Conditions: Ovarian Neoplasms
Keywords: Ovarian Cancer Homologous Recombination Deficiency (HRD) Interval debulking surgery (IDS) Niraparib Paclitaxel Carboplatin
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: no

Brief summary:
The goal of the study is to learn whether Niraparib or Platinum-Taxane Doublet chemotherapy is better in treating participants with Homologous Recombination Deficient (HRd) Stage III/IV Ovarian Cancer (OC). This study is a sub-study of the Master protocol -OPAL (NCT03574779)

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Niraparib intervention 2: Carboplatin intervention 3: Paclitaxel
Intervention descriptions: intervention 1: Niraparib will be administered intervention 2: Carboplatin will be administered intervention 3: Paclitaxel will be administered

Protocol document:
Prot_000.pdf: 
Protocol
Study ID: 213357-Cohort-C
Study Official Title: A Phase 1B/2 Multicohort Umbrella Study to Evaluate the 
Safety and Efficacy of Novel Treatments and/or Combinations of Treatments in 
Participants with Ovarian Cancer (OPAL) (PR-3000-02-005/213357)
Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter Study 
Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as 
Neoadjuvant Treatment in Participants with Homologous Recombination-
deficient Stage III/IV Ovarian Cancer
NCT ID: NCT06964165
Date of Document: 31 Oct 2023
Note:  213357 is a master protocol, registered under the identifier 
NCT03574779. It includes independent sub-studies, Cohort A (NCT05751629) 
and Cohort C (NCT06964165), each separately registered on ClinicalTrials.Gov. 
This is a cohort C-specific protocol. Please refer to the Master Protocol 
(NCT03574779) for general protocol elements.


1. 
TITLE PAGE 
 
SUPPLEMENT C 
3000-02-005 
COHORT C: OPEN-LABEL PHASE 2, RANDOMIZED, 
CONTROLLED MULTICENTER STUDY COMPARING 
NIRAPARIB VERSUS PLATINUM-TAXANE DOUBLET 
CHEMOTHERAPY AS NEOADJUVANT TREATMENT 
IN PARTICIPANTS WITH HOMOLOGOUS 
RECOMBINATION-DEFICIENT STAGE III/IV 
OVARIAN CANCER 
Sponsor: 
TESARO Inc., 
a GlaxoSmithKline Company 
1000 Winter Street, Suite 3300 
Waltham, MA 02451 
+1 339 970 0900 
TESARO Bio Netherlands B.V., 
a GlaxoSmithKline Company 
Joop Geesinkweg 901  
1114AB Amsterdam-Duivendrecht 
The Netherlands 
+45 31664608 
Medical Monitor: Medical monitor name and contact can be found in the cohort-specific 
Study Reference Manual 
Clinical Research Organization: 
Not applicable 
IND No.: 
100,996 
EudraCT No.: 
2021-005392-39 
EU CT Number 
2023-505097-16-00 
Development Phase: 
2 
Date of Original (Version 1.0) Master Protocol: 
20 March 2018 
Date of Master Protocol Amendment 1 (Version 2.0): 
15 October 2021 
Date of Master Protocol Amendment 2 (Version 3.0):  
26 October 2023 
Version of Protocol Supplement C: 
2.0 
Date of Original (Version 1.0) Protocol Supplement C: 
15 October 2021 
Date of Protocol Supplement C Amendment 1 (Version 2.0): 
31 Oct 2023 
 
©2023 GSK group of companies or its licensor. 


SPONSOR SIGNATURE PAGE 
 
Declaration of Sponsor or Responsible Medical Officer 
 
Title (Study Number): A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and 
Efficacy of Novel Treatments and/or Combinations of Treatments in Participants with Ovarian 
Cancer (OPAL) (PR-3000-02-005/213357) 
Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter Study Comparing 
Niraparib Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in 
Participants with Homologous Recombination-Deficient Stage III/IV Ovarian Cancer 
 
This cohort-specific protocol supplement was subjected to critical review and has been approved 
by the Sponsor. The information it contains is consistent with the current risk/benefit evaluation 
of the investigational product as well as with the moral, ethical, and scientific principles 
governing clinical research as set out in the Declaration of Helsinki and the guidelines on Good 
Clinical Practice. 
 
 
 
 
 
_________________________________ 
_________________________________ 
Jimmy Belotte, MD, PhD 
Date 
Medical Director, GSK 
 
 
 


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INVESTIGATOR’S AGREEMENT 
 
I have read this cohort-specific protocol supplement, including all appendices. By signing this 
supplement, I agree to conduct the clinical study, following approval by an Independent Ethics 
Committee (IEC)/Institutional Review Board (IRB), in accordance with the study protocol 
(comprising the master protocol and this cohort-specific supplement), the current International 
Council for Harmonisation (ICH) Guideline for Good Clinical Practice (GCP), the Declaration of 
Helsinki (2013), and applicable regulatory requirements. I will ensure that all personnel involved 
in the study under my direction will be informed about the contents of this cohort-specific 
protocol supplement and will receive all necessary instructions for performing the study 
according to the study protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 (Version 2.0) 
31 Oct 2023 
Original Protocol (Version 1.0) 
15 October 2021 
Amendment 1 (31 Oct 2023) 
This amendment is considered substantial based on the criteria defined in European Union (EU) 
Clinical Trial Regulation No 536/2014 of the European Parliament and the Council of the 
European Union because the changes significantly impact the scientific value of the study and 
safety of the participants. 
Overall Rationale for the Current Amendment:  
Amendment 1 is a global amendment resulting from changes in the Statstical Analysis Plan 
(SAP) and analysis populations, as well as clarification for study conduct.  
A general description and brief rationale for the changes are provided in the table below. The 
synopsis was updated to align with the changes in the protocol body. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Headers, title page, 
abbreviations, Protocol 
Amendment Summary 
of Changes (new), List 
of Abbreivations, 
Procedures in Case of 
Emergency, 
References, and 
throughout 
Headers and title 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, minor corrections and 
formatting adjustments, and to add 
clarification and/or remove discrepancies. 
Editorial changes to align with the 
Sponsor’s standard protocol template, 
style guide, and ways of working and 
for accuracy, clarity, conformity, flow, 
and typographical error correction. 


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Section # and title 
Description of change 
Brief rationale 
Section 6.3 Exploratory 
Objectives 
Section 7.2 Number of 
Participants 
Section 11.2 Secondary 
Efficacy Endpoints 
Section 11.4 
Exploratory Endpoints 
Section 13.2 Planned 
Analyses 
Section 13.2.1 Analysis 
Populations 
Section 13.2.2.1 
Primary Efficacy 
Analysis 
Section 13.2.2.2. 
Secondary Efficacy 
Analysis 
Section 13.2.2.3 
Exploratory Efficacy 
Analysis 
Section 13.2.5 Interim 
Analysis 
Changes in statistical endpoints and 
analysis text include the following: 
• 
Updated the primary analysis 
population to the Intent-to-Treat (ITT) 
Population 
• 
 
 
 
 
 
 
 
• 
Clarification included regarding timing 
and minimum maturity for time-to-event 
endpoints of the planned analyses 
• 
Progression-free survival (PFS) rates 
removed as secondary endpoints and 
will instead be assessed as part of the 
PFS analysis 
• 
Analysis Populations revised to remove 
additional analysis populations 
Clarifications and corrections made to 
planned statistical analyses. Additional 
analysis populations removed from 
protocol but included in the SAP to 
prevent duplication. 
Additional exploratory efficacy 
endpoints were added to further 
evaluate clinical efficacy. 
Section 7.4.1.1 
Niraparib, (Niraparib 
Dose Interrupation and 
Modification) 
Table 3 Nirapairb Dose 
Modifications for 
Nonhematological 
Toxicity 
Table 4 Niraparib Dose 
Modifications for 
Hematologial Toxicity 
Niraparib interruption updated to indicate 
interruption allowed for up to 28 days 
To align with Global Data Sheet 
(GDS)/Investigator’s Brochure (IB) 
Section 10.5.1 Niraparib Study drug administration updated to 
include guidance for niraparib starting dose 
in the maintenance period for participants 
who received niraparib in the neoadjuvant 
period and experienced dose reductions 
To clarify and provide guidance on 
maintenance period starting dose for 
participants who experienced niraparib 
dose reductions due to AEs in the 
neodjuvant period to ensure participant 
safety. 
Table 5 (Schedule of 
Events) 
Section 7.6.7 Safety 
Assessments 
Baseline electrocardiogram (ECG) 
monitoring added for all participants and as 
needed throughout the study based on 
patient cardiovascular risk profile. Footnote 
included in Table 5 for clarification. 
To align with safety monitoring for 
participants receiving niraparib 
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Section # and title 
Description of change 
Brief rationale 
Section 8.1 Inclusion 
Criteria 
Update inclusion criterion C7 to permit 
enrollment of participants with gBRCA test 
To allow enrollment of patients with 
permitted gBRCA test without waiting 
for results of the central test, as high 
concordance is expected between 
Sponsor’s permitted test and central 
test results. 
Section 8.3.1 
Discontinuation from 
Treatment 
Section 8.3.2 
Discontinuation from 
Study 
Additional text surrounding data collection 
including overall survival (OS) data 
collection in long-term follow-up after 
withdrawal of consent or lost-to-follow up 
Clarification for study conduct and 
collection of OS data for analysis 
Section 11.1 Primary 
Efficacy Endpoint 
Section 11.3 Patient-
reported Outcome 
Endpoints 
Section 13.2.4 Safety 
Analyses 
• 
Updated primary endpoint wording to 
unconfirmed ORR for clarification 
• 
Correction to exploratory patient-
reported outcome (PRO) endpoint 
wording to align with data collection in 
Table 5 
• 
Clarification to define population for 
Safety Analyses 
Clarification statistical endpoints, data 
collection, and analyses 
Section 7.1 Overall 
Study Design 
Table 5 Schedule of 
Events 
Clarification surrounding the Safety Follow-
up Visit. 
Removed text regarding EOT scan for those 
with PD in text and footnotes, which was 
included in error. 
Clarification for study conduct. Safety 
Follow-up visits required for all 
participants following end-of-treatment. 
Title Page 
Section 5.5 Benefit/Risk 
Assessment (new) 
Section 7.1.6 End of 
study definition 
EU CT number added 
Benefit-risk text added 
End of study definition included along with 
follow-up time 
To align with the Sponsor’s protocol 
template and components aligned with 
EU CTR 
Figure 2 (Study 
Schema) 
Section 7.1.2 
Neoadjuvant Treatment 
Period 
Section 9.4 
Randomization and 
Blinding 
Section 13.1 Sample 
Size Determination 
Section 13.2.2.2 
Secondary Efficacy 
Analysis 
Clarified stratification for BRCA mutational 
status (BRCAmut vs BRCAwt/unknown) 
Added text in sample size determination 
section indicating additional participants 
may be randomized for drop-out 
Clarification for study conduct 


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Section # and title 
Description of change 
Brief rationale 
Section 7.1.2 
Neoadjuvant Treatment 
Period 
Section 7.1.3 IDS 
Period 
Updates, including new figure (Figure 1) to 
better describe the process for going into 
IDS after pre-IDS scan 
Clarification in study conduct 
Section 7.1.5 
Maintenance Treatment 
Period 
Table 5 Schedule of 
Events (footnote) 
Section 7.6.3.1 RECIST 
v1.1 
Extended visit window for imaging 
assessments at 6 months to ± 14 days 
Adjusted visit window for maintenance 
assessment for visits after 1 year 
Table 5 Schedule of 
Events 
Section 7.4.1.1 
Niraparib 
(Hypertension, 
Including Hypertensive 
Crisis) 
Clarifications added in table foonote 
regarding regarding blood pressure and 
heart rate monitoring and timing of 
assessments and data collection. 
Clarification for study conduct for 
participant safety monitoring 
Table 5 Schedule of 
Events 
Section 7.6.6 Patient-
reported Outcome 
Questionnaires 
Updated text (and footnote added in 
Table 5) to indicate ePROs should be done 
before any procedure at all visits 
Clarification for study conduct to align 
with intended procedures 
Table 5 Schedule of 
Events 
Section 7.6.7 Safety 
Assessments 
Updated text to indicate adverse event (AE) 
collection/reporting should begin at the time 
of signing Prescreening Informed Consent 
Form (ICF) 
Clarification in study conduct for AE 
reporting 
Table 5 Schedule of 
Events (footnote) 
Section 7.6.10 Tumor 
Tissue and Blood 
Sampling 
Clarification added regarding number of PK 
samples collected predose and window for 
taking samples 
Clarification in study conduct to align 
with procedures outlined in the Study 
Reference Manual 
Table 5 Schedule of 
Events (footnote) 
Clarification added surrounding complete 
blood count (CBC) and timing of 
assessements. 
Clarification for study conduct and 
safety monitoring in the niraparib arm. 
Section 8.2 Exclusion 
Criteria 
Minor updates in wording to exclusion 
criterion #C9 for clarification  
Clarification in study conduct  
Section 9.1, Table 6 
Study Drugs 
Added row to clarify which study treatments 
are investigational medicinal (IMP) products 
vs non-IMP/auxiliary medicinal products. 
Clarification per regulatory feedback 
received during first submission, and for 
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Section # and title 
Description of change 
Brief rationale 
Table 5 Schedule of 
Events (footnote) 
Section 9.2.2 
Contraception 
Contraception and pregnancy testing 
requirements clarified 
Clarification for study conduct 
Section 7.6.2 Treatment 
Cycles 
Section 7.6 Study 
Conduct, Table 5 
Schedule of Events 
• 
Visit windows added to Schedule of 
Events (C1D8, C1D15, C1D1, C2D1, 
C3D1) and language surrounding Long-
term Follow-up Visits 
• 
Symptom-directed physical examination 
included for C1D8 and C1D15 
• 
Clarifications added in footnotes 
regarding AE and concomitant 
medications data collection 
Clarification and consistency within the 
protocol, with intended procedures, with 
Informed Consent Form (ICF) wording 
and local standard of care practice 
Section 10.2 Study 
Drug Packaging and 
Labeling 
Section 10.7 Study 
Drug Handling and 
Disposal 
Updated to include location of detailed 
information for additional study 
interventions. 
Clarity and completeness and 
clarification for details related to 
carboplatin-paclitaxel, and 
bevacizumab, as well as description of 
niraparib study drug. 
Section 13.2.4.1 
Pharmacokinetic and 
Pharmacodynamic 
Analyses 
Removed statement regarding responsibility 
for analysis. 
Clarification and alignment with anlaysis 
process. 
Appendix B, Table 7 
Liver Chemistry 
Stopping Criteria and 
Required Follow-up 
Assessments 
Updated langauge to reference liver event 
eCRF 
Updated timing for obtaining blood PK 
sample 
Clarification in study conduct and 
sample collection surrounding liver 
event assessment 
 


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PROCEDURES IN CASE OF EMERGENCY 
Procedures in case of emergency are outlined in the Supplement C Study Reference Manual. 
 


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2. 
SYNOPSIS 
Name of Sponsor/Company: TESARO Inc., a GSK company 
Name of Investigational Product: Niraparib 
Name of Active Ingredient: Niraparib 
Title of Study: Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of 
Novel Treatments and/or Combinations of Treatments in Participants with Ovarian Cancer 
Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter Study Comparing Niraparib 
Versus Platinum-Taxane Doublet Chemotherapy as Neoadjuvant Treatment in Participants with 
Homologous Recombination-Deficient Stage III/IV Ovarian Cancer 
Study center(s): Multicenter global 
Principal Investigator: To be determined 
Investigators: Multicenter (a list is provided in the Study Reference Manual) 
Studied period (years): 
Estimated date first participant enrolled: Q4 2021 
Estimated date last participant completed: Q4 2025 
Phase of development: 2 
Objectives: 
Primary: 
• 
To evaluate the efficacy of neoadjuvant niraparib compared with neoadjuvant platinum-
taxane doublet chemotherapy after 1 induction cycle of carboplatin-paclitaxel per Response 
Evaluation Criteria in Solid Tumors (RECIST) v1.1 in participants with confirmed 
homologous recombination-deficient (HRd) Stage III to IV ovarian cancer (OC) 
Secondary: 
• 
To evaluate clinical benefit by Gynecological Cancer InterGroup (GCIG) cancer antigen 125 
(CA-125) response criteria 
• 
To evaluate clinical benefit as measured by progression-free survival (PFS) per RECIST 
v1.1 by investigator assessment 
• 
To evaluate participants’ reported overall tolerability toward treatment, overall health status, 
OC-specific health-related quality of life (HRQoL) and symptoms, and work productivity 
• 
To evaluate clinical benefit as measured by overall survival (OS) 
• 
To evaluate clinical benefit as measured by time to first subsequent treatment (TFST) 
• 
To evaluate the safety and tolerability of neoadjuvant niraparib and neoadjuvant platinum-
taxane doublet chemotherapy 
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Methodology: 
This is a global, multicenter, randomized, open-label, Phase 2 cohort in participants with newly 
diagnosed, Stage III or IV, high-grade non-mucinous epithelial ovarian, fallopian tube, or peritoneal 
cancer (collectively referred to as “ovarian cancer” or OC) who are eligible for neoadjuvant 
platinum-taxane doublet chemotherapy followed by interval debulking surgery (IDS). This study will 
enroll participants with HRd OC as determined by the central tumor homologous recombination 
deficiency (HRD) testing using a fully validated assay. All prescreened participants would have 
received, prior to enrollment, 1 cycle of standard of care (SOC) chemotherapy (i.e., carboplatin-
paclitaxel) to allow sufficient time for receipt and review of the biomarker test results.  
After confirmation that the tumor is HRd, participants will be randomized 1:1 to three 21-day cycles 
of platinum-taxane doublet chemotherapy (Arm 1; carboplatin-paclitaxel, unless not tolerated by the 
participant) or neoadjuvant niraparib (Arm 2). After 3 cycles of treatment, the participants will 
undergo IDS. 
After IDS, all participants will receive up to three 21-day cycles of platinum-taxane doublet 
chemotherapy (Cycles 4, 5, and 6), with the third cycle (Cycle 6) being optional (any site choosing to 
give the third cycle must offer the third cycle to all eligible participants treated at that site regardless 
of the arm the participant was enrolled onto). The Investigator may choose to administer 
bevacizumab or bevacizumab biosimilar in addition to platinum-taxane doublet chemotherapy as 
SOC therapy for a participant deemed high-risk. Any site that chooses to provide optional 
bevacizumab or bevacizumab biosimilar as SOC must offer it to all eligible high-risk participants 
treated at that site, regardless of enrollment arm. 
Adjuvant chemotherapy is followed by niraparib maintenance treatment for up to 36 months or until 
adverse event (AE), progression of disease (PD) per RECIST v1.1, risk to participant or participant’s 
severe noncompliance with protocol as judged by the Investigator or Sponsor, participant’s request, 
pregnancy, or end of study. Participants that are administered bevacizumab or bevacizumab 
biosimilar with chemotherapy after IDS may continue to receive it in addition to niraparib during the 
maintenance treatment period for up to 22 cycles (including adjuvant chemotherapy period). 
Participants who discontinue study treatment prior to an investigator assessment of PD per RECIST 
v1.1 will continue radiographic imaging until PD per RECIST v1.1, start of alternate anticancer 
therapy, participant discontinuation of the study, withdrawal of consent to study procedures, 
becoming lost to follow-up, death, or end of the study. 
Participants will be followed up for safety for 30 days (±7 days) after completion of study treatment. 
After the Safety Follow-up Visit, all participants will enter the posttreatment follow-up period of 
telephone assessment for survival status, assessment of subsequent anticancer therapy, and the 
occurrence of any adverse event of special interest (AESI) every 90 days (±14 days) until participant 
discontinuation of the study, withdrawal of consent, death, or end of study. Radiographic imaging 
will continue as scheduled during the posttreatment follow-up period for all participants without PD 
per RECIST v1.1 until PD per RECIST v1.1, start of alternate anticancer therapy, participant 
discontinuation of the study, withdrawal of consent to study procedures, becoming lost to follow-up, 
death, or end of the study. 
Primary efficacy endpoint is pre-IDS unconfirmed ORR; defined as the percentage of participants 
with unconfirmed complete or partial response) per RECIST v1.1 by investigator assessment. 
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Secondary endpoints include CA-125 progression by GCIG CA-125 response criteria; PFS; patient-
reported outcomes to evaluate overall tolerability to treatment, overall health status, OC-specific 
HRQoL and symptoms, and work productivity; OS; TFST; and safety and tolerability. Exploratory 
endpoints include surgical and postsurgical outcomes, as well as pre-IDS DCR, pre-maintenance 
unconfirmed ORR, and pre-maintenance DCR. 
 
 
  
All participants must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides if blocks 
are not available) with sufficient tumor content (as confirmed by the sponsor’s designated central 
and/or testing laboratory) for central HRD testing at Prescreening and exploratory biomarker testing 
at Prescreening or Screening. If sufficient tumor tissue is provided at Prescreening, participants do 
not need to provide additional tissue at Screening. Participants will be required to provide sufficient 
tumor sample collected during IDS. Blood samples will be collected for exploratory biomarker 
testing, including evaluation of circulating plasma biomarkers 
) and 
. Blood samples will be collected at Prescreening, Cycle 1 Day 1, pre-IDS, Cycle 4 
Day 1, Maintenance Cycle 1 Day 1 and every 3 months thereafter, the End-of-Treatment Visit, and 
the Safety Follow-up Visit. 
The Cohort C study schema is provided below.  
Note: Duration of study periods are as follows: 
 Prescreening: 5 weeks 
 Screening: 1 week 
 Neoadjuvant treatment: up to 12 weeks 
 IDS: up to 6 weeks 
 Adjuvant platinum-taxane chemotherapy and optional bevacizumab or bevacizumab biosimilar: 6 to 
9 weeks* 
 Niraparib maintenance: up to 36 months. Optional bevacizumab or bevacizumab biosimilar may be 
administered for up to 22 cycles (including adjuvant chemotherapy period). 
*Note: Cycle 6 is optional. If a site chooses to administer cycle 6 (C6) of adjuvant chemotherapy, all 
participants treated at this study site must be offered C6 of adjuvant chemotherapy, regardless of treatment 
received during the neoadjuvant treatment period. Any site that chooses to provide optional bevacizumab or 
bevacizumab biosimilar as SOC to eligible high-risk participants must offer it to all eligible high-risk 
participants treated at that site, regardless of enrollment arm. 
Stratification: BRCAmut (deleterious or suspected deleterious BRCA1 or BRCA2 mutation) vs 
BRCAwt/unknown (no deleterious or suspected deleterious BRCA1 or BRCA2 mutation; including unknown) 
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Abbreviations: BRCA=breast cancer gene; BRCAmut=BRCA mutant; BRCAwt=BRCA wildtype; C=cycle; 
carbo=carboplatin; chemo=chemotherapy; CR=complete response; Cx=cycle number; endpt=endpoint; 
EU=European Union; HR=homologous recombination; HRd=homologous recombination-deficient; 
ICF=informed consent form; IDS=interval debulking surgery; mPFS=median progression-free survival; 
NVRD=no visual residual disease; ORR=overall response rate; OS=overall survival; pathCR=pathological 
complete response; PD=pharmacodynamics; PFS=progression-free survival; PK=pharmacokinetics; 
PRO=patient-reported outcome; QD=once daily; R=randomization; SOC=standard of care; TFST=time to first 
subsequent treatment; xxm=xx months 
 
 
Diagnosis and main criteria for inclusion: 
The overall list of eligibility criteria for entry into this study is provided in the master protocol. All 
eligibility criteria for this cohort (Cohort C) are included in this cohort-specific supplement. 
Participants must meet all criteria to be eligible for enrollment in this cohort. 
Key inclusion criteria are as follows: 
Key inclusion criteria from the master protocol 
• 
Participant must be female ≥18 years of age, able to understand the study procedures, and 
agree to participate in the study by providing written informed consent. 
• 
Participant must have measurable disease according to RECIST v1.1. 
Key inclusion criteria specific to this cohort (Cohort C) 
• 
Participant has newly diagnosed Stage III or IV ovarian, fallopian tube, or primary peritoneal 
cancer according to the International Federation of Gynecology and Obstetrics staging 
criteria. 
• 
Participants must provide sufficient tumor tissue at Prescreening and agree to undergo a 
central HRD tumor testing using a fully validated assay. The participants must be HRd as per 
central HRD tumor testing result for eligibility. 
o Participants with a documented germline breast cancer gene (BRCA)1/2 deleterious 
or suspected deleterious mutations by Sponsor’s permitted test (e.g., 
 
 may be allowed to enroll prior to receiving the central test results, provided all 
inclusion criteria are met. However, tumor sample submitted by these participants 
will still be required for central HRD confirmation. The list of Sponsor’s permitted 
tests will be provided by the Sponsor. 
o All participants must agree to provide tumor tissue collected from IDS. 
o Participant must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides 
if blocks are not available) with sufficient tumor content (as confirmed by the 
Sponsor’s designated central and/or testing laboratory) for central HRD testing at 
Prescreening and for exploratory biomarker testing at Prescreening or Screening. If 
sufficient tumor tissue is provided at Prescreening, participants do not need to 
provide additional tissue at Screening. 
• 
Participant must have completed 1 run-in cycle of carboplatin-paclitaxel and not experienced 
disease progression after this treatment. Completion is defined as receiving ≥50% of the 
prescribed dose of therapy within 5 weeks. 
• 
Participant must not have known contraindication or uncontrolled hypersensitivity to 
carboplatin and paclitaxel and their excipients and no known pre-existing conditions that 
would preclude treatment with these agents. 
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• 
Participant must not have known contraindication or uncontrolled hypersensitivity to 
niraparib and its excipients. 
• 
Participant must not have symptomatic ascites or pleural effusions as defined by the 
following criterion: presence of fluid in the abdominal or pleural cavities requiring removal 
within 1 week prior to signing the informed consent. 
• 
Participant must agree to complete patient-reported outcome (PRO) and work productivity 
questionnaires throughout the study. 
Main criteria for exclusion: 
Key exclusion criteria are as follows: 
Key exclusion criteria from the master protocol (none) 
Key exclusion criteria specific to this cohort (Cohort C) 
• 
Participant has low-grade or Grade 1 epithelial OC or mucinous, germ cell, transitional cell, 
carcinosarcoma, or undifferentiated tumor. 
• 
Participant has contraindications to surgery. 
• 
Participant has a bowel obstruction by clinical symptoms or computed tomography scan, 
subocclusive mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal 
perforation, or intra-abdominal abscess. 
• 
Participant has any known history or current diagnosis of myelodysplastic syndrome or acute 
myeloid leukemia. 
• 
Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries or 
major surgery within the past 28 days prior to the start of study treatment and/or history of 
hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically 
significant hemorrhage within the past 3 months). 
• 
Participant received prior treatment for high-grade non-mucinous epithelial ovarian, 
fallopian tube, or peritoneal cancer (e.g., prior surgery, immunotherapy, anticancer therapy 
[with the exception of 1 run-in cycle of carboplatin-paclitaxel], or radiation therapy). 
• 
Participant is unable to swallow orally administered medication or has a gastrointestinal 
disorder likely to interfere with absorption of the study medication. 
• 
Participant received whole blood transfusions in the 2 weeks prior to entry to the study 
(packed red blood cells and platelet transfusions are acceptable outside of 2 weeks prior to 
treatment). 
Investigational product, dosage, and mode of administration: 
Niraparib: 
Niraparib will be supplied as 
. 
For participants randomized to niraparib neoadjuvant treatment, the starting dose will be as follows: 
• 
200 mg 
) for participants with an actual body weight <77 kg OR 
screening platelet count <150 000/µL on Cycle 1 Day 1 (C1D1) 
• 
300 mg (
) for participants with an actual body weight ≥77 kg AND 
screening platelet count ≥150 000/µL on C1D1 
For participants receiving niraparib maintenance treatment, independent of the treatment they 
received during the neoadjuvant treatment period, the starting dose will be as follows: 
• 
200 mg 
) for participants with an actual body weight <77 kg OR 
platelet count <150 000/µL on C1D1 of the niraparib maintenance treatment period (M1D1) 
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• 
300 mg 
) for participants with an actual body weight ≥77 kg AND 
platelet count ≥150 000/µL on M1D1 
• 
For participants who received niraparib in the neoadjuvant period and experienced niraparib 
dose reductions due to AEs, the Investigator, in consultation with the Sponsor’s Medical 
Monitor, will determine the safest starting dose in the maintenance setting  
Participants will be instructed to take niraparib at the same time each day. Bedtime administration 
may be a potential method for managing nausea. Participants must swallow and not chew all 
 The consumption of water and food is permissible. Niraparib will be dispensed to 
participants on each scheduled visit until the participant discontinues study treatment. The Study 
Reference Manual contains descriptions of the packaging of niraparib and instructions for the 
preparation and administration of niraparib. 
Duration of treatment: 
Neoadjuvant therapy (niraparib or platinum-taxane doublet chemotherapy) will consist of three 
21-day cycles. 
Adjuvant therapy (platinum-taxane doublet chemotherapy with optional bevacizumab or 
bevacizumab biosimilar for participants deemed high-risk) will consist of up to three 21-day cycles, 
with the last cycle (C6) for all therapies being optional. Any site choosing to give the last cycle 
and/or bevacizumab or bevacizumab biosimilar must offer the final cycle (C6) to all participants 
treated at that site regardless of the arm the participant was enrolled onto. 
Maintenance treatment with niraparib (with optional bevacizumab or bevacizumab biosimilar for 
participants deemed high-risk up to a total of 22 cycles including adjuvant chemotherapy period) will 
continue for up to 36 months. 
Participants will continue to receive their assigned treatment until radiographic PD is documented 
per RECIST v1.1, AE, risk to participant or participant’s severe noncompliance with protocol as 
judged by the Investigator or Sponsor, participant’s request, pregnancy, or end of study. 
Reference therapy, dosage, and mode of administration: 
Carboplatin-paclitaxel: 
Carboplatin will be infused intravenously over 60 minutes at the prescribed dose of area under the 
concentration versus time curve of 5 to 6 mg/mL•min on Day 1 of every 21-day cycle. Paclitaxel will 
be administered in a similar fashion over 180 minutes at the prescribed dose of 175 mg/m2 on Day 1 
of every 21-day cycle. 
Prior to each chemotherapy administration, all of the following criteria must be met: 1) absolute 
neutrophil count ≥1500/µL or ≥1000/µL if granulocyte colony-stimulating factor is to be 
administered, 2) platelet count ≥100 000/µL, 3) hemoglobin ≥9 g/dL. For participants who did not 
tolerate carboplatin-paclitaxel during the run-in period, cisplatin and docetaxel are accepted 
alternatives. 
Bevacizumab or bevacizumab biosimilar (optional): 
Bevacizumab or bevacizumab biosimilar 7.5 mg/kg or 15 mg/kg will be infused intravenously on 
Day 1 of each 21-day cycle. Bevacizumab or bevacizumab biosimilar may be administered for up to 
22 cycles during the adjuvant and maintenance periods. 
Criteria for evaluation: 
Efficacy: 
The primary efficacy endpoint is pre-IDS unconfirmed ORR, defined as the percentage of 
participants with unconfirmed complete or partial response on study treatment pre-IDS as assessed 
per RECIST v1.1 by the Investigator. 
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Secondary efficacy endpoints are as follows: 
• 
CA-125 progression by GCIG CA-125 response criteria 
• 
PFS, defined as the time from the date of treatment randomization to the date of first 
documentation of PD per RECIST v1.1 or death by any cause, whichever occurs first, as 
determined by the Investigator 
• 
OS, defined as the time from the date of treatment randomization to the date of death by any 
cause 
• 
TFST, defined as the time from the date of treatment randomization to the date of first 
subsequent anticancer therapy or death 
Safety: 
Safety endpoints include frequency and severity of treatment-emergent adverse events, serious 
adverse events, AESIs, and dose modification (i.e., interruptions and discontinuations). 
Other secondary endpoints: 
Additional secondary endpoints, include PRO endpoints, arranged in order of clinical importance, 
are as follows: 
• 
Change over time in frequency and severity of the items on the Patient Reported Outcomes-
Common Terminology Criteria for Adverse Events during neoadjuvant treatment 
• 
Change from baseline in Functional Assessment of Cancer Therapy-Item GP5 during 
neoadjuvant treatment 
• 
Change from baseline in European Organisation for Research and Treatment of Cancer 
(EORTC) Quality of Life Questionnaire-Core 30 items (EORTC Item Library 136) pre-IDS 
• 
Change from baseline in EORTC Quality of Life Questionnaire for OC gastrointestinal items 
(EORTC Item Library 137) pre-IDS 
Biomarkers: 
Tumor tissue and/or blood samples may be assessed to identify potential disease- or treatment-
related biomarkers that would associate with tumor responses to treatment. Additionally, samples 
may be assessed to evaluate the evolution of the molecular profile of the tumor and tumor 
microenvironment in response to treatment. 
Pharmacokinetics and Pharmacodynamics: 
The pharmacokinetic (PK) endpoints are as follows: 
• 
Residual plasma concentrations of carboplatin and paclitaxel at C1D1 
• 
Niraparib concentration throughout the neoadjuvant treatment period 
• 
Niraparib concentration in tumor tissue from IDS biopsy 
Statistical methods: 
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Enrollment will be stratified by BRCA mutational status (BRCAmut vs BRCAwt/unknown). 
Interim analysis:
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................4 
PROCEDURES IN CASE OF EMERGENCY ...............................................................................9 
2. 
SYNOPSIS .................................................................................................................10 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............18 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................24 
5. 
INTRODUCTION ......................................................................................................29 
5.1. 
Ovarian Cancer ...........................................................................................................29 
5.2. 
Niraparib .....................................................................................................................29 
5.3. 
Other PARP Inhibitors as Treatment for Ovarian Cancer ..........................................30 
5.4. 
Rationale of the Current Cohort .................................................................................30 
5.5. 
Benefit/Risk Assessment ............................................................................................31 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................32 
6.1. 
Primary Objective .......................................................................................................32 
6.2. 
Secondary Objectives .................................................................................................32 
6.3. 
Exploratory Objectives ...............................................................................................32 
7. 
INVESTIGATIONAL PLAN .....................................................................................33 
7.1. 
Overall Study Design ..................................................................................................33 
7.1.1. 
Overall Screening Period ............................................................................................34 
7.1.1.1. 
Prescreening ................................................................................................................34 
7.1.1.2. 
Screening ....................................................................................................................35 
7.1.2. 
Neoadjuvant Treatment Period ...................................................................................35 
7.1.3. 
IDS Period ..................................................................................................................36 
7.1.4. 
Adjuvant Chemotherapy Treatment Period ................................................................36 
7.1.5. 
Maintenance Treatment Period ...................................................................................37 
7.1.6. 
End of Study Definition ..............................................................................................37 
7.2. 
Number of Participants ...............................................................................................41 


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7.3. 
Treatment Assignment ................................................................................................41 
7.4. 
Dose Adjustment Criteria ...........................................................................................41 
7.4.1. 
Safety Criteria for Adjustment or Stopping Doses .....................................................41 
7.4.1.1. 
Niraparib .....................................................................................................................41 
7.4.1.2. 
Platinum-Taxane Doublet Chemotherapy ..................................................................45 
7.4.1.3. 
Bevacizumab or Bevacizumab Biosimilar ..................................................................45 
7.4.2. 
Pharmacokinetic Criteria for Adjustment or Stopping Doses ....................................46 
7.5. 
Criteria for Cohort Termination ..................................................................................46 
7.6. 
Study Conduct ............................................................................................................46 
7.6.1. 
Schedule of Events .....................................................................................................46 
7.6.2. 
Treatment Cycles ........................................................................................................46 
7.6.3. 
Evaluation of Tumor Response ..................................................................................46 
7.6.3.1. 
RECIST V1.1 ..............................................................................................................46 
7.6.3.2. 
GCIG CA-125 Response Criteria ...............................................................................47 
7.6.3.3. 
Pathological Complete Response ...............................................................................47 
7.6.4. 
Overall Survival ..........................................................................................................47 
7.6.5. 
Time to First Subsequent Treatment ...........................................................................47 
7.6.6. 
Patient-reported Outcome Questionnaires ..................................................................47 
7.6.6.1. 
PRO-CTCAE ..............................................................................................................48 
7.6.6.2. 
FACT-GP5 ..................................................................................................................48 
7.6.6.3. 
EORTC IL136 (a Subset of Items from EORTC QLQ-C30) .....................................49 
7.6.6.4. 
EORTC IL137 (a Subset of Items from EORTC QLQ-OV28) ..................................49 
7.6.6.5. 
WPAI:GH ...................................................................................................................50 
7.6.7. 
Safety Assessments .....................................................................................................50 
7.6.8. 
Surgical and Postsurgical Outcomes ..........................................................................50 
7.6.9. 
Healthcare Resource Utilization Questionnaire ..........................................................51 
7.6.10. 
Tumor Tissue and Blood Sampling ............................................................................51 
7.6.11. 
Genetic Sample ...........................................................................................................51 
8. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS.....................................60 
8.1. 
Inclusion Criteria ........................................................................................................60 
8.2. 
Exclusion Criteria .......................................................................................................62 
8.3. 
Withdrawal Criteria ....................................................................................................64 
8.3.1. 
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8.3.1.1. 
Liver Chemistry Stopping Criteria .............................................................................64 
8.3.1.2. 
Study Intervention Restart or Rechallenge After Liver Stopping Criteria Met ..........65 
8.3.2. 
Discontinuation from the Study ..................................................................................66 
9. 
TREATMENT OF PARTICIPANTS .........................................................................67 
9.1. 
Description of Study Drug ..........................................................................................67 
9.2. 
Concomitant Medications ...........................................................................................68 
9.2.1. 
Prohibited Medications ...............................................................................................68 
9.2.2. 
Contraception ..............................................................................................................69 
9.2.3. 
Rescue Medications and Supportive Care Guidelines ................................................69 
9.2.4. 
Other Study Restrictions .............................................................................................69 
9.3. 
Treatment Compliance ................................................................................................69 
9.4. 
Randomization and Blinding ......................................................................................69 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................71 
10.1. 
Study Drug ..................................................................................................................71 
10.1.1. 
Niraparib .....................................................................................................................71 
10.1.2. 
Carboplatin and Paclitaxel ..........................................................................................71 
10.1.3. 
Optional Bevacizumab or Bevacizumab Biosimilar ...................................................71 
10.2. 
Study Drug Packaging and Labeling ..........................................................................71 
10.3. 
Study Drug Storage .....................................................................................................71 
10.4. 
Study Drug Preparation ..............................................................................................71 
10.5. 
Administration ............................................................................................................72 
10.5.1. 
Niraparib .....................................................................................................................72 
10.5.2. 
Carboplatin and Paclitaxel ..........................................................................................72 
10.5.3. 
Optional Bevacizumab or Bevacizumab Biosimilar ...................................................73 
10.6. 
Study Drug Accountability .........................................................................................73 
10.7. 
Study Drug Handling and Disposal ............................................................................73 
11. 
ASSESSMENT OF EFFICACY ................................................................................74 
11.1. 
Primary Efficacy Endpoint .........................................................................................74 
11.2. 
Secondary Efficacy Endpoints ....................................................................................74 
11.3. 
Patient-reported Outcome Endpoints ..........................................................................74 
11.4. 
Exploratory Endpoints ................................................................................................75 
11.4.1.1. 
Surgical and Postsurgical Outcomes ..........................................................................75 
11.4.1.2. 
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11.4.1.3. 
Pathological Complete Response ...............................................................................75 
11.4.1.4. 
Biomarker Endpoints ..................................................................................................76 
11.4.1.5. 
Pharmacokinetic and Pharmacodynamic Endpoints ...................................................76 
12. 
ASSESSMENT OF SAFETY .....................................................................................77 
12.1. 
Safety Parameters .......................................................................................................77 
12.2. 
Adverse Events and Special Situations .......................................................................77 
13. 
STATISTICS ..............................................................................................................78 
13.1. 
Sample Size Determination ........................................................................................78 
13.2. 
Planned Analyses ........................................................................................................78 
13.2.1. 
Analysis Populations ..................................................................................................78 
13.2.2. 
Efficacy Analyses .......................................................................................................78 
13.2.2.1. 
Primary Efficacy Analysis ..........................................................................................78 
13.2.2.2. 
Secondary Efficacy Analysis ......................................................................................79 
13.2.2.3. 
Exploratory Efficacy Analysis ....................................................................................79 
13.2.3. 
Patient-reported Outcome Analyses ...........................................................................79 
13.2.4. 
Safety Analyses ..........................................................................................................79 
13.2.4.1. 
Pharmacokinetic and Pharmacodynamic Analyses ....................................................80 
13.2.4.2. 
Biomarker Analysis ....................................................................................................80 
13.2.4.3. 
Additional Exploratory Analyses ...............................................................................80 
13.2.5. 
Interim Analysis ..........................................................................................................80 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................81 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................82 
16. 
ETHICS ......................................................................................................................83 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................84 
18. 
PUBLICATION POLICY ..........................................................................................85 
19. 
LIST OF REFERENCES ............................................................................................86 
APPENDIX A. GENETICS ........................................................................................................88 
APPENDIX B. LIVER SAFETY: REQUIRED ACTIONS AND FOLLOW-UP 
ASSESSMENTS AND STUDY INTERVENTION 
RESTART/RECHALLENGE GUIDELINES............................................................89 
 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................24 
Table 2: 
Niraparib Dose Reductions for Hematologic and Nonhematologic Toxicity .............42 
Table 3: 
Niraparib Dose Modifications for Nonhematologic Toxicity ....................................42 
Table 4: 
Niraparib Dose Modifications for Hematologic Toxicity ..........................................43 
Table 5: 
Schedule of Events ....................................................................................................53 
Table 6: 
Study Drugs ................................................................................................................67 
Table 7: 
Liver Chemistry Stopping Criteria and Required Follow-up Assessments ................89 
Table 8: 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued 
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LIST OF FIGURES 
Figure 1: 
Criteria for Selecting Participants for IDS..................................................................36 
Figure 2: 
Cohort C Study Schema..............................................................................................39 
Figure 3: 
Cohort C Liver Stopping and Monitoring Event Algorithm ......................................65 
 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
ADR 
Adverse drug reaction; An adverse event where a causal 
relationship between a medicinal product and the adverse event is 
at least a reasonable possibility, i.e., the relationship cannot be 
ruled out. 
a. In the context of a clinical trial, an ADR can be serious or non-
serious. Serious ADRs may be subject to expedited reporting if 
they are considered unexpected (see SUSAR definition). 
b. For marketed products, ADRs are subject to expedited 
reporting within the country where they are authorized 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immunodeficiency syndrome 
AML 
acute myeloid leukemia 
AxMP 
auxiliary medicinal product; Medicinal products used in the 
context of a clinical trial but not as investigational medicinal 
products, such as medicinal products used for background 
treatment, challenge agents, rescue medication, or used to assess 
endpoints in a clinical trial. AxMPs should not include 
concomitant medications, this is medications unrelated to the 
clinical trial and not relevant for the design of the clinical trial.  
Authorized AxMP 
Medicinal product authorized in accordance with Regulation 
(EC) No 726/2004, or in any Member State concerned in 
accordance with Directive 2001/83/EC, irrespective of changes to 
the labelling of the medicinal product. 
• 
Safety reporting with regard to auxiliary medicinal products 
shall be made in accordance with Chapter 3 of Title IX of 
Directive 2001/83/EC. 
Unauthorized AxMP 
Medicinal product not authorized in accordance with Regulation 
(EC) No 726/2004 
• 
Safety reporting for unauthorized auxiliary medicinal 
products will follow the same processes and procedures as 
SUSAR safety reporting 
BRCA 
breast cancer gene 
BRCAm/BRCAmut 
breast cancer gene mutated 
CA-125 
cancer antigen 125  
CBC 
complete blood count 


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Abbreviation or Specialist Term 
Explanation 
CI 
confidence interval 
CNS 
central nervous system 
Co-administered (concomitant) 
products 
A product given to clinical trial participants as required in the 
protocol as part of their standard care for a condition which is not 
the indication for which the IMP is being tested and is therefore 
not part of the objective of the study. 
Comparator 
Any product used as reference (including placebo, marketed 
product, GSK or non-GSK) for an investigational product being 
tested in a clinical trial. This is any product that is being used to 
assess the safety, efficacy, or other measurable value against the 
test product (IMP). 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CxDx 
Cycle x Day x 
CYP 
cytochrome P450 enzyme 
DCR 
disease control rate 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EORTC 
European Organisation for Research and Treatment of Cancer  
EORTC IL136 
European Organisation for Research and Treatment of Cancer 
Item Library 136 
EORTC IL137 
European Organisation for Research and Treatment of Cancer 
Item Library 137 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire-Core 30 
EORTC QLQ-OV28  
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire for Ovarian Cancer 
EOT 
End-of-Treatment 
FACT-G 
Functional Assessment of Cancer Therapy – General 
FACT-GP5 
Functional Assessment of Cancer Therapy-Item GP5 
FDA 
Food and Drug Administration 
GCIG 
Gynecological Cancer InterGroup 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 


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Abbreviation or Specialist Term 
Explanation 
HCRU 
healthcare resource utilization 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
HRd  
homologous recombination-deficient  
HRp 
homologous recombination-proficient  
HRQoL 
health-related quality of life 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICU 
intensive care unit 
IDS 
interval debulking surgery  
IMP 
investigational medicinal product (investigational product); 
A pharmaceutical form of an active substance or placebo being 
tested or used as a reference in a clinical trial, including products 
already with a marketing authorization but used or assembled 
(formulated or packaged) in a way different from the authorized 
form, or when used for an unauthorized indication, or when used 
to gain further information about the authorized form. 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IV 
Intravenous 
MDS 
myelodysplastic syndrome 
mPFS 
median progression-free survival  
MRI 
magnetic resonance imaging 
MxDx 
Cycle x Day x during maintenance treatment period 
NACT 
neoadjuvant chemotherapy  
NCI 
National Cancer Institute 
NED 
no evidence of disease 
NIMP 
non-investigational medicinal product 
non-BRCA 
breast cancer gene unmutated 
NVRD 
no visible residual disease 
OC  
ovarian cancer 
ODWG 
Organ Dysfunction Working Group 


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Abbreviation or Specialist Term 
Explanation 
OPC 
Oncology Patient Council 
ORR 
overall response rate 
OS 
overall survival 
PARP 
poly-ADP-ribose polymerase  
pCR 
pathological complete response 
PD 
progression of disease 
PDS 
primary debulking surgery 
PFS 
progression-free survival  
PK 
pharmacokinetic(s) 
PR 
partial response 
PRES 
posterior reversible encephalopathy syndrome  
PRO 
patient-reported outcome 
PRO-CTCAE 
Patient Reported Outcomes-Common Terminology Criteria for 
Adverse Events 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
RECIST 
Response Evaluation Criteria in Solid Tumors 
Rescue medication 
Medicines identified in the protocol as those that may be 
administered to the participants when the efficacy of the IMP is 
not satisfactory, or the effect of the IMP is too great and is likely 
to cause a hazard to the patient, or to manage an emergency 
situation 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SOC 
standard of care; 
Medicine(s) for a specific indication, or a component of the 
standard care for a particular medical indication, based on 
national and/or international consensus; there is no regulatory 
significance to this term. 
• Products/regimens considered standard of care may differ 
country to country, depending on consensus in individual 
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Abbreviation or Specialist Term 
Explanation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction; in a clinical 
trial, a serious adverse reaction that is considered unexpected, 
i.e., the nature or severity of which is not consistent with the 
reference safety information (e.g., Investigator's Brochure for an 
unapproved investigational medicinal product). All adverse drug 
reactions (ADRs) that are both serious and unexpected are 
subject to expedited reporting 
TFST 
time to first subsequent treatment 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
WONCBP 
woman of non-childbearing potential 
WPAI:GH 
Work Productivity and Activity Impairment – General Health 
TRADEMARK INFORMATION 
Trademarks of the GSK group of 
companies 
 
Trademarks not owned by the GSK group of 
companies 
Zejula 
 
FluMist 
 
 
 
 
CCI


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5. 
INTRODUCTION 
An introduction to the overall study is provided in the master protocol. The intent of this cohort 
is to evaluate the efficacy and safety of neoadjuvant niraparib compared to neoadjuvant 
platinum-taxane doublet chemotherapy for the treatment of participants with confirmed 
homologous recombination-deficient (HRd) Stage III to IV ovarian cancer (OC). 
5.1. 
Ovarian Cancer 
Epithelial ovarian, fallopian tube, and primary peritoneal cancers are collectively referred to as 
OC. In the United States, OC is the fifth most common cause of cancer death in women and the 
most lethal of all gynecologic cancers, with 21 410 new cases of OC estimated to be diagnosed 
in 2021 and 13 770 women expected to die from this disease [American Cancer Society]. 
Worldwide, 313 959 new cases of OC and 207 252 deaths were estimated for 2020 [Global 
Cancer Observatory]. The majority (84%) of OC is diagnosed in advanced stages (III to IV), 
making the prognosis very unfavorable. The mainstay of OC management includes surgery, 
chemotherapy, and targeted therapy [Berkenblit, 2005; Hoskins, 1992; Hoskins, 1994; Kehoe, 
2015; Burger, 2011]. Generally, primary debulking surgery (PDS) with no visible residual 
disease (NVRD) followed by adjuvant platinum-taxane doublet chemotherapy offers the best 
prognosis [Bristow, 2002; van der Burg, 1995; Bristow, 2006; Chang, 2013]. PDS was compared 
with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in 2 
international Phase 3 clinical studies, the European Organisation for Research and Treatment of 
Cancer (EORTC) 55971 study and the CHORUS study [Kehoe, 2015; Vergote, 2010]. Results of 
these studies demonstrated that the IDS is not inferior to PDS. For both studies, the Grade 3 and 
Grade 4 postoperative adverse events (AEs) and deaths within 28 days of surgery were 
significantly more common in the PDS group. A per-protocol pooled analysis of long-term 
follow-up data for these 2 studies demonstrated that PDS and IDS result in similar overall 
survival (OS), with better survival with NACT in Stage IV disease [Vergote, 2018]. IDS is 
therefore considered to be an acceptable alternative to PDS and is a growing practice worldwide 
for patients with high volume Stage III or IV disease. 
5.2. 
Niraparib 
Overall clinical experience with niraparib is summarized in the master protocol and the niraparib 
Investigator’s Brochure (IB) [Niraparib IB]. 
Niraparib (GSK3985771, formerly MK-4827) is an orally available, potent, highly selective 
poly-ADP-ribose polymerase (PARP)-1 and PARP-2 inhibitor approved globally for first-line 
maintenance treatment of OC across various biomarkers. Niraparib has demonstrated activity in 
participants with HRd (including breast cancer gene [BRCA] mutated [BRCAm] and BRCA 
unmutated [non-BRCA] diseases) and participants with homologous recombination-proficient 
(HRp) tumors. 
In the Phase 3 PRIMA study (ClinicalTrials.gov number NCT02655016), the median 
progression-free survival (mPFS) in participants with advanced HRd OC who responded to first-
line platinum-based chemotherapy was 21.9 months with niraparib and 10.4 months with placebo 
(hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.31 to 0.59; p<0.001). In the overall 
population (all participants, independent of homologous recombination status), the mPFS was 


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13.8 months with niraparib and 8.2 months with placebo (HR 0.62; 95% CI 0.50 to 0.76; 
p<0.001). 
In the Phase 3 NOVA study (ClinicalTrials.gov number NCT01847274) in participants with 
recurrent epithelial OC who responded to second-line platinum-based chemotherapy, the mPFS 
for niraparib was longer than placebo in the germline BRCAm cohort: 21.0 versus 5.5 months 
(HR 0.27; 95% CI 0.17 to 0.41; p<0.001); longer than placebo in the HRd non-BRCA cohort: 
12.9 versus 3.8 months (HR 0.38; 95% CI 0.24 to 0.59; P<0.001); and longer than placebo in 
overall non-BRCA cohort: 9.3 versus 3.9 months (HR 0.45; 95% CI 0.34 to 0.61; p<0.001). In 
both PRIMA and NOVA studies, a continuum of benefit was demonstrated with efficacy in 
BRCAm > HRd > HRp disease. 
In addition to approvals by the Food and Drug Administration (FDA) and the European 
Medicines Agency in the front-line and recurrent maintenance setting for OC, niraparib was also 
studied for the treatment of women with recurrent OC. In the Phase 2 QUADRA study 
(ClinicalTrials.gov number NCT02354586), the safety and efficacy of niraparib was evaluated in 
women with metastatic, relapsed, platinum-sensitive, advanced, HRd OC who have received 3 or 
more lines of chemotherapy. Consistent with the results in NOVA, a continuum of clinical 
benefit defined by clinical and molecular biomarkers was shown in the QUADRA study with an 
overall response rate (ORR) of 28% (95% CI 15.6 to 42.6; one-sided p=0.00053). The mPFS in 
this tumor HRd population was 5.5 months (95% CI 3.5 to 8.2), and the median duration of 
response was 9.2 months; 68% achieved disease control (95% CI 53 to 81). 
5.3. 
Other PARP Inhibitors as Treatment for Ovarian Cancer 
Niraparib is not the only PARP inhibitor that demonstrated improvements in ORR and PFS as 
treatment for relapsed OC. In the Phase 3 SOLO3 study (ClinicalTrials.gov number 
NCT02282020), olaparib demonstrated statistically significant improvements in ORR and PFS 
as compared with non-platinum chemotherapy in women with platinum-sensitive, relapsed, 
BRCAm OC [Penson, 2020]. ORR and mPFS assessed by blinded independent central review 
were significantly higher for olaparib than chemotherapy, with an ORR of 72.2% versus 51.4% 
(odds ratio 2.53; 95% CI 1.40 to 4.58; p=0.002) and mPFS of 13.4 versus 9.2 months (HR 0.62; 
95% CI 0.43 to 0.91; p=0.013), respectively. AEs were consistent with expectations. Recently, 
the Phase 3 ARIEL4 study (ClinicalTrials.gov number NCT02855944) reported positive results 
for rucaparib showing increased mPFS with rucaparib (7.4 months) compared with standard of 
care (SOC) chemotherapy (5.7 months; HR 0.639) in women with relapsed, BRCAm OC 
[Kristeleit, 2021]. 
5.4. 
Rationale of the Current Cohort 
Despite promising results with PDS and IDS, the majority of patients with advanced OC at 
diagnosis will relapse after initial treatment. Recurrence within 6 months of platinum-based 
chemotherapy is defined as platinum-resistant disease, which confers a significantly worse 
prognosis, with median OS reported in clinical studies ranging from less than a year to 
19 months. Therefore, OC remains a deadly disease with a poor prognosis for many of the 
affected women. Improvements in the neoadjuvant therapy resulting in a greater percentage of 
women with NVRD at IDS is expected to translate into better survival outcomes. Niraparib is an 


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active oral agent and has the potential to minimize or even replace the use of intravenous 
cytotoxic chemotherapy in the neoadjuvant setting. 
With PARP inhibitors moving into the front-line setting, there is a need to understand the 
evolution of the molecular landscapes of the tumor and its associated tumor microenvironment 
following PARP inhibitor treatment, in order to generate insights to develop rationale for future 
treatment combinations aiming to broaden and deepen treatment responses. Neoadjuvant therapy 
settings offer unique sampling opportunities pre- and post-PARP inhibitor treatment that will 
enable exploratory translational research. 
Therefore, the aim for this cohort is to evaluate the efficacy, safety, and tolerability of 
neoadjuvant niraparib compared with neoadjuvant platinum-taxane doublet chemotherapy after 
one induction cycle of platinum-taxane doublet chemotherapy in participants with advanced OC. 
Given the continuum of benefit demonstrated with niraparib, participants with advanced OC with 
HRd tumors will be enrolled in Cohort C. 
5.5. 
Benefit/Risk Assessment 
Niraparib, a once daily oral treatment, prolonged the effect of platinum-based chemotherapy, 
substantially improved PFS and significantly reduced the risk of recurrence or death in a broad 
OC population of patients; thereby enabling a delay in disease recurrence and the need for 
additional platinum-based or other chemotherapy with its associated cumulative toxicities as 
demonstrated in multiple clinical trials (see [Niraparib IB]). 
The AE profile of niraparib consisted of AEs that are commonly managed in the patient 
population with advanced cancer. The key safety concerns included hematological toxicities, 
hypertension, MDS/AML, and potential risks of secondary malignancies. Common AEs 
including Grade 3 and higher AEs were generally manageable with dose modification and 
clinical treatment; most of which resolved without discontinuation of study drug.  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of niraparib may be found in the prescribing information (SmPC, USPI) and in the 
latest edition of the niraparib IB. Detailed information about the benefit-risk and expected AEs 
for carboplatin, paclitaxel, and bevacizumab (or bevacizumab biosimilar) may be found in the 
respective package inserts/prescribing information.  
Overall, the benefit-risk profile of niraparib is anticipated to be favorable in the population for 
Study 213357. The risk mitigation strategies are implemented in the study protocol. The Sponsor 
will continue to closely monitor the available safety data for known and emergent risks.  
 


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6. 
TRIAL OBJECTIVES AND PURPOSE 
The following are the cohort-specific objectives for this study, which have been further specified 
from the overall study objectives presented in the master protocol. 
6.1. 
Primary Objective 
• To evaluate the efficacy of neoadjuvant niraparib compared with neoadjuvant 
platinum-taxane doublet chemotherapy after 1 induction cycle of 
carboplatin-paclitaxel per Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 in participants with confirmed HRd Stage III to IV OC 
6.2. 
Secondary Objectives 
• To evaluate clinical benefit by Gynecological Cancer InterGroup (GCIG) cancer 
antigen 125 (CA-125) response criteria 
• To evaluate clinical benefit as measured by progression-free survival (PFS) per 
RECIST v1.1 by investigator assessment 
• To evaluate participants’ reported overall tolerability toward treatment, overall health 
status, OC-specific health-related quality of life (HRQoL) and symptoms, and work 
productivity 
• To evaluate clinical benefit as measured by OS 
• To evaluate clinical benefit as measured by time to first subsequent treatment (TFST) 
• To evaluate the safety and tolerability of neoadjuvant niraparib and neoadjuvant 
platinum-taxane doublet chemotherapy 
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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
The overall study design is described in the master protocol. 
This is a global, multicenter, randomized, open-label, Phase 2 cohort in participants with newly 
diagnosed, Stage III or IV, high-grade non-mucinous epithelial ovarian, fallopian tube, or 
peritoneal cancer (collectively referred to as “ovarian cancer” or OC) who are eligible for 
neoadjuvant platinum-taxane doublet chemotherapy followed by IDS. This study will enroll 
participants with HRd OC as determined by the central tumor homologous recombination 
deficiency (HRD) testing using a fully validated assay. All prescreened participants would have 
received, prior to enrollment, 1 cycle of SOC chemotherapy (i.e., carboplatin-paclitaxel) to allow 
sufficient time for receipt and review of the biomarker test results. After confirmation that the 
tumor is HRd, participants will be randomized in a 1:1 ratio to 3 cycles of platinum-taxane 
doublet chemotherapy (carboplatin-paclitaxel, unless not tolerated by the participant; Arm 1) or 
3 cycles of neoadjuvant niraparib (Arm 2).  
After IDS, all participants will receive up to three 21-day cycles of adjuvant chemotherapy 
(Cycles 4, 5, and 6) treatment: platinum-taxane doublet chemotherapy (and optional 
bevacizumab or bevacizumab biosimilar per SOC for participants deemed high-risk as judged by 
the Investigator), with the last cycle of chemotherapy (C6) being optional. Any site choosing to 
give the last cycle (C6) for all therapies must offer the final cycle (C6) to all participants treated 
at that site regardless of the arm the participant was enrolled onto. 
After adjuvant chemotherapy treatment, all participants will receive niraparib maintenance 
treatment (with optional bevacizumab or bevacizumab biosimilar as SOC for up to 22 cycles 
including adjuvant chemotherapy period) for up to 36 months or until AE, progression of disease 
(PD) per RECIST v1.1, risk to participant or participant’s severe noncompliance with protocol as 
judged by the Investigator or Sponsor, participant’s request, pregnancy, or end of study. 
Participants may discontinue treatment for any reason. All participants will undergo an End-of-
Treatment (EOT) Visit within 7 days after the last dose of study treatment or at the time of PD 
per RECIST v1.1, whichever occurs first. Participants who discontinue study treatment due to 
treatment toxicity or intolerability prior to an investigator assessment of PD per RECIST v1.1 
will continue radiographic imaging until PD per RECIST v1.1, start of alternate anticancer 
therapy, participant discontinuation of the study, withdrawal of consent to study procedures, 
becoming lost to follow-up, death, or end of the study.  
A Safety Follow-up Visit will be conducted 30 days (±7 days) after the last dose of study 
treatment. After the 30-day (±7 days) Safety Follow-up Visit, all participants will enter the long-
term follow-up period of telephone assessment for survival status, assessment of subsequent 
anticancer therapy, and the occurrence of any adverse event of special interest (AESI) every 90 
days (±14 days) until participant discontinuation of the study, withdrawal of consent, death, or 
end of study.  
Radiographic imaging will continue as scheduled during the posttreatment follow-up period for 
all participants without PD per RECIST v1.1 at treatment discontinuation until PD per 
RECIST v1.1, start of alternate anticancer therapy, participant discontinuation of the study, 


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withdrawal of consent to study procedures, becoming lost to follow-up, death, or end of the 
study. 
The study duration for each participant will be up to approximately 43 months. The study will be 
divided in 5 periods: overall screening (Prescreening and Screening), neoadjuvant treatment, 
IDS, adjuvant chemotherapy treatment, and niraparib maintenance. The study periods are 
described in more detail in Section 7.1.1 through Section 7.1.5. The Cohort C study schema is 
provided in Figure 2. 
The visit frequency is every 3 weeks in the neoadjuvant and adjuvant treatment periods and 
during the first 13-14 months in the niraparib maintenance treatment period (depending on 
whether participants will be offered 3 or 2 cycles of adjuvant chemotherapy, respectively). 
Subsequently, the visit frequency will change to every 3 months for the remainder of the 
niraparib maintenance treatment period. An overview of study procedures and the timing of 
assessments are provided in Section 7.6. 
To safeguard the interest and safety of the participants in this cohort, a GSK Data Review 
Committee, independent of the GSK study team directly involved in the conduct of the trial will 
be used to conduct review of incoming data to monitor efficacy and emerging safety signals. The 
panel may recommend modifications to the design of the protocol or discontinuation of the 
cohort, if necessary. 
7.1.1. 
Overall Screening Period 
The overall screening period will include Prescreening and Screening periods and be 
approximately 6 weeks. 
7.1.1.1. 
Prescreening 
Prior to main study enrollment, a Prescreening period of approximately 5 weeks is required to 
ensure that all potential participants meet preliminary eligibility criteria and have tumor tissue 
testing and baseline assessments (including blood sampling to evaluate complete blood counts 
for study eligibility), if not already done, performed consistent with the protocol. Participants 
must sign a Prescreening informed consent form (ICF) documenting their agreement for 
collection and submission of the required central tumor tissue and blood samples for biomarker 
analysis (central HRD testing for eligibility and tissue- and blood-based exploratory biomarker 
testing). Adequate tissue and other biologic specimens are required to proceed to randomization 
and enrollment in the study. Given the urgency of commencing treatment and the timeline for 
return of central HRD testing results to determine study eligibility, participants are expected to 
receive 1 run-in cycle of carboplatin-paclitaxel in accordance with local SOC treatment prior to 
enrollment in the study. 
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7.1.1.2. 
Screening 
Following recovery from the run-in cycle of carboplatin-paclitaxel (up to 5 weeks), participants 
who have confirmed tumor HRd status and signed an ICF will have their eligibility criteria 
confirmed after the complete review of inclusion and exclusion criteria, including confirmation 
that the participant will provide tumor tissue for exploratory biomarker testing (if not already 
done so during Prescreening) over a 1-week period. The screening procedures include, but are 
not limited to, hematology, chemistry, CA-125, ECG, and a RECIST v1.1 scan. The 
RECIST v1.1 scan, performed after the run-in cycle of carboplatin-paclitaxel, will be considered 
the baseline scan. 
7.1.2. 
Neoadjuvant Treatment Period 
After completing the screening procedures, participants will be randomized in a 1:1 ratio to 
platinum-taxane doublet chemotherapy (carboplatin-paclitaxel, unless not tolerated; Arm 1) or 
daily niraparib (Arm 2) for three 21-day cycles. Randomization will be stratified by BRCA 
mutational status (BRCAmut vs BRCAwt/unknown). 
Participants can start Cycle 1 Day 1 (C1D1) following recovery from the run-in cycle of 
carboplatin-paclitaxel. C1D1 is to occur up to 5 weeks after Day 1 of administration of the run-in 
cycle of carboplatin-paclitaxel. For details on study drug administration, see Section 10.5. 
After completion of 3 cycles of neoadjuvant therapy (i.e., NACT or niraparib), participants will 
undergo a pre-IDS assessment per RECIST v1.1 by the Investigator. The pre-IDS assessments 
should begin after completion of the final cycle of neoadjuvant therapy and up to 2 weeks prior 
to IDS. The neoadjuvant treatment period, from C1D1 to IDS, can be up to 12 weeks. Criteria for 
selecting participants for IDS are outlined in Figure 1.  
Participants with unconfirmed complete response (CR) or unconfirmed partial response (PR) 
according to RECIST v1.1 will proceed to IDS to be performed by a qualified 
gynecological/surgical oncologist, with the aim of achieving NVRD. Participants with stable 
disease (SD) per RECIST v1.1 may proceed to IDS or alternative therapy at the Investigator’s 
discretion. Surgical and postsurgical outcomes will be collected. Postsurgical safety will be 
assessed according to local SOC for 30 days (± 7 days) after IDS and before adjuvant 
chemotherapy. Participants with PD will discontinue study treatment and proceed to an 
alternative therapy at the Investigator’s discretion.  
Clinical progression as determined by signs, symptoms, physical examination results, or 
increased CA-125 (≥15% from nadir) are not acceptable reasons for neoadjuvant treatment 
discontinuation but may trigger an additional scan for RECIST v1.1 evaluation. If the participant 
does not meet SD or PD per RECIST v1.1 but the Investigator believes that it is in the best 
interest of the participant to discontinue neoadjuvant treatment, the treatment may be 
discontinued after discussion with the Medical Monitor for this cohort. The additional scan 
performed for this evaluation will be used for the primary efficacy analysis. 
Participants who discontinue treatment for reasons other than PD per RECIST v1.1 should 
continue to be scanned until RECIST v1.1 PD or start of alternate therapy. 
Participants who receive additional cycle(s) of platinum-taxane doublet chemotherapy prior to 
IDS, when clinically indicated, will be considered as having discontinued treatment and must 


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provide imaging per RECIST v1.1 after 3 cycles of on-study neoadjuvant therapy and undergo 
procedures as per EOT. 
Figure 1: 
Criteria for Selecting Participants for IDS 
 
Pre-IDS assessment per RECIST v1.1 by the Investigator will occur after completion of 3 cycles of neoadjuvant therapy (i.e., 
NACT or niraparib). Pre-IDS assessments should begin after completion of the final cycle of neoadjuvant therapy and up to 
2 weeks prior to IDS.  
 
7.1.3. 
IDS Period 
Participants who have unconfirmed CR or unconfirmed PR per RECIST v1.1 at their pre-IDS 
tumor evaluation (pre-IDS assessments are outlined in Section 7.1.2) will undergo IDS by a 
trained gynecologic/surgical oncologist with the aim of maximum surgical effort toward NVRD. 
IDS will be performed after the final cycle of neoadjuvant therapy; approximately 3 to 6 weeks 
after C3D1. The IDS period, from IDS to C4D1, can take up to 6 weeks. Surgical and 
postsurgical outcomes will be collected during this period.  
Participants will undergo postsurgical safety evaluations per local SOC for up to 30 days after 
IDS and prior to the start of adjuvant chemotherapy. Participants who experience PD per 
RECIST v1.1 should discontinue study treatment and proceed to alternative therapy at the 
Investigator’s discretion. 
7.1.4. 
Adjuvant Chemotherapy Treatment Period 
Per standard practice, platinum-taxane doublet chemotherapy is given for more than 4 cycles. 
Therefore, after surgical recovery (up to 6 weeks), all participants randomized to neoadjuvant 
platinum-taxane doublet chemotherapy (Arm 1) will receive up to 3 additional 21-day cycles of 
platinum-taxane doublet chemotherapy (and optional bevacizumab or bevacizumab biosimilar as 
SOC for participants deemed high-risk as determined by the Investigator); Cycle 6 is optional. If 
a site chooses to administer a third cycle of platinum-taxane doublet chemotherapy (and optional 
bevacizumab or bevacizumab biosimilar for participants deemed high-risk), all participants 


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treated at this study site must be offered the third cycle (Cycle 6) of platinum-taxane doublet 
chemotherapy (and optional bevacizumab or bevacizumab biosimilar for participants deemed 
high-risk), regardless of treatment received during the neoadjuvant treatment period.  
In order to balance the 2 treatment arms, all participants randomized to neoadjuvant niraparib 
(Arm 2) will also receive up to three 21-day cycles of platinum-taxane doublet chemotherapy 
(and optional bevacizumab or bevacizumab biosimilar for participants deemed high-risk) after 
surgical recovery (up to 6 weeks; Cycle 6 is optional). 
The adjuvant chemotherapy treatment period will take up to approximately 6 to 9 weeks. 
7.1.5. 
Maintenance Treatment Period 
To assess disease status following adjuvant chemotherapy, diagnostic imaging per RECIST v1.1 
will be performed within 14 days prior to Cycle 1 Day 1 of the maintenance treatment period 
(M1D1). Participants who completed the adjuvant chemotherapy period without PD per 
RECIST v1.1 will start the niraparib (and optional bevacizumab or bevacizumab biosimilar for 
participants deemed high-risk) maintenance treatment in cycles of 3 weeks. The start of 
maintenance treatment can be delayed at least 6 weeks and up to 9 weeks after C5D1 (or C6D1 if 
a third cycle of adjuvant chemotherapy therapy was received) to allow for adequate recovery of 
hematologic and nonhematologic toxicity. Maintenance treatment will be up to 36 months 
(including 22 cycles of optional bevacizumab or bevacizumab biosimilar starting in adjuvant 
chemotherapy period) or until AE, PD per RECIST v1.1, risk to participant or participant’s 
severe noncompliance with protocol as judged by the Investigator or Sponsor, participant’s 
request, pregnancy, or end of study. 
Maintenance imaging assessments will start at M1D1 or within 14 days prior to M1D1. 
Additional assessments will be performed every 3 months (±7 days) for 1 year after M1D1, 
followed by every 6 months (±14 days) during the second year, and every year thereafter until 
PD per RECIST v1.1, start of alternate anticancer therapy, participant discontinuation of the 
study, withdrawal of consent to study procedures, becoming lost to follow-up, death, or end of 
the study. Additional unscheduled RECIST v1.1 computed tomography (CT) or magnetic 
resonance imaging (MRI) scans may be performed if the participant has increasing CA-125 
values or suspicious symptoms. 
7.1.6. 
End of Study Definition 
The end of the study is defined as the date of the last scheduled procedure shown in the Schedule 
of Events (Table 5) for the last participant in the study globally. 
A participant will be considered to have completed the study if the participant dies during the 
Intervention Period or Follow-up Period, or has been in follow-up for up to 4 years after 
enrollment of the last participant, whichever is sooner. The cause of death must be documented 
in the eCRF. In addition, participants who are receiving ongoing study intervention or are in the 
follow-up period at the time of the Sponsor’s decision to close the study will be considered to 
have completed the study. A participant will be considered to have withdrawn from the study if 
the participant has not died and is lost to follow-up, has withdrawn consent, or is no longer being 
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Participants who continue to derive benefit from niraparib in the opinion of the Investigator, may 
be provided an option to continue to receive niraparib under an extension study, rollover study, 
expanded access, or other program, as applicable. 
 


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Figure 2: 
Cohort C Study Schema 
 
Note: Duration of study periods are as follows: 
 Prescreening: 5 weeks 
 Screening: 1 week 
 Neoadjuvant treatment: up to 12 weeks 
 IDS: up to 6 weeks 
 Adjuvant platinum-taxane chemotherapy and optional bevacizumab or bevacizumab biosimilar: 6 to 9 weeks* 
 Niraparib maintenance: up to 36 months. Optional bevacizumab or bevacizumab biosimilar may be administered for up to 22 cycles (including adjuvant 
chemotherapy period). 
*Note: Cycle 6 is optional. If a site chooses to administer cycle 6 (C6) of adjuvant chemotherapy, all participants treated at this study site must be offered C6 of 
adjuvant chemotherapy, regardless of treatment received during the neoadjuvant treatment period. Any site that chooses to provide optional bevacizumab or 
bevacizumab biosimilar as SOC to eligible high-risk participants must offer it to all eligible high-risk participants treated at that site, regardless of enrollment 
arm. 
Stratification: BRCAmut (deleterious or suspected deleterious BRCA1 or BRCA2 mutation) vs BRCAwt/unknown (no deleterious or suspected deleterious BRCA1 
or BRCA2 mutation; including unknown) 
Abbreviations: BRCA=breast cancer gene; BRCAmut=BRCA mutant; BRCAwt=BRCA wildtype; C=cycle; carbo=carboplatin; chemo=chemotherapy; 
CR=complete response; Cx=cycle number; endpt=endpoint; EU=European Union; HR=homologous recombination; HRd=homologous recombination-deficient; 
ICF=informed consent form; IDS=interval debulking surgery; mPFS=median progression-free survival; NVRD=no visual residual disease; ORR=overall 
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response rate; OS=overall survival; pathCR=pathological complete response; PD=pharmacodynamics; PFS=progression-free survival; PK=pharmacokinetics; 
PRO=patient-reported outcome; QD=once daily; R=randomization; SOC=standard of care; TFST=time to first subsequent treatment; xxm=xx months. 
 


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7.2. 
Number of Participants 
 
7.3. 
Treatment Assignment 
Participants enrolled in this cohort will be randomized in a 1:1 ratio to 3 cycles of neoadjuvant 
platinum-taxane doublet chemotherapy (carboplatin-paclitaxel, unless not tolerated by the 
participant; Arm 1) or 3 cycles of neoadjuvant niraparib (Arm 2). After IDS, all participants will 
receive up to three 21-day cycles of adjuvant platinum-taxane doublet chemotherapy (and 
optional bevacizumab for participants deemed high-risk); third cycle is optional followed by 
niraparib (and optional bevacizumab or bevacizumab biosimilar for participants deemed high-
risk) maintenance treatment. 
7.4. 
Dose Adjustment Criteria 
7.4.1. 
Safety Criteria for Adjustment or Stopping Doses 
Dosing regimens for niraparib, carboplatin-paclitaxel, and optional bevacizumab or bevacizumab 
biosimilar are described in Section 7.1. 
7.4.1.1. 
Niraparib 
Niraparib Dose Interruption and Modification 
Dose interruption, no longer than 28 days during the neoadjuvant and maintenance treatment 
periods, or dose reduction will be allowed based on treatment side effects. For participants whose 
initial dose is 300 mg/day (
), dose reductions to 200 mg/day 
 
 and subsequently to 100 mg/day 
) will be 
allowed. For participants whose initial dose is 200 mg/day 
), dose 
reduction to 100 mg/day (
 will be allowed. 
Treatment must be interrupted for any nonhematologic Common Terminology Criteria for 
Adverse Events (CTCAE) Grade 3 or Grade 4 AE that the Investigator considers to be related to 
administration of niraparib (Table 3). If the nonhematologic toxicity is appropriately resolved to 
baseline or Grade ≤1 within 4 weeks (28 days) of the dose interruption period, the participant 
may restart treatment with niraparib but with a dose level reduction if prophylaxis is not 
considered feasible (see Table 2). If the event recurs at a similar or worse grade, treatment should 
be interrupted again and, upon resolution, a further dose reduction must be made. No more than 
2 dose reductions will be permitted (i.e., to a minimum dose of 100 mg once daily). 
If the toxicity requiring dose interruption has not resolved completely or to CTCAE Grade 1 
during the maximum 4-week (28 days) dose interruption period, or the participant has already 
undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg once daily), the 
participant must permanently discontinue treatment with niraparib. 
The dose interruption and modification criteria for niraparib for hematologic parameters will be 
based on blood counts and are outlined in Table 4. If the hematologic toxicity has not recovered 
to the specified levels within 4 weeks (28 days) of the dose interruption period, or the participant 
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has already undergone a maximum of 2 dose reductions (to a minimum dose of 100 mg once 
daily), the participant must permanently discontinue treatment with niraparib. 
Table 2: 
Niraparib Dose Reductions for Hematologic and Nonhematologic Toxicity 
 
Body weight <77 kg OR screening 
platelet count <150 000/μL 
Body weight ≥77 kg AND screening 
platelet count ≥150 000/μL 
Starting dose 
200 mg/day 
 
300 mg/day 
 
First dose reduction 
100 mg/day 
 
200 mg/day (
 
Second dose reduction 
Discontinue medication. 
100 mg/daya (
 
a If further dose reduction below 100 mg/day is required, discontinue niraparib. 
 
Table 3: 
Niraparib Dose Modifications for Nonhematologic Toxicity 
Abnormality 
Intervention 
Nonhematologic CTCAE Grade ≥3 adverse reaction 
where prophylaxis is not considered feasible or adverse 
reaction persists despite treatment 
Withhold niraparib for a maximum of 28 days 
(neoadjuvant and maintenance periods) or until 
resolution of adverse reaction. 
Resume niraparib at a reduced dose per Table 2. Up to 
2 dose reductions are permitted for the starting dose of 
300 mg; only 1 dose reduction is permitted for the 
starting dose of 200 mg. 
CTCAE Grade ≥3 treatment-related adverse reaction 
lasting more than 28 days while patient is administered 
niraparib 100 mg/day 
Discontinue niraparib. 
Abbreviation: CTCAE=Common Terminology Criteria for Adverse Events. 
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Table 4: 
Niraparib Dose Modifications for Hematologic Toxicity 
Laboratory Abnormality 
Intervention 
Monitor complete blood counts weekly for the first cycle and once every treatment cycle thereafter. 
Platelet count <100 000/μL 
First occurrence: 
Withhold niraparib for a maximum of 28 days (neoadjuvant and 
maintenance periods) and monitor blood counts weekly until platelet 
counts return to ≥100,000/μL. 
Resume niraparib at same or reduced dose.a 
If platelet count is <75 000/μL, resume niraparib at a reduced dose.b 
Second occurrence: 
Withhold niraparib for a maximum of 28 days (neoadjuvant and 
maintenance periods) and monitor blood counts weekly until platelet 
counts return to ≥100 000/μL. 
Resume niraparib at a reduced dose.a 
Discontinue niraparib if the platelet count has not returned to acceptable 
levels within 28 days (neoadjuvant and maintenance periods) of the dose 
interruption period, or if the patient has already undergone dose 
reduction to 100 mg QD. 
Neutrophil count <1000/μL 
Withhold niraparib for a maximum of 28 days (neoadjuvant and 
maintenance periods) and monitor blood counts until neutrophil counts 
return to ≥1 500/μL. 
Resume niraparib at a reduced dose..a 
Discontinue niraparib if neutrophil level has not returned to acceptable 
levels within 28 days (neoadjuvant and maintenance periods) of the dose 
interruption period, or if the patient has already undergone dose 
reduction to 100 mg QD. 
Note: Prophylactic cytokines (i.e., granulocyte colony-stimulating 
factor) should not be administered in the first cycle of the study but may 
be administered in subsequent cycles according to current ASCO 
guidelines. 
Hemoglobin ≤8 g/dL 
Withhold niraparib for a maximum of 28 days (neoadjuvant and 
maintenance periods) and monitor blood counts until hemoglobin returns 
to ≥9 g/dL. 
Resume niraparib at a reduced dose..a 
Discontinue niraparib if hemoglobin has not returned to acceptable 
levels within 28 days (neoadjuvant and maintenance periods) of the dose 
interruption period, or if the patient has already undergone dose 
reduction to 100 mg QD. 
Hematologic adverse reaction 
requiring transfusion 
For patients with platelet count ≤10 000/μL, platelet transfusion should 
be considered. If there are other risk factors for bleeding such as 
co-administration of anticoagulation or antiplatelet drugs, consider 
interrupting these drugs or transfusion at a higher platelet count. 
Red blood cell transfusion may be given at the discretion of the 
Investigator. 
Resume niraparib at a reduced dose..a 


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Laboratory Abnormality 
Intervention 
Confirmed diagnosis of MDS or 
AML 
Permanently discontinue niraparib. 
Abbreviation: AML=acute myeloid leukemia; ASCO=American Society of Clinical Oncology; 
MDS = myelodysplastic syndrome; QD = once daily. 
.a Niraparib dose must not be decreased below 100 mg daily. Additional details on dose reduction are described in 
Table 2. 
b If platelet count is <75 000/μL at any time, resume niraparib at a reduced dose. 
 
If dose interruption or modification is required at any point during study treatment because of 
hematologic toxicity, weekly blood draws for complete blood count (CBC) will be monitored 
until the AE resolves to the specified blood count levels. To ensure the safety of the new dose, 
weekly blood draws for CBC will be required for an additional 4 weeks after the AE has 
resolved, after which monitoring every treatment cycle may resume. Based on individual 
laboratory values, weekly monitoring for the second month may be warranted. Also see Table 5. 
Any participant requiring transfusion of platelets or red blood cells (≥1 unit) must undergo a 
dose reduction upon recovery if study treatment is resumed. 
If a diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is 
confirmed by a hematologist, the patient must permanently discontinue study treatment. 
For major surgery while on study treatment, study treatment interruption is allowed up to up to 4 
weeks (28 days) during the neoadjuvant and maintenance treatment periods. 
Once the dose of study treatment has been reduced, any re-escalation must be discussed with the 
Sponsor’s Medical Monitor. 
All dose interruptions and reductions (including any missed doses), and the reasons for the 
reductions/interruptions, are to be recorded in the electronic case report form (eCRF). Reasons 
for the discontinuation of niraparib must also be recorded in the electronic case report form. 
Hypertension, Including Hypertensive Crisis 
Hypertension, including hypertensive crisis, has been reported with the use of niraparib. Pre-
existing hypertension should be adequately controlled before starting niraparib treatment. While 
receiving treatment, hypertension should be medically managed with antihypertensive medicinal 
products with or without niraparib dose adjustment. BP and heart rate is to be monitored as 
outlined in Table 5. 
Niraparib should be discontinued in case of hypertensive crisis or if medically significant 
hypertension cannot be adequately controlled with antihypertensive therapy. 
Posterior Reversible Encephalopathy Syndrome 
There have been rare reports of niraparib-treated participants developing signs and symptoms 
that are consistent with posterior reversible encephalopathy syndrome (PRES). PRES is a rare, 
reversible neurologic disorder that can present with the following signs and symptoms: seizures, 
headache, altered mental status, visual disturbance, or cortical blindness, with or without 
associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, 


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preferably MRI. In patients developing PRES, treatment of specific symptoms including control 
of hypertension is recommended, along with discontinuation of niraparib. The safety of 
reinitiating niraparib therapy in participants previously experiencing PRES is not known. 
Lifestyle and/or Dietary Restrictions 
Cases of photosensitivity have been reported for participants on niraparib treatment. Participants 
must be informed on measures to decrease exposure to ultraviolet light, such as minimizing time 
under direct sunlight, unless wearing hats and long-sleeves, and application of sun protection 
creams. 
7.4.1.2. 
Platinum-Taxane Doublet Chemotherapy 
Dose modifications and supportive care for platinum-taxane doublet chemotherapy will follow 
guidelines provided in the prescribing information for each agent or local SOC. 
7.4.1.3. 
Bevacizumab or Bevacizumab Biosimilar 
Dose modifications and supportive care for bevacizumab will follow guidelines provided in the 
prescribing information or local SOC. Key supportive care considerations are provided below. 
Restrictions: 
• Do not start bevacizumab or bevacizumab biosimilar for at least 28 days following major 
surgery and until adequate wound healing 
• Do not administer bevacizumab or bevacizumab biosimilar to a participant with recent 
history of hemoptysis 
• Do not administer bevacizumab or bevacizumab biosimilar to a participant with 
uncontrolled hypertension 
• Do not administer bevacizumab or bevacizumab biosimilar to a participant with OC with 
evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on a 
CT scan or clinical symptoms of bowel obstruction 
Precautions: 
• Monitor proteinuria by dipstick urine analysis prior to each bevacizumab or bevacizumab 
biosimilar infusion for the development or worsening of proteinuria with serial urinalyses 
during bevacizumab or bevacizumab biosimilar therapy. Participants with a 2+ or greater 
urine dipstick reading should undergo further assessment with a 24-hour urine collection. 
Bevacizumab or bevacizumab biosimilar treatment should be withheld for proteinuria 
greater than or equal to 2 grams per 24 hours and resumed when less than 2 grams per 
24 hours. Bevacizumab or bevacizumab biosimilar treatment should be discontinued in 
participants who develop nephrotic syndrome. 
• Bevacizumab or bevacizumab biosimilar treatment should be discontinued for 
participants who develop gastrointestinal perforation, tracheoesophageal fistula or any 
Grade 4 fistula, and fistula formation involving any internal organ. 
• Monitor blood pressure every 2 to 3 weeks during bevacizumab or bevacizumab 
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with bevacizumab-induced or bevacizumab-exacerbated hypertension after 
discontinuation. 
7.4.2. 
Pharmacokinetic Criteria for Adjustment or Stopping Doses 
Not applicable. 
7.5. 
Criteria for Cohort Termination 
In addition to the criteria for study termination as described in the master protocol, this cohort 
may be terminated based on the results of the planned interim analysis for futility 
(Section 13.2.5). 
7.6. 
Study Conduct 
7.6.1. 
Schedule of Events 
The schedule of study procedures is provided in Table 5. 
7.6.2. 
Treatment Cycles 
Cycles 1 through 6 (neoadjuvant and adjuvant treatment periods) and all remaining cycles 
(maintenance treatment period) are 21 days (±3 days) long. Visits should occur within ±3 days of 
the scheduled visit as outlined in Table 5, except for visits C1D8 and C1D15, which should 
occur within ±1 day. 
All times should be recorded using the 24-hour clock (e.g., 23:20, not 11:20 PM). 
7.6.3. 
Evaluation of Tumor Response 
7.6.3.1. 
RECIST V1.1 
All participants are required to undergo radiographic evaluation throughout the study as 
described in Table 5. Details on the evaluation of tumor response per RECIST v1.1 are provided 
in the master protocol. 
Radiographic evaluations to assess extent of disease will be conducted as follows: 
• Overall Screening Period: during Screening after the run-in cycle of 
carboplatin-paclitaxel and within 7 days immediately prior to C1D1 (i.e., baseline 
RECIST v1.1 scan) 
• Neoadjuvant Treatment Period: after completion of 3 cycles of neoadjuvant therapy 
(i.e., pre-IDS assessment), up to 2 weeks prior to IDS 
• Maintenance Treatment Period: at M1D1 or within 14 days prior to M1D1, every 
3 months (±7 days) for 1 year after M1D1, every 6 months (±14 days) during the 
second year, and every year thereafter 
• Radiographic evaluations, for participants on treatment and participants who 
discontinued treatment for reasons other than PD per RECIST v1.1, will continue 
until PD per RECIST v1.1, start of alternate anticancer therapy, participant 


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discontinuation of the study, withdrawal of consent to study procedures, becoming 
lost to follow-up, death, or end of the study. 
• As surgery is considered as part of the treatment paradigm of this study, if a 
participant has no visible lesion on the pre-maintenance scan, the overall response 
will be defined as CR. If a participant has visible lesion(s) on the pre-maintenance 
scan, the overall response will be defined as PR or SD depending on the extent of the 
disease compared to the baseline (Screening) scan. There will be no censoring as a 
result of the removal of the lesion(s) identified at Screening during IDS. 
7.6.3.2. 
GCIG CA-125 Response Criteria 
Serum samples to evaluate CA-125 will be taken throughout the study (Table 5). GCIG CA-125 
response criteria will be used to determine CA-125 progression [Rustin, 2004]. PD will not be 
diagnosed in case of CA-125 progression in the absence of radiologic evidence of PD per 
RECIST v1.1. 
7.6.3.3. 
Pathological Complete Response 
 
 
7.6.4. 
Overall Survival 
Survival status will be collected for all participants until up to 4 years after the enrollment of the 
last participant, provided that this allows the collection of sufficient OS events. 
7.6.5. 
Time to First Subsequent Treatment 
Survival status and subsequent anticancer therapy assessment will be evaluated for all 
participants until up to 4 years after the enrollment of the last participant. 
7.6.6. 
Patient-reported Outcome Questionnaires 
Participants will complete the following patient-reported outcome (PRO) and work productivity 
questionnaires as per Schedule of Events prior to any other study procedures: 
• Patient Reported Outcomes-Common Terminology Criteria for Adverse Events 
(PRO-CTCAE) – weekly during the neoadjuvant treatment period and at EOT Visit 
• Work Productivity and Activity Impairment – General Health (WPAI:GH) 
questionnaire – weekly during the neoadjuvant treatment period and at EOT Visit 
• European Organisation for Research and Treatment of Cancer Item Library 136 
(EORTC IL136) (a subset of items from the EORTC Quality of Life 
Questionnaire-Core 30 [EORTC QLQ-C30]) – at site visits during the neoadjuvant 
and maintenance treatment periods and at EOT Visit 
• European Organisation for Research and Treatment of Cancer Item Library 137 
(EORTC IL137) (a subset of items from the EORTC Quality of Life Questionnaire 
for OC [EORTC QLQ-OV28]) – at site visits during the neoadjuvant and 
maintenance treatment periods and at EOT Visit 
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• Functional Assessment of Cancer Therapy-Item GP5 (FACT-GP5) – weekly during 
the neoadjuvant treatment period, at site visits during the maintenance treatment 
period, and at EOT Visit 
The PROs will be administered to participants in different regions based on the availability of 
translated versions. PROs that are done weekly will be done at home by the participant on a 
provisioned device, the remaining PROs will be done at the site. 
7.6.6.1. 
PRO-CTCAE 
Descriptive data will be presented using items from the PRO-CTCAE as a secondary endpoint. 
The PRO-CTCAE is a PRO measure developed to evaluate symptomatic toxicity in participants 
of cancer clinical studies [Basch, 2014]. The PRO-CTCAE was designed to be used as a 
companion to the CTCAE, the standard lexicon for AE reporting in cancer studies. The 
PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities 
drawn from the CTCAE. The PRO-CTCAE provides a systematic yet flexible tool for 
descriptive reporting of symptomatic treatment side effects in cancer clinical studies. In the 
present study, a selection of items from the PRO-CTCAE Version 1.0 Item Library will be 
administered to participants (see Study Reference Manual for further details). 
A subset of items from the PRO-CTCAE will be assessed. Symptoms for inclusion in the 
PRO-CTCAE are the following: 
• Taste changes 
• Nausea 
• Vomiting 
• Abdominal pain 
• Bloating 
• Constipation 
• Diarrhea 
• Concentration 
• Memory 
• Muscle pain 
• Joint pain 
• Fatigue 
• Anxiety 
• Neuropathy 
• Sadness 
7.6.6.2. 
FACT-GP5 
The change from baseline in the FACT-GP5 will be assessed as a secondary endpoint. The 
Functional Assessment of Cancer Therapy–- General (FACT-G) (now in Version 4) is a 27-item 
compilation of general questions divided into 4 primary quality of life domains: physical well-
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The FACT-GP5, a single item from the FACT-G that assesses how bothersome the side effects 
of treatment are for patients with cancer, will be the only question used for this cohort. The recall 
period is the past 7 days, and the item has a 5-category response scale ranging from “0=Not at 
all” to “4=Very much.” This item is being included to assess the overall tolerability of treatment 
from the participant’s perspective.  
7.6.6.3. 
EORTC IL136 (a Subset of Items from EORTC QLQ-C30) 
The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer, and it 
is the most widely used cancer-specific HRQoL instrument. 
The EORTC QLQ-C30 is a 30-item questionnaire used to measure HRQoL in participants with 
cancer; it has been translated and validated in over 100 languages and has been used in more 
than 3000 studies worldwide [EORTC]. The EORTC QLQ-C30 is composed of both multi-item 
scales and single-item measures. These include 5 functional scales (physical functioning, role 
functioning, emotional functioning, cognitive functioning, and social functioning), 3 symptom 
scales (fatigue, nausea and vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, 
constipation, diarrhea, and financial difficulties), and a global health status/HRQoL scale. The 
EORTC QLQ-C30 uses a 1-week recall period for all items and a 4-point scale for the functional 
and symptom scales/items with response categories of “Not at all,” “A little,” “Quite a bit,” and 
“Very much.” The 2 items assessing global health status/quality of life utilize a 7-point scale 
ranging from 1 (“Very Poor”) to 7 (“Excellent”) [Aaronson, 1993]. 
Select domains from the EORTC QLQ-C30 will be administered and will be referred to as the 
EORTC IL136. The EORTC IL136 will include the following items: 
• Global health status/HRQoL scale 
• Functional scale of physical functioning 
• Functional scale of social functioning 
• Single item of dyspnea 
The change from baseline in EORTC IL136 pre-IDS will be assessed as a secondary endpoint. 
7.6.6.4. 
EORTC IL137 (a Subset of Items from EORTC QLQ-OV28) 
The OC module (QLQ-OV28) supplements the QLQ-C30 and was designed for patients with 
local or advanced disease who receive treatment by surgery with or without chemotherapy. It 
was developed according to the EORTC guidelines. It consists of 28 items and includes 3 
functional scales (body image, sexuality, and attitude to disease/treatment burden) and 
5 symptom scales/items (abdominal/gastrointestinal symptoms, peripheral neuropathy, 
hormonal/menopausal symptoms, other chemotherapy side effects, and hair loss). 
The scoring approach for the OC module is identical in principle to that used for the scales/items 
of the EORTC QLQ-C30. 
A subset of the questions (9 questions) will be utilized for this cohort and will be referred to as 
the EORTC IL137. The change from baseline in EORTC IL137 pre-IDS will be assessed as a 
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7.6.6.5. 
WPAI:GH 
The WPAI:GH consists of 6 questions that elicit the following: employment status; hours missed 
due to health problems; hours missed due to other reasons; hours actually worked; and 
2 questions that measure the degree of health problems affecting productivity while working 
(presenteeism) and regular daily activities, on a scale from 0 to 10. Scores for absenteeism, 
presenteeism, overall work productivity loss (combined absenteeism plus presenteeism), and 
impairment in regular daily (nonwork) activities, such as work around the house, shopping, child 
care, exercising, studying, etc., are derived for the interval of the past 7 days; scores are 
expressed as percent of impairment/productivity loss, with higher scores indicating greater 
impairment. 
All 6 questions from the WPAI:GH will be utilized for this cohort. 
7.6.7. 
Safety Assessments 
Safety assessments conducted during this study include collection of AEs, vital sign 
measurements, symptom-directed physical examinations, clinical laboratory assessments, 
Eastern Cooperative Oncology Group (ECOG) performance status, and use of concomitant 
medications. ECGs will be taken at baseline (Screening) and as clinically indicated throughout 
the study (see Table 5). 
Blood pressure and heart rate should be monitored weekly for the first 8 weeks for those 
participants receiving niraparib as neoadjuvant therapy and for all participants receiving 
niraparib as maintenance treatment as outlined in Table 5. In between the on-site visits, a home 
monitoring device will be provided to participants who will need to record values at home. 
Where applicable country and local regulations and infrastructure for home healthcare allow, 
home healthcare may take place at a location other than the clinical trial site to perform study 
assessments, which may include collection of blood samples and measurement of vital signs and 
weight. See master protocol for details. 
All AEs and serious adverse events (SAEs), regardless of causality, will be collected and 
recorded for each participant from the day the Prescreening ICF is signed until 30 days after the 
last dose of study treatment. Any pregnancies that occur are to be reported. All AEs and SAEs 
experienced by a participant, 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 
participant is lost to follow-up or withdraws consent, or until the participant has died. The AESIs 
for this study are MDS, AML, and secondary cancer (new malignancies other than MDS or 
AML). AESIs will be collected throughout the study participation and must be reported to the 
Sponsor as soon as the Investigator becomes aware of them or within 24 hours. 
7.6.8. 
Surgical and Postsurgical Outcomes 
The key surgical outcome will be based 
 
 
Other surgical and postsurgical outcomes will be determined based on the collection of 
peri-operative and postoperative data prior to C4D1 on operation time, estimated blood loss, 
blood transfusions (i.e., red blood cells, platelets, whole blood, and albumin), hospitalization 
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length of stay, re-admission for complications, intensive care unit (ICU) stay, infection and other 
Grade 3 or Grade 4 AEs, and additional procedures. 
7.6.9. 
Healthcare Resource Utilization Questionnaire 
A healthcare resource utilization (HCRU) questionnaire will be filled out for all participants 
randomized to study treatment and may be used to conduct exploratory economic analyses. 
HCRU includes non-protocol healthcare encounters and associated data, such as provider visits, 
emergency room visits, hospitalizations (including ward, admission and discharge dates, and 
primary discharge diagnosis), medications, tests, and procedures. 
7.6.10. 
Tumor Tissue and Blood Sampling 
All participants must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides if 
blocks are not available) with sufficient tumor content (as confirmed by the Sponsor’s designated 
central and/or testing laboratory) for central HRD testing at Prescreening and exploratory 
biomarker testing at Prescreening or Screening. If sufficient tumor tissue is provided at 
Prescreening, participants do not need to provide additional tissue at Screening. 
 
 
 For participants in Arm 2 only, IDS tumor tissue will also be used 
for pharmacokinetic (PK) analysis (niraparib concentration). 
 
 Blood 
samples will be collected at Prescreening, C1D1, pre-IDS, C4D1, M1D1 and every 3 months 
thereafter, the EOT Visit, and the Safety Follow-up Visit (Table 5). 
Blood samples will be used to evaluate serum-based tumor markers (including CA-125) and 
other (potential) biomarkers.  
Blood samples used to determine the plasma concentrations of niraparib and carboplatin-
paclitaxel will be drawn at the following time points: 
• For participants randomized to carboplatin-paclitaxel (Arm 1): predose C1D1 only 
• For participants randomized to niraparib (Arm 2): predose and 3-hour postdose 
(± 15 minutes) at C1D1, C2D1, and C3D1 and at the time of IDS (can be done at the 
pre-IDS assessment) 
Details on tumor tissue and blood sample requirements, collection, processing, and management 
can be found in the Study Laboratory Manual. Any remaining blood and tumor tissue samples 
may be stored for up to 15 years for future biospecimen research, which may include biomarker 
testing. 
7.6.11. 
Genetic Sample 
A blood sample for DNA isolation will be collected on C1D1 from participants who have 
consented to participate in the genetics analysis component of the study. Participation is optional. 
Those who do not wish to participate in the genetic research may still participate in the study. 
Participants may withdraw their consent and have their specimens and all derivates destroyed.  
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In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the participant. Signed informed consent will be required to obtain a replacement sample 
unless it was included in the original consent. Information on the use/analysis of DNA from the 
genetic sample is provided in Appendix A. 
Details on blood sample requirements, collection, processing, and management can be found in 
the Study Laboratory Manual. 
 


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Table 5: Schedule of Events 
Procedure 
Pre-
screening Screening 
Neoadjuvant 
Pre-
IDS 
evalua- 
tion 
IDSa 
Adjuvant 
Mainte- 
nance 
EOT 
Safety 
Follow-
up 
Long-
term 
Follow-
up 
Cycle and 
Day 
Up to -42d Up to -7d C1D1b 
(±3d) 
C1D8 
(±1d) 
C1D15 
(±1d) 
C2D1b 
(±3d) 
C3D1b 
(±3d) 
≤2 wks 
prior 
to IDS 
Within 
3-6 wks 
post 
C3D1 
C4D1  
≤6 wks 
after 
IDS 
C5D1 
(±3d) 
C6D1c 
(±3d) 
option
-al 
M(n)D1 
6-9 wks 
after C5D1 
(or C6D1)d 
(±3d) 
≤7d 
of 
last 
dose 
≤30d 
(±7d) 
after 
last 
dose 
Every 
90d 
(±14d) 
Informed 
consent 
X 
pre-
screening 
ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion 
criteria 
review 
 
Xe 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical, 
surgical, and 
cancer 
history, run-
in chemo 
information 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, 
temperature 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood 
pressure and 
pulse ratef 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Symptom-
directed PE 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 


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Procedure 
Pre-
screening Screening 
Neoadjuvant 
Pre-
IDS 
evalua- 
tion 
IDSa 
Adjuvant 
Mainte- 
nance 
EOT 
Safety 
Follow-
up 
Long-
term 
Follow-
up 
Cycle and 
Day 
Up to -42d Up to -7d C1D1b 
(±3d) 
C1D8 
(±1d) 
C1D15 
(±1d) 
C2D1b 
(±3d) 
C3D1b 
(±3d) 
≤2 wks 
prior 
to IDS 
Within 
3-6 wks 
post 
C3D1 
C4D1  
≤6 wks 
after 
IDS 
C5D1 
(±3d) 
C6D1c 
(±3d) 
option
-al 
M(n)D1 
6-9 wks 
after C5D1 
(or C6D1)d 
(±3d) 
≤7d 
of 
last 
dose 
≤30d 
(±7d) 
after 
last 
dose 
Every 
90d 
(±14d) 
Peri- and 
post-
operative 
surgical datag 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
ECOG 
performance 
status 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
PRO-
CTCAE, 
WPAI:GHh 
 
 
X 
X 
X 
Xh 
Xh 
 
 
 
 
 
 
X 
 
 
FACT-GP5h 
 
 
X 
X 
X 
Xh 
Xh 
X 
 
 
 
 
Xh 
X 
 
 
EORTC 
IL136, 
EORTC 
IL137h 
 
 
X 
 
 
X 
X 
X 
 
 
 
 
Xh 
X 
 
 
Tumor tissue 
samples 
X 
Xi 
 
 
 
 
 
 
Xj 
 
 
 
 
 
 
 
RECIST v1.1 
assessment 
(chest, 
abdomen, 
pelvis, and 
suspected 
areas)  
CT or MRI 
 
Xk 
 
 
 
 
 
Xk 
 
 
 
 
Xl 
 
 
 


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Procedure 
Pre-
screening Screening 
Neoadjuvant 
Pre-
IDS 
evalua- 
tion 
IDSa 
Adjuvant 
Mainte- 
nance 
EOT 
Safety 
Follow-
up 
Long-
term 
Follow-
up 
Cycle and 
Day 
Up to -42d Up to -7d C1D1b 
(±3d) 
C1D8 
(±1d) 
C1D15 
(±1d) 
C2D1b 
(±3d) 
C3D1b 
(±3d) 
≤2 wks 
prior 
to IDS 
Within 
3-6 wks 
post 
C3D1 
C4D1  
≤6 wks 
after 
IDS 
C5D1 
(±3d) 
C6D1c 
(±3d) 
option
-al 
M(n)D1 
6-9 wks 
after C5D1 
(or C6D1)d 
(±3d) 
≤7d 
of 
last 
dose 
≤30d 
(±7d) 
after 
last 
dose 
Every 
90d 
(±14d) 
Laboratory assessments 
Pregnancy 
test (WOCBP 
only): serum 
or urine u 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
Serum-based 
tumor 
markers (e.g., 
CA-125)  
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
 
 
 
CBC with 
differential 
Xm 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
Coagulation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
chemistry 
 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
PK/pharmaco
-dynamic 
samplesn 
 
 
X 
 
 
X 
X 
 
Xo 
 
 
 
 
 
 
 
Xp 
 
Xq 
 
 
 
 
X 
 
Xq 
 
 
Xr 
X 
X 
 
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Procedure 
Pre-
screening Screening 
Neoadjuvant 
Pre-
IDS 
evalua- 
tion 
IDSa 
Adjuvant 
Mainte- 
nance 
EOT 
Safety 
Follow-
up 
Long-
term 
Follow-
up 
Cycle and 
Day 
Up to -42d Up to -7d C1D1b 
(±3d) 
C1D8 
(±1d) 
C1D15 
(±1d) 
C2D1b 
(±3d) 
C3D1b 
(±3d) 
≤2 wks 
prior 
to IDS 
Within 
3-6 wks 
post 
C3D1 
C4D1  
≤6 wks 
after 
IDS 
C5D1 
(±3d) 
C6D1c 
(±3d) 
option
-al 
M(n)D1 
6-9 wks 
after C5D1 
(or C6D1)d 
(±3d) 
≤7d 
of 
last 
dose 
≤30d 
(±7d) 
after 
last 
dose 
Every 
90d 
(±14d) 
Blood sample 
for 
sequencing 
Xs 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genetic 
sample 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomi- 
zation 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Platinum/ 
taxane 
infusion 
X 
Run-in 
cycle of 
carboplatin
-paclitaxel 
 
X 
Arm 1 
 
 
X 
Arm 1 
X 
Arm 1 
 
 
X 
X 
X 
 
 
 
 
Optional 
bevacizumab 
or 
bevacizumab 
biosimilar 
infusion (for 
participants 
deemed high-
risk)  
 
 
 
 
 
 
 
 
 
Xt 
Xt 
Xt 
Xt 
 
 
 
Niraparib 
dispensation 
 
 
X 
Arm 2 
 
 
X 
Arm 2 
X 
Arm 2 
 
 
 
 
 
X 
 
 
 
AEs, SAEs, 
and AESIs v 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 


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Procedure 
Pre-
screening Screening 
Neoadjuvant 
Pre-
IDS 
evalua- 
tion 
IDSa 
Adjuvant 
Mainte- 
nance 
EOT 
Safety 
Follow-
up 
Long-
term 
Follow-
up 
Cycle and 
Day 
Up to -42d Up to -7d C1D1b 
(±3d) 
C1D8 
(±1d) 
C1D15 
(±1d) 
C2D1b 
(±3d) 
C3D1b 
(±3d) 
≤2 wks 
prior 
to IDS 
Within 
3-6 wks 
post 
C3D1 
C4D1  
≤6 wks 
after 
IDS 
C5D1 
(±3d) 
C6D1c 
(±3d) 
option
-al 
M(n)D1 
6-9 wks 
after C5D1 
(or C6D1)d 
(±3d) 
≤7d 
of 
last 
dose 
≤30d 
(±7d) 
after 
last 
dose 
Every 
90d 
(±14d) 
Concomitant 
medication v 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
HCRU 
questionnaire 
 
 
X 
 
 
X 
X 
X 
 
 
 
 
X 
X 
X 
 
Follow-up 
anticancer 
therapies and 
PD per 
RECIST v1.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
ECGw 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE=adverse event; AESI=adverse event of special interest; CA-125=cancer antigen 125; CBC=complete blood count; CT=computerized 
tomography; CxDx=Cycle x Day x; d=day; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; EOT=end-of-treatment; FACT-
GP5=Functional Assessment of Cancer Therapy-Item GP5; FFPE=formalin-fixed paraffin-embedded; HCRU=healthcare resource utilization; 
HRD=homologous recombination deficiency; ICF=informed consent form; ICU=intensive care unit; IDS=interval debulking surgery; MRI=magnetic 
resonance imaging; MxDx=Cycle x Day x of niraparib maintenance treatment period; PD=progression of disease; PE=physical examination; 
PK=pharmacokinetics; PRO=patient-reported outcome; PRO-CTCAE=Patient Reported Outcomes-Common Terminology Criteria for Adverse Events; 
EORTC IL136=European Organisation for Research and Treatment of Cancer Item Library 136; EORTC IL137=European Organisation for Research and 
Treatment of Cancer Item Library 137; RECIST=Response Evaluation Criteria in Solid Tumors; SAE=serious adverse event; SOC=standard of care; 
VTE=venous thromboembolism; wk=week; WOCBP=woman of childbearing potential; WPAI:GH=Work Productivity and Activity Impairment-General 
Health. 
a Sufficient time for recovery of hematologic AEs is allowed before IDS. Pre-IDS evaluations must be done taking into consideration the actual date of IDS and 
be performed up to 2 weeks prior to IDS. 
b C1D1 is to be performed up to 5 weeks after Day 1 of the run-in cycle of carboplatin-paclitaxel to accommodate resolution of AEs, HRD test result, and 
screening procedures. CBC and vital signs must be collected and reviewed prior to dosing on Day 1 of each cycle. 
c Cycle 6 is optional. If a site chooses to administer a third cycle of adjuvant chemotherapy, all participants treated at this study site must be offered the last cycle 
(C6) of adjuvant chemotherapy, regardless of treatment received during the neoadjuvant treatment period. 
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e Some inclusion and exclusion criteria can be checked at the Prescreening stage (ECOG and CBC). 
f Weekly blood pressure and heart rate for the first 8 weeks for those participants receiving niraparib as neoadjuvant therapy and for all participants receiving 
niraparib as maintenance treatment. Measurements should be taken prior to dosing on Day 1 of the cycle. In between on-site visits, a home monitoring device 
will be provided to participants who will need to record values at home. The values will be reviewed by site personnel during the on-site visits. Paper diaries 
will be provided to participants to record readings and then be transcribed to the EDC.  
g Surgical data collected include assessment of no visual residual disease, operation time, estimated blood loss, blood transfusions (i.e., red blood cells, platelets, 
whole blood, and albumin), hospitalization length of stay, re-admission for complications, ICU stay, infection and other Grade 3 or Grade 4 AEs, and additional 
procedures. 
h All PROs are to be done prior to any other study procedure. PRO-CTCAE and WPAI:GH are to be completed weekly during neoadjuvant chemotherapy. 
EORTC IL136 and EORTC IL137 are to be completed at every site visit during the neoadjuvant treatment period and at M1D1 and every 3 cycles for the first 
13-14 months and every 3 months thereafter during niraparib maintenance treatment. FACT-GP5 is to be completed weekly during the neoadjuvant treatment 
period and at M1D1 and every 3 cycles for the first 13-14 months and every 3 months thereafter during niraparib maintenance treatment. PROs that are done 
weekly will be done at home by the participant on a provisioned device; the remaining PROs will be done at the site. 
i If tumor tissue with sufficient tumor content (FFPE blocks or FFPE slides if blocks are not available) is not provided at Prescreening for exploratory biomarker 
testing, additional tumor tissue should be sent at Screening. Specifications on the collection of tumor tissue are provided in the Study Laboratory Manual. 
j Sufficient IDS tissue sample will be required for all participants to determine 
 and for exploratory biomarker testing. For participants 
randomized to niraparib neoadjuvant treatment (Arm 2), snap-frozen tumor biopsy tissue will be also collected (see footnote n). 
k RECIST v.1.1 tumor assessment via CT or MRI scan of the chest, abdomen, pelvis, and clinically indicated areas is required and will be taken after infusion 
with platinum-taxane therapy, within the 7 days immediately prior to C1D1. This scan will be referred as “baseline scan.” IV contrast-enhanced CT is 
preferred; in case of contraindication to IV CT contrast (iodine-based), non-contrast CT of chest and IV contrast-enhanced MRI (Gadolinium-based) of the 
abdomen and pelvis is recommended. Another scan is to be taken after C3D21 and during the neoadjuvant treatment period prior to IDS. If there are lesions 
noted in the chest and/or other clinically indicated areas at Screening, then repeat scans of these areas at each follow-up will be performed; otherwise, only 
scans of the abdomen and pelvis are required at each follow-up visit. 
l During the maintenance treatment period, imaging to assess disease status must occur at M1D1 or within 14 days prior to M1D1 and then every 3 months 
(±7 days) for 1 year after M1D1, followed by every 6 months (±14 days) during the second year, and every year thereafter until PD per RECIST v1.1, start of 
alternate anticancer therapy, participant discontinuation of the study, withdrawal of consent to study procedures, becoming lost to follow-up, death, or end of 
the study. Additional unscheduled RECIST v1.1 CT or MRI scans may be performed if the participant has increasing CA-125 values or suspicious symptoms. 
Participants who discontinue study treatment due to treatment toxicity or intolerability prior to an investigator assessment of PD per RECIST v1.1 will continue 
radiographic imaging until PD per RECIST v1.1, start of alternate anticancer therapy, participant discontinuation of the study, withdrawal of consent to study 
procedures, becoming lost to follow-up, death, or end of the study. Following the completion of 3 years of maintenance treatment, participants will be 
evaluated clinically and with CA-125-triggered imaging every 6 to 12 months or per local practice. 
m CBC done per SOC prior to the run-in cycle of carboplatin-paclitaxel must be used to determine eligibility. CBC are to be done within 7 days prior to CxD1 to 
determine ability to participant to receive the next cycle of platinum-taxane doublet chemotherapy or niraparib.  
For the niraparib Arm (Arm 2) only: CBC are to be performed weekly for the first 4 weeks in the neoadjuvant treatment period and for the first 4 weeks in the 
maintenance treatment period (locally or at the site) for safety monitoring. Assessments should be done prior to dosing on dosing days. Subsequently, CBC will 
be done at each study visit (every 3 weeks) for the next 10 months of the maintenance treatment period, after which blood tests should be performed every 3 
months (following visit Schedule). Note: If dose interruption or modification is required at any point on study because of hematologic toxicity (AE), weekly 
blood draws for CBC will be monitored until the AE resolves. To ensure safety of the new dose, weekly blood draws for CBC will also be required for an 
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additional 4 weeks after the AE has been resolved to the specified levels, after which monitoring every 4 weeks may resume. CBC will be done at every visit 
and as clinically indicated throughout the study. 
n Niraparib Arm (Arm 2): 3 predose samples at C1D1 (1 each for niraparib concentration, carboplatin, and paclitaxel concentration), one 3-hour postdose sample 
(± 15 minutes) at C1D1, 1 predose sample and one 3-hour (± 15 minutes) postdose sample each at C2D1 and C3D1, and 1 sample at the time of IDS (can be 
done at the pre-IDS visit).  
Control Arm (Arm 1): 2 predose samples at C1D1 are required (1 each for carboplatin and paclitaxel concentrations). Actual date and time are to be recorded. 
o In addition to blood samples mentioned in footnote n, niraparib concentration in snap-frozen tumor tissue from the IDS biopsy for pharmacodynamic analysis 
should be collected in participants randomized to niraparib (Arm 2). 
p Sample must be collected before the run-in cycle of carboplatin-paclitaxel. 
q Sample to be collected predose. 
r To be collected prior to niraparib administration at M1D1 and every 4 cycles (±7 days) after M1D1 during the maintenance treatment when imaging is 
performed. 
s Sample must be collected before the run-in cycle of carboplatin-paclitaxel. 
t Bevacizumab or bevacizumab biosimilar is optional (≤15 months including adjuvant chemotherapy period) for participants deemed high-risk. Monitor by 
dipstick urine analysis prior to each bevacizumab or bevacizumab biosimilar infusion for the development or worsening of proteinuria with serial urinalyses 
during bevacizumab therapy. Participants with a 2+ or greater urine dipstick reading should undergo further assessment with a 24-hour urine collection. 
Bevacizumab or bevacizumab biosimilar treatment should be withheld for proteinuria greater than or equal to 2 grams per 24 hours and resumed when less than 
2 grams per 24 hours. Bevacizumab or bevacizumab biosimilar treatment should be discontinued in participants who develop nephrotic syndrome. Monitor 
blood pressure every 2 to 3 weeks during bevacizumab or bevacizumab biosimilar treatment. Continue to monitor blood pressure at regular intervals in patients 
with bevacizumab-induced or bevacizumab-exacerbated hypertension after discontinuation. Bevacizumab or bevacizumab biosimilar treatment should be 
discontinued for participants who develop gastrointestinal perforation, tracheoesophageal fistula or any Grade 4 fistula, and fistula formation involving any 
internal organ. 
u Pregnancy testing for WOCBP only can be done at site/local lab, at home via the home health clinician, or at a local clinic. If a participant becomes a WONCBP 
(defined in Appendix 1 of the master protocol) during the study (e.g., post-IDS), then pregnancy testing and contraception will not be required. 
v Discussions can be held at the site or via a phone call to the participant at home (involving home health clinician or a direct phone call to the participant by site 
staff). 
w Baseline ECG is required for all participants. ECG monitoring at other visits are as clinically indicated (at the Investigator’s discretion), based on the 
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8. 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
The overall list of eligibility criteria for entry into this study is provided in the master protocol. 
The following are all eligibility criteria for this cohort (Cohort C) and include eligibility criteria 
from the master protocol as well as cohort-specific eligibility criteria. Participants must meet all 
criteria in this cohort-specific supplement in order to be eligible for enrollment in this cohort. 
8.1. 
Inclusion Criteria 
Participants will be eligible for entry in this cohort if all of the following criteria for inclusion are 
met: 
Inclusion criteria from the master protocol 
C1. Participant must be female ≥18 years of age, able to understand the study procedures, and 
agree to participate in the study by providing written informed consent. 
C2. Participant must have measurable disease according to RECIST v1.1. 
C3. Participant has an ECOG performance status of 0 to 2. 
C4. Participant has adequate organ function, defined as follows: 
a. Absolute neutrophil count ≥1500/μL, without growth factor support (granulocyte 
colony-stimulating factor or granulocyte-macrophage colony-stimulating factor 
administration is not permitted within 2 weeks of Screening) 
b. Platelets ≥100 000/μL without platelet transfusion support within 2 weeks prior to 
Screening 
c. Hemoglobin ≥9 g/dL without transfusion or growth factor (recombinant 
erythropoietin) within 2 weeks of Screening 
d. Serum creatinine ≤1.5× upper limit of normal (ULN) or calculated creatinine 
clearance ≥50 mL/min using Cockcroft-Gault equation 
e. Total bilirubin ≤1.5× ULN, except in participants with Gilbert’s syndrome. 
Participants with Gilbert’s syndrome may enroll if direct bilirubin is ≤1.5× ULN. 
f. Aspartate aminotransferase and alanine aminotransferase ≤2.5× ULN, unless liver 
metastases are present, in which case they must be ≤5× ULN 
g. International normalized ratio or prothrombin time (PT) ≤1.5× ULN, unless 
participant is receiving anticoagulant therapy as long as PT or partial thromboplastin 
time (PTT) is within therapeutic range of intended use of anticoagulants 
h. Activated PTT ≤1.5× ULN unless participant is receiving anticoagulant therapy as 
long as PT or PTT is within therapeutic range of intended use of anticoagulants. 
Participants with known lupus anticoagulant and elevated PTT may be eligible on a 
case-by-case basis after discussion with the Sponsor’s Medical Monitor. 
C5. Participant is not pregnant or breastfeeding, and at least 1 of the following conditions 
apply: 
− Is not a woman of childbearing potential (WOCBP), as defined in Appendix 1 in the 
master protocol. 


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OR 
− Is a WOCBP using a contraceptive method that is highly effective (with a failure rate 
of <1% per year) with low user dependency, as described in Appendix 1 in the master 
protocol, during the treatment periods and for at least 180 days after the last dose of 
study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The Investigator should evaluate the effectiveness of 
the contraceptive method in relation to the first dose of study treatment. 
o A WOCBP must have a negative pregnancy test (highly sensitive urine test or 
serum test as required by local regulations) within 72 hours before the first dose 
of study treatment.  
If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a 
serum pregnancy test is required. In such cases, the participant must be excluded 
from participation if the serum pregnancy result is positive. 
o Additional requirements for pregnancy testing during and after study treatment 
are described in Section 11.3.8 of the master protocol. 
The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Inclusion criteria specific to this cohort (Cohort C) 
C6. Participant has newly diagnosed Stage III or IV ovarian, fallopian tube, or primary 
peritoneal cancer according to the International Federation of Gynecology and Obstetrics 
staging criteria. 
C7. Participants must provide sufficient tumor tissue at Prescreening and agree to undergo a 
central HRD tumor testing using a fully validated assay. The participants must be HRd as 
per central HRD tumor testing result for eligibility. 
a. Participants with a documented germline BRCA1/2 deleterious or suspected 
deleterious mutations by Sponsor’s permitted test 
 may be 
allowed to enroll prior to receiving the central test results, provided all inclusion 
criteria are met. However, tumor sample submitted by these participants will still be 
required for central HRD confirmation. The list of Sponsor’s permitted tests will be 
provided by the Sponsor. 
b. All participants must agree to provide tumor tissue collected from IDS. 
c. Participant must provide 2 formalin-fixed paraffin-embedded tissue blocks (or slides 
if blocks are not available) with sufficient tumor content (as confirmed by the 
Sponsor’s designated central and/or testing laboratory) for central HRD testing at 
Prescreening and for exploratory biomarker testing at Prescreening or Screening. If 
sufficient tumor tissue is provided at Prescreening, participants do not need to provide 
additional tissue at Screening. 
C8. Participant must have completed 1 run-in cycle of carboplatin-paclitaxel and not 
experienced disease progression after this treatment. Completion is defined as receiving 
≥50% of the prescribed dose of therapy within 5 weeks. 
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C9. Participant must not have known contraindication or uncontrolled hypersensitivity to 
carboplatin and paclitaxel and their excipients and no known pre-existing conditions that 
would preclude treatment with these agents. 
C10. Participant must not have known contraindication or uncontrolled hypersensitivity to 
niraparib and its excipients. 
C11. Participant must not have symptomatic ascites or pleural effusions as defined by the 
following criterion: presence of fluid in the abdominal or pleural cavities requiring 
removal within 1 week prior to signing the informed consent. 
C12. Participant must agree to complete PRO and work productivity questionnaires throughout 
the study. 
8.2. 
Exclusion Criteria 
Participants will not be eligible for entry in this cohort if any of the criteria for exclusion in the 
master protocol or in this cohort-specific supplement are met: 
Exclusion criteria from the master protocol 
C1. Participant has not recovered (i.e., to Grade ≤1 or to Baseline) from prior 
chemotherapy-induced AEs. Note: Participant with Grade ≤2 neuropathy or alopecia is 
an exception to this criterion and may qualify for the study. 
C2. Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid 
therapy exceeding an equivalent of prednisone 10 mg daily or any other form of 
immunosuppressive therapy within 7 days prior to the first dose of study treatment. 
C3. Participant is currently participating in a treatment study or has participated in a study of 
an investigational agent within 4 weeks of the first dose of treatment. 
C4. Participant has received prior systemic anticancer therapy including cytotoxic 
chemotherapy, PARP inhibitor, immune checkpoint inhibitors, hormonal therapy given 
with the intention to treat cancer, or biological therapy within 3 weeks of the first dose of 
study treatment. This washout period is required to ensure prior therapy is not 
confounding the toxicity profile of the investigational study drug or study drug 
combinations in cohorts. 
Note: For this cohort (Cohort C), this criterion will not apply because the population will 
include only participants who are eligible for neoadjuvant chemotherapy. 
C5. Participant has received live vaccine within 14 days of planned start of study therapy. 
C6. Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (To be 
considered "controlled", central nervous system [CNS] disease must have undergone 
treatment [e.g., radiation or chemotherapy] at least 1 month prior to study entry. The 
participant must not have any new or progressive signs or symptoms related to the CNS 
disease and must be taking ≤10 mg of prednisone or equivalent per day or no steroids.) 
Participant who has untreated brain metastases and who is not symptomatic may enroll if 
the Investigator feels that the treatment of these metastases is not indicated. A scan to 
confirm the absence of brain metastases is not required. Participant with spinal cord 


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compression may be considered if she has received definitive treatment for this and 
evidence of clinically SD for 28 days prior to the first dose of study treatment. 
C7. Participant had major surgery within 4 weeks of starting the study or participant has not 
recovered from any effects of any major surgery. 
C8. Participant has a known additional malignancy that progressed or required active 
treatment within the last 2 years because reoccurrence of another malignancy would 
confound interpretation of ORR by RECIST v1.1 criteria. Exceptions include basal cell 
carcinoma of the skin, squamous cell carcinoma of the skin that has undergone 
potentially curative therapy, or in situ cancer that is considered to be low risk for 
progression by the Investigator. 
C9. Participant is considered to be in poor medical condition or at high medical risk due to a 
serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, 
uncontrolled infection. These include, but are not limited to, coronavirus disease 2019, 
significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, 
myocardial infarction, cardiac arrhythmia or unstable angina within 6 months prior to 
enrollment, New York Heart Association Grade ≥2 congestive heart failure, uncontrolled 
hypertension, serious cardiac arrhythmia requiring medication, Grade ≥2 peripheral 
vascular disease, and history of cerebrovascular accident within 6 months prior to 
enrollment), uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, and any psychiatric disorder that prohibits obtaining 
informed consent. 
C10. Participant has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the study, might interfere with the 
participant’s participation for the full duration of the study treatment, or is not in the best 
interest of the participant to participate. 
C11. Participant has known active hepatitis B (e.g., hepatitis B surface antigen reactive) or 
hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected). 
Exclusion criteria specific to this cohort (Cohort C) 
C12. Participant has low-grade or Grade 1 epithelial OC or mucinous, germ cell, transitional 
cell, carcinosarcoma, or undifferentiated tumor. 
C13. Participant has contraindications to surgery. 
C14. Participant has a bowel obstruction by clinical symptoms or CT scan, subocclusive 
mesenteric disease, abdominal or gastrointestinal fistula, gastrointestinal perforation, or 
intra-abdominal abscess. 
C15. Participant has any known history or current diagnosis of MDS or AML. 
C16. Participant is at increased bleeding risk due to concurrent conditions (e.g., major injuries 
or major surgery within the past 28 days prior to the start of study treatment and/or 
history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or 
clinically significant hemorrhage within the past 3 months). 
C17. Participant is immunocompromised. Participants with splenectomy are allowed. 
Participants with known HIV are allowed if they meet all of the following criteria: 


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a. Cluster of differentiation 4-positive T cell count ≥350/μL and viral load 
<400 copies/mL 
b. No history of AIDS-defining opportunistic infections within 12 months prior to 
enrollment 
c. No history of HIV-associated malignancy for the past 5 years 
d. Concurrent antiretroviral therapy as per the most current National Institutes of Health 
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living 
with HIV started >4 weeks prior to study enrollment 
C18. Participant received prior treatment for high-grade non-mucinous epithelial ovarian, 
fallopian tube, or peritoneal cancer (e.g., prior surgery, immunotherapy, anticancer 
therapy [with the exception of 1 run-in cycle of carboplatin-paclitaxel], or radiation 
therapy). 
C19. Participant has an active autoimmune disease that has required systemic treatment in the 
past 2 years. Replacement therapy is not considered a form of systemic therapy 
(e.g., thyroid hormone or insulin). 
C20. Participant is unable to swallow orally administered medication or has a gastrointestinal 
disorder likely to interfere with absorption of the study medication. 
C21. Participant received whole blood transfusions in the 2 weeks prior to entry to the study 
(packed red blood cells and platelet transfusions are acceptable outside of 2 weeks prior 
to treatment). 
8.3. 
Withdrawal Criteria 
8.3.1. 
Discontinuation from Treatment 
Examples of reasons for discontinuing study treatment applicable across cohorts are presented in 
the master protocol. Details of required dose modifications related to toxicity, including 
interruptions, reductions, and permanent discontinuations, are provided in Section 7.4.1. 
Discontinuation of study treatment does not affect a participant’s participation in the study. The 
participant should comply with the protocol Schedule of Events (Table 5) and data collection 
should continue (e.g., safety). The participant must be followed for survival, up to the end of the 
study as defined in Section 7.1.6. 
If the participant considers study withdrawal at the time of study treatment discontinuation, 
modified follow-up options should be discussed, if appropriate (see Section 8.3.2). 
8.3.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
participant safety and evaluate liver event etiology. 
Discontinuation of study intervention for abnormal liver tests is required when: 
• a participant meets one of the conditions outlined in Figure 3 or  
• in the presence of abnormal liver chemistry not meeting protocol-specified stopping 
rules, if the Investigator believes that it is in the best interest of the participant 


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Figure 3: 
Cohort C Liver Stopping and Monitoring Event Algorithm 
 
Abbreviations: ALT=alanine aminotransferase; INR=international normalized ratio; SAE=serious adverse event; 
ULN=upper limit of normal. 
 
Refer to Appendix B for required liver safety actions and follow-up assessments and for required 
process for study intervention restart/rechallenge if considered for the participant. 
8.3.1.2. 
Study Intervention Restart or Rechallenge After Liver Stopping Criteria Met 
Study intervention restart/rechallenge after liver chemistry stopping criteria are met is allowed in 
Cohort C of this study. If participant meets liver chemistry stopping criteria, do not 
restart/rechallenge participant with study intervention unless all of the following occur: 
• GSK Medical Governance approval is granted 
• Ethics and/or IRB approval is obtained, if required, and 
• Separate consent for intervention restart/rechallenge is signed by the participant and 
participant is informed of any associated risks  
Refer to Appendix B Liver Safety: Required Actions and Follow-up Assessments and Study 
Intervention Restart/Rechallenge Guidelines for details on restart/rechallenge process.  


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If GSK Medical Governance approval to restart/rechallenge the participant with study 
intervention is not granted, then the participant must permanently discontinue study intervention 
and should continue in the study for protocol-specified follow-up assessments. 
8.3.2. 
Discontinuation from the Study 
Guidance on discontinuation of participants from the study is provided in the master protocol. 
All participants must be followed for survival, up to the end of the study as defined in 
Section 7.1.6 and Section 8.3.1.  
For participants considering withdrawal from study, a modified follow-up option should be 
discussed if appropriate, to allow reduced collection of data such as vital status (at minimum) 
and subsequent anticancer therapy. When appropriate, this can be done via a telephone contact 
with the participant, a contact with others e.g., a relative or treating physician, or collecting 
information from medical records. The agreed approach should be recorded in the medical 
records. A participant who agrees to modified follow-up is not considered to have withdrawn 
from the study. 
Site personnel, or a trusted independent third party, will attempt to collect the vital status 
information for all randomized participants who discontinued from the study due to consent 
withdrawal or loss-to-follow-up, including those who did not receive study intervention, within 
legal and ethical boundaries. Public sources may be searched for vital status information. If the 
vital status of a participant is determined as known alive or deceased, this will be documented 
along with other relevant study information. Sponsor personnel will not be involved in any 
attempts to collect vital status information. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. Use of vital status 
information obtained from independent third party or review of public sources (public records or 
other allowable routes) for those participants withdrawn or lost-to-follow-up is permitted, 
dependent upon local regulations.  
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records.  
 


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9. 
TREATMENT OF PARTICIPANTS 
9.1. 
Description of Study Drug 
The study drugs for this cohort are described in Table 6. The investigational product is niraparib, 
carboplatin-paclitaxel (or alternative platinum-taxane doublet chemotherapy as relevant) is the 
reference therapy. 
Table 6: 
Study Drugs 
 
Investigational 
Product 
Reference Therapy 
Product name 
Niraparib 
Carboplatin 
Paclitaxel 
Bevacizumab or 
bevacizumab 
biosimilar 
(optional) 
Type 
Drug 
Drug 
Drug 
Drug 
Dosage form 
(formulation) 
 
Solution for 
Infusion (vial) 
Solution for 
Infusion (vial) 
Solution for 
Infusion (vial) 
Unit dose 
Dose Level 
See Section 10.5.1 
See Section 10.5.2 
See Section 10.5.2 
See Section 10.5.3 
Route of 
administration 
Oral 
IV 
IV 
IV 
Physical 
description 
(Packaging 
and Labeling; 
also see 
Section 10.2) 
 in 
high-density 
polyethylene 
bottles. Each bottle 
will be labeled as 
required per 
country 
requirement. 
Solution for IV 
infusion 
Each package/vial 
will be labeled as 
required per 
country 
requirement. 
Solution for IV 
infusion 
Each package/vial 
will be labeled as 
required per 
country 
requirement. 
Solution for IV 
infusion 
Each package/vial 
will be labeled as 
required per 
country 
requirement. 
Use 
Experimental 
Active comparator 
(SOC) 
Active comparator 
(SOC) 
SOC 
IMP and 
NIMP/AxMP 
IMP 
IMP 
IMP 
AxMP/NIMP 
Sourcing 
Provided centrally 
by the Sponsor 
Provided locally 
by the study site 
(or centrally if 
required) 
Provided locally 
by the study site 
(or centrally if 
required) 
Provided locally 
by the study site  
Abbreviations: AUC=area under the concentration versus time curve; AxMP=auxiliary medicinal product; 
IMP=investigational medicinal product; IV=intravenous; NIMP=non-investigational medicinal product; 
SOC=standard of care; QxW=every x weeks. 
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9.2. 
Concomitant Medications 
Details on the definition and recording of concomitant medications are provided in the master 
protocol. 
9.2.1. 
Prohibited Medications 
Known prior medications that exclude a patient from participating in this cohort are described in 
the exclusion criteria (see Section 8.2). 
Participants are prohibited from receiving the following therapies during the Screening and 
treatment periods of this study: 
• Systemic anticancer or biological therapy 
• Immunotherapy (except study treatment specified in the relevant cohort-specific 
supplement) 
• Chemotherapy (except study treatment specified in the relevant cohort-specific 
supplement) 
• Hormonal therapy given with the intention to treat the primary cancer 
• Radiation therapy is prohibited within 3 weeks prior to Day 1 and during study 
treatment. Note: Palliative radiation therapy to a small field while on study should be 
discussed with the Sponsor’s Medical Monitor on a case-by-case basis. 
• Any surgery not prespecified in the cohort-specific Schedule of Events that involves 
tumor lesions; however, specific situations should be discussed on a case-by-case 
basis with the Sponsor’s Medical Monitor. Paracentesis while the participant is on 
study will be permitted after discussion with the Sponsor. Note: Administration of 
radiation therapy or surgery done that involves tumor lesions will be considered as 
disease progression at the time the procedure is performed. 
• Live vaccines within 14 days prior to the first dose of study treatment. Seasonal flu 
vaccines that do not contain live viruses are allowed. Examples of live vaccines 
include, but are not limited to, the following: measles, mumps, rubella, chicken pox, 
yellow fever, rabies, Bacillus CalmetteGuérin, and typhoid (oral) vaccine. Seasonal 
influenza vaccines for injection are generally killed virus vaccines and are allowed. 
The use of live COVID-19 adenoviral vaccines within 14 days prior to the first dose 
of treatment or while participating in the study must be discussed with the Sponsor’s 
Medical Monitor. Intranasal influenza vaccines (e.g., FluMist) are live attenuated 
vaccines and are not allowed. 
• Investigational agents other than niraparib 
• Prophylactic cytokines (i.e., granulocyte colony-stimulating factor) should not be 
administered in the first cycle of the study but may be administered in subsequent 
cycles according to current American Society of Clinical Oncology guidelines 
The niraparib safety profile includes risk for thrombocytopenia and bevacizumab may increase 
the potential for bleeding (hemorrhage); therefore, participants should be advised to use caution 
when taking anticoagulants (e.g., warfarin) and antiplatelet drugs (e.g., aspirin). 


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Caution is recommended when niraparib is combined with active substances with cytochrome 
P450 enzyme (CYP)3A4-dependent metabolism and, notably, those having a narrow therapeutic 
range (e.g., cyclosporine, tacrolimus, alfentanil, ergotamine, pimozide, quetiapine, and 
halofantrine). 
Caution is recommended when niraparib is combined with active substances with CYP1A2-
dependent metabolism and, notably, those having a narrow therapeutic range (e.g., clapzine, 
theophylline, and ropinirole). Caution is then recommended when niraparib is combined with 
substrates of breast cancer resistance protein (e.g., irinotecan, rosuvastatin, simvastatin, 
atorvastatin, and methotrexate). 
Niraparib is an inhibitor of multidrug and toxin extrusion transporter 1 and 2 with a 
half-maximal inhibitory concentration of 0.18 µM and ≤0.14 µM, respectively. Increased plasma 
concentrations of co-administered medicinal products that are substrates of these transporters 
(e.g., metformin) cannot be excluded. 
Caution is recommended when niraparib is combined with active substances that undergo an 
uptake transport by organic cation transporter 1 (e.g., metformin). 
Physicians should follow the prescribing information for Zejula, carboplatin, paclitaxel, and 
bevacizumab or bevacizumab biosimilar, and the niraparib IB for information on the general 
recommendation and management of the participants receiving these therapies. 
9.2.2. 
Contraception 
Contraception guidelines are provided in the master protocol. 
If a participant becomes a WONCBP (defined in Appendix 1 of the master protocol) during the 
study (e.g., post-IDS), then pregnancy testing and contraception will not be required. 
9.2.3. 
Rescue Medications and Supportive Care Guidelines 
Supportive care measures for AEs during treatment with niraparib should be provided as deemed 
necessary by the treating Investigator according to local institutional practice and/or guidance in 
the appropriate prescribing information. 
9.2.4. 
Other Study Restrictions 
Other study restrictions are provided in the master protocol. 
9.3. 
Treatment Compliance 
Overall study treatment compliance information is presented in the master protocol. Study 
treatment will be administered by investigational site personnel at investigational sites as detailed 
in Section 10.5. 
9.4. 
Randomization and Blinding 
All participants will be centrally randomized using an Interactive Voice/Web Response System. 
Before the study is initiated, the telephone number and call-in directions for the Interactive Voice 
Response System and/or the log in information and directions for the Interactive Web Response 


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System will be provided to each site. Randomization will be stratified by BRCA mutational status 
(BRCAmut vs BRCAwt/unknown). 
This study is open-label. 
To mitigate the risk of introducing bias in the assessment of treatment effect, various 
treatment-sensitive clinical data types are required to remain blinded to specified roles on the 
central study team until Database Freeze. No data aggregation (efficacy, safety, or PK) by 
treatment arm is to be performed, except for prespecified interim analyses. Details of 
blinding/masking treatment-sensitive data are included in the study-level treatment-sensitive data 
plan, which describes how these data will be managed. This study will be monitored by a GSK 
Data Review Committee that is independent of the GSK study team who are directly involved in 
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10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Study Drug 
10.1.1. 
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. 
10.1.2. 
Carboplatin and Paclitaxel 
Carboplatin (platinum, diamine [1,1-cyclobutanedicarboxylato(2-)-O,O’]-,[SP-4-2]) is a 
platinum coordination compound. The main target of carboplatin is DNA. Carboplatin for 
infusion is supplied as a sterile, pyrogen-free, aqueous solution for infusion. 
Paclitaxel (5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 
2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine) is a natural product with 
antitumor activity, derived from Taxus baccata. Paclitaxel for infusion is a clear, colorless to 
slightly yellow viscous solution. It is supplied as a nonaqueous solution intended for dilution 
prior to intravenous infusion. 
Additional information on carboplatin and paclitaxel can be found in the prescribing information 
for each agent as well as in the Study Reference Manual. 
10.1.3. 
Optional Bevacizumab or Bevacizumab Biosimilar 
Bevacizumab or bevacizumab biosimilar is an antiangiogenic recombinant humanized 
immunoglobulin G1 monoclonal antibody against the vascular endothelial growth factor. 
Bevacizumab for infusion is a clear to slightly opalescent, colorless to pale brown, sterile 
solution. 
Additional information on bevacizumab or bevacizumab biosimilar can be found in the 
prescribing information as well as in the Study Reference Manual. 
10.2. 
Study Drug Packaging and Labeling 
Overall, niraparib packaging and labeling is described in the master protocol, Study Reference 
Manual, and IB. Carboplatin, paclitaxel, and bevacizumab are described in their respective 
prescribing information as per the local label. 
10.3. 
Study Drug Storage 
Study treatment storage is described in the master protocol. 
10.4. 
Study Drug Preparation 
The Study Reference Manual contains specific instructions for the preparation of each dose of 
the niraparib 
 Refer to local prescribing information for instructions for the preparation 
of platinum-taxane doublet chemotherapy and bevacizumab. 
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10.5. 
Administration 
10.5.1. 
Niraparib 
Niraparib will be supplied as 
. Participants will be instructed to take their 
niraparib dose once a day continuously throughout each cycle or as instructed by the 
Investigator. Niraparib will be dispensed to participants at each scheduled visit. 
Participants will be instructed to take niraparib at the same time each day. Bedtime 
administration may be a potential method for managing nausea. Participants must swallow and 
not chew all 
 The consumption of water and food with 
 is permissible. If a 
participant vomits or misses a dose of niraparib, a replacement dose should not be taken. 
For participants randomized to niraparib neoadjuvant treatment, the starting dose will be as 
follows: 
• 200 mg 
 for participants with an actual body weight <77 kg 
OR screening platelet count <150 000/µL on C1D1 
• 300 mg (
) for participants with an actual body weight ≥77 kg 
AND screening platelet count ≥150 000/µL on C1D1 
Niraparib will be administered orally once daily continuously throughout each of the three 
21-day cycles. 
For participants receiving niraparib maintenance treatment, independent of the treatment they 
received during the neoadjuvant treatment period, the starting dose will be as follows: 
• 200 mg 
) for participants with an actual body weight <77 kg 
OR platelet count <150 000/µL on M1D1 
• 300 mg (
) for participants with an actual body weight ≥77 kg 
AND platelet count ≥150 000/µL on M1D1 
• For participants who received niraparib in the neoadjuvant period and experienced 
niraparib dose reductions due to AEs, the Investigator, in consultation with the 
Sponsor’s Medical Monitor, will determine the safest starting dose in the maintenance 
setting  
Niraparib will be taken once daily continuously throughout each 21-day cycle. 
Dose modifications, if any, will be based on treatment side effects (Section 7.4.1.1), not upon 
changes in the participant’s actual body weight during study participation. 
The Study Reference Manual contains descriptions of the packaging of niraparib and instructions 
for the preparation and administration of niraparib. Niraparib can be shipped direct-to-patient 
from the investigational site to the participant’s home address, details are provided in the master 
protocol and the Study Reference Manual. 
10.5.2. 
Carboplatin and Paclitaxel 
Carboplatin will be infused intravenously over 60 minutes at the prescribed dose of area under 
the concentration versus time curve of 5 to 6 mg/mL•min on Day 1 of every 21-day cycle. The 
carboplatin dose will be determined by the Investigator, taking into consideration the 
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participant’s pre-existing medical conditions and the recommendations provided in the 
prescribing information. 
Paclitaxel will be administered in a similar fashion over 180 minutes at the prescribed dose of 
175 mg/m2 on Day 1 of every 21-day cycle. All participants should be pretreated with 
corticosteroids, diphenhydramine, and H2 antagonists as indicated in the prescribing information. 
Paclitaxel is recommended to be administered before carboplatin, however, carboplatin may be 
administered first, if this is the current local institutional practice. 
Prior to each chemotherapy administration, all of the following criteria must be met: 1) absolute 
neutrophil count ≥1500/µL or ≥1000/µL if granulocyte colony-stimulating factor is to be 
administered, 2) platelet count ≥100 000/µL, 3) hemoglobin ≥9 g/dL. 
If a participant experiences a hypersensitivity to carboplatin, then cisplatin may be used in place 
of carboplatin. Desensitization to carboplatin will not be allowed on the study. If a participant 
experiences hypersensitivity or clinically significant neuropathy on paclitaxel treatment, 
docetaxel can be substituted per the Investigator’s discretion. 
Carboplatin (or cisplatin) and paclitaxel (or docetaxel) must be given on the same day; hence, 
delays in 1 study treatment should result in delay of all study treatments until they can all safely 
be given. 
10.5.3. 
Optional Bevacizumab or Bevacizumab Biosimilar  
The initial dose of optional bevacizumab or bevacizumab biosimilar will be infused 
intravenously over 90 (±15) minutes at the prescribed dose of 7.5 mg/kg or 15 mg/kg on Day 1 
of every 21-day cycle. If the first infusion is tolerated without infusion-associated AEs (fever 
and/or chills), the second infusion may be delivered over 60 (±10) minutes. If the 60-minute 
infusion is well tolerated, all subsequent infusions may be delivered over 30 (±10) minutes. Sites 
can defer to local practice for administration if different from the process described here and if 
bevacizumab or bevacizumab biosimilar should be given before or after carboplatin-paclitaxel. 
Prior to administering bevacizumab or bevacizumab biosimilar, monitor by dipstick urine 
analysis for the development or worsening of proteinuria. Participants with a 2+ or greater urine 
dipstick reading should undergo further assessment with a 24-hour urine collection. 
10.6. 
Study Drug Accountability 
Study treatment accountability is described in the master protocol. 
10.7. 
Study Drug Handling and Disposal 
Study treatment handling and disposal are described in the master protocol and the cohort-
specific Study Reference Manual. 


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11. 
ASSESSMENT OF EFFICACY 
11.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint for this cohort is pre-IDS unconfirmed ORR, defined as the 
percentage of participants with unconfirmed CR or PR on study treatment pre-IDS as assessed 
per RECIST v1.1 by the Investigator. 
A description of evaluation of tumor response by RECIST v1.1. is provided in the master 
protocol. 
11.2. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints for this cohort are as follows: 
• Incidence of CA-125 progression per GCIG CA-125 response criteria 
• PFS, defined as the time from the date of treatment randomization to the date of first 
documentation of PD per RECIST v1.1 or death by any cause, whichever occurs first, 
as determined by the Investigator 
• OS, defined as the time from the date of treatment randomization to the date of death 
by any cause 
• TFST, defined as the time from the date of treatment randomization to the date of first 
subsequent anticancer therapy or death 
11.3. 
Patient-reported Outcome Endpoints 
Secondary PRO endpoints, arranged in order of clinical importance, are as follows: 
• To determine overall tolerability toward treatment: change over time in frequency and 
severity of the items on the PRO-CTCAE during neoadjuvant treatment 
• To determine symptom tolerability: change from baseline in FACT-GP5 during 
neoadjuvant treatment 
• To determine overall health status: change from baseline in EORTC QLQ-C30 items 
(EORTC IL136) pre-IDS 
• To determine OC-specific HRQoL and symptoms: change from baseline in EORTC 
QLQ-OV28 gastrointestinal items (EORTC IL137) pre-IDS 
Exploratory PRO endpoints, arranged in order of clinical importance, are as follows: 
• To determine overall health status: change from baseline in EORTC QLQ-C30 items 
(EORTC IL136) during the niraparib maintenance treatment period 
• To determine OC-specific HRQoL and symptoms: change from baseline in EORTC 
QLQ-OV28 items (EORTC IL137) during the niraparib maintenance treatment period 
• To determine work productivity: change from baseline in WPAI:GH during 
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11.4. 
Exploratory Endpoints 
Exploratory Efficacy Endpoints include the following: 
11.4.1.1. Surgical and Postsurgical Outcomes 
The key exploratory endpoint to evaluate surgical outcome is the 
 
 by the gynecologic/surgical oncologist. 
Additional exploratory endpoints to evaluate other surgical and postsurgical outcomes are as 
follows: 
11.4.1.2. Healthcare Resource Utilization 
Medical resource utilization and health economics will be collected using a HCRU questionnaire 
and results may be compared between participants who receive neoadjuvant niraparib and 
participants who received neoadjuvant platinum-taxane doublet chemotherapy. 
11.4.1.3. Pathological Complete Response 
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11.4.1.4. Biomarker Endpoints 
Tumor tissue and/or blood samples may be assessed to identify potential disease- or treatment-
related biomarkers that would associate with tumor responses to treatment. Additionally, samples 
may be assessed to evaluate the evolution of the molecular profile of the tumor and tumor 
microenvironment in response to treatment. 
11.4.1.5. Pharmacokinetic and Pharmacodynamic Endpoints 
The PK endpoints are as follows: 
• Residual plasma concentrations of carboplatin and paclitaxel at C1D1 
• Niraparib concentration throughout the neoadjuvant treatment period 
• Niraparib concentration in tumor tissue from IDS biopsy 
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12. 
ASSESSMENT OF SAFETY 
12.1. 
Safety Parameters 
Safety parameters for this study are described in the master protocol. 
Safety endpoints include frequency and severity of treatment-emergent AEs, SAEs, AEs of 
special interest, and dose modification (i.e., interruptions and discontinuations). 
12.2. 
Adverse Events and Special Situations 
The severity of AEs will be graded according to CTCAE v5.0. Guidance on AEs and special 
situations is provided in the master protocol. 


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13. 
STATISTICS 
An overall description of the statistics for this study is provided in the master protocol. 
Additional details are provided in the statistical analysis plan (SAP). 
All analyses will include summary statistics, including the number and percentage for categorical 
variables and the number of participants, mean, standard deviation, median, minimum, and 
maximum for continuous variables. Time-to-event analyses will be performed using the 
Kaplan-Meier method. 
13.1. 
Sample Size Determination 
Sample size calculation was performed using 
 
Randomization will be stratified based on BRCA mutational status (Section 9.4). 
13.2. 
Planned Analyses 
13.2.1. 
Analysis Populations 
• ITT Population: All randomized participants whether or not randomized treatment 
was administered. 
• Safety Population: All randomized participants who receive at least one dose of study 
treatment. 
• PK Population: All participants in the safety analysis set from whom at least one 
postdose PK sample has been obtained and analyzed. 
Additional analysis populations may be defined in the SAP. 
13.2.2. 
Efficacy Analyses 
All efficacy analyses will include summary statistics as described in the master protocol. 
13.2.2.1. Primary Efficacy Analysis 
The primary endpoint of pre-IDS ORR will be analyzed in the ITT Population. The pre-IDS 
ORR difference will be evaluated between the niraparib and the platinum-taxane doublet 
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chemotherapy neoadjuvant treatments. The 2-sided 80% CI of the pre-IDS ORR difference will 
be provided. 
13.2.2.2. Secondary Efficacy Analysis 
The PFS analysis will be assessed by RECIST v.1.1 criteria based on investigator assessment. 
The distribution of PFS, OS, and TFST for each treatment arm will be estimated using the 
Kaplan-Meier method and will be compared between the 2 treatment arms using log-rank test 
stratified by the stratification factor used for randomization (i.e., BRCA mutational status; 
Section 9.4). The HR and corresponding 95% CI will be estimated from Cox proportional hazard 
model stratified by randomization factors with treatment arm as the explanatory variable. The 
PFS rates at 12, 18, and 24 months will also be estimated from the Kaplan-Meier curve. The 
censoring rules for the PFS, OS, and TFST analyses will be detailed in the SAP. 
The CA-125 progression analysis will be based on GCIG CA-125 response criteria using the 
following rules: 
• Participants with elevated CA-125 pretreatment and a reduction of CA-125 to within 
the normal range on study must show evidence of CA-125 ≥2× ULN on 2 occasions 
at least 1 week apart 
• Participants with elevated CA-125 pretreatment that never reduces to within the 
normal range on study must show evidence of CA-125 ≥2× the nadir value on 
2 occasions at least 1 week apart 
• Participants with CA-125 in the normal range pretreatment must show evidence of 
CA125 ≥2× ULN on study on 2 occasions at least 1 week apart 
Additional details will be provided in the SAP. 
13.2.2.3. Exploratory Efficacy Analysis 
 
 
 
 The 2-sided 80% CI of the difference will be provided. 
13.2.3. 
Patient-reported Outcome Analyses 
The PRO assessments will be analyzed descriptively by changes from baseline in overall score, 
sub-scores, and individual items when applicable. A repeated measures model adjusting for 
covariates may be conducted. 
13.2.4. 
Safety Analyses 
Safety will be evaluated in the Safety Analysis Population based on the incidence and severity of 
treatment-emergent AEs, SAEs, treatment discontinuations or dose delays or reductions due to 
AEs, AESIs, changes in ECOG performance status, changes in clinical laboratory results 
(hematology and chemistry), vital sign measurements, observations during symptom-directed 
physical examination, and use of concomitant medications. All AEs will be coded using the 
current version of the Medical Dictionary for Regulatory Activities coding system. 
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13.2.4.1. Pharmacokinetic and Pharmacodynamic Analyses 
A summary of niraparib plasma concentration measurements will be provided for participants in 
the PK population. A by-participant listing and summary of the residual carboplatin and 
paclitaxel plasma concentrations predose at C1D1 will be provided for all randomized 
participants.  
Data from this study may be combined with data from other niraparib studies for population PK 
analysis. If performed, the analysis will be fully described in stand-alone analysis plans and 
reported separately from the main clinical study report. 
An overview of the niraparib tumor tissue exposure will be provided for all participants 
randomized to niraparib neoadjuvant treatment (Arm 2). 
13.2.4.2. Biomarker Analysis 
13.2.4.3. Additional Exploratory Analyses 
Details on additional exploratory analyses will be provided in the SAP. 
13.2.5. 
Interim Analysis 
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14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access to source data and documents is described in the master protocol. 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Quality tolerance limits will be pre-defined in the Study Reference Manual to identify systematic 
issues that can impact participant safety and/or reliability of study results. These pre-defined 
parameters will be monitored during the study and deviations from the quality tolerance limits 
and remedial actions taken will be summarized in the clinical study report. 
Additional information on quality control and quality assurance is provided in the master 
protocol. 


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16. 
ETHICS 
Ethics is described in the master protocol. 


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17. 
DATA HANDLING AND RECORDKEEPING 
Data handling and recordkeeping is described in the master protocol. 


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18. 
PUBLICATION POLICY 
Publication policy is described in the master protocol. 


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19. 
LIST OF REFERENCES 
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and 
Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials 
in oncology. J Natl Cancer Inst. 1993;85(5):365-376. 
American Cancer Society. https://cancerstatisticscenter.cancer.org, accessed on May 19, 2021. 
Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute's patient-
reported outcomes version of the common terminology criteria for adverse events (PRO-
CTCAE). J Natl Cancer Inst. 2014;106(9);dju244. 
Berkenblit A, Cannistra SA, Advances in the management of epithelial ovarian cancer. J Reprod 
Med, 2005;50(6):426-38. 
Bristow RE and Chi DS. Platinum-based neoadjuvant chemotherapy and interval surgical 
cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol, 
2006;103(3):1070-6. 
Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal 
cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. 
J Clin Oncol, 2002;20(5):1248-59. 
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 
Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy scale: 
development and validation of the general measure. J Clin Oncol. 1993;11(3):570-579. 
Chang SJ, Hodeib M, Chang J, Bristow RE. Survival impact of complete cytoreduction to no 
gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecol Oncol, 
2013;130(3):493-8. 
EORTC. http://groups.eortc.be/qol/eortc-qlq-c30 
Global Cancer Observatory. Global Cancer Observatory (iarc.fr), accessed on May 19, 2021. 
Hoskins WJ, Bundy BN, Thigpen JT, Omura GA. The influence of cytoreductive surgery on 
recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a 
Gynecologic Oncology Group study. Gynecol Oncol. 1992;47(2):159-66. 
Hoskins WJ, McGuire WP, Brady MF, et al. The effect of diameter of largest residual disease on 
survival after primary cytoreductive surgery in patients with suboptimal residual epithelial 
ovarian carcinoma. Am J Obstet Gynecol. 1994;170(4):974-9; discussion 979-80. 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of Acetaminophen-Adduct in Adults 
with Acetaminophen Overdose and Acute Liver Failure. Drug Metab Dispos. 2009; 37:1779-84. 
Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly 
diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-
inferiority trial. Lancet, 2015;386(9990):249-57. 


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Kristeleit R. Rucaparib versus chemotherapy in patients with advanced, relapsed ovarian cancer 
and a deleterious BRCA mutation: Efficacy and safety from ARIEL4, a randomized phase III 
study. Society of Gynecologic Oncology Virtual Annual Meeting on Women’s Cancer. 
2021;Abstract ID: 11479. 
Le Gal F, Gordien E, Affolabi D, et al. Quantification of Hepatitis Delta Virus RNA in Serum by 
Consensus Real-Time PCR Indicates Different Patterns of Virological Response to Interferon 
Therapy in Chronically Infected Patients. J Clin Microbiol. 2005;43(5):2363-9. 
Niraparib Investigator’s Brochure. GSK document No. RPS-CLIN-053021 (or most current 
available version). 
Penson RT, Villalobos Valencia R, Cibula D, et al. Olaparib versus nonplatinum chemotherapy 
in Patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation 
(SOLO3): a Randomized Phase III trial. J Clin Oncol. 2020;38(11):1164-74. 
Rustin GJS, Quinn M, Thigpen T, et al. RE: New guidelines to evaluate the response to treatment 
in solid tumors (ovarian cancer). J Natl Cancer Inst. 2004;96(6):487-8. 
van der Burg ME, van Lent M, Buyse M, et al. The effect of debulking surgery after induction 
chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer 
Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl 
J Med, 1995;332(10):629-34. 
Vergote I, Tropé CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage 
IIIC or IV ovarian cancer. N Engl J Med, 2010;363(10):943-53. 
Vergote I, Coens C, Nankivell M, et al. Neoadjuvant chemotherapy versus debulking surgery in 
advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 
55971 and CHORUS trials. Lancet Oncol. 2018;19(12):1680-7. 
 


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APPENDIX A. GENETICS 
Use/analysis of DNA: 
• Genetic variation may impact a participant’s response to study treatment, 
susceptibility, severity, and progression of disease. Variable response to study 
treatment may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and Institutional Review Board/Independent Ethics Committee 
allow, a blood sample will be collected for DNA analysis. 
• DNA samples will be used for research related to niraparib or ovarian cancer and 
related diseases. They may also be used to develop tests/assays (including diagnostic 
tests) related to niraparib (monotherapy or combination therapy, or study treatments 
of this drug class) and ovarian cancer (or related cancer indications). Genetic research 
may consist of the analysis of one or more candidate genes or the analysis of genetic 
markers throughout the genome (as appropriate). 
• Additional analyses of DNA samples may be conducted if it is hypothesized that this 
may help further understand the clinical data.  
• The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to niraparib (monotherapy or combination therapy) or study 
treatments of this class. The results of genetic analyses may be reported in the clinical 
study report or in a separate study summary. 
• The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• The samples will be retained while research on niraparib (or study treatments of this 
class) continues but no longer than 15 years after the last participant’s last visit or 
other period as per local requirements. 
 


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APPENDIX B. LIVER SAFETY: REQUIRED ACTIONS AND FOLLOW-
UP ASSESSMENTS AND STUDY INTERVENTION 
RESTART/RECHALLENGE GUIDELINES  
Table 7: 
Liver Chemistry Stopping Criteria and Required Follow-up Assessments 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT Absolute 
Both ALT 5× ULN and 2× baseline value 
ALT Increase 
Both ALT 3× ULN and ≥1.5× baseline value that persists for 4 weeks 
Bilirubin1, 2 
ALT 3× ULN and total bilirubin 2× ULN (>35% direct bilirubin)  
INR2  
ALT 3× ULN and INR >1.5 
Cannot Monitor 
Both ALT 3× ULN and ≥1.5× baseline value that cannot be monitored for 
4 weeks 
Symptomatic3 
 
Both ALT 3× ULN and ≥1.5× baseline value associated with symptoms (new 
or worsening) believed to be related to liver injury or hypersensitivity 
Required Actions, Monitoring, and Follow-up Assessments 
Actions 
Follow-up Assessments 
• Immediately discontinue study intervention 
• Report the event to GSK within 24 hours 
• Complete the liver event eCRF and complete 
SAE data collection tool if the event also 
meets the criteria for an SAE2 
• Perform liver event follow-up assessments as 
described in the Follow-up Assessments 
column 
• Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline 
(see MONITORING) 
MONITORING: 
If ALT 3× ULN AND total bilirubin 2× ULN 
or INR >1.5:  
• 
Repeat liver chemistries (include ALT, AST, 
ALP, total bilirubin, and INR) and perform 
• Viral hepatitis serology4 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward 
trend 
• Blood sample for PK analysis, obtained 
within 144 hours after last dose5 
• Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH), gamma 
glutamyl transferase (GGT), glutamate 
dehydrogenase (GLDH), and serum albumin 
• Fractionate bilirubin, if total bilirubin 
2× ULN 
• Obtain CBC with differential to assess 
eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury or 
hypersensitivity on the liver event eCRF 
• Record use of concomitant medications on 
the concomitant medications report form, 
including acetaminophen, herbal remedies, 


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liver event follow-up assessments within 
24 hours 
• Monitor participants twice weekly until liver 
chemistries resolve, stabilize, or return to 
within baseline 
• A specialist or hepatology consultation is 
recommended 
For all other criteria (total bilirubin <2× ULN 
and INR ≤1.5):  
• Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin, and INR) 
and perform liver event follow-up assessments 
within 24 to 72 hours 
• Monitor participants weekly until liver 
chemistries resolve, stabilize, or return to 
within baseline 
RESTART/RECHALLENGE 
• Restart/rechallenge is allowed per protocol, 
but do not resume study intervention unless 
GSK approval is granted 
• If restart/rechallenge is not granted, 
permanently discontinue study intervention 
and continue participant in the study for any 
protocol-specified follow-up assessments. 
 
recreational drugs, and other over the counter 
medications 
• Record alcohol use on the liver event alcohol 
intake form 
If ALT 3× ULN AND total bilirubin 
2× ULN or INR >1.5, obtain the following in 
addition to the assessments listed above: 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total 
immunoglobulin G (IgG or gamma globulins) 
• Serum acetaminophen adduct assay should be 
conducted (where available) to assess 
potential acetaminophen contribution to liver 
injury unless acetaminophen use is very 
unlikely in the preceding week. (e.g., where 
the participant has been resident in the 
clinical unit throughout) [James, 2009] 
• Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography to 
evaluate liver disease); complete liver 
imaging form 
• Liver biopsy may be considered and 
discussed with local specialist if available, 
for instance: 
o In participants when serology raises the 
possibility of autoimmune hepatitis 
(AIH) 
o In participants when suspected DILI 
progresses or fails to resolve on 
withdrawal of study intervention 
o In participants with acute or chronic 
atypical presentation 
• If liver biopsy conducted, complete liver 
biopsy form. 
Abbreviations: ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
CBC=complete blood count; DILI=drug-induced liver injury; eCRF=electronic case report form; 
GSK=GlaxoSmithKline; IgG=immunoglobulin G; IgM=immunoglobulin M; INR=international normalized ratio; 
PCR=polymerase chain reaction; PK=pharmacokinetics; SAE=serious adverse event; SRM=Study Reference 
Manual; ULN=upper limit of normal. 
1 Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3× ULN and total bilirubin 
2× ULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2 All events of ALT 3× ULN and total bilirubin 2× ULN (>35% direct bilirubin) or ALT 3× ULN and 
INR >1.5, which may indicate severe liver injury (possible “Hy’s Law”), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving 
anticoagulants. 


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3 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
4 Includes Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis 
C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
obtain heterophile antibody or monospot testing); and Hepatitis E IgM antibody. In those with underlying 
chronic hepatitis B at study entry (identified by positive hepatitis B surface antigen) quantitative hepatitis B 
DNA and hepatitis delta antibody. If hepatitis delta antibody assay cannot be performed, it can be replaced with a 
PCR of hepatitis D RNA virus (where needed) [Le Gal, 2005]. 
5 Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM. 
 
Table 8: 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued 
Study Intervention 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study Intervention 
Liver Monitoring Event 
Criteria 
Actions 
ALT ≥3× ULN and ≥1.5× baseline value and 
not meeting any stopping criteria, without 
symptoms believed to be related to liver 
injury or hypersensitivity, and who can be 
monitored weekly for 4 weeks 
• 
Notify the GSK Medical Monitor within 
24 hours of learning of the abnormality to 
discuss participant safety  
• 
Participant can continue study intervention 
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
total bilirubin, and INR) until they resolve, 
stabilize, or return to within baseline  
• 
If at any time participant meets the liver 
chemistry stopping criteria, proceed as 
described above 
• 
If, after 4 weeks of monitoring, ALT 
<3× ULN and <1.5× baseline value, and 
bilirubin <2× ULN and INR ≤1.5, monitor 
participants twice monthly until liver 
chemistries resolve or return to within 
baseline 
Abbreviations: ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
GSK=GlaxoSmithKline; INR=international normalized ratio; ULN=upper limit of normal. 
 
 
 


Signature Page for  213357 TMF-16429478 v2.0
Signature Page for TMF-16429478 v2.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 31-Oct-2023 14:22:25 GMT+0000
PPD

SAP_001.pdf: 
Statistical Analysis Plan
Study ID: 213357-Cohort-C
Study Official Title: A Phase 1B/2 Multicohort Umbrella Study to Evaluate the 
Safety and Efficacy of Novel Treatments and/or Combinations of Treatments in 
Participants with Ovarian Cancer (OPAL) (PR-3000-02-005/213357)
Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter Study 
Comparing Niraparib Versus Platinum-Taxane Doublet Chemotherapy as 
Neoadjuvant Treatment in Participants with Homologous Recombination-
deficient Stage III/IV Ovarian Cancer
NCT ID: NCT06964165
Date of Document: 17 July 2023
Note:  213357 is a master protocol, registered under the identifier 
NCT03574779. It includes independent sub-studies, Cohort A (NCT05751629) 
and Cohort C (NCT06964165), each separately registered on ClinicalTrials.Gov. 
On Page 1 of the Cohort C-specific SAP, the master protocol study record NCT 
ID (NCT03574779) is referenced, as the development of this SAP preceded the 
availability of the cohort specific NCT ID. 


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
213357 Cohort C 
1 
Information Type: 
Statistical Analysis Plan (SAP) 
TITLE PAGE 
Protocol Title: 
A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and 
Efficacy of Novel Treatments and/or Combinations of Treatments in 
Participants with Ovarian Cancer (OPAL) (PR-3000-02-005/213357) 
Cohort C: Open-label Phase 2, Randomized, Controlled Multicenter 
Study Comparing Niraparib Versus Platinum-Taxane Doublet 
Chemotherapy as Neoadjuvant Treatment in Participants with 
Homologous Recombination-deficient Stage III/IV Ovarian Cancer 
Study Number: 
213357 (formerly 3000-02-005) 
Compound Number: 
Niraparib (GSK3985771) 
Abbreviated Title: 
N/A 
Sponsor Name: GlaxoSmithKline Research & Development Limited 
Regulatory Agency Identifier Number(s) 
Registry 
ID 
ClinicalTrials.gov 
NCT03574779 
SAP Author(s): 
Author 
Date 
Lead 
26-Jun-2023
PPD


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
213357 Cohort C 
2  
 
SAP Team Review Confirmations (E-mail Confirmation): 
Reviewer 
Date 
22-Jun-2023 
 Dev Biostats Prog Onc 
 
 
Principal Programmer, Dev Biostats Prog Onc 
26-Jun-2023 
26-Jun-2023 
 Oncology Clinical Development 
 
26-Jun-2023 
Clinical Scientist, Oncology Clinical Development   
 
26-Jun-2023 
Clinical Scientist, Oncology Clinical Development  
 
26-Jun-2023 
 CPMS 
 
26-Jun-2023 
 Pharma Safety 
 
26-Jun-2023 
 Oncology, Patient Centered Outcomes 
 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
213357 Cohort C 
3  
SAP Biostatistics Line Approval (Pharma TMF eSignature):  
Approver 
 Head of SL Statistics 
 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved.  Unauthorized 
copying or use of this information is prohibited. 
PPD


CONFIDENTIAL 
 
 
213357 Cohort C 
4  
TABLE OF CONTENTS 
1. 
INTRODUCTION ............................................................................................... 7 
1.1. 
Objectives, Estimands and Endpoints ........................................................... 7 
1.1.1. 
Objective and Endpoints ................................................................ 7 
1.2. 
Study Design .............................................................................................. 11 
2. 
STATISTICAL HYPOTHESES ........................................................................ 14 
2.1. 
Multiplicity Adjustment ................................................................................ 15 
3. 
ANALYSIS SETS ............................................................................................ 16 
4. 
STATISTICAL ANALYSES .............................................................................. 16 
4.1. 
General Considerations .............................................................................. 16 
4.1.1. 
General Methodology .................................................................. 16 
4.1.2. 
Baseline Definition ....................................................................... 17 
4.1.3. 
Study Day and Reference Date ................................................... 17 
4.1.4. 
Durations ..................................................................................... 18 
4.2. 
Primary Endpoint(s) Analyses ..................................................................... 18 
4.2.1. 
Definition of endpoint ................................................................... 18 
4.2.2. 
Main analytical approach ............................................................. 20 
4.2.3. 
Subgroup Analyses ...................................................................... 20 
4.3. 
Secondary Endpoint(s) Analyses ................................................................ 20 
4.3.1. 
Incidence of CA-125 progression per GCIG criteria ..................... 21 
4.3.2. 
Progression Free Survival (PFS) ................................................. 21 
4.3.3. 
Overall Survival (OS) ................................................................... 23 
4.3.4. 
Time to First Subsequent Therapy (TFST) ................................... 23 
4.3.5. 
Patient-reported Outcomes .......................................................... 24 
4.4. 
Exploratory Analyses .................................................................................. 30 
4.4.1. 
Surgical and Postsurgical Outcomes ........................................... 30 
4.4.2. 
Pathological Complete Response (pCR) ...................................... 31 
4.4.3. 
Healthcare Resource Utilization ................................................... 31 
4.4.4. 
Patient-reported Outcomes .......................................................... 31 
4.4.5. 
Biomarker Analyses ..................................................................... 32 
4.4.6. 
Pharmacokinetic and Pharmacodynamic Analyses ...................... 33 
4.5. 
Safety Analyses .......................................................................................... 34 
4.5.1. 
Extent of Exposure ...................................................................... 34 
4.5.2. 
Adverse Events............................................................................ 37 
4.5.3. 
Additional Safety Assessments .................................................... 39 
4.5.4. 
Data Review Committee (DRC) Analyses .................................... 41 
4.6. 
Interim Analyses ......................................................................................... 42 
5. 
SAMPLE SIZE DETERMINATION................................................................... 44 
6. 
SUPPORTING DOCUMENTATION ................................................................ 45 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 45 
6.1.1. 
Participant Disposition ................................................................. 45 
6.1.2. 
Demographic and Baseline Characteristics .................................. 45 
6.1.3. 
Protocol Deviations ...................................................................... 46 
6.1.4. 
Prior and Concomitant Medications ............................................. 46 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic .................. 47 
6.2. 
Appendix 2 Data Derivations Rule .............................................................. 48 


CONFIDENTIAL 
 
 
213357 Cohort C 
5  
6.2.1. 
Criteria for Potential Clinical Importance ...................................... 48 
6.2.2. 
Study Period ................................................................................ 48 
6.2.3. 
Assessment Windows .................................................................. 49 
6.2.4. 
Multiple measurements at One Analysis Time Point .................... 51 
6.2.5. 
Handling of Partial Dates ............................................................. 51 
6.2.6. 
Extended Time without a PFS Assessment ................................. 53 
6.3. 
Appendix 3 Population Pharmacokinetic Analysis Methodology .................. 56 
6.4. 
Changes from Protocol Defined Analyses ................................................... 57 
6.5. 
List of Abbreviations ................................................................................... 58 
7. 
REFERENCES ................................................................................................ 62 
 
 
 
 
LIST OF TABLES 
 
Table 1 
RECIST v1.1 Visit Response for Participants with Measurable Disease 
(i.e., Target Disease) ......................................................................................................... 19 
Table 2  
Censoring rules for PFS analysis ................................................................... 21 
Table 3 
PRO-CTCAE Levels ..................................................................................... 25 
Table 4 
Scoring the QLQ-C30 version 3.0 ................................................................. 26 
Table 5 
Scoring the QLQ-OV28 ................................................................................. 29 
Table 6 
Criteria for CRS assignment .......................................................................... 31 
Table 7 
Adverse Events of Special Interest ................................................................ 39 
Table 8 
Neoadjuvant period: PRO-CTCAE/WPAI:GH/FACT-GP5 windowing ...... 49 
Table 9 
Neoadjuvant period: EORTC-IL136/137 windowing ................................... 50 
Table 10 
Maintenance period: FACT-GP5/EORTC-IL136/137 windowing ............... 50 
Table 11 
Tumor Assessment Windowing ..................................................................... 54 
 
 


CONFIDENTIAL 
 
 
213357 Cohort C 
6  
Version history 
SAP 
Version 
Approval Date 
Protocol 
Version (Date) 
on which SAP is 
Based 
Change 
Rationale 
1.0 
28 Mar 2022 
Version 1.0 (15-
Oct-2021) 
Not 
Applicable 
Original 
version 
2.0 
      17 Jul 2023 
Version 1.0 (15-
Oct-2021) 
Multiple 
Multiple 
analyses 
clarified and 
re-reviewed 
by team 
 


CONFIDENTIAL 
 
 
213357 Cohort C 
7  
1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the Clinical 
Study Report (CSR) for Study 213357 (OPAL) Cohort C, the planned analyses to support 
DRC reviews (as per DRC charter) and some supplementary analyses that may not form 
part of the CSR.  
1.1. 
Objectives, Estimands and Endpoints 
1.1.1. 
Objective and Endpoints  
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of neoadjuvant 
niraparib compared with neoadjuvant 
platinum-taxane doublet chemotherapy after 1 
induction cycle of carboplatin-paclitaxel per 
Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 in participants with confirmed 
homologous recombination-deficient (HRd) 
Stage III to IV ovarian cancer (OC) 
Pre-interval debulking surgery (pre-IDS) 
Overall Response Rate (ORR), defined as the 
percentage of participants with unconfirmed 
complete response (CR) or partial response 
(PR) on study intervention pre-IDS as 
assessed per RECIST v1.1 by the investigator  
Secondary 
To evaluate clinical benefit by Gynecological 
Cancer InterGroup (GCIG) cancer antigen 125 
(CA-125) response criteria 
Incidence of CA-125 progression per GCIG 
CA-125 response criteria 
To evaluate clinical benefit as measured by 
progression-free survival (PFS) per RECIST 
v1.1 by investigator assessment 
PFS, defined as the time from the date of 
treatment randomization to the date of first 
documentation of progression of disease 
(PD) per RECIST v1.1 or death by any cause, 
whichever occurs first, as determined by the 
investigator 
PFS12 (PFS18, PFS24), defined as the 
proportion of participants without 
documented PD per RECIST v1.1 or death 
within 12 (18, 24) months after the date of 
treatment randomization 
To evaluate clinical benefit as measured by 
overall survival (OS) 
OS defined as the time from the date of 
treatment randomization to the date of death 
by any cause 
To evaluate clinical benefit as measured by 
time to first subsequent treatment (TFST) 
TFST defined as the time from the date of 
treatment randomization to the date of first 
subsequent anticancer therapy or death 


CONFIDENTIAL 
 
 
213357 Cohort C 
8  
Objectives 
Endpoints 
To evaluate the safety and tolerability of 
neoadjuvant niraparib and neoadjuvant 
platinum-taxane doublet chemotherapy 
Frequency and severity of treatment-
emergent adverse events (TEAEs), serious 
adverse events (SAEs), adverse events of 
special interest (AESIs), and dose 
modification (i.e., interruptions and 
discontinuations) 
To evaluate participants’ reported overall 
tolerability toward treatment, overall health 
status, OC-specific health-related quality of 
life (HRQoL) and symptoms 
Arranged in order of clinical importance as 
follows 
To determine overall tolerability toward 
treatment: change over time in frequency and 
severity of the items on the Patient Reported 
Outcomes Common Terminology Criteria for 
Adverse Events (PRO-CTCAE) during 
neoadjuvant treatment 
To determine symptom tolerability: change 
from baseline in Functional Assessment of 
Cancer Therapy-Item GP5 [FACT-GP5] 
during neoadjuvant treatment 
To determine overall health status: change 
from baseline in European Organisation for 
Research and Treatment of Cancer Quality of 
Life Questionnaire-Core 30 (EORTC QLQ-
C30) items (European Organisation for 
Research and Treatment of Cancer Item 
Library 136 [EORTC IL136]) pre-IDS 
To determine OC-specific HRQoL and 
symptoms: change from baseline in European 
Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire for 
Ovarian Cancer (EORTC QLQ-OV28) 
gastrointestinal items (European 
Organisation for Research and Treatment of 
Cancer Item Library 137 [EORTC IL137]) 
pre-IDS 
Exploratory 
CCI


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213357 Cohort C 
9  
Objectives 
Endpoints 
CCI


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213357 Cohort C 
10  
Objectives 
Endpoints 
 
CCI


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213357 Cohort C 
11  
1.2. 
Study Design 
Overview of Study Design and Key Features 
Note: Duration of study periods are as follows: 
Prescreening: 5 weeks 
Screening: 1 week 
Neoadjuvant treatment: up to 12 weeks 
IDS: up to 6 weeks 
Adjuvant platinum-taxane chemotherapy and optional bevacizumab or bevacizumab biosimilar: 6 to 9 weeks* 
Niraparib maintenance: up to 36 months. Optional bevacizumab or bevacizumab biosimilar may be administered for up to 22 cycles 
(including adjuvant chemotherapy period). 
*Note: Cycle 6 (C6) is optional. If a site chooses to administer Cycle 6 of adjuvant chemotherapy, all participants treated at this study 
site must be offered C6 of adjuvant chemotherapy, regardless of treatment received during the neoadjuvant treatment period. Any site 
CCI


CONFIDENTIAL 
 
 
 
 
 
213357 Cohort C 
12  
Overview of Study Design and Key Features 
that chooses to provide optional bevacizumab or bevacizumab biosimilar as SoC to eligible high-risk participants must offer it to all 
eligible high-risk participants treated at that site, regardless of enrollment arm. 
Abbreviations: BRCA=breast cancer gene; C=cycle; carbo=carboplatin; chemo=chemotherapy; CR=complete response; Cx=cycle 
number; endpt=endpoint; EU=European Union; HR=homologous recombination; HRd=homologous recombination-deficient; 
ICF=informed consent form; IDS=interval debulking surgery; mPFS=median progression-free survival; NVRD=no visual residual 
disease; ORR=overall response rate; OS=overall survival; pathCR=pathological complete response; PD=pharmacodynamics; 
PFS=progression-free survival; PK=pharmacokinetics; PRO=participant-reported outcome; QD=once daily; R=randomization; 
SoC=standard-of-care; TFST=time to first subsequent treatment; xxm=xx months. 


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Design 
Features 
This is a global, multicenter, randomized, open-label, Phase 2 cohort in participants 
with newly diagnosed, Stage III or IV, high-grade non-mucinous epithelial ovarian, 
fallopian tube, or peritoneal cancer (collectively referred to as “ovarian cancer” or OC) 
who are eligible for neoadjuvant platinum-taxane doublet chemotherapy followed by 
IDS. This study will enroll participants with HRd OC as determined by the central 
tumor homologous recombination deficiency (HRD) testing using a fully validated 
assay. All prescreened participants would have received, prior to enrollment, 1 cycle 
of standard-of-care (SoC) chemotherapy (i.e., carboplatin+paclitaxel) to allow 
sufficient time for receipt and review of the biomarker test results. 
After confirmation that the tumor is HRd, participants will be randomized 1:1 to three 
21-day cycles of platinum-taxane doublet chemotherapy (Arm 1); (Arm 1 Optional: 
carboplatin-paclitaxel, unless platinum-taxane not tolerated by the participant) or 
neoadjuvant niraparib (Arm 2). After 3 cycles of neoadjuvant treatment, the 
participants will undergo IDS. After IDS, all participants will receive up to three 21-
day cycles of adjuvant chemotherapy treatment: platinum/taxane doublet 
chemotherapy (and optional bevacizumab or bevacizumab biosimilar per SoC for 
participants deemed high-risk as judged by the investigator), with the last cycle of 
chemotherapy (C6) being optional. After adjuvant chemotherapy treatment, all 
participants will receive niraparib maintenance treatment (with optional bevacizumab 
or bevacizumab biosimilar as SoC for up to 22 cycles including adjuvant 
chemotherapy period) for up to 36 months or until AE, PD per RECIST v1.1, risk to 
participant or participant’s severe noncompliance with protocol as judged by the 
investigator or sponsor, participant’s request, pregnancy, or end of study. 
The study duration for each participant will be up to approximately 43 months. The 
study will be divided in 5 periods: overall screening (prescreening and screening), 
neoadjuvant treatment, IDS, adjuvant chemotherapy treatment, and niraparib 
maintenance (up to 36 months). 
Study 
intervention 
Investigational product, dosage, and mode of administration: 
Niraparib: 
Niraparib will be supplied as 
. 
For participants randomized to niraparib neoadjuvant treatment, the starting dose will 
be as follows: 
• 
200 mg 
) for participants with an actual body weight <77 kg 
OR screening platelet count <150,000/µL on C1D1 
• 
300 mg 
) for participants with an actual body weight ≥77 
kg AND screening platelet count ≥150,000/µL on C1D1 
For participants receiving niraparib maintenance treatment, independent of the 
treatment they received during the neoadjuvant treatment period, the starting dose will 
be as follows: 
• 
200 mg 
 for participants with an actual body weight <77 kg 
OR platelet count <150,000/µL on C1D1 of the niraparib maintenance treatment 
period (M1D1) 
• 
300 mg 
) for participants with an actual body weight ≥77 
kg AND platelet count ≥150,000/µL on M1D1 
Duration of treatment: 
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Neoadjuvant therapy (niraparib or platinum-taxane doublet chemotherapy) will consist 
of three 21-day cycles. 
Adjuvant therapy (platinum-taxane doublet chemotherapy with optional bevacizumab 
or bevacizumab biosimilar for participants deemed high-risk) will consist of up to 
three 21-day cycles, with the last cycle (C6) for all therapies being optional. Any site 
choosing to give the last cycle and/or bevacizumab or bevacizumab biosimilar must 
offer the final cycle (C6) to all participants treated at that site regardless of the arm the 
participant was enrolled onto. 
Maintenance treatment with niraparib (with optional bevacizumab or bevacizumab 
biosimilar for participants deemed high-risk up to a total of 22 cycles including 
adjuvant chemotherapy period) will continue for up to 36 months. 
Participants will continue to receive their assigned treatment until radiographic PD is 
documented per RECIST v1.1, AE, risk to participant or participant’s severe 
noncompliance with protocol as judged by the investigator or sponsor, participant’s 
request, pregnancy, or end of study. 
Reference therapy, dosage, and mode of administration: 
Carboplatin-paclitaxel: 
Carboplatin will be infused intravenously (IV) over 60 minutes at the prescribed dose 
of area under the concentration versus time curve of 5 to 6 mg/mL•min on Day 1 of 
every 21-day cycle. Paclitaxel will be administered in a similar fashion over 180 
minutes at the prescribed dose of 175 mg/m2 on Day 1 of every 21-day cycle. 
Bevacizumab or bevacizumab biosimilar (optional): 
Bevacizumab or bevacizumab biosimilar 7.5 mg/kg or 15 mg/kg will be infused IV on 
Day 1 of each 21-day cycle. Bevacizumab or bevacizumab biosimilar may be 
administered for up to 22 cycles during the adjuvant and maintenance phase. 
Study 
intervention 
assignment 
 
 
  
Randomization will be stratified based on BRCA mutational status (BRCA1/2mut vs 
BRCA1/2wt).  
Interim 
Analysis 
 
2. 
STATISTICAL HYPOTHESES  
The primary objective of the study is to estimate the treatment effect in pre-IDS ORR. No formal 
hypothesis testing will be conducted. The difference in pre-IDS ORR between treatment arms 
and its 80% confidence interval will be calculated as described in the primary endpoint analysis 
section.  
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The primary analysis will be performed after all pre-IDS scans have been evaluated (about 6 
months after last patient first visit). The following endpoints will not be analysed at this point: 
PFS, OS, TFST if their maturity is low (<30%), 
 
 
   
 
 
2.1. 
Multiplicity Adjustment 
Not Applicable.  
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3. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened 
All participants who signed the main ICF.  
Study population 
Screen Failures 
Intent-to-treat 
(ITT) 
All randomized participants whether or not randomized 
treatment was administered. 
Study Population 
Efficacy 
PRO 
Safety 
All randomised participants who receive at least one dose of 
study treatment.  
Safety 
Pre-IDS Response 
Evaluable  
All participants in the safety analysis set with measurable 
disease at baseline, excluding participants who received 3 
cycles of neoadjuvant treatment whose pre-IDS scan is 
outside the –7 days window from C3D21. 
Efficacy (pre-IDS 
ORR) 
Per Protocol (PP)  
All randomised participants who do not have important 
protocol deviations.  
 
Efficacy  
Pharmacokinetic 
(PK) 
All participants in the safety analysis set from whom at least 
one post-dose PK sample has been obtained and analysed.  
 
PK 
 
Participants in all analysis sets will be analysed according to the planned study treatment as there 
is no distinction between planned and actual study treatment in this study (planned maps to 
actual). 
 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
General Methodology 
The ITT analysis set will be used for all study population and efficacy analyses unless otherwise 
specified (i.e., screening status will be based on the screened population, exposure will be based 
on the safety population, pre-IDS ORR will be based on the pre-IDS response evaluable analysis 
set). The Safety Analysis Set will be used for all safety analyses unless otherwise specified.  
For analysis purposes, the run-in chemotherapy treatment is not considered study treatment. 
Study treatment is any treatment received per the study protocol after randomisation.   
 


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Stratified analyses will control for the randomisation stratification factors (BRCA mutational 
status). For such analyses and reporting of stratification factors, the RTSM strata levels will be 
used for all participants randomised unless otherwise specified. In the case of wrong 
stratification assigned at the time of randomisation, the analyses for the wrongly stratified 
participants will be performed based on the actual data received from Myriad, not the assigned 
stratum at randomisation. If a stratum contains < 10 participants or < 10 events (for TTE 
endpoints) in total at the time of analysis, then the strata will be pooled and only an unstratified 
analysis will be conducted. 
Unless otherwise specified, continuous data will be summarized using descriptive statistics: n, 
mean, standard deviation (std), median, minimum and maximum. Categorical data will be 
summarized as the number and percentage of participants in each category. 
Confidence intervals will use 95% confidence level unless otherwise specified.  
Summaries and listings will include all data collected per the SoA, unless otherwise specified.  
Data will be listed and summarized according to the GSK reporting standards, where applicable.  
4.1.2. 
Baseline Definition 
For all endpoints, unless otherwise specified, the baseline value will be the latest assessment with 
a non-missing value prior to C1D1 (in neoadjuvant period), including those from unscheduled 
visits. If time (pre-dose/post-dose information) is not collected, C1D1 assessments are assumed 
to be taken prior to first dose and used as baseline. For participants who did not receive study 
intervention during the study, baseline will be defined as the latest, non-missing collected value. 
If there are multiple measurements defined as baseline measurements, the mean of them will be 
used.  
For tumour assessments, the RECIST v1.1 scan performed after the run-in cycle of carboplatin-
paclitaxel is the baseline scan (per SoA scans prior to the run-in cycle are not expected). 
Unless otherwise stated, if baseline data are missing no derivation will be performed and 
baseline will be set to missing.  
4.1.3. 
Study Day and Reference Date 
The efficacy reference date is the date of randomization and will be used to calculate study day 
for efficacy measures and baseline characteristics, as well as efficacy durations.  
The safety reference date is the study intervention start date will be used to calculate study day 
for safety measures.  
Calculated as the number of days from First Dose Date (C1D1): 
• 
Event Date = Missing              → Study Day = Missing  
• 
Event Date < First Dose Date → Study Day = Event Date – First Dose Date 


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• 
Event Date ≥ First Dose Date → Study Day = Event Date – (First Dose Date) + 1  
Note: The earlier date of first dosing date from each treatment will be considered as first dose 
date for the participant. 
4.1.4. 
Durations  
Unless otherwise specified, time-to-event endpoints will be calculated in months as: (event or 
censoring date – randomization date + 1)/30.4375. 
Durations (e.g., the duration of an AE, etc.) are calculated as the stop date - the start date + 1, 
unless otherwise specified.  
For converting all durations (in days) to weeks, months or years use the following: 
• 
To report in months, divide the number of days by 30.4375  
• 
To report in weeks, divide the number of days by 7  
• 
To report in years, divide the number of days by 365.25.  
 
These algorithms return decimal numbers and ignore the actual numbers of days in the months or 
years between start date and stop date. The “year” used in these algorithms is 365.25 days long, 
and the “month” is one twelfth of that year. 
 
4.2. 
Primary Endpoint(s) Analyses 
4.2.1. 
Definition of endpoint 
Pre-IDS ORR is defined as the percentage of participants in the analysis set with unconfirmed 
CR or PR prior to IDS as their best overall response (BOR), evaluated using RECIST v1.1 by the 
investigator.  
Pre-IDS BOR definition per RECIST 1.1 
Pre-IDS BOR is the best response recorded from the start of study treatment administration to 
the date of IDS or first documented PD or initiation of follow-up anticancer therapy (includes 
drug therapy as captured in the follow up anticancer therapy page, e.g., platinum-taxane doublet 
after neoadjuvant treatment, surgery as captured in the follow up surgery page), whichever is 
earlier (unconfirmed for the purposes of this study). The order from best to worst for the 
available responses is CR, PR, SD, PD, and NE, NA (not available/missing). 
To be assigned a status of SD as BOR, the minimum time for SD must be met, i.e., follow-up 
disease assessment must have met the SD criteria at least once after the first dose at a minimum 
interval of 56 days after randomisation. 


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If the minimum time for SD is not met, BOR will depend on the subsequent assessments. For 
example, if an assessment of PD follows the assessment of SD and SD does not meet the 
minimum time requirement, the best response will be PD. Alternatively, participants lost to 
follow-up after an SD assessment not meeting the minimum time criterion will be considered 
NE. 
Participants in the analysis set with NE or NA as BOR will be assumed to be non-responders.  
Table 1 
RECIST v1.1 Visit Response for Participants with Measurable Disease 
(i.e., Target Disease) 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
CR/Non-CR/non-PD/NE 
No 
PR 
SD 
CR/Non-CR/non-PD/NE 
No 
SD 
PD 
Any 
Yes or no 
PD 
Any 
PDb 
Yes or no 
PD 
Any 
Any 
Yes 
PD 
NE 
Non-PD 
No 
NE 
CR 
NAc 
No 
CR 
PR 
NAc 
No 
PR 
SD 
NAc 
No 
SD 
Source: Eisenhauer, 2009.  
Abbreviations: CR = complete response; PD = progressive disease; PR = partial response; RECIST v1.1 = Response Evaluation 
Criteria in Solid Tumors version 1.1; SD = stable disease; NE=not evaluated. 
Note: Participants 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. 
a. 
See RECIST v1.1 publication for further details on what is evidence of a new lesion. 
b. 
In exceptional circumstances, unequivocal progression in nontarget lesions may be accepted as disease progression. 
c. 
No non-target lesions identified at Screening.  
 
Pre-IDS maximum percent change from baseline in tumour size  
The pre-IDS maximum percent change from baseline in tumour size will also be derived. This is 
defined as the maximum percent change in sum of diameters for all target lesions (SDL) from the 
baseline sum of diameters from the start of study treatment administration to the date of IDS or 
first documented PD or initiation of follow-up anticancer therapy (drug therapy, e.g., platinum-
taxane doublet after neoadjuvant treatment).  
The calculation will be based on the formula: 


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Maximum percent change from baseline in SDL (%) = (Smallest SDL during the on-treatment 
period / Baseline SDL - 1) x 100 
 
4.2.2. 
Main analytical approach 
Pre-IDS ORR will be analyzed in the pre-IDS response-evaluable analysis set. The pre-IDS ORR 
for each treatment arm will be estimated and its 95% CI calculated using the Clopper Pearson 
method. The number and percentage of participants with pre-IDS BOR of CR, PR, SD, PD, NE, 
NA will be summarised.  
The difference in pre-IDS ORR between the niraparib and the platinum-taxane doublet 
chemotherapy neoadjuvant treatments will be estimated and its 2-sided 80% CI calculated using 
the stratified (BRCA mutation stratification factor) Miettinen and Nurminen method [Miettinen, 
1985].  
Pre-IDS maximum percent change from baseline in tumour size 
Maximum percent change from baseline in tumour size (sum of diameter lesions – SDL) will be 
summarised (median, sd, min, max) by treatment arm. A waterfall plot showing maximum 
percent change from baseline in tumour size by participant will be produced for each treatment 
arm.  
Additionally, a spider plot showing the change in tumour size from baseline over time by 
participant will be produced for each treatment arm.  
 
4.2.2.1. 
Sensitivity analyses 
SA1: The difference in pre-IDS ORR between the two treatment arms will be estimated and its 
80% CI calculated using the Mantel-Haenszel test (BRCA mutation stratification factor).  
SA2: An unstratified analysis using the Miettinen and Nurminen method will be conducted.  
SA3: An analysis as described in Section 4.2.2. but based on the ITT population will be 
conducted.  
4.2.3. 
Subgroup Analyses 
The treatment effect will be presented by BRCA status if the sample size of the BRCA strata 
allows, i.e., if there are at least 20 participants in each stratum.  
4.3. 
Secondary Endpoint(s) Analyses 
Safety endpoint analyses are described in Section 4.5. 


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4.3.1. 
Incidence of CA-125 progression per GCIG criteria 
CA-125 progression will be derived programmatically based on GCIG CA-125 response criteria 
using the following rules: 
• Participants with elevated CA-125 pre-treatment and a reduction of CA-125 to within the 
normal range on study must show evidence of CA-125 ≥2× upper limit of normal (ULN) 
on 2 occasions at least 1 week apart 
• Participants with elevated CA-125 pre-treatment that never reduces to within the normal 
range on study must show evidence of CA-125 ≥2× the nadir value on 2 occasions at 
least 1 week apart 
• Participants with CA-125 in the normal range pre-treatment must show evidence of 
CA125 ≥2× ULN on study on 2 occasions at least 1 week apart 
 
Normal range for CA-125 is 0-35 units/mL 
Main Analysis 
The percentage of CA-125 progression per GCIG criteria for each treatment arm will be 
estimated and its 95% exact CI calculated using the Clopper Pearson method. The difference in 
CA-125 progression will be estimated and its 95% CI calculated using the stratified (BRCA 
mutation stratification factor) Miettinen and Nurminen method.  
4.3.2. 
Progression Free Survival (PFS) 
PFS is defined as the time from the date of randomisation to the date of first documented PD per 
RECIST 1.1 by investigator assessment, or death by any cause, whichever occurs first. 
The censoring rules for PFS at the time of analysis are summarised in Table 2.  
Table 2  
Censoring rules for PFS analysis 
Scenario 
Censoring Rule 
Outcome 
No baseline tumour assessment and no 
death* 
Date of randomisation 
Censored 
No adequate post-baseline tumour 
assessments and no death*  
Date of randomisation 
Censored 
No documented progression and no death  
Date of last adequate tumour 
assessment 
Censored 
Follow up anticancer therapy initiated 
without documented progression 
Date of last adequate tumour 
assessment prior to or on initiation of 
follow up anticancer therapy 
Censored 


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Documented progression or death after ≤ 1 
missed or inadequate assessment 
Date of documented progression or 
death, whichever occurs first. 
Event 
Documented progression or death after ≥ 2 
consecutive missed or inadequate 
assessments (see Section 6.2.6 for 
programmatic derivation) 
Date of last adequate tumour 
assessment prior to ≥ 2 consecutive 
missed or inadequate assessments 
Censored 
*If there is death with death date < date of the 2nd scheduled assessment then it contributes as an event, otherwise if death date 
is ≥ date of the 2nd scheduled assessment it does not  
Note: Adequate tumour assessment is defined as a tumour assessment result that is not NE or NA. 
Note: In case of missing baseline or post-baseline tumour assessments, deaths occurring within the <2 missed visit window from 
randomization will count as events  
Note: Follow-up anticancer therapy includes drug therapy as captured in the follow up anticancer therapy eCRF page and 
surgery as captured in the follow up surgery eCRF page. 
Note: If a documented progression and new anticancer therapy occur on the same day, assume the progression was 
documented first. The outcome is progression (event) and the event date is the date of the assessment of progression. 
 
Main Analysis 
The frequency (number and percentage) of participants with an event (PD or death) and 
participants censored will be presented by treatment arm, together with the reason for censoring. 
The corresponding listing will also be presented. Reasons for censoring are: 
• 
No documented PD or death at data cut-off (sub-reason will be reported) 
o 
Participant ongoing 
o 
Withdrawal of consent 
o 
Lost to follow-up 
• 
No baseline assessment 
• 
No adequate post-baseline assessment 
• 
Initiation of follow up anti-cancer therapy without documented progression 
• 
Documented PD after 2 or more missing or inadequate post-baseline assessments 
The PFS curve for each treatment arm will be estimated using the nonparametric Kaplan Meier 
(KM) product limit method. KM plots will be presented by treatment arm.  KM estimates for the 
median and the first and third quartiles, together with their 95% CIs calculated using the 
Brookmeyer-Crowley method [Brookmeyer, 1982] will be presented.  
The KM PFS rates at 12, 18 and 24 months and their 95% CIs will be presented by treatment 
arm. 


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The hazard ratio (HR) will be estimated, and its 95% CI calculated using a stratified (BRCA 
mutation stratification factor) Cox proportional hazards model with exact method for tie handling 
and randomized treatment as the single covariate.  
4.3.3. 
Overall Survival (OS) 
OS is defined as the time from the date of randomisation to the date of death due to any cause. 
Participants without documented death at the time of the analysis will be censored at the last date 
they were known to be alive. The last known alive date will be determined by the maximum 
collection/assessment date from among selected data domains within the clinical database. 
Specifically, for participants not known to have died, the date of last contact will be derived at 
the analysis cut-off date using the latest complete date among the following:  
• 
Participant assessment dates (blood sampling [laboratory, PK, biomarker], vital 
signs, ECGs, tumour assessments) 
• 
Start and end date of AEs 
• 
Start and end date of study treatment 
• 
Start date of follow up anti-cancer therapies administered after study treatment 
discontinuation (including surgery) 
• 
Date of contact on survival assessment page for current patient status = alive  
 
Main Analysis 
The OS curve for each treatment arm will be estimated using the nonparametric Kaplan Meier 
(KM) product limit method. KM plots will be presented by treatment arm.  KM estimates for the 
median and the first and third quartiles, together with their 95% CIs calculated using the 
Brookmeyer-Crowley [Brookmeyer, 1982] method will be presented. The KM OS rates at 12, 24 
and 36 months and their 95% CIs will be presented by treatment arm. 
The hazard ratio (HR) will be estimated, and its 95% CI calculated using a stratified (BRCA 
mutation stratification factor) Cox proportional hazards model with exact method for tie handling 
and randomized treatment as the single covariate.  
4.3.4. 
Time to First Subsequent Therapy (TFST)  
TFST is defined as the time from the date of randomization to the date of first subsequent 
anticancer therapy (includes drug therapy/surgery) or death. Participants who have not initiated 
first subsequent therapy or have not died at the time of the analysis will be censored at the last 
time known to not have received first subsequent anticancer therapy (includes surgery). For 
participants without EOT (i.e., study treatment not discontinued) this will be their last known 
alive date. For participants with EOT and no information on receipt of first subsequent therapy 
this equals the EOT date. For participants with EOT who have knowingly not received first 
subsequent therapy (i.e., for whom the response to “has the participant received any subsequent 
therapy/surgery?” is “No” for all relevant visits, this equals the last contact date as captured in 
the survival assessment eCRF form.   


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Main Analysis 
TFST will be analysed using the same methodology as PFS.  
 
4.3.5. 
Patient-reported Outcomes 
PRO-CTCAE and WPAI:GH are to be completed weekly during neoadjuvant chemotherapy and 
at EOT. FACT-GP5 is to be completed weekly during the neoadjuvant treatment period and at 
M1D1 and every 3 cycles for the first 13-14 months and every 3 months thereafter during 
niraparib maintenance treatment and at EOT. EORTC IL136 and EORTC IL137 are to be 
completed at every site visit during the neoadjuvant treatment period, at M1D1 and every 3 
cycles for the first 13-14 months and every 3 months thereafter during niraparib maintenance 
treatment and at EOT.  
The ITT analysis set will be used for all PRO analyses. For assessment windows for PRO 
endpoints refer to Appendix Section 6.3.   
4.3.5.1. 
Compliance  
The overall compliance and compliance by visit will be summarized for each PRO instrument. 
Compliance will be reported separately for the neoadjuvant and maintenance periods as part of 
the secondary and exploratory endpoints respectively. The reasons for missingness will also be 
reported.  
% Overall compliance = 100 x (number of participants with an evaluable baseline form and at 
least one evaluable post-baseline form/number of participants expected to complete the baseline 
form) 
% Compliance by visit = 100 x (number of participants with evaluable form/number of 
participants expected to have completed a form) 
 
Participants expected to have completed a PRO instrument at an analysis point exclude those 
missing by design, i.e., due to death, study discontinuation, translation not available. 
Evaluable forms are those with at least one non-missing scale or item, depending on the 
corresponding questionnaire’s scoring instructions as defined in the SAP.  
To characterise missingness, the number and percentage of participants who did not complete 
their PRO forms when expected to will be summarised by reason for missingness:  
• PRO assessment form not received – missed study visit 
• PRO assessment form not received – site staff unable to administer including device 
malfunction 
• PRO assessment form not received – participant too ill 


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• PRO assessment form not received – unable to accommodate disability or 
language/comprehension 
• PRO assessment form not received – other 
 
 
4.3.5.2. 
PRO-CTCAE  
A subset of items from the PRO-CTCAE Version 1.0 Item Library will be administered to 
participants (see Study Reference Manual for further details). These are: taste changes, nausea, 
vomiting, abdominal pain, bloating, constipation, diarrhea, memory, muscle pain, joint pain, 
fatigue, anxiety, neuropathy, sadness. 
The levels and related code values for PRO-CTCAE scoring are shown in Table 3.  
Table 3 
PRO-CTCAE Levels 
 
Levels and related code values 
Response scale 
0 
1 
2 
3 
4 
Frequency 
Never 
Rarely 
Occasionally 
Frequently 
Almost 
Constantly 
Severity 
None 
Mild 
Moderate 
Severe 
Very severe 
Interference 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
Present/Absence No 
Yes 
 
 
 
 
For each PRO-CTCAE item and attribute (frequency, severity, interference, presence/absence), 
the number and percentage of participants in each response category (0, 1, 2, 3, 4) will be 
summarised by scheduled visit and treatment arm.  
For each item and attribute, the change from baseline will be assessed by reporting the number 
and percentage of participants with any worsening in symptoms compared to their baseline score. 
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4.3.5.3. 
FACT-GP5 
FACT-GP5 is a single item from the FACT-G, which assesses how bothersome the side effects 
of treatment are for participants. 
 
The number and percentage of participants in each category of FACT-GP5 (0 = Not at all, 1 = A 
little bit, 2 = Somewhat, 3 = Quite a bit, 4 = Very much) will be reported by scheduled visit and 
treatment arm. In addition, the number and percentage of participants who moved ≤1, 2, and ≥3 
categories with respect to baseline will be reported by scheduled visit and treatment arm. The 
analyses will be restricted to the neoadjuvant period. 
 
4.3.5.4. 
EORTC IL136 (a Subset of Items from EORTC QLQ-C30) 
The EORTC QLQ-C30 is a 30-item questionnaire used to measure HRQoL in participants with 
cancer and is composed of both multi-item scales and single-item measures. It includes 5 
functional scales (physical functioning, role functioning, emotional functioning, cognitive 
functioning, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), 
6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial 
difficulties)Aaronson, 1993].  
A subset of 10 items from the EORTC QLQ-C30 (see Table 4) will be administered and will be 
referred to as the EORTC IL136, as shown in Table 4.  
 
Table 4 
Scoring the QLQ-C30 version 3.0 
Scale 
Abbr. 
Number 
of Items 
Item 
Range* 
Included in 
IL136 
EORTC QLQ C30 
Item Numbers 
Global Health Status/Qol 
 
 
 
 
 
Global Health Status/Qol 
QL 
2 
6 
29, 30 
29, 30 
Functional Scales 
 
 
 
 
 
Physical Functioning 
PF 
5 
3 
1 to 5 
1 to 5 
Social Functioning 
SF 
2 
3 
26, 27 
26, 27 
Symptom Scales/Items 
 
 
 
 
 
Dyspnea 
DY 
1 
3 
8 
8 
Abbreviations: Qol=quality of life;  
 
Questionnaire Scoring 
The multi-item EORTC-QLQC30 domains of interest represent full scales and therefore the 
usual questionnaire scoring methodology can be applied, as described below.   
Scale scores are calculated by averaging items within scales and transforming average scores 
linearly. The same is done for item scores, only the average equals the item’s score. All scales 


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and single-item measures range in score from 0 to 100. A high score for a functional scale 
represents a high/healthy level of functioning whereas a high score for a symptom scale/item 
represents a high level of symptomatology or problems. 
The principle for scoring these scales is the same in all cases and detailed below: 
1. Estimate the raw score by averaging of the items that contribute to the scale 
2. Use a linear transformation to standardize the raw score, so that scores range from 0 to 100  
For all scales, the RawScore (RS) is the mean of the component items: 
𝑅𝑎𝑤𝑆𝑐𝑜𝑟𝑒= 𝑅𝑆= 𝐼1 + 𝐼2 + ⋯+ 𝐼𝑛
𝑛
 
For QLQ-C30 Global health status/QoL Scale:  
𝑆𝑐𝑜𝑟𝑒= {
(𝑅𝑆−1)
𝑟𝑎𝑛𝑔𝑒} × 100 
Thus, a higher score represents a higher (“better”) level of health status/QoL.  
For QLQ-C30 Functional Scales: 
𝑆𝑐𝑜𝑟𝑒= {1 −(𝑅𝑆−1)
𝑟𝑎𝑛𝑔𝑒} × 100 
Thus, a higher score represents a higher (“better”) level of functioning. 
For QLQ-C30 Symptom Scales/Items: 
𝑆𝑐𝑜𝑟𝑒= {
(𝑅𝑆−1)
𝑟𝑎𝑛𝑔𝑒} × 100 
Thus, a higher score represents a higher (“worse”) level of symptoms. 
Missing questionnaire data  
 
If there are missing items in a scale, the scale score will be calculated on the completed items if 
at least 50% of the component items have been completed; otherwise, the scale score is regarded 
as missing. 
Statistical Analyses 
Secondary analyses are restricted to the neoadjuvant treatment period.  


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Summary statistics for observed values and change from baseline (mean, median, standard 
deviation, min, max) will be provided for the scales and items by treatment arm at each 
scheduled visit.  
Additionally, the scale/item score change from baseline will also be summarised in a categorical 
fashion with respect to a 10-point change. A change of 10 points in IL136 scale score is 
considered to be the minimum clinically important difference (MCID) [Osoba et al. 1998]. The 
categories are: 
Definition  
Description  
For Global Health Status/QoL & functional scales: 
• Improved  
change from baseline ≥ 10 points  
• Stable  
-10 points < change from baseline < 10 points  
• Worsened  
change from baseline ≤ -10 points  
For symptom scales  
• Improved  
change from baseline ≤ -10 points  
• Stable  
-10 points < change from baseline < 10 points  
• Worsened  
change from baseline ≥ 10 points  
 
The number and percentage of participants in each of the above categories will be summarized 
by treatment group at each scheduled visit.  
MMRM Analysis  
Mixed effects models for repeated measures will be used to assess the effect of niraparib 
compared to platinum+taxane during the neoadjuvant treatment period for the change from 
baseline in EORTC IL136 scale scores (global health, physical functioning, social functioning, 
and dyspnea). Participant will be treated as a random effect. All other covariates will be fixed 
effects. The fixed effects will include treatment, scheduled visit, BRCA mutation status (if there 
are at least 20 participants in each stratum), treatment-by-scheduled visit interaction as well as 
the respective baseline value for the scale being measured. All scheduled visits in the 
neoadjuvant period will be included apart from those with excessive missing data at a visit 
(defined as >75% missing data).  
An unstructured covariance matrix will be used to model the within and between participant 
variance and the Kenward and Rogers approximation [Kenward, 2009] will be used to estimate 
the degrees of freedom. Restricted maximum likelihood (REML) estimation will be used. The 
following provides sample code for implementing the MMRM analysis:  


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proc mixed data=EORTC method=reml;  
class TRT(ref=”PBO”) AVISIT SUBJID;  
model EORTCCHG = TRT AVISIT TRT*AVISIT BLEORTC BRCASTAT (conditional)/s 
ddfm=kr;  
repeated AVISIT / type=UN participant=SUBJID;  
lsmeans TRT*AVISIT / slice=AVISIT diff alpha=0.05 cl;  
run;  
quit;  
where TRT is the randomized treatment, AVISIT is the analysis visit, EORTCCHG is the change 
from baseline in the EORTC IL136 scale score and BLEORTC is the baseline EORTC 1L136 
scale score.  
 
If the fit of the unstructured covariance structure fails to converge, the following repeated 
covariance structures together with a random effect for participant (random intercept / 
participant=SUBJID;) will be used in order until convergence is reached: toeplitz with 
heterogeneity (TOEPH) and Toeplitz (TOEP). If there are still issues with the fit of the model or 
estimation of the treatment effects, PARTICIPANT will be treated as a fixed effect.  
 
Least square (LS) means and LS mean differences will be presented by visit and treatment group 
along with their 95% confidence intervals. 
 
4.3.5.5. 
EORTC IL137 (a Subset of Items from EORTC QLQ-OV28) 
The ovarian cancer module (QLQ-OV28) supplements the QLQ-C30, consists of 28 items and 
includes 3 functional scales (body image, sexuality, and attitude to disease/treatment burden) and 
5 symptom scales/items (abdominal/gastrointestinal symptoms, peripheral neuropathy, 
hormonal/menopausal symptoms, other chemotherapy side effects, and hair loss). Table 5 
summarizes the EORTC QLQ-OV28 scales and component items.  
A subset of the EORTC QLQ-OV28 will be utilized (see Table 5) and will be referred to as the 
EORTC IL137.  
The scoring approach for the OC module is identical in principle to that used for the scales/items 
of the EORTC QLQ-C30. However, the items included in IL137 do not represent full scales and 
will be analysed as single items.   
Table 5 
Scoring the QLQ-OV28 
Scale 
Abbr. 
Number 
of Items 
Item 
Range 
Included in 
IL137 
 QLQ-OV28 
Item Numbers 
Functional Scales 
 
 
 
 
 
Body Image 
BI 
2 
3 
50 
50, 51 
Attitude to Disease/Treatment 
AT 
3 
3 
52, 53 
52 to 54 
Symptom Scales/Items 
 
 
 
 
 
Abdominal/gastrointestinal 
AG 
7 
3 
32, 34 to 37 
31 to 37 


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Peripheral Neuropathy 
PN 
3 
3 
43 
41 to 43 
 
Statistical Analyses 
Secondary analyses are restricted to the neoadjuvant period.  
The linear transformation of scores, the treatment of missing values, the descriptive statistics to 
be presented, the classification of scale scores as improved, stable or worsened by 10 points and 
the use of MMRM to assess the effect of treatment on change from baseline will be the same for 
the EORTC QLQ OV28 library 137 as described above for the EORTC QLQ C30 library 136. 
4.4. 
Exploratory Analyses 
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4.5. 
Safety Analyses 
The safety analyses will be based on the Safety analysis set, unless otherwise specified.  
4.5.1. 
Extent of Exposure 
4.5.1.1. 
Niraparib Treatment Exposure 
Duration of treatment  
Summaries will be done by treatment arm and treatment period (neoadjuvant, maintenance). 
During the neoadjuvant treatment period, the number and percentage of participants beginning 1, 
2, or 3 cycles of niraparib treatment will be summarized.  
During the maintenance period, the following will be summarized by treatment arm: 
• 
Number and percent of participants beginning 1, 2, 3, …, 12, and >12 cycles  
• 
Number of cycles started, summarized as a continuous variable 
• 
Treatment exposure (months), defined as the [last dose date of maintenance treatment - first 
dose date of maintenance treatment + 1] / 30.4375. Last dose of maintenance treatment 
equals last cycle entered in the eCRF + 20 days (for ongoing subjects) to account for the 
daily dosing after dispensation or last dose date (for subjects who have discontinued 
treatment). 
• 
Actual treatment exposure (months), defined as the maintenance treatment exposure minus 
the duration of dose interruptions 
Treatment Compliance 
The following will be summarised by treatment period (neoadjuvant, maintenance) and treatment 
arm: 
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• 
The cumulative actual dose, i.e., the sum of the daily doses consumed (mg), defined as the 
total number of 
 consumed multiplied by the dosage (mg). The total number of 
 consumed is the sum of the number of 
 dispensed minus the sum of the 
number of 
 returned by the participant.  
• 
Dose intensity (mg/day), defined as the cumulative actual dose divided by overall treatment 
exposure (converted to days) 
• 
Relative dose intensity (RDI, %), defined as dose intensity (mg/day) divided by intended 
dose intensity (mg/day) multiplied by 100, where intended dose intensity is the intended 
starting dose [dose prescribed in C1D1] (descriptive statistics, as well as number and 
percentage of participants in the <80%, 80%-105%, and >105% categories). 
Dose modifications 
Dose reductions and interruptions will be summarized. 
Dosing information and 
counts for each participant will be presented in a data listing. 
4.5.1.2. 
Chemotherapy Treatment Exposure 
Duration of treatment 
The following will be summarised by treatment arm and treatment period (neoadjuvant, 
adjuvant): 
• 
Number and percentage of participants beginning 1, 2, 3 cycles. 
• 
Neoadjuvant treatment exposure (months), defined as the [last dose date of neoadjuvant 
treatment - first dose date + 21] / 30.4375 
• 
Adjuvant treatment exposure (months), defined as the [last dose date of adjuvant treatment - 
first dose date of adjuvant treatment + 21] / 30.4375 
Treatment compliance 
The following will be summarised by treatment period (neoadjuvant, adjuvant) and treatment 
arm: 
• 
Cumulative dose (mg/m2 for paclitaxel/docetaxel/cisplatin, mg for carboplatin), calculated as 
the sum of all actual doses infused divided by the body surface area  
• 
Dose intensity (mg/m2/wk for paclitaxel/docetaxel/cisplatin, mg/wk for carboplatin), 
calculated as cumulative dose divided by duration of treatment ([last dose date of 
neoadjuvant/adjuvant treatment - first dose date of neoadjuvant/adjuvant treatment + 21]/7) 
• 
RDI (%), calculated as dose intensity divided by intended dose intensity multiplied by 100 
• For paclitaxel, cisplatin, docetaxel intended dose intensity (mg/m2/wk) is calculated as 
(intended dose level/3)/body surface area (intended dose level, body surface area as 
collected in the study treatment eCRF pages for the first dose of treatment). Further 
details on intended dose level may be found in the study protocol.  
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• For carboplatin, intended dose intensity (mg/wk) is calculated by converting the intended 
dose unit (as collected in the eCRF page for the first dose of treatment) from AUC to mg 
using Calvert’s formula then dividing by 3: 
➢ Intended dose (mg) = Intended dose (AUC) * (GFR + 25), where GFR = 0.85 * (140 – 
age in years) * weight in kg / (72 * serum creatinine (mg/dL)) 
➢ Intended dose intensity (mg/week) = Intended dose (mg)/3 
 
Dose modifications 
Infusion delays and interruptions will be summarized. 
Infusion information for each participant will be presented in a data listing. 
4.5.1.3. 
Bevacizumab/Bevacizumab Biosimilar Treatment Exposure 
Duration of treatment 
The following will be summarised by treatment arm for the overall treatment period (adjuvant + 
maintenance):  
• 
Number and percentage of participants beginning 1, 2, 3, …, 12, and >12 cycles. 
• 
Number of cycles started summarized as a continuous variable. 
• 
Treatment exposure (months), defined as the [last dose date of bevacizumab/bevacizumab 
biosimilar treatment - first dose date of bevacizumab/bevacizumab biosimilar treatment + 
21] / 30.4375 
Treatment Compliance 
The following will be summarized by treatment arm for the overall period (adjuvant + 
maintenance): 
• 
Cumulative dose (mg/kg), calculated as the sum of all actual doses infused divided by 
weight 
• 
Dose intensity (mg/kg/week), calculated as cumulative dose divided by duration of 
treatment ([last dose date of bevacizumab/bevacizumab biosimilar treatment - first dose date 
of bevacizumab/bevacizumab biosimilar treatment + 21]/7) 
• 
RDI (%), calculated as dose intensity (mg/kg/week) divided by intended dose intensity 
(mg/kg/week) multiplied by 100, where the intended dose intensity is either (7.5/3) 
mg/kg/week or (15/3) mg/kg/week 
Dose modifications 
Infusion delays and interruptions will be summarized. 
Infusion information for each participant will be presented in a data listing. 


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4.5.2. 
Adverse Events 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs), 
Adverse Events of Special Interest (AESI) and other significant AEs will be based on GSK Core 
Data Standards. 
Adverse events will be coded using the latest MedDRA version available at the time of the 
analysis and grouped by System Organ Class. AEs will be graded by the Investigator according 
to the NCI-CTCAE v5.0. 
Summaries will focus on treatment emergent adverse events (TEAEs). TEAEs are defined as 
AEs with start date on or after the initiation of neoadjuvant study treatment (C1D1) and within 
30 days of the last dose of study treatment. AEs with missing date of onset and missing stop date 
will be considered to have started on the date of initiation of study treatment and will therefore 
be classified as TEAEs. AEs with missing date of onset and stop date after the initiation of study 
treatment will be considered to be concomitant. TEAEs will be further classified in the following 
categories, defined by period of occurrence: 
Neoadjuvant TEAEs: From the first dose of study treatment (neoadjuvant, C1D1) to the date of 
IDS or 30 days after the last dose of neoadjuvant study treatment, whichever is earlier. Events 
associated with IDS are not included.  
IDS TEAEs: From the date of IDS until the first dose of adjuvant therapy or 30 days after the 
date of IDS, whichever is earlier.  
Adjuvant TEAEs: From the first dose of adjuvant therapy until the first dose of maintenance 
therapy or 30 days after the last dose of adjuvant study treatment, whichever is earlier. 
Maintenance TEAEs: From the first dose of maintenance therapy to 30 days after the last dose of 
maintenance study treatment.  
Overall TEAEs: From the first dose of neoadjuvant study treatment (C1D1) to 30 days after the 
last dose of study treatment.  
All AEs, not just TEAEs, will be listed for participants in the Safety analysis set. The listing will 
include the treatment period of occurrence of the AE and AESI flag.  
4.5.2.1. 
Treatment Emergent Adverse Events (TEAEs) 
The number and percentage of participants experiencing a TEAE will be presented by treatment 
arm and treatment period (neoadjuvant, adjuvant, maintenance, overall), sorted by SOC and PT 
unless otherwise specified. Participants will be counted once within each SOC or PT. For by-
maximum grade summaries, participants experiencing the same TEAE multiple times, with 
different grade, will only be counted once under the maximum grade recorded. The following 
summary tables will be produced by treatment arm:  
• 
TEAEs by SOC, PT and maximum grade 


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• 
Treatment related TEAEs by SOC, PT and maximum grade (related to any 
treatment) 
• 
Serious TEAEs by SOC, PT and maximum grade 
• 
Serious TEAEs by SOC and PT (if needed)  
• 
Serious TEAEs by SOC and PT (number of participants and occurrences)  
• 
Serious fatal and non-fatal treatment related TEAEs by Overall Frequency 
(related to any treatment) 
• 
Common (≥5%) TEAEs by Overall Frequency  
• 
Common (≥5%) Non-serious TEAEs by SOC and PT   
• 
Non-serious treatment related TEAEs by Overall Frequency (related to any 
treatment) 
• 
TEAEs leading to permanent study treatment discontinuation (by chemo combo, 
bevacizumab/bevacizumab biosimilar, niraparib, any treatment) 
• 
TEAEs leading to dose reduction (applies to niraparib only) 
• 
TEAEs leading to dose interruption (by chemo combo, 
bevacizumab/bevacizumab biosimilar, niraparib, any treatment) 
• 
TEAEs leading to dose delay (by chemo combo, bevacizumab/bevacizumab 
biosimilar, niraparib, any treatment) 
• 
TEAE Overview (include TEAEs, treatment related TEAEs, TEAEs Grade≥3, 
treatment related TEAEs Grade≥3, Serious TEAEs, Serious treatment related TEAEs, 
TEAEs leading to niraparib dose reduction, TEAEs leading to chemo 
combo/bevacizumab/bevacizumab biosimilar/niraparib/any treatment dose interruption, 
TEAEs leading to chemo combo/bevacizumab/bevacizumab biosimilar/niraparib/any 
treatment dose delay, TEAEs leading to permanent discontinuation of chemo 
combo/bevacizumab/bevacizumab biosimilar/niraparib/any treatment, Fatal TEAEs) 
 
For common (≥5%) TEAEs that occurred in strictly 5% of the participants or above, no rounding 
for the percentage will be used in terms of 5% threshold, e.g., events with 4.9% incidence rate 
should not be included in these tables. 
 
Relatedness of TEAE to study treatment will be assessed by the investigator and captured in the 
eCRF. In cases where relatedness is missing, the TEAE will be classified as related to study 
treatment. Treatment related TEAEs will be presented at the treatment arm level (i.e., by 
relatedness to any treatment component).  
 
4.5.2.2. 
TEAEs of Special Interest 
The AESIs for this study are myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), 
or second primary cancer (new malignancies other than MDS or AML), identified by the terms 
shown in Table 7.  
Each AESI will be summarized by grouped term and PT for the neoadjuvant and overall periods: 
• 
TEAESI by grouped term, PT and maximum grade 


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• 
Treatment related TEAESI by grouped term, PT and maximum grade (related to any 
treatment) 
• 
Serious TEAESI by grouped term, PT and maximum grade 
• 
TEAESI leading to permanent discontinuation of any study treatment  
• 
TEAESI leading to dose modification (interruption/reduction/delay) of any study treatment 
 
Table 7 
Adverse Events of Special Interest 
Group Term 
MedDRA 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 tumors (SMQ Narrow) 
• 
Non-haematological malignant tumors (SMQ Narrow) 
• 
Malignant neoplasm progression (PT) 
Note: exclude MDS/AML, ovarian, and related metastases 
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. 
 
4.5.2.3. 
Deaths 
All deaths will be summarized. The summary will include status (death, alive at last contact, 
follow-up ended, follow-up ongoing), primary cause of death and number of deaths relative to 
the last dose of study treatment (>30 days, or ≤30 days). A supportive listing will be generated 
on participants who died. 
 
4.5.2.4. 
Pregnancy 
A listing of participants who became pregnant during the study will be produced. 
 
4.5.3. 
Additional Safety Assessments 
4.5.3.1. 
ECOG Performance Status 
ECOG performance status will be reported in a data listing. A summary of worst-case change 
from baseline will be provided.  
4.5.3.2. 
Laboratory Data 
Laboratory evaluations including the analyses of chemistry, hematology and urinalysis 
laboratory tests and other screening tests will be based on GSK Core Data Standards. Descriptive 


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statistics (mean, std, median, range) will be used to summarize worst change from baseline in 
observed value (increase or decrease as applicable). 
Summaries of worst-case grade increase from baseline grade will be provided for hematology 
and chemistry laboratory tests that can be graded by CTCAE v5.0. These summaries will display 
the number and percentage of participants with a maximum post-baseline grade increasing from 
their baseline grade. Any increase in grade from baseline will be summarized along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. Missing baseline 
grade will be assumed as grade 0. For laboratory tests that are graded for both low and high 
values, summaries will be done separately and labeled by direction, e.g., sodium will be 
summarized as hyponatremia and hypernatremia separately. 
For laboratory tests that cannot be graded by CTCAE v5.0, summaries of worst-case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes to 
normal or no changes from baseline, and increases to high will be summarized for the worst-case 
post-baseline. If a participant has a decrease to low and an increase to high during the same time 
interval, then the participant is counted in both the “Decrease to Low” categories and the 
“Increase to High” categories. 
The calculation of worst-case change will use data from both scheduled and unscheduled visits.  
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be provided 
in addition to what has been described above. The summary will be produced for worst-case 
post-baseline only. 
Possible Hy’s law cases are defined as: 
• 
ALT ≥3×ULN and total bilirubin ≥2×ULN (with direct bilirubin ≥35% of total bilirubin or 
direct bilirubin missing) or, 
• 
ALT ≥3×ULN and INR >1.5 or missing 
 
The total bilirubin elevation and/or INR value must occur on or up to 28 days after the ALT 
elevation. 
An e-DISH plot of maximum post-baseline total bilirubin versus maximum post-baseline ALT 
will be created. 
Summary of liver monitoring and stopping events, as well as summary of hepatobiliary 
laboratory abnormalities will be summarized according to GSK Core Data Standards and will be 
used to summarize data specific to participants who meet the protocol-specified liver stopping or 
monitoring events.  
If a laboratory value, which is expected to have a numeric value for summary purposes, has a 
non-detectable level reported in the database, where the numeric value is missing, but typically a 
character value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the 
comment field) is present, the number of significant digits in the observed values will be used to 
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• 
Example 1: 2 Significant Digits = ‘<x’ becomes x – 0.01 
• 
Example 2: 1 Significant Digit = ‘>x’ becomes x + 0.1 
• 
Example 3: 0 Significant Digits = ‘<x’ becomes x – 1 
 
4.5.3.3. 
Vital Signs 
Baseline values of vital signs (temperature, heart rate, systolic and diastolic blood pressure), as 
well as the worst-case change from baseline will be summarized by treatment arm using n, mean, 
median, std, minimum and maximum. The determination of the worst-case post-baseline vital 
signs will consider both scheduled and unscheduled assessments. 
A summary of post-baseline worst-case vital signs results relative to baseline with respect to 
normal range or grade will be presented. The determination of the worst-case post-baseline vital 
signs will consider both scheduled and unscheduled assessments. Participants with missing 
baseline values are assumed to have a normal/Grade 0 baseline value.  
For temperature and heart rate worst-case will be presented with respect to normal range 
according to the following normal ranges: 
• 
Temperature: anything ≤35 and ≥38 deg C falls outside of normal range 
• Heart rate: 50-90 bpm (beats/minute) 
 
For systolic and diastolic blood pressure worst-case increase will be presented with respect to 
maximum grade according to the following NCI-CTCAE grades: 
• 
SBP (mmHg): Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159), Grade 3 (≥160).  
• 
DBP (mmHg): Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), Grade 3 (≥100). 
 
Vital sign measurements will be presented for each participant in a data listing. 
 
4.5.4. 
Data Review Committee (DRC) Analyses 
The DRC will convene for meetings during the study at the following times: 
• 
After the first 5 participants in the pre-IDS response evaluable population in each arm have 
undergone their RECIST v1.1 primary endpoint assessment (prior to IDS) to review 
preliminary safety and efficacy data  
• 
 
 
• 
At the primary efficacy analysis to assess if the primary efficacy endpoint, defined as the 
percentage of participants with unconfirmed CR or PR on study intervention pre-IDS as 
assessed per RECIST v1.1, has been met 
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Additional ad-hoc data reviews by the DRC may also be triggered by any concerns raised by the 
DRC itself during these meetings. 
The following outputs will be produced for DRC review purposes. Safety TEAE summaries will 
be provided for the neoadjuvant and overall periods.   
1. Subject status (summary) 
2. Treatment status (summary) 
3. Extent of exposure by study treatment component (summary) 
4. Demographic characteristics (summary) 
5. Disease characteristics (summary) 
6. Pre-IDS overall response rate – based on pre-IDS evaluable and ITT analysis sets (summary, 
listing, waterfall and swimmer plots) 
7. TEAE overview 
8. TEAEs by SOC, PT and maximum grade (summary) 
9. Treatment related TEAEs by SOC, PT and maximum grade (summary) 
10. Serious TEAEs by SOC, PT and maximum grade (summary) 
11. Serious fatal and non-fatal treatment related TEAEs by Overall Frequency (summary) 
12. TEAESIs by category, PT and maximum grade (summary) 
13. Serious TEAESIs by category, PT and maximum grade (summary) 
14. TEAEs leading to permanent treatment discontinuation of any treatment (summary) 
15. TEAEs leading to interruption of any treatment (summary) 
16. TEAEs leading to delay of any treatment (summary) 
17. TEAEs leading to dose reduction (summary, applies to niraparib only) 
18. Summary of deaths 
19. All AEs (listing, include column with study period, include chemotherapy run-in AEs for pts in the 
Safety analysis set) 
20. Worst-case change from baseline with respect to grade/normal-range chemistry/hematology 
laboratory data (summary) 
21. Worst-case change from baseline in vital signs (blood pressure & heart rate summary) 
22. Listing of all laboratory date for participants with values outside of normal range in 
chemistry/hematology laboratory data 
23. Liver toxicity events (summary) 
 
The population used for each output will be the one identified in the SAP.  
 
4.6. 
Interim Analyses 
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5. 
SAMPLE SIZE DETERMINATION 
Sample size calculation was performed using
 
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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 Study Population Analyses 
Unless otherwise specified, the study population analyses will be based on the ITT analysis set 
(i.e., screening status will be based on the Screened analysis, treatment status will be based on 
the Safety analysis set).  
Analyses will be based on GSK Core and Oncology Data Standards. 
6.1.1. 
Participant Disposition 
Participant disposition summaries will include screening status (participants screened, 
participants randomised, screen failures and reasons for failure based on the Screened analysis 
set), participant status (ongoing on study treatment, ongoing in follow-up, died, withdrawn from 
study and reason for study withdrawal), treatment status (ongoing by treatment period, 
discontinued from all study treatment within the treatment arm and reason for discontinuation of 
last treatment discontinued based on the Safety analysis set), and number and percentage of 
randomised participants belonging to each analysis population (ITT, pre-IDS response evaluable, 
safety, per-protocol, etc.).  
All disposition data will be summarised by treatment arm and overall. For treatment status, 
participants are considered to have discontinued from a treatment if they have discontinued all 
treatment components within it.  
Participants in the ITT analysis set will be summarised by country and site ID.  
6.1.2. 
Demographic and Baseline Characteristics 
Demographic characteristics will be summarised by treatment arm and overall and include the 
following categories:  
• 
Sex: male, female 
• 
Age (years): summary statistics 
• 
Age Group (years): < 18, 18-49, 50-65, ≥65 
• 
Ethnicity 
• 
Race Detail 
• 
Height (cm): summary statistics 
• 
Weight (kg): summary statistics 
• 
ECOG performance status at Screening: 0, 1 
• 
BMI (kg/m2): summary statistics 
 
Past medical conditions and current medical conditions, including other cancer history, will be 
summarized. 
Disease characteristics at initial diagnosis and at screening will be summarised by treatment arm 
and overall and include the following categories:  


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• Primary tumour site: ovarian, primary peritoneal, fallopian tube 
• Time from initial diagnosis to randomization (weeks): summary statistics 
• Cancer stage (FIGO) at initial diagnosis: 0, Stage I A-C, Stage II A-C, Stage III A-C, 
Stage IV 
• BRCA status: BRCA 1/2 mutated, BRCA 1/2 wild type or unknown according to RTSM 
and Myriad results 
• Histologic subtype at initial diagnosis: as captured in eCRF ovarian cancer pathology 
page 
• Tumour grade at initial diagnosis: as captured in eCRF ovarian cancer pathology page 
• Metastatic disease sites at screening: as captured in eCRF primary cancer history page 
 
Summary statistics, unless otherwise indicated, will include mean, standard deviation, minimum, 
median, and maximum. The count and percentage will be computed for the categorical variables. 
6.1.3. 
Protocol Deviations 
Important protocol deviations will be summarized. 
Protocol deviations will be tracked by the study team throughout the conduct of the study. These 
protocol deviations will be reviewed to identify those considered as important as follows: 
• 
Data will be reviewed prior to unblinding and freezing the database to ensure all important 
deviations are captured and categorized in the protocol deviations dataset.  
• 
This dataset will be the basis for the summaries of important protocol deviations. 
Protocol deviations which result in exclusion from the analysis set will also be summarized.  
• 
Data will be reviewed prior to unblinding and freezing the database to ensure all deviations 
leading to analysis population exclusions are captured and categorized in the protocol 
deviations ADaM dataset (note these exclusions are not captured in the SDTM dataset). 
A separate listing of all inclusion/exclusion criteria deviations will also be provided.  
Further details are outlined in the Protocol Deviation Management Plan. 
6.1.4. 
Prior and Concomitant Medications 
Concomitant medications are medications, other than study treatment with a start date prior to, 
on or after the start of the first dose of neoadjuvant study treatment (C1D1) and a stop date 
within 30 days after the last dose of study treatment.  
Derivations or concomitant medications will use imputed dates where possible/necessary. If the 
medication start date is prior to the treatment start date and the stop date is missing or start and 
stop date are missing, then the medication will be classified as concomitant. 


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Prior and concomitant medications will be coded using the WHO Drug dictionary. The 
summaries of prior and concomitant medications will be provided by ingredient, i.e. multi-
ingredient medications will be summarized for each individual ingredient rather than a 
combination of ingredients. The summary will be created using ingredient base names, i.e. 
ingredients with the same base name but different salt will appear under one base name in the 
summary. Anatomical Therapeutic Chemical (ATC) classifications will not appear in the 
summary. Each participant will be counted once within a unique ingredient.  
6.1.4.1. 
Follow Up Anti-Cancer Therapy 
Follow up anti-cancer therapy will be coded using the WHO Drug dictionary. The number and 
percentage of participants initiating follow up anti-cancer therapy will be summarised by therapy 
type as collected in the eCRF (including radiotherapy, surgery) and treatment arm. The summary 
will include the time from study treatment discontinuation to start of follow up therapy (weeks). 
Follow-up anti-cancer therapy will be listed.  
 
6.1.4.2. 
Duration of Follow Up 
The duration of follow-up will be summarised in months (median, IQR, min, max) by treatment 
arm. Follow-up time is defined as: 
Follow-up time (months) = (date of death or last known date alive – date of randomisation + 
1)/30.4375  
 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic 
A participant is defined as having a suspected, probable or confirmed COVID-19 infection 
during the study if the answer is “Confirmed”, “Probable” or “Suspected” to the case diagnosis 
question from the COVID-19 coronavirus infection assessment eCRF. Numbers of participants 
with a suspected, probable or confirmed COVID-19 infection, and of COVID-19 test results will 
be summarized by treatment arm. 


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6.2. 
Appendix 2 Data Derivations Rule 
6.2.1. 
Criteria for Potential Clinical Importance 
6.2.1.1. 
Laboratory Data 
Reference ranges for all laboratory parameters collected throughout the study are provided by the 
laboratory. A laboratory value that is outside the reference range is considered either high 
abnormal (value above the upper limit of the reference range) or low abnormal (value below the 
lower limit of the reference range). Note: a high abnormal or low abnormal laboratory value is 
not necessarily of clinical concern.  
6.2.1.2. 
Vital Signs 
See Section 4.5.3.3 for the grading of systolic and diastolic pressure and for the normal ranges 
for temperature and heart rate.  
6.2.2. 
Study Period 
The study phases/flags for calculation of concomitant medications and safety assessments are 
defined in the Sections below. For analysis purposes, study treatment is considered any 
treatment received after randomisation.  
6.2.2.1. 
Study Phase  
Study Phase 
Definition 
Chemotherapy 
Run-in 
Chemotherapy Run-in Study Treatment Start Date ≤ Date ≤ min(Chemotherapy Run-in 
Study Treatment Stop Date + 30 days, Neoadjuvant Study Treatment Start Date-1) 
*For participants who do not start neoadjuvant treatment, set neoadjuvant treatment start 
date to Infimum 
Neoadjuvant  
Neoadjuvant Study Treatment Start Date  ≤ Date ≤ min(Neoadjuvant Study Treatment 
Stop Date + 30 days, IDS date-1) 
*For participants who do not get IDS, set IDS date to Infimum 
IDS 
IDS Date ≤ Date ≤ min(IDS Date+30 days, Adjuvant Treatment Start Date -1) 
*For participants who do not start adjuvant treatment, set adjuvant treatment start date to 
Infimum 
Adjuvant  
Adjuvant Study Treatment Start Date ≤ Date ≤ min (Adjuvant Study Treatment Stop Date 
+ 30 days, Maintenance Study Treatment Start Date-1) 
*For participants who do not start maintenance treatment, set maintenance treatment date 
to Infimum 
Maintenance  
Maintenance Study Treatment Start Date ≤ Date ≤ Study Treatment Stop Date + 30 days  
Overall 
Study Treatment Start Date (of any study treatment) ≤ AE Start Date ≤ Study Treatment 
Stop Date (of any study treatment) + 30 days   
 
 


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6.2.2.2. 
Study Phase for Concomitant Medication  
Study Phase 
Definition 
Concomitant 
Study Treatment Start Date ≤ Start Date ≤ Study Treatment Stop Date + 30 days  
NOTES:  
 
Refer to Section 6.2.5 for Handling of Partial dates for concomitant medication. Use the rules in that table if concomitant 
medication date is completely missing. 
 
If Start Date < Study Treatment Start Date and Stop Date is missing, then Study Phase = Concomitant 
 
If Start and Stop Date are missing, then Study Phase = Concomitant 
 
If Start Date is missing and Stop Date > Study Treatment Start date, then Study Phase = Concomitant 
 
6.2.2.3. 
Study Phases for Treatment Emergent Adverse Events 
Study Phase 
Definition 
Overall  
Study Treatment Start Date (of any study treatment) ≤ AE Start Date ≤ Study Treatment 
Stop Date (of any study treatment) + 30 days   
Neoadjuvant   
Neoadjuvant Study Treatment Start Date ≤ AE Start Date ≤ min (IDS date-1, Neoadjuvant 
Study Treatment Stop Date + 30 days) 
IDS 
IDS Date ≤ AE Start Date ≤ min (Adjuvant Treatment Start Date - 1, IDS Date+30 days) 
Adjuvant 
Adjuvant Study Treatment Start Date ≤ AE Start Date ≤ min (Maintenance Study 
Treatment Start Date-1, Adjuvant Study Treatment Stop Date + 30 days) 
Maintenance 
Maintenance Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date + 
30 days 
 
If AE start date is missing, then the AE will be considered to be treatment emergent with start date falling in the overall and 
neoadjuvant periods.  
 
If AE start date and stop dates are missing, then the AE is treatment emergent with start date falling in the overall and 
neoadjuvant periods.  
 
If AE start date is missing and stop date > treatment start date, then the AE is considered to be treatment emergent with 
start date falling in the overall and neoadjuvant periods. 
 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 
 
6.2.3. 
Assessment Windows  
Generally, for data summaries by visit, scheduled visits with nominal visit description, as well as 
the worst-case post-baseline will be displayed. Unscheduled visits will not be displayed or 
slotted into a visit window but will be included in the derivation of worst-case post-baseline 
assessment. All unscheduled visits will be displayed in the listing. 
For PRO endpoints, the following windowing will be applied.  
Table 8 
Neoadjuvant period: PRO-CTCAE/WPAI:GH/FACT-GP5 windowing 
Visit 
Scheduled days from 
baseline (nominally C1D1) 
Window (days) 
C1D8 
7 
4-10 


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C1D15 
14 
11-17 
C2D1 
21 
18-24 
C2D8 
28 
25-31 
C2D15 
35 
32-38 
C3D1 
42 
39-45 
C3D8 
49 
46-52 
C3D15 
56 
53-59 
*C1D1 is the first dose of study treatment (nominal) 
Table 9 
Neoadjuvant period: EORTC-IL136/137 windowing 
Visit 
Scheduled days from 
baseline (nominally C1D1) 
Window (days) 
C2D1 
21 
14-28 
C3D1 
42 
35-49 
*C1D1 is the first dose of study treatment (nominal) 
Table 10 
Maintenance period: FACT-GP5/EORTC-IL136/137 windowing 
Visit 
Scheduled weeks from 
maintenance treatment 
start (nominally M1D1) 
Window (weeks) 
M4D1 
9  
6-12 
M7D1 
18 
15-21 
M10D1 
27 
24-31 
M13D1 
36 
33-39 
M17D1 
45 
42-48 
M20D1 
54 
51-57 


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M24D1 (schedule change 
after M20D1) 
62 
59-65 
M28D1 
74 
71-77 
… continue as above 
 
 
*M1D1 is the first dose of maintenance treatment 
 
6.2.4. 
Multiple measurements at One Analysis Time Point 
For laboratory tests on a study day, if more than one assessment is taken on the same day, the 
test from a central laboratory will be taken over the test from a local laboratory (if this is relevant 
and data are captured from both central and local laboratories). If multiple assessments are taken 
from the same type of laboratory, the worst case will be used. For continuous change from 
baseline summaries, the mean of the measurements will be used. 
6.2.5. 
Handling of Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays.   
• 
However, where necessary, display macros may impute dates as 
temporary variables for sorting data in listings only. In addition, partial 
dates may be imputed for ‘slotting’ data to study phases or for specific 
analysis purposes as outlined below. 
• 
Imputed partial dates will not be used to derive study day, time to onset 
or duration (e.g., time to onset or duration of AEs), or elapsed time 
variables (e.g., time since diagnosis). In addition, imputed dates are not 
used for deriving the last contact date in OS analysis dataset. 
Adverse Events 
• 
Partial dates for AE recorded in the eCRF will be imputed using the 
following conventions: 
Missing start 
day 
If study intervention start date is missing (i.e., 
participant did not start study intervention), then set 
start date = 1st of month. 
Else if study intervention start date is not missing: 
• 
If month and year of start date = month and year 
of study intervention start date, then 
• 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date= 1st of 
month. 
• 
Else set start date = study intervention 
start date. 


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Element 
Reporting Detail 
• 
Else set start date = 1st of month. 
Missing start 
day and month 
If study intervention start date is missing (i.e., 
participant did not start study intervention), then set 
start date = January 1. 
Else if study intervention start date is not missing: 
• 
If year of start date = year of study intervention 
start date, then 
• 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date = January 1. 
• 
Else set start date = study intervention 
start date.  
• 
Else set start date = January 1. 
Missing end day  A '28/29/30/31' will be used for the day (dependent on the 
month and year). 
Missing end day 
and month 
No Imputation 
Completely 
missing 
start/end date 
No imputation 
Concomitant 
Medications/Procedures 
• 
Partial dates for any concomitant medications recorded in the eCRF will 
be imputed using the following convention: 
 
Missing start 
day 
If study intervention start date is missing (i.e., 
participant did not start study intervention), then set 
start date = 1st of month. 
Else if study intervention start date is not missing: 
• 
If month and year of start date = month and year 
of study intervention start date, then 
• 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date= 1st of 
month. 
• 
Else set start date = study intervention 
start date. 
• 
Else set start date = 1st of month. 


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Element 
Reporting Detail 
Missing start 
day and month 
If study intervention start date is missing (i.e. 
participant did not start study intervention), then set 
start date = January 1. 
Else if study intervention start date is not missing: 
• 
If year of start date = year of study intervention 
start date, then 
• 
If stop date contains a full date and stop 
date is earlier than study intervention 
start date, then set start date = 
January 1. 
• 
Else set start date = study intervention 
start date. 
• 
Else set start date = January 1. 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on 
the month and year).  
Missing end day 
and month 
A '31' will be used for the day and 'Dec' will be used 
for the month. 
Completely 
missing 
start/end date 
No imputation 
Note: If imputed date is greater than study end date or death date, then 
earliest of these dates will be used as an end date. 
Exposure 
• 
Partial dates will not be imputed. 
• 
Completely missing dates will not be imputed. 
Death date 
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 (as 
collected in the long-term follow up eCRF page) 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 
 
6.2.6. 
Extended Time without a PFS Assessment 
Tumor scans are obtained within 7 days prior to C1D1, at C3D21 (+/-7 days), at M1D1 (-14 
days), every 3 months (+/-7 days) for the first year of maintenance therapy, every 6 months (+/-7 
days) for the second year and yearly thereafter.  
The definition of 2 missed/inadequate consecutive visits varies according to the scan schedule 
and is defined by matching the LATA prior to an event (PD/death) to a scheduled visit using the 


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midpoint as described in Table 11. LATA on or before the midpoint is assigned to the scheduled 
visit prior to it. LATA after the midpoint is assigned to the scheduled visit after it. 
Table 11 
Tumor Assessment Windowing 
Assessment 
Schedule 
Scheduled visit -
1-2 weeks (7-14 
days) 
Scheduled visit 
(from 
randomization) 
Scheduled visit 
+0-1 weeks (0-7 
days) 
Midpoint (floor 
for non-integers) 
Neoadjuvant 
8 weeks 
9 weeks 
10 weeks 
(M1D1 weeks 
from 
randomization)/2 
+ 4weeks 
Maintenance 
M1D1-14days 
M1D1 
M1D1+0days 
M1D1+1.5months
-3days 
 
M1D1+3months-
7days 
M1D1+3months 
M1D1+3months+
7days 
M1D1+4.5months 
 
M1D1+6months-
7days 
M1D1+6months 
M1D1+6months+
7days 
M1D1+7.5months 
 
M1D1+9months-
7days 
M1D1+9months 
M1D1+9months+
7days 
M1D1+10.5month
s 
 
M1D1+12month
s-7days 
M1D1+12month
s 
M1D1+12months
+7days 
M1D1+15months 
 
M1D1+18month
s-7days 
M1D1+18month
s 
M1D1+18months
+7days 
M1D1+21months 
 
M1D1+24month
s-7days 
M1D1+24month
s 
M1D1+24months
+7days 
M1D1+30months 
 
M1D1+36month
s-7days 
M1D1+36month
s 
M1D1+36months
+7days 
M1D1+42months 
 
M1D1+48month
s-7days 
M1D1+48month
s 
M1D1+48months
+7days 
M1D1+54months 
  


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Any event occurring after LATA + T2, is considered to have occurred after 2 consecutive missed 
assessments, where T2 is defined as follows: 
• 
If LATA prior to event is within (M1D1 weeks from randomization)/2 + 4weeks, T2 = 
2*(M1D1 weeks from randomization in days) + 3months = 2*(M1D1 weeks from 
randomization in days) + 92days + 14days=2*(M1D1 weeks from randomization 
in days) + 106days 
• 
If LATA prior to event is after (M1D1 weeks from randomization)/2 + 4weeks and on or 
before M1D1+1.5months, T2 = 3months*2+21days = 218 days  
• 
If LATA prior to event is after M1D1+1.5months and on or before M1D1+10.5months, 
T2 = 3months*2+14days = 197 days 
• 
If LATA prior to event is after M1D1+10.5months and on or before M1D1+21months, 
T2 = 3months + 6months +14days = 288 days 
• 
If LATA prior to event is after M1D1+21months and on or before M1D1+42months, T2 
= 6months + 12months + 14days = 562 days 
• 
If LATA prior to event is after M1D1+42months, T2 = 12months*2+14 = 745 days 
 


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6.3. 
Appendix 3 Population Pharmacokinetic Analysis Methodology 
Niraparib plasma concentration-time data may be analyzed by population PK methods using a 
nonlinear mixed-effects modeling approach. The key objective of this analysis is to predict 
individual PK parameter values for niraparib.  
If done, the analysis will be performed by, or under the direct auspices of, CPMS, GSK using the 
currently supported versions of all software packages. The population PK analysis will be 
performed using NONMEM (ICON Solutions) and PsN or another software platform deemed 
appropriate. Graphical displays and data summary will be produced using R (The R Foundation 
for Statistical Computing).  
Participant data will be collected in the eCRF and will be transmitted into a validated database by 
GSK data management. Derived/processed variables will be provided by or under the guidance 
of Clinical Programming. Plasma samples will be analyzed using approved analytical 
methodology. Data will be transferred electronically to data managers to be processed and stored 
in the GSK database. GSK or a designated third party will generate the NONMEM input dataset. 
Previously combined niraparib PK data may be merged with the PK data in Study 213357 in 
order to provide a pooled NONMEM data set. 
Post hoc or empirical Bayes estimates will be derived applying the current population PK model 
to the study-specific dataset with the MAXEVAL=0 option. If the corresponding model 
diagnostics indicate that this population PK model is appropriate to represent the niraparib data 
from this study, then individual PK parameter estimates will be based on the current population 
PK parameter values.  
If the parameter set of the current population PK model applied to the Study 213357 dataset 
results in substantial bias or if a further exploration of the covariate effect in the Study 213357 
population is deemed necessary, the parameters of the current population PK model will be re-
estimated for the Study 213357 PK data alone and/or for a pooled dataset before generating the 
individual PK parameter estimates. Certain parameter values may be fixed to the value in the 
current population PK model, if they cannot be estimated with sufficient precision within the 
Study 213357 PK population. Covariates not available for the Study 213357 PK Population but 
present in the current population PK model may be removed from the Study 213357 population 
PK model. Lastly, a model refinement step, if needed, will include, but may not be limited to, a 
qualification and possible modification of the model’s random effect structure. 
The model development and final model will be supported and qualified using the following 
criteria where appropriate: 
• 
Scientific plausibility of parameter estimates 
• 
Goodness of fit plots 
• 
Relative standard errors (RSE) of the parameter estimates 
• 
Objective function value 
• 
Distribution and shrinkage of random effects 


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• 
Successful minimization and execution of covariance step 
• 
Condition number (ratio of the largest and smallest eigenvalue of the covariance matrix 
• 
Visual predictive check Bootstrap (if deemed necessary/feasible) 
 
The PK parameter values will be listed and summarized. If done, the analysis will be performed 
by, or under the direct auspices of, CPMS, GSK, using the currently supported versions of all 
software packages. These analyses will be performed using R (The R Foundation for Statistical 
Computing), NONMEM (ICON Solutions) with PsN, or another software platform deemed 
appropriate. 
 
6.4. 
Changes from Protocol Defined Analyses 
• 
The analysis sets do not fully align to the corresponding version of the protocol and have been 
redefined in the SAP. The SAP is to be followed.  
• 
For WPAI:GH, the protocol defines a maintenance period endpoint that is not defined in the SAP due 
to data for WPAI:GH not being collected during the maintenance period per SoA.  


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6.5. 
List of Abbreviations 
Abbreviation or Specialist 
Term 
Explanation 
AE 
adverse event 
AESI 
adverse event of special interest 
AML 
acute myeloid leukemia 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AUC 
area under the concentration-time curve 
BRCA 
breast cancer gene 
BRCAm 
breast cancer gene mutated 
CA-125 
cancer antigen 125  
CI 
confidence interval 
CPMS 
Clinical Pharmacology Modeling and Simulation 
CR 
complete response 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Cx 
cycle number 
CxDx 
Cycle x Day x 
DRC 
Data Review Committee 
ECOG 
Eastern Cooperative Oncology Group 
EORTC 
European Organisation for Research and Treatment of Cancer  
EORTC IL136 
European Organisation for Research and Treatment of Cancer 
Item Library 136 
EORTC IL137 
European Organisation for Research and Treatment of Cancer 
Item Library 137 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire-Core 30 
EORTC QLQ-OV28  
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire for Ovarian Cancer 
EOT 
end of treatment 
FACT-G 
Functional Assessment of Cancer Therapy - General 
FACT-GP5 
Functional Assessment of Cancer Therapy-Item GP5 
GCIG 
Gynecological Cancer InterGroup 


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Abbreviation or Specialist 
Term 
Explanation 
GFR  
glomerular filtration rate 
GSK 
GlaxoSmithKline 
HCRU 
healthcare resource utilization 
HR 
hazard ratio/homologous recombination 
HRD 
homologous recombination deficiency 
HRd  
homologous recombination-deficient  
HRQoL 
health-related quality of life 
IA 
interim analysis 
ICF 
informed consent form 
ICU 
intensive care unit 
IDS 
interval debulking surgery  
IV 
intravenous(ly) 
ITT 
intent-to-treat 
MCID 
minimum clinically important difference 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effects model for repeated measures 
mPFS 
median progression-free survival  
MxDx 
Cycle x Day x during maintenance treatment period 
NACT 
neoadjuvant chemotherapy  
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NVRD 
no visible residual disease 
OC  
ovarian cancer 
OS 
overall survival 
ORR 
overall response rate 
pCR 
pathological complete response 
PD 
progression of disease/pharmacodynamics 
PFS 
progression-free survival  
PK 
pharmacokinetic(s) 
PopPK 
population PK 


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Abbreviation or Specialist 
Term 
Explanation 
PP 
per protocol 
PR 
partial response 
PRO 
participant-reported outcome 
PRO-CTCAE 
Participant Reported Outcomes-Common Terminology Criteria 
for Adverse Events 
PsN 
Perl Speaks NONMEM 
PT 
preferred term 
QD 
once daily 
Qol 
quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors 
REML 
restricted maximum likelihood 
SAE 
serious adverse event 
SAF 
safety 
SAP 
statistical analysis plan 
SD 
stable disease 
SDF 
survival distribution function 
SMQ 
Standardized MedDRA Query 
SoA 
Schedule of assessments 
SoC 
standard of care 
SOC 
system organ class 
std 
standard deviation 
TEAE 
treatment-emergent adverse event 
TFST 
time to first subsequent treatment 
ULN 
upper limit of normal 
WPAI:GH 
Work Productivity and Activity Impairment – General Health 
 
Trademarks 
Trademarks of the GlaxoSmithKline Group 
of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None  
 
EAST 
 
 
EORTC QLQ-C30 
 
 
FACT GP-5 


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ICON Solutions  
 
MedDRA  
 
PRO-CTCAE  
 
SAS 
 
WHO 


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7. 
REFERENCES 
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and 
Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials 
in oncology. J Natl Cancer Inst. 1993;85(5):365-376. 
Basch E, Reeve BB, Mitchell SA, et. al. Development of the National Cancer Institute’s 
participant-reported outcomes version of the common terminology criteria for adverse events  
(PRO-CTCAE). J Natl Cancer Inst. 2014;106:1-11. 
 
Brookmeyer, R., & Crowley, J. (1982). A confidence interval for the median survival time. 
Biometrics., 29-41. 
 
Cella DF, Tulsky DS, Gray G, et al. The Functional Assessment of Cancer Therapy scale: 
development and validation of the general measure. J Clin Oncol. 1993;11(3):570-579. 
East 6 (2020). Statistical software for the design, simulation and monitoring clinical trials. 
Cytel Inc., Cambridge MA. 
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 
EORTC. http://groups.eortc.be/qol/eortc-qlq-c30 
Kenward, M., & Roger, J. An improved approximation to the precision of fixed effects from 
restricted maximum likelihood. Computational Statistics & Data Analysis. 2009; 53(7): 2583-95. 
Miettinen O, Nurminen M. Comparative analysis of two rates. Statistics in Medicine 1985; 
4:213–226.  
Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in 
health-related quality-of-life scores. J Clin Oncol. 1998 Jan;16(1):139-44. doi: 
10.1200/JCO.1998.16.1.139. PMID: 9440735. 
SAS Institute Inc. 2018. SAS/STAT® 15.1 User’s Guide. Cary, NC: SAS Institute Inc.