A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer.
Phase: PHASE3
Conditions: Ovarian Neoplasms, Platinum Sensitive Ovarian Cancer
Sponsor: Tesaro, Inc.

 
 
 
 
 
 
 
 
 
 
 
Protocol 
213356 
A Phase 3 Randomized Double-Blind Trial of Maintenance with  
Niraparib Versus Placebo in Patients with  
Platinum Sensitive Ovarian Cancer 
EudraCT No.: 2013-000685-11 
Date of Document: 29-JANUARY-2019 (The date is redacted on page 3) 

Niraparib 
 
Clinical Study Protocol PR-30-5011-C Version 8 
Confidential 
 
 
 
 
 
1 of 103 
TITLE PAGE  
 
A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib 
Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer 
Sponsor: 
TESARO, Inc. 
1000 Winter Street, Suite 3300 
Waltham, MA 02451 
+1 339 970 0900 
TESARO Bio Netherlands 
B.V  
 Joop Geesinkweg 901  
 1114AB Amsterdam-
Duivendrecht  
 The Netherlands 
+45 31664608 
Clinical Research 
Organization: 
PAREXEL International, LLC 
195 West Street 
Waltham, MA 02451 
 
Sponsor Protocol No.: 
PR-30-5011-C  
IND No.: 
100,996 
 
EudraCT No.: 
2013-000685-11 
 
Study Drug Name: 
Niraparib capsules 
 
Development Phase: 
3 
 
Date of Original Protocol: 
21 March 2013 
 
Date of Amendment 1: 
03 May 2013 
 
Date of Amendment 2: 
03 March 2014 (amendment 2 never issued) 
Date of Amendment 3: 
09 April 2014 
 
Date of Amendment 4: 
04 December 2014 
 
Date of Amendment 5: 
Date of Amendment 6: 
Date of Amendment 7: 
11 September 2015 
09 March 2016 
31 May 2017 
 
Date of Amendment 8: 
29 January 2019 
 
Version of Protocol: 
8.0 
 
The study will be conducted according to the protocol and in compliance with Good Clinical Practice 
(GCP), with the Declaration of Helsinki, and with other applicable regulatory requirements. 
CONFIDENTIAL 
This document contains confidential information of TESARO Inc. Do not copy or distribute 
without written permission from the Sponsor. 

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Niraparib 
 
Clinical Study Protocol PR-30-5011-C Version 8 
Confidential 
 
 
 
 
 
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PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Declaration of the Principal Investigator 
 
Title: A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo 
in Patients with Platinum Sensitive Ovarian Cancer 
 
I have read this study protocol, including all appendices. By signing this protocol, I agree to 
conduct the clinical study, following approval by an Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB), in accordance with the study protocol, the current 
International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP), 
and applicable regulatory requirements. I will ensure that all personnel involved in the study under 
my direction will be informed about the contents of this study protocol and will receive all 
necessary instructions for performing the study according to the study protocol. 
 
Principal Investigator 
 
 
_____________________________________ 
_____________________ 
Name: 
Date 
Title: 
Institution: 

Niraparib 
 
Clinical Study Protocol PR-30-5011-C Version 8 
Confidential 
 
 
 
 
 
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PROTOCOL SYNOPSIS 
Title 
A Phase 3 Randomized Double-blind Trial of Maintenance with Niraparib Versus 
Placebo in Patients with Platinum Sensitive Ovarian Cancer 
Protocol No. 
PR-30-5011-C 
Phase 
3 
Sponsor 
TESARO, Inc. 
Study Center(s) 
Approximately 100 centers worldwide 
Objective(s) 
Main Study – Double Blind, Placebo Control 
The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have 
platinum sensitive ovarian cancer as assessed by the prolongation of progression-free survival (PFS). This objective 
will be independently evaluated in a cohort of patients with germline BRCA mutation (gBRCAmut) and in a cohort 
of patients who have high grade serous or high grade predominantly serous histology but without such gBRCAmut 
(non-gBRCAmut). In the non-gBRCAmut cohort, the endpoint will be hierarchically evaluated first in a subgroup of 
patients positive for homologous recombination deficiency HRD+ (somatic BRCAmut and HRD positive/BRCAwt) 
and then in all non-gBRCAmut patients. 
Secondary objectives include the following: (1) concordance of a candidate companion BRACanalysis diagnostic 
test compared to the centralized BRCA mutation test used in this study, if needed; (2) concordance of a candidate 
companion HRD diagnostic test compared to the HRD test used in this study, if needed (3) to evaluate additional 
measures of clinical benefit including patient reported outcomes (PROs), time to first subsequent treatment (TFST), 
time to second subsequent treatment (TSST), time from treatment randomization to the earlier date of assessment 
of progression on the next anticancer therapy following study treatment or death by any cause (progression-free 
survival 2; PFS2), chemotherapy-free interval (CFI), and overall survival (OS); (4) to evaluate the safety and 
tolerability of niraparib compared to placebo in the indicated target population; (5) to evaluate QTc in a subset of 
niraparib-treated ovarian cancer patients. 
Sub-Study – Food Effect 
To assess the effect of a high fat meal on the pharmacokinetics (PK) of a single 300 mg dose of niraparib in patients 
with ovarian cancer. 
Design 
Main Study 
This main study is a double-blind, 2:1 randomized, placebo controlled study in platinum sensitive ovarian cancer 
patients who have either gBRCAmut or a tumor with high grade serous or high grade predominantly serous histology 
but without such gBRCAmut (non-gBRCAmut). The patients must have received at least 2 platinum-based regimens 
with the last treatment course being a platinum containing regimen, must have had a response assessed by a 
physician as complete response (CR) or partial response (PR) to their last regimen, must not have any measurable 
lesion > 2 cm, and must have normal cancer antigen (CA)-125 (or > 90% decrease during the last platinum regimen 
which is stable for at least 7 days). The study will assess whether maintenance with niraparib will extend PFS in 
this population. There will be 2 independent patient cohorts as determined by the results of Myriad Integrated 
BRACAnalysis® testing, one with deleterious gBRCAmut and the other with high grade serous or high grade 
predominantly serous histology but without such gBRCAmut based on the hypothesis that patients with gBRCAmut 
will be enriched for responsiveness to niraparib. In the non-gBRCAmut cohort, PFS will be hierarchically evaluated 
first in a subgroup of HRD+ (somatic BRCAmut and HRD positive/BRCAwt) patients and then in all non-gBRCAmut 
patients. 
A blood sample will be sent to Myriad for immediate Integrated BRACAnalysis® testing. The sample may be sent 
in advance of the protocol-defined screening period in order to facilitate the screening and enrollment process. 
Patients who have not had Myriad BRCA mutation testing completed in the past must wait for the results from the 
on-study Myriad Integrated BRACAnalysis® test prior to randomization. Patients who have had a prior Myriad 

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Integrated BRACAnalysis® test must still provide a sample for testing prior to randomization, but may be 
randomized based on the results from the prior Myriad test. 
Patients with Integrated BRACAnalysis® result will be assigned within a gBRCAmut cohort or a non-gBRCAmut 
cohort as follows: 
MYRIAD Report Results 
Cohort for Randomization 
Positive for a Deleterious Mutation 
gBRCAmut cohort 
Genetic Variant, Suspected Deleterious 
gBRCAmut cohort 
Genetic Variant, Favor Polymorphism 
Non-gBRCAmut cohort 
Genetic Variant of Uncertain Significance 
Non-gBRCAmut cohort 
No Mutation Detected 
Non-gBRCAmut cohort 
A separate randomization list will be created for each cohort. Stratification factors will include: time to progression 
after the penultimate (next to last) platinum therapy before study enrollment (6 to < 12 months and ≥ 12 months), 
use of bevacizumab in conjunction with the penultimate or last platinum regimen (yes/no), and best response during 
the last platinum regimen (CR and PR). An analysis of outcome by (1) concomitant chemotherapy with platinum 
in the last and penultimate regimens (yes/no); (2) and number of prior platinum courses (2 and > 2) will also be 
performed. 
A tissue sample will be sent for centralized testing to classify patients by HRD status. Testing may be completed 
any time prior to database lock. Details on tissue sample collection can be found in the laboratory manual. 
Clinic visits will occur in each cycle (every 4 weeks ± 3 days). Response Evaluation Criteria in Solid Tumors 
(RECIST) will be used for tumor assessment via a computed tomography (CT) or magnetic resonance imaging 
(MRI) scan of abdomen/pelvis and clinically indicated areas, which is required at the end of every 2 cycles (8 
weeks with a window of ± 7 days from date of visit) through Cycle 14 (56 weeks), then at the end of every 6 cycles 
(24 weeks with a window of ± 7 days from date of visit) until progression. Cycle timing will not be delayed for 
treatment interruptions, and tumor assessment should occur according to this schedule regardless of whether study 
treatment is interrupted. If a patient discontinues treatment for a reason other than progression, death, withdrawal 
of consent, or lost to follow-up, scans should continue at the specified intervals. If a patient discontinues treatment 
for clinical progression and does not meet the criteria specified in the protocol, scans and CA-125 testing should 
continue at the specified intervals until progression is confirmed or until the start of subsequent anticancer 
treatment. 
PROs (Functional Assessment of Cancer Therapy–Ovarian Symptom Index [FOSI]; European Quality of Life 
scale, 5-Dimensions [EQ-5D-5L]; and a neuropathy questionnaire) will be collected in a coordinated fashion with 
RECIST tumor imaging while on study treatment and following discontinuation of treatment, regardless of 
progression status (at the nearest study visit to the imaging exam, after every 2 cycles through Cycle 14, then after 
every 3 cycles). If the patient discontinues study treatment, assessment of PROs will be performed at that time and 
then 8 weeks (± 2 weeks) later, regardless of subsequent treatment. The PROs may be completed remotely. It is 
estimated that PRO evaluations will take less than 20 minutes at each time point. Since these are questionnaires, 
their completion will not interfere with, or preclude, future treatment or clinical studies. After treatment 
discontinuation, study information on PROs, response, tolerability with subsequent anticancer treatment, and 
survival will continue to be collected. 
Patients will continue to receive their assigned treatment until disease progression (determined using RECIST v.1.1 
criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, or lost to follow-up, whichever 
comes first. Dose interruption and/or reduction may be implemented at any time for any grade toxicity considered 
intolerable by the patient. 
An independent data monitoring committee (IDMC) will be established to provide independent review and 
assessment of the efficacy and safety data in a systematic manner and to safeguard the interest and safety of the 
participating patients in the study. The composition of the IDMC will consist of 3 independent individuals, 
including 1 biostatistician and 2 physicians. The IDMC is tasked with making a recommendation to the Sponsor 
based on their review to continue or stop the trial based on their assessment of efficacy and safety information. 

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niraparib at 300 mg once daily (QD). These 12 patients will only be assessed for safety for the duration of the study 
and may continue until Investigator-determined progression. 
Criteria for Discontinuation of Treatment and Discontinuation from Study 
Discontinuation from treatment 
Patients may be discontinued from study treatment at any time. Specific reasons for discontinuing treatment are 
given below: 
 
Any treatment-related Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 
events (see separate guidelines for platelets below) that have not reverted to CTCAE Grade 1 or 
better within 4 weeks (28 days) of dose interruption. At the Investigator’s discretion, following dose 
interruption (no longer than 28 days), patients may be considered for dose reductions, providing 
they have not already undergone the maximum number of 2 dose reductions allowed. If upon re-
challenging with study treatment at the lowest allowable dose, any CTCAE Grade 3 or 4 adverse 
events (AEs) recur, the patient must be discontinued. 
 
If the platelet count has not reverted to > 100,000 within 4 weeks (28 days) of dose interruption, the 
patient should be discontinued. 
 
Disease progression according to RECIST v.1.1 criteria or clinical criteria 
 
Risk to patients as judged by the Investigator and/or Sponsor 
 
Severe non-compliance to protocol as judged by the Investigator and/or Sponsor 
 
Patient request 
 
The patient becomes pregnant 
Patients who are benefitting from treatment will have access to their assigned treatment as long as considered 
acceptable by their treating physician or until they are discontinued for one of the above reasons. 
Patients who discontinue from treatment will continue to receive follow-up assessments (eg, PRO, treatment 
outcome with next therapy, and OS) as part of the study unless they are discontinued from study by one of the 
following events: 
Discontinuation from the study 
 
Withdrawal of consent by the patient, who is at any time free to discontinue their participation in the 
study, without prejudice to further treatment  
 
Death from any cause 
 
Patient lost to follow-up 
 
 
Unblinding Procedures 
Patients and Investigators will not be unblinded to study treatment except in a  situation where knowledge of 
treatment arm is required as determined necessary by the Investigator.. 
After the blind is broken, the Investigator (or designee) must document the reason for breaking the blind on the 
appropriate electronic case report form (eCRF) page. Patients who require unblinding will be discontinued from 
study treatment permanently but will enter long-term follow-up and will be followed for Overall Survival (OS). 

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Treatment 
Main Study 
Blinded study treatment (niraparib or placebo capsules) will be packed in high-density polyethylene (HDPE) bottles 
with child-resistant closures. Study treatment will be dispensed to patients on Cycle 1/Day 1 and every cycle 
(28 days) thereafter until the patient discontinues study treatment. 
Study treatment will be administered orally QD continuously. Three capsules of 100 mg strength will be taken at 
each dose administration. Dose interruption (no longer than 28 days) will be allowed. In addition, dose reduction 
will be allowed based on treatment side effects. Dose reductions to 2 capsules daily (200 mg) and subsequently to 
1 capsule daily (100 mg) will be allowed. No further dose reductions will be allowed. The timing of efficacy or 
safety evaluations should not be affected by dose interruptions or reductions. 
Food Effect Sub-Study 
For the approximately 12 FE sub-study patients, a single dose of 300 mg niraparib (3 x 100 mg) will be given each 
on FE Days 1 and 8. After the completion of the 14-day FE sub-study, patients will begin 300 mg QD niraparib on 
Cycle 1/Day 1, approximately 2 weeks after the start of the FE sub-study. 
Number of Patients 
The primary analysis of PFS will be based on 180 patients randomized in the gBRCAmut cohort and up to 310 
patients randomized in the non-gBRCAmut cohort, for a total of 490 patients. Enrollment is expected to occur over 
approximately 24 months for gBRCAmut and 20 months for non-gBRCAmut. An additional approximately 12 
patients will be enrolled into the open-label, crossover, FE sub-study. Thus, a total of approximately 502 patients 
is the target for enrollment in this study. 
Population 
Inclusion Criteria – Main Study: 
To be considered eligible to participate in this study, all of the following requirements must be met: 
1. Female, age at least 18 years 
2. Patient agrees to undergo analysis of their gBRCA status. (Testing must be completed prior to 
randomization. The sample may be submitted at any time prior to the screening period if it 
appears that the patient is likely to meet other eligibility requirements. To facilitate early testing, 
a separate informed consent form [ICF] specific for genotyping will be available to be signed 
prior to gBRCA status testing.) 
3. Histologically diagnosed ovarian cancer, fallopian tube cancer, or primary peritoneal cancer 
4. High grade (or Grade 3) serous or high grade predominantly serous histology or known to have 
gBRCAmut 
5. Patients must have completed at least 2 previous courses of platinum-containing therapy (eg, 
carboplatin, oxaliplatin, or cisplatin): 
a. For the penultimate (next to last) platinum-based chemotherapy course prior to enrollment 
on the study: 
i. 
A patient must have platinum sensitive disease after this treatment; defined as 
achieving a response (CR or PR) and disease progression > 6 months after 
completion of their last dose of platinum chemotherapy (document 6-12 months or  
> 12 months). (Source documentation required and may include physician or clinic 
notes.) 
b. For the last chemotherapy course prior to being randomized in the study: 
i. 
Patients must have received a platinum-containing regimen for a minimum of 4 
cycles 
ii. 
Patients must have achieved a partial or complete tumor response 

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iii. 
Following the last regimen, patients must have either 
1. CA-125 in the normal range OR 
2. CA-125 decrease by more than 90% during their last platinum regimen 
which is stable for at least 7 days (ie, no increase > 15%) 
iv. 
Following the last regimen, patients must not have any measurable lesion > 2 cm at 
the time of study entry 
c. Patients must be randomized within 8 weeks after completion of their final dose of the 
platinum-containing regimen. 
Note: The last platinum regimen does not necessarily have to immediately follow the next to last (penultimate) 
platinum regimen. For example, if a patient received a non-platinum regimen between the penultimate platinum 
regimen and last platinum regimen, they could be eligible, so long as they meet all entry criteria. 
6. The patient agrees to complete PROs during study treatment and at 1 additional time point 8 
weeks following study treatment discontinuation. It is estimated that completion of PROs will 
take less than 20 minutes at each time point. Since these are questionnaires, their completion 
will not interfere with, or preclude, future treatment or clinical studies. 
7. Formalin fixed, paraffin-embedded archival tumor available from the primary or recurrent 
cancer required for all patients 
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 
9. Adequate organ function 
a. Absolute neutrophil count (ANC) ≥ 1,500/µL 
b. Platelets ≥ 100,000/µL 
c. Hemoglobin ≥ 9 g/dL 
d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 
60 mL/min using Cockcroft-Gault equation 
e. Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN 
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN unless 
liver metastases are present, in which case they must be ≤ 5 x ULN 
10. Able to take oral medications 
11. Women of childbearing potential must use adequate birth control for the duration of study 
participation. 
Additional Inclusion Criteria for Food Effect Sub-Study: 
With the exception of inclusion criteria 2, 4, 5, 6, 7, and 8 (above), all main study inclusion criteria apply. In 
addition, the following inclusion criteria apply to the FE sub-study only: 
1. Entry criteria are broadened to include patients with ovarian cancer regardless of platinum sensitivity and 
burden of disease as long as no standard therapy exists or the patient has refused standard therapy. 
2. ECOG 0-2 
3. Must be able to eat a high fat meal and fast for 12 hours 
Exclusion Criteria – Main Study: 
Patients will not be eligible for study entry if any of the following criteria are met: 
1. Drainage of ascites during last 2 cycles of last chemotherapy 
2. Palliative radiotherapy within 1 week encompassing > 20% of the bone marrow 
3. Persistent > Grade 2 toxicity from prior cancer therapy 

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4. Symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered “controlled,” 
central nervous system [CNS] disease must have undergone treatment [eg, radiation or 
chemotherapy] at least 1 month prior to study entry. The patient must not have any new or 
progressive signs or symptoms related to the CNS disease and must be taking a stable dose of 
steroids or no steroids.) A scan to confirm the absence of brain metastases is not required. 
Patients with spinal cord compression may be considered if they have received definitive 
treatment for this and evidence of clinically stable disease (SD) for 28 days. 
5. Known hypersensitivity to the components of niraparib 
6. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects 
of any major surgery 
7. Diagnosis, detection, or treatment of invasive cancer other than ovarian cancer ≤ 2 years prior 
to randomization (except basal or squamous cell carcinoma of the skin that has been definitively 
treated) 
8. 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 90 days) myocardial infarction, 
uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava 
syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 
9. History or current evidence of any condition, therapy, or lab abnormality that might confound 
the results of the study, interfere with the patient’s participation for the full duration of the study 
treatment, or is not in the best interest of the patient to participate 
 
Patients must not have received a transfusion (platelets or red blood cells) within 4 weeks of 
the first dose of study treatment 
10. Patient is pregnant or breast feeding, or expecting to conceive children within the projected 
duration of the study treatment. 
11. Immunocompromised patients (Note: patients with splenectomy are allowed.) 
12. Patients with known active hepatic disease (ie, Hepatitis B or C) 
13. Prior treatment with a known poly(ADP-ribose) polymerases (PARP) inhibitor 
14. Patients with a baseline QT prolongation > 470 milliseconds 
15. Patients are receiving concomitant medications that prolong QTc and are unable to discontinue 
use for the duration of the study (see Appendix 8 for a list). 
Additional Exclusion Criteria for Food Effect Sub-Study: 
With the exception of exclusion criteria 1 and 13 (above), all main study exclusion criteria apply. In addition, the 
following exclusion criteria apply to the FE sub-study only: 
1. Chemotherapy within 3 weeks of study start 
2. Patient taking a proton pump inhibitor, antacids, or H2 blocker within 48 hours of dose 
Criteria for Evaluation of Efficacy 
Primary Efficacy Endpoint: Progression-Free Survival 

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PFS is defined as the time from treatment randomization to the earlier date of assessment of 
progression or death by any cause in the absence of progression. Progression will be assessed by 
RECIST v.1.1 criteria and clinical criteria using blinded central review by 2 independent radiologists 
and an arbiter, if necessary, as well as per blinded central clinician review.  In the non-gBRCAmut 
cohort, the endpoint will be hierarchically evaluated first in HRD+ (somatic BRCAmut and HRD 
positive/BRCAwt) patients and then in all non-gBRCAmut patients. 
Secondary Endpoints: 
1. Concordance of a candidate companion BRACanalysis diagnostic test compared to the 
centralized BRCA mutation test used in this study, if needed 
2. Concordance of a candidate companion HRD diagnostic test compared to the HRD test used in 
this study, if needed 
3. Observed changes from baseline in the following PROs: 
a. FOSI 
b. EQ-5D-5L 
c. Neuropathy questionnaire 
4. Outcomes for the next anticancer therapy following study treatment (best response, dose limiting 
toxicities, and date of progression) will be collected using source documentation. 
5. PFS2 is defined as the time from treatment randomization to the earlier date of assessment of 
progression on the next anticancer therapy following study treatment or death by any cause. 
Determination of progression will be by site physician clinical and radiographic assessment 
(clinic and radiology notes may serve as source documentation). 
6. Time to first subsequent therapy (TFST) is defined as the date of randomization in the current 
study to the start date of the first subsequent anticancer therapy. 
7. Time to second subsequent therapy (TSST) is defined as the date of randomization in the current 
study to the start date of the second subsequent anticancer therapy. 
8. Chemotherapy-free interval (CFI) the time from last platinum dose until initiation of next 
anticancer therapy (excluding maintenance therapy). CFI relative to CFI from prior 
chemotherapy regimens will be evaluated (clinic notes may serve as source documentation). 
9. OS as measured from the date of randomization to the date of death by any cause 
10. Time to CA-125 progression from time of randomization 
11. Evaluation of the effects of food on the PK of niraparib 
Criteria for Evaluation of Safety 
Safety endpoints include the incidence of treatment-emergent AEs (TEAEs), changes in clinical 
laboratory parameters (hematology, chemistry), vital signs, ECG parameters, physical examinations, and 
usage of concomitant medications. Any Adverse Events of Special Interest (AESI) must be reported as 
Serious Adverse Events (SAEs) to the Sponsor as soon as the Investigator becomes aware of them. 
Biomarkers 
A biomarker classifier of DNA repair will be evaluated in tumor samples. 
Pharmacokinetics 

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For all patients in the main study, blood samples for measurements of plasma levels of niraparib and 
the major metabolite M1 will be obtained on Cycle 1/Day 1 and on Cycle 2/ Day 1 at the following 
time points: 0 (predose within 30 minutes) and 2 hours (± 15 minutes) postdose. In subsequent cycles, 
blood samples for measurement of plasma levels of niraparib and the major metabolite M1 will be 
obtained on Cycle 4/Day 1 and Cycle 8/Day 1 predose (within 30 minutes) only. 
In addition, a subset of patients (approximately 24, selected sites in the US) will undergo intensive PK 
evaluation on Day 1. In these patients, blood samples for measurements of plasma levels of niraparib 
and the major metabolite M1 will be obtained at predose (within 30 minutes) and at 1, 1.5, 2, 3, 4, 6, 
and 8 hours postdose (± 2 minutes at all postdose time points). 
For patients in the FE sub-study, blood samples for PK determination will be taken at baseline 
(predose) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose on FE Days 1 and 8. 
Additional blood samples for PK will be collected predose (within 30 minutes) and 2 hours (± 15 
minutes) postdose on Cycle 1/Day 1 and Cycle 2/Day 1 and predose only (within 30 minutes) on Cycle 
4/Day 1 and Cycle 8/Day 1. 
Statistical Methods 
Within each cohort, the overall family-wise error rate will be controlled at 1-sided alpha=0.025. 
For the gBRCAmut cohort, superiority of niraparib relative to placebo for PFS will be tested at a 1-sided 
alpha=0.025.  
Within the non-gBRCAmut cohort, PFS will be hierarchically evaluated first in the subgroup of HRD+ 
(somatic BRCAmut and HRD positive/BRCAwt) patients and then in all non-gBRCAmut patients. If the 
treatment effect is significant in the non-gBRCAmut HRD+ subgroup, then PFS will be tested in the full 
non-gBRCAmut cohort. The overall 1-sided alpha level for both tests in the non-gBRCAmut cohort will be 
0.025. 
HRD classification HRD+ (gBRCAmut, somatic BRCAmut and HRD positive/BRCAwt) or HRD- will be 
based on results from tissue testing.).Details of this testing are provided in the SAP. 
For each cohort, separately, PFS will be analyzed using a 1-sided log-rank test stratifying for time to 
progression after the penultimate platinum therapy before study enrollment, prior use of bevacizumab in 
conjunction with the penultimate or last platinum regimen, and best response during the last platinum 
regimen. 
Overall survival will be collected and monitored throughout the study duration. 
Analysis of Food Effect Sub-Study 
The effect of a high fat meal on the PK of niraparib in the FE sub-study will be estimated by point 
estimates and 90% confidence intervals (CI) for the ratios of geometric means for niraparib maximum 
concentration (Cmax), area under the curve from time zero to time t (AUC0-t), and area under the curve 
from time zero extrapolated to infinity (AUC0-∞). 
Sample Size Considerations: 
The main study is sized to address the PFS endpoint and to ensure adequate data to monitor safety and 
OS. The gBRCAmut cohort sample size is determined based on the assumption that niraparib will result 
in an improvement in median PFS of 4.8 to 9.6 months (corresponding to a hazard ratio [HR] = 0.50) 
(niraparib relative to placebo). For a true HR = 0.50, 100 PFS events will provide > 90% power assuming 
a 2:1 randomization (1-sided alpha = 0.025). It is assumed that 180 gBCRAmut patients will be enrolled 
over approximately 24 months. 
The non-gBCRAmut sample size was determined to maintain consistency with the intended hierarchical 
testing procedure under the assumption that approximately 40% of the non-gBRCAmut cohort is expected 
to be classified as HRD+. PFS sample size for the HRD+ (somatic BRCAmut and HRD positive/BRCAwt) 
subgroup is determined based on the same PFS assumption used for the gBRCAmut cohort. For a true HR 
= 0.50, based on a median PFS of 9.6 months for the niraparib-treated patients and 4.8 months for 

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placebo patients, in the non-gBRCAmut cohort who are HRD+, 98 PFS events will provide 90% power 
assuming a 2:1 randomization (1-sided alpha = 0.025). A total of approximately 310 patients will be 
enrolled into the non-gBRCAmut cohort in order to obtain a sufficient number of events in the HRD+ 
subset(somatic BRCAmut and HRD positive/BRCAwt). 
At selected sites in the US, a subset of approximately 36 patients will undergo intensive PK/ECG 
monitoring on Day 1 only; 24 of these patients will be enrolled from the main study and 12 patients from 
the open-label FE sub-study. 
At least 10 fully evaluable patients (defined as completing both the fasted and fed portion) are targeted 
to appropriately test for comparison between the fasted and fed states. If the number of evaluable patients 
falls below 10, replacement patients may be used at the discretion of the Sponsor. This is a descriptive 
sub-study and no formal sample size calculations were performed. 
Schedule of Procedures 
See Table 7, Table 8, and Table 9 . 

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ...................................................................3 
PROTOCOL SYNOPSIS ................................................................................................................4 
LIST OF STUDY PERSONNEL AND CONTACT INFORMATION ........................................14 
TABLE OF CONTENTS ...............................................................................................................15 
LIST OF TABLES .........................................................................................................................19 
LIST OF FIGURES .......................................................................................................................20 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................21 
1. 
INTRODUCTION ......................................................................................................24 
1.1. 
Background of PARP and PARP Inhibition ...............................................................24 
1.2. 
Background of Niraparib ............................................................................................25 
1.3. 
Rationale for Current Trial .........................................................................................27 
2. 
STUDY OBJECTIVES ..............................................................................................28 
2.1. 
Primary Objective .......................................................................................................28 
2.2. 
Secondary Objectives .................................................................................................28 
2.3. 
Food Effect Sub-Study Objective ...............................................................................28 
3. 
OVERALL DESIGN AND PLAN OF THE STUDY ................................................29 
3.1. 
Overview .....................................................................................................................29 
3.1.1. 
Main Study..................................................................................................................29 
3.1.2. 
Food Effect Sub-Study (Study Completed) ................................................................32 
3.2. 
Justification of Study Design and Choice of Endpoints .............................................33 
4. 
STUDY POPULATION .............................................................................................35 
4.1. 
Inclusion Criteria ........................................................................................................35 
4.1.1. 
Additional Inclusion Criteria for Food Effect Sub-Study ...........................................36 
4.2. 
Exclusion Criteria .......................................................................................................36 
4.2.1. 
Additional Exclusion Criteria for Food Effect Sub-Study: ........................................37 
4.3. 
Restrictions During Study...........................................................................................37 
4.4. 
Patient Withdrawal and Replacement .........................................................................39 
4.4.1. 
Discontinuation from Treatment .................................................................................39 
4.4.2. 
Discontinuation from the Study ..................................................................................39 

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4.5. 
Planned Sample Size and Number of Study Centers ..................................................40 
4.6. 
Patient Identification and Randomization ..................................................................40 
4.6.1. 
Patient Identification ...................................................................................................40 
4.6.2. 
Randomization Scheme ..............................................................................................40 
5. 
STUDY MEDICATION .............................................................................................42 
5.1. 
Identity ........................................................................................................................42 
5.2. 
Administration ............................................................................................................42 
5.2.1. 
Main Study..................................................................................................................42 
5.2.2. 
Food Effect Sub-Study (Completed) ..........................................................................42 
5.3. 
Dose Modification ......................................................................................................43 
5.4. 
Packaging, Labeling and Storage ...............................................................................45 
5.5. 
Blinding and Breaking the Blind ................................................................................45 
5.6. 
Drug Accountability ...................................................................................................45 
5.7. 
Previous and Concomitant Medications .....................................................................46 
6. 
VARIABLES AND METHODS OF ASSESSMENT ...............................................47 
6.1. 
Primary Efficacy: Progression Free Survival .............................................................47 
6.1.1. 
Central Blinded Clinician Review ..............................................................................48 
6.1.2. 
Date of Progression .....................................................................................................49 
6.2. 
Secondary Efficacy .....................................................................................................49 
6.2.1. 
Concordance of BRCA Tests ......................................................................................49 
6.2.2. 
Concordance of HRD Tests ........................................................................................50 
6.2.3. 
Patient Reported Outcomes ........................................................................................50 
6.2.4. 
Outcomes for Next Anticancer Therapy Following Study Treatment ........................50 
6.2.5. 
PFS2 ............................................................................................................................51 
6.2.6. 
Time to First Subsequent Therapy (TFST) .................................................................51 
6.2.7. 
Time to Second Subsequent Therapy (TSST) ............................................................51 
6.2.8. 
Chemotherapy Free Interval .......................................................................................51 
6.2.9. 
Overall Survival Time ................................................................................................51 
6.2.10. Time to CA-125 Progression ......................................................................................51 
6.3. 
Safety Variables ..........................................................................................................52 
6.3.1. 
Adverse Events ...........................................................................................................52 
6.3.1.1. Definitions ..................................................................................................................52 
6.3.1.2. Assessment of Adverse Events ...................................................................................52 

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6.3.1.3. Recording Adverse Events .........................................................................................54 
6.3.1.4. Reporting Disease Progression ...................................................................................54 
6.3.1.5. Reporting Serious Adverse Events .............................................................................54 
6.3.1.6. Follow-up of Adverse Events .....................................................................................55 
6.3.1.7. Suspected Unexpected Serious Adverse Reactions ....................................................55 
6.3.2. 
Pregnancy ...................................................................................................................56 
6.3.3. 
Overdose .....................................................................................................................56 
6.3.4. 
Adverse Events of Special Interest .............................................................................56 
6.3.5. 
Laboratory Variables ..................................................................................................57 
6.3.6. 
Physical Examination and Vital Signs ........................................................................58 
6.3.7. 
Additional Safety Assessments...................................................................................59 
6.3.8. 
Concomitant Medication ............................................................................................59 
6.4. 
Demographics and Baseline Characteristics ...............................................................59 
6.4.1. 
Patient Eligibility ........................................................................................................59 
6.4.2. 
Patient Demography ...................................................................................................59 
6.4.3. 
Disease History ...........................................................................................................60 
6.4.4. 
Medical and Surgical History .....................................................................................60 
6.5. 
Pharmacokinetics ........................................................................................................60 
6.6. 
Biomarkers ..................................................................................................................61 
7. 
STUDY CONDUCT ...................................................................................................62 
7.1. 
Schedule of Procedures ...............................................................................................62 
7.2. 
Procedures by Visit – Main Study ..............................................................................67 
7.2.1. 
Screening (Visit 1, Day -28 to Day -1) .......................................................................67 
7.2.2. 
Cycle 1, Day 1 ............................................................................................................68 
7.2.3. 
Cycle 1, Day 8 ............................................................................................................69 
7.2.4. 
Cycle 1, Day 15 ..........................................................................................................69 
7.2.5. 
Cycle 1, Day 21 ..........................................................................................................69 
7.2.6. 
Cycle 2, Day 1 ............................................................................................................69 
7.2.7. 
Day 1, Subsequent Cycles ..........................................................................................70 
7.2.8. 
Study Treatment Discontinuation (within 7 days of last dose) ...................................70 
7.2.9. 
Post Study Treatment Assessments (Study Visit Not Required) ................................71 
7.2.10. Unscheduled Assessments ..........................................................................................71 
7.3. 
Procedures by Visit – Food Effect Study ...................................................................74 

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7.3.1. 
Screening (Visit 1, Day -28 to Day -1) .......................................................................74 
7.3.2. 
Food Effect, Day 1 ......................................................................................................74 
7.3.3. 
Food Effect, Day 8 ......................................................................................................75 
7.3.4. 
Cycle 1, Day 1 (Approximately 2 Weeks After Start of Food Effect Sub-
Study) .....................................................................................................................75 
7.3.5. 
Cycle 1, Day 15 ..........................................................................................................76 
7.3.6. 
Cycle 2, Day 1 ............................................................................................................76 
7.3.7. 
Day 1, Subsequent Cycles ..........................................................................................76 
7.3.8. 
Study Treatment Discontinuation (Within 7 Days of Last Dose) ...............................77 
7.3.9. 
Unscheduled Assessments ..........................................................................................77 
7.4. 
Procedures by Visit – Main Study Extended Visit Cycles .........................................79 
7.4.1. 
Day 1, Subsequent Cycles ..........................................................................................79 
7.4.2. 
Day 1, Extended Cycles (every three cycles, 84 days) ...............................................79 
7.4.3. 
Study Treatment Discontinuation (within 7 days of last dose) ...................................80 
7.4.4. 
Post Study Treatment Assessments (Study Visit Not Required) ................................80 
7.4.5. 
Unscheduled Assessments ..........................................................................................81 
8. 
STATISTICAL METHODS .......................................................................................82 
8.1. 
Study Populations .......................................................................................................82 
8.2. 
Demographics, Medical History, Baseline Characteristics, and Concomitant 
Medications ..............................................................................................................82 
8.3. 
Efficacy Analyses .......................................................................................................82 
8.3.1. 
Primary Efficacy Parameter ........................................................................................82 
8.3.2. 
Secondary Endpoints Analyses ...................................................................................83 
8.4. 
Safety Analyses ..........................................................................................................84 
8.5. 
Post-Treatment Analyses ............................................................................................84 
8.6. 
Food Effect Analyses ..................................................................................................84 
8.7. 
QTc Analyses ..............................................................................................................84 
8.8. 
Interim Analyses .........................................................................................................84 
8.9. 
Determination of Sample Size ....................................................................................84 
9. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS ....................................86 
9.1. 
Data Quality Assurance ..............................................................................................86 
9.2. 
Access to Source Data/Documents .............................................................................86 
9.3. 
Archiving Study Documents .......................................................................................87 

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9.4. 
Good Clinical Practice ................................................................................................87 
9.5. 
Informed Consent .......................................................................................................87 
9.6. 
Protocol Approval and Amendment ...........................................................................87 
9.7. 
Independent Data Monitoring Committee ..................................................................88 
9.8. 
Study Monitoring ........................................................................................................88 
9.9. 
Audits and Inspections ................................................................................................88 
9.10. 
Ethical Considerations ................................................................................................88 
9.11. 
Publication Policy .......................................................................................................88 
10. 
REFERENCES ...........................................................................................................89 
APPENDIX 1. DRUGS KNOWN TO INHIBIT OR INDUCE CYP1A2 ..................................91 
APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS V.1.1 ............92 
APPENDIX 3. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS 
(CTCAE) V.4.02 .........................................................................................................95 
APPENDIX 4. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .......................................................................................96 
APPENDIX 5. SAMPLE FUNCTIONAL ASSESSMENT OF CANCER THERAPY – 
OVARIAN SYMPTOM INDEX (FOSI) ...................................................................97 
APPENDIX 6. SAMPLE EUROPEAN QUALITY OF LIFE SCALE, 5-
DIMENSIONS (EQ-5D-5L) .......................................................................................98 
APPENDIX 7. NEUROPATHY QUESTIONNAIRE ..............................................................102 
APPENDIX 8. DRUGS ASSOCIATED WITH QT PROLONGATION AND 
TORSADES DE POINTES ......................................................................................103 
LIST OF TABLES 
Table 1: 
Progression-Free Survival in Ovarian Cancer Patients in NOVA ..............................26 
Table 2: 
Cohort Assignment Based on Myriad Report .............................................................30 
Table 3: 
Dose Reductions for Non-Hematologic Toxicities .....................................................43 
Table 4: 
Dose Modification/Reduction for Hematologic Toxicities ........................................43 
Table 5: 
Determination of Overall Response per Central RECIST and Central 
Clinical Review ..........................................................................................................48 
Table 6: 
Reference Table for Determining the Date of Progression ........................................49 
Table 7 
Schedule of Events – Main Study ...............................................................................63 
Table 8 
Schedule of Events – Open-Label Food Effect Sub-Study (Study Completed) .........72 
Table 9: 
Schedule of Events – Main Study –Extended Visit Cycle .........................................78 

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Table 10: Censoring Rules for Primary PFS Analysis ................................................................83 
Table 11: For Patients with Measurable Disease (ie, Target Disease) .......................................93 
Table 12: For Patients with Non-Measurable Disease (ie, Non-Target Disease) .......................93 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................31 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADL 
activities of daily living 
AE 
adverse event 
AESI 
Adverse Event of Special Interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
APTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical [Classification System] 
AUC 
area under the curve 
AUC0-t 
area under the curve from time 0 to time t 
AUC0-∞ 
area under the curve from time 0 extrapolated to infinity 
BER 
base excision repair 
BUN 
blood urea nitrogen 
CBC 
complete blood cell count 
CFI 
chemotherapy-free interval 
CFR  
Code of Federal Regulations 
CI 
confidence interval 
CL 
Clearance 
CNS 
central nervous system 
CR 
complete response 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture system 
EQ-5D-5L 
European Quality of Life Scale, 5-Dimensions 
FE 
food effect 

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FOSI 
Functional Assessment of Cancer Therapy – Ovarian Symptom Index 
gBRCAmut 
germline BRCA mutation 
GCIG 
Gynecologic Cancer Intergroup 
GCP 
Good Clinical Practice 
GCSF 
granulocyte colony-stimulating factor 
GGT 
gamma glutamyl transferase 
HDPE 
high-density polyethylene 
HR 
hazard ratio  
HRD 
homologous recombination deficiency 
ICF 
informed consent form 
IDMC 
independent data monitoring committee 
IEC 
independent ethics committee  
ICH 
International Conference on Harmonisation  
INR 
international normalized ratio 
IRB 
institutional review board 
ITT 
intent-to-treat  
IWRS 
interactive web response system 
LDH 
lactic dehydrogenase 
LOH 
loss of heterozygosity 
LST 
large-scale state transitions 
MCV 
mean corpuscular volume 
MPV 
mean platelet volume 
NHEJ 
non-homologous end joining 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDS 
myelodysplastic syndrome 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute  
NE 
not evaluable  
OS 
overall survival  
PARP 
poly(ADP-ribose) polymerases  
PD 
progressive disease  
PFS 
progression-free survival  
PK 
Pharmacokinetics 
PP 
per-protocol  

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PR 
partial response  
PRO 
patient reported outcomes 
QD 
once daily 
QoL 
quality of life 
RECIST  
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease  
SUSAR 
suspected unexpected serious adverse reaction 
TAI 
telomeric allelic imbalance 
TEAE 
TFST 
TSST 
treatment-emergent adverse event 
Time to First Subsequent Therapy 
Time to Second Subsequent Therapy 
ULN 
upper limit of normal 
US 
United States 
UV 
Ultraviolet 
VAS 
visual analog scale 
WBC 
white blood cells 
WHO 
World Health Organization 

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1. 
INTRODUCTION 
1.1. 
Background of PARP and PARP Inhibition 
Poly(ADP-ribose) polymerases (PARP1 and PARP2) are zinc-finger deoxyribonucleic acid 
(DNA)-binding enzymes that play a crucial role in DNA repair. Upon formation of single-strand 
DNA breaks, PARP binds at the end of broken DNA strands, a process which activates its 
enzymatic activity. Activated PARP catalyzes addition of long polymers of ADP-ribose on 
several proteins associated with chromatin, including histones and various DNA repair proteins 
including PARP itself. This results in chromatin relaxation, fast recruitment of DNA repair 
proteins and efficient repair of DNA breaks. In this manner PARP plays a key role in sensing 
DNA damage and converting it into intracellular signals that activate the base excision repair 
(BER) and single strand break repair pathways. 
Normal cells repair up to 10,000 DNA defects daily and single strand breaks are the most 
common form of DNA damage. Cells that are unable to repair this burden of DNA damage, such 
as those with defects in the BER pathway, or those treated with PARP inhibitors, are at risk for 
accumulating multiple lesions that will ultimately trigger apoptosis. They enter the S (DNA 
replication) phase of the cell cycle with unrepaired single strand breaks. Pre-existing single 
strand breaks are converted to double strand breaks as the replication machinery passes. 
Accumulated double strand breaks present during S phase are repaired by homologous 
recombination. Homologous recombination is the preferred repair pathway because it is 
associated with a much lower error rate than other forms of repair. Cells unable to perform DNA 
repair via homologous recombination (eg, due to inactivation of genes required for homologous 
recombination, such as BRCA1 or BRCA2) are at risk for accumulating multiple lesions that will 
ultimately trigger apoptosis. These cells accumulate stalled replication forks during S phase and 
are more likely to use the error-prone non-homologous end joining (NHEJ) pathway to repair 
double strand breaks in DNA. Accumulation of errors in DNA by NHEJ contributes to mutations 
that promote the development of cancer. Over time, the buildup of excessive DNA errors in 
combination with the inability to complete S phase (because of stalled replication forks) 
contributes to cell death. 
A hypothesis is that treatment with PARP inhibitors represents a novel opportunity to selectively 
kill a subset of cancer cells with deficiencies in DNA repair pathways. For example, a tumor 
arising in a patient with a germline BRCA mutation (gBRCAmut) has a defective homologous 
recombination DNA repair pathway and would be increasingly dependent on BER, a pathway 
blocked by PARP inhibitors, for maintenance of genomic integrity. DNA-repair defects can be 
caused by germline or somatic alterations to the homologous recombination DNA repair 
pathway. In a recent analysis of ~500 HGS-OvCa tumors, approximately 50% contained 
homologous recombination defects.3 A subset of these tumors had biologically plausible 
molecular alterations that may make them sensitive to PARP inhibition by niraparib. This 
concept of inducing tumor cell death by use of PARP inhibitors to block one DNA repair 
pathway in tumors with pre-existing deficiencies in a complementary DNA repair pathways is 
called synthetic lethality4; the 2 insults together induce cell death when neither alone would have 
this effect. 
Non-BRCA deficiencies in homologous recombination DNA repair genes could also enhance 
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tumors without a gBRCAmut (non-gBRCAmut) is they share distinctive DNA repair defects with 
gBRCAmut carriers, a phenomenon broadly described as “BRCAness.”5 A tumor arising in a non-
gBRCAmut patient that has a homologous recombination deficiency (HRD+; ie, deficiencies in 
homologous recombination DNA repair genes) could also enhance tumor cell sensitivity to 
PARP inhibitors. In a recent study, the patterns of genome-wide loss of heterozygosity (LOH) 
were analyzed in 3 different epithelial ovarian cancer data sets extensively characterized for 
BRCA1 and BRCA2 defects by evaluating HRD status.6 The HRD analysis is a DNA-based 
assay that is capable of detecting HRD independent of its etiology based on genome-wide single 
nucleotide polymorphism data. An HRD-(LOH) score was developed that is strongly associated 
with functional defects in BRCA1 and BRCA2. This score also strongly correlated with 
promoter methylation of RAD51C, a gene implicated in the homologous recombination pathway. 
Additional DNA-based algorithms of HRD have been developed based on whole genome tumor 
telomeric allelic imbalance, HRD-(TAI),7 and large-scale state transitions, HRD-(LST).8 
In a subsequent study, all 3 HRD algorithms were independently associated with BRCA1/2 
deficiency and response to cisplatin treatment in triple-negative breast cancer.9 The arithmetic 
mean of the 3 HRD algorithms was significantly associated with BRCA1/2 status in a breast all-
comers cohort and with cisplatin response in a second independent triple-negative breast cancer 
cohort. The final clinical HRD score results from the sum of HRD-LOH, HRD-TAI and HRD-
LST scores, and is a single value along a continuous scale from 0 to 100. Analysis of more than 
1,000 breast and ovarian cancer tumor samples have identified 2 distinct HRD populations, 
HRD- and HRD+, with 95% of all gBRCAmut tumors with concomitant LOH at the BRCA gene 
in the sample classified as HRD+. Details of procedures used to classify patients in this study are 
provided in the statistical analysis plan (SAP). 
Clinical studies have shown that PARP inhibitors are active for recurrent ovarian cancer.10-14 
Clinical anticancer activity has been observed in patients with and without gBRCAmut and in 
patients who are platinum sensitive and platinum resistant. However, PARP inhibition appears to 
be most active in patients with gBRCAmut platinum sensitive disease.11,12,14 This clinical 
experience to date is largely in patients who have received multiple prior treatments (median ~3; 
range, 1-10) in multiple Phase 1 and 2 clinical studies. In a Phase 2 study of maintenance therapy 
in 265 patients with relapsed, platinum sensitive ovarian cancer, daily olaparib therapy compared 
to placebo treatment was associated with a progression-free survival (PFS) benefit (hazard ratio 
[HR] = 0.35) and prolongation of the median PFS from 4.8 months to 8.4 months.14 The subset 
of patients with known gBRCAmut had a PFS HR of 0.18.15 Patient reported outcomes (PROs), 
including the Functional Assessment of Cancer Therapy–Ovarian Symptoms Index (FOSI), were 
measured and did not show a significant difference between the placebo and treatment groups; 
suggesting that maintenance treatment did not decrease functioning or quality of life (QoL) in 
these patients. 
1.2. 
Background of Niraparib 
Niraparib is an orally active PARP1/2 inhibitor with nanomolar potency being developed as a 
monotherapy agent for tumors with defects in the homologous recombination DNA repair 
pathway or that are driven by PARP-mediated transcription factors. 
In nonclinical models, niraparib has been observed to inhibit normal DNA repair mechanisms 
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defects. In a BRCA1 mutant xenograft study, niraparib dosed orally caused tumor regression 
which was mirrored by > 90% reduction in tumor weight compared to control; in a BRCA2 
mutant xenograft study, niraparib-dosed mice showed 55% to 60% growth inhibition, both by 
tumor volume and weight. 
Additional nonclinical data on niraparib in ovarian cancer are described in the Investigator’s 
Brochure. 
In the NOVA study, a total of 553 patients were randomized into this Phase 3 study at 107 
centers worldwide. The study population comprises 203 patients randomized into the gBRCAmut 
cohort and 350 patients randomized into the non-gBRCAmut cohort. Among the 350 patients in 
the non-gBRCAmut cohort, 162 had tumors that were defined as HRDpos and 134 had tumors 
that were HRD negative (HRDneg). HRD status was not determined (HRDnd) for 54 patients.  
Table 1 shows the results for the PFS primary endpoint for each of the 3 primary efficacy 
populations (ie, gBRCAmut cohort, HRDpos cohort, and overall non-gBRCAmut cohort). In 
addition, median PFS in patients with HRD negative (HRDneg) tumors was 6.9 months (95% CI: 
5.6, 9.6) in the niraparib arm compared to 3.8 months (95% CI: 3.7, 5.6) in the placebo arm with 
an HR of 0.58 (95% CI: 0.361, 0.922) (p=0.0226).    
Table 1: 
Progression-Free Survival in Ovarian Cancer Patients in NOVA 
  
gBRCAmut Cohort 
non-gBRCAmut Cohort 
(regardless of HRD status) 
HRDpos  
(within non-gBRCAmut cohort) 
Niraparib 
(N=138) 
Placebo 
(N=65) 
Niraparib 
(N=234) 
Placebo 
(N=116) 
Niraparib 
(N=106) 
Placebo (N=56) 
PFS Median 
(95% CI)a 
21.0 
(12.9, NR) 
5.5 
(3.8, 7.2) 
9.3 
(7.2, 11.2) 
3.9 
(3.7, 5.5) 
12.9 
(8.1, 15.9) 
3.8 
(3.5, 5.7) 
p-value 
<0.0001 
<0.0001 
<0.0001 
Hazard 
Ratio 
(Nir:Plac) 
(95% CI) 
0.27 
(0.173, 0.410) 
0.45 
(0.338, 0.607) 
0.38 
(0.243, 0.586) 
Progression-free survival is defined as the time in months from the date of randomization to progression or 
death. 
 
The primary data to support the safety of treatment with niraparib in the proposed indication are 
derived from the NOVA main study in which a total of 546 patients received study treatment. 
Niraparib appears to have a predictable adverse event (AE) profile that is readily managed 
through routine laboratory testing (i.e., complete blood count [CBC]) and clinical monitoring 
(i.e., blood pressure monitoring and adherence to the recommended dose modifications). In the 
NOVA study, both all grade and high grade treatment emergent adverse events (TEAE) tend to 
decrease over time. Most TEAEs following one year of study treatment are readily managed with 
dose modifications and/or widely available supportive measures; events occurring in ≥ 5% of 
patients after one year of niraparib treatment include nausea, constipation, vomiting, diarrhea, 
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following one year of treatment include ≥ Grade 3 hypertension and MDS/AML, both of which 
are routinely monitored for all patients on study. 
The niraparib clinical safety data reported to date, including Phase 1 results, dose limiting 
toxicities, and toxicity profile are provided in detail in the Investigator’s Brochure. 
Hypertension, including hypertensive crisis, has been reported with the use of niraparib. Blood 
pressure will be monitored at each study visit.  Hypertension should be medically managed with 
antihypertensive medications as well as adjustment of the niraparib dose, if necessary. 
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been observed in 
patients receiving treatment with olaparib, a PARP inhibitor; given the common mechanism of 
action, MDS and AML therefore represent a potential risk to patients receiving niraparib. 
Guidance on monitoring patients for new events of MDS/AML and the follow-up of patients 
with suspected MDS/AML is provided in Section 6.3.5 and Section 7.1. 
1.3. 
Rationale for Current Trial 
Collectively, the data from multiple published Phase 1 and 2 clinical studies of PARP inhibitors 
used as monotherapy to treat patients with recurrent ovarian cancer suggest that the agents are 
active in this population; the strongest activity being observed in the platinum sensitive, 
gBRCAmut subgroup. Data from a randomized Phase 2 study of olaparib vs placebo in patients 
with relapsed, platinum sensitive ovarian cancer, in response to their most recent platinum 
regimen showed a significant prolongation of PFS, this effect being strongest in patients with 
known gBRCAmut.14 
The niraparib Phase 3 study is designed to address certain deficiencies in the design of the 
olaparib maintenance study14 and to document and power for PFS benefit in this setting. 
Improvements include: (1) prospective identification, enrichment, and randomization of patients 
with gBRCAmut; (2) prospective identification and randomization of non-gBRCAmut patients to 
enable assessment of niraparib activity in the group without enrichment; (3) prespecified and 
adequately powered statistical analyses that enable a primary endpoint analysis on the enriched 
gBRCAmut cohort and the non-gBRCAmut HRD+ subgroup (somatic BRCAmut and HRD 
positive/BRCAwt); (4) support of PFS data with PRO data that extends beyond progression to 
enable data collection during subsequent chemotherapy; (5) collection of tumor and blood 
samples to enable analyses with different molecular classifiers that may further identify or enrich 
for those patients that could benefit from niraparib treatment, or those patients in either cohort 
who may not benefit from niraparib treatment; and (6) ongoing follow-up to provide overall 
survival (OS) information. 
At selected sites in the United States (US), this study will include a 14-day, open-label, crossover 
FE sub-study in approximately 12 patients with ovarian cancer to assess the effect of a high fat 
meal on the single-dose pharmacokinetics (PK) of niraparib 300 mg. 

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2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in 
patients who have platinum sensitive ovarian cancer as assessed by the prolongation of PFS. This 
objective will be independently evaluated in a cohort of patients with germline BRCA mutation 
(gBRCAmut) and in a cohort of patients who have high grade serous or high grade predominantly 
serous histology but without such gBRCAmut (non-gBRCAmut).  The statistical analysis of the 
primary endpoint of PFS for the non-gBRCAmut cohort in the NOVA study will be performed in 
a hierarchical manner, with a test for the HRD positive subset (somatic BRCAmut and HRD 
positive/BRCAwt) performed first, followed by a test of the overall non-gBRCAmut cohort if the 
first test is statistically significant.  
2.2. 
Secondary Objectives 
Secondary objectives include the following: 
1. Concordance of a candidate companion BRACanalysis diagnostic test compared to the 
centralized BRCA mutation test used in this study, if needed. 
2. Concordance of a candidate companion HRD diagnostic test compared to the HRD test 
used in this study, if needed 
3. To evaluate additional measures of clinical benefit, including PROs, time to first 
subsequent treatment (TFST), time to second subsequent treatment (TSST), time from 
treatment randomization to the earlier date of assessment of progression on the next anti-
cancer therapy following study treatment or death by any cause (PFS2), chemotherapy-
free interval (CFI) and OS. 
4. To evaluate the safety and tolerability of niraparib compared to placebo in the indicated 
target population. 
5. To evaluate QTc in a subset of niraparib-treated ovarian cancer patients. 
2.3. 
Food Effect Sub-Study Objective 
To assess the effect of a high fat meal on the PK of a single 300 mg dose of niraparib in patients 
with ovarian cancer. 

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3. 
OVERALL DESIGN AND PLAN OF THE STUDY 
3.1. 
Overview 
Niraparib is a potent inhibitor of PARP, a clinically validated target in breast and ovarian cancer. 
Current standard of care for patients with platinum sensitive, recurrent ovarian cancer that has 
responded to the last platinum regimen is close follow-up with no treatment. 
3.1.1. 
Main Study 
The main study is a double-blind, 2:1 randomized, placebo controlled study in platinum sensitive 
ovarian cancer patients who have either gBRCAmut or a tumor with high grade serous or high 
grade predominantly serous histology but without such gBRCAmut (non-gBRCAmut). The patients 
must have received at least 2 platinum-based regimens with the last regimen prior to being 
randomized in the study being platinum-based, had a response assessed by a physician of 
complete response (CR) or partial response (PR) to their last regimen, must not have any 
measurable lesion > 2 cm, and must have normal cancer antigen (CA)-125 (or >90% decrease) 
following their last treatment. The study will assess whether maintenance with niraparib will 
extend PFS in this population. There will be 2 independent patient cohorts as determined by the 
results of Myriad Integrated BRACAnalysis® testing, one cohort of patients with results 
indicating either a positive deleterious gBRCA mutation or genetic variant or a suspected 
deleterious mutation (gBRCAmut) and the other with high grade serous or high grade 
predominantly serous histology but without such gBRCAmut(non-gBRCAmut) based on the 
hypothesis that patients with gBRCAmut will be enriched for responsiveness to niraparib. The 
statistical analysis of the primary endpoint of PFS for the non-gBRCAmut cohort in the NOVA 
study will be performed in a hierarchical manner, with a test for the HRD positive subset 
(somatic BRCAmut and HRD positive/BRCAwt) performed first, followed by a test of the overall 
non-gBRCAmut cohort if the first test is statistically significant. 
A blood sample will be sent to Myriad for immediate Integrated BRACAnalysis® testing. The 
sample may be sent in advance of the protocol-defined screening period in order to facilitate the 
screening and enrollment process. 
Patients who have not had Myriad BRCA mutation testing completed in the past must wait for 
the results from the on-study Myriad Integrated BRACAnalysis® test prior to randomization. 
Patients who have had a prior Myriad Integrated BRACAnalysis® test must still provide a sample 
for testing prior to randomization, but may be randomized based on the results from the prior 
Myriad test. 
Patients with Integrated BRACAnalysis® result will be assigned within a gBRCAmut cohort or a 
non-gBRCAmut cohort as per Table 2. 

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Table 2: 
Cohort Assignment Based on Myriad Report 
MYRIAD Report Results 
Cohort for Randomization 
Positive for a Deleterious Mutation 
gBRCAmut cohort 
Genetic Variant, Suspected Deleterious 
gBRCAmut cohort 
Genetic Variant, Favor Polymorphism 
Non-gBRCAmut cohort 
Genetic Variant of Uncertain Significance 
Non-gBRCAmut cohort 
No Mutation Detected 
Non-gBRCAmut cohort 
A separate randomization list will be created for each cohort. Stratification factors will include 
time to progression after the penultimate (next to last) platinum therapy before study enrollment 
(6 to < 12 months and ≥ 12 months), use of bevacizumab in conjunction with the penultimate or 
last platinum regimen (yes/no) and best response during the last platinum regimen (CR and PR). 
An analysis of outcome by (1) concomitant chemotherapy with platinum in the last and 
penultimate regimens (yes/no), and (2) number of prior platinum courses (2 and > 2) will also be 
performed. 
A tissue sample will be sent for centralized testing to classify patients by HRD status. Testing 
may be completed any time prior to database lock. Details on tissue sample collection can be 
found in the laboratory manual. 
Clinic visits will occur in each cycle (4 weeks ± 3 days). Response Evaluation Criteria in Solid 
Tumors (RECIST) will be used for tumor assessment via a computed tomography (CT) or 
magnetic resonance imaging (MRI) scan of abdomen/pelvis and clinically indicated areas, which 
is required at the end of every 2 cycles (8 weeks with a window of ± 7 days from date of visit) 
through Cycle 14 (56 weeks), then at the end of every 6 cycles (24 weeks with a window of ± 7 
days) until progression. Cycle timing will not be delayed for treatment interruptions, and tumor 
assessment should occur according to this schedule regardless of whether study treatment is 
interrupted. If a patient discontinues treatment for a reason other than progression or death, 
withdrawal of consent, or lost to follow-up, scans should continue at the specified intervals. If a 
patient discontinues treatment for clinical progression and does not meet the criteria specified in 
the protocol, scans and CA-125 testing should continue at the specified intervals until 
progression is confirmed or until the start of subsequent anticancer treatment. 
PROs (FOSI; European Quality of Life scale, 5-Dimensions [EQ-5D-5L]; and a neuropathy 
questionnaire) will be collected in a coordinated fashion with RECIST tumor imaging while on 
study treatment and following discontinuation of treatment, regardless of progression status (at 
the nearest study visit to the imaging exam, and after every 2 cycles through Cycle 14, then after 
every 3 cycles). If the patient discontinues study treatment, assessment of PROs will be 
performed at that time and then 8 weeks (±2 weeks) later, regardless of subsequent treatment. 
The PROs may be completed remotely. It is estimated that PRO evaluations will take less than 
20 minutes at each time point. Since these are questionnaires, their completion will not interfere 
with, or preclude, future treatment or clinical studies. After treatment discontinuation, study 
information on PROs, response, tolerability with subsequent anticancer treatment, and survival 
will continue to be collected (see Figure 1). 

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treatment and remain on study treatment will have an Extended Visit Cycle, which allow for the 
patient to have in-clinic visits approximately every 84 days, rather than every 28 days.  All study 
procedures and assessments for the in-home visits will be completed through telephone contact 
and home nursing visits. The study specific procedures and assessments are not reduced with the 
introduction of the Extended Visit Cycle; thus there will be no impact on the collection or 
evaluation of safety and efficacy data for these patients.   
The study sponsor, TESARO, will offer the in-home nursing visits to mitigate the need for 
monthly travel to the study site for evaluation.  An in-home nurse will travel to the patient’s 
home and perform study procedures on the Extended Visit Cycle; the nurse will measure vital 
signs, confirm that the specimens from the previous visit have been tested per protocol, collect 
and prepare new laboratory specimens for testing and dispense study medication. For patients 
who live greater than two hours from the study clinic, the Sponsor will offer the option to courier 
the study drug to the patient’s home.  The in-home nurse will ensure that the patient specimens 
arrive at the laboratory for testing and that the data from the patient evaluation is provided to the 
study site.  In alignment with the timeframe of the in-home nurse visits, the site staff will contact 
the patient by phone to obtain the evaluation for the ECOG performance status, adverse event 
monitoring and concomitant medications. 
An independent data monitoring committee (IDMC) will be established to provide independent 
review and assessment of the efficacy and safety data in a systematic manner and to safeguard 
the interest and safety of the participating patients in the study. The composition of the IDMC 
will consist of 3 independent individuals, including 1 biostatistician and 2 physicians. The IDMC 
is tasked with making a recommendation to the Sponsor based on their review to continue or stop 
the trial based on their assessment of efficacy and safety information. The membership, the key 
responsibilities of the IDMC, and the corresponding procedures will be defined in an IDMC 
charter. 
No crossover to niraparib is permitted for patients randomized to placebo. Patient outcome 
information will be collected during treatment as well as after treatment, including PRO, 
response, tolerability with subsequent anticancer treatment, and OS. 
3.1.2. 
Food Effect Sub-Study (Study Completed) 
Note: As of Amendment 3, enrollment on the FE sub-study has been completed; preliminary 
results indicate that the PK profile of niraparib is not affected by food intake. The description of 
planned assessments for these patients is retained in the protocol for completeness. 
At selected sites in the US, approximately 12 patients will be enrolled into a 14-day, open-label, 
2-treatment, crossover sub-study to evaluate the effect of a high fat meal on niraparib (single 
dose) exposure. For this FE sub-study, entry criteria will be broadened to include patients with 
ovarian cancer regardless of platinum sensitivity and burden of disease as long as no standard 
therapy exists or the patient has refused standard therapy. 
Patients will be randomized to either Group A or Group B with 6 patients assigned to each 
group. In Group A, patients will fast (nothing to eat or drink except water) for at least 10 hours 
before receiving a single dose of 300 mg niraparib; patients will continue to fast for at least 
2 hours following the dose. In Group B, patients will fast for at least 10 hours before consuming 
a high fat meal. Within 5 minutes of finishing the meal, a single dose of 300 mg niraparib will be 

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administered orally and patients will resume fasting for at least 4 hours. After a 7-day PK 
assessment and wash-out period, all patients will receive their second single dose of niraparib on 
Day 8 under the opposite (fasting vs high fat meal) circumstance: the previous 6 patients in 
Group A will receive their single dose of niraparib after a high fat meal and patients in Group B 
will receive their second single dose of niraparib under fasting conditions (Section 5.2). 
The high fat meal (approximately 50% of total caloric content of the meal) and high calorie 
(approximately 800–1,000 calories) is recommended as for food-effect bioavailability and fed 
bioequivalence studies. This meal should derive approximately 150, 250, and 500 to 600 calories 
from protein, carbohydrate, and fat, respectively. An example high fat breakfast meal is 2 eggs 
fried in butter, 2 strips of bacon, 2 slices of toast with butter, 4 ounces of hash brown potatoes 
and 8 ounces of whole milk. Substitutions in this test meal can be made as long as the meal 
provides a similar amount of calories from protein, carbohydrate, and fat and has comparable 
meal volume and viscosity.16 
Niraparib will be administered in the clinical facility. After administration of niraparib, an 
examination of the oral cavity is required to verify that a patient has swallowed the capsules. The 
patient should drink the entire aliquot of water given to swallow the capsules. The examiner 
should have the patient open the mouth and stick out the tongue far enough to permit 
visualization of the posterior most part of the tongue. A light source should be used to ensure 
complete visualization and in some cases it may be necessary to use a tongue blade. The patient 
should be directed to move the tongue up and then from side to side. It may be necessary to use a 
tongue blade to move the tongue far enough to permit full visualization of the area under the 
tongue. The tongue blade should then be used to inspect the sulcus between the gums and the 
inner cheeks in all 4 quadrants. The patient should then be asked to lift the upper and lower lips 
to permit visualization of the sulcus between the inner lip and the gums. 
For the FE sub-study, if emesis should occur within 4 hours of dosing, this patient will be 
considered non-evaluable from a PK perspective and will need to be replaced. 
FE sub-study patients will undergo intensive (triplicate) ECG monitoring on FE Days 1 and 8 at 
baseline (predose) and 1, 1.5, 2, 3, 4, 6, and 8 hours postdose to coincide with blood sampling for 
PK determination. Triplicate ECGs should be performed between 2 and 5 minutes apart and 
should be performed prior to blood draws for PK. Patients will be supine and rested for 
approximately 2 minutes before ECGs are recorded. The average of each of the triplicate 
measures will be used for analysis. Additional blood samples for PK will be collected at 12, 24, 
48, 72, 96, and 120 hours postdose on FE Days 1 and 8; predose and 2 hours postdose on Cycle 
1/Day 1 and Cycle 2/Day 1; and predose (only) on Cycle 4/Day 1 and Cycle 8/Day 1. 
Upon completion of the 14-day FE sub-study, participating patients will then conform to the 
schedule in the main study on Cycle 1/Day 1 (approximately 2 weeks after the start of the FE 
sub-study) and will begin dosing with open-label niraparib at 300 mg once daily (QD). These 12 
patients will only be assessed for safety for the duration of the study and may continue until 
Investigator-determined progression. 
3.2. 
Justification of Study Design and Choice of Endpoints 
Platinum-containing regimens are considered the treatment of choice for recurrent ovarian cancer 
patients who are platinum sensitive. However, studies demonstrate that the PFS times for 

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patients are relatively short after treatment, so there is a need to find treatments that will prolong 
the progression free interval. 
The current study design allows patients to complete their platinum-containing regimen prior to 
enrollment. Niraparib has demonstrated significant anti-tumor activity in patients with platinum 
sensitive ovarian cancer. In Protocol PN001, a Phase 1 trial of niraparib, anti-tumor activity was 
observed for monotherapy in patients with advanced platinum sensitive and refractory tumors at 
various dose levels ranging from 60 to 400 mg. Among the 104 patients enrolled in this study, 
including diverse malignancies and clinical presentations, 14 patients achieved confirmed or 
unconfirmed PR by RECIST v.1.1 and/or by CA-125 criteria. Six of 10 patients (60%) with 
platinum sensitive ovarian cancer achieved response. The 300 mg QD dose was chosen based on 
the efficacy, PK/pharmacodynamics, safety, and tolerability profiles of niraparib in early clinical 
testing. 
The proposed study design incorporates what has been learned previously in similar studies. A 
key focus of this study will be on patients with high-grade serous or high-grade predominantly 
serous ovarian cancer and gBRCAmut. Based on data from the completed dose escalation study 
with niraparib as well as data from clinical studies with the PARP inhibitor olaparib 11,12,14, it is 
believed that the subset of patients with gBRCAmut will be enriched for response to PARP 
inhibition. The Myriad BRACAnalysis® test has been developed to determine gBRCAmut status 
of individual tumors and identify patients likely to respond to PARP inhibitor treatment. 
Furthermore, recent studies have demonstrated a high incidence of HRD+ in tumors that are 
responsive to platinum and are non-gBRCAmut from patients with high grade serous histology.3,17 
HRD+ status may explain the sensitivity of non-gBRCAmut patients to treatment with PARP 
inhibitors.3 A molecular classifier has been developed to determine HRD status of individual 
tumors and identify patients likely to respond or be resistant to PARP inhibitor treatment. 
Therefore, the broader population of patients with platinum sensitive, relapsed, high grade serous 
or high grade predominantly serous ovarian cancer in response to a platinum-based regimen will 
be evaluated utilizing a design that incorporates a patient enrichment strategy to prospectively 
identify, independently randomize, and independently evaluate gBRCAmut and non-gBRCAmut 
cohorts. Within the non-gBRCAmut cohort, the primary PFS analysis will also prospectively 
identify HRD+ patients and hierarchically evaluate the non-gBRCAmut HRD+ (somatic BRCAmut 
and HRD positive/BRCAwt) subgroup and the full non-gBRCAmut cohort. 

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4. 
STUDY POPULATION 
4.1. 
Inclusion Criteria 
To be considered eligible to participate in this study, all of the following requirements must be 
met: 
1. Female, age at least 18 years 
2. Patient agrees to undergo analysis of their gBRCA status. (Testing must be completed 
prior to randomization. The sample may be submitted at any time prior to the screening 
period if it appears patient is likely to meet other eligibility requirements. To facilitate 
early testing, a separate informed consent form [ICF] specific for genotyping will be 
available to be signed prior to gBRCA status testing.) 
3. Histologically diagnosed ovarian cancer, fallopian tube cancer, or primary peritoneal 
cancer 
4. High grade (or Grade 3) serous or high grade predominantly serous histology or known 
to have gBRCAmut 
5. Patients must have completed at least 2 previous courses of platinum-containing therapy 
(eg, carboplatin, oxaliplatin, or cisplatin): 
a. For the penultimate (next to last) platinum-based chemotherapy course prior to 
enrollment on the study: 
i. 
A patient must have platinum sensitive disease after this treatment; defined as 
achieving 
a 
response 
(CR 
or 
PR) 
and 
disease 
progression  
> 6 months after completion of their last dose of platinum therapy (document 
6-12 months or > 12 months). (Source documentation required and may include 
physician or clinic notes.) 
b. For the last chemotherapy course prior to being randomized in the study: 
i. 
Patients must have received a platinum-containing regimen for a minimum of 
4 cycles 
ii. 
Patients must have achieved a partial or complete tumor response 
iii. 
Following the last regimen, patients must have either 
1. CA-125 in the normal range OR 
2. CA-125 decrease by more than 90% during their last platinum regimen 
which is stable for at least 7 days (ie, no increase > 15%) 
iv. 
Following the last regimen, patients must not have any measurable lesion  
> 2 cm at the time of study entry 
c. Patients must be randomized within 8 weeks after completion of their final dose of 
the platinum-containing regimen. 
Note: The last platinum regimen does not necessarily have to immediately follow the next to last 
(penultimate) platinum regimen. For example, if a patient received a non-platinum regimen 
between the penultimate platinum regimen and last platinum regimen, they could be eligible, so 
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6. The patient agrees to complete PROs during study treatment and at 1 additional time 
point 8 weeks following study treatment discontinuation. It is estimated that completion 
of PROs will take less than 20 minutes at each time point. Since these are questionnaires, 
their completion will not interfere with, or preclude, future treatment or clinical studies 
7. Formalin fixed, paraffin-embedded archival tumor available from the primary or 
recurrent cancer required for all patients 
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 
9. Adequate organ function 
a. Absolute neutrophil count (ANC) ≥ 1,500/µL 
b. Platelets ≥ 100,000/µL 
c. Hemoglobin ≥ 9 g/dL 
d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 60 mL/min using Cockcroft-Gault equation 
e. Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN 
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN 
unless liver metastases are present, in which case they must be ≤ 5 x ULN 
10. Able to take oral medications 
11. Women of childbearing potential must use adequate birth control for the duration of 
study participation (Section 4.3) 
4.1.1. 
Additional Inclusion Criteria for Food Effect Sub-Study 
With the exception of inclusion criteria 2, 4, 5, 6, 7, and 8 (above), all main study inclusion 
criteria apply. In addition, the following inclusion criteria apply to the FE sub-study only: 
1. Entry criteria are broadened to include patients with ovarian cancer regardless of 
platinum sensitivity and burden of disease as long as no standard therapy exists or the 
patient has refused standard therapy. 
2. ECOG 0-2 
3. Must be able to eat a high fat meal and fast for 12 hours 
4.2. 
Exclusion Criteria 
Patients will not be deemed eligible for entry into this study if any of the following criteria are 
met: 
1. Drainage of ascites during last 2 cycles of last chemotherapy 
2. Palliative radiotherapy within 1 week encompassing > 20% of the bone marrow 
3. Persistent > Grade 2 toxicity from prior cancer therapy 
4. Symptomatic uncontrolled brain or leptomeningeal metastases. (To be considered 
“controlled”, central nervous system (CNS) disease must have undergone treatment [eg, 
radiation or chemotherapy] at least 1 month prior to study entry. The patient must not 
have any new or progressive signs or symptoms related to the CNS disease and must be 
taking a stable dose of steroids or no steroids.) A scan to confirm the absence of brain 

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metastases is not required. Patients with spinal cord compression may be considered if 
they have received definitive treatment for this and evidence of clinically stable disease 
(SD) for 28 days. 
5. Known hypersensitivity to the components of niraparib 
6. Major surgery within 3 weeks of starting the study or patient has not recovered from any 
effects of any major surgery 
7. Diagnosis, detection or treatment of invasive cancer other than ovarian cancer ≤ 2 years 
prior to randomization (except basal or squamous cell carcinoma of the skin that has been 
definitively treated) 
8. 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 90 days) 
myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord 
compression, superior vena cava syndrome, or any psychiatric disorder that prohibits 
obtaining informed consent. 
9. History or current evidence of any condition, therapy, or lab abnormality that might 
confound the results of the study, interfere with the patient’s participation for the full 
duration of the study treatment, or is not in the best interest of the patient to participate 
 
Patients must not have received a transfusion (platelets or red blood cells) within 4 
weeks of the first dose of study treatment 
10. Patient is pregnant or breast feeding, or expecting to conceive children within the 
projected duration of the study treatment 
11. Immunocompromised patients (Note: patients with splenectomy are allowed.) 
12. Patients with known active hepatic disease (ie, Hepatitis B or C) 
13. Prior treatment with a known PARP inhibitor 
14. Patients with a baseline QT prolongation > 470 milliseconds 
15. Patients are receiving concomitant medications that prolong QTc and are unable to 
discontinue use for the duration of the study (see Appendix 8 for a list) 
4.2.1. 
Additional Exclusion Criteria for Food Effect Sub-Study: 
With the exception of exclusion criteria 1 and 13 (above), all main study exclusion criteria apply. 
In addition, the following exclusion criteria apply to the FE sub-study only: 
1. Chemotherapy within 3 weeks of study start 
2. Patient taking a proton pump inhibitor, antacids, or H2 blocker within 48 hours of dose 
4.3. 
Restrictions During Study 
1. Patients of child bearing potential and their partners who are sexually active (exception: 
abstinence for the total duration of the trial, defined as the time from the patient’s signing 
of the main ICF through the drug washout period which is at least 90 days) must agree to 

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the use of 2 highly effective forms of contraception throughout their participation during 
the study treatment and for 90 days after last dose of study treatment(s): 
a. Condom with spermicide and 1 of the following: 
 Oral contraceptive or hormonal therapy (eg, hormone implants) 
 Placement of an intrauterine device (IUD) 
Acceptable non-hormonal birth control methods include: 
a. Total sexual abstinence for the total duration of the trial, defined as the time from the 
patient’s signing of the main ICF through the drug washout period. The washout 
period for niraparib is at least 90 days 
b. Vasectomised sexual partner plus male condom with spermicide and participant 
assurance that partner received post-vasectomy confirmation of azoospermia 
c. Tubal occlusion plus male condom with spermicide 
d. IUD plus male condom with spermicide 
Acceptable hormonal methods include: 
a. Etonogestrel implants (eg, Implanon, Norplan) plus male condom with spermicide 
b. Normal and low dose combined oral pills plus male condom with spermicide 
c. Norelgestromin/ethinyl estradiol transdermal system plus male condom with 
spermicide 
d. Intravaginal device plus male condom with spermicide (eg, ethinyl estradiol and 
etonogestrel) 
e. Cerazette (desogestrel) plus male condom with spermicide. Cerazette is currently the 
only highly efficacious progesterone-based pill 
2. No other anticancer therapy is permitted during the course of the study treatment for any 
patient (the patient can receive a stable dose of corticosteroids during the study as long as 
these were started at least 4 weeks prior to enrollment, as per exclusion criteria above). If 
the patient discontinues study treatment, this restriction no longer applies, however the 
patient will remain enrolled in the study for the purpose of collecting subsequent 
outcomes, including tolerance of subsequent anticancer treatments. Palliative 
radiotherapy is allowed for pre-existing small areas of painful metastases that cannot be 
managed with local or systemic analgesics as long as no evidence of disease progression 
is present 
3. Prophylactic cytokine (granulocyte colony-stimulating factor [GCSF]) administration 
should not be given in the first cycle of the study, but may be administered in subsequent 
cycles according to local guidelines 
4. An increased risk of infection by the administration of live virus and bacterial vaccines 
has been observed with conventional chemotherapy drugs. Effects with niraparib are 
unknown and therefore they should not be administered to patients in the study 
5. Patients participating in the FE sub-study are not permitted to take a proton pump 
inhibitor, antacids, or H2 blocker within 48 hours of dose (FE Days 1 and 8) 
6. Patients who are blood donors should not donate blood during the study and for 90 days 
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4.4. 
Patient Withdrawal and Replacement 
4.4.1. 
Discontinuation from Treatment 
Patients may be discontinued from treatment or from the study for the following reasons: 
 
Any treatment-related Common Terminology Criteria for Adverse Events (CTCAE) 
Grade 3 or 4 events that have not reverted to CTCAE Grade 1 or better within 
4 weeks (28 days) of dose interruption. At the Investigator’s discretion, following 
dose interruption (no longer than 28 days), patients may be considered for dose 
reductions, providing they have not already undergone the maximum number of 
2 dose reductions allowed. If upon re-challenging with study treatment at the lowest 
allowable dose, any CTCAE Grade 3 or 4 AEs recur, the patient must be discontinued 
 
If the platelet count has not reverted to > 100,000 within 4 weeks (28 days) of dose 
interruption, the patient should be discontinued 
 
Disease progression according to RECIST v.1.1 criteria or clinical criteria 
 
Risk to patients as judged by the Investigator and/or Sponsor 
 
Severe non-compliance with the protocol as judged by the Investigator and/or 
Sponsor 
 
Patient request 
 
The patient becomes pregnant 
Patients who are benefitting from treatment will have access to their assigned treatment as long 
as considered acceptable by their treating physician or until they are discontinued for one of the 
above reasons. 
4.4.2. 
Discontinuation from the Study 
Patients who discontinue from treatment will continue to receive follow-up assessments  as part 
of the study unless they are discontinued from the study by one of the following events: 
 
Withdrawal of consent by the patient, who is at any time free to discontinue their 
participation in the study, without prejudice to further treatment 
 
Death from any cause 
Patients who withdraw from the main study will not be replaced. In the FE sub-study, at the 
discretion of the Sponsor, replacement patients may be used. 
If a patient withdraws consent, the investigator must not access the patient’s medical record or 
other confidential records requiring the consent for purposes of the study unless the patient 
expressly agreed to continued collection of their disease history information until the end of the 
study. Study data related to the patient collected prior to the patient’s withdrawal from the study 
or loss to follow-up is permitted to be retained. The inclusion of information on survival status 
obtained from Investigator review of public records for those patients withdrawn or lost to 
follow-up is also permitted, dependent upon local regulations. 

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4.5. 
Planned Sample Size and Number of Study Centers 
The primary analysis of PFS will be based on 180 patients randomized in the gBRCAmut cohort 
and up to 310 patients randomized in the non-gBRCAmut cohort for a total of 490 patients. 
Enrollment is expected to occur over approximately 24 months for gBRCAmut and 20 months for 
non-gBRCAmut. An additional approximately 12 patients will be enrolled into the open-label, 
crossover, FE sub-study. Thus, a total of approximately 502 patients is the target for enrollment 
in this study. 
At selected sites in the US, a subset of approximately 36 patients will undergo intensive PK/ECG 
monitoring on Day 1 only; 24 of these patients will be enrolled from the main study and 
12 patients from the open-label FE sub-study. There will be approximately 100 centers 
worldwide. 
4.6. 
Patient Identification and Randomization 
4.6.1. 
Patient Identification 
All patients who enter into the Screening Period of the study (defined as the point at which the 
patient signs the main ICF) will receive a unique patient identification number. This number will 
be used to identify the patient throughout the study and must be used on all study documentation 
related to that patient. The patient identification number must remain constant throughout the 
entire study; it must not be changed at the time of enrollment or randomization. This number will 
not necessarily be the same as the randomization numbers for the study. 
4.6.2. 
Randomization Scheme 
For the main study, patients will be randomized (must occur within 72 hours prior to first dose) 
using a 2:1 allocation ratio to niraparib:placebo. A 2:1 allocation ratio is being used as it is 
believed it will improve recruitment. A separate randomization list will be created for each 
cohort. Stratification factors will include time to progression after the penultimate platinum 
therapy before study enrollment (6 to < 12 months and ≥ 12 months), use of bevacizumab in 
conjunction with the penultimate or last platinum regimen (yes/no), and best response during the 
last platinum regimen (CR and PR). 
Patients with Integrated BRACAnalysis® result will be assigned within a gBRCAmut cohort or a 
non-gBRCAmut cohort as per Table 2. 
For the FE sub-study (selected US sites only), patients will be randomized into 2 sequence 
groups (Group A or Group B) with 6 patients per group, 12 in total (Section 5.2). 
Each patient who completes the study screening assessments, meets all eligibility criteria, and is 
accepted for the main study will be assigned a unique identification number and will receive the 
corresponding treatment according to a randomization scheme generated by the interactive web 
response system (IWRS) vendor. The randomization schedule will be prepared by the IWRS 
vendor using a validated program. The IWRS will assign a randomization number to patients in 
the main study, which will be used to link the patient to a treatment group and will specify a 
unique medication number for the study drug to be dispensed to the patient. Randomized patients 
who terminate their study participation for any reason, regardless of whether study treatment was 
taken or not, will retain their randomization number. IWRS personnel not involved with any of 

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the protocol operations will prepare the randomization schedule. The subset of patients 
(approximately 24 enrolled from the main study at selected sites) who will undergo intensive 
PK/ECG testing on Day 1 will be selected at those sites. 
Patients in the FE sub-study will be randomized separately. 

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5. 
STUDY MEDICATION 
5.1. 
Identity 
Niraparib ([3S]-3-[4-{7-(aminocarbonyl)-2H-indazol-2-yl} phenyl] piperidine [tosylate 
monohydrate salt]) is an orally available, potent, highly selective PARP1/2 inhibitor. The 
excipients for niraparib are lactose monohydrate and magnesium stearate. 
5.2. 
Administration 
5.2.1. 
Main Study 
In the main study, niraparib 300 mg (3 x 100 mg niraparib capsules) or placebo (3 appearance-
matched capsules) will be administered orally QD continuously in a double-blind fashion. 
Patients will be instructed to take their dose at the same time of the day, preferably in the 
morning. Patients must swallow and not chew all capsules. The consumption of water is 
permissible. The first dose will be administered at the site. 
Dose interruption (no longer than 28 days) or dose reduction (no more than 2 dose reductions) 
will be allowed based on treatment side effects. Dose reductions to 2 capsules daily 
(200 mg/day) and subsequently to 1 capsule daily (100 mg/day) will be allowed. No further dose 
reductions will be allowed. The timing of efficacy or safety evaluations will not be affected by 
dose interruptions or reductions. 
5.2.2. 
Food Effect Sub-Study (Completed) 
In the open-label, crossover, FE sub-study, a single dose of niraparib 300 mg  
(3 x 100 mg niraparib capsules) will be administered orally on 2 separate occasions (FE Day 1 
and FE Day 8) as presented below: 
FE Day 1 
Group A 
3 x 100 mg capsules of niraparib administered orally with 240 mL of water 
following a minimum 10-hour overnight fast. Patients will continue to fast for at least 2 hours 
following the dose. 
Group B 
3 x 100 mg capsules of niraparib administered orally with 240 mL of water 
following a minimum 10-hour overnight fast. Patients will then consume a high fat meal. The dose 
of niraparib will be administered orally within 5 minutes of finishing the meal and they will resume 
fasting for at least 4 hours. 
FE Day 8 
Group A 
3 x 100 mg capsules of niraparib administered orally with 240 mL of water 
following a minimum 10-hour overnight fast. Patients will then consume a high fat meal. The dose 
of niraparib will be administered orally within 5 minutes of finishing the meal and they will resume 
fasting for at least 4 hours. 
Group B 
3 x 100 mg capsules of niraparib administered orally with 240 mL of water 
following a minimum 10-hour overnight fast. Patients will continue to fast for at least 2 hours 
following the dose. 

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A 7-day PK evaluation and washout period will occur between the 2 single dose administrations. 
Upon completion of the 14-day FE sub-study, participating patients will begin daily dosing with 
niraparib 300 mg, approximately 2 weeks after the start of the FE sub-study. These patients will 
be assessed for safety for the duration of the study and may continue until Investigator-
determined progression. 
5.3. 
Dose Modification 
Dose interruption and/or reduction may be implemented at any time for any grade toxicity 
considered intolerable by the patient. Treatment must be interrupted for any non-hematologic 
National Cancer Institute (NCI)-CTCAE (v.4.02) Grade 3 or 4 AE which the Investigator 
considers to be related to administration of niraparib or matching placebo. If toxicity is 
appropriately resolved to baseline or Grade 1 or less within 28 days, the patient may restart 
treatment with niraparib or matching placebo, but with a dose level reduction according to 
Table 3 if prophylaxis is not considered feasible. If the event recurs at similar or worse grade, 
treatment should be interrupted again and, upon resolution, a further dose reduction must be 
made. No more than 2 dose reductions will be permitted.  
Table 3: 
Dose Reductions for Non-Hematologic Toxicities 
Event1 
Dose2 
Initial dose 
300 mg QD 
1st dose reduction for NCI-CTCAE Grade 3 or 4 treatment-
related SAE/AE where prophylaxis is not considered 
feasible 
200 mg QD 
2nd dose reduction for NCI-CTCAE Grade 3 or 4 treatment-
related SAE/AE where prophylaxis is not considered 
feasible 
100 mg QD 
Continued NCI-CTCAE Grade 3 or 4 treatment-related 
SAE/AE ≥ 28 days 
Discontinue study medication 
Abbreviations: AE=adverse event; NCI-CTCAE=National Cancer Institute - Common Terminology Criteria for 
Adverse Events; QD=once daily; SAE=serious adverse events 
1 Dose interruption and/or reduction may be implemented at any time for any grade toxicity considered intolerable by 
the patient. 
2 Dose not to be decreased below 100 mg QD 
If the toxicity requiring dose interruption has not resolved completely or to NCI-CTCAE Grade 1 
during the maximum 4 week (28 day) dose interruption period, and/or the patient has already 
undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg QD), the patient 
must permanently discontinue treatment with niraparib or matching placebo. 
The dose interruption/modification criteria for hematologic parameters will be based on blood 
counts and are outlined in Table 4. 
Table 4: 
Dose Modification/Reduction for Hematologic Toxicities 
Finding 
Modification 
Platelet count 75,000-99,999/µL 
Study medications must be interrupted until 
platelet counts are ≥ 100,000/µL, with weekly 

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blood counts for CBC monitored until recovery. 
Study medication may then be resumed at same 
dose or reduced dose based on clinical 
judgment. 
2nd occurrence of platelet count 75,000-
99,999/µL 
Study medications must be interrupted until 
platelet counts are ≥ 100,000/µL, with weekly 
blood counts for CBC monitored until recovery. 
Study medication may then be resumed at a 
reduced dose. 
Platelet count < 75,000/µL* 
Study medications must be interrupted until 
platelet counts are ≥ 100,000/µL, with weekly 
blood counts for CBC monitored until recovery. 
Study medication may then be resumed at a 
reduced dose. 
Neutrophil < 1,000/µL 
Study medications must be interrupted until 
neutrophil counts ≥ 1,500/µL, with weekly 
blood counts for CBC monitored until recovery. 
Study medication may then be resumed at a 
reduced dose. 
Hemoglobin < 8 g/dL 
Study medications must be interrupted until 
hemoglobin is ≥ 9 g/dL, with weekly blood 
counts for CBC monitored until recovery. Study 
medication may then be resumed at a reduced 
dose. 
Abbreviation: CBC = complete blood cell count 
*For patients with platelet count ≤ 10,000/μL prophylactic platelet transfusion per guidelines may be considered.18 19 
For patients taking anticoagulation or antiplatelet drugs consider the risk/benefit of interrupting these drugs and/or 
prophylactic transfusion at an alternate threshold, such as ≤ 20,000/μL. 
If dose interruption or modification is required at any point on study because of hematologic 
toxicity, to ensure safety of the new dose, weekly blood draws for complete blood cell count (CBC) 
will be required for an additional 4 weeks after the AE has been resolved to the specified levels, 
after which monitoring every 4 weeks may resume. Weekly blood draws for CBC can be collected 
either at study site or local laboratories. If the hematologic toxicity has not recovered to the 
specified levels within 4 weeks (28 days) of the dose interruption period, and/or the patient has 
already undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg QD), the 
patient must permanently discontinue treatment with niraparib or matching placebo. 
Any patient requiring transfusion of platelets or red blood cells (1 or more units) or hematopoietic 
growth factor support must undergo a dose reduction upon recovery if study treatment is resumed. 
The patient must be referred to a hematologist for further evaluation (1) if transfusions are required 
on more than 1 occasion or (2) if the treatment-related hematologic toxicities have not recovered 
to CTCAE Grade 1 or less after 4 weeks. If a diagnosis of MDS/AML is confirmed by a 
hematologist, the patient must permanently discontinue study treatment. 
For major surgery while on treatment, up to 28 days of drug interruption is allowed. 
Once the dose of study treatment has been reduced, any re-escalation must be discussed with the 
medical monitor. 

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All dose interruptions and reductions (including any missed doses), and the reasons for the 
reductions/interruptions, are to be recorded in the electronic case report from (eCRF). 
5.4. 
Packaging, Labeling and Storage 
The study treatment will be packed in high-density polyethylene (HDPE) bottles with child-
resistant closures. The label text of the study treatment will comply with Good Manufacturing 
Practice and national legislation to meet the requirements of the participating countries. The study 
treatment will be labeled in a blinded fashion (niraparib or placebo capsules). 
Study treatment will be dispensed to patients on Cycle 1/Day 1 and every cycle (28 days) thereafter 
until the patient discontinues study treatment. 
For the approximate 12 FE sub-study patients, a single dose of 300 mg niraparib will be given each 
on FE Days 1 and 8. After the completion of the 14-day FE sub-study, participating patients will 
begin dosing with niraparib at 300 mg QD on Cycle 1/Day 1, approximately 2 weeks after the start 
of the FE sub-study. These patients will then receive a supply of open-label niraparib on Cycle 
1/Day 1 and then every cycle (28 days) thereafter until the patient discontinues study treatment. 
All study treatment supplies must be stored in accordance with the Pharmacy Manual instructions 
and package labeling. Until dispensed to the patients, the study treatment will be stored in a 
securely locked area, accessible to authorized personnel only. 
5.5. 
Blinding and Breaking the Blind 
The patient, Investigator, study coordinator(s), and the Sponsor study team and its representatives 
will be blinded to the identity of the assigned treatment in the main study from the time of 
randomization until database lock. Study treatment assignment will be available to the investigator 
upon request for post-study treatment planning. 
The identity of the treatments will be concealed by the use of study treatments that are all identical 
in packaging, labeling, and schedule of administration. 
Patients and investigators will not be unblinded to study treatment except in cases as determined 
necessary by the Investigator. The process for unblinding the identity of the assigned treatment is 
outlined in the Pharmacy Manual.  
After the blind is broken, the Investigator (or designee) must document the reason for breaking the 
blind on the appropriate eCRF page. Patients who require unblinding will be discontinued from 
study treatment permanently but will enter long-term follow-up including overall survival.   
5.6. 
Drug Accountability 
The Investigator or designee is responsible for maintaining accurate dispensing records of the 
study drug throughout the clinical study. The drug accountability log includes information 
including the enrollment number, amount dispensed, and amount returned to the pharmacy, if 
applicable. Product returned to the pharmacy will be stored under the same conditions as products 
not yet dispensed but will be marked as “returned” and kept separate from the products not yet 
dispensed. 

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All dispensing and accountability records will be available for Sponsor review. The study monitor 
will assume the responsibility to reconcile the drug accountability log. The pharmacist will 
dispense study drug for each patient according to the protocol and pharmacy manual, if applicable. 
5.7. 
Previous and Concomitant Medications 
Any medication the patient takes other than the study treatment, including herbal and other non-
traditional remedies, is considered a concomitant medication. All concomitant medications must 
be recorded in eCRF. The following information must be recorded in the eCRF for each 
concomitant medication: generic name, route of administration, start date, stop date, dosage, and 
indication. Any changes in the dosage or regimen of a concomitant medication must be recorded 
in the eCRF. 
At Screening, patients will be asked what medications they have taken during the last 30 days. At 
each subsequent study visit, patients will be asked what concomitant medications they are 
currently taking. Patients must not be receiving medications that prolong QTc at Screening and 
for the duration of the study (see Appendix 8). 
Niraparib has potential to induce cytochrome P450 (CYP)1A2; therefore, use caution with drugs 
metabolized by CYP1A2 (see Appendix 1). Niraparib is a substrate for P-glycoprotein; therefore, 
use caution with drugs that are inhibitors or substrates of P-glycoprotein. Niraparib safety profile 
includes thrombocytopenia; therefore, use caution with anticoagulation and antiplatelet drugs. 

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6. 
VARIABLES AND METHODS OF ASSESSMENT 
A schedule of procedures is provided in Table 7, Table 8, and Table 9 . 
6.1. 
Primary Efficacy: Progression Free Survival 
Determination of the date of progressive disease (PD) will be determined by central blinded 
review. This review will be based first, but not exclusively, on imaging assessment according to 
RECIST v.1.1 (Appendix 2, Table 5) criteria. Because of the pelvic location of the primary tumor 
and the frequent occurrence of peritoneal disease, imaging may not always be reliable for 
documentation of PD. 
Criteria other than RECIST may be applicable to define PD; thus, PD will be determined if at least 
1 of the following criteria is met: 
1. Tumor assessment by CT/MRI unequivocally shows PD according to RECIST v.1.1 
criteria (Appendix 2, Table 5) 
a. If a patient had a CT/MRI of the abdomen/pelvis and clinically indicated areas within 
the 28-day screening window before Cycle 1/Day 1 but prior to signing the main ICF, 
the patient is not required to complete an additional CT/MRI scan for study screening. 
CT/MRI scans completed during screening prior to signing the main ICF must have 
been performed and be able to be submitted per the image acquisition guidelines. 
2. Additional diagnostic tests (eg, histology/cytology, ultrasound techniques, endoscopy, 
positron emission tomography) identify new lesions or determine existing lesions qualify 
for unequivocal PD AND CA-125 progression according to Gynecologic Cancer 
Intergroup (GCIG)-criteria (below) 
3. Definitive clinical signs and symptoms of PD unrelated to non-malignant or iatrogenic 
causes ([1] intractable cancer-related pain; [2] malignant bowel obstruction/worsening 
dysfunction; or [3] unequivocal symptomatic worsening of ascites or pleural effusion) 
AND CA-125 progression according to GCIG criteria (below). 
PD will not be diagnosed in case of CA-125 progression in the absence of at least 1 of the criteria 
defined above. 
The investigator will describe why PD was diagnosed in the eCRF. The date of PD is defined as 
the earliest time point when one of the PD criteria is met. When required to determine progression, 
CA-125 levels should be evaluated ± 2 weeks from the primary PD assessments (ie, diagnostic test 
or 
clinical 
parameters) 
and 
must 
be 
confirmed 
by 
a 
second 
determination  
≥ 7 days later. In case assessments of CA-125 levels occur greater than 2 weeks from the primary 
PD assessments, the date of the primary assessment of PD will be used to define the date of PD. 
GCIG criteria for CA-125 progression are as follows: (Note: CA-125 progression alone will not 
be considered disease progression.) 
1. Patients with elevated CA-125 pretreatment and normalization of CA-125 must show 
evidence of CA-125 ≥ 2 x ULN on 2 occasions at least 1 week apart, OR 
2. Patients with elevated CA-125 pretreatment, which never normalizes must show evidence 
of CA-125 ≥ 2 x the nadir value on 2 occasions at least 1 week apart, OR 

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3. Patients with CA-125 in the normal range pretreatment must show evidence of  
CA-125 ≥ 2 x ULN on 2 occasions at least 1 week apart. 
If CT/MRI shows existing (baseline) lesions which only equivocally suggest PD and additional 
diagnostic tests are required to determine unequivocal PD, the official date of PD will be the date 
PD was unequivocally determined. Alternatively with new lesions (except ascites and effusions) 
that are initially equivocal that are later unequivocally determined, the date of progression will be 
the date the lesion was initially identified. Note: If the Investigator determines clinical PD, they 
can consult an imaging clinician prior to receiving results from the central reader. Pursuant to 
consultation with the clinician, the Investigator can keep the patient on study treatment as long as 
it is considered safe, or the Investigator can discontinue the patient. 
The central review process will be as follows: 
1. When the patient discontinues treatment and/or Investigator believes the patient has 
progressed, all imaging and supportive clinical data will be submitted for central review 
2. RECIST imaging assessment by 2 independent radiologists along with adjudicator, if 
necessary 
3. Central blinded clinician will review clinical information for determination of PD 
4. Notify site of central PD determination 
5. In the case where the Investigator determines PD (eg, RECIST PD), but central review 
does not determine PD, the patient may continue study treatment as long as it is considered 
safe and the patient continues to meet other treatment criteria. In any case, the patient 
should continue to undergo scheduled imaging until central PD is determined or subsequent 
therapy initiated 
Table 5: 
Determination of Overall Response per Central RECIST and Central Clinical 
Review 
Central RECIST Review 
Central Clinical Review 
Overall Response 
PD 
PD 
PD 
PD 
SD or improvement 
PD 
SD, PR, CR, NE 
PD 
PD 
SD, PR, CR, NE 
SD or improvement 
Per central RECIST 
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; RECIST = Response 
Evaluation Criteria in Solid Tumors; SD = stable disease 
6.1.1. 
Central Blinded Clinician Review 
The central blinded clinician will review clinical and radiographic data supporting clinical 
progression and will determine if the patient had protocol-defined clinical progression, and at 
which time points. The central blinded clinician will not provide an opinion on the presence or 
timing of radiographic progression. The central blinded clinician may not modify lesion selection 
performed by the independent radiologists. They may not select target lesions from clinical 
sources, even if no radiographic target lesions are present as determined by the independent 
radiologists. If lesions assessed by physical exam are documented by the investigator sites and the 

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assessments provided to the central blinded clinician, they will be assessed qualitatively and 
incorporated into the central blinded clinician’s assessment. 
6.1.2. 
Date of Progression 
For the purpose of the primary endpoint, the date of progression will be determined using 
information from radiology review, the central blinded clinician, and the Investigator at the site. 
For radiology progression date, the central review will be used. For clinical progression, both the 
central blinded clinician review and the Investigator review will be used. If the Investigator does 
not determine clinical PD, this cannot be overturned by the central blinded clinician determination 
of PD. Alternatively, an Investigator assessment of PD will be invalidated if it is not substantiated 
by central blinded clinician. The actual date of progression will be designated by either the 
radiology review or the Investigator; the central blinded clinician cannot specify the date of 
progression, he/she can only verify whether or not PD occurred at specified dates  
(± 7 days). For the purpose of determining the date of progression, Table 6 will be used. 
Table 6: 
Reference Table for Determining the Date of Progression 
Central Radiology 
Central 
Blinded 
Clinician 
Investigator 
Date of PD 
PD 
PD 
Clinical PD 
Earliest of Radiology 
and Investigator 
PD 
No PD 
Clinical PD 
Radiology 
PD 
PD 
Non-PD 
Radiology 
PD 
No PD 
Non-PD 
Radiology 
Non-PD 
PD 
Non-PD 
No PD 
Non-PD 
No PD 
Clinical PD 
No PD 
Non-PD 
PD 
Clinical PD 
Investigator 
Abbreviations:  PD = progressive disease 
6.2. 
Secondary Efficacy 
6.2.1. 
Concordance of BRCA Tests 
For each patient in the study, baseline blood samples will be prospectively collected and archived 
to support the possibility of bridging the centralized BRCA mutation test used in this study to a 
candidate companion BRACanalysis diagnostic test. Before any of these archived samples are 
assayed, the single candidate companion BRACanalysis diagnostic test will be specified. These 
archived samples will then be evaluated by that specific candidate companion diagnostic test in a 
laboratory that is blinded to treatment outcomes. The concordance of the candidate companion 
BRACanalysis diagnostic test and the centralized BRCA mutation test used in this study, with 
respect to identification of gBRCAmut patients, will be assessed. 

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 Date of progression 
6.2.5. 
PFS2 
PFS2 is defined as the time from treatment randomization to the earlier date of assessment of 
progression on the next anticancer therapy following study treatment or death by any cause. 
6.2.6. 
Time to First Subsequent Therapy (TFST) 
TFST is defined as the date of randomization in the current study to the start date of the first 
subsequent anticancer therapy. 
6.2.7. 
Time to Second Subsequent Therapy (TSST) 
TSST is defined as the date of randomization in the current study to the start date of the second 
subsequent anticancer therapy. 
6.2.8. 
Chemotherapy Free Interval 
CFI is defined as the time from last platinum dose until initiation of next anticancer therapy 
(excluding maintenance therapy). CFIs relative to CFI from prior chemotherapy regimens will be 
evaluated. Clinic notes may serve as source documentation. 
6.2.9. 
Overall Survival Time 
OS is defined as the time of randomization to the date of death by any cause. Following the 
treatment discontinuation visit, survival status will be collected for all patients using acceptable 
means including telephone contact. New malignancy information will also be collected as part of 
this assessment. 
6.2.10. 
Time to CA-125 Progression 
Time to CA-125 progression will be measured from time of randomization. CA-125 progression 
will be defined according to the following (Note: CA-125 progression alone will not be considered 
disease progression.): 
1. Patients with elevated CA-125 pretreatment and normalization of CA-125 during treatment 
with niraparib/placebo must show evidence of CA-125 ≥ 2 x ULN on 2 occasions at least 
1 week apart; OR 
2. Patients with elevated CA-125 pretreatment, which never normalizes must show evidence 
of CA-125 ≥ 2 x the nadir value on 2 occasions at least 1 week apart; OR 
3. Patients with CA-125 in the normal range pretreatment must show evidence of CA-125 ≥ 2  
x ULN on 2 occasions at least 1 week apart. 
CA-125 levels must be normal at screening or have a >90% decrease compared to baseline prior 
to their last platinum-based chemotherapy course. Abnormal CA-125 levels on-study do not 
represent disease progression; however, they may prompt imaging if clinically indicated. 

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6.3. 
Safety Variables 
6.3.1. 
Adverse Events 
6.3.1.1. 
Definitions 
An AE is any untoward medical occurrence that occurs in a patient or clinical investigation subject 
administered a pharmaceutical product, and which does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including clinically significant abnormal laboratory findings), symptom, or disease temporally 
associated with the use of an investigational product, whether or not considered related to the 
product. 
AEs may include the onset of new illness and the exacerbation of pre-existing medical conditions. 
An AE can include an undesirable medical condition occurring at any time, including baseline or 
washout periods, even if no study treatment has been administered. 
All AEs, including intercurrent illnesses, occurring from the time of signing the main ICF through 
study treatment discontinuation visit will be documented in the eCRF. Concomitant illnesses that 
existed before entry into the study will not be considered AEs unless they worsen during the 
treatment period. Pre-existing conditions will be recorded in the eCRF on the medical history or 
other appropriate page. 
All AEs, regardless of the source of identification (eg, physical examination, laboratory 
assessment, ECG, reported by patient), must be documented. 
A treatment-emergent AE (TEAE) will be defined as an AE that begins or that worsens in severity 
after at least 1 dose of study treatment has been administered. 
6.3.1.2. 
Assessment of Adverse Events 
Each AE will be assessed by the Investigator with regard to the following categories. 
6.3.1.2.1. Seriousness 
Serious adverse events (SAEs) will be collected from the time of signing the main ICF through 
treatment discontinuation. New SAEs (including deaths) will be collected for 30 days after 
treatment discontinuation. 
A serious AE (SAE) is defined as any untoward medical occurrence that at any dose: 
 
Results in death 
 
Is life-threatening 
 This means that the patient is at immediate risk of death at the time of the event; it 
does not mean that the event hypothetically might have caused death if it were 
more severe 
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
Results in persistent or significant disability or incapacity 
 
Is a congenital anomaly or birth defect 

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are protected by third party copyright laws and therefore have been excluded.

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drugs or chemicals cannot explain. The response to withdrawal of the treatment should 
be clinically plausible. 
 
Likely related:  A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to administration of the treatment, unlikely to be attributed 
to concurrent disease or other drugs or chemicals. 
 
Unlikely to be related:  A clinical event, including laboratory test abnormality, with a 
temporal relationship to treatment administration which makes a causal relationship 
improbable, or in which other drugs, chemicals or underlying disease provide likely 
explanations. 
 
Unrelated:  A clinical event, including laboratory test abnormality, with little or no 
temporal relationship with treatment administration. Typically explained by extraneous 
factors (eg, concomitant disease, environmental factors or other drugs or chemicals). 
6.3.1.3. 
Recording Adverse Events 
AEs and SAEs will be collected from the time of signing the main ICF through treatment 
discontinuation. New SAEs (including deaths) will be collected for 30 days after treatment 
discontinuation (see Table 7, Table 8, and Table 9 for schedules of events). SAEs assessed as 
related to the study medication will be reported through the end of the Post Study Treatment 
Assessments.  SAEs can also be reported, if in the assessment of the Investigator, the SAE is 
related to the study medication. 
AEs may be volunteered spontaneously by the patient or discovered by the study staff during 
physical examinations or by asking an open, non-leading question such as: “How have you been 
feeling since you were last asked?” All AEs and any required remedial action will be recorded. 
The nature of AE, date (and time, if known) of AE onset, date (and time, if known) of AE outcome 
to date, severity, and action taken of the AE will be documented together with the Investigator’s 
assessment of the seriousness of the AE and causal relationship to study drug and/or study 
procedure. 
All AEs should be recorded individually in the patient's own words (verbatim) unless, in the 
opinion of the Investigator, the AEs constitute components of a recognized condition, disease, or 
syndrome. In the latter case, the condition, disease, or syndrome should be named rather than each 
individual symptom. All AEs will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). 
6.3.1.4. 
Reporting Disease Progression 
The event of disease progression is an efficacy criterion and is therefore not considered an AE. If 
AEs/SAEs occur in relation to disease progression, the AEs/SAEs must be reported per AE/SAE 
reporting requirements described in Section 6.3.1.3 and Section 6.3.1.5, respectively. 
6.3.1.5. 
Reporting Serious Adverse Events 
The Investigator must report all SAEs and any follow up information to the Sponsor on an SAE 
Report Form within 24 hours of becoming aware of the initial event or additional information. The 
Investigator must provide a causality assessment and must sign and date all SAEs Report Forms. 

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SAE REPORTING CONTACT INFORMATION 
It is the responsibility of the Investigator to review source documentation and describe pertinent 
information on the SAE Report Form.  
After receipt of the initial report, the Sponsor (or designee) will review the information and, if 
necessary, contact the Investigator, to obtain further information for assessment of the event. 
If supporting documentation is requested (e.g., hospital reports, consultant reports, death 
certificates, autopsy reports, etc.), the Investigator should highlight all relevant and pertinent 
information within such documents, ensure that any patient's personal identifiers (including 
Medical Record number) are removed, and submit the documents with the SAE Form to the 
Sponsor. The Sponsor (or designee) will return a confirmation of receipt for all email reports (if 
received from other than a "no reply" domain) within 1 business day.  
The Investigator and the Sponsor (or Sponsor’s designated agent) will review each SAE report and 
the Sponsor/contract research organization (CRO) will evaluate the seriousness and the causal 
relationship of the event to study treatment. In addition, the Sponsor (or Sponsor’s designated 
agent) will evaluate the expectedness according to the reference document (Investigator Brochure 
or Summary of Product Characteristics). Based on the Investigator and Sponsor’s assessment of 
the event, this information will be reported to the relevant competent authorities and Ethics 
Committees as required by regulations. 
All SAEs will be recorded from signing of the main ICF until 30 days following study treatment 
discontinuation. SAEs occurring after this 30 day period and coming to the attention of the 
Investigator must be reported only if they are considered (in the opinion of the Investigator) 
causally related to study drug. 
6.3.1.6. 
Follow-up of Adverse Events 
All AEs and SAEs experienced by a patient, irrespective of the suspected causality, will be 
monitored until the AE or SAE has resolved, any abnormal laboratory values have returned to 
baseline or normalized, until there is a satisfactory explanation for the changes observed, until the 
patient is lost to follow-up, or until the patient has died. 
6.3.1.7. 
Suspected Unexpected Serious Adverse Reactions 
For any AE that is serious, associated with the use of the study treatment, and unexpected (as 
defined as not listed in the appropriate section of the current Investigator Brochure) additional 
reporting requirements are described below. These types of reports are referred to as suspected 
unexpected serious adverse reactions (SUSARs). 
 
If the SUSAR is fatal or life-threatening, associated with the use of the study treatment, 
and unexpected, Regulatory Authorities and Independent Ethics Committees (IECs) 
will be notified within 7 calendar days after the Sponsor or designee learns of the event. 
Additional follow-up (cause of death, autopsy report, and hospital report) information 
should be reported within an additional 8 days (15 days total). 
 
If the SUSAR is not fatal or life-threatening but is otherwise serious, associated with 
the use of the study treatment, and unexpected, Regulatory Authorities and IECs will 
be notified within 15 calendar days after the Sponsor or designee learns of the event. 

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The Sponsor or designee will notify the Investigators in a timely fashion of relevant information 
about SUSARs that could adversely affect the safety of patients. Follow-up information may be 
submitted if necessary.  
The Sponsor or designee will also provide updated safety information for the study to the 
Regulatory Authorities and IECs responsible for the study in the Development Safety Update 
Report (DSUR). Information on SUSARs and other relevant safety findings will be included in 
the DSUR. 
6.3.2. 
Pregnancy 
The Sponsor has a responsibility to monitor the outcome of all pregnancies reported during the 
clinical study.  
Each pregnancy must be reported by the Investigator to the Sponsor/CRO on an Initial Pregnancy 
Report Form within 24 hours of becoming aware of the pregnancy. Pregnancy is not an AE, and 
therefore does not need to be reported as such in the eCRF unless there is a suspicion that the study 
drug may have interfered with the effectiveness of a contraceptive medication.  
The investigator must follow up all pregnancies, document the course and the outcome, and report 
this information to the Sponsor on a Pregnancy Outcome Report Form within 24 hours of 
becoming aware - even if the patient was withdrawn from the study or the study has finished.   
Elective abortion without complications should not be regarded as an AE, however, it should be 
reported as the pregnancy outcome on the Pregnancy Outcome Report Form.  
Therapeutic abortions should be reported as a treatment procedure and the reason for the 
therapeutic abortion should be reported on the Pregnancy Outcome Report Form and as an AE in 
the eCRF.  
Any SAE that occurs during pregnancy must be recorded on the Pregnancy Outcome Report Form, 
reported as an SAE on the SAE Report Form (eg, maternal serious complications, therapeutic 
abortion, ectopic pregnancy, stillbirth, neonatal death, congenital anomaly, birth defect) and 
reported to the Sponsor within 24 hours. Hospitalization for normal delivery of a healthy newborn 
should not be considered an SAE. 
6.3.3. 
Overdose 
An overdose is defined as the accidental or intentional ingestion or infusing of any dose of study 
treatment that exceeds the dose described in the protocol. Overdoses are not considered AEs; 
however, all overdoses should be recorded on a Serious Adverse Event Form (Section 6.3.1.5, 
within 24 hours. An overdose should be reported even if it does not result in an AE. Overdoses do 
not need to be recorded on the CRF; dosing information is recorded on the CRF.  
6.3.4. 
Adverse Events of Special Interest 
Selected non-serious AEs and SAEs are also known as Adverse Events of Special Interest (AESI) 
and must be recorded as such on the eCRF and reported within 24 hours to the Sponsor as noted 
for SAEs in Section 6.3.1.5. AESIs must be reported to the Sponsor at any time the Investigator 
becomes aware of them.  
 MDS and AML 

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 Secondary primary cancers (other than MDS and AML) 
 Pneumonitis 
 Embryo-fetal toxicity 
 
6.3.5. 
Laboratory Variables 
The following laboratory variables will be determined in accordance with Table 7, Table 8, and 
Table 9: 
Complete Blood Cell Count (CBC): 
 
hemoglobin 
 
platelets 
 
mean platelet volume (MPV), optional (see Section 6.3.7) 
 
mean corpuscular volume (MCV) 
 
white blood cells (WBC) 
 
differential white cell count 
Coagulation Factors (not required during the Extended Visit Schedule): 
 
activated partial thromboplastin time (APTT) 
 
international normalized ratio (INR) 
Serum Chemistry assessments for safety include: 
 
sodium 
 
potassium 
 
calcium 
 
magnesium 
 
chloride 
 
glucose 
 
creatinine 
 
total bilirubin 
 
gamma glutamyl transferase (GGT) 
 
alkaline phosphatase (ALP) 
 
aspartate aminotransferase (AST) 
 
alanine aminotransferase (ALT) 
 
urea or blood urea nitrogen (BUN) 
 
total protein 

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 
albumin 
 
lactic dehydrogenase (LDH) 
 
amylase 
Urinalysis: 
 
specific gravity 
 
leukocyte esterase 
 
nitrite 
 
blood 
 
protein 
 
glucose 
 
ketones 
 
urobilinogen 
 
bilirubin 
These tests will be performed by the local laboratory at the clinical site or at the laboratory local 
to the patient home during the Extended Visit Schedule. 
In addition, serum CA-125 and serum pregnancy testing will be performed. 
Hematological testing may occur more frequently than is specified in Table 7, Table 8, or Table 9 
when additional testing is medically indicated per PI judgment. Additional tests may be performed 
at a laboratory facility other than the study site, but test results must be reported to the study site, 
the study site must keep a copy of test results with the patient’s study file, and the results must be 
entered into the electronic data capture system (EDC). 
For any suspected MDS/AML case reported while a patient is receiving treatment or being 
followed for post-treatment assessments, bone marrow aspirate and biopsy testing must be 
completed by a local hematologist. Testing completed as part of standard of care is sufficient as 
long as the methods are acceptable to the Sponsor's Medical Monitor. The study site must 
receive a copy of the hematologist's report of aspirate/biopsy findings (which must include a 
classification according to World Health Organization (WHO) criteria20) and other sample 
testing reports related to MDS/AML. Report data will be entered into EDC on the appropriate 
eCRF pages and the site must keep a copy of all reports with the patient’s study file. 
6.3.6. 
Physical Examination and Vital Signs 
Physical examinations and vital sign assessments will be performed in accordance with the 
schedule of events (Table 7, Table 8, and Table 9). 
Physical examinations will be performed (including vital signs: BP, pulse, and temperature) at the 
screening visit and as outlined in the study schedule. If a patient develops hypertension while on 
study medication, the hypertension should be medically managed with antihypertensive 
medications as well as adjustment of the niraparib dose, if necessary. 

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Weight will be measured according to the study schedule. Height will be measured at screening 
only. 
Performance status will be assessed using the ECOG scale (see Appendix 4) at screening and 
baseline and as outlined in the study schedules. The same observer should assess performance 
status each time. 
6.3.7. 
Additional Safety Assessments 
Standard 12-lead ECGs will be performed for patients in the main study in accordance with the 
procedures outlined in Table 7. In addition, at selected sites, a subset of patients (approximately 
36, including 24 enrolled in the main study and 12 enrolled in the FE sub-study) will undergo 
intensive ECG monitoring to coincide with PK on Day 1 (Table 7); for this intensive ECG 
monitoring subset, triplicate ECGs should be performed between 2-5 minutes apart and should be 
performed prior to blood draws for PK. Patients will be supine and rested for approximately 2 
minutes before ECGs are recorded. The average of each of the triplicate measures will be used for 
analysis. This subset of patients will undergo all other assessments in the main study. 
For patients participating in the FE sub-study (approximately 12 at selected sites), in addition to 
standard 12-lead ECGs (outlined in Table 8), triplicate ECGs will be performed on FE Days 1 and 
8 to coincide with PK assessments; ECG monitoring is to be completed prior to PK blood draws. 
Although MPV collection is optional (see Section 6.3.5), it is highly encouraged especially for 
patients with high grade thrombocytopenia. 
6.3.8. 
Concomitant Medication 
Previous (within the past month) and concomitant medication will be documented as described in 
Section 5.7. Medications will be coded using World Health Organization (WHO) Anatomical 
Therapeutic Chemical (ATC) classification. 
6.4. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics consist of those variables that are assessed at 
Screening/Baseline. 
6.4.1. 
Patient Eligibility 
Compliance with inclusion and exclusion criteria will be assessed as outlined in Sections 4.1 
and 4.2, respectively. 
6.4.2. 
Patient Demography 
Patient demography consists of: 
 
Age at screening 
 
Race 
 
Ethnicity 
 
Sex 

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6.4.3. 
Disease History 
For disease history the following will be documented: 
 
Date of first diagnosis 
 
Tumor type 
 
Stage at time of initial diagnosis 
 
Histology and grade of disease at diagnosis and most recent biopsy, if additional biopsy 
performed 
 
Date of start of first treatment 
 
Agents in first treatment 
 
Date of last dose of first treatment 
 
Dates of start of all subsequent treatments 
 
Agents in all subsequent treatments 
 
Dates of last dose of all subsequent treatments 
 
Best response for each prior treatment 
 
Date of recurrence for each treatment 
 
ECOG performance status 
 
Collection of hematologic events during prior therapy 
6.4.4. 
Medical and Surgical History 
Major medical and surgical history (including medication history) will be collected. Details of any 
prior invasive malignancy will be collected. Medical and surgical history will be obtained by 
interviewing the patient or by inspecting his/her medical records. 
6.5. 
Pharmacokinetics 
In the main study, blood samples for measurements of plasma levels of niraparib and the major 
metabolite M1  will be obtained on Cycle 1/Day 1 and on Cycle 2, Day 1 at the following time 
points: 0 (predose within 30 minutes) and 2 hours(± 15 minutes) post dose. In subsequent cycles, 
a blood sample for measurements of plasma levels of niraparib and the major metabolite M1 will 
be obtained on Cycle 4/Day 1 and Cycle 8/Day 1 predose (within 30 minutes) only. In addition, a 
subset of patients (approximately 36, including 24 patients enrolled in the main study and 12 
enrolled in the FE sub-study) at selected sites will undergo intensive PK evaluation on Day 1. In 
these patients blood samples for measurements of plasma levels of niraparib and the major 
metabolite M1 will be obtained within 30 minutes predose and at 1, 1.5, 2, 3, 4, 6, and 8 hours (± 
2 minutes for all time points) postdose. 
The time of last dose prior to PK blood draw should be recorded.  
Model predicted AUCs will be derived. Parameters of interest are AUC, Cmin, Cmax, CL/F and 
Vz/F, AUCss, Cmin,ss, Cmax,ss. For the FE sub-study (approximately 12 patients, selected sites), 
blood samples (1 x 5 mL) will be drawn predose (30 minutes prior to dosing) and at the 

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following time points after each of the two single doses (FE Days 1 and 8): 1, 1.5, 2, 3, 4, 6, 8, 
12, 24, 48, 72, 96, and 120 hours. Additional samples for PK will be collected predose and 
2 hours postdose on Day 1 of Cycles 1 and 2 and predose (only) on Cycle 4/Day 1 and 
Cycle 8/Day 1. The primary PK parameters for the food effect sub-study include the following: 
Cmax, AUC0-t, and AUC0-∞, tmax and t½. 
Complete instructions for collection, processing, shipping, and handling are detailed in the 
Laboratory Manual. 
6.6. 
Biomarkers 
A biomarker classifier of DNA repair will be evaluated in tumor samples.  

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7. 
STUDY CONDUCT 
7.1. 
Schedule of Procedures 
A schedule of events for the main study is provided in Table 7. A schedule of events for patients 
participating in the open-label FE sub-study is provided in Table 8. A schedule of events for the 
extended visit cycle for patients in the main study is provided in Table 9.

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Table 7 
Schedule of Events – Main Study 
Cycle1 
Screening 
1 
2 
Subsequent 
Cycles2 
Study Treatment 
Discontinuation (visit 
within 7 days of last 
dose) 
Post 
Treatment 
Assessments 
Day 
-28 to -1 
13 
8 
15 
21 
1 
Cycle n, Day 1 
 
 
Informed Consent4 
X 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical, surgical, cancer, medication 
history 
X 
 
 
 
 
 
 
 
 
Record local gBRCA mutation result, if 
done5 
X 
 
 
 
 
 
 
 
 
Blood sample for centralized gBRCA 
mutation testing 
X6 
 
 
 
 
 
 
 
 
Blood sample for DNA repair typing  
 
X 
 
 
 
 
 
 
 
Pregnancy test 
X7 
 
 
 
 
 
X7 
 
 
                                                 
Abbreviations:  C = Cycle; CA = cancer antigen; CBC =  complete blood cell count; CT = computed tomography; D = Day; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; eCRF = electronic case report form; EQ-5D-5L = European Quality of Life Scale, 5-Dimensions; FOSI = Functional 
Assessment of Cancer Therapy – Ovarian Symptom Index; gBRCA = germline BRCA; gBRCAmut = germline BRCA mutation; ICF = informed consent form; 
MRI = magnetic resonance imaging; PET = positron emission tomography; PK = pharmacokinetic(s); PRO = patient reported outcome; RECIST = Response 
Evaluation Criteria in Solid Tumors; SAE = serious adverse event. 
1 Treatment cycles are 28 days long, visits on Day 1 of each cycle unless otherwise specified. 
2 Visits continue every 4 weeks until study treatment discontinuation. 
3 C1/D1 is day of first dose. 
4 A separate ICF may be signed prior to the screening period for Myriad Integrated BRACAnalysis® testing in order to facilitate early testing. Depending on local 
site requirements, patients may sign a single study ICF prior to the screening period to facilitate early gBRCAmut testing only. All other study tests and 
procedures must be done in the screening window (Day -28 to Day -1). 
5 Local gBRCAmut results that had been performed previously should be entered into eCRF at screening. 
6 Centralized gBRCAmut testing of DNA by Integrated BRACAnalysis® at Myriad must be completed prior to randomization. The sample may be submitted prior 
to the screening period for patients who are identified for a Screening Visit to occur. DNA from this sample will be stored and may be used at a later time for 
biomarker testing including potential to bridging to candidate companion diagnostic assays. 
7 Negative serum pregnancy test required within 72 hours from first dose of study treatment for females of childbearing potential; repeated every 3 months for 
duration of study (ie, Cycle 4, Cycle 7, etc). 

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Cycle1 
Screening 
1 
2 
Subsequent 
Cycles2 
Study Treatment 
Discontinuation (visit 
within 7 days of last 
dose) 
Post 
Treatment 
Assessments 
Day 
-28 to -1 
13 
8 
15 
21 
1 
Cycle n, Day 1 
 
 
Randomization 
X8 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
X 
 
X 
X 
X 
 
Vital signs, height, 9 weight 
X 
X 
 
X 
 
X 
X 
X 
 
ECOG performance status 
X 
X 
 
 
 
X 
X 
X 
 
Adverse event monitoring 
X 
X 
 
X 
 
X 
X 
X10 
 
Concomitant medications 
X 
X 
 
X 
 
X 
X 
X 
 
Coagulation/serum chemistry 
X 
X11 
 
X 
 
X 
X 
X 
 
CBC12 
X 
X 
X 
X 
X 
X 
X 
X 
 
Serum CA-12513,14 
X 
X 
 
 
 
X 
X 
X 
 
Urinalysis15 
X 
 
 
 
 
 
 
 
 
12-lead ECG16 
X 
X 
 
 
 
X 
 
X 
                                                 
8 Randomization must occur within 72 hours prior to first dose. 
9 Height obtained at screening only. 
10 SAEs recorded up to 30 days after study treatment discontinuation. 
11 If Screening laboratory testing (serum chemistry, CBC, coagulation) performed within 72 hours of Day 1, repeat testing not required. 
12 If dose interruption or modification is required at any point on study because of hematologic toxicity, weekly blood draws for CBC will be monitored until the 
adverse event resolves, and to ensure safety of the new dose, weekly blood draws for CBC will be also be required for an additional 4 weeks after the adverse 
event has been resolved to the specified levels, after which monitoring every 4 weeks may resume. 
13 CA-125 levels must be normal at screening or > 90% decrease as compared with baseline prior to last platinum-based chemotherapy course. Abnormal 
CA-125 levels during study do not represent disease progression; however, they may prompt imaging if clinically indicated. CA-125 sample within 72 hours of 
dose on Cycle 1/Day 1. 
14 For determination of CA-125 progression, at least 2 CA-125 values at least 1 week apart are required for confirmation (Section 6.1). 
15 Urinalysis parameters must include: specific gravity, leukocyte esterase, nitrite, blood, protein, glucose, ketones, urobilinogen, and bilirubin. 
16 Patients will have a 12-lead ECG at Screening, Baseline (predose, within 30 minutes), 2 hours postdose on Day 1(within 30 minutes), Cycle 2/Day 1, (predose, 
2 hours postdose, within 30 minutes) and upon study treatment discontinuation. Note that the ECG is to be completed prior to the PK blood draw.  

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Cycle1 
Screening 
1 
2 
Subsequent 
Cycles2 
Study Treatment 
Discontinuation (visit 
within 7 days of last 
dose) 
Post 
Treatment 
Assessments 
Day 
-28 to -1 
13 
8 
15 
21 
1 
Cycle n, Day 1 
 
 
Triplicate ECGs (selected sites only) 
 
X17 
 
 
 
 
 
 
 
Tumor sample18 
X 
 
 
 
 
 
 
 
 
Blood sample for PK 
 
X19,20 
 
 
 
X 
X21 
 
 
Tumor Assessment (RECIST)22 
X 
 
 
 
 
 
X 
X 
X 
Chest CT/MRI23 
X 
 
 
 
 
 
 
 
 
FOSI, EQ-5D-5L, neuropathy 
questionnaire24 
X 
 
 
 
 
 
X 
X 
X 
                                                 
17 At selected sites, a subset of patients (approximately 24) will undergo triplicate ECG testing on Day 1 only at baseline (predose) and 1, 1.5, 2, 3, 4, 6 and 
8 hours postdose. Triplicate ECGs should be performed between 2-5 minutes apart and should be performed prior to blood draws for PK. 
18 Formalin fixed, paraffin-embedded tumor sample (primary or metastatic site) consisting of 100 micron thickness of sections (≥ 80 micron minimum) or 
unsectioned paraffin block. 
19 Blood samples for PK collected on Cycle 1/Day 1 and Cycle 2/Day 1 collected predose (within 30 minutes) and 2 hours postdose (within 30± 15 minutes Note:  
The exact time of the PK blood draw will be recorded and ECG monitoring is to be completed prior to the PK blood draw. 
20 At selected sites, a subset of patients (approximately 12) undergoing intensive PK on Day1 will have samples collected at baseline (within 30 minutes predose) 
and 1, 1.5, 2, 3, 4, 6 and 8 hours (± 2 minutes at all time points) postdose. Note:  The exact time of the PK blood draw will be recorded and the ECG monitoring 
is to be completed prior to the PK blood draw. 
21 Additional blood samples for PK on Cycle 4/Day 1 and Cycle 8/Day 1 will be collected at predose (trough) within 30 minutes only. 
22 RECIST tumor assessment via CT or MRI scan of abdomen/pelvis and clinically indicated areas required at baseline, then after every 2 cycles (ie, 8 weeks 
with a window of ± 7 days from date of visit) through Cycle 14 (56 weeks), then after every 6 cycles (24 weeks with a window of ± 7 days) until study 
treatment discontinuation; at this point, a final follow-up set of imaging is required. PET/CT may be used according to RECIST guidelines. Cycle timing will 
not be delayed for treatment interruptions, and tumor assessment should occur according to this schedule regardless of whether study treatment is interrupted. If 
a patient discontinues treatment for clinical progression and does not meet the criteria specified in the protocol, scans and CA-125 testing should continue at the 
specified intervals until progression is confirmed or until the start of subsequent anticancer treatment. 
23 Chest CT/MRI if not done as part of RECIST tumor assessment at Screening. If the chest CT/MRI is clear at screening, repeat chest imaging is not required in 
the absence of lesions to be followed or in the absence of clinical indication requiring follow‐up. 
24 PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) will be collected while on study treatment every 8 weeks through the first year, then every 12 weeks 
thereafter. If the patient discontinues study treatment, assessment will occur at that time and then 8 weeks (± 2 weeks) later, regardless of status of subsequent 
treatment. PROs should be administered before conducting any other procedures. 

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Cycle1 
Screening 
1 
2 
Subsequent 
Cycles2 
Study Treatment 
Discontinuation (visit 
within 7 days of last 
dose) 
Post 
Treatment 
Assessments 
Day 
-28 to -1 
13 
8 
15 
21 
1 
Cycle n, Day 1 
 
 
Study treatment dispensed/collected 
 
X 
 
 
 
X 
X 
X25 
 
Anti-cancer therapies assessment 
 
 
 
 
 
 
 
 
X26 
Survival assessment27 
 
 
 
 
 
 
 
 
X 
 Bone marrow aspirate and biopsy  
 
X28 
                                                 
25 No new capsules dispensed 
26 Every 90 days following study treatment discontinuation. 
27 In addition to survival, this assessment includes outcomes for subsequent anticancer therapies including any new malignancy information. 
28 For any suspected MDS/AML case reported while a patient is receiving treatment or being followed for post-treatment assessments, bone marrow aspirate and 
biopsy testing must be completed by a local hematologist. Testing completed as part of standard of care is sufficient as long as the methods are acceptable to 
the Sponsor’s Medical Monitor. The study site must receive a copy of the hematologist's report of aspirate/biopsy findings (which must include a classification 
according to WHO criteria20) and other sample testing results related to MDS/AML. 

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7.2. 
Procedures by Visit – Main Study 
Visits should occur within ± 3 days of the scheduled visit. All times should be recorded using the 
24-hour clock (eg, 23:20, not 11:20 PM). 
7.2.1. 
Screening (Visit 1, Day -28 to Day -1) 
At Screening, the following procedures/tests will be performed: 
 
Written informed consent 
 Based on local site requirements, the following ICF procedures are acceptable:  
o 
Two separate ICFs will be signed. An ICF for the Myriad Integrated 
BRACAnalysis® test will be signed before the blood sample is drawn, prior 
to randomization. A main ICF will be signed prior to any other screening 
procedures (Day -28 to Day -1). 
o 
A single study ICF will be signed before any study procedures 
 
Demographics 
 
Medical/surgical/medication history, including history of prior myelosuppression 
(thrombocytopenia, neutropenia, leukopenia, or anemia) within the 1 year prior to 
signing the main ICF 
 
Cancer history 
 
Blood sample for centralized gBRCA mutation testing sent to Myriad for immediate 
Integrated BRACAnalysis® testing. (Testing must be completed prior to randomization. 
The sample may be submitted at any time prior to the screening period if it appears that 
the patient is likely to meet other eligibility requirements). DNA from this sample will 
be stored and may be used at a later time for biomarker testing including potential to 
bridging to candidate companion diagnostic assays 
 
Ascertainment of any prior gBRCA mutation test results, if performed 
 
Serum pregnancy test (within 72 hours prior to first dose) (for females of child-bearing 
potential only) 
 
Randomization (within 72 hours prior to first dose) 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
Height 
 
ECOG performance status 
 
CBC 
 
Coagulation 
 
Serum chemistry 
 
Serum CA-125 

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 
Urinalysis (parameters must include: specific gravity, leukocyte esterase, nitrite, blood, 
protein, glucose, ketones, urobilinogen and bilirubin) 
 
12-lead ECG  
 
Formalin fixed paraffin-embedded tumor sections of 100 micron thickness (≥ 80 
micron minimum) or unsectioned paraffin block 
 
RECIST v.1.1 tumor assessment of the abdomen/pelvis and other areas (if clinically 
indicated) 
 
Chest CT/MRI if not done as part of RECIST tumor assessment. (If the chest CT/MRI 
is clear at screening, repeat chest imaging is not required in the absence of lesions to 
be followed or in the absence of clinical indication requiring follow‐up)  
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire). 
 Note that PROs should be administered before conducting any other procedures. 
 
AE monitoring 
 
Concomitant medications 
7.2.2. 
Cycle 1, Day 1  
 
Physical examination 
 
Vital signs (BP, pulse, temperature, and weight) 
 
ECOG performance status 
 
AEs 
 
Concomitant medications 
 
CBC (repeat testing not required if Screening testing was done within 72 hours of 
Day 1)  
 
Coagulation (repeat testing not required if Screening testing was done within 72 hours 
of Day 1) 
 
Serum chemistry (repeat testing not required if Screening testing was done within 
72 hours of Day 1) 
 
Serum CA-125 
 
12-lead ECG predose and 2 hours postdose (prior to blood draws for PK) 
 
Blood sample for PK determination (predose within 30 minutes and 2 hours  
± 15 minutes postdose); blood draws for PK are to be done after ECG monitoring and 
the exact time of the blood draw is to be recorded 
 
Blood sample for retrospective analysis of typing markers of DNA repair (eg, BRCA) 
 
For subset of patients (select sites), triplicate ECGs on Day 1 only at baseline (predose) 
and 1, 1.5, 2, 3, 4, 6 and 8 hours postdose 

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 
For subset of patients (select sites) undergoing intensive PK on Day 1, blood sample at 
baseline (within 30 minutes predose) and 1, 1.5, 2, 3, 4, 6 and 8 hours (± 2 minutes at 
all time points) postdose. 
 
Study treatment capsules dispensed; first dose administered at the site 
7.2.3. 
Cycle 1, Day 8 
 
CBC 
7.2.4. 
Cycle 1, Day 15 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
AEs 
 
Concomitant medications 
 
CBC 
 
Coagulation 
 
Serum chemistry 
7.2.5. 
Cycle 1, Day 21 
 
CBC  
7.2.6. 
Cycle 2, Day 1 
 
Physical examination 
 
AEs 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
Concomitant medications 
 
CBC 
 
Coagulation 
 
Serum chemistry 
 
Serum CA-125 
 
12-lead ECG predose and 2 hours postdose (prior to blood draws for PK) 
 
Blood sample for PK determination (predose within 30 minutes and 2 hours ± 15 
minutes postdose); blood draws for PK are to be done after ECG monitoring and the 
exact time of the blood draw is to be recorded. 
 
Study treatment capsules dispensed/collected, as appropriate 

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7.2.7. 
Day 1, Subsequent Cycles  
 
Physical examination 
 
AEs 
 
Vital Signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
Concomitant medications 
 
CBC 
 
Coagulation 
 
Serum chemistry 
 
Serum pregnancy test at 3 month intervals from screening (Cycles 4, 7, etc) 
 
Serum CA-125 
 
Blood sample for PK determination predose only (within 30 minutes) on Cycle 4/Day 1 
and Cycle 8/Day 1 only; the exact time of the PK blood draw will be recorded 
 
RECIST (v.1.1) tumor assessment of the abdomen/pelvis and other areas (if clinically 
indicated) after every 2 cycles through Cycle 14 and then after every 3 cycles 
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) every 2 cycles through Cycle 14, 
then after every 3 cycles. 
 Note that PROs should be administered before conducting any other procedures 
 
Study treatment capsules dispensed/collected, as appropriate 
7.2.8. 
Study Treatment Discontinuation (within 7 days of last dose) 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
AEs (SAEs recorded 30 days post study treatment discontinuation) 
 
Concomitant medications 
 
CBC 
 
Coagulation 
 
Serum chemistry 
 
Serum CA-125 
 
12-lead ECG 
 
RECIST (v.1.1) tumor assessment of the abdomen/pelvis and other areas (if clinically 
indicated) radiographic assessment will continue until progression in the study-
specified schedule for patients terminating study for reasons other than disease 
progression 

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 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) 
 Note that PROs should be administered before conducting any other procedures. 
 
Study treatment capsules collected 
7.2.9. 
Post Study Treatment Assessments (Study Visit Not Required) 
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) will be completed one additional 
time at 8 (± 2 weeks) weeks following the study treatment discontinuation visit. 
 Note that PROs should be administered before conducting any other procedures. 
 
Assessment of next subsequent anticancer therapies will be assessed every 90 days (± 
28days) following study treatment discontinuation visit. The following will be 
collected using source documentation: 
 Next anticancer therapy (name and/or class) 
 Date of start of subsequent therapies 
 Dose limiting toxicities 
 Best response (CR, PR, SD, PD) 
 Date of progression 
 
Survival status will be assessed every 90 days (± 28days) following study treatment 
discontinuation visit. New malignancy information will also be collected as part of this 
assessment. 
7.2.10. 
Unscheduled Assessments 
 
For any suspected MDS/AML case reported while a patient is receiving treatment or 
being followed for post-treatment assessments, bone marrow aspirate and biopsy 
testing must be completed by a local hematologist. Testing completed as part of 
standard of care is sufficient as long as the methods are acceptable to the Sponsor's 
Medical Monitor. The study site must receive a copy of the hematologist's report of 
aspirate/biopsy findings (which must include a classification according to WHO 
criteria20) and other sample testing results related to MDS/AML.

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Table 8 
Schedule of Events – Open-Label Food Effect Sub-Study (Study Completed) 
 
Screening 
14-Day Food 
Effect 
Cycle1 
Subsequent 
Cycles2 
Treatment Discontinuation  
(within 7 days of last dose) 
C1 
C2 
Day 
-28 to -1 
FE 1 
FE 8 
1 
15 
1 
Cycle n, Day 1 
 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical, cancer, surgical, medication history 
X 
 
 
 
 
 
 
 
Pregnancy test 
X3 
 
 
X3 
 
 
 
 
Randomization 
X4 
 
 
 
 
 
 
 
Study treatment dispensed/collected 
 
X5 
X5 
X 
 
X 
X 
X6 
Consumption of high fat meal, as applicable 
 
X 
X 
 
 
 
 
 
Physical examination 
X 
X 
 
X 
X 
X 
X 
X 
Vital signs, height7, weight 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
 
X 
X 
X 
Hematology/serum chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis8 
X 
 
 
 
 
 
 
 
12-lead ECG9 
X 
X10 
X10 
X 
 
X 
 
X 
Blood sample for PK11 
 
X 
X 
X 
 
X 
X 
 
                                                 
Abbreviations:  C = cycle; FE = food effect; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; PK = pharmacokinetic(s); QD  = once 
daily. 
1 Treatment cycles are 28 days long, visits on Day 1 of each cycle unless otherwise specified. 
2 Visits continue every 4 weeks until study treatment discontinuation. 
3 Negative serum pregnancy test required within 72 hours prior to study treatment for females of childbearing potential; repeated every 3 months for duration of 
study (ie, Cycle 4, Cycle 7, etc). 
4 Patients will be randomized in a crossover design within 72 hours prior to FE Day 1 (first single dose). 
5 Patients receive a single oral dose of niraparib 300 mg on FE Days 1 and 8. 
6 No new capsules dispensed. 
7 Height obtained at screening only. 
8 Urinalysis parameters must include: specific gravity, leukocyte esterase, nitrite, blood, protein, glucose, ketones, urobilinogen and bilirubin. 
9 12-lead ECG at Screening, Cycle 1/Day 1 (predose and 2 hours postdose), Cycle 2/Day 1 (predose and 2 hours postdose), and at treatment discontinuation. 
ECG monitoring is to be performed prior to PK blood draws. 
10 Triplicate ECG monitoring to coincide with PK on FE Days 1 and 8 at baseline (predose) and at 1, 1.5, 2, 3, 4, 6, and 8 hours post-dose. Triplicate ECGs 
should be performed between 2-5 minutes apart and should be performed prior to blood draws for PK. 
11 Blood samples for PK will be taken on FE Days 1 and 8 at baseline (within 30 minutes prior to dosing) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 
hours postdose. Additional blood samples will be collected predose and 2 hours postdose on Day 1 of Cycles 1 and 2 and predose only on Day 1 of Cycles 4 
and 8. The exact time of the PK blood draw will be recorded and PK blood draws are to be completed after ECG monitoring.  

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Table 8 
Schedule of Events – Open-Label Food Effect Sub-Study (Study Completed) (Continued) 
 
Screening 
14-Day Food 
Effect 
Cycle12 
Subsequent 
Cycles13 
Treatment Discontinuation  
(within 7 days of last dose) 
C1 
C2 
Day 
-28 to -1 
FE 1 
FE 8 
1 
15 
1 
Cycle n, Day 1 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X14 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Bone marrow aspirate and biopsy  
 
X15 
Note: Patients in food effect sub-study will receive a single oral dose of niraparib 300 mg on FE Days 1 and 8. Upon completion of the 14-day sub-study, patients 
will then start open-label treatment with daily niraparib (300 mg QD) on Day 1/Cycle 1 (approximately 2 weeks after start of food effect sub-study) and will be 
followed using the main study visit schedule for safety. 
                                                 
Abbreviations:  C = cycle; FE = food effect; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; PK = pharmacokinetic(s); QD  = once 
daily. 
12 Treatment cycles are 28 days long, visits on Day 1 of each cycle unless otherwise specified. 
13 Visits continue every 4 weeks until study treatment discontinuation. 
14 SAEs recorded up to 30 days after study treatment discontinuation. 
15 For any suspected MDS/AML case reported while a patient is receiving treatment or being followed for post-treatment assessments, bone marrow aspirate and 
biopsy testing must be completed by a local hematologist. Testing completed as part of standard of care is sufficient as long as the methods are acceptable to 
the Sponsor’s Medical Monitor. The study site must receive a copy of the hematologist's report of aspirate/biopsy findings (which must include a classification 
according to WHO criteria20) and other sample testing results related to MDS/AML. 

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7.3. 
Procedures by Visit – Food Effect Study 
Visits should occur at the scheduled visit day. All times should be recorded using the 24-hour 
clock (eg, 23:20, not 11:20 PM). 
7.3.1. 
Screening (Visit 1, Day -28 to Day -1) 
At Screening, the following procedures/tests will be performed: 
 
Written informed consent 
 
Demographics 
 
Medical/surgical/medication history 
 
Cancer history 
 
Serum pregnancy test (within 72 hours prior to first dose) 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
Height 
 
ECOG performance status 
 
Hematology  
 
Serum chemistry 
 
Urinalysis (parameters must include: specific gravity, leukocyte esterase, nitrite, blood, 
protein, glucose, ketones, urobilinogen and bilirubin) 
 
12-lead ECG 
 
AE monitoring 
 
Concomitant medications 
7.3.2. 
Food Effect, Day 1 
 
Randomization (within 72 hours prior to first dose) 
 
Consumption of high fat meal within 30 minutes, as applicable 
 
Physical examination 
 
Vital signs (BP, pulse, temperature, and weight) 
 
ECOG performance status 
 
AEs 
 
Concomitant medications 
 
Hematology  
 
Serum chemistry 

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 
Triplicate ECGs (prior to blood draws for PK) predose and at 1, 1.5, 2, 3, 4, 6, and 
8 hours post-dose (2-5 minutes between ECGs) 
 
Blood samples for PK determination at baseline (predose within 30 minutes) and at 1, 
1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; blood draws for PK are to 
be done after ECG monitoring and the exact time of the blood draw is to be recorded 
 
Study treatment capsules dispensed and doses administered at site 
7.3.3. 
Food Effect, Day 8 
 
Consumption of high fat meal within 30 minutes, as applicable 
 
Physical examination 
 
ECOG performance status 
 
Vital signs (BP, pulse, temperature) and weight 
 
Hematology 
 
Serum chemistry 
 
Triplicate ECGs (prior to blood draws for PK) predose and at 1, 1.5, 2, 3, 4, 6, and 
8 hours post-dose (2-5 minutes between ECGs) 
 
Blood samples for PK determination at baseline (predose within 30 minutes) and at 1, 
1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose; blood draws for PK are to 
be done after ECG monitoring and the exact time of the blood draw is to be recorded 
 
AEs 
 
Concomitant medications 
 
Study treatment capsules dispensed and doses administered at site 
7.3.4. 
Cycle 1, Day 1 (Approximately 2 Weeks After Start of Food Effect Sub-Study) 
 
Physical examination 
 
ECOG performance status 
 
Vital signs (BP, pulse, temperature) and weight 
 
AEs 
 
Concomitant medications 
 
Hematology 
 
Serum chemistry 
 
12-lead ECG predose and 2 hours postdose (prior to blood draws for PK) 
 
Blood sample for PK determination (predose within 30 minutes and 2 hours postdose); 
blood draws for PK are to be done after ECG monitoring and the exact time of the 
blood draw is to be recorded. 
 
Study treatment capsules dispensed and first dose administered at site 

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7.3.5. 
Cycle 1, Day 15  
 
Physical examination 
 
Vital signs 
 
AEs 
 
Concomitant medications 
 
Hematology 
 
Serum chemistry 
7.3.6. 
Cycle 2, Day 1 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
AEs 
 
Concomitant medications 
 
Hematology 
 
Serum chemistry 
 
12-lead ECG predose and 2 hours postdose (prior to blood draws for PK) 
 
Blood sample for PK determination (predose within 30 minutes and 2 hours postdose); 
the exact time of the PK blood draw is to be recorded and is to be done following ECG 
monitoring 
 
Study treatment capsules dispensed/collected 
7.3.7. 
Day 1, Subsequent Cycles  
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
Hematology 
 
Serum chemistry 
 
Serum pregnancy test at 3 month intervals from screening (Cycle 4, 7, etc) 
 
Blood sample for PK determination at predose (within 30 minutes) on Cycle 4/Day 1 
and Cycle 8/Day 1 only; the exact time of the PK blood draw is to be recorded 
 
AEs 
 
Concomitant medications 
 
Study treatment capsules dispensed/collected, as appropriate 

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7.3.8. 
Study Treatment Discontinuation (Within 7 Days of Last Dose) 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG 
 
AEs 
 
Concomitant medications 
 
Hematology 
 
Serum chemistry 
 
12-lead ECG 
 
Study treatment capsules collected 
7.3.9. 
Unscheduled Assessments 
 
For any suspected MDS/AML case reported while a patient is receiving treatment or 
being followed for post-treatment assessments, bone marrow aspirate and biopsy 
testing must be completed by a local hematologist. Testing completed as part of 
standard of care is sufficient as long as the methods are acceptable to the Sponsor's 
Medical Monitor. The study site must receive a copy of the hematologist's report of 
aspirate/biopsy findings (which must include a classification according to WHO 
criteria20) and other sample testing results related to MDS/AML. 

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Table 9: 
Schedule of Events – Main Study –Extended Visit Cycle 
Cycle 
Subsequent 
Cycles1 
 
Subsequent 
Cycles2 
 
Subsequent 
Cycles3 
Study Treatment 
Discontinuation (visit 
within 7 days of last dose) 
Post-Treatment 
Assessments 
Day 
Extended Cycle, 
Day 1 
Cycle n, Day 1 
Cycle n,  
Day 1 
 
 
Location 
In Clinic 
Site Staff 
Telephone 
Contact to Patient 
Patient Visit to 
Local Clinic or  
In-Home Nursing 
In Clinic 
 
Physical examination 
X 
 
 
X 
 
Vital signs, weight 
X 
 
X4 
X 
 
ECOG performance status 
X 
X 
 
X 
 
Adverse event monitoring 
X 
X 
 
X5 
 
Concomitant medications 
X 
X 
 
X 
 
Serum chemistry 
X 
 
X 
X 
 
CBC6 
X 
 
X 
X 
 
Serum CA-1257,8 
X 
 
X 
X 
 
12-lead ECG9 
 
 
 
X 
Tumor Assessment (RECIST)10 
X 
 
 
X 
X 
FOSI, EQ-5D-5L, neuropathy 
questionnaire11 
X 
 
 
X 
X 
Study treatment dispensed/collected 
X 
 
X 
X12 
 
Anticancer therapies assessment 
 
 
 
 
X13 
Survival assessment14 
 
 
 
 
X 
Bone marrow aspirate and biopsy  
X15 
 
                                                 
1 During the in-clinic visit extended cycle, all study procedures and assessments required will be performed. 
2 The study coordinator will contact the patient by telephone to obtain information for the ECOG performance status, adverse event monitoring, and concomitant 
medications when the study assessments are not performed in clinic. 
3 The collection of blood samples for CBC and chemistry analysis, vital signs and weight may be collected during visit to local clinic or at in-home nursing visit 
when the study assessments are not performed in clinic.  

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7.4. 
Procedures by Visit – Main Study Extended Visit Cycles 
Visits should occur within ± 3 days of the scheduled visit. All times should be recorded using the 
24-hour clock (eg, 23:20, not 11:20 PM). 
7.4.1. 
Day 1, Subsequent Cycles  
The following study assessments will be performed during the patient visit to local 
clinic or in-home nursing visit: 
 
Vital Signs (BP, pulse, temperature) and weight 
 
CBC 
 
Serum chemistry  
 
Serum CA-125 
 
Study treatment capsules dispensed/collected, as appropriate 
The following study assessments will be performed during the study coordinator telephone 
contact to patient: 
 
AEs 
 
Concomitant medications 
 
ECOG performance status 
7.4.2. 
Day 1, Extended Cycles (every three cycles, 84 days) 
The following study assessments will be performed during the patient visit to the study 
site: 
 
Physical examination 
 
AEs 
 
Vital Signs (BP, pulse, temperature) and weight (only measured during in-clinic visits) 
 
ECOG performance status 
 
Concomitant medications 
 
CBC 
 
Serum chemistry 
 
Serum CA-125 
 
RECIST (v.1.1) tumor assessment of the abdomen/pelvis and other areas (if clinically 
indicated) after every 2 cycles through Cycle 14 and then after every 3 cycles 
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) every 3 cycles. 
 Note that PROs should be administered before conducting any other procedures 
 
Study treatment capsules dispensed/collected, as appropriate 

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7.4.3. 
Study Treatment Discontinuation (within 7 days of last dose) 
 
Physical examination 
 
Vital signs (BP, pulse, temperature) and weight 
 
ECOG performance status 
 
AEs (SAEs recorded 30 days post study treatment discontinuation) 
 
Concomitant medications 
 
CBC 
 
Serum chemistry 
 
Serum CA-125 
 
12-lead ECG 
 
RECIST (v.1.1) tumor assessment of the abdomen/pelvis and other areas (if clinically 
indicated) radiographic assessment will continue until progression in the study-
specified schedule for patients terminating study for reasons other than disease 
progression 
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) 
 Note that PROs should be administered before conducting any other procedures. 
 
Study treatment capsules collected 
7.4.4. 
Post Study Treatment Assessments (Study Visit Not Required) 
 
PROs (FOSI, EQ-5D-5L, neuropathy questionnaire) will be completed one additional 
time at 8 (± 2 weeks) weeks following the study treatment discontinuation visit. 
 Note that PROs should be administered before conducting any other assessments. 
 
Assessment of next subsequent anticancer therapies will be assessed every 90 days (± 
28 days) following study treatment discontinuation visit. The following will be 
collected using source documentation: 
 Next anticancer therapy (name and/or class) 
 Date of start of subsequent therapies 
 Dose limiting toxicities 
 Best response (CR, PR, SD, PD) 
 Date of progression 
 
Survival status will be assessed every 90 days (± 28 days) following study treatment 
discontinuation visit. New malignancy information will also be collected as part of 
this assessment. 

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7.4.5. 
Unscheduled Assessments 
 
For any suspected MDS/AML case reported while a patient is receiving treatment or 
being followed for post-treatment assessments, bone marrow aspirate and biopsy 
testing must be completed by a local hematologist. Testing completed as part of 
standard of care is sufficient as long as the methods are acceptable to the Sponsor's 
Medical Monitor. The study site must receive a copy of the hematologist's report of 
aspirate/biopsy findings (which must include a classification according to WHO 
criteria) and other sample testing results related to MDS/AML.  

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8. 
STATISTICAL METHODS 
Details of the statistical analyses presented below will be provided in the study’s SAP. A change 
to the data analysis methods described in the protocol will require a protocol amendment only if it 
alters a principal feature of the protocol. The SAP will be finalized prior to database lock. Any 
changes to the methods described in the plan will be described and justified in the final clinical 
study report (CSR). The descriptive and analytical statistics outlined in this section will be applied 
separately and independently to the efficacy data generated within each of the 2 study cohorts 
unless otherwise indicated; demographic and safety data will be presented for each cohort 
separately as well as combined. Specification of which analyses and summaries will be performed 
separately for the gBRCAmut and non-gBRCAmut cohorts (HRD+ and full, if necessary) will be 
provided in the SAP. 
8.1. 
Study Populations 
The intent-to-treat (ITT) population will be defined as all patients randomized into the main study 
(not FE study). The ITT population is the primary analysis population for the efficacy analysis. 
For this analysis, patients will be analyzed as randomized. 
Efficacy will also be analyzed using a per-protocol (PP) population. The PP population will consist 
of all patients randomized in the main study who do not have protocol deviations that may 
significantly impact the interpretation of efficacy results. A detailed specification of the PP 
population will be provided in the SAP. Patients will be analyzed according to the treatment they 
actually receive. 
The safety population includes all patients who received at least 1 dose of study medication. The 
safety population will be the primary analysis population for the safety analyses. Patients will be 
analyzed as treated. 
8.2. 
Demographics, Medical History, Baseline Characteristics, and 
Concomitant Medications 
Descriptive statistics will be used to summarize demographics and baseline characteristics. 
Medical history, medications used prior to treatment, and concomitant medications will be 
summarized by treatment group. 
8.3. 
Efficacy Analyses 
Primary analyses of efficacy endpoints are described below. Supportive analyses, including any 
sensitivity analyses that may be performed are detailed in the SAP. 
8.3.1. 
Primary Efficacy Parameter 
The primary endpoint is PFS, which is defined as the time from the date of treatment randomization 
to the date of first documentation of progression (by blinded central review) or death by any cause 
in the absence of documented progression whichever occurs first. For the primary analysis, PFS 
data will be censored according to Table 10 . 

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Table 10: 
Censoring Rules for Primary PFS Analysis 
Situation 
Date of Censoring 
No baseline radiologic assessment 
Date of randomization 
No post-baseline radiologic assessment (and no 
death or clinical  progression prior to first 
scheduled radiologic assessment) 
Date of randomization.  
No progression or death on study 
Date of last radiologic assessment 
Documented progression or death after two or 
more 
consecutive 
missing 
radiologic 
assessments 
Date of last radiologic assessment 
New anticancer therapy started prior to 
progression 
Date of last radiologic assessment prior to 
new anticancer therapy 
Within each cohort, the overall family-wise error rate will be controlled at a 1-sided alpha of 0.025. 
Within the non-gBRCAmut cohort, PFS will be hierarchically evaluated first in the HRD+ subgroup 
(somatic BRCAmut and HRD positive/BRCAwt) and then in all non-gBRCAmut patients. If the 
treatment effect is significant in the non-gBRCAmut HRD+ subgroup, then PFS will be tested in the 
full non-gBRCAmut cohort. The overall 1-sided alpha level for both tests in the non-gBRCAmut 
cohort will be 0.025. 
HRD classification HRD+ (gBRCAmut, somatic BRCAmut and HRD positive/BRCAwt) or HRD- 
will be based on results from tissue testing. Details of this testing are provided in the SAP. 
The primary PFS analysis will be performed using a 1-sided log-rank test, stratified for time to 
progression from penultimate platinum therapy before study enrollment, use of bevacizumab in 
conjunction with the penultimate or last platinum regimen and best response during the last 
platinum regimen (CR and PR). In addition, a stratified Cox proportional hazards models will be 
used to estimate the treatment HR and its 95% confidence interval (CI). PFS will also be 
descriptively summarized using Kaplan-Meier methodology. 
Subgroups will also be explored for the primary efficacy endpoint based on: age, race, geographic 
region, time to progression after the penultimate platinum therapy before study enrollment, use of 
bevacizumab in conjunction with the penultimate or last platinum regimen, best response during 
the last platinum regimen (CR and PR), concomitant chemotherapy with platinum in the last and 
penultimate regimens (yes, no), and the number of prior platinum regimens (2, >2). 
8.3.2. 
Secondary Endpoints Analyses 
Concordance of a candidate companion BRACanalysis diagnostic test with the centralized BRCA 
mutation test used in this study with respect to identifying gBRCAmut patients may be evaluated 
using archived study samples. If evaluated, the sensitivity and specificity of a candidate companion 
BRACanalysis test to the centralized test with respect to gBRCA status will be determined along 
with the corresponding 95% CI. 

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Concordance of the companion HRD and BRACanalysis diagnostic tests may also be evaluated as 
described in the SAP. 
The FOSI, the EQ-5D-5L, and a neuropathy questionnaire will be used in this study. Changes from 
baseline in overall score, sub-scores, and individual items will be analyzed descriptively by 
treatment group. A repeated measures model adjusting for covariates and subject evaluating 
change in symptoms and  QoL as measured by the FOSI and the EQ-5D-5L will be conducted. 
Time to symptom worsening on the FOSI will be analyzed using time-to-event methodology. 
PFS2, OS, CFI, and time to CA-125 progression will be analyzed using a stratified log-rank test. 
The stratified Cox proportional hazards models will be used to estimate the treatment HR and its 
95% CI. In addition, Kaplan-Meier methodology will be used to descriptively summarize the data. 
8.4. 
Safety Analyses 
Safety and tolerability of niraparib relative to placebo will be analyzed separately for the 
gBRCAmut, non-gBRCAmut, and FE cohorts as well as overall. Incidence of TEAEs and usage of 
concomitant medications will be summarized by treatment group. Clinical laboratory parameters, 
vital signs, and ECG parameters will be summarized by treatment group and by study visits. 
Descriptive summary statistics for observed values as well as changes from baseline will be 
presented. In addition, thresholds of marked abnormalities will be predefined for specific safety 
parameters. Incidence of marked abnormalities and shift tables will be presented. 
8.5. 
Post-Treatment Analyses 
Descriptive summary statistics will be used to summarize post-treatment data (ie, subsequent 
anticancer therapy and any new malignancy). 
8.6. 
Food Effect Analyses 
The effect of a high fat meal on the PK of niraparib will be estimated by point estimates and 90% 
CI for the ratios of geometric means for niraparib Cmax, AUC0-t, and AUC0-∞. For each of the PK 
parameters, a general linear model will be used to account for the following sources of variation: 
sequence, patient nested in sequences, period, and treatment (fasted/fed). Cmax and AUC will be 
log-transformed prior to analysis. 
8.7. 
QTc Analyses 
Descriptive statistics and categorical analyses of ECG variables will be provided for the subset of 
patients (approximately 36) with intensive ECG collection. 
A separate population PK analysis plan will be written to describe the analyses of ECG variables 
and PK parameters. 
8.8. 
Interim Analyses 
An interim analysis will not be performed for this study. 
8.9. 
Determination of Sample Size 
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H0: PFS(t)placebo = PFS(t)niraparib 
Ha: PFS(t)placebo < PFS(t)niraparib 
where PFS(t) represents the progression free survivorship function at time, t. 
The gBRCAmut and non-gBRCAmut cohorts are treated as 2 independent cohorts/studies where 
each cohort is allocated 1-sided alpha = 0.025. Each cohort will have a separate randomization 
and the primary PFS analysis will be performed separately for each cohort. It is anticipated a 
priori that niraparib will have a positive effect in each cohort. The gBRCAmut cohort is 
conservatively powered by assuming an HR of 0.5, to ensure a robust dataset to address the PFS 
endpoint and ensure adequate data to monitor safety and OS. The sample size assumptions are 
primarily based on a Phase 2 study of maintenance therapy in 265 patients with relapsed, 
platinum sensitive ovarian cancer where daily olaparib therapy compared to placebo treatment 
was associated with a PFS benefit (HR = 0.35).14 The subset of patients with known gBRCAmut 
(approximately 22% of the patients) had a PFS HR = 0.18.15 
The gBRCAmut cohort sample size is determined based on the assumption that niraparib will 
result in an improvement in median PFS of 4.8 to 9.6 months (corresponding to a HR = 0.50) 
(niraparib relative to placebo). For a true HR = 0.50, 100 PFS events in the gBRCA cohort, to 
maintain 90% power assuming a 2:1 randomization (1-sided alpha=0.025). It is assumed that 180 
gBCRAmut patients will be enrolled over approximately 24 months. 
The non-gBCRAmut sample size was determined to maintain consistency with the intended 
hierarchical testing procedure under the assumption that approximately 40% of the non-
gBRCAmut cohort is expected to be classified as HRD+. PFS sample size for the HRD+ subgroup 
(somatic BRCAmut and HRD positive/BRCAwt) is determined based on the same PFS assumption 
used for the gBRCAmut cohort. For a true HR = 0.50, based on a median PFS of 9.6 months for 
the niraparib-treated patients and 4.8 months for placebo patients, in the non-gBRCAmut cohort 
who are HRD+, 98 PFS events will provide 90% power assuming a 2:1 randomization (1-sided 
alpha = 0.025). A total of approximately 310 patients will be enrolled into the non-gBRCAmut 
cohort in order to obtain a sufficient number of events in the HRD+ subset (somatic BRCAmut 
and HRD positive/BRCAwt). 
In addition, approximately 12 patients will be enrolled into the open-label food effect sub-study. 
At least 10 fully evaluable patients (defined as completing both the fasted and fed portion) are 
targeted to appropriately test for comparison between the fasted and fed states. If the number of 
evaluable patients falls below 10, replacement patients may be used at the discretion of the 
Sponsor. This is a descriptive sub-study and no formal sample size calculations were performed. 

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9. 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS 
9.1. 
Data Quality Assurance 
The Sponsor or its designee will conduct a study initiation visit to verify the qualifications of the 
Investigator, inspect the facilities, and inform the Investigator of responsibilities and procedures 
for ensuring adequate and correct documentation. 
The Investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertinent to the clinical study for each study participant. Frequent communication 
between the clinical site and the Sponsor is essential to ensure that the safety of the study is 
monitored adequately. The Investigator will make all appropriate safety assessments on an 
ongoing basis. The Sponsor’s Medical Monitor may review safety information as it becomes 
available throughout the study. 
All aspects of the study will be carefully monitored with respect to Good Clinical Practices 
(GCP) and standard operating procedures (SOPs) for compliance with applicable government 
regulations. The Study Monitor will be an authorized individual designated by the Sponsor. The 
Study Monitor will have access to all records necessary to ensure integrity of the data and will 
periodically review the progress of the study with the Investigator or designee. 
9.2. 
Access to Source Data/Documents 
An electronic data capture system to manage data collection will be utilized during this trial. The 
electronic data capture system is a software tool designed to ensure quality assurance and 
facilitate data capture during clinical trials. The system is fully Code of Federal Regulations 
(CFR) 21 part 11 compliant. 
The Investigator will ensure the accuracy, completeness, and timeliness of the data reported to 
the Sponsor. Data collection processes and procedures will be reviewed and validated to ensure 
completeness, accuracy, reliability, and consistency. A complete audit trail will be maintained of 
all data changes. The Investigator or designee will cooperate with the Sponsor’s representative(s) 
for the periodic review of study documents to ensure the accuracy and completeness of the data 
capture system at each scheduled monitoring visit. 
Electronic consistency checks and manual review will be used to identify any errors or 
inconsistencies in the data. This information will be provided to the respective study sites by 
means of electronic or manual queries. 
The Investigator or designee will prepare and maintain adequate and accurate study documents 
(medical records, ECGs, AE reporting, and concomitant medication reporting, raw data 
collection forms, etc) designed to record all observations and other pertinent data for each patient 
receiving study treatment. 
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the Institutional Review Board (IRB) to have direct access to all 
documents pertaining to the study. 

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9.3. 
Archiving Study Documents  
Essential clinical documents will be maintained to demonstrate the validity of the study and the 
integrity of the data collected. Master files should be established at the beginning of the study, 
maintained for the duration of the study, and retained according to the appropriate regulations. 
According to International Conference on Harmonization (ICH) guidelines, essential documents 
should be retained for a minimum of 2 years after the last approval of a marketing application in 
an ICH region and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years have elapsed since the formal discontinuation of clinical development 
of the study treatment. 
9.4. 
Good Clinical Practice 
This study will be conducted in accordance with ICH GCP and the Declaration of Helsinki 
(Version 2008). The clinical study will also be carried out in keeping with national and local 
regulatory requirement(s). 
9.5. 
Informed Consent 
Before each patient is enrolled in the clinical study, written informed consent will be obtained 
from the patient according to the regulatory and legal requirements of the participating country. 
As part of this procedure, the Investigator must explain orally and in writing the nature, duration, 
and purpose of the study, and the action of the study treatment in such a manner that the patient 
is aware of the potential risks, inconveniences, or AEs that may occur. The patient should be 
informed that he/she is free to withdraw from the study at any time. The patient will receive all 
information that is required by regulatory authorities and ICH guidelines. The Investigator or 
designee will provide the Sponsor with a copy of the IRB/IEC-approved ICF prior to the start of 
the study. 
The ICF must be signed and dated; 1 copy will be given to the patient and the Investigator will 
retain 1 copy as part of the clinical study records. The Investigator will not undertake any 
investigation specifically required for the clinical study until written consent has been obtained. 
The terms of the consent and when it was obtained must also be documented. 
If a protocol amendment is required, then the ICF may need to be revised to reflect the changes 
to the protocol. If the ICF is revised, it must be reviewed and approved by the responsible 
IRB/IEC, and signed by all patients subsequently enrolled in the clinical study as well as those 
currently enrolled in the clinical study. 
9.6. 
Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents will be approved 
by the responsible IRB/IEC/Competent Authorities, in accordance with local legal requirements. 
The Sponsor must ensure that all ethical and legal requirements have been met before the first 
patient is enrolled in the study. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC/Competent Authority 
approval prior to implementation (if appropriate). In the US: Following approval, the protocol 
amendment(s) will be submitted to the IND under which the study is being conducted. 

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Administrative changes (not affecting the patient benefit/risk ratio) may be made without the 
need for a formal amendment. All amendments will be distributed to all protocol recipients with 
appropriate instructions. 
9.7. 
Independent Data Monitoring Committee 
An IDMC will be established to provide independent review and assessment of the efficacy and 
safety data in a systematic manner and to safeguard the interest and safety of the participating 
patients in the study. The composition of the IDMC will consist of 3 independent individuals, 
including 1 biostatistician and 2 physicians. The IDMC is tasked with making a recommendation 
to the Sponsor based on their review to continue or stop the trial based on their assessment of 
efficacy and safety information. 
9.8. 
Study Monitoring 
Monitoring and auditing procedures approved by the Sponsor will be followed, in order to 
comply with GCP guidelines. On-site checking of the CRFs for completeness and clarity, cross-
checking with source documents, and clarification of administrative matters will be performed. 
The study will be monitored by the Sponsor or its designee. Monitoring will be done by personal 
visits from a representative of the Sponsor (site monitor) who will review the CRFs and source 
documents. The site monitor will ensure that the investigation is conducted according to protocol 
design and regulatory requirements by frequent site visits and by communications (letter, 
telephone, and fax). 
All unused study treatment and other study materials will be returned to the Sponsor after the 
clinical phase of the study has been completed. 
9.9. 
Audits and Inspections 
Responsible IRB/IEC/Competent Authorities and/or the Sponsor's clinical quality assurance 
group, or its designee, may request access to all source documents, CRFs, and other study 
documentation for on-site audit or inspection. Direct access to these documents must be 
guaranteed by the Investigator, who must provide support at all times for these activities. 
9.10. 
Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the Declaration of 
Helsinki (Version 2008). The IRB/IEC will review all appropriate study documentation in order 
to safeguard the rights, safety and well-being of the patients. The study will only be conducted at 
sites where IRB/IEC approval has been obtained. The protocol, Investigator Brochure, ICF, 
advertisements (if applicable), written information given to the patients, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB/IEC by the 
Investigator. 
9.11. 
Publication Policy 
Information regarding publication of study results is contained in the Steering Committee 
Charter. 

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10. 
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Conner-Spady B, Cumming C, Nabholtz JM, Jacobs P, Stewart D. Responsiveness of the EuroQol in breast 
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Popova T, Manie E, Rieunier G, et al. Ploidy and large-scale genomic instability consistently identify 
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Timms K, Reid J, Abkevich V, Neff C, Morris B, Potter J. Association between BRCA1/2 status and DNA-
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Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in 
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Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA 
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Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or 
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Kummar S, Ji J, Morgan R, et al. A phase I study of veliparib in combination with metronomic 
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Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed 
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Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive 
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CDER. Guidance for Industry, Food-Effect Bioavailability and, Fed Bioequivalence Studies. 2002. 
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Mukhopadhyay A, Plummer ER, Elattar A, et al. Clinicopathological features of homologous 
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Slichter SJ. Evidence-based platelet transfusion guidelines. 2007:172-178. 
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Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) 
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CDER. Guidance for Industry, Drug Interaction Studies. 2012. 
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Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 
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Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative 
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pharmacotherapy. 2013;47(10):1330-1341. 
 

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APPENDIX 1. DRUGS KNOWN TO INHIBIT OR INDUCE CYP1A2 
Inhibitors of CYP1A2 
Strong 
≥ 5-fold increase in 
AUC or >80% decrease 
in CL 
Moderate 
≥ 2-fold but < 5-fold increase in AUC or 
50% to 80% decrease in CL 
Weak 
≥ 1.25-fold but < 2-fold increase in 
AUC or 20% to 50% decrease in CL 
Ciprofloxacin, 
enoxacin, fluvoxamine 
methoxsalen, mexiletine, oral 
contraceptives, phenylpropanolamine, 
thiabendazole, vemurafenib, zileuton 
acyclovir, allopurinol, caffeine, 
cimetidine, daidzein, disulfiram, 
echinacea, famotidine, norfloxacin, 
propafenone, propranolol, terbinafine, 
ticlopidine, verapamil 
Inducers of CY1A2 
Strong 
80% decrease in AUC 
Moderate 
50% to 80% decrease in AUC 
Weak 
20% to 50% decrease in AUC 
 
Montelukast, phenytoin, smokers vs non-
smokers 
moricizine, omeprazole, phenobarbital 
Substrates of CYP1A2 
Sensitive substrates1 
Substrates with narrow therapeutic 
range2 
Alosetron, caffeine, duloxetine, melatonin, ramelteon, tacrine, 
tizanidine  
Theophylline, tizanidine, Warfarin 
Abbreviations: AUC=area under the curve; CL=clearance; CYP=Cytochrome P450 
1 Sensitive CYP substrates refers to drugs whose plasma AUC values have been shown to increase 5-fold or higher 
when co-administered with a known CYP inhibitor or AUC ratio in poor metabolizers vs extensive metabolizers is 
greater than 5-fold. 
2 CYP substrates with narrow therapeutic range refers to drugs whose exposure-response relationship indicates that 
small increases in their exposure levels by the concomitant use of CYP inhibitors may lead to serious safety 
concerns (eg, Torsades de Pointes). 
Source:  21 

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APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS V.1.1 
Response Criteria by RECIST v.1.1 22 
Evaluation of Target Lesions 
Complete Response (CR):   Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR):  At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters 
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 
on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm. (Note:  the appearance of one or more new lesions is also considered 
progressions). 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study 
Evaluation of Non-Target Lesions 
Complete Response (CR):   Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10 mm short axis) 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for a patient 
to be considered in complete clinical response. 
Non-CR/Non-PD: 
  Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits. 
Progressive Disease (PD): 
  Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally trump 
target lesion status. It must be representative of overall disease status change, not a single lesion 
increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating 
physician should prevail in such circumstances, and the progression status should be confirmed at 
a later time by the review panel (or Principal Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started). The patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria. 

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Table 11: 
For Patients with Measurable Disease (ie, Target Disease) 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-PD/not 
evaluated 
No 
PR 
SD 
Non-CR/Non-PD/not 
evaluated 
No 
SD 
documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** 
Only for non-randomized trials with response as primary endpoint. 
*** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease 
progression. 
Note: 
Patients with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic deterioration.”  
Every effort should be made to document the objective progression even after discontinuation of 
treatment. 
Table 12: 
For Patients with Non-Measurable Disease (ie, Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as an 
endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is 
not advised 

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Duration of Response 
Duration of overall response:  The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented. 
Duration of SD:  SD is measured from the start of the treatment until the criteria for progression 
are met, taking as reference the smallest measurements recorded since the treatment started, 
including the baseline measurements. 

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APPENDIX 3. COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS (CTCAE) V.4.02 
http://www.acrin.org/Portals/0/Administration/Regulatory/CTCAE_4.02_2009-09-
15_QuickReference_5x7.pdf 

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APPENDIX 6. SAMPLE EUROPEAN QUALITY OF LIFE SCALE, 5-
DIMENSIONS (EQ-5D-5L) 

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APPENDIX 8. DRUGS ASSOCIATED WITH QT PROLONGATION AND 
TORSADES DE POINTES 
Antiarrhythmics Antimicrobials 
Antidepressants Antipsychotics 
Others 
(including 
Selected 
Antiemetics) 
Amiodarone 
Sotalol 
Quinidine 
Procainamide 
Dofetilide 
Ibutilide 
Levofloxacin 
Ciprofloxacin 
Gatifloxacin 
Moxifloxacin 
Clarithromycin 
Erythromycin 
Ketoconazole* 
Itraconazole 
Amitriptyline 
Doxepin 
 
Haloperidol 
Droperidol 
Quetiapine 
Thioridazine 
Ziprasidone 
Cisapride 
Sumatriptan 
Zolmitriptan 
Arsenic 
Dolasetron 
Methadone 
 
*Topical use only allowed for ketoconazole 
Sources: 24,25