Clinical trial NCT03326193
Conditions: Ovarian Neoplasms
Keywords: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor Ovarian Cancer Primary Peritoneal carcinoma Fallopian Tube Vascular endothelial growth factor (VEGF) inhibitor Bevacizumab Niraparib
Sponsor: Tesaro, Inc.
Start date: 2017-12-12; Completion date: 2024-07-12
Enrollment: 105 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Niraparib is an oral inhibitor of poly adenosine diphosphate-ribose polymerase (PARP)-1 and PARP-2. This study will evaluate safety and efficacy of niraparib combined with bevacizumab as maintenance treatment in participants with advanced (stage IIIB-IV) ovarian cancer, fallopian tube cancer, or primary peritoneal cancer following front-line platinum-based chemotherapy with bevacizumab. Eligible participants who achieve complete response (CR), partial response (PR), or no evidence of disease (NED) following treatment with platinum-based chemotherapy in addition to bevacizumab will be enrolled in the study and will receive maintenance treatment with niraparib (for up to 3 years) combined with bevacizumab (for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of the approximately 5 months of bevacizumab received with chemotherapy) or until disease progression, unacceptable toxicity, participant withdrawal, Investigator's decision, or death, whichever comes first. Participants who have not progressed after 3 years of niraparib maintenance treatment may continue with niraparib beyond 3 years if they are benefiting from treatment, upon consultation with Sponsor.

Detailed description:

Arms: arm 1: Participants will be administered bevacizumab 15 milligram per kilogram (mg/kg) via a 30 minute (min) intravenous (IV) infusion on Day 1 of each 21-day cycle. Niraparib will be administered orally once a day continuously throughout each 21-day cycle (84-day cycle after amendment 2). On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab infusion. The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count.
Interventions: intervention 1: Niraparib intervention 2: Bevacizumab
Intervention descriptions: intervention 1: Niraparib will be administered orally once a day continuously throughout each 21 day cycle (84-day cycle after amendment 2). The starting dose of niraparib will be based on the participant's Baseline actual body weight or platelet count. Participants with a Baseline actual body weight of greater than equal to (\>=) 77 kg and Baseline platelet count of \>=150,000/ microliter (μL) will take 300 mg/day (3X100mg) at each dose administration. Participants with a Baseline actual body weight of less than (\<) 77 kg and/or Baseline platelet count of \<150,000/μL will take 200 mg (2X100 mg) at each dose administration. intervention 2: Maintenance bevacizumab 15 mg/kg will be administered via a 30-minute IV infusion on Day 1 of every 21-day cycle in the absence of progressive disease (PD), unacceptable toxicity, participant withdrawal, Investigator's decision, or death. Bevacizumab will be administered for up to 10 months during the maintenance phase or up to a total of 15 months inclusive of approximately 5 months of bevacizumab received with chemotherapy.

Protocol documents:
Prot_002.pdf: 
TITLE PAGE 
 
NIRAPARIB (GSK3985771); BEVACIZUMAB 
3000-02-004/GSK 213358 
A PHASE 2, SINGLE-ARM, OPEN-LABEL STUDY TO 
EVALUATE THE SAFETY AND EFFICACY OF NIRAPARIB 
COMBINED WITH BEVACIZUMAB AS MAINTENANCE 
TREATMENT IN PATIENTS WITH ADVANCED OVARIAN 
CANCER, FALLOPIAN TUBE CANCER, OR PRIMARY 
PERITONEAL CANCER FOLLOWING FRONT-LINE 
PLATINUM-BASED CHEMOTHERAPY WITH BEVACIZUMAB 
Sponsor: 
TESARO, Inc. 
1000 Winter Street, Suite 3300 
Waltham, MA 02451 
+1 339 970 0900 
TESARO UK, Limited 
55 Baker Street 
London W1U7EU 
United Kingdom 
+44 1753 910398 
Medical Monitor: 
MD, PhD; FACOG 
Clinical Research 
Organization: 
Not applicable 
IND No.: 
100,996 
EudraCT No.: 
2017-003738-10 
NCT No. 
03326193 
Development Phase: 
2 
Date of Original Protocol: 
08 September 2017 
Date of Amendment 1: 
05 December 2017 
Date of Amendment 2: 
21 Apr 2022 
Version of Protocol: 
03 
Confidentiality Statement 
All information contained in this document is privileged and confidential to TESARO. Any 
distribution, copying, or disclosure is strictly prohibited without prior written approval by 
TESARO. 
PPD
PPD


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INVESTIGATOR’S AGREEMENT 
I have received and read the Investigator’s Brochure for niraparib.  I have read the 3000-02-
004/GSK 213358 protocol and agree to conduct the study as outlined.  I agree to maintain the 
confidentiality of all information received or developed in connection with this protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 
 


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Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Protocol Amendment 02 
21 Apr 2022 
TMF-14428002 
Protocol Amendment 01 
05 December 2017 
TMF-11848774 
Original Protocol 
08 September 2017 
TMF-13835520 
 
Amendment 02  21 Apr 2022 
Where this Protocol Amendment applies: 
Protocol Amendment 02 applies to all sites. 
Overall Rationale for Amendment 02:  
The protocol has been amended to incorporate program revisions and/or updates as well as to 
provide clarifications and/or remove discrepancies. 
A description and rationale for each change is provided in the following table. 
 
 


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Section # and Name 
Description of Change 
Brief Rationale 
Throughout 
Study Number changed from TESARO (3000-02-
004) to (GSK 213358) 
Administrative change 
Medical Monitor name and contact details 
updated 
Administrative change 
Updated the tumor assessment to every 24 weeks 
+/- 14 days instead of +/- 7 days 
Updated to increase the allowable 
time frame. 
Patients who continue to derive benefit from 
study treatment based on continuation of non-
progression indicated by imaging, remain 
clinically stable, and are willing to continue study 
visits and assessments may continue to receive 
niraparib beyond 3 years following consultation 
with the Investigator and the medical monitor. 
Updated to include the option for 
participation of patient beyond 3 
years 
Headers and cover page were updated with new 
document number and amendment information; 
Protocol Amendment Summary of Changes 
section was updated to include rationale for this 
amendment; editorial revisions for consistency 
with Sponsor’s ways of working and to add 
clarification and/or remove discrepancies 
Editorial changes to align with 
the Sponsor’s standard protocol 
template and ways of working 
and for accuracy, clarity, 
conformity, flow, and 
typographical error correction 
Summary of changes 
table 
Updated the list of changes per template 
Alignment per process/template 
Synopsis 
Updated the ‘first patient first visit’ date  
Updated per latest data 
Updated the study design schema 
Updated to include the option for 
participation of patient beyond 3 
years. 
Study conduct updated with “Only one set of 
imaging is required showing unequivocal disease 
progression while on study treatment and/or prior 
to beginning follow-up therapy.” 
Updated to clarify that only one 
set of imaging declaring 
progressive disease is required 
instead of additional 
confirmational imaging. 
Event of pneumonitis and embryo-fetal toxicity 
removed from niraparib adverse events of special 
interest (AESIs). 
Updated to reflect new safety 
data. There are no additional 
pharmacovigilance activities for  
pneumonitis and embryo-fetal 
toxicity associated with niraparib.  
Transition from 21-day cycles to 84-day cycles. 
Updated to inform patients and 
Investigator of transition from 21-
day cycles to 84-day cycles which 
reduces patients visits from every 
3 weeks to every 12 weeks. 
Added information on possibility of continuing 
treatment after the study is terminated. 
Added to inform patients and 
Investigators of the possibility of 
continuing treatment. 


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Section # and Name 
Description of Change 
Brief Rationale 
3.3. Background of 
Bevacizumab 
Added current regulatory approval status for 
Bevacizumab in the US as a front-line treatment 
in adult patients with advanced ovarian cancer. 
Updated to reflect current 
regulatory approval status. 
3.4. Disease 
Background and 
Current Treatment 
Options 
Added text ‘At the time of study initiation’ for 
background information 
To clarify language 
5.1. Overall Study 
Design 
Updated the study schema 
Updated to include the option for 
participation of patient beyond 3 
years. 
Overall Survival guidance language updated to 
add clarity 
Overall survival language 
updated per latest guidance to add 
clarity. 
5.4. Dose Adjustment 
Criteria 
Updated niraparib dose modifications criteria for 
hematologic adverse reactions by addition of 
myelodysplastic syndrome (MDS)/ acute myeloid 
leukemia (AML) 
Updated to reflect current safety 
language. 
Section 5.5. Criteria for 
Study Termination 
Information added on possibility of continuing 
treatment after the study is terminated  
Added to inform patients and 
Investigators of the possibility of 
continuing treatment. 
Table 6. Schedule of 
Events 
Survival assessment (telephone assessment 
allowed) 
Added to align with latest overall 
survival guidance. 
Footnote updated for Treatment cycles which are 
for 21 days with “until the implementation of 
protocol amendment 2 at which time cycles will 
be 84-days” 
Updated to inform patients and 
Investigator of transition from 21-
day cycles to 84-day cycles which 
reduces patients visits from every 
3 weeks to every 12 weeks. 
6.3.1. Discontinuation 
from Treatment 
Overall survival wordings updated as per latest 
guidance 
Overall survival language 
updated per latest guidance to add 
clarity. 
6.3.3. 
Withdrawal of 
Consent 
Updated language for ‘withdrawal of consent’ in 
line with latest template guidance 
Updated for alignment with 
sponsor template guidance. 
6.3.3.1. Further 
Research Maintaining 
Confidential Patient 
Information 
Details added to include a possibility of Sponsor 
conducting further research on specimens 
collected during the study. 
Added to include an option of 
using patient’s biological samples 
for research that is not within the 
scope of the current trial. 
6.4. Loss to Follow Up 
Section added to include overall survival 
language per latest guidance 
Overall survival language 
updated per latest guidance to add 
clarity. 
8.5.1. Niraparib 
Administration 
Clarified niraparib administration after 
implementation of amendment 2. 
Updated to inform patients and 
Investigator of transition from 21-
day cycles to 84-day cycles which 
reduces patients visits from every 
3 weeks to every 12 weeks. 


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Section # and Name 
Description of Change 
Brief Rationale 
9.2.4. Patient Reported 
Outcome - Functional 
Assessment of Cancer 
Therapy–Ovarian 
Symptom Index 
Added detail on PROs - “If a  patient is unable to 
attend a study visit when a Functional 
Assessment of Cancer Therapy-Ovarian 
Symptom Index (FOSI) is due per the schedule of 
events, the Sponsor recommends that a copy is 
sent to the patient. The patient can return the form 
during the next schedule visit or by return mail, 
whichever is more convenient.” 
Updated to allow remote 
completion of a FOSI. 
10.1.6. ECOG 
Performance Status 
ECOG performance status updated with details on 
allowing remote assessments in case of 
COVID-19-related restrictions or other 
hindrances. 
Updated to allow remote 
assessment. 
10.2. General Guidance 
for Treatment 
Continuity when 
Patients are Unable to 
Come into the Clinic 
Section added to include guidance for treatment 
continuity 
Added text to include guidance 
for treatment continuity. 
10.3.7. Adverse Events 
of Special Interest 
Updated AESIs 
• 
Myelodysplastic syndrome/acute 
myeloid leukaemia 
AESIs updated to reflect current 
safety information. 
Removed instructions on reporting special 
situations (misuse, medication error, overdose, 
accidental or occupational exposure). 
Special situation paragraph was 
removed because it refers to a 
form and process that does not 
exist in currently in Sponsor 
organization.  All relevant 
information and corresponding 
processes are covered in 
Section 10.3.1.5 
 
Event of pneumonitis and embryo-fetal toxicity 
removed from niraparib adverse events of special 
interest (AESIs). 
Updated to reflect new safety 
data. There are no additional 
pharmacovigilance activities for  
pneumonitis and embryo-fetal 
toxicity associated with niraparib.  
17. List of References 
Reference of ICH E15 added 
Reference of ICH E15 added 
Appendix 6. Protocol 
Amendment History 
Added the summary of previous amendments 
Alignment per process/template 
 
 


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SYNOPSIS 
Name of Sponsor/Company:  TESARO 
Name of Investigational Product:  Niraparib (GSK3985771) and bevacizumab 
Name of Active Ingredient:  Niraparib and bevacizumab 
Title of Study:  A Phase 2, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of 
Niraparib Combined with Bevacizumab as Maintenance Treatment in Patients with Advanced Ovarian 
Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Following Front-Line Platinum-Based 
Chemotherapy with Bevacizumab 
Study center(s):  Approximately 35 sites 
Principal Investigator:  To be determined  
Studied period (years):  
First patient enrolled:  12 December 2017 
Estimated date last patient completed:  Q4 2022 
Phase of development:  
Phase 2 
Objectives:  
Primary: 
• 
To evaluate the efficacy of niraparib in combination with bevacizumab, as assessed by 18-
month progression-free survival (PFS) landmark analysis, in patients with Stage IIIB to IV 
ovarian cancer who have complete response (CR), partial response (PR), or no evidence of 
disease (NED) following front-line, platinum-based chemotherapy with bevacizumab 
Secondary: 
• 
To evaluate additional measures of clinical benefit, including PFS, RECIST or CA-125 
progression free survival, overall survival (OS), patient-reported outcome (PRO) measures, 
time to first subsequent therapy (TFST), and time to second subsequent therapy (TSST) 
• 
To evaluate the safety and tolerability of niraparib and bevacizumab combination in the 
indicated target population 
Exploratory 
• 
To evaluate PFS rate at 6 months (PFS6) and 12 months (PFS12) 
• 
Retrospective analysis to evaluate homologous recombination deficiency (HRD) per the 
Myriad myChoice® HRD test as a potential biomarker for response to the niraparib and 
bevacizumab combination 
Methodology: 
Overall Study Design 
This is a multicenter, Phase 2, single-arm, open-label study to evaluate niraparib combined with 
bevacizumab as maintenance treatment in patients with advanced (Stage IIIB-IV) ovarian cancer, 
fallopian tube cancer, or primary peritoneal cancer with completely or incompletely resected disease 
who are recovered from primary debulking surgery. 
Approximately 90 patients will be enrolled. 
Eligible patients who achieve CR, PR, or NED following treatment with platinum-based chemotherapy 
in addition to bevacizumab will be enrolled in the study and receive maintenance treatment with 
niraparib (for up to 3 years) combined with bevacizumab (for up to 10 months during the maintenance 


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phase or up to a total of 15 months inclusive of the approximately 5 months of bevacizumab received 
with chemotherapy) until disease progression, unacceptable toxicity, patient withdrawal, Investigator’s 
decision, or death, whichever comes first (see Study Design Schema). Patients who continue to derive 
benefit from study treatment based on continuation of non-progression indicated by imaging, remain 
clinically stable, and are willing to continue study visits and assessments may continue to receive 
niraparib beyond 3 years following consultation with the Investigator and the medical monitor. 
Study Design Schema 
 
Abbreviations:  CR = complete response; NED = no evidence of disease; PR = partial response. 
*Patients ≥77 kg and with platelet count of ≥150,000/µL will receive 300 mg/day; patients <77 kg and/or with 
platelet count of <150,000 u/L will receive 200 mg/day 
 
Study Conduct 
Safety assessments conducted throughout the treatment period include treatment-emergent adverse 
events (TEAEs), serious adverse events (SAEs), treatment discontinuations or dose reductions due to 
adverse events (AEs), changes in Eastern Cooperative Oncology Group (ECOG) performance status, 
changes in clinical laboratory results (hematology and chemistry), vital sign measurements, 
observations during physical examination, and use of concomitant medications.  
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 tumor assessment via computed 
tomography (CT) or magnetic resonance imaging (MRI) scan of the abdomen/pelvis and clinically 
indicated areas is required at screening, then every 12 weeks (±7 days) from Cycle 1/Day 1 visit for the 
first 48 weeks, then every 24 weeks (±14 days) until disease progression, at which point a final set of 
imaging scans is required. Only one set of imaging is required showing unequivocal disease 
progression while on study treatment and/or prior to beginning follow-up therapy. Positron emission 
tomography (PET)/CT may be used according to RECIST v1.1 guideline, but its use is not a study 
requirement.  
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 loss to follow-up, scans should continue at the specified intervals 
RECIST v1.1 is used to define progressive disease (PD) in this study. Tumor assessment by CT/MRI 
must unequivocally show PD according to RECIST v1.1 criteria. PD will not be diagnosed in case of 
CA-125 progression in the absence of radiologic evidence of progressive disease. 


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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 informed consent form (ICF), the 
patient is not required to complete an additional CT/MRI scan for study screening.  
PROs (Functional Assessment of Cancer Therapy-Ovarian Symptom Index [FOSI]) will be collected 
every 6 weeks (±7 days) for 6 months, then every 12 weeks (±7 days) thereafter while the patient is 
receiving study treatment. Once a patient discontinues treatment, PRO evaluations will be performed 
4 weeks (±7 days), 8 weeks (±7 days), 12 weeks (±7 days), and 24 weeks (±7 days) after treatment 
discontinuation, regardless of subsequent treatment.  
All patients will undergo an End of Treatment Visit within 7 days of the decision to discontinue 
treatment  for any reason. Post-treatment follow-up visits will be conducted every 12 weeks (±14 days) 
after the last dose of study treatment.  
All AEs and SAEs, regardless of causality, will be collected and recorded for each patient from the day 
the ICF is signed until 90 days after the last dose of study treatment. Any pregnancies that occur are to 
be reported. All AEs and SAEs experienced by a patient, regardless of the suspected causality, will be 
monitored until the AE or SAE has resolved, until any abnormal laboratory values have returned to 
baseline or normalized, until there is a satisfactory explanation for the change(s) observed, until the 
patient is lost to follow-up or withdraws consent, or until the patient has died. 
The niraparib adverse events of special interest (AESIs) for this study are myelodysplastic syndrome 
(MDS), acute myeloid leukemia (AML), and secondary cancer (new malignancies other than 
MDS/AML). AESIs must be reported to the Sponsor as soon as the Investigator becomes aware of 
them or within 24 hours. 
Number of patients (planned):  Approximately 90 patients will be enrolled into the study 
Diagnosis and main criteria for inclusion: 
Criteria for inclusion 
To be considered eligible to participate in this study, all of the following inclusion criteria must be met: 
1. Patients must be female, be ≥ 18 years of age, be able to understand the study procedures, and 
agree to participate in the study by providing written informed consent. 
2. Patients must have newly diagnosed International Federation of Gynecology and Obstetrics 
(FIGO) Stage IIIB to IV epithelial ovarian, fallopian tube, or peritoneal cancer and have 
recovered from debulking surgery. 
3. Patients must have high-grade serous or endometrioid or high-grade predominantly serous or 
endometrioid histology, regardless of HRD or germline breast cancer susceptibility gene 
(gBRCA) mutation status. Patients with non-mucinous epithelial ovarian cancer and gBRCA 
mutation are eligible. 
4. Patients must have completed front-line, platinum-based chemotherapy with CR, PR, or NED 
and have first study treatment dose within 12 weeks of the first day of the last cycle of 
chemotherapy: 
a. A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 
9 treatment cycles. Patients who discontinued platinum-based therapy early as a result of 
non-hematologic toxicity specifically related to the platinum regimen (ie, neurotoxicity or 
hypersensitivity) are eligible if they have received a minimum of 4 cycles of the platinum 
regimen. 


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b. Intravenous (IV), intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; 
for weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed. 
5. Patients must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab in 
combination with the last 3 cycles of platinum-based chemotherapy. Patients who undergo 
interval debulking surgery are eligible if they have received only 2 cycles of bevacizumab in 
combination with the last 3 cycles of platinum-based chemotherapy. 
6. Patients must have had 1 attempt at optimal debulking surgery. 
7. Patients must have either CA-125 in the normal range or CA-125 decrease by more than 90% 
during front-line therapy that is stable for at least 7 days (ie, no increase >15% from nadir). 
8. Patients must have adequate organ function, defined as (Note: complete blood count [CBC] 
test should be obtained without transfusion or receipt of stimulating factors within 2 weeks 
before obtaining screening blood sample): 
a. Absolute neutrophil count (ANC) ≥ 1,500/µL 
b. Platelet count ≥ 100,000/µL 
c. Hemoglobin ≥ 9 g/dL 
d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance 
≥ 60 mL/min using Cockcroft-Gault equation 
e. Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ 1 × ULN 
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN 
unless liver metastases are present, in which case they must be ≤ 5 × ULN 
9. Patients must have an ECOG score of 0 or 1. 
10. Patients must have normal blood pressure or well-controlled hypertension. 
11. Patient must agree to complete PROs (FOSI) throughout the study, including after study 
treatment discontinuation. 
12. Patients must be able to take oral medication. 
13. Patient must agree to undergo tumor HRD testing at screening. The tumor sample must be 
confirmed to be available during the screening period and submitted after the patient has been 
enrolled; patients do not have to wait for the HRD test result to be enrolled. If archival tumor 
tissue is not available for testing, the patient must agree to undergo a fresh biopsy. 
14. Patients of childbearing potential must have a negative serum or urine pregnancy test 
(beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of study 
treatment. 
15. Patients must be postmenopausal, free from menses for >1 year, surgically sterilized, or willing 
to use adequate contraception to prevent pregnancy or must agree to abstain from activities that 
could result in pregnancy throughout the study, starting with enrollment through 180 days after 
the last dose of study treatment. 
Criteria for exclusion 
A patient will be considered ineligible for study participation if any of the following exclusion criteria 
are met: 


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1. Patients with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any low-grade 
tumors. 
2. Patients with clinically significant cardiovascular disease (eg, significant cardiac conduction 
abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or 
unstable angina < 6 months to enrollment, New York Heart Association [NYHA] Grade II or 
greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade II or 
greater peripheral vascular disease, and history of cerebrovascular accident [CVA] within 6 
months). 
3. Patients with gastrointestinal disorders or abnormalities that would interfere with absorption of 
study treatment. 
4. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease 
or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. 
Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on CT 
scan or clinical symptoms of bowel obstruction. 
5. Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥ 1.0 at screening or 
urine dipstick for proteinuria ≥ 2 (patients discovered to have ≥ 2 proteinuria on dipstick at 
baseline should undergo a 24-hour urine collection and must demonstrate < 2 g of protein in 
24 hours to be eligible). 
6. Patient has any known history or current diagnosis of MDS or AML. 
7. Patient has received treatment previously with a poly(ADP-ribose) polymerase (PARP) 
inhibitor. 
8. Other than ovarian cancer, the patient has been diagnosed or treated for invasive cancer less 
than 5 years prior to study enrollment. Patients with cervical carcinoma in situ, 
non-melanomatous skin cancer, and ductal carcinoma in situ definitively treated are allowed. 
9. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
non-malignant systemic disease, or active, uncontrolled infection. 
10. Patient has known contraindication to PARP inhibitors or vascular endothelial growth factor 
(VEGF) inhibitors. 
11. Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries or surgery 
within the past 28 days prior to start of study treatment, history of CVA, transient ischemic 
attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 
3 months). 
12. Patient is immunocompromised (patients with splenectomy are allowed). 
13. Patient has known, active hepatic disease (ie, hepatitis B or C). 
14. Patient has a QT interval prolongation > 480 ms at screening. If a patient has a prolonged QT 
interval and the prolongation is deemed to be due to a pacemaker upon Investigator evaluation 
(ie, the patient otherwise has no cardiac abnormalities), then the patient may be eligible to 
participate in the study following discussion with the Medical Monitor. 


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15. Patient is pregnant or is expecting to conceive children while receiving study drug and for up 
to 180 days after the last dose of study drug; additionally, female patients should not breastfeed 
during treatment with niraparib and for 30 days after receipt of the last dose due to the 
potential for serious adverse reactions from niraparib in breastfed infants.  
Investigational product, dosage and mode of administration:  
On Day 1 of each 21-day cycle (84-day cycle after implementation of amendment 2), bevacizumab 
15 mg/kg will be administered via IV infusion.1 Bevacizumab will be administered for up to 10 months 
during the maintenance phase or up to a total of 15 months inclusive of the approximately 5 months of 
bevacizumab received with chemotherapy.  Niraparib will be administered orally once a day, 
continuously throughout each 21-day cycle (84-day cycle after implementation of amendment 2), for 
up to 3 years in the absence of PD, unacceptable toxicity, patient withdrawal, Investigator’s decision, 
or death. On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab 
infusion. 
Patients who continue to derive benefit from study treatment based on continuation of non-progression 
indicated by imaging, remain clinically stable, and are willing to continue study visits and assessments 
may continue to receive niraparib beyond 3 years following consultation with the Investigator and the 
medical monitor. 
The starting dose of niraparib will be based on the patient’s baseline actual body weight or platelet 
count. Patients with a baseline actual body weight of ≥77 kg and screening platelet count of 
≥150,000/µL will take three capsules of 100 mg strength (300 mg) at each dose administration. 
Patients with a baseline actual body weight of <77 kg and/or screening platelet count of <150,000/µL 
will take two capsules of 100 mg strength (200 mg) at each dose administration. Additional dose 
modifications will not be based upon changes in the patient’s actual body weight during study 
participation.   
Patients will be instructed to take their niraparib dose once a day or as instructed by the Investigator.  
Patients must swallow and not chew all capsules. The consumption of water and food is permissible. 
For patients whose starting dose is 2 capsules (200 mg/day), escalation to 3 capsules (300 mg/day) is 
permitted if no treatment interruptions or discontinuations were required during the first 2 cycles of 
therapy. This escalation will occur at the discretion of the Investigator, following discussion with the 
Medical Monitor.  
Dose interruption (no longer than 28 days) or dose reduction will be allowed based on treatment side 
effects. For patients whose initial dose is 3 capsules daily (300 mg/day), dose reductions to 2 capsules 
daily (200 mg/day) and subsequently to 1 capsule daily (100 mg/day) will be allowed. No further dose 
reduction will be allowed without discussion with the Medical Monitor. 
For patients whose initial dose is 2 capsules (200 mg/day), dose reduction to 1 capsule once daily (100 
mg/day) will be allowed. No further dose reduction will be allowed without discussion with the 
Medical Monitor.  
Duration of treatment:  
Planned study conduct duration:   
The primary efficacy analysis will occur approximately 18 months after the last patient has initiated 
treatment with maintenance niraparib combined with bevacizumab. 
Planned study treatment duration:   
Patients may continue bevacizumab maintenance treatment for up to approximately 15 months (up to 
10 months during the maintenance phase or up to a total of 15 months inclusive of approximately 5 
months of bevacizumab received with chemotherapy) and niraparib maintenance treatment for up to 


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3 years in the absence of PD, unacceptable toxicity, patient withdrawal, Investigator’s decision, or 
death. Patients who have not progressed after 3 years of niraparib maintenance treatment will be given 
the option to continue with niraparib beyond 3 years if they are tolerating and benefiting from 
treatment and after consultation with the Sponsor. Per Investigator discretion and in consultation with 
the Sponsor, patients who are still receiving and benefiting from study treatment at the time of study 
termination may have an option to continue to receive study treatment. 
Reference therapy, dosage and mode of administration:  Not applicable.  
Criteria for evaluation: 
Efficacy: 
Primary endpoint 
The primary efficacy endpoint is PFS rate at 18 months (PFS18), which is defined as the proportion of 
patients who have not progressed or died within 18 months after niraparib combined with bevacizumab 
treatment initiation. Progression will be assessed by RECIST v1.1 criteria per Investigator assessment. 
Secondary endpoints 
The following secondary endpoints will be evaluated: 
• 
PFS, defined as the time from niraparib combined with bevacizumab treatment initiation to the 
earlier date of assessment of progression, as assessed by RECIST v1.1 criteria, based on 
Investigator assessment, or death by any cause in the absence of progression 
• 
RECIST or CA-125 progression-free survival, defined as the time from initiation of treatment of 
niraparib in combination with bevacizumab to the earliest date of progression assessed by RECIST 
v1.1 or CA-125 progression, or death by any cause.  
• 
OS as measured from the date of initiation of treatment of niraparib in combination with 
bevacizumab treatment to the date of death by any cause 
• 
The observed change from baseline in the FOSI PRO assessment 
• 
TFST, defined as the date of initiation of niraparib treatment in combination with bevacizumab 
treatment in the current study to the start date of the first subsequent anticancer therapy 
• 
TSST, defined as the date of initiation of niraparib treatment in combination with bevacizumab in 
the current study to the start date of the second subsequent anticancer therapy 
• 
Safety and tolerability of the combination 
Exploratory endpoints 
The following exploratory endpoints will be evaluated: 
• 
PFS rate at 6 months (PFS6) and 12 months (PFS12) 
• 
HRD status as a potential biomarker for response to niraparib-bevacizumab treatment 
Statistical methods: 
Sample size considerations 
The sample size of the study is driven by the primary endpoint: PFS18. A sample size of 90 patients 
will provide an 11% precision on the 95% exact confidence interval (CI) of PFS18, assuming a true 
PFS18 rate of 48%, which corresponds to a median PFS of 17 months based on exponential PFS 


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assumption. The primary endpoint analysis will occur after approximately 3 months of enrollment and 
an additional 18 months of follow-up. 
 
Analysis populations 
Three analysis populations will be defined as follows: 
• 
Safety population:  All patients who receive any amount of study treatment (ie, any amount of 
bevacizumab or niraparib during the study). All safety endpoints will be assessed in the safety 
population. 
• 
Efficacy population:  All patients who receive any amount of niraparib (at least 1 dose). Analyses 
of baseline characteristics and the primary analysis of efficacy endpoints will be performed on the 
efficacy population. 
• 
Per-protocol population:  All patients in the efficacy population who have no major protocol 
violations during the study and have at least 1 protocol-required postbaseline tumor assessment. 
 
General methods 
The primary endpoint for the study, PFS18, will be estimated using percentage with 95% exact CI. In 
addition, the probability of PFS at 18 months will be estimated using the Kaplan-Meier method.  
All analyses will include summary statistics, including number and percentage for categorical variables 
and number of patients, mean, standard deviation, median, minimum, and maximum for continuous 
variables. Time-to-event analyses will be performed using the Kaplan-Meier method. Two-sided 
95% CIs will be provided where appropriate. No formal statistical testing will be performed. Further 
details will be provided in the study statistical analysis plan (SAP). 


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1. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................3 
SYNOPSIS 7 
1. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............15 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................21 
3. 
INTRODUCTION ......................................................................................................24 
3.1. 
Background of PARP and PARP Inhibition ...............................................................24 
3.2. 
Background of Niraparib ............................................................................................24 
3.3. 
Background of Bevacizumab ......................................................................................28 
3.4. 
Disease Background and Current Treatment Options ................................................29 
3.5. 
Background of Combination of Niraparib and Bevacizumab ....................................29 
3.6. 
Rationale for Current Trial .........................................................................................30 
4. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................32 
4.1. 
Primary Objective .......................................................................................................32 
4.2. 
Secondary Objectives .................................................................................................32 
4.3. 
Exploratory Objectives ...............................................................................................32 
5. 
INVESTIGATIONAL PLAN .....................................................................................33 
5.1. 
Overall Study Design ..................................................................................................33 
5.2. 
Number of Subjects ....................................................................................................34 
5.3. 
Treatment Assignment ................................................................................................34 
5.4. 
Dose Adjustment Criteria ...........................................................................................35 
5.4.1. 
Niraparib .....................................................................................................................35 
5.4.2. 
Bevacizumab ...............................................................................................................37 
5.5. 
Criteria for Study Termination ...................................................................................37 
6. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................41 
6.1. 
Subject Inclusion Criteria ...........................................................................................41 
6.2. 
Subject Exclusion Criteria ..........................................................................................42 


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6.3. 
Subject Withdrawal Criteria .......................................................................................43 
6.3.1. 
Discontinuation from Treatment .................................................................................43 
6.3.2. 
Discontinuation from the Study ..................................................................................45 
6.3.3. 
Withdrawal of Consent ...............................................................................................45 
6.3.3.1. 
Further Research Maintaining Confidential Patient Information ...............................45 
6.4. 
Lost to Follow Up .......................................................................................................46 
7. 
TREATMENT OF SUBJECTS ..................................................................................47 
7.1. 
Description of Study Drug ..........................................................................................47 
7.2. 
Concomitant Medications ...........................................................................................47 
7.3. 
Treatment Compliance ................................................................................................48 
7.4. 
Randomization and Blinding ......................................................................................48 
8. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................49 
8.1. 
Study Drug ..................................................................................................................49 
8.1.1. 
Niraparib .....................................................................................................................49 
8.1.2. 
Bevacizumab ...............................................................................................................49 
8.2. 
Study Drug Packaging and Labeling ..........................................................................49 
8.3. 
Study Drug Storage .....................................................................................................49 
8.4. 
Study Drug Preparation ..............................................................................................49 
8.5. 
Administration ............................................................................................................49 
8.5.1. 
Niraparib .....................................................................................................................49 
8.5.2. 
Bevacizumab ...............................................................................................................50 
8.6. 
Study Drug Accountability .........................................................................................50 
8.7. 
Study Drug Handling and Disposal ............................................................................51 
9. 
ASSESSMENT OF EFFICACY ................................................................................52 
9.1. 
Primary Efficacy Endpoint .........................................................................................52 
9.2. 
Secondary Efficacy Endpoints ....................................................................................53 
9.2.1. 
Progression-free Survival ...........................................................................................53 
9.2.2. 
Overall Survival ..........................................................................................................53 
9.2.3. 
RECIST or CA-125 Progression-free Survival ..........................................................53 
9.2.4. 
Patient Reported Outcome - Functional Assessment of Cancer Therapy–
Ovarian Symptom Index .............................................................................................53 
9.2.5. 
Time to First Subsequent Therapy ..............................................................................54 


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9.2.6. 
Time to Second Subsequent Therapy .........................................................................54 
9.3. 
Exploratory Efficacy Endpoints .................................................................................54 
9.4. 
Biomarker Analysis ....................................................................................................54 
10. 
ASSESSMENT OF SAFETY .....................................................................................55 
10.1. 
Safety Parameters .......................................................................................................55 
10.1.1. 
Demographic/Medical History ...................................................................................55 
10.1.1.1. 
Disease History ...........................................................................................................55 
10.1.1.2. 
Medical and Surgical History .....................................................................................55 
10.1.1.3. 
Previous and Concomitant Medications .....................................................................56 
10.1.2. 
Vital Signs ..................................................................................................................56 
10.1.3. 
Weight and Height ......................................................................................................56 
10.1.4. 
Physical Examination .................................................................................................56 
10.1.5. 
Laboratory Assessments .............................................................................................56 
10.1.5.1. 
Hematology .................................................................................................................57 
10.1.5.2. 
Blood Chemistry .........................................................................................................57 
10.1.5.3. 
Urinalysis ....................................................................................................................57 
10.1.5.4. 
Drug Screen ................................................................................................................58 
10.1.5.5. 
Pregnancy Screen ........................................................................................................58 
10.1.6. 
ECOG Performance Status .........................................................................................58 
10.1.7. 
Electrocardiogram .......................................................................................................58 
10.2. 
General Guidance for Treatment Continuity when Patients are Unable to 
Come into the Clinic ...................................................................................................59 
10.3. 
Adverse and Serious Adverse Events .........................................................................60 
10.3.1. 
Definitions ..................................................................................................................60 
10.3.1.1. 
Adverse Event .............................................................................................................60 
10.3.1.2. 
Serious Adverse Event ................................................................................................60 
10.3.1.3. 
Treatment-Emergent Adverse Event (TEAE) ............................................................61 
10.3.1.4. 
Adverse Events of Special Interest (AESI) ................................................................61 
10.3.1.5. 
Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure ........................................................................61 
10.3.2. 
Assessment of Adverse Events ...................................................................................61 
10.3.2.1. 
Severity Assessment ...................................................................................................61 


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10.3.2.2. 
Relationship to Study Intervention .............................................................................62 
10.3.2.3. 
Expectedness ...............................................................................................................62 
10.3.3. 
Collection and Recording Adverse Events .................................................................62 
10.3.4. 
Follow-Up of Adverse Events ....................................................................................63 
10.3.5. 
Reporting ....................................................................................................................63 
10.3.6. 
Submission and Distribution of Serious Adverse Event Reports ...............................64 
10.3.7. 
Adverse Events of Special Interest .............................................................................64 
10.3.8. 
Myelodysplastic syndrome/acute myeloid leukaemia ................................................64 
10.3.9. 
Pregnancy ...................................................................................................................64 
11. 
STATISTICS ..............................................................................................................66 
11.1. 
Sample Size Determination ........................................................................................66 
11.2. 
Analysis Populations ..................................................................................................66 
11.3. 
Demographics, Medical History, Baseline Characteristics, and Concomitant 
Medications .................................................................................................................66 
11.4. 
Efficacy Analyses .......................................................................................................67 
11.5. 
Safety Analyses ..........................................................................................................67 
12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................69 
12.1. 
Study Monitoring ........................................................................................................69 
12.2. 
Audits and Inspections ................................................................................................69 
12.3. 
Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) ..................70 
13. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................71 
14. 
ETHICS ......................................................................................................................72 
14.1. 
Ethics Review .............................................................................................................72 
14.2. 
Ethical Conduct of the Study ......................................................................................72 
14.3. 
Written Informed Consent ..........................................................................................72 
15. 
DATA HANDLING AND RECORDKEEPING .......................................................73 
15.1. 
Inspection of Records .................................................................................................73 
15.2. 
Retention of Records ..................................................................................................73 
16. 
PUBLICATION POLICY ..........................................................................................74 
17. 
LIST OF REFERENCES ............................................................................................75 
18. 
APPENDICES ............................................................................................................77 
APPENDIX 1. CONTRACEPTION GUIDELINES ..................................................................77 


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APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS V.1.1 ............78 
APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS .......................................................................................81 
APPENDIX 4. SAMPLE FUNCTIONAL ASSESSMENT OF CANCER THERAPY – 
OVARIAN SYMPTOM INDEX (FOSI) ...................................................................82 
APPENDIX 5. WORLD MEDICAL ASSOCIATION DECLARATION OF 
HELSINKI ..................................................................................................................83 
APPENDIX 6. PROTOCOL AMENDMENT HISTORY ..........................................................89 
 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................21 
Table 2: 
Progression-Free Survival in Ovarian Cancer Patients in NOVA ..............................25 
Table 3: 
Recommended Dose Modifications for Adverse Reactions .......................................35 
Table 4: 
Dose Modifications for Non-hematologic Adverse Reactions ...................................35 
Table 5: 
Dose Modifications for Hematologic Adverse Reactions ..........................................36 
Table 6: 
Schedule of Events .....................................................................................................38 
Table 7: 
Investigational Products ..............................................................................................47 
Table 8: 
Recommended Initial Starting Dose ...........................................................................50 
Table 9: 
For Patients with Measurable Disease (ie, Target Disease) .......................................79 
Table 10: For Patients with Non-measurable Disease (ie, Non-target Disease) .........................79 
 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................34 
 
  


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2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or 
Specialist Term 
Explanation 
ADL 
activity of daily living 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
AST 
aspartate aminotransferase 
BER 
base excision repair 
BRCA 
breast cancer susceptibility gene 
CA-125 
cancer antigen 125 
CBC 
complete blood count 
CI 
confidence interval 
CR 
complete response 
CT 
computed tomography 
CVA 
cerebrovascular accident 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ESMO 
European Society for Medical Oncology 
EU 
European Union 
FIGO 
International Federation of Gynecology and Obstetrics 
FOSI 
Functional Assessment of Cancer Therapy–Ovarian Symptoms Index 
gBRCA 
germline breast cancer susceptibility gene 
gBRCAmut 
germline BRCA mutation 
GCIG 
Gynecologic Cancer Intergroup 
GCP 
Good Clinical Practice 


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Abbreviation or 
Specialist Term 
Explanation 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ICF 
informed consent form 
IV 
intravenous 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network 
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria for Adverse 
Events 
NED 
no evidence of disease 
OAE 
other adverse events 
OS 
overall survival 
PARP 
poly(ADP-ribose) polymerase 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS6 
PFS rate at 6 months 
PFS12 
PFS rate at 12 months 
PFS18 
PFS rate at 18 months 
PR 
partial response 
PRO 
patient-reported outcome 
QD 
once daily 
QoL 
quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sBRCA 
somatic BRCA 
TEAE 
treatment-emergent adverse event 


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Abbreviation or 
Specialist Term 
Explanation 
TFST 
time to first subsequent therapy 
TSST 
time to second subsequent therapy 
ULN 
upper limit of normal 
US 
United States 
VEGF 
vascular endothelial growth factor 
WHO 
World Health Organization 
 


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3. 
INTRODUCTION 
Homologous recombination deficiency (HRD) and dependency on neo-angiogenesis are 2 major 
vulnerabilities of human cancers that have been successfully exploited therapeutically, as 
evidenced by recent approvals of poly(ADP-ribose) polymerase (PARP) inhibitors including 
niraparib (Zejula®) for ovarian cancer and angiogenesis inhibitors including bevacizumab 
(Avastin®; Genentech/Roche United States [US]) for several indications including ovarian 
cancer. Emerging pre-clinical and clinical data suggest that combination of these 2 classes of 
agents may increase therapeutic options for women with ovarian cancer. 
3.1. 
Background of PARP and PARP Inhibition 
PARP1 and PARP2 are key enzymes for repairing single-strand deoxyribonucleic acid (DNA) 
breaks. When they are inhibited, single-strand DNA breaks become double-strand DNA breaks 
after DNA replication, forcing cancer cells to rely on double-strand break repair mechanisms, in 
particular homologous recombination, for survival and proliferation. 
PARP inhibitors selectively kill a subset of cancer cells with deficiencies in DNA repair 
pathways. For example, a tumor arising in a patient with a germline breast cancer susceptibility 
gene mutation (gBRCAmut) has a defective homologous recombination DNA repair pathway and 
would be increasingly dependent on base excision repair (BER), a pathway blocked by PARP 
inhibitors, for maintenance of genomic integrity. In addition to breast cancer susceptibility gene 
(BRCA) mutations, DNA-repair defects can be caused by germline or somatic alterations to 
dozens of genes in the homologous recombination DNA repair pathway. In a recent analysis of 
~500 high-grade serous ovarian cancer tumors, approximately 50% contained homologous 
recombination defects, which could sensitize tumors to PARP inhibitors.2 This concept of 
inducing tumor cell death in tumors with inherent defects in DNA repair using PARP inhibitors 
is called synthetic lethality.3 
3.2. 
Background of Niraparib 
Niraparib (GSK3985771) is a PARP inhibitor indicated for the maintenance treatment of adult 
patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who 
exhibit a complete response (CR) or partial response (PR) to platinum-based chemotherapy. 
Niraparib is an oral inhibitor of PARP-1 and PARP-2, which play a role in DNA repair. In vitro 
studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP 
enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA 
damage, apoptosis, and cell death. Increased niraparib-induced cytotoxicity was observed in 
tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in 
mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human 
patient-derived xenograft tumor models with homologous recombination deficiency that had 
either mutated or wild type BRCA1/2. 
Niraparib has been evaluated in a series of Phase 1 clinical studies in patients with solid tumors, 
as well as in a Phase 3 study of 546 patients with platinum-sensitive recurrent ovarian cancer 
who had received at least 2 previous chemotherapy regimens and received niraparib or placebo 
maintenance (“ENGOT-OV16/NOVA” study).  


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The ENGOT-OV16/NOVA study4 is a double-blind, 2:1 (niraparib:placebo) randomized, 
placebo-controlled study of maintenance treatment with niraparib compared with placebo in 
patients with platinum- sensitive ovarian cancer who have received at least 2 platinum-based 
regimens, had a response to their last regimen, and have no measurable disease >2 cm and 
normal cancer antigen 125 (CA-125) (or >90% decrease) following their last treatment. There 
were 2 independent patient cohorts comprising patients who have deleterious gBRCAmut versus 
those who have a tumor with high-grade serous histology but without gBRCAmut (non-
gBRCAmut). Patients in the non- gBRCAmut cohort are further characterized by tumor HRD 
status (positive or negative). 
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.  
Demographic and baseline characteristics were well-balanced. 
Table 2 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 2: 
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 this proposed indication are 
derived from the ENGOT-OV16/NOVA main study in which a total of 546 patients received 
study treatment. Safety presentations for the NOVA study are derived from the analyses included 
in the clinical study report and include comparisons of the safety profile of niraparib 
maintenance treatment versus placebo in women with platinum-sensitive recurrent ovarian 
cancer. 
All patients who received niraparib and 171 (96%) of 179 patients who received placebo 
experienced at least 1 treatment-emergent adverse event (TEAE). The high rate of TEAEs in the 
placebo group indicates the burden of prior chemotherapy and the patient’s underlying ovarian 


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cancer. Review of the data across study cohorts for TEAE incidence showed that, in general, the 
results were similar in the gBRCAmut and non-gBRCAmut cohorts. In the overall safety 
population, for the niraparib versus placebo treatment arms, the incidences of Grade 3/4 TEAEs 
(74% vs 23%), serious adverse events (SAEs) (30% vs 15%), TEAEs leading to treatment 
interruption (69% vs 5%), TEAEs leading to dose reduction (67% vs 15%), and TEAEs leading 
to treatment discontinuation (15% vs 2%) were higher for niraparib. There were no on-treatment 
deaths reported. The incidence of myelodysplastic syndrome (MDS)/acute myeloid leukemia 
(AML) in patients who received niraparib (5 of 367; 1.4%) was similar to the incidence in 
patients who received placebo (2 of 179; 1.1%). MDS/AML and secondary cancers (new 
malignancies other than MDS or AML) are potential risks of PARP inhibitors.  
The selection of the 300 mg starting dose of niraparib for the phase 3 randomized double-blind 
trial of maintenance with niraparib versus placebo in the ENGOT-OV16/NOVA study was based 
on data from the Phase 1 MAD study PN001 conducted by Merck & Co. There were no formal 
Phase 2 dose-ranging studies conducted. The Phase 1 study included both a dose escalation 
phase to determine the maximal tolerated dose and an expansion arm to further evaluate the 
selected dose. A total of 104 patients with advanced solid tumors were evaluated in this study, 
including 60 during dose escalation from 30 mg to 400 mg and 54 during expansion at the 300 
mg dose level. The dose escalation stage determined that 400 mg exceeded the maximal tolerated 
dose (by traditional dose-limiting toxicity evaluations and by using the pooled adjacent violators 
algorithm). No dose-limiting toxicities were observed at 290 or 300 mg dose levels. In the Phase 
3 study, daily niraparib improved progression-free survival (PFS) in a cohort of patients with 
gBRCA mutation as well as in a cohort of patients without gBRCA mutation. Within the 
gBRCAmut cohort, the median PFS was 21.0 months in patients on niraparib versus 5.5 months 
on placebo (hazard ratio [HR], 0.27; p < 0.0001). In recurrent ovarian cancer patients, efficacy 
was assessed in patients with HRD-positive tumors as identified by the Myriad’s myChoice 
HRD test as well in the overall non-gBRCA mutation cohort regardless of HRD status. As 
observed in the gBRCAmut cohort, PFS was significantly longer with niraparib in the 
homologous recombination deficient-positive group of the non-gBRCAmut (without germline 
BRCA mutation) cohort (median, 12.9 months vs 3.8 months; HR, 0.38; p < 0.0001). Lastly, PFS 
was significantly improved in the overall non-gBRCAmut cohort (median, 9.3 months vs 
3.9 months; HR, 0.45; p < 0.0001). Secondary endpoints, including chemotherapy-free interval, 
time to first subsequent therapy (TFST), and progression-free survival 2 (PFS2), confirmed the 
PFS benefit of niraparib treatment in both cohorts. This provides compelling evidence that 
niraparib does not diminish responsiveness to subsequent therapy and that the niraparib treatment 
effect persists. Subsequently in 2017, a recommendation to consider niraparib maintenance 
therapy in this setting in cases of CR and PR was added to the National Comprehensive Cancer 
Network (NCCN) guidelines.5  
The most commonly observed non-hematologic treatment-emergent adverse events (TEAEs) of 
any National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-
CTCAE) grade were nausea, fatigue, constipation, and vomiting; the majority of the non-
hematologic TEAEs were mild to moderate in severity. The most commonly observed 
hematologic TEAEs (any grade) were anemia (48.5%), thrombocytopenia 66.2%), and 
neutropenia (31.4%).  


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TEAEs leading to treatment interruption, reduction or discontinuation were 68.9%, 66.5% and 
14.7% respectively. Approximately 50% of patients required dose interruption during the first 
month of niraparib therapy, and 47% required dose reduction during the second month of 
therapy. Most patients achieved their individual maximal tolerated dose by the third month. The 
average dose of niraparib during the study was 206 mg. After Month 3 or 4, new incidents of 
thrombocytopenia were reported in < 1% of patients. Although Grade 3 or 4 hematologic 
laboratory events were common at the initiation of treatment, no severe clinical sequelae were 
observed, and relatively few patients discontinued due to these AEs (discontinuation rate was 
3.3% for thrombocytopenia, 1.4% for anemia and 1.9% for neutropenia). Dose adjustment based 
on individual tolerability during the first 3 cycles substantially reduced the incidence of these 
events beyond Cycle 3. Furthermore, PFS in patients who were dose reduced to either 200 mg or 
100 mg was consistent with PFS for the patients who remained at 300 mg indicating that patients 
who required dose reduction do not appear to have decreased efficacy relative to those who 
remain at the 300 mg starting dose.  
These data support that each patient has an optimal benefit/risk at their individualized dose. As 
lower doses are associated with substantial improvements in the incidence of TEAEs while not 
appearing to compromise efficacy, approaches to quickly transition patients to their 
individualized optimal dose, particularly patients at the highest risk of grade 3 or 4 
thrombocytopenia in cycle 1were further evaluated. In addition, an exploratory analysis was 
conducted to determine if risk factors could be identified for a subgroup of patients which were 
associated with higher rates of hematologic toxicity.  In the updated analysis, two factors were 
identified as being associated with thrombocytopenia, baseline platelet count and baseline body 
weight. 
Baseline Platelet Count and Weight as Predictors of Thrombocytopenia. 
An analysis was conducted using the data collected in ENGOT-OV16/NOVA and the initial 
phase 1 study, PN001. This analysis determined that only baseline platelets had an impact on 
platelet nadir; lower baseline platelets (<180,000/µL) were associated with an increased 
frequency of thrombocytopenia Grade ≥1 (76%) or Grade ≥ 3 (45%) compared to patients with 
higher baseline platelet counts. Further, an exploratory analysis of clinical data versus baseline 
body weight from ENGOT-OV16/NOVA was conducted. For this analysis, the weight categories 
were based on quartiles with the lowest quartile (patients with a body weight less than 58 kg at 
baseline) compared to the highest quartile (patients with a body weight greater than or equal to 
77 kg at baseline).  While TEAEs occurred in most patients regardless of body weight, Grade ≥3 
TEAEs, SAEs, and TEAEs leading to dose modification or treatment discontinuation occurred 
more commonly in the weight <58 kg cohort than in the ≥77 kg cohort. In the cohort of patients 
with a body weight <58 kg, approximately 80% of patients had a dose reduction compared to 
59% of patients with a weight greater than or equal to 77 kg. Treatment discontinuations were 
increased in the subjects with lower body weight (24%) compared to patients in the highest 
quartile (10%).      
The potential relationship between body weight and TEAEs was further explored in an analysis 
to evaluate the correlation of grade 3 or 4 thrombocytopenia and baseline body weight. The 
lowest platelet count in the first 30 days was plotted versus baseline body weight to determine if 


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low body weight identified a subgroup of patients with higher levels of thrombocytopenia during 
Cycle 1. In the first 30 days of treatment, a baseline body weight >77 kg is associated with a 
lower incidence of grade 3 or 4 thrombocytopenia (14%) relative to the group with body weight 
<58 kg (43%).  
Finally, a classification tree approach was used to refine the best cut-off points for predicting the 
likelihood of a patient developing ≥Grade 3 thrombocytopenia within 30 days after the first dose 
of niraparib. The results of the model show that the subgroup of patients with a baseline body 
weight <77 kg or baseline platelet count <150,000/µL had a grade 3/4 thrombocytopenia rate in 
the first 30 days of 35.4% compared to 11.5% in the group of patients with a body weight >77 kg 
and a platelet count >150,000/µL. Further, the average daily dose was 258 mg through the first 
two cycles for patients with a body weight >77 kg and platelet count >150,000/µL, and was only 
206 mg for patients with body weight < 77 kg or platelet count <150,000/µL. Thus, the actual 
delivered dose approximated a starting dose of 200 mg despite the intended delivery of a starting 
dose of 300 mg. These observations are to be confirmed in the present study with the inclusion of 
study treatment dosed at 200 mg (2 capsules of niraparib or placebo) in patients whose baseline 
weight is <77 kg or baseline platelet count is <150,000/µL. 
Guidance on monitoring patients for new events of MDS and AML and the follow-up of patients 
with suspected MDS or AML is provided in Section 10.3.7. Additional niraparib clinical safety 
data reported to date, including Phase 1 and NOVA results, dose limiting- toxicities, and toxicity 
profile, are provided in detail in the Investigator’s Brochure. 
3.3. 
Background of Bevacizumab 
Bevacizumab is an antiangiogenic recombinant humanized monoclonal immunoglobulin G1 
antibody against the vascular endothelial growth factor (VEGF) protein. Bevacizumab (Avastin; 
Genentech/Roche US) has been approved in the US and European Union (EU) for the treatment 
of multiple tumor types in combination with certain other treatments. In the US and EU, 
bevacizumab is approved for the front-line treatment of adult patients with advanced 
(International Federation of Gynecology and Obstetrics [FIGO] Stages IIIB, IIIC, and IV) 
ovarian cancer. In the US, bevacizumab is approved for the treatment of patients with platinum-
sensitive recurrent ovarian cancer, either in combination with carboplatin and paclitaxel or in 
combination with carboplatin and gemcitabine, followed by bevacizumab as a single agent.  
Bevacizumab has been evaluated in multiple clinical studies, including in 1,873 patients with 
newly diagnosed, Stage III (incompletely resected) or Stage IV epithelial ovarian cancer who had 
undergone debulking surgery as part of a Phase 3 study (GOG218).6 Patients receiving 
bevacizumab administered concurrently with chemotherapy and as a maintenance treatment 
showed statistically significant improvement in PFS compared to placebo (14.1 months vs 
10.3 months; HR, 0.717; p < 0.001).  
Bevacizumab was also evaluated in 1,528 patients with ovarian cancer, regardless of FIGO stage 
as part of a Phase 3 study (ICON7).7 Patients receiving bevacizumab administered concurrently 
with chemotherapy and as a maintenance treatment showed statistically significant improvement 
in PFS compared to chemotherapy alone (19.0 months vs 17.3 months; HR, 0.81; p = 0.004), 
with maximum improvement compared to chemotherapy alone at 12 months (15.1%; 


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95% confidence interval [CI], 10.7-19.5). The improvement was even more pronounced in 
patients at high risk of progression (ie, FIGO Stage IV or FIGO Stage III and >1.0 cm of residual 
disease after debulking surgery; 15.9 months vs 10.5 months; HR, 0.68; p = <0.001). 
3.4. 
Disease Background and Current Treatment Options 
Approximately 75% of ovarian cancer patients respond to front-line, platinum-based therapy and 
are considered platinum sensitive, standardly defined as a minimum duration of 6 months with 
no relapse or progression following treatment. Up to 70% of these patients, however, relapse 
within 1 to 3 years.8,9 
Maintenance or consolidation treatments have been explored in patients with platinum-sensitive 
disease, with the goal of delaying disease progression and the subsequent intensive 
chemotherapy, which may present tolerability issues for many patients. Studies conducted in the 
maintenance setting have produced conflicting results. A meta-analysis of 8 randomized studies 
in which maintenance chemotherapy was compared with no further intervention, maintenance 
radiotherapy, or another type of maintenance treatment demonstrated no significant difference in 
PFS or 3-, 5-, or 10-year overall survival (OS).10 Another meta-analysis of 20 consolidation and 
9 maintenance treatment studies, however, demonstrated a significant improvement in PFS 
(HR, 0.82; 95% CI, 0.70-0.96; p < 0.02).11 Recent clinical trials of anti-angiogenic agents 
(such as bevacizumab and pazopanib) administered in a maintenance setting have demonstrated a 
benefit in PFS6,12,13 but resulted in an increase in toxicity. 
At the time of study initiation, given the expectation of disease recurrence for patients who 
demonstrate a CR to front-line, platinum therapy, the NCCN guidelines recommend observation, 
clinical trial participation, or maintenance therapy with paclitaxel (Level 3 recommendation) or 
pazopanib (Level 2B recommendation); observation is the most common approach.1 It is also 
recommended that patients initiated on bevacizumab in combination with front-line paclitaxel 
and carboplatin continue single-agent bevacizumab as maintenance therapy. For patients who 
demonstrate a PR to front-line therapy, NCCN guidelines recommend clinical trial participation, 
recurrence therapy, or best supportive care. Recommendations from the European Society for 
Medical Oncology (ESMO) include bevacizumab in front-line therapy followed by single agent  
bevacizumab maintenance for a total duration of up to 15 months.1,14 
A Phase 3 clinical study of niraparib maintenance treatment in patients with advanced ovarian 
cancer following response to front-line, platinum-based therapy, excluding patients who receive 
bevacizumab in combination with their front-line chemotherapy, is ongoing (PRIMA). In the 
current study, maintenance with niraparib combined with bevacizumab following front-line, 
platinum-based therapy with bevacizumab will be explored.1,14 
3.5. 
Background of Combination of Niraparib and Bevacizumab 
The combination of a PARP inhibitor and an angiogenesis inhibitor has the potential for 
improved PFS benefits in patients with or without HRD.  
As described earlier, tumor cells with a deficiency in homologous recombination are exquisitely 
sensitive to PARP inhibitors due to synthetic lethality. It has been observed that, for tumors 
without genetic or epigenetic defects in homologous recombination pathway genes, a functional 


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state of HRD may be induced by hypoxia through transcriptional downregulation of homologous 
recombination-related genes, including RAD51 and BRCA1. In addition, cyclic (acute) hypoxia 
and reoxygenation can induce both single-strand and double-strand DNA breaks within tumor 
cells due to increased levels of reactive oxygen species. These 2 mechanisms working together 
lead to heightened sensitivity to PARP inhibitors when cells are under hypoxic stress exerted by 
angiogenesis inhibitors. It has been observed that PARP inhibitors selectively induce apoptosis 
in hypoxic tumor regions in vivo, supporting the idea of contextual synthetic lethality between 
hypoxia-induced functional HRD and PARP inhibition. In the clinical setting, preliminary 
evidence of clinical efficacy has been observed in patients with platinum-sensitive ovarian 
cancer treated with either niraparib combined with bevacizumab (ENGOT-OV24/AVANOVA 
trial) or olaparib combined with cediranib (Phase II), irrespective of their BRCA mutation or 
HRD status. These data provide a strong rationale for combining a PARP inhibitor with an 
angiogenesis inhibitor. 
To validate the hypothesis that tumors without HRD can be effectively treated with the 
combination of niraparib and bevacizumab, the HRD status for pretreatment tumor tissue will be 
determined using the Myriad myChoice® HRD test. 
The combination of niraparib and bevacizumab treatment is currently being explored in patients 
with recurrent platinum-sensitive ovarian cancer as part of an ongoing Phase 1/2 study 
(AVANOVA).15 Phase 1 of the study (dose escalation) has determined the recommended Phase 2 
dose in this population to be 300 mg niraparib orally once daily and 15 mg/kg bevacizumab via 
intravenous (IV) infusion every 3 weeks. Results to date, although limited, indicate clinical 
activity of the combination in this patient population. 
Overall, the combination of niraparib and bevacizumab appears to be safe for administration, 
with a manageable safety profile. AEs observed to date are consistent with those of the 
individual components and are readily managed through routine laboratory testing (ie, CBC), 
clinical surveillance (ie, blood pressure monitoring), and adherence to the recommended dose 
modifications. 
3.6. 
Rationale for Current Trial 
Niraparib is approved in the US for the maintenance treatment of women with recurrent ovarian 
cancer who have a CR or PR to platinum-based chemotherapy following at least 2 previous 
chemotherapy regimens. In addition, a Phase 3 clinical study to evaluate the safety and efficacy 
of niraparib maintenance treatment in patients with advanced ovarian cancer following response 
to front-line, platinum-based therapy, excluding patients who receive bevacizumab in 
combination with their front-line chemotherapy, is ongoing (“PRIMA” study). 
Recent data suggest that the combination of a PARP inhibitor, like niraparib, with a VEGF 
inhibitor, like bevacizumab, in maintenance treatment has the potential for improved PFS 
benefits after front-line chemotherapy in platinum-responsive (CR or PR) ovarian cancer 
patients. This hypothesis is supported by the mechanism of action of both treatments, nonclinical 
studies, and an ongoing Phase 1/2 study in this patient population. To date, the combination has 
proven to be safe for administration for extended periods in patients with advanced ovarian 
cancer.15 


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Based upon the above preclinical and clinical data, the current study is being conducted to 
explore the safety and efficacy of maintenance with PARP inhibitor combined with 
anti-angiogenic agent following front-line, platinum-based therapy combined with bevacizumab. 


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4. 
TRIAL OBJECTIVES AND PURPOSE 
4.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy of niraparib in combination with 
bevacizumab, as assessed by 18-month PFS landmark analysis, in patients with Stage IIIB to IV 
ovarian cancer who have CR, PR, or no evidence of disease (NED) following front-line, 
platinum-based chemotherapy with bevacizumab. 
4.2. 
Secondary Objectives 
Secondary objectives include the following: 
1. To evaluate additional measures of clinical benefit, including PFS, RECIST or CA-125 
progression-free survival, OS, patient-reported outcome (PRO) measures, TFST, and 
time to second subsequent therapy (TSST) 
2. To evaluate the safety and tolerability of niraparib and bevacizumab combination in the 
indicated target population 
4.3. 
Exploratory Objectives 
Exploratory objectives include the following: 
1. To evaluate PFS rate at 6 months (PFS6) and 12 months (PFS12) 
2. Retrospective analysis to evaluate HRD per the Myriad myChoice® HRD test as a 
potential biomarker for response to the niraparib and bevacizumab combination 
 


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5. 
INVESTIGATIONAL PLAN 
5.1. 
Overall Study Design 
This is a multicenter, Phase 2, single-arm, open-label study to evaluate niraparib combined with 
bevacizumab as maintenance treatment in patients with advanced (Stage IIIB-IV) ovarian cancer 
with completely or incompletely resected disease who are recovered from primary debulking 
surgery. 
Approximately 90 eligible patients who achieve CR, PR, or NED following treatment with 
platinum-based chemotherapy in addition to bevacizumab will receive maintenance treatment 
with niraparib (for up to 3 years) combined with bevacizumab (administered for up to 10 months 
during the maintenance phase or up to a total of 15 months inclusive of approximately 5 months 
of bevacizumab received with chemotherapy) or until disease progression, unacceptable toxicity, 
patient withdrawal, Investigator’s decision, or death, whichever comes first (see Figure 1). 
Patients who continue to derive benefit from study treatment based on continuation of non-
progression indicated by imaging, remain clinically stable, and are willing to continue study 
visits and assessments may continue to receive niraparib beyond 3 years following consultation 
with the Investigator and the medical monitor.  Per Investigator discretion and in consultation 
with the Sponsor, patients who are still receiving and benefiting from study treatment at the time 
of study termination may have an option to continue to receive study treatment. 
Sponsor may request that updated survival data be collected on all treated patients outside the 
protocol window noted in the schedule of events. At the time of the request, the site will 
determine survival status for each patient by the method agreed with the patient, unless the 
patient has withdrawn consent for survival FU. 
Study assessments and their timing are outlined in Figure 1. 


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Figure 1: 
Study Schema 
 
 
Abbreviations:  CR = complete response; NED = no evidence of disease; PR = partial response. 
*Patients ≥77 kg and with platelet count of ≥150,000/µL will receive 300 mg/day; patients <77 kg and/or with 
platelet count of <150,000/µL will receive 200 mg/day 
5.2. 
Number of Subjects 
Approximately 90 patients will be enrolled into the study. 
5.3. 
Treatment Assignment 
All patients in this single-arm study will receive maintenance treatment with niraparib in 
combination with bevacizumab. 


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5.4. 
Dose Adjustment Criteria 
5.4.1. 
Niraparib 
To manage adverse reactions, consider interruption of treatment, dose reduction, or dose 
discontinuation, the recommended dose modifications for adverse reactions should be followed 
as listed in Table 3, Table 4, and Table 5.16 Niraparib should be discontinued for selected adverse 
events that persist beyond 28 days as noted in the tables.  
For patients whose initial dose is 3 capsules daily, dose reductions to 2 capsules daily (200 
mg/day) and subsequently to 1 capsule once daily (100 mg/day) will be allowed. No further dose 
reduction will be allowed.  
For patients whose initial dose is 2 capsules, dose reduction to 1 capsule once daily (100 mg/day) 
will be allowed. No further dose reduction will be allowed without discussion with the Medical 
Monitor.  
Table 3: 
Recommended Dose Modifications for Adverse Reactions 
Dose level 
Initial Dose: 3 capsules per day
 
 
Initial Dose: 2 capsules per day 
Starting dose  
300 mg/day (three 100-mg capsules) 
200 mg/day (two 100-mg capsules) 
First dose reduction 
200 mg/day (two 100-mg capsules) 
100 mg/day (one 100-mg capsules) 
Second dose reductiona 
100 mg/day (one 100-mg capsules) 
N/A 
a If further dose reduction is required due to adverse event management, discussion with the Medical Monitor is 
required. 
 
Table 4: 
Dose Modifications for Non-hematologic Adverse Reactions 
Non-hematologic NCI-CTCAE ≥ Grade 3 adverse reaction 
where prophylaxis is not considered feasible or adverse reaction 
event persists despite treatment 
• 
Withhold niraparib for a maximum of 
28 days or until resolution of adverse 
reaction. 
• 
For those adverse reactions that do not 
resolve within 28 days, niraparib 
should be discontinued. Otherwise, 
discussion with the Medical Monitor is 
required to resume niraparib. 
• 
Resume niraparib at a reduced dose 
per Table 3.  
NCI-CTCAE ≥ Grade 3 treatment-related adverse reaction event 
lasting more than 28 days while patient is administered niraparib 
100 mg/day 
Discontinue medication. 
Abbreviations:  NCI-CTCAE = National Cancer Institute - Common Terminology Criteria for Adverse Events. 


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Table 5: 
Dose Modifications for Hematologic Adverse Reactions 
Monitor complete blood counts weekly for the first 2 cycles, and on Day 1 of every cycle thereafter.  
Platelet count < 100,000/µL 
First occurrence: 
• 
Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until platelet counts return to 
≥ 100,000/µL.  
• 
For those adverse reactions that do not resolve within 28 
days, niraparib should be discontinued. Otherwise, 
discussion with the Medical Monitor is required to resume 
niraparib. 
• 
Resume niraparib at same or reduced dose per Table 3: . 
• 
If nadir platelet count was < 75,000/µL, resume at a reduced 
dose after recovery. 
 
Second occurrence: 
• 
Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until platelet counts return to 
≥ 100,000/µL.  
• 
For those adverse reactions that do not resolve within 28 
days, niraparib should be discontinued. Otherwise, 
discussion with the Medical Monitor is required to resume 
niraparib. 
• 
Resume niraparib at a reduced dose per Table 3 . 
• 
Discontinue niraparib if the platelet count has not returned to 
acceptable levels within 28 days of the dose interruption 
period, or if the patient has already undergone dose reduction 
to 100 mg QD.a 
Neutrophil < 1,000/µL or  
Hemoglobin < 8 g/dL 
• 
Withhold niraparib for a maximum of 28 days and monitor 
blood counts weekly until neutrophil counts return to 
≥ 1,500/µL or hemoglobin returns to ≥ 9 g/dL.  
• 
For those adverse reactions that do not resolve within 28 
days, niraparib should be discontinued. Otherwise, 
discussion with the Medical Monitor is required to resume 
niraparib.  
• 
Resume niraparib at a reduced dose per Table 3. 
• 
Discontinue niraparib if neutrophil or hemoglobin level has 
not returned to acceptable levels within 28 days of the dose 
interruption period or if the patient has already undergone 
dose reduction to 100 mg QD.a 
Hematologic adverse reaction 
requiring transfusion 
• 
For patients with platelet count ≤ 10,000/μL, platelet 
transfusion should be considered. If there are other risk 
factors, such as co-administration of anticoagulation or 
antiplatelet drugs, consider interrupting these drugs and/or 
transfusion at a higher platelet count. 
• 
Resume niraparib at a reduced dose. 


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MDS/AML 
• Any suspected case of MDS/AML reported while a 
patient is receiving treatment or followed for post-
treatment assessments must be referred for evaluation 
to a local hematologist to perform bone marrow 
aspirate and biopsy as per local practice. The study site 
must receive a copy of the hematologist’s report of 
aspirate/biopsy findings, which must include a 
classification according to WHO, and other sample 
testing reports related to MDS/AML. If a diagnosis 
of MDS/AML is confirmed by a hematologist, the 
patient must permanently discontinue study treatment.  
Abbreviations:  AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; QD = once daily. 
 
a If MDS/AML is confirmed, discontinue niraparib. 
5.4.2. 
Bevacizumab 
The Investigator is advised to consult the current bevacizumab label. Dose reductions of 
bevacizumab are not permitted in this study.1,17  
Interrupt bevacizumab treatment for the following adverse events: proteinuria, medically 
significant hypertension that cannot be adequately controlled with antihypertensive therapy, 
hypertension in the presence of posterior reversible encephalopathy syndrome, development of 
hypertensive crisis or hypertensive encephalopathy, or nephrotic syndrome. In case of 
uncontrolled hypertension, niraparib should also be held in addition to bevacizumab.  
Resume bevacizumab treatment only when 1) hypertension is controlled by hypertensive 
regimen, or 2) urine protein is < 2 g per 24 hours urine collection.17 Niraparib should be resumed 
with bevacizumab when hypertension is controlled by hypertensive regimen. If hypersensitivity 
or infusion reactions occur during bevacizumab infusion, the infusion should be discontinued. 
Except in cases where permanent discontinuation of bevacizumab is indicated, resumption of the 
standard dose of bevacizumab upon resolution of other adverse reactions is at the discretion of 
the Investigator. 
Bevacizumab treatment should be withheld 4 weeks prior to elective surgery. In patients who 
experience wound healing complications during the study, treatment with bevacizumab should 
be withheld until the wound is fully healed.  
5.5. 
Criteria for Study Termination 
The Sponsor may terminate this study at any time. The Sponsor will notify the Investigators 
when the study is to be placed on hold, completed, or terminated. Per Investigator discretion and 
in consultation with the Sponsor, patients who are still receiving and benefiting from study 
treatment may have an option to continue to receive study treatment. 


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Table 6: 
Schedule of Events 
Visit/Procedure 
Screening 
Cycle 1a 
Cycle 2a 
Subsequent 
cyclesa 
EOTb 
Post- 
treatment 
assessments 
Day 
-28 to -1 
1 
1 
C(n)/D1 
Within 7 days of 
the decision to 
discontinue 
treatment  
Every 
12 weeks  
Visit Window 
 
±3 days 
±3 days 
±3 days 
 
±14 days 
(unless 
otherwise 
specified) 
Informed consent 
X 
 
 
 
 
 
Demographics and height 
X 
 
 
 
 
 
Medical, surgical, cancer (including genotyping), and medication 
history  
X 
 
 
 
 
 
Medical history/concomitant medications 
 
X 
X 
X 
X 
 
Sample collection (tumor) for HRD testingc 
X 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
Serum or urine pregnancy testd 
Xd 
X  
X 
X 
X 
 
Physical examination 
X 
X 
X 
X 
X 
 
Vital signs and weight 
X 
X 
X 
X 
X 
 
ECOG performance status 
X 
X 
X 
X 
X 
 
CBCe 
X 
Days 1, 8, and 15 of 
Cycle 1f and Cycle 2 
X 
X 
 
Serum chemistry and coagulation 
X 
Xf 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 


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Visit/Procedure 
Screening 
Cycle 1a 
Cycle 2a 
Subsequent 
cyclesa 
EOTb 
Post- 
treatment 
assessments 
Day 
-28 to -1 
1 
1 
C(n)/D1 
Within 7 days of 
the decision to 
discontinue 
treatment  
Every 
12 weeks  
Visit Window 
 
±3 days 
±3 days 
±3 days 
 
±14 days 
(unless 
otherwise 
specified) 
Urine sample for proteing 
X 
Xg 
Xg 
Xg 
 
 
Serum CA-125 
X 
X 
X 
X 
X 
X 
RECIST v1.1 assessmenth 
X 
 
 
Xh 
X 
X 
Chest CT or MRIi 
X 
 
 
 
 
 
PRO 
X 
Q6W (±7 days) for 6 months, then 
Q12W (±7 days) 
4, 8, 12, and 24 weeks (±7 days) 
after last dose 
Niraparib dispensed or collected 
 
X 
X 
X 
X 
 
Bevacizumab infusion 
 
X 
X 
X 
 
 
Adverse event monitoringj 
X 
X 
X 
X 
X 
X 
Anticancer therapies assessment 
 
 
 
 
 
X 
Survival assessment (telephone assessment allowed)k  
 
 
 
 
 
X 
Bone marrow aspirate and biopsy 
 
For any suspected case of MDS/AML or secondary cancer (new malignancy 
other than MDS/AML) reported while on study, a bone marrow 
aspirate/biopsy must be completed by a local hematologist. 


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Abbreviations:  AE = adverse event; AML = acute myelogenous leukemia; C = cycle; CA-125 = cancer antigen 125; CBC = complete blood count; 
CT = computed tomography; D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; FOSI = Functional 
Assessment of Cancer Therapy–Ovarian Symptom Index; HRD = homologous recombination deficiency; MDS = myelodysplastic syndrome; MRI = magnetic 
resonance imaging; PE = physical examination; QxW = every x weeks; RECIST = Response Evaluation Criteria in Solid Tumors 
a Treatment cycles are 21 days (±3 days) until the implementation of protocol amendment 2 at which time cycles will be 84-days (+/- 7 days).  
b EOT is defined as the discontinuation of treatment for any reason.  
c The tumor sample must be confirmed to be available during the screening period and submitted after the patient has been enrolled; patients do not have need to 
wait for the HRD test result to be enrolled. If archival tumor tissue is not available for testing, the patient must agree to undergo a fresh biopsy. 
d For patients of childbearing potential only. If completed within 72 hours of the first dose, pregnancy testing does not need to be repeated. 
e 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 
AE resolves, and to ensure safety of the new dose, weekly blood draws for CBC will also 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. 
f Screening assessments completed within 7 days of the first dose do not need to be repeated, unless otherwise specified.   
g Urine dipstick for protein determination should be performed prior to each bevacizumab administration. Patients discovered to have ≥ 2 proteinuria on dipstick 
should not be administered bevacizumab, should undergo a 24-hour urine collection, and must demonstrate < 2 g of protein in 24 hours to be eligible for 
bevacizumab treatment to resume. 
h RECIST v1.1 tumor assessment via CT or MRI scan of the abdomen/pelvis and clinically indicated areas required at screening, every 12 weeks (±7 days) from 
Cycle 1/Day 1 for the first 48 weeks, then every 24 weeks (±14 days) until disease progression.  Once patients transition to an 84-day cycle (every 12 weeks) 
the next scan should be at a regularly scheduled visit such that the follow-up scan is no less than 21 weeks and no more than 30 weeks after the last scan. 
i Chest CT or MRI if not done as part of RECIST tumor assessment. If the chest CT or 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; otherwise, repeat chest imaging should be completed at the same 
time as RECIST imaging. 
j All AEs and SAEs, regardless of causality, will be collected and recorded for each patient from the day the ICF is signed until 90 days (±14 days) after the last 
dose of study treatment or until alternate anticancer therapy has been initiated, whichever occurs first. 
k Patients will be followed until study closeout for survival status and study-drug related SAEs. Patients will be followed for AESI as outlined in Section 10.3.7. 
Sponsor may request that updated survival data be collected on all treated patients outside the protocol window. At the time of the request, the site will 
determine survival status for each patient by the method agreed with the patient, unless the patient has withdrawn consent for survival FU. 
 


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6. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1. 
Subject Inclusion Criteria 
To be considered eligible to participate in this study, all of the following inclusion criteria must 
be met: 
1. Patients must be female, be ≥ 18 years of age, be able to understand the study procedures, 
and agree to participate in the study by providing written informed consent. 
2. Patients must have newly diagnosed FIGO Stage IIIB to IV epithelial ovarian, fallopian 
tube, or peritoneal cancer and have recovered from debulking surgery. 
3. Patients must have high-grade serous or endometrioid or high-grade predominantly 
serous or endometrioid histology, regardless of HRD or gBRCA mutation status. Patients 
with non-mucinous epithelial ovarian cancer and gBRCA mutation are eligible. 
4. Patients must have completed front-line, platinum-based chemotherapy with CR, PR, or 
NED and have first study treatment dose within 12 weeks of the first day of the last cycle 
of chemotherapy: 
a. A platinum-based regimen must have consisted of a minimum of 6 and a maximum of 
9 treatment cycles. Patients who discontinued platinum-based therapy early as a result 
of non-hematologic toxicity specifically related to the platinum regimen 
(ie, neurotoxicity or hypersensitivity) are eligible if they have received a minimum of 
4 cycles of the platinum regimen. 
b. IV, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for 
weekly therapy, 3 weeks is considered 1 cycle. Interval debulking is allowed. 
5. Patients must have received, prior to enrollment, a minimum of 3 cycles of bevacizumab 
in combination with the last 3 cycles of platinum-based chemotherapy. Patients who 
undergo interval debulking surgery are eligible if they have received only 2 cycles of 
bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy.  
6. Patients must have had 1 attempt at optimal debulking surgery. 
7. Patients must have either CA-125 in the normal range or CA-125 decrease by more than 
90% during front-line therapy that is stable for at least 7 days (ie, no increase > 15% from 
nadir). 
8. Patients must have adequate organ function, defined as (Note:  CBC test should be 
obtained without transfusion or receipt of stimulating factors within 2 weeks before 
obtaining screening blood sample): 
a. Absolute neutrophil count (ANC) ≥ 1,500/µL 
b. Platelet count ≥ 100,000/µL 
c. Hemoglobin ≥ 9 g/dL 
d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 60 mL/min using Cockcroft-Gault equation 


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e. Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ 1 × ULN 
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN 
unless liver metastases are present, in which case they must be ≤ 5 × ULN 
9. Patients must have an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. 
10. Patients must have normal blood pressure or well-controlled hypertension. 
11. Patient must agree to complete PROs (FOSI) throughout the study, including after study 
treatment discontinuation. 
12. Patients must be able to take oral medication. 
13. Patient must agree to undergo tumor HRD testing at screening. The tumor sample must 
be confirmed to be available during the screening period and submitted after the patient 
has been enrolled; patients do not have to wait for the HRD test result to be enrolled. If 
archival tumor tissue is not available for testing, the patient must agree to undergo a fresh 
biopsy.  
14. Patients of childbearing potential must have a negative serum or urine pregnancy test 
(beta human chorionic gonadotropin) within 72 hours prior to receiving the first dose of 
study treatment. 
15. Patients must be postmenopausal, free from menses for > 1 year, surgically sterilized, or 
willing to use adequate contraception to prevent pregnancy (see Appendix 1)or must 
agree to abstain from activities that could result in pregnancy throughout the study, 
starting with enrollment through180 days after the last dose of study treatment. 
6.2. 
Subject Exclusion Criteria 
A patient will be considered ineligible for study participation if any of the following exclusion 
criteria are met: 
1. Patients with ovarian tumors of non-epithelial origin (eg, germ cell tumor) or any 
low-grade tumors. 
2. Patients with clinically significant cardiovascular disease (eg, significant cardiac 
conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac 
arrhythmia or unstable angina < 6 months to enrollment, New York Heart Association 
[NYHA] Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring 
medication, Grade II or greater peripheral vascular disease, and history of 
cerebrovascular accident [CVA] within 6 months). 
3. Patients with gastrointestinal disorders or abnormalities that would interfere with 
absorption of study treatment. 
4. History of bowel obstruction, including sub-occlusive disease, related to the underlying 
disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal 
abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel 
involvement on computed tomography (CT) scan or clinical symptoms of bowel 
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5. Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥ 1.0 at 
screening or urine dipstick for proteinuria ≥ 2 (patients discovered to have ≥ 2 proteinuria 
on dipstick at baseline should undergo a 24-hour urine collection and must demonstrate 
< 2 g of protein in 24 hours to be eligible). 
6. Patient has any known history or current diagnosis of MDS or AML. 
7. Patient has received treatment previously with a PARP inhibitor. 
8. Other than ovarian cancer, the patient has been diagnosed or treated for invasive cancer 
less than 5 years prior to study enrollment. Patients with cervical carcinoma in situ, 
non-melanomatous skin cancer, and ductal carcinoma in situ definitively treated are 
allowed. 
9. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, 
non-malignant systemic disease, or active, uncontrolled infection. 
10. Patient has known contraindication to PARP inhibitors or VEGF inhibitors. 
11. Patient is at increased bleeding risk due to concurrent conditions (eg, major injuries or 
surgery within the past 28 days prior to start of study treatment, history of CVA, transient 
ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within 
the past 3 months). 
12. Patient is immunocompromised (patients with splenectomy are allowed). 
13. Patient has known, active hepatic disease (ie, hepatitis B or C). 
14. Patient has a QT interval prolongation > 480 ms at screening. If a patient has a prolonged 
QT interval and the prolongation is deemed to be due to a pacemaker upon Investigator 
evaluation (ie, the patient otherwise has no cardiac abnormalities), then the patient may 
be eligible to participate in the study following discussion with the Medical Monitor. 
15. Patient is pregnant or expecting to conceive children while receiving study drug and for 
180 days after the last dose of study drug; additionally, female patients should not 
breastfeed during treatment with niraparib and for 30 days after receipt of the last dose 
due to the potential for serious adverse reactions from niraparib in breastfed infants. 
6.3. 
Subject Withdrawal Criteria 
6.3.1. 
Discontinuation from Treatment 
Patients may be discontinued from either study treatment at any time. Patients who discontinue 
from study treatment or from the study will not be replaced. 
Specific reasons for discontinuing either treatment include the following, in addition to those 
indicated in Section 5.4: 
• AE 
− Any treatment-related NCI-CTCAE v4.03 Grade 3 or 4 events (see separate guidelines 
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within 28 days. Patients determined to be deriving clinical benefit may continue study 
treatment following discussion with the medical monitor. 
− At the Investigator's discretion, following dose interruption (no longer than 28 days), 
patients may be considered for niraparib dose reductions, provided they have not already 
undergone the maximum number of 2 dose reductions allowed. If upon re-challenge with 
study treatment at the lowest allowable dose any NCI-CTCAE v4.03 Grade 3 or 4 AEs 
recur, the patient must be discontinued from niraparib treatment. 
• In the case of thrombocytopenia, if the platelet count has not returned to ≥ 100,000/µL within 
28 days of dose interruption, then the patient should be discontinued. Patients determined to 
be deriving clinical benefit may continue study treatment following discussion with the 
medical monitor. 
• Disease progression according to Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 criteria per Investigator assessment 
• Risk to patients as judged by the Investigator, Sponsor, or both 
• Severe noncompliance with protocol as judged by the Investigator, Sponsor, or both 
• Patient becomes pregnant 
• Withdrawal of consent 
• Loss to follow-up 
• Death 
In addition, specific reasons for permanently discontinuing bevacizumab treatment include the 
following: 
• Gastrointestinal perforation 
• Tracheosophageal fistula or any NCI-CTCAE v4.03 Grade 4 fistula 
• NCI-CTCAE v4.03 Grade 3 or 4 bleeding 
• Arterial thromboembolic reactions 
• NCI-CTCAE v4.03 Grade 4 thromboembolic reactions, including pulmonary embolism 
• Medically significant hypertension that cannot be adequately controlled with 
antihypertensive therapy, hypertension in the presence of posterior reversible encephalopathy 
syndrome, or development of hypertensive crisis or hypertensive encephalopathy 
• Nephrotic syndrome 
 
All patients must be followed for survival until median OS is met and reported. Discontinuation 
of study treatment does not impact a patient’s participation in the study. The patient should 
comply to the protocol schedule of events and data collection should continue.  


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If the patient does not agree to continue in-person visits, a modified follow-up must be arranged 
to ensure the collection of endpoints and safety information. This could be a telephone contact 
with the patient, a contact with a relative or treating physician, or collecting information from 
medical records. The approach taken should be recorded in the medical records. A patient who 
agrees to modified follow-up is not considered to have withdrawn consent or to have withdrawn 
from the study. 
6.3.2. 
Discontinuation from the Study 
Specific reasons for discontinuing from the study include the following: 
• Withdrawal of consent by the patient, who is at any time free to discontinue participation in 
the study, without prejudice to further treatment 
• Loss to follow-up 
• Death from any cause 
• Sponsor decision to terminate study 
If a patient is thought to be lost to follow-up, discontinues study treatment, or discontinues the 
study, attempts should be made to contact the patient to determine the reason for discontinuation. 
For patients who are thought to be lost to follow-up, at least 3 documented attempts, including 1 
attempt via certified mail, should be made to contact the patient before the patient is deemed lost 
to follow-up. 
6.3.3. 
Withdrawal of Consent 
If a patient withdraws consent, the Investigator is to determine whether the patient is willing to 
be followed up for subsequent procedures in the long-term follow-up period and for OS. Such 
patients will be required to indicate whether they agree to continue these procedures as well as 
whether they agree to collection of their disease history information until the end of the study. 
This information will be recorded on the appropriate eCRF page. 
6.3.3.1. 
Further Research Maintaining Confidential Patient Information 
The Sponsor may conduct further research on specimens collected during this study. This 
research may include genetic/genomic, proteomic, metabolomic, and transcriptional analyses. 
The data generated may be combined with clinical and histological image analysis. Such 
research helps to address emergent questions not described in the protocol and will only be 
conducted on specimens from properly consented patients. 
In an effort to optimize the research that can be conducted with further research specimens, it is 
essential to link study patient clinical study data with further research test results. The clinical 
study data allow specific analyses to be conducted. Knowing patient characteristics like gender, 
age, medical history, treatment type, and treatment outcomes are critical to understanding the 
clinical context of further research analytical results. 
To maintain privacy of information collected from specimens obtained for further research, the 
Sponsor has developed secure policies and procedures. All specimens will be single coded per 


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International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) E15 guidelines, “Definitions for Genomic Biomarkers, Pharmacogenomics, 
Pharmacogenetics, Genomic Data and Sample Coding Categories18”. 
At the clinical study site, unique codes will be placed on the further research specimens for 
transfer to the storage facility. This first code is a random number that does not contain any 
personally identifying information embedded within it in order to maintain patient privacy. The 
link (or key) between patient identifiers and this first unique code will be held at the study site. 
No personal identifiers will appear on the specimen tube. 
Documentation of patient life-time consent for further research will be captured in the eCRFs. 
Any specimens for which such an informed consent cannot be verified will be destroyed, as will 
those requested to be destroyed at time of consent withdrawal. 
Patients may withdraw their consent for further research and have their specimens and all 
derivatives destroyed. Patients may withdraw consent at any time by contacting the Investigator. 
6.4. 
Lost to Follow Up 
A patient will be considered lost to follow-up if she repeatedly fails to return for scheduled visits 
and is unable to be contacted by the study site.  
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible, counsel the patient on the importance of maintaining the assigned visit schedule and 
ascertain whether the patient wishes to and/or should continue in the study. 
• Before a patient is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the patient (where possible, telephone calls and, if necessary, a 
certified letter to the patient’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, she will be considered to have withdrawn 
from the study.  
• Site personnel, or an independent third party, will attempt to collect the vital status of the 
patient within legal and ethical boundaries for all patients. Public sources may be searched 
for vital status information. If vital status is determined as deceased, this will be documented, 
and the patient will not be considered lost to follow-up. Sponsor personnel will not be 
involved in any attempts to collect vital status information. 
 


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7. 
TREATMENT OF SUBJECTS 
7.1. 
Description of Study Drug 
Table 7: 
Investigational Products 
 
Investigational product 
Product name 
Niraparib 
Bevacizumab (Avastin) 
Dosage form 
Capsule 
Infusion 
Unit dose 
100 mg per capsule 
15 mg/kg infusion 
Route of administration 
Oral 
Intravenous 
Physical description 
Capsules in high-density 
polyethylene bottles 
Clear to slightly opalescent, 
colorless to pale brown, sterile 
solution 
Manufacturer 
7.2. 
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 the electronic case report form (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.  
Niraparib has potential to weakly induce cytochrome P450 (CYP) 1A2. Therefore, patients 
should be advised to use caution with drugs that are substrates of CYP1A2 with narrow 
therapeutic range. The substrates of CYP1A2 with narrow therapeutic range include theophylline 
and tizanidine. The niraparib safety profile includes risk for thrombocytopenia, and bevacizumab 
may increase the potential for bleeding. Therefore, patients should be advised to use caution with 
anticoagulants (eg, warfarin) and antiplatelet drugs (eg, aspirin). 
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; therefore, 
live virus and bacterial vaccines should not be administered to patients in the study. 
No other anticancer therapy is permitted during the course of the study treatment for any patient. 
Palliative radiotherapy (excluding the pelvic region and/or palliative radiotherapy encompassing 
> 20% of the bone marrow within 1 week of the first dose of study treatment) is allowed for 
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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. 
Prophylactic cytokines (granulocyte colony-stimulating factor) should not be administered in the 
first cycle of the study but may be administered in subsequent cycles according to local 
guidelines. 
7.3. 
Treatment Compliance 
Compliance with inclusion and exclusion criteria will be assessed as outlined in Section 6.1 and 
Section 6.2, respectively. 
Niraparib and bevacizumab will be administered by site personnel at study sites as detailed in 
Section 8.5. 
Study drug accountability will be monitored as detailed in Section 8.6. 
7.4. 
Randomization and Blinding 
Not applicable; this is a single-arm, open-label study. 


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8. 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1. 
Study Drug 
8.1.1. 
Niraparib 
Niraparib ([3S]-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl] piperidine [tosylate 
monohydrate salt]) is an orally available, potent, highly selective PARP1 and PARP2 inhibitor. 
The excipients for niraparib are lactose monohydrate and magnesium stearate. Niraparib will be 
supplied as 100-mg capsules. 
8.1.2. 
Bevacizumab 
Bevacizumab (Avastin) is a clear to slightly opalescent, colorless to pale brown, sterile, pH 6.2 
solution for IV infusion17. The excipients for bevacizumab are trehalose dihydrate, sodium 
phosphate, polysorbate 20, and water for injections. Bevacizumab is obtained from commercial 
sources according to local practice standards and it is provided as a commercially available 
dosage.  
8.2. 
Study Drug Packaging and Labeling 
The label text of the study treatments will comply with Good Manufacturing Practice and 
national legislation to meet the requirements of the participating countries. The study treatment 
will be open-label and not patient-specific. 
8.3. 
Study Drug Storage 
All study treatment supplies must be stored in accordance with the Pharmacy Manual 
instructions and package labeling. Until dispensed or administered to the patients, the study 
treatment will be stored in a securely locked area that is accessible only to authorized personnel. 
8.4. 
Study Drug Preparation 
Please refer to the Bevacizumab USPI for instructions and precautions regarding preparation. 
8.5. 
Administration 
8.5.1. 
Niraparib 
Niraparib will be administered orally once a day, continuously throughout each 21-day cycle 
(84-day cycle after implementation of amendment 2), for up to 3 years in the absence of 
progressive disease (PD), unacceptable toxicity, patient withdrawal, Investigator’s decision, or 
death.  On Day 1 of each cycle, niraparib will be administered upon completion of bevacizumab 
infusion.  
Patients who continue to derive benefit from study treatment based on continuation of non-
progression indicated by imaging, remain clinically stable, and are willing to continue study 
visits and assessments may continue to receive niraparib beyond 3 years following consultation 
with the Investigator and the medical monitor.   


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The starting dose of niraparib will be based on the patient’s baseline actual body weight or 
platelet count. Patients with a baseline actual body weight of ≥77 kg and baseline platelet count 
of ≥150,000/µL will take three capsules of 100 mg strength (300 mg/day) at each dose 
administration. Patients with a baseline actual body weight of <77 kg and/or baseline platelet 
count of <150,000/µL will take two capsules of 100 mg strength (200 mg) at each dose 
administration. Additional dose modifications will not be based upon changes in the patient’s 
actual body weight during study participation.  
For patients whose starting dose is 2 capsules (200 mg/day), escalation to 3 capsules (300 
mg/day) is permitted if no treatment interruptions or discontinuations were required during the 
first 2 cycles of therapy. This escalation will occur at the discretion of the Investigator, following 
discussion with the Medical Monitor. 
Table 8: 
Recommended Initial Starting Dose 
Baseline Criteria 
Starting Dose 
≥77 kg and ≥150,000/μL 
300 mg (3 X 100 mg capsules) daily 
<77 kg and/or <150,000/μL 
200 mg (2 X 100 mg capsules) daily 
Patients will be instructed to take their niraparib dose once daily or as instructed by the 
Investigator. Patients must swallow and not chew all capsules. The consumption of water and 
food is permissible. If a patient vomits or misses a dose of niraparib, a replacement dose should 
not be taken.  
Details on the administration of niraparib can be found in the Pharmacy Manual. 
Niraparib can be shipped direct-to-patient from the investigational site to the patient’s home 
address, details are provided in the Study Pharmacy Manual. 
8.5.2. 
Bevacizumab 
Maintenance bevacizumab 15 mg/kg will be administered at the study site via a 30-minute IV 
infusion on Day 1 of every 21-day cycle in the absence of PD, unacceptable toxicity, patient 
withdrawal, Investigator’s decision, or death.1 Bevacizumab will be administered for up to 10 
months during the maintenance phase or up to a total of 15 months inclusive of approximately 5 
months of bevacizumab received with chemotherapy. 
Details on the administration of bevacizumab can be found in the bevacizumab USPI. 
8.6. 
Study Drug Accountability 
The Investigator or designee is responsible for maintaining accurate dispensing records of the 
study treatments throughout the clinical study. 
Details of maintaining drug accountability, including information on the accountability log, will 
be provided in the Pharmacy Manual. 
All dispensation and accountability records will be available for Sponsor review. The Study 
Monitor will assume the responsibility to reconcile the study treatment accountability log. The 


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Pharmacist will dispense study treatment for each patient according to the protocol and 
Pharmacy Manual, if applicable. 
8.7. 
Study Drug Handling and Disposal 
At the end of study, when all patients have stopped protocol treatment, complete drug 
reconciliation per batch should be available at the site for verification in order to allow drug 
destruction or return procedure. After receiving Sponsor approval in writing, the investigational 
site is responsible for destruction of study drug according to local regulations. If a site does not 
have the capability for onsite destruction, the Sponsor will provide a return for destruction 
service through a third party. Both the unused and expired study treatment must be destroyed, 
upon authorization of the Sponsor, according to local regulations and procedures, and a copy of 
the destruction form must be filed in the study binder. 
The medication provided for this study is to be used only as indicated in this protocol and only 
for the patients entered in this study. 


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9. 
ASSESSMENT OF EFFICACY 
9.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is PFS rate at 18 months (PFS18), which is defined as the 
proportion of patients who have not progressed or died within 18 months after niraparib 
combined with bevacizumab treatment initiation. Progression will be assessed by RECIST v1.1 
criteria per Investigator assessment. PFS18 will be estimated using percentage with 95% exact 
CI. In addition, the probability of PFS at 18 months will be estimated using the Kaplan-Meier 
method. 
The date of PD will be determined by Investigator assessment. This review will be based on 
imaging assessment according to RECIST v1.1 criteria (Appendix 2). Positron emission 
tomography (PET)/CT may be used according to RECIST v1.1 guidelines, but its use is not a 
study requirement.  
RECIST v1.1 is used to define PD in this study. Tumor assessment by CT/magnetic resonance 
imaging (MRI) must unequivocally show PD according to RECIST v1.1 criteria (Appendix 2). 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 informed consent form 
(ICF), the patient is not required to complete an additional CT/MRI scan for study screening.  
The Investigator will describe how PD criteria is met. When required to determine CA-125 
progression, CA-125 levels should be evaluated ± 2 weeks from the primary PD assessments and 
must be confirmed by a second determination ≥ 7 days later. In case assessments of CA-125 
levels that occur > 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:  
Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence 
of CA-125 ≥ 2 × ULN on 2 occasions at least 1 week apart, OR 
1. Patients with elevated CA-125 pretreatment that never normalizes must show evidence of 
CA-125 ≥ 2 × the nadir value on 2 occasions at least 1 week apart, OR 
2. Patients with CA-125 in the normal range pretreatment must show evidence of 
CA-125 ≥ 2 × ULN on 2 occasions at least 1 week apart. 
PD will not be diagnosed in case of CA-125 progression in the absence of radiologic evidence of 
progressive disease.  
If CT/MRI shows existing (baseline) lesions that 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 and are later unequivocally determined, the date of progression will be 
the date the lesion was initially identified. 


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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 loss to follow-up, scans should continue at the specified intervals.  
9.2. 
Secondary Efficacy Endpoints 
9.2.1. 
Progression-free Survival 
For each patient in the study, PFS will be assessed. PFS is defined as the time from niraparib 
combined with bevacizumab treatment initiation to the earlier date of assessment of progression, 
as assessed by RECIST v1.1 criteria, based on Investigator assessment, or death by any cause in 
the absence of progression. 
9.2.2. 
Overall Survival 
OS is defined as the date of initiation of niraparib treatment in combination with bevacizumab to 
the date of death by any cause. Following the End of Treatment 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. 
9.2.3. 
RECIST or CA-125 Progression-free Survival  
RECIST or CA-125 progression-free survival is defined as the time from initiation of niraparib 
treatment in combination with bevacizumab to the earliest date of progression assessed by 
RECIST v1.1. or CA-125 progression or death by any cause. CA-125 progression will be defined 
as described in Section 9.1. (Note:  CA-125 progression without radiologic evidence of 
progressive disease will not be considered disease progression.) 
CA-125 levels must be normal at screening or have a > 90% decrease compared to baseline prior 
to their last platinum-based chemotherapy course that is stable for at least 7 days (i.e., no 
increase > 15% from nadir). Abnormal CA-125 levels on study do not represent disease 
progression; however, they may prompt imaging if clinically indicated. 
9.2.4. 
Patient Reported Outcome - Functional Assessment of Cancer Therapy–Ovarian 
Symptom Index 
Observed changes from baseline in the Functional Assessment of Cancer Therapy–Ovarian 
Symptom Index (FOSI) PRO will be assessed (see Appendix 4). 
The FOSI is a validated 8-item measure of symptom response to treatment for ovarian cancer.19 
Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale 
scored from
 to 
 The average score is calculated as an average of 
the 8 items. The total symptom index is calculated as the total of the 8 symptoms. 
PROs will be collected every 6 weeks (± 7 days) for 6 months, then every 12 weeks (± 7 days) 
thereafter while the patient is receiving study treatment. Once a patient discontinues treatment, 
PRO evaluations will be performed 4 weeks (± 7 days), 8 weeks (± 7 days), 12 weeks (± 7 days), 
and 24 weeks (± 7 days) after treatment discontinuation, regardless of subsequent treatment. 
CCI
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PROs may be completed remotely. If a  patient is unable to attend a study visit when a FOSI is 
due per the schedule of events, the Sponsor recommends that a copy is sent to the patient. The 
patient can return the form during the next schedule visit or by return mail, whichever is more 
convenient. It is estimated that PRO evaluations will take less than 20 minutes at each timepoint. 
Since these are questionnaires, their completion will not interfere with or prevent future 
treatment or clinical studies. PRO evaluations should be administered prior to conducting any 
other procedures at each visit. 
9.2.5. 
Time to First Subsequent Therapy 
TFST is defined as the date of initiation of niraparib treatment in combination with bevacizumab 
treatment in the current study to the start date of the first subsequent anticancer therapy. 
9.2.6. 
Time to Second Subsequent Therapy 
TSST is defined as the date of initiation of treatment of niraparib in combination with 
bevacizumab treatment in the current study to the start date of the second subsequent anticancer 
therapy. 
9.3. 
Exploratory Efficacy Endpoints 
The exploratory efficacy endpoints are PFS rate at 6 months (PFS6) and 12 months (PFS12), 
which are defined as the proportion of patients who have not progressed or died within 6 months 
and 12 months after initiation of treatment of niraparib in combination with bevacizumab 
treatment, respectively. Progression will be assessed by RECIST v1.1 criteria based on 
Investigator assessment. Additional landmark PFS analyses may be performed as deemed 
appropriate. 
9.4. 
Biomarker Analysis 
HRD will be evaluated retrospectively as a potential biomarker for response to niraparib 
combined with bevacizumab maintenance treatment using archival tumor sample. For patients 
who do not have archival tissue, tissue from a fresh biopsy must be obtained prior to study 
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10. 
ASSESSMENT OF SAFETY 
10.1. 
Safety Parameters 
Safety will be evaluated based on the incidence of TEAEs, serious adverse events (SAEs), 
treatment discontinuations or dose reductions due to AEs, changes in ECOG performance status, 
changes in clinical laboratory results (hematology and chemistry), vital sign measurements, 
observations during physical examination, and use of concomitant medications. All AEs will be 
coded using the current version of the Medical Dictionary for Regulatory Activities (MedDRA) 
coding system. 
10.1.1. 
Demographic/Medical History 
Demographic and baseline characteristics consist of those variables that are assessed at 
screening/baseline. Patient demographics consist of age at screening, race, ethnicity, and sex. 
10.1.1.1. Disease History 
For disease history, the following will be documented: 
• Date of diagnosis 
• Tumor type 
• Stage at time of initial diagnosis 
• Histology and grade of disease at diagnosis 
• Genotyping, such as gBRCA or somatic BRCA (sBRCA) status, if known 
• Information on first anticancer treatment: 
− Adjuvant or neoadjuvant and adjuvant chemotherapy 
− Date of start and end of platinum-based treatment and date of start and end of 
bevacizumab treatment 
− Number of cycles (21 days = 1 cycle) of platinum-based chemotherapy and number of 
cycles of bevacizumab 
− Agents used in treatment 
• Best response (CR, PR, or NED) following first-line anticancer treatment 
• Toxicities (including hematologic events) due to first-line anticancer treatment 
10.1.1.2. Medical and Surgical History 
Major medical and surgical history (including medication history and history of 
thrombocytopenia, neutropenia, leukopenia, or anemia) will be collected. Details of any prior 
invasive malignancy will be collected. Medical and surgical history will be obtained by 
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10.1.1.3. Previous and Concomitant Medications 
Previous and concomitant medications will be documented as described in Section 7.2. 
Medications will be coded using World Health Organization (WHO) Anatomical Therapeutic 
Chemical classification. 
10.1.2. 
Vital Signs 
Vital signs include blood pressure, pulse rate, and temperature and will be measured in 
accordance with the schedule of events (Table 6). 
10.1.3. 
Weight and Height 
Weight and height will be measured in accordance with the schedule of events (Table 6). Height 
will be measured at screening only. 
10.1.4. 
Physical Examination 
Physical examinations will be performed in accordance with the schedule of events (Table 6). 
Any physical examination or vital signs assessed as clinically significant should be recorded as 
an AE or SAE. If SAE criteria are met, the finding should be recorded and reported according to 
the SAE reporting process (see Section 10.3.5). 
10.1.5. 
Laboratory Assessments 
The following laboratory variables will be determined in accordance with the schedule of events 
(Table 6). These tests will be performed by the local laboratory at the clinical site. 
Any laboratory values assessed as clinically significant should be recorded as an AE. If SAE 
criteria are met or if the laboratory abnormality is an adverse event of special interest (AESI; see 
Section 10.3.7), the event should be recorded and reported according to the SAE reporting 
process (see Section 10.3.5). 
Hematologic testing may occur more frequently than is specified in Section 10.1.5.1, if 
additional testing is medically indicated per Investigator judgment or if the event meets the 
criteria for niraparib dose modification (see Section 5.4.1). Additional tests may be performed at 
a laboratory facility other than the study site, but the 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 eCRF. 
Any suspected case of MDS/AML or secondary cancer (new malignancy other than MDS/AML) 
reported while a patient is receiving treatment or followed for post-treatment assessments must 
be referred to a local hematologist to perform bone marrow aspirate and biopsy. 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 WHO20, and other 
sample testing reports related to MDS/AML. Report data will be entered in the appropriate eCRF 
pages, and the site must keep a copy of all reports with the patient’s study file. 


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10.1.5.1. Hematology 
The following hematologic parameters will be measured: 
• CBC: 
− Hemoglobin 
− Platelet count 
− Mean corpuscular volume 
− White blood cell count 
− Differential white blood cell count 
• Coagulation factors: 
− International normalized ratio 
− Activated partial thromboplastin time 
10.1.5.2. Blood Chemistry 
The following blood chemistry parameters will be measured: 
• Serum chemistry: 
− Sodium 
− Potassium 
− Total bilirubin 
− Calcium 
− Magnesium 
− AST 
− Chloride 
−  Glucose  
− ALT 
− Total protein 
− Creatinine 
− Albumin 
− Urea or blood urea nitrogen 
10.1.5.3. Urinalysis 
Urinalysis will be performed at screening, as follows: 
• Specific gravity 


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• Protein 
• Leukocyte esterase 
• Glucose 
• Nitrite 
• Ketones 
• Blood 
• Urobilinogen 
• Bilirubin 
In addition, urine dipstick for protein determination will be performed at screening and prior to 
each bevacizumab administration. Patients discovered to have ≥ 2 proteinuria on dipstick should 
not be administered bevacizumab, should undergo a 24-hour urine collection, and must 
demonstrate < 2 g of protein in 24 hours to be eligible for bevacizumab treatment to resume. 
10.1.5.4. Drug Screen 
Not applicable. 
10.1.5.5. Pregnancy Screen 
A negative serum or urine pregnancy test is required within 72 hours prior to Day 1 of Cycle 1 
for females of childbearing potential. Urine pregnancy testing will be performed on Day 1 of 
each subsequent cycle and at the End of Treatment Visit. Any pregnancies that occur within 180 
days post-treatment are to be reported as described in Section 10.3.9. 
10.1.6. 
ECOG Performance Status 
Performance status will be assessed using the ECOG scale (see Appendix 3) in accordance with 
the schedule of events (Table 6). The same observer should assess performance status each time. 
If the patient is unable to come to the site for assessment, such as due to COVID-19-related 
restrictions or other hindrances, Sponsor recommends that this assessment be done by telehealth 
visit or, as a final option, a phone visit. The same observer should continue to assess ECOG 
performance status for the virtual visit. 
10.1.7. 
Electrocardiogram 
Standard 12-lead electrocardiograms will be performed at screening. 


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10.2. 
General Guidance for Treatment Continuity when Patients are 
Unable to Come into the Clinic  
In the spirit of global diversity in the COVID-19 pandemic and its impact on healthcare in each 
individual country as well as the recently issued guidance by several regulatory authorities, the 
autonomy of each investigative site to assess the benefit/risk for their patients participating in the 
niraparib clinical studies should be maintained.  Due to the significant challenges that currently 
face the healthcare system and patients due to COVID-19 as well as the potential for enduring or 
additional quarantine measures alternative means of performing study assessments may be 
implemented by the site after consultation and approval from the Sponsor. 
These alternative means of performing study assessments may extend beyond COVID-19 to 
patients who are unable to attend clinic visits after consultation with the Sponsor. 
It is expected that sites participating in niraparib clinical studies will make every effort to ensure 
proper monitoring and wellbeing of enrolled patients by adhering to safety monitoring as 
outlined in the protocol schedule of events.  
General rules for patient with limited possibility to travel:  
• If possible, replace in person visits with telephone contact, or alternative location for 
assessment such as local labs and imaging centers   
• Local lab facilities and/or radiology centers should be added to regulatory documents as 
required.  
• In instances where it is desired to reduce patient exposure in clinic, in person visits every 
other cycle are acceptable if no ongoing AEs or new AEs. These missed visits will be 
considered protocol deviations.  
• Delay in oral niraparib treatment for up to 28 days is acceptable if the patients don’t have 
access to local labs and whereby the site’s pharmacy would not dispense the study drug 
unless patient is cleared with lab tests by Principal Investigator per institution standard 
operating procedure (SOP). − If longer than 28 days interruption is required, contact the 
medical monitor around Day 28 of interruption. This will be reviewed, and recommendations 
will be made on a case-by-case basis.  
• Drug dispensation for niraparib is possible for multiple cycles, with multiple bottles 
dispensed at once to patients who have not experienced an SAE related to the study treatment 
within the last 3 months (no ongoing “related” SAE). 
 
Additionally, regulatory guidance issued in response to the COVID-19 pandemic supports the 
use of central and remote monitoring programs to maintain oversight of clinical sites. Any 
restrictions in place at the site that will impact monitoring and/or patient access to the site and 
care providers should be communicated to the Sponsor. 


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10.3. 
Adverse and Serious Adverse Events 
10.3.1. 
Definitions 
10.3.1.1. Adverse Event 
Any untoward medical occurrence that occurs in a patient or clinical investigation subject 
administered a medicinal 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 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 after the 
signing of the informed consent, including baseline or washout periods, even if no study 
treatment has been administered. (See Section 10.3.3 for information about AE collecting and 
reporting.) 
10.3.1.2. Serious Adverse Event 
Any untoward medical occurrence, that, at any dose: 
• Results in death; 
• Is life threatening (i.e., an event in which the patient was at risk of death at the time of the 
event; it does not refer to an event that 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 abnormality or birth defect;  
• Is an important medical event**  
*Exception: Preplanned (at time of informed consent) hospitalization for elective procedures, for 
protocol compliance or social reasons, or for observation will not be considered criteria for an 
SAE. The reason for the planned hospitalization should be captured in medical history section in 
the eCRF. Complications experienced during these hospitalizations must be reported as AEs (or 
SAEs, if hospitalization is prolonged due to the AE).  
**Medical and scientific judgment should be exercised in determining whether situations or 
events should be considered serious adverse events: an important medical event may not be 
immediately life-threatening or result in death or require hospitalization but may jeopardize the 
patient or require intervention to prevent one of the above outcomes. Examples of such events 
are allergic bronchospasm, blood dyscrasias, or convulsions that may require intensive treatment 
in an emergency room or at home but do not result in hospitalization, development of drug 
dependency or drug abuse, and transmission of disease associated with the administration of the 
study drug. (See Section 10.3.5 for information about SAE reporting.) 


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10.3.1.3. Treatment-Emergent Adverse Event (TEAE) 
Any event that was not present prior to the initiation of study treatment or any event already 
present that worsens in either intensity or frequency following exposure to study treatment.  
10.3.1.4. Adverse Events of Special Interest (AESI) 
Any AE (serious or non-serious) that is of scientific and medical concern specific to the study 
treatment, for which ongoing monitoring and rapid communication by the Investigator to the 
Sponsor is appropriate. 
10.3.1.5. Special Situations: Abuse, Misuse, Medication Errors, Overdose, and Accidental 
or Occupational Exposure 
• Abuse: the persistent or sporadic, intentional excessive use of the study treatment which is 
accompanied by harmful physical or psychological effects.  
• Misuse: medicinal product is intentionally and inappropriately used not in accordance with 
the authorized/approved product information. 
• Medication error: any preventable incident that may cause or lead to inappropriate study 
treatment use or patient harm while the study treatment is in the control of the health care 
professionals or patients. Such incident may be due to health care professional practice, 
product labeling, packaging and preparation, procedures for administration, and systems, 
including the following: prescribing, order communication, nomenclature, compounding, 
dispensing, distribution, administration, education, monitoring, and use. 
• Overdose: a deliberate or accidental administration of study treatment to a study patient, at a 
dose greater than that which was assigned to that patient per the study protocol and under the 
direction of the Investigator.  If an overdose occurs, the Investigator and the Sponsor should 
be notified immediately, and the patient should be observed closely for AEs. Associated AEs 
should be treated and monitored by the Investigator. The dosage of study drug administered, 
any associated AEs, and/or treatment provided to the patient because of the overdose, should 
be documented on the applicable sections within the eCRF. 
• Accidental /Occupational exposure: the unintentional exposure to a study treatment as a 
result of one's professional or non-professional occupation, or accidental exposure to a non-
professional to whom exposure was not intended (i.e., study product given to wrong patient).  
10.3.2. 
Assessment of Adverse Events  
10.3.2.1. Severity Assessment  
All AEs will be assessed by the Investigator for severity* according to Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03: 14 June 2010; National Institutes of Health (NIH), 
National Cancer Institute (NCI). The CTCAE severity grades 1 through 5 provide unique clinical 
descriptions of severity of each adverse event. The CTCAE v4.03 is available on the NCI/NIH 
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Please note that there is a distinction between serious and severe AEs: Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Section 10.3.1.2. For example, a mild 
degree of gastrointestinal bleeding requiring an overnight hospitalization for monitoring 
purposes may be considered an SAE but is not necessarily severe. 
10.3.2.2. Relationship to Study Intervention 
The Investigator must provide a causality assessment regarding the relationship of the event with 
the study drug and/or study procedure for all AEs.  One of the following categories should be 
selected based on medical judgment, considering all contributing factors: 
• Related: A causal relationship between the medicinal product (and/or study procedures) and 
AE is a reasonable possibility. For example, the occurrence of the AE cannot be explained by 
other causative factors. The AE, however, can be explained by pharmacological effect of the 
medicinal product such as a similar event having been reported previously, alteration of the 
dose effect, or the timing or seriousness of the AE, etc. Positive rechallenge/dechallenge is 
supportive.  
• Not Related: A causal relationship between the medicinal product (and/or study procedures) 
and AE is not a reasonable possibility: there is no temporal relationship between the 
medicinal product and event, or an alternative etiology is more reasonable. 
10.3.2.3. Expectedness 
The Sponsor will be responsible for determining whether an adverse event is ‘expected’ or 
‘unexpected’. An AE will be considered unexpected if the nature, severity, or frequency of the 
event is not consistent with the risk information provided in the Reference Safety Information of 
the effective niraparib Investigator Brochure (IB). 
10.3.3. 
Collection and Recording Adverse Events 
AEs may be volunteered spontaneously by the study patient, or discovered by the study staff 
during physical examinations or by asking an open, nonleading question such as, “How have you 
been feeling since your last study visit?” The Investigator will document the nature of AE, date 
of onset of the AE (and time, if known), date of outcome of the AE (and time, if known), 
severity of the AE, action taken with study drug as a result of the AE, assessment of the 
seriousness of the AE, and assessment of the causal relationship of the AE to study drug and/or 
study procedure. 
AEs, including laboratory abnormalities that are assessed as clinically significant or require 
intervention, should be described using a diagnosis whenever possible, rather than individual 
underlying signs and symptoms. When a clear diagnosis cannot be identified, each sign or 
symptom should be recorded as a separate AE. 
All SAEs will be collected from the signing of the ICF for this study up to 90 days (±14 days) 
after the last dose of study treatment and recorded in the eCRF. SAEs will also be reported on an 
SAE form as described in Section 10.3.5 of this protocol. SAEs considered by the Investigator to 
be related to study treatment are reported until study closeout.  


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All AEs, regardless of the source of identification (e.g., physical examination, laboratory 
assessment, ECG, or reported by patient), will be collected and recorded in the eCRF for each 
patient from the signing of the ICF for this study up to 90 days (±14 days) after the last dose of 
study treatment. 
Concomitant illnesses that existed before entry into the study will not be considered AEs unless 
the illness worsens during the Treatment Period. Pre-existing conditions will be recorded as 
Medical History in the eCRF and on the SAE Report Form. 
Disease progression is an efficacy criterion and is therefore not considered an AE or SAE (even 
if fatal). Disease progression should be reported within the eCRF. If AEs/SAEs occur in relation 
to disease progression that are not consistent with the natural progression of the patient’s disease, 
these AEs/SAEs must be reported per AE/SAE reporting requirements described in 
Section 10.3.5. 
10.3.4. 
Follow-Up of Adverse Events 
All AEs experienced by a patient, regardless of the suspected causality, will be monitored until 
the AE or SAE has resolved, until any abnormal laboratory values have returned to baseline or 
normal levels, until stabilized with a satisfactory explanation for the changes observed, until the 
patient is lost to follow-up, or until the patient has died. 
If an Investigator becomes aware of an SAE after the specified follow up period and considers 
the SAE related to the study drug, the Investigator should report the SAE to the Sponsor 
according to timelines for reporting SAEs described in Section 10.3.3.    
10.3.5. 
Reporting 
The Investigator must report all SAEs, and all follow up information to the Sponsor on an SAE 
Report Form within 24 hours of becoming aware of the initial event or follow-up information. 
The Investigator must provide a causality assessment and must sign and date all SAE Report 
Forms.   
It is the responsibility of the Investigator to review source documentation and describe pertinent 
information on the SAE Report Form. 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.  
After receipt of the initial report, the Sponsor (or designee) will review the information and, if 
necessary, contact the Investigator to obtain further information. The Investigator must promptly 
respond to queries from the Sponsor. 


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10.3.6. 
Submission and Distribution of Serious Adverse Event Reports 
Per regulatory requirements, if an event is assessed by the Sponsor as a Serious Unexpected 
Adverse Reaction (SUSAR), it is the responsibility of the Sponsor to submit the SUSAR 
Regulatory Authorities according to applicable regulations. 
In addition, the SUSAR will be distributed to the Investigators/sites, utilizing a Council for 
International Organizations of Medical Sciences (CIOMS) report form, or the MedWatch 3500A 
form). The Investigator/site will submit a copy of the report to their respective Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) per the governing institutional 
requirements and in compliance with local laws and guidelines. 
10.3.7. 
Adverse Events of Special Interest 
Adverse Events of Special Interest (AESI) for niraparib are the following:  
• Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) 
• Secondary cancers (new malignancies [other than MDS or AML]) 
AESI should be collected and reported as follows: 
• MDS and AML along with other secondary cancers should be reported to the Sponsor until 
death or loss to follow-up. 
10.3.8. 
Myelodysplastic syndrome/acute myeloid leukaemia 
MDS and AML, including cases with fatal outcome, have been reported with the use of 
niraparib. In clinical trials, the duration of niraparib treatment in patients prior to developing 
MDS/AML varied from 1 month to >4 years. The cases were typical of secondary, cancer 
therapy-related MDS/AML. All patients had received platinum-containing chemotherapy 
regimens, and many had also received other DNA-damaging agents and radiotherapy. Some of 
the patients had a history of bone marrow suppression. For suspected MDS/AML or prolonged 
haematological toxicities, the patient should be referred to a haemaotologist for further 
evaluation. If MDS and/or AML is confirmed, then niraparib should be permanently 
discontinued and the patient should be treated appropriately. 
10.3.9. 
Pregnancy 
The Investigator must report all pregnancies and the outcomes to the Sponsor. The Sponsor has 
the responsibility to monitor the outcome of all pregnancies reported during the clinical study. 
Each pregnancy must be reported by the Investigator to the Sponsor 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 an AE 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. 


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An elective abortion without complications should not be regarded as an AE, however, it should 
be reported as the outcome to the pregnancy on the Pregnancy Outcome Report Form. 
Therapeutic abortions should be reported as a treatment procedure; the reason for the therapeutic 
abortion should be reported on the Pregnancy Outcome Report Form and as an AE in the eCRF. 
Hospitalization for normal delivery of a healthy newborn should not be considered an SAE. 
Any SAE that occurs during pregnancy must be recorded on the Pregnancy Outcome Report 
Form, reported as an SAE on the SAE Report Form (e.g., 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.  


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11. 
STATISTICS 
Details of the statistical analyses presented below will be provided in the study’s statistical 
analysis plan (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. 
All analyses will include summary statistics, including the number and percentage for categorical 
variables and the number of patients, mean, standard deviation, median, minimum, and 
maximum for continuous variables. Time-to-event analyses will be performed using the 
Kaplan-Meier method. Two-sided 95% CIs will be provided where appropriate. Time-to-event 
data may be censored according to criteria provided in the SAP. Further details will be provided 
in the SAP. 
No formal statistical testing will be performed. 
11.1. 
Sample Size Determination 
The sample size of the study is driven by the primary endpoint:  PFS18. A sample size of 
90 patients will provide an 11% precision on the 95% exact CI of PFS18, assuming a true PFS18 
rate of 48%, which corresponds to a median PFS of 17 months based on exponential PFS 
assumption. The primary endpoint analysis will occur after approximately 3 months of 
enrollment and an additional 18 months of follow-up.  
11.2. 
Analysis Populations 
Three analysis populations will be defined as follows: 
• Safety population:  All patients who receive any amount of study treatment (ie, any amount 
of bevacizumab or niraparib during the study). All safety endpoints will be assessed in the 
safety population.  
• Efficacy population:  All patients who receive any amount of niraparib (at least 1 dose). 
Analyses of baseline characteristics and the primary analysis of efficacy endpoints will be 
performed on the efficacy population. 
• Per-protocol population:  All patients in the efficacy population who have no major protocol 
violations during the study and have at least 1 protocol-required postbaseline tumor 
assessment. 
11.3. 
Demographics, Medical History, Baseline Characteristics, and 
Concomitant Medications 
Demographics, baseline characteristics, and medical history information will be summarized for 
the Safety population using descriptive statistics. No formal statistical comparisons will be 
performed. 
Demographics, baseline characteristics, concomitant medications, and medical history data for 
each patient will be provided in data listings. 


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11.4. 
Efficacy Analyses 
All analyses will include summary statistics, including number and percentage for categorical 
variables and number of patients, mean, standard deviation, median, minimum, and maximum 
for continuous variables. Time-to-event analyses will be performed using the Kaplan-Meier 
method. Two-sided 95% CIs will be provided where appropriate. Time-to-event data may be 
censored according to criteria provided in the SAP. Further details will be provided in the SAP. 
The primary endpoint for the study, PFS18, will be estimated using percentage with 95% exact 
CI. In addition, the probability of PFS at 18 months will be estimated using the Kaplan-Meier 
method.   
Time-to-events endpoints (ie, PFS, RECIST or CA-125 progression-free survival, OS, TFST, 
and TSST) will be summarized descriptively using the Kaplan-Meier method. A sensitivity 
analysis will be performed on PFS18 by including CA-125 progression, in addition to RECIST 
progression and death, to define progression events. 
The FOSI will be used in this study. Changes from baseline in overall score, subscores, and 
individual items will be analyzed descriptively. A repeated-measures model adjusting for 
covariates and subject evaluating change in symptoms and QoL will be conducted. Time to 
symptom worsening on the FOSI will be analyzed using time-to-event methodology. 
No formal statistical testing will be performed. 
 
In addition, biomarkers will be evaluated retrospectively. Further details will be provided in the 
SAP. 
11.5. 
Safety Analyses 
The safety and tolerability of niraparib in combination with bevacizumab will be analyzed based 
on the incidence of TEAEs, SAEs, changes in ECOG performance status, changes in clinical 
laboratory results (hematology and chemistry), vital sign measurements, observations during 
physical examination, and use of concomitant medications. The incidence of TEAEs and use of 
concomitant medications will be summarized. Clinical laboratory parameters and vital signs will 
be summarized by study visits. Descriptive summary statistics for observed values as well as 
changes from baseline will be presented.  
All AEs will be coded using the current version of the MedDRA coding system and displayed in 
tables and data listings using system organ class and preferred term. AESIs will be summarized 
for each AESI category and preferred term. 
The number and percentage of patients with any TEAE, with any TEAE assessed by the 
Investigator as related to treatment (definite, probable, or possible relationship), and with any 
SAE will be summarized. In these tabulations, each patient will contribute only once (ie, the 
most related occurrence or the most intense occurrence) to each of the incidence rates in the 
descriptive analysis, regardless of the number of episodes.  


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The occurrence of and reasons for any requirement for dose interruption or modification will be 
tabulated and distinguished as to presumptive causality from niraparib or bevacizumab, if 
known. 
All AEs occurring on study will be listed in patient data listings. By-patient listings will also be 
provided for the following: patient deaths, SAEs, and AEs leading to treatment discontinuation. 


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12. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
12.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of the Sponsor 
will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of the Sponsor or its representatives. This 
will be documented in a Clinical Study Agreement between the Sponsor and the 
Investigator. 
During the study, a monitor from the Sponsor or representative will have regular contacts with 
the investigational site, for the following: 
• Provide information and support to the Investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• Perform source data verification. This includes a comparison of the data in the case report 
forms with the patient’s medical records at the hospital or practice, and other records 
relevant to the study. This will require direct access to all original records for each patient 
(eg, clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor 
• Confirm AEs and SAEs have been properly documented on eCRFs, and confirm any 
SAEs have been forwarded to the Sponsor and those SAEs that met criteria for reporting 
have been forwarded to the IRB 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
12.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee or an Institutional Review Board may visit the site to perform audits or inspections, 
including source data verification. The purpose of a Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and 
accurately reported according to the protocol, Good Clinical Practice (GCP) guidelines of the 
International Conference on Harmonization, and any applicable regulatory requirements. The 
Investigator should contact the Sponsor immediately if contacted by a regulatory agency about 
an inspection. 


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12.3. 
Institutional Review Board (IRB)/Institutional Ethics Committee 
(IEC) 
The Principal Investigator must obtain IRB or IEC approval, as appropriate, for the investigation. 
Initial IRB/IEC approval, and all materials approved by the IRB/IEC for this study including the 
patient consent form and recruitment materials must be maintained by the Investigator and made 
available for inspection. 


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13. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCPs and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance audit. Please see Section 12.2 for more details regarding the audit 
process. 


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14. 
ETHICS 
14.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC, as appropriate. The Investigator must submit 
written approval to the Sponsor before he or she can enroll any patient into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit patients for the study. The protocol must be re-approved by the IRB or 
IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product. The Sponsor will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
14.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki (please see Appendix 5) and are consistent with ICH/GCP guidelines, 
applicable regulatory requirements, and the Sponsor’s policy on Bioethics. 
14.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk, and benefit of the study. 
Patients must also be notified that they are free to discontinue from the study at any time. The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICF. A copy of the signed ICF 
must be given to the patient. 


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15. 
DATA HANDLING AND RECORDKEEPING 
15.1. 
Inspection of Records 
The Sponsor will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 
15.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval or, if not approved, 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for the Sponsor or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 


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16. 
PUBLICATION POLICY 
Information regarding publication of study results is contained in the Clinical Trial Agreement 
for this study. 


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17. 
LIST OF REFERENCES 
1. 
NCCN. Clinical Practice Guidelines in Oncology: Ovarian Cancer. National 
Comprehensive Cancer Network; 2015. 
2. 
TCGA. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-
615. 
3. 
Kaelin WG, Jr. The concept of synthetic lethality in the context of anticancer therapy. 
Nat Rev Cancer. 2005;5(9):689-698. 
4. 
Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-
Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016. 
5. 
NCCN. Clinical Practice Guidelines in Oncology (NCCN Guidelines) - Ovarian Cancer, 
Including Fallopian Tube Cancer and Primary Peritoneal Cancer. 2017. 
6. 
Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary 
treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-2483. 
7. 
Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. 
N Engl J Med. 2011;365(26):2484-2496. 
8. 
du Bois A, Quinn M, Thigpen T, et al. 2004 consensus statements on the management of 
ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup 
Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann Oncol. 2005;16 Suppl 
8:viii7-viii12. 
9. 
Pfisterer J, Plante M, Vergote I, et al. Gemcitabine plus carboplatin compared with 
carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup 
trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 
2006;24(29):4699-4707. 
10. 
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with 
platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of 
outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014;15(8):852-
861. 
11. 
Hess LM, Rong N, Monahan PO, Gupta P, Thomaskutty C, Matei D. Continued 
chemotherapy after complete response to primary therapy among women with advanced 
ovarian cancer: a meta-analysis. Cancer. 2010;116(22):5251-5260. 
12. 
du Bois A, Floquet A, Kim JW, et al. Incorporation of pazopanib in maintenance therapy 
of ovarian cancer. J Clin Oncol. 2014;32(30):3374-3382. 
13. 
Oza AM, Castonguay V, Tsoref D, et al. Progression-free survival in advanced ovarian 
cancer: a Canadian review and expert panel perspective. Curr Oncol. 2011;18 Suppl 
2:S20-27. 
14. 
Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial 
ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and 
follow-up. Ann Oncol. 2013;24 Suppl 6:vi24-32. 
15. 
Mirza MR, Mortensen CE, Christensen RdP, et al. ENGOT-OV24/AVANOVA1 - A 
Phase 1 study of bevacizumab in combination with niraparib in patients with platinum-
sensitive epithelial ovarian cancer. Poster presented at the American Society of Clinical 
Oncology (ASCO) meeting June 3-7, 2016 in Chicago, Illinois. 
16. 
ZEJULATM (niraparib) capsules, for oral use [prescribing information]. Waltham, MA: 
TESARO.; 2017. 


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17. 
AVASTIN® (bevacizumab) solution for intravenous infusion [prescribing information]. 
San Francisco, CA: Genetech Inc. 2016. 
18. 
ICH E15. INTERNATIONAL CONFERENCE ON HARMONISATION GUIDELINES 
- DEFINITIONS FOR GENOMIC BIOMARKERS, PHARMACOGENOMICS, 
PHARMACOGENETICS, GENOMIC DATA AND SAMPLE CODING 
CATEGORIES. 2007. 
19. 
Beaumont J, Yount S, Lalla D, et al. Validation of the Functional Assessment of Cancer 
Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a Phase II Clinical Trial of 
Pertuzumab in Patients with Advanced Ovarian Cancer. Journal of Clinical Oncology, 
2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007;25(18S):16021. 
20. 
Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health 
Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale 
and important changes. Blood. 2009;114(5):937-951. 
21. 
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. 
22. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 
23. 
World Medical Association. World medical association declaration of Helsinki: ethical 
principles for medical research involving human subjects. JAMA 2013;Vol. 310, No. 20 
Abstract available at http://jama.jamanetwork.com/article.aspx?articleid=1760318. . 


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18. 
APPENDICES 
APPENDIX 1. CONTRACEPTION GUIDELINES 
Patients of childbearing potential who are sexually active and their partners must agree to the use 
of a highly effective form of contraception throughout their participation during the study 
treatment and for 180 days after last dose of study treatment(s): 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
− oral route 
− intravaginal route 
− transdermal route 
• Progestogen-only hormonal contraception associated with inhibition of ovulation  
− oral 
− injectable 
− implantable  
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized partner 
• Sexual abstinence, if the preferred and usual lifestyle of the subject  


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APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS V.1.1 
Response Criteria by RECIST v.1.121  
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 9: 
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 10: 
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. 


Nira pari b , Be v aciz u ma b  
C O N FI D E N TI A L  
T M F -1 4 4 2 8 0 0 2  
3 0 0 0 -0 2 -0 0 4/ G S K 2 1 3 3 5 8  
Cli nical St u d y Pr ot oc ol A me n d me nt 0 2 Versi o n 0 3  
 
C o nfi de ntial  
 
Pa ge 8 1  of 8 9  
 
 
A P P E N DI X  3.  E A S T E R N C O O P E R A TI V E O N C O L O G Y G R O U P ( E C O G ) 
P E R F O R M A N C E S T A T U S  
Descri pti o n  
Gr a de  
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


Nira pari b , Be v aciz u ma b  
C O N FI D E N TI A L  
T M F -1 4 4 2 8 0 0 2  
3 0 0 0 -0 2 -0 0 4/ G S K 2 1 3 3 5 8  
Cli nical St u d y Pr ot oc ol A me n d me nt 0 2 Versi o n 0 3  
 
C o nfi de ntial  
 
Pa ge 8 2  of 8 9  
 
 
A P P E N DI X  4.  S A M P L E F U N C TI O N A L A S S E S S M E N T O F C A N C E R 
T H E R A P Y –  O V A RI A N S Y M P T O M I N D E X ( F O SI)  
Bel o w is a list of state me nts t hat ot her pe o ple wit h y o ur ill ness ha ve sai d are i m p orta nt. Pl e ase 
circle o r m ar k o ne n u m ber per li ne t o i n dic ate y o ur res p o nse as it a p plies t o t he p ast 7 
d a ys . 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


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APPENDIX 5. WORLD MEDICAL ASSOCIATION DECLARATION OF 
HELSINKI 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by 
the: 
• 29th WMA General Assembly, Tokyo, Japan, October 1975 
• 35th WMA General Assembly, Venice, Italy, October 1983 
• 41st WMA General Assembly, Hong Kong, September 1989 
• 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
• 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
• 53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification 
added) 
• 55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
• 59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
• 64th WMA General Assembly, Fortaleza, Brazil, October 2013 
Preamble 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement of ethical principles for medical research involving human subjects, including 
research on identifiable human material and data. 
The Declaration is intended to be read as a whole and each of its constituent paragraphs 
should be applied with consideration of all other relevant paragraphs. 
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to 
physicians. The WMA encourages others who are involved in medical research involving 
human subjects to adopt these principles. 
General Principles 
3. The Declaration of Geneva of the WMA binds the physician with the words, “The health 
of my patient will be my first consideration,” and the International Code of Medical 
Ethics declares that, “A physician shall act in the patient’s best interest when providing 
medical care.” 
4. It is the duty of the physician to promote and safeguard the health, well-being and rights 
of patients, including those who are involved in medical research. The physician’s 
knowledge and conscience are dedicated to the fulfilment of this duty. 
5. Medical progress is based on research that ultimately must include studies involving 
human subjects. 
6. The primary purpose of medical research involving human subjects is to understand the 
causes, development, and effects of diseases and improve preventive, diagnostic and 


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therapeutic interventions (methods, procedures, and treatments). Even the best proven 
interventions must be evaluated continually through research for their safety, 
effectiveness, efficiency, accessibility, and quality. 
7. Medical research is subject to ethical standards that promote and ensure respect for all 
human subjects and protect their health and rights. 
8. While the primary purpose of medical research is to generate new knowledge, this goal 
can never take precedence over the rights and interests of individual research subjects. 
9. It is the duty of physicians who are involved in medical research to protect the life, 
health, dignity, integrity, right to self-determination, privacy, and confidentiality of 
personal information of research subjects. The responsibility for the protection of 
research subjects must always rest with the physician or other health care professionals 
and never with the research subjects, even though they have given consent. 
10. Physicians must consider the ethical, legal, and regulatory norms and standards for 
research involving human subjects in their own countries, as well as applicable 
international norms and standards. No national or international ethical, legal, or 
regulatory requirement should reduce or eliminate any of the protections for research 
subjects set forth in this Declaration. 
11. Medical research should be conducted in a manner that minimises possible harm to the 
environment. 
12. Medical research involving human subjects must be conducted only by individuals with 
the appropriate ethics and scientific education, training, and qualifications. Research on 
patients or healthy volunteers requires the supervision of a competent and appropriately 
qualified physician or other health care professional. 
13. Groups that are underrepresented in medical research should be provided appropriate 
access to participation in research. 
14. Physicians who combine medical research with medical care should involve their patients 
in research only to the extent that this is justified by its potential preventive, diagnostic, 
or therapeutic value and if the physician has good reason to believe that participation in 
the research study will not adversely affect the health of the patients who serve as 
research subjects. 
15. Appropriate compensation and treatment for subjects who are harmed as a result of 
participating in research must be ensured. 
Risks, Burdens, and Benefits 
16. In medical practice and in medical research, most interventions involve risks and 
burdens. 
 
Medical research involving human subjects may only be conducted if the importance of 
 
the objective outweighs the risks and burdens to the research subjects. 
17. All medical research involving human subjects must be preceded by careful assessment 
of predictable risks and burdens to the individuals and groups involved in the research in 


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comparison with foreseeable benefits to them and to other individuals or groups affected 
by the condition under investigation. 
Measures to minimise the risks must be implemented. The risks must be continuously 
monitored, assessed, and documented by the researcher. 
18. Physicians may not be involved in a research study involving human subjects unless they 
are confident that the risks have been adequately assessed and can be satisfactorily 
managed. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof 
of definitive outcomes, physicians must assess whether to continue, modify, or immediately 
stop the study. 
Vulnerable Groups and Individuals 
19. Some groups and individuals are particularly vulnerable and may have an increased 
likelihood of being wronged or of incurring additional harm. 
All vulnerable groups and individuals should receive specifically considered protection. 
20. Medical research with a vulnerable group is only justified if the research is responsive to 
the health needs or priorities of this group and the research cannot be carried out in a non-
vulnerable group. In addition, this group should stand to benefit from the knowledge, 
practices, or interventions that result from the research. 
Scientific Requirements and Research Protocols 
21. Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and adequate laboratory and, as appropriate, animal 
experimentation. The welfare of animals used for research must be respected. 
22. The design and performance of each research study involving human subjects must be 
clearly described and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations involved and should 
indicate how the principles in this Declaration have been addressed. The protocol should 
include information regarding funding, sponsors, institutional affiliations, potential conflicts 
of interest, incentives for subjects, and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in the research 
study. 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial 
provisions. 
Research Ethics Committees 
23. The research protocol must be submitted for consideration, comment, guidance, and 
approval to the concerned research ethics committee before the study begins. This 
committee must be transparent in its functioning, must be independent of the researcher, 
the sponsor, and any other undue influence and must be duly qualified. It must take into 


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consideration the laws and regulations of the country or countries in which the research is 
to be performed, as well as applicable international norms and standards but these must 
not be allowed to reduce or eliminate any of the protections for research subjects set forth 
in this Declaration. 
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse 
events. No amendment to the protocol may be made without consideration and approval by 
the committee. After the end of the study, the researchers must submit a final report to the 
committee containing a summary of the study’s findings and conclusions. 
Privacy and Confidentiality 
24. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information. 
Informed Consent 
25. Participation by individuals capable of giving informed consent as subjects in medical 
research must be voluntary. Although it may be appropriate to consult family members or 
community leaders, no individual capable of giving informed consent may be enrolled in 
a research study unless he or she freely agrees. 
26. In medical research involving human subjects capable of giving informed consent, each 
potential subject must be adequately informed of the aims, methods, sources of funding, 
any possible conflicts of interest, institutional affiliations of the researcher, the 
anticipated benefits and potential risks of the study, and the discomfort it may entail, 
post-study provisions, and any other relevant aspects of the study. The potential subject 
must be informed of the right to refuse to participate in the study or to withdraw consent 
to participate at any time without reprisal. Special attention should be given to the 
specific information needs of individual potential subjects, as well as to the methods used 
to deliver the information. 
After ensuring that the potential subject has understood the information, the physician or 
another appropriately qualified individual must then seek the potential subject’s freely-given 
informed consent, preferably in writing. If the consent cannot be expressed in writing, the 
non-written consent must be formally documented and witnessed. 
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study. 
27. When seeking informed consent for participation in a research study the physician must 
be particularly cautious if the potential subject is in a dependent relationship with the 
physician or may consent under duress. In such situations the informed consent must be 
sought by an appropriately qualified individual who is completely independent of this 
relationship. 
28. For a potential research subject who is incapable of giving informed consent, the 
physician must seek informed consent from the legally authorised representative. These 
individuals must not be included in a research study that has no likelihood of benefit for 


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them unless it is intended to promote the health of the group represented by the potential 
subject, the research cannot instead be performed with persons capable of providing 
informed consent, and the research entails only minimal risk and minimal burden. 
29. When a potential research subject who is deemed incapable of giving informed consent is 
able to give assent to decisions about participation in research, the physician must seek 
that assent in addition to the consent of the legally authorised representative. The 
potential subject’s dissent should be respected. 
30. Research involving subjects who are physically or mentally incapable of giving consent, 
for example, unconscious patients, may be done only if the physical or mental condition 
that prevents giving informed consent is a necessary characteristic of the research  group. 
In such circumstances, the physician must seek informed consent from the legally 
authorised representative. If no such representative is available and if the research cannot 
be delayed, the study may proceed without informed consent provided that the specific 
reasons for involving subjects with a condition that renders them unable to give informed 
consent have been stated in the research protocol and the study has been approved by a 
research ethics committee. Consent to remain in the research must be obtained as soon as 
possible from the subject or a legally authorised representative. 
31. The physician must fully inform the patient which aspects of their care are related to the 
research. The refusal of a patient to participate in a study or the patient’s decision to 
withdraw from the study must never adversely affect the patient-physician relationship. 
32. For medical research using identifiable human material or data, such as research on 
material or data contained in biobanks or similar repositories, physicians must seek 
informed consent for its collection, storage, and/or reuse. There may be exceptional 
situations where consent would be impossible or impracticable to obtain for such 
research. In such situations, the research may be done only after consideration and 
approval of a research ethics committee. 
Use of Placebo 
33. The benefits, risks, burdens, and effectiveness of a new intervention must be tested 
against those of the best proven intervention(s), except in the following circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or 
Where for compelling and scientifically sound methodological reasons the use of any 
intervention less effective than the best proven one, the use of placebo, or no intervention is 
necessary to determine the efficacy or safety of an intervention 
and the patients who receive any intervention less effective than the best proven one, 
placebo, or no intervention will not be subject to additional risks of serious or irreversible 
harm as a result of not receiving the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
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34. In advance of a clinical trial, sponsors, researchers, and host country governments should 
make provisions for post-trial access for all patients who still need an intervention 
identified as beneficial in the trial. This information must also be disclosed to patients 
during the informed consent process. 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human subjects must be registered in a publicly 
accessible database before recruitment of the first subject. 
36. Researchers, authors, sponsors, editors, and publishers all have ethical obligations with 
regard to the publication and dissemination of the results of research. Researchers have a 
duty to make publicly available the results of their research on human subjects and are 
accountable for the completeness and accuracy of their reports. All parties should adhere 
to accepted guidelines for ethical reporting. Negative and inconclusive, as well as 
positive results, must be published or otherwise made publicly available. Sources of 
funding, institutional affiliations, and conflicts of interest must be declared in the 
publication. Reports of research not in accordance with the principles of this Declaration 
should not be accepted for publication. 
Unproven Interventions in Clinical Practice 
37. In the treatment of an individual patient, where proven interventions do not exist or other 
known interventions have been ineffective, the physician, after seeking expert advice, 
with informed consent from the patient or a legally authorised representative, may use an 
unproven intervention if in the physician’s judgement it offers hope of saving life, 
re-establishing health or alleviating suffering. This intervention should subsequently be 
made the object of research, designed to evaluate its safety and efficacy. In all cases, new 
information must be recorded and, where appropriate, made publicly available. 
Source:  23 
 
 


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APPENDIX 6. PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC).  
Summary of Previous Amendments: 
Type of 
Amendment 
Title 
Date / DNG Number 
Summary 
Global 
Protocol 
Amendment 
01 
TMF-14428002 
The dosing guidance for niraparib was 
altered to reflect the most current guidance 
across the program following the release of 
additional data. This information was also 
included in the background and the 
rationale for the study. 
 


Signature Page for  213358 TMF-14428002 v2.0
Signature Page for TMF-14428002 v2.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 21-Apr-2022 13:56:44 GMT+0000
PPD

SAP_003.pdf: 
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Statistical Analysis Plan, Protocol 3000-02-004 
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Page 1 of 45 
 
STATISTICAL ANALYSIS PLAN 
A PHASE 2, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE 
SAFETY AND EFFICACY OF NIRAPARIB COMBINED WITH 
BEVACIZUMAB AS MAINTENANCE TREATMENT IN PATIENTS 
WITH ADVANCED OVARIAN CANCER, FALLOPIAN TUBE CANCER, 
OR PRIMARY PERITONEAL CANCER FOLLOWING FRONT-LINE 
PLATINUM-BASED CHEMOTHERAPY WITH BEVACIZUMAB 
Protocol 3000-02-004/GSK 213358 
Protocol Number: 
3000-02-004/GSK 213358 
Protocol Version and Date: 
Version 3.0: 21 April 2022 (Amendment 2) 
Version 2.0: 05 December 2017 (Amendment 1) 
Version 1.0: 19 April 2017 (Original) 
Study Drug Name: 
Niraparib; Bevacizumab 
Phase: 
Phase 2 
Methodology: 
Open-Label, Single-Arm 
Sponsor: 
GSK/TESARO, Inc. 
1000 Winter Street 
Waltham MA 02451 
+1 339 970 0900 
GSK/TESARO UK, Limited 55 Baker 
Street 
London W1U7EU United 
Kingdom 
+44 1753 910398 
Sponsor Representative: 
MD, PhD 
 
 
Analysis Plan Date: 
07 Jun 2024 
Analysis Plan Version: 
Final Version 2.0  
 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of 
TESARO, Inc., and any unauthorized use or disclosure of such information 
without the prior written authorization of TESARO, Inc., is expressly prohibited. 
PPD
PPD


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SPONSOR SIGNATURE PAGE 
 
Protocol Title: 
A Phase 2, Single-Arm, Open-Label Study to Evaluate the 
Safety and Efficacy of Niraparib Combined with Bevacizumab 
as Maintenance Treatment in Patients with Advanced Ovarian 
Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer 
Following Front-Line Platinum-Based Chemotherapy with 
Bevacizumab 
Protocol Number: 
3000-02-004/GSK 213358 
Sponsor: 
GSK/TESARO, Inc. 
1000 Winter Street 
Waltham MA 02451 
GSK/TESARO UK, Limited 
55 Baker Street 
London W1U7EU 
United Kingdom 
By signing this document, I acknowledge that I have read the document and approve of 
the planned statistical analyses described herein. I agree that the planned statistical 
analyses are appropriate for this study, are in accordance with the study objectives, and 
are consistent with the statistical methodology described in the protocol, clinical 
development plan, and all applicable regulatory guidance and guidelines. 
I also understand that any subsequent changes to the planned statistical analyses, as 
described herein, may have a regulatory impact and/or result in timeline adjustments. All 
changes to the planned analyses will be described in the clinical study report. 
Author: 
Emily Moore 
Principal Statistician, 
Oncology Statistics 
Approver: 
 
Natalie Compton 
Statistician 
 


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TABLE OF CONTENTS 
Table of Contents 
STATISTICAL ANALYSIS PLAN .................................................................................................... 1 
TABLE OF CONTENTS ..................................................................................................................... 3 
SAP AMENDMENT SUMMARY OF CHANGES ............................................................................ 5 
Rationale for the Amendment ...................................................................................... 5 
Summary of Changes ................................................................................................... 5 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................................ 7 
Table 1: 
Abbreviations and Specialist Terms ............................................................. 7 
1. 
INFORMATION FROM THE STUDY PROTOCOL .......................................................... 10 
1.1. 
Introduction and Objectives ................................................................................................... 10 
1.2. 
Study Design .......................................................................................................................... 11 
Synopsis of Study Design ...................................................................................................... 11 
Table 2: 
Schedule of Events ...................................................................................... 14 
2. 
PATIENT POPULATION ..................................................................................................... 19 
2.1. 
Population Definitions ........................................................................................................... 19 
2.2. 
Protocol Deviations ................................................................................................................ 19 
3. 
GENERAL STATISTICAL METHODS .............................................................................. 21 
3.1. 
Sample Size Justification ....................................................................................................... 21 
3.2. 
General Methods .................................................................................................................... 21 
3.3. 
Computing Environment ........................................................................................................ 22 
3.4. 
Baseline Definitions ............................................................................................................... 22 
3.5. 
Methods of Pooling Data ....................................................................................................... 22 
3.6. 
Adjustments for Covariates .................................................................................................... 22 
3.7. 
Multiple Comparisons/Multiplicity ........................................................................................ 22 
3.8. 
Subpopulations ....................................................................................................................... 22 
3.9. 
Withdrawals, Dropouts, Loss to Follow-up ........................................................................... 23 
3.10. Missing Data .......................................................................................................................... 23 
3.11. Visit Windows ........................................................................................................................ 24 
Table 3: 
Windows (Inclusive) for PRO Assessments after EOT .............................. 24 
3.12. Interim Analyses .................................................................................................................... 24 
4. 
STUDY ANALYSES ............................................................................................................ 24 


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4.1. 
Patient Disposition ................................................................................................................. 24 
4.2. 
Demographics, Baseline Characteristics, and Medical History ............................................. 25 
Table 4: 
Reported Anti-cancer Therapies ................................................................. 26 
4.3. 
Efficacy Evaluation ................................................................................................................ 27 
4.4. 
Safety Analyses ...................................................................................................................... 33 
Table 5: 
Adverse Events of Special Interest ............................................................. 37 
Table 6: 
Adverse Events of Medical interest ............................................................ 38 
5. 
CHANGES TO PLANNED ANALYSES ............................................................................. 40 
5.1. 
Protocol Changes ....................................................................................................... 40 
5.2. 
Final Analysis ............................................................................................................ 40 
6. 
REFERENCES ....................................................................................................................... 43 
7. 
APPENDIX ............................................................................................................................ 44 
7.1. 
Sample Functional Assessment of Cancer Therapy – Ovarian Symptom Index (FOSI) ....... 44 
7.2. 
Scoring Algorithm for the FACT/NCCN Ovarian Symptom Index (FOSI) .......................... 45 
8. 
STATISTICAL OUTPUT SHELLS ...................................................................................... 45 
9. 
REVISION HISTORY ........................................................................................................... 45 
 


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SAP AMENDMENT SUMMARY OF CHANGES 
Rationale for the Amendment 
To define requirements for the final analysis assessing long-term endpoints following primary CSR 
and align to latest protocol amendment.  
Summary of Changes  
Section(s) Affected 
Description of Change 
Brief Rationale 
Cover pages 
Administrative changes 
To reflect current team members & 
latest protocol version  
1.1.2 (Study Objectives) 
1.2 (Study Design) 
1.2.3 (Study Procedures) 
 
Updated protocol version and 
corrected discrepancies to protocol  
Updated design schema 
Updated Schedule of Events table  
 
 To align content with protocol 
amendment 2 
1.2.4.3 (Safety Parameters) 
4.4.3.1 (Safety Analyses Overview) 
Added summary of deaths 
Add information that was omitted 
from the original SAP. 
 5 (Changes to Planned Analyses) 
Section describes outputs to be 
produced at final analyses and how 
analyses to be repeated after primary 
read-out may be impacted by protocol 
amendment 2 (implemented after 
primary read-out) 
To determine final analysis 
deliverables   
2.2 (Protocol Deviations)  
Updated GSK SOP number 
To align with protocol amendment 2  


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TABLES INCLUDED IN THE TEXT 
TABLE 1:    ABBREVIATIONS AND SPECIALIST TERMS ..................................................................................7 
TABLE 2:    SCHEDULE OF EVENTS ....................................................................................................................14 
TABLE 3:    WINDOWS (INCLUSIVE) FOR PRO ASSESSMENTS AFTER EOT ...............................................24 
TABLE 4:    REPORTED ANTI-CANCER THERAPIES ........................................................................................26 
TABLE 5:   ADVERSE EVENTS OF SPECIAL INTEREST ..................................................................................37 
TABLE 6:   ADVERSE EVENTS OF MEDICAL INTEREST .................................................................................38 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or 
Specialist Term 
Explanation 
ADL 
activity of daily living 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
AST 
aspartate aminotransferase 
BER 
base excision repair 
BRCA 
breast cancer susceptibility gene 
CA-125 
cancer antigen 125 
CBC 
complete blood count 
CI 
confidence interval 
CR 
complete response 
CT 
computed tomography 
CVA 
cerebrovascular accident 
CYP 
cytochrome P450 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ESMO 
European Society for Medical Oncology 
EU 
European Union 
FIGO 
International Federation of Gynecology and Obstetrics 
FOSI 
Functional Assessment of Cancer Therapy–Ovarian Symptoms Index 
gBRCA 
germline breast cancer susceptibility gene 
gBRCAmut 
germline BRCA mutation 
GCIG 
Gynecologic Cancer Intergroup 
GCP 
Good Clinical Practice 


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Abbreviation or 
Specialist Term 
Explanation 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ICF 
informed consent form 
IV 
intravenous 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network 
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria for Adverse 
Events 
NED 
no evidence of disease 
OAE 
other adverse events 
OS 
overall survival 
PARP 
poly(ADP-ribose) polymerase 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS6 
PFS rate at 6 months 
PFS12 
PFS rate at 12 months 
PFS18 
PFS rate at 18 months 
PR 
partial response 
PRO 
patient-reported outcome 
QD 
once daily 
QoL 
quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sBRCA 
somatic BRCA 
TEAE 
treatment-emergent adverse event 


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Abbreviation or 
Specialist Term 
Explanation 
TFST 
time to first subsequent therapy 
TSST 
time to second subsequent therapy 
ULN 
upper limit of normal 
US 
United States 
VEGF 
vascular endothelial growth factor 
WHO 
World Health Organization 


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1. 
INFORMATION FROM THE STUDY PROTOCOL 
1.1. 
Introduction and Objectives 
1.1.1. 
Introduction 
Homologous recombination deficiency (HRD) and dependency on neo-angiogenesis are 2 major 
vulnerabilities of human cancers that have been successfully exploited therapeutically, as 
evidenced by recent approvals of poly(ADP-ribose) polymerase (PARP) inhibitors including 
niraparib (Zejula® ) for ovarian cancer and angiogenesis inhibitors including bevacizumab 
(Avastin®; Genentech/Roche United States [US]) for several indications including ovarian 
cancer. Emerging pre-clinical and clinical data suggest that combination of these 2 classes of 
agents may increase therapeutic options for women with ovarian cancer. 
PARP-1 and PARP-2 are key enzymes for repairing single-strand deoxyribonucleic acid (DNA) 
breaks. When they are inhibited, single-strand DNA breaks become double-strand DNA breaks 
after DNA replication, forcing cancer cells to rely on double-strand break repair mechanisms, in 
particular homologous recombination, for survival and proliferation. 
PARP inhibitors selectively kill a subset of cancer cells with deficiencies in DNA repair 
pathways. For example, a tumor arising in a patient with a germline breast cancer susceptibility 
gene mutation (gBRCAmut) has a defective homologous recombination DNA repair pathway 
and would be increasingly dependent on base excision repair (BER), a pathway blocked by 
PARP inhibitors, for maintenance of genomic integrity. 
Niraparib is an oral inhibitor of PARP-1 and PARP-2, which play a role in DNA repair. 
Niraparib is indicated for the maintenance treatment of adult patients with recurrent epithelial 
ovarian, fallopian tube, or primary peritoneal cancer who exhibit a complete response (CR) or 
partial response (PR) to platinum-based chemotherapy. 
Bevacizumab is an antiangiogenic recombinant humanized monoclonal immunoglobulin G1 
antibody against the vascular endothelial growth factor (VEGF) protein. Bevacizumab 
(Avastin®; Genentech/Roche US) has been approved in the US and European Union (EU) for 
the treatment of multiple tumor types in combination with certain other treatments. In the EU, 
bevacizumab is approved for the front-line treatment of adult patients with advanced 
(International Federation of Gynecology and Obstetrics [FIGO] Stages IIIB, IIIC, and IV) 
ovarian cancer. In the US, bevacizumab is approved for the treatment of patients with platinum- 
sensitive recurrent ovarian cancer, either in combination with carboplatin and paclitaxel or in 
combination with carboplatin and gemcitabine, followed by bevacizumab as a single agent. 
Recent data suggest that the combination of a PARP inhibitor, like niraparib, with a VEGF 
inhibitor, like bevacizumab, in maintenance treatment has the potential for improved PFS 
benefits after front-line chemotherapy in platinum-responsive (CR or PR) ovarian cancer 
patients. This hypothesis is supported by the mechanism of action of both treatments, 
nonclinical studies, and an ongoing Phase 1/2 study (AVANOVA) in this patient population. To 
date, the combination has proven to be safe for administration for extended periods in patients 
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Based upon the above preclinical and clinical data, the current study is being conducted to 
explore the safety and efficacy of maintenance with PARP inhibitor combined with 
anti-angiogenic agent following front-line, platinum-based therapy combined with 
bevacizumab. 
1.1.2. 
Study Objectives 
The primary objective of this study is to evaluate the efficacy of niraparib in combination with 
bevacizumab, as assessed by 18-month progression-free survival (PFS) landmark analysis, in 
patients with Stage IIIB to IV ovarian cancer who have CR, PR, or no evidence of disease 
(NED) following front-line, platinum-based chemotherapy with bevacizumab. 
The secondary objectives include the following: 
• To evaluate additional measures of clinical benefit, including PFS, RECIST or CA-125 
progression-free survival, OS, patient-reported outcome (PRO) measures, TFST, and 
time to second subsequent therapy (TSST) 
• To evaluate the safety and tolerability of niraparib and bevacizumab combination in the 
indicated target population 
The exploratory objectives include the following: 
• To evaluate PFS rate at 6 months (PFS6) and 12 months (PFS12) 
• Retrospective analysis to evaluate HRD per the Myriad myChoice® HRD test as a 
potential biomarker for response to the niraparib and bevacizumab combination 
This statistical analysis plan (SAP) is designed to outline the methods to be used in the analyses 
of study data in order to answer the study objectives. Patient populations to be used for analyses, 
data handling rules, statistical methods, and formats for data presentation are identified and 
provided. The statistical analyses and summary tabulations described in this SAP will provide 
the basis for the results sections of the clinical study report (CSR) for this trial. 
This SAP will also outline any differences in the currently planned analytical objectives relative 
to those planned in the study protocol. 
The SAP is based upon Study Protocol v3.0 dated 21 April 2022. Since the primary analysis 
reporting was based on SAP V1.0, the main body of SAP V2.0 has been kept consistent to V1.0 
apart from updates to align to Study Protocol v3.0 and to latest project-level reporting requirements. 
The outputs to be produced for the final analysis and any changes to endpoint derivations from SAP 
V1.0 are outlined in Section 5.  
1.2. 
Study Design 
Synopsis of Study Design 
This is a multicenter, Phase 2, single-arm, open-label study to evaluate niraparib combined with 
bevacizumab as maintenance treatment in patients with advanced (Stage IIIB-IV) ovarian 
cancer, fallopian tube cancer, or primary peritoneal cancer with completely or incompletely 
resected disease who are recovered from primary debulking surgery. 
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Eligible patients who achieve CR, PR, or NED following treatment with platinum-based 
chemotherapy in addition to bevacizumab will be enrolled in the study and receive maintenance 
treatment with niraparib (for up to 3 years) combined with bevacizumab (for up to 10 months 
during the maintenance phase or up to a total of 15 months inclusive of the approximately 5 
months of bevacizumab received with chemotherapy) or until disease progression, unacceptable 
toxicity, patient withdrawal, Investigator’s decision, or death, whichever comes first (see Study 
Design Schema). Patients who continue to derive benefit from study treatment based on 
continuation of non-progression indicated by imaging, remain clinically stable, and are willing 
to continue study visits and assessments may continue to receive niraparib beyond 3 years 
following consultation with the Investigator and the medical monitor. 
Study Design Schema 
 
 
Abbreviations: CR = complete response; NED = no evidence of disease; PR = partial response. 
*Patients ≥77 kg and with platelet count of ≥150,000/µL will receive 300 mg/day; patients <77 kg and/or with 
platelet count of <150,000 u/L will receive 200 mg/day 
Safety assessments conducted throughout the treatment period include treatment-emergent adverse 
events (TEAEs), serious adverse events (SAEs), treatment discontinuations or dose reductions due to 
adverse events (AEs), changes in Eastern Cooperative Oncology Group (ECOG) performance status, 
changes in clinical laboratory results (hematology and chemistry), vital sign measurements, observations 
during physical examination, and use of concomitant medications. 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 tumor assessment via computed 
tomography (CT) or magnetic resonance imaging (MRI) scan of the abdomen/pelvis and clinically 
indicated areas is required at screening, then every 12 weeks (±7 days) from Cycle 1/Day 1 visit for 
the first 48 weeks, then every 24 weeks (±14 days) until disease progression, at which point a final 
set of imaging scans is required. Only one set of imaging is required showing unequivocal disease 
progression while on study treatment and/or prior to beginning follow-up therapy. Note that as of 
Protocol Amendment 2, the tumor scan schedule has been aligned to the reduced-frequency 
treatment dispensation schedule to lessen patient burden; see footnotes in Table 2 
for further information. Positron emission tomography (PET)/CT may be used according to 
RECIST v1.1 guidelines, but its use is not a study requirement. 


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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 loss to follow-up, scans should continue at the specified 
intervals. 
RECIST v1.1 is used to define progressive disease (PD) in this study. Tumor assessment by 
CT/MRI must unequivocally show PD according to RECIST v1.1 criteria. PD will not be 
diagnosed in case of CA-125 progression in the absence of radiologic evidence of progressive 
disease. 
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 informed consent 
form (ICF), the patient is not required to complete an additional CT/MRI scan for study 
screening. 
PROs (Functional Assessment of Cancer Therapy-Ovarian Symptom Index [FOSI]) will be 
collected every 6 weeks (±7 days) for 6 months, then every 12 weeks (±7 days) thereafter 
while the patient is receiving study treatment. Once a patient discontinues treatment, PRO 
evaluations will be performed 4 weeks (±7 days), 8 weeks (±7 days), 12 weeks (±7 days), 
and 24 weeks (±7 days) after treatment discontinuation, regardless of subsequent treatment. 
All patients will undergo an End of Treatment Visit within 7 days of the decision to 
discontinue treatment for any reason. Post-treatment follow-up visits will be conducted every 
12 weeks (±14 days) after the last dose of study treatment. 
All AEs and SAEs, regardless of causality, will be collected and recorded for each patient from 
the day the ICF is signed until 90 days after the last dose of study treatment. Any pregnancies 
that occur are to be reported. All AEs and SAEs experienced by a patient, regardless of the 
suspected causality, will be monitored until the AE or SAE has resolved, until any abnormal 
laboratory values have returned to baseline or normalized, until there is a satisfactory 
explanation for the change(s) observed, until the patient is lost to follow-up or withdraws 
consent, or until the patient has died. 
The niraparib adverse events of special interest (AESIs) for this study are myelodysplastic 
syndrome (MDS), acute myeloid leukemia (AML), pneumonitis, embryo-fetal toxicity, and 
secondary cancer (new malignancies other than MDS/AML). AESIs must be reported to the 
Sponsor as soon as the Investigator becomes aware of them or within 24 hours. 
1.2.1. 
Randomization Methodology 
Not applicable as this is a single-arm study. 
1.2.2. 
Stopping Rules and Unblinding 
There are no pre-specified stopping rules for the study. Unblinding is not applicable as this is a 
single-arm, open-label study. 
1.2.3. 
Study Procedures 
The schedule of events, as outlined in the study protocol, is provided in Table 2 


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Table 2: 
Schedule of Events 
Visit/Procedure 
Screening 
Cycle 1a 
Cycle 2a 
Subsequent 
cyclesa 
EOTb 
Post- 
treatment 
assessments 
Day 
-28 to -1 
1 
1 
C(n)/D1 
Within 7 days of 
the decision to 
discontinue 
treatment 
Every 
12 weeks 
Visit Window 
±3 days 
±3 days 
±3 days 
±14 days 
(unless 
otherwise 
specified) 
Informed consent 
X 
Demographics and height 
X 
Medical, surgical, cancer (including genotyping), and medication 
history 
X 
Medical history/concomitant medications 
X 
X 
X 
X 
Sample collection (tumor) for HRD testingc 
X 
12-lead ECG 
X 
Serum or urine pregnancy testd 
Xd 
X 
X 
X 
X 
Physical examination 
X 
X 
X 
X 
X 
Vital signs and weight 
X 
X 
X 
X 
X 
ECOG performance status 
X 
X 
X 
X 
X 
CBCe 
X 
Days 1, 8, and 15 of 
Cycle 1f and Cycle 2 
X 
X 
Serum chemistry and coagulation 
X 
Xf 
X 
X 
X 


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Visit/Procedure 
Screening 
Cycle 1a 
Cycle 2a 
Subsequent 
cyclesa 
EOTb 
Post- 
treatment 
assessments 
Day 
-28 to -1 
1 
1 
C(n)/D1 
Within 7 days of 
the decision to 
discontinue 
treatment 
Every 
12 weeks 
Visit Window 
±3 days 
±3 days 
±3 days 
±14 days 
(unless 
otherwise 
specified) 
Urinalysis 
X 
Urine sample for proteing 
X 
Xg 
Xg 
Xg 
Serum CA-125 
X 
X 
X 
X 
X 
X 
RECIST v1.1 assessmenth 
X 
Xh 
X 
X 
Chest CT or MRIi 
X 
PRO 
X 
Q6W (±7 days) for 6 months, then 
Q12W (±7 days) 
4, 8, 12, and 24 weeks (±7 days) 
after last dose 
Niraparib dispensed or collected 
X 
X 
X 
X 
Bevacizumab infusion 
X 
X 
X 
Adverse event monitoringj 
X 
X 
X 
X 
X 
X 
Anticancer therapies assessment 
X 
Survival assessment (telephone assessment allowed)k 
X 
Bone marrow aspirate and biopsy 
For any suspected case of MDS/AML or secondary cancer (new malignancy 
other than MDS/AML) reported while on study, a bone marrow 
aspirate/biopsy must be completed by a local hematologist. 


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Abbreviations: AE = adverse event; AML = acute myelogenous leukemia; C = cycle; CA-125 = cancer antigen 125; CBC = complete blood count; 
CT = computed tomography; D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; FOSI = Functional 
Assessment of Cancer Therapy–Ovarian Symptom Index; HRD = homologous recombination deficiency; MDS = myelodysplastic syndrome; MRI = magnetic 
resonance imaging; PE = physical examination; QxW = every x weeks; RECIST = Response Evaluation Criteria in Solid Tumors 
a Treatment cycles are 21 days (±3 days) until the implementation of protocol amendment 2 at which time cycles will be 84-days (+/- 7 days). 
b EOT is defined as the discontinuation of treatment for any reason.  
c The tumor sample must be confirmed to be available during the screening period and submitted after the patient has been enrolled; patients do not have need to  
wait for the HRD test result to be enrolled. If archival tumor tissue is not available for testing, the patient must agree to undergo a fresh biopsy. 
d For patients of childbearing potential only. If completed within 72 hours of the first dose, pregnancy testing does not need to be repeated. 
e 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  
AE resolves, and to ensure safety of the new dose, weekly blood draws for CBC will also 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. 
f Screening assessments completed within 7 days of the first dose do not need to be repeated, unless otherwise specified.  
g Urine dipstick for protein determination should be performed prior to each bevacizumab administration. Patients discovered to have ≥ 2 proteinuria on dipstick  
should not be administered bevacizumab, should undergo a 24-hour urine collection, and must demonstrate < 2 g of protein in 24 hours to be eligible for  
bevacizumab treatment to resume. 
h RECIST v1.1 tumor assessment via CT or MRI scan of the abdomen/pelvis and clinically indicated areas required at screening, every 12 weeks (±7 days) from  
Cycle 1/Day 1 for the first 48 weeks, then every 24 weeks (±14 days) until disease progression. Once patients transition to an 84-day cycle (every 12 weeks)  
the next scan should be at a regularly scheduled visit such that the follow-up scan is no less than 21 weeks and no more than 30 weeks after the last scan. 
i Chest CT or MRI if not done as part of RECIST tumor assessment. If the chest CT or 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; otherwise, repeat chest imaging should be completed at the same  
time as RECIST imaging. 
j All AEs and SAEs, regardless of causality, will be collected and recorded for each patient from the day the ICF is signed until 90 days (±14 days) after the last  
dose of study treatment or until alternate anticancer therapy has been initiated, whichever occurs first. 
k Patients will be followed until study closeout for survival status and study-drug related SAEs. Patients will be followed for AESI as outlined in Section 10.3.7. Sponsor 
may request that updated survival data be collected on all treated patients outside the protocol window. At the time of the request, the site will determine survival status 
for each patient by the method agreed with the patient, unless the patient has withdrawn consent for survival FU.


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1.2.4. 
Efficacy, Pharmacokinetic, and Safety Parameters 
1.2.4.1. 
Efficacy Parameters 
Protocol-specified efficacy parameters include: 
• PFS rate at 18 months (PFS18), which is defined as the proportion of patients who have 
not progressed or died within 18 months after niraparib combined with bevacizumab 
treatment initiation. Progression will be assessed by RECIST v1.1 criteria per 
Investigator assessment. 
• PFS, which is defined as the time from niraparib combined with bevacizumab treatment 
initiation to the earlier date of assessment of progression, as assessed by RECIST v1.1 
criteria, based on Investigator assessment, or death by any cause in the absence of 
progression. 
• OS, which is defined as the date of initiation of niraparib treatment in combination with 
bevacizumab to the date of death by any cause. 
• RECIST or CA-125 progression-free survival, which is defined as the time from 
initiation of niraparib treatment in combination with bevacizumab to the earliest date of 
progression assessed by RECIST v1.1. or CA-125 progression or death by any cause. 
The date of CA-125 progression will be the date of the first measurement that meets the 
CA-125 progression criteria: Patients with elevated CA-125 pretreatment and 
normalization of CA-125 must show evidence of CA-125 ≥ 2 × ULN on 2 occasions at 
least 1 week apart, OR 
o Patients with elevated CA-125 pretreatment that never normalizes must show 
evidence of CA-125 ≥ 2 × the nadir value on 2 occasions at least 1 week apart, 
OR 
o  Patients with CA-125 in the normal range pretreatment must show evidence of 
CA-125 ≥ 2 × ULN on 2 occasions at least 1 week apart. 
• TFST (Time to First Subsequent Therapy), which is defined as the date of initiation of 
niraparib treatment in combination with bevacizumab treatment in the current study to 
the start date of the first subsequent anticancer therapy. 
• TSST (Time to Second Subsequent Therapy), which is defined as the date of initiation of 
treatment of niraparib in combination with bevacizumab treatment in the current study to 
the start date of the second subsequent anticancer therapy. 
• Observed changes from baseline in the Functional Assessment of Cancer Therapy– 
Ovarian Symptom Index (FOSI) PRO will be assessed (see Appendix 7.1). 
The exploratory efficacy endpoints are PFS rate at 6 months (PFS6) and 12 months (PFS12), 
which are defined as the proportion of patients who have not progressed or died within 6 
months and 12 months after initiation of treatment of niraparib in combination with 
bevacizumab treatment, respectively. Progression will be assessed by RECIST v1.1 Criteria 
based on Investigator assessment. Additional landmark PFS analyses may be performed as 
deemed appropriate. 


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1.2.4.2. 
Pharmacokinetic Parameters 
No PK samples are collected in this study. 
1.2.4.3. 
Safety Parameters 
Safety will be evaluated based on the incidence of TEAEs, serious adverse events (SAEs), 
treatment discontinuations or dose modifications due to AEs, changes in ECOG performance 
status, changes in clinical laboratory results (hematology and chemistry), vital sign 
measurements, observations during physical examination, and use of concomitant medications. 
All AEs will be coded using the current version of the Medical Dictionary for Regulatory 
Activities (MedDRA) coding system. The safety endpoints are: 
• TEAEs 
• Deaths 
• Clinical laboratory: 
o Complete blood count (CBC): hemoglobin, WBC (Leukocytes), mean 
corpuscular volume, Neutrophils, Eosinophils, Basophils, Lymphocytes, 
Monocytes, and platelet count. 
o Serum chemistry: albumin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), total bilirubin, blood urea nitrogen, calcium, chloride, 
creatinine, glucose, magnesium, potassium, sodium, total protein and urea. 
o Urinalysis: Bilirubin, Glucose, Ketones, Leukocyte esterase, Nitrites, Occult 
Blood, Urobilinogen, and Specific gravity. 
o Urine Protein 
o Serum or Urine pregnancy testing 
• Vital signs: 
o Height 
o Weight 
o Temperature 
o Systolic Blood Pressure 
o Diastolic Blood Pressure 
o Pulse 
• ECOG performance status 
• ECG (Standard 12-lead electrocardiograms at screening) 
• Concomitant medications 
Additional safety parameters include study treatment exposure and compliance. 


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2. 
PATIENT POPULATION 
2.1. 
Population Definitions 
The following patient populations will be evaluated and used for presentation and analysis of 
the data: 
• Safety population: All patients who receive any amount of study treatment (ie, any 
amount of bevacizumab or niraparib during the study). All safety endpoints will be 
assessed in the safety population. 
• Efficacy population: All patients who receive any amount of niraparib (at least 1 dose). 
The primary analysis of efficacy endpoints will be performed on the efficacy population. 
• Per-protocol population: All patients in the efficacy population who have no major 
protocol violations during the study and have at least 1 protocol-required postbaseline 
tumor assessment. 
Given the single arm study design, the safety population will be used to summarize the patient 
disposition and baseline characteristics in this study. The efficacy population, which is the ITT 
(intent-to-treat) population in this study, is the primary population for the analysis of efficacy 
endpoints. The safety population is the primary population for the analysis of safety endpoints. 
The patients in the Per-protocol population are subjects that have neither GSK important nor 
Tesaro significant protocol deviations and have at least 1 protocol-required postbaseline tumor 
assessment. The Per-protocol population will be used in supportive analyses when applicable. 
2.2. 
Protocol Deviations 
2.2.1. 
GSK definitions 
A protocol deviation is any failure to comply with the study protocol as approved by the 
relevant regulatory authority, ethics committee and/or institutional review board, whether 
planned or unplanned. Protocol Deviations will be assessed as important per Sponsor’s SOP 
(VQD-SOP-034480– v2.0). 
GSK Important protocol deviations are those deviations which directly or indirectly have an 
impact on: 
• subject's rights, safety, or well-being, and/or on 
• data integrity and/or 
• Regulatory compliance, as per ICH E3. 
Examples per ICH E3 include: 
• Subjects who are entered into the study even though they did not satisfy key entry 
criteria. [ICH E3 10.2] 
• Subjects who developed withdrawal criteria during the study but were not withdrawn. 
[ICH E3 10.2] 
• Subjects who received the wrong treatment or incorrect dose. [ICH E3 10.2] 
• Subjects who received an excluded concomitant treatment. [ICH E3 10.2] 
• Any study specific procedure or assessment deviation, which the study team determines 
may compromise subject rights, safety, or well-being, or has a significant impact on 
study conclusions. 


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2.2.2. 
Tesaro definitions 
A protocol deviation is any failure to comply with the study protocol as approved by the 
relevant regulatory authority, ethics committee and/or institutional review board, whether 
planned or unplanned. 
A protocol deviation is classified as a Tesaro important protocol deviation if there is the 
potential to: 
• Impact the completeness, accuracy, and/or reliability of the study data, or 
• Affect a subject's rights, safety, or well-being. 
Tesaro important protocol deviations require review to confirm whether or not they are 
significant. The following are PDs that will always be considered important (SOP 1000-00021- 
CLN): 
• Failure to obtain informed consent for participation in the clinical trial 
• Enrollment of ineligible subject 
• Subject developed withdrawal criteria during the study but was not withdrawn 
• Subject received incorrect treatment (patient received non-study drug to treat ovarian 
cancer) 
• Incorrect or non-compliant dosing of a subject, i.e. dosing that is inconsistent with the 
protocol 
• Administration of an excluded concomitant treatment to a trial subject 
A protocol deviation is classified as a Tesaro significant PD if it has been confirmed to: 
• Adversely impact the completeness, accuracy, and/or reliability of the study data 
• Affect a subject’s rights, safety, or well-being. 
2.2.3. 
Deviation Analyses 
All protocol deviations will be identified and finalized prior to database lock. Patients excluded 
from the Per-protocol population due to either a GSK important or a Tesaro significant protocol 
deviation will be identified prior to database lock. 
The following protocol deviation summaries will be provided: 
• Summary of GSK Important Protocol Deviations not related to COVID-19 (ITT) 
• Summary of GSK Important Protocol Deviations related to COVID-19 (ITT) 
• Summary of Tesaro Significant Deviations related to COVID-19 (ITT) 
• Summary of Tesaro Significant Deviations not related to COVID-19 (ITT) 
• Listing of GSK Protocol Deviations not related to COVID-19 (ITT) 
• Listing of GSK Protocol Deviations related to COVID-19 (ITT) 
• Listing of Tesaro Protocol Deviations not related to COVID-19 (ITT) 
• Listing of Tesaro Protocol Deviations related to COVID-19 (ITT) 


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3. 
GENERAL STATISTICAL METHODS 
3.1. 
Sample Size Justification 
The sample size of the study is driven by the primary endpoint: PFS18. A sample size of 
90 patients will provide an 11% precision on the 95% exact CI of PFS18, assuming a true 
PFS18 rate of 48%, which corresponds to a median PFS of 17 months based on exponential PFS 
assumption. The primary endpoint analysis will occur after approximately 3 months of 
enrollment and an additional 18 months of follow-up. 
3.2. 
General Methods 
All safety data listings that contain an evaluation date will also contain a relative study day. 
Pre-treatment and on-treatment study days are numbered relative to the day of the first dose of 
study drug which is designated as Day 1. The preceding day is Day -1, the day before that is 
Day -2, etc. The last day of study drug is designated with an “L” (eg, Day 14L). Post-treatment 
study days are numbered relative to the last dose and are designated as Day +1, Day +2, etc. In 
addition to relative day, cycle and day of treatment within cycle will be calculated and 
presented. 
All output will be incorporated into Microsoft Word or Excel files or Adobe Acrobat PDF files, 
sorted and labeled according to the International Conference on Harmonisation (ICH) 
recommendations, and formatted to the appropriate page size(s). 
Tabulations will be produced for appropriate demographic, baseline, efficacy, and safety 
parameters. 
For categorical variables, summary tabulations of the number and percentage of patients within 
each category of the parameter will be presented. Percentages will be based on the patients with 
a non-missing parameter. Percentages will be reported to 1 decimal place. Percentages will not 
be presented for zero counts. 
For continuous variables, the number of patients, mean, standard deviation (SD), median, first 
quartile (Q1), third quartile (Q3), minimum, and maximum values will be presented. 
Time-to-event data will be summarized using Kaplan-Meier (KM) methodology using 25th, 50th 
(median), and 75th percentiles with associated 2-sided 95% confidence intervals (CIs), as well as 
percentage of censored observations. 
No formal statistical hypothesis testing will be performed. 
In addition: 
• P-values greater than or equal to 0.001, in general, will be presented to 3 decimal places; 
p-values less than 0.001 will be presented as “<0.001” 
• CIs will be presented to 1 more decimal place than the raw data 
• Weeks will be calculated as Number of days divided by 7 
• Months will be calculated as Number of days divided by 30.4375 
• Years will be calculated as Number of days divided by 365.25 
• Day 1 will be considered as the first day of treatment 
• End of Study is defined as the last available study assessment 


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• All tables, figures, and listings will include footers at the bottom of the page reflecting 
the path and date of the datasets, datasets used to generate the tables, figures, and 
listings, and date and time of the generation of the output 
3.3. 
Computing Environment 
All statistical analyses will be performed using SAS statistical software v9.4 or later, unless 
otherwise noted. Medical history and AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) v20.0 or later. Laboratory parameter changes will be 
described using shift tables, relative to the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) v4.03. Concomitant medications will be 
coded using the latest version of the World Health Organization’s (WHO) Anatomical 
Therapeutic Chemical (ATC) classification. 
3.4. 
Baseline Definitions 
For all analyses, baseline is defined as the most recent measurement prior to the first 
administration of study drug (including Cycle 1 Day 1). 
3.5. 
Methods of Pooling Data 
Data will be pooled across study sites. 
3.6. 
Adjustments for Covariates 
No formal statistical analyses that adjust for possible covariate effects are planned for the 
efficacy or safety endpoints. 
3.7. 
Multiple Comparisons/Multiplicity 
Not applicable. 
3.8. 
Subpopulations 
3.8.1. 
Study Subpopulations 
• Best response during front-line platinum regimen (CR/NED or PR) 
• Age categories [<65 or ≥65] 
• ECOG status [ 0 or 1] 
• Stage of disease at initial diagnosis [III or IV] 
• Neoadjuvant vs Adjuvant chemotherapy during front-line platinum regimen 
• Macroscopic visible residual disease after surgery [Yes, No or unknown] 
3.8.2. 
Biomarker Subpopulations 
3.8.2.1. 
Biomarker Definitions 
Germline BRCA mutation (gBRCAmut): An inherited deleterious or suspected deleterious 
mutation in either a BRCA1 or BRCA2 tumor suppressor gene found in blood. 
BRCA mutation (BRCAmut): A deleterious or suspected deleterious BRCA1 or BRCA2 
mutation found in a tumor. 
BRCA wild type (BRCAwt): A tumor does not possess either a deleterious or suspected 
deleterious BRCA mutation. 


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Homologous recombination deficiency (HRD): Dysregulation in the homologous recombination 
pathway (due to genetic mutations or alterations) leading to cellular genomic instability and an 
inability to efficiently repair damaged DNA. 
HRD positive (HRDpos): HRD positive status may be determined by the myChoice HRD test. 
Any tumor that scores ≥42 or has a deleterious or suspected deleterious BRCA mutation would 
be considered HRD positive. 
HRD negative (HRDneg): HRD negative status may be determined by the myChoice HRD test. 
Any tumor that scores <42 and does not possess a deleterious or suspected deleterious BRCA 
mutation would be considered HRD negative. 
3.8.2.2. 
Study-Specific Biomarker Populations 
In this study, BRCA and HRD status are determined by tumor samples at screening via the 
Myriad myChoice HRD test. The gBRCA status is recorded in the eCRF form. 
All patients will be summarized by BRCA status as follows: 
• BRCAmut 
• BRCAwt 
• Not determined 
All patients will be summarized by HRD status in the following subgroups: 
• HRDpos 
o HRDpos/BRCAmut 
o HRDpos/BRCAwt 
• HRDneg 
• Not determined 
If applicable, other exploratory biomarker subpopulations may be further defined and analyzed. 
3.8.3. 
Other Study-Specific Subpopulations 
Starting dose of study medication will be determined for each newly enrolled patient based on 
baseline weight and platelet count. The following subpopulations are defined for subgroup 
analysis when applicable. 
• Starting dose 200 mg/day (Recommended for patients with baseline weight < 77kg 
and/or baseline platelet count < 150,000/µL) 
• Starting dose 300 mg/day (Recommended for patients with baseline weight ≥ 77kg and 
baseline platelet count ≥ 150,000/µL) 
3.9. 
Withdrawals, Dropouts, Loss to Follow-up 
Patients who are withdrawn or discontinue from the study will not be replaced. 
3.10. 
Missing Data 
In general, there will be no substitutions made to accommodate missing data points. Methods 
for handling incomplete PRO instruments are performed according to their scoring manuals. All 
data recorded on the eCRF will be included in data listings that will accompany the CSR. 
When tabulating AE data, partial dates will be handled as follows. 


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• If the day of the month is missing, the onset day will be set to the first day of the month 
unless it is the same month and year as study treatment. In this case, in order to 
conservatively report the event as treatment-emergent, the onset date will be assumed to 
be the date of treatment. 
• If the onset day and month are both missing, the day and month will be assumed to be 
January 1, unless the event occurred in the same year as the study treatment. In this case, 
the event onset will be coded to the day of treatment in order to conservatively report the 
event as treatment-emergent. 
• A missing onset date will be coded as the day of treatment. If the resulting onset date is 
after a reported date of resolution, the onset date will be set equal to the date of 
resolution. 
• 
 Imputation of partial dates is used only to determine whether an event is treatment- 
emergent; data listings will present the partial date as recorded in the eCRF. 
3.11. 
Visit Windows 
It is expected that all visits should occur according to the protocol schedule. By-visit summaries 
and analyses will be by nominal visit (all data will be tabulated per the evaluation visit as 
recorded on the eCRF even if the assessment is outside of the visit window for analysis). In data 
listings, the relative day of all dates will be presented. 
For PRO endpoints, visit windows will be applied to PRO assessments after EOT as shown in 
Table 3 when applicable. If multiple assessments are observed in a window, the visit closest to 
the scheduled assessment date will be used. If equally close, the earlier visit will be used. 
Table 3: 
Windows (Inclusive) for PRO Assessments after EOT 
Visit after EOT 
Scheduled Day after EOT 
Window (Days) 
4 weeks 
28 
14 to 42 
8 weeks 
56 
43 to 70 
12 weeks 
84 
71 to 126 
24 weeks 
168 
127 to 210 
3.12. 
Interim Analyses 
No formal interim analysis is planned. 
4. 
STUDY ANALYSES 
4.1. 
Patient Disposition 
Patient disposition will be tabulated and include the numbers of screened patients (who have 
signed informed consent), the numbers who discontinued treatment and discontinued study and 
reason(s) for withdrawal, and the number of patients who died. 
A by-patient data listing of study completion information including the reasons for treatment 
discontinuation and/or study discontinuation will be presented. 


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4.2. 
Demographics, Baseline Characteristics, and Medical History 
Demographics, baseline characteristics, and medical history information will be summarized 
using descriptive statistics. No formal statistical comparisons will be performed. 
Demographic and baseline data for each patient will be provided in data listings. 
The demographic and baseline characteristics tables will include the following variables: 
• Age at time of screening (years) calculated as date of screening minus date of birth / 
365.25, unless local regulations prevent the collection of date of birth, in which case age, 
as reported on the eCRF, will be used 
• Age categories (18 to <65, 65 to <75, ≥75; and ≥65) 
• Race (White, Black or African American, Asian, American Indian/Alaska native, native 
Hawaiian or other Pacific Islander, and other) 
• Ethnicity (Hispanic, non-Hispanic, unknown, and not reported) 
• Time from first diagnosis to first dose (years) 
• Primary tumor site (ovarian, primary peritoneal, or fallopian tube) 
• International Federation of Gynecology and Obstetrics (FIGO) stage at time of initial 
diagnosis 
• Baseline weight (in kilograms, last value prior to first dose; if weight is reported in 
pounds, convert to kilograms by dividing by 2.2) 
• Baseline height (in centimeters, last value prior to first dose; if height is reported in 
inches, convert to centimeters by multiplying by 2.54) 
• Baseline body mass index (BMI) (kg/m2), calculated using the patient’s height and 
weight at Baseline [BMI (kg/m2) = weight (kg) / height (m)2] 
• ECOG performance status at baseline 
• Baseline CA-125 level 
• Baseline platelet count 
• History of myelosuppression (thrombocytopenia, leukopenia, anemia, or neutropenia) 
• History of blood transfusion and growth factors 
• Prior ovarian cancer treatment and surgery 
• Ovarian cancer pathology 
• BRCA and HRD status by Myriad myChoice® HRD test 
Medical history will be coded using MedDRA v20.0 or later, and the number and percentage of 
patients experiencing at least 1 such diagnosis by MedDRA System Organ Class (SOC) and 
preferred term (PT) will be reported. 
Prior and follow-up anti-cancer therapy will be summarized according to Table 4 when 
applicable 


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Table 4: 
Reported Anti-cancer Therapies 
Therapy 
Regimens (Preferred Terms) 
Platinum 
CARBOPLATIN 
CARBOPLATIN W/GEMCITABINE 
CARBOPLATIN W/PACLITAXEL CISPLATIN 
CISPLATIN W/DOXORUBICIN CISPLATIN 
W/PACLITAXEL OXALIPLATIN 
PACLITAXEL W/CARBOPLATIN 
Carboplatin 
CARBOPLATIN 
CARBOPLATIN W/GEMCITABINE 
CARBOPLATIN W/PACLITAXEL 
PACLITAXEL W/CARBOPLATIN 
Cisplatin 
CISPLATIN 
CISPLATIN W/DOXORUBICIN CISPLATIN 
W/PACLITAXEL 
Taxane 
DOCETAXEL ABRAXANE 
PACLITAXEL PACLITAXEL 
ALBUMIN 
PACLITAXEL W/CARBOPLATIN 
CARBOPLATIN W/PACLITAXEL 
CISPLATIN W/PACLITAXEL 
Doxorubicin 
DOXORUBICIN 
DOXORUBICIN HYDROCHLORIDE 
LIPOSOMAL DOXORUBICIN HYDROCHLORIDE PEGYLATED 
LIPOSOMAL DOXORUBICIN 
PEGYLATED LIPOSOMAL DOXORUBICIN HYDROCHLORIDE 
CYCLOPHOSPHAMIDE W/DOXORUBINCIN 
CISPLATIN W/DOXORUBICIN 
Gemcitabine 
GEMCITABINE 
GEMCITABINE HYDROCHLORIDE 
CARBOPLATIN W/GEMCITABINE 
CARBOPLATIN W/GEMCITABINE HYDROCHLORIDE 
CISPLATIN W/GEMCITABINE HYDROCHLORIDE 
Pemetrexed 
PEMETREXED 
Topotecan 
TOPOTECAN 
Mirvetuximab 
Soravtansine 
MIRVETUXIMAB SORAVTANSINE 
Bevacizumab 
BEVACIZUMAB 
Cyclophosphamide 
CYCLOPHOSPHAMIDE CYCLOPHOSPHAMIDE 
W/DOXORUBINCIN 
PARP inhibitor 
OLAPARIB NIRAPARIB 
RUCAPARIB 
RUCAPARIB CAMSYLATE TALAZOPARIB 
VELIPARIB 


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Therapy 
Regimens (Preferred Terms) 
PD(L)-1 inhibitor 
PEMBROLIZUMAB 
ATEZOLIZUMAB 
DURVALUMAB 
NIVOLUMAB AVELUMAB 
CEMIPLIMAB 
4.3. 
Efficacy Evaluation 
All analyses will include summary statistics, including number and percentage for categorical 
variables and number of patients, mean, standard deviation, median, minimum, and maximum 
for continuous variables. Time-to-event analyses will be performed using Kaplan-Meier 
methodology. Two-sided 95% CIs will be provided where appropriate. Subgroups will also be 
analyzed for the primary efficacy endpoint based on age, ECOG, disease stage, HRD and BRCA 
status, neoadjuvant vs adjuvant, macroscopic visible residual disease after surgery, and best 
response to first-line platinum regimen. No formal statistical testing will be performed. 
4.3.1. 
Primary efficacy analyses 
The primary efficacy endpoint is PFS rate at 18 months (PFS18), which is defined as the 
proportion of patients who have not progressed or died within 18 months after niraparib 
combined with bevacizumab treatment initiation. Progression will be assessed by RECIST v1.1 
criteria per Investigator assessment. For the primary analysis, PFS18 will be estimated by 
• Number of ITT patients without documented progression or death by month of 18 
divided by number of ITT patients 
The 95% exact confidence interval will also be provided. 
In addition, the probability of PFS at 18 months will be estimated using the Kaplan-Meier 
method. 
The following subgroup analyses will be performed for PFS18 and PFS: 
• Age categories [<65 or ≥65] 
• ECOG status [ 0 or 1] 
• Stage of disease at initial diagnosis [III or IV] 
• HRD status [HRDpos, HRDpos/BRCAmut, HRDpos/BRCAwt, HRDneg, or Not 
determined] 
• BRCA status [BRCAmut, BRCAwt, or Not determined] 
• Neoadjuvant vs Adjuvant chemotherapy during front-line platinum regimen 
• Macroscopic visible residual disease after surgery [Yes, No or unknown] 
• Best response during front-line platinum regimen [CR/NED, or PR] 
4.3.2. 
Secondary Efficacy Variables 
4.3.2.1. 
Time to Event Endpoints 
The time to event endpoints (PFS, OS, RECIST or CA-125 PFS, TFST, TSST) will be analyzed 
using Kaplan-Meier methodology. Except for the RECIST or CA-125 PFS that progression will 
be based on either RECIST v1.1 or CA-125, the progression in other endpoints will be based on 


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RECIST v1.1 only. 
Quartiles (i.e., 25th percentile, median, 75th percentile) and associated 95% CIs from 
Brookmeyer and Crowley method with log-log transformation for event time will be estimated 
from the product-limit (KM) method. The KM estimate of the survival distribution function 
(SDF) will be computed. Estimates of the SDF will be presented at 6 months, 12 months, 18 
months, 24 months, and so on as data allow. Kaplan-Meier plots of the SDF will be presented 
and will include the number of patients at risk over time. Summaries of the number and 
percentage of subjects experiencing an event, and the type of event will also be provided. 
For PFS analysis, the following censoring rules will apply: 
1. No evaluable baseline or post-baseline radiological tumor assessments, and no death or 
progression occurred within the two consecutive radiological tumor assessment intervals 
following the first dose (25-weeks time frame): censored at the first dose date 
2. Start of subsequent anti-cancer therapy without a prior progression: censored at the date 
of last evaluable radiological tumor assessment on or prior to the start date of subsequent 
anti-cancer therapy, or the first dose date (whichever is later). 
3. No progression or death and no subsequent anti-cancer therapy: censored at the date of 
last evaluable radiological tumor assessment or the first dose date (whichever is later) 
4. Progression or death after two or more consecutive missing radiological assessments: 
censored at the date of last evaluable radiological tumor assessment prior to the 
consecutive missing assessments or the first dose date (whichever is later) 
5. Progression or death: event (whichever is earlier) 
For RECIST or CA-125 PFS, the following censoring rules will apply: 
1. No evaluable baseline or post-baseline radiological tumor assessment, and no death or 
progression based on either RECIST v1.1 or CA-125 occurred within the two 
consecutive radiological tumor assessment intervals following the first dose (25 weeks 
time frame): censored at the first dose date 
2. Start of subsequent anti-cancer therapy without a prior progression based on either 
RECIST v1.1 or CA-125: censored at the date of last evaluable radiological tumor 
assessment or CA-125 assessment on or prior to the start date of subsequent anti-cancer 
therapy, or the first dose date (whichever is later). 
3. No progression based on either RECIST v1.1 or CA-125, or death and no subsequent 
anti-cancer therapy: censored at the date of last evaluable radiological tumor or CA-125 
assessment, or the first dose date (whichever is later) 
4. Progression based on either RECIST v1.1 or CA-125, or death after two or more 
consecutive missing radiological assessments and CA-125 assessment: censored at the 
date of last evaluable radiological tumor or CA-125 assessment prior to the consecutive 
missing assessments, or the first dose date (whichever is later) 
5. Progression based on either RECIST v1.1 or CA-125, or death: event (whichever is 
earlier) 
For TFST analysis, the following censoring rules will apply: 
1. Any patient not known to have died at the time of analysis and not known to have had 
started the first line subsequent anti-cancer therapy will be censored at the last known 
time to have not received any subsequent therapy, i.e. the last assessment where this 


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was confirmed. 
2. Start of the first line subsequent anti-cancer therapy or death: event (whichever is 
earlier) 
For TSST analysis, the following censoring rules will apply: 
1. Any patient not known to have died at the time of analysis and not known to have had 
started any second line subsequent anti-cancer therapy will be censored at the last known 
time to have not received any second line subsequent therapy, i.e. the last assessment 
where this was confirmed. 
2. Start of the second line subsequent anti-cancer therapy or death: event (whichever is 
earlier) 
For OS, if no death: censored at the last date that patient was known to be alive. 
4.3.2.2. 
Patient Reported Outcomes 
FOSI will be collected every 6 weeks (± 7 days) for 6 months, then every 12 weeks (± 7 days) 
thereafter while the patient is receiving study treatment. Once a patient discontinues treatment, 
FOSI evaluations will be performed 4 weeks (± 7 days), 8 weeks (± 7 days), 12 weeks (± 7 
days), and 24 weeks (± 7 days) after treatment discontinuation, regardless of subsequent 
treatment. 
FOSI may be completed remotely. It is estimated that FOSI evaluations will take less than 
20 minutes at each timepoint. Since these are questionnaires, their completion will not interfere 
with or prevent future treatment or clinical studies. FOSI evaluations should be administered 
prior to conducting any other procedures at each visit. 
The FOSI is a validated 8-item measure of symptom response to treatment for ovarian cancer. 
Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale 
scored from 
 to 
 
The FOSI score will be derived in accordance with the FOSI scoring manual (Appendix 7.2). 
Negatively stated items are reversed by subtracting the response from
 After reversing 
proper items, all subscale items are summed to a total. A higher score indicates a better Quality 
of Life (QOL). 
If there are missing items, subscale scores will be prorated as long as more than 50% of the 
items were answered (i.e. at least 5 of 8 items). The proration is done by multiplying the sum of 
the subscale by the number of items in the subscale, then dividing by the number of items 
actually answered. 
FOSI score = 
 
Summary statistics for observed FOSI score and changes from baseline at each post baseline 
visit will be provided. A mixed-effects model for repeated measures (MMRM) will be used to 
model the FOSI score changes over time. Least squares means and 95% CIs at each post 
baseline visit will be presented. Least squares means and standard error bars will be plotted over 
time. The analysis visits include baseline, post baseline visits, unless there is excessive missing 
data at a visit (defined as >75% missing data). 
The MMRM model via PROC MIXED will include FOSI score changes from baseline at post 
baseline scheduled visits from week 6 (Cycle 3 Day 1) through EOT and up to 24 weeks after 
EOT (Follow-Up Week 24) as dependent variables; post baseline visit as fixed effect; baseline 
CCI
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FOSI score as a continuous covariate along with the baseline-by-visit interaction; and subject as 
a random effect. An unstructured covariance matrix will be used to model the within subject 
variance and the Kenward-Roger approximation will be used to estimate the degrees of 
freedom. Restricted maximum likelihood (REML) estimation will be used. An overall least 
squares means estimate will be derived, representing the average treatment effect over visits 
giving each visit equal weight. If the fit of the unstructured covariance structure fails to 
converge, the following covariance structures will be used in order until convergence is reached: 
toeplitz with heterogeneity (TOEPH), autoregressive with heterogeneity (ARH(1)), Toeplitz 
(TOEP), and autoregressive (AR(1)). If there are still issues with the fit of the model or 
estimation of the treatment effects, SUBJECT will be treated as a fixed effect. 
The FOSI categorical variables defined according to the minimum clinically important 
difference (MCID) levels will be summarized by visit. The FOSI score ranges from 
 
 to 
 A change of 2 points in FOSI score is considered as a 
MCID. The FOSI score change from baseline will be categorized at each post baseline visit as 
follows: 
• Improved: change from baseline ≥ 2 
• Stable: -2 < change from baseline < 2 
• Worsened: change from baseline ≤ -2 or “Patient was too ill” is answered as the reason 
for not completing the FOSI form at visit. 
In the reporting of the proportion of patients who have a response of Improved, Stable, or 
Worsened, the denominator will be all patients with non-missing FOSI scores at baseline and at 
each corresponding post baseline visit. 
The Time to symptom worsening in FOSI score will be defined as the time from the date of first 
study dose date to the date of first worsened FOSI score (change from baseline ≤ -2). 
Any patient without a worsened FOSI score will be censored at the date of the last evaluable 
FOSI assessment, i.e. FOSI score is not missing. Patients who have no valid baseline FOSI 
assessment or any post baseline FOSI assessment will be censored at the date of first study dose 
date. 
The overall compliance and compliance by visit will be summarized, based on the following 
definitions. 
• Expected forms: number of patients expected to complete PRO form. Date of study 
discontinuation and/or date of death will be used to determine the last visit at which a 
patient is still expected under PRO follow-up. 
• Received forms: number of PRO forms received back. 
• Evaluable forms: number of Received forms with at least one non-missing scale value 
plus number of forms not received back for reasons of “Patient was too ill”. 
The overall compliance rate is defined as the number of patients with an evaluable baseline and 
at least one evaluable post-baseline form, divided by the number of patients expected to 
complete the baseline form. 
Compliance by visit will be calculated as the number of patients with an evaluable form at that 
visit, divided by the number of patients expected to complete the form at that visit. 
The distribution of forms received and the reasons for forms not received back will be reported 
at each visit. To ensure the representativeness of the reported PRO data, a comparison of 
baseline characteristics for compliant vs. non-compliant patients may be performed if 
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compliance is considered inadequate. 
Descriptive summaries of individual items in each questionnaire and percentage of missing data 
at each visit will be reported. 
The analyses will be performed on ITT population and a subject listing will be provided. 
4.3.2.3. 
Outcomes for Next Anticancer Therapy Following Study Treatment 
The following data are collected in the eCRF for the next anticancer therapy following study 
treatment: Name of drug (and/or class), Start and Stop date, Progression date, Best response and 
Dose-limiting toxicities. 
The lines of follow-up therapy are determined for each patient based on the reported start date(s) 
of follow-up therapies (excluding hormonal therapy) and the reported progression date(s) after 
the start of any follow-up therapy. 
Hormonal therapy (PT: tamoxifen, tamoxifen citrate, toremifene, raloxifene, ospemifene, 
bazedoxifene, letrozole, anastrozole, exemestane) will not be considered for lines of follow-up 
therapy. 
If there are one or more progression dates, all the reported follow-up therapies will be grouped 
into lines of therapies by comparing their reported start dates to the reported progression dates. 
The follow-up therapies started prior to the first progression date following the start of any 
follow-up therapy are grouped as the first line of follow-up therapy. The follow-up therapies 
started after the first progression date and prior to the second progression date are grouped as 
the second line of follow-up therapy, and so forth. If there is none of progression date reported, 
the reported follow-up therapies are grouped as the first line of follow-up anticancer therapy. 
For each line of follow-up therapy, the start date of the line is the earliest start date of reported 
therapies in the line; the stop date of the line is the latest stop date of reported therapies in the 
line. All reported follow-up anticancer treatments will be summarized, including 
• Any follow-up surgeries (yes or no) 
• Any follow-up radiotherapy (yes or no) 
• Number of lines of follow-up anticancer therapies 
• Follow-up anticancer therapies 
The follow-up anticancer therapies will be summarized according to Table 4 when applicable. 
4.3.3. 
Efficacy Sensitivity Analysis 
For the primary PFS 18 and secondary PFS, a sensitivity analysis will be performed based on 
the Per Protocol population. 
In addition, the following sensitivity analysis will be performed for PFS in ITT population by 
using different censoring rules. 
• PFS Sensitivity analysis 1 (SA1): Ignore subsequent anti-cancer therapy 
o No evaluable baseline or post-baseline radiological tumor assessments, and no 
death or progression occurred within the two consecutive radiological tumor 
assessment intervals following the first dose (25-weeks time frame): censored at 
the first dose date 
o No progression or death: censored at the date of last evaluable radiological tumor 
assessment or the first dose date (whichever is later) 
o Progression or death after two or more consecutive missing radiological 


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assessments: censored at the date of last evaluable radiological tumor assessment 
prior to the consecutive missing assessments or the first dose date (whichever is 
later) 
o Progression or death: event (whichever is earlier) 
• PFS Sensitivity analysis 2 (SA2): Ignore missing tumor assessment 
o No evaluable baseline or post-baseline radiological tumor assessments, and no 
death or progression occurred within the two consecutive radiological tumor 
assessment intervals following the first dose (25-weeks time frame): censored at 
the first dose date 
o Start of subsequent anti-cancer therapy without a prior progression: censored at 
the date of last evaluable radiological tumor assessment on or prior to the start 
date of subsequent anti-cancer therapy, or the first dose date (whichever is later). 
o No progression or death and no subsequent anti-cancer therapy: censored at the 
date of last evaluable radiological tumor assessment or the first dose date 
(whichever is later) 
o Progression or death: event (whichever is earlier) 
• PFS Sensitivity analysis 3 (SA3): Include subsequent anti-cancer therapy as an event 
o No evaluable baseline or post-baseline radiological tumor assessments, and no 
death or progression or subsequent anti-cancer therapy occurred within the two 
consecutive radiological tumor assessment intervals following the first dose (25- 
weeks time frame): censored at the first dose date 
o No progression or death and no subsequent anti-cancer therapy: censored at the 
date of last evaluable radiological tumor assessment or the first dose date 
(whichever is later) 
o Progression or death or start of subsequent anti-cancer therapy after two or more 
consecutive missing radiological assessments: censored at the date of last 
evaluable radiological tumor assessment prior to the consecutive missing 
assessments or the first dose date (whichever is later) 
o Progression or death or start of subsequent anti-cancer therapy: event (whichever 
is earlier) 
The PFS sensitivity censoring rules will impact the PFS event definition, which will 
consequently impact the primary PFS 18 evaluation. As such, the PFS 18 sensitivity analysis in 
the ITT population will also be performed accordingly. 
The sensitivity analyses will not be performed at subgroup-levels. 
4.3.4. 
Exploratory Efficacy Evaluations 
The exploratory efficacy endpoints are PFS rate at 6 months (PFS6) and 12 months (PFS12), 
which are defined as the proportion of patients who have not progressed or died within 6 months 
and 12 months after initiation of treatment of niraparib in combination with bevacizumab 
treatment, respectively. Progression will be assessed by RECIST v1.1 criteria based on 
Investigator assessment. Additional landmark PFS analyses may be performed as deemed 
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4.3.5. 
Biomarker Analysis 
HRD will be evaluated retrospectively as a potential biomarker for response to niraparib 
combined with bevacizumab maintenance treatment using archival tumor sample. For patients 
who do not have archival tissue, tissue from a fresh biopsy must be obtained prior to study 
treatment initiation. 
4.4. 
Safety Analyses 
Safety analyses will be conducted using the Safety population. 
4.4.1. 
Niraparib Treatment Exposure 
Extent of treatment will be summarized as follows: 
• Number and percent of patients beginning 1, 2, 3, ..., 12, and >12 cycles. 
• Number of cycles started summarized as a continuous variable. 
• Overall treatment exposure (months), defined as the [last dose date - first dose date + 1] / 
30.4375, will be summarize as a continuous variable. 
• Actual treatment exposure (months), defined as the overall treatment exposure minus the 
duration of dose interruptions, will be summarized as a continuous variable. 
• Time on study (months), defined as the [last contact date or date of death - first dose date 
+ 1] / 30.4375, will be summarized as a continuous variable. 
Treatment compliance will be summarized using study treatment data up to the last dose date by 
data cut-off date as follows: 
• The total number of capsules consumed is the sum of the number of capsules dispensed 
minus the sum of the number of capsules returned by the patient during the study. The 
sum of the daily doses consumed (mg) is the total number of capsules consumed 
multiplied by the dosage (mg). 
• Dose intensity (mg/day), defined as sum of the daily doses actually consumed divided by 
overall treatment exposure (converted to days), will be summarized as a continuous 
variable. 
• Relative dose intensity (RDI, %), defined as dose intensity (mg/day) divided by intended 
dose intensity (mg/day), where intended dose intensity is the intended starting dose, will 
be summarized as a continuous variable. 
Dose intensity, dose reductions and dose interruptions will be summarized by cycle: 
• Number and percentage of patients with a dose reduction, as indicated on the dose 
modification eCRF, for any reason and due to an AE. 
• Number and percentage of patients with a dose interruption, as indicated on the dose 
modification eCRF, for any reason and due to an AE. 
Dosing information and capsule counts for each patient will be presented in a data listing. 
4.4.2. 
Bevacizumab Treatment Exposure 
Treatment exposure will be summarized as follows: 
• Number and percent of patients beginning 1, 2, 3, ..., 12, and >12 cycles. 


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• Number of cycles started summarized as a continuous variable. 
• Overall treatment exposure (months), defined as the [last dose date - first dose date + 21] 
/ 30.4375, will be summarize as a continuous variable. 
Treatment compliance will be summarized using study treatment data up to the last dose date by 
data cut-off date as follows: 
• Cumulative dose (mg) is calculated as sum of all actual dose infused. 
• Dose intensity (mg/kg/cycle) is calculated as cumulative dose divided by weight and 
duration of treatment ([last dose date - first dose date + 21]/21). 
• Relative dose intensity (RDI, %) is calculated as dose intensity (mg/kg/cycle) divided by 
intended dose intensity (mg/kg/cycle) multiplied by 100, where the intended dose 
intensity is 15mg/kg/cycle. 
• Dose intensity, infusions missing, and infusion interruptions will be summarized by 
cycle 
Infusion information for each patient will be presented in a data listing. 
4.4.3. 
Adverse Events 
4.4.3.1. 
Overview 
All AEs will be classified using MedDRA v20.0 or later. The severity of the toxicities will be 
graded according to the NCI CTCAE v4.03. Any AEs leading to death or discontinuation of 
study treatment, events classified as NCI CTCAE v4.03 Grade 3 or higher, study treatment- 
related events, and SAEs will be presented. 
Treatment emergent AEs (TEAEs) will be defined as: 
• Any new AE (one that was not seen prior to the start of treatment) that occurs for the 
first time after at least 1 dose of study treatment has been administered; or, 
• A preexisting condition (one that was seen prior to the start of treatment) that worsens in 
severity or is deemed by the investigator to be related to study drug after at least 1 dose 
of study treatment has been administered. 
• Note: If the start date is missing for an AE and the actual start date cannot be determined 
from a partial date, the AE will be considered treatment-emergent. 
• Note: AEs with a start date after 90 days after the last dose of study treatment will not be 
considered treatment emergent. 
AEs and SAEs will be collected and recorded in the eCRF for each patient from the day of 
signed main informed consent until 90 days after the last dose of study treatment or until the 
patient begins participation in a new clinical trial or initiates a new chemotherapy regimen, 
whichever occurs first. Patients will be followed until study closeout for study-drug related 
SAEs. 
MDS/AML and secondary cancers (new malignancies other than MDS or AML) must be 
reported until death or loss to follow-up. Pneumonitis must be reported for up to 90 days after 
the last dose of study treatment and any pregnancy must be reported. 
Any AEs recorded in the database that occur from the time of informed consent to first dose will 
be listed only and not included in safety analyses. Pre-existing conditions will be recorded in the 
eCRF on the Medical History or appropriate page. 


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Related TEAEs are defined as TEAEs related to treatment as judged by the Investigator. Any 
AEs for which the relationship to study drug is missing will be considered as related to study 
treatment. Unless otherwise specified, related analysis will be based on related to niraparib, 
bevacizumab, and any study treatment, respectively. 
The number and percentage of patients reporting a TEAE will be summarized by system organ 
class (SOC), preferred term (PT), toxicity grade, and relationship to study drug. 
The toxicity grade of AEs as assessed by the investigator will be graded using NCI CTCAE 
v4.03. Within the same MedDRA PT, only the most severe AE for each patient will be counted 
in tabulations by severity. Within a MedDRA SOC, patients with more than 1 MedDRA PT will 
be counted only once for the most severe AE reported. 
The relationship of each AE to the study drug will be summarized as assessed by the 
Investigator. All AEs for which the relationship to study drug is missing will be considered as 
related. Within the same MedDRA PT, only the AE with the highest ranked relationship to 
treatment for each patient will be counted in tabulations by relationship to treatment. Within a 
MedDRA SOC, patients with more than 1 MedDRA PT will be counted only once for the AE 
that is most related to treatment. The imputation for a missing relationship will take place prior 
to determining the most related AE within a SOC or PT for a given patient. 
The following lists the AE tables to be displayed for all safety population. Summaries 
designated with an asterisk (“*”) were produced for the safety population for the subgroup of 
age (< 65 years vs ≥ 65 years). 
• Overview of TEAEs* 
• TEAE by SOC and PT* 
• TEAE by PT (sorted by frequency) 
• Related TEAE by SOC and PT 
• Related TEAE by PT (sorted by frequency) 
• Treatment-emergent SAEs by SOC and PT* 
• Related treatment-emergent SAEs by SOC and PT 
• Grade ≥3 TEAEs by SOC and PT* 
• Related Grade ≥3 TEAEs by SOC and PT 
• Grade ≥3 treatment-emergent SAEs by SOC and PT 
• Related Grade ≥3 treatment-emergent SAEs by SOC and PT 
• Grade ≥3 TEAE by PT (sorted by frequency) 
• Related Grade ≥3 TEAE by PT (sorted by frequency) 
• SAE by PT (sorted by frequency) 
• Related SAE by PT (sorted by frequency) 
• Grade ≥3 treatment-emergent SAEs by PT (sorted by frequency) 
• Related Grade ≥3 treatment-emergent SAEs by PT (sorted by frequency) 
• TEAE by SOC, PT, and maximum grade 
• Related TEAE by SOC, PT, and maximum grade 


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• Grade ≥3 TEAE by SOC, PT, and maximum grade 
• Grade ≥3 Related TEAE by SOC, PT, and maximum grade 
• TEAEs leading to death by SOC and PT 
• Related TEAEs leading to death by SOC and PT 
• TEAEs leading to study drug dose interruption by SOC and PT 
• TEAEs leading to study drug dose reduction by SOC and PT 
• TEAEs leading to study drug discontinuation by SOC and PT* 
• TEAEs leading to study drug infusion delay by SOC and PT 
• Adverse events of special interest (AESI), by the grouped event and PT within each 
group 
o All AESI 
o Grade ≥3 AESI 
o Serious AESI 
o Grade ≥3 Serious AESI 
o AESI leading to study drug dose interruption 
o AESI leading to study drug dose reduction 
o AESI leading to study drug discontinuation 
o AESI leading to study drug infusion delay 
• Treatment-emergent Adverse events of medical interest (AEMI), by the grouped event 
and PT within each group 
o All TEAE* 
o Grade ≥3 TEAE* 
o Treatment-emergent SAEs 
o Grade ≥3 Treatment-emergent SAEs 
o TEAEs leading to study drug dose interruption 
o TEAEs leading to study drug dose reduction 
o TEAEs leading to study drug discontinuation * 
o TEAEs leading to study drug infusion delay 
• Non-serious TEAEs observed in at least 5% of patients by SOC and PT 
• Summary of Treatment Related Treatment-Emergent non-Serious Adverse Events by 
MedDRA Preferred Term in Descending Frequency Order 
• Summary of Niraparib Related Treatment-Emergent non-Serious Adverse Events by 
MedDRA Preferred Term in Descending Frequency Order 
• Summary of Bevacizumab Related Treatment-Emergent non-Serious Adverse 
Events by MedDRA Preferred Term in Descending Frequency Order 
For COVID-19 positive subjects who were diagnosed with probable, suspected or confirmed 
COVID-19, the following AE summary will be provided. 
• COVID-19 related TEAE by SOC and PT 


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• COVID-19 related Grade ≥3 TEAE by SOC and PT 
• COVID-19 related treatment-emergent SAEs by SOC and PT 
• COVID-19 related Grade ≥3 treatment-emergent SAEs by SOC and PT 
The COVID-19 related AE SOC and PT list is provided in a separate document. 
Tables structured as listings will be provided for the following: 
• AEs 
• SAEs 
• TEAE leading to Death 
• TEAEs leading to study drug dose interruption 
• TEAEs leading to study drug dose reduction 
• TEAEs leading to study drug discontinuation 
• TEAEs leading to study drug infusion delay 
• AESI 
• Treatment-emergent Adverse events of medical interest 
• Listing of COVID-19 Assessments and Symptom Assessments for COVID-19 Positive 
Subjects 
Adverse event summaries will be ordered in terms of decreasing frequency for SOC 
(alphabetically for SOCs with the same number of AEs reported) and decreasing frequency for 
PT within SOC (alphabetically for PTs with the same number of AEs reported within a SOC). 
4.4.3.2. 
Adverse Events of Special Interest 
The AESIs for this study are myelodysplastic syndrome (MDS), acute myeloid leukemia 
(AML), secondary cancers (new malignancies other than MDS/AML), pneumonitis, and 
embryo-fetal toxicity. Table 5 outlines the AESI with the criteria of mapping MedDRA PTs for 
each AESI using Standardized MedDRA Queries (SMQs), High Level Terms (HLTs), and/or 
PTs. 
Table 5: 
Adverse Events of Special Interest 
Group Term 
MedDRA V18.1 Criteria for Selection of Preferred Terms1 
AESI (MDS/AML events) 
MedDRA PTs associated with MDS/AML 
AESI (new malignancies other 
than MDS/AML) 
Malignant tumor SMQ (other than MDS/AML) 
AESI (pneumonitis) 
Lower respiratory tract inflammatory and immunologic conditions (HLT) 
AESI (embryo-fetal toxicity) 
Pregnancy and neonatal topics SMQ 
Abbreviations: AESI = adverse event of special interest; AML = acute myelogenous leukemia; HLT = high-level term; 
MDS = myelodysplastic syndrome; MedDRA = medical dictionary for regulatory activities; PT = preferred term; 
SMQ = Standardized MedDRA Query. 


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4.4.3.3. 
Adverse Events of Medical interest 
AEs of Medical interest (AEMI) such as myelosuppression and hypertension will be 
summarized in the similar manner as the AESIs. Table 6 outlines all the grouped events with the 
criteria of mapping MedDRA PTs for each group using Standardized MedDRA Queries 
(SMQs), High Level Terms (HLTs), and/or PTs. 
Table 6: 
Adverse Events of Medical interest 
Group Term 
MedDRA Criteria for Selection of Preferred Terms1 
Thrombocytopenia events 
Haematopoietic thrombocytopenia SMQ (Broad) 
Anemia events 
Haematopoietic erythropenia SMQ (Broad) 
Leukopenia events 
Haematopoietic leukopenia SMQ (Broad) 
Neutropenia events 
Selected PTs related to neutropenia in the Haematopoietic leukopenia SMQ 
(Broad) 
Pancytopenia events 
Haematopoietic cytopenias SMQ (Broad) 
Hypertension events 
Hypertension SMQ 
Abbreviations: AESI = adverse event of special interest; AML = acute myelogenous leukemia; HLT = high-level term; 
MDS = myelodysplastic syndrome; MedDRA = medical dictionary for regulatory activities; PT = preferred term; 
SMQ = Standardized MedDRA Query. 
The MedDRA PTs for AESI and adverse Events of Medical interest list are provided in a 
separate document. 
4.4.4. 
Laboratory Data 
Laboratory assessments will be performed locally at each center’s laboratory by means of their 
established methods. All laboratory values will be converted to SI units and classified as 
normal, low, or high based on normal ranges supplied by the local laboratories. 
Hematologic and chemistry laboratory results will be graded according to the cut points defined 
in the NCI CTCAE v4.03 severity grade. Laboratory results will be summarized by maximum 
CTCAE grade as available. Abnormal laboratory findings will be summarized by CTCAE grade 
1-4 and grade 3-4, respectively and sorted by frequency of grade 3-4. 
Continuous results will be analyzed using change from baseline and shift values. Change from 
baseline will be summarized and analyzed according to the largest increase, decrease, and at 
EOT, irrespective of scheduled or unscheduled visit. Graphical line mean changes over time 
may be provided, but due to the varying visits, no repeated measures analysis will be performed. 
Shift from baseline to the smallest value, the largest value, and the EOT value, categorized as 
low, normal, or high relative to the normal range, will be reported using number and percentage 
of patients. Shift from baseline CTCAE grade to the post-baseline maximum CTCAE grade will 
also be reported. 
A listing of potential Hy’s Law cases (patients with AST or ALT ≥3 ×upper limit of normal 
[ULN] in combination with bilirubin ≥2 ×ULN) will be also presented. 
Additionally, a Hy’s Law (DILI) plot will be produced which plots peak ALT and peak total 
bilirubin in 1 panel and peak AST and peak total bilirubin in a second panel. 
A by-patient listing of all laboratory data will be provided, with laboratory reference ranges and 
abnormal values highlighted, CTCAE grade if applicable, and including center, patient 
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4.4.5. 
Vital Signs and Physical Examination 
Summaries of vital signs parameters (systolic and diastolic blood pressures, pulse rate, and 
temperature) and weight will be presented by visit. Summary statistics will be produced for both 
observed and change from baseline values, for each parameter. 
Change from baseline will be summarized and analyzed according to the largest increase, 
decrease, and at the EOT, irrespective of scheduled or unscheduled visit. Graphical line mean 
changes over time may be provided, but due to the varying visits no repeated measures analysis 
will be performed. 
A summary table of the number and percent of patients categorized as low or high at any time 
on study after baseline according to the below criteria will be presented. 
• SBP (mm Hg): 
o Low: <90 and decrease from baseline ≥20 
o High: >160 and increase from baseline ≥20 
• DBP (mm Hg): 
o Low: <50 and decrease from baseline ≥10 
o High: >100 and increase from baseline ≥10 
Vital sign measurements will be presented for each patient in a data listing. 
The number and percentage of patients experiencing at least 1 abnormal result at the baseline 
physical examination will be summarized by body system. Physical examination findings will 
also be presented for each patient in a data listing. 
ECOG performance status will be reported in a data listing. 
Screening ECG data will be summarized for each ECG parameter and will be provided in a data 
listing for each patient. 
4.4.6. 
Concomitant Medications 
All medications will be coded using the September 2017 or later version of the WHO Drug 
Dictionary (WHODD). 
Medication start and stop dates will be compared to the date of first dose of study drug to allow 
medications to be classified as either Prior only, both Prior and Concomitant, or Concomitant 
only. Medications starting after the treatment withdrawal date will be listed but will not be 
classified or summarized. 
Medications that start and stop prior to the date of first dose of study drug will be classified as 
Prior only. If a medication starts before the date of first dose of study drug and stops on or after 
the date of first dose of study drug, then the medication will be classified as both Prior and 
Concomitant. Medications will be classified as Concomitant only if they have a start date on or 
after the date of first dose of study drug. Concomitant medication will be summarized by ATC 
level 3 and PT in frequency tables by treatment. Patients with more than 1 medication in a given 
ATC level and PT will be counted only once in that category. 


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If medication start and/or stop dates are missing or partial, the dates will be compared as far as 
possible with the date of first dose of study drug. Medications will be assumed to be 
Concomitant only, unless there is clear evidence (through comparison of partial dates) to 
suggest that the medication started prior to the first dose of study drug. If there is clear evidence 
to suggest that the medication started prior to the first dose of study drug, the medication will be 
assumed to be both Prior and Concomitant, unless there is clear evidence to suggest that the 
medication stopped prior to the first dose of study drug. If there is clear evidence to suggest that 
the medication stopped prior to the first dose of study drug, the medication will be assumed to 
be Prior only. The following lists the concomitant medication tables to be displayed: 
• Number and percentage with at least 1 prior medication by ATC level 3 and PT 
• Number and percentage with at least 1 concomitant medication by ATC level 3 and PT 
• Number and percentage with at least 1 prior and concomitant medication by ATC level 3 
and PT 
The use of concomitant medications will be included in a by-patient data listing. 
5. 
CHANGES TO PLANNED ANALYSES 
5.1. 
Protocol Changes 
The following changes were implemented to the protocol (through amendment 02) after the 
primary analysis and may impact the analyses performed at the final analysis: 
• Treatment cycles were extended from 21 days (±3 days) to 84 days (±7 days) for patients 
still on treatment at time of the protocol amendment’s implementation. Once patients 
transitioned to an 84-day cycle their next scan was required no less than 21 weeks and no 
more than 30 weeks after the last scan. 
• Pneumonitis and embryo-fetal toxicity were removed as AESI and will not be 
summarized at the final analysis. The updated Table 5 is provided below: 
Group Term 
MedDRA V18.1 Criteria for Selection of Preferred Terms1 
AESI (MDS/AML events) 
 Myelodysplastic syndrome (SMQ Narrow) 
Leukemias acute myeloid (HLT) 
AESI (new malignancies other 
than MDS/AML) 
• 
Hematological malignant tumor (SMQ Narrow) 
• 
Non-haematological malignant tumors (SMQ Narrow) 
Selected PTs not considered a second primary malignancy will be flagged and 
removed upon clinical/safety team review. 
5.2. 
Final Analysis 
The final analysis data cut will be approximately 5 years after the enrolment of the last patient 
(Feb 2019).  The following analyses that were conducted as part of the primary analysis package 
will be repeated:  
• Patient disposition (all summaries described in Section 4.1), protocol deviations (Section 
2.2.3, except COVID-19 deviations will not be reported separately.) and concomitant 
medications only (Section 4.4.6) will be summarized. The PP population will not be re-
defined since it is not required for the final analysis. 
• All secondary efficacy endpoints (time-to-event, PRO) as described in Section 4.3.2, with the 
following considerations: 
o All subgroups described in Section 4.3.1 will be analyzed for the OS endpoint. Only 
BRCA status and HRD status subgroups will be analyzed for PFS. All other 


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secondary endpoints will not be analyzed by subgroup. 
o Sensitivity and exploratory analyses for PFS will not be conducted (Section 4.3.3 and  
4.3.4). 
o Kaplan Meier plots will be produced for PFS, OS, TFST and TSST (Section 4.3.2.1) 
o The analysis of OS will include data collected while on study and data retrieved post-
study discontinuation. Death dates collected in the Participant Survival Status – Post 
Study Withdrawal form will be accounted for. Last known alive dates collected in the 
same form will be included in the calculation of Last Known Alive date.  
• Follow-up anticancer therapy summary as described in Section 4.3.2.3. Note that the list of 
anti-cancer therapies given in  Table 4 will be updated and provided in a separate document. 
• Safety analyses: 
o Subgroups will not be analyzed for safety endpoints. 
o Treatment exposure and compliance as described in Sections 4.4.1 and 4.4.2 
▪ Only for niraparib as all patients who were exposed to bevacizumab had 
discontinued bevacizumab at the time of primary analysis. 
o Adverse events as described in Section 4.4.3 for the overall Safety population only. 
▪ Adverse events will only be summarized as related to either treatment 
(niraparib or bevacizumab) as all bevacizumab participants discontinued at the 
time of the primary analysis. 
▪ Adverse Events of Medical Interest will not be repeated at the final analysis. 
▪ Adverse Events leading to bevacizumab treatment modifications will not be 
analyzed as all patients who were exposed to bevacizumab had discontinued 
bevacizumab at the time of primary analysis. 
▪ A summary of deaths will be produced: this will be based on participant death 
data collected while on-study and data retrieved post-study discontinuation 
(Discontinuation of Study form, and Participant Survival Status – Post Study 
Withdrawal form).  
o Laboratory data as described in Section 4.4.4 (summaries of change from baseline and 
shift to maximum grade for graded tests/normal range for non-graded tests only) 
o Vital sign data as described in Section 4.4.5 (summary of vital signs by scheduled 
visit only) 
o Safety figures and COVID-19 displays will not be produced for final analysis. 
▪ Protocol deviations related to COVID-19 will not be produced separately.  
• Only key efficacy listings and safety listings (Liver events, AEs & deaths, Labs) will be 
produced. 


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All endpoints are to be analyzed as for the primary CSR; no methodological changes are proposed. 
Programmatic derivation and data mapping adjustments may be introduced to niraparib exposure 
and PFS censoring to incorporate the schedule assessments as of Protocol Amendment 2. For 
exposure, the calculation of number of capsules consumed will need to account for the multiple 
bottles dispensed in the more dispersed cycles. For PFS, where patients are censored if they 
experience an event after a long time without tumor assessment (quantified as at least 2 consecutive 
missing visits), the 2 missed visits window definition may be updated. Details of the derivation 
updates (if any) will be provided in the programming specifications document.  
When tabulating death data, the following rules will be applied to handle partial dates: If a 
participant is known to have died where only a partial death date is available, then the date of death 
will be imputed as the latest of the last complete known to be alive date + 1 from the database and 
the death date using the available information provided:  
• 
For missing day only – use the 1st of the month 
• 
For missing day and month- use the 1st of January  


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6. 
REFERENCES 
Beaumont J, Yount S, Lalla D, et al. Validation of the Functional Assessment of Cancer 
Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a Phase II Clinical Trial of Pertuzumab 
in Patients with Advanced Ovarian Cancer. Journal of Clinical Oncology, 2007 ASCO Annual 
Meeting Proceedings (Post-Meeting Edition). 2007;25(18S):16021. 
Clopper C, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika. 1934;26:404-13. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal 
of cancer. 2009;45(2):228-47. 
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. Journal of the 
American Statistical Association. 1958;53:457–81 


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7. 
APPENDIX 
7.1. 
Sample Functional Assessment of Cancer Therapy – Ovarian 
Symptom Index (FOSI) 
Below is a list of statements that other people with your illness have said are important. Please 
circle or mark one number per line to indicate your response as it applies to the past 7 
days. 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party 
copyright laws and therefore have been excluded.


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7.2. 
Scoring Algorithm for the FACT/NCCN Ovarian Symptom Index 
(FOSI) 
FACT/NCCN Ovarian Symptom Index (FOSI) 
Scoring Guidelines (Version 4) 
8. 
STATISTICAL OUTPUT SHELLS 
The list of statistical output and corresponding table/figure/listing shells are provided in a 
separate document. 
9. 
REVISION HISTORY 
N/A 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright laws 
and therefore have been excluded.