Clinical trial NCT02855944
Conditions: Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer
Keywords: ovarian cancer fallopian tube cancer primary peritoneal cancer peritoneal cancer platinum sensitive relapsed disease PARP Inhibitor PARP rucaparib ruca homologous recombination homologous recombination deficiency genomic scarring loss of heterozygosity CO-338 PF-01367338 PF 01367338 CO-338-043 platinum sensitive ovarian cancer platinum sensitive fallopian tube cancer platinum sensitive primary peritoneal cancer platinum sensitive peritoneal cancer gynecological cancer Clovis Clovis oncology ARIEL2 ARIEL 2 ARIEL-2 ARIEL-3 ARIEL 3 ARIEL3 ARIEL4 ARIEL-4 ARIEL 4 A4 advanced OC platinum resistant ovarian cancer platinum resistant primary ovarian cancer Rubraca High grade serous Partially platinum sensitive
Sponsor: pharmaand GmbH
Start date: 2017-03-01; Completion date: 2022-09-16
Enrollment: 349 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

Detailed description:
Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.

While PARP inhibitors have demonstrated consistent robust clinical activity in patients with relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy and safety of PARPi versus standard of care chemotherapy have been limited. The primary purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious BRCA1/2 mutation in their tumor.

Arms: arm 1: Drug: Oral rucaparib

600 mg BID (twice a day)

Other Names:

* CO-338
* PF 01367338
* AG 14699
* Rubraca arm 2: Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.
Interventions: intervention 1: Chemotherapy intervention 2: Rucaparib
Intervention descriptions: intervention 1: Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision. intervention 2: Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice a day

Protocol documents:
Prot_000.pdf: 




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PROTOCOL APPROVAL SIGNATURE PAGE 
Protocol: 
CO-338-043 
Title: 
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 
Multicenter, Randomized Study of Rucaparib versus Chemotherapy in 
Patients with Relapsed, BRCA-Mutant, High-Grade Epithelial Ovarian, 
Fallopian Tube, or Primary Peritoneal Cancer 
Amendment 2 
Date: 
23 October 2020 
 
 
 
 
 
DocuSign Envelope ID: 297184CF-0D85-4EC8-BC5C-A8C350B20D68


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PROTOCOL ACCEPTANCE FORM 
Protocol: 
CO-338-043 
Title: 
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 
Multicenter, Randomized Study of Rucaparib versus Chemotherapy in 
Patients with Relapsed, BRCA-Mutant, High-Grade Epithelial Ovarian, 
Fallopian Tube, or Primary Peritoneal Cancer 
 
Date: 
23 October 2020 
Version: 
Amendment 2 
 
 
 
 
I have carefully read this protocol and agree that it contains all of the necessary information 
required to conduct this study. I agree to conduct this study as described and according to the 
Declaration of Helsinki, International Council for Harmonisation (ICH) E6(R2) Guidelines for 
Good Clinical Practice (GCP), and all applicable regulatory requirements. 
 
 
 
  
Investigator’s Signature 
 Date 
(DD-MMM-YYYY) 
 
 
 
  
Name (printed) 
  


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1 
SYNOPSIS 
Sponsor 
Clovis Oncology, Inc. 
Name of Finished Product 
Rucaparib tablets  
Name of Active Ingredient 
Rucaparib camsylate (CO-338) 
Study Title 
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, 
Randomized Study of Rucaparib versus Chemotherapy in Patients with Relapsed, 
BRCA-Mutant, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal 
Cancer 
Study Number 
CO-338-043 
Study Phase 
Phase 3 
Study Duration 
Approximately 4 years 
Rationale 
Globally, ovarian cancer is the eighth most common cancer and the seventh leading cause 
of cancer death among women, responsible for approximately 140,000 deaths each year.1 
Additionally, it is the second most common gynecologic malignancy worldwide and the 
leading cause of death attributed to gynecological cancer.2, 3 The standard of care is 
cytoreductive surgery followed by carboplatin and paclitaxel chemotherapy. Despite a 
70-80% initial response rate, most women have disease relapse.3-5 The choice of treatment 
for relapsed disease is based on the treatment-free interval relative to last therapy 
administered, and also prior chemotherapy agents used. The treatment-free interval 
typically decreases with each course administered and almost all patients will develop 
acquired resistance, hypersensitivity, or intolerable toxicity upon repeated courses of 
treatment, and ultimately will succumb to their disease. Recently, inhibitors of poly 
(adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes, which play critical 
roles in DNA repair, have demonstrated clinical activity in patients with a breast cancer 
gene 1 or 2 (BRCA1/2) mutation or other evidence of homologous recombination 
deficiency (HRD) and have emerged as a new treatment option for relapsed ovarian 
cancer.  
Rucaparib is a potent, oral small molecule inhibitor of PARP enzymes (PARPi), including 
PARP-1, PARP-2, and PARP-3. Rucaparib has demonstrated in vitro and in vivo 
anti-tumor activity in BRCA1 and BRCA2 homozygous mutant cell lines. These findings 
provided rationale for the clinical assessment of rucaparib as monotherapy in patients with 
hereditary (germline) and acquired (somatic) deficiencies of BRCA1 and/or BRCA2.  


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The safety and efficacy profile of rucaparib have been evaluated in several Phase 1 and 
Phase 2 studies. 
On 19 December 2016, the United States (US) Food and Drug Administration (FDA) 
granted accelerated approval for the marketing of rucaparib (Rubraca®) for monotherapy 
treatment of patients with deleterious BRCA mutation (germline and/or somatic) 
associated advanced ovarian cancer who have been treated with ≥ 2 chemotherapies. The 
recommended starting dose of rucaparib is 600 mg twice a day (BID). Refer to the 
Investigator’s Brochure for updated approval status. 
The basis for the approval of rucaparib as monotherapy for the treatment of ovarian cancer 
are the datasets and analyses for patients with Epithelial Ovarian Cancer (EOC), Fallopian 
Tube Cancer (FTC), or Primary Peritoneal Cancer (PPC) comprising the primary efficacy 
analysis population. The primary efficacy analysis population included 106 patients pooled 
from the open-label, single-arm Phase 2 studies, Study CO-338-010 (Study 10) Part 2A 
and Study CO-338-017 (ARIEL2) Parts 1 and 2, with BRCA-mutant ovarian cancer (EOC, 
FTC, or PPC), who had received ≥ 2 prior chemotherapy regimens, at least 2 of which 
were platinum-based, and who had received at least 1 dose of 600 mg rucaparib.6  
The primary outcome measure on which approval was based is investigator-assessed ORR 
per RECIST v1.1, with ORR by central independent radiological review (IRR) conducted 
as a supportive analysis. ORR by investigator was 53.8%, while ORR by IRR was 41.5%, 
confirming the results of investigator assessment for this endpoint.7 Responses were 
durable, indicated by a duration of response (DOR) by investigator assessment of 
approximately 9.2 months. 
While PARP inhibitors have demonstrated consistent robust clinical activity in patients 
with relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy 
and safety of PARPi versus standard of care chemotherapy have been limited. The primary 
purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib versus 
chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious 
BRCA1/2 mutation in their tumor. 
Primary Objective 
To determine investigator-assessed progression-free survival (invPFS) by 
RECIST Version 1.1 for rucaparib versus chemotherapy. 
 


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Secondary Objectives: 
• To evaluate progression-free survival (PFS) by RECIST Version 1.1, as assessed 
by blinded independent central review (BICR; bicrPFS) 
• To compare efficacy of rucaparib versus chemotherapy as measured by overall 
survival (OS) 
• To compare efficacy of rucaparib versus chemotherapy as measured by ORR using 
RECIST Version 1.1 by investigator assessment 
• To compare efficacy of rucaparib versus chemotherapy as measured by DOR by 
investigator assessment 
• To compare efficacy of rucaparib versus chemotherapy as measured by ORR using 
RECIST Version 1.1 by investigator assessment and Gynecologic Cancer 
InterGroup (GCIG) CA-125 response criteria 
• To evaluate patient-reported outcome (PRO) for rucaparib versus chemotherapy as 
assessed by the: 
 European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire (EORTC QLQ)-C30 
 EORTC ovarian cancer module QLQ-OV28 
• To evaluate the safety and tolerability of rucaparib versus chemotherapy 
Exploratory Objectives: 
• To evaluate PFS of study treatment and the subsequent line of treatment received 
(PFS2), both by investigator assessment 
• To evaluate disease control rate (RECIST Version 1.1 complete response [CR], 
partial response [PR], and prolonged stable disease [SD > 12 weeks], by 
investigator assessment) 
• To evaluate PRO utilizing the Euro-Quality of Life 5D (EQ-5D) 
• To assess molecular changes in tumor samples over time in matched pairs 
• To assess circulating cell-free tumor DNA (ctDNA) as a molecular marker of 
efficacy 
• To evaluate the impact of gene expression molecular subgroups on PFS and OS 
• To assess efficacy in BRCA-mutation subgroups (ie, germline/somatic and 
BRCA1/BRCA2) 
• To characterize steady-state trough concentrations of rucaparib 
• To explore the relationship between rucaparib exposure and responses (safety and 
efficacy) 
Study Design 
This is a Phase 3 multicenter, randomized study evaluating rucaparib versus chemotherapy 
for treatment of patients with relapsed, high-grade epithelial serous or Grade 2 or 3 
endometrioid ovarian, fallopian tube, or primary peritoneal ovarian cancer. The study will 
enroll patients with a deleterious BRCA1/2 mutation in their tumor. All patients will be 
required to have received at least 2 prior chemotherapy regimens. Patients with 
platinum-refractory disease (ie, disease progression during or within 4 weeks after last 
dose of the most recent platinum-based chemotherapy) and patients who have received 


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prior PARPi treatment will be excluded. Patients with platinum-resistant (ie, disease 
progression ≥ 1 to < 6 months after the last dose of most recent platinum-based 
chemotherapy) or partially platinum-sensitive disease (ie, disease progression ≥ 6 to 
< 12 months after last dose of most recent platinum-based chemotherapy) will be 
randomized 2:1 to receive either rucaparib or weekly paclitaxel. Patients with 
platinum-sensitive disease (ie, disease progression ≥ 12 months after last dose of most 
recent platinum-based chemotherapy) will be randomized 2:1 to receive either rucaparib or 
platinum-based chemotherapy consisting of the Investigator’s selection of monotherapy 
platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy 
(carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine).  
A 2:1 randomization to receive either rucaparib or chemotherapy will allow for statistical 
comparison of PFS, OS, and ORR between the treatment arms and provide access to 
rucaparib for a larger number of patients who would otherwise receive standard 
chemotherapy. Stratification by progression-free interval after most recent 
platinum-containing therapy (ie, platinum-resistant, partially platinum-sensitive, or 
platinum-sensitive) will occur upon study entry to maintain balance between treatment 
groups.  
The chemotherapy agents that were selected as comparators for this study have 
demonstrated activity in advanced ovarian cancer. Weekly paclitaxel has robust clinical 
activity, a favorable safety profile, and is recommended by the National Comprehensive 
Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines 
for the treatment of relapsed ovarian cancer.8-10 Cisplatin and carboplatin are effective 
single-agent therapies as well as in combination (doublet therapy) with gemcitabine or 
paclitaxel for treatment of ovarian cancer in patients with platinum-sensitive disease as 
recommended by NCCN and ESMO guidelines.8, 10, 11 Therefore, these chemotherapies are 
appropriate comparators to confirm rucaparib benefit for the planned patient population. 
Screening: 
All patients, with the exception of those known to harbor a deleterious BRCA1/2 mutation 
(germline or somatic), will be required to provide archival tumor tissue or a screening 
biopsy for central laboratory analysis prior to enrollment. Tumor analysis will be 
performed using the Foundation Medicine, Inc (FMI) next generation sequencing (NGS) 
test. Results of the FMI panel test will be provided to patients who consent to receive this 
information.  
Patients with a known deleterious BRCA1/2 mutation (germline or somatic) must also 
submit archival tumor tissue for central laboratory testing; however, enrollment is not 
contingent upon central laboratory analysis of tissue before enrollment. A local BRCA1/2 
mutation result from previous testing will be adequate for enrollment. Patients with a 
deleterious BRCA1/2 mutation who meet all other entry criteria will be eligible for the 
study. If archival tissue is not available, the patient may undergo a screening biopsy. 
Additional screening assessments will include demographics and medical history, prior 
treatments for serous or endometrioid epithelial ovarian, fallopian tube, or primary 
peritoneal cancer (and other malignancies, if applicable), prior and current medications and 
procedures, 12-lead ECG, ECOG performance status, local laboratory hematology, serum 
chemistry, and CA-125 measurement, serum pregnancy (for women of childbearing 
potential only), urinalysis, physical examination, height, weight, and vital signs 


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measurements, blood samples for ctDNA and genomic analyses, adverse events, and 
radiologic assessment by computed tomography (CT) or magnetic resonance imaging 
(MRI). Patient-reported outcomes (PRO) will be collected using the EORTC 
QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other collection format as appropriate.  
Randomization: 
Following classification (ie, deleterious BRCA1/2 mutation) detected by FMI (central 
laboratory) analysis or documented local results for deleterious germline or somatic 
BRCA1/2 mutation, with confirmation of adequate tumor tissue availability for known 
deleterious BRCA1/2 mutant patients, and confirmation of all other eligibility criteria in 
the screening phase, patients will be randomized 2:1 to receive rucaparib or chemotherapy.  
Treatment and Follow-up: 
Patients will receive treatment with either rucaparib or chemotherapy until disease 
progression by RECIST Version 1.1, as assessed by the investigator; unacceptable toxicity 
or inability to tolerate further treatment, as assessed by the investigator; pregnancy; death; 
loss to follow-up; withdrawal of consent; or another appropriate clinical reason. Patients 
will receive up to a maximum of 8 cycles of platinum monotherapy or doublet therapy and 
will be followed thereafter until disease progression or other reason for discontinuation. 
CT scans will be submitted to a central imaging vendor to allow for independent review of 
PFS. 
Assessments and procedures during the study will include: AEs; physical examinations; 
12-lead ECGs, vital signs and weight measurements; local laboratory hematology, serum 
chemistry, and CA-125 measurements; serum pregnancy for women of childbearing 
potential; blood samples for ctDNA and genomic analyses (before dosing in Cycles 1 to 6); 
plasma samples for pharmacokinetic (PK) analysis; concomitant medications, therapies, 
and procedures; disease/ tumor assessments; study drug administration and accountability; 
and PRO. Urinalysis will be performed as clinically indicated.  
Patients randomized to chemotherapy have the option to cross over to receive rucaparib 
upon radiological progression per RECIST Version 1.1 following Sponsor (or designee) 
review and approval of the radiology report confirming disease progression. If clinical 
progression is diagnosed, confirmation of disease progression by radiologic assessment per 
RECIST Version 1.1 is required before cross over to rucaparib. If a patient randomized to 
rucaparib has radiologic progression, but continues to derive clinical benefit per the 
investigator, continuation of treatment beyond progression will be permitted. In such cases, 
the documented decision to continue will be made jointly between the investigator and the 
Sponsor (or designee), and the patient must provide consent within a reasonable timeframe 
of the documented decision to continue treatment with rucaparib. The patient will continue 
to have all protocol-required assessments. 
Patients will be followed for safety and efficacy assessments for 28 days after the last dose 
of study drug. An optional tumor biopsy will be collected from patients who experience 
disease progression/discontinue treatment and provide appropriate consent. There will be 
long-term follow-up (LTFU) assessments every 12 weeks (± 14 days) until death, loss to 
follow-up, withdrawal of consent, or study closure. Information regarding subsequent 
treatments, secondary malignancies, and survival will be collected. For patients who have 
not had radiologic disease progression, LTFU will also include tumor scans every 
8 calendar weeks until radiologic disease progression by RECIST Version 1.1, per 


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investigator, death, loss to follow-up, withdrawal, study closure, or initiation of subsequent 
treatment. 
Study Population 
The study will consist of patients with confirmed high-grade serous or Grade 2 or Grade 3 
endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and harbor a 
deleterious BRCA1/2 mutation. Patients with a histology other than serous or endometrioid 
known to harbor a deleterious BRCA1/2 mutation may also be eligible. 
Number of Patients and Sites 
Approximately 345 patients will be enrolled, with 230 patients randomized to rucaparib 
and 115 patients randomized to chemotherapy. 
Study enrollment will be across approximately 100 study sites worldwide. 
Inclusion Criteria 
Eligible patients must meet the following inclusion criteria. Unless otherwise specified, the 
criteria below apply to all patients. 
1. Have signed an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)-approved informed consent form prior to any study-specific evaluation 
2. Be ≥ 18 years of age at the time the informed consent form is signed 
3. Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or 
Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal 
cancer 
a. If mixed histology, > 50% of the primary tumor must be confirmed to be 
high-grade serous or endometrioid upon review by local pathology  
b. Patients with a histology of other than serous or endometrioid are also 
eligible if they are known to harbor a deleterious germline or somatic 
BRCA1/2 mutation 
4. Received ≥ 2 prior chemotherapy regimens, with at least 1 regimen including a 
platinum, and have relapsed or progressive disease as confirmed by radiologic 
assessment 
a. Had documented treatment-free interval of ≥ 6 months following the first 
chemotherapy regimen received 
b. Hormonal agents (eg, tamoxifen, letrozole, etc.), anti-angiogenic agents 
(eg, bevacizumab, pazopanib, cediranib, etc.), and other non-chemotherapy 
agents will not be counted as a chemotherapy regimen for the purpose of 
determining patient eligibility 
c. Agents administered in the maintenance setting will not be counted as a 
separate regimen 
5. Have a deleterious BRCA1/2 mutation as confirmed by the central laboratory. 
Note: patients known to harbor a deleterious germline or somatic BRCA1/2 
mutation based on local assessment may be enrolled without central tissue analysis 
provided there is confirmation that tumor tissue is available to be provided to the 
central laboratory. 


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a. Sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue 
must be available for planned analyses; cytospin blocks from ascites are not 
acceptable 
i. The most recently obtained tumor tissue that is of adequate quality 
(at least 20% tumor content with a minimum of 80% nucleated 
cellular content) should be submitted.  
b. In the event archival tumor tissue is not available, a screening biopsy 
sample may be collected and provided to the central laboratory 
6. Have evaluable disease: ie, at least 1 target or non-target lesion that can be assessed 
per RECIST Version 1.1 
7. Have adequate organ function confirmed by the following laboratory values 
obtained within 14 days prior to randomization: 
a. Bone Marrow Function 
i. Absolute neutrophil count (ANC) ≥ 2.0 × 109/L 
ii. Platelets > 100 × 109/L  
iii. Hemoglobin > 10 g/dL  
b. Hepatic Function 
i. Aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) ≤ 3 × upper limit of normal (ULN); if liver metastases, then 
≤ 5 × ULN 
ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to 
Gilbert’s syndrome 
iii. Serum albumin ≥ 30 g/L (3.0 g/dL) 
c. Renal Function 
i. Serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate 
(GFR) ≥ 45 mL/min using the Cockcroft-Gault formula 
8. Women of childbearing potential must have a negative serum pregnancy test 
≤ 3 days prior to administration of the first dose of study drug 
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 
0 or 1 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study. 
1. Active second malignancy, ie, patient known to have potentially fatal cancer 
present for which she may be (but not necessarily) currently receiving treatment 
a. Patients with a history of malignancy that has been completely treated, with 
no evidence of that cancer currently, are permitted to enroll in the trial 
provided all chemotherapy was completed > 6 months prior and/ or bone 
marrow transplant > 2 years prior to first dose of study drug. Ongoing 
hormonal treatment for previously treated breast cancer is permitted 
2. Prior treatment with any PARP inhibitor, including rucaparib, regardless of 
duration 


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3. Prior treatment with single-agent paclitaxel or nab-paclitaxel  
4. Prior known clinically significant hypersensitivity (per investigator judgement 
despite implementation of a desensitization protocol) to: 
a. paclitaxel treatment for patients with a progression-free interval of 
< 12 months after last platinum-based regimen, or 
b. platinum treatment for patients with a progression-free interval of 
≥ 12 months after last platinum-based regimen 
5. Platinum refractory disease: disease that progressed by radiologic assessment 
during or within 4 weeks after completing treatment with most recent 
platinum-based therapy  
6. Symptomatic and/or untreated central nervous system (CNS) metastases. Patients 
with asymptomatic previously-treated CNS metastases are eligible provided they 
have been clinically stable for at least 4 weeks after completion of therapy 
7. Pre-existing duodenal stent and/ or any gastrointestinal disorder or defect that 
would, in the opinion of the Investigator, interfere with absorption of rucaparib 
8. Known human immunodeficiency virus (HIV) or acquired immunodeficiency 
syndrome (AIDS)-related illness, or history of chronic hepatitis B or C, with 
exception of patients with sustained virologic response after completion of 
treatment for hepatitis C 
9. Women who are pregnant or breast feeding  
10. Received treatment with chemotherapy, radiation, antibody therapy or other 
immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or 
experimental drugs ≤ 14 days prior to first dose of study drug 
11. Ongoing toxicity from prior cancer treatment ≥ Grade 2 by National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
(ongoing Grade 2 non-hematologic toxicity, with the exception of peripheral 
neuropathy, may be permitted with prior advanced approval from Sponsor) 
12. Non study-related minor surgical procedure ≤ 5 days, or major surgical procedure 
≤ 21 days, prior to first dose of study drug; in all cases, the patient must be 
sufficiently recovered and stable before treatment administration 
13. Requires regular blood transfusions, granulocyte colony-stimulating factor, or 
platelet transfusions 
14. Drainage of ascitic fluid 2 or more times in the 4 weeks prior to the first dose of 
study drug, uncontrolled pleural effusion, or permanent drain in place (eg, PleurX®) 
for ascites or pleural effusion 
15. Hospitalization for bowel obstruction within 3 months prior to randomization 
16. Presence of any other condition that may increase the risk associated with study 
participation or may interfere with the interpretation of study results, and, in the 
opinion of the investigator, would make the patient inappropriate for entry into the 
study 


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To be eligible for participation in the crossover part of the study, patients must fulfill the 
following criteria and initiate treatment with rucaparib ≤ 8 weeks after radiologic disease 
progression: 
1. Have documented radiological progression per RECIST Version 1.1 during or 
following completion of comparator arm chemotherapy 
2. Receive Sponsor approval to cross over from chemotherapy to rucaparib treatment 
3. Have adequate hematological and biological function, confirmed by the following 
local laboratory values ≤ 14 days prior to first dose of rucaparib: 
a. Bone Marrow Function 
i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L 
ii. Platelets > 100 × 109/L  
iii. Hemoglobin > 10 g/dL  
b. Hepatic Function 
i. AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 × ULN 
ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to 
Gilbert’s syndrome 
iii. Serum albumin ≥ 30 g/L (3.0 g/dL) 
c. Renal Function 
i. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 45 mL/min using 
the Cockcroft-Gault formula 
4. Grade 3 and 4 hematologic and non-hematologic toxicities (except alopecia, 
nausea, vomiting, or adequately controlled diarrhea) have resolved to baseline or 
≤ CTCAE Grade 1 
5. Women of childbearing potential must have a negative serum pregnancy test 
≤ 3 days prior to administration of the first dose of rucaparib in the crossover  
6. Have an ECOG performance status of 0 or 1 
7. Written consent on an IRB/IEC-approved ICF 
In addition, any of the following will exclude patients from receiving rucaparib in the 
crossover part: 
1. Active second malignancy, ie, patient known to have potentially fatal cancer 
present for which she may be (but not necessarily) currently receiving treatment 
a. Patients with a history of malignancy that has been completely treated, with 
no evidence of that cancer currently, are permitted to enroll in the trial 
provided all chemotherapy was completed > 6 months prior and/ or bone 
marrow transplant > 2 years prior to first dose of study drug (non-melanoma 
skin cancer excepted) 
2. Received treatment with chemotherapy, antibody therapy or other immunotherapy, 
gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs after 
discontinuation of study chemotherapy  


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3. Non study-related minor surgical procedure ≤ 5 days, or major surgical procedure 
≤ 21 days, prior to first dose of rucaparib in the crossover portion; in all cases, the 
patient must be sufficiently recovered and stable before treatment administration 
4. Women who are pregnant or breastfeeding  
5. Withdrawal of consent during treatment with the comparator arm chemotherapy  
6. Presence of any other condition that may increase the risk associated with study 
participation and, in the opinion of the investigator, would make the patient 
inappropriate (including general noncompliance with study procedures during 
treatment with the comparator arm chemotherapy, per investigator judgement) for 
continuing in the study with crossover to rucaparib treatment 
Randomization 
Patients classified as having a deleterious BRCA1/2 mutation by central laboratory 
analysis or documented local results and confirmation of adequate tumor tissue availability 
for known BRCA1/2 mutant patients and confirmation of all other eligibility criteria in the 
screening phase, will be randomized 2:1 to receive rucaparib or chemotherapy. The 
following will be included as a randomization stratification factor at study entry to ensure 
treatment groups are balanced: 
• Platinum resistant: patients who progressed ≥ 1 to < 6 months after the last dose of 
platinum-based chemotherapy; 
• Partially platinum-sensitive: patients who progressed ≥ 6 to < 12 months after last 
dose of platinum-based chemotherapy; and 
• Platinum sensitive: patients who progressed ≥ 12 months after last dose of 
platinum-based chemotherapy. 
Patients with platinum-resistant or partially platinum-sensitive disease will be randomized 
2:1 to receive rucaparib or weekly paclitaxel. Patients with platinum-sensitive disease will 
be randomized 2:1 to receive rucaparib or platinum-based chemotherapy. The investigator 
will select the appropriate platinum monotherapy (carboplatin or cisplatin) or 
platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or 
cisplatin/gemcitabine). Prior to randomization, the Investigator must notify the Sponsor (or 
designee) which platinum chemotherapy a platinum-sensitive patient will receive if 
randomized to the chemotherapy arm.  
Randomization will occur by a central randomization procedure using interactive response 
technology (IRT). 
Study Treatment 
The starting dose of rucaparib is 600 mg BID orally in 28-day cycles. Patients may take 
rucaparib with or without food. Each dose should be taken with at least 8 oz (240 mL) of 
water.  
The starting dose of weekly paclitaxel is 60 to 80 mg/m2 (dose per institutional standard of 
care) administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a 
week break from dosing on Day 22 in each cycle).  


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The dosage and administration of single-agent cisplatin or carboplatin or doublet 
carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion will 
follow institutional guidelines for each agent.  
Chemotherapy will be prepared and administered by study site personnel. 
Treatment will continue until: a maximum of 8 cycles of platinum monotherapy or doublet 
therapy are administered to platinum-sensitive patients; disease progression by 
RECIST Version 1.1, per the investigator; unacceptable toxicity or inability to tolerate 
further treatment, as assessed by the investigator; pregnancy; death; loss to follow-up; 
withdrawal of consent; or other appropriate clinical reason. Eligible patients who were 
randomized to chemotherapy may cross over to rucaparib treatment following disease 
progression and Sponsor (or designee) approval. 
Concomitant Medications 
Premedication should be administered in accordance with standard of care associated with 
the comparator chemotherapy. Additional supportive care may be used at the investigator’s 
discretion and in accordance with institutional procedures. 
Withdrawal Criteria 
A patient must be discontinued from protocol-prescribed therapy if any of the following 
apply: 
• Consent withdrawal for any reason at the patient’s own request or at the request of their 
legally authorized representative; 
• Progression of patient’s underlying cancer per RECIST Version 1.1 (unless, in the 
opinion of the investigator, the patient continues to derive clinical benefit; treatment 
beyond progression must be approved by the Sponsor); 
• Any event, adverse or otherwise, that, in the opinion of the investigator, would pose an 
unacceptable safety risk to the patient 
• An intercurrent illness that, in the opinion of the investigator, would affect assessments 
of the clinical status to a significant degree and requires discontinuation of therapy; 
• Non-compliance by the patient with protocol-mandated procedures; or 
• A positive pregnancy test at any time during the study. 
Efficacy Assessments 
Efficacy measures will include tumor assessments using computed tomography (CT) scans 
of the chest, abdomen, and pelvis with appropriate slice thickness per 
RECIST Version 1.1, CA-125 measurement, and clinical examination; other studies 
(magnetic resonance imaging [MRI], X-ray, positron emission tomography [PET], and 
ultrasound) may also be performed if required. Disease/ tumor assessments will be 
performed during screening, at the end of every 8 calendar weeks relative to Cycle 1 Day 1 
(within 5 days before is permitted) until radiologically confirmed disease progression by 
RECIST Version 1.1, as assessed by the investigator, or death. Patients who cross over to 
treatment with rucaparib will have tumor assessments every 8 calendar weeks relative to 
Day 1 of initiating treatment with rucaparib. Tumor assessments should be performed at 
the time of treatment discontinuation if the reason was other than radiologically-confirmed 
disease progression and it has been ≥ 8 weeks since the last assessment. Patients who have 


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been on study at least 18 months will decrease the frequency of tumor assessments to 
every 16 weeks (within 5 days before is permitted). A CA-125 result < ULN will be 
required to designate a CR. Copies of CT scans (and other imaging, as appropriate) will be 
collected from all patients for BICR. BICR will review CT scans for a given patient in 
batches throughout the conduct of the study, but not necessarily in real-time. All treatment 
decisions will be made by the investigator based on local radiology results. 
Safety Assessments 
Safety and tolerability will be assessed based on the following: 
• Incidence, type, seriousness, and severity of AEs reported; 
• Clinical laboratory investigations (hematology and serum chemistry); 
• Vital signs (blood pressure, heart rate, and body temperature); 
• 12-lead ECGs; 
• Physical examinations; and 
• ECOG performance status 
Statistical Methods 
Sample Size Justification 
Approximately 345 patients will be randomized, with 230 patients randomized to rucaparib 
and 115 patients to chemotherapy. 
The median PFS is assumed to be 12 months for rucaparib and 8 months for the 
comparator. Assuming an accrual over about 3 years; a dropout rate of 2%; with a hazard 
ratio of 0.65; and at least 275 events, a sample size of 345 patients (230 patients 
randomized to rucaparib and 115 patients randomized to chemotherapy) would yield at 
least 80% power at a two-sided 0.05 significance level.  
Efficacy Analysis  
The primary endpoint of invPFS will be analyzed using the stratified Cox proportional 
hazard methodology. The stratified hazard ratio from the Cox proportional hazards model 
will be used to estimate the HR between the randomized treatment groups. 
All efficacy analyses will be performed for the Efficacy Population and the intent-to-treat 
(ITT) Population. The Efficacy Population consists of all randomized patients with a 
deleterious BRCA mutation, excluding those identified to have a BRCA reversion 
mutation, and the ITT Population consists of all randomized patients. 
In order to preserve the overall Type 1 error rate, the primary endpoint will first be tested 
in the Efficacy Population. If the primary endpoint in the Efficacy Population is 
statistically significant, then the primary endpoint in the ITT Population will be tested. If 
the primary endpoint is significant for both populations, then the secondary efficacy 
endpoints will be tested, first in the Efficacy Population and then in the ITT Population in 
the order specified below for each endpoint. Statistical significance will only be declared 
for secondary endpoints if the primary endpoint and previous secondary endpoints are also 
statistically significant. 


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The key secondary endpoints and the testing order are listed below: 
1. ORR by RECIST Version 1.1;  
2. DOR by RECIST Version 1.1; 
3. ORR by RECIST Version 1.1 and CA-125 response; and 
4. PRO as assessed by the EORTC QLQ-C30 Global Health Status score. 
 
Safety Analyses 
Adverse events, clinical laboratory results, vital signs, ECOG performance status, body 
weight, and concomitant medications/ procedures will be tabulated and summarized. 
Adverse events will be summarized overall and separately for serious adverse events 
(SAEs), AEs leading to discontinuation, AEs leading to death, and NCI CTCAE 
Version 4.0 Grade 3 or higher AEs. Body weight and vital signs will be summarized 
descriptively (N, mean, standard deviation, median, minimum, and maximum). ECOG 
performance status will be summarized categorically.  
Independent Data Monitoring Committee (IDMC) 
An IDMC will meet to review the efficacy and safety data from this study. The IDMC will 
review efficacy and safety of rucaparib versus chemotherapy to ensure the study remains 
beneficial to patients.  
The IDMC may recommend that the study be stopped if the data indicate that the invPFS 
benefit will very likely not be achieved or there is excessive toxicity observed in the rates 
of serious and/or Grade 3 and 4 AEs. Details regarding the IDMC will be documented in a 
committee charter. 
Date of Protocol Amendment 2 Approval 
23 October 2020 


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TABLE OF CONTENTS 
1 
SYNOPSIS .........................................................................................................................5 
2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................24 
3 
INTRODUCTION ...........................................................................................................28 
3.1 
Investigational Product ..........................................................................................28 
3.2 
Background and Rationale for PARP Inhibition ...................................................28 
3.3 
Ovarian Cancer ......................................................................................................29 
3.3.1 
Treatment of Ovarian Cancer .......................................................................29 
3.3.2 
PARP Inhibitors in Ovarian Cancer .............................................................31 
3.4 
Prior Experience with Rucaparib ...........................................................................31 
3.4.1 
Nonclinical Experience with Rucaparib ......................................................31 
3.4.2 
Clinical Experience with Rucaparib ............................................................32 
3.5 
Rationale for this Study of Rucaparib ....................................................................37 
4 
STUDY OBJECTIVES ....................................................................................................38 
4.1 
Primary Objective ..................................................................................................38 
4.2 
Secondary Objectives .............................................................................................38 
4.3 
Exploratory Objectives ..........................................................................................38 
5 
INVESTIGATIONAL PLAN ..........................................................................................40 
5.1 
Overall Study Design and Plan ..............................................................................40 
5.1.1 
Screening Phase ...........................................................................................40 
5.1.2 
Assignment / Randomization .......................................................................41 
5.1.3 
Treatment Phase ...........................................................................................41 
5.1.4 
Post-treatment Phase ....................................................................................43 
5.2 
Study Schema.........................................................................................................44 
5.3 
End of Study ..........................................................................................................46 
5.4 
Rationale for Study Design and Control Group .....................................................46 
6 
STUDY POPULATION SELECTION ...........................................................................48 
6.1 
Number of Patients and Sites .................................................................................48 
6.2 
Inclusion Criteria ...................................................................................................48 
6.3 
Exclusion Criteria ..................................................................................................49 
6.4 
Criteria for Rucaparib Crossover Treatment Eligibility Following 
Radiological Progression on or after Comparator Arm Therapy ...........................51 
6.5 
Patients or Partners of Patients of Reproductive Potential ....................................52 
6.6 
Waivers of Inclusion/Exclusion Criteria ................................................................53 
7 
STUDY TREATMENT(S) ..............................................................................................54 
7.1 
Description of Treatment(s) and Storage ...............................................................54 
7.1.1 
Investigational Drug Product - Rucaparib ...................................................54 
7.1.2 
Chemotherapeutic Drug Products ................................................................54 


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7.2 
Packaging and Labeling .........................................................................................54 
7.2.1 
Rucaparib .....................................................................................................54 
7.2.2 
Chemotherapy ..............................................................................................55 
7.3 
Blinding..................................................................................................................55 
7.4 
Method of Assigning Patients to Treatment Groups ..............................................55 
7.5 
Preparation and Administration of Protocol-specified Treatment .........................56 
7.5.1 
Rucaparib .....................................................................................................56 
7.5.2 
Single-agent Weekly Paclitaxel Preparation, Administration, and 
Restrictions ..................................................................................................59 
7.5.3 
Single-agent Cisplatin and Carboplatin Preparation, Administration, and 
Restrictions ..................................................................................................59 
7.5.4 
Platinum-based Doublet Chemotherapy Preparation, Administration, 
and Restrictions ............................................................................................60 
7.5.5 
Re-treatment and Dose Modification for All Chemotherapy ......................60 
7.5.6 
Treatment with Rucaparib beyond Progression ...........................................60 
7.6 
Treatment Compliance ...........................................................................................61 
7.6.1 
Rucaparib Treatment Compliance ...............................................................61 
7.6.2 
Chemotherapy Treatment Compliance ........................................................62 
7.7 
Accountability of Protocol-specified Treatment ....................................................62 
7.8 
Prior and Concomitant Therapy .............................................................................62 
7.8.1 
Anticancer or Experimental Therapy ...........................................................63 
7.8.2 
Hematopoietic Growth Factors and Blood Products ...................................63 
7.8.3 
CYP450 Isoenzyme Inhibitors, Inducers, and Substrates ............................63 
7.8.4 
Transporter Inhibitors, Inducers, and Substrates .........................................63 
7.8.5 
Bisphosphonates ..........................................................................................63 
7.8.6 
Anticoagulants .............................................................................................63 
7.8.7 
Other Concomitant Medications ..................................................................64 
8 
STUDY PROCEDURES AND ACTIVITIES BY VISIT ...............................................65 
8.1 
Schedule of Assessments .......................................................................................65 
8.2 
Informed Consent...................................................................................................74 
8.3 
Initial Study Screening Prior to Randomization ....................................................74 
8.3.1 
Within 60 Days Prior to Randomization ......................................................74 
8.3.2 
Up to 28 Days Prior to Randomization ........................................................75 
8.3.3 
Up to 14 Days Prior to Randomization ........................................................76 
8.3.4 
Up to 3 Days Prior to First Dose of Study Drug ..........................................76 
8.4 
Treatment Phase (Day 1 to Day 28 per Cycle) ......................................................76 
8.4.1 
Day 1 of Every Cycle (Rucaparib and Chemotherapy Arms, Including 
Continuation of Rucaparib Treatment after Radiologic Disease 
Progression) .................................................................................................76 


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8.4.2 
Days 8 and 15 of Every Cycle (Weekly Paclitaxel Arm) ............................78 
8.4.3 
Intra-Cycle (Single-agent Platinum or Doublet Chemotherapy of 
Investigator’s Selection) ..............................................................................79 
8.4.4 
Day 15 of Cycles 1 and 2 (Rucaparib Arm) ................................................80 
8.5 
Post-treatment Phase ..............................................................................................80 
8.5.1 
Randomized Treatment Discontinuation .....................................................80 
8.5.2 
28-Day Safety Follow-up Visit (Randomized Treatment/ Cross Over to 
Rucaparib) ....................................................................................................82 
8.5.3 
Long-term Follow-up (Randomized Treatment/Cross Over to 
Rucaparib) ....................................................................................................83 
8.6 
Informed Consent for Patients Who Cross Over to Rucaparib after Disease 
Progression on Study Chemotherapy .....................................................................84 
8.7 
Screening Prior to Cross Over to Rucaparib ..........................................................84 
8.7.1 
Up to 14 Days Prior to the First Dose of Rucaparib for Crossover 
Patients: ........................................................................................................84 
8.7.2 
Up to 3 Days Prior to First Dose of Rucaparib for Crossover Patients: ......85 
8.8 
Treatment with Rucaparib in Patients Who Cross Over from Chemotherapy 
(Day 1 to Day 28 per Cycle) ..................................................................................85 
8.8.1 
Day 1 of Every Cycle (Crossover to Rucaparib) .........................................85 
8.8.2 
Day 15 of Cycles 1 and 2 (Crossover to Rucaparib) ...................................86 
8.9 
Post-treatment for Patients Who Cross Over to Rucaparib ...................................87 
8.9.1 
Treatment Discontinuation for Patients Who Cross Over to Rucaparib ......87 
9 
METHODS OF DATA COLLECTION ..........................................................................89 
9.1 
Medical History and Demographic/ Baseline Characteristics ...............................89 
9.2 
Prior and Concomitant Medication Assessments ..................................................89 
9.3 
Efficacy Evaluations ..............................................................................................89 
9.3.1 
Disease/ Tumor Assessments .......................................................................89 
9.3.2 
Tumor Markers ............................................................................................90 
9.4 
Safety Evaluations .................................................................................................90 
9.4.1 
Adverse Event Assessment ..........................................................................90 
9.4.2 
Clinical Laboratory Investigations ...............................................................90 
9.4.3 
Vital Signs ....................................................................................................91 
9.4.4 
12-Lead Electrocardiogram .........................................................................92 
9.4.5 
Body Weight and Height .............................................................................92 
9.4.6 
Physical Examinations .................................................................................92 
9.4.7 
ECOG Performance Status ..........................................................................92 
9.5 
Biomarker Analysis – FFPE Tumor Tissue ...........................................................92 
9.6 
Biomarker Analysis – Blood ..................................................................................93 
9.7 
Pharmacokinetics Evaluation .................................................................................93 


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9.8 
Patient Reported Outcomes (Health and Quality of Life Questionnaires) ............94 
10 ADVERSE EVENT MANAGEMENT ...........................................................................95 
10.1 
Definition of an Adverse Event .............................................................................95 
10.2 
Definition of a Serious Adverse Event ..................................................................95 
10.3 
Definition of an Adverse Event of Special Interest ...............................................96 
10.4 
Events or Outcomes Not Qualifying as Serious Adverse Events ..........................96 
10.5 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse 
Events .....................................................................................................................96 
10.6 
Pregnancy or Drug Exposure during Pregnancy ....................................................97 
10.7 
Recording of Adverse Events, Serious Adverse Events, and Adverse Events of 
Special Interest .......................................................................................................97 
10.7.1 
Onset Date of Adverse Events .....................................................................98 
10.7.2 
Resolution Date of Adverse Events .............................................................98 
10.7.3 
Intensity of Adverse Events .........................................................................98 
10.7.4 
Causal Relationship of Adverse Events to Study Drug ...............................98 
10.7.5 
Outcome and Action Taken .........................................................................99 
10.8 
Follow-Up of Adverse Events, Serious Adverse Events, and Adverse Events 
of Special Interest ................................................................................................100 
10.9 
Potential Drug-induced Liver Injury ....................................................................100 
10.10 Regulatory Aspects of Serious Adverse Event and Adverse Events of Special 
Interest Reporting.................................................................................................100 
11 PLANNED STATISTICAL METHODS ......................................................................102 
11.1 
General Considerations ........................................................................................102 
11.2 
Determination of Sample Size .............................................................................102 
11.3 
Analysis Populations ............................................................................................103 
11.4 
Patient Disposition ...............................................................................................103 
11.5 
Demographics and Baseline Characteristics ........................................................103 
11.6 
Efficacy Analyses ................................................................................................104 
11.6.1 
Primary Efficacy Analyses ........................................................................104 
11.6.2 
Secondary Efficacy Analyses ....................................................................104 
11.6.3 
Exploratory Efficacy Analyses ..................................................................105 
11.6.4 
Exploratory Pharmacokinetic Analyses .....................................................106 
11.7 
Safety Analyses ....................................................................................................106 
11.7.1 
Adverse Events ..........................................................................................107 
11.7.2 
Clinical Laboratory Evaluations ................................................................108 
11.7.3 
Vital Sign Measurements ...........................................................................108 
11.8 
Interim Analysis ...................................................................................................109 
12 PATIENT DISPOSITION .............................................................................................110 
12.1 
Removal of Patients from the Study or Study Drug ............................................110 


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13 STUDY ADMINISTRATION ......................................................................................111 
13.1 
Regulatory and Ethical Considerations ................................................................111 
13.1.1 
Regulatory Authority Approvals................................................................111 
13.1.2 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) Approval ..........................................................................................111 
13.2 
Patient Information and Consent .........................................................................112 
13.3 
Patient Confidentiality .........................................................................................112 
13.4 
Study Monitoring .................................................................................................113 
13.5 
Case Report Forms and Study Data .....................................................................113 
13.6 
Independent Data Monitoring Committee ...........................................................114 
13.7 
Study Termination and Site Closure ....................................................................114 
13.8 
Modification of the Study Protocol......................................................................115 
13.9 
Retention of Data .................................................................................................115 
13.10 Quality Control and Assurance ............................................................................116 
13.10.1 Changes to the Protocol and Deviations ....................................................116 
13.10.2 Study Site Training and Ongoing Monitoring ...........................................116 
13.10.3 Direct Access to Source Data/ Documents for Audits and Inspections .....117 
13.11 Clinical Study Report ...........................................................................................117 
13.12 Publication and Disclosure Policy .......................................................................117 
13.13 Investigator Oversight ..........................................................................................117 
14 REFERENCE LIST .......................................................................................................118 
15 APPENDICES ...............................................................................................................123 
15.1 
Appendix 1 ...........................................................................................................123 
15.2 
Appendix 2 ...........................................................................................................128 
15.3 
Appendix 3 ...........................................................................................................129 
15.4 
Appendix 4 ...........................................................................................................130 
15.5 
Appendix 5 ...........................................................................................................131 
 
 
 


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LIST OF IN-TEXT TABLES 
Table 1. Treatments by Progression-free Interval after Most Recent Platinum .....................42 
Table 2. Rucaparib Formulation and Storage .........................................................................54 
Table 3. Rucaparib Dose Reduction Steps ..............................................................................59 
Table 4. Schedule of Assessments for All Patients (Randomization to Therapy at Study 
Initiation) ..................................................................................................................66 
Table 5. Schedule of Assessments for Patients Who Cross Over to Rucaparib After 
Being Randomized to and Receiving Chemotherapy ...............................................71 
 
LIST OF IN-TEXT FIGURES 
Figure 1. Study Schema ...........................................................................................................45 
 
 


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2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALCOA+ 
attributable, legible, contemporaneous, original or certified copy, accurate, and 
complete, consistent, enduring, and available 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
AUC0-24 
area under the plasma concentration-time curve from 0 to 24 hours 
BCRP 
breast cancer resistance protein 
BER 
base excision repair 
BICR 
blinded independent central review 
BID 
twice a day 
bp 
base-pair 
BRCA 
breast cancer 1 or breast cancer 2 
BRCA 1/2 
breast cancer gene 1 or breast cancer gene 2 
CI 
confidence interval 
CL 
clearance 
CL/F 
apparent total clearance of drug after oral administration 
cm 
centimeter 
Cmax 
maximum plasma concentration 
CR 
complete response 
CRF 
case report form 
CRM 
continual reassessment model 
CRP 
C-reactive protein 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
circulating cell-free tumor DNA 
CV 
coefficient of variation 
CYP 
cytochrome P450 
DILI 
drug-induced liver injury 
DLT 
dose-limiting toxicities 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EC50 
concentration producing 50% of maximum effect 


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ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EMA 
European Medicines Agency 
EOC 
epithelial ovarian cancer 
EORTC 
QLQ-C30 
European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire C30 
EORTC 
QLQ-OV28 
European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire Ovarian Cancer Module OV28 
EQ-5D 
Euro-Quality of Life 5D 
ESMO 
European Society for Medical Oncology 
F 
bioavailability 
FD & C 
colorants that have been approved by the Food and Drug Administration for use in 
food, drugs and cosmetics 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FMI 
Foundation Medicine, Inc. 
gBRCA 
germline breast cancer gene 1 or 2 mutation 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
H & E 
hematoxylin and eosin 
HDPE 
high-density polyethylene 
HPMC 
hydroxypropyl methylcellulose 
HGSOC 
high-grade serous ovarian cancer 
HNSTD 
highest non-severely toxic dose 
HPLC 
high-performance liquid chromatography 
hr 
hour 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
HRR 
homologous recombination repair 
IC50 
50% inhibitory concentration 
ICH 
International Council for Harmonisation 
IRR 
independent radiology review 
IRT 
interactive response technology 
ITT 
intent-to-treat 
IV 
intravenous 
Ki 
inhibition constant 
Kic 
inhibition constant competitive 
LOH 
loss of heterozygosity 
LTFU 
long-term follow-up 


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MATE 
multidrug and toxin extrusion transporter 
MDR1 
multidrug resistance protein 1 
MDS 
myelodysplastic syndrome 
mRNA 
messenger ribonucleic acid 
MRP 
multidrug resistance associated protein 
MS 
mass spectrometry 
MTD 
maximum tolerated dose 
NAD 
nicotinamide adenine dinucleotide 
NADPH 
nicotinamide adenine dinucleotide phosphate 
NCCN 
National Comprehensive Cancer Network 
NOAEL 
no-observed-adverse-effect level 
NOEL 
no-observed-effect-level 
OAT 
organic ion transporter 
OCT 
organic cation transporter 
ORR 
objective response rate 
Papp 
apparent permeability coefficient 
PARPi 
poly(ADP-ribose) polymerase inhibitor 
PD 
progressive disease (in context of disease monitoring) 
PD 
pharmacodynamic (in context of pharmacology discussion) 
PDX 
patient-derived xenograft 
PEG 
polyethylene glycol 
PFS 
progression-free survival 
PFS2 
the second event of PFS, in subsequent line of treatment 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PLD 
pegylated liposomal doxorubicin 
PO 
orally 
PR 
partial response 
PRO 
patient-reported outcome 
PV 
pharmacovigilance 
QD 
once a day 
RAD51C 
RAD51 homolog C 
RAD51D 
RAD51 homolog D 
RBC 
red blood cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
sBRCA 
somatic breast cancer gene 1 or 2 mutation 


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SD 
stable disease (in context of disease monitoring) 
SD 
standard deviation (in context of biostatistics) 
SOC 
system organ class 
t1/2 
terminal half-life 
tBRCA 
tumor tissue alteration in BRCA1 or BRCA2, includes gBRCA and sBRCA 
TK 
toxicokinetics 
Tmax  
time of occurrence of Cmax 
TMZ 
Temozolomide 
UGT 
uridine diphosphate-glucuronosyl transferase 
UK 
United Kingdom 
ULN 
upper limit of normal 
US 
United States 
USAN 
United States Adopted Name 
USP 
US Pharmacopeia 
Vss 
volume of distribution at steady-state 
WBC 
white blood cell 
wt 
wild-type 
 


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3 
INTRODUCTION 
3.1 
Investigational Product 
Rucaparib (CO-338) is a small molecule inhibitor of poly (adenosine diphosphate 
[ADP]-ribose) polymerase (PARP) being developed for the treatment of ovarian cancer 
associated with homologous recombination deficiency (HRD). Rucaparib has been shown to 
potently inhibit PARP-1, PARP-2, and PARP-3 and has demonstrated activity in a 
background of breast cancer gene 1 and 2 (BRCA1 and BRCA2) mutations in both clinical 
and nonclinical studies. 
Clovis Oncology, Inc. (Clovis) is developing rucaparib for oral administration in patients 
with relapsed ovarian cancer who have a BRCA mutation based on analysis of tumor tissue 
DNA. The therapeutic rationale for PARP inhibition with rucaparib in the presence of HRD 
is induction of synthetic lethality.  
3.2 
Background and Rationale for PARP Inhibition 
Normal cells repair single-strand breaks in DNA primarily through base excision repair 
(BER). While there are several variations of BER, all pathways rely on PARP enzymes, of 
which PARP-1 is the best characterized. Single-strand breaks that are not repaired result in 
stalled replication forks and the development of double-strand breaks, which are primarily 
repaired by homologous recombination repair (HRR) of DNA, a complex process involving 
multiple proteins, including those encoded by BRCA1 and BRCA2, as well as RAD51, 
Fanconi anemia core complex, ataxia telangiectasia mutated (ATM), and ataxia telangiectasia 
and RAD3-related (ATR) protein, among others. 
Defects in the HRR pathway (ie, HRD), either as an initiating or late event in carcinogenesis, 
may be responsible for the genetic instability observed in many cancers. It has been 
estimated that approximately 50% of high-grade serous ovarian cancer (HGSOC) has 
alterations in the HRR pathway.12 Germline mutations in the BRCA1 and BRCA2 genes 
(gBRCA1/2) are the strongest known hereditary factors for epithelial ovarian cancer (EOC), 
accounting for up to 15% of all EOC.13, 14 Epithelial ovarian cancer patients carry 
heterozygous deleterious mutations in their germline DNA and develop tumors when the 
remaining wild-type functional allele is inactivated (ie, “second hit”). Approximately 6% to 
8% of HGSOC patients have somatic mutations in BRCA1 or BRCA2 (sBRCA1/2).12, 15 
However, HRD is not limited to mutations of BRCA1/2. Approximately 27% of HGSOC 
patients have an alteration in an HRR gene other than BRCA1/2 or due to other molecular 
alteration or modification (eg, epigenetic silencing). 
Inhibition of DNA damage repair in cancer cells, which are intrinsically genetically unstable, 
represents an attractive opportunity for therapeutic development. Given the overlap in 
various DNA repair pathways, inhibition of a single pathway is unlikely to have a significant 
effect. Inhibition of multiple DNA repair pathways in parallel, such as having a deleterious 
mutation in a critical BER gene in the presence of a PARP inhibitor, may lead to cell death, a 
concept known as synthetic lethality. Normal cells, with only one DNA repair pathway 
affected by inhibition of PARP, still have an intact DNA repair pathway that can compensate 


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for the defect. This concept of synthetic lethality has been demonstrated in key in vitro and 
in vivo studies, as well as in several clinical trials with PARP inhibitors.16-21  
While up to 15% of patients may have a hereditary form of ovarian cancer (based on 
germline mutations), approximately 6% to 8% of HGSOC patients have sBRCA1/2 
mutations.12, 15 Both gBRCA1/2 and sBRCA1/2 mutations result in HRD, and patients whose 
tumors harbor these mutations derive clinical benefit from PARP inhibitor therapy.22 
Collectively, these mutations comprise a group known as tumor BRCAmut (tBRCAmut). 
Patients without evidence of a gBRCA1/2 or sBRCA1/2 mutation also derive benefit from 
PARP inhibitor treatment.22, 23 The molecular signature associated with PARP inhibitor 
response in a BRCA wild-type (BRCAwt) setting is not yet fully understood, but may be 
linked to other mechanisms of HRD.  
3.3 
Ovarian Cancer 
Globally, ovarian cancer is the eighth most common cancer and the seventh leading cause of 
cancer death among women, responsible for approximately 140,000 deaths each year.1 
Additionally, it is the second most common gynecologic malignancy worldwide and the 
leading cause of death attributed to gynecological cancer.2, 3 Unfortunately because of 
delayed presentation and diagnosis, almost 75% of women with ovarian cancer are diagnosed 
with stage III/IV disease and 75% of women with advanced stage disease ultimately relapse 
or die from their disease despite treatment.1 
After initial therapy, most women will have a progression-free interval of approximately 
1.5 to 2 years, depending on the extent of post-operative residual disease and response to 
chemotherapy.24 Relapse still occurs; however, in the majority of cases, and only 10% to 
30% of women experience long-term survival.24 Advanced stage disease is associated with a 
5 year survival rate of only 30% to 40%.2  
Approximately 90% of ovarian tumors are surface epithelial in origin, and the papillary 
serous histology subtype accounts for approximately 75%, of which the large majority (70%) 
is high-grade.24 The site of origin of EOC remains unclear. Some studies suggest that serous 
EOC and primary peritoneal cancer (PPC) arise from the fallopian tube epithelium; however, 
other studies suggest an origin within stem cells of the ovarian surface epithelium.24-28 EOC, 
PPC and fallopian tube cancer behave very similarly and are therefore treated in the same 
way. 
The median age at presentation of EOC is 60 years. Due to the non-specific nature of 
symptoms, many women present with advanced disease and therefore have a poor prognosis. 
3.3.1 
Treatment of Ovarian Cancer 
The standard approach to treatment of advanced HGSOC is cytoreductive surgery (either at 
time of diagnosis or interval debulking), with the goal of minimizing residual tumor to no 
visible residual disease, a major prognostic indicator for improved survival. Six to 8 cycles of 
platinum- and taxane-based chemotherapy is the global standard of care. If initial 
cytoreduction is not performed, interval debulking surgery is considered. This surgery may 


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be carried out after 3 or 4 cycles of primary chemotherapy, followed by 3 further cycles of 
chemotherapy. Platinum analogues, such as carboplatin and cisplatin, are the most active 
agents, mediating their effects through the formation of inter- and intra-strand cross-links 
with DNA.24, 29  
Despite a 70-80% initial response rate, most women have disease relapse.3-5 The choice of 
treatment for relapsed disease is based on the treatment-free interval relative to last therapy 
administered and chemotherapy agents used. Platinum-based regimens dominate ovarian 
cancer therapy and define treatment groups.30 In general, patients whose disease progresses 
during treatment with a platinum-based regimen are considered to have platinum-refractory 
disease; patients whose disease relapses within 6 months after the last platinum agent was 
administered are considered to have platinum-resistant disease; and patients whose disease 
relapses more than 6 months after last platinum-based therapy was administered are 
considered to have platinum-sensitive disease. However, these classifications are somewhat 
arbitrary as resistance to platinum-based therapy is a time continuum, not a categorical 
variable, and a status of ‘platinum-resistant’ is not absolute as it can be partially overcome. In 
addition, ‘platinum-sensitivity’ was defined when there was no alternative to platinum-based 
treatment and in clinical practice typically only refers to second-line treatment. These 
definitions also do not take into account the molecular characteristics of a patient’s tumor 
(ie, HRD such as BRCA1/2 mutations) and thus are used as a guide to define platinum status 
in this study.  
Treatment decisions for relapsed ovarian cancer are driven in part by type of response 
achieved and the duration between completion of treatment and disease relapse. Patients with 
platinum-sensitive disease are typically retreated with platinum-based therapy until they no 
longer respond to or can no longer tolerate such treatment.3-5 Patients with platinum-resistant 
disease receive single-agent treatment with pegylated liposomal doxorubicin (PLD), 
topotecan, gemcitabine, or weekly paclitaxel, or a combination of bevacizumab and 
chemotherapy (paclitaxel, PLD, or topotecan).31-33 However, these agents have limited utility 
due to poor efficacy (objective response rates ranging 20-30% with median progression-free 
survival [PFS] < 6 months) and significant toxicities. In later lines of therapy, treatment 
choice is often restricted according to the individual patient situation (eg, performance status, 
organ function, residual toxicities from prior treatment, other comorbidities, and patient 
choice). 
As many patients experience multiple relapses, prognosis and response to therapy decreases 
as the interval between last chemotherapy exposure and disease relapse shortens. The 
treatment-free, or specifically the platinum-free interval, provides further prognostic 
information for patients, as therapeutic options lessen and survival shortens as a patient’s 
tumor becomes less responsive to repeated courses of platinum-based therapy. Patients who 
have received several prior lines of treatment are known to have strongly diminished 
treatment-free intervals and response rates and the benefits of continued treatment with 
conventional chemotherapy often does not outweigh the risk of hypersensitivity and 
additional, intolerable toxicity. This patient population is a group with limited treatment 
options, so the development of therapies that offer improved benefit-risk is critically needed 
that could benefit from treatment with a targeted agent that takes the molecular 
characteristics of their disease into account.34, 35  


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3.3.2 
PARP Inhibitors in Ovarian Cancer 
Refer to current Investigator’s Brochure for comprehensive information on PARP 
inhibitors. 
PARP inhibitors have demonstrated clinical activity in patients with BRCA1/2-mutant 
tumors, and have emerged as a new treatment option for relapsed ovarian cancer. In the 
United States (US), olaparib was approved 19 December 2014 for treatment of patients with 
gBRCA1/2 ovarian cancer who had received ≥ 3 prior chemotherapy regimens 
(http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206162lbl.pdf) based on results 
of a Phase 2 study.36 Rucaparib was subsequently approved in the US for use in women with 
a BRCA mutation (germline or somatic) who had received at least 2 prior chemotherapy 
regimens, based on a response rate of 54%. 
PARP inhibitor maintenance therapy has also been established as an effective strategy for 
improving outcomes in recurrent, second-line and beyond, platinum-sensitive ovarian cancer. 
As of January 2019, rucaparib, niraparib, and olaparib were all approved as second-line 
switch maintenance therapies for ovarian cancer patients in the US37-39 and Europe.40-42 
Three randomized, double-blind studies demonstrated statistically significant improvements 
in median progression-free survival (PFS) as compared to placebo in the ITT Population 
regardless of BRCA1/2 mutation or HRD status (Study 19, NOVA, and ARIEL3).43-45 
Study 19 was the first study to show that the outcomes of somatic BRCA (sBRCA)-mutant + 
gBRCA-mutant patients were the same as gBRCA-mutant patients alone, suggesting that it is 
appropriate to not differentiate between germline and somatic mutations. These switch 
maintenance studies also demonstrated statistically significant benefit in the overall 
unselected patient population. Recently, olaparib38, 41 and niraparib39, 42 were also approved 
as front-line switch maintenance for ovarian cancer patients in US and Europe. 
In the European Union (EU), olaparib is approved as maintenance treatment following a 
response to platinum-based chemotherapy in patients with BRCA1/2-mutant (germline or 
somatic) relapsed ovarian cancer who received at least 2 prior platinum-based regimens. 
(http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/ 
human/medicines/003726/human_med_001831.jsp&mid=WC0b01ac058001d124). Olaparib 
has also demonstrated clinical activity in patients without a BRCA1/2 mutation21, 46, 47; 
however, the molecular signature associated with olaparib response in those trials was not 
fully understood. 
3.4 
Prior Experience with Rucaparib 
Refer to the current Investigator’s Brochure for comprehensive nonclinical and clinical 
information for rucaparib.  
3.4.1 
Nonclinical Experience with Rucaparib 
The results from nonclinical studies are consistent with the anticipated mechanism of action 
and pharmacological effects of PARP inhibition. Further information can be found in the 
rucaparib IB.  


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Pharmacological assessment demonstrated that rucaparib is a potent and selective inhibitor of 
PARP-1, PARP-2, and PARP-3 and has robust and durable in vitro and in vivo activity in 
multiple BRCA1/2 mutant cell lines and xenograft models. Rucaparib was also active in a 
BRCA wild-type model, consistent with in vitro data suggesting that rucaparib is active in 
cells with other defects in HRR through synthetic lethality. In vitro screens suggested that 
rucaparib has a limited potential for off-target effects. Safety pharmacology studies suggest 
that when given orally, rucaparib poses a low-risk for causing neurobehavioral and cardiac 
effects in patients. 
In pharmacokinetic (PK) studies, rucaparib demonstrated species-dependent oral 
bioavailability, moderate plasma protein binding, and large volumes of distribution in 
nonclinical species. As a P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) 
substrate, rucaparib demonstrated minimal penetration of rucaparib-derived radioactivity 
through the blood-brain barrier. In vitro data suggested slow metabolism by cytochrome 
P450 enzymes, with CYP2D6 and to a lesser extent CYP1A2 and CYP3A4 contributing to 
the metabolism of rucaparib. Rucaparib was mainly excreted in feces in rats and dogs. 
Rucaparib reversibly inhibited CYP1A2, CYP2C9, CYP2C19, and CYP3A, and to a lesser 
extent CYP2C8, CYP2D6, and UDP-glucuronosyltransferase 1A1 (UGT1A1). Rucaparib 
induced CYP1A2, and down-regulated CYP2B6 and CYP3A4 in human hepatocytes at 
clinically relevant exposures. Rucaparib is a potent inhibitor of multidrug and toxin extrusion 
1 (MATE1) and MATE2-K, a moderate inhibitor of organic cationic transporter 1 (OCT1), 
and may inhibit P-gp and BCRP in the gut. 
Oral dosing of rucaparib in single and repeat dose toxicity studies in rats and dogs resulted in 
toxicity to the hematopoietic, lymphopoietic, and gastrointestinal (GI) systems. These 
toxicities were generally both reversible upon recovery and predictive of toxicities observed 
in patients. Rucaparib was shown to be clastogenic in an in vitro chromosomal aberration 
assay suggesting potential genotoxicity in humans. Reproductive and development toxicity 
studies in rat showed that rucaparib caused maternal toxicity and was embryo-toxic. 
Although no rucaparib related effects on sperm total count, density, motility, or morphology 
were identified, based on published studies, PARP inhibitors have the potential to impair 
spermatogenesis and reduce fertility.48-51  
3.4.2 
Clinical Experience with Rucaparib 
Information regarding clinical studies with rucaparib is available in the current 
Investigator’s Brochure. 
Rucaparib is being evaluated in Phase 1, 2, and 3 clinical studies in patients with advanced 
cancer who have evidence of HRD. Rucaparib clinical studies have/are evaluating patients 
with relapsed, high-grade ovarian, fallopian tube, or primary peritoneal cancer in both the 
treatment and maintenance settings.  
Rucaparib is also being evaluated as treatment for patients with metastatic castration-resistant 
prostate cancer (mCRPC) associated with HRD, both as monotherapy and in combination 
with nivolumab. 


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Clinical pharmacology studies in patients with advanced solid tumors continue to more fully 
characterize rucaparib drug-drug interactions, mass balance and drug metabolism, as well as 
PK in special populations. 
Additional studies of rucaparib as monotherapy and in combination with other anticancer 
therapies are planned in ovarian and prostate cancer, as well as other tumor types. 
Additional information on the clinical studies is provided in the rucaparib IB. 
3.4.2.1 
Overview of Pharmacokinetics and Drug-Drug Interactions 
Assessment of rucaparib PK in cancer patients showed an approximate dose proportional 
exposure after once a day (QD) or twice a day (BID) dosing, rapid absorption with maximum 
plasma concentration (Cmax) achieved within 1.5 to 6 hours, and distribution into tissue. The 
oral bioavailability was 36% and elimination half-life (t1/2) ranged from 11 to 29.8 hours. 
Rucaparib was moderately bound to human plasma proteins in vitro. 
At a dose of 600 mg BID rucaparib, steady state was achieved after approximately 1 week. A 
high-fat meal increased the Cmax and AUC0-24h of rucaparib by 20% and 38%, respectively, as 
compared with that under fasted conditions. 
In vitro, CYP enzymes were shown to contribute to rucaparib metabolism. In a preliminary 
assessment of rucaparib metabolism in patients, rucaparib biotransformation pathways 
included hydroxylation or oxidation, N-demethylation, deamination, and phase II 
methylation. A carboxylic acid metabolite (M324) and a phase II N-methylated metabolite of 
M324 (M338) were identified as major metabolites. 
Drug interactions with rucaparib as a substrate were assessed in a population PK (Pop PK) 
analysis. CYP2D6 phenotypes (poor metabolizers, intermediate metabolizers, normal 
metabolizers, and ultra-rapid metabolizers) and CYP1A2 phenotypes (normal metabolizers 
and hyper-inducers) did not significantly impact the steady-state exposure of rucaparib at 
600 mg BID. Concomitant administration of strong CYP1A2 or CYP2D6 inhibitors did not 
significantly impact rucaparib PK. Current smokers had overlapping rucaparib exposures as 
compared to nonsmokers and former smokers. Collectively, the results suggest that CYP1A2 
and CYP2D6 play limited role in rucaparib metabolism, and no rucaparib dose adjustment is 
needed when concomitantly administered with CYP1A2 or CYP2D6 inhibitors. 
No clinically significant effect of concomitant administration of strong P-gp inhibitors on 
rucaparib PK was observed. Concomitant treatment with proton pump inhibitors did not 
show clinically significant effect on rucaparib PK. No dose modification is recommended 
based on concomitant use of P-gp inhibitors or PPIs. 
In a “cocktail” DDI study (CO-338-044), the effects of steady-state rucaparib at 600 mg BID 
on CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp were evaluated with single oral doses 
of sensitive probes (caffeine [CYP1A2], S-warfarin [CYP2C9], omeprazole [CYP2C19], 
midazolam [CYP3A4], and digoxin [P-gp], respectively). Data suggest that rucaparib is a 
moderate inhibitor of CYP1A2, a weak inhibitor of CYP2C9, CYP2C19, and CYP3A. 
Rucaparib also marginally inhibits P-gp, and the effect is unlikely to be clinically significant. 


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In another DDI study (Study CO-338-095) in cancer patients, effects of rucaparib on oral 
rosuvastatin as BCRP substrate and oral contraceptives were determined following 14 days 
of dosing at 600 mg BID. Rucaparib weakly inhibited BCRP and caused mild increases in 
plasma exposures to ethinylestradiol and levonorgestrel. 
In Study CO-338-078, PK of a single-dose rucaparib was compared between cancer patients 
with normal hepatic function and moderate hepatic impairment. Patients with moderate 
hepatic impairment showed an approximately 46% increase in area under the concentration-
time curve from 0 to infinity (AUC0-inf) without apparent change in Cmax. 
Details of these clinical DDI studies are provided in the rucaparib IB. 
3.4.2.2 
Overview of Efficacy 
Evaluation of rucaparib efficacy has largely focused on patients with advanced ovarian 
cancer in both the treatment and maintenance settings. A summary of efficacy data from 
two fully-enrolled, ongoing single-arm Phase 2 studies (Study CO-338-010 Part 2A; 
Study CO-338-017 Parts 1 and 2) evaluating rucaparib efficacy in the treatment setting of 
ovarian cancer, and from one fully-enrolled, ongoing Phase 3 study (Study CO-338-014) 
evaluating rucaparib efficacy compared to placebo in the maintenance setting of ovarian 
cancer is provided below.  
Additional efficacy data for rucaparib in ovarian cancer, in other tumors, and in combination 
with chemotherapy (completed studies in early development) are provided in the rucaparib 
IB. 
In both the treatment and maintenance setting of advanced ovarian cancer, rucaparib 
administered at the starting dose of 600 mg BID demonstrated robust clinical activity. 
Ovarian Cancer Treatment Indication 
On 19 December 2016, FDA granted accelerated approval for the marketing of rucaparib 
(Rubraca®) for monotherapy treatment of patients with deleterious BRCA mutation (germline 
and/or somatic) associated advanced ovarian cancer who have been treated with 
≥ 2 chemotherapies. The recommended dose of rucaparib is 600 mg BID.  
The basis for the approval of rucaparib as monotherapy for the treatment of ovarian cancer 
are the datasets and analyses for patients with EOC, FTC, or PPC comprising the primary 
efficacy analysis population. The primary efficacy analysis population included 106 patients 
pooled from the open-label, single-arm Phase 2 studies, Study CO-338-010 (Study 10) 
Part 2A and Study CO-338-017 (ARIEL2) Parts 1 and 2, with BRCA-mutant ovarian cancer 
[EOC, FTC, or PPC], who had received ≥ 2 prior chemotherapy regimens, at least 2 of which 
were platinum-based, and who had received at least 1 dose of 600 mg rucaparib.6  
The primary outcome measure on which approval was based is investigator-assessed ORR 
per RECIST v1.1, with ORR by central independent radiological review (IRR) conducted as 
a supportive analysis. ORR by investigator was 53.8%, while ORR IRR was 41.5%, 
confirming the results of investigator assessment for this endpoint.52 Responses were durable, 


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indicated by a duration of response (DOR) by investigator assessment of approximately 
9.2 months. 
Ovarian Cancer in the Maintenance Setting 
In the maintenance setting of rucaparib monotherapy for treatment of patients with EOC, 
FTC, or PPC, the results of Study CO-338-014 (ARIEL3) clearly demonstrate that rucaparib 
offers significant benefit compared to placebo. For the primary endpoint of 
investigator-assessed (invPFS), the median PFS was significantly prolonged by rucaparib 
compared to placebo; a result demonstrated across the tBRCA, HRD (tBRCA + non-tBRCA 
LOHhigh), and ITT populations (p < 0.0001 for each population). 53 The median invPFS for 
the 3 analysis populations ranged from 10.8 months to 16.6 months following rucaparib 
treatment and was consistently 5.4 months for the placebo group, regardless of the population 
analyzed, with a hazard ratio (HR) = 0.231 for the tBRCA subpopulation (p < 0.0001), 
HR = 0.317 for the HRD subpopulation (p < 0.0001), and HR = 0.365 for the ITT population 
(p < 0.0001). The benefit of rucaparib in terms of tumor response was observed early in 
treatment. The invPFS results were confirmed by a key, stand-alone secondary endpoint 
analysis of PFS assessed by blinded independent central review (BICR; bicrPFS); each 
population receiving rucaparib had a statistically significant prolonged median bicrPFS 
compared to placebo. 
The overall response rate (ORR) per RECIST v1.1, as assessed by the investigator, was 
analyzed in the subgroup of patients who had measurable disease (ie, measurable target 
lesions) at baseline. In the tBRCA population, the confirmed ORR was 15/40 (37.5%) for the 
rucaparib group and 2/23 (8.7%) for the placebo group (p = 0.0055). In the HRD population, 
the confirmed ORR was 23/85 (27.1%) for the rucaparib group and 3/41 (7.3%) for the 
placebo group (p = 0.0031), and in the ITT population, the confirmed ORR was 
26/141 (18.4%) for the rucaparib group and 5/66 (7.6%) for the placebo group (p = 0.0069). 
Results of the exploratory endpoint of ORR, along with that of invPFS in the non-nested 
populations, support the clinically meaningful impact of delaying disease recurrence in 
women with advanced ovarian cancer, and show a further response to rucaparib treatment in 
patients with measurable disease. 
3.4.2.3 
Overview of Safety 
Consistent with the efficacy evaluation of rucaparib, evaluation of rucaparib safety has 
largely focused on patients with advanced ovarian cancer in both the treatment and 
maintenance settings. A summary of safety data from 2 fully-enrolled, ongoing single-arm 
Phase 1/2 studies (Study CO-338-010 Part 2A and Part 2B; Study CO-338-017 Part 1 and 
Part 2) evaluating rucaparib safety in the treatment setting of ovarian cancer, and from one 
fully-enrolled, ongoing Phase 3 study (Study CO-338-014) evaluating rucaparib efficacy 
compared to placebo in the maintenance setting of ovarian cancer is provided below. 
Additional safety data for rucaparib in ovarian cancer, in other tumors, and in combination 
with chemotherapy (completed studies in early development) are provided in the rucaparib 
IB. 


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The safety profile of rucaparib is similar in ovarian cancer patients treated with rucaparib in 
either the treatment or maintenance setting. 
Integrated Safety Analysis in Ovarian Cancer 
The most recent integrated safety information for the treatment indication is provided in the 
rucaparib IB. Pooled safety data are provided as of the 01 September 2017 cut-off date for 
the ongoing Studies CO-338-010 (Parts 2A and 2B) and CO-338-017 (ARIEL2; Parts 1 and 
2), in which 545 patients with relapsed ovarian cancer received 600 mg BID rucaparib. 
Safety data in the maintenance setting are provided as of the 15 April 2017 cut-off date for 
Study CO-338-014 (ARIEL3), in which a total of 561 patients have been treated 
(372 patients in the rucaparib group and 189 patients in the placebo group). 
Patients with ovarian cancer who received 600 mg BID rucaparib in treatment setting as well 
as in the maintenance setting), the most common TEAEs reported were primarily mild to 
moderate (Grade 1-2) in severity and include gastrointestinal disorders (nausea, vomiting, 
diarrhea, constipation, and abdominal pain), asthenia/fatigue, decreased appetite, and 
dysgeusia. The most common TEAE ≥ Grade 3 include anemia/decreased hemoglobin, 
ALT/AST increased, neutropenia/decreased ANC, and asthenia/fatigue. 
The laboratory abnormalities were consistent with the TEAEs, with decreased hemoglobin 
(and associated increase in mean corpuscular volume and mean corpuscular hemoglobin), 
increased ALT, increased AST, and increased serum creatinine, being most common. 
Decreased platelets, neutrophils, leukocytes, lymphocytes and increased cholesterol were 
observed to a lesser extent. The reported elevations in ALT/AST with rucaparib treatment in 
either the treatment or maintenance settings were not associated with any events of 
drug-induced liver injury (DILI). 
Effects on cardiac channel activity in vitro and a comprehensive assessment of the effects of 
rucaparib on ECG parameters in cancer patients demonstrated a low risk of cardiac effects by 
rucaparib. 
Photosensitivity was initially reported in the Phase 1 dose-escalation part of 
Study CO-338-010 (n=6; 10.7%) and based on these reports of photosensitivity, guidance for 
sun protection was included in rucaparib clinical studies. In the recent integrated safety 
analysis from 917 patients treated with rucaparib in either placebo-controlled 
Study CO-338-014 (ARIEL3) and two open-label, single-arm trials (Studies CO-338-010 and 
CO-338-017 [ARIEL2]), 118 patients (12.9%]) experienced All Grade photosensitivity and 
2 patients (0.2%) experienced ≥ Grade 3 (Clovis, data on file). Patients should use typical 
precautions when going outside, such as applying sunscreen (sun protection factor 50 or 
greater) and/or covering exposed skin with clothing and wearing a hat and sunglasses. 
3.4.2.4 
Adverse Events of Special Interest 
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are considered 
adverse events of special interest (AESI), as these events have been observed in patients 
exposed to cytotoxic chemotherapy (eg, platinum and anthracyclines) used for treatment of 
ovarian cancer as well as with PARP inhibitors, including rucaparib. 


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Exposure to DNA-damaging therapies for ovarian and breast cancer present an increased risk 
of developing MDS or AML.54 In addition, the patients who have developed MDS and AML 
have/had significant confounding risk factors, including prior cytotoxic chemotherapy, as 
well as a deleterious BRCA mutation presenting a higher risk of developing one or more 
malignancy(ies).54, 55 Based upon the above confounding factors, there is insufficient 
scientific evidence to conclude that MDS and AML are causally related to rucaparib. 
Adverse events (AEs) of pneumonitis have been reported with PARP inhibitor treatment, 
including in clinical trials evaluating rucaparib. Currently, however, there is a lack of 
understanding of a mechanistic link between pneumonitis and PARP inhibitor treatment, and 
causality assessment is often confounded by lack of a consistent clinical pattern as well as 
other pre-disposing factors, such as cancer and/or metastases in lungs, underlying pulmonary 
disease, smoking history, and/or previous chemotherapy and radiotherapy. Clovis is seeking 
to understand whether or not there is a relationship between pneumonitis and rucaparib 
treatment; thus, Clovis is designating pneumonitis as an AESI to gather data to enable a 
thorough evaluation and assessment of the event and associated terms specified in 
Section 10.7. 
More information on AESIs is provided in the rucaparib IB. 
3.5 
Rationale for this Study of Rucaparib 
PARPi, including rucaparib, have demonstrated consistent robust clinical activity in patients 
with deleterious BRCA1/2-mutant tumors, including in patients with relapsed deleterious 
BRCA1/2-mutant (germline or somatic) ovarian cancer. Clinical activity of PARPi versus 
standard of care chemotherapy has not yet been extensively evaluated in prospective trials 
enrolling only patients with known deleterious BRCA1/2 mutant tumors (germline or 
somatic). Assessment of chemotherapy response in patients with BRCA1/2 mutant tumors 
has been primarily examined in small retrospective analyses.  
The primary purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib 
versus chemotherapy as treatment for relapsed ovarian cancer patients with deleterious 
BRCA1/2 mutation in their tumor.  


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4 
STUDY OBJECTIVES 
4.1 
Primary Objective  
The primary objective of this study is: 
• To determine investigator-assessed progression-free survival (invPFS) by 
RECIST Version 1.1 of rucaparib versus chemotherapy. 
4.2 
Secondary Objectives  
The secondary objectives of this study are: 
• To evaluate PFS by RECIST Version 1.1, as assessed by BICR (bicrPFS) 
• To compare efficacy of rucaparib versus chemotherapy as measured by overall 
survival (OS)  
• To compare efficacy of rucaparib versus chemotherapy as measured by ORR using 
RECIST Version 1.1 by investigator assessment 
• To compare efficacy of rucaparib versus chemotherapy as measured by DOR by 
investigator assessment 
• To compare efficacy of rucaparib versus chemotherapy as measured by ORR using 
RECIST Version 1.1 by investigator assessment and Gynecologic Cancer InterGroup 
(GCIG) cancer antigen-125 (CA-125) response criteria 
• To evaluate patient-reported outcome (PRO) for rucaparib versus chemotherapy as 
assessed by the European Organization for Research and Treatment of Cancer Quality 
of Life Questionnaire (EORTC QLQ)-C30 and ovarian cancer module QLQ-OV28 
• To evaluate the safety and tolerability of rucaparib versus chemotherapy. 
4.3 
Exploratory Objectives 
Exploratory objectives in this study are:  
• To evaluate the second event of PFS, in subsequent line of treatment (PFS2), both by 
investigator assessment 
• To evaluate disease control rate (RECIST Version 1.1 CR, PR, and prolonged SD 
≥ 12 weeks, by investigator assessment)  
• To evaluate PRO utilizing the Euro-Quality of Life 5D (EQ-5D) 
• To assess molecular changes in tumor samples over time in matched pairs 


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• To assess circulating cell-free tumor DNA (ctDNA) as a molecular marker of efficacy 
• To evaluate the impact of gene expression molecular subgroups on PFS and OS 
• To assess efficacy in BRCA-mutation subgroups (ie, germline/somatic and 
BRCA1/BRCA2) 
• To characterize steady-state trough concentrations of rucaparib 
• To explore the relationship between rucaparib exposure and responses (safety and 
efficacy) 
 


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5 
INVESTIGATIONAL PLAN 
5.1 
Overall Study Design and Plan 
This is a Phase 3 multicenter, randomized study evaluating rucaparib versus chemotherapy 
for treatment of relapsed, high-grade epithelial serous or Grade 2 or 3 endometrioid ovarian, 
fallopian tube, or primary peritoneal cancer. The study will enroll patients with a deleterious 
BRCA1/2 mutation in their tumor. All patients will be required to have received at least 
2 prior chemotherapy regimens, with at least one that includes a platinum. Patients with 
platinum-refractory disease (ie, progression during or within 4 weeks after last dose of the 
most recent platinum-based therapy) and patients who have received prior PARPi treatment 
will be excluded.  
5.1.1 
Screening Phase 
All patients will undergo screening assessments within 60 days prior to randomization. 
Informed consent may be completed outside the 60-day screening window as informed 
consent does not expire, except as required by applicable regulatory requirements, or if 
withdrawn by the patient.  
All patients, with the exception of those known to harbor a deleterious BRCA1/2 mutation 
(germline or somatic), will be required to provide archival tumor tissue or a screening biopsy 
for central laboratory analysis prior to enrollment. Patients with a known deleterious 
BRCA1/2 mutation (germline or somatic) must also submit archival tumor tissue for central 
laboratory testing; however, enrollment is not contingent upon the central laboratory analysis 
of tissue. A local BRCA1/2 mutation result from previous testing will be adequate for 
enrollment. Patients with a deleterious BRCA1/2 mutation who meet all other entry criteria 
will be eligible for the study. If archival tumor tissue is not available, the patient may 
undergo a screening biopsy.  
Tumor analysis will be performed using a next-generation sequencing (NGS) test by 
Foundation Medicine Inc (FMI). Results of the FMI panel test will be provided to patients 
who consent to receive this information. In the event a BRCA1/2 is identified in tumor tissue, 
the patient may be referred by the investigator for genetic counseling and potential germline 
testing per institutional guidelines. If the patient chooses to have germline testing, this result 
will be entered in the clinical trial database for this study. 
Additional screening assessments will include demographics and medical history, prior 
treatments for serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal 
cancer (and other malignancies, if applicable), prior and current medications and procedures, 
12-lead ECG, ECOG performance status, local laboratory hematology, serum chemistry, and 
CA-125 measurement, serum pregnancy (for women of childbearing potential only), 
urinalysis, physical examination, height, weight, and vital signs measurements, blood 
samples for ctDNA and genomic analyses, adverse events, and radiologic assessment by 
computed tomography (CT) or magnetic resonance imaging (MRI). Patient-reported 
outcomes (PRO) will be collected using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D 
instruments, or other collection format as appropriate.  


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Enrollment will require Sponsor (or designee) review and confirmation of eligibility, 
including, but not limited to: 
• local BRCA1/2 test result if patient has previously been tested;  
• number of prior chemotherapy regimens, including treatment-free interval after first 
platinum-containing regimen and progression-free interval after most recent 
platinum-containing regimen; 
• if known deleterious BRCA1/2 mutation (germline or somatic), confirmation that a 
sufficient quantity of tumor tissue is available and will be submitted to the central 
laboratory. 
5.1.2 
Assignment / Randomization 
Patients classified as having a deleterious BRCA1/2 mutation by FMI (central laboratory) 
analysis or documented local results for deleterious germline or somatic BRCA1/2 mutation, 
with confirmation of adequate tumor tissue availability for known deleterious BRCA1/2 
mutant patients, and confirmation of all other eligibility criteria in the screening phase, 
patients will be randomized 2:1 to receive rucaparib or chemotherapy. Randomization will 
occur by a central randomization procedure using interactive response technology (IRT), 
which is described in more detail in Section 7.4. Study treatment must be initiated within 
3 days after randomization. 
5.1.3 
Treatment Phase 
During the treatment phase (continuous 28-day treatment cycles), patients will receive 
rucaparib or chemotherapy and be monitored for safety and efficacy. Patients randomized to 
chemotherapy will receive treatment based upon the progression-free interval after their most 
recent platinum therapy and also Investigator selection for platinum-sensitive patients. 
Treatments available to patients by progression-free interval after most recent platinum are 
displayed in Table 1. 
 
 


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Table 1. 
Treatments by Progression-free Interval after Most Recent 
Platinum 
 
Progression-free Interval after 
Most Recent Platinum 
Treatments 
Rucaparib 
or 
Chemotherapy 
Platinum-resistant 
(≥ 1 to < 6 months) 
Rucaparib 
or 
Weekly paclitaxel 
Partially platinum-sensitive 
(≥ 6 to < 12 months) 
Rucaparib 
or 
Weekly paclitaxel 
Platinum-sensitive 
(≥ 12 months) 
Rucaparib 
or 
Platinum-based chemotherapy 
per investigator choice of the 
followinga: 
• Monotherapy cisplatin; 
• Monotherapy carboplatin; 
• Carboplatin and 
paclitaxel; 
• Carboplatin and 
gemcitabine; or 
• Cisplatin and gemcitabine 
Abbreviations: ESMO = European Society for Medical Oncology; NCCN = National Comprehensive Cancer 
Network. 
a 
Chemotherapy listed for platinum-sensitive patients is based on NCCN and ESMO guidelines.8, 10  
Rucaparib will be administered as 600 mg BID. Weekly paclitaxel 60 to 80 mg/m2 (dose per 
institutional standard of care), will be administered via IV infusion on Days 1, 8, and 15 of 
every 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dose and 
administration of monotherapy cisplatin or carboplatin or doublet carboplatin/paclitaxel, 
carboplatin/gemcitabine, or cisplatin/gemcitabine infusion will follow institutional guidelines 
for each agent. No more than 8 cycles of platinum monotherapy or doublet therapy are to be 
administered in this study. Patients will receive the same chemotherapy in 21-day or 28-day 
cycles, as appropriate, throughout the study.  
Assessments and procedures during the study will include AEs; physical examinations; vital 
signs, 12-lead ECGs, and weight measurements; local laboratory hematology, serum 
chemistry, and CA-125 measurements; serum pregnancy for women of childbearing 
potential; blood samples for ctDNA and genomic analyses; plasma samples for PK analysis; 
concomitant medications, therapies, and procedures; disease/ tumor assessment; study drug 
administration and accountability; and PRO. During treatment, urinalysis will be performed 
as clinically indicated. 
Patients will be assessed for disease status per RECIST Version 1.1 at baseline (screening), at 
the end of every 8 calendar weeks relative to Cycle 1 Day 1 (within 5 days before is 


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permitted) until radiologically confirmed disease progression by RECIST Version 1.1, as 
assessed by the investigator, or death. Tumor assessments should be performed at the time of 
treatment discontinuation if the reason was other than radiologically-confirmed disease 
progression or it has been ≥ 8 weeks since the last assessment. Patients experiencing disease 
progression by RECIST Version 1.1, as assessed by the investigator, will be discontinued 
from treatment and enter follow-up, unless a patient on rucaparib is still receiving benefit 
and, jointly, the investigator and Sponsor agree with continued rucaparib treatment. Patients 
initially receiving chemotherapy have the option to cross over to rucaparib treatment. 
Patients with rising CA-125 should not be discontinued based on this result alone, but should 
have a radiologic assessment and be assessed for disease progression by 
RECIST Version 1.1. If the radiologic assessment does not confirm disease progression, 
patients should continue on treatment and continue to be assessed by RECIST Version 1.1 
per the protocol schedule of assessments. Patients who have been on study at least 18 months 
will decrease the frequency of tumor assessments to every 16 weeks (within 5 days before is 
permitted). All CT scans (and other imaging, as appropriate) performed at baseline, during 
the treatment period, and at treatment discontinuation will be collected for bicrPFS, which 
will constitute a supportive analysis. BICR will review CT scans for a given patient in 
batches throughout the conduct of the study, but not necessarily in real-time. All treatment 
decisions will be made by the investigator based on local radiology results. 
Patients will be continuously monitored for safety and efficacy. An Independent Data 
Monitoring Committee (IDMC) with multidisciplinary representation will evaluate safety 
and efficacy data in compliance with a prospective charter. The IDMC will have access to 
study data including treatment assignments. 
Patients randomized to chemotherapy have the option to cross over to receive rucaparib upon 
radiological progression per RECIST Version 1.1, provided that disease progression is 
confirmed with supporting documentation and approval is obtained from the Sponsor (or 
designee). If clinical progression is diagnosed, then confirmation of disease progression by 
radiologic assessment per RECIST Version 1.1 is required along with Sponsor (or designee) 
approval of the radiology report confirming disease progression before a patient is considered 
eligible to cross over to rucaparib.  
If a patient randomized to rucaparib has radiologic progression, but continues to derive 
clinical benefit per the investigator, then continuation of rucaparib treatment beyond 
progression will be permitted. In such cases, the documented decision to continue will be 
made jointly between the investigator and the Sponsor (or designee), it must be documented 
in the patient’s chart, and the patient must provide consent within a reasonable timeframe of 
the documented decision to continue treatment with rucaparib. Patients will continue to have 
all protocol-required assessments specified in Table 4.  
5.1.4 
Post-treatment Phase 
Upon treatment discontinuation, patients will have a treatment discontinuation visit. The 
following assessments will be performed at the discontinuation of treatment to the extent 
possible: PRO; ECOG performance status; concomitant medications and procedures; 12-lead 
ECG; physical examination; vital signs and weight measurements; hematology and serum 


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chemistry; serum pregnancy for women of childbearing potential; blood samples for ctDNA 
and genomic analyses; CA-125 measurement; disease/ tumor assessment; study drug 
accountability; and AE monitoring. Concomitant medications and procedures, AE 
monitoring, and PRO will also be collected following the last dose of study drug at the 
28 (± 3) days Safety Follow-up Visit. Ongoing serious adverse events (SAEs), AEs of special 
interest (AESIs), and treatment-related Grade 3/4 AEs will be followed until either resolution 
or stabilization has been determined or until lost to follow-up. An optional tumor biopsy will 
be collected from patients who experience disease progression/discontinue treatment and 
provide appropriate consent. The Sponsor (or designee) should be notified of all study 
terminations as soon as possible. The date and reason for cessation of study drug must be 
documented in the electronic case report form (eCRF) and source documents. 
After the 28-day Safety Follow-up Visit, only SAEs considered as potentially related to study 
drug should be reported per Clovis Pharmacovigilance (PV) requirements and captured in the 
Clovis PV database. This includes serious reports of pneumonitis or similar events 
(ie, interstitial lung disease, pulmonary fibrosis, acute interstitial pneumonitis, alveolitis 
necrotizing, alveolitis, hypersensitivity pneumonitis, and organizing pneumonia), if 
considered to be related to study drug. 
After the 28-day Follow-up Visit, AESIs of MDS and AML, irrespective of causality, should 
be reported per Clovis PV requirements and captured in the Clovis PV database. 
• AESIs of pneumonitis or similar events should only be reported up to, but not beyond, 
the 28-Day Follow-up Visit (28 days after the last dose of rucaparib). 
 
Disease/ tumor assessment will continue (using the same methodology as was used at initial 
study screening [eg, CT scan]) if reason for treatment discontinuation was other than death or 
disease progression based on radiologic assessment. Disease/ tumor assessments should 
continue to be performed every 8 calendar weeks (within 5 days before is permitted) relative 
to Cycle 1 Day 1 until radiologic disease progression by RECIST Version 1.1, as assessed by 
the investigator, death, loss to follow-up, withdrawal, study closure, or initiation of 
subsequent treatment. PRO assessments should also be collected at every cycle for all 
patients through disease progression in association with the radiologic assessments for 
disease progression. 
All patients will be followed for survival, subsequent treatments, and monitoring for 
secondary malignancy every 12 weeks (± 14 days) until death, loss to follow-up, withdrawal 
of consent, or study closure. 
If a patient begins subsequent anti-cancer therapy, the Sponsor will terminate collection of 
SAEs, with the exception of AESIs MDS and AML. 
5.2 
Study Schema 
The study schema is provided in Figure 1. 




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5.3 
End of Study 
The study is monitored on an ongoing basis by an IDMC for the number of PFS events 
required for the primary endpoint and for safety signals. Upon formal closure of the study, 
individual patients who are continuing to benefit from treatment with rucaparib at the time of 
study closure, and who do not meet any of the criteria for withdrawal, will have the option of 
receiving rucaparib via another access mechanism. In addition, individuals who are 
continuing in long-term follow-up (LTFU) may transition to have their LTFU and scans, if 
applicable, captured via another mechanism. 
The Sponsor may discontinue the study early for any reason as noted in Section 13.7. 
5.4 
Rationale for Study Design and Control Group 
This study will evaluate the efficacy and safety of rucaparib versus chemotherapy as 
treatment for relapsed high-grade serous or endometrioid ovarian cancer in patients who have 
received two or more prior lines of chemotherapy and have evidence of HRD. There is unmet 
need in the third-line treatment setting for a therapy that provides benefit and does not add to 
the cumulative toxicity of prior chemotherapy regimens. 
This study will directly compare the PFS of treatment with rucaparib versus chemotherapy in 
patients with a deleterious BRCA1/2 mutation. Patients with platinum-resistant disease 
(ie, progressed ≥ 1 to < 6 months after the last dose of platinum) or with partially 
platinum-sensitive disease (ie, progressed ≥ 6 to < 12 months after the last dose of platinum) 
will be randomized 2:1 to receive either rucaparib or weekly paclitaxel. Patients with 
platinum-sensitive disease (ie, progressed ≥ 12 months after the last dose of platinum) will be 
randomized 2:1 to receive either rucaparib or platinum-based chemotherapy. The choice of 
platinum-based chemotherapy will be per Investigator’s discretion; options include 
monotherapy (carboplatin or cisplatin) or combination therapy (carboplatin and paclitaxel, 
carboplatin and gemcitabine, or cisplatin and gemcitabine). These chemotherapy options are 
among the recommended standard-of-care treatments (per National Comprehensive Cancer 
Network [NCCN] and European Society for Medical Oncology [ESMO] guidelines) for 
patients with relapsed, platinum-sensitive ovarian cancer.8, 10  
A 2:1 randomization to receive either rucaparib or chemotherapy will allow for statistical 
comparison of PFS, OS, and ORR between the treatment arms and provide access to 
rucaparib for a larger number of patients who would otherwise receive standard 
chemotherapy. Stratification by progression-free interval after most recent 
platinum-containing therapy will occur upon study entry to maintain balance between 
treatment groups. 
The study drug is open label. Blinding of the Investigators and patients is not possible 
because rucaparib is a tablet taken orally and chemotherapy in this study will be administered 
via IV infusion. Additionally, the dosing regimens differ, making it impossible to blind the 
patients to treatment. Rucaparib will be administered as 600 mg BID based upon supportive 
Phase 1/2 clinical efficacy and safety. Paclitaxel will be administered as 60 to 80 mg/m2 
(dose per institutional standard of care) on Days 1, 8, and 15 of a 28-day cycle (with a week 


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break from dosing on Day 22 in each cycle) via IV infusion. This regimen of paclitaxel was 
selected instead of the conventional 3-weekly schedule as studies have shown that weekly 
administration provides clinical benefit similar to the 3-weekly schedule and causes less 
neutropenia and peripheral neuropathy.56-61 Other single-agent and doublet chemotherapy 
dosage and administration will follow institutional guidelines/Prescribing Information for 
each agent in 28-day cycles.  
There is limited data regarding the activity of weekly paclitaxel in patients with BRCA1/2 
mutated ovarian cancer, but the data that are available support the use of this schedule of 
paclitaxel in this patient population. A retrospective study has shown that single-agent 
paclitaxel is active in patients with relapsed ovarian cancer harboring a deleterious BRCA1/2 
mutation, with ORRs of 60% and 27%, in platinum-sensitive and platinum-resistant disease, 
respectively. Notably, of the platinum-sensitive patients who received single-agent paclitaxel 
(15/26), the ORR observed with weekly paclitaxel (60%) was identical to the ORR (60%) 
observed with standard 3-weekly paclitaxel.57 In addition, a study conducted by Ang et al, 
demonstrated a 50% (5/10) RECIST ORR in heavily pretreated patients with BRCA1/2 
mutations who had been treated with olaparib and subsequently re-challenged with weekly 
paclitaxel.62 
Overall, the chemotherapy agents that were selected as comparators for this study have 
demonstrated activity in advanced ovarian cancer. Weekly paclitaxel has robust clinical 
activity, a favorable safety profile, and is recommended by NCCN and ESMO guidelines for 
the treatment of relapsed ovarian cancer.8-10 Cisplatin and carboplatin are effective 
single-agent therapies as well as in combination (doublet therapy) with paclitaxel or 
gemcitabine for treatment of ovarian cancer in patients with platinum-sensitive disease as 
recommended by NCCN and ESMO guidelines.8, 10, 11 Therefore, these chemotherapies are 
appropriate comparators to confirm rucaparib benefit for the planned patient population.  


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6 
STUDY POPULATION SELECTION 
6.1 
Number of Patients and Sites 
The enrollment planned for this study is approximately 345 patients at approximately 
100 study sites worldwide, with 230 patients randomized to rucaparib and 115 patients 
randomized to chemotherapy (ie, comparator). 
Patients will be randomized 2:1 to receive rucaparib or chemotherapy.  
6.2 
Inclusion Criteria 
Eligible patients must meet the following inclusion criteria. Unless otherwise specified, the 
criteria below apply to all patients. 
1. Have signed an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)-approved informed consent form prior to any study-specific evaluation 
2. Be ≥ 18 years of age at the time the informed consent form is signed 
3. Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or Grade 3 
endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer 
a. If mixed histology, > 50% of the primary tumor must be confirmed to be 
high-grade serous or endometrioid upon review by local pathology  
b. Patients with a histology of other than serous or endometrioid are also eligible 
if they are known to harbor a deleterious germline or somatic BRCA1/2 
mutation 
4. Received ≥ 2 prior chemotherapy regimens, with at least 1 regimen including a 
platinum, and have relapsed or progressive disease as confirmed by radiologic 
assessment 
a. Had documented treatment-free interval of ≥ 6 months following the first 
chemotherapy regimen received 
b. Hormonal agents (eg, tamoxifen, letrozole, etc.), anti-angiogenic agents 
(eg, bevacizumab, pazopanib, cediranib, etc.), and other non-chemotherapy 
agents will not be counted as a chemotherapy regimen for the purpose of 
determining patient eligibility 
c. Agents administered in the maintenance setting will not be counted as a 
separate regimen 
5. Have a deleterious BRCA1/2 mutation as confirmed by the central laboratory. 
Note: patients known to harbor a deleterious germline or somatic BRCA1/2 mutation 
based on local assessment may be enrolled without central tissue analysis provided 
there is confirmation that tumor tissue is available to be provided to the central 
laboratory. 
a. Sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue 
must be available for planned analyses; cytospin blocks from ascites are not 
acceptable.  


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i. The most recently obtained tumor tissue that is of adequate quality (at 
least 20% tumor content with a minimum of 80% nucleated cellular 
content) should be submitted.  
b. In the event archival tumor tissue is not available a screening biopsy sample 
may be collected and provided to the central laboratory 
6. Have evaluable disease: ie at least 1 target or non-target lesion that can be assessed 
per RECIST Version 1.1 (Appendix 1) 
7. Have adequate organ function confirmed by the following laboratory values obtained 
within 14 days prior to randomization: 
a. Bone Marrow Function 
i. Absolute neutrophil count (ANC) ≥ 2.0 × 109/L 
ii. Platelets > 100 × 109/L  
iii. Hemoglobin > 10 g/dL  
b. Hepatic Function 
i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 3 × upper limit of normal (ULN); if liver metastases, then 
≤ 5 × ULN 
ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to 
Gilbert’s syndrome 
iii. Serum albumin ≥ 30 g/L (3.0 g/dL) 
c. Renal Function 
i. Serum creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate 
(GFR) ≥ 45 mL/min using the Cockcroft-Gault formula 
8. Women of childbearing potential must have a negative serum pregnancy test ≤ 3 days 
prior to administration of the first dose of study drug 
9. Have an ECOG performance status of 0 or 1 (Appendix 2). 
6.3 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study. 
1. Active second malignancy, ie, patient known to have potentially fatal cancer present 
for which she may be (but not necessarily) currently receiving treatment 
a. Patients with a history of malignancy that has been completely treated, with 
no evidence of that cancer currently, are permitted to enroll in the trial 
provided all chemotherapy was completed > 6 months prior and/ or bone 
marrow transplant > 2 years prior to first dose of study drug. Ongoing 
hormonal treatment for previously treated breast cancer is permitted. 
2. Prior treatment with any PARP inhibitor, including rucaparib, regardless of duration 
3. Prior treatment with single-agent paclitaxel or nab-paclitaxel 
4. Prior known clinically significant hypersensitivity (per investigator judgement despite 
implementation of a desensitization protocol) to: 


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a. paclitaxel treatment for patients with a progression-free interval of 
< 12 months after last platinum-based regimen, or 
b. platinum treatment for patients with a progression-free interval of 
≥ 12 months after last platinum-based regimen 
5. Platinum refractory disease: disease progressed by radiologic assessment during or 
within 4 weeks after completing treatment with most recent platinum-based therapy  
6. Symptomatic and/or untreated central nervous system (CNS) metastases. Patients 
with asymptomatic previously-treated CNS metastases are eligible provided they 
have been clinically stable for at least 4 weeks after completion of therapy 
7. Pre-existing duodenal stent and/ or any gastrointestinal disorder or defect that would, 
in the opinion of the Investigator, interfere with absorption of rucaparib 
8. Known human immunodeficiency virus (HIV) or acquired immunodeficiency 
syndrome (AIDS)-related illness, or history of chronic hepatitis B or C, with the 
exception of patients with a sustained virologic response after completion of 
treatment for hepatitis C 
9. Women who are pregnant or breast feeding  
10. Received treatment with chemotherapy, radiation, antibody therapy or other 
immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or 
experimental drugs ≤ 14 days prior to first dose of study drug 
11. Ongoing toxicity from prior cancer treatment ≥ Grade 2 by National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) (ongoing Grade 2 
non-hematologic toxicity, with the exception of peripheral neuropathy, may be 
permitted with prior advanced approval from Sponsor) 
12. Non study-related minor surgical procedure ≤ 5 days, or major surgical procedure 
≤ 21 days, prior to first dose of study drug; in all cases, the patient must be 
sufficiently recovered and stable before treatment administration 
13. Requires regular blood transfusions, granulocyte colony-stimulating factor, or platelet 
transfusions 
14. Drainage of ascitic fluid 2 or more times in the 4 weeks prior to the first dose of study 
drug, uncontrolled pleural effusion, or permanent drain in place (eg, PleurX®) for 
ascites or pleural effusion 
15. Hospitalization for bowel obstruction within 3 months prior to randomization 
16. Presence of any other condition that may increase the risk associated with study 
participation or may interfere with the interpretation of study results, and, in the 
opinion of the investigator, would make the patient inappropriate for entry into the 
study 
 


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6.4 
Criteria for Rucaparib Crossover Treatment Eligibility Following 
Radiological Progression on or after Comparator Arm Therapy 
To be eligible for participation in the crossover part of the study, patients must fulfill the 
following criteria and initiate treatment with rucaparib ≤ 8 weeks after radiologic disease 
progression: 
1. Have documented radiological progression per RECIST Version 1.1 during or 
following completion of comparator arm chemotherapy 
2. Receive Sponsor approval to cross over from chemotherapy to rucaparib treatment 
3. Have adequate hematological and biological function, confirmed by the following 
local laboratory values ≤ 14 days prior to first dose of rucaparib: 
a. Bone Marrow Function 
i. ANC ≥ 1.5 × 109/L 
ii. Platelets > 100 × 109/L  
iii. Hemoglobin > 10 g/dL  
b. Hepatic Function 
i. AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 × ULN 
ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to 
Gilbert’s syndrome 
iii. Serum albumin ≥ 30 g/L (3.0 g/dL) 
c. Renal Function 
i. Serum creatinine ≤ 1.5 x ULN or estimated GFR ≥ 45 mL/minute 
using the Cockcroft-Gault formula 
4. All Grade 3 and 4 hematologic and non-hematologic toxicities (except alopecia, 
nausea, vomiting, or adequately controlled diarrhea) improved to baseline or 
≤ CTCAE Grade 1 
5. Women of childbearing potential must have a negative serum pregnancy test ≤ 3 days 
prior to administration of the first dose of rucaparib in the crossover 
6. Have an ECOG performance status of 0 to 1 (Appendix 2). 
7. Written consent on an IRB/IEC-approved ICF 
In addition, any of the following will exclude patients from receiving rucaparib in the 
crossover part: 
1. Active second malignancy, ie, patient known to have potentially fatal cancer present 
for which she may be (but not necessarily) currently receiving treatment 
a. Patients with a history of malignancy that has been completely treated, with 
no evidence of that cancer currently, are permitted to continue in the trial 
provided all prior chemotherapy was completed > 6 months prior and/ or bone 
marrow transplant > 2 years prior to first dose of study drug (non-melanoma 
skin cancer excepted) 


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2. Received treatment with chemotherapy, antibody therapy or other immunotherapy, 
gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs after 
discontinuation of study chemotherapy  
3. Non study-related minor surgical procedure ≤ 5 days, or major surgical procedure 
≤ 21 days, prior to first dose of rucaparib in crossover patients; in all cases, the patient 
must be sufficiently recovered and stable before treatment administration 
4. Women who are pregnant or breast feeding 
5. Withdrawal of consent during treatment with the comparator arm chemotherapy  
6. Presence of any other condition that may increase the risk associated with study 
participation and, in the opinion of the investigator, would make the patient 
inappropriate (including general noncompliance with study procedures during 
treatment with the comparator arm chemotherapy, per investigator judgement) for 
continuing in the study with crossover to rucaparib treatment 
6.5 
Patients or Partners of Patients of Reproductive Potential 
Pregnancy is an exclusion criterion and women of childbearing potential must not be 
considering getting pregnant during the study. Female patients are considered to be of 
childbearing potential unless 1 of the following applies: 
• Is postmenopausal, defined as no menses for at least 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level consistently in the 
postmenopausal range (30 mIU/mL or higher) may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy; however, in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient to confirm a postmenopausal state: or  
• Considered to be permanently sterile. Permanent sterilization includes hysterectomy, 
bilateral salpingectomy, and/or bilateral oophorectomy. 
Female patients of childbearing potential must have a negative serum pregnancy test result 
≤ 3 days prior to administration of the first dose of study drug. In addition, a serum 
pregnancy test must be performed ≤ 3 days prior to Day 1 of every cycle during the treatment 
phase and at the time of treatment discontinuation. Pregnancy testing will be conducted 
locally.  
Female patients of reproductive potential and their male partners must practice highly 
effective methods (failure rate < 1% per year) of contraception during treatment and for 
6 months following the last dose of study drug. Highly effective contraception includes: 
• Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo 
Provera, Implanon, Nexplanon); 
• Placement of an intrauterine device (IUD) or intrauterine system (IUS); 
• Bilateral tubal occlusion;  


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• Male sterilization, with appropriate post-vasectomy documentation of absence of sperm 
in ejaculate; or 
• Sexual abstinence as defined as complete or true abstinence, acceptable only when it is 
the usual and preferred lifestyle of the patient; periodic abstinence (eg, calendar, 
symptothermal, post-ovulation methods) is not acceptable. 
 
Patients will be instructed to notify the investigator if pregnancy is discovered either during 
or within 6 months of completing treatment with study drug.  
6.6 
Waivers of Inclusion/Exclusion Criteria 
No waivers of these inclusion or exclusion criteria will be granted by the investigator and the 
Sponsor or its designee for any patient enrolling into the study. 


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7 
STUDY TREATMENT(S) 
7.1 
Description of Treatment(s) and Storage 
This study will assess the investigational drug rucaparib compared to chemotherapy using a 
parallel-group study design. 
7.1.1 
Investigational Drug Product - Rucaparib 
Rucaparib camsylate (also known as CO-338) is an oral formulation. Rucaparib tablets for 
oral administration will be supplied to the study sites by the Sponsor. A brief description of 
the investigational product is provided below with details in the Pharmacy Guidelines. 
Table 2. 
Rucaparib Formulation and Storage 
Drug Name: 
Rucaparib 
INN: 
Rucaparib 
Formulation:  
(strengths expressed as 
free base) 
Tablet; film coated; 200 mg (blue, round, debossed with C2), 250 mg 
(white, rounded diamond shape, debossed with C25), 300 mg (yellow, 
oval, debossed with C3)  
How Supplied: 
200, 250, and 300 mg (as free base) strength tablets in high-density 
polyethylene bottles or equivalent with child-resistant caps. Patients 
may receive one or more strengths.  
Storage Conditions: 
15–30° C (59–86° F).  
 
7.1.2 
Chemotherapeutic Drug Products 
Single-agent chemotherapy will consist of paclitaxel, cisplatin, or carboplatin. Doublet 
platinum-based chemotherapy will consist of carboplatin and paclitaxel, carboplatin and 
gemcitabine, or cisplatin and gemcitabine. Each of these individual drugs will either be 
procured by the study site or supplied by the Sponsor. Each product will be stored according 
to the manufacturer’s prescribing information/ product packaging and as described in the 
Pharmacy Guidelines.  
Single-agent weekly paclitaxel will be assigned to patients per study randomization. 
Single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, 
carboplatin/gemcitabine, or cisplatin/gemcitabine will be selected by the Investigator for 
treatment of platinum-sensitive patients randomized to chemotherapy. The selected 
chemotherapy should be based on what is appropriate for the patient and the Investigator 
must have experience with the single-agent or doublet chemotherapy that is selected. 
7.2 
Packaging and Labeling 
7.2.1 
Rucaparib 
All tablets are provided in high-density polyethylene (HDPE) bottles with child-resistant 
caps and should be stored in the provided containers between 15° and 30° C (59 and 86° F). 


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Patients will be dispensed one or more strengths depending on their current dose of 
rucaparib. The number of bottles of each strength dispensed will be sufficient to supply 
28 days treatment per cycle, including a small overage. 
Study drug containers containing rucaparib tablets will be labeled in accordance with local 
regulatory requirements. 
7.2.2 
Chemotherapy 
Depending on local health authority guidelines, the chemotherapy agents will be obtained 
through commercial supply, the site pharmacy, or from the Sponsor. The packaging and 
labeling will vary depending on the source of the supply.  
Products will be labeled to meet local country requirements. Where sites source their own 
chemotherapy, they are responsible for the quality and security of the supply and for ensuring 
it is appropriately labeled and dispensed in compliance with local regulations. 
7.3 
Blinding 
This is an open-label study; the study drugs will not be blinded or masked to the Investigator 
or patient, so each will know the treatment being administered. A plan will be put in place to 
limit bias for Sponsor personnel. 
7.4 
Method of Assigning Patients to Treatment Groups 
The following will be included as a randomization stratification factor at study entry to 
ensure treatment groups are balanced: 
• Platinum resistant: patients who progressed ≥ 1 to < 6 months after the last dose of 
platinum-based chemotherapy;  
• Partially platinum-sensitive: patients who progressed ≥ 6 months to < 12 months after 
last dose of platinum-based chemotherapy; and 
• Platinum sensitive: patients who progressed ≥ 12 months after last dose of 
platinum-based chemotherapy;  
Platinum-resistant patients and partially platinum-sensitive patients will be randomized 2:1 to 
receive rucaparib or weekly paclitaxel. 
Platinum-sensitive patients will be randomized 2:1 to receive rucaparib or platinum-based 
chemotherapy. The investigator will select an appropriate monotherapy platinum (carboplatin 
or cisplatin) or platinum-based doublet (carboplatin and paclitaxel, carboplatin and 
gemcitabine, or cisplatin and gemcitabine). The Investigator should have experience using 
the chemotherapy that is selected and prior to randomization must notify the Sponsor (or 
designee) which platinum chemotherapy a platinum-sensitive patient will receive if 
randomized to the chemotherapy arm.  
Study treatment must be initiated within 3 days after randomization. 


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7.5 
Preparation and Administration of Protocol-specified Treatment 
The investigator or designee will be responsible for distributing study drug to all patients. 
Study drug (ie, rucaparib or chemotherapy) will be assigned by IRT according to the 
patient’s randomization assignment. The Investigator will select the most appropriate 
monotherapy platinum or platinum-based doublet for platinum-sensitive patients randomized 
to chemotherapy (see Section 7.1.2).  
The IRT will manage all study drug supplied by the Sponsor. The system should be accessed 
to record each dispensation of rucaparib and each administration of chemotherapy 
comparators according to the patient’s randomized treatment. Guidelines for the use of the 
IRT will be provided to study sites. Study sites should follow local guidelines for the 
handling of cytotoxic chemotherapy. 
7.5.1 
Rucaparib 
The starting dose of rucaparib is 600 mg ingested BID. Patients may take rucaparib with or 
without food. Each dose should be taken with at least 8 oz. (240 mL) of water. Tablets should 
be swallowed whole without crushing or chewing.  
Patients should take rucaparib doses as close to 12 hours apart as possible, preferably at the 
same times every day. If a patient misses a dose (ie, does not take it within 4 hours of the 
scheduled time), the patient should skip the missed dose and resume taking rucaparib with 
the next scheduled dose. Missed or vomited doses should not be made up. 
Dosing with rucaparib may be held or reduced as described in Section 7.5.1.1. 
Each treatment cycle of rucaparib is 28 days. Patients will be provided a sufficient quantity 
of study drug to last until Day 1 of the next treatment cycle. Patients will be instructed to 
bring their rucaparib tablets and all containers (empty, partially used, and/or unopened) to the 
next scheduled visit for reconciliation by site personnel. After the last dose of rucaparib is 
taken (initial or crossover treatment), the patient will be followed for 28 (± 3) days for safety 
and efficacy data. 
7.5.1.1 
Rucaparib Dose Modification Criteria 
Treatment with rucaparib should be held if any of the following are observed and a dose 
reduction should be considered or implemented. 
• Grade 3 or 4 hematologic toxicity 
• Grade 3 or 4 non-hematologic toxicity (except for alopecia, nausea, vomiting, or diarrhea 
adequately controlled with systemic antiemetic/antidiarrheal medication administered in 
standard doses according to the study center routines). Grade 3 or Grade 4 ALT/AST 
elevations should be managed as described below. 
• At the discretion of the investigator, oral study drug may be interrupted or continued if 
new or worsening unexplained pulmonary symptoms suggestive of pneumonitis 


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(including, but not limited to, dyspnea) occur and while evaluation to rule out 
pneumonitis or confirm such a diagnosis as well as etiology are ongoing; these events 
should be managed as described below. 
• In addition, and at the discretion of the investigator, the dose of rucaparib may be held 
and/or reduced for Grade 2 toxicity not adequately controlled by concomitant 
medications and/or supportive care. 
MANAGEMENT OF ANEMIA 
If anemia CTCAE Grade ≥ 3 occurs and persists for > 14 days, or a dependence upon blood 
transfusions occurs, then weekly complete blood counts are recommended until resolution of 
the anemia to ≤ Grade 1. If after 42 days of treatment interruption anemia has not improved 
to Grade ≤ 1, a referral to a hematologist and analysis of the bone marrow according to 
institutional standard practice is recommended. 
• Refer to Sections 10.3 and 10.7 of the protocol for additional information regarding 
classification and reporting of MDS or AML as an AESI. 
MANAGEMENT OF RUCAPARIB TREATMENT-EMERGENT ALT/AST ELEVATIONS  
• Grade 4 ALT/AST elevations: hold rucaparib until values have returned to Grade 2 or 
better, then resume rucaparib with a dose reduction. Monitor liver function tests 
weekly for 3 weeks after rucaparib has been restarted. 
• Grade 3 ALT/AST elevations, in the absence of other signs of liver dysfunction, 
should be managed as follows:  
– Monitor liver function tests weekly until improvement to ≤ Grade 2. 
– Continuation of rucaparib with elevation of ALT/AST up to Grade 3 is 
permitted provided bilirubin is < ULN and alkaline phosphatase is < 3 x ULN.  
– If patient has Grade 3 ALT/AST and continues on rucaparib, and levels do not 
decline within 2 weeks or they continue to rise, treatment interruption and 
resolution to ≤ Grade 2 will be required before rucaparib can be resumed, 
either at the current dose or at a reduced dose. 
Treatment with rucaparib should be held until the toxicity resolves to ≤ CTCAE Grade 2. 
Twice daily dosing may then be resumed at either the same dose or a lower dose, per 
investigator discretion. If treatment is resumed at the same dose, and the patient experiences 
the same toxicity, the dose should be reduced following resolution of the event to ≤ CTCAE 
Grade 2. If the patient continues to experience toxicity, additional dose reduction steps are 
permitted; however, the investigator should consult with the Sponsor’s medical monitor 
before reducing to 300 mg BID. If a patient continues to experience toxicity despite dose 
reduction steps to 300 mg BID, or if dosing with rucaparib is interrupted for > 14 consecutive 
days due to toxicity, treatment should be discontinued, unless otherwise agreed between the 
investigator and the Sponsor. 


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DILI is described in the FDA Guidance for Industry, Drug-Induced Liver Injury: 
Premarketing Clinical Evaluation 63 and should be referenced when managing 
treatment-emergent ALT/AST elevations. 
Rucaparib treatment must be interrupted if biochemical criteria for suspected DILI are met, 
according to presence of the following laboratory abnormalities:  
ALT or AST > 3x ULN AND bilirubin > 2x ULN. 
While treatment is interrupted, the patient should be evaluated for the presence of 
confounding factors including malignant disease in the liver, co-administration of other 
suspect drugs, cholestasis, and viral or autoimmune hepatitis that could have caused the 
laboratory abnormalities. Other laboratory investigations of liver function such as monitoring 
of international normalized ratio (INR) should be implemented as indicated. If no alternative 
cause is identified, rucaparib must be permanently discontinued. 
All cases of possible DILI must be reported as SAEs (see Section 10.9) and will be followed 
until all abnormalities have returned to normal, returned to baseline levels, or an alternative 
cause is found to explain the combination of the increased transaminases and total bilirubin.  
MANAGEMENT OF NEW OR WORSENING PULMONARY SYMPTOMS 
If new or worsening unexplained pulmonary symptoms suggestive of pneumonitis 
(including, but not limited to, dyspnea) occur, or a deterioration of pulmonary function is 
observed, and/or radiologic abnormality is detected in the lungs, and this occurs in the 
absence of any clear diagnosis, a diagnostic workup (including high resolution CT scan) in 
consultation with a pulmonologist should be performed in order to rule out pneumonitis. 
During this time, treatment with rucaparib may be interrupted or continued per investigator 
discretion. 
Following investigation, if pneumonitis is not confirmed, treatment with rucaparib may be 
resumed/continued as deemed appropriate by the investigator and in accordance with the 
study protocol directions for management of AEs. All confirmed events of pneumonitis 
should be treated as appropriate per medical judgement and institutional guidelines. If the 
event resolves and retreatment with rucaparib is being considered, please consult the 
Sponsor’s Medical Monitor. Re-treatment with rucaparib may be resumed at the current or a 
reduced dose, if appropriate.  
Refer to Sections 10.3 and 10.7 of the protocol for additional information regarding 
classification and reporting of pneumonitis (and associated events) as an AESI. 


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DOSE REDUCTION STEPS 
Dose reduction steps are presented in Table 3. 
Dose escalation upon resolution of toxicity to ≤ CTCAE Grade 1 is permitted at the 
discretion of the Investigator. 
Dose modifications must be recorded for each patient in the appropriate section of the eCRF. 
Table 3. 
Rucaparib Dose Reduction Steps 
Starting Dose 
600 mg BID 
Dose Level – 1 
500 mg BID 
Dose Level – 2 
400 mg BID 
Dose Level - 3a 
300 mg BID 
Abbreviation: BID = twice a day. 
a 
Consult with Sponsor’s medical monitor before reducing to dose level 3. Further dose reduction may be 
possible, but requires consultation with the Sponsor’s medical monitor. 
 
7.5.2 
Single-agent Weekly Paclitaxel Preparation, Administration, and 
Restrictions 
The starting dose of weekly paclitaxel is 60 to 80 mg/m2 (dose per institutional standard of 
care) administered via IV infusion on Days 1, 8, and 15 in each 28-day cycle (with a week 
break from dosing on Day 22 in each cycle). Body surface area (BSA) will be determined 
before the start of each cycle, based on baseline height and most recent weight, or as 
determined by institutional guidelines. All patients should be pre-medicated prior to 
paclitaxel administration in order to prevent severe hypersensitivity reactions. Such 
pre-medication may consist of dexamethasone 20 mg PO administered approximately 12 and 
6 hours before paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes 
prior to paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before 
paclitaxel. Pre-medications should be recorded in the appropriate eCRF. 
Handling, preparation, administration, precautions, and restrictions for the use of paclitaxel 
are to follow Prescribing Information provided in the Pharmacy Guidelines or approved 
institutional or local guidelines. Paclitaxel must be diluted prior to infusion. 
7.5.3 
Single-agent Cisplatin and Carboplatin Preparation, Administration, and 
Restrictions 
Body surface area will be determined before the start of each cycle, based on baseline height 
and most recent weight, or as determined by institutional guidelines. The dosage, dosing 
schedule, and administration of single-agent cisplatin or carboplatin will follow institutional 
guidelines for each agent. Appropriate site personnel should prepare and administer study 
drug. A maximum of 8 cycles of single-agent cisplatin or carboplatin are to be administered. 


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Caution should be exercised in handling the aqueous solution. Procedures for proper 
handling and disposal of anticancer drugs should be utilized. Qualified personnel 
(eg, pharmacist) should be designated to prepare cisplatin or carboplatin. Needles or 
intravenous sets containing aluminum parts that may come in contact with cisplatin or 
carboplatin should not be used for preparation or administration. Aluminum reacts 
with these drugs, causing precipitate formation and a loss of potency. 
Handling, preparation, administration, precautions, restrictions and other information for the 
use of each drug are in the Prescribing Information provided in the Pharmacy Guidelines or 
approved institutional or local guidelines. 
7.5.4 
Platinum-based Doublet Chemotherapy Preparation, Administration, and 
Restrictions 
Body surface area will be determined before the start of each cycle, based on baseline height 
and most recent weight, or as determined by institutional guidelines. The dosage, dosing 
schedule, and administration of doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or 
cisplatin/gemcitabine IV infusion will follow institutional guidelines for each agent. A 
maximum of 8 cycles of platinum doublet therapy are to be administered in this study. 
Appropriate site personnel should prepare and administer study drug.  
Caution should be exercised in handling and preparing chemotherapeutic agents. Procedures 
for proper handling and disposal of anticancer drugs should be utilized. Qualified personnel 
(eg, pharmacist) should be designated to prepare chemotherapy.  
Handling, preparation, administration, precautions, restrictions and other information for the 
use of each drug are in the Prescribing Information provided in the Pharmacy Guidelines or 
approved institutional or local guidelines. 
7.5.5 
Re-treatment and Dose Modification for All Chemotherapy 
In the event of toxicities, dose delays and modifications should occur in accordance with the 
highest toxicity observed per the recommendations and guidelines provided in the approved 
Prescribing Information provided in the Pharmacy Guidelines or according to institutional 
guidelines or local dose reduction protocols. Dose modifications must be recorded for each 
patient in the appropriate section of the eCRF.  
7.5.6 
Treatment with Rucaparib beyond Progression 
Patients will receive the study drug to which they are randomized (rucaparib or 
chemotherapy) until radiologic disease progression by investigator-assessed 
RECIST Version 1.1; unacceptable toxicity or inability to tolerate further treatment, as 
assessed by the investigator; pregnancy; death; loss to follow-up; withdrawal of consent, or 
other appropriate clinical reason.  
If a patient receiving study drug has met criteria for confirmed radiologic disease progression 
by RECIST Version 1.1 criteria, but continues to derive clinical benefit per the investigator, 
continuation of treatment will be permitted. In such cases, the documented decision to 


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continue rucaparib treatment will be provided to the Sponsor (or designee) and the 
investigator’s decision to continue treatment must be documented in the source documents. 
The patient must provide additional consent that should be obtained within reasonable 
timeframe of the documented decision to continue treatment with rucaparib. Clinical 
scenarios where continuation of study drug after radiographic progression may be considered 
include 1) a patient for whom radiographic progression develops slowly while disease-related 
symptoms remain well controlled, 2) a patient who experiences progression in a site of 
disease that is unlikely to adversely affect prognosis (eg, enlargement of a solitary lymph 
node), or 3) a patient with general disease control but limited progression in sites of disease 
that can be managed with local therapies such as surgery or radiation. 
Patients continuing to receive rucaparib will continue to have all protocol required 
assessments as described in Section 8. 
7.5.6.1 
Crossover to Rucaparib Treatment 
Patients initially randomized to chemotherapy have the option to cross over to rucaparib 
treatment upon radiologic disease progression with Sponsor (or designee) approval of the 
radiology report confirming disease progression, signed consent for crossover, and meeting 
eligibility for the crossover as listed in Section 6.4. Patients who cross over to receive 
rucaparib will continue to have all protocol-required assessments as described in Section 8. 
Crossover to rucaparib can occur after toxicities related to chemotherapy have resolved or 
sufficiently stabilized and patient meets all criteria for initiation of treatment with rucaparib. 
Initiation of treatment with rucaparib should occur within 8 weeks following radiologic 
disease progression.  
7.5.6.2 
Continuation of Rucaparib 
If a patient receiving rucaparib (either initial randomization or as crossover treatment) has 
met criteria for radiologic disease progression by RECIST Version 1.1, but the patient 
continues to derive clinical benefit per the investigator, then continuation of treatment will be 
permitted. In such cases, the documented decision to continue will be made jointly between 
the investigator and the Sponsor (or designee) (see Section 7.5.6). The patient must provide 
additional consent that should be obtained within reasonable timeframe following the 
decision to continue treatment with rucaparib. Patients continuing to receive rucaparib will 
continue to have all protocol-required assessments as described in Section 8. 
7.6 
Treatment Compliance 
7.6.1 
Rucaparib Treatment Compliance 
Study-site personnel will review dosing information with the patient (or legally authorized 
representative) on scheduled clinic visit days, providing instructions regarding dose, dose 
frequency and the number of tablets to be taken for each dose. Patients (or legally authorized 
representative) will be instructed to keep all unused tablets and containers (empty, partially 
used, and/or unopened) for accountability at the next scheduled clinic visits. A compliance 
check and tablet count will be performed by study personnel during clinic visits. Study site 
personnel will record compliance information on the electronic case report form (eCRF). 


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Every effort should be made to ensure patients return to the clinic with their study drug 
containers/unused study drug at the end of each cycle of treatment. Study site personnel 
should conduct a verbal review of dosing with the patient and document the discussion in the 
patient’s medical record. This may serve as source documentation for the purpose of entering 
dosing data on the appropriate eCRF. 
7.6.2 
Chemotherapy Treatment Compliance 
Chemotherapy will be administered by study-site personnel as an infusion during study-site 
visits. Drug dosing and administration will be managed by the study-site for each patient 
following the institutional guidelines or Prescribing Information for each agent.  
7.7 
Accountability of Protocol-specified Treatment 
Study personnel will maintain accurate records of study drug receipt, dispensation, use, 
return, destruction, and reconciliation for study drugs provided by the Sponsor. The IRT will 
be used to manage study drug inventory at all sites. In order to function properly, the system 
will require real-time entry of study drug receipt, dispensation, destruction, etc. by study 
personnel at the study center. 
The site is responsible for the return or destruction of study drug supplied by the Sponsor as 
required. Authorization to destroy study drug at the site that has not been dispensed to a 
patient (eg, expired study drug), must be requested from the Sponsor prior to destruction. 
Any study drug supplied by the Sponsor accidentally or deliberately destroyed must be 
accounted for. All study drug containers must be accounted for prior to their destruction at 
the study center, according to institutional procedures for disposal of cytotoxic 
chemotherapeutic drugs. Unused study drug containers should be destroyed on-site if 
possible. If destruction on site is not possible, supply should be returned to the drug depot. 
During the course of the study and at completion of the study, the number of study drug 
containers received, dispensed, returned, and destroyed must be reconciled. 
For comparator chemotherapy that is sourced locally, the study site should follow local drug 
accountability practices. 
7.8 
Prior and Concomitant Therapy 
Patients who have received prior treatment with a PARP inhibitor including IV or oral 
rucaparib or with single-agent paclitaxel or nab-paclitaxel are not eligible to participate in 
this study.  
During the study, supportive care (eg, antiemetics; analgesics for pain control) may be used 
at the investigator’s discretion and in accordance with institutional procedures. Supportive 
care must be recorded for each patient in the appropriate section of the eCRF.  
All procedures performed (eg, thoracentesis, etc.) during the study must be documented on 
the eCRF. 


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7.8.1 
Anticancer or Experimental Therapy 
No other anticancer therapies (including chemotherapy, radiation, antibody or other 
immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or other 
experimental drugs) of any kind will be permitted while the patient is participating in the 
study with the exception of hormonal treatment for prior breast cancer. Prior treatment with 
such excluded anticancer therapies must have been completed > 14 days prior to the first 
dose of study drug. 
7.8.2 
Hematopoietic Growth Factors and Blood Products 
Erythropoietin, darbepoetin alfa, and/or hematopoietic colony-stimulating factors for 
treatment of cytopenias should be administered according to institutional guidelines. 
Transfusion thresholds for blood product support will be in accordance with institutional 
guidelines. 
7.8.3 
CYP450 Isoenzyme Inhibitors, Inducers, and Substrates 
Based on the results from the in vivo CYP interaction study (CO-338-044), rucaparib is a 
moderate inhibitor of CYP1A2, and a weak inhibitor of CYP2C9, CYP2C19, and CYP3A. 
Caution should be used in patients taking concomitant medicines that are sensitive substrates 
of CYP1A2, CYP2C9, and/or CYP3A (Appendix 3).  
Patients taking phenytoin, a CYP2C9 substrate with a narrow therapeutic window, should 
have therapeutic drug level monitored while using concomitantly with rucaparib.  
Although in vitro rucaparib metabolism mediated by CYP3A4 was slow, a significant 
contribution of CYP3A4 in vivo cannot be excluded. Caution should be used for concomitant 
use of strong CYP3A4 inhibitors or inducers. 
7.8.4 
Transporter Inhibitors, Inducers, and Substrates 
Based on the results from Study CO-338-095, rucaparib weakly inhibited BCRP. Caution 
should be used for concomitant use of BCRP substrates (eg, rosuvastatin, sulfasalazine). 
7.8.5 
Bisphosphonates 
Bisphosphonates are permitted. 
7.8.6 
Anticoagulants 
Rucaparib is a weak inhibitor of CYP2C9 in vivo. Caution should be exercised in patients 
receiving rucaparib and concomitant warfarin (Coumadin). Patients taking warfarin should 
have INR monitored regularly per standard clinical practice. 


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7.8.7 
Other Concomitant Medications 
Therapies considered necessary for the patient’s well-being may be given at the discretion of 
the investigator and should be documented on the eCRF. Other concomitant medications, 
except for analgesics, chronic treatments for concomitant medical conditions, or agents 
required for life-threatening medical problems, should be avoided. Herbal and 
complementary therapies should not be encouraged because of unknown side effects and 
potential drug interactions, but any taken by the patient should be documented appropriately 
on the eCRF.  
Rucaparib marginally increased digoxin AUC by 20%. Caution should be exercised for 
patients receiving rucaparib and requiring concomitant medication with digoxin. Patients 
taking digoxin should have their digoxin levels monitored after starting rucaparib and then 
regularly per standard clinical practice. 
Rucaparib marginally increased the Cmax and mildly increased the AUC of oral 
contraceptives (ethinylestradiol and levonorgestrel). No clinically meaningful DDIs are 
expected for concomitant use of oral contraceptives and rucaparib. 
In vitro, rucaparib is a potent inhibitor of MATE 1 and MATE2-K, a moderate inhibitor of 
OCT1, and a weak inhibitor of OCT2. As inhibition of these transporters could increase 
metformin renal elimination and decrease liver uptake of metformin, caution is advised when 
metformin is co-administered with rucaparib. Although in vitro rucaparib metabolism 
mediated by CYP3A4 was slow, a significant contribution of CYP3A4 in vivo cannot be 
excluded. Caution should be used for concomitant use of strong CYP3A4 inhibitors or 
inducers. 


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8 
STUDY PROCEDURES AND ACTIVITIES BY VISIT 
8.1 
Schedule of Assessments 
Table 4 summarizes the procedures and assessments to be performed for all patients. Study 
procedures and assessments should be performed as close to the scheduled time as possible, 
but within ± 3 days of the scheduled time unless otherwise stated.  






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Table 4. 
Schedule of Assessments for All Patients (Randomization to Therapy at Study Initiation) 
a 
= The study visit window in the treatment phase is ± 3 days, unless noted otherwise for a particular assessment.  
b 
= First dose of study drug in Cycle 1 must be administered within 3 days after randomization. All procedures on Day 1 of any cycle are to be performed before 
administration of paclitaxel, monotherapy cisplatin, monotherapy carboplatin, or platinum-based doublet therapy. Procedures required on Cycle 1 Day 1 may 
be omitted, if completed successfully ≤ 3 days prior to first dose of study drug during the screening period. 
c 
= Patients randomized to rucaparib will visit the study site on Day 15 of Cycles 1 and 2 for study procedures. Beginning with Cycle 3, patients receiving 
rucaparib will only need to visit the study site on Day 1 of each cycle. 
d 
= Patient’s medical record must include prior surgeries/treatments received, dates of administration, date of progression and how assessed, radiology reports, 
best response achieved, and progression-free interval after last platinum regimen. If known, BRCA1/2 mutation status will also be recorded on the appropriate 
case report form. 
e 
= Adequate archival tumor tissue sample or a new sample, if needed, must be provided to the central laboratory to enable determination of HRD status for 
eligibility, randomization, determination of HRD status prior to final analysis (if required), and storage for potential bridging to the final companion diagnostic 
test. Patients with a known deleterious BRCA1/2 mutation (germline or somatic) must also have sufficient quantity of archival tumor tissue for central 
laboratory testing; however, may enroll based upon previous documented local laboratory results. The most recently collected sample available of adequate 
quality and quantity must be provided or a new sample acquired. Tumor tissue content ≥ 20% with ≥ 80% nucleated cellular content is required. If archival 
tumor tissue is not available, patients may undergo a screening biopsy. A sufficient quantity of archival tumor tissue or tumor tissue from a screening biopsy 
must be submitted to the central laboratory at least 3 weeks prior to planned randomization for determination of eligibility. 
f 
= PRO instruments must be completed before other scheduled study procedures and dosing (if applicable) at Screening, on Day 1 of each treatment cycle, at 
treatment discontinuation, and at the 28-day Safety Follow-up Visit (randomized treatment discontinuation and/or crossover rucaparib treatment 
discontinuation) for all patients.  
g 
= Height at screening only. Weight at screening, Day 1 of each cycle, during each visit before administration of chemotherapy, at randomized treatment 
discontinuation, and at the 28-day Safety Follow-up Visit. Chemotherapy will be administered after completion of the physical examination during a study 
visit. 
h 
= Vital signs (blood pressure, pulse, and body temperature) after the patient has been resting for at least 5 minutes. For patients receiving chemotherapy, vital 
signs will be assessed before administration. 
i 
= Heart rate, PR, QRS, QT, QTc, and rhythm. Investigator to review results and assess as normal or abnormal, and if abnormal whether clinically significant or 
not clinically significant. ECGs are to be completed on Day 1 of each cycle for patients receiving rucaparib and chemotherapy. ECGs on intracycle visits 
(Day 8 and Day 15) may be performed if clinically indicated per investigator judgement. An ECG is not performed at Day 15 in Cycles 1 and 2 of rucaparib 
treatment. ECG assessments may be repeated as clinically indicated. 
j 
= Concomitant medications/procedures will be reviewed with patients at each study visit and updated as needed. 
k 
= Disease/ tumor assessments to consist of clinical examination and appropriate imaging techniques (ie, CT scans of the chest, abdomen, and pelvis with 
appropriate slice thickness per RECIST Version 1.1); other studies (MRI, X-ray, PET, and ultrasound) may be performed if required. The same methods used 
to detect lesions at baseline (ie, initial study screening) are to be used to follow the same lesions throughout the clinical study. If a patient has known brain 
metastases, this disease should be evaluated by CT scan at each required assessment time.  


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Table 4. 
Schedule of Assessments for All Patients (Randomization to Therapy at Study Initiation) 
l 
= Disease/ tumor assessments to be performed at baseline (screening) and at the end of every 8 calendar weeks relative to Cycle 1 Day 1 after randomization 
(within 5 days before is permitted). Disease progression will only be determined by RECIST Version 1.1. Patients who meet GCIG CA-125 criteria for disease 
progression should have a radiologic assessment and be assessed by RECIST Version 1.1. If the radiologic assessment does not confirm GCIG CA-125 
disease progression, patients should continue on treatment and continue to be assessed by RECIST Version 1.1 per the protocol schedule of assessments.  
m 
= Disease/ tumor assessments to be performed at the end of every 8 calendar weeks relative to Cycle 1 Day 1 (within 5 days before is permitted) until 
investigator-assessed radiologic disease progression by RECIST Version 1.1 for any patient who discontinued from study treatment for reason other than 
disease progression or death (scans occur at treatment discontinuation or 28-day safety follow-up if it has been ≥ 8 weeks since last scan or disease progression 
was noted on the last scan). Patients who cross over to with rucaparib will have tumor assessments every 8 calendar weeks relative to Day 1 of initiation of 
treatment with rucaparib. 
n 
= ECOG performance status is to be completed before administration of chemotherapy during a study visit. 
o 
= Includes RBC and parameters (Hgb, Hct, MCV, MCH, MCHC) and reticulocyte count, WBC and differential (with ANC), and platelet count. Blood will be 
analyzed by a local laboratory. The hematology blood sample is to be collected before administration of chemotherapy during a study visit. Additional and 
more frequent tests may be performed at the investigator’s discretion. 
p 
= Includes total protein, albumin, creatinine or estimated GFR using the Cockcroft Gault formula, BUN or urea, total bilirubin, ALP, ALT, AST, glucose, 
sodium, potassium, chloride, bicarbonate, calcium, phosphorus, and lipid panel (total cholesterol, LDL, HDL, and triglycerides). Blood will be analyzed by a 
local laboratory. The serum chemistry blood sample is to be collected before administration of chemotherapy during a study visit, except at Day 8 visits where 
serum chemistry may be performed at investigator’s discretion. Additional and more frequent tests may be performed at the investigator’s discretion. 
q 
= Women of childbearing potential must have a negative serum pregnancy test result ≤ 3 days prior to the first dose of study drug. A serum pregnancy test must 
be performed ≤ 3 days prior to Day 1 of every cycle during the treatment phase and at the treatment discontinuation visit. All tests will be performed by a local 
laboratory. 
r 
= Includes dipstick for protein, glucose, blood, pH, and ketones. If dipstick findings abnormal based on investigator’s judgment, perform microscopic evaluation 
to assess abnormal findings. Urinalysis to be repeated as clinically indicated.  
s 
= CA-125 measurement should be performed at screening, on Cycle 1 Day 1, at the start of every 2nd cycle thereafter (ie, Day 1 of Cycles 3, 5, 7, etc.), at 
randomized treatment discontinuation, at the 28-day Safety Follow-up Visit, and as clinically indicated. All CA-125 measurements will be performed by a 
local laboratory. 
t 
= Randomization will occur by a central randomization procedure using IRT. Patients will be stratified at study entry based on the interval between completion 
of the most recent platinum regimen and disease progression by radiologic assessment. Platinum-resistant and partially platinum-sensitive patients will be 
randomized 2:1 to receive rucaparib or weekly paclitaxel. Platinum-sensitive patients will be randomized 2:1 to receive rucaparib or chemotherapy. The 
investigator will select an appropriate single-agent or doublet chemotherapy from those offered in the study, which include single-agent cisplatin or 
carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine. No more than 8 cycles of platinum monotherapy or doublet 
therapy are to be administered. 
u 
= Blood for germline/somatic (g/s) BRCA status: Blood samples will be collected from all enrolled patients for g/sBRCA mutation analysis on Day 1 of Cycle 1. 
If sample is not collected on Day 1 of Cycle 1, it should be collected as soon as possible thereafter.  
Blood sample for ctDNA analysis: Blood samples for ctDNA analysis will be collected for all patients at screening, before dosing on Day 1 of Cycles 1 to 6, 
and at treatment discontinuation. Refer to the Laboratory Manual for details.  


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Table 4. 
Schedule of Assessments for All Patients (Randomization to Therapy at Study Initiation) 
v 
= Plasma samples for PK analysis are to be collected in patients randomized to receive rucaparib. Samples should be collected before the morning dose on Day 1 
of Cycles 2 to 6 as close to 12 hours after the previous dose as possible. If the start of the next treatment cycle is delayed, the PK sample should still be 
collected during this visit instead of on Day 1 of the delayed start of the next treatment cycle. Samples are not to be collected in patients receiving 
chemotherapy or crossing over to rucaparib. Refer to the Laboratory Manual for sample collection details. 
w 
= Study procedures are to be completed before administration of chemotherapy. 
x 
= Paclitaxel treatment visits occur on Days 1, 8, and 15 of each 28-day cycle (with a break from dosing on Day 22 in each cycle). Single-agent platinum or 
doublet chemotherapy will be administered in 21- or 28-day cycles, per institutional guidelines. Treatment visits may vary dependent upon the chemotherapy 
selected and patients should return to the study site for treatment according to the appropriate institutional schedule for each respective chemotherapy. No 
more than 8 cycles of platinum monotherapy or doublet therapy are to be administered. 
y 
= Study visits should take into account the patient’s rucaparib supply. A quantity of rucaparib sufficient to complete 1 cycle will be dispensed to the subject on 
Day 1 of each cycle. Each treatment cycle is 28 days. 
z 
= AEs that occur after first administration of study drug through to 28 days after last dose of study drug will be recorded. SAEs that are deemed related to a 
screening procedure will be recorded/submitted. All treatment-related SAEs, and the AESIs myelodysplastic syndrome (MDS) and acute myeloid leukemia 
(AML) of any causality, are to be reported, even if they occur after the 28-day safety follow-up.  
aa 
= Ongoing SAEs, AESIs, and treatment-related Grade 3/4 AEs will be followed until resolution, stabilization, or lost to follow up. SAEs/AESIs are collected per 
Clovis PV guidelines and reported in the Clovis PV database through the 28-day Follow-up Visit after the last dose of rucaparib. After this visit, only SAEs 
considered as potentially related to study drug (including serious reports of pneumonitis or similar events, ie, interstitial lung disease, pulmonary fibrosis, 
acute interstitial pneumonitis, alveolitis necrotizing, alveolitis, hypersensitivity pneumonitis, and organizing pneumonia, if considered to be related to 
study drug), and AESIs of MDS and AML irrespective of causality, will be reported. If a patient discontinues from treatment and begins a subsequent 
anti-cancer therapy, the Sponsor will terminate collection of SAEs, with the exception of AESIs MDS and AML. 
bb 
= An optional tumor biopsy may be collected from patients from time of radiographic disease progression/randomized treatment discontinuation until the start of 
the next treatment. The option will also be available to patients allowed by the investigator and Sponsor to continue rucaparib after radiologic disease 
progression at the time of first disease progression. Additional consent is required. Refer to the Pathology Charter for detailed sample handling instructions. If 
disease progression is caused by appearance of a new lesion(s), the lesion(s) should be prioritized for the optional biopsy. 
cc 
= Patients will have 28-day (±3 days) safety follow-up after the last dose of study drug (initial treatment or rucaparib as crossover treatment, as applicable). 
Patients randomized to rucaparib or who cross over to receive rucaparib will have the safety follow-up visit at 28-days after discontinuation of rucaparib. 
Patients randomized to chemotherapy will have a safety follow-up visit 28 (±3) days after the last dose of chemotherapy and continue with long-term 
follow-up (LTFU) until disease progression. 
dd 
= Following disease progression or other reason for treatment discontinuation, patients will be followed for subsequent treatments, secondary malignancy, and 
survival every 12 weeks (± 14 days) until death, loss to follow-up, withdrawal of consent from study, or closure of the study. Follow-up can be performed via 
the telephone. Diagnosis of any secondary malignancy requires appropriate documentation (ie, laboratory and/ or pathology reports) and should be reported as 
specified in Section 10.10. 
 




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Table 5. 
Schedule of Assessments for Patients Who Cross Over to Rucaparib After Being Randomized to 
and Receiving Chemotherapy 
Abbreviations: AE = adverse event, AESI = adverse event of special interest, ALP = alkaline phosphatase, ALT = alanine transaminase, AML = acute myeloid 
leukemia, ANC = absolute neutrophil count, AST = aspartate transaminase, BRCA1/2 = breast cancer gene, BUN = blood urea nitrogen, CA-125 = cancer antigen 
125, CT = computed tomography, ctDNA = circulating cell-free tumor DNA, ECG = electrocardiogram, ECOG = Eastern Cooperative Oncology Group, EORTC 
QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, EORTC QLQ-OV28 = European Organization for 
Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer Module OV28, EQ-5D = Euro-QoL 5D, QoL= quality of life, GCIG = gynecologic 
cancer intergroup, GFR = glomerular filtration rate, Hct = hematocrit, HDL= high density lipoprotein, Hgb = hemoglobin, HRD = homologous recombination 
deficiency, IRT = interactive response technology, LDL= low density lipoprotein, MCH = mean corpuscular hemoglobin, MCHC, = mean corpuscular hemoglobin 
concentration, MCV = mean corpuscular volume, MDS = myelodysplastic syndrome, MRI = magnetic resonance imaging, PET = positron emission tomography, 
PRO = patient-reported outcome, RBC= red blood cell count, RECIST = Response Evaluation Criteria in Solid Tumors, SAE = serious adverse event, WBC = white 
blood cell  
a 
= The study visit window in the treatment phase is ± 3 days, unless noted otherwise for a particular assessment.  
b 
= First dose of rucaparib in Cycle 1 of the crossover treatment must be administered ≤ 8 weeks after radiologic disease progression on chemotherapy. 
c 
= Patients will visit the study site on Day 15 of Cycles 1 and 2 for study procedures. Beginning with Cycle 3, patients will only need to visit the study site on 
Day 1 of each cycle. 
d 
= PRO instruments must be completed before other scheduled study procedures and dosing (if applicable) at Screening, on Day 1 of each treatment cycle, at 
treatment discontinuation, and at the 28-day Safety Follow-up Visit for rucaparib crossover patients. 
e 
= Weight at screening, Day 1 of each cycle, at cross over to rucaparib treatment discontinuation, and at the 28-day Safety Follow-up Visit. 
f 
= Vital signs (blood pressure, pulse, and body temperature) after the patient has been resting for at least 5 minutes. 
g 
= Heart rate, PR, QRS, QT, QTc, and rhythm. Investigator to review results and assess as normal or abnormal, and if abnormal whether clinically significant or 
not clinically significant. ECGs are to be completed at screening, Day 1 of each cycle and repeated as clinically indicated. 
h 
= Concomitant medications/procedures will be updated at each study visit. 
i 
= Disease/ tumor assessments to consist of clinical examination and appropriate imaging techniques (ie, CT scans of the chest, abdomen, and pelvis with 
appropriate slice thickness per RECIST Version 1.1); other studies (MRI, X-ray, PET, and ultrasound) may be performed if required. The same methods used 
to detect lesions at baseline (ie, initial study screening) are to be used to follow the same lesions throughout the clinical study. If a patient has known brain 
metastases, this disease should be evaluated by CT scan at each required assessment time. 
j 
= Disease/ tumor assessments to be performed at screening (if it has been ≥ 6 weeks since last scan or disease progression was noted on the last scan), at the end 
of every 8 calendar weeks after Cycle 1 Day 1 in the crossover period, relative in timing to Cycle 1 Day 1 (within 5 days before is permitted) of rucaparib 
treatment in the crossover period. Disease progression will only be determined by RECIST Version 1.1. Patients who meet GCIG CA-125 criteria for disease 
progression should have a radiologic assessment and be assessed by RECIST Version 1.1. If the radiologic assessment does not confirm GCIG CA-125 
disease progression, patients should continue on treatment and continue to be assessed by RECIST Version 1.1 per the protocol schedule of assessments.  
k 
= Disease/ tumor assessments to be performed at the end of every 8 calendar weeks relative to Cycle 1 Day 1 (within 5 days before is permitted) of rucaparib in 
the crossover period until investigator-assessed radiologic disease progression by RECIST Version 1.1 for any patient who discontinued from study treatment 
for reason other than disease progression, death, or initiation of subsequent treatment (scans occur at treatment discontinuation or 28-day safety follow-up if it 
has been ≥ 8 weeks since last scan or disease progression was noted on the last scan).  


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Table 5. 
Schedule of Assessments for Patients Who Cross Over to Rucaparib After Being Randomized to 
and Receiving Chemotherapy 
l 
= Includes RBC and parameters (Hgb, Hct, MCV, MCH, MCHC) and reticulocyte count, WBC and differential (with ANC), and platelet count. Blood will be 
analyzed by a local laboratory. Additional and more frequent tests may be performed at the investigator’s discretion. 
m 
= Includes total protein, albumin, creatinine or estimated GFR using the Cockcroft Gault formula, BUN or urea, total bilirubin, ALP, ALT, AST, glucose, 
sodium, potassium, chloride, bicarbonate, calcium, phosphorus, and lipid panel (total cholesterol, LDL, HDL, and triglycerides). Blood will be analyzed by a 
local laboratory. Additional and more frequent tests may be performed at the investigator’s discretion. 
n 
= Women of childbearing potential must have a negative serum pregnancy test result ≤ 3 days prior to the first dose of crossover rucaparib treatment. A serum 
pregnancy test must be performed ≤ 3 days prior to Day 1 of every cycle during the treatment with rucaparib and at the treatment discontinuation visit. All 
tests will be performed by a local laboratory. 
o 
= Includes dipstick for protein, glucose, blood, pH, and ketones. If dipstick findings abnormal based on investigator’s judgment, perform microscopic 
evaluation to assess abnormal findings. Urinalysis to be repeated as clinically indicated.  
p 
= CA-125 measurement should be performed during the rucaparib crossover period at screening, on Cycle 1 Day 1, at the start of every 2nd cycle thereafter 
(ie, Day 1 of Cycles 3, 5, 7, etc.), at crossover rucaparib treatment discontinuation, at the 28-day Safety Follow-up Visit, and as clinically indicated. All CA-
125 measurements will be performed by a local laboratory. 
q 
= Blood samples will be collected from all patients for ctDNA analysis during the rucaparib crossover period at screening, before the rucaparib dose on Day 1 
of Cycles 1 to 6, and at crossover rucaparib treatment discontinuation. Refer to the Laboratory Manual for details.  
r 
= Study visits should take into account the patient’s rucaparib supply. A quantity of rucaparib sufficient to complete 1 cycle will be dispensed to the subject on 
Day 1 of each cycle. Each treatment cycle is 28 days. 
s 
= AEs that occur after first administration of study drug through to 28 days after last dose of study drug will be recorded. In addition, AEs/SAEs that were 
related to a screening procedure will also be recorded. All treatment-related SAEs, and the AESIs of myelodysplastic syndrome (MDS) and acute myeloid 
leukemia (AML) of any causality, are to be reported, even if they occur after the 28-day safety follow-up. 
t 
= Ongoing SAEs, AESIs, and treatment-related Grade 3/4 AEs will be followed until resolution, stabilization, or lost to follow up. SAEs/AESIs are collected 
per Clovis PV guidelines and reported in the Clovis PV database through the 28-day Follow-up Visit after the last dose of rucaparib. After this visit, only 
SAEs considered as potentially related to study drug (including serious reports of pneumonitis or similar events, if considered to be related to study drug), and 
AESIs of MDS and AML irrespective of causality, will be reported. If a patient discontinues from treatment and begins a subsequent anticancer therapy, the 
Sponsor will terminate collection of SAEs, with the exception of AESIs MDS and AML. 
u 
= An optional tumor biopsy may be collected from patients any time after radiographic disease progression, cross over to rucaparib, or treatment 
discontinuation until the start of the next non-study treatment. Additional consent is required. Refer to the Pathology Charter for detailed sample handling 
instructions. If disease progression is caused by appearance of a new lesion(s), the lesion(s) should be prioritized for the optional biopsy. 
v 
= Patients will have 28-day (±3 days) safety follow-up after the last dose of rucaparib in the crossover part. 
w 
= Patients discontinued from cross over to rucaparib treatment, regardless of reason, are to be followed for subsequent treatments, secondary malignancy, and 
survival every 12 weeks (± 14 days) until death, loss to follow-up, withdrawal of consent from study, or closure of the study. Follow-up can be performed via 
the telephone. Diagnosis of any secondary malignancy requires appropriate documentation (ie, laboratory and/ or pathology reports) and should be reported as 
an SAE. 


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8.2 
Informed Consent 
The investigator or their designee shall discuss with each patient the nature of the study and 
its requirements. To participate in the study, informed consent must be obtained from each 
potential patient prior to any study activities. The information on the IRB/ ERC-approved 
consent form should be translated and communicated in the language the patient (or legally 
authorized representative) can understand. Obtaining written informed consent does not 
signify the start of the Screening Phase. The first study-specific, screening activity performed 
after signature of the informed consent form begins the Screening Phase. Informed consent 
does not expire unless specifically withdrawn by the patient. 
Analysis of tumor tissue for a deleterious BRCA1/2 mutation (germline or somatic) will be 
performed using Foundation Medicines NGS test. Results of the FMI test will be provided to 
patients who consent to receive this information. In the event a BRCA1/2 alteration is 
identified in tumor tissue, the patient may be referred by the investigator for genetic 
counseling and potential germline testing per institutional guidelines. If the patient chooses to 
have germline testing, this result will be entered in the clinical trial database for this study. 
Additionally, patients participating in the optional tumor tissue biopsy at the time of 
radiographic disease progression/randomized treatment discontinuation must provide 
additional consent for this procedure.  
Patients who cross over to treatment with rucaparib after radiologic disease progression per 
RECIST Version 1.1 by investigator assessment must provide additional consent to continue 
treatment, as well as Sponsor (or designee) approval of the radiology report confirming 
disease progression. Details regarding crossover to rucaparib begin in Section 8.6. 
Patients randomized to rucaparib with radiologic disease progression who are still receiving 
benefit and are allowed to continue rucaparib treatment must also provide consent for 
continued treatment. 
All procedures and assessments are to be completed within ± 3 days of the scheduled time 
unless otherwise stated. 
8.3 
Initial Study Screening Prior to Randomization 
Following written informed consent, and unless otherwise specified, the following 
assessments will be performed prior to randomization within the allowable windows of time 
as indicated below. Assessments performed within the specified windows, but prior to patient 
signing informed consent, are acceptable only if confirmed to have been standard of care. 
Screening procedures may be repeated if the findings/results are considered invalid or not 
representative of the patient’s baseline medical status. When screening procedures are 
repeated, the rationale should be documented in the source file. 
8.3.1 
Within 60 Days Prior to Randomization 
• Medical/oncology history, including demographic information (birth date, race, gender, 
etc.), smoking status, and oncology history, including date of diagnosis for epithelial 


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ovarian, primary peritoneal, or fallopian tube cancer (and other malignancy, if 
applicable), prior surgeries/ treatments received for cancer, dates of treatment 
administration, best response achieved, date of progression and how assessed, 
progression-free interval after last platinum regimen, radiology reports, and BRCA1/2 
mutation status (if known); 
• FFPE archival tumor tissue or screening biopsy sample. Sufficient archival FFPE tumor 
tissue (enough for 1 x 4 µm section for H&E and approximately 8 to 12 x 10 µm sections 
[unstained], or equivalent) for planned analyses should be provided. Refer to Section 9.5 
for more information and to the Pathology Charter for detailed sample handling 
instructions.  
◦ 
The most recently collected tumor tissue sample available that is of adequate 
quality (at least 20% tumor content with a minimum of 80% nucleated cellular 
content) must be provided or a new sample acquired;  
◦ 
Sample must be submitted to the central laboratory at least 3 weeks prior to 
planned randomization for determination of HRD status to assess eligibility. A 
documented local BRCA1/2 result from previous testing will be adequate for 
enrollment of patients with known deleterious BRCA1/2 mutation (germline or 
somatic); however, these patients must provide tumor tissue for central 
laboratory testing during the study (archival tumor tissue or biopsy) 
◦ 
Another sample may be obtained and testing repeated if the tumor tissue sample 
is determined to be inadequate for analysis. In those patients, it may take more 
than 60 days to complete screening assessments.  
• AE monitoring (only record if related to screening procedures). 
8.3.2 
Up to 28 Days Prior to Randomization 
• PRO collected using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or 
other collection format as appropriate (complete before other procedures); 
• Physical examination by body system, including height and weight; 
• Vital signs (blood pressure, pulse, and body temperature); 
• 12-lead ECG; 
• Prior and concomitant medications, any surgical/ medical procedures, and update medical 
history;  
• Disease/tumor assessment: assessments should consist of clinical examination and 
appropriate imaging techniques (preferably CT scans of the chest, abdomen, and pelvis 
with appropriate slice thickness per RECIST Version 1.1); other studies (magnetic 
resonance imaging [MRI], X-ray, positron emission tomography [PET], and ultrasound) 
may be performed if required. The same methods used to detect lesions at baseline are to 
be used to follow lesions throughout the clinical study. If a patient has known brain 
metastases, this disease should be evaluated at each required assessment time; 
• ECOG performance status (Appendix 2);  


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• Blood sample for ctDNA analysis (all patients); and 
• AE monitoring (only record if related to screening procedure). 
8.3.3 
Up to 14 Days Prior to Randomization 
• Hematology: includes RBC and parameters (hemoglobin, hematocrit, MCV, MCH, and 
MCHC) and reticulocyte count, WBC and differential (with ANC), and platelet count; 
• Serum chemistry: includes total protein, albumin, creatinine, or estimated GFR using the 
Cockcroft Gault formula, blood urea nitrogen (BUN) or urea, total bilirubin, ALP, ALT, 
AST, glucose, sodium, potassium, chloride, bicarbonate, calcium, phosphorus, and lipid 
panel (total cholesterol, LDL, HDL, and triglycerides). Note: fasting is not required; 
• Urinalysis (performed on freshly voided clean sample): includes dipstick for protein, 
glucose, blood, pH, and ketones. If dipstick findings are abnormal based on investigator 
judgment, then a microscopic evaluation will be performed to assess the abnormal 
findings; 
• CA-125 measurement (Appendix 4);  
• Update medical history; and 
• AE monitoring (only record if related to screening procedure). 
8.3.4 
Up to 3 Days Prior to First Dose of Study Drug 
• Serum pregnancy test for women of childbearing potential;  
• Update medical history; and 
• AE monitoring (only record if related to screening procedure) 
8.4 
Treatment Phase (Day 1 to Day 28 per Cycle) 
Patients are to be randomized to receive either rucaparib or chemotherapy (Section 5.1.2) 
after meeting eligibility criteria (Sections 6.2 and 6.3) and having completed screening 
assessments (Section 8.3).  
The first dose of study drug must be administered ≤ 3 days after randomization. Procedures 
required on Cycle 1 Day 1 may be omitted if successfully completed during the screening 
period within ≤ 3 days prior to first dose of study drug. 
Serum pregnancy testing for women of childbearing potential must occur ≤ 3 days prior to 
the first dose of study drug (Section 8.3.4). 
8.4.1 
Day 1 of Every Cycle (Rucaparib and Chemotherapy Arms, Including 
Continuation of Rucaparib Treatment after Radiologic Disease Progression) 
The following procedures/assessments will be completed for all patients before initiation of 
randomized treatment on Cycle 1 Day 1 and on Day 1 of every cycle thereafter, including 


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patients randomized to rucaparib who are allowed by the Investigator and Sponsor and 
consent to continue treatment after radiologic disease progression.  
Patients initially randomized and treated with chemotherapy who have crossed over to 
rucaparib following radiographic progression per RECIST Version 1.1 will follow the 
procedures/assessments beginning in Section 8.6. Patients who cross over to rucaparib will 
be required to sign a crossover ICF, meet eligibility criteria for the crossover described in 
Section 6.4, and have Sponsor (or designee) approval prior to crossing over to rucaparib 
treatment.  
Patients will be instructed to refrain from taking their first dose of rucaparib at home on the 
day of their Day 1 visits for Cycles 2 to 6 to collect blood/plasma samples for PK and/or 
ctDNA testing. 
• PRO using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other 
collection format as appropriate (complete before other procedures and dosing; Appendix 
5); 
• Physical examination; 
• Weight; 
• Vital Signs; 
• 12-lead ECG;  
• Concomitant medications and procedures; 
• Disease/ tumor assessment (using the same methodology as was used at screening 
[eg, CT scan]) every 8 calendar weeks (within 5 days before is permitted) relative to start 
of treatment on Day 1 of Cycle 1 through to 18 months on study, then every 16 calendar 
weeks (within 5 days before is permitted) relative to the start of treatment on Day 1 of 
Cycle 1. Timing of disease/tumor assessments is relative to Day 1 of Cycle 1 after 
randomization;  
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential; (≤ 3 days prior to start of every 
cycle); 
• CA-125 measurement (Cycle 1 and every 2nd cycle thereafter [ie, Cycles 3, 5, 7, etc.]); 
• Blood sample for ctDNA analysis (all patients – sampling before the dose on Day 1 of 
Cycles 1 to 6);  
• Blood sample for g/sBRCA analysis (one sample per randomized patient – sampling on 
Day 1 of Cycle 1 [preferred]). If sample is not collected on Day 1 of Cycle 1, it should be 
collected as soon as possible thereafter. This sample is a requirement for all patients; 


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• Plasma samples for PK analysis are to be collected in all patients receiving rucaparib (not 
in cross-over patients). Samples should be collected before the morning dose on Day 1 of 
Cycles 2 to 6 as close to 12 hours after the previous dose as possible. If the start of the 
next treatment cycle is delayed, the PK sample should still be collected during this visit 
instead of on Day 1 of the delayed start of the next treatment cycle; 
• AE monitoring; and  
• Study drug administration (weekly paclitaxel, single-agent, or doublet chemotherapy) or 
dispensation (rucaparib). 
Rucaparib tablets will be dispensed to the patient in sufficient quantity to last until Day 1 of 
the next treatment cycle. Patients will ingest rucaparib BID at about the same times every day 
as close to 12 hours apart as possible. Rucaparib should be taken with at least 8 oz (240 mL) 
of water with or without food. Patients will keep all unused tablets and containers (empty, 
partially used, and/or unopened) for accountability at the next visit. In the event of toxicities, 
re-treatment or dose modification will be according to the criteria described in Section 7.5.1). 
Paclitaxel will be prepared and administered by study site personnel after study procedures 
are completed. Weekly paclitaxel is to be administered at a starting dose of 60 to 80 mg/m2 
(dose per institutional standard of care) via IV infusion. Additional information on paclitaxel 
preparation and administration is in Section 7.5.2. In the event of toxicities, re-treatment or 
dose modification will be according to the approved Prescribing Information provided in the 
Pharmacy Guidelines or according to institutional guidelines or local dose reduction 
protocols (see Section 7.5.5). 
Single-agent platinum or doublet chemotherapy for platinum-sensitive patients will be 
prepared and administered by study site personnel after study procedures are completed and 
according to institutional guidelines. Additional information on preparation and 
administration is in Sections 7.5.3 and 7.5.4. In the event of toxicities, re-treatment or dose 
modification will be according to the approved Prescribing Information provided in the 
Pharmacy Guidelines or according to institutional guidelines or local dose reduction 
protocols (see Section 7.5.5). 
Site personnel will account for study drug that is administered or dispensed to the patient 
during the study visit and document appropriately. 
8.4.2 
Days 8 and 15 of Every Cycle (Weekly Paclitaxel Arm) 
The following procedures/assessments will be completed before weekly paclitaxel is 
administered: 
• Physical examination; 
• Weight 
• Vital Signs; 
• 12-lead ECG (as clinically indicated per investigator judgement);  
• Concomitant medications and procedures; 


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• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required) (Day 8 serum chemistry may be omitted based 
on investigator judgement); 
• AE monitoring; and 
• Study drug administration. 
Paclitaxel will be prepared and administered by study site personnel. Weekly paclitaxel is to 
be administered as 60 to 80 mg/m2 (dose per institutional standard of care) via IV infusion. 
There will be a week break from dosing on Day 22 in each 28-day cycle. In the event of 
toxicities, re-treatment or dose modification will be according to the approved Prescribing 
Information provided in the Pharmacy Guidelines or according to institutional guidelines or 
local dose reduction protocols (see Section 7.5.5). 
Site personnel will account for study drug that is administered or dispensed to the patient 
during the study visit and document appropriately.  
8.4.3 
Intra-Cycle (Single-agent Platinum or Doublet Chemotherapy of 
Investigator’s Selection) 
Based on the dosing schedule, per institutional guidelines, for the single-agent platinum or 
doublet chemotherapy that was selected by the investigator, the patient may need to return to 
the study site for dosing/procedures during a treatment cycle. Minimally, the following 
procedures/assessments are to be completed before the single-agent platinum or doublet 
chemotherapy is administered. If there are other procedures and laboratory assessments 
required per institutional guidelines for the selected treatment, they should also be completed 
at the appropriate times during each cycle: 
• Physical examination; 
• Weight 
• Vital Signs; 
• 12-lead ECG (as clinically indicated per investigator judgement);  
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• AE monitoring; and 
• Study drug administration. 
Single-agent platinum or platinum-based doublet chemotherapy for platinum-sensitive 
patients will be prepared and administered by study site personnel after study procedures are 


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completed and according to institutional guidelines. Additional information on preparation 
and administration is in Sections 7.5.3.and 7.5.4. In the event of toxicities, re-treatment or 
dose modification will be according to the approved Prescribing Information provided in the 
Pharmacy Guidelines or according to institutional guidelines or local dose reduction 
protocols (see Section 7.5.5). 
Site personnel will account for study drug that is administered or dispensed to the patient 
during the study visit and document appropriately. 
8.4.4 
Day 15 of Cycles 1 and 2 (Rucaparib Arm) 
The following procedures/assessments will be completed: 
• Physical examination; 
• Vital Signs; 
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• AE monitoring; and 
• Study drug continuation. 
Patients will continue BID dosing with rucaparib with or without food, taking doses at about 
the same times every day as close to 12 hours apart as possible. Rucaparib should be taken 
with at least 8 oz. (240 mL) of water. Patients will keep all unused tablets and containers 
(empty, partially used, and/or unopened) for accountability at the next visit. In the event of 
toxicities, re-treat or dose modify according to the criteria described in Section 7.5.1). 
8.5 
Post-treatment Phase 
8.5.1 
Randomized Treatment Discontinuation 
Upon randomized treatment discontinuation, regardless of the reason, patients will have a 
treatment discontinuation visit. However, patients receiving rucaparib with radiologic disease 
progression by RECIST Version 1.1, as assessed by the investigator, but still receiving 
benefit, per the investigator, may be considered for treatment continuation. A joint, 
documented decision between the investigator and Sponsor (or designee) may allow for 
continued rucaparib treatment with patient consent. If the patient does continue to receive 
rucaparib, then the patient will continue cycles of rucaparib as described starting in 
Section 8.4.1 and a treatment discontinuation visit as described in Section 8.5.1 will occur at 
the end of all rucaparib treatment. Patients who continue treatment with rucaparib after 
radiologic disease progression and thus do not have a treatment discontinuation visit will 
have the option of tumor tissue biopsy collection at time of first disease progression on study 


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(requires additional consent). Tumor tissue will be processed locally as FFPE tissue. Refer to 
the Pathology Charter for detailed sample handling instructions. 
Patients randomized and treated with chemotherapy will have the following procedures 
performed when chemotherapy is discontinued for any reason. These patients may be eligible 
to cross over to treatment with rucaparib upon radiologic disease progression by 
RECIST Version 1.1, as assessed by the investigator. Following an additional consent to 
cross over to rucaparib treatment (Section 8.6), these patients may be evaluated for eligibility 
to cross over to treatment as described in Sections 6.4 and 8.7.  
The following procedures will be performed when treatment to which the patient is 
randomized has been completed or is discontinued: 
• PRO using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other 
collection format as appropriate (complete before other procedures; Appendix 5);  
• Physical examination; 
• Weight; 
• Vital Signs; 
• 12-lead ECG; 
• Concomitant medications and procedures; 
• Disease/ tumor assessment (using the same methodology as was used at screening [eg, 
CT scan]) if reason for treatment discontinuation was other than death or disease 
progression based on radiologic assessment and it has been ≥ 8 weeks since last scan or 
disease progression was noted on the last scan;  
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential; 
• CA-125 measurement (Appendix 4); 
• Blood sample for ctDNA analysis (all patients);  
• AE monitoring; and 
• Optional tumor tissue biopsy collection from the time of disease progression/ randomized 
treatment discontinuation until the start of the next treatment (requires additional 
consent). Tumor tissue will be processed locally as FFPE tissue. Refer to the Pathology 
Charter for detailed sample handling instructions.  


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8.5.2 
28-Day Safety Follow-up Visit (Randomized Treatment/ Cross Over to 
Rucaparib) 
The following procedures will be performed for all patients at 28 (±3) days after the last dose 
of randomized study drug and/or cross over to rucaparib.  
Patients initially randomized to rucaparib and patients who cross over to receive rucaparib 
after chemotherapy will have a safety follow-up visit 28 (±3) days after the last dose of 
rucaparib.  
Patients randomized to chemotherapy who do not cross over to receive rucaparib will have a 
safety follow-up visit 28 (±3) days after the last dose of randomized chemotherapy and 
continue with LTFU (Section 8.5.3). 
• PRO using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other 
collection format as appropriate (complete before other procedures; Appendix 5); 
• Physical examination; 
• Weight; 
• Vital Signs; 
• 12-lead ECG; 
• Concomitant medications and procedures; 
• If applicable, disease/ tumor assessment (using the same methodology as was used at 
initial study screening [eg, CT scan]) when the reason for treatment discontinuation was 
other than death or disease progression based on radiologic assessment and it has been 
≥ 8 weeks since last scan or disease progression was noted on the last scan. 
Disease/ tumor assessment should continue to be performed every 8 calendar weeks 
relative to Cycle 1 Day 1 (within 5 days before is permitted) until radiologic disease 
progression by RECIST Version 1.1, as assessed by the investigator, death, loss to 
follow-up, withdrawal of consent, study closure, or initiation of subsequent treatment;  
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• CA-125 measurement (Appendix 4); 
• AE monitoring (Note: all SAEs, AESIs, and treatment-related Grade 3/4 AEs are to be 
followed to outcome, if longer than the 28-day follow-up period); and 
• Any pregnancy is to be followed to outcome (Section 10.6). 
• Information collected for subsequent treatments and/or secondary malignancy. Diagnosis 
of any secondary malignancy will require appropriate documentation (ie, laboratory 
and/ or pathology reports) and should be reported as indicated in Section 10.10. 


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Patients who do not withdraw from the study at this visit will continue with LTFU as 
described in Section 8.5.3.  
8.5.3 
Long-term Follow-up (Randomized Treatment/Cross Over to Rucaparib) 
Patients randomized to rucaparib who complete a safety follow-up visit 28 (±3) days after the 
last dose of rucaparib will continue in LTFU as described below. 
Patients randomized to chemotherapy who discontinue treatment due to radiologic disease 
progression and are ineligible or do not consent to cross over to rucaparib treatment will 
continue in LTFU as described below, after a safety follow-up visit.  
Patients randomized to chemotherapy who discontinue treatment before radiologic disease 
progression and complete a safety follow-up visit 28 (±3) days after the last dose of 
randomized chemotherapy will continue in LTFU as described below. At the time of 
radiologic disease progression, the patient may be eligible and consent to cross over to 
treatment with rucaparib. The patient may also be ineligible or not consent to cross over to 
rucaparib treatment and will continue in LTFU. 
Patients who cross over to rucaparib treatment will follow the procedures beginning in 
Section 8.6. These patients will have appropriate follow-up visits after discontinuation of 
cross over rucaparib treatment. 
• If applicable, disease/ tumor assessment (using the same methodology as was used at 
initial study screening [eg, CT scan]) when the reason for treatment discontinuation was 
other than death or disease progression based on radiologic assessment and it has been 
≥ 8 weeks since last scan or disease progression was noted on the last scan. 
Disease/ tumor assessment should continue to be performed every 8 calendar weeks 
relative to Cycle 1 Day 1 (within 5 days before is permitted), every 16 weeks (±5 days 
before is permitted) for patients who have been on study (including cross over to 
rucaparib in patients randomized to chemotherapy) for at least 18 months, until radiologic 
disease progression by RECIST Version 1.1, as assessed by the investigator, death, loss 
to follow-up, withdrawal, study closure, or initiation of subsequent non-study treatment  
• All patients discontinued from treatment, regardless of reason, will be followed and 
information collected for subsequent treatments, secondary malignancy, and survival 
every 12 weeks (± 14 days) after treatment discontinuation until death, loss to follow-up, 
withdrawal of consent from study, or closure of the study. Follow-up can be performed 
via the telephone. Diagnosis of any secondary malignancy will require appropriate 
documentation (ie, laboratory and/ or pathology reports) and should be reported as 
indicated in Section 10.10. 
• SAEs assessed as potentially related to study drug (including serious reports of 
pneumonitis or similar events, ie, interstitial lung disease, pulmonary fibrosis, acute 
interstitial pneumonitis, alveolitis necrotizing, alveolitis, hypersensitivity pneumonitis, 
and organizing pneumonia, if considered to be related to study drug), and the AESIs of 
MDS and AML, irrespective of causality, are to be reported as specified in Section 10.10. 


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AESIs of pneumonitis or similar events should only be reported up to, but not beyond, 
the 28-Day Follow-up Visit (28 days after the last dose of rucaparib). 
  
8.6 
Informed Consent for Patients Who Cross Over to Rucaparib after 
Disease Progression on Study Chemotherapy 
Patients who initially received chemotherapy and then cross over to treatment with rucaparib 
after radiologic disease progression per RECIST Version 1.1 by investigator assessment must 
provide additional consent to receive rucaparib treatment, as well as Sponsor (or designee) 
approval. Patients who are eligible to cross over as described in Section 6.4 and receive 
approval must receive the first dose of rucaparib ≤ 8 weeks following radiographic 
progression on chemotherapy. Ineligible patients will continue with a 28-day Safety 
Follow-up Visit and LTFU as in Sections 8.5.2 and 8.5.3. 
Additionally, patients participating in the optional tumor tissue biopsy at the time of 
radiographic disease progression/treatment discontinuation after cross over to rucaparib must 
provide additional consent for this procedure.  
All procedures and assessments are to be completed within ± 3 days of the scheduled time, 
unless otherwise stated. 
8.7 
Screening Prior to Cross Over to Rucaparib 
Following written informed consent, and unless otherwise specified, the following 
assessments will be performed prior to initiating treatment with rucaparib within the 
allowable windows of time as indicated below. Assessments performed within the specified 
windows, but prior to patient signing informed consent, are acceptable only if confirmed to 
have been standard of care. Assessments performed at treatment discontinuation and/or at the 
28-day safety follow-up following discontinuation of chemotherapy may be utilized, 
provided they were within the allowable windows of time as indicated below. 
Screening procedures may be repeated if the findings/results are considered invalid or not 
representative of the patient’s baseline medical status. When screening procedures are 
repeated, the rationale should be documented in the source file. 
8.7.1 
Up to 14 Days Prior to the First Dose of Rucaparib for Crossover Patients: 
• PRO collected using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or 
other collection format as appropriate (complete before other procedures; Appendix 5); 
• Physical examination; 
• Weight;  
• Vital signs (blood pressure, pulse, and body temperature); 
• 12-lead ECG; 
• Concomitant medications and procedures;  


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• Disease/ tumor assessment (using the same methodology as was used at screening 
[eg, CT scan]) if it has been ≥ 6 weeks since last scan or disease progression was noted 
on the last scan;  
• ECOG performance status (Appendix 2);  
• Hematology;  
• Serum Chemistry (fasting is not required);  
• Urinalysis (freshly voided sample);  
• CA-125 measurement (Appendix 4);  
• Blood sample for ctDNA analysis; and 
• AE monitoring. 
8.7.2 
Up to 3 Days Prior to First Dose of Rucaparib for Crossover Patients: 
• Serum pregnancy test for women of childbearing potential. 
8.8 
Treatment with Rucaparib in Patients Who Cross Over from 
Chemotherapy (Day 1 to Day 28 per Cycle) 
Patients will begin to receive rucaparib after approval by the Sponsor/designee to cross over, 
meeting eligibility criteria (Sections 6.4), and having completed screening assessments 
(Section 8.7).  
The first dose of rucaparib must be administered ≤ 8 weeks after radiologic disease 
progression on chemotherapy.  
Serum pregnancy testing for women of childbearing potential must occur ≤ 3 days prior to 
the first dose of study drug (Section 8.3.4). 
8.8.1 
Day 1 of Every Cycle (Crossover to Rucaparib) 
Patients initially randomized and treated with chemotherapy who have crossed over to 
rucaparib following radiographic progression per RECIST Version 1.1 will have these 
assessments on Day 1 of every cycle of treatment with rucaparib.  
Patients will also be instructed to refrain from taking their first dose of rucaparib at home on 
the day of their Day 1 visits for Cycles 1 through 6 to collect blood samples for ctDNA 
testing. 
• PRO using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other 
collection format as appropriate (complete before other procedures and dosing; Appendix 
5); 
• Physical examination; 
• Weight; 


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• Vital Signs; 
• 12-lead ECG;  
• Concomitant medications and procedures; 
• Disease/ tumor assessment (using the same methodology as was used at initial study 
screening [eg, CT scan]) every 8 calendar weeks (within 5 days before is permitted) 
relative to the start of treatment on Day 1 of Cycle 1 in the crossover period through 
to18 months in crossover period of the study, then every 16 calendar weeks (within 
5 days before is permitted) thereafter. The first disease/ tumor assessment on the 
crossover part of the study should be performed approximately 8 weeks after the last 
assessment was performed. 
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential; (≤ 3 days prior to start of every 
cycle); 
• CA-125 measurement (Cycle 1 and every 2nd cycle thereafter [ie, Cycles 3, 5, 7, etc.]); 
• Blood sample for ctDNA analysis (sampling before the rucaparib dose on Day 1 of 
Cycles 1 through 6);  
• AE monitoring; and  
• Study drug dispensation (rucaparib). 
Rucaparib tablets will be dispensed to the patient in sufficient quantity to last until Day 1 of 
the next treatment cycle. Patients will ingest rucaparib BID at about the same times every day 
as close to 12 hours apart as possible. Rucaparib should be taken with at least 8 oz (240 mL) 
of water with or without food. Patients will keep all unused tablets and containers (empty, 
partially used, and/or unopened) for accountability at the next visit. In the event of toxicities, 
re-treatment or dose modification will be according to the criteria described in Section 7.5.1). 
Site personnel will account for study drug that is dispensed to the patient during the study 
visit and document appropriately. 
8.8.2 
Day 15 of Cycles 1 and 2 (Crossover to Rucaparib) 
The following procedures/assessments will be completed: 
• Physical examination; 
• Vital Signs; 
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 2); 
• Hematology; 


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• Serum chemistry (fasting is not required); 
• AE monitoring; and 
• Study drug continuation. 
Patients will continue BID dosing with rucaparib with or without food, taking doses at about 
the same times every day as close to 12 hours apart as possible. Rucaparib should be taken 
with at least 8 oz. (240 mL) of water. Patients will keep all unused tablets and containers 
(empty, partially used, and/or unopened) for accountability at the next visit. In the event of 
toxicities, re-treat or dose modify according to the criteria described in Section 7.5.1). 
8.9 
Post-treatment for Patients Who Cross Over to Rucaparib 
8.9.1 
Treatment Discontinuation for Patients Who Cross Over to Rucaparib 
Upon discontinuation of rucaparib treatment in patients who crossed over from 
chemotherapy, regardless of the reason, there will be a treatment discontinuation visit.  
The following procedures will be performed: 
• PRO using the EORTC QLQ-C30/ QLQ-OV28, and EQ-5D instruments, or other 
collection format as appropriate (complete before other procedures; Appendix 5);  
• Physical examination; 
• Weight; 
• Vital Signs; 
• 12-lead ECG; 
• Concomitant medications and procedures; 
• Disease/ tumor assessment (using the same methodology as was used at initial study 
screening [eg, CT scan]) if reason for treatment discontinuation was other than death or 
disease progression based on radiologic assessment and it has been ≥ 8 weeks since last 
scan or disease progression was noted on the last scan;  
• ECOG performance status (Appendix 2); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• Serum pregnancy for women of childbearing potential; 
• CA-125 measurement (Appendix 4); 
• Blood sample for ctDNA analysis;  
• AE monitoring; and 
• Optional tumor tissue biopsy collection any time after disease progression, cross over to 
rucaparib, or treatment discontinuation until the start of the next non-study treatment 


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(requires additional consent). Tumor tissue will be processed locally as FFPE tissue. 
Refer to the Pathology Charter for detailed sample handling instructions.  
Patients will continue to be followed for 28 (±3) days after discontinuation of rucaparib as 
crossover treatment in the 28-day follow-up visit as described in Section 8.5.2 and in LTFU 
as described in Section 8.5.3.  


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9 
METHODS OF DATA COLLECTION 
9.1 
Medical History and Demographic/ Baseline Characteristics 
Basic demographic and baseline characteristics will be collected during screening. In addition 
to the evaluation of a patient’s medical history in terms of study eligibility, all relevant medical 
conditions will be documented on the appropriate eCRF. Events that occur after signing of 
informed consent but prior to initiation of study drug, unless due to a protocol-mandated 
procedure, should be recorded on the Medical History eCRF.  
The patient’s entire oncology history will be collected on the appropriate eCRF including 
date of diagnosis for epithelial ovarian, primary peritoneal, or fallopian tube cancer (and 
other malignancy, if applicable), prior surgeries/ treatments received for cancer, dates of 
treatment administration, best response achieved, date of progression and how assessed, 
progression-free interval after last platinum regimen, radiology reports, and gBRCA mutation 
status (if known).  
9.2 
Prior and Concomitant Medication Assessments 
Medications being used by the patient will be recorded as prior medications during screening 
and as concomitant medications following receipt of the first dose of study drug through the 
completion of the 28-day Safety Follow-up Visit after treatment discontinuation. Medications 
information will be entered in the appropriate eCRF after it is obtained at each study visit. 
9.3 
Efficacy Evaluations 
9.3.1 
Disease/ Tumor Assessments 
Disease/ tumor assessments will be performed during screening (baseline), at the end of 
every 8 calendar weeks after Cycle 1 Day 1 (within 5 days before is permitted) during 
treatment, and continue post-treatment every 8 calendar weeks, relative to Cycle 1 Day 1, 
until radiologically confirmed disease progression by RECIST Version 1.1, as assessed by 
the investigator, or death (unless these were the reasons for treatment discontinuation), or 
initiation of subsequent treatment. Tumor assessments should be performed at the time of 
treatment discontinuation if the reason was other than death or radiologically-confirmed 
disease progression and it has been ≥ 8 weeks since the last assessment. Patients who have 
been on study at least 18 months, may decrease the frequency of tumor assessments to every 
16 weeks (within 5 days before is permitted).  
Tumor response will be interpreted using RECIST Version 1.1 (Appendix 1). Patients who 
meet GCIG CA-125 criteria for disease progression should have a radiologic assessment and 
be assessed by RECIST Version 1.1. If the radiologic assessment does not confirm GCIG 
CA-125 disease progression, patients should continue on treatment and continue to be 
assessed by RECIST Version 1.1 per the protocol schedule of assessments. 
Disease/ tumor assessments should consist of clinical examination and appropriate imaging 
techniques (ie, computed tomography [CT] scans of the chest, abdomen, and pelvis with 


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appropriate slice thickness per RECIST Version 1.1); other studies (magnetic resonance 
imaging [MRI], X-ray, positron emission tomography [PET], and ultrasound) may also be 
performed if required. The same methods used to detect lesions at baseline are to be used to 
follow the same lesions throughout the clinical study. If a patient has known brain 
metastases, this disease should be evaluated at each required assessment time. 
Copies of CT scans (and other imaging, as appropriate) will be collected from all patients for 
Independent Radiology Review (IRR).  
9.3.2 
Tumor Markers 
Blood samples to assess CA-125 will be collected at screening, on Day 1 of Cycle 1, at the 
start of every 2nd cycle thereafter (ie, Day 1 of Cycles 3, 5, 7, etc.), at treatment 
discontinuation, and as clinically indicated. All CA-125 tests will be performed by a local 
laboratory. 
CA-125 < ULN will be required to designate a CR.  
9.4 
Safety Evaluations 
9.4.1 
Adverse Event Assessment 
The investigator has the responsibility for assessing the safety of the patients and for 
compliance with the protocol to ensure study integrity. Patients will be monitored for AEs 
during study participation (beginning at the time informed consent is obtained) and until 
28 days after the last dose of study drug. After the 28-day window, only treatment-related 
SAEs assessed as potentially related to study drug (including serious reports of pneumonitis 
or similar events, ie, interstitial lung disease, pulmonary fibrosis, acute interstitial 
pneumonitis, alveolitis necrotizing, alveolitis, hypersensitivity pneumonitis, and organizing 
pneumonia, if considered to be related to study drug), and the AESIs of MDS and AML 
irrespective of causality, need to be reported. In the time after informed consent is provided 
but before study drug is administered, AEs/ SAEs are to be recorded if they are the result of a 
study-related procedure. Any ongoing SAEs, AESIs, or treatment-related Grade 3/4 AEs will 
be followed until resolution or stabilization. AEs and laboratory abnormalities will be graded 
according to the NCI CTCAE grading system (Version 4.03) and recorded on the eCRF. 
Complete details for monitoring AEs, including the definition of drug-related AEs, are 
provided in Section 10. 
If a patient discontinues from treatment and begins subsequent anti-cancer therapy, the 
Sponsor will terminate collection of SAEs, with the exception of the AESIs of MDS and 
AML. 
9.4.2 
Clinical Laboratory Investigations 
Samples for hematology, serum chemistry, urinalysis, and serum pregnancy will be analyzed 
by a local laboratory. Fasting is not required before blood sampling. The panels of laboratory 
tests to be performed are shown below: 


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Hematology: red blood cells (RBC) and parameters (hemoglobin, hematocrit, mean 
corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], and mean corpuscular 
hemoglobin concentration [MCHC]) and reticulocyte count, white blood cells (WBC) and 
differential (with ANC), and platelet count will be assessed at screening, during treatment at 
each study visit, and at the treatment discontinuation visit for all patients. Hematology results 
must be reviewed by the investigator before the start of treatment with study drug and 
ongoing at times testing occurs. Additional and more frequent tests may be performed at the 
investigator’s discretion. 
Serum Chemistry: total protein, albumin, creatinine or estimated GFR using the Cockcroft 
Gault formula, BUN or urea, total bilirubin, alkaline phosphatase (ALP), ALT, AST, 
glucose, sodium, potassium, chloride, bicarbonate (optional), calcium, phosphorus, and lipid 
panel (total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL], and 
triglycerides), at screening, during treatment at each study visit, and at the treatment 
discontinuation visit for all patients. Testing of bicarbonate is optional and should be 
performed when clinically indicated or evaluated through arterial blood gas at the 
investigator’s judgement. With the exception of bicarbonate, phosphorus, and the lipid panel, 
serum chemistry results must be reviewed by the investigator before the start of treatment 
with study drug and ongoing at times testing occurs. 
Urinalysis: performed locally on a freshly voided clean sample by dipstick for protein, 
glucose, blood, pH, and ketones. If dipstick findings are abnormal based on the investigator’s 
judgment, then a microscopic evaluation will be performed to assess the abnormal findings. 
Urinalysis will be performed at screening only, but may be conducted at other times as 
clinically indicated.  
Serum Pregnancy: for women of childbearing potential only. A serum pregnancy test must 
be performed ≤ 3 days prior to first dose of study drug (a negative result is required before 
dosing can begin) and at the treatment discontinuation visit. A serum pregnancy test must be 
performed ≤ 3 days prior to Day 1 of every cycle during the Treatment Phase, and a serum 
pregnancy test performed at Treatment Discontinuation. A positive serum pregnancy test 
during study participation must be reported to the Sponsor. Refer to Section 10.6 for details. 
Laboratory reports will be reviewed by the investigator or delegated physician who will then 
comment on out-of-range parameters and assess clinical significance. Clinically significant 
abnormalities and associated panel results, as well as results of any additional tests performed 
as follow-up to the abnormalities, will be documented on the eCRF as an AE. Refer to 
Section 10.5 for guidelines on reporting of abnormal laboratory values as AEs. 
9.4.3 
Vital Signs 
Vital signs will include blood pressure, heart rate, and body temperature and will be taken 
after the patient has been resting for at least 5 minutes during screening, at study visits during 
the Treatment Phase, and at the treatment discontinuation visit. 


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9.4.4 
12-Lead Electrocardiogram 
For all patients, 12-lead ECGs will be performed at the following times: 
• Screening (within 28 days prior to randomization) 
• At each study visit 
• Treatment discontinuation 
The following will be measured or calculated: heart rate, PR, QRS, QT, QTc, and rhythm. 
The investigator or qualified designee will review the ECGs locally and assess the results as 
normal or abnormal (clinically significant or not clinically significant). 
If it is clinically indicated, ECGs can be performed at other times during the study.  
9.4.5 
Body Weight and Height 
Height will be measured during the screening visit only. Weight will be measured per 
institutional guidelines during screening, on Day 1 of each cycle, at each study visit prior to 
chemotherapy administration, and at the treatment discontinuation visit. 
9.4.6 
Physical Examinations 
Physical examinations will include an assessment of all the major body systems. Complete 
physical examinations will be performed during screening and at treatment discontinuation. 
Physical examinations at study visits during the Treatment Phase will be limited as 
appropriate.  
9.4.7 
ECOG Performance Status 
ECOG performance status (Appendix 2) will be assessed during screening, at study visits 
during the Treatment Phase, and at the treatment discontinuation visit. The ECOG 
performance status should be assessed by the same study personnel at each visit, if possible. 
For eligibility purposes, patients with borderline ECOG performance status should be 
considered carefully to avoid enrolling patients who may have significant impairment. 
9.5 
Biomarker Analysis – FFPE Tumor Tissue 
All patients, with the exception of those known (ie, documented) to harbor a deleterious 
BRCA1/2 mutation (germline or somatic), will be required to provide sufficient quantity of 
archival tumor tissue or a screening biopsy for central laboratory analysis prior to enrollment.  
A sufficient quantity of archival tumor tissue or tumor tissue from a screening biopsy must 
be submitted directly to the central laboratory at least 3 weeks prior to the planned 
randomization for determination of HRD status. 
Patients with a known deleterious BRCA1/2 mutation (germline or somatic) must also submit 
archival tumor tissue for central laboratory testing; however, enrollment is not contingent 
upon the central laboratory analysis of tissue. A local BRCA1/2 mutation result from 


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previous testing will be adequate for enrollment. Sufficient quantity of archival tumor tissue 
must be confirmed by central laboratory testing in these patients during the study. If archival 
tumor tissue of sufficient quantity is not available, the patient may undergo a screening 
biopsy.  
Patients with a deleterious BRCA1/2 mutation who meet all other entry criteria will be 
eligible for the study.  
Sufficient archival FFPE tumor tissue (enough for 1 x 4 µm section for H&E and 
approximately 8 to 12 x 10 µm sections [unstained], or equivalent) for planned analyses 
should be provided. In addition to determining HRD status, gene expression profiling on 
extracted RNA will be analyzed to classify tumors into gene expression molecular subtypes, 
which have been shown to associate with patient survival in HGSOC.64 Refer to the 
Pathology Charter for details. The most recently collected tumor tissue sample available that 
is of adequate quality (at least 20% tumor content with a minimum of 80% nucleated cellular 
content) must be provided or a new sample acquired.  
An optional tumor tissue biopsy sample is requested any time after disease progression, 
crossover to rucaparib, or treatment discontinuation until the start of the next non-study 
treatment. Patients must provide additional consent for this optional tumor tissue biopsy 
sample. If disease progression is caused by appearance of a new lesion(s), the lesion(s) 
should be prioritized for the optional biopsy. Detailed sample handling instructions are 
located in the Pathology Charter. 
9.6 
Biomarker Analysis – Blood 
Blood samples will be collected as specified in the Schedule of Assessments during 
screening, before dosing on Day 1 of Cycles 1 to 6, and at treatment discontinuation from all 
patients entered in the study for plasma ctDNA and genomic (g/sBRCA) analyses. Blood 
samples will also be collected at the same times in patients who cross over to rucaparib 
treatment. Genomic DNA will be extracted from the cellular portion of these blood samples 
and analyzed to determine whether the BRCA1/2 mutation is germline or somatic prior to 
final data analysis. Sample collection details are provided in the Laboratory Manual. 
9.7 
Pharmacokinetics Evaluation 
For patients receiving rucaparib, plasma samples are to be collected for trough level PK 
analysis of rucaparib before the morning dose on Day 1 of Cycles 2 to 6 as close to 12 hours 
after the previous dose as possible. If the start of the next treatment cycle is delayed, the PK 
sample should still be collected during this visit instead of on Day 1 of the delayed start of 
the next treatment cycle. Samples are not to be collected in patients receiving chemotherapy 
or crossing over to rucaparib. Refer to the Laboratory Manual for sample collection details 
for PK samples. 


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9.8 
Patient Reported Outcomes (Health and Quality of Life 
Questionnaires) 
Patient reported outcomes (PROs) consisting of the EORTC QLQ-30/ QLQ-OV28, and  
EQ-5D instruments, or other collection format as appropriate (see Appendix 5), will be 
assessed during screening, on Day 1 of every treatment cycle, at treatment discontinuation, 
and at the 28-day Safety Follow-up Visit. Patients should complete the instruments before 
any other scheduled study procedures are performed and dosing occurs (if applicable).  
PRO assessments should be collected at every cycle for all patients through disease 
progression in association with the radiologic assessments for disease progression. 


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10 ADVERSE EVENT MANAGEMENT 
10.1 Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a patient administered a medicinal 
product that does not necessarily have a causal relationship with this treatment. An AE can, 
therefore, be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an investigational 
product, whether or not related to the investigational medicinal product. This includes an 
exacerbation of pre-existing conditions or events, intercurrent illnesses, drug interaction, or 
the significant worsening of the indication under investigation that is not recorded elsewhere 
on the eCRF under specific efficacy assessments. Anticipated fluctuations of pre-existing 
conditions, including the disease under study, that do not represent a clinically significant 
exacerbation or worsening are not considered AEs. 
It is the responsibility of the investigator to document all AEs that occur during the study. 
AEs should be elicited by asking the patient a non-leading question (eg, “Have you 
experienced any new or changed symptoms since we last asked/since your last visit?”). The 
existence of an AE may be concluded from a spontaneous report of the patient; from the 
physical examination; or from special tests such as the ECG, laboratory assessments, or other 
study-specified procedure (source of AE). Symptoms reported spontaneously by the patient 
during the physical examination would also qualify as an AE (and hence documented on the 
AE eCRF, not on the physical examination eCRF, which is reserved for physical signs or 
findings). 
10.2 Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence that occurs at any dose (or, occurs after 
informed consent is given and prior to dosing if the SAE is related to a study procedure) that: 
• Results in death. Any event resulting in death during the reporting period (from date of 
first dose of study drug through 28 days after last dose) must be treated as an SAE and 
reported as such. An event related to a study procedure that occurs after informed 
consent, but prior to dosing that results in death must also be reported as an SAE.  
• Is life-threatening (patient is at immediate risk of death from the event as it occurred) 
• Requires in-patient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization 
• Results in persistent or significant disability/ incapacity 
• Results in a congenital anomaly or birth defect 
• Important medical events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home or the development of drug dependency or drug abuse. 


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10.3 Definition of an Adverse Event of Special Interest 
AESIs (serious or nonserious) are defined as AEs of scientific and medical concern specific 
to the Sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the investigator to the Sponsor can be appropriate. Such an event might 
warrant further investigation in order to characterize and understand it. Depending on the 
nature of the event, rapid communication by the trial Sponsor to other parties (eg, regulators) 
might also be warranted. 
Details on the Sponsor’s currently agreed list of AESIs for rucaparib can be found in the 
current rucaparib IB. These AESIs are to be reported to the Sponsor within 24 hours of 
knowledge of the event (see Section 10.10 for reporting instructions).  
10.4 Events or Outcomes Not Qualifying as Serious Adverse Events 
The following are not considered SAEs and therefore do not need to be reported as such: 
• Pre-planned or elective hospitalization including social and/ or convenience situations 
(eg, respite care) 
• Hospital visits of less than 24 hours duration (eg, patient presents to the emergency room, 
but is not admitted to a ward)  
• Overdose of either Clovis study drug or concomitant medication unless the event meets 
SAE criteria (eg, hospitalization). However, the event should still be captured as a 
nonserious AE on the appropriate eCRF page 
• Events of progression of the patient’s underlying cancer as well as events clearly related 
to progression of the patient’s cancer (signs and symptoms of progression) should not be 
reported as an SAE. 
• Events that meet the SAE criteria (as outlined in Section 10.2) and occur after informed 
consent, but before the first dose of study drug that are considered unrelated to 
protocol-mandated screening procedures. 
10.5 Clinical Laboratory Assessments as Adverse Events and Serious 
Adverse Events 
It is the responsibility of the investigator to assess the clinical significance of all abnormal 
values as defined by the list of reference ranges from the local laboratory. In some cases, 
significant changes in lab values within the normal range will require similar judgment. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as 
an AE only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 


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• at the discretion of the investigator should the abnormality be deemed clinically 
significant 
10.6 Pregnancy or Drug Exposure during Pregnancy 
If a patient becomes pregnant during the study the investigator is to stop dosing with study 
drug(s) immediately. 
A pregnancy is not considered to be an AE or SAE; however, any pregnancy occurring in a 
study patient or partner of a study patient during study participation or within 6 months of 
last dosing must be reported to the Sponsor using the Pregnancy Report Form within the 
same timelines as an SAE. 
A pregnancy should be followed through to outcome, whenever possible. Once the outcome 
of the pregnancy is known, the Pregnancy Outcome Report Form should be completed and 
reported to the Sponsor. 
AEs, SAEs, or AESIs that occur during pregnancy will be assessed and processed according 
to the AE or SAE/AESI processes using the appropriate AE or SAE/AESI forms.  
10.7 Recording of Adverse Events, Serious Adverse Events, and 
Adverse Events of Special Interest 
Events that occur after signing of informed consent but prior to initiation of study drug, 
unless due to a protocol-mandated procedure, should be recorded on the Medical History 
eCRF; however, events are to be reported as SAEs if serious and related to a 
protocol-mandated procedure during this time. Any AE that occurs after first dose of study 
drug through 28 days after receiving the last dose of [study drug] will be recorded on the AE 
eCRF.  
In order to avoid vague, ambiguous, or colloquial expressions, the AE should be recorded in 
standard medical terminology rather than the patient’s own words. Whenever possible, the 
investigator should combine signs and symptoms that constitute a single disease entity or 
syndrome into a final diagnosis, if appropriate. For example, fever, cough, and shortness of 
breath may be reported as pneumonia, if that is a reasonable diagnosis. 
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the 
investigational drug. The action taken and the outcome must also be recorded. 
SAEs and AESIs that occur during the study or within 28 days after receiving the last dose of 
study drug, whether or not related to study drug, must be reported immediately (ie, within 
24 hours of knowledge of the event or additional information for a previously-reported 
event) to the Sponsor/ SAE designee. The contact information for reporting of SAEs/ AESIs 
can be found on the SAE/ AESI Reporting Form. After the 28-day reporting window after 
discontinuation of randomized treatment and/or cross over to rucaparib for patients 
randomized to chemotherapy, only SAEs assessed as potentially related to study drug need to 
be reported. This includes serious reports of pneumonitis or similar events, ie, interstitial lung 
disease, pulmonary fibrosis, acute interstitial pneumonitis, alveolitis necrotizing, alveolitis, 


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hypersensitivity pneumonitis, and organizing pneumonia, if considered to be related to study 
drug. 
After the 28-day reporting window after discontinuation of randomized treatment, the AESIs 
of MDS and AML, irrespective of causality, should be reported.  
• AESIs of pneumonitis or similar events should only be reported up to, but not beyond, 
the 28-day Follow-up Visit (28 days after the last dose of rucaparib). 
 
Information on the follow-up of AEs, SAEs, and AESIs is provided in Section 10.8. 
10.7.1 
Onset Date of Adverse Events 
The onset date is the date that the event or the signs/symptoms attributed to the event started. 
10.7.2 
Resolution Date of Adverse Events 
The resolution date is the date that the event or the signs/symptoms attributed to the event 
resolved or resolved with sequelae or it is the date when the patient has reached a new 
baseline if the event is not expected to resolve. 
10.7.3 
Intensity of Adverse Events 
The severity of each AE will be graded using the NCI CTCAE, Version 4.03 grading scale 
(http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_8.5x11.pdf).65  
Severity is not the same as Serious 
For AEs not covered by NCI CTCAE, the severity will be characterized as mild, moderate, 
severe, life-threatening, or fatal according to the following definitions: 
• Mild events are usually transient and do not interfere with the patient’s daily activities 
• Moderate events introduce a low level of inconvenience or concern to the patient and 
may interfere with daily activities 
• Severe events interrupt the patient’s usual daily activities and hospitalization (or 
prolongation of hospitalization) may be required 
• Life-threatening events require urgent intervention to prevent death 
• Fatal events are those that led to the patient’s death 
 
10.7.4 Causal Relationship of Adverse Events to Study Drug 
Medical judgment should be used to determine the cause of the AE considering all relevant 
factors such as, but not limited to, the underlying study indication, coexisting disease, 
concomitant medication, relevant history, pattern of the AE, temporal relationship to the 
study medication, dechallenge or rechallenge with the study drug.  


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Not Related 
To Study Drug • An AE that is clearly due to extraneous causes (eg, concurrent disease, 
concomitant medications, disease under study, etc.) 
• It does not follow a reasonable temporal sequence from administration of 
the study drug. 
• It does not follow a known pattern of response to study drug 
• It does not reappear or worsen when study drug is restarted. 
• An alternative explanation is likely, but not clearly identifiable. 
Related to 
Study Drug 
• An AE that is difficult to assign to alternative causes. 
• It follows a strong or reasonable temporal sequence from administration of 
study drug. 
• It could not be reasonably explained by the patient’s clinical state, 
concurrent disease, or other concomitant therapy administered to the 
patient.  
• It follows a known response pattern to study drug 
• It is confirmed with a positive rechallenge or supporting laboratory data. 
 
10.7.5 Outcome and Action Taken 
The investigator will record the action taken and outcome for each AE according to the 
following criteria: 
Action Taken with Study Drug (note all that apply) 
• None;  
• Dose reduced/delayed;  
• Study drug temporarily interrupted;  
• Study drug permanently discontinued; and/or 
• Other (specify). 
 
Outcome 
• Recovered;  
• Recovered with sequelae;  
• Recovering/Resolving/Improving;  
• Ongoing;  
• Death; or 
• Lost to follow-up. 
 


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10.8 Follow-Up of Adverse Events, Serious Adverse Events, and 
Adverse Events of Special Interest 
All AEs (including SAEs and AESIs) occurring during the study are to be followed up in 
accordance with good medical practice until resolved; judged no longer clinically significant; 
or, if a chronic condition, until fully characterized through 28 days after the last dose of study 
drug. Any SAEs, AESIs, and treatment-related Grade 3/4 AEs must be followed until 
resolution or stabilization, or until lost to follow-up. After the 28-day window, only SAEs 
assessed as potentially related to study drug (including serious reports of pneumonitis or 
similar events, ie, interstitial lung disease, pulmonary fibrosis, acute interstitial pneumonitis, 
alveolitis necrotizing, alveolitis, hypersensitivity pneumonitis, and organizing pneumonia, if 
considered to be related to study drug), and the AESIs of MDS and AML irrespective of 
causality, need to be reported. AESIs of pneumonitis or similar events should only be 
reported up to, but not beyond, the 28-Day Follow-up Visit. 
10.9 Potential Drug-induced Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities 
should occur prior to the reporting of a potential drug-induced liver injury (DILI) event. All 
occurrences of potential DILIs, meeting the defined criteria,63 must be reported as SAEs (see 
Section 10.7 for reporting details). 
Potential drug induced liver injury is defined as: 
1. ALT or AST elevation > 3 × upper limit of normal (ULN) 
AND 
2. Total bilirubin > 2 × ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase), 
AND 
3. No other immediately apparent possible causes of ALT/AST elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or 
acute liver disease, or the administration of other drug(s) known to be hepatotoxic. 
 
10.10 Regulatory Aspects of Serious Adverse Event and Adverse Events 
of Special Interest Reporting 
It is important that the Investigator provide an assessment of relationship of the SAE or AESI 
to study treatment at the time of the initial report. For reporting SAEs/AESIs or pregnancies, 
use the applicable report forms. The contact information for reporting of SAEs and AESIs 
can be found on each of the forms. 
The Sponsor or its designee is responsible for submitting reports of AEs associated with the 
use of the drug that are both serious and unexpected to the U.S. Food and Drug 
Administration (FDA), according to 21 Code of Federal Regulations (CFR) 312.32; to the 
Japanese Pharmaceuticals and Medical Devices Agency (PMDA); to the European regulatory 
authorities according to the European Commission Clinical Trials Directive (2001/20/EC); 
and to other applicable regulatory authorities, according to national law and/or local 


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regulations. All investigators participating in ongoing clinical studies with the study 
medication will receive copies of these reports for prompt submission to their IRB or IEC. In 
accordance with the European Commission Clinical Trials Directive (2001/20/EC), the 
Sponsor or its designee will notify the relevant ethics committees in concerned member 
states of applicable suspected unexpected serious adverse reactions (SUSARs) as individual 
notifications or through periodic line listings. 
The Sponsor or its designee will submit all safety updates and periodic reports to the 
regulatory authorities as required by applicable regulatory requirements. 
 


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11 PLANNED STATISTICAL METHODS 
11.1 General Considerations 
All efficacy analyses will be performed at a two-sided 0.05 significance level. All efficacy 
analyses will be analyzed for the Efficacy Population and for the ITT Population. The 
Efficacy Population is defined as all randomized patients with a deleterious BRCA mutation, 
excluding those patients identified to have a BRCA reversion mutation. The methodology 
used to identify patients with a BRCA reversion mutation based on analysis of a blood 
sample obtained prior to randomization will be detailed in a separate document.  
All safety analyses will be summarized for all patients who received at least one dose of 
protocol-specified treatment.  
This study has a randomized part and a crossover part, and all efficacy, disposition, 
demographics and baseline, and safety will be presented separately for these study parts.  
Quantitative variables will typically be summarized using frequencies and percentages for 
appropriate categorizations and may also be summarized using descriptive statistics. For 
variables summarized with descriptive statistics, the following will be presented: N, mean, 
standard deviation, median, minimum, and maximum. Categorical variables will be presented 
using frequencies and percentages.  
The Kaplan-Meier methodology will be used to summarize time-to-event variables. If 
estimable, the 50th (median) percentile with the 95% confidence interval (CI) will be 
summarized for each randomized treatment group. The stratified hazard ratio from the Cox 
proportional hazards model will be used to estimate the HR between the randomized 
treatment groups.  
The number of patients with events and the number of censored patients will also be 
presented.  
Unless otherwise specified, baseline is defined as the last measurement on or prior to the first 
day of study drug administration in each of the study parts.  
All statistical analyses will be conducted with the SAS® System, Version 9.4 or higher. 
Further details around the statistical analyses planned in this study will be outlined in the 
Statistical Analysis Plan (SAP). 
11.2 Determination of Sample Size 
The enrollment planned for this study is approximately 345, with 230 patients randomized to 
rucaparib and 115 patients to chemotherapy.  
The median PFS is assumed to be 12 months for rucaparib and 8 months for the comparator. 
Assuming an accrual over about 3 years; a dropout rate of 2%; with a hazard ratio of 0.65; 
and at least 275 events, a sample size of 345 patients (230 patients randomized to rucaparib 


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and 115 patients randomized to chemotherapy) would yield at least 80% power at a 
two-sided 0.05 significance level.  
11.3 Analysis Populations  
The following analysis populations are defined for the treatment part of the study: 
Safety Population – Patients who received at least one dose of protocol-specified treatment. 
ITT population – All randomized patients. 
Efficacy Population – All randomized patients with a deleterious BRCA mutation, 
excluding those identified to have a BRCA reversion mutation. 
The crossover part will only be summarized for the Safety Population, which is defined as all 
patients who crossed over to rucaparib treatment and received at least one dose of rucaparib. 
11.4 Patient Disposition 
Patient disposition will be summarized using frequency counts and the corresponding 
percentages. The number of patients in each analysis population, number of patients 
discontinued, and the primary reason for discontinuation will be summarized. 
11.5 Demographics and Baseline Characteristics 
All demographic (eg, age, race, and ethnicity as allowed by local regulations) and baseline 
characteristics will be summarized for the Safety Population. 
The following baseline variables will be summarized with frequency tabulations: 
• Time since diagnosis of primary tumor (months): 0 to 12, > 12 to 24, > 24; 
• The randomization factor or progression-free interval for the most recent prior 
platinum-based regimen:  
• Platinum resistant: patients who progressed ≥ 1 to < 6 months after the last dose 
of platinum-based chemotherapy; 
• Partially platinum-sensitive: patients who progressed ≥ 6 to < 12 months after last 
dose of platinum-based chemotherapy; and 
• Platinum sensitive: patients who progressed ≥ 12 months after last dose of 
platinum-based chemotherapy  
• The following BRCA1/2 mutation characteristics will also be summarized:  
• BRCA1/2 mutation status (germline or somatic)  
• BRCA mutation gene (BRCA1 or BRCA2) 
Descriptive statistics may also be used to summarize the continuous variables.  


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11.6 Efficacy Analyses 
All efficacy analyses will be performed both in the Efficacy Population and in the 
ITT Population. The primary endpoint and key secondary endpoints will be tested using a 
hierarchical step-down procedure starting with the primary efficacy endpoint in the 
Efficacy Population then testing the primary endpoint for the ITT Population.  
If the primary endpoint is statistically significant, then the secondary efficacy endpoints will 
be tested in the order specified below where for each endpoint, first in the Efficacy 
Population, and then in the ITT Population. In order to preserve the overall Type 1 error rate, 
statistical significance will only be declared for the secondary endpoints, listed below, if the 
primary endpoint and previous secondary endpoints are also statistically significant; 
1. ORR by RECIST Version 1.1;  
2. DOR by RECIST Version 1.1; 
3. ORR by RECIST Version 1.1 and CA-125 response; and 
4. PRO as assessed by the EORTC QLQ-C30 Global Health Status score.  
 
The stratification factor used for randomization is the progression-free interval after most 
recent platinum-containing therapy (ie, platinum-resistant, partially platinum-sensitive, or 
platinum-sensitive). All efficacy analyses will be based on the randomization strata given at 
randomization, however, a sensitivity analysis of invPFS may be performed using the actual 
strata if patients have been allocated incorrectly.  
11.6.1 
Primary Efficacy Analyses 
The primary efficacy endpoint for the study is disease progression according to RECIST 
Version 1.1 as assessed by the Investigator, or death from any cause for the treatment part. 
Patients without a documented event of progression will be censored on the date of their last 
tumor assessment (ie, radiologic assessment) or date of randomization if no tumor 
assessments have been performed. Patients who withdraw from treatment prior to 
progression will be followed for disease status and survival whenever possible. 
The primary endpoint of invPFS will be analyzed using the stratified Cox proportional 
hazard methodology. The stratified hazard ratio from the Cox proportional hazards model 
will be used to estimate the HR between the randomized treatment groups.  
11.6.2 
Secondary Efficacy Analyses 
The secondary endpoint of bicrPFS by RECIST Version 1.1 is defined as the time from 
randomization to disease progression, according to RECIST v1.1 criteria as assessed by 
BICR, or death due to any cause, whichever occurs first. Only tumor scans prior to start of 
any subsequent anti-cancer treatment are included.  
OS will be analyzed using Cox proportional hazard methodology. The stratified hazard ratio 
from the Cox proportional hazards model will be used to estimate the HR between the 
randomized treatment groups. 


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ORR by RECIST Version 1.1 as assessed by the investigator: The proportion of responders 
will be analyzed using a stratified Cochran-Mantel-Haenszel (CMH) test. 
Duration of Response (DOR) as assessed by the investigator: DOR is defined as the time 
from the first response (RECIST Version 1.1 CR or PR) until the first date that PD is 
documented. Duration of response will be summarized and analyzed using the same 
methodology as described for the primary endpoint. 
ORR by RECIST Version 1.1 as assessed by the investigator and CA-125 response: The 
proportion of responders will be analyzed using a stratified chi-square test. 
Change from baseline during the first 6 treatment cycles for PRO endpoints by EORTC 
QLQ-C30 Global Health Status score. 
PRO endpoints by EORTC QLQ-C30 and QLQ-OV28 will be summarized according to the 
scoring manual.  
Analyses of changes from baseline will be analyzed for each scheduled post-baseline visit 
and for the final visit for each subscale and total score. Patients that do not have both a 
baseline measurement and at least one post-baseline measurement will not be included. 
At a given visit, the change from baseline will be compared between the randomized 
treatment groups using an ANCOVA using the treatment and stratification variable as a 
categorical factor and baseline measurement for the parameter as a continuous covariate. In 
addition, further analyses using repeated measures modeling or time to event might be used 
and will be described in the SAP. 
11.6.3 
Exploratory Efficacy Analyses 
The endpoints for exploratory analyses are: 
• To evaluate PFS of study treatment followed by the subsequent line of treatment 
(PFS2), defined as the time from randomization to the second event of disease 
progression or death, as assessed by the investigator;  
• To evaluate PRO utilizing the EQ-5D;  
• To assess molecular changes in tumor samples over time in matched pairs;  
• To assess circulating ctDNA as a molecular marker of efficacy; 
• To assess efficacy in BRCA-mutation subgroups (ie, germline/somatic and 
BRCA1/BRCA2) 
• To evaluate the impact of gene expression molecular subgroups on PFS and OS; 
• To evaluate disease control rate (RECIST Version 1.1 CR, PR, and prolonged SD 
> 12 weeks, by investigator assessment).  


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11.6.3.1 
Progression-free Survival 2 (PFS2) 
The second event of PFS, PFS2, is defined as the time from randomization to the second 
event of disease progression as assessed by the investigator, or death due to any cause. The 
first event of disease progression will be captured as the primary endpoint in this study and 
thus the second event will be the next event of disease progression as assessed by the 
investigator. This second event of PFS may be a documented event per RECIST Version 1.1 
guidelines or may be an event of symptomatic progression. Progression-free survival 2 will 
be analyzed using Cox proportional hazard method. The stratified hazard ratio from the Cox 
proportional hazards model will be used to estimate the HR between the randomized 
treatment groups. 
11.6.3.2 
Patient-reported Outcome EQ-5D 
Analyses of changes and/or percent changes from baseline will be analyzed for each 
scheduled post-baseline visit and for the final visit for the EQ-5D assessment and the 
EQ VAS. Patients who do not have both a baseline measurement and at least one 
post-baseline measurement will not be included. 
At a given visit, the change and/or percent change from baseline will be compared between 
the randomized treatment groups using an ANCOVA using the treatment as a categorical 
factor and baseline measurement for the parameter as a continuous covariate. 
11.6.3.3 
Changes in Tumor Samples and Changes in Circulating Cell-free Tumor DNA 
Changes in the molecular profile of tumor samples over time in matched pairs of pre- and 
post-treatment tissue, if available, will be evaluated in addition to the circulating ctDNA. 
11.6.3.4 
Disease Control Rate 
Disease control rate is defined as RECIST Version 1.1 evaluation of CR, PR or SD 
> 12 weeks and SD > 24 weeks as assessed by the investigator. The number and percent of 
patients meeting the criteria for disease control rate for each treatment group will be 
summarized. The proportion of patients will be analyzed using a stratified chi-square test.  
11.6.4 
Exploratory Pharmacokinetic Analyses 
In all patients with at least one PK sample collected, the trough plasma rucaparib PK data 
(Cmin) and summary statistics (N, mean, SD, minimum, median, max, CV%) will be reported. 
The PK data and selected safety and efficacy endpoints will be included in exploratory 
population PK and exposure-response analyses, if data allow, and the results will be reported 
separately. 
11.7 Safety Analyses 
All safety analyses will be summarized by randomization treatment group for the randomized 
part and for all patients in the crossover part.  


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Safety endpoints are incidence of AEs, clinical laboratory abnormalities, and dose 
modifications. 
Data from all patients who receive at least one dose of study drug will be included in the 
safety analyses. AEs, clinical laboratory results, vital signs, ECG results, ECOG performance 
status, body weight, and concomitant medications/ procedures will be tabulated and 
summarized. 
11.7.1 
Adverse Events 
AEs will be classified using the Medical Dictionary for Drug Regulatory Activities 
(MedDRA) classification system. The severity of the toxicities will be graded according to 
the NCI CTCAE v4.03 or later. Only treatment-emergent adverse events (TEAEs) will be 
collected: Treatment-emergent during the treatment part is defined as safety data with an 
onset date on or after the date of first dose of randomized study medication until the date of 
the last study medication plus 28 days, or up to the date of first dose of rucaparib for those 
patients who cross over from chemotherapy, whichever is first. 
Safety data will be presented for the crossover part separately, using the safety assessment 
before or on the date of first dose of rucaparib as the baseline value for the crossover part for 
the patients who cross over. The data that is deemed treatment emergent for the crossover 
part is defined as safety data with an onset date on or after the date of first dose of rucaparib 
in the crossover part until the date of the last study medication plus 28 days. 
The number and percentage of patients who experienced TEAEs for each system organ class 
(SOC) and preferred term will be presented. Multiple instances of the TEAE in each SOC 
and multiple occurrences of the same preferred term are counted only once per patient. The 
number and percentage of patients with at least one TEAE will also be summarized.  
Separate tables will be presented as follows: 
• All TEAEs; 
• TEAEs by CTCAE grade; 
• Grade 3 or greater TEAEs; 
• Treatment-related TEAEs; 
• Serious TEAEs; 
• TEAEs with an outcome of death; 
• TEAEs leading to discontinuation of study medication; 
• TEAEs resulting in interruption/delay of study medication; and 
• TEAEs resulting in dose reduction of study medication. 


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The incidence of TEAEs will be summarized by relationship to study drug according to the 
following categories: “treatment-related,” or “not treatment-related”. If a patient experiences 
multiple occurrences of the same AE with different relationship categories, the patient will be 
counted once, as a relationship category of treatment related.  
If a patient experiences multiple occurrences of the same AE with different toxicity grades, 
the patient will be counted once for the maximum (most severe) toxicity grade. AEs with a 
missing toxicity grade will be presented in the summary table with a toxicity grade of 
“Missing.” For each toxicity grade, the number and percentage of patients with at least one 
TEAE of the given grade will be summarized.  
11.7.2 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations include the continuous variables for hematology, serum 
chemistry, and urinalysis. The laboratory values will be presented in SI units. The 
on-treatment period for the treatment part will be defined as data with an onset date on or 
after the date of first dose of study medication until the date of the last dose of study 
medication plus 28 days, or date of first dose of rucaparib for those patients who cross over 
from chemotherapy, whichever is first. The on-treatment period for the laboratory values for 
cross-over part will be defined as all laboratory values on or after first dose of rucaparib in 
the crossover until the date of the last dose of rucaparib plus 28 days. 
Laboratory values collected during the on-treatment period will be included in the summary 
tables. The laboratory values collected after the on-treatment period will only be presented in 
the data listings.  
The summary of laboratory data will include shift tables based on CTCAE for shifts in grade 
from baseline to maximum, minimum and last value during the on-treatment period.  
Supporting laboratory data including normal ranges and abnormal laboratory flags will be 
provided using by-patient listings. Separate listings will be produced for clinically significant 
laboratory abnormalities (ie, those that meet Grade 3 or 4 criteria according to CTCAE). 
11.7.3 
Vital Sign Measurements 
The on-treatment period for the treatment part will be defined as the time from first dose of 
study drug to 28 days after the last dose of study drug, or start of first dose of rucaparib for 
those patients who cross over from chemotherapy, whichever is first. The on-treatment 
period for the vital signs for crossover part will be defined as all vital sign values on or after 
first dose of rucaparib in the crossover until the date of the last dose of rucaparib plus 
28 days. Vital sign measurements collected during the on-treatment period will be included 
in the summary tables. The vital sign measurements collected after the on-treatment period 
will only be presented in the data listings.  
The summary of vital sign data will include descriptive statistics (N, mean, SD, minimum, 
median, third quartile, and maximum) of the maximum, minimum and last value during the 
on-treatment period. Summaries using descriptive statistics (N, mean, SD, minimum, median 


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and maximum) of the change from baseline to the maximum, minimum, and last value during 
the on-treatment period will also be given.  
11.8 Interim Analysis 
No formal interim efficacy analyses are planned; however, ongoing review of data will 
occur. 
An IDMC will meet to review the efficacy and safety data from this study. The IDMC will 
review efficacy and safety of rucaparib versus chemotherapy to ensure the study remains 
beneficial to patients. 
The IDMC will have access to study data including patient treatment.  
Individual patient treatment assignments will not be available to the Sponsor during an 
IDMC review. A plan will be put in place to limit bias for Sponsor personnel. 
The IDMC may recommend that the study be stopped if the data indicate that the invPFS 
benefit will very likely not be achieved and/or there is excessive toxicity observed in the 
rates of serious and/or Grade 3 and 4 AEs. 
Details regarding the IDMC will be documented in a separate committee charter. 


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12 PATIENT DISPOSITION 
12.1 Removal of Patients from the Study or Study Drug 
A patient must be discontinued from protocol-prescribed therapy if any of the following 
apply: 
• Consent withdrawal for any reason at the patient’s own request or at the request of 
their legally authorized representative; 
• Progression of patient’s underlying cancer per RECIST Version 1.1 (unless, in the 
opinion of the investigator, the patient continues to derive clinical benefit; treatment 
beyond progression must be approved by the Sponsor); 
• Any event, adverse or otherwise, that, in the opinion of the investigator, would pose 
an unacceptable safety risk to the patient; 
• An intercurrent illness that, in the opinion of the investigator, would affect 
assessments of the clinical status to a significant degree and requires discontinuation 
of therapy;  
• Non-compliance by the patient with protocol-mandated procedures; or 
• A positive pregnancy test at any time during the study. 
Discontinuation of treatment does not necessarily indicate study discontinuation for a patient. 
Samples collected for research will continue to be used unless the patient explicitly 
withdraws consent for their use. If patient samples are tested before consent is withdrawn, the 
information collected up to the point of the withdrawn consent may still be used. If the 
patient withdraws consent to continue in the study or discontinues the study for another 
reason it will be documented on the appropriate eCRF. A patient may withdraw consent to 
participate in an additional part of a study that has an additional consent (ie, optional tumor 
biopsy) yet continue to participate and be treated/ followed in the main part of the study.  
The Sponsor may discontinue the study early for any of the reasons noted in Section 13.7. 


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13 STUDY ADMINISTRATION 
13.1 Regulatory and Ethical Considerations 
This study will be conducted in compliance with the protocol; Good Clinical Practices 
(GCPs), including International Council for Harmonisation (ICH) Technical Requirements 
for Registration of Pharmaceuticals for Human Use Guidelines; ICH E6(R2); FDA 
regulatory requirements; and in accordance with the ethical principles of the Declaration of 
Helsinki and the ethical principles underlying the European Union Directive 2001/20/EC and 
the US CFR, Title 21, Part 50 (21CFR50) and applicable local requirements. 
13.1.1 
Regulatory Authority Approvals 
The Sponsor or designee will submit the study protocol plus all relevant study documents to 
concerned regulatory agencies for approval prior to the study start. No patient will be 
admitted to the study until appropriate regulatory approval of the study protocol has been 
received. 
Each investigator must complete a Form FDA 1572 (or equivalent) and provide the 
completed form according to written instructions to the Sponsor (or designee). Each 
investigator must submit to the Sponsor (or designee) financial disclosure information 
according to national law and/or local regulations. 
U.S.-generated data will be handled in accordance with the Health Information Portability 
and Accountability Act (HIPAA). This clinical study will be registered on 
www.clinicaltrials.gov, EudraCT, and other applicable clinical study registry systems, as 
appropriate. 
13.1.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval 
This protocol and any material to be provided to the patient (such as advertisements, patient 
information sheets, drug dosing diaries, or descriptions of the study used to obtain informed 
consent) will be submitted by the investigator to an IEC/ IRB. This also applies to protocol 
amendments.  
The Sponsor will supply relevant data for the investigator to submit the study protocol and 
additional study documents to the IEC/ IRB. The principal investigator will submit the study 
protocol for review and approval by an IEC/ IRB, according to national law and/or local 
regulations, and will provide the IEC/ IRB with all appropriate materials.  
Verification of the IEC’s/ IRB’s unconditional approval of the study protocol and the written 
informed consent form will be transmitted to the Sponsor. This approval must refer to the 
study by exact study protocol title and number, identify the documents reviewed, and state 
the date of the review.  


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No patient will be admitted to the study until appropriate IEC/ IRB approval of the study 
protocol has been received, the investigator has obtained the signed and dated informed 
consent form, and the Sponsor is notified.  
The principal investigator will submit appropriate reports on the progress of the study to the 
IEC/ IRB at least annually in accordance with applicable national law and/ or local 
regulations and in agreement with the policy established by the IEC/ IRB and Sponsor.  
The IEC/ IRB must be informed by the principal investigator of all subsequent study protocol 
amendments and of SAEs or SUSARs occurring during the study that are likely to affect the 
safety of the patients or the conduct of the study.  
13.2 Patient Information and Consent 
All information about the clinical study, including the patient information and the ICF, is 
prepared and used for the protection of the human rights of the patient according to 
ICH E6(R2) GCP guidelines and the Declaration of Helsinki. 
It is the responsibility of the investigator to obtain signed ICFs from each patient 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and prior to undertaking any study-related procedures.  
The ICF, prepared by the investigator with the assistance of the Sponsor, must be approved 
along with the study protocol by the IEC/ IRB and be acceptable to the Sponsor.  
The patient must be provided with the patient information and ICF consistent with the study 
protocol version used and approved by the relevant IEC/ IRB. The ICF must be in a language 
fully comprehensible to the prospective patient. Patients (and/ or relatives, guardians, or legal 
representatives, if necessary) must be given sufficient time and opportunity to inquire about 
the details of the study and to discuss and decide on their participation in the study with the 
investigator concerned. Both the patient and the person explaining the study and with whom 
the patient can discuss the informed consent will sign and date the ICF. A copy of the signed 
ICF will be retained by the patient and the original ICF will be filed in the investigator file 
unless otherwise agreed.  
The patient will have the option to provide additional consent to allow or not allow the 
Sponsor to retain residual samples for future unspecified research. 
13.3 Patient Confidentiality 
The investigator must assure that patients’ anonymity is strictly maintained and that their 
identities are protected from unauthorized parties. Only patient identifiers such as initials, 
year of birth, and an identification code (ie, not names) should be recorded on any form 
submitted to the Sponsor and the IRB/ IEC. The investigator must record all enrolled patients 
in the eCRF. The investigator must maintain a list with the identity of all treated patients, but 
not intended for use by the Sponsor.  


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The investigator agrees that all information received from the Sponsor, or designee including, 
but not limited to, the Investigator’s Brochure, this protocol, eCRFs, the protocol specified 
treatment, and any other study information, remain the sole and exclusive property of the 
Sponsor during the conduct of the study and thereafter. This information is not to be 
disclosed to any third party (except employees or agents directly involved in the conduct of 
the study or as required by law) without prior written consent from the Sponsor. The 
investigator further agrees to take all reasonable precautions to prevent the disclosure by any 
employee or agent of the study center to any third party or otherwise into the public domain. 
13.4 Study Monitoring 
On behalf of the Sponsor, a contract research organization (CRO) or contract monitor will 
contact and visit the investigator at the study center prior to the entry of the first patient 
(unless the Sponsor or the CRO has worked with the center recently, in which case this initial 
visit maybe waived) and at appropriate intervals during the study until after the last patient is 
completed. The monitor will also perform a study closure visit. Visits may also be conducted 
by Sponsor personnel.  
In accordance with ICH GCP guidelines, the investigator must ensure provision of sufficient 
time, reasonable space, and adequate qualified personnel for the monitoring visits. The visits 
are for the purpose of verifying adherence to the study protocol and the completeness, 
consistency, and accuracy of data entered on the eCRF and other documents.  
The investigator will make all source data (ie, the various study records, the eCRFs, 
laboratory test reports, other patient records, drug accountability forms, and other pertinent 
data available for the monitor and allow access to them throughout the entire study period. 
Monitoring is done by comparing the relevant site records of the patients with the entries on 
the eCRF (ie, source data verification). It is the monitor’s responsibility to verify the 
adherence to the study protocol and the completeness, consistency, and accuracy of the data 
recorded on the eCRFs.  
By agreeing to participate in the study, the investigator agrees to cooperate with the monitor 
to ensure that any problems detected in the course of the monitoring visits are resolved. 
Contact information for the study monitor is located in the investigator file.  
13.5 Case Report Forms and Study Data 
Data collection is the responsibility of the clinical study staff at the site under the supervision 
of the site investigator. The investigator is responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Data recorded in the eCRF should be consistent with the data recorded 
on the source documents.  
Clinical data, including AEs, concomitant medications, and laboratory data will be entered 
into Medidata RAVE, a 21 CFR Part 11-compliant data capture system. The data system 


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includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered 
directly from the source documents. 
13.6 Independent Data Monitoring Committee 
An IDMC will be established to review safety and efficacy data in compliance with a 
prospective charter. The IDMC will be comprised of medical oncologists with experience in 
treating patients with the cancer being studied and a statistician, all of whom are not 
otherwise involved in the study as investigators. The IDMC responsibilities, authorities, and 
procedures for this study will be documented in the IDMC charter, which will be endorsed 
and signed by the IDMC prior to the first data review meeting. 
Following data review, the IDMC will recommend continuation, revision, or termination of 
the study and/ or continuing or halting enrollment into a particular subgroup. The IDMC will 
also ensure the study is beneficial to patients (see Section 11.8). The IDMC will meet at least 
semi-annually after sufficient data has been collected. The IDMC chairperson may convene a 
formal IDMC meeting if there are safety concerns. The Sponsor can also request an IDMC 
review of safety data. Details regarding the IDMC will be in the committee charter.  
13.7 Study Termination and Site Closure 
Both the Sponsor and the investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange discontinuation procedures. In terminating 
the study, the Sponsor and the investigator will assure that adequate consideration is given to 
the protection of the patients’ interests. Refer to Section 5.3 for additional details. 
The Sponsor reserves the right to discontinue the study at any time for medical or 
administrative reasons. When feasible, a 30-day written notification will be given. 
The entire study will be stopped if any of the following apply: 
• The protocol-specified treatment is considered too toxic to continue the study; 
• Evidence has emerged that, in the opinion of the Sponsor or the investigator(s), makes the 
continuation of the study unnecessary or unethical; 
• The stated objectives of the study are achieved; or 
• The sponsor discontinues the development of rucaparib. 
Regardless of the reason for termination, all data available for the patient at the time of 
discontinuation of follow-up must be recorded on the eCRF. All reasons for discontinuation 
of treatment must be documented.  
If the study is terminated prematurely, the Sponsor will promptly inform the 
investigators/institutions, and the regulatory authority(ies) of the termination or suspension 
and the reason(s) for the termination or suspension. The investigators will promptly inform 


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their IRB/IEC, providing the reason(s) for the termination or suspension by the Sponsor, or 
by the investigator/institution, as specified by the applicable regulatory requirement(s). 
13.8 Modification of the Study Protocol 
Protocol amendments, except when necessary to eliminate an immediate hazard to patients, 
must be made only with the prior approval of the Sponsor. Agreement from the investigator 
must be obtained for all protocol amendments and amendments to the informed consent 
document. The IEC/ IRB must be informed of all amendments and give approval prior to 
their implementation. The Sponsor will submit any study protocol amendments to the 
concerned regulatory authorities for approval and keep the investigator(s) updated as detailed 
in the ICH GCP guidelines. 
13.9 Retention of Data 
The study site will maintain a study file, which should contain, at minimum, the 
Investigator’s Brochure, the protocol and any amendments, drug accountability records, 
correspondence with the IEC/ IRB and the Sponsor, and other study-related documents.  
The investigator should have control of all essential documents generated by the site. Source 
documents must be maintained and meet standard criteria of source documentation practices 
to ensure data is attributable, legible, contemporaneous, original or certified copy, accurate, 
and complete, consistent, enduring, and available (ALCOA+), and any changes to data 
should be traceable, should not obscure the original entry, and should be explained if 
necessary (via an audit trail). The investigator must implement procedures to ensure the 
integrity of any data generated. 
The Sponsor and the investigator will maintain a record of the location(s) of their respective 
essential documents including source documents. The storage systems used during the trial 
and for archiving (irrespective of media used) must provide for documentation identification, 
version history, search and retrieval. 
The investigator agrees to keep records and those documents that include (but are not limited 
to) the identification of all participating patients, medical records, study-specific source 
documents, source worksheets, all original signed and dated informed consent forms, copies 
of all eCRFs, query responses, and detailed records of drug disposition to enable evaluations 
or audits from regulatory authorities and the Sponsor or its designees. The investigator 
should have control of and continuous access to the eCRF data. 
The investigator shall retain records required to be maintained for a period of 5 years 
following the date a marketing application in an ICH region is approved for the drug for the 
indication for which it is being investigated or, if no application is to be filed or if the 
application is not approved for such indication, until at least 5 years after the investigation is 
discontinued. However, these documents should be retained for a longer period if required by 
the applicable regulatory requirement(s) or if needed by the Sponsor. In addition, the 
investigator must make provision for the patients’ medical records to be kept for the same 
period of time. 


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No data should be destroyed without the agreement of the Sponsor. Copies of original 
documents that are used for source document verification should fulfill the requirements for 
certified copies. Should the investigator wish to assign the study records to another party or 
move them to another location, the Sponsor must be notified in writing of the new 
responsible person and/or the new location. The Sponsor will inform the investigator, in 
writing, when the trial-related records are no longer needed. 
Patients’ medical records and other original data will be archived in accordance with the 
archiving regulations or facilities of the investigational site. 
13.10 Quality Control and Assurance 
The Sponsor will implement and maintain quality control and quality assurance procedures 
with written standard operating procedures (SOPs) to ensure that the study is conducted and 
data are generated, documented, and reported in compliance with the protocol, GCP, and 
applicable regulatory requirements.  
Aspects of the study that are essential to ensure human subject protection and reliability of 
trial results should be the focus of these procedures. 
13.10.1 Changes to the Protocol and Deviations 
The Investigator may not deviate from the protocol unless necessary to eliminate immediate 
hazards to the patient. A deviation may result in the subject having to be withdrawn from the 
study and rendering that subject non-evaluable. Any deviation must be documented in the 
source documents and reported to the Sponsor. 
If changes to the study are required, they must be provided in a formal protocol amendment 
having been approved by an appropriate IRB/IEC.  
13.10.2 Study Site Training and Ongoing Monitoring 
Each investigator and the site personnel for this study will be trained by the Sponsor and/ or a 
designee (ie, a CRO) on the design, conduct, procedures, and administrative aspects of this 
study. This may include, but is not limited to, on-site training, Investigator Meeting(s), 
and/ or tele/ videoconferencing. Training may be ongoing as refresher, to address specific 
items, or to introduce changes in the study.  
In accordance with Code of Federal Regulations 21 CFR 312.56, ICH GCP and local 
regulations, the clinical monitor will periodically inspect eCRFs, study documents, medical 
records (office, clinic, or hospital) for patients in this study (anonymity is to be preserved), 
research facilities, and clinical laboratory facilities associated with this study at mutually 
convenient times during and after completion of the study. If these requirements are in 
conflict with local regulatory restrictions or institutional requirements, the investigator must 
inform the Sponsor of these restrictions before initiation of the study. 


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13.10.3 Direct Access to Source Data/ Documents for Audits and Inspections 
The study site is to maintain a record of locations of essential documents and study source 
documents. Members of the Sponsor’s GCP Quality Assurance Department or designees may 
conduct an audit of a clinical site at any time during or after completion of the study. The 
purpose of an audit, which is independent of and separate from routine monitoring or quality 
control functions, is to evaluate clinical study conduct and compliance with the protocol, 
SOPs, ICH GCPs, and the applicable regulatory requirements. The investigator will be 
informed if an audit is to take place and advised as to the scope of the audit. The investigator 
and the Sponsor may also be subject to an inspection by FDA, European Regulatory 
authorities, or other applicable regulatory authorities at any time. The auditor and regulatory 
authorities will require authority from the investigator to have direct access to the clinical 
supplies, study site facilities, and laboratory, and that all data (including original source 
documentation) and all study files are available, if requested. It is important that the 
investigator(s) and their staff cooperate with the auditor or regulatory authorities during an 
audit or inspection. 
13.11 Clinical Study Report 
A CSR will be prepared, regardless of whether the trial is completed, under the responsibility 
and supervision of the Sponsor and signed by the Sponsor’s Chief Medical Officer, thereby 
indicating their agreement with the analyses, results, and conclusions of the CSR. The CSR 
will be provided to the regulatory agency(ies) as required by the applicable regulatory 
requirements. 
13.12 Publication and Disclosure Policy 
All data generated from this study are the property of the Sponsor and shall be held in strict 
confidence along with all information furnished by the Sponsor. Independent analysis and/or 
publication of these data by the investigator(s) or any member of their staff are not permitted 
without the prior written consent of the Sponsor. Written permission to the investigator will 
be contingent on the review by the Sponsor of the statistical analysis and manuscript, and 
will provide for nondisclosure of the Sponsor confidential or proprietary information. In all 
cases, the parties agree to provide all manuscripts or abstracts to all other parties 30 days 
prior to submission. This will enable all parties to protect proprietary information and to 
provide comments based on information that may not yet be available to other parties.  
13.13 Investigator Oversight 
The investigator has a responsibility for supervising any individual or party to whom they 
delegate trial related duties or functions conducted at the trial site. This includes the services 
of any party or individual retained by the investigator for this purpose. All staff delegated 
study responsibilities must be documented on an approved Delegation of Authority log for 
the study and this filed with the essential documents. In addition, the investigator must ensure 
that delegated staff are qualified by training, experience and licensure (as applicable). The 
investigator should implement procedures to ensure integrity of the study and data generated. 


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15 APPENDICES 
15.1 Appendix 1 
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS CRITERIA 
The RECIST guidelines (Version 1.1) are described in Eisenhauer (2009) and at 
http://www.eortc.be/Recist/Default.htm.66 A short summary is given below. 
Measurable Disease: 
Tumor lesions: measurable lesions are defined as those that can be accurately measured in at 
least one dimension (longest diameter to be recorded) with the following: 
• A minimum size of 10 mm by CT scan (CT scan thickness no greater than 5 mm) 
• A minimum size of 10 mm caliper measurement by clinical exam (lesions that cannot be 
accurately measured with calipers should be recorded as nonmeasurable) 
• A minimum size of 20 mm by chest X-ray 
All tumor measurements must be recorded in millimeters (or decimal fractions of 
centimeters). 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be not greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed.  
Nonmeasurable Disease: 
All other lesions (or sites of disease), including small lesions (longest diameter < 10 mm or 
pathological lymph nodes with ≥ 10 to < 15 mm short axis), as well as truly nonmeasurable 
lesions, are considered nonmeasurable disease. Lesions considered truly nonmeasurable 
include leptomeningeal disease, ascites, pleural/pericardial effusions, inflammatory breast 
disease, lymphangitic involvement of skin and lung, and abdominal masses/abdominal 
organomegaly identified by physical exam that is not measurable by reproducible imaging 
techniques.  
Bone Lesions 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require 
particular comment. Bone scan, PET scan, or plain films are not considered adequate 
imaging techniques to measure bone lesions. However, these techniques can be used to 
confirm the presence or disappearance of bone lesions. 
 
 


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Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft tissue components that 
can be evaluated by cross-sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above. 
Blastic bone lesions are nonmeasurable. 
Cystic Lesions 
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor nonmeasurable) because they are, by 
definition, simple cysts. 
Cystic lesions thought to represent cystic metastases can be considered as measurable lesions 
if they meet the definition of measurability described above. However, if noncystic lesions 
are present in the same patient, these are preferred as target lesions. 
Lesions with Prior Local Treatment 
Tumor lesions situated in a previous irradiated area or in an area subjected to other 
locoregional therapy are usually not considered measurable unless there has been 
demonstrated progression in the lesion. 
Target Lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline. Target lesions should be selected on the basis of their size (lesions with 
the longest diameter) and their suitability for accurate repeated measurements (either by 
imaging techniques or clinically). A sum of the longest diameter (LD) for all target lesions 
will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as 
reference by which to characterize the objective tumor response.  
Nontarget Lesions 
RECIST Version 1.1 criteria require unequivocal quantification of the changes in tumor size 
for adequate interpretation of the sum of target lesions. Consequently, when the boundaries 
of the primary are difficult to delineate, this tumor should not be considered a target lesion. 
Guidelines for Evaluation of Measurable Disease 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination when both methods have been used to assess 
the antitumor effect of a treatment. 


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Evaluation of Target Lesions 
Complete Response 
Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or nontarget) must have reduction in short axis to < 10 mm. 
Partial Response 
At least a 30% decrease in the sum of the LD of target lesions, taking as 
reference the baseline sum LD. 
Stable Disease 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum LD since the treatment 
started. 
Progressive Disease 
At least a 20% increase in the sum of the LD of target lesions, taking as 
reference the smallest sum on study (this includes the baseline sum if that 
is the smallest on study). In addition to the relative increase of 20%, the 
sum must also demonstrate an absolute increase of at least 5 mm. The 
appearance of one or more new lesions is also considered progression. 
Evaluation of Nontarget Lesions 
Complete Response 
Disappearance of all nontarget lesions and normalization of tumor marker 
level. 
Stable 
Disease/Incomplete 
Response 
Persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor 
marker level above the normal limits. 
Progressive Disease 
Appearance of 1 or more new lesions and/or unequivocal progression of 
existing nontarget lesions. 
If tumor markers are initially above the institutional ULN, they must normalize for a patient 
to be considered a complete responder.  
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for PD the smallest measurements 
recorded since the treatment started).  


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Evaluation of Best Overall Response: Patients with Target (+/- Non-Target) Disease 
 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not evaluated 
No 
PR 
SD 
Non-PD or not evaluated 
No 
SD 
Not Evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = complete response; NE = nonevaluable; PD = progressive disease; stable disease = 
stable disease. 
 
Evaluation of Best Overall Response: Patients with Non-Target Disease Only 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PDa 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR = complete response; NE = nonevaluable; PD = progressive disease; SD = stable 
disease. 
b 
‘Non-CR/non-PD’ is preferred over ‘stable disease’ (SD) for non-target disease since SD is 
increasingly used as endpoint for assessment of efﬁcacy in some trials so to assign this category when 
no lesions can be measured is not advised. 
Patients with global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be classified as having 
symptomatic deterioration. Every effort should be made to document the objective 
progression, even after discontinuation of treatment. 
In some circumstances, it may be difficult to distinguish residual disease from normal tissue. 
When evaluation of CR depends on this determination, it is recommended that the residual 
lesion be investigated (fine needle aspiration/biopsy) prior to confirming the complete 
response status. 


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Duration of Response 
CT scans are required for this study at screening and every 8 calendar weeks (within 5 days 
before is permitted) thereafter. Patients who have been on study at least 18 months, may 
decrease the frequency of disease/ tumor assessments to every 16 weeks (within 5 days 
before is permitted).  
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are met for 
CR or PR (whichever is first recorded) until the first date that recurrent or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded since the 
treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for 
CR until the first date that recurrent disease is objectively documented. 
Duration of Stable Disease 
SD is measured from the start of the treatment until the criteria for progression are met, 
taking as reference the smallest measurements recorded since the treatment started. 


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15.2 Appendix 2 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS SCALE 
ECOG Performance Status 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature (eg, light house work or office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours. 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead. 
 
In the event performance status is assessed by the Karnofsky Performance Status scale, the 
following conversion chart applies. 
Karnofsky Performance Status 
ECOG 
Performance 
Status 
General Description 
Score 
Specific Description 
Score 
Able to carry on 
normal activity and 
to work; no special 
care needed 
100 
Normal; no complaints; no evidence of 
disease 
0 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease 
1 
80 
Normal activity with effort; some signs 
or symptoms of disease 
Unable to work; able 
to live at home and 
care for most 
personal needs; 
varying amount of 
assistance needed 
70 
Cares for self, unable to carry on normal 
activity or to do active work 
2 
60 
Requires occasional assistance, but is 
able to care for most of personal needs 
50 
Requires considerable assistance and 
frequent medical care 
3 
Unable to care for 
self; requires 
equivalent of 
institutional or 
hospital care; disease 
may be progressing 
rapidly 
40 
Disabled; requires special care and 
assistance 
30 
Severely disabled; hospital admission is 
indicated although death not imminent 
4 
20 
Very sick; hospital admission necessary; 
active supportive treatment necessary 
10 
Moribund; fatal processes progressing 
rapidly 
0 
Dead 
5 
 


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15.3 Appendix 3 
EXAMPLES OF SENSITIVE CLINICAL CYTOCHROME 
P450 (CYP) SUBSTRATES 
Enzyme or 
Transporter 
Sensitive Substrate Drugsa 
CYP1A2 
Tizanidine, theophylline, alosetron, caffeine, duloxetine, melatonin, 
ramelteon, tasimelteon 
CYP2C9 
Celecoxib 
CYP2C19 
S-mephenytoin, omeprazole 
CYP3A 
Alfentanil, sirolimus, tacrolimus, avanafil, buspirone, conivaptan, 
darifenacin, darunavir, ebastine, everolimus, ibrutinib, lomitapide, 
lovastatin, midazolam, naloxegol, nisoldipine, saquinavir, 
simvastatin, tipranavir, triazolam, vardenafil, budesonide, dasatinib, 
dronedarone, eletriptan, eplerenone, felodipine, indinavir, 
lurasidone, maraviroc, quetiapine, sildenafil, ticagrelor, tolvaptan 
Source: FDA Guidance on Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- 
and Transporter-mediated Drug Interactions, January 2020.67 Refer to this website for 
updated list of sensitive and moderate sensitive substrates. https://www.fda.gov/drugs/drug-
interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-
inducers#table3-1 
Abbreviations: AUC = area under the plasma concentration-time curve; CYP = cytochrome 
P450; DDI = drug-drug interaction; FDA = Food and Drug Administration. 
a 
Sensitive substrates are drugs that demonstrate an increase in AUC of ≥ 5-fold with 
strong index inhibitors of a given metabolic pathway in clinical DDI studies. 
 
 


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15.4 Appendix 4 
MODIFIED GYNECOLOGICAL CANCER INTERGROUP (GCIG) GUIDELINES FOR RESPONSE USING 
CA-125 
Adapted from Rustin et al., Int J Gynecol Cancer. 2011.68  
GCIG CA-125 definitions are available at http://gcig.igcs.org/CA-125.html.  
To be evaluable for response by CA-125 requires an elevated baseline value of at least twice 
the upper limit of normal and at least two additional samples after the start of treatment.  
A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 
1. in a sample collected after initiation of study treatment AND  
2. that is confirmed in a subsequent sample collected ≥ 21 days after the prior 
sample. The absolute value of this confirmatory sample must be ≤ 110% of the 
prior sample. 
The date when the first sample with a 50% decrease from baseline is observed is the date of 
the CA-125 response. 
In patients who have measureable disease by RECIST Version 1.1 and CA-125, the date of 
response will be the date of the earlier of the two events. When assessing progression, the 
objective change in tumor size should be used for treatment decisions. For example, if a 
patient has a reduction in measurable disease, but an increase in CA-125 that suggests 
progression, treatment should continue. 
 
 


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15.5 Appendix 5 
European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire (EORTC QLQ)-C30, EORTC Ovarian Cancer Module QLQ-OV28, and 
Euro-Quality of Life 5D (EQ-5D) Patient Reported Outcomes 
Sample forms for the EORTC QLQ-C30 and EORTC QLQ-OV28 are below and background 
for each questionnaire, respectively, is available at: http://groups.eortc.be/qol/eortc-qlq-c30 
and http://groups.eortc.be/qol/why-do-we-need-modules. 
A sample form for the EQ-5D is below and background for the questionnaire is available at 
http://www.euroqol.org/home.html. 
 
 
 


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EORTC QLQ-C30 Sample Questionnaire 
 
 


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EORTC QLQ-OV28 Sample Questionnaire 
 
 


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Euro-QoL5D (EQ-5D) – English Version for the US 
By placing a checkmark in one box in each group below, please indicate which statements best 
describe your own health state today. 
Mobility 
I have no problems in walking about 
  
I have some problems in walking about 
  
I am confined to bed 
  
Self-Care 
I have no problems with self-care 
  
I have some problems washing or dressing myself 
  
I am unable to wash or dress myself 
  
Usual Activities (e.g. work, study, housework, family or leisure activities) 
I have no problems with performing my usual activities 
  
I have some problems with performing my usual activities 
  
I am unable to perform my usual activities 
  
Pain/Discomfort 
I have no pain or discomfort 
  
I have moderate pain or discomfort 
  
I have extreme pain or discomfort 
  
Anxiety/Depression 
I am not anxious or depressed 
  
I am moderately anxious or depressed 
  
I am extremely anxious or depressed 
  
 


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SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): 
A Phase 3 Multicenter, Randomized Study of Rucaparib versus 
Chemotherapy in Patients with Relapsed, BRCA-Mutant, 
High-Grade Epithelial Ovarian, Fallopian Tube, or Primary 
Peritoneal Cancer 
PROTOCOL: 
 CO-338-043 
VERSION: 
 Primary Efficacy Endpoint Version 
DATE FINAL: 
 28 October 2020 
SPONSOR: 
 Clovis Oncology 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or 
regulations. Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them. 


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APPROVAL PAGE 
 
This document was reviewed by the following Clovis team members:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The document was authored by:  
 
  
 
 The document is hereby approved and signed by: 
DocuSign Envelope ID: 3AAD4296-492A-4EF6-A0D5-F0804D5E0711


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TABLE OF CONTENTS 
APPROVAL PAGE ...................................................................................................................2 
ABBREVIATIONS AND SPECIALIST TERMS ....................................................................6 
1 
INTRODUCTION ...........................................................................................................8 
2 
OBJECTIVES AND OVERALL STUDY DESIGN ......................................................9 
2.1 
Study Objectives Outlined in Protocol ....................................................................9 
2.2 
Overall Study Design .............................................................................................10 
2.3 
Sample Size Determination ....................................................................................11 
2.4 
Independent Data Monitoring Committee .............................................................12 
3 
GENERAL ANALYSIS CONVENTIONS ..................................................................12 
3.1 
Analysis Populations ..............................................................................................13 
3.2 
BRCA Subgroups...................................................................................................13 
4 
PATIENT DISPOSITION .............................................................................................14 
4.1 
Disposition and Summary of COVID-19 Impact ..................................................14 
5 
PROTOCOL DEVIATIONS .........................................................................................14 
6 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS ....................................14 
6.1 
Demographics ........................................................................................................14 
6.2 
Baseline Clinical Characteristics ...........................................................................15 
6.2.1 
Summary of Disease Characteristics ...........................................................15 
6.2.2 
Cancer History and Prior Anti-cancer Treatment ........................................15 
6.2.3 
Summary of BRCA mutation Status and Type ............................................16 
6.3 
Medical History .....................................................................................................16 
7 
STUDY DRUG EXPOSURE AND COMPLIANCE ...................................................16 
8 
PRIOR AND CONCOMITANT MEDICATIONS ......................................................17 
9 
EFFICACY ENDPOINT VARIABLES .......................................................................17 
9.1 
Primary Efficacy Endpoint ....................................................................................17 
9.2 
Secondary Efficacy Endpoints ...............................................................................17 
9.2.1 
Hierarchical Step-down Order for Secondary Endpoints ............................17 
9.2.2 
Stand-alone Secondary Endpoints ...............................................................18 
9.3 
Exploratory Efficacy Variables ..............................................................................18 
10 
EFFICACY ANALYSIS ...............................................................................................18 
10.1 
Primary Efficacy Analysis .....................................................................................18 
10.1.1 
Sensitivity Analyses for PFS .......................................................................19 
10.2 
Secondary Efficacy Analyses in the Step-down Procedure ...................................19 
10.2.1 
Overall Response Rate by RECIST v1.1. as Assessed by Investigator .......19 
10.2.2 
Duration of Response by RECIST v1.1. as Assessed by Investigator .........20 
10.2.3 
ORR by RECIST v1.1. as Assessed by Investigator and/or CA-125 
Response ......................................................................................................20 


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10.2.4 
Patient-reported Outcome Endpoint by EORTC QLQ-C30 Global 
Health Status ................................................................................................20 
10.3 
Secondary Efficacy Analyses Outside the Step-down Procedure ..........................21 
10.3.1 
PFS by BICR................................................................................................21 
10.3.2 
Interim Overall Survival ..............................................................................21 
10.3.3 
Patient-reported Outcome Endpoint by EORTC QLQ-C30 and QLQ-
OV28 ............................................................................................................21 
10.4 
Exploratory Efficacy Analyses ..............................................................................22 
10.4.1 
Progression-free Survival 2 (PFS2) .............................................................22 
10.4.2 
Disease Control Rate ....................................................................................22 
10.4.3 
Patient Reported Outcome of EQ-5D ..........................................................22 
10.4.4 
Assessing Efficacy in BRCA Mutation Subgroups .....................................22 
10.4.5 
Efficacy During the Crossover Part .............................................................23 
11 
STATISTICAL / ANALYTICAL ISSUES ..................................................................23 
11.1 
Statistical Hypothesis .............................................................................................23 
11.2 
Handling of Dropouts or Missing Data ..................................................................23 
11.3 
Multiple Comparison / Multiplicity .......................................................................23 
11.4 
Examination of Efficacy in Subgroups ..................................................................26 
12 
SAFETY ANALYSIS ...................................................................................................26 
12.1 
Adverse Events ......................................................................................................26 
12.2 
Clinical Laboratory Evaluations ............................................................................28 
12.3 
Vital Signs ..............................................................................................................28 
12.4 
Electrocardiograms ................................................................................................29 
12.5 
Examination of Safety in Subgroups .....................................................................29 
13 
PROTOCOL SPECIFIED ANALYSES NOT PERFOMED AS PART OF THIS 
SAP ................................................................................................................................30 
14 
REFERENCES ..............................................................................................................31 
15 
APPENDICES ...............................................................................................................32 
 
 
 


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LIST OF IN-TEXT TABLES 
Table 1 
Primary , Secondary and Exploratory Objectives .....................................................9 
Table 2 
Algorithm for Determination of Germline/Somatic Status .....................................13 
 
LIST OF IN-TEXT FIGURES 
Figure 1 Schema of Study Design .........................................................................................11 
Figure 2 Ordered Step-down Procedure ................................................................................25 


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ABBREVIATIONS AND SPECIALIST TERMS 
AE 
adverse event 
ANCOVA 
analysis of covariance 
ATC 
Anatomical Therapeutic Chemical 
BICR 
blinded independent central review 
BID 
twice a day 
BRCA 
breast cancer gene 
BRCA1/2 
breast cancer gene 1 or breast cancer gene 2 
CA-125 
cancer antigen-125 
CI 
confidence interval  
CMH 
Cochran-Mantel-Haenszel 
CR 
complete response 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
circulating cell-free tumor DNA 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaire (EORTC QLQ)-C30 
EORTC QLQ-OV28 
EORTC ovarian cancer module QLQ-OV28 
EQ-5D 
Euro-Quality of Life 5D 
FMI 
Foundation Medicine, Inc. 
gBRCA 
germline BRCA1/2 mutation  
GCIG 
Gynecologic Cancer InterGroup 
HR 
hazard ratio 
IDMC 
Independent Data Monitoring Committee 
invPFS 
progression-free survival, investigator assessed 
ITT 
intent-to-treat 
KM 
Kaplan-Meier 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NE 
not evaluable 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 


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PFI 
progression-free interval 
PFS 
progression-free survival  
PFS2 
the second event of PFS, in subsequent line of treatment 
PK 
pharmacokinetic(s) 
PR 
partial response 
PRO 
patient-reported outcome 
PT 
Preferred Term 
QTcB 
QT interval corrected using Bazett’s method 
QTcF 
QT interval corrected using Fridericia’s method 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAP  
statistical analysis plan 
SD 
stable disease 
SOC 
System Organ Class 
StdD 
standard deviation 
tBRCA 
tumor tissue mutation in BRCA1 or BRCA2, includes germline 
and somatic BRCA 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
VAS 
visual analogue scale 


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1 
INTRODUCTION 
This document describes the statistical analyses and data presentations to be performed for 
the blind break and initial clinical study report (CSR) for Clovis Oncology protocol 
CO-338-043 “ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 
Multicenter, Randomized Study of Rucaparib versus Chemotherapy in Patients with 
Relapsed, BRCA-Mutant, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary 
Peritoneal Cancer”.  
This initial CSR is intended to capture the efficacy and safety analyses up to the timing of the 
snapshot for the blind break and analysis of the primary endpoint. The purpose of the 
statistical analysis plan (SAP) is to ensure the credibility of the study findings by 
pre-specifying the statistical approaches to the analysis of study data prior to snapshot for the 
primary endpoint in this study.  
The data included and summarized in this SAP is all data up to and including the data cutoff 
visit date of 30 September 2020.  
This SAP provides additional details concerning the statistical analyses that were already 
outlined in the original protocol, dated 15 June 2016, Protocol Amendment 1 (dated 
11 January 2018), and Amendment 2 (dated 23 October 2020). All statistical analyses 
detailed in this SAP will be conducted using Statistical Analysis Software (SAS)® 
Version 9.4 or higher. 
 




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2.2 
Overall Study Design 
This is a Phase 3 multicenter, randomized study evaluating rucaparib versus chemotherapy 
for treatment of patients with relapsed, high-grade epithelial serous or Grade 2 or Grade 3 
endometrioid ovarian, fallopian tube, or primary peritoneal ovarian cancer. The study will 
enroll patients with a deleterious BRCA1 or BRCA 2 (BRCA1/2) mutation in their tumor. 
All patients will be required to have received at least 2 prior chemotherapy regimens. 
Patients with platinum-refractory disease (ie, disease progression during or within 4 weeks 
after last dose of the most recent platinum-based chemotherapy) and patients who have 
received prior poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor 
(PARPi) treatment will be excluded. Patients with platinum-resistant (ie, disease progression 
≥ 1 to < 6 months after the last dose of most recent platinum-based chemotherapy) or 
partially platinum-sensitive disease (ie, disease progression ≥ 6 to < 12 months after last dose 
of most recent platinum-based chemotherapy) will be randomized 2:1 to receive either 
rucaparib or weekly paclitaxel. Patients with platinum-sensitive disease (ie, disease 
progression ≥ 12 months after last dose of most recent platinum-based chemotherapy) will be 
randomized 2:1 to receive either rucaparib or platinum-based chemotherapy consisting of the 
Investigator’s selection of monotherapy platinum (cisplatin or carboplatin) or platinum-based 
doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or 
cisplatin/gemcitabine). 
A 2:1 randomization to receive either rucaparib or chemotherapy will allow for statistical 
comparison of PFS, OS, and ORR between the treatment arms and provide access to 
rucaparib for a larger number of patients who would otherwise receive standard 
chemotherapy. The randomization assignments are stratified by the patients’ progression-free 
interval (PFI) after most recent platinum-containing therapy (ie, platinum-resistant, partially 
platinum-sensitive, or platinum-sensitive) to maintain balance between treatment groups.  
Patients will be randomized following classification (ie, deleterious BRCA1/2 mutation) 
detected by Foundation Medicine Inc. (FMI; central laboratory) analysis or documented local 
results for deleterious germline or somatic BRCA1/2 mutation, with confirmation of 
adequate tumor tissue availability for central confirmation testing of a deleterious BRCA1/2 
mutation, and confirmation that all other eligibility criteria in the screening phase have been 
met.  
Patients will receive treatment with either rucaparib or chemotherapy until disease 
progression by RECIST1 Version 1.1, as assessed by the investigator; unacceptable toxicity 
or inability to tolerate further treatment, as assessed by the investigator; pregnancy; death; 
loss to follow-up; withdrawal of consent; or another appropriate clinical reason. Patients 
receiving platinum-based chemotherapy (monotherapy or doublet therapy) will receive up to 
a maximum of 8 cycles of treatment and will be followed thereafter until disease progression 
or other reason for discontinuation. Figure 1 shows the schedule of the study design with the 
screening phase following by the randomized treatment phase and lastly the post-treatment 
phase with an option for crossover for patients randomized to chemotherapy. 




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0.65; and at least 275 events, a sample size of 345 patients (230 patients randomized to 
rucaparib and 115 patients randomized to chemotherapy) would yield at least 80% power at a 
two-sided 0.05 significance level.  
2.4 
Independent Data Monitoring Committee  
The Independent Data Monitoring Committee (IDMC) will be responsible for safeguarding 
the interests of trial participants, assessing the safety and efficacy of the interventions during 
the trial, and for monitoring the overall conduct of the clinical trial. The IDMC will provide 
recommendations about the continuation, revision, or termination of the study. Details 
regarding the IDMC will be documented in a separate committee charter. 
3 
GENERAL ANALYSIS CONVENTIONS 
All efficacy analyses will be performed at a two-sided 0.05 significance level for the 
treatment part. This is a two part study, where all efficacy and safety for the randomized 
treatment part and the crossover part will be presented separately. All summary tables will be 
presented by randomized treatment group (rucaparib vs chemotherapy) for the treatment part.  
The efficacy data for the patients crossing over from chemotherapy to rucaparib will be 
presented descriptively in patient listings and as exploratory endpoint as outlined in 10.4.5.  
All patients identified retrospectively to have a BRCA reversion mutation will be removed 
from the Efficacy Population. Efficacy analyses will be performed for both the 
Efficacy Population and the Intent-to-treat (ITT) Population, which include all randomized 
patients with or without a BRCA reversion mutation. The methodology used to identify 
patients with a BRCA reversion mutation will be detailed in a separate document.  
It is anticipated that the data for the OS endpoint will be heavily censored at the time of the 
initial CSR analysis, thus only an interim OS will be presented and described here. Further 
details around this endpoint is described in Section 10.3.2. 
Quantitative variables will typically be summarized using frequencies and percentages for 
appropriate categorizations and may also be summarized using descriptive statistics. For 
variables summarized with descriptive statistics, the following will be presented: N, mean, 
standard deviation (StdD), median, minimum, and maximum. Categorical variables will be 
presented using frequencies and percentages. The Kaplan-Meier (KM) methodology will be 
used to summarize time-to-event variables. If estimable, 50th (median) with 95% confidence 
intervals (CIs) will be presented. The number of patients with events and the number of 
censored patients will also be presented. The stratified HR from the Cox proportional hazards 
model will be used to estimate the HR between the randomized treatment groups. Months 
will be calculated as number of days divided by 30.4375. 


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3.1 
Analysis Populations 
The following patient populations will be summarized for the treatment part:  
Safety Population – Patients who received at least one dose of protocol-specified treatment. 
Intent-to-treat (ITT) Population – All randomized patients.  
Efficacy Population – All randomized patients with a deleterious BRCA mutation, 
excluding those identified to have a BRCA reversion mutation.  
The crossover part will only be summarized both for the Safety Population and Efficacy 
Population as defined above.   
3.2 
BRCA Subgroups 
Patients are required to have a BRCA positive result as part of inclusion criteria to the study 
protocol from either local labs or centralized tumor tissue test with FMI. Both the local lab 
and the central lab will read out the BRCA status (BRCA1, BRCA2, or non-BRCA).  
In addition, a central blood test of germline BRCA (gBRCA) will be performed by an 
external vendor in order to assess the BRCA mutation type. The germline and somatic 
designation for BRCA1/2 mutation in tumor tissue (tBRCA) will be based on the information 
from local and/or central germline BRCA testing as described in Table 2. 
Table 2 Algorithm for Determination of Germline/Somatic Status 
Tumor Tissue 
BRCA Result 
Germline Blood Test Result  
(centrala and/or local testb resultc) 
Designation 
BRCA Positive 
BRCA Positive 
Germline 
BRCA Negative 
BRCA Positive 
Germline 
BRCA Positive 
BRCA Negative 
Somatic 
BRCA Positive 
Not tested 
Unknown 
Abbreviation: BRCA = breast cancer gene. 
a 
Blood sample. 
b 
Blood or buccal sample. 
c 
If either the central or local test is BRCA positive, then the patient is considered BRCA positive. 
 
All patients randomized to this study will also be tested for BRCA reversion mutation by an 
external vendor. The Efficacy Population for this study consists of all randomized patients 
with a deleterious BRCA mutation, excluding those that have BRCA reversion mutation 
identified. The hypothesis around excluding these patients is that the patients who have a 
BRCA reversion mutation will not benefit from treatment with rucaparib. The BRCA 


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reversion status for all patients and identification of the Efficacy Population will be 
completed prior to any unblinding of treatment assignments for the initial CSR. 
4 
PATIENT DISPOSITION 
Patient disposition (analysis population allocation, randomized, discontinued, and primary 
reason for discontinuation for the treatment part) will be summarized using frequency counts, 
and the corresponding percentages. In addition, the number of patients who cross over to 
rucaparib, and their primary reason for discontinuation of the crossover part or ongoing status 
will be summarized.  
4.1 
Disposition and Summary of COVID-19 Impact  
Number of patients who were ongoing and impacted by COVID-19 will be summarized. This 
is defined as all patients ongoing either in the treatment part, crossover part, or long-term 
follow up starting with visits dated on and after 01 March 2020. The number of tumor scans 
missed, visits missed, and the number of telehealth visits will also be summarized. A patient 
listing summarizing the COVID-19 impacted visits will also be produced. 
5 
PROTOCOL DEVIATIONS 
Major protocol deviations will be identified prior to releasing the treatment codes for primary 
efficacy analysis in accordance with Clovis Standard Operating Procedure (SOP) CR019 
(Identification, Documentation, Management and Review of Protocol Deviations). A listing 
with all the major protocol deviations will be presented. No patients will be excluded from 
the Efficacy Population due to a major protocol violation. 
6 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS 
All demographic and baseline characteristics variables will be summarized separately for the 
ITT Population, Efficacy Population, and Safety Population by randomized treatment group 
and overall for the treatment part. The demographic and baseline characteristics for the 
treatment part is defined as the last measurement on or prior to treatment start date. For 
patients randomized but not treated the last measurement on or prior to randomization will be 
used. 
In addition, the demographics and baseline characteristics for the patients who cross over to 
rucaparib will be summarized for the Safety Population. The demographic and baseline 
characteristics for patients who cross over to rucaparib is defined the last measurement on or 
prior to first dose of rucaparib in the crossover part. 
6.1 
Demographics 
The demographic variables will be summarized with frequency tabulations that will focus on 
identifying differences between treatment groups in the extreme values of the distributions. 
Descriptive statistics may also be used to summarize the quantitative variables. The 
demographic variables presented will include age, height, weight, gender, race, and Eastern 


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Cooperative Oncology Group (ECOG) performance status using the following 
categorizations: 
• Age (years): ≤ 50, 51-60, 61-70, 71-80, 81-90, > 90; and < 65, 65-74, ≥ 75 
• Gender: Female 
• Race: American Indian or Alaska Native, Asian, Black, Native Hawaiian or Other Pacific 
Islander, White, Other 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not reported)  
• Country  
• Height (cm): ≤ 75, > 75-100, > 100-125, > 125-150, > 150-175, > 175 
• Weight (kg): ≤ 50, > 50-75, > 75-100, > 100-125, > 125-150, > 150 
• Body mass index 
• ECOG performance status: 0, 1 
• Smoking status (Current Smoker, Former Smoker, Never Smoked) 
 
These categorizations may be adjusted if the majority of the data lies in only 2 or 3 of the 
categories.  
6.2 
Baseline Clinical Characteristics 
6.2.1 
Summary of Disease Characteristics  
• Measurable disease per Investigator (Yes, No) 
• Number of Target lesions per investigator (0, 1, 2, 3, 4, 5) 
• Sum of Diameters of Target Lesions per Investigator  
 
6.2.2 
Cancer History and Prior Anti-cancer Treatment  
The following variables will be summarized with frequency tabulations: 
• Time since diagnosis (months): 0-12, > 12-24, > 24 
• Type of ovarian cancer: epithelial, primary peritoneal, fallopian tube, other 
• Histological classification: serous, endometrioid, mixed, other  
• Histological grade: high, low 
• FIGO stage at diagnosis  
• Number of prior anti-cancer treatment regimens  
• Number of prior chemotherapy regimens  
• Number of prior platinum-based chemotherapy regimens  
• Number of intervening non-platinum regimens prior to enrollment  
• The randomization factor of PFI status for the most recent prior platinum-based regimen:  


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- 
Platinum resistant: patients who progressed ≥ 1 to < 6 months after the last dose of 
platinum-based chemotherapy; 
- 
Partially platinum-sensitive: patients who progressed ≥ 6 to < 12 months after last 
dose of platinum-based chemotherapy; and 
- 
Platinum sensitive: patients who progressed ≥ 12 months after last dose of 
platinum-based chemotherapy  
• Platinum status subgroups based electronic case report form (eCRF) data: 
- 
Platinum status based on most recent prior platinum-based regimen (resistant, 
partially-sensitive, sensitive);  
- 
PFI on most recent prior platinum-based regimen (0-6 months, 6 to < 12 months, 
12 to < 24 months, ≥ 24 months) 
 
Descriptive statistics may also be used to summarize these variables.  
 
6.2.3 
Summary of BRCA mutation Status and Type  
The following BRCA mutation characteristics will also be summarized:  
 
• BRCA status by central test: BRCA1, BRCA2, non-BRCA, Unknown  
• BRCA status by local test: BRCA1, BRCA2, non-BRCA, Unknown 
• BRCA mutation status (germline, somatic, or unknown)  
• BRCA mutation gene (BRCA1 or BRCA2) 
• BRCA reversion status (detected, not detected, failed)  
 
6.3 
Medical History 
The medical history will be summarized for the Safety Population. Medical history events 
will be classified using the Medical Dictionary for Regulatory Activities (MedDRA) 
classification system Version 23.0 or higher. Medical history data will be summarized using 
frequency tabulations by System Organ Class (SOC) and Preferred Term (PT). 
7 
STUDY DRUG EXPOSURE AND COMPLIANCE 
Study drug exposure will be summarized for all patients in the Safety Population for the 
treatment part. The duration of treatment will be calculated as the number of days from the 
first dose of study drug to the day of the last dose of study drug +1. The duration will be 
summarized with summary statistics and by categories (0 to < 6 months, ≥ 6 to < 12 months, 
≥ 12 to < 24 months, ≥ 24 months) for each treatment arm. 
 
For the patients randomized to rucaparib; dose intensity and the number of patients who 
reduced study drug will be summarized. The dose intensity is defined as time normalized 
actual dose received divided by the starting dose of 600 mg twice a day (BID), The number 
of patients with at least 1 dose reduction will be summarized with frequencies and 
percentages, and the number of patients on each dose level will be summarized 


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(ie, 500 mg BID, 400 mg BID, and 300 mg BID) in order to assess patients with multiple 
levels of dose reductions.  
 
For the patients randomized to chemotherapy; the number of cycles received, the type of 
chemotherapy assigned, and the number of patients who dose reduced will be summarized.  
 
In addition, the exposure for the crossover part will be summarized for the Safety Population 
as outlined above.  
8 
PRIOR AND CONCOMITANT MEDICATIONS 
Prior and concomitant medications will be summarized for all patients in the 
Safety Population for the treatment part and crossover part separately. Prior/concomitant 
medication coding will utilize the World Health Organization (WHO) Drug Dictionary 
Version 2019MAR Global B3 or later. All concomitant treatments documented during the 
treatment part will be summarized in frequency tabulations for each randomized treatment 
group using Anatomical Therapeutic Chemical (ATC) level 4. All concomitant treatments 
documented during the crossover part will be summarized in frequency tabulations using 
ATC level 4. For the crossover part, the prior medications are defined as any medications 
that has both start and stop date that is after the last dose of randomized treatment in the 
treatment part. If either the start date and/or the stop date of the medication is missing such 
that it is unclear whether the medication was stopped, then the medication will be included in 
the summary of the concomitant medications for that study part. 
Prior medications will only be presented in listings. Prior medications will be defined as 
those medications with both a start and a stop date that is before the day of the first dose of 
study drug administration in the treatment part. 
9 
EFFICACY ENDPOINT VARIABLES 
9.1 
Primary Efficacy Endpoint 
The primary efficacy variable is invPFS for the treatment part. 
9.2 
Secondary Efficacy Endpoints  
9.2.1 
Hierarchical Step-down Order for Secondary Endpoints 
The following secondary endpoints for the treatment part of the study are part of the 
hierarchical step down model2, 3 as presented in Section 11.3 for the initial CSR.  
1. ORR by RECIST Version 1.1 
2. DOR by RECIST Version 1.1 
3. ORR by RECIST Version 1.1 and/or CA-125 response 
4. PRO as assessed by the EORTC QLQ-C30 Global Health Status score 
 


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9.2.2 
Stand-alone Secondary Endpoints 
Stand-alone secondary endpoints for the treatment part of the study outside of the step down 
are as follows: 
• PFS by BICR  
• Interim OS  
• PRO as assessed by the EORTC QLQ-C30 and QLQ-OV28 
 
9.3 
Exploratory Efficacy Variables 
• To evaluate PFS of study treatment followed by PFS2, defined as the time from 
randomization to the second event of disease progression or death, as assessed by the 
investigator 
• To evaluate disease control rate (RECIST Version 1.1 defined as confirmed CR, PR, or 
prolonged SD > 12 weeks, by investigator assessment) 
• To evaluate PRO utilizing the EQ-5D assessment 
• To assess efficacy in BRCA-mutation subgroups (ie, germline/somatic and 
BRCA1/BRCA2) 
• To explore the efficacy during the crossover part 
 
10 EFFICACY ANALYSIS 
All efficacy analyses will be performed both in the Efficacy and the ITT Populations. The 
primary endpoint and key secondary endpoints will be tested using a hierarchical step-down 
procedure as outlined in Section 11.3. 
10.1 Primary Efficacy Analysis 
The primary efficacy endpoint is invPFS for the treatment part. The time to invPFS will be 
calculated in months as the time from randomization to disease progression +1 day, as 
determined by RECIST 1.1 criteria or death due to any cause, whichever occurs first. Patients 
without a documented event of progression (or death) will be censored on the date of their 
last tumor assessment (ie, radiologic assessment) or date of randomization if no post-baseline 
tumor assessments have been performed. Patients who withdraw from treatment prior to 
progression will be followed for disease status and survival whenever possible. Only tumor 
scans and deaths up to and within 6 weeks of start of any subsequent anti-cancer treatment 
are included.  
The primary endpoint of invPFS will be analyzed using the stratified Cox proportional 
hazard methodology. The stratified HR from the Cox proportional hazards model will be 
used to estimate the HR between the randomized treatment groups.  


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10.1.1 
Sensitivity Analyses for PFS 
10.1.1.1 
Censoring Distribution 
Sensitivity analyses for invPFS will be performed to evaluate the impact of censored patients. 
The following analyses will be performed: 
• All scans regardless if they are after start of subsequent anti-cancer treatment will be 
included as per European Medicines Agency (EMA) guidelines for PFS (Appendix 1 of 
the guidelines for the evaluation of anti-cancer medicinal products in man, EMA/ 
Committee for Medicinal Products for Human Use [CHMP]/27994/2008/Rev.1/20212). 
• Patients who discontinued treatment in the randomized study part due to clinical 
progression or withdrew consent to treatment will be considered events of invPFS on the 
date of the last dose of study drug. Patients who are randomized but never took any study 
drug will use the date of randomization instead of last dose of study drug. 
 
Additional sensitivity analyses may also be performed to evaluate the robustness of the study 
results. These analyses will be considered exploratory and will likely be motivated by the 
observed results. 
10.2 Secondary Efficacy Analyses in the Step-down Procedure 
10.2.1 
Overall Response Rate by RECIST v1.1. as Assessed by Investigator  
The ORR as assessed by the investigator will be analyzed in the subgroup of patients who are 
response evaluable at baseline (ie, measurable target lesions) for both the Efficacy Population 
and the ITT Population. The ORR is defined as proportion of patients with a confirmed CR 
or PR response by RECIST v1.1. The confirmed response is defined as a CR or PR on 
subsequent tumor assessment at least 28 days after first response documentation. The ORR 
will be summarized with frequencies and proportion together with 95% CI and compared 
between treatments by using a stratified Cochran-Mantel-Haenszel (CMH) test. In addition, 
the best confirmed response by RECIST v1.1. will be summarized with frequency and 
proportion by: 
• Complete Response (CR) 
• Partial Response (PR)  
• Stable disease (SD), met the SD criteria at least once after study entry at a minimal of 49 
days after randomization.  
• Progressive disease (PD) 
• Not evaluable (NE), discontinuations or deaths before first tumor assessment 
 
Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment 
are included. 
 


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10.2.2 
Duration of Response by RECIST v1.1. as Assessed by Investigator  
The DOR as assessed by investigator will be analyzed in the subgroup of patients who have a 
confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be 
measured from the date of the first response until the first date that PD is documented. DOR 
will be calculated in months as the time from the first date of the scan showing a response to 
the first scan with disease progression +1 day. Any patients with an ongoing response will be 
censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks 
of start of any subsequent anti-cancer treatment are included. 
The DOR will be analyzed using the stratified Cox proportional hazard methodology and a 
stratified log-rank test. The stratified HR from the Cox proportional hazards model will be 
used to estimate the HR between the randomized treatment groups.  
10.2.3 
ORR by RECIST v1.1. as Assessed by Investigator and/or CA-125 
Response 
The ORR and/or CA-125 response will be analyzed in the subgroup of patients who are 
response evaluable at baseline (ie, measurable target lesions) for both the Efficacy Population 
and ITT Population. 
The ORR is defined as proportion of patients with a confirmed CR or PR by RECIST v1.1. 
The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 
28 days after first response documentation. Only tumor scans up to and within 6 weeks of 
start of any subsequent anti-cancer treatment are included. 
Patients evaluable for CA-125 response must have a baseline CA-125 value at least twice the 
upper limit of normal (ULN; ie, 70 IU/mL) and at least 2 post baseline values. The endpoint 
of CA-125 response rate is defined as a 50% reduction from baseline. The response needs to 
be confirmed in a subsequent sample collected ≥ 21 days after the prior sample. The value of 
this confirmatory sample must be ≤ 110% of the prior sample. The date when the first sample 
with a 50% decrease from baseline is observed is the date of the CA-125 response. In 
patients who have measureable disease by RECIST Version 1.1, the date of response will be 
the date of the earlier of the two events. The number of patients evaluable for GCIG CA-125 
response will also be summarized descriptively.  
The proportion of patients with a confirmed RECIST v1.1. response and/or CA-125 response 
will be summarized with frequencies and proportion with 95% CI and compared between 
treatments by using a stratified CMH test.  
10.2.4 
Patient-reported Outcome Endpoint by EORTC QLQ-C30 Global Health 
Status 
The PRO data will be scored and summarized in accordance with the scoring manual for the 
EORTC QLQ-C30 outlined in Appendix 1 (English version). The score of interest that will 
be used for the step-down testing is the EORTC QLQ-C30 Global Health Status score.  


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Changes from baseline for the EORTC QLQ-C30 global health status score using a repeated 
analysis of covariance (ANCOVA) over the first 6 treatment cycles in the treatment part will 
be analyzed and used as a covariate in the step down. Any patient with a baseline value and 
at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during 
the first 6 cycles will be included in the analysis. The repeated measures ANCOVA model 
will be used to estimate the average treatment effect over the first 6 cycles (months) using 
treatment, stratification variables, and baseline EORTC QLQ-C30 Global Health Status score 
as between-subject factors and change from baseline to each visit as a within-subject factor.  
10.3 Secondary Efficacy Analyses Outside the Step-down Procedure 
10.3.1 
PFS by BICR  
The PFS by BICR may, but is not required to, be performed at the time of the initial CSR. 
The same statistical test used for the primary endpoint (ie, stratified Cox proportional model) 
will be used to compare rucaparib to chemotherapy for this endpoint. 
10.3.2 
Interim Overall Survival  
The time to OS will be calculated in months as the time from randomization to date of death 
due to any cause. Patients who are still alive will be censored on the date of their last 
available visit or last date known to be alive.  
It is anticipated that the data for OS will be heavily censored at the time of the initial CSR 
analysis. In order to adjust for multiple analyses of OS at a later stage, a stopping rule will be 
applied. The Haybittle-Peto4, 5 stopping rule will be applied where an OS result with a 
p-value < 0.001 can be used to claim superiority of rucaparib compared to chemotherapy. 
This means that a p-value < 0.05 can be utilized at the final analysis which is projected to be 
once 70% of the death events have been collected.  
The same statistical test used for the primary endpoint (ie, stratified Cox proportional model) 
will be used to compare rucaparib to chemotherapy for this endpoint. 
10.3.3 
Patient-reported Outcome Endpoint by EORTC QLQ-C30 and QLQ-OV28 
The PRO data will be scored and summarized in accordance with the scoring manual for the 
questionnaire. Appendix 1 and Appendix 2 includes the English version of the questionnaires 
used. Changes and/or percent changes from baseline will be analyzed for each scheduled 
post-baseline visit and for the final visit for each subscale and total score. Patients that do not 
have both a baseline measurement and at least one post-baseline measurement will not be 
included. 
At a given visit, the change from baseline will be compared between the randomized 
treatment groups using an ANCOVA using the treatment and stratification variable as a 
categorical factor and baseline measurement for the parameter as a continuous covariate. 


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10.4 Exploratory Efficacy Analyses 
The purpose of the exploratory endpoint is to further explore the efficacy and no multiple 
adjustment is performed for these analyses.  
10.4.1 
Progression-free Survival 2 (PFS2)  
The second event of PFS, PFS2, is defined as the time from randomization to the second 
event of disease progression as assessed by the investigator, or death due to any cause. This 
second event of PFS may be a documented event per RECIST Version 1.1 guidelines or may 
be an event of symptomatic progression. Patients without a second event of progression (or 
death) will be censored on the last date the patient was known to be alive, study visit , or on 
the date of randomization if no post-baseline visits have been performed. 
PFS2 will be analyzed using Cox proportional hazard method. The stratified HR from the 
Cox proportional hazards model will be used to estimate the HR between the randomized 
treatment groups. 
10.4.2 
Disease Control Rate  
Disease control rate during the treatment part is defined as RECIST Version 1.1 evaluation of 
CR, PR or SD ≥ 12 weeks and SD ≥ 24 weeks as assessed by the investigator. The number 
and percent of patients meeting the criteria for disease control rate will be summarized with 
frequencies and proportion with 95% CI and compared between treatments by using a 
stratified CMH test.  
10.4.3 
Patient Reported Outcome of EQ-5D 
Analyses of changes and/or percent changes from baseline will be analyzed for each 
scheduled post-baseline visit and for the final visit for the EQ-5D assessment and the 
EQ Visual Analogue Scale (VAS). Patients who do not have both a baseline measurement 
and at least one post-baseline measurement will not be included. 
At a given visit, the change and/or percent change from baseline will be compared between 
the randomized treatment groups using an ANCOVA using the treatment as a categorical 
factor and baseline measurement for the parameter as a continuous covariate. 
10.4.4 
Assessing Efficacy in BRCA Mutation Subgroups  
The primary endpoint and secondary efficacy endpoints will be further analyzed in the 
following subgroups based on BRCA mutation type:  
 
• Mutation: BRCA1 vs BRCA2 
• Mutation type: germline, somatic, or unknown  
• BRCA reversion mutation-detected patients  
 


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In addition, the primary endpoint of PFS will be explored using a treatment-by-BRCA 
mutation type variable in the model.  
10.4.5 
Efficacy During the Crossover Part  
The efficacy data for the patients crossing over from chemotherapy to rucaparib will be 
presented descriptively in patient listings. In addition, since the patients will be re-baselined 
for tumor assessment the invPFS, ORR rate, disease control rate and CA-125 response will 
be summarized for both the Safety Population and Efficacy Population for the crossover part. 
11 STATISTICAL / ANALYTICAL ISSUES 
11.1 Statistical Hypothesis  
The primary statistical hypothesis for this study is to test for differences in PFS  
using a stratified log-rank test. 
H0: HR (rucaparib/chemotherapy) ≥ 1 
Ha: HR (rucaparib /chemotherapy) < 1 
The stratification factor used for randomization is the PFI after most recent 
platinum-containing therapy (ie, platinum-resistant, partially platinum-sensitive, or 
platinum-sensitive). All efficacy analyses will be based on the randomization strata given at 
randomization, however, a sensitivity analysis of invPFS may be performed using the actual 
strata if patients have been allocated incorrectly.  
11.2 Handling of Dropouts or Missing Data 
 
All data will be used to their maximum possible extent without any imputations for missing 
data, except for sensitivity analyses of PROs. 
Imputation of missing baseline values for the PROs will be performed as supportive analyses. 
For patients without a baseline value, the baseline value will be imputed by using the PRO 
assessment performed closest to the date of randomization and may include assessments 
performed up to and including Cycle 2 Day 1. 
  
11.3 Multiple Comparison / Multiplicity 
In order to preserve the overall Type 1 error rate, an ordered step-down (ie, fixed sequence) 
testing procedure for the primary endpoint and secondary endpoints have been  
pre-specified2, 3. The Efficacy Population will be tested first for each endpoint then it will 
step over to the full ITT Population. The primary and secondary endpoints for the Efficacy 
and ITT Populations will be tested using the ordered step-down procedure as illustrated 
in Figure 2, below. 


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If the primary efficacy endpoint reaches statistical significance at the 0.05 significance level 
(ie, two-sided) in the Efficacy Population, then the primary endpoint will be tested in the 
ITT Population. If both populations reaches statistical significance at the 0.05 significance 
level (ie, two-sided), then first secondary endpoint will be tested. The significance will only 
be declared for secondary endpoints if the primary endpoint and previous secondary 
endpoints are also statistically significant at the 0.05 significance level. 
 
The secondary endpoints will be tested in the following order:  
1. ORR by RECIST Version 1.1 
2. DOR by RECIST Version 1.1 
3. ORR by RECIST Version 1.1 and/or CA-125 response 
4. PRO as assessed by the EORTC QLQ-C30 Global Health Status score 
 
 




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11.4 Examination of Efficacy in Subgroups 
Subgroup analyses of the primary endpoint (invPFS) will be presented for the following:  
• The stratification factor used for randomization is the PFI after most recent 
platinum-containing therapy (ie, platinum-resistant, partially platinum-sensitive, or 
platinum sensitive).  
• Age groups (< 65, 65-74, ≥ 75) 
• Race (White, non-White) 
 
In addition, subgroups based on BRCA mutation and type is also presented as part of 
exploratory endpoint specified in Section 10.4.4. 
12 SAFETY ANALYSIS 
The safety analyses will be presented for the Safety Population presenting the data by each 
treatment group separately for the treatment part. All safety data during the treatment part 
which is considered treatment-emergent will be summarized. Treatment-emergent during the 
treatment part is defined as safety data with an onset date on or after the date of first dose of 
randomized study medication until the date of the last study medication plus 28 days, or up to 
the date of first dose of rucaparib for those patients who cross over from chemotherapy, 
whichever is first.  
Safety data will be presented for the crossover part separately, using the safety assessment 
before or on the date of first dose of rucaparib as the baseline value for the crossover part for 
the patients who cross over. The data that is deemed treatment emergent for the crossover 
part is defined as safety data with an onset date on or after the date of first dose of rucaparib 
in the crossover part until the date of the last study medication plus 28 days. These tables will 
not be split out by prior randomized treatment, but only presented overall for the crossover 
part.  
Also, AEs will be considered treatment-emergent if all or part of the date of onset of the AE 
is missing and it cannot be determined if the AE meets the definition for treatment-emergent. 
12.1 Adverse Events 
AEs will be classified using the MedDRA Version 23.0 or higher classification system. The 
severity of the toxicities will be graded according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) whenever possible. 
The number and percentage of patients who experienced treatment-emergent adverse events 
(TEAEs) for each SOC and PT will be presented. Multiple instances of the TEAE in each 
SOC and multiple occurrences of the same PT are counted only once per patient. The number 
and percentage of patients with at least one TEAE will also be summarized.  


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Separate tables will be presented as follows: 
• All TEAEs 
• TEAEs by CTCAE grade 
• Grade 3 or greater TEAEs 
• Treatment-related TEAEs 
• Serious TEAEs 
• TEAEs with an outcome of death 
• TEAEs leading to discontinuation of study medication 
• TEAEs resulting in reduction study medication 
• TEAEs resulting in interruption of study medication 
• TEAEs resulting in reduction or interruption of study medication 
• Time to the first TEAE that results in a reduction or interruption of study drug 
 
The incidence of TEAEs will be summarized by relationship to study drug according to the 
following categories: “treatment-related,” or “not treatment-related”. If a patient experiences 
multiple occurrences of the same AE with different relationship categories, the patient will be 
counted once, as a relationship category of treatment related.  
If a patient experiences multiple occurrences of the same AE with different toxicity grades, 
the patient will be counted once for the maximum (most severe) toxicity grade. AEs with a 
missing toxicity grade will be presented in the summary table with a toxicity grade of 
“Missing.” For each toxicity grade, the number and percentage of patients with at least one 
TEAE of the given maximum grade will be summarized.  
The time to the first TEAE and first treatment-related TEAE that results in a dose reduction, 
delay, interruption, or discontinuation of study drug is defined as 1+ the number of days from 
the first dose of study drug to the start of the first AE. The cumulative incidence is presented 
in a 1-KM graph for just the patients with an event and the median time to onset will be 
calculated together with the 95% CI.  
Non-TEAEs (pre-treatment and post-treatment) will be presented in the by patient data 
listings for the Safety Population.  
MedDRA PTs were combined for the following similar terms  
• Asthenia/Fatigue  
• Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) Increased  
• Anaemia / Decreased Haemoglobin  
• Thrombocytopenia /Decreased Platelets  
• Neutropenia /Decreased Absolute Neutrophil Count (ANC)  
 


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In addition, the analysis of combined terms for anemia is explored as a time to first event 
analysis as described above. Transfusions (blood or plasma) are provided in patient listings. 
The number of transfusions per patient will also be summarized.  
12.2 Clinical Laboratory Evaluations 
Clinical laboratory evaluations include the continuous variables for hematology, serum 
chemistry, and urinalysis. The laboratory values will be presented in standard international 
(SI) units. The on-treatment period for the treatment part will be defined as data with an 
onset date on or after the date of first dose of study medication until the date of the last study 
medication plus 28 days, or up to the date of first dose of rucaparib for those patients who 
cross over from chemotherapy, whichever is first. Laboratory values collected during the on-
treatment period will be included in the summary tables.  
The on-treatment period for the laboratory values for crossover part will be defined as all 
laboratory values on or after first dose of rucaparib in the crossover part until the date of the 
last study medication plus 28 days. The laboratory assessment before or on the date of first 
dose of rucaparib as the baseline value for the crossover part for the patients who cross over. 
These tables will not be split out by prior randomized treatment, but only presented overall 
for the crossover part.  
The summary of laboratory data will include descriptive statistics (N, mean, StdD, minimum, 
median, and maximum) of the maximum, minimum, and last value during the on-treatment 
period. Summaries using descriptive statistics of the change from baseline to the maximum, 
minimum, and last value during the on-treatment period will also be given.  
Shift summary tables from baseline to the maximum on-treatment toxicity grade (CTCAE 
Version 4.03 or later) for each lab parameter will be summarized. 
In addition, laboratory data including will be provided using by-patient listings. 
12.3 Vital Signs 
The on-treatment period for the treatment part will be defined as the time from first dose of 
study drug to 28 days after the last dose of study drug or start of first dose of rucaparib for 
those patients who cross over from chemotherapy, whichever is first. Vital sign 
measurements collected during the on-treatment period will be included in the summary 
tables.  
The on-treatment period for the vital sign measurements for crossover part will be defined as 
all vital sign values on or after first dose of rucaparib in the crossover until the date of the last 
study medication plus 28 days. The vital sign assessment before or on the date of first dose of 
rucaparib as the baseline value for the crossover part for the patients who cross over. These 
tables will not be split out by prior randomized treatment, but only presented overall for the 
crossover part. The vital sign measurements collected after the on-treatment period will only 
be presented in the data listings.  


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The summary of vital sign data will include descriptive statistics (N, mean, StdD, minimum, 
median, and maximum) of the maximum, minimum and last value during the on-treatment 
period. Summaries using descriptive statistics (N, mean, StdD, minimum, median, and 
maximum) of the change from baseline to the maximum, minimum, and last value during the 
on-treatment period will also be given. The data will be presented separately for each 
randomized treatment group.  
12.4 Electrocardiograms 
Local reads of heart rate, pulse rate, QRS, QT, QTc, and rhythm were collected in this study. 
ECGs were to be completed on Day 1 of each cycle for patients receiving rucaparib and 
chemotherapy. ECGs on intracycle visits (Day 8 and Day 15) may be performed if clinically 
indicated per investigator judgement. The on-treatment period for the treatment part will be 
defined as the time from first dose of study drug to 28 days after the last dose of study drug 
or start of first dose of rucaparib for those patients who cross over from chemotherapy, 
whichever is first. The on-treatment period for ECG for crossover part will be defined as all 
values on or after first dose of rucaparib in the crossover until the date of the last study 
medication plus 28 days. The ECG data will be presented with descriptive statistics (N, 
mean, StdD, minimum, median, and maximum) of the maximum, minimum and last value 
during the on-treatment period. The data will be presented separately for each randomized 
treatment group.  
The QT interval was corrected by using both Fridericia’s (QTcF) and Bazett’s (QTcB) 
formula. The QTcF and QTcB intervals will be stratified into categories indicative of 
potential clinical significance. Each patient’s maximum QTc intervals from baseline to end 
of treatment visits will be classified into the following categories: ≥ 450, ≥ 481, and 
≥ 501 msec. For each patient’s maximum change from the pretreatment ECG visit for QT 
and QTc, intervals will be classified into < 30 msec, ≥ 30 to < 60 msec, and ≥ 60 msec. The 
number and percentage of patients in each classified category will be presented. 
12.5 Examination of Safety in Subgroups 
Safety will be further explored in the following subgroups:  
• BRCA mutation (BRCA1, BRCA2) 
• BRCA mutation type (germline, somatic, unknown) 
• Age groups (< 65, 65-74, ≥ 75) 
• Race (White, Other, Unknown) 
 


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13 PROTOCOL SPECIFIED ANALYSES NOT PERFOMED AS PART 
OF THIS SAP  
The following secondary endpoints will likely not be analyzed at the time of this blind break 
and initial CSR (primary efficacy snapshot) and thus will be summarized in the final CSR.  
Final OS will likely not have reached 70% maturity of death events by the time of the 
primary endpoint analysis.  
In addition, the following exploratory endpoints may be summarized in the final CSR:  
• To assess molecular changes in tumor samples over time in matched pairs 
• To assess circulating ctDNA as a molecular marker of efficacy 
• To evaluate the impact of gene expression molecular subgroups on PFS and OS 
• To explore the relationship between rucaparib exposure and responses (safety and 
efficacy) 
 
 


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14 REFERENCES 
1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45(2):228-47. 
2. Maurer W, Hothorn L, Lehmacher W. Multiple comparisons in drug clinical trials and 
preclinical assays: a priori ordered hypotheses. In: Vollmar J, editor. Biometrics in the 
Pharmaceutical Industry (Biometrie in der chemisch-pharmazeutischen Industrie). 6. 
Stuttgart: Fischer; 1995. p. 3-21. 
3. Westfall PH, Krishen A. Optimally weighted, fixed sequence and gatekeeper multiple 
testing procedures. J Stat Plan Inference. 2001;99:25-40. 
4. Haybittle JL. Repeated assessment of results in clinical trials of cancer treatment. Br J 
Radiol. 1971;44(526):793-7. 
5. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, et al. Design and 
analysis of randomized clinical trials requiring prolonged observation of each patient. I. 
Introduction and design. Br J Cancer. 1976;34(6):585-612. 
 
 


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15 APPENDICES 
Appendix 1 
EORTC QLQ-C30 (version 3)  
We are interested in some things about you and your health. Please answer all of the questions yourself by circling the number that 
best applies to you. There are no "right" or "wrong" answers. The information that you provide will remain strictly confidential. 
 
Please fill in your initials: 
 
Your birthdate (Day, Month, Year): 
 
Today's date (Day, Month, Year):  
 
_______________________________________________________________________________________________________________ 
 
Not at  
A 
 
Quite 
Very 
  
                                                                                                                                 
 
 
All  
 
Little 
a Bit 
Much 
1. 
Do you have any trouble doing strenuous activities,  
like carrying a heavy shopping bag or a suitcase?  
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
2. 
Do you have any trouble taking a long walk?  
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
3. 
Do you have any trouble taking a short walk outside of the house? 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
4. 
Do you need to stay in bed or a chair during the day?  
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4  
 
5. 
Do you need help with eating, dressing, washing  
yourself or using the toilet? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
 
During the past week:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not at  
A 
 
Quite 
Very 
                                                                                                                                                              All  
 
Little 
a Bit 
Much 
 
6. 
Were you limited in doing either your work or other daily activities?  
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
7. 
Were you limited in pursuing your hobbies or other 
leisure time activities?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
8. 
Were you short of breath?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
9. 
Have you had pain? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
10. Did you need to rest?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
 
11. Have you had trouble sleeping?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
12. Have you felt weak?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
13. Have you lacked appetite?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
14. Have you felt nauseated?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
15. Have you vomited? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
16. Have you been constipated? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
Please go on to the next page 


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During the past week:   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not at  
A 
 
Quite 
Very 
                                                                                                                                                        
All  
 
Little 
a Bit       Much 
 
17. Have you had diarrhea? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
18. Were you tired?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
19. Did pain interfere with your daily activities?  
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
 
20. Have you had difficulty in concentrating on things, 
like reading a newspaper or watching television?  
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
21. Did you feel tense? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
22. Did you worry?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
23. Did you feel irritable?  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
24. Did you feel depressed? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
25. Have you had difficulty remembering things? 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
26. Has your physical condition or medical treatment 
interfered with your family life? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
27. Has your physical condition or medical treatment 
interfered with your social activities? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
28. Has your physical condition or medical treatment 
caused you financial difficulties? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
2 
 
3 
 
4 
 
 
For the following questions please circle the number between 1 and 7 that  
best applies to you 
 
29. How would you rate your overall health during the past week? 
 
1 
                2  
 
3 
 
 
4 
 
 
5 
 
 
6 
 
 
7 
 
 Very poor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excellent 
 
 
30. How would you rate your overall quality of life during the past week? 
 
1 
             2 
 
 
3 
 
 
4 
 
 
5 
 
 
6 
 
 
7 
 
 Very poor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excellent 
 
 


Rucaparib 
 
 
Clovis Oncology 
CO-338-043 SAP – Primary Efficacy Endpoint Version  
 28 October 2020 
 
Confidential 
34 of 35 
Appendix 2 
EORTC QLQ-OV28 
Patients sometimes report that they have the following symptoms or problems.  Please indicate the 
extent to which you have experienced these symptoms or problems during the past week. 
 
 
During the past week: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not at  
A     Quite      Very  
                                                                                                             
All  
 
Little a Bit     Much 
 
1. 
Did you have abdominal pain? 
1 
2 
3 
4 
 
2. 
Did you have a bloated feeling in your abdomen / stomach? 
1 
2 
3 
4 
 
3. 
Did you have problems with your clothes feeling too tight?  
1 
2 
3 
4 
 
4. 
Did you experience any change in bowel habit as a result of  
your disease or treatment?  
1 
2 
3 
4 
 
5. 
Were you troubled by passing wind / gas / flatulence?  
1 
2 
3 
4 
 
6. 
Have you felt full too quickly after beginning to eat?  
1 
2 
3 
4 
 
7. 
Have you had indigestion or heartburn?  
1 
2 
3 
4 
 
8. 
Have you lost any hair?  
1 
2 
3 
4 
 
9. 
Answer this question only if you had any hair loss: 
 Were you upset by the loss of your hair?  
1 
2 
3 
4 
 
10. Did food and drink taste different from usual?  
1 
2 
3 
4 
 
11. Have you had tingling hands or feet?  
1 
2 
3 
4 
 
12. Have you had numbness in your fingers or toes?  
1 
2 
3 
4 
 
13. Have you felt weak in your arms or legs?  
1 
2 
3 
4 
 
14. Did you have aches or pains in your muscles or joints?  
1 
2 
3 
4 
 
15. Did you have problems with hearing?  
1 
2 
3 
4 
 
16. Did you urinate frequently?  
1 
2 
3 
4 
 
17. Have you had skin problems (e.g. itchy, dry)?  
1 
2 
3 
4 
 
18. Did you have hot flushes?  
1 
2 
3 
4 
 
19. Did you have night sweats?  
1 
2 
3 
4 
 
Please go on to next page 


Rucaparib 
 
 
Clovis Oncology 
CO-338-043 SAP – Primary Efficacy Endpoint Version  
 28 October 2020 
 
Confidential 
35 of 35 
During the past week: 
 
 
 
  
      Not at        A          Quite     Very  
 
 
 
All 
Little 
a Bit 
Much 
 
20. Have you felt physically less attractive as a result  
 
of your disease or treatment?  
1 
2 
3 
4 
21. Have you been dissatisfied with your body?  
1 
2 
3 
4 
 
22. How much has your disease been a burden to you?  
1 
2 
3 
4 
 
23. How much has your treatment been a burden to you?  
1 
2 
3 
4 
 
24. Were you worried about your future health?  
1 
2 
3 
4 
 
 
During the past 4 weeks:  
 
 
 
 
 
 
 
 
 
 
 
 
 Not at  
A  
Quite Very  
 
 
 
All 
Little 
a Bit 
Much 
 
25. To what extent were you interested in sex? 
1 
2 
3 
4 
 
26. To what extent were you sexually active? 
1 
2 
3 
4 
 
 
Answer the following two questions only if you were sexually active: 
 
27. To what extent was sex enjoyable for you?  
1 
2 
3 
4 
 
28. Did you have a dry vagina during sexual activity?  
1 
2 
3 
4