is always reserved for the final analysis. This approach allows flexibility in 
the number of analyses while appropriately controlling the overall type 1 error. Three analyses 
are planned for DDFS and four for OS for which some alpha will be reserved for significance 
testing. If additional analyses are required beyond the planned analyses and some alpha is still 
available for testing then any remaining alpha can be further split to strongly control the type 
1 error (based on process described above). If no alpha remains then the additional analyses 
will be considered supportive updates of the already conducted analyses. 
Given the split in alpha between DDFS and OS, if OS is significant based on the assigned 
significance level then the alpha assigned to OS will be recycled to DDFS and split across the 
planned analyses (and vice versa if DDFS is significant alpha for DDFS will be recycled to 
OS and split across analyses). The recycled alpha will be split based on the ratio of the 
originally assigned alpha split. For example if the original alpha allocation was split 1/3 for 
each analysis time point then the recycled alpha would also be split 1/3 across each analysis 
time point. For example, at the first interim analysis, assume IDFS is statistically significant 
and the secondary endpoint OS is also statistically significant. The significance level for 
testing DDFS is therefore 0.005 + (alpha assigned to OS recycled to DDFS and split across the 
planned analyses), i.e. 0.005 + (1% * 0.005/0.04 = 0.00125) = 0.00625, or alternatively 
thought of as 0.005 * 5/4.
Secondary endpoints will be assessed based on the ITT population. Table 10 shows the 
different 2-sided significance levels that will be applied to the primary and secondary 
endpoints across the planned analyses, as well as the total alpha spend for each endpoint.
Note: the significance level for the final analyses of each endpoint will be calculated using the 
relevant correlation. This is based on the actual number of events for each analysis, the 
previous alpha spend and the total allocated alpha for that endpoint.
The significance level for the final analyses of each endpoint can be calculated using the 
software package EAST by selecting the ‘boundary family p-value (HP)’ option. The 
following information is required:
!
Total allocated alpha for the endpoint being analysed
!
Significance levels used for all previous analyses
!
Proportion of events at each previous analysis (derived as actual number of events at 
analysis time point divided by total number of events at final analysis time point) 

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Table 10
Summary of 2-sided significance levels and total alpha spend across the 
endpoints and analyses
Endpoints
Estimated 
timings from 
FSI [1]
Interim 
analysis
5.3 years
Final IDFS 
analysis 
6.5 years 
DDFS and OS 
analysis
10 years 
Final OS 
analysis
15 years
Significance 
level
Significance level
Significance 
level
Significance 
level
Total alpha 
spend (2-
sided)
IDFS
0.005
TBC [2]
N/A
N/A
5%
If IDFS is  statistically significant and alpha is not recycled between secondary endpoints at the analysis
[3]
DDFS
0.005
0.02
TBC*
N/A
4%
OS
0.002
0.003
0.004
TBC*
1%
If IDFS is statistically significant and alpha is recycled between secondary endpoints at the analysis [4]
DDFS
0.00625 
0.025
TBC*
N/A
5%
OS
0.01
0.015
0.02
TBC*
5%
[1] FSI: first subject randomised
[2] TBC: to be calculated; significance level to be calculated once relevant correlation based on the actual 
number of events for each analysis is known taking account of previous alpha spend and total allocated 
alpha
[3] i.e. both OS and DDFS rejected or accepted
[4] If the null is rejected for OS and not for DDFS then alpha will be recycled to DDFS from OS. If the null is 
rejected for DDFS and not for OS then alpha will be recycled to OS from DDFS.
The IDMC will review the data from the interim analysis. The boundaries defined by the 
interim p-values for efficacy will be used as guidelines by the IDMC along with all other 
relevant trial information, including the safety data, to decide if it is appropriate to make a 
recommendation other than that to continue the trial as planned. 
Simultaneously to the interim analysis for superiority, an assessment of futility will be 
performed. This futility assessment will be based on the probability of eventually showing 
statistical significance for the primary endpoint when the final number of IDFS events 
(n=330) is reached (Lachin 2005). The determination of this probability will be conditional on 
the observed data in the ITT population at the time of the interim analysis for superiority and 
on the assumed hazard ratio for the alternative hypothesis (IDFS HR=0.7). If the probability is 
less than 0.1, the IDMC will consider the option of declaring futility.
This study will use an IDMC whose members include therapeutic area experts and statisticians 
who are not employed by AstraZeneca and do not have any major conflict of interest. BIG, 

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AstraZeneca, CTEP and NSABP will jointly select members of the IDMC and the IDMC will 
report their recommendations to the steering committee.
The IDMC will meet approximately every 6 months and will review ongoing study progress 
including safety and, when appropriate, efficacy data. They will also review the data presented 
at the time of the protocol-defined interim analysis. The IDMC will have the ability to 
recommend suspension of enrolment if safety concerns are identified at any of the six monthly 
assessments. At the interim analysis, both efficacy and safety will be reviewed and trial 
recommendations will be based on the totality of the data. The IDMC can recommend changes 
to the trial, including stopping of the trial, if they have concerns over the benefit risk profile 
for olaparib.
Reports for the IDMC will be prepared by an Independent Statistical Centre (ISC) and will be 
presented to the IDMC in closed session. Following review of data, the IDMC will make a 
recommendation regarding the future conduct of the trial to the steering committee. The 
IDMC recommendation will not contain any unblinded information or any information related 
to treatment outcomes of the trial. A separate IDMC Charter will be developed defining the 
responsibilities and procedures for the IDMC.
6.
CHANGES OF ANALYSIS FROM PROTOCOL
The analyses described here are based on the protocol edition 5, dated 18 May 2018, with file 
name “OlympiA Protocol v5 (Amendment) effective 18-May-2018.pdf”.
6.1
Censoring of patients not at risk for disease evaluated
The protocol states the following with regards to censoring for IDFS, DDFS and OS
-
Patients who have not had a recorded IDFS event at the time of the analysis will be 
censored at the date of their last disease evaluation.
-
Any patient not known to have died at the time of analysis will be censored based on 
the last recorded date on which the patient was known to be alive.
-
Patients who do not have documented evidence of DDFS at the time of the analysis of 
DDFS will be censored at the date of their last clinical examination (i.e. last physical 
exam or radiological evaluation).
The study team identified that patients had been randomised that are not at risk for the 
endpoint evaluated in OlympiA. The decision by the SST and wider AZ team was to censor 
these patients at 0.5 days (rationale for 0.5 days is discussed previously).
This process would leave the information in the database as submitted by the investigator 
unchanged and define the ITT population as all randomized patients. 
We specify above that observations from patients who are retrospectively (after 
randomization) discovered to have had an IDFS event prior to randomization will be 
considered in the data analysis as censored 0.5 days this assures that the baseline number at 

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risk on the Kaplan-Meier curves matches the number in the ITT population reported in the 
CONSORT diagram).
This approach has been widely used for the analyses of adjuvant breast cancer trials by 
cooperative groups for decades, this approach does not require a protocol amendment, just a 
specification in the SAP about how data will be handled for the analysis. The 3 scenarios 
under which patients are censored at 0.5 days are:
!
Patients who have had an event prior to randomisation.
!
Patients who were identified as inadvertent randomisations (i.e. patient was randomised 
and the site noticed afterwards that they should not have been randomised, they have had 
no follow-up nor did they receive treatment).
!
Patients who have withdrawn consent, received no treatment, and will not be providing 
any follow-up data.

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7.
REFERENCES
Anderson et al 2004
Anderson P.K, Hansen, M.G., Klein, J.P. Regression analysis of restricted mean survival time 
based on Pseudo-observations. Lifetime Data Anal. 2004; 10(4): 335-350.
Bernhard et al 2007
Bernhard J, Zahrieh D, Castiglione-Gertsch M, et al. Adjuvant chemotherapy followed by 
goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and 
quality of life in premenopausal patients—the International Breast Cancer Study Group Trial 
VIII. J Clin Oncol 2007; 25:263-270.
Cella et al 2002
Cella D, Eton DT, Lai JS, et al. Combining anchor and distribution-based methods to derive 
minimal clinically important differences on the Functional Assessment of Cancer Therapy 
(FACT) anemia and fatigue scales. J Pain Symptom Manage 2002; 24(6):547-561
Collett 2003
Collett, D. (2003) Modeling Survival Data in Medical Research. 2nd Edition, Chapman @ 
Hall/CRS A CRC Press Company, London, New York, Washington, D.C.
Cortazar et al 2014
Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical 
benefit in breast cancer: the CTNeoBC pooled analysis. The Lancet, 2014: 384(9938), pp.164-
172.
Dent et al 2007
Dent R, Trudeau M, Pritchard K, Hanna W, Kahn H, Sawka C, Lickley L, Rawlinson E, Sun 
P, Narod S. Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence. 
Clinical Cancer Research 2007; 13(15), 4429-4434.
Dmitrenko et al 2005
Dmitrienko A, Molenberghs G, Chuang-Stein C, Offen W. 2005 Analysis of Clinical Trials 
Using SAS: A Practical Guide. Cary, NC. SAS Insitute Inc
Fine and Gray 1999
Fine, J. and Gray, R. A Proportional Hazards Model for the Subdistribution of a Competing 
Risk, Journal of the American Statistical Association, 1999: 94, 496–509.
Gail and Simon 1985
Gail M, Simon R. Testing for qualitative interactions between treatment effects and patient 
subsets. Biometrics 1985;41:361-72.
Glimm et al 2009
Glimm, E., Maurer, W., and Bretz, F. Hierarchical testing of multiple endpoints in group-
sequential trials. Statistics in Medicine 2009;29, 219–228.

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Date 12th  June 2019
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Grambsch and Therneau 1994
Grambsch P, and Therneau T. Proportional hazards tests and diagnostics based on weighted 
residuals. Biometrika 1994; 81: 515-26.
Hudis et al 2007
Hudis CA, William E, Barlow JP, Costantino RJ, Gray KI, Pritchard J-AW, et al. Proposal for 
Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials: The 
STEEP System. J Clin Oncol 2007;25(15):2127-32.
Jeruss et al 2008
Jeruss SJ, Mittendorf EA et al. Combined Use of Clinical and Pathologic Staging Variables to 
Define Outcomes for Breast Cancer Patients Treated With Neoadjuvant Therapy. J Clin Oncol 
2008; J Clin Oncol 26:246-252.
Lachin 2005
Lachin, J. M. (2005). A review of methods for futility stopping based on conditional power. 
Statist. Med., 24: 2747–2764. Statist Med 24:2747-2764
Mittendorf et al 2011
Mittendorf EA, Jeruss JS, Tucker SL, Kolli A, Newman LA, Gonzalez-Angulo AM, Buchholz 
TA, Sahin AS, Cormier JN, Buzdar AU, Hortobagyi GN, Hunt KH. Validation of a Novel 
Staging System for Disease-Specific Survival in Patients With Breast Cancer Treated With 
Neoadjuvant Chemotherapy. Journal of Clinical Oncology 2011 vol 29 no 15 may.
Personal communication with B-38 protocol statistician, Joseph Costantino, 12/01/2015, 
Email.
Pintilie M.  
Competing risks: A practical perspective.  Wiley.
Robins and Tsiatis 1991
Robins JM, Tsiatis AA. Correcting for noncompliance in randomized trials using rank 
preserving structural failure time models. Communications in Statistics - Theory and Methods 
1991; 20:2609-2631.
Stone 2009
A Stone. The application of bespoke spending functions in group-sequential designs and the 
effect of delayed treatment switching in survival trials. Pharmaceutical statistics 2009; 9, 151-
161
Swain et al 2013
Swain S, Tang G, Geyer C, Rastogi P, Atkins J, Donnellan P, Fehrenbacher L, Azar C, 
Robidoux A, Polikoff J, Brufsky A, Biggs D, Levine E, Zapas J, Provencher L, Northfelt D, 
Paik S, Costantino J, Mamounas E, Wolmark N. Definitive Results of a Phase III Adjuvant 
Trial Comparing Three Chemotherapy Regimens in Women With Operable, Node-Positive 

Statistical Analysis Plan
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Breast Cancer: The NSABP B-38 Trial. Journal of Clinical Oncology 2013; 31(26), 3197-
3204.
Therneau and Grambsch 2000
Therneau T and Grambsch P.Modeling Survival Data: Extending the Cox Model. Springer, 
New York. 2000; ISBN 0-387-98784-3.
Therneau 2015
Therneau T. A Package for Survival Analysis in S. version 2.38, 2015. https://CRAN.R-
project.org/package=survival.
Yellen et al 1997
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E. Measuring fatigue and other 
anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) 
measurement system. J Pain Symptom Manage 1997; 13(2), 63-74.
Clinicaltrials.gov, (2015). A Study of Palbociclib in Addition to Standard Endocrine 
Treatment in Hormone Receptor Positive Her2 Normal Patients With Residual Disease After 
Neoadjuvant Chemotherapy and Surgery - Full Text View - ClinicalTrials.gov. [online] 
Available at: https://clinicaltrials.gov/ct2/show/NCT01864746?term=PENELOPE&rank=2 
[Accessed 9 Apr. 2015].

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8.
APPENDIX A
Background
To support the addition of the ER+ cohort in protocol version 4 a simulation study was 
undertaken with the objective to predict accrual of events and therefore the timing of the 
interim and primary analyses. 
The simulation study included relevant operating characteristics for the anticipated possible 
proportions enrolled in each of the 4 subgroups, survival was modelled by piecewise 
exponential distribution for which annualized hazard according to the respective subgroups 
were taken from the most recent published data (Dent et al 2007, Cortazar et al 2014, B 38 
data, and GBG data).
Following the observation of lower than anticipated event rate, it was clear that the published 
data used for the simulations were too pessimistic with respect to event rates for the Triple 
negative BRCA carrier population that would be recruited into OlympiA since 2014.
Further predictions were run using the current data (extract date 10Nov2017) and applying 
AZ’s ‘Shiny’ oncology event prediction R package. A survival model assuming a Weibull 
distribution was fitted to the previous study data and used to predict future survival times. 
Whilst the simulation study simulated over varying proportions enrolled in each sub group, by 
using the current data, the predictions were based on 1153 patients of whom 15% were ER+ 
and the ratio of Adjuvant to Neoadjuvant was roughly 1:1. An 8% drop-out rate for the first 12 
months, not previously included, was incorporated based on the rate observed so far. The 
program predicted the future enrolment to 1800 based on the recent observed enrolment rate.
Given the predictions for timing of the interim and primary analysis it was decided to increase 
the sample size to 1800 and for the power to remain at 90%. Because the event rate was lower
than anticipated rather than higher than anticipated, the restriction to have a minimum 2 year 
follow-up after the last patient enrolled could be removed. Patient enrolment would continue 
about one year longer than originally anticipated and more patients would be enrolled, thus 
providing an increase in the number of patient years of follow-up at the time of primary 
analysis even without the 2 year minimum follow-up criteria.

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9.
APPENDIX B
As described in Section 3.3.2, treatment exposure of olaparib/placebo will be defined as 
follows:
!
Total (or intended) exposure = last dose date – first dose date + 1
!
Actual exposure = intended exposure – total duration of dose interruptions, where intended 
exposure will be calculated as above.
!
Number of days on 300 mg olaparib/placebo bd. = actual exposure for the dose assigned.
Table 11
Example of patient who permanently discontinued during a dose 
interruption, documented on eCRF page “Administration of 
Olaparib/Placebo”
Start date
Stop date
Total daily 
dose (mg)
Was 
dose 
reduced?
Reason dose 
reduced
Was treatment 
interrupted?
Reason for 
interruption
23/01/2015
14/02/2015
600
No
No
15/02/2015
28/02/2015
600
No
Yes
Adverse 
Event
02/03/2015
13/03/2015
500
Yes
Adverse 
Event
No
14/03/2015
15/03/2015
500
No
Yes
Adverse 
Event
When treatment stops (on 15/03/2015 in this example), the investigator will then complete the 
“Treatment completion” page of the eCRF. The stop date recorded on the administration page 
should correspond with the date of last dose on the completion page. In this example, the 
reason for non-completion (discontinuation of the study drug) should be recorded as adverse
event, matching the reason for interruption. 
However, there is an exception where reason for interruption can differ from reason for non-
completion. When a patient experiences an AE and interrupts treatment, the reason for 
interruption should be recorded as AE. If the patient does not restart treatment due to disease 
progression, resulting in discontinuation of treatment, the reason for non-completion should be 
recorded as progression of disease. Therefore, the reason of interruption does not match the 
reason of non-completion. 

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10.
APPENDIX C
Figure 4
Examples of dose intensity for olaparib/placebo dosing
Patients 1-4 progressed on Day 15, so the intended dose through to progression was 14 * 300 
mg * 2 of olaparib/placebo = 8400 mg. 
All 4 patients received less treatment due to: 
!
Missed/forgotten doses (Patient 1) 
!
Dose reduction and early stopping (Patient 2) 
!
Dose interruption (Patient 3) 
!
Early stopping (Patient 4)
Patient 1:
RDI = PID = ((12 * 300 mg * 2) + (2 * 300 mg))/ 8400 mg = 93%
Patient 2:
RDI = ((7 * 300 mg * 2) + (4 * 150 mg * 2))/ (11 * 300 mg * 2) mg = 82%
PID = ((7 * 300 mg * 2) + (4 * 150 mg * 2))/ 8400 mg = 64%
Patient 3:
PID = (7 * 300 mg * 2)/ 8400 mg = 50%
RDI = (7 * 300 mg * 2)/4200 mg = 100 %
Patient 4:
RDI = ((5 * 300 mg * 2) + (1 * 300 mg))/ (6 * 300 mg * 2) = 92%
PID = ((5 * 300 mg * 2) + (1 * 300 mg))/ 8400 mg = 39%
Due to the eCRF design, the actual cumulative dose does not capture all missed or forgotten 
doses within an individual day. This will be recorded as if the patient took a full daily dose, 
which could lead to an overestimation of RDI and PID.
RDI
PID
progression/death/censored
D   treatment discontinuation
15
X
300 mg olaparib/placebo b.i.d.
82%
64%
Patient 2
X
150 mg olaparib/placebo b.i d.
100%
50%
92%
39%
93%
Patient 1
3
11
12
Patient 3
X
300 mg olaparib/placebo o d.
Patient 4
X
D
13
14
D
0 mg olaparib/placebo
X
Study day
7
8
9
10
4
5
6
1
2

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11.
APPENDIX D
GailSimon macro (Dmitrenko et al 2005)

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12.
APPENDIX E
Derivation of central pathology review result for analysis.
Central pathology review specification:
12.1
Purpose
The detail contained in this appendix aims to specify the process for identifying the central 
pathology review result for each patient, depending on what we receive from IEO. 
The study team agreed the following;
1
If the site cannot identify which time point the patient was randomised under then the 
earliest should be used.
2
If there are duplicate accession numbers for a time point that has been identified as the 
one randomised under then the following algorithm will be applied.
o
If all the results are the same then the combined result is used
o
If the results are not the same then the sample in which the HR status is the 
same as the HR status reported on the eCRF (i.e. the local result) is used.
See HR status memo (AZ document)  for further details.
12.2
Derivation of Central pathology results from the data provided by 
IEO
Table 12
IEO data HR status (ER & PgR) and HER2 results (See DTS)
Variable name
Variable label
Valid values
ER
% of estrogen receptor expression
0-100,NA 
PgR
% of progesterone receptor 
expression
0-100,NA 
HER2 IHC
HER2 score
0,1,2,3,NA 
HER2 IHC %
% of HER2 expression
0-100,NA
HER2 FISH
HER2 Fish result
amplified, not amplified, NA 

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Table 13
Derivations for classifications of HR status and HER2 results for CSR
Classification presented in the CSR
Derivation from IEO data
ER status
Positive, Negative, Missing
ER positive is defined as >=1% ER 
receptor expression
PgR status
Positive, Negative, Missing
PgR positive is defined as >=1% PgR 
receptor expression
HR status
Positive, Negative, Missing
HR positive is defined as >=1% ER or PgR 
receptor expression. 
HER2 FISH results
Amplified, Not amplified, Not 
assessable,, Missing
Amplified = Amplified
Not amplified = Not amplified
NA = Not assessable
‘’ = Missing
HER2 IHC results
0, 1+ ,2+ , 3+, NA, Missing
0 = 0
1 = 1+
2 = 2+
3 = 3+
NA = NA
. = Missing
12.3
Identification of Patient’s central pathology result
The classification of each result from IEO will be done before identifying which sample 
should be used for the central result.
12.3.1
Considerations
For the RoW patients the CRF data will be available for each accession number comprising;
Accession number, date sample taken, and time point either archival or surgical (see 
Blood/Tumour Samples (Screening)).

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For the US patients CRF data is only available for archival samples and not necessarily all 
archival samples. The time point archival or surgical sample was taken will be available from 
IEO for the US patients as this is sent directly from NRG to IEO.
12.3.2
Identifying the central pathology result
This flow will be followed to programmatically identify the result to be used in the central 
pathology analysis.
1
Only one central time point result for an individual patient in the IEO data
1.1
No duplicates accession numbers for that result
Use this accession number to identify the result by central testing 
1.2
Duplicate accession number for that result
Follow point 2 above (section 1.1) to identify the result by central testing
2
More than one central time point result for an individual patient in the IEO data
2.1
RoW
2.1.1
Site know what time point they were randomised under
2.1.1.1
No duplicate accession numbers for that time point
Use this accession number to identify the result by central testing 
2.1.1.2
Duplicate accession number for that time point
Follow point 2 above (section 1.1) to identify the result by central testing 
2.1.2
Site don’t know what time point they were randomised under
Identify the earliest sample collection date reported on the CRF
2.1.2.1
No duplicate accession numbers for that date
Use this accession number to identify the result by central testing 
2.1.2.2
That date has duplicate accession numbers
Follow point 2 above (section 1.1) to identify the result by central testing 
2.2
US
2.2.1
Site know what time point they were randomised under
2.2.1.1
No duplicate accession numbers for that time point
Use this accession number to identify the result by central testing 
2.2.1.2
Duplicate accession number for that time point
Follow point 2 above (section 1.1) to identify the result by central testing 
2.2.2
Site don’t know what time point they were randomised under
Use the archival time point sample 
2.2.2.1
No duplicate accession numbers for the sample from the archival time point
Use this accession number to identify the result by central testing 
2.2.2.2
The sample from the archival time point has duplicate accession numbers
Follow point 2 above (section 1.1) to identify the result by central testing