A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer Following First Line Platinum Based Chemotherapy.
Phase: PHASE3
Conditions: Newly Diagnosed, Advanced Ovarian Cancer, FIGO Stage III-IV, BRCA Mutation, Complete Response, Partial Response, First Line Platinum Chemotherapy
Sponsor: AstraZeneca



Revised Clinical Study Protocol 
Drug Substance AZD2281 
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GOG Code GOG-3004 
Date 05 November 2021 
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• 
response to first line platinum chemotherapy (clinical complete response or partial 
response) 
 
Patients will be randomised within 8 weeks after their last dose of chemotherapy (last dose is 
the day of the last infusion). 
 
Patients in both treatment arms will have tumour assessments according to RECIST at 
baseline and every 12 weeks (±1 week) up to 3 years (156 weeks) and then every 24 weeks 
(±1 week) relative to date of randomisation, until objective radiological disease progression 
according to RECIST. Five years after the last patient was randomized, patients who have 
completed their study treatment and who continue on study without evidence of disease (i.e., 
continue to have no evidence of disease (NED) or have achieved a complete response (CR) 
while participating in the study) and remain progression free will no longer be required to 
undergo scheduled RECIST assessments. For these patients, further RECIST assessments will 
occur when clinically indicated (e.g. rising CA-125 and/or signs and symptoms suggesting 
PD, according to the investigator’s clinical judgment). 
 
All CT/MRI scans will be sent to an AstraZeneca appointed Clinical Research Organisation 
(CRO) for blinded independent central review. After the primary Progression Free Survival 
(PFS) analysis, central review of scans will no longer be required. 
 
Patients should continue to receive study treatment for up to two years or until objective 
radiological disease progression as per RECIST as assessed by the investigator, whichever is 
earlier, and as long as in the investigator’s opinion they are benefiting from treatment and they 
do not meet any other discontinuation criteria. Patients who continue to have evidence of 
disease that remains stable (i.e., no evidence of disease progression) at two years or those who 
have progressed may continue to receive study treatment if, in the opinion of the investigator, 
it is in the patient’s best interest. However, if at two years the patient has no evidence of 
disease, study treatment should be discontinued. A decision about continuing treatment with 
the investigational product beyond two years should be made after assessing the patient’s 
disease status according to RECIST guidelines at week 108, and/or by assessing the patient’s 
clinical condition. Continuation of treatment beyond week 108, based solely on clinical 
progression, is permissible only after case-by-case discussion with the AZ study physician. 
 
All patients will continue to be assessed for radiological tumour assessments according to the 
study schedule (see Table 1, Table 2, Table 3 and Table 4), until objective radiological disease 
progression, irrespective of their continuation on study treatment. From CSP v5 onwards: 
Study patients who discontinued treatment at two years per protocol with no evidence of 
disease (either NED from baseline or CR achieved while receiving study treatment) and who 
not yet had disease progression will have radiological (RECIST) tumour assessments only 
when clinically indicated e.g. rising CA-125 and/or signs and symptoms suggesting PD, 
according to the investigator’s clinical judgment. 

Revised Clinical Study Protocol 
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Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
28 
 
 
assessment of disease progression by RECIST; however, sensitivity analyses will be 
performed including using the blinded independent central review (BICR) of disease 
progression. 
 
Subgroup analyses will be conducted to assess consistency of treatment effect across potential 
or expected prognostic factors (see Section 12.2.2 for all predefined subgroups). Included will 
be a subgroup analysis by Myriad gBRCA mutation status (gBRCAm status confirmed by 
Myriad test vs gBRCA wildtype (wt) or missing by Myriad gBRCA test). An analysis will not 
be performed if there are too few events available for a meaningful analysis of a particular 
subgroup (i.e., if there are less than 20 events in a subgroup). An initial OS and PFS2 analysis 
will be performed at the same time as the primary analysis of PFS and will use the same 
methodology and model. 
Analyses of time to first subsequent therapy (TFST) and time to second subsequent therapy 
(TSST) will be conducted, using the same methodology as specified for the primary analyses 
of PFS. 
Supportive analyses of time to earliest progression by RECIST or CA-125 or death and TDT 
will be provided, using the same methodology as specified for the primary analyses of PFS, 
however no multiple adjustment will be applied as these are viewed as supportive endpoints. 
 
In order to describe the nature of the benefits of olaparib maintenance treatment, PFS, PFS2, 
TFST, TSST, change from baseline in TOI score and OS will be tested at a 2-sided 
significance level of 5%. However, in order to strongly control the type I error, a multiple 
testing procedure will also be employed where PFS is tested first using the full test mass, 
PFS2 will be tested if the null hypothesis for PFS is rejected, and OS will only be tested if 
statistical significance is shown for PFS and PFS2. 
An interim analysis for PFS2 will be performed at the time of the PFS analysis (approximately 
100 OS events). A further analysis of PFS2 will be performed when the OS data are 
approximately 60% mature. 
 
OS will be tested at the time of the primary analysis of PFS, after approximately 206 OS 
events have occurred (approximately 53% maturity of the 391 patients randomised in SOLO1) 
and after approximately 60% maturity (approximately 235 events/391 patients who were 
randomized in SOLO1). In addition, a descriptive OS analysis will be performed at the 
clinically important timepoint of 7 years post the last subject randomised (LSR) as part of 
global enrolment. 
Exploratory analyses of OS adjusting for impact of subsequent PARP inhibitor trial or 
treatment (or other potentially active investigational agents) may be performed if a sufficient 
proportion of patients switch. Methods such as Rank Preserving Structural Failure Time 
(RPSFT) (Robins et al 1991), Inverse Probability of Censoring Weighting (IPCW) (Robins 
1993) and other methods in development will be explored. The decision to adjust and final 
choice of methods will be based on a blinded review of the data and the plausibility of the 

Revised Clinical Study Protocol 
Drug Substance AZD2281 
Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ............................................................................................................................ 1 
VERSION HISTORY ............................................................................................................... 2 
PROTOCOL SYNOPSIS ........................................................................................................ 20 
TABLE OF CONTENTS ........................................................................................................ 31 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................... 38 
1. 
INTRODUCTION .................................................................................................. 44 
1.1 
Background ............................................................................................................ 44 
1.1.1 
Ovarian cancer and its treatment ............................................................................ 44 
1.1.2 
BRCA mutation positive ovarian cancer ................................................................ 44 
1.1.3 
PARP inhibition as a target for BRCA mutation positive ovarian cancer .............. 45 
1.1.4 
Pre-clinical experience ........................................................................................... 45 
1.1.5 
Toxicology and safety pharmacology summary ..................................................... 45 
1.1.6 
Clinical experience ................................................................................................. 46 
1.2 
Research hypothesis ............................................................................................... 46 
1.3 
Rationale for conducting this study ........................................................................ 46 
1.3.1 
Rationale for Study Design .................................................................................... 47 
1.3.2 
 
1.4 
Benefit/risk and ethical assessment ........................................................................ 49 
2. 
STUDY OBJECTIVES .......................................................................................... 51 
2.1 
Primary objective .................................................................................................... 51 
2.2 
Secondary objectives .............................................................................................. 51 
2.3 
Safety objective ...................................................................................................... 52 
2.4 
Exploratory objectives ............................................................................................ 52 
3. 
STUDY PLAN AND PROCEDURES ................................................................... 53 
3.1 
Overall study design and flow chart ....................................................................... 53 
3.2 
Rationale for study design, doses and control groups ............................................ 74 
4. 
PATIENT SELECTION CRITERIA ...................................................................... 75 
4.1 
Inclusion criteria ..................................................................................................... 75 
4.2 
Exclusion criteria .................................................................................................... 78 
4.3 
Study Conduct Mitigation During Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis .................................................... 81 

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5. 
STUDY CONDUCT .............................................................................................. 81 
5.1 
Restrictions during the study .................................................................................. 81 
5.1.1 
Olaparib and CYP3A4 ............................................................................................ 82 
5.1.2 
Contraception ......................................................................................................... 82 
5.2 
Patient enrolment and randomisation and initiation of investigational 
product .................................................................................................................... 82 
5.2.1 
Procedures for randomisation ................................................................................. 82 
5.3 
Procedures for handling patients incorrectly enrolled or randomised or 
initiated on investigational product ........................................................................ 83 
5.4 
Blinding and procedures for unblinding the study ................................................. 84 
5.4.1 
Methods for ensuring blinding ............................................................................... 84 
5.4.2 
Methods for unblinding the study .......................................................................... 84 
5.5 
Treatments .............................................................................................................. 84 
5.5.1 
Identity of investigational product(s) ..................................................................... 84 
5.5.2 
Doses and treatment regimens ................................................................................ 85 
5.5.2.1 
Olaparib and matching placebo (study treatment) .................................................. 85 
5.5.3 
Labelling ................................................................................................................. 86 
5.5.4 
Storage .................................................................................................................... 86 
5.5.5 
Management of toxicity of study treatment ............................................................ 86 
5.6 
Concomitant and post-study treatment(s) ............................................................... 89 
5.6.1 
Medications that may NOT be administered .......................................................... 90 
5.6.2 
CYP3A4 inhibitors, inducers, and other substrates ................................................ 90 
5.6.3 
Anticoagulant Therapy ........................................................................................... 93 
5.6.4 
Anti-emetics/Anti-diarrhoeals ................................................................................. 93 
5.6.5 
Palliative radiotherapy ............................................................................................ 93 
5.6.6 
Administration of other anti-cancer agents ............................................................ 93 
5.6.7 
Subsequent therapies for cancer ............................................................................. 94 
5.7 
Treatment compliance ............................................................................................ 94 
5.7.1 
Accountability ........................................................................................................ 94 
5.8 
Discontinuation of investigational product ............................................................ 94 
5.8.1 
Procedures for discontinuation of a patient from investigational product .............. 95 
5.9 
Withdrawal from study ........................................................................................... 96 
6. 
COLLECTION OF STUDY VARIABLES ........................................................... 97 
6.1 
Recording of data ................................................................................................... 97 
6.2 
Data collection at enrolment and follow-up ........................................................... 97 
6.2.1 
Enrolment/Screening procedures ........................................................................... 97 
6.2.2 
On study assessments ............................................................................................. 99 
6.2.3 
Follow-up procedures ........................................................................................... 101 
6.2.3.1 
Treatment Discontinuation Visit .......................................................................... 101 

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GOG Code GOG-3004 
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6.2.3.2 
Treatment discontinuation due to objective radiological disease 
progression or any other discontinuation criteria ................................................. 101 
6.2.4 
Follow-up 30 day after last dose of study medication (follow-up visit) ............... 101 
6.2.5 
Survival ................................................................................................................ 102 
6.2.6 
Second Progression .............................................................................................. 102 
6.2.7 
Patient management post primary analysis .......................................................... 103 
6.2.8 
Patient management post final analysis ................................................................ 103 
6.3 
Efficacy ................................................................................................................ 104 
6.3.1 
CT and MRI scans Tumour assessments (modified RECIST 1.1) ....................... 104 
6.3.2 
Tumour Evaluation ............................................................................................... 105 
6.3.3 
Central reading of scans ....................................................................................... 106 
6.4 
Safety .................................................................................................................... 106 
6.4.1 
Definition of adverse events ................................................................................. 106 
6.4.2 
Definitions of serious adverse event ..................................................................... 107 
6.4.3 
Olaparib adverse events of special interest ........................................................... 107 
6.4.4 
Recording of adverse events ................................................................................. 107 
6.4.5 
Reporting of serious adverse events ..................................................................... 112 
6.4.6 
Laboratory safety assessment ............................................................................... 112 
6.4.6.1 
Full haematology assessments for safety; ............................................................ 113 
6.4.6.2 
Coagulation .......................................................................................................... 113 
6.4.6.3 
Biochemistry assessments for safety .................................................................... 113 
6.4.6.4 
Disease specific tumour marker samples (CA-125) ............................................. 114 
6.4.6.5 
Urinalysis .............................................................................................................. 115 
6.4.6.6 
Bone marrow or blood cytogenetic samples ......................................................... 115 
6.4.7 
Physical examination ............................................................................................ 115 
6.4.8 
ECG ...................................................................................................................... 115 
6.4.8.1 
Resting 12-lead ECG ............................................................................................ 115 
6.4.9 
Vital signs ............................................................................................................. 115 
6.4.9.1 
Pulse and blood pressure ...................................................................................... 116 
6.4.9.2 
Body temperature ................................................................................................. 116 
6.4.10 
Other safety assessments – Not applicable ........................................................... 116 
6.4.11 
Serum or urine pregnancy test .............................................................................. 116 
6.5 
Patient reported outcomes (PRO): FACT-O and EQ-5D-5L ............................... 116 
6.5.1 
Administration of PRO questionnaires ................................................................. 116 
6.5.2 
FACT-O ................................................................................................................ 117 
6.5.3 
PRO method or questionnaire for other purposes ................................................ 117 
6.5.4 
EQ-5D-5L ............................................................................................................ 118 
6.6 
Pharmacokinetics – Not Applicable ..................................................................... 118 
6.7 
Biomarkers ........................................................................................................... 118 
6.7.1 
Biomarker samples ............................................................................................... 118 
6.7.2 
Exploratory Biomarker Research on Archival Tumour Samples 
(Mandatory) .......................................................................................................... 119 
6.7.3 
Exploratory Biomarker Research on Tumour Biopsy Samples (Optional) .......... 119 

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GOG Code GOG-3004 
Date 05 November 2021 
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6.8 
Pharmacogenetics ................................................................................................. 120 
6.8.1 
Collection of blood sample for Myriad germline BRCA1 and BRCA2 
testing ................................................................................................................... 120 
6.8.1.1 
Guidance for BRCA testing of patients with known BRCA status ...................... 120 
6.8.1.2 
Guidance for BRCA testing of patients with unknown BRCA status .................. 120 
6.8.2 
 
6.8.3 
Exploratory blood sample for biomarker analysis (e.g. cfDNA) (Optional) ........ 123 
6.8.4 
Collection of pharmacogenetic samples (optional) .............................................. 123 
6.9 
Health economics .................................................................................................. 123 
6.9.1 
Resource Use ........................................................................................................ 123 
7. 
BIOLOGICAL SAMPLING PROCEDURES ..................................................... 123 
7.1 
Volume of blood ................................................................................................... 123 
7.2 
Handling, storage and destruction of biological samples ..................................... 127 
7.2.1 
Pharmacogenetic (optional exploratory) samples ................................................. 127 
7.3 
Labelling and shipment of biohazard samples ..................................................... 127 
7.4 
Chain of custody of biological samples ................................................................ 128 
7.5 
Withdrawal of informed consent for donated biological samples ........................ 128 
8. 
ETHICAL AND REGULATORY REQUIREMENTS ........................................ 129 
8.1 
Ethical conduct of the study ................................................................................. 129 
8.2 
Patient data protection .......................................................................................... 129 
8.3 
Ethics and regulatory review ................................................................................ 129 
8.4 
Informed consent .................................................................................................. 130 
8.5 
Changes to the protocol and informed consent form ........................................... 131 
8.6 
Audits and inspections .......................................................................................... 131 
8.7 
Study and site Closure .......................................................................................... 131 
9. 
STUDY MANAGEMENT BY ASTRAZENECA ............................................... 132 
9.1 
Pre-study activities ............................................................................................... 132 
9.2 
Training of study site personnel ............................................................................ 133 
9.3 
Monitoring of the study ........................................................................................ 133 
9.3.1 
Source data ........................................................................................................... 133 
9.4 
Study agreements .................................................................................................. 133 
9.4.1 
Archiving of study documents .............................................................................. 134 
9.5 
Study timetable and end of study ......................................................................... 134 
10. 
DATA MANAGEMENT BY ASTRAZENECA ................................................. 134 

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GOG Code GOG-3004 
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11. 
EVALUATION AND CALCULATION OF VARIABLES BY 
ASTRAZENECA ................................................................................................. 135 
11.1 
Calculation or derivation of efficacy variable(s) .................................................. 135 
11.1.1 
Progression Free Survival (PFS) .......................................................................... 135 
11.1.2 
Secondary endpoints ............................................................................................. 136 
11.1.2.1 Overall Survival ................................................................................................... 136 
11.1.2.2 Time to earliest progression by RECIST 1.1 or CA-125 or death ....................... 136 
11.1.2.3 Time from randomisation to second progression (PFS2) ..................................... 137 
11.1.2.4 Time to first subsequent therapy or death (TFST) ............................................... 137 
11.1.2.5 Time to second subsequent therapy or death (TSST) ........................................... 137 
11.1.2.6 Time to study treatment discontinuation or death (TDT) ..................................... 138 
11.1.2.7 Best Overall RECIST Response (BoR) ................................................................ 138 
11.2 
Calculation or derivation of safety variable(s) ..................................................... 139 
11.2.1 
Other significant adverse events (OAE) ............................................................... 139 
11.3 
Calculation or derivation of patient reported outcome variables .......................... 139 
11.3.1 
EQ-5D-5L (exploratory analysis) ......................................................................... 141 
11.4 
Calculation or derivation of pharmacokinetic variables – Not Applicable ........... 142 
11.5 
Calculation or derivation of pharmacodynamic variables – Not Applicable ........ 142 
11.6 
Calculation or derivation of pharmacogenetic variables ...................................... 142 
11.7 
Calculation or derivation of resource use ............................................................. 142 
12. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION 
BY ASTRAZENECA ........................................................................................... 142 
12.1 
Description of analysis sets .................................................................................. 142 
12.1.1 
Full analysis set .................................................................................................... 142 
12.1.2 
Safety analysis set ................................................................................................. 143 
12.2 
Methods of statistical analyses ............................................................................. 143 
12.2.1 
Multiplicity strategy for primary and key secondary endpoints ........................... 145 
12.2.2 
Analysis of primary endpoint ............................................................................... 147 
12.2.2.1 Sensitivity Analyses for Primary Endpoint .......................................................... 149 
12.2.3 
Analysis of secondary endpoints .......................................................................... 151 
12.2.3.1 Analysis of PFS2 endpoint ................................................................................... 151 
12.2.3.2 Analysis of OS endpoint ....................................................................................... 151 
12.2.3.3 Analysis of TFST, TSST, TDT endpoints ............................................................ 151 
12.2.3.4 Analysis of time to earliest progression by RECIST 1.1 or CA-125 or 
death ..................................................................................................................... 152 
12.2.3.5 Summary of Best overall RECIST Response (BoR) ............................................ 152 
12.2.3.6 Analysis of PRO endpoints................................................................................... 152 
12.2.3.7 Health State Utility – EQ-5D-5L .......................................................................... 153 
12.2.3.8 Impact of Switching to PARP inhibitors (or other potentially active 
investigational agents) on Overall Survival Analyses .......................................... 153 
12.2.4 
Exploratory endpoints .......................................................................................... 153 

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Study Code D0818C00001 
GOG Code GOG-3004 
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12.2.5 
Interim analyses .................................................................................................... 153 
 
 
12.3 
Determination of sample size ............................................................................... 155 
12.4 
Data monitoring committee .................................................................................. 156 
13. 
MEDICAL EMERGENCIES ............................................................................... 156 
13.1 
Overdose ............................................................................................................... 157 
13.2 
Pregnancy ............................................................................................................. 157 
13.2.1 
Maternal exposure ................................................................................................ 157 
14. 
LIST OF REFERENCES ..................................................................................... 158 
 
 
LIST OF TABLES 
Table 1 
Screening (Visit 1) Study Schedule For Patients with Unknown 
BRCA Mutation Status at Presentation – Complete Parts 1, 2 and 
3:  .......................................................................................................... 62 
Table 2 
Screening (Visit 1) Study Schedule For Patients with Known 
BRCA Mutation Status at Presentation – complete Parts 2 and 3: ........... 65 
Table 3 
Study Schedule – On Study Treatment and Discontinuation .................... 67 
Table 4 
Study Schedule: Follow-up post discontinuation of study treatment ........ 71 
Table 5 
Dose reductions for study treatment ......................................................... 89 
Table 6 
Restricted concomitant medications ......................................................... 90 
Table 7 
Samples for Biomarker Research ............................................................ 118 
Table 8 
Estimated maximum volume of blood to be drawn from each 
patient ...................................................................................................... 125 
Table 9 
Health Related Quality of Life ................................................................ 140 
Table 10 
Health Related Quality of Life : Change rates - overall score. ............... 141 
Table 11 
Summary of Outcome Variables and Analysis Populations .................... 143 
Table 12 
Formal Statistical Analyses to be Conducted and Pre-Planned 
Sensitivity Analyses ................................................................................ 143 
LIST OF FIGURES 
Figure 1 
Overall Study Design Flow Chart ............................................................. 57 

Revised Clinical Study Protocol 
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Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
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Figure 2 
Screening Plan ........................................................................................... 59 
Figure 3 
Study Flow Chart Up to 108 Weeks on Treatment ................................... 60 
Figure 4 
Study Flow Chart At 108 Weeks on Treatment ........................................ 61 
Figure 5 
Flow diagram for patients with known or unknown BRCA 
mutation status ........................................................................................ 122 
Figure 6 
Multiple Testing Procedure..................................................................... 145 
 
 
 
 
LIST OF APPENDICES 
Appendix A 
Signatures – not applicable for CSP edition number 6 as signed 
electronically per current process 
 
Appendix B 
Additional Safety Information 
 
Appendix C 
International Airline Transportation Association (IATA) 6.2 Guidance 
Document 
 
Appendix D 
Actions Required in Cases of Increases in Liver Biochemistry and 
Evaluation of Hy’s Law 
 
Appendix E 
Acceptable Birth Control Methods 
 
Appendix F 
Guidelines for Evaluation of Objective Tumour Response Using Modified 
RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumours) 
 
Appendix G 
Performance Status (ECOG/Karnofsky Scale) 
Appendix H 
Patient Reporting Outcomes (FACT-O and EQ-5D-5L) 
Appendix I 
FIGO Staging 
Appendix J 
Guidance on grading of serous ovarian carcinomas 
 
Appendix K 
Changes Related to Mitigation of Study Disruptions Due to Cases of Civil 
Crisis, Natural Disaster, or Public Health Crisis 
 
Appendix L 
Olaparib Product-Specific Guidance in Relation to the COVID-19 
Pandemic 

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Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
38 
 
 
 
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) 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukaemia 
ANC 
Absolute neutrophil count 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
Baseline 
Refers to the most recent assessment of any variable prior to dosing with 
study treatment 
BD 
Twice daily 
BICR 
Blinded Independent Central Review 
BoR 
Best Overall RECIST Response 
BP 
Blood pressure 
BRCA 
Breast Cancer susceptibility gene 
BRACAnalysis 
Gene sequencing and large rearrangement analysis for Hereditary Breast 
and Ovarian Cancer, registered trademark of Myriad Genetics, Inc 
BRCA mutation or 
BRCAm 
Breast Cancer susceptibility gene mutation (see gBRCA mutation or 
gBRCAm) 
BUN 
Blood urea nitrogen 
CA-125 
Cancer Antigen – 125 
cfDNA 
Circulating free DNA 
CHO 
Chinese hamster ovary 
CI 
Confidence Interval 

Revised Clinical Study Protocol 
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Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
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Abbreviation or 
special term 
Explanation 
 
 
CCR 
Clinical Complete Response. ‘Response’ is used throughout the protocol 
and refers to patients being, in the opinion of the investigator, in clinical 
complete response or partial response on the post-treatment scan. Clinical 
complete response is defined as no evidence of RECIST measurable or 
non-measurable disease on the post-treatment scan and a normal CA-125. 
Partial response is defined as ≥30% reduction in tumour volume 
demonstrated from the start to finish of chemotherapy OR no evidence of 
RECIST measurable disease on the post-treatment scan with a CA-125 
which has not decreased to within the normal range. 
CR 
Complete response 
CRF 
Case Report Form (electronic/paper) 
CRO 
Clinical Research Organisation 
CSA 
Clinical Study Agreement 
CSR 
Clinical Study Report 
CT 
Computed tomography 
CTC / CTCAE 
Common Terminology Criteria for Adverse Event 
CYP450 
Cytochrome P450 (enzyme) 
DAE 
Discontinuation of Investigational Product due to Adverse Event 
DCIS 
Ductal Carcinoma in Situ 
DCO 
Data Cut Off 
DNA 
Deoxyribonucleic acid 
DSB 
Double strand break 
DUS 
Disease under Study 
ECG 
Electrocardiogram 
EC 
Ethics Committee, synonymous to Institutional Review Board (IRB) and 
Independent Ethics Committee (IEC) 
E-code 
Enrolment code (allocated by IVRS/IWRS) 
ECOG 
Eastern Cooperative Oncology Group: A performance status using scales 
and criteria to assess how a patients disease is progressing 
EMA 
European Medicines Agency 
EQ-5D-5L / EQ-5D 
EuroQoL five dimensions, five level (EQ-5D-5L) health state utility index 
EWB 
Emotional well being 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FACT-O 
Functional Assessment of Cancer Therapy – Ovarian: A multidimensional 
questionnaire for patients with ovarian cancer 

Revised Clinical Study Protocol 
Drug Substance AZD2281 
Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
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Abbreviation or 
special term 
Explanation 
 
 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FFPE 
Formalin Fixed Paraffin Embedded 
FIGO 
International Federation of Gynecology and Obstetrics 
FSH 
Follicle stimulating hormone 
FSI 
First Subject In 
FWB 
Functional well being 
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 (Richards et al 2008). 
GBRCA wt 
gBRCA wildtype 
GCIG 
Gynecologic Cancer Intergroup 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony-stimulating factor 
GGT 
Gamma glutamyl transferase 
GMP 
Good Manufacturing Practice 
GOG 
Gynecologic Oncology Group 
Grand 
AZ Global Randomisation system 
Hb 
Haemoglobin 
HCT 
Haematocrit 
HDPE 
High-density polyethylene 
HGSOC 
High-grade serous ovarian cancer 
HIV 
Human Immunodeficiency Virus 
HR 
Hazard Ratio 
HR 
Homologous recombination repair 
HRCT 
High Resolution Computed Tomography 
HRD 
Homologous recombination repair deficiencies 
HRT 
Hormone replacement therapy 
HRQoL 
Health-related Quality of Life 
IATA 
International Air Transport Association 
IB 
Investigator’s brochure 

Revised Clinical Study Protocol 
Drug Substance AZD2281 
Study Code D0818C00001 
GOG Code GOG-3004 
Date 05 November 2021 
41 
 
 
Abbreviation or 
special term 
Explanation 
 
 
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. 
ICR 
Independent Central Review 
ICU 
Intensive Care Unit 
IDMC 
Independent Data Monitoring Committee 
INR 
International Normalised Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intentions to Treat 
IPCW 
Inverse Probability of Censoring Weighting 
IVR System 
Interactive Voice Response System 
IWR System 
Interactive Web Response System 
KM 
Kaplan Meier 
LDH 
Lactic dehydrogenase 
LH 
Luteinizing hormone 
LIMS 
Laboratory Information Management System 
LPLV 
Last Patient Last Visit 
LSR 
MCH 
Last Subject Randomised 
Mean cell haemoglobin 
MCHC 
Mean cell haemoglobin concentration 
MCV 
Mean cell volume 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milli-gram 
MMRM 
Mixed Model for Repeated Measures 
MRI 
Magnetic resonance imaging 
MTP 
Multiple Testing Procedure 
NCI 
National Cancer Institute 
NE 
Not evaluable 
NED 
No Evidence of Disease 

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Abbreviation or 
special term 
Explanation 
 
 
NTL 
Non-target lesions 
OAE 
Other Significant Adverse Event (see definition in Section 11.2.1) 
ORR 
Objective response rates 
OS 
Overall survival 
PARP 
Polyadenosine 5’diphosphoribose [poly (ADP ribose)] polymerisation 
PD 
Progressive disease 
PFS / PFS1 
Progression Free Survival 
PFS2 
Time from randomisation to second progression 
PGx 
Pharmacogenetic research 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
p.o. 
Per os (by mouth, orally) 
PR 
Partial response. ‘Response’ is used throughout the protocol and refers to 
patients being, in the opinion of the investigator, in clinical complete 
response or partial response on the post-treatment scan. Clinical complete 
response is defined as no evidence of RECIST measurable disease on the 
post-treatment scan and a normal CA-125. Partial response is defined as 
≥30% reduction in tumour volume demonstrated from the start to finish of 
chemotherapy OR no evidence of RECIST measurable disease on the post- 
treatment scan with a CA-125 which has not decreased to within the normal 
range. 
PRO 
Patient Reported Outcomes 
PWB 
Physical well being 
QoL 
Quality of Life 
R&D 
Research and Development 
RBC 
Red blood cell 
RECIST 
Response Evaluation Criteria In Solid Tumours. This study will use 
modified RECIST version 1.1 
RI 
Reticulocyte index 
RPSFT 
Rank Preserving Structural Failure Time 
SAE 
Serious adverse event (see definition in Section 6.4.2). 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
SD 
Severe Acute Respiratory Syndrome Coronavirus 2 
Stable disease 

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Abbreviation or 
special term 
Explanation 
 
 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvate Transaminase 
SSB 
Single strand break 
SUSARs 
Suspected Unexpected Serious Adverse Reactions 
SWB 
Social well being 
Study treatment 
Olaparib or matching placebo 
tBRCA mutation or 
tBRCAm 
The term "tBRCA mutation" is used to refer to a somatic tumour 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 (Richards et al 2008). 
TDT 
Time from randomisation to study treatment discontinuation or death 
TFST 
Time from randomisation to first subsequent therapy or death 
TL 
Target lesions 
TOI 
Trial Outcome Index 
TSST 
Time from randomisation to second subsequent therapy or death 
UCL 
Upper Confidence Limit 
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 Ovarian cancer and its treatment 
Ovarian cancer is the fifth most common cause of death from cancer in women (Colombo et al 
2010; NCCN Clinical Practice Guidelines in Oncology). In the United States there are about 
21,550 new cases and 14,600 deaths estimated annually. In the European Community, 
approximately 28,000 new cases of ovarian cancer and approximately 17,000 deaths are 
reported annually, ranking ovarian cancer as the leading cause of death from gynaecological 
cancer. The incidence of ovarian cancer increases with age and is most prevalent in the eighth 
decade of life. More than 70% of the patients are diagnosed with advanced disease and less 
than 40% of women with ovarian cancer are cured (Fleming et al 2009; Jemal et al 2010). 
 
The standard therapy for advanced ovarian cancer consists of radical debulking surgery 
followed by post-operative platinum-based first-line chemotherapy. Since 1996, platinum and 
paclitaxel combination therapy has become the standard-of-care first-line chemotherapy 
regimen (McGuire et al 1996). Worldwide, the use of carboplatin has replaced that of cisplatin 
because of carboplatin’s superior tolerability profile together with equal effectiveness. 
However, the success of this approach is limited and approximately 70% of patients fail to 
achieve complete responses, or eventually relapse, after a varying disease-free interval. 
1.1.2 BRCA mutation positive ovarian cancer 
An important risk factor for ovarian cancer is genetic predisposition with BRCA1 or BRCA2 
mutations (ie, gBRCAm) which account for the majority of hereditary ovarian cancer. If a 
lifetime risk for ovarian cancers among women in the general population is estimated to be 1.4 
percent (14 out of 1,000), a woman with BRCA1 or BRCA2 deleterious mutation has a 
lifetime risk of 15 to 40 percent (150–400 out of 1,000). BRCA mutated ovarian cancer 
patients can also develop ovarian cancer earlier in their life than those without the mutation. 
Deficiency in BRCA ultimately leads to the accumulation of genetic alterations as a result of 
the failure of cells to arrest and repair DNA damage or to undergo apoptosis, resulting in 
tumourigenesis. If all ovarian cancer patients underwent gBRCA testing, current estimates 
indicate that 13% to 14% of the overall ovarian cancer population would have gBRCA1/2 
mutations, and the proportion of patients with gBRCA mutations may be as high as 22% in 
patients with high-grade serous ovarian cancer (HGSOC). In addition, a population of ovarian 
cancer patients whose tumours harbour BRCA1 and BRCA2 mutations that are not detected in 
the germline (~7%) also exist and are defined as somatic BRCA mutations (tBRCAm). 
Patients with BRCA-mutated ovarian cancer currently have identical treatment options as 
sporadic ovarian cancer patients. They seem to have a better prognosis compared with the 
overall relapsed ovarian cancer patient population but the pattern of disease is similar, with 
patients eventually dying from their disease. Ovarian cancer patients with BRCA mutation 

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represent a small, well defined and medically recognised subpopulation for whom, despite the 
potential for personalised healthcare, no targeted treatment currently exists. 
1.1.3 PARP inhibition as a target for BRCA mutation positive ovarian cancer 
Investigators should be familiar with the current olaparib (AZD2281) Investigator Brochure 
(IB). 
Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5’diphosphoribose [poly (ADP 
ribose)] polymerisation (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. 
 
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 (HR). Tumours with HR deficiencies (HRD), such as ovarian cancers in 
patients with 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 HR 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 knock-out models, either as a stand-alone treatment or in combination with established 
chemotherapies. 
 
1.1.4 Pre-clinical experience 
The pre-clinical experience is fully described in the current version of the olaparib IB. 
 
1.1.5 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 
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. 

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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. 
 
1.1.6 Clinical experience 
Clinical experience with olaparib is fully described in the current version of the olaparib IB. 
 
1.2 
Research hypothesis 
Olaparib administered as monotherapy in the maintenance setting improves progression free 
survival compared to placebo in patients with newly diagnosed BRCA mutated high risk 
advanced ovarian cancer who are in clinical complete response or partial response following 
first line platinum-based chemotherapy. 
 
1.3 
Rationale for conducting this study 
Based on the results of a pivotal phase II trial (D0810C00019), investigating olaparib 
maintenance therapy in relapsed ovarian cancer patients AstraZeneca is planning to conduct 
the current phase III trial to investigate the benefit of olaparib as maintenance monotherapy in 
the first line setting in patients with newly diagnosed high risk advanced BRCA mutation 
positive ovarian cancer. The phase II study was conducted with the capsule formulation of 
olaparib. The phase III trial will be conducted with the more patient friendly tablet 
formulation. 
 
Study D0810C00019 is a randomised, double-blind, placebo-controlled study to evaluate 
maintenance treatment with olaparib (capsule formulation) in patients with platinum-sensitive 
relapsed HGSOC who had received ≥2 previous platinum regimens and were in partial or 
complete response following their last platinum-containing regimen. The primary endpoint 
was investigator-assessed PFS. In total, 265 patients were randomised to olaparib 400 mg 
twice daily (136) or placebo (129). The primary analysis was carried out following 153 PFS 
events and demonstrated that maintenance treatment with olaparib led to a significant PFS 
improvement vs placebo [HR 0.35 (95% confidence interval (CI) 0.25 -0.49); p<0.00001] 
(Ledermann et al 2012). A subgroup analysis (pre-specified in the SAP) suggested that 
olaparib may lead to a greater clinical benefit in patients with a known germline BRCAm. 
gBRCAm status was determined retrospectively for all consenting patients (n=166) using 
blood samples taken before randomisation. tBRCAm status was determined from archival 

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tumour samples of 196 patients. Since gBRCA wild-type patients may develop somatic 
tumour BRCA mutations, efficacy analyses were performed by known gBRCA mutation 
status and known total BRCA mutation status. gBRCAm patients had the greatest PFS benefit 
with olaparib maintenance vs placebo (HR, 0.17; 95% CI 0.09-0.31; median: 11.2 vs 4.1 
months; P<0.001). The PFS benefit was consistent when tBRCAm patients were included 
(HR, 0.18; 95% CI 0.11-0.31; median: 11.2 vs 4.3 months; P<0.0001). In an interim analysis 
of OS (58% maturity), OS HRs from the gBRCAm and gBRCAwt subgroups were similar 
(0.85 and 0.84, respectively), however 30% gBRCAm placebo patients received a subsequent 
PARP inhibitor, confounding the OS data in this subgroup. The analysis of all BRCAm 
patients was less confounded and resulted in an OS HR of 0.74 (95% CI 0.46-1.19; median: 
34.9 vs 31.9 m). Olaparib tolerability was similar in BRCAm patients and the overall 
population. 
 
The phase II study D0810C00019 demonstrated the efficacy of olaparib maintenance when 
using the capsule formulation (8 capsules twice daily). A more patient friendly tablet 
formulation (2 tablets twice daily) has been developed and this phase III study will investigate 
the efficacy of the tablet formulation when given as a maintenance therapy to newly 
diagnosed high risk advanced BRCA mutated ovarian cancer patients. The tablet dose of 
olaparib that will be investigated in this study is 300 mg twice daily. This tablet dose has been 
chosen based on data from an ongoing 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 twice daily is considered to 
have similar efficacy in terms of tumour shrinkage in BRCA mutated ovarian cancer patients 
to the 400 mg twice daily capsule together with an acceptable tolerability profile. 
The tolerability profile of the 300 mg twice daily tablet dose in study D0810C00024 was 
considered similar to the 400 mg twice daily capsule formulation. The most common adverse 
events were consistent with the known safety profile of olaparib, namely low grade nausea, 
vomiting, fatigue and anaemia. Further information is provided in the IB. 
 
A preliminary analysis of the effect of food (a light snack) on the pharmacokinetics of 
olaparib tablets was also investigated in study D0810C00024 and preliminary analysis of this 
data suggest that the intake of a light snack does not impact the pharmacokinetics (PK) of 
olaparib. Patients will be allowed to take olaparib tablets with a light snack during the phase 
III study. 
 
The findings from study D0810C00019 are supported by clinical data from over 350 
additional patients with BRCAm ovarian cancer in six other olaparib trials demonstrating 
consistent response rates. 
 
1.3.1 Rationale for Study Design 
The magnitude of PFS benefit demonstrated in patients with gBRCA mutation positive 
ovarian cancer in Study D0810C00019 (median PFS delay of approximately 7 months 
following completion of chemotherapy; (HR, 0.18; 95% CI 0.11-0.31; median: 11.2 vs 4.3 
months; P<0.0001) is considered to be clinically meaningful and robust, with the upper CI of 

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1.4 
Benefit/risk and ethical assessment 
Olaparib in this current study is considered to have a positive benefit-risk profile for the 
treatment of first line BRCA mutated platinum responsive advanced (FIGO Stage III-IV) 
ovarian cancer patients who are considered at high risk of disease progression. 
 
Ovarian cancer is the leading cause of death from gynaecological tumours in the Western 
world. Olaparib has demonstrated a large clinically meaningful prolongation of PFS as a 
maintenance therapy in BRCA mutated platinum responsive patients in the relapsed ovarian 
setting (D0810C00019) and has a tolerability profile that is considered suitable for use in the 
maintenance setting. In the phase II maintenance study in the relapsed ovarian cancer setting 
(D0810C00019) a number of patients have remained on therapy for periods >3 years (21 
patients remained on olaparib maintenance therapy for >3 years and 32 patients for >2 years). 
Refer to the current IB for a complete description of the safety and tolerability profile. 
Platinum-containing therapy is considered the treatment of choice for patients with newly 
diagnosed advanced ovarian cancer, including those patients with BRCA1/2 mutated high risk 
ovarian cancer, however the duration of response and the prolongation of the progression free 
interval are usually brief and these chemotherapy regimens cannot be continued until 
progression as they are associated with neurological, renal and haematological toxicity and 
cannot generally be tolerated for more than about 6 cycles. Since chemotherapy is not a viable 
treatment option in the maintenance setting, there is a need for a well tolerated maintenance 
treatment (following completion of chemotherapy) that can be taken until disease progression 
to extend the progression free interval in this patient population. Recently, the European 
Medicines Agency (EMA) approved bevacizumab, in combination with carboplatin and 
paclitaxel, for the first-line treatment or first recurrence of platinum sensitive advanced (FIGO 
stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer; the 
approval was based on improved PFS in trials of bevacizumab in combination with 
chemotherapy followed by bevacizumab maintenance monotherapy. 
 
Patients with BRCA mutation ovarian cancer, however, represent a targeted and clinically 
identifiable subpopulation for whom, despite the potential for personalised healthcare, no 
targeted treatment is currently available. 
 
The current study design will allow patients to complete their platinum-containing regimen as 
per normal clinical practice prior to enrolment. The use of olaparib as a maintenance therapy 
after completion of chemotherapy may provide further benefit to patients in terms of 
prolongation of the progression free interval, increasing the interval between lines of 
chemotherapy, delaying further hospitalisation and the cumulative toxicities associated with 
chemotherapy. Additionally, PARP inhibition with olaparib is expected to have less effect on 
normal cells that are wild type or heterozygous for both BRCA1 and BRCA2 (Farmer et al 
2005). In patients with gBRCA mutations, their normal tissues will carry only one mutated 
copy of the relevant BRCA gene, but their tumours are expected to have lost both functional 
copies. This is important for the selective therapeutic window of olaparib (i.e., effect on the 
tumour versus the effect on normal tissue) and leads to an acceptable tolerability profile for 

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long term clinical use in a clearly identifiable and targeted patient population most likely to 
derive benefit. 
Since ovarian cancer patients who respond to platinum based chemotherapy do not routinely 
receive additional treatment at this point in their therapy, the use of a placebo comparator to 
olaparib following completion of the platinum-containing regimen in those patients who, in 
the investigator’s opinion, have achieved a clinical complete response or partial response is 
acceptable in order to objectively test the hypothesis of improved efficacy with the addition of 
olaparib maintenance treatment after a platinum regimen. The study will be conducted as a 
double-blind placebo-controlled study in which patients are randomised 2:1 to receive 
olaparib or matching olaparib placebo (tablet formulation), with a primary efficacy endpoint 
of PFS. 
The tablet formulation is considered to be a more patient friendly formulation for long term 
use requiring patients to take up to 2 tablets twice daily as compared to the capsule 
formulation requiring 8 capsules twice daily. 
 
In view of the potential for olaparib maintenance monotherapy to have a clinically meaningful 
PFS advantage in BRCA1/2 mutated patients with ovarian cancer, the current study is 
designed to allow patients to continue on olaparib therapy for up to two years or until 
progression of disease, whichever is earlier. Patients who continue to have evidence of disease 
that remains stable (i.e., no evidence of disease progression) at two years or those who have 
progressed may continue to receive study treatment if, in the opinion of the investigator, it is 
in the patient’s best interest. However, if at two years the patient has no evidence of disease, 
study treatment should be discontinued. Patients may stop treatment at any time if they choose 
to do so or if the investigator believes it is in the best interest of the patient. Additionally, in 
the event of unmanageable toxicity, directions for reducing, interrupting or discontinuing 
olaparib are provided. 
 
In the current study, prior to entry some patients will already know their germline BRCA 
mutation status. In addition, in some rare circumstances the patient may know their tumour 
BRCA mutation status. For those who do not know their BRCA mutation status but wish to 
participate in the study, patients will have to consent to undergo gBRCA testing. Any 
counselling procedures required before such testing will be carried out in accordance with 
local hospital practice. Patients who then chose to undergo testing and in whom a gBRCA 
mutation is identified will be eligible to continue study screening procedures. 
 
During screening, patients will be required to consent to provide a sample of archival tumour 
tissue (to be submitted only if they are subsequently randomised), as well as a blood sample to 
either ascertain or reconfirm their BRCA mutation status. An additional blood sample will 
also be taken to support the development and delivery of the companion diagnostic for 
olaparib which is required in order to comply with the FDA draft guidance on In Vitro 
Companion Diagnostic Devices. A further (optional) blood sample will also be collected for 
future biomarker research. This research may further identify correlates for the response and 
possible resistance mechanisms that may exist for olaparib, a targeted therapy that is being 

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developed for ovarian cancer patients with BRCA 1/2 mutations. Such an understanding of 
response and resistance to olaparib may assist in ultimately ensuring that AstraZeneca will be 
able to prospectively identify patients most likely to benefit from treatment with olaparib. 
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also 
referred to as COVID-19) presents a potential safety risk for patients and therefore several risk 
mitigation factors have been implemented in this study (see Section 4.3, Appendix K and 
Appendix L). 
 
 
2. 
STUDY OBJECTIVES 
2.1 
Primary objective 
To determine the efficacy by progression free survival (using investigator assessment of scans 
according to modified RECIST 1.1) of olaparib maintenance monotherapy compared to 
placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical 
complete response or partial response following first line platinum based chemotherapy. 
 
2.2 
Secondary objectives 
1. 
To determine the efficacy of olaparib maintenance monotherapy compared to 
placebo in BRCA mutated high risk advanced ovarian cancer patients who are in 
clinical complete response or partial response following first line platinum based 
chemotherapy by assessment of overall survival (OS), time to earliest progression 
by RECIST or CA-125, or death, and time from randomisation to second 
progression (PFS2) 
2. 
To compare the effects of olaparib maintenance monotherapy compared to placebo 
on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index 
(TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) in 
BRCA mutated high risk advanced ovarian cancer patients who are in clinical 
complete response or partial response following first line platinum based 
chemotherapy 
3. 
To assess 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 potential future BRCA mutation assays (gene sequencing and large 
rearrangement analysis) 
 
4. 
To determine the efficacy of olaparib maintenance monotherapy compared to 
placebo in BRCA mutated high risk advanced ovarian cancer patients who are in 
clinical complete response or partial response following first line platinum based 
chemotherapy by assessment of time from randomisation to first subsequent therapy 
or death (TFST), time from randomisation to second subsequent therapy or death 

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3. 
STUDY PLAN AND PROCEDURES 
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
standard procedures. 
 
3.1 
Overall study design and flow chart 
This is a phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess 
the efficacy of olaparib maintenance monotherapy in high risk advanced ovarian cancer 
patients (including patients with primary peritoneal and / or fallopian tube cancer) with BRCA 
mutations [documented 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) who have 
responded following first line platinum based chemotherapy. 
 
Approximately 344 patients will be randomised using an Interactive Voice Response System / 
Interactive Web Response System (IVR/IWR system) in a 2:1 ratio to the treatments as 
specified below: 
• 
Olaparib tablets p.o. 300 mg twice daily 
• 
Placebo tablets p.o. twice daily 
 
 
Eligible patients will be those patients with newly diagnosed, histologically confirmed, high 
risk advanced (FIGO stage III-IV) BRCA mutated high grade serous or high grade 
endometrioid (based on local histopathological findings) ovarian cancer, primary peritoneal 
cancer and / or fallopian-tube cancer who are in clinical complete response or partial response 
following completion of first line platinum-based chemotherapy. Patients who re-present 
following prior diagnosis at an earlier stage of disease are not eligible. Stage III patients 
should have had one attempt at optimal debulking surgery (upfront or interval debulking). 
Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery. 
 
Patients must have completed a minimum of six and maximum of nine treatment cycles of 
first line platinum-based therapy (e.g., carboplatin or cisplatin) before randomisation to the 
study and should be in the opinion of the investigator in clinical complete response or partial 
response. However, if platinum based therapy must be discontinued early as a result of 
toxicities specifically related to the platinum regimen, patients must have received a minimum 
of four cycles of the platinum regimen. 
Patients must not have received bevacizumab (either in combination or as maintenance 
therapy following combination therapy) or any investigational agent during their first line 
course of treatment. 
 
Patients known to have germline BRCA mutation/s (gBRCAm i.e., blood) prior to 
randomisation can enter the study based on this result. The result must be made available to 

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will be at the discretion of the investigator. Any further systemic anti-cancer treatment will be 
collected until death, loss to follow-up or withdrawal of consent. In addition, patients will be 
contacted in the 7 days following a specified date (data cut off date) for each survival analysis. 
 
Assessments will be performed as described in Table 3, and Table 4. 
 
Patients in both treatment arms will have tumour assessments according to RECIST at 
baseline and every 12 weeks (±1week) up to 156 weeks and then every 24 weeks (±1 week) 
relative to date of randomisation until objective radiological disease progression according to 
RECIST. From CSP v5 onwards: Study patients who discontinued treatment at two years per 
protocol with no evidence of disease (either NED from baseline or CR achieved while 
receiving study treatment) and who not yet had disease progression will have radiological 
(RECIST) tumour assessments only when clinically indicated e.g. rising CA-125 and/or signs 
and symptoms suggesting PD, according to the investigator’s clinical judgment. All CT/MRI 
scans will be sent to an AstraZeneca appointed Clinical Research Organisation (CRO) for 
blinded independent central review. All treatment decisions will be based on site assessment 
of scans. After the primary progression free survival (PFS) analysis, central review of scans 
will no longer be required and investigators will be advised when to stop sending copies of the 
scans to the CRO conducting the central review. Ongoing collection of site review tumour 
assessment is required and must be recorded in the electronic case report form (eCRF). 
 
RECIST will be modified to assess patients with clinical CR at entry who will be assessed as 
having no evidence of disease (NED) unless they have progressed based on the appearance of 
new lesions. 
 
Any patient who discontinues study treatment for reasons other than objective radiological 
progression should continue, to undergo scheduled objective tumour assessments according to 
the study plan (see Table 3 and Table 4) in order to assess objective radiological progression 
of disease. From CSP v5 onwards: Study patients who discontinued treatment at two years per 
protocol with no evidence of disease (either NED from baseline or CR achieved while 
receiving study treatment) and who not yet had disease progression will have radiological 
(RECIST) tumour assessments only when clinically indicated e.g. rising CA-125 and/or signs 
and symptoms suggesting PD, according to the investigator’s clinical judgment. Failure to do 
so may result in bias to the study results. 
Once a patient has progressed the patient will be followed for second progression (PFS2) 
every 12 weeks and then survival until the final analysis. Patients will be contacted in the 
week following last patient last visit for each analysis of survival. 
 
The primary analysis of the study will occur when approximately 196 events have occurred or 
after the last patient randomised has had the opportunity to have been on the study for at least 
36 months, whichever comes first (there will be no interim analysis of progression free 
survival). The primary analysis will be based on investigator assessment of scans; however, a 
sensitivity analysis will be performed using the BICR data. All efficacy variables including 

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overall survival will be analysed at the time of the primary analysis (providing sufficient 
events are available to make the analyses meaningful). 

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Perform screening part 1 
Consent patient and take BRCA blood sample to test 
for gBRCA mutation 
Patient must receive first line treatment with platinum containing chemotherapy 
as per local standard practicea 
Patient is a 
screen fail 
Patient is a 
screen fail 
Patient is a 
screen fail 
Does result confirm 
BRCA mutation? 
No 
Is the patient in 
response based on 
Investigator opinion? 
Is the patient 
eligible? 
Figure 1 
Overall Study Design Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
† 
No 
Is the patient newly diagnosed, 
with histologically confirmed, 
advanced (FIGO stage III- IV) high grade serous or 
high grade endometrioid ovarian, primary 
peritoneal or fallopian-tube cancer? 
Yes 
No 
Does the patient 
fulfil criteria to allow the 
BRCA sample 
to be taken? 
No 
Is the patient 
known to have a BRCA 
mutation (either gBRCA 
or tBRCA)? 
Yes 
Has patient 
had one attempt at 
optimal debulking surgery 
(upfront or interval debulking) 
(stage III patients only) OR had 
either a biopsy and/or upfront 
or interval debulking 
surgery (stage IV 
patients 
only)? 
No 
Yes 
Yes 
Has patient 
received first line 
platinum containing 
chemotherapy 
as per local 
Standarda? 
No 
Yes 
Patient Identified 
Patient is 
not 
eligible 
Patient is 
not 
eligible 
Patient is not 
eligible – Do not 
take BRCA 
sample 
Patient is not 
eligible 
No 
Yes 
Yes 
No 
Yes 
No 
Is the patient 
eligible? 
Yes 
Patients will be randomised within 8 weeks after their last dose of chemotherapy (last dose is the day of the last infusion) 
Perform 
screening part 3 
Patient is a 
screen fail 
Treat for up to 2 years or until disease progression bc (PFS1) 
Follow up for second progression (PFS2) 
Perform 
screening part 2 
Consent patient within 28 
days of day 1, following PR or 
CCR based on investigator 
opinion. These patients have 
a confirmatory Myriad test 
post randomisation 
Follow up for survival 

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a 
First line chemotherapy must comprise of a minimum of 6 and a maximum of 9 cycles of platinum based 
chemotherapy) and not containing bevacizumab. However if platinum based therapy must be discontinued 
early as a result of toxicities specifically related to the platinum regimen, patients may be eligible if they 
have received a minimum of four cycles of platinum regimen 
b 
Patients should continue to receive study treatment for up to two years or until objective radiological 
disease progression as per RECIST as assessed by the investigator, whichever is earlier, and as long as in 
the investigator’s opinion they are benefiting from treatment and they do not meet any other discontinuation 
criteria as outlined in Section 5.8. Patients should continue with study treatment to RECIST progression as 
described above despite rises in CA-125. Patients who continue to have evidence of disease that remains 
stable (i.e., no evidence of disease progression) at two years or those who have progressed may continue to 
receive study treatment if, in the opinion of the investigator, it is in the patient’s best interest. However, if at 
two years the patient has no evidence of disease, study treatment should be discontinued. A decision about 
continuing treatment with the investigational product beyond two years should be made after assessing the 
patient’s disease status according to RECIST guidelines at week 108, and/or by assessing the patient’s 
clinical condition. Continuation of treatment beyond week 108, based solely on clinical progression, is 
permissible only after case-by-case discussion with the AZ study physician. From CSP v5 onwards: Study 
patients who discontinued treatment at two years per protocol with no evidence of disease (either NED from 
baseline or CR achieved while receiving study treatment) and who not yet had disease progression will have 
radiological (RECIST) tumour assessments only when clinically indicated e.g. rising CA-125 and/or signs 
and symptoms suggesting PD, according to the investigator’s clinical judgment. 
c  All ongoing adverse events/serious adverse events (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. 
See Section 6.4.4 for post 30 day safety follow up adverse event reporting. 

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Figure 2 
Screening Plan 
 
 
 
Screening Part 1 (From diagnosis to –28d) applicable to: 
• 
only those patients who do not know their gBRCA or tBRCA 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. 
The BRCA test may be performed from diagnosis to –28 days at the discretion of the investigator. To 
perform the BRCA testing from diagnosis to the end of cycle 3, investigator judgement of patient’s 
potential eligibility to enter the study should be assessed as per Table 1 and by reviewing the 
inclusion/exclusion criteria. For post cycle 3 of first line chemotherapy gBRCA status testing the 
patient must meet the inclusion criteria in Section 4.1 and none of the exclusion criteria in Section 4.2, 
and be showing a response to their current platinum chemotherapy prior to having the blood sample 
taken for the Myriad gBRCA status test. Once part 1 has been successfully completed these patients 
will continue to part 2 and have all procedures performed as described for part 2 in Table 1. 
 
 
 
Screening Part 2 (-28d to –1) applicable to: 
• 
those patients who already know their BRCA mutation status and have a deleterious or 
suspected deleterious mutation. These patients will undergo screening assessments as 
described for part 2 in Table 2 and have confirmatory Myriad test post randomisation. 
• 
those patients who have a confirmed mutation after completing screening part 1. These 
patients will undergo screening assessments as described for part 2 in Table 1. 
 
 
 
Screening Part 3 (-7d to –1) applicable to: 
• 
those patients who are still deemed eligible to continue with screening after completing part 1 
and / or part 2. 
Once screening has been completed and eligibility confirmed these patients will continue to visit 2 and 
have procedures performed as described in Table 3. 

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Figure 3 
Study Flow Chart Up to 108 Weeks on Treatment 
 
 
 

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Figure 4 
Study Flow Chart At 108 Weeks on Treatment 
 
 
a 
Patients off treatment: Off-treatment follow-up visits and scans will continue to be conducted every 12 
weeks (±1 week) up to 156 weeks (3 years), then every 24 weeks (±1 week) relative to date of 
randomization. From CSP v5 onwards: Study patients who discontinued treatment at two years per protocol 
with no evidence of disease (either NED from baseline or CR achieved while receiving study treatment) 
and who not yet had disease progression will have radiological (RECIST) tumour assessments only when 
clinically indicated e.g. rising CA-125 and/or signs and symptoms suggesting PD, according to the 
investigator’s clinical judgment. 
 
b 
Patients continuing treatment: Treatment visits will continue every 4 weeks (±3 days) up to 156 weeks (3 
years), then every 12 weeks (±1 week) relative to date of randomization. Scans will continue every 12 
weeks (±1 week) up to 156 weeks (3 years), then every 24 weeks (±1 week) relative to date of 
randomization. 

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3.2 
Rationale for study design, doses and control groups 
The proposed Phase III study is designed to investigate the efficacy and clinical benefit of 
olaparib as maintenance therapy for the treatment of newly diagnosed high risk advanced 
BRCA mutation positive ovarian cancer based upon the benefit demonstrated in the phase II 
study D0810C00019 (see Section 1.3). The primary assessment of PFS will be based on 
investigator assessment of objective radiological findings as per the RECIST guidelines. A 
number of secondary endpoints will provide further support for the clinical benefit of olaparib 
in this patient population, and will include OS, time from randomisation to progression by 
RECIST 1.1 or CA-125, time from randomisation to second progression (PFS2; see details in 
the study plan) and patient reported outcome measures. 
The study design will allow patients to complete their platinum-containing regimen as per 
normal clinical practice prior to enrolment. The use of olaparib as a maintenance therapy after 
completion of chemotherapy may provide further benefit to patients in terms of prolongation 
of the progression free interval, increasing the interval between lines of chemotherapy, 
delaying further hospitalisation and the cumulative toxicities associated with chemotherapy. 
Additionally, PARP inhibition with olaparib is expected to have no effect on normal cells that 
are wild type or heterozygous for both BRCA1 and BRCA2 (Farmer et al 2005). In patients 
with gBRCA mutations, their normal tissues will carry only one mutated copy of the relevant 
BRCA gene, but their tumours are expected to have lost both functional copies. This is 
important for the selective therapeutic window of olaparib (i.e., effect on the tumour versus 
the effect on normal tissue) and leads to an acceptable tolerability profile for long term clinical 
use in a clearly identifiable and targeted patient population most likely to derive benefit. 
Since ovarian cancer patients who respond to platinum based chemotherapy do not routinely 
receive additional treatment at this point in their therapy, the use of a placebo comparator to 
olaparib following completion of the platinum-containing regimen in those patients who have 
achieved in the opinion of the investigator a clinical complete response or partial response is 
considered acceptable in order to objectively test the hypothesis of improved efficacy with the 
addition of olaparib maintenance treatment after a platinum regimen. Given the promising 
phase II data from Study D0810C00019 (see Section 1.3), the phase III study will be 
conducted with a 2:1 randomisation for olaparib:placebo to minimise the number of patients 
receiving placebo. 
A more patient friendly tablet formulation (2 tablets twice daily) has been developed and this 
phase III study will investigate the efficacy of the tablet formulation when given as a 
maintenance therapy to BRCA mutated ovarian cancer patients following first line platinum 
based chemotherapy. The tablet dose of olaparib that will be investigated in this study is 
300mg twice daily. This tablet dose has been chosen based on data from an ongoing 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 300mg twice daily is considered to have similar efficacy in terms of tumour shrinkage 
in BRCA mutated ovarian cancer patients to the 400mg twice daily capsule together with an 
acceptable tolerability profile. The tolerability profile of the 300mg twice daily tablet dose in 

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study D0810C00024 was considered similar to the 400mg twice daily capsule formulation. 
The most common adverse events were consistent with the known safety profile of olaparib, 
namely low grade nausea, vomiting, fatigue and anaemia. Further information is provided in 
the IB. 
 
4. 
PATIENT SELECTION CRITERIA 
The patient population should be selected without bias. 
 
Investigator(s) should keep a record, the 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. 
 
4.1 
Inclusion criteria 
Patients that already know they have a mutation in BRCA1 or BRCA2 gene that is predicted 
to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of 
function) must fulfil all of the criteria below. Patients that do not know their mutation status, 
and who are being considered for this trial should be identified early so that the appropriate 
BRCA mutation screening procedures can be put in place in a timely manner. Patients that do 
not know their BRCA mutation status and who are being tested post cycle 3 of their first line 
chemotherapy must fulfil all of the criteria marked with an asterisk (*) below prior to BRCA 
mutation testing being carried out. To perform the BRCA testing from diagnosis to the end of 
cycle 3, investigator judgement of patient’s potential eligibility to the study should be assessed 
as per Table 1 and by reviewing the inclusion/exclusion criteria. All inclusion criteria will 
then be assessed following confirmation that they harbour an appropriate BRCA mutation. 
Any patient that fulfils the eligibility criteria for the BRCA test, are required to have their 
eligibility assessed again prior to randomisation. 
 
All patients must provide informed consent prior to any study specific procedures. 
 
1. 
*Patients must be ≥18 years of age. 
 
2. 
*Female patients with newly diagnosed, histologically confirmed, high risk 
advanced (FIGO stage III – IV) BRCA mutated high grade serous or high grade 
endometriod (based on local histopathological findings) ovarian cancer, primary 
peritoneal cancer and / or fallopian-tube cancer who have completed first line 
platinum based chemotherapy (intravenous or intraperitoneal). Guidance on grading 
of serous ovarian carcinomas is covered by Appendix J. 

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3. 
* Stage III patients must have had one attempt at optimal debulking surgery 
(upfront or interval debulking). Stage IV patients must have had either a biopsy 
and/or upfront or interval debulking surgery. 
 
4. 
Documented 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) 
5. 
Patients who have completed first line platinum (e.g. carboplatin or cisplatin), 
containing therapy (intravenous or intraperitoneal) prior to randomisation: 
 
− 
Patients must have, in the opinion of the investigator, clinical complete 
response or partial response and have no clinical evidence of disease 
progression on the post-treatment scan or a rising CA-125 level, 
following completion of this chemotherapy course. Patients with stable 
disease on the post-treatment scan at completion of first line platinum- 
containing therapy are not eligible for the study. 
 
− 
‘Response’ is used throughout the protocol and refers to patients being, in the 
opinion of the investigator, in clinical complete response or partial 
response on the post-treatment scan. Clinical complete response is 
defined as no evidence of RECIST measurable or non-measurable disease 
on the post-treatment scan and a normal CA-125. Partial response is 
defined as ≥30% reduction in tumour volume demonstrated from the start 
to finish of chemotherapy OR no evidence of RECIST measurable 
disease on the post-treatment scan with a CA-125 which has not 
decreased to within the normal range. 
 
− 
Platinum based chemotherapy course must have consisted of a minimum of 6 
treatment cycles and a maximum of 9, however if platinum based therapy 
must be discontinued early as a result of toxicities specifically related to 
the platinum regimen, patients must have received a minimum of 4 cycles 
of the platinum regimen. 
 
− 
*Patients must not have received bevacizumab during their first line course of 
treatment, either in combination or as maintenance therapy following 
combination therapy. 
 
− 
Patients must not have received an investigational agent during their first line 
course of chemotherapy 
 
− 
Patients must be randomised within 8 weeks after their last dose of 
chemotherapy (last dose is the day of the last infusion). 
 
6. 
Pre-treatment CA-125 measurements must meet criterion specified below: 

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− 
If the first value is less than or equal to the upper limit of normal (ULN) the 
patient is eligible to be randomised and a second sample is not required 
 
− 
If the first value is greater than ULN a second assessment must be performed at 
least 7 days after the first. If the second assessment is ≥ 15% more than 
the first the patient is not eligible 
 
7. 
Patients must have normal organ and bone marrow function measured within 28 
days prior to administration of study treatment as defined below: 
− 
Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days 
− 
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
− 
Platelet count ≥ 100 x 109/L 
− 
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) 
− 
Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase 
(SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate 
Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless 
liver metastases are present in which case they must be ≤ 5x ULN 
 
− 
Serum creatinine ≤ 1.5 x institutional ULN 
8. 
*Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see 
Appendix G). 
 
9. 
*Patients must have a life expectancy ≥ 16 weeks. 
 
10. 
*Postmenopausal or evidence of non-childbearing status for women of childbearing 
potential: negative urine or serum pregnancy test prior to Myriad BRCA test during 
screening part 1, within 28 days of study treatment and confirmed prior to treatment 
on day 1. 
 
Postmenopausal is defined as: 
 
− 
Amenorrhoeic for 1 year or more following cessation of exogenous hormonal 
treatments 
 
− 
Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in 
the post menopausal range for women under 50 
 
− 
radiation-induced oophorectomy with last menses >1 year ago 
− 
chemotherapy-induced menopause with >1 year interval since last menses 

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− 
surgical sterilisation (bilateral oophorectomy or hysterectomy) 
11. 
*Patients is willing and able to comply with the protocol for the duration of the 
study including undergoing treatment and scheduled visits and examinations. 
12. 
*Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary 
cancer must be available for central testing. If there is not written confirmation of 
the availability of an archived tumour sample prior to enrolment the patient is not 
eligible for the study. 
 
For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker 
research, patients must fulfil the following criteria: 
− 
Provision of informed consent for genetic research 
− 
Provision of informed consent for biomarker research 
If a patient declines to participate in the optional exploratory genetic research or the optional 
biomarker research, there will be no penalty or loss of benefit to the patient. The patient will 
not be excluded from other aspects of the study. 
 
4.2 
Exclusion criteria 
Patients must not enter the study if any of the following exclusion criteria are fulfilled (any 
asterisked* are also applicable as an exclusion criteria for patients that are being screened post 
cycle 3 of their first line chemotherapy to determine their BRCA mutation status via Myriad. 
To perform the BRCA testing from diagnosis to the end of cycle 3, investigator judgement of 
patient’s potential eligibility to the study should be assessed as per Table 1 and by reviewing 
the below exclusion criteria): 
1. 
*Involvement in the planning and/or conduct of the study (applies to both 
AstraZeneca staff and/or staff at the study site). 
2. 
BRCA 1 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. 
*Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC) 
 
4. 
Stable disease or progressive disease on the post-treatment scan or clinical evidence 
of progression at the end of the patient’s first line chemotherapy treatment 
5. 
*Patients where more than one debulking surgery has been performed before 
randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be 
unresectable and undergo only a biopsy or oophorectomy but then go on to receive 
chemotherapy and interval debulking surgery are eligible). 

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6. 
*Patients who have previously been diagnosed and treated for earlier stage ovarian, 
fallopian tube or primary peritoneal cancer. 
7. 
*Patients who have previously received chemotherapy for any abdominal or pelvic 
tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, 
fallopian tube or primary peritoneal cancer. (Patients who have received prior 
adjuvant chemotherapy for localised breast cancer may be eligible, provided that it 
was completed more than three years prior to registration, and that the patient 
remains free of recurrent or metastatic disease). 
8. 
*Patients with synchronous primary endometrial cancer unless both of the following 
criteria are met: 
 
(i) 
stage <2 
 
(ii) 
less than 60 years old at the time of diagnosis of endometrial cancer with 
stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid 
adenocarcinoma OR ≥ 60 years old at the time of diagnosis of 
endometrial cancer with Stage IA grade 1 or 2 endometrioid 
adenocarcinoma. Patients with serous or clear cell adenocarcinoma or 
carcinosarcoma of the endometrium are not eligible. 
9. 
Patients who have had drainage of their ascites during the final 2 cycles of their last 
chemotherapy regimen prior to enrolment on the study. 
 
10. 
*Previous randomisation in the present study. 
 
11. 
*Participation in another clinical study with an investigational product during their 
chemotherapy course immediately prior to randomisation. 
 
12. 
*Any previous treatment with PARP inhibitor, including olaparib. 
 
13. 
*Other malignancy within the last 5 years except: adequately treated non-melanoma 
skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ 
(DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including 
lymphomas (without bone marrow involvement) curatively treated with no evidence 
of disease for ≥5 years. Patients with a history of localised breast cancer may be 
eligible, provided they completed their adjuvant chemotherapy more than three 
years prior to registration, and that the patient remains free of recurrent or 
metastatic disease 
 
14. 
*Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour 
period or family history of long QT syndrome 

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15. 
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative 
reasons) within 3 weeks prior to study treatment (or a longer period depending on 
the defined characteristics of the agents used). 
 
16. 
*Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, 
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and 
nelfinavir. 
 
17. 
*Persistent toxicities (≥Common Terminology Criteria for Adverse Event (CTCAE) 
grade 2) caused by previous cancer therapy, excluding alopecia. 
18. 
*Patients with myelodysplastic syndrome/acute myeloid leukaemia. 
 
19. 
*Patients with symptomatic uncontrolled brain metastases. A scan to confirm the 
absence of brain metastases is not required. The patient can receive a stable dose of 
corticosteroids before and during the study as long as these were started at least 4 
weeks prior to treatment. Patients with spinal cord compression unless considered to 
have received definitive treatment for this and evidence of clinically stable disease 
for 28 days. 
20. 
Major surgery within 2 weeks of starting study treatment and patients must have 
recovered from any effects of any major surgery. 
21. 
*Patients considered a 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, 
unstable spinal cord compression, superior vena cava syndrome, extensive 
interstitial bilateral lung disease on High Resolution Computed Tomography 
(HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. 
 
22. 
*Patients unable to swallow orally administered medication and patients with 
gastrointestinal disorders likely to interfere with absorption of the study medication. 
23. 
*Breast feeding women. 
 
24. 
*Immunocompromised patients, e.g., patients who are known to be serologically 
positive for human immunodeficiency virus (HIV). 
25. 
*Patients with a known hypersensitivity to olaparib or any of the excipients of the 
product. 
 
26. 
*Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of 
transmitting the infection through blood or other body fluids 
 
27. 
*Previous allogeneic bone marrow transplant 

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28. 
*Whole blood transfusions in the last 120 days prior to entry to the study (packed 
red blood cells and platelet transfusions are acceptable, for timing refer to inclusion 
criteria no.7) 
 
Procedures for withdrawal of incorrectly enrolled patients see Section 5.3. 
 
4.3 
Study Conduct Mitigation During Study Disruptions Due to Cases 
of Civil Crisis, Natural Disaster, or Public Health Crisis 
The guidance given below supersedes instructions provided elsewhere in this CSP and should 
be implemented only during cases of civil crisis, natural disaster, or public health crisis (eg, 
during quarantines and resulting site closures, regional travel restrictions, and considerations if 
site personnel or study participants become infected with severe acute respiratory syndrome 
coronavirus 2 [SARSCoV-2] or similar pandemic infection) which would prevent the conduct 
of study-related activities at study sites, thereby compromising the study site staff or the 
participant’s ability to conduct the study. The investigator or designee should contact the 
study Sponsor to discuss whether the mitigation plans below should be implemented. 
 
To ensure continuity of the clinical study during a civil crisis, natural disaster or public health 
crisis, changes may be implemented to ensure the safety of study participants, maintain 
compliance with Good Clinical Practice, and minimise risks to study integrity. 
Where allowable by local health authorities, ethics committees, healthcare provider guidelines 
(eg, hospital policies) or local government, these changes may include the following options: 
 
• Obtaining consent/reconsent for the mitigation procedures (note, in the case of verbal 
consent/reconsent, the Informed Consent Form (ICF) should be signed at the participant’s 
next contact with the study site). 
• Home or Remote visit: Performed by a site qualified Health Care Professional (HCP) 
or HCP provided by a third-party vendor (TPV). 
• Telemedicine visit: Remote contact with the participants using telecommunications 
technology including phone calls, virtual or video visits, and mobile health devices. 
• At-home or Remote Delivery of study intervention olaparib/placebo). 
 
For further details on study conduct during civil crisis, natural disaster, or public health crisis, 
refer to Appendix K. For further guidance during the COVID-19 pandemic refer to 
Appendix L. 
 
5. 
STUDY CONDUCT 
5.1 
Restrictions during the study 
The following restrictions apply while the patient is receiving olaparib and for the specified 
times before and after: 

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5.1.1 Olaparib and CYP3A4 
Patients should avoid concomitant use of drugs, herbal supplements and/or ingestion of foods 
known to modulate CYP3A4 enzyme activity (see Section 5.6.2) from the time they enter the 
screening period until 30 days after the last dose of study medication. 
 
5.1.2 Contraception 
Female patients of child bearing potential and their partners, who are sexually active, must 
agree to the use of one highly effective form of contraception and their partners must use a 
male condom (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(s), or they must totally/truly abstain from any form of 
sexual intercourse (as described in Appendix E). 
5.2 
Patient enrolment and randomisation and initiation of 
investigational product 
The Principal Investigator will: 
 
1. 
Obtain signed informed consent from the potential patients before any study 
specific procedures are performed. 
 
2. 
Assign potential patients a unique enrolment number, beginning with ‘E#’. (This 
number will be obtained through Interactive Voice/Web Response System 
[IVRS/IWRS]). 
 
3. 
Determine patient’s eligibility (see Sections 4.1 and 4.2). 
 
4. 
Obtain the randomisation code (patient number) through IVRS/IWRS 
 
As patients are screened for the study, they must be allocated an enrolment code (E-code). The 
E-code is a 7-digit number made up of the centre number and the patient number within that 
particular centre (e.g., the first patient screened at centre number 0001 would be assigned the 
E-code E0001001, the second patient screened would be E0001002 and so on). This number is 
the patient unique identifier and is used to identify the patient on the eCRFs. If a patient 
withdraws from participation in the study, then his/her enrolment/randomisation code cannot 
be reused. 
 
5.2.1 Procedures for randomisation 
Patient eligibility will be established before treatment randomisation. Once the eligibility of a 
patient has been confirmed, the Investigator (or nominated assistant) should contact the 
IVRS/IWRS Centralised Randomisation Centre for allocation of randomised study treatment. 
 
The actual treatment given to individual patients will be determined by a randomisation 
scheme that has been loaded into the (IVRS/IWRS) database. The randomisation scheme will 

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be produced by a computer software program called GRand (AZ Global Randomisation 
system) that incorporates a standard procedure for generating random numbers. 
A blocked randomisation will be generated and all centres will use the same list in order to 
minimise any imbalance in the number of patients assigned to each treatment group. 
 
The randomisation scheme will be stratified based on: 
 
• 
response to first line platinum chemotherapy (clinical complete response or partial 
response) 
 
Patients will be identified to the Centralised Randomisation Centre using patient initials, 
Ecode and date of birth. 
Randomisation codes will be assigned strictly sequentially within each strata as patients 
become eligible for randomisation. 
 
Eligible patients will be randomised in a 2:1 ratio as specified below: 
 
• 
olaparib tablets p.o. 300 mg twice daily 
• 
placebo tablets p.o. twice daily 
It is recommended that patients commence study treatment as soon as possible after 
randomisation, and ideally within 3 days. 
The IVRS/IWRS Centralised Randomisation Centre will inform the Investigator of the Kit ID 
number to be allocated to the patient at the randomisation visit. The Investigator will call/log 
in to the IVRS/IWRS for each subsequent dispensing visit for assignment of a new Kit ID 
number. 
 
The Kit ID number dispensed at each visit will correspond to the treatment to which the 
patient was originally randomised 
 
5.3 
Procedures for handling patients incorrectly enrolled or 
randomised or initiated on investigational product 
Patients who fail to meet the inclusion/exclusion criteria should not, under any 
circumstances, be randomised or receive study medication. There can be no exceptions to this 
rule. 
Where patients that do not meet the selection criteria are randomised in error or incorrectly 
started on treatment, or where patients subsequently fail to meet the study criteria post 
initiation, a discussion should occur between the AstraZeneca Study Team Physician 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. 

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5.5.2 Doses and treatment regimens 
 
5.5.2.1 
Olaparib and matching placebo (study treatment) 
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 
treatment will be dispensed to patients. Each dosing container will contain sufficient 
medication for at least each treatment period plus overage. Multiple bottles of study treatment 
may be required for dispensing in order to make up the desired dose. 
 
Patients will be administered their randomised study treatment tablets orally at a dose of 
300mg twice daily. 
Study treatment is available as a green film-coated tablet containing 150mg or 100mg of 
olaparib or matching placebo Tablets are to be taken orally, twice daily (bd). Doses of study 
treatment should be taken at the same times each day approximately 12 hours apart. All doses 
should be taken with approximately 240 mL of water. The study treatment tablets should be 
swallowed whole and not chewed, crushed, dissolved or divided. Study treatment tablets can 
be taken with a light meal/snack (e.g., two pieces of toast or a couple of 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 allotted dose at 
the next scheduled time. 
 
Patients should continue to receive study treatment for up to two years or until objective 
radiological disease progression as per RECIST as assessed by the investigator, whichever is 
earlier, and as long as in the investigator’s opinion they are benefiting from treatment and they 
do not meet any other discontinuation criteria as outlined in Section 5.8. Patients should 
continue with study treatment to RECIST progression as described above despite rises in CA- 
125. Patients who continue to have evidence of disease that remains stable (i.e., no evidence 
of disease progression) at two years or those who have progressed may continue to receive 
study treatment if, in the opinion of the investigator, it is in the patient’s best interest. 
However, if at two years the patient has no evidence of disease, study treatment should be 
discontinued. A decision about continuing treatment with the investigational product beyond 
two years should be made after assessing the patient’s disease status according to RECIST 
guidelines at week 108, and/or by assessing the patient’s clinical condition. Continuation of 
treatment beyond week 108, based solely on clinical progression, is permissible only after 
case-by-case discussion with the AZ study physician. 
Once patients have been discontinued from study treatment, other treatment options will be at 
the discretion of the investigator. Patients and investigators will not be routinely unblinded to 

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study treatment prior to the final OS analysis. Within this study patients are not permitted to 
switch over to the opposite arm from which they were randomised. 
5.5.3 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 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 
 
5.5.4 Storage 
All study drugs should be kept in a secure place under appropriate storage conditions. The 
investigational product label on the bottle specifies the appropriate storage. 
 
5.5.5 Management of toxicity of study treatment 
Any toxicity observed during the study treatment phase could be managed by interruption of 
the dose of study treatment if deemed appropriate by the Investigator. Repeat dose 
interruptions are allowed as required, for a maximum of 14 days on each occasion. If the 
interruption is any longer than this the AstraZeneca study team must be informed. Study 
treatment must be interrupted until the patient recovers completely or the toxicity reverts to 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(current version) grade 1 or less. 
 
Where toxicity reoccurs following re-challenge with study treatment, and where further dose 
interruptions are considered inadequate for management of toxicity, then the patient should be 
considered for dose reduction or must permanently discontinue study treatment. Treatment 
must be interrupted if any NCI-CTCAE grade 3 or 4 adverse event occurs which the 
Investigator considers to be related to administration of study treatment. 
 
NB. In case a patient shows an AST or ALT ≥3xULN or total bilirubin ≥ 2xULN please refer 
to Appendix D ‘Actions required in cases of combined increase of Aminotransferase and Total 
Bilirubin – Hy’s Law’, for further instructions. 
 
Management of anaemia: 
Adverse events of anaemia CTCAE grade 1 or 2 (Haemoglobin (Hb) > 8 g/dl) should be 
investigated and managed as deemed appropriate by the investigator with or without 
interruption of study drug or change in dose, taking into account previous history of anaemia. 
Common treatable causes of anaemia (e.g. iron, vitamin B12 or folate deficiencies and 
hypothyroidism) should be excluded. In some cases management of anaemia may require 

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blood transfusions. However, if patient develops anaemia CTCAE grade 3 (Hb < 8g/dl) or 
worse, study treatment should be interrupted for up to maximum of 4 weeks to allow for bone 
marrow recovery and patient should be managed appropriately. Study treatment can be 
restarted at the same dose if Hb has recovered to > 9 g/dl. Any subsequently required anemia 
related interruptions, considered likely to be dose related, or coexistent with newly developed 
neutropenia, and or thrombocytopenia, will require study treatment dose reductions to 250 mg 
bd as a first step and to 200 mg bd as a second step. 
 
If a patient has been treated for anaemia with multiple blood transfusions without study 
treatment interruptions and becomes blood transfusion dependant as judged by investigator, 
study treatment should be interrupted for up to a maximum of 4 weeks to allow for bone 
marrow recovery. Study treatment should be restarted at a reduced dose. 
 
Management of neutropenia and leukopenia: 
Adverse event of neutropenia and leukopenia should be managed as deemed appropriate by 
the investigator with close follow up and interruption of study drug if CTC grade 3 or worse 
neutropenia occurs. 
 
Study treatment can be interrupted for CTCAE Grade 1 or 2 neutropenia as per investigator’s 
judgement. In the case of CTCAE Grade 3 or 4 neutropenia, study treatment should be 
interrupted for a maximum of 4 weeks. 
 
Study treatment can be restarted at the same dose if an AE of neutropenia or leukopenia has 
recovered to CTCAE Grade 1 or below (absolute neutrophil count ≥1.5 x 109/L). 
Primary prophylaxis with Granulocyte colony-stimulating factor (G-CSF) is not 
recommended, however, if patient develops febrile neutropenia, study treatment should be 
stopped and appropriate management including G-CSF should be given according to local 
hospital guidelines. Please note that G-CSF should not be used within at least 24 hours of the 
last dose of study treatment unless absolutely necessary. Growth factor support should be 
stopped at least 24 hours before restarting study treatment (7 days for pegylated G-CSF). 
Any subsequent interruptions will require study treatment dose reductions to 250 mg bd as a 
first step and to 200 mg bd as a second step. 
 
Management of thrombocytopenia 
An adverse event of thrombocytopenia should be managed as deemed appropriate by the 
investigator. If patient develops thrombocytopenia CTCAE grade 3 or worse study treatment 
should be interrupted for a max of 4 weeks. In some cases management of thrombocytopenia 
may require platelet transfusions. Platelet transfusions should be done according to local 
hospital guidelines. 
 
Management of prolonged haematological toxicities while on study treatment: 
 
If patient develops prolonged haematological toxicity such as: 

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• 
≥2 week interruption/delay in study treatment due to CTC grade 3 or worse anaemia 
and/or development of blood transfusion dependence 
 
• 
≥2 week interruption/delay in study treatment due to CTC grade 3 or worse 
neutropenia (ANC < 1 x 109/L) 
• 
≥2 week interruption/delay in study treatment due to CTC grade 3 or worse 
thrombocytopenia (Platelets < 50 x 109/L) 
Weekly differential blood counts including reticulocytes (calculate reticulocyte index (RI), RI 
= reticulocyte count x haematocrit (Hct)/normal Hct; a value of 45 is usually used for normal 
Hct) (Bessman JD 1990) and peripheral blood smear should be performed. If any blood 
parameters remain clinically abnormal after 4 weeks of dose interruption, the patient should 
be referred to haematologist for further investigations. Bone marrow analysis and/or blood 
cytogenetic analysis should be considered at this stage according to standard haematological 
practice. 
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. Study treatment should be discontinued if diagnosis of myelodysplastic 
syndrome is confirmed. 
 
Management of new or worsening pulmonary symptoms: 
If new or worsening pulmonary symptoms (e.g. dyspnoea) or radiological abnormality occurs, 
an interruption in study treatment dosing is recommended 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 
AstraZeneca Study Physician. 
 
Management of nausea and vomiting 
Events of nausea and vomiting are known to be associated with olaparib treatment. In study 
D0810C00019 nausea was reported in 71% of the olaparib treated patients and 36% in the 
placebo treated patients and vomiting was reported in 34% of the olaparib treated patients and 
14% in the placebo treated patients. They are generally mild to moderate (CTCAE grade 1 or 
2) severity, intermittent and manageable on continued treatment. The first onset generally 
occurs in the first month of treatment with the incidence of nausea and vomiting not showing 
an increase over the treatment cycles. 
 
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. 

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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 progression or toxicity, the case should be 
discussed with AstraZeneca study physician. 
 
If a patient discontinues treatment for intercurrent condition and progresses while off 
treatment, they can restart study treatment if the investigator feels the patient is receiving 
clinical benefit. Please note that evidence of objective radiological disease progression is 
required. 
 
All dose reductions and interruptions (including any missed doses), and the reasons for the 
reductions/interruptions are to be recorded in the eCRF. 
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 biopsy procedure. 
 
Study treatment should be discontinued for a minimum of 3 days before a patient undergoes 
therapeutic palliative radiation treatment. Study treatment should be restarted within 4 weeks 
as long as any bone marrow toxicity has recovered. 
 
Table 5 
Dose reductions for study treatment 
 
 
Initial Dose 
Following re-challenge 
post interruption: Dose 
reduction 1 
Dose reduction 2 
 
 
300mg 
250mg 
200mg 
 
 
 
5.6 
Concomitant and post-study treatment(s) 
The use of any natural/herbal products or other “folk remedies” should be discouraged but use 
of these products, as well as use of all vitamins, nutritional supplements and all other 
concomitant medications must be recorded. 
 
Any medications (with the detailed exceptions) which are considered necessary for the 
patient's welfare, and which it is believed will not interfere with the study medication, may be 
given at the discretion of the investigator, providing the medications, the doses, dates and 
reasons for administration are recorded. 
 
In addition, any 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. 

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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 as per Table 1, Table 2, Table 3 and 
Table 4. 
 
 
5.6.1 Medications that may NOT be administered 
No other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (Hormone 
replacement therapy (HRT) is acceptable), radiotherapy, biological therapy or other novel 
agent) is to be permitted while the patient is receiving study medication. 
 
Live virus and bacterial vaccines should not be administered whilst the patient is receiving 
study medication 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. 
 
 
5.6.2 CYP3A4 inhibitors, inducers, and other substrates 
Table 6 
Restricted concomitant medications 
Note: While the restricted concomitant medications listed below refer to olaparib, they apply 
to all patients in SOLO1 receiving blinded study treatment. 

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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 twice 
daily 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 twice 
daily 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 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 

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Medication/class of drug: 
Usage (including limits for duration permitted and 
special situations in which it’s allowed ): 
• CYP3A4 substrates: with narrow 
therapeutic margin: e.g. cisapride, 
cyclosporine, ergot alkaloids, fentanyl, 
pimozide, sirolimus, tacrolimus and 
warfarin. 
• Sensitive CYP3A4 substrates: e.g. 
buspirone, felodipine, fluticasone, 
lovastatin, quetiapine, saquinavir, 
sildenafil and simvastatin 
• CYP2B6 substrates: bupropion, 
efavirenz 
• OATP1B1substrates: bosentan, 
glibenclamide, repaglinide, statins and 
valsartan 
• OCT1, MATE1 and MATE2K 
substrates: metformin 
• OCT2 substrates: cimetidine and 
metformin 
• OAT3 substrates: furosemide, 
methotrexate 
• BCRP substrates: e.g. methotrexate and 
rosuvastatin. 
• P-gp substrates: e.g. simvastatin, 
pravastatin, dabigatran, digoxin and 
colchicine 
Effect of olaparib on other drugs 
 
Based on limited in vitro data, olaparib may 
increase the exposure to substrates of CYP3A4, 
BCRP, OATP1B1, OCT1, OCT2, OAT3, 
MATE1 and MATE2K. 
 
Based on limited in vitro data, olaparib may 
reduce the exposure to substrates of 2B6 (and 
potentially substrates of CYP2C9, CYP2C19 and 
P-gp). The efficacy of some hormonal 
contraceptives may be reduced if co- 
administered with olaparib. 
 
Caution should be observed if statins or sensitive 
CYP3A4 substrates are co-administered. 
 
Appropriate clinical monitoring is recommended 
for patients receiving P-gp substrates or CYP3A 
substrates with a narrow therapeutic margin 
concomitantly with olaparib. 

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Medication/class of drug: 
Usage (including limits for duration permitted and 
special situations in which it’s allowed ): 
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. 
Non-vitamin K antagonist oral anticoagulants 
(NOACs), subcutaneous heparin and low 
molecular weight heparin may be given 
concomitantly with olaparib and INR monitoring 
is not required. If NOACs are used, it is 
preferable to avoid CYP3A substrates (e.g 
apixaban and rivaroxaban) if possible. 
 
 
 
5.6.3 Anticoagulant Therapy 
Patients who are taking warfarin may participate in this trial; however, it is recommended that 
prothrombin time (international normalised ratio (INR) and activated partial thromboplastin 
time (APTT)) 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. 
 
Non-vitamin K antagonist oral anticoagulants (NOACs), subcutaneous heparin and low 
molecular weight heparin may be given concomitantly with olaparib/placebo. If NOACs are 
used, it is preferable to avoid CYP3A substrates (e.g. apixaban and rivaroxaban) if possible. 
 
5.6.4 Anti-emetics/Anti-diarrhoeals 
From screening part 2 onwards, should a patient develop nausea, vomiting and / or diarrhoea, 
then these symptoms should be reported as AEs (see Section 6.4.4) and appropriate treatment 
of the event given. 
 
5.6.5 Palliative radiotherapy 
Palliative radiotherapy may be used for the treatment of pain at the site of bony metastases 
that were present at baseline, provided the investigator does not feel that these are indicative 
of clinical disease progression during the study period. Study treatment should be 
discontinued for a minimum of 3 days before a patient undergoes therapeutic palliative 
radiation treatment. Study treatment should be restarted within 4 weeks as long as any bone 
marrow toxicity has recovered. 
5.6.6 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 

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denosumab for bone disease and corticosteroids for the symptomatic control of brain 
metastases provided the dose is stable before and during the study and they were started at 
least 4 weeks prior to beginning study treatment. 
 
5.6.7 Subsequent therapies for cancer 
Details of first and subsequent therapies for cancer and/or details of surgery for the treatment 
of the cancer, after discontinuation of treatment, will be collected. Reasons for starting 
subsequent anti-cancer therapies including access to other PARP inhibitors or investigational 
drugs will be collected and included in the exploratory assessments of OS. 
 
5.7 
Treatment compliance 
The administration of all study drugs (including investigational products) 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 will make tablet counts at regular 
intervals during treatment. Compliance will be assessed by the tablet count and the 
information will 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 will be instructed to notify study site personnel of missed 
doses. Dates of missed or held doses will be recorded by the site staff on the eCRF. 
Patients must return all containers and any remaining tablets at the end of the study. 
 
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. Any discrepancies must be accounted for on the appropriate forms. 
 
5.8 
Discontinuation of investigational product 
Patients may be discontinued from investigational product (IP) in the following situations: 
 
• 
Patients decision. The patient is at any time free to discontinue treatment, without 
prejudice to further treatment 
 
• 
Adverse Event 

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• 
Severe non-compliance to study protocol 
• 
Bone marrow findings consistent with myelodysplastic syndrome (MDS)/acute 
myeloid leukaemia (AML). 
 
• 
Objective radiological disease progression according to RECIST criteria (unless in 
the Investigator’s opinion they are benefiting from treatment and they do not meet 
any other discontinuation criteria as outlined in Section 5.8) 
 
• 
If at two years of study treatment the patient has no evidence of disease. 
Presence of structural disease should be assessed according to RECIST guidelines 
at week 108. 
 
5.8.1 Procedures for discontinuation of a patient from investigational product 
A patient that decides to discontinue investigational product will 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(s). Adverse events will be followed up (see Sections 6.4.4 and 6.4.5); 
questionnaires (e.g., for patient reported outcomes) and all study drugs should be returned by 
the patient. 
 
By discontinuing from treatment, the patient is not withdrawing from the study. Patients 
should be followed for progression (if discontinuation in the absence of progression), PFS2 
and OS following treatment discontinuation as per the protocol schedule. If a patient is 
withdrawn from study, see Section 5.9. 
 
Any patient discontinuing investigational product should be seen at 30 days post 
discontinuation for the evaluations outlined in the study schedule. The patient’s tumour status 
should be assessed clinically and, if appropriate, disease progression should be confirmed by 
radiological assessment. After discontinuation of study medication, the principal 
Investigator/Sub-Investigator will perform the best possible observation(s), test(s) and 
evaluation(s) as well as give appropriate medication and all possible measures for the safety of 
the patient. In addition, they will record on the eCRF the date of discontinuation, the reasons, 
manifestation and treatment at the time of discontinuation. If patients discontinue study 
treatment, the AstraZeneca monitor must be informed immediately. Patients will be required 
to attend the treatment discontinuation visit. The patient should return all study medication. 
 
After discontinuation of the study medication at any point 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 6.4.4 and 6.4.5). 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 within 24 hours as described in Section 6.4.5) 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. Procedures for handling of any untoward events occurring 

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subsequent to the 30-day follow-up AE reporting period are described in Section 6.4.4 under 
Post follow-up adverse event reporting. 
Any patient who has not yet shown objective radiological disease progression at withdrawal 
from IP should continue to be followed as per RECIST as detailed in Section 6.2.3.1. From 
CSP v5 onwards: Study patients who discontinued treatment at two years per protocol with no 
evidence of disease (either NED from baseline or CR achieved while receiving study 
treatment) and who not yet had disease progression will have radiological (RECIST) tumour 
assessments only when clinically indicated eg rising CA-125 and/or signs and symptoms 
suggesting PD, according to the investigator’s clinical judgment. All patients must be 
followed for survival, up to the final analysis. 
 
5.9 
Withdrawal from study 
Patients are at any time free to withdraw from study (investigational product and 
assessments), without prejudice to further treatment (withdrawal of consent). Such patients 
will 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 6.4.4 and 6.4.5); questionnaires (e.g., for patient reported outcomes) and all study 
drugs should be returned by the patient. 
 
The status of ongoing, withdrawn (from the study) and “lost to follow-up” patients at the time 
of an overall survival analysis should be obtained by the site personnel by checking the patient 
notes, hospital records, contacting the patient’s general practitioner and checking publicly 
available death registries. In the event that the patient has actively withdrawn consent to the 
processing of their personal data the vital status of the patient can be obtained by site 
personnel from publicly available resources where it is possible to do so under applicable 
local laws. 
 
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. 
 
• 
Severe non-compliance to protocol as judged by the Investigator and/or 
AstraZeneca. 
 
• 
Incorrectly enrolled patients i.e., the patient does not meet the required 
inclusion/exclusion criteria for the study. 
 
• 
Patient lost to follow-up. 
• 
Death 

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*If a patient withdraws consent, they will be specifically asked if they are withdrawing 
consent to: 
− 
to further participation in the study including any further follow up (e.g., 
survival calls) 
 
− 
withdrawal of consent to the use of their study generated data 
− 
withdrawal to the use of any samples (see Section 7.5) 
 
6. 
COLLECTION OF STUDY VARIABLES 
6.1 
Recording of data 
The Rave Web Based Data Capture (WBDC) system will be used for data collection and 
query handling. 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 ensures the accuracy, completeness, and timeliness of the data recorded and 
of the provision of answers to data queries according to the Clinical Study Agreement (CSA). 
 
The investigator will sign the completed eCRFs. A copy of the completed eCRFs will be 
archived at the study site. 
 
6.2 
Data collection at enrolment and follow-up 
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 Table 1, Table 2, Table 3 and Table 4. 
 
6.2.1 Enrolment/Screening procedures 
The following assessments and procedures should be performed during screening prior to –28 
days and / or within 28 days prior to first dose of study treatment as per Table 1 and Table 2. 
For details of the schedule and nature of the assessments, see below: 
 
• 
Date of birth, race and ethnicity 
• 
Current and concomitant medications including previous cancer therapies 
• 
Medical and surgical history including previous cancer and radiotherapy, history of 
blood transfusions in previous 120 days and response to current therapies 
 
• 
Physical examination, ECOG performance status, vital signs (blood pressure and 
pulse; body temperature), body weight, height and ECG (within 7 days prior to the 
start of the study treatment). 

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• 
In screening part 1 only SAEs related to study procedures (e.g. blood sampling for 
BRCA & pregnancy test [if applicable]) must be reported (AEs do not require 
reporting). From screening part 2 onwards - all AEs/SAEs must be reported. 
• 
Confirmed availability and collection of an archival paraffin embedded tumour 
tissue sample (see Section 6.7.2) 
 
• 
Tumour biopsy (optional) (see Section 6.7.3) 
• 
Baseline scores (prior to dosing on Day 1) for patient reported outcomes and quality 
of life will be obtained (EQ-5D-5L and FACT-O) (see Section 6.5 and Appendix H) 
 
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 study assessments 
Study treatment is self administered by the patient twice daily as instructed. The visit schedule 
is based on 28-day periods. Patients will attend the clinic on days 1 (1st day of treatment), 8, 
15, 22, 29, and every 4 weeks from visit 7 until 108 weeks (if not progressed and still on 
treatment). Patients who remain on treatment post progression or after week 108 continue to 
attend clinic visits every 4 weeks for up to 156 weeks (3 years), after which they will attend 
clinic for every 12 weeks (relative to date of randomisation), unless more visits are clinically 
indicated. Treatment beyond 108 weeks can only be continued at the discretion of the 
investigator and only after fulfilling specific conditions (see Table 3). The following 
assessments will be performed at time points specified in the study schedule (see Table 3): 
• 
Physical examination (data is not required to be captured on an eCRF, however any 
significant changes from baseline must be reported as an AE). 
 
• 
ECOG performance status: required at day 1 of 1st day of study treatment, if it has 
not been assessed within 7 days of randomisation, then as per information provided 
in Table 3 and Table 4. 
 
• 
Vital signs: day 1 and day 29. Body weight is only required at day 1 of 1st day of 
study treatment, if it has not been assessed within 7 days of randomization and then 
any other time as clinically indicated. From visit 7, temperature and weight are only 
required if clinically indicated, blood pressure and pulse are to be taken in line with 
RECIST assessments. 
 
• 
ECG: Day 57 (i.e., week 9), at safety follow up and at any other time if clinically 
indicated. 
 
• 
Haematology and clinical chemistry: Safety blood samples do not need to be 
repeated on Day 1 of study treatment if assessed at least 3 weeks after the last dose 

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of chemotherapy and within 7 days before starting study treatment, unless the 
investigator believes that it is likely to have changed significantly 
• 
Serum or urine pregnancy test for women of childbearing potential (prior to 
treatment on day 1 of 1st day of study treatment). If the test is positive then a 
confirmatory test should be performed. 
 
• 
gBRCA1/2 mutation status: Confirmation of BRCA mutation status result using 
Myriad test (for those patients that knew their gBRCA status prior to study entry) 
 
• 
tBRCA1/2 mutation status: Determination of germline BRCA mutation status using 
the Myriad test for those patients that knew their tumour BRCA status prior to study 
entry. Confirmation of tumour BRCA mutation status for all patient result using a 
central laboratory 
 
• 
Disease specific Tumour marker (CA-125) 
• 
Tumour assessments scans of the chest*, abdomen and pelvis with other regions as 
clinically indicated for assessment of disease (CT/MRI) (see Section 6.3). 
 
− 
*Chest, abdomen and pelvis CT/MRI scans should be performed at base-line. 
− 
*In those patients with disease present in the chest or upper abdomen 
lymphadenopathy chest, abdomen and pelvis should be performed at 
follow-up. 
 
− 
*In those patient with no disease present in the chest and no upper abdomen 
lymphadenopathy then follow-up is by abdomen and pelvis only. 
 
• 
AE and concomitant medications (including any blood transfusions) at every visit. 
• 
Patient Reported Outcomes and Quality of Life questionnaire: EQ-5D- 5L and 
FACT-O: at baseline, Day 29, every 12 weeks (+/- 7 days) for 156 weeks, then 
every 24 weeks (+/- 7 days) or until the data cut off for the primary analysis. In 
addition, Quality of Life questionnaire will be collected at the discontinuation of 
study treatment visit and 30 days post last dose. Patients who had RECIST 1.1 
disease progression will complete the questionnaires during the 12 weekly survival 
follow-ups either in person or over the phone. 
 
• 
Resource use will be captured including inpatient admissions, ICU and length of 
stay in hospital 
 
• 
An optional pharmacogenetic sample will be obtained from consenting patients and 
stored for future exploratory pharmacogenetic analysis (see Section 6.8.4) 
 
• 
Optional tumour biopsy at objective progression (see Section 6.7.3) 

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• 
Optional blood sample for biomarker analysis (e.g. cfDNA) at randomisation (see 
Section 6.8.3) 
 
Patients will continue with study treatment for up to two years or until objective radiological 
disease progression by RECIST, whichever is earlier. Patients who continue to have evidence 
of stable disease at two years or who have progressed may continue to receive study treatment 
if, in the opinion of the investigator, it is in the patient’s best interest. However, if at two years 
the patient has no evidence of disease, study treatment should be discontinued. A decision 
about continuing treatment with the investigational product beyond two years should be made 
after assessing the patient’s disease status according to RECIST guidelines at week 108, 
and/or by assessing the patient’s clinical condition. Continuation of treatment beyond week 
108, based solely on clinical progression, is permissible only after case-by-case discussion 
with the AZ study physician. Once patients have been discontinued from study treatment, 
other treatment options will be at the discretion of the Investigator. Within this study patients 
are not permitted to switch over to the opposite arm from which they were randomised. 
 
6.2.3 Follow-up procedures 
6.2.3.1 
Treatment Discontinuation Visit 
Patients should be discontinued from study treatment if any discontinuation criteria are 
fulfilled (see Section 5.8). The assessments to be carried out at the visit are detailed in the 
study schedule (see Table 3). 
 
6.2.3.2 
Treatment discontinuation due to objective radiological disease progression or 
any other discontinuation criteria 
Patients should be discontinued from study treatment if they have radiological objective 
disease progression according to RECIST (see Appendix F), unless in the investigator’s 
opinion they are benefiting from treatment, or if they meet any other discontinuation criteria 
as outlined in Section 5.8. The assessments to be carried out are detailed in the study schedule 
(Table 3) and include: 
 
• 
An optional tumour biopsy sample 
• 
An optional blood sample for biomarker analysis (e.g. cfDNA) 
• 
EQ-5D-5L and FACT-O questionnaires 
Following the discontinuation visit and safety follow up visit patients who have discontinued 
due to radiological disease progression will be followed for PFS2 and OS as per Table 4 and 
patients who have discontinued but do not have radiological disease progression will continue 
to be followed for PFS1 as per Table 4. 
 
6.2.4 Follow-up 30 day after last dose of study medication (follow-up visit) 
A follow-up visit should be conducted 30 days after the last dose of study treatment. Any 
serious and/or non-serious AEs ongoing at the time of the Discontinuation Visit or which have 

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occurred during the defined 30-day follow-up period must be followed-up (in accordance with 
Section 6.4.4). Appropriate safety evaluations should be repeated and/or 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 (see Table 3). 
 
6.2.5 Survival 
Assessments for survival should be made every 12 weeks following radiological objective 
disease progression according to RECIST. Survival information may be obtained via 
telephone contact with the patient, patient’s family or by contact with the patient’s current 
physician. Survival data will be collected up to the time of the final overall survival (OS) 
analysis. In addition, patients should be contacted in the week following the data cut-off for 
the primary PFS and each planned OS analysis to provide complete survival data. 
Patients will be followed up as per Table 3 or Table 4 to the point of the final analysis. At this 
point Investigators will be notified that no further data collection for the study is required. 
Monitoring and recording of SAEs will continue as per Section 6.4.5. Since some cases 
MDS/AML or new primary malignancies developed after discontinuing treatment with 
olaparib, investigators will be asked during the regular follow up for overall survival if the 
patient has developed MDS/AML or a new primary malignancy and prompted to report any 
cases as SAE (or AE for non-melanoma skin cancers, if at least one of the criteria for SAE is 
not met, see Section 6.4.2) even after discontinuation of therapy and regardless of 
investigator’s assessment of causality or knowledge of the treatment arm. 
 
The status of ongoing, withdrawn (from the study) and lost to follow up patients at the time of 
an overall survival analysis should be obtained by the site personnel by checking the patient 
notes, hospital records, contacting the patient’s general practitioner and checking publicly 
available death registries. In the event that the patient has actively withdrawn consent to the 
processing of their personal data, the vital status of the patient can be obtained by site 
personnel from publicly available resources where it is possible to do so under applicable 
local laws. 
 
6.2.6 Second Progression 
Following objective progression, copies of the patient’s radiological scans are no longer 
required to be sent for blinded independent central review. Patients will be assessed every 12 
weeks for a second progression (using the patients status at first progression as the reference 
for assessment of second progression). A patient’s progression status is defined according to 
local standard clinical practice and may involve any of; objective radiological, CA-125, 
symptomatic progression or death. RECIST measurements will not be collected for 
assessment of PFS2. The date of PFS2 assessment and investigator opinion of progression 
status (progressed or non-progressed) at each assessment will be recorded in the eCRF. 

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6.2.7 Patient management post primary analysis 
The data cut off date for the statistical analysis for the primary objective of the study will be 
established when approximately 196 confirmed progression events have occurred or after the 
last patient randomised has had the opportunity to have been on the study for at least 
36 months, whichever comes first. 
 
Patients on study treatment at the time of the data cut-off will continue to receive study 
treatment until they meet any discontinuation criteria as per Section 5.8. 
 
Patients on study treatment will be followed for core safety assessments and disease 
progression (haematology, clinical chemistry, AEs/SAEs and concomitant medications 
(including any subsequent cancer therapy), study treatment dosing details, objective 
radiological disease progression according to RECIST, as per Table 3). These patients should 
be followed according to routine clinical practice but visits should take place at least every 12 
weeks (see Table 3). 
 
All patients (patients still on study treatment and patients withdrawn from study treatment) 
will be followed for survival and disease progression. 
 
6.2.8 Patient management post final analysis 
The data cut off date for the final statistical analysis of the study will be established at ~60% 
maturity for OS. 
 
At this time point, the clinical study database will close to new data and post the data cut off 
all patients will be unblinded. Patients who are receiving active treatment can either choose to 
discontinue from the study or where the investigator believes patients are gaining clinical 
benefit; patients may continue to receive study treatment. All patients will receive follow up 
care in accordance with standard local clinical practice. 
 
Patients that are on placebo will not be offered olaparib as a study treatment. 
 
AstraZeneca will continue to supply olaparib after completion of this study until either 
olaparib is licenced in that country and available for the patient under the approved indication 
(with no restrictions or cost barriers), or it is determined that the benefit to risk profile does 
not support continued development of olaparib, or the national health authority has deemed 
the drug not approvable. In all these scenarios, AstraZeneca will work with investigators on 
the proper transition of patients to alternative therapies if possible. 
 
SAEs will continue to be reported to AstraZeneca Patient Safety Department, for any patients 
who continue on olaparib until 30 days after study treatment is discontinued, in accordance 
with Section 6.4.5. Additionally as stated any SAE or non-serious adverse event, that is 
ongoing at the end of the study, 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. If an 
investigator learns of any SAEs, including death, at any time after a patient has completed the 

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study, 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. 
Drug accountability should continue to be performed until the patient stops study treatment 
completely. 
 
In the event that a roll-over or safety extension study is available at the time of the final DCO 
and database closure, participants currently receiving treatment with olaparib may be 
transitioned to such a study, and the current study would reach its end. The roll-over or 
extension study would ensure treatment continuation with visit assessments per its protocol, as 
applicable. Any participant who would be proposed to move to such a study would be given a 
new informed consent, as applicable. 
 
6.3 
Efficacy 
6.3.1 CT and MRI scans Tumour assessments (modified RECIST 1.1) 
Following the baseline assessment, subsequent tumour assessments according to RECIST 
should be performed at the end of every 12 weeks (±1week) up to 156 weeks then every 24 
weeks (±1 week) relative to date of randomisation, according to the planned study schedule 
(see Table 3 and Table 4) up to objective progression by RECIST. 
 
For those patients with no evidence of disease at baseline, following a clinical complete 
response to chemotherapy, progression is defined by the detection of new lesions on follow up 
radiological assessments (modified RECIST 1.1). From CSP v5 onwards: Study patients who 
discontinued treatment at two years per protocol with no evidence of disease (either NED 
from baseline or CR achieved while receiving study treatment) and who not yet had disease 
progression will have radiological (RECIST) tumour assessments only when clinically 
indicated eg rising CA-125 and/or signs and symptoms suggesting PD, according to the 
investigator’s clinical judgment. 
 
The imaging modalities used for RECIST assessment will be CT or MRI scans of the chest, 
abdomen and pelvis with other regions as clinically indicated for the assessment of disease, 
see Section 6.2.2. Any other sites at which new disease is suspected should also be 
appropriately imaged. 
 
Radiological examinations performed in the conduct of this study should be retained at site as 
source data. 
 
Anonymised copies of the scans are to be sent to an AstraZeneca appointed CRO for blinded 
independent central review. 
All treatment decisions will be based on site assessment of scans. After the primary PFS 
analysis, central review of scans will no longer be required and investigators will be advised 
when to stop sending copies of the scans to the CRO conducting the central review. Ongoing 
collection of site review tumour assessment is required and must be recorded in the eCRF. 

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It is important to follow the assessment schedule as closely as possible. If scans are performed 
outside of scheduled visit ± 1 week window interval and the patient has not progressed, every 
attempt should be made to perform the subsequent scans at their scheduled time points. 
Patients will be evaluated until objective radiological disease progression by RECIST as per 
the study schedule (see Table 3 and Table 4), and then followed for second progression and 
survival, regardless of whether study treatment is discontinued or delayed and/or protocol 
violations, unless they withdraw consent. 
 
6.3.2 Tumour Evaluation 
Modified RECIST 1.1 criteria will be used to assess patient response to treatment by 
determining progression free survival (PFS) times. (The modified RECIST 1.1 guidelines for 
measurable, non-measurable, target and non-target lesions and the objective tumour response 
criteria (complete response, partial response, stable disease or progression of disease, no 
evidence of disease) are presented in Appendix F). 
 
Although CA-125 is measured in this study it will not be directly used for assessing objective 
response or progression and patients should be continued on treatment until objective 
radiological disease progression as defined by RECIST. 
 
The methods of assessment of tumour burden used at baseline - CT or MRI scans of chest, 
abdomen and pelvis, with other regions as clinically indicated for the assessment of disease 
must be used at each subsequent follow-up assessment, (see Section 6.2.2). 
 
Following the baseline assessment, efficacy for all patients will be assessed by objective 
tumour assessments every 12 weeks (±1 week) up to 156 weeks then every 24 weeks ((±1 
week) relative to date of randomisation, according to the planned study schedule Table 3 and 
Table 4 until objective radiological disease progression as defined by RECIST. 
 
If a patient discontinues treatment (and/or receives a subsequent cancer therapy) prior to 
progression then the patient should still continue to be followed until objective radiological 
disease progression as defined by RECIST. From CSP v5 onwards: Study patients who 
discontinued treatment at two years per protocol with no evidence of disease (either NED 
from baseline or CR achieved while receiving study treatment) and who not yet had disease 
progression will have radiological (RECIST) tumour assessments only when clinically 
indicated eg rising CA-125 and/or signs and symptoms suggesting PD, according to the 
investigator’s clinical judgment. 
 
Categorisation of objective tumour response assessment will be based on the RECIST criteria 
of response: complete response (CR), partial response (PR), stable disease (SD), progression 
of disease (PD), no evidence of disease (NED) and not evaluable (NE). Target lesion (TL) 
progression will be calculated in comparison to when the tumour burden was at a minimum 
(i.e., smallest sum of diameters previously recorded on study). In the absence of a best 
response of progression, tumour response (CR, PR, SD) will be calculated in comparison to 
the baseline tumour measurements obtained before randomisation. 

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For patients with non-measurable disease only at baseline, categorisation of objective tumour 
response assessment will be based on the RECIST criteria of response: CR (complete 
response), PD (progression of disease) and Non CR/Non PD. 
 
Patients with no disease at baseline will be assessed according to RECIST criteria for new 
lesions with responses of No Evidence of Disease (NED) or progression of disease. 
If the Investigator is in doubt as to whether progression has occurred, particularly with 
response to NTL (non-target lesion) or the appearance of a new lesion, it is advisable to 
continue treatment until the next scheduled assessment or sooner if clinically indicated and 
reassess the patient’s status. If repeat scans confirm progression, then the date of the initial 
scan should be declared as the date of progression. 
 
To achieve ‘unequivocal progression’ on the basis of non-target disease, there must be an 
overall level of substantial worsening in non-target disease such that, even in presence of SD 
or PR in target disease, the overall tumour burden has increased sufficiently to merit 
discontinuation of study treatment. A modest ‘increase’ in the size of one or more non-target 
lesions is usually not sufficient to qualify for unequivocal progression status. 
 
Following progression, patients should continue to be followed up for survival every 12 weeks 
as outlined in the study plan (Table 4 or Table 5). It is important to follow the assessment 
schedule as closely as possible. Please refer to the study plan (Table 4 or Table 5) and 
CT/MRI scans in Section 6.3.1. 
 
6.3.3 Central reading of scans 
An independent review of all scans used in the assessment of tumours according to RECIST 
will be conducted. All imaging assessments including unscheduled visit scans will be 
collected on an ongoing basis and sent to an AstraZeneca appointed Contract Research 
Organisation (CRO) for central analysis. Results of this independent review will not be 
communicated to investigators, and the management of patients will be based solely upon the 
results of the RECIST assessment conducted by the investigator. 
A sensitivity analysis for this study will be based on the independent central review (ICR) of 
the radiological scans. 
 
6.4 
Safety 
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section. 
 
6.4.1 Definition of adverse events 
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 

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abnormal results of an investigation (e.g., laboratory findings, electrocardiogram). In clinical 
studies, an AE can include an undesirable medical condition occurring at any time, including 
run-in or washout periods, even if no study treatment has been administered. 
 
The term AE is used to include both serious and non-serious AEs. 
 
6.4.2 Definitions of serious adverse event 
A serious adverse event is an AE occurring during any study phase (i.e., run-in, treatment, 
washout, 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 a SAE, see Appendix B to the Clinical Study 
Protocol. 
 
6.4.3 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 the Important Identified Risk of MDS/AML and the Important Potential Risks of 
new primary malignancy (other than MDS/AML) and pneumonitis. 
 
6.4.4 Recording of adverse events 
Time period for collection of adverse events 
Adverse Events, including Serious Adverse Events, will be collected from time of signature of 
informed consent*, throughout the treatment period and 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 last dose of study medication must be followed to resolution. After any 
interim analysis, any ongoing AEs/SAEs need to be unlocked and followed for resolution. 
 
*Exception: In screening part 1 only SAEs related to study procedures must be reported (AEs 
do not require reporting). From screening part 2 onwards - all AEs/SAEs must be reported. 

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Follow-up of unresolved adverse events 
Any SAE or non-serious adverse event that is ongoing at the time of the 30 day follow up, 
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 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. 
 
Post Follow-up adverse events 
For Pharmacovigilance purposes and characterisation of events of special interest, any case of 
MDS/AML or new primary malignancy occurring after the 30 day follow up period should be 
reported as SAE (or AE for non-melanoma skin cancers, if at least one of the criteria for SAE 
is not met, see Section 6.4.2) to AstraZeneca Patient Safety regardless of investigator’s 
assessment of causality or knowledge of the treatment arm. A Questionnaire will be sent to 
any investigator reporting MDS/AML or new primary malignancy as an aid to provide 
detailed information on the case. 
 
At any time after a patient has completed the study, if an Investigator learns of any SAEs, 
including death, 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. 
 
If patients who are gaining clinical benefit are allowed to continue study treatment post data 
cut off and / or post study completion then all SAEs must continue to be collected and 
reported to Patient Safety within the usual timeframe. 
 
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 former 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). 
 
Variables 
The following variables will be collected for each AE: 
 
• 
AE (verbatim) 
• 
The date when the AE started and stopped 
• 
Changes in CTCAE grade 
• 
Whether the AE is serious or not 
• 
Investigator causality rating against the Investigational Product (yes or no) 

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• 
Action taken with regard to investigational product 
• 
Outcome. 
In addition, the following variables will be collected for SAEs: 
 
• 
Date AE met criteria for serious AE 
• 
Date Investigator became aware of serious AE 
• 
AE is serious due to 
• 
Date of hospitalisation 
• 
Date of discharge 
• 
Probable cause of death 
• 
Date of death 
• 
Autopsy performed 
• 
Causality assessment in relation to study procedure(s) 
• 
Causality assessment in relation to other medication 
• 
Description of AE. 
Severity of AE 
For each episode on 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 need not necessarily be considered serious. For example, nausea that persists for 
several hours may be considered severe nausea, but not a 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 (this would be recorded as an SAE as per the guidance found in this section (Section 
6.4.4)). 
 
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 without assigned 
CTCAE grades the recommendation is that the CTCAE criteria that convert mild, moderate 
and severe events into CTCAE grades should be used. 

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A copy of the CTCAE version can be downloaded from the Cancer Therapy Evaluation 
Program website. 
Causality collection 
The Investigator will assess causal relationship between Investigational Product 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 investigational product?’ 
 
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 B 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 CRF. 
When collecting AEs, the recording of diagnoses is preferred (when possible) to 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 results from protocol mandated laboratory tests and vital signs will be summarised in the 
clinical study report. Deterioration as compared to baseline in protocol-mandated laboratory 
values, vital signs should therefore only be reported as AEs if they fulfil any of the SAE 
criteria or are the reason for discontinuation of treatment with the investigational product. 
 
If deterioration in a laboratory value/vital sign/ECG is associated with clinical signs and 
symptoms, the sign or symptom will be reported as an AE and the associated laboratory 
result/vital sign/ECG 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 progression, 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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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 
combined increase of Aminotransferase and Total Bilirubin – Hy’s Law’, for further 
instructions. 
 
Disease progression 
Disease progression can be considered as a worsening of a patient’s condition attributable to 
the disease for which the investigational product is being studied. It may be an increase in the 
severity of the disease under study and/or increases in the signs and symptoms of the cancer. 
The development of new, or progression of existing metastasis to the primary cancer under 
study should be considered as disease progression and not an AE. Events, which are 
unequivocally due to disease progression, should not be reported as an AE during the study. 
New cancers 
The development of a new primary cancer (including skin cancer) should be regarded as an 
AE and will generally meet at least one of the serious criteria (see Section 6.4.2). 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 progression. 
 
Lack of efficacy 
When there is deterioration in the ovarian cancer, for which the study treatment(s) is being 
used, there may be uncertainty as to whether this is lack of efficacy or an AE. In such cases, 
unless the Sponsor or the reporting physician considers that the study treatment contributed to 
the deterioration of the condition, or local regulations state to the contrary, the deterioration 
should be considered to be a lack of efficacy and not an AE. 
 
Deaths 
All deaths that occur in screening part 1 related to study procedures should be reported as a 
SAE. 
All deaths that occur from screening part 2 onwards, including within the protocol-defined 30- 
day post-study follow-up period after the administration of the last dose of study treatment, 
must be reported as follows: 
• 
Death clearly the result of disease 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 progression of the disease under 
study, the AE causing the death must be reported to the study monitor as a SAE 
within 24 hours (see Section 6.4.5 for further details). The report should contain a 
comment regarding the co-involvement of progression of disease, if appropriate, 

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and should assign main and contributory causes of death. This information can be 
captured in the ‘death eCRF’. 
• 
Deaths with an unknown cause should always be reported as a 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 within the usual 
timeframes. 
 
6.4.5 Reporting of serious adverse events 
In Screening part 1, only SAEs related to study procedures must be reported. From Screening 
part 2 onwards, all SAEs have to be reported, whether or not considered causally related to the 
investigational product, or to the study procedure(s). All SAEs will be recorded in the CRF. 
 
If any reportable SAE occurs in the course of the study, then investigators or other site 
personnel inform appropriate AstraZeneca representatives immediately, or no later than 24 
hours of when he or she becomes aware of it. 
 
The designated AstraZeneca representative works with the investigator to ensure that all the 
necessary information is provided to the AstraZeneca Patient Safety data entry site 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 
AstraZeneca representatives of any follow-up information on a previously reported SAE 
immediately, or no later than 24 hours of when he or she becomes aware of it. 
 
Once the Investigators or other site personnel indicate an AE is serious in the WBDC system, 
an automated email alert is sent to the designated AstraZeneca representative. 
If the WBDC system is not available, then the Investigator or other study site personnel 
reports a SAE to the appropriate AstraZeneca representative by telephone. 
 
The AstraZeneca representative will advise the Investigator/study site personnel how to 
proceed. 
 
The reference document for definition of expectedness/listedness is the IB for the AstraZeneca 
drug. 
6.4.6 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, Table 2 
and Table 3). 

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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: 
 
6.4.6.1 
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. 
 
6.4.6.2 
Coagulation 
• 
activated partial thromboplastin time {APTT}will be performed if clinically 
indicated 
 
• 
international normalised ratio {INR} will be performed 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. 
 
6.4.6.3 
Biochemistry assessments for safety 
• 
sodium 
• 
potassium 

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• 
calcium 
• 
magnesium 
• 
creatinine 
• 
total bilirubin 
• 
gamma glutamyltransferase [GGT] 
• 
alkaline phosphatase [ALP] 
• 
aspartate transaminase [AST] 
• 
alanine transaminase [ALT] 
• 
urea or blood urea nitrogen [BUN] 
• 
total protein 
• 
albumin 
• 
lactic dehydrogenase [LDH]) 
NB. In case a patient shows an AST or ALT ≥3xULN or total bilirubin ≥ 2xULN please refer 
to Appendix D ‘Actions required in cases of combined increase of Aminotransferase and Total 
Bilirubin – Hy’s Law’, for further instructions. 
 
6.4.6.4 
Disease specific tumour marker samples (CA-125) 
As part of the routine safety blood samples, all patients will supply blood sample for CA-125 
(2 mL) for assessment at the beginning of each 28 day period prior to the patient receiving 
study treatment. 
 
It is important to follow the assessment schedule as closely as possible. If CA-125 assessment 
is performed outside of scheduled visit ± 1 week window interval, every attempt should be 
made to assess the CA-125 at the scheduled time points. Patients will be evaluated until 
objective disease progression, based on progressive serial elevation of serum CA-125 
according to the modified Gynecologic Cancer InterGroup criteria GCIG criteria (note GCIG 
criteria is not validated for this trial population) (see Section 11.1.2.2.). 
 
Further assessment of CA 125 post serological progression will be at the discretion of the 
investigator according to local clinical practice. 
 
For blood volume see Section 7.1. 

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6.4.6.5 
Urinalysis 
Urinalysis by dipstick should be performed as stated in Table 1, Table 2 and Table 3. 
Microscopic analysis should be performed by the hospital’s local laboratory if required. 
 
6.4.6.6 
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 5.5.5. 
 
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. 
 
6.4.7 Physical examination 
For timing of individual measurement refer to study schedule (see Table 1, Table 2 and Table 
3). 
 
A physical examination will be performed and include an assessment of the following: general 
appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, 
nose and throat), lymph nodes, thyroid, abdomen, musculo-skeletal (including spine and 
extremities) and neurological systems. 
 
6.4.8 ECG 
6.4.8.1 
Resting 12-lead ECG 
ECGs are required prior to obtaining the Myriad blood samples during screening for patients 
with unknown BRCA status, within 7 days prior to starting study treatment, at week 9 after 
starting study treatment when clinically indicated and at the follow up visit after patient has 
discontinued study medication. 
 
Twelve-lead ECGs will be obtained after the patient has been rested in a supine position for at 
least 5 minutes in each case. The Investigator or designated physician will review the paper 
copies of each of the timed 12-lead ECGs on each of the study days when they are collected. 
 
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. 
 
6.4.9 Vital signs 
Height will be assessed at screening only. 

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Weight will be assessed according to the Study Schedule (see Table 1, Table 2 and Table 3) 
and as clinically indicated at any other time. 
Any changes in vital signs should be recorded as an AE, if applicable. 
 
6.4.9.1 
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 after 10 minutes rest on a bed. For timings of 
assessments refer to the Study Schedule (see Table 1, Table 2 and Table 3). 
 
The date of collection and measurement will be recorded on the appropriate eCRF. 
 
6.4.9.2 
Body temperature 
Body temperature will be measured in degrees Celsius using an automated thermometer at the 
times indicated in the Study Schedule (see Table 1, Table 2 and Table 3). 
 
The date of collection and measurement will be recorded on the appropriate eCRF. 
 
6.4.10 Other safety assessments – Not applicable 
6.4.11 Serum or urine pregnancy test 
Pregnancy tests on blood or urine samples will be performed for pre-menopausal women of 
childbearing potential, prior to obtaining the Myriad blood samples during screening for 
patients with unknown BRCA status, within 28 days prior to the start of study treatment and 
on Day 1 of the study prior to commencing treatment. Tests will be performed by the 
hospital’s local laboratory. If results are positive the patient is ineligible/must be discontinued 
from the study. In the event of a suspected pregnancy during the study, the test should be 
repeated. 
 
6.5 
Patient reported outcomes (PRO): FACT-O and EQ-5D-5L 
No longer collected as study after primary analysis. Therefore, removed from assessments 
tables in CSP ed 5. 
 
6.5.1 Administration of PRO questionnaires 
Paper questionnaires will be given to the patient at baseline, at Day 29 and then every 12 
weeks (+/- 7 days) for 156 weeks, then every 24 weeks (+/- 7 days) or until the data cut off for 
the primary analysis. In addition, Quality of Life questionnaire will be collected at the 
discontinuation of study treatment visit and 30 days post last dose. Patients who had RECIST 
1.1 disease progression will complete the questionnaires during the 12 weekly survival follow- 
ups either in person or over the phone (see Table 3 and Table 4). Following collection of the 
paper questionnaire (in person or over the phone), the site staff can either enter the 
information directly into the WBDC (RAVE) electronic database system or arrange to have 
the paper questionnaires transcribed into the WBDC (RAVE) database. 

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Each centre must allocate the responsibility for the administration of the questionnaires to a 
specific individual (e.g., a research nurse, study coordinator) and if possible assign a 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: 
 
• 
It must be completed 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 
 
• 
It must be completed in private by the patient, where a visit to the clinic is not 
planned, i.e. for patients followed up for survival with no scheduled clinic visits, the 
site staff will administer questionnaires via telephone. 
• 
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 questionnaire (e.g., is 
blind or illiterate) the questionnaire may be read out by trained clinic staff and 
responses recorded 
 
• 
On completion of the questionnaire it should be handed back to the person 
responsible for questionnaires who should check for completeness 
 
Only 1 answer should be recorded for each question 
 
6.5.2 FACT-O 
Patient-reported health-related quality of life (HRQoL) will be assessed using the FACT-O 
questionnaire (Basen-Engquist K et al 2001). The FACT-O is composed of the following sub- 
scales: physical, social/family, emotional, and functional well-being as well as the additional 
concerns scales consisting of specific ovarian cancer symptoms. 
 
6.5.3 PRO method or questionnaire for other purposes 
The end point for health-related quality of life analysis will be the Trial Outcome Index (TOI), 
an established single targeted index derived from the FACT-O questionnaire and it is 
considered to target the most relevant symptoms together with function and physical well- 
being and can be directly related to signs and symptoms and AEs. The TOI is composed of the 
following scales of the FACT-O: physical and functional well-being and additional concerns. 

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When a patient presents with a biopsiable tumour, an on-study tumour biopsy sample should 
be obtained, (only in patients that have signed the additional optional consent). A sample 
should be taken prior to dosing with study drug but must be taken after the baseline RECIST 
scan has been performed and a second tumour biopsy sample taken at documented RECIST 
progression. The provision of tumour tissue is encouraged only if clinically appropriate and 
not considered detrimental to patient care. 
The biopsied tumour must not be used as part of the RECIST assessments. 
Patients will not be excluded from the study if these samples are not collected. 
On-study tumour tissue collected during the study should be immediately fixed and processed 
to a FFPE block. 
 
Please refer to Investigator Laboratory Manual for further details of on-study tumour tissue 
collection, shipping and storage. 
 
6.8 
Pharmacogenetics 
6.8.1 Collection of blood sample for Myriad germline BRCA1 and BRCA2 testing 
All patients must have a known deleterious or suspected deleterious BRCA mutation to be 
randomised; this may have been determined prior to study entry or may be assessed as part of 
the enrolment procedure for the study (via Myriad). 
 
6.8.1.1 
Guidance for BRCA testing of patients with known BRCA status 
For patients that can be randomised to the study on the basis of a pre-existing known BRCA 
mutation test result, a blood sample for a confirmatory BRCA mutation test by Myriad must 
be taken once the patient has consented to the study. Should the result from the Myriad test 
indicates the patient does not have a deleterious or suspected deleterious BRCA mutation, the 
patient can continue in the study and can continue to receive their allocated study treatment. 
 
For blood volume see Section 7.1. 
 
6.8.1.2 
Guidance for BRCA testing of patients with unknown BRCA status 
Patients that do not know their BRCA status, must have a Myriad test prior to randomisation 
to the study. If the result shows that the patient has a deleterious/suspected deleterious gBRCA 
mutation, the patient can then be randomised to the study. In order to limit the time that the 
patient is not receiving study treatment after their last dose of chemotherapy, it may be 
necessary for the patient to have a Myriad BRCA test performed after initial diagnosis. 
Patients will need to have met the local ethical requirements for such genetic tests (e.g., 
genetic counseling) prior to the test procedure. 
 
The following clinicopathological features are known to be associated with an increased 
probability of BRCA mutations: 

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1. 
Family history of breast or ovarian cancer, ethnicity and age (Pal et al 2005; Risch 
et al 2006) 
2. 
High grade serous ovarian cancer (Alsop et al 2012) 
 
The BRCA test may be performed from diagnosis to – 28 days at the discretion of the 
investigator. To perform the BRCA testing from diagnosis to the end of cycle 3, investigator 
judgement of patient’s potential eligibility to the study should be assessed as per Table 1 and 
by reviewing the inclusion/exclusion criteria. For post cycle 3 of first line chemotherapy 
gBRCA status testing the patient must meet the inclusion criteria in Sections 4.1 and 4.2, and 
be showing a response to their current platinum chemotherapy prior to having the blood 
sample taken for the Myriad gBRCA status test. This response is in the opinion of the 
investigator but there should be documented evidence eg CA-125 results, radiological 
assessments. 
The blood and tumour sample collection algorithm for patients with known or unknown 
BRCA mutation status is documented in the flow diagram below: 

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Extra blood samples may also be collected if, for example, additional samples are required for 
repeat safety assessments. 

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Assessment 
Sample 
volume 
(mL) 
 
Serum pregnancy test 
Site 
dependent 
No. of 
samples - 
screening 
 
Site may use 
urine instead 
No. of samples 
-month 1 
(including day 
29) 
Site may use 
urine instead 
Months 
2-6 
Treatment 
discontinuation visit 
and 30 day follow-up 
visit 
Objective 
radiological 
disease 
progression 
Total 
volume 
(mL) 
Blood sample for CA-125 
(locally assessed) 
2 
3 
1(x2) 
1x4 
1(x1) (only treatment 
20 
discontinuation visit) 
Optional exploratory 
pharmacogenetics 
9 
1 
9 
Total volume (ml) 
34 
75 
48 
22 
12 
191 

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7.2 
Handling, storage and destruction of biological samples 
The samples will be used up or disposed of after analyses or retained for further use as described 
here. 
Biological samples for future research can be retained at R&D site or CRO, on behalf of 
AstraZeneca for a maximum of 15 years following the Last Patient’s Last Visit in the study. The 
results from future additional exploratory analysis will not be reported in the Clinical Study 
Report but separately in a Scientific Report. 
 
7.2.1 Pharmacogenetic (optional exploratory) samples 
The processes adopted for the coding and storage of samples for genetic analysis are important to 
maintain patient confidentiality. 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. 
 
For all samples irrespective of the type of coding used the 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 relevant sample tracking system 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. 
 
7.3 
Labelling and shipment of biohazard samples 
The Principal Investigator ensures 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 C ‘International Air Transport Association (IATA) 6.2 Guidance Document’. 
 
Any samples identified as Infectious Category A materials are not shipped and no further 
samples will be taken from the patient unless agreed with AstraZeneca and appropriate labelling, 
shipment and containment provisions are approved. 

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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 keeps full traceability of collected biological samples 
from the patients while in storage at the centre until shipment or disposal (where appropriate) and 
keeps documentation of receipt of arrival. 
 
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 keeps oversight of the entire life cycle through internal procedures, monitoring of 
study sites and auditing of external laboratory providers. 
Samples retained for further use are registered in the AstraZeneca biobank system during the 
entire life cycle. 
 
If required, AstraZeneca will ensure that 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, AstraZeneca 
is 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. 
 
Tumour biopsy sample: As collection of the biological samples is an optional part of the study, 
the patient may continue in the study. 
 
Blood samples for biomarker analysis (e.g. cfDNA): As collection of the biological samples is an 
optional part of the study, the patient may continue in the study. 
The Principal Investigator: 
 
• 
Ensures patients’ withdrawal of informed consent to the use of donated samples is 
notified immediately to AstraZeneca. 
 
• 
Ensures that biological samples from that patient, if stored at the study site, are 
immediately identified, disposed of /destroyed, and the action documented. 

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• 
Ensures the laboratory(ies) holding the samples is/are informed about the withdrawn 
consent immediately and that samples are disposed/destroyed (the archival tumour 
samples may be returned to site), the action documented and the signed document 
returned to the study site. 
 
• 
Ensures that the patient and AstraZeneca are informed about the sample disposal. 
AstraZeneca ensures 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 International Conference on Harmonisation 
(ICH)/Good Clinical Practice (GCP), 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. 
 
The exception to the above is the result of the Myriad gBRCA test, this will be made available to 
the investigator and patient. 
 
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, an AstraZeneca Physician 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. 
 
8.3 
Ethics and regulatory review 
An Institutional Review Board (IRB)/Ethics Committee (EC) should approve the final study 
protocol, including the final version of the Informed Consent Form(s) including biomarker 
and/or pharmacogenetic sample consents and any other written information and/or materials to 

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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 IRB/Ethics Committee should be given in writing. The investigator should 
submit the written approval to AstraZeneca before enrolment of any patient into the study. 
 
The IRB/Ethics Committee should approve all advertising used to recruit patients for the study. 
 
AstraZeneca should approve any 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 IRB/Ethics Committee 
annually. 
 
Before enrolment of any patient into the study, the final study protocol, including the final 
version of the Informed Consent Form, is approved by the national regulatory authority or a 
notification to the national regulatory authority is done, according to local regulations. 
 
AstraZeneca will handle the distribution of any of these documents to the national regulatory 
authorities. 
AstraZeneca will provide Regulatory Authorities, Ethics Committees and Principal Investigators 
with safety updates/reports according to local requirements, including Suspected Unexpected 
Serious Adverse Reactions (SUSARs), where relevant. 
 
Each Principal Investigator is responsible for providing the IRB/Ethics Committees 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, including any information on 
the mandatory and optional sampling; e.g. BRCA testing and tumour biopsies. 
 
• 
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. 

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• 
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. 
• 
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, the Principal Investigator and AstraZeneca. 
 
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). 
 
The amendment is to be approved by the relevant Ethics Committee and if applicable, also the 
national regulatory authority approval, before implementation. Local requirements are to be 
followed for revised 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 
and the centre’s Ethics Committee are to approve the revised Informed Consent Form before the 
revised form is used. 
 
If local regulations require, any administrative change 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 will contact AstraZeneca immediately if contacted by a 
regulatory agency about an inspection at the centre. 
 
8.7 
Study and site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. The study may be stopped if, in the judgment 

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of AstraZeneca, trial subjects are placed at undue risk because of clinically significant findings 
that: 
• meet individual stopping criteria or are otherwise considered significant 
• are assessed as causally related to study drug, 
• are not considered to be consistent with continuation of the study 
Regardless of the reason for termination, all data available for the subject at the time of 
discontinuation of follow-up must be recorded in the CRF. All reasons for discontinuation of 
treatment must be documented. 
In terminating the study, the Sponsor will ensure that adequate consideration is given to the 
protection of the subjects’ interests 
 
Study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has 
been performed. 
 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
 
9. 
STUDY MANAGEMENT BY ASTRAZENECA 
9.1 
Pre-study activities 
Before the first patient is entered into the study, it is necessary for a representative of 
AstraZeneca to visit the investigational study site to: 
 
• 
Determine the adequacy of the facilities. 
• 
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 or its representatives. This will be documented in a CSA between 
AstraZeneca and the investigator. 

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9.2 
Training of study site personnel 
Before the first patient is entered into the study, an AstraZeneca representative 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 
system(s) utilised. 
 
The Principal Investigator will ensure that appropriate training relevant to the study is given to 
all of these 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, an AstraZeneca representative 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 and timely recorded in the CRFs, 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 CRFs with the 
patient’s medical records at the hospital or practice, and other records relevant to the 
study) including verification of informed consent of participating patients. This will 
require direct access to all original records for each patient (e.g., clinic charts). 
 
• 
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. 
 
The AstraZeneca 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 CSA for location of source data. 
 
9.4 
Study agreements 
The Principal Investigator at each/the centre should comply with all the terms, conditions, and 
obligations of the CSA, or equivalent, for this study. In the event of any inconsistency between 

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this Clinical Study Protocol and the CSA, 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 CSA shall prevail. 
 
Agreements between AstraZeneca 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 follows the principles outlined in the CSA. 
 
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 has started in Quarter 3 2013 and is expected to end by Quarter 1 2024.The study may 
be 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 if 
concerns for safety arise within this study or in any other study with olaparib. 
 
10. 
DATA MANAGEMENT BY ASTRAZENECA 
Data management will be performed by AstraZeneca Data Management Centre staff. 
 
The data collected through third party sources will be obtained and reconciled against study data. 
 
Adverse events and medical/surgical history will be classified according to the terminology of 
the latest version the Medical Dictionary for Regulatory Activities (MedDRA). Medications will 
be classified according to the AstraZeneca Drug Dictionary. From October 2019 onwards the 
MedDRA dictionary will be implemented replacing the AZDD (AstraZeneca Drug Dictionary). 
 
All coding will be performed by the Medical Coding Team at the AstraZeneca Data 
Management. 
 
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. 
 
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. 
 
Data associated with biological samples will be transferred from laboratories internal or external 
to AstraZeneca. Data from external providers (e.g. central laboratories) will be validated as 

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appropriate to ensure it is consistent with the clinical data and included in the final database. In 
the case of biomarker (tumour tissue or blood for exploratory analyses) data, the results of any 
analyses will not be recorded in the database, but information relating to the processing of the 
sample, including the original date of biopsy (historical tumour tissue sample and the actual date 
the sample(s) were collected) will be recorded in the eCRF and database. 
Exploratory genotype data generated in this study will be stored in the AstraZeneca genotyping 
LIMS database, or other appropriate secure system within AstraZeneca and/or third party 
contracted to work with AstraZeneca to analyse samples. The results from this exploratory 
research will not be reported in the CSR. 
 
Some or all of the clinical datasets from the main study may be merged with the genetic data in a 
suitable secure environment separate from the clinical database. 
 
11. 
EVALUATION AND CALCULATION OF VARIABLES BY 
ASTRAZENECA 
A comprehensive SAP will be prepared before the first patient is entered. 
 
11.1 
Calculation or derivation of efficacy variable(s) 
At each visit patients will be programmatically assigned a RECIST visit response of CR, PR, SD, 
PD, NED, NE depending on the status of their disease compared to baseline and previous 
assessments, based on the BICR review. This will be repeated using the investigator assessed 
RECIST data. 
 
11.1.1 Progression Free Survival (PFS) 
PFS is defined as the time from randomisation until the date of objective radiological disease 
progression according to RECIST or death (by any cause in the absence of progression) 
regardless of whether the patient withdraws from randomised study treatment or receives another 
anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of 
analysis will be censored at the time of the latest date of assessment from their last evaluable 
RECIST assessment. However, if the patient progresses or dies after two or more missed visits, 
the patient will be censored at the time of the latest evaluable RECIST assessment. If the patient 
has no evaluable visits or does not have a baseline assessment they will be censored at day 1 
unless they die within two visits of baseline. (25 weeks allowing for visit window). 
The PFS time will always be derived based on scan/assessment dates not visit dates. 
 
RECIST assessments/scans contributing towards a particular visit may be performed on different 
dates. The following rules will be applied: 
 
(a) 
Date of progression will be determined based on the earliest of the RECIST 
assessment/scan dates of the component that triggered the progression 

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(b) 
When censoring a patient for PFS the patient will be censored at the latest of the 
RECIST assessment/scan dates contributing to a particular overall visit assessment 
Overall visit assessments will be determined for each assessment (scheduled or unscheduled) and 
will contribute to the derivation of PFS. 
 
Objective progression is defined as at least a 20% increase in the sum of the diameters of the 
target lesions (compared to previous minimum sum) or an overall non-target lesion assessment 
of progression or a new lesion. For patients with no evidence of disease at baseline, following a 
clinical complete response to chemotherapy, progression is defined by the detection of new 
lesions on follow-up radiological assessments. 
 
The primary analysis will be based on the programmatically derived PFS based on investigator- 
recorded assessment of the radiological scans. A sensitivity analysis based on the independent 
central review (ICR) of the radiological scans will be carried out. A charter for the ICR will be 
developed in advance of the start of the study. 
 
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. 
 
Note: Survival calls will be made in the week following the date of Data Cut Off (DCO) for the 
analyses, and if patients are confirmed to be alive or if the death date is post the DCO date these 
patients will be censored at the date of DCO. 
 
11.1.2.2 Time to earliest progression by RECIST 1.1 or CA-125 or death 
Progression or recurrence based on serum CA-125 levels will be defined on the basis of a 
progressive serial elevation of serum CA-125, according to the following modified GCIG criteria 
(note GCIG criteria is not validated for this trial population): 
• 
Patients with elevated CA-125 pre-treatment (i.e. greater than the upper limit of 
normal (ULN)):- 
 
(a) 
If CA-125 does not fall to within the normal range whilst on treatment then 
there must be evidence of CA-125 greater than, or equal to, 2 times the nadir 
value in the 28 day period before day 1 on 2 occasions at least 1 week apart. 
 
(b) 
Where CA-125 does fall to within the normal range whilst on study 
treatment (and the patient has not already progressed by way of (a) above) 
then there must be evidence of CA-125 greater than, or equal to, 2 times the 
ULN on 2 occasions at least 1 week apart. 

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• 
Patients with CA-125 in the normal range pre-treatment must show evidence of CA- 
125 greater than, or equal to, 2 times the ULN on 2 occasions at least 1 week apart 
CA-125 progression will be assigned the date of the first measurement that meets the 
criteria as noted. 
 
Time to progression by RECIST or CA-125 progression or death is defined as the time from 
randomisation to the earlier date of RECIST or CA-125 progression or death by any cause. 
Patients without a CA-125 progression or a RECIST progression who are still alive at the time of 
analysis will be censored at their last evaluable RECIST assessment or their last available CA- 
125 measurement, whichever is the most recent at the time of the analysis. If a patient progresses 
or dies after two or more missed RECIST and CA-125 assessments, then the patient will be 
censored at the time of their last evaluable assessment. If only one assessment is missing during 
this period, no censoring is required. 
11.1.2.3 Time from randomisation to second progression (PFS2) 
Time from randomisation to second progression is defined as the time from the date of 
randomisation to the earliest of the progression event subsequent to that used for the primary 
variable PFS or death. The date of second progression will be recorded by the investigator and 
defined according to local standard clinical practice and may involve any of; objective 
radiological, CA-125 or symptomatic progression or death. Second progression status will be 
reviewed every 12 weeks following the progression event used for the primary variable PFS (the 
first progression) and status recorded. Patients alive and for whom a second disease progression 
has not been observed should be censored at the last time known to be alive and without a second 
disease progression, i.e. censored at the latest of the PFS or PFS2 assessment date if the patient 
has not had a second progression or death). 
 
11.1.2.4 Time to first subsequent therapy or death (TFST) 
Time to start of first subsequent therapy or death (TFST) will be assessed (see Section 12.2.3.3). 
TFST is defined as the time from the date of randomisation to the earlier of the date of therapy 
start date following study treatment discontinuation, or death. Subsequent therapies will be 
reviewed to assess which represent clinically important treatments intended to control ovarian 
cancer. Any patient not known to have died at the time of the analysis and not known to have had 
a further intervention of this type will be censored at the last known time to have not received 
subsequent therapy, i.e. the last follow-up visit where this was confirmed. 
 
11.1.2.5 Time to second subsequent therapy or death (TSST) 
Time to start of second subsequent therapy or death (TSST) will be assessed (see Section 
12.2.3.3). TSST is defined as the time from the date of randomisation to the earlier of the date of 
second subsequent therapy start date following study treatment discontinuation, or death. Any 
patient not known to have died at the time of the analysis and not known to have had a second 
further intervention of this type will be censored at the last known time to have not received 
second subsequent therapy, i.e. the last follow-up visit where this was confirmed. 

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11.1.2.6 Time to study treatment discontinuation or death (TDT) 
Time to study treatment discontinuation or death (TDT) will be assessed (see Section 12.2.3.3). 
TDT is defined as the time from the date of randomisation to the earlier of the date of study 
treatment discontinuation or death. Any patient not known to have died at the time of analysis 
and not known to have discontinued study treatment will be censored based on the last recorded 
date on which the patient was known to be alive. 
 
Note: Survival calls will be made in the week following the date of Data Cut Off (DCO) for the 
analysis, and if patients are confirmed to be alive or if the death date is post the DCO date these 
patients will be censored at the date of DCO. 
 
11.1.2.7 Best Overall RECIST Response (BoR) 
Best overall RECIST response (BoR) is calculated based on the overall visit responses from each 
RECIST assessment, described in Appendix F. It is the best response a patient has had during 
their time in the study following randomisation but prior to starting any subsequent cancer 
therapy and prior to RECIST progression or the last evaluable assessment in the absence of 
RECIST progression. 
 
Categorisation of best overall response will be based on the RECIST criteria (Appendix F) using 
the following response categories: complete response (CR), partial response (PR), stable disease 
(SD), No Evidence of Disease (NED; applies only to those patients entering the study with no 
disease at baseline), progressive disease (PD) and not evaluable (NE). 
 
Best overall response will be determined programmatically based on the RECIST criteria using 
investigator data. 
 
For patients whose progression event is death, BoR will be calculated based on data up until the 
last evaluable RECIST assessment prior to death. 
 
For patients who die with no evaluable RECIST assessments, if the death occurred ≤25 weeks 
(i.e. 24 weeks ±1 week) after randomisation then BoR will be assigned to the progression (PD) 
category. For patients who die with no evaluable RECIST assessments, if the death occurred 
> 25 weeks (i.e. 24 weeks ±1week) after randomisation then BoR will be assigned to the non- 
evaluable (NE) category. 
Progression events that have been censored due to them being >25 weeks after the last evaluable 
assessment will not contribute to the BoR derivation. 
 
A patient will be classified as a responder if the RECIST criteria for a CR or PR are satisfied at 
any time up to the earliest of the defined analysis cut-off point or the start of subsequent therapy. 
For each treatment group, the objective response rate (ORR) is the number of CR and PR divided 
by the number of patients in the group in the FAS with measurable disease at baseline. Only 
patients with PR and measurable disease at enrolment can achieve an objective response of CR 
or PR, other permissible categories of BoR are NE, PD. 

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12.1.2 Safety analysis set 
All patients who received at least one dose of randomised investigational product, olaparib or 
placebo and as part of the global enrolment will be included in the primary safety analysis set. 
Throughout the safety results sections, erroneously treated patients (e.g., those randomised to 
treatment A but actually given treatment B) will be accounted for in the treatment group of the 
treatment they actually received. 
 
Table 11 
Summary of Outcome Variables and Analysis Populations 
 
Outcome Variable 
Populations 
Efficacy Data 
- PFS 
ITT 
- OS, PFS2, TFST, TSST, TDT, symptom/QoL 
ITT 
endpoints 
Demography 
ITT 
Safety Data 
- Adverse Events 
Safety 
- Lab measurements 
Safety 
- Vital Signs 
Safety 
 
12.2 
Methods of statistical analyses 
The treatment comparison is olaparib 300 mg bd vs placebo. 
 
All efficacy analyses will be performed on the ITT population. In addition, as a sensitivity to the 
main analyses of PFS, PFS2, OS, TDT, TFST and TSST, analyses of these endpoints will be 
performed in those patients whose gBRCAm status is confirmed by the central Myriad test. 
 
Results of all statistical analysis will be presented using a 95% confidence interval and 2-sided p- 
value. 
The following table details which endpoints are to be subject to formal statistical analysis, 
together with pre-planned sensitivity analyses making clear which analysis is regarded as 
primary for that endpoint 
 
Table 12 
Formal Statistical Analyses to be Conducted and Pre-Planned Sensitivity 
Analyses 
 
Endpoints Analysed 
Notes 
PFS (Time from randomisation to first 
progression or death) 
Primary analysis: stratified log-rank test using 
investigator data 

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Endpoints Analysed 
Notes 
Sensitivity Analysesa 
1) Evaluation time bias analysis; stratified log- 
rank test using investigator data 
2) Attrition bias analysis (using alternative 
censoring rules); stratified log-rank test using 
investigator data 
3) Ascertainment bias analysis; stratified log-rank 
test using BICR data 
4) Deviation bias (if meaningful to do); stratified 
log-rank test using investigator data 
5) Analysis in randomised patients confirmed as 
gBRCA mutation positive by central Myriad test; 
stratified log rank test using investigator data 
Overall Survival (Time from randomisation to 
death due to any cause) 
Stratified log-rank test 
Sensitivity analysis: Stratified log rank test using 
investigator data in randomised patients 
confirmed as gBRCA mutation positive by central 
Myriad test 
PFS2 (Time from randomisation to second 
progression or death) 
Stratified log rank test based on investigator 
assessment of second progression 
Sensitivity analysis: Stratified log rank test using 
investigator data in randomised patients 
confirmed as gBRCA mutation positive by central 
Myriad test 
TFST (Time to first subsequent therapy or death) 
Stratified log rank test using investigator data 
Sensitivity analysis: Stratified log rank test using 
investigator data in randomised patients 
confirmed as gBRCA mutation positive by central 
Myriad test 
TSST (Time to second subsequent therapy or 
death) 
Stratified log rank test using investigator data 
Sensitivity analysis: Stratified log rank test using 
investigator data in randomised patients 
confirmed as gBRCA mutation positive by central 
Myriad test 
Change from baseline in TOI score 
Mixed model for repeated measures (MMRM) 
analysis of the change from baseline in TOI score 

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Endpoints Analysed 
Notes 
Time to earliest progression by RECIST 1.1, CA- 
125 or death 
Stratified log rank test using investigator data 
TDT (Time to study treatment discontinuation or 
death) 
Stratified log rank test using investigator data 
Sensitivity analysis: Stratified log rank test using 
investigator data in randomised patients 
confirmed as gBRCA mutation positive by central 
Myriad test 
a 
See Section 12.2.2.1 for further details 
12.2.1 Multiplicity strategy for primary and key secondary endpoints 
In order to describe the nature of the benefits of olaparib maintenance treatment, PFS, PFS2, 
TFST, TSST, change from baseline in TOI score and OS will be tested at a 2-sided significance 
level of 5%. 
 
In addition to these planned analyses, which will be performed and reported in the CSR, in order 
to strongly control the type I error at 2.5% 1-sided for key label claims, a multiple testing 
procedure (MTP) will also be employed across the primary endpoint (PFS) and key secondary 
endpoints (PFS2 and OS). There is no requirement to adjust for multiplicity due to PFS interim 
analyses, since there are no planned interim PFS analyses with the opportunity to make an early 
claim of efficacy. 
A hierarchical testing strategy will be employed where PFS is tested first using the full test mass 
(full test mass = alpha ) and key secondary endpoints of PFS2 and OS will then be tested using a 
MTP with a recycling strategy (i.e., the MTP will recycle the test mass to the endpoint not yet 
rejected in the hierarchy outlined in Figure 6). The MTP is detailed below. 
 
Figure 6 
Multiple Testing Procedure 
 
 
PFS2 will only be tested (with the test mass split between interim and final PFS2 analyses) if 
statistical significance is shown for PFS. OS will only be tested if the null hypothesis (of no 
difference) is rejected for PFS2. 

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PFS2 will be tested at the time of the primary analyses of PFS and again when there are 
approximately 60% deaths. OS will be tested at the time of the primary analysis of PFS, again 
after approximately 206 events (approximately 53% maturity of the 391 patients randomised) 
and then again when there are approximately 60% deaths (~235 events out of 391 patients 
randomised). A proportion of alpha will be spent at this first analyses time point for both 
endpoints to control for multiple testing however different spending functions will be applied for 
each. 
 
An interim analysis for PFS2 will be performed at the time of the PFS analysis (approximately 
180 PFS2 events expected at this time). Statistical significance will be declared at the interim 
analysis for PFS2 if the 1-sided p<0.0125. Assuming 180 PFS2 events, a HR ≤ 0.70 would 
equate to a 1-sided p-value <0.0125. 
 
If the null hypothesis for PFS2 is not rejected at this first analyses time point then PFS2 will be 
tested again when the final analysis of OS occurs. The type I error will be controlled at 2.5% 1- 
sided by assigning approximately 1.8% significance level (1-sided) to the final analysis of PFS2 
(final significance level to be determined accounting for correlation between the interim and 
final PFS2 analyses) (Stone 2010). Assuming 300 PFS2 events, a HR ≤ 0.77 would equate to a 1- 
sided p-value <0.018. If PFS2 is significant at either the interim or final analyses, the full test 
mass (alpha) will be carried forward to OS. 
 
The first interim analysis for OS will be performed at the time of the PFS analysis 
(approximately 100 OS events). Statistical significance will be declared at the first interim 
analysis for OS if the null hypothesis for PFS2 is rejected at the PFS analysis and the observed p- 
value for OS is p<0.0001. 
 
In addition, a descriptive OS analysis will be performed at the clinically important timepoint of 
7 years post the LSR as part of global enrolment (DCO March 2022). An administrative alpha 
spend of 0.0001 will be assigned to account for this analysis. The descriptive interim OS analysis 
7 years after the LSR is proposed as a clinically relevant timepoint since most events of disease 
recurrence and subsequently ovarian cancer deaths occur 5-10 years after diagnosis after which 
death rates approach that of women in the general population (Harter P et al 2010, Tewari K et al 
2019). 
 
The second interim analysis for OS will be performed when approximately 206 OS events have 
occurred (~53% maturity of the 391 patients who were randomised in SOLO1). The final OS 
analysis will be performed at approximately 60% maturity (~235 events/391 patients who were 
randomised in SOLO1). 
 
The significance level will be controlled at the 5% level (2-sided) by subtracting the alpha spend 
at the first interim analysis for OS (0.0001) and the administrative alpha spend at the descriptive 
OS analysis 7 years post last subject randomised (0.0001) from the overall 5% alpha (i.e., 0.05 – 
0.0001 – 0.0001 = 0.0498) and then assigning the remaining alpha to the second interim OS 
analysis timepoint (206 OS events; approximately 53% maturity) and the final OS analysis 
timepoint (235 OS events; approximately 60% maturity) using the Lan De Mets O’Brien- 

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Fleming spending function. The significance level applied at the second interim analysis for OS 
will depend upon the proportion of information (i.e., information fraction) available. 
With an alpha level of 4.98%, if 88% of the target OS events are available at the time of the 
second interim OS analysis (i.e., 206 of 235 OS events have occurred), then the 2-sided 
significance levels of 0.0332, and 0.0405 will be applied to the second interim and final analysis 
for OS, respectively. Note, the final OS analysis boundary will ultimately be derived based on 
the actual number of events observed at the second interim and final analyses of OS. 
 
12.2.2 Analysis of primary endpoint 
PFS will be analysed when approximately 196 events have occurred or after the last patient 
randomised has had the opportunity to have been on the study for at least 36 months, whichever 
comes first. No further analyses of PFS are planned beyond this point unless requested by Health 
Authorities. 
 
PFS will be analysed using a log rank test stratified by response to first line platinum 
chemotherapy (clinical complete response partial response) for generation of the p-value and 
using the Breslow approach for handling ties. The hazard ratio (HR) and confidence interval will 
be estimated from a Cox Proportional Hazards model (with ties = Efron and the stratification 
variable as a covariate) and the CI will be calculated using a profile likelihood approach. 
 
Stratification variables will be defined according to data from the interactive voice/web response 
system (IVRS/IWRS). If there are any patients who were mis-stratified, a sensitivity analysis 
will be carried out using the (correct) baseline data collected in the eCRF. 
 
The HR (olaparib vs placebo) together with its corresponding 95% confidence interval (CI) and 
p-value will be presented (a HR less than 1 will favour olaparib). 
 
A Kaplan-Meier (KM) plot of PFS will be presented by treatment group. Summaries of the 
number and percentage of subjects experiencing a PFS event, and the type of event (RECIST or 
death) will be provided along with median PFS for each treatment. 
 
The assumption of proportionality will be assessed. Note that in the presence of non- 
proportionality, the HR will be interpreted as an average HR over the observed extent of follow- 
up. Proportionality will be tested firstly by examining pots 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. 
 
The primary analysis will be based on the programmatically derived PFS based on Investigator 
recorded assessments, and using all scans regardless of whether they were scheduled or not. 
The proportion of patients alive and progression free at 6 months and 12 months will be 
summarised (using the KM curve) and presented by treatment group. 

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If there are too few events available for a meaningful analysis of a particular subgroup (where 
there are less than 20 events per subgroup level no formal statistical tests will be performed), the 
relationship between that subgroup and PFS will not be formally analysed. In this case, only 
descriptive summaries will be provided. 
 
No adjustment to the significance level for testing will be made since all these subgroup analyses 
will be considered exploratory and may only be supportive of the primary analysis of PFS. 
 
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, 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 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. 
A further analyses of PFS (using investigator assessed RECIST) may be performed at the time of 
the OS analyses, if requested by Health authorities. 
 
12.2.2.1 Sensitivity Analyses for Primary Endpoint 
As a sensitivity analysis to the primary endpoint of PFS, the primary analysis will be repeated 
excluding any patients who did not have a gBRCA mutation status confirmed by the central 
Myriad test. The same methodology and model will be used and the HR and associated 95% CI 
from a Cox Proportional Hazards model will be reported. A KM plot of PFS in this subset of 
patients will be presented by treatment group. 
Sensitivity analyses will be performed to assess the possible presence of time-assessment bias 
(i.e., differential assessment times between treatment groups). 
 
Summary statistics for the number of weeks between the time of progression and the last 
evaluable RECIST assessment prior to progression will be presented for each treatment group. 
(a) 
Evaluation-Time bias 

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Sensitivity analyses will be performed to assess possible evaluation-time bias that may be 
introduced if scans are not performed at the protocol-scheduled time points. The midpoint 
between the time of progression and the previous evaluable RECIST assessment will be analysed 
using a stratified log rank test, as described for the primary analysis of PFS. This approach has 
been shown to be robust to even highly asymmetric assessment schedules (Sun and Chen 2010). 
This approach will use the investigator RECIST assessments. 
(b) 
Attrition bias 
 
Attrition bias will be assessed by repeating the primary PFS analysis except that the actual PFS 
event times, rather than the censored times, of patients who progressed or died in the absence of 
progression immediately following two, or more, non-evaluable tumour assessments will be 
included. In addition, patients who take subsequent therapy prior to progression or death will be 
censored at their last evaluable assessment prior to taking the subsequent therapy. 
 
Additionally a Kaplan-Meier plot of the time to censoring where the censoring indicator of the 
primary PFS analysis is reversed will be presented. 
(c) 
Ascertainment bias 
 
A stratified log-rank test will be repeated using BICR assessed RECIST data to 
programmatically derive PFS. The HR and 95% Confidence Interval will be presented. 
If there is an important discrepancy between the primary analysis using investigator assessments 
and this sensitivity analysis using ICR assessments, then the proportion of subjects with central 
but no site confirmation of progression will be summarised. The approach of imputing an event 
at the next visit in the investigator assessed analysis may help inform the most likely HR value, 
but only if an important discrepancy exists. 
 
(d) 
Deviation bias (if meaningful to do) 
 
As a sensitivity to the primary endpoint of PFS, an analyses excluding patients with deviations 
that may affect the efficacy of the trial study treatment will be performed if >10% of patients: 
 
• 
Did not have the intended disease or indication or 
• 
Did not receive any randomised study treatment 
A stratified log-rank test will be repeated using the investigator RECIST data, using the same ties 
and stratification factor as described for the primary analysis of PFS. The HR and 95% 
Confidence Interval will be presented. 

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12.2.3 Analysis of secondary endpoints 
12.2.3.1 Analysis of PFS2 endpoint 
An initial PFS2 analysis will be performed at the same time as the primary analysis of PFS and 
will use the same methodology and model. A further analysis of PFS2 will be performed when 
the OS data are approximately 60% mature. 
 
As a sensitivity, the analysis of PFS2 will be repeated in those patients whose gBRCAm status is 
confirmed by the central Myriad test. A KM plot of PFS2 in this subset of patients will be 
presented by treatment group. 
The sensitivity analysis outlined for 12.2.2.1 will not be repeated for PFS2 with the exception of 
a Kaplan-Meier plot of the time to censoring where the censoring indicator of the primary PFS2 
is reversed. 
 
12.2.3.2 Analysis of OS endpoint 
OS data will be analysed at the time of the primary analysis of PFS and will use the same 
methodology and model (provided there are sufficient events available for a meaningful analysis 
[≥20 deaths], if not descriptive summaries will be provided). A further interim analysis of OS 
will be performed when ~206 events are observed and a final analysis of OS will be performed 
when the OS data are approximately 60% mature. 
 
An additional descriptive analysis for OS will also be performed at 7 years post the last patient 
randomised as part of global enrolment (DCO March 2022). 
As a sensitivity, the analysis of OS will be repeated in those patients whose gBRCAm status is 
confirmed by the central Myriad test. A KM plot of OS in this subset of patients will be 
presented by treatment group. 
 
The sensitivity analysis outlined for 12.2.2.1 will not be repeated for OS with the exception of a 
Kaplan-Meier plot of the time to censoring where the censoring indicator of the primary OS is 
reversed. 
 
12.2.3.3 Analysis of TFST, TSST, TDT endpoints 
Time to first subsequent therapy or death (TFST), time to second subsequent therapy or death 
(TSST) and time to study treatment discontinuation or death (TDT) will be analysed at the same 
time as the primary analysis of PFS and using the same methodology and model. The HRs for 
the treatment effect together with 95% CIs will be presented. Kaplan Meier plots will be 
presented by treatment arm. In addition, the time between first progression and starting first 
subsequent therapy will be summarised. 
 
Summary tables of first and second subsequent therapies by treatment arm will be provided, as 
well as response to first and second subsequent therapy by treatment arm. 

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Further analyses of these endpoints will be performed at the time of each planned analysis of OS 
data. 
As a sensitivity, the analyses of TFST, TSST and TDT will be repeated in those patients whose 
gBRCAm status is confirmed by the central Myriad test. KM plots of TFST, TSST and TDT in 
this subset of patients will be presented by treatment group. 
12.2.3.4 Analysis of time to earliest progression by RECIST 1.1 or CA-125 or death 
Time to progression by RECIST 1.1or CA-125 will be performed at the same time as the primary 
analysis of PFS and will use the same methodology and model. 
The number (%) of patients reporting a CA-125progression, an objective RECIST 1.1 
progression and both a CA-125 and/or objective RECIST progression will be tabulated. 
 
No multiplicity adjustment will be applied as this is viewed as a supportive endpoints (to PFS). 
 
12.2.3.5 Summary of Best overall RECIST Response (BoR) 
For each treatment arm, Best Overall Response (BoR) will be summarised by n (%) for each 
category (CR, PR, SD, NED, PD, NE). No formal statistical analyses are planned. 
 
The objective response rate (ORR) will be summarised (i.e., number of patients (%)) by 
treatment group. 
12.2.3.6 Analysis of PRO endpoints 
The analysis population for HRQoL data will be the subset of the FAS (ITT) set. 
 
Change from baseline in TOI score will be regarded as the primary analysis of the FACT-O 
questionnaire and will be analysed using a mixed model for repeated measures (MMRM) 
analysis of the change from baseline in TOI score for each visit. The primary analysis will be to 
compare the average treatment effect from the point of randomisation for the first 24 months 
(which will include visit data obtained at baseline, day 29 (week 4), weeks 12, 24, 36, 48, 60, 72, 
84, 96 and the discontinuation and follow-up visits if occurring within the first 24 months) unless 
there is excessive missing data (defined as >75% missing data). If the time to first subsequent 
chemotherapy when approximately 50% of placebo patients receive chemotherapy does not 
occur by 24 months post-randomisation then additional time periods will be analysed and will be 
included on supportive summaries and graphical displays as appropriate. 
 
The MMRM model will include patient, treatment, visit and treatment by visit interaction as 
explanatory variables and the baseline TOI score as a covariate. Treatment, visit and treatment 
by visit interaction will be fixed effects in the model; patient will be included as a random effect. 
The treatment by visit interaction will remain in the model regardless of significance. Calculation 
of a suitable adjusted mean estimate will be detailed in the SAP that will estimate the average 
treatment effect over visits which gives each visit equal weight. The adjusted mean estimates and 
corresponding 95% confidence intervals will be presented for the overall treatment comparison 
and by visit for each treatment group. 

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A further interim analysis of OS may be performed at approximately 206 events. Assuming that 
the true OS treatment effect is 0.85 and this point estimate for the HR of 0.85 was observed, the 
95% UCL for the HR would be 1.13. A final OS analysis may be performed at approximately 
60% maturity (~235 events/391 patients who were randomised in SOLO1). Assuming that the 
true OS treatment effect is 0.85 and this point estimate for the HR of 0.85 was observed, the 95% 
UCL for the HR would be 1.11. Note that these estimates are based on the assumption that no 
confounding will occur. AstraZeneca anticipates potential confounding of OS data due to 
availability of PARP inhibitors for BRCA mutated ovarian cancer patients during follow up in 
this study, which are likely to disproportionately affect OS in one arm of the study (placebo- 
treated patients). 
 
Pharmacogenetic research (PGx) The number of patients that will agree to participate in the 
genetic research is unknown. It is therefore not possible to establish whether sufficient data will 
be collected to allow a formal statistical evaluation or whether only descriptive statistics will be 
generated. A statistical analysis plan will be prepared where appropriate. 
 
12.4 
Data monitoring committee 
This study will use an external Independent Data Monitoring Committee (IDMC) to perform 
interim reviews of accumulating study safety data. This committee will be composed of 
therapeutic area experts and a statistician, who are not employed by AZ, and do not have any 
major conflict of interest. Following the review, the IDMC will recommend whether the study 
should continue unchanged, be terminated, or be modified in any way. Once the IDMC has 
reached a recommendation, a report will be provided to AstraZeneca. The report will only 
include the recommendation and any potential protocol amendments. It will not contain any 
unblinded information. A separate IDMC charter will be developed which will contain details of 
the IDMC members and clearly define the responsibilities of the IDMC. 
In addition to the periodic review of safety data by an IDMC, the safety of all AstraZeneca 
clinical studies is closely monitored on an on-going basis by AstraZeneca representatives in 
consultation with the Patient Safety Department. Issues identified will be addressed; this could 
involve, for instance, amendments to the study protocol and letters to investigators. 
 
13. 
MEDICAL EMERGENCIES 
The Principal Investigator is responsible for ensuring that procedures and expertise are available 
to handle medical emergencies during the study. A medical emergency usually constitutes an 
SAE and is to be reported as such, see Section 6.4.5 
For further guidance of the definition of a SAE, see Appendix B of CSP. 

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13.1 
Overdose 
There is currently no specific treatment in the event of overdose of olaparib and possible 
symptoms of overdose are not established. 
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 CRF and on the Overdose CRF module. 
 
• 
An overdose without associated symptoms is only reported on the Overdose CRF 
module. 
 
If an overdose on an AstraZeneca study drug occurs in the course of the study, then investigators 
or other site personnel inform appropriate AstraZeneca representatives immediately, or no later 
than 24 hours of when he or she becomes aware of it. 
 
The designated AstraZeneca 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 6.4.5. For 
other overdoses, reporting should be done within 30 days. 
 
13.2 
Pregnancy 
All outcomes of pregnancy should be reported to AstraZeneca. 
 
13.2.1 Maternal exposure 
If a patient becomes pregnant during the course of the study 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 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 AstraZeneca representatives immediately, or no later than 24 hours of when 
he or she becomes aware of it. 

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The designated AstraZeneca 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 6.4.5 and within 30 days for all other pregnancies. 
 
The same timelines apply when outcome information is available. 
 
The PREGREP module in the CRF is used to report the pregnancy and the PREGOUT is used to 
report the outcome of the pregnancy. 
 
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