ATHENA (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy)
Phase: PHASE3
Conditions: Epithelial Ovarian Cancer, Primary Peritoneal, Fallopian Tube Cancer, Newly Diagnosed, FIGO Stage III-IV, Partial Response, Complete Response
Sponsor: pharmaand GmbH

Clinical Study Protocol: CO-338-087 
GOG-3020 / ENGOT-ov45/NCRI/ATHENA 
Study Title: 
ATHENA (A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled Phase 3 Study in Ovarian Cancer Patients 
Evaluating Rucaparib and Nivolumab as Maintenance Treatment 
Following Response to Front-Line Platinum-Based Chemotherapy) 
Study Number: 
CO-338-087/ GOG-3020/ ENGOT-ov45/NCRI/ATHENA 
Study Phase: 
Phase 3 
Product Name: 
Rucaparib (CO-338); Nivolumab (BMS-936558) 
IND Number: 
106,289 
EUDRACT 
Number: 
[2017-004557-17] 
Indication: 
Newly diagnosed, high-grade epithelial ovarian, primary peritoneal, 
or fallopian tube cancer 
Investigators: 
Multicenter; 
Lead Investigator: 
 
Sponsor Name: 
pharmaand GmbH (pharma&) 
Sponsor 
Address: 
  
 
Phone Number: 
 
Responsible 
Medical Officer: 
 
Date 
Original Protocol: 
02 March 2018 
Amendment 1 
05 July 2018 
Amendment 2 
26 October 2020 
Amendment 3 
08 September 2021 
Amendment 4 
29 November 2021 
Amendment 5 
16 June 2023 
Confidentiality Statement 
This document contains confidential information belonging to pharma&. Except as otherwise agreed 
to in writing, by accepting or reviewing this document, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes. In the event of any actual or suspected breach of this obligation, pharma&, 
must be promptly notified. 
NCT #: NCT03522246

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PROTOCOL APPROVAL SIGNATURE PAGE 
Protocol: 
CO-338-087 
Title: 
ATHENA (A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled Phase 3 Study in Ovarian Cancer Patients 
Evaluating Rucaparib and Nivolumab as Maintenance Treatment 
Following Response to Front-Line Platinum-Based Chemotherapy) 
Date: 
16 June 2023 
Version: 
Amendment 5 
 
Reviewed and Approved by: 
 
 
 
 
 
, pharma& 
 
 
 
Signature:
Email:
Title:

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PROTOCOL ACCEPTANCE FORM 
Protocol: 
CO-338-087 
Title: 
ATHENA (A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled Phase 3 Study in Ovarian Cancer Patients 
Evaluating Rucaparib and Nivolumab as Maintenance Treatment 
Following Response to Front-Line Platinum-Based Chemotherapy) 
Date: 
16 June 2023 
Version: 
Amendment 5 
 
 
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, ICH Guidelines for GCP, and all applicable 
regulatory requirements. 
 
 
 
 
 
Investigator’s Signature 
 
Date 
(DD-MMM-YYYY) 
 
 
 
 
 
Name (printed) 
 
 
 
 
 

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COORDINATING INVESTIGATORS 
Lead Investigator and Coordinating Investigator for North America: 
 
 
 
 
 
 
 
Telephone: 
 
E-mail: 
 
 
 
Coordinating Investigator for Europe and the Middle East 
 
 
 
 
United Kingdom 
Telephone: 
 
E-mail: 
 
 
Coordinating Investigator for Asia: 
 
 
 
 
Japan 
Telephone: 
 
Facsimile:  
 
E-mail: 

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SPONSOR’S MEDICAL EXPERT FOR THE STUDY 
Medical Expert: 
  
 
pharmaand GmbH (pharma&) 
  
 
Phone Number: 
 
E-mail: 
 
 
Contact for Medical Monitor Questions: 
Japan, South Korea, Singapore, and Taiwan: CL01MM@cmicgroup.com 
All other countries: athenamedmon@synteract.com 
 
Clinical Investigators, Study Sites, and Laboratories: 
This is a multicenter study. Information on investigators, institutions, and laboratories 
involved in the study are maintained in the clinical study file and can be provided upon 
request. 
 

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SYNOPSIS 
Sponsor 
pharmaand GmbH (pharma&) 
Name of Finished Product 
Rucaparib tablets; 
Nivolumab injection 
Name of Active Ingredient 
Rucaparib camsylate (CO-338); 
Nivolumab (BMS-936558) 
Study Title 
ATHENA (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study 
in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance 
Treatment following Response to Front-Line Platinum-Based Chemotherapy) 
Study Number 
CO-338-087; 
GOG-3020; 
ENGOT-ov45/NCRI/ATHENA 
Study Phase 
Phase 3 
Rationale 
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes play a critical 
role in base excision repair (BER).1 When PARP function and effective BER is impaired, 
double-stranded deoxyribonucleic acid (DNA) breaks accumulate. In cells deficient in 
homologous recombination, these breaks cannot be accurately repaired, resulting in 
synthetic lethality.2 While mutated breast cancer genes (BRCA)1 and BRCA2 are most 
commonly associated with homologous recombination deficiency (HRD), other essential 
homologous recombination repair (HRR) proteins may be mutated or functionally deficient 
in ovarian cancer. Recently, it has also been determined that measuring genomic loss of 
heterozygosity (LOH) is a phenotypic approach that can be utilized to identify HRD 
regardless of underlying mechanism.3 
The rationale for combining rucaparib, a potent PARP inhibitor, with nivolumab, a 
programmed death receptor-1 (PD-1) blocking antibody, derives from emerging data that 
demonstrate an important association between high neoantigen load (increased mutational 
burden) and high expression of PD-1 and/or its ligand, PD-L1 in ovarian tumors with gene 
mutations in the HRR pathways compared to ovarian cancers without these mutations.4-7 
BRCA1 and BRCA2 mutations have been reported to increase the number of tumor 
infiltrating lymphocytes (TILs); BRCA mutations are associated with improved overall 
survival (OS).7-9 In addition, internal data (Clovis Oncology, Inc.) indicated a significant 
association between levels of genomic LOH and tumor mutational burden (TMB). A high 
TMB increases the likelihood of the development of tumor-specific neoepitopes that could 
confer clinical benefit from PD-1 blockade. Thus, it is hypothesized that increased DNA 

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damage by PARP inhibition will increase the number of tumor neoantigens, creating a more 
antigenic environment in which to stimulate the immune microenvironment.  
This study will investigate the safety and efficacy of the combination of the PARP inhibitor, 
rucaparib, and the PD-1 monoclonal antibody, nivolumab, with the hypothesis that this drug 
combination may preferentially benefit an HRD-positive ovarian cancer patient population, 
which in turn may extend progression-free survival (PFS) following standard treatment 
(surgery and platinum-based chemotherapy) for ovarian cancer in the frontline setting. 
Primary Objective: 
 To evaluate PFS by Response Evaluation Criteria in Solid Tumors (RECIST), as 
assessed by the investigator (invPFS) using the following separate comparisons: 
- 
Monotherapy: Arm B (oral rucaparib + intravenous [IV] placebo) vs Arm D 
(placebo [oral and IV]) in the HRD and intent-to-treat (ITT) sub/populations 
- 
Combination: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib 
+ IV placebo) in the ITT Population 
Secondary Objectives: 
 To evaluate PFS by RECIST, as assessed by blinded independent central review 
(BICR; bicrPFS) 
 To evaluate survival benefit 
 To evaluate the objective response rate (ORR) and duration of response (DOR), as 
assessed by the investigator, in patients with measurable disease at baseline  
 To evaluate safety  
Exploratory Objectives: 
 To evaluate PFS2 (PFS on the subsequent line of treatment) 
 To evaluate the contribution of nivolumab monotherapy vs placebo (invPFS, 
bicrPFS, OS, ORR, DOR, safety) 
 To evaluate the comparison of combination rucaparib + nivolumab vs placebo 
(invPFS, bicrPFS, OS, ORR, DOR, safety) 
 To evaluate efficacy and safety in the tBRCA subgroup for the comparison of 
rucaparib vs placebo (invPFS, bicrPFS, OS, ORR, DOR, safety) 
 To evaluate efficacy and safety in HRD, tBRCA, and PD-L1 subgroups for the 
comparison of combination vs rucaparib (invPFS, bicrPFS, OS, ORR, DOR, safety) 
 To evaluate Health-related Quality of Life (HRQoL) as assessed by the trial 
outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian 
(FACT-O) 
 To evaluate patient-reported outcome (PRO) utilizing the Euro-Quality of Life 
5D-5L (EQ-5D-5L) 
 To assess mutations in non-tumor BRCA (where tBRCA defines a tumor tissue 
alteration in BRCA1 or BRCA2) HRR genes as a molecular marker of efficacy 
 To assess PD-L1 expression and TMB as molecular markers of efficacy 
 To study variants in circulating tumor DNA (ctDNA) as markers of response and 
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 To characterize pharmacokinetics (PK) of rucaparib as monotherapy and in 
combination with nivolumab 
 To characterize PK of nivolumab as a monotherapy and in combination with 
rucaparib 
 To evaluate immunogenicity of nivolumab when administered as a monotherapy and 
in combination with rucaparib  
 To explore exposure-response relationship between selected exposure measures of 
rucaparib and nivolumab, and safety and efficacy endpoints 
Study Design 
This is a randomized, multinational, double-blind, dual placebo-controlled, 4-arm, Phase 3 
study evaluating rucaparib and nivolumab as monotherapy and in combination as 
maintenance treatment following response to front-line treatment (surgery and 
platinum-based chemotherapy) in newly diagnosed ovarian cancer patients.  
The study will enroll patients with high-grade epithelial ovarian, primary peritoneal, or 
fallopian tube cancer who achieved a response to their first platinum-based regimen. 
This study consists of a Screening Phase, a Treatment Phase, and a Post-treatment Phase. 
Screening Phase 
All patients will undergo screening assessments within 120 days prior to randomization. 
Submission of tumor tissue from the cytoreductive surgery (peritoneal cytology alone is not 
sufficient) will be required prior to enrollment to determine the mutation status of 
homologous recombination pathway genes, including BRCA1/2. In addition, biomarkers 
related to response or resistance to immunotherapies will be assessed. Tumor DNA will also 
be assessed to determine the percentage of the genome with LOH.3,10-12 Analysis of tumor 
LOH will allow patients without a BRCA mutation to be classified as non-tBRCA LOHhigh 
or non-tBRCA LOHlow. For the Double-blind Treatment Phase, patients will be stratified 
into 1 of 4 HRD subgroups (tBRCA, non-tBRCA LOHhigh, or non-tBRCA LOHlow, or 
non-tBRCA LOHunknown) for randomization based on the results obtained. 
Patients must meet all inclusion and exclusion criteria as specified in the protocol. 
Enrollment/randomization to study treatment must occur within 8 weeks of the first day of 
the last cycle of chemotherapy, and study treatment must be initiated within 3 days of 
enrollment/randomization. 
Treatment Phase 
The treatment phase will consist of 28-day treatment cycles. In Cycle 1, patients will 
receive treatment with oral study drug only, beginning on Day 1. Oral study drug will be 
taken twice a day (BID) continuously thereafter. Dosing with IV study drug will begin on 
Cycle 2 Day 1 (C2D1); IV study drug will be administered every 4 weeks. Patients will 
come into the study site for a visit on Day 1 and Day 15 of Cycles 1 and 2, and on Day 1 of 
every cycle thereafter. A blood sample will be collected from all patients at Cycle 1 Day 1 
and stored for subsequent genomic DNA testing and determination of germline status.  
Study drug treatment will continue in 28-day cycles until 24 months after initiating oral/IV 
combination study treatment, disease progression, or unacceptable toxicity, whichever 
occurs first. Patients will undergo procedures and assessments, including regular safety, PK, 
and efficacy evaluations, during the entire conduct of the study. 

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Patients will be assessed for disease status per RECIST v1.1 every 12 calendar weeks 
(flexibility with scheduling within 1 week prior to planned imaging date is permitted) 
relative to C2D1 (the first scan will be 16 weeks after initiation of oral study treatment) for 
the first 3 years and then every 24 weeks thereafter until objective radiological disease 
progression, as assessed by the investigator. Patients experiencing disease progression by 
RECIST v1.1 will be discontinued from treatment and enter follow-up. If the patient has 
met criteria for radiologic progression by RECIST, but the patient is still receiving benefit 
from the study drug(s) (eg, patient has mixed radiologic response or is continuing to have 
symptomatic benefit), according to the investigator, then continuation of treatment will be 
considered for a maximum cumulative duration of 24 months after initiation of oral/IV 
combination study treatment. In such cases, the decision to continue receiving treatment 
with study drug(s) must be documented in source documents, and the patient must provide 
additional consent prior to continuing treatment with study drug(s). Patients will continue to 
have all protocol-required assessments specified in the Schedule of Assessments. 
Safety and efficacy data will be periodically reviewed by an Independent Data Monitoring 
Committee (IDMC). 
Prior to randomization of patients in the Double-blind Treatment Phase of the study, a 
minimum of 6 patients may be enrolled into an open-label safety cohort and analyzed for 
safety after completion of at least 1 cycle of combination therapy. The eligibility criteria 
and study assessments will be the same for the safety cohort as those described above for 
the Double-blind Treatment Phase.  
Evaluation of a Japanese safety cohort will proceed in the same manner as the initial safety 
cohort, once the rucaparib monotherapy dose is established in an ongoing Phase 1 study in 
Japan. 
Post-Treatment Follow-up Phase 
All patients will be followed for at least 5 months after the last dose of IV study drug 
treatment. There will be 2 safety follow-up visits: Safety Follow-up Visit 1 (SFU1) should 
occur 28 days (± 7 days) after last dose of the oral and/or IV study drug (whichever occurs 
later), and Safety Follow-up Visit 2 (SFU2) should occur approximately 5 months 
(± 7 days) after the last dose of IV study drug treatment. If a patient remains on oral study 
drug after discontinuation of IV study drug, the 5-month Safety Follow-up Visit (SFU2) can 
be performed at a cycle visit, provided it has been at least 5 months since the last IV study 
drug dose.  
Patients who discontinued treatment for reason other than disease progression or death 
should continue to have tumor scans performed at 12-week intervals relative to C2D1 for 
the first 3 years and then every 24 weeks thereafter until objective radiological disease 
progression by RECIST v1.1, as assessed by the investigator, is documented. An optional 
tumor biopsy will be collected from patients who experience disease 
progression/randomized treatment discontinuation and provide appropriate consent. 
Patients will also be followed long-term for survival, subsequent treatments, and monitoring 
for secondary malignancy every 12 weeks (± 14 days) after SFU1 until death, loss to 
follow-up, withdrawal of consent, or study closure. 

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Number of Patients 
Approximately 1000 patients will be randomized in the Double-blind Treatment Phase.  
Overall, the double-blind randomization assumes a 4:4:1:1 allocation to treatment with 
Arm A: oral rucaparib + IV nivolumab (n = 400), Arm B: oral rucaparib + IV placebo 
(n = 400), Arm C: oral placebo + IV nivolumab (n = 100) and Arm D: oral placebo + IV 
placebo (n = 100). 
At least 6 patients may be enrolled to an open-label safety cohort prior to randomization of 
patients in the Double-blind Treatment Phase. 
A maximum of 500 patients with a deleterious mutation in BRCA1 or BRCA2 (tBRCA) 
will be randomized.  
Patients who withdraw consent from the study or terminate participation prematurely will 
not be replaced. 
Number of Sites 
This is a multicenter, multinational study. Patients will be enrolled from approximately 
290 study sites.  
Inclusion Criteria 
Eligible patients must meet the following inclusion criteria: 
1. Have signed an Institutional Review Board (IRB)/ Independent Ethics Committee 
(IEC)-approved informed consent form (ICF) prior to any study-specific evaluation. 
2. Be ≥ 18 years of age at the time the ICF is signed (patients enrolled in South Korea, 
Taiwan, and Japan must be ≥ 20 years of age at the time the ICF is signed). 
a.  Patients enrolled in the open-label safety cohort in Japan must be of Japanese 
ethnicity (ie, both parents are native Japanese and were born in Japan) 
3. Have newly diagnosed, histologically confirmed, advanced (International Federation of 
Gynecology and Obstetrics [FIGO] stage III-IV), high-grade epithelial ovarian, 
fallopian tube, or primary peritoneal cancer. 
4. Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy 
and partial omentectomy, either prior to chemotherapy (primary surgery) or following 
neoadjuvant chemotherapy (interval debulking). 
5. Have received 4 to 8 cycles of first-line platinum-doublet treatment per standard clinical 
practice, including a minimum of 4 cycles of a platinum/ taxane combination. 
a. A patient with best response of partial response (PR) must have received at least 
6 cycles.  
b. Bevacizumab is allowed during the chemotherapy phase, but not during 
maintenance ie, during therapy directed by this protocol. 
6. Have completed first-line platinum-based chemotherapy and surgery with a response, in 
the opinion of the investigator, defined as no evidence of disease progression 
radiologically or through rising CA-125 (per Gynecologic Cancer Intergroup [GCIG] 
guidelines) at any time during front-line treatment; and: 
a. No evidence of measurable disease by RECIST v1.1 (if complete resection/R0 at 

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primary or interval cytoreductive surgery); or 
b. A partial or complete response per RECIST v1.1 (if measurable disease was present 
after surgery and prior to chemotherapy); or 
c. A GCIG CA-125 response (if only non-measurable disease was present after surgery 
and prior to chemotherapy). 
7. Pre-treatment CA-125 measurements must meet criterion specified below: 
If the first value is within upper limit of normal (ULN), the patient is eligible to be 
randomized and a second sample is not required; 
If the first value is greater than ULN, a second assessment must be performed at 
least 7 days after the first. If the second assessment is ≥ 15% than the first value, the 
patient is not eligible. 
8. Patient must be randomized within 8 weeks of the first day of the last cycle of 
chemotherapy. 
9. Have sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue (1 × 4 µm 
section for hematoxylin and eosin [H&E] stain and approximately 8 to 12 × 10 µm 
sections, or equivalent) available for planned analyses. 
a. Submission of a tumor block is preferred; if sections are provided, these must all be 
from the same tumor sample. 
b. Tumor tissue from the cytoreductive surgery is required. 
c. Sample must be received at the central laboratory at least 3 weeks prior to planned 
start of treatment to enable stratification for randomization. 
10. 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) ≥ 1.5 × 109/L 
ii. 
Platelets ≥ 100 × 109/L  
iii. 
Hemoglobin ≥ 9 g/dL  
b. Hepatic Function 
i. 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 1.5 × 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 × ULN unless estimated glomerular filtration rate (GFR) 
≥ 30 mL/min using the Cockcroft Gault formula 
11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 

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Exclusion Criteria 
Patients will be excluded from participation if any of the following criteria apply: 
1. Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential 
(ie, borderline tumors) or mucinous tumors. Mixed mullerian tumors/carcinosarcomas 
are allowed. 
2. 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 active cancer for 3 years prior to enrollment, or patients with 
surgically-cured low-risk tumors, such as early-stage cervical or endometrial cancer 
are allowed to enroll. 
3. Known central nervous system brain metastases. 
4. Any prior treatment for ovarian cancer, other than the first-line platinum regimen, 
including any maintenance treatment between completion of the platinum regimen and 
initiation of study drug in this study. 
a. Ongoing hormonal treatment for previously treated breast cancer is permitted. 
Hormonal maintenance treatment for ovarian cancer is not allowed. 
5. Has evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of 
myocarditis. 
6. Patients with an active, known or suspected autoimmune disease (eg, autoimmune 
hepatitis). Patients with type I diabetes mellitus, hypothyroidism only requiring 
hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not 
requiring systemic treatment, or conditions not expected to recur in the absence of an 
external trigger are permitted to enroll. 
7. Patients with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 
14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent, are permitted in the absence of active 
autoimmune disease. 
8. Drainage of ascites during the final 2 cycles of treatment with the platinum regimen. 
9. Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in 
the opinion of the investigator, interfere with absorption of study treatment. 
10. Known history of positive test for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be 
performed at all sites where mandated locally. 
11. Any positive test result for hepatitis B and/or known history of hepatitis B infection 
including patients with undetectable hepatitis B virus (HBV) DNA and inactive carriers; 
positive test result for hepatitis C antibody (anti-HCV; except if HCV-RNA negative). 
12. Pregnant, or breast feeding. All study participants must agree to avoid pregnancy 
achieved through assisted reproductive technology for the duration of study treatment 

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and for a minimum of 6 months following the last dose of study drug (oral or IV, 
whichever is later).  
13. Received chemotherapy within 14 days prior to first dose of study drug and/or ongoing 
adverse effects from such treatment > National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 1, with the exception of 
Grade 2 non-hematologic toxicity such as alopecia, peripheral neuropathy, Grade 2 
anemia with hemoglobin ≥ 9 g/dL, and related effects of prior chemotherapy that are 
unlikely to be exacerbated by treatment with study drug. 
14. Non-study related minor surgical procedure (eg, placement of a central venous access 
port) ≤ 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. 
15. 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. 
16. Hospitalization for bowel obstruction within 12 weeks prior to enrollment. 
No waivers of these inclusion or exclusion criteria will be granted by the investigator and 
the sponsor or its designee for any patient randomized into the study. 
Enrollment/ Randomization and Study Treatment 
For the Double-blind Treatment Phase, eligible patients will be randomized 4:4:1:1 to the 
following arms: Arm A: rucaparib + nivolumab (n = 400), Arm B: rucaparib + IV placebo 
(n = 400), Arm C: oral placebo + nivolumab (n = 100) or Arm D: placebo (oral and IV) 
(n = 100). 
Randomization will occur by a central randomization procedure using interactive response 
technology (IRT). The following will be included as randomization stratification factors at 
study entry to ensure treatment groups are balanced:  
• 
HRD classification (tBRCA, non-tBRCA LOHhigh, non-tBRCA LOHlow, or 
non-tBRCA LOHunknown) by central laboratory analysis 
• 
Disease status post-chemotherapy (residual disease vs. no residual disease) 
• 
Timing of surgery (primary surgery vs. interval debulking) 
Rucaparib 600 mg, or matching placebo, is administered orally BID (as close to 12 hours 
apart as possible, preferably at the same times every day) with at least 8 ounces (240 mL) of 
water starting on Day 1. Oral study drug may be taken with or without food. Rucaparib, or 
matching placebo, will be provided as 200, 250, and 300 mg (as free base) dose strength 
tablets.  
Nivolumab, or matching placebo, is administered as 480 mg via a 30-minute IV infusion on 
Day 1 of every 4-week cycle, starting with Cycle 2. 
Patients will receive both study drugs for a maximum of 24 months after initiation of 
oral/IV combination study treatment, or until disease progression by RECIST as assessed 
by the investigator, unacceptable toxicity, or other reason for discontinuation, whichever 
occurs first. Treatment interruption or dose reduction of oral study drug are permitted in the 

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event of unacceptable toxicity. Doses of IV study drug may be interrupted or delayed, but 
may not be reduced. 
Prior to randomizing patients in the Double-blind Treatment Phase of the study, an 
open-label safety cohort will enroll and evaluate a minimum of 6 patients; patients who 
provide informed consent and meet all eligibility criteria will participate using the same 
study assessments as patients enrolled to the Double-blind Treatment Phase. Safety will be 
evaluated for this cohort after each patient has been dosed with the combination therapy for 
a minimum of 1 cycle. 
Enrollment to a Japanese safety cohort will be conducted in the same manner as the initial 
safety cohort, for patients of Japanese ethnicity that meet all eligibility criteria, prior to 
randomizing any patients in Japan. Enrollment to this cohort will be contingent upon the 
determination of the monotherapy rucaparib dose in Japan. 
Withdrawal Criteria 
A patient must be discontinued from treatment with study drug if any of the following 
apply: 
• 
Consent withdrawal at the patient’s own request or at the request of their legally 
authorized representative. 
• 
Progression of patient’s underlying disease by RECIST v1.1 as assessed by the 
investigator unless patient is still receiving benefit from the study drug(s) 
according to the investigator, and the patient has provided additional consent.  
• 
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. 
Efficacy Assessments 
Tumor assessment measurements will be performed at screening, at the end of every 
12 weeks of treatment (up to 7 days prior permitted) relative to C2D1 for the first 3 years 
and then every 24 weeks thereafter until objective radiological disease progression, and as 
clinically indicated. 
Disease assessment will comprise clinical examination and appropriate imaging techniques 
per RECIST v1.1 (computed tomography [CT] and/or magnetic resonance imaging [MRI] 
scans of the chest, abdomen, and pelvis with appropriate slice thickness per RECIST). 
Other complementary studies (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 the same lesions throughout the clinical study. CT/MRI scans of the chest, 
abdomen, and pelvis performed to determine the extent of disease at baseline should also be 
performed at each time of disease assessment, even if the scans were negative at baseline. 
Investigators should perform scans of other anatomical sites that, in their judgment, are 
appropriate to assess based on each patient’s tumor status. Imaging guidelines provided by 
the BICR vendor should be followed for the collection of images and the radiological 
assessment of disease. 

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Tumor response will be interpreted using RECIST v1.1. Disease progression will only be 
determined by RECIST v1.1. Patients with a CR at study entry will only be considered to 
have disease progression if a new lesion is identified based on guidelines outlined in 
RECIST v1.1. Patients who meet GCIG CA-125 criteria for disease progression should 
have a radiologic assessment and be assessed by RECIST. If the radiologic assessment does 
not confirm disease progression, patients should continue on treatment and continue to be 
assessed by RECIST v1.1 per the protocol schedule of assessments. 
Patients who discontinued treatment for reason other than disease progression or death 
should continue to have tumor scans performed at 12-week intervals (up to 7 days prior 
permitted) relative to C2D1 for the first 3 years and every 24 weeks thereafter until 
objective radiologic disease progression by RECIST v1.1, as assessed by the investigator, is 
documented, or initiating subsequent anticancer treatment. 
Blood samples to assess CA-125 will be collected throughout the study and assessed by a 
central laboratory.  
Safety Assessments 
Safety and tolerability will be assessed based on the following: 
• 
Incidence, type, seriousness, and severity of adverse events (AEs) reported; 
• 
Clinical laboratory investigations (hematology, serum chemistry, urinalysis); 
• 
Vital signs (blood pressure, heart rate, and body temperature); 
• 
12-lead electrocardiograms (ECGs); 
• 
Physical examinations;  
• 
ECOG performance status. 
Statistical Methods 
Sample Size  
Approximately 1000 patients will be randomized in a 4:4:1:1 ratio to receive treatment with 
one of the following 4 arms: 
Arm A: Oral rucaparib + IV nivolumab (n = 400),  
Arm B: Oral rucaparib + IV placebo (n = 400),  
Arm C: Oral placebo + IV nivolumab (n = 100), or  
Arm D: Oral placebo + IV placebo (n = 100). 
The randomization is stratified by the following factors; HRD classification (tBRCA, 
non-tBRCA LOHhigh, non-tBRCA LOHlow, and non-tBRCA LOHunknown), disease status (no 
residual disease vs. residual disease), and timing of surgery (primary surgery vs. interval 
debulking).  
Two separate comparisons of the treatment arms will be evaluated independently, and at 
different timepoints based on the maturity of the parts of the study: 
• Monotherapy: Arm B (oral rucaparib + IV placebo) vs Arm D (placebo [oral and IV]) 
• Combination: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib + IV 
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The level of statistical significance will be split into 2 so that each of the above comparisons 
will be made independently at a one-sided 0.0125 (two-sided 0.025) significance level.  
The sample size is based on setting the power for each of the 2 independent treatment 
comparisons at 90% power. The power assumptions are based on the median PFS for 
patients in Arm A (oral rucaparib + IV nivolumab) from the total patient population (ie, the 
ITT population inclusive of both tBRCA and non-tBRCA subgroups) is expected to be 
approximately 28 months while the median PFS for patients in Arm B (rucaparib 
monotherapy [oral rucaparib + IV placebo]) is expected to be about 20 months.  
The following table provides the sample size and power for the combination treatment 
comparison of Arm A (oral rucaparib + IV nivolumab) to Arm B (rucaparib monotherapy) 
for the ITT Population.  
Group 
Hazard 
Ratio 
Cumulative 
N (4:4) 
Number of 
Events 
Median PFS 
(months) 
Power 
One-sided 
Alpha 
ITT 
0.725 
800 (400:400) 
600 
20 vs 28 
90% 
0.0125 
Abbreviations: ITT = intent-to-treat; PFS = progression free survival. 
 
The following table provides the sample size and power for the monotherapy treatment 
comparison of Arm B (rucaparib monotherapy) to Arm D (placebo) for the HRD and ITT 
sub/populations. 
Group 
Hazard 
Ratio 
Cumulative 
N (4:1) 
Number of 
Events 
Median PFS 
(months) 
Power 
One-sided 
Alpha 
HRD 
0.45 
205 (164:41) 
123 
12 vs 26.7 
90% 
0.0125 
ITT 
0.60 
500 (400:100) 
300 
12 vs 20 
90% 
0.0125 
Abbreviations: HRD = homologous recombination deficiency (tBRCA + non-tBRCA LOHhigh); 
ITT = intent-to treat; PFS = progression free survival; tBRCA = tumor tissue alteration in BRCA1 or 
BRCA2, includes gBRCA and sBRCA. 
The results of the comparisons of Arm C (nivolumab monotherapy [oral placebo + 
IV nivolumab]) to Arm D (placebo [oral and IV]) will be considered exploratory since these 
comparisons are not included in the multiple testing procedure described above. 
A minimum of 6 patients will be treated in a small, open-label safety cohort with rucaparib 
and nivolumab. Additionally, a minimum of 6 patients of Japanese ethnicity will be 
enrolled into an open-label safety cohort at investigational sites in Japan, contingent upon 
the recommended rucaparib dose in Japan. These 2 safety cohorts will be evaluated 
individually after each patient receives a minimum of one cycle of combination therapy. 
Efficacy Analysis  
Primary Efficacy Endpoint 
The primary efficacy endpoint for the study is investigator-determined PFS (invPFS) by 
RECIST v1.1. Investigator-determined PFS is defined as the time from randomization to 
disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or 

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death due to any cause, whichever occurs first. 
Only tumor scans prior to the start of any subsequent anticancer treatment are considered 
for the primary endpoint. The primary endpoint is analyzed using both a stratified log-rank 
test and a Cox proportional hazard model comparing the treatment groups stratified by the 
randomization stratification factors (ie, HRD classification [tBRCA, non-tBRCA LOHhigh, 
non-tBRCA LOHlow, and non-tBRCA LOHunknown], disease status [no residual disease vs. 
residual disease], and timing of surgery [primary surgery vs interval debulking]).  
The stratified log-rank test will be used to calculate the hazard ratio (HR) between the 
treatment groups and will be used as the official test for the step-down procedure outlined 
below. 
Step-down Procedure to Adjust for Multiplicity 
The primary endpoint of invPFS and key secondary endpoints of OS and ORR will be 
tested among the HRD and ITT sub/populations for the monotherapy comparison and 
among the ITT Population for the combination comparison, using separate ordered 
step-down multiple comparison procedures. 
That is, for the monotherapy treatment comparison, the invPFS in the HRD subpopulation 
will be tested first at a one-sided 0.0125 significance level. If invPFS in the HRD subgroup 
is statistically significant, then invPFS will be tested in the ITT Population. If both the HRD 
and ITT sub/populations reach statistical significance for the primary endpoint, then the 
first secondary endpoint of OS will be tested at the one-sided 0.0125 significance level in 
the HRD and ITT sub/populations for that treatment comparison. If both the HRD and ITT 
sub/populations reach statistical significance, then testing will continue in an ordered 
step-down fashion to the last key secondary endpoint of ORR. Once statistical significance 
is not achieved for one test, the statistical significance will not be declared for all 
subsequent analyses in the ordered step-down procedure for the monotherapy treatment 
comparison. 
Enrollment of tBRCA is much lower than originally anticipated in the sample size 
assumptions in the original protocol. Thus, the monotherapy treatment comparison will start 
with the HRD analysis population, then ITT Population for the step-down hierarchical 
testing. The tBRCA subgroup will be an exploratory endpoint for monotherapy treatment, 
in order to estimate the contribution within the HRD and ITT sub/populations. 
For the combination treatment comparison, invPFS in the ITT Population will be tested first 
at a one-sided 0.0125 significance level. If invPFS is statistically significant, then the first 
secondary endpoint of OS will be tested at the one-sided 0.0125 significance level in the 
ITT Population and testing will continue in an ordered step-down fashion to the last key 
secondary endpoint of ORR. Once statistical significance is not achieved, the statistical 
significance will not be declared for subsequent analyses in the ordered step-down 
procedure for the combination comparison in the ITT Population. An exploratory endpoint 
evaluating efficacy within subgroups based on HRD, tBRCA, and PD-L1 for the 
combination treatment comparison will be evaluated. 
Secondary Efficacy Endpoints 
PFS as assessed by BICR review (bicrPFS) by RECIST will be tested as a stand-alone 
secondary endpoint, outside of the step-down procedure for multiplicity adjustment, due to 

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it being supportive of the primary endpoint. BicrPFS 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 anticancer treatment are included.  
OS is defined as the time from randomization to death due to any cause. 
Analyses of ORR will be performed in the subgroup of patients with measurable disease at 
baseline and will be summarized with frequencies and percentages. DOR will be tested as a 
stand-alone secondary endpoint, outside of the step-down procedure for multiplicity 
adjustment. DOR is defined as the interval from the first documentation of objective 
response (RECIST v1.1) to the earlier of the first documentation of disease progression (per 
RECIST v1.1) or death from any cause.  
Safety Analyses 
All safety analyses will be presented by randomized treatment group for all patients in the 
safety population (ie, all treated patients). Any patients enrolled in the open-label safety 
cohorts will be included in this safety analysis population. 
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/treatment interruptions/dose reductions, AEs 
leading to death, and NCI CTCAE v5.0 Grade 3 or higher AEs. Body weight and vital signs 
will be summarized descriptively (N, mean, standard deviation, median, minimum, and 
maximum).  
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 oncologists with experience in treating 
women with ovarian cancer and a statistician, all of whom are not otherwise involved in the 
study as investigators. 
The IDMC will: 
• 
Review safety and efficacy of rucaparib and nivolumab compared with placebo, as 
well as the rucaparib + nivolumab combination compared to monotherapy to ensure 
the study is beneficial to patients. 
• Ensure the study is conducted in a high-quality manner. 
• Monitor the size of the tBRCA subgroup. 
Results from the open-label safety cohort(s) will be shared with the IDMC. 
Following data review, the IDMC will recommend continuation, revision, or termination of 
the study and/or continuing or halting enrollment into a particular subgroup. 
No formal efficacy interim analyses for early stopping are planned.  
Steering Committee 
A Study Steering Committee, consisting of selected participating investigators representing 
Gynecologic Oncology Group (GOG) and the European Network for Gynecological 
Oncological Trial groups (ENGOT), will meet regularly to advise the sponsor regarding 

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study-related issues, including safety concerns. The Study Steering Committee will 
participate in a safety review of data from patients enrolled in the safety lead-in cohort(s). 
Date of Protocol Amendment 5 Approval 
16 June 2023  

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TABLE OF CONTENTS 
PROTOCOL APPROVAL SIGNATURE PAGE .....................................................................2 
PROTOCOL ACCEPTANCE FORM .......................................................................................3 
COORDINATING INVESTIGATORS ....................................................................................4 
SPONSOR’S MEDICAL EXPERT FOR THE STUDY ...........................................................5 
SYNOPSIS .................................................................................................................................6 
LIST OF IN-TEXT TABLES ..................................................................................................25 
LIST OF IN-TEXT FIGURES.................................................................................................25 
LIST OF APPENDICES ..........................................................................................................25 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..........................................27 
1 
INTRODUCTION ...........................................................................................................32 
1.1 
Background ............................................................................................................32 
1.1.1 
Rucaparib .....................................................................................................34 
1.1.1.1 
Nonclinical Experience ......................................................................36 
1.1.1.2 
Clinical Experience ............................................................................36 
1.1.2 
Nivolumab....................................................................................................40 
1.1.2.1 
Mechanism of Action .........................................................................41 
1.1.2.2 
Nonclinical Experience ......................................................................42 
1.1.2.3 
Clinical Experience ............................................................................42 
1.1.3 
PARP Inhibitors and Checkpoint Inhibitors ................................................44 
1.1.3.1 
Non-clinical Overview .......................................................................44 
1.1.3.2 
Clinical Overview ..............................................................................45 
1.2 
Rationale for the Study and Benefit-Risk Assessment ..........................................45 
1.3 
Dose Rationale .......................................................................................................47 
1.3.1 
Dose Rationale for Nivolumab ....................................................................47 
1.3.1.1 
Rationale for Nivolumab 30-minute Infusion ....................................49 
1.3.2 
Dose Rationale for Nivolumab and Rucaparib Combination ......................49 
1.4 
Rationale for Duration of Treatment......................................................................50 
1.4.1 
Nivolumab....................................................................................................50 
1.4.2 
Rucaparib .....................................................................................................51 
2 
STUDY OBJECTIVES ....................................................................................................52 
2.1 
Primary Objective ..................................................................................................52 
2.2 
Secondary Objectives.............................................................................................52 
2.3 
Exploratory Objectives ..........................................................................................52 
3 
STUDY DESIGN.............................................................................................................53 
3.1 
Overall Study Design and Plan ..............................................................................53 
3.1.1 
Screening Phase ...........................................................................................53 
3.1.2 
Enrollment/ Randomization .........................................................................55 
3.1.3 
Double-blind Treatment Phase ....................................................................55 

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3.1.4 
End of Treatment .........................................................................................56 
3.1.5 
Open-label Safety Lead-in ...........................................................................56 
3.1.6 
Post-treatment Follow-up Phase ..................................................................57 
3.2 
Removal of Patients from Therapy or Assessment ................................................58 
3.3 
Study Schema.........................................................................................................58 
3.4 
End of Study ..........................................................................................................60 
3.5 
Discussion of Study Design ...................................................................................60 
4 
STUDY POPULATION SELECTION ...........................................................................62 
4.1 
Number of Patients and Sites .................................................................................62 
4.2 
Inclusion Criteria ...................................................................................................62 
4.3 
Exclusion Criteria ..................................................................................................63 
4.4 
Patients or Partners of Patients of Reproductive Potential ....................................65 
4.5 
Waivers of Inclusion/Exclusion Criteria ................................................................65 
5 
STUDY TREATMENT(S) ..............................................................................................66 
5.1 
Description of Treatment(s) and Storage ...............................................................66 
5.1.1 
Investigational Drug Product – Rucaparib or Placebo .................................66 
5.1.2 
Investigational Drug Product – Nivolumab or Placebo ...............................66 
5.2 
Packaging and Labeling .........................................................................................67 
5.2.1 
Rucaparib or Placebo Tablets ......................................................................67 
5.2.2 
Nivolumab or IV Placebo ............................................................................67 
5.3 
Blinding/Masking of Treatments ...........................................................................67 
5.4 
Method of Assigning Patients to Treatment Groups..............................................68 
5.5 
Preparation and Administration of Protocol-specified Treatment .........................69 
5.5.1 
Rucaparib/Oral Placebo ...............................................................................69 
5.5.2 
Nivolumab/IV Placebo.................................................................................69 
5.6 
Dose Modification Criteria ....................................................................................69 
5.6.1 
Treatment Delay and/or Interruption ...........................................................72 
5.6.1.1 
Rucaparib/Oral Placebo .....................................................................72 
5.6.1.2 
Nivolumab/IV Placebo.......................................................................73 
5.6.2 
Retreatment Criteria .....................................................................................75 
5.6.2.1 
Rucaparib/Oral Placebo .....................................................................75 
5.6.2.2 
Nivolumab/IV Placebo.......................................................................75 
5.6.3 
Dose Reduction ............................................................................................76 
5.6.3.1 
Rucaparib/Oral Placebo .....................................................................76 
5.6.4 
Study Drug Discontinuation ........................................................................76 
5.6.4.1 
Rucaparib/Oral Placebo .....................................................................77 
5.6.4.2 
Nivolumab/IV Placebo.......................................................................77 
5.7 
Management Algorithms for Oral Study Drug ......................................................79 
5.7.1 
Management of Anemia ...............................................................................79 

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5.7.2 
Management of New or Worsening Pulmonary Symptoms Suggestive 
of Pneumonitis .............................................................................................79 
5.8 
Management Algorithms for Immuno-Oncology Agents ......................................79 
5.9 
Treatment of Infusion-related Reactions ...............................................................80 
5.10 
Interruption of Study Drug for On-study Procedures ............................................81 
5.11 
Treatment Compliance ...........................................................................................82 
5.11.1 
Rucaparib/Oral Placebo Treatment Compliance .........................................82 
5.11.2 
Nivolumab/IV Placebo Treatment Compliance ...........................................82 
5.12 
Accountability of Protocol-specified Treatment ....................................................82 
5.13 
Treatment of Study Drug Beyond Disease Progression ........................................83 
6 
PRIOR AND CONCOMITANT THERAPY ..................................................................84 
6.1 
Supportive Care .....................................................................................................84 
6.2 
Radiotherapy ..........................................................................................................84 
6.3 
Anticancer or Experimental Therapy .....................................................................84 
6.4 
CYP450 Isoenzyme Inhibitors, Inducers, and Substrates ......................................84 
6.4.1 
Transporter Inhibitors, Inducers, and Substrates .........................................85 
6.5 
Anticoagulants .......................................................................................................85 
6.6 
Immunosuppressive Agents ...................................................................................85 
6.7 
Other Concomitant Medications ............................................................................85 
6.8 
Imaging Restrictions and Precautions ....................................................................86 
6.9 
General Restrictions ...............................................................................................86 
7 
STUDY PROCEDURES AND METHODS ...................................................................87 
7.1 
Schedule of Assessments .......................................................................................87 
7.2 
Informed Consent...................................................................................................94 
7.3 
Screening Phase .....................................................................................................94 
7.3.1 
Within 120 Days Prior to Randomization ....................................................94 
7.3.2 
Up to 28 days Prior to Randomization .........................................................95 
7.3.3 
Up to 14 days Prior to Randomization .........................................................96 
7.3.4 
Up to 3 days Prior to First Dose of Study Drug ...........................................96 
7.4 
Treatment Phase .....................................................................................................97 
7.4.1 
Day 1 of Cycle 1 ..........................................................................................97 
7.4.2 
Days 15 of Cycle 1 and 2 .............................................................................97 
7.4.3 
Cycle 2 Day 1...............................................................................................98 
7.4.4 
Day 1 of Cycles 3 and Beyond ....................................................................99 
7.4.5 
Post-treatment Follow-up Phase ................................................................100 
7.4.5.1 
End of Treatment .............................................................................100 
7.4.5.2 
28-day Safety Follow-up (Safety Follow-up Visit 1 [SFU1]) .........100 
7.4.5.3 
5-month Safety Follow-up (Safety Follow-up Visit 2 [SFU2]) .......101 
7.4.6 
Long-term Follow-up (LTFU) ...................................................................102 

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7.5 
Methods of Data Collection .................................................................................103 
7.5.1 
Medical History and Demographic/ Baseline Characteristics ...................103 
7.5.2 
Prior and Concomitant Medication Assessments ......................................103 
7.5.3 
Efficacy Evaluations ..................................................................................103 
7.5.3.1 
Disease/ Tumor Assessments ...........................................................103 
7.5.3.2 
Tumor Markers ................................................................................104 
7.5.4 
Safety Evaluations .....................................................................................104 
7.5.4.1 
Adverse Event Assessment ..............................................................104 
7.5.4.2 
Clinical Laboratory Investigations ...................................................105 
7.5.4.3 
Vital Signs ........................................................................................106 
7.5.4.4 
12-Lead Electrocardiogram .............................................................106 
7.5.4.5 
Body Weight and Height .................................................................106 
7.5.4.6 
Physical Examinations .....................................................................106 
7.5.4.7 
ECOG Performance Status ..............................................................106 
7.5.5 
Patient-reported Outcomes .........................................................................107 
7.5.6 
Pharmacokinetic and Immunogenicity Evaluations...................................107 
7.5.6.1 
Rucaparib Pharmacokinetic Sample Collection...............................107 
7.5.6.2 
Nivolumab Pharmacokinetic Sample Collection .............................107 
7.5.6.3 
Nivolumab Immunogenicity Assessments .......................................108 
7.5.7 
Biomarker Analysis ...................................................................................108 
7.5.7.1 
Biomarker Analysis – Tumor Tissue ...............................................108 
7.5.7.2 
Biomarker Analysis – ctDNA ..........................................................109 
7.5.7.3 
Biomarker Analysis - Genomic DNA from Blood ..........................109 
7.5.7.4 
Additional Research .........................................................................109 
8 
ADVERSE EVENT MANAGEMENT .........................................................................110 
8.1 
Definition of an Adverse Event ...........................................................................110 
8.2 
Definition of a Serious Adverse Event ................................................................110 
8.3 
Definition of an Adverse Events of Special Interest ............................................111 
8.4 
Events or Outcomes Not Qualifying as Serious Adverse Events ........................111 
8.5 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse 
Events ...................................................................................................................111 
8.6 
Pregnancy or Drug Exposure During Pregnancy .................................................112 
8.7 
Recording of Adverse Events, Serious Adverse Events, and Adverse Events of 
Special Interest .....................................................................................................112 
8.7.1 
Onset Date of Adverse Events ...................................................................113 
8.7.2 
Resolution Date of Adverse Events ...........................................................113 
8.7.3 
Intensity of Adverse Events .......................................................................113 
8.7.4 
Causal Relationship of Adverse Events to Study Drug .............................114 
8.7.5 
Outcome and Action Taken .......................................................................114 
8.8 
Follow-Up of Adverse Events, Serious Adverse Events, and Adverse Events 
of Special Interest ................................................................................................115 
8.9 
Potential Drug-Induced Liver Injury ...................................................................115 

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8.10 
Regulatory Aspects of Serious Adverse Event and Adverse Events of Special 
Interest Reporting.................................................................................................116 
8.11 
Independent Data Monitoring Committee ...........................................................116 
9 
PLANNED STATISTICAL METHODS ......................................................................118 
9.1 
General Considerations ........................................................................................118 
9.2 
Determination of Original Sample Size ...............................................................118 
9.2.1 
Determination of Sample Size in Original Protocol ..................................118 
9.2.2 
Changes to Sample Size Assumptions as of Implementation of 
Protocol Amendment 2 ..............................................................................120 
9.2.3 
Sample Size Assumptions as of Implementation of 
Protocol Amendment 3 ..............................................................................122 
9.3 
Analysis Populations ............................................................................................123 
9.4 
Patient Disposition ...............................................................................................123 
9.5 
Demographics and Baseline Characteristics ........................................................123 
9.6 
Efficacy Analyses ................................................................................................123 
9.6.1 
Primary Efficacy Analyses ........................................................................123 
9.6.1.1 
Step-down Procedure to Adjust for Multiplicity .............................124 
9.6.2 
Secondary Efficacy Analysis .....................................................................126 
9.6.2.1 
Progression-free Survival as Assessed by BICR .............................126 
9.6.2.2 
Overall Survival ...............................................................................126 
9.6.2.3 
Investigator determined ORR per RECIST .....................................126 
9.6.2.4 
Duration of Response .......................................................................127 
9.7 
Safety Analyses ....................................................................................................127 
9.7.1 
Adverse Events ..........................................................................................127 
9.7.2 
Clinical Laboratory Evaluations ................................................................128 
9.7.3 
Vital Sign Measurements ...........................................................................128 
9.8 
Pharmacokinetic Analysis ....................................................................................129 
9.8.1 
Rucaparib Pharmacokinetic Analysis ........................................................129 
9.8.2 
Nivolumab Pharmacokinetic Analysis .......................................................129 
9.9 
Interim Analysis ...................................................................................................129 
9.9.1 
Open-label Safety Cohort ..........................................................................129 
9.9.2 
Double-blind Treatment Phase ..................................................................129 
10 STUDY ADMINISTRATION.......................................................................................131 
10.1 
Regulatory and Ethical Considerations ................................................................131 
10.1.1 
Regulatory Authority Approvals ................................................................131 
10.1.2 
Institutional Review Board or Independent Ethics Committee Approval .131 
10.2 
Patient Information and Consent .........................................................................132 
10.3 
Patient Confidentiality .........................................................................................132 
10.4 
Study Monitoring .................................................................................................133 
10.5 
Case Report Forms and Study Data .....................................................................133 

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10.6 
Study Termination and Site Closure ....................................................................134 
10.7 
Modification of the Study Protocol......................................................................134 
10.8 
Retention of Study Documents ............................................................................134 
10.9 
Quality Control and Assurance ............................................................................135 
10.9.1 
Changes to the Protocol and Deviations ....................................................135 
10.9.2 
Study Site Training and Ongoing Monitoring ...........................................136 
10.9.3 
Direct Access to Source Data/ Documents for Audits and Inspections .....136 
10.10 Clinical Study Report ...........................................................................................136 
10.11 Publication and Disclosure Policy .......................................................................136 
10.12 Investigator Oversight ..........................................................................................137 
11 REFERENCE LIST .......................................................................................................138 
12 APPENDICES ...............................................................................................................144 
 
LIST OF IN-TEXT TABLES 
Table 1. 
Progression-free Survival per Investigator and per BICR in Primary 
Analysis Populations in Study CO-338-014 .......................................................34 
Table 2. 
Description of Rucaparib Tablets .......................................................................66 
Table 3. 
Description of Nivolumab for Injection..............................................................66 
Table 4. 
Oral Study Drug Dose Reduction Steps .............................................................76 
Table 5. 
Schedule of Assessments for All Patients...........................................................88 
Table 6. 
Pharmacokinetic and Immunogenicity Sample Collections ...............................93 
 
LIST OF IN-TEXT FIGURES 
Figure 1. 
Study Schema .....................................................................................................59 
Figure 2. 
Integrated Dose Modification Guidance for Events Related to IV and/ or 
Oral Drug by CTCAE Grade (CTCAE v5.0) .....................................................71 
Figure 3. 
ATHENA Statistical Design .............................................................................125 
 
LIST OF APPENDICES 
Appendix 1 Response Evaluation Criteria in Solid Tumors Criteria ...................................144 
Appendix 2 Modified Gynecological Cancer Intergroup (GCIG) Guidelines for 
Response or Progression using CA-125 ...........................................................150 
Appendix 3 ECOG Performance Status Scale ......................................................................152 
Appendix 4 Examples of Sensitive Clinical Cytochrome P450 (CYP) Substrates ..............153 
Appendix 5 FACT-O ............................................................................................................154 
Appendix 6 Euro-QoL5D-5L ...............................................................................................158 

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Appendix 7 Management Algorithms for Immuno-Oncology Agents .................................161 
Appendix 8 Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab ...170 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
2QW 
twice a week 
ADP 
adenosine diphosphate 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BCRP 
breast cancer resistance protein 
BER 
base excision repair 
BICR 
blinded independent central review 
bicrPFS 
disease progression according to RECIST v1.1 as assessed by blinded central 
radiology review, or death from any cause; also known as irrPFS 
BID 
twice a day 
BRCA1 
breast cancer susceptibility gene 1 
BRCA2 
breast cancer susceptibility gene 2 
BUN 
blood urea nitrogen 
C2D1 
Cycle 2 Day 1 
Cav,ss 
average nivolumab steady-state exposures 
CA-125 
cancer antigen 125 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL 
clearance 
CLss 
steady-state clearance 
Cmax 
maximum concentration 
Cmax,ss 
steady-state maximal concentrations 
Cmin,ss 
steady-state trough concentrations 
CO2/HCO3- 
bicarbonate 
CR 
complete response  
CRA 
clinical research associate 
CRO 
contract research organization  
CT 
computed tomography 
ctDNA 
circulation tumor DNA 

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CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA 
cytotoxic T-lymphocyte-associated protein 4 
CV% 
percent coefficient of variation 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
DILI 
drug-induced liver injury 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
ECG 
electrocardiogram 
ECL 
electrochemiluminescent 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EC50 
half-maximal effective concentration 
EMA 
European Medicines Agency 
ENGOT 
European Network for Gynecological Oncological Trial groups 
EOC 
epithelial ovarian cancer 
EQ-5D-5L 
Euro-Quality of Life 5D-5L 
EU 
European Union 
FACT-O 
Functional Assessment of Cancer Therapy - Ovarian 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FIGO 
International Federation of Gynecology and Obstetrics 
fT3 
free thyroxine 
fT4 
free triiodothyronine 
FTC 
fallopian tube cancer 
gBRCA 
germline BRCA 
GBS 
Guillain-Barre Syndrome 
GCIG 
Gynecologic Cancer Intergroup 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
GOG 
Gynecological Oncology Group 
H&E 
hematoxylin and eosin 
HGSOC 
high grade serous ovarian cancer 
HIPAA 
Health Information Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 

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HRD 
homologous recombination deficiency 
HRQoL 
Health-related Quality of Life 
HRR 
homologous recombination repair 
HuMAb 
human monoclonal antibody 
IB 
Investigator’s Brochure 
IC50 
half-maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IFN 
interferon 
IgG4 
immunoglobulin G4 
IMAE 
immunotherapy-related adverse event 
INN 
International Nonproprietary Name 
INR 
international normalized ratio 
invPFS 
progression from disease according to RECIST v1.1 as assessed by the 
investigator, or death from any cause 
I-O 
immune-oncology 
IRB 
Institutional Review Board  
IRT 
interactive response technology 
ITT 
Intent-to-treat 
IUD 
intrauterine device 
IUS 
intrauterine system 
IV 
intravenous 
LDH 
lactate dehydrogenase 
LOH 
loss of heterozygosity 
MATE 
multidrug and toxin extrusion transporter 
mCRPC 
metastatic castration-resistant prostate cancer 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Drug Regulatory Activities 
MG 
myasthenia gravis 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
NGS 
next-generation sequencing 
NSCLC 
non-small cell lung cancer 

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OCT 
organic cation transporter 
ORR 
objective response rate 
OS 
overall survival 
PARP 
poly (adenosine diphosphate [ADP]-ribose) polymerase 
PARPi 
inhibitor of PARP enzyme 
PD-1 
programmed death-1 cell surface membrane receptor 
PD-L1/PD-L2 
ligands of PD-1 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS2 
second event of progression-free survival 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PMDA 
Japanese Pharmaceuticals and Medical Devices Agency 
PPC 
primary peritoneal cancer 
PPI 
proton pump inhibitors 
PPK 
population pharmacokinetics 
PR 
partial response 
PRO 
patient-reported outcome 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 
Q4W 
every 4 weeks 
QD 
once a day 
RBC 
red blood cell 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis software 
sBRCA 
somatic breast cancer gene 1 or 2 mutation 
SCCHN 
squamous cell carcinoma of the head and neck 
SD 
standard deviation 
SFU1 
Safety Follow-up Visit 1 
SFU2 
Safety Follow-up Visit 2 
SJS 
Stevens-Johnson Syndrome 
SOC 
system organ class 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 

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t1/2 
half-life 
tBRCA 
tumor tissue alteration in BRCA1 or BRCA2, includes gBRCA and sBRCA 
TCGA 
The Cancer Genome Atlas 
TEAE 
treatment-emergent adverse event 
TEN 
toxic epidermal necrolysis 
TIL 
tumor infiltrating lymphocyte 
TOI 
trial outcome index 
TMB 
tumor mutational burden 
TSH 
thyroid stimulating hormone 
UGT 
uridinediphosphate-glucuronosyletransferase 
UK 
United Kingdom 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States prescribing information 
v 
version 
VEGF 
vascular-endothelial growth factor 
Vss 
volume of distribution at steady-state 
WBC 
white blood cell 
 

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1 
INTRODUCTION 
ATHENA is a Phase 3, randomized, double-blind, dual placebo-controlled study of 
nivolumab in combination with rucaparib in patients with newly diagnosed epithelial ovarian, 
fallopian tube, or primary peritoneal cancer who have responded to their first-line 
platinum-based regimen. 
1.1 
Background 
Globally, ovarian cancer is the seventh most common cancer and the eighth leading cause of 
cancer death among women, responsible for approximately 150,000 deaths each year.13 The 
median age at presentation of epithelial ovarian cancer (EOC) is 60 years. Unfortunately, 
because of delayed presentation and diagnosis, almost 70% of women with ovarian cancer 
are diagnosed in the later stage of disease (III/IV), and these women have particularly poor 
outcomes.14 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.15 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.15-18 EOC, PPC and fallopian tube cancer (FTC) behave very similarly and are 
therefore treated in the same way. 
The standard approach to treatment of advanced ovarian cancer 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 
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 deoxyribonucleic acid (DNA).15,19 Despite a 70% to 80% initial response rate, most 
women with advanced ovarian cancer will experience disease relapse, usually within 
15 months of initial diagnosis. 
Maintenance therapy following a response to standard treatment provides an opportunity to 
extend the disease-free period. Maintenance strategies in ovarian cancer initially focused on 
the prolonged use of single-agent chemotherapy, anti-angiogenesis agents, hormonal therapy, 
vaccines, and intraperitoneal chemotherapy. The OCEANS study evaluated carboplatin and 
gemcitabine with or without bevacizumab as part of the initial treatment and then as 
maintenance in women with platinum-sensitive ovarian, primary peritoneal, or fallopian tube 
cancer who were in their first relapse following primary chemotherapy.20 The addition of 
bevacizumab resulted in a statistically significant improvement in progression-free survival 
(PFS) (median 12.4 vs. 8.4 months; hazard ratio [HR] = 0.484 [95% confidence interval (CI), 
0.388-0.605; log-rank p < 0.00001]). The PFS benefit of bevacizumab administered together 
with chemotherapy followed by single-agent bevacizumab maintenance treatment compared 
to chemotherapy alone and placebo maintenance was further established in 2 front-line Phase 
3 studies, respectively, Gynecological Oncology Group-218 (GOG-218; median PFS 14.1 vs. 

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10.3 months; HR = 0.717 [95% CI, 0.625-0.824; log-rank p < 0.001])21 and ICON-7 (median 
PFS 19.0 vs. 17.3 months, HR = 0.81 [95% CI, 0.70-0.94; log--rank p < 0.004]).22 Based on 
these studies, the European Medicines Agency (EMA) approved bevacizumab, in 
combination with carboplatin and paclitaxel, for front-line treatment of advanced 
(International Federation of Gynecology and Obstetrics [FIGO] stages III B, III C and IV) 
epithelial ovarian, fallopian-tube, or primary peritoneal cancer and in combination with 
carboplatin and gemcitabine, for treatment of first recurrence of platinum-sensitive epithelial 
ovarian, fallopian-tube or primary peritoneal cancer in women who have not received prior 
therapy with bevacizumab or other vascular endothelial growth factor (VEGF) inhibitors or 
VEGF-receptor-targeted agents. Notably, only a study adding bevacizumab to chemotherapy 
in the recurrent setting (GOG-213) showed an extension of median overall survival (OS) in 
patients who received bevacizumab combined with chemotherapy treatment (42.2 months) 
versus the chemotherapy arm (37.3 months; HR = 0.83, p = 0.056). The median PFS benefit 
in this study was 3.4 months with the addition of bevacizumab to chemotherapy compared to 
chemotherapy alone (median PFS 13.8 vs. 10.4 months; HR = 0.61 [95% CI, 0.51-0.72, 
p < 0.0001]).23 
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor maintenance 
therapy has also been evaluated as a strategy for improving outcomes in recurrent, 
second-line and beyond, platinum-sensitive ovarian cancer. Three randomized, double-blind 
studies have demonstrated statistically significant improvements in median PFS as compared 
to placebo in the intent-to-treat (ITT) population regardless of breast cancer gene 
(BRCA1)1/2 mutation or homologous recombination deficiency (HRD) status.  
PARP maintenance was first evaluated in a Phase 2, randomized study, Study 19. This study 
demonstrated an improved median PFS in those treated with olaparib versus placebo in 
patients with a BRCA mutation (11.2 vs. 4.3 months; HR 0.18 [95% CI, 0.10-0.31; 
p < 0.0001]) and the ITT Population (8.4 vs. 4.8 months; HR 0.35 [95% CI 0.25–0.49; 
p < 0.001]).24,25 A Phase 3 study of niraparib vs. placebo (NOVA) demonstrated a 
statistically significant improvement in median PFS, as assessed by blinded independent 
central review (BICR), in the germline BRCA (gBRCA) cohort (21.0 vs. 5.5 months; 
HR 0.27 [95% CI, 0.17-0.41; p < 0.001]) and the non-gBRCA cohort (9.3 vs. 3.9 months; 
HR 0.45 [95% CI, 0.34-0.61; p < 0.001]).26 A sensitivity analysis of investigator-assessed 
PFS (invPFS) also showed a PFS benefit in the gBRCA cohort (14.8 vs. 5.5 months; HR 0.27 
[95% CI, 0.182-0.401; p < 0.0001]) and the non-gBRCA cohort (8.7 vs. 4.3 months; HR 0.53 
[95% CI, 0.405-0.683; p < 0.0001]).27 ARIEL3, the Phase 3 study assessing rucaparib versus 
placebo, also demonstrated benefit in this setting with statistically significant improvements 
in PFS in patients with a BRCA mutation (median PFS 16.6 vs. 5.4 months) and the 
ITT group (10.8 vs. 5.4 months; Table 1).28 Analysis of the key secondary endpoint, PFS, as 
assessed by BICR, were consistent and showed a benefit in the BRCA cohort, as well as the 
ITT Population in patients treated with rucaparib versus placebo. Results of a randomized, 
Phase 3 SOLO2 study also showed a significant improvement in median invPFS with 
                                                 
1 The typical convention is to use italicized names for genes and plain text names for proteins. However, in this 
document, BRCA mutations which occur at both the gene and protein level are often discussed. Therefore, for 
enhanced readability, BRCA is written in plain text only throughout this document. 

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olaparib maintenance vs. placebo in patients with platinum-sensitive ovarian cancer with 
gBRCA mutations (19.1 vs. 5.5 months; HR 0.30 [95% CI 0.22-0.41; p < 0.0001).29 
Table 1. 
Progression-free Survival per Investigator and per BICR in 
Primary Analysis Populations in Study CO-338-014 
Analysis Population 
PFS by Investigator Review 
(Primary Endpoint) 
PFS by BICR 
(Key Secondary Endpoint) 
Median PFS 
(months) 
Rucaparib vs 
Placebo 
Hazard Ratio 
Median PFS 
(months) 
Rucaparib vs 
Placebo 
Hazard Ratio 
Primary Analysis Groups 
tBRCA  
(rucaparib n = 130; 
placebo n = 66) 
16.6 vs 5.4 
(p < 0.0001)a 
0.231 
(p < 0.0001)b 
26.8 vs 5.4 
(p < 0.0001)a 
0.201 
(p < 0.0001)b 
HRD  
(rucaparib n = 236; 
placebo n = 118) 
13.6 vs 5.4 
(p < 0.0001)a 
0.317 
(p < 0.0001)b 
22.9 vs 5.5 
(p < 0.0001)a 
0.336 
(p < 0.0001)b 
ITT 
(rucaparib n = 375; 
placebo n = 189) 
10.8 vs 5.4 
(p < 0.0001) 
0.365 
(p < 0.0001)b 
13.7 vs 5.4 
(p < 0.0001)a 
0.354 
(p < 0.0001)b 
Exploratory Analysis of Non-nested Subgroups 
Non-tBRCA LOH+c 
(rucaparib n = 106; 
placebo n = 52) 
9.7 vs 5.4 
(p < 0.0001)a 
0.440 
(p < 0.0001)b 
11.1 vs 5.6 
(p = 0.0114)a 
0.554 
(p = 0.0135) 
Non-tBRCA LOH-c 
(rucaparib n = 107; 
placebo n = 54) 
6.7 vs 5.4 
(p = 0.0040)a 
0.583 
(p = 0.0049)b 
8.2 vs 5.3 
(p = 0.0002)a 
0.470 
(p = 0.0003) 
Abbreviations: BICR = blinded independent central review (analogous to the term independent radiology 
review [IRR]); HRD = homologous recombination deficiency; ITT = intent-to-treat; LOH = loss of 
heterozygosity; PFS = progression-free survival; tBRCA = deleterious tumor alteration in BRCA1 or 
BRCA2, includes gBRCA and sBRCA. 
a 
Stratified log-rank analysis. 
b 
Cox proportional hazard model. 
c 
LOH+ and LOH- was the terminology used in the ARIEL3 study and is analogous to LOHhigh and 
LOHlow used in the current ATHENA study. 
 
Despite advances in treatment, including targeted therapies such as anti-angiogenesis agents 
and PARP inhibitors for advanced treatment settings, there has been little improvement in 
ovarian cancer outcomes, highlighting a clear need for new and more effective primary 
treatments for patients with advanced ovarian cancer.30,31 
1.1.1 
Rucaparib 
Rucaparib is a potent, oral small molecule inhibitor of PARP enzymes (PARPi), including 
PARP-1, PARP-2, and PARP-3, that play a critical role in base excision repair (BER).1 

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When PARP function is impaired, double-stranded DNA breaks accumulate in the absence of 
effective BER; in cells deficient in homologous recombination, these breaks cannot be 
accurately repaired, resulting in synthetic lethality.2 An analysis of the Cancer Genome Atlas 
(TCGA), which examined molecular changes associated with high-grade serous ovarian 
cancer (HGSOC), estimated that approximately 50% of patients with HGSOC have HRD.4 
Approximately, 1 in 4 women with ovarian cancer may have a BRCA mutation.32 Germline 
mutations in the BRCA1 and BRCA2 genes (gBRCA) are the strongest known hereditary 
factors and occur in 18% of all ovarian, fallopian tube, and primary peritoneal cancers.32-34 
These patients carry heterozygous deleterious mutations in their germline DNA and develop 
tumors when the remaining wild-type functional allele is inactivated (ie, “second hit”). 
Acquired BRCA1/2 mutations, known as somatic mutations (sBRCA), also account for 
approximately 6 to 8% of HGSOC patients.4,32,35  
While mutations in BRCA1 and BRCA2 are gene mutations most commonly associated with 
HRD, other essential homologous recombination repair (HRR) proteins may be mutated or 
functionally deficient in ovarian cancer. Over the past decade, it has been determined that 
patterns of genomic loss of heterozygosity (LOH) can predict HRD.3 Comprehensive 
genomic profiling based on next-generation sequencing (NGS) can be utilized to identify 
non-BRCA patients with HRD. The main advantage of detecting tumor genomic LOH is that 
it can identify HRD tumors regardless of the underlying mechanisms.3,12 An analysis of 
mature data from previous rucaparib clinical studies which enrolled platinum-sensitive 
patients, suggested that an LOH cut-off of 16% or greater for the BRCA wild-type subgroup 
provided the optimum discrimination of rucaparib treatment benefit; this group is referred to 
as LOH-high or the non-tBRCA LOHhigh subgroup.28,36 Accordingly, the patients 
participating in this study with non-BRCA tumors will be categorized into 1 of 3 HRD 
groups: non-tBRCA LOHhigh (LOH ≥16%), non-tBRCA LOHlow (LOH < 16%), or 
non-tBRCA LOHunknown.  
Rucaparib has shown preclinical and clinical activity in cancers associated with a deleterious 
mutation in BRCA1/2 or other HRR genes and/or genomic LOH.36,37 The previous Sponsor, 
Clovis Oncology, Inc., focused clinical development efforts of oral rucaparib on the 
treatment of cancer associated with HRD, defined by the presence of a deleterious BRCA1 or 
BRCA2 mutation or other deleterious mutation associated with HRD, and/or high percentage 
of genome-wide LOH, which is a phenotypic consequence of HRD. Although HRD was 
predictive of response to rucaparib, activity was also observed in HRD-negative patients, 
suggesting an incomplete understanding of the biomarkers responsible for PARPi sensitivity. 
Rucaparib is approved in the United States (US) for the treatment of patients with deleterious 
BRCA mutation (germline and/or somatic) for the maintenance treatment of adult patients 
with recurrent EOC, FTC, or PPC who are in a complete or partial response to platinum-
based chemotherapy.38-40 Rucaparib is additionally approved in the US  for the treatment of 
adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated 
metastatic castration-resistant prostate cancer (mCRPC) who have been treated with 
androgen receptor-directed therapy and a taxane-based chemotherapy.38,39 Rucaparib is 
approved in the European Union (EU) and the United Kingdom (UK) as monotherapy for the 
maintenance treatment of adult patients with platinum-sensitive relapsed high-grade ovarian 
cancer who are in response (complete or partial) to platinum-based chemotherapy.40-42  

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Summaries of approvals (above) and overviews of data from nonclinical and clinical studies 
(below) are described in detail in the rucaparib Investigator’s Brochure (IB). A summary of 
the benefit: risk is also provided in the rucaparib IB. 
1.1.1.1 
Nonclinical Experience 
The results from nonclinical studies are consistent with the mechanism of action and 
pharmacological effects of PARP inhibition.  
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 (CYP) 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 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.43-46  
1.1.1.2 
Clinical Experience 
Rucaparib is being evaluated in Phase 1, 2, and 3 clinical studies in patients with advanced 
cancer with and without 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.  

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Rucaparib is being evaluated as treatment for patients with metastatic castration-resistant 
prostate cancer (mCRPC), both as monotherapy and in combination with nivolumab. 
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 are ongoing. 
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. 
1.1.1.2.1 
OVERVIEW OF PHARMACOKINETICS AND DRUG-DRUG INTERACTIONS 
Assessment of rucaparib PK in cancer patients showed an approximate dose proportional 
exposure after once daily (QD) or twice a day (BID) dosing, rapid absorption with 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 (70%). The steady-state was achieved following 
1 week of dosing with rucaparib BID, with approximately 4-fold accumulation. 
At a dose of 600 mg BID rucaparib, steady state was achieved after approximately 1 week. A 
high-fat meal increased the Cmax and area under the curve (AUC)0-24h of rucaparib by 20% 
and 38%, respectively, as compared with that under fasted conditions. 
In vitro, rucaparib showed slow enzymatic turnover in human liver microsomes and 
hepatocytes. Recombinant CYP2D6, and to a lesser extent CYP1A2 and CYP3A4, were able 
to metabolize rucaparib.  
Drug interactions with rucaparib as a substrate were assessed in a population PK (PPK) 
analysis. CYP2D6 phenotypes (poor metabolizers, intermediate metabolizers, normal 
metabolizers, and ultrarapid 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 CYP inhibitors. 
Concomitant treatment with proton pump inhibitors (PPIs) showed no clinically significant 
effect on rucaparib PK. No dose modification of rucaparib is required for patients who are 
receiving concomitant treatment with a PPI. 
Results from Study CO-338-044 evaluating potential drug-drug interactions (DDI) with 
rucaparib, indicated that rucaparib, at 600 mg BID, moderately inhibited CYP1A2, weakly 
inhibited CYP2C9, CYP2C19, and CYP3A, and showed no clinically significant effect on 
P-gp. Caution should be exercised in the concomitant use of drugs that are substrates of the 
above CYP enzymes with narrow therapeutic windows. 

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1.1.1.2.2 
OVERVIEW OF EFFICACY 
1.1.1.2.2.1 
Ovarian Cancer Treatment Indication 
On 19 December 2016, the 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 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.47  
The primary outcome measure on which approval was based is investigator-assessed 
objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 
(RECIST v1.1), with ORR by central independent radiological review conducted as a 
supportive analysis. ORR by investigator was 53.8%, while ORR by independent review was 
41.5%, confirming the results of investigator assessment for this endpoint.48 Responses were 
durable, indicated by a duration of response (DOR) by investigator assessment of 
approximately 9.2 months.  
Study CO-338-043 (ARIEL4) was conducted as a confirmatory study comparing rucaparib to 
chemotherapy in patients with deleterious BRCA mutation (germline and/or somatic) 
associated advanced ovarian cancer who have been treated with ≥ 2 chemotherapies. Clovis 
voluntarily withdrew this indication in the US, Europe, UK, and Israel in 2022 based on the 
detriment in OS observed for patients randomized to rucaparib versus chemotherapy 
ARIEL4. 
1.1.1.2.2.2 
Rucaparib as Maintenance Treatment in Ovarian Cancer  
Rucaparib monotherapy for treatment of patients with advanced ovarian cancer in the 
maintenance setting demonstrated significant benefit of rucaparib compared to placebo 
across primary, secondary, and exploratory endpoints in the randomized, placebo-controlled 
Phase 3 study, Study CO-338-014 (ARIEL3).23 In this study, investigator-assessed PFS 
(invPFS) was the primary efficacy endpoint, with PFS by BICR (bicrPFS) conducted as a 
key, stand-alone, secondary endpoint. Rucaparib maintenance treatment significantly 
improved PFS compared with placebo in all primary analysis groups of patients with 
recurrent ovarian cancer after a complete or partial response to platinum-based therapy 
(Table 1). Overall, rucaparib as maintenance treatment reduced the risk of progression or 
death by 63.5% (HR 0.365 [95% CI, 0.295-0.451]; p < 0.0001) in the ITT Population, 
demonstrating a strong treatment effect over placebo. Analysis of non-nested, 
non-overlapping patient subpopulations indicate that the significant improvement in PFS 
observed in the ITT Population was not driven only by the HRD or tBRCA (tumor tissue 

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deleterious alteration in BRCA1 or BRCA2) subpopulations. Nearly half (44.6%) of the ITT 
patients in the rucaparib group showed benefit at 1 year compared to 8.8% in the placebo 
group.28 At 18 and 24 months, 32.0% and 26.0%, respectively, of patients who received 
rucaparib were still progression-free compared to 5.8% and 2.6% in the placebo group. These 
investigator-assessed results were confirmed by results of BICR.  
The 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, demonstrated that rucaparib delayed disease recurrence and showed a further 
response to rucaparib treatment in patients with measurable disease in women with advanced 
ovarian cancer. 
1.1.1.2.3 
OVERVIEW OF SAFETY 
Results of a recent integrated safety analysis in over 1500 patients with ovarian cancer who 
received 600 mg BID rucaparib in clinical trials, including ARIEL3, showed that the most 
common TEAEs reported were primarily mild to moderate (Grade 1 to 2) in severity and 
include gastrointestinal disorders (nausea, vomiting, diarrhea, constipation, and abdominal 
pain), asthenia/fatigue, anemia/decreased hemoglobin, ALT/AST increased, decreased 
appetite, and dysgeusia.38 The most common TEAEs ≥ Grade 3 include anemia/decreased 
hemoglobin, ALT/AST increased, neutropenia/decreased absolute neutrophil count (ANC), 
and asthenia/fatigue. 
The laboratory abnormalities were consistent with the TEAEs, with decreased hemoglobin 
(and associated increase in mean corpuscular volume [MCV] and mean corpuscular 
hemoglobin [MCH]), increased ALT, increased AST, and increased serum creatinine, most 
commonly occurring. Decreased platelets, neutrophils, leukocytes, lymphocytes, and 
increased cholesterol were observed to a lesser extent. The transient elevations in ALT/AST 
with rucaparib treatment in either the treatment or maintenance settings were not associated 
with abnormal increases in bilirubin or other criteria for drug-induced hepatotoxicity and 
generally resolved over time. Furthermore, no cases met Hy’s law criteria for drug-induced 
liver injury (DILI)49,50, and few patients discontinued rucaparib due to ALT/AST 
elevations.28,48 Similarly, elevations in creatinine were self-limiting and stabilized over time. 
The majority of creatinine elevations were Grade 1 or Grade 2. Elevated serum creatinine 
levels resolved upon interruption or discontinuation of rucaparib, were not accompanied by 
changes in blood urea nitrogen (BUN), and did not lead to discontinuation of rucaparib 
treatment. Increased creatinine with rucaparib treatment is likely due to the potent inhibition 
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Effects on cardiac channel activity in vitro and a comprehensive assessment of the effects of 
rucaparib on electrocardiogram (ECG) parameters in cancer patients demonstrated a low risk 
of cardiac effects by rucaparib. 
1.1.1.2.3.1 
Safety: 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. Patients in rucaparib 
clinical studies diagnosed with MDS or AML had significant confounding risk factors 
including prior cytotoxic chemotherapy, and in some cases a deleterious BRCA mutation, 
which increases risk for developing cancer(s). Based on these 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. pharmaand GmbH 
(pharma&) is seeking to understand whether or not there is a relationship between 
pneumonitis and rucaparib treatment; thus, pharma& 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 8.7.  
More information on AESIs experienced by patients in rucaparib clinical studies is provided 
in the rucaparib IB. 
1.1.2 
Nivolumab 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human 
immunoglobulin G4 (IgG4) monoclonal antibody (HuMAb; IgG4-S228P) that binds to the 
programmed death-1 (PD-1) cell surface membrane receptor and blocks its interaction with 
PD-L1 and PD-L2, releasing PD-1 pathway-medicated inhibition of the immune response, 
including anti-tumor immune response. 
Nivolumab (OPDIVO®) is approved as monotherapy and in combination with other 
therapeutic agents in multiple regions, including the US51 and EU52. Indications include 
unresectable or metastatic melanoma, adjuvant treatment of melanoma, metastatic non-small 
cell lung cancer (NSCLC), advanced renal cell carcinoma (RCC), classical Hodgkin 
Lymphoma (cHL), squamous cell carcinoma of the head and neck (SCCHN), urothelial 
carcinoma (UC), microsatellite instability-high (MSI-H) or mismatch repair deficient 
(dMMR) metastatic colorectal cancer (CRC), and esophageal cancer. In addition, nivolumab 
has been approved for use in combination with ipilimumab for unresectable melanoma, 
unresectable pleural mesothelioma, hepatocellular carcinoma (HCC), RCC, and NSCLC, in 

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combination with cabozantinib for RCC, and in combination with chemotherapy for gastric 
cancer, gastroesophageal cancer (GEJ), and esophageal adenocarcinoma (excluding EU) in 
multiple countries, including the US and EU. Nivolumab is being investigated both as 
monotherapy and in combination with chemotherapy, targeted therapies, and other 
immunotherapies for the treatment of several types of cancer.  
Refer to the current OPDIVO® US Prescribing Information (USPI) and European Union 
(EU) Summary of Product Characteristics (SmPC) for updated indications and recommended 
dosage. 
The approved recommended dose of nivolumab as monotherapy is 3 mg/kg or 240 mg 
administered intravenously over 60 minutes every 2 weeks. 
Overviews of results/data from nonclinical and clinical studies are provided below and 
described in detail in the nivolumab IB and the current prescribing information for 
nivolumab (SmPC,52 USPI,51 or country-specific label) for more information. 
1.1.2.1 
Mechanism of Action 
Cancer immunotherapy rests on the premise that tumors can be recognized as foreign rather 
than as self and can be effectively attacked by an activated immune system. An effective 
immune response in this setting is thought to rely on immune surveillance of tumor antigens 
expressed on cancer cells that ultimately results in an adaptive immune response and cancer 
cell death. Meanwhile, tumor progression may depend upon acquisition of traits that allow 
cancer cells to evade immunosurveillance and escape effective innate and adaptive immune 
responses.53-55 Current immunotherapy efforts attempt to break the apparent tolerance of the 
immune system to tumor cells and antigens by either introducing cancer antigens by 
therapeutic vaccination or by modulating regulatory checkpoints of the immune system. 
T-cell stimulation is a complex process involving the integration of numerous positive, as 
well as negative, co-stimulatory signals in addition to antigen recognition by the T-cell 
receptor.56 Collectively, these signals govern the balance between T-cell activation and 
tolerance. 
PD-1 is a member of the CD28 family of T-cell co-stimulatory receptors that also includes 
CD-28, CTLA 4, ICOS, and BTLA.57 PD-1 signaling has been shown to inhibit 
CD-28-mediated upregulation of IL-2, IL-10, IL-13, interferon-γ (IFN-γ), and Bcl-xL. PD-1 
expression also has been noted to inhibit T-cell activation and expansion of previously 
activated cells. Evidence for a negative regulatory role of PD-1 comes from studies of 
PD-1-deficient mice, which develop a variety of autoimmune phenotypes.58 These results 
suggest that PD-1 blockade has the potential to activate anti-self T-cell responses, but these 
responses are variable and dependent upon various host genetic factors. Thus, PD-1 
deficiency or inhibition is not accompanied by a universal loss of tolerance to self-antigens. 
In vitro, nivolumab binds to PD-1 with high affinity (half-maximal effective concentration 
[EC50] 0.39-2.62 nM), and inhibits the binding of PD-1 to its ligands PD-L1 and PD-L2 
(half-maximal inhibitory concentration [IC50] ± 1 nM). Nivolumab binds specifically to PD-1 
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Blockade of the PD-1 pathway by nivolumab results in a reproducible enhancement of both 
proliferation and IFN-γ release in the mixed lymphocyte reaction. Using a cytomegalovirus 
re stimulation assay with human peripheral blood mononuclear cells, the effect of nivolumab 
on antigen-specific recall response indicates that nivolumab augmented IFN-γ secretion from 
CMV-specific memory T-cells in a dose-dependent manner versus isotype-matched control. 
In vivo blockade of PD-1 by a murine analog of nivolumab enhances the anti-tumor immune 
response and result in tumor rejection in several immunocompetent mouse tumor models 
(MC38, SA1/N, and PAN02).59 
1.1.2.2 
Nonclinical Experience 
No mass balance or metabolism studies with nivolumab have been conducted in animals. The 
expected in vivo degradation of monoclonal antibodies is to small peptides and amino acids 
via biochemical pathways that are independent of drug metabolism enzymes. 
No formal PK drug-drug interaction (DDI) studies have been conducted with nivolumab. 
Nivolumab is not expected to have any effect on CYP P450 or other drug metabolizing 
enzymes in terms of inhibition or induction, and is, therefore, not expected to induce these 
types of PK-based drug interactions.  
In intravenous (IV) repeat-dose toxicology studies in cynomolgus monkeys, nivolumab was 
well tolerated at doses up to 50 mg/kg, administered weekly for 5 weeks, and at doses up to 
50 mg/kg, administered twice a week (2QW) for 27 doses. While nivolumab alone was well 
tolerated in cynomolgus monkeys, combination studies have highlighted the potential for 
enhanced toxicity when combined with other immunostimulatory agents. 
Administration of nivolumab at up to 50 mg/kg twice 2QW was well tolerated by pregnant 
monkeys; however, nivolumab was determined to be a selective developmental toxicant 
when administered from the period of organogenesis to parturition at ≥ 10 mg/kg. 
Specifically, increased developmental mortality was noted in the absence of overt maternal 
toxicity. There were no nivolumab-related changes in surviving infants tested throughout the 
6-month postnatal period. Although the cause of these pregnancy failures was undetermined, 
nivolumab-related effects on pregnancy maintenance are consistent with the established role 
of PD-L1 in maintaining fetomaternal tolerance in mice.60 Human IgG4 is known to cross the 
placental barrier and nivolumab is an IgG4; therefore, nivolumab has the potential to be 
transmitted from the mother to the fetus. 
1.1.2.3 
Clinical Experience 
The PK, clinical activity, and safety of nivolumab have been assessed in patients with 
NSCLC, melanoma, clear-cell RCC, classical Hodgkin Lymphoma, urothelial carcinoma, 
SCCHN, in addition to other tumor types.  
1.1.2.3.1 
OVERVIEW OF PHARMACOKINETICS 
The PK of nivolumab was studied in patients with cancer over a dose range of 0.1 to 
20 mg/kg administered as a single dose or as multiple doses of nivolumab every 2 or 
3 weeks. Nivolumab clearance (CL) decreases over time, with a mean maximal reduction 

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(% coefficient of variation [CV%]) from baseline values of approximately 24.5% (47.6%) 
resulting in a geometric mean steady state clearance (CLSS) (CV%) of 8.2 mL/h (53.9%); the 
decrease in CLss is not considered clinically relevant. The geometric mean volume of 
distribution at steady state (VSS) was 6.8 L (27.3%), and geometric mean elimination t1/2 was 
25 days (77.5%). Steady-state concentrations of nivolumab were reached by 12 weeks when 
administered at 3 mg/kg every 2 weeks (Q2W), and systemic accumulation was 
approximately 3.7-fold. The exposure to nivolumab increased dose proportionally over the 
dose range of 0.1 to 10 mg/kg administered Q2W. 
Population PK (PPK) and exposure-response analyses have been performed to support use of 
nivolumab 240 mg Q2W, 360 mg every 3 weeks (Q3W), and 480 mg every 4 weeks (Q4W) 
dosing regimens in patients with cancer, in addition to the 3 mg/kg Q2W regimen. A flat 
dose of nivolumab 240 mg Q2W was selected since it is identical to a dose of 3 mg/kg for 
patients weighing 80 kg, the observed median body weight in nivolumab-treated cancer 
patients, while the nivolumab 360 mg Q3W and 480 mg Q4W regimens allow flexibility of 
dosing with less frequent visits and in combination with other agents using alternative dosing 
schedules to Q2W. Using a PPK model, the overall distributions of nivolumab exposures 
(Cav,ss, Cmin,ss, Cmax,ss, and Cmin1) are comparable after treatment with either nivolumab 
3 mg/kg or 240 mg Q2W. Following nivolumab 360 mg Q3W and 480 mg Q4W, Cav,ss are 
expected to be similar to those following nivolumab 3 mg/kg or 240 mg Q2W, while Cmin,ss 
are predicted to be 6% and ~16% lower, respectively, and are not considered to be clinically 
relevant. Following nivolumab 360 mg Q3W and 480 mg Q4W, Cmax,ss are predicted to be 
approximately 23% and 43% greater, respectively, relative to that following nivolumab 
3 mg/kg Q2W dosing. However, the range of nivolumab exposures (median and 90% 
prediction intervals) following administration of 240 mg Q2W, 360 mg Q3W, and 480 mg 
Q4W regimens across the 35 to 160 kg weight range are predicted to be maintained well 
below the corresponding exposures observed with the well-tolerated 10 mg/kg nivolumab 
Q2W dosing regimen. 
1.1.2.3.2 
OVERVIEW OF EFFICACY 
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy and in 
combination with ipilimumab in several tumor types, including NSCLC, melanoma, RCC, 
classical Hodgkin Lymphoma, small-cell lung cancer, gastric cancer, SCCHN, urothelial 
cancer, hepatocellular carcinoma, and colorectal cancer. In confirmatory trials, nivolumab as 
monotherapy demonstrated a statistically significant improvement in OS as compared with 
the current standard of care in subjects with advanced or metastatic NSCLC, unresectable or 
metastatic melanoma, advanced RCC, or SCCHN. Nivolumab in combination with 
ipilimumab improved PFS and ORR over ipilimumab alone in subjects with unresectable or 
metastatic melanoma. 
In a small, open-label study conducted in Japan, Hamanishi, et al61 assessed the safety and 
anti-tumor activity of nivolumab in 20 patients with platinum-resistant, recurrent, or 
advanced ovarian cancer. Patients received up to 6 cycles of nivolumab at 1 mg/kg (n = 10) 
or 3 mg/kg Q2W (n = 10) (4 doses per cycle) or until disease progression. The best ORR by 
RECIST v1.1 was 15% with 2 patients experiencing a durable complete response, and 4 
patients achieving prolonged disease control. The activity of nivolumab was similar to what 

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has been observed with chemotherapy in the platinum-resistant setting.62-64 However, the 
durability of the responses was atypical, and the results were promising in a heavily 
pretreated difficult to treat patient population. Notably, PD-L1 expression did not 
significantly correlate with response, highlighting the need to identify other markers that may 
be associated with activity. 
1.1.2.3.3 
OVERVIEW OF SAFETY 
For monotherapy, the safety profile is similar across tumor types. There is no pattern in the 
incidence, severity, or causality of AEs to nivolumab dose level. As monotherapy, the most 
common adverse reactions (≥ 20%) were fatigue, rash, musculoskeletal pain, pruritus, 
diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, 
arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and 
urinary tract infection.51 The most common treatment-related AEs (≥ 10%) across all studies 
evaluating monotherapy nivolumab were diarrhea, fatigue, rash, and pruritus (refer to the 
nivolumab IB). 
The nivolumab IB, the current prescribing information for nivolumab (SmPC, USPI, or 
country-specific label) should be consulted for regarding special warnings and precautions 
and specific guidance on treatment modifications. 
The majority of treatment-related AEs observed with nivolumab treatment of ovarian cancer 
patients, including hypothyroidism and lymphocytopenia, had been reported in previous 
clinical studies of nivolumab in other solid tumors.61 The most frequently observed AEs were 
those related to thyroid function; nearly all events were Grade 1. The frequency and severity 
of treatment-related AEs were not different between the 2 dose cohorts.  
1.1.2.3.4 
IMMUNOGENICITY 
Of 2085 patients who were treated with nivolumab 3 mg/kg Q2W and evaluable for the 
presence of anti-product antibodies, 233 patients (11.2%) tested positive for 
treatment-emergent anti-product antibodies by an electrochemiluminescent (ECL) assay. 
Neutralizing antibodies were detected in 15 patients (0.7%). There was no evidence of 
altered pharmacokinetic profile or toxicity profile with anti-product binding antibody 
development based on the PPK and exposure-response analyses. 
Clinically relevant AEs typical of stimulation of the immune system were infrequent and 
manageable by delaying or stopping nivolumab treatment and timely immunosuppressive 
therapy or other supportive care. 
1.1.3 
PARP Inhibitors and Checkpoint Inhibitors 
1.1.3.1 
Non-clinical Overview 
Recent translational data suggest that ovarian cancer patients with a BRCA mutation may 
have a preferential response to immune checkpoint inhibitors targeting the PD-1/PD-L1 
pathway.7 BRCA1 or BRCA2 mutant ovarian cancer patients have a higher number of 
protein coding mutations that can be potentially targeted by the immune system (termed 

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neoantigens), a higher expression of PD-1 and PD-L1 in intra-tumoral immune cells, and an 
elevated number of CD3-positive and CD8-positive tumor infiltrating lymphocyctes (TILs).7 
These data suggest that PD-1/PD-L1-targeting immunotherapies may preferentially benefit 
BRCA1 or BRCA2 mutant ovarian cancer patients. In addition, non-tBRCA patients with 
HRD that can be identified by a NGS HRD test may well preferentially benefit from 
PD-1/PD-L1-targeting agents.36 Published data and internal data (Clovis Oncology, Inc.) 
have demonstrated a significant association between genomic LOH and protein coding 
mutations, which provides an estimate of the tumor mutational burden (TMB) that may 
predict response to immune checkpoint inhibitors.11 
1.1.3.2 
Clinical Overview 
The combination of immune checkpoint inhibitors and PARP inhibitors has been recently 
evaluated in 3 early-phase studies.8,9,65 In a Phase 1 dose-escalation study of PD-L1 inhibitor, 
durvalumab, in combination with PARP inhibitor, olaparib, in 12 heavily pretreated 
participants (10 with ovarian cancer and 2 with triple-negative breast cancer), there were 
4 participants with partial response (duration of response ≥ 15 months and ≥ 11 months) and 
8 participants with stable disease ≥ 4 months (median, 8 months [4 to 14.5 months]), yielding 
an 83% disease control rate.8 The most common treatment-emergent AE with durvalumab 
plus olaparib was hematologic toxicity, with no dose-limiting toxicity reported at the highest 
dose combination tested (olaparib 300 mg twice a day [BID] and durvalumab 1500 mg every 
4 weeks [Q4W]).  
In a Phase 1/1b study, the combination of anti-PD-1 BGB-A317 and PARP inhibitor 
BGB-290 was generally well tolerated in 43 participants with advanced solid tumors.65 
Liver-related AEs were observed in 12 participants; all events were reversible with or 
without corticosteroid treatment. Complete or partial response was observed in 
11 participants, 4 of whom had confirmed partial response (PR) or complete response (CR); 
responses were durable and observed in participants with wild-type and mutant gBRCA 
status. Taken together, these studies have not identified any new safety signals with the 
combination of a PARP inhibitor and a PD-L1 inhibitor. 
Preliminary data from an ongoing Phase 2 study of the combination of durvalumab and 
olaparib in an unselected population with mCRPC demonstrated that the combination was 
well-tolerated and there was evidence of durable activity.9 
1.2 
Rationale for the Study and Benefit-Risk Assessment 
The purpose of this Phase 3 study is to evaluate the PFS of the combination of nivolumab 
and rucaparib in the front-line maintenance setting of advanced ovarian cancer. 
There is a clear and urgent clinical need for novel therapeutic approaches in advanced 
ovarian cancer. Despite progress in therapy, ovarian cancer remains a major cause of death, 
with an estimated quarter of a million new cases per year worldwide and only 25% of 
patients with advanced ovarian cancer surviving long term.13  
As discussed in Section 1.1, PARP inhibitors, including rucaparib, have demonstrated a clear 
extension of PFS in patients with platinum-sensitive disease in the second line and beyond 

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maintenance setting. In addition, the most mature maintenance study conducted with a PARP 
inhibitor (Study 19) recently showed an increase in median OS in patients treated with 
olaparib as compared to placebo in the BRCA mutation group (34.9 vs. 30.2 months; 
HR 0.62 [95% CI, 0.41-0.94; p = 0.025]) and the ITT Population (29.8 vs. 27.8 months, 
HR 0.73 [95% CI, 0.55–0.96; p = 0.025]) after the third interim analysis of OS.66 Nivolumab 
has also shown dramatic durable responses in initial studies of recurrent ovarian cancer, 
including those with platinum-resistant disease (Section 1.1.2.3.2). Combining rucaparib with 
nivolumab in the front-line setting provides an opportunity to further extend PFS and to 
increase the degree of clinical responses and, therefore, has the potential to provide a more 
efficacious front-line maintenance treatment option. 
The preclinical rationale for combining rucaparib with nivolumab is supported by emerging 
data that demonstrate an association between high neoantigen load and high expression of 
PD-1/PD-L1 in HRD tumors when compared with homologous recombinant-proficient 
ovarian cancers.4-7 BRCA1 and BRCA2 mutations have been reported to increase the number 
of TILs and are associated with improved OS.7 In addition, internal data (Clovis Oncology, 
Inc.) indicate a significant association between genomic LOH and TMB. A high TMB 
increases the likelihood of the development of tumor-specific neoepitopes that would confer 
clinical benefit from CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1 
blockade. Thus, it is hypothesized that increased DNA damage by PARP inhibition will 
increase the number of tumor neoantigens, creating a more antigenic environment in which to 
stimulate the immune microenvironment.  
Monotherapy oral study drug will be administered in Cycle 1 prior to the initiation of the 
combination oral and IV study drug administration in Cycle 2 within this study to further 
explore the hypothesis that priming the TMB will enhance activity of the combination. In 
addition, this approach provides the opportunity to establish a baseline safety profile of the 
oral study drug for each patient prior to administering the IV study drug. Overall, the safety 
profiles of both rucaparib and nivolumab are manageable and generally consistent across 
completed and ongoing clinical studies. Most AEs were low-grade (Grade 1 to 2) with 
relatively few related high-grade (Grade 3 to 4) AEs. A pattern of immune-mediated adverse 
events (IMAEs) associated with nivolumab has been defined, for which management 
algorithms have been developed; these are provided in Appendix 7. Most high-grade events 
were manageable with the use of corticosteroids or hormone replacement therapy (in the case 
of endocrinopathy) as instructed in these algorithms.  
Elevations in ALT, AST, and creatinine are commonly observed in patients receiving 
rucaparib and typically are observed beginning with Day 15 of the first cycle of treatment 
with rucaparib. The ALT/AST elevations typically peak after two weeks of dosing and are 
generally not accompanied by substantial concomitant elevation in bilirubin or alkaline 
phosphatase. There have been no cases of Hy’s law observed across the clinical development 
program, and based on the data available to date, rucaparib does not appear to be associated 
with drug induced liver injury. In addition, mean creatinine values increase soon after 
initiation with rucaparib treatment but subsequently plateau. Creatinine elevation resolves 
with dose holds of rucaparib and recurs with rechallenge. Rucaparib associated creatinine 
elevation has not been associated with evidence or reports of permanent renal impairment. 
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renal transporters.48 Elevations in ALT, AST, and creatinine are not typically observed with 
nivolumab treatment, however elevations in any of these laboratory parameters can be early 
signs of immune-mediated hepatitis or nephritis. Since Cycle 1 will only include oral study 
drug, this allows for Cycle 1 laboratory values to be assessed prior to initiation of the oral/IV 
study drug combination and ultimately should facilitate more accurate attribution to oral or 
IV study drug so the proper AE management algorithm may be followed.  
Additional details on the safety profile of nivolumab and rucaparib, including results from 
other clinical studies, are also available in the respective drug IBs.  
To assure an ongoing favorable risk/benefit assessment for participants enrolled into the 
present study, the following measures will be employed throughout the conduct of the study: 
• Oral study drug administration will begin 28 days (1 cycle) prior to IV study drug 
administration to explore the hypothesis that priming the TMB with monotherapy 
rucaparib will enhance the activity in combination with nivolumab. It will also allow the 
baseline safety profile for oral drug to be established, which will guide appropriate AE 
management, if needed, during combination therapy. 
• Institution of an Independent Data Monitoring Committee (IDMC) to provide 
independent oversight of safety, study conduct, and efficacy including regular and 
systematic reviews of safety data by treatment arm. 
• Rigorous safety monitoring by the sponsor to ensure participants’ safety, including close 
follow-up of reported safety events, and intensive site and study investigator 
training/education on the implementation of the nivolumab toxicity management 
algorithms and toxicity management of the rucaparib and nivolumab combination.  
• An open-label safety cohort will be conducted to evaluate the safety of oral rucaparib 
(600 mg BID) and IV nivolumab (480 mg on Day 1 of every 28-day cycle). 
• A Study Steering Committee (consisting of selected participating investigators) will meet 
regularly to advise the sponsor regarding study-related issues, including safety concerns. 
 
In conclusion, the overall risk-benefit of nivolumab in combination with rucaparib in women 
with ovarian cancer is deemed acceptable. Detailed information about the known and 
expected benefits and risks and reasonably anticipated AEs of nivolumab and rucaparib may 
be found in their respective IBs. 
1.3 
Dose Rationale 
1.3.1 
Dose Rationale for Nivolumab 
Nivolumab is currently approved for treatment of various tumors, using regimens that 
include nivolumab at doses of 240 mg Q2W, 480 mg Q4W, or 3 mg/kg Q2W as a single 
agent, and at 360 mg Q3W, 1 mg/kg Q3W, 3 mg/kg Q2W, or 3 mg/kg Q3W when used in 
combination with other therapeutic agents. Refer to the current prescribing information for 
dosing information.  

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The nivolumab dose of 480 mg Q4W was selected for this study based on clinical data and 
modeling and simulation approaches using PPK and exposure-response analyses examining 
relationships between nivolumab exposures and efficacy and safety responses, using data 
from studies in multiple tumor types with body weight-normalized dosing (mg/kg). A flat 
dose of 480 mg Q4W is expected to reduce prescription dosing errors, shorten pharmacy 
preparation time, and improve ease of administration. Extending the dosing interval to 
4 weeks provided numerous benefits to participants as they would have increased flexibility 
between clinical visits. 
The PPK analyses have shown that exposure to nivolumab increased dose proportionally 
over the dose range of 0.1 to 10 mg/kg administered Q2W, and no clinically meaningful 
differences in PK across ethnicities and tumor types were observed. Nivolumab clearance 
and volume of distribution were found to increase as body weight increased but less than 
proportionally with increasing weight, indicating that milligram-per-kilogram dosing 
represents an over-adjustment for the effect of body weight on nivolumab PK. 
Using the PPK and exposure-response models, nivolumab exposures and probabilities of 
efficacy responses and risks of AEs were predicted following nivolumab 480 mg Q4W 
administration and compared to those following nivolumab 3 mg/kg Q2W administration. 
The overall distributions of average nivolumab steady-state exposures (Cav,ss) are comparable 
following administration with either nivolumab 3 mg/kg Q2W or nivolumab 480 mg Q4W 
over a wide range of body weights. Nivolumab 480 mg Q4W administration is predicted to 
result in approximately 43% greater steady-state peak concentrations (Cmax,ss) compared to 
nivolumab 3 mg/kg Q2W. Although the Cmax,ss of nivolumab is expected to be greater 
following nivolumab 480 mg Q4W compared to nivolumab 3 mg/kg Q2W, the predicted 
Cmax,ss following nivolumab 480 mg Q4W is well below the median Cmax,ss achieved 
following administration of nivolumab 10 mg/kg Q2W, a safe and tolerable dose level across 
a wide body range (35 to 160 kg). 
Exposure-safety analysis demonstrated that the exposure margins for safety are maintained 
following nivolumab 480 mg Q4W, and the predicted risks of AEs due to discontinuation or 
death, ≥ Grade 3 AEs, and ≥ Grade 2 immunotherapy-mediated AEs (IMAEs) are predicted 
to be similar following administration of nivolumab 480 mg Q4W relative to nivolumab 
3 mg/kg Q2W across tumor types. Safety analyses using available data following nivolumab 
3 mg/kg Q2W and 10 mg/kg Q2W administration indicated there were no differences in AE 
profiles across body-weight groups. Finally, initial clinical evidence demonstrates that, 
following administration of nivolumab 480 mg Q4W, nivolumab is well tolerated. 
Nivolumab 480 mg Q4W is predicted to have approximately 16% lower steady-state trough 
concentrations (Cmin,ss) compared to nivolumab 3 mg/kg Q2W. While these exposures are 
predicted to be lower, they are on the flat part of the exposure-response curves and are not 
predicted to affect efficacy. Exposure-efficacy analyses of multiple PK measures and 
efficacy endpoints indicated that following administration of nivolumab 480 mg Q4W, 
efficacy is predicted to be similar to that following administration of nivolumab 3 mg/kg 
Q2W across multiple tumor types. Based on these data, nivolumab 480 mg Q4W is expected 
to have similar efficacy and safety profiles to nivolumab 240 mg Q2W or nivolumab 3 mg/kg 
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Nivolumab at a dose of 3 mg/kg Q2W has been studied in Japanese patients with ovarian 
cancer and found to be tolerable and associated with responses (see Section 1.1.2.3.2).61 In 
addition, nivolumab at a dose of 240 mg IV over 30 minutes Q2W is being studied in patients 
with advanced or recurrent ovarian cancer in a randomized Phase 3 study.67 The ATHENA 
study will use a 480 mg Q4W regimen for all patients, which was selected based on the 
equivalence (as described above) to the approved dose of nivolumab in Japan (3 mg/kg 
Q2W) for 6 indications, including melanoma, lung, and gastric cancers. 
Refer to the nivolumab IB for additional details. 
1.3.1.1 
Rationale for Nivolumab 30-minute Infusion 
Long infusion times place a burden on participants and treatment centers. Establishing that 
nivolumab can be safely administered using shorter infusion times of 30-minute duration in 
participants will diminish the burden, provided there is no change in the safety profile. 
Previous clinical studies show that nivolumab has been administered safely over 60 minutes 
at doses ranging up to 10 mg/kg over long treatment durations. In Study CA209010 (a 
Phase 2, randomized, double-blind, dose-ranging study of nivolumab in participants with 
advanced/metastatic clear cell RCC), a dose association was observed for infusion site 
reactions and hypersensitivity reactions (1.7% at 0.3 mg/kg, 3.7% at 2 mg/kg, and 18.5% at 
10 mg/kg). All the events were Grade 1 to 2 and were manageable. An infusion duration of 
30 minutes for 360 mg or 480 mg doses of nivolumab is not expected to present safety 
concerns compared to the prior experience at 10 mg/kg nivolumab dose infused over a 
60-minute duration. Nivolumab 480 mg Q4W and nivolumab 360 mg Q3W infused over 
30 minutes are also being investigated in several ongoing clinical studies. Overall, 
preliminary safety analysis suggests that the safety profile of nivolumab administered IV 
over 30 minutes at 480 mg Q4W or 360 mg Q3W is consistent with nivolumab 240 mg Q2W 
or 3 mg/kg Q2W administered IV over 30 or 60 minutes across multiple tumor types with 
respect to Grade 3 to 4 AEs, serious adverse events (SAEs), AEs leading to discontinuation, 
and IMAEs including hypersensitivity/infusion reaction IMAEs. There were no new safety 
concerns identified. For Study CA2099KD, the protocol specifies monitoring and 
management of safety events including nivolumab-related infusion reactions. In summary, 
nivolumab 360 mg Q3W or nivolumab 480 mg Q4W infused over 30 minutes is expected to 
provide a comparable safety profile to that seen with a 60-minute infusion, and is not 
expected to present additional safety concerns. 
1.3.2 
Dose Rationale for Nivolumab and Rucaparib Combination 
The recommended starting dose of rucaparib is 600 mg BID administered orally.47 Dose 
modifications should be implemented as described in Section 5.6. 
The starting dose for the combination of nivolumab (or IV placebo) plus rucaparib (or oral 
placebo) in this study will be the same as the monotherapy arms. Rucaparib or matching 
placebo, will be administered orally at 600 mg BID (as close to 12 hours apart as possible) on 
a 28-day cycle. Nivolumab, or IV placebo, will be administered at 480 mg via a 30-minute 
IV infusion on Day 1 of every 28-day cycle, starting with Cycle 2. The mechanisms of action 
of the 2 agents are different, and their toxicities are not predicted to be cumulative. Extending 

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the dosing interval of IV study drug to every 4 weeks, as described above, provides a 
convenience to patients on a 28-day treatment cycle. 
Further justification for these doses is provided based on previous early-phase clinical studies 
of PARP inhibitors plus PD-1/PD-L1 inhibitors as discussed in Section 1.1.3.2. A Phase 1 
dose-escalation study of durvalumab in combination with olaparib in pretreated ovarian and 
triple-negative breast cancer patients was conducted.8 The dose levels for this combination 
are also being evaluated in an ongoing Phase 2 study in participants with mCRPC and 
appears to be well tolerated, with the most common Grade 3/4 AEs also being hematologic 
toxicity.9 These studies have not identified any new safety signals when giving PARP 
inhibitor and an anti-PD-L1 antibody in combination. The maximum tolerated dose (MTD) 
of the combination of rucaparib and another checkpoint PD-L1 inhibitor, atezolizumab, was 
recently achieved at the currently-approved dose of each agent (600 mg BID rucaparib and 
1200 mg IV on Day 1 every 21 days) in an ongoing Phase 1/2 study (Study WO39409; 
internal data on file). Further, Study CA2099KD is an ongoing study in patients with prostate 
cancer to evaluate the combination of rucaparib and nivolumab, using the same doses of each 
agent that are proposed for this study. In addition, a small open-label safety lead-in will be 
performed prior to starting the randomized portion of this study. Further, establishment of 
baseline laboratory values for each patient following monotherapy oral drug and prior to 
beginning the combination therapy will help guide AE management during administration of 
the oral/IV combination therapy. The design is described in Section 3.1.3, and the analysis is 
described in Section 9.9. 
Please see Section 5.6 regarding appropriate dose modifications of the study drugs. 
1.4 
Rationale for Duration of Treatment 
1.4.1 
Nivolumab 
The optimal duration of immunotherapy is currently unknown. However, because 
immunotherapy engages the immune system to control the tumor, continuous treatment as is 
required with targeted agents or cytotoxic therapy may not be necessary. Accumulating 
evidence from different clinical studies in different tumor types treated with nivolumab 
indicates that most of the responses are generally occurring early, with a median time to 
response of 2 to 4 months.68-72 A recent analysis in a melanoma study suggests the majority 
of participants who discontinue nivolumab and/or ipilimumab for toxicity maintain disease 
control in the absence of further treatment. Furthermore, a limited duration of ipilimumab 
including only 4 induction doses resulted in long-term survival in participants with metastatic 
melanoma, with a sustained plateau in survival starting at around year 3.73 For these reasons, 
in the current study, treatment with nivolumab (or IV placebo) will be given for up to 
24 months after initiation of oral/IV combination study treatment, in the absence of disease 
progression, unacceptable toxicity, withdrawal of participant consent, or the end of the study, 
whichever occurs sooner. 

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1.4.2 
Rucaparib 
Rucaparib (or oral placebo) will be given initially as monotherapy and for up to 24 months in 
combination with nivolumab, or IV placebo in the absence of disease progression, 
unacceptable toxicity, withdrawal of participant consent, or the end of the study, whichever 
occurs sooner. The rucaparib duration of treatment was chosen to align with the duration of 
treatment for nivolumab (or IV placebo). 
 

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2 
STUDY OBJECTIVES 
2.1 
Primary Objective  
The primary objective of this study is: 
• To evaluate PFS by RECIST, as assessed by the investigator (invPFS) using the 
following separate comparisons: 
- 
Monotherapy: Arm B (oral rucaparib + IV placebo) vs Arm D (placebo [oral and IV]) 
in the HRD and intent-to-treat (ITT) sub/populations 
- 
Combination: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib + IV 
placebo) in the ITT Population 
 
2.2 
Secondary Objectives  
The secondary objectives of this study, using the same comparisons as the primary objective, 
are: 
• To evaluate PFS by RECIST, as assessed by the BICR (bicrPFS) 
• To evaluate survival benefit 
• To evaluate ORR and DOR, as assessed by the investigator, in patients with measurable 
disease at baseline  
• To evaluate safety  
 
2.3 
Exploratory Objectives 
Exploratory objectives in this study are:  
• To evaluate PFS2 (PFS on the subsequent line of treatment) 
• To evaluate the contribution of nivolumab monotherapy vs placebo (invPFS, bicrPFS, 
OS, ORR, DOR, safety) 
• To evaluate the comparison of combination rucaparib + nivolumab vs placebo (invPFS, 
bicrPFS, OS, ORR, DOR, safety) 
• To evaluate efficacy and safety in the tBRCA subgroup for the comparison of rucaparib 
vs placebo (invPFS, bicrPFS, OS, ORR, DOR, safety) 
• To evaluate efficacy and safety in the HRD, tBRCA, and PD-L1 subgroups for the 
comparison of combination vs rucaparib (invPFS, bicrPFS, OS, ORR, DOR, safety) 
• To evaluate Health-related Quality of Life (HRQoL) as assessed by the trial outcome 
index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) 

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• To evaluate patient-reported outcome (PRO) utilizing the Euro-Quality of Life 5D-5L 
(EQ-5D-5L) 
• To assess mutations in non-tBRCA (where tBRCA defines a tumor tissue alteration in 
BRCA1 or BRCA2) HRR genes as a molecular marker of efficacy 
• To assess PD-L1 expression and TMB as molecular markers of efficacy 
• To study variants in circulating tumor DNA (ctDNA) as markers of response and 
resistance 
• To characterize PK of rucaparib as monotherapy and in combination with nivolumab 
• To characterize PK of nivolumab as a monotherapy and in combination with rucaparib 
• To evaluate immunogenicity of nivolumab when administered as a monotherapy and in 
combination with rucaparib  
• To explore exposure-response relationship between selected exposure measures of 
rucaparib and nivolumab, and safety and efficacy endpoints 
 
3 
STUDY DESIGN 
3.1 
Overall Study Design and Plan 
This is a randomized, multinational, double-blind, dual placebo-controlled, 4-arm, Phase 3 
study evaluating rucaparib and nivolumab in combination and alone as switch maintenance 
therapy in newly diagnosed ovarian cancer patients who have completed first-line 
chemotherapy and who had a response. 
3.1.1 
Screening Phase 
All patients will undergo screening assessments within 120 days prior to randomization.  
The study will enroll patients with high-grade epithelial ovarian, primary peritoneal, or 
fallopian tube cancer who achieved either a CR or a PR, defined as RECIST v1.1 PR or a 
cancer antigen (CA-125) PR by Gynecologic Cancer Intergroup (GCIG) criteria,74 to their 
first platinum-based regimen. Patients must have received 4 to 8 cycles of first-line 
platinum-doublet treatment per standard clinical practice, including a minimum of 4 cycles of 
a platinum/ taxane combination; no other prior treatment for ovarian cancer, including 
maintenance treatment, is permitted. Prior hormonal therapy for previously-treated breast 
cancer is permitted.  
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, Eastern Cooperative Oncology Group (ECOG) performance status, central laboratory 
hematology and serum chemistry, and CA-125 measurement, urinalysis, physical 
examination, height, weight, and vital signs measurements, adverse events, radiologic 
assessment by computed tomography (CT) or magnetic resonance imaging (MRI), and a 

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blood sample for ctDNA analysis. PROs will be collected using the FACT-O and EQ-5D-5L 
instruments or other collection format, as appropriate. Assessments performed within the 
specified windows, but prior to patient signing informed consent, are acceptable to be used as 
a study procedure only if confirmed to have been standard of care. With the exception of 
samples for urinalysis, all other samples collected will be analyzed by a central laboratory; a 
duplicate sample may be collected and analyzed by the local laboratory for immediate 
eligibility/ treatment decisions. 
A patient will be required to provide archival tumor tissue or a screening biopsy for central 
laboratory analysis prior to enrollment. Genes of interest will be sequenced using Foundation 
Medicine’s NGS test, which examines a panel of cancer-related genes, including BRCA1/2 
and other homologous recombination pathway genes, as well as those related to response or 
resistance to immunotherapies. The degree of tumor LOH will also be assessed for each 
patient.3,10-12  
An analysis of mature data from previous rucaparib clinical studies that enrolled 
platinum-sensitive patients, suggested that a cut-off of 16% or greater for the BRCA 
wild-type, LOH-high (termed non-tBRCA LOHhigh) subgroup provided the optimum 
discrimination of rucaparib treatment benefit.28,36 Accordingly, the patients participating in 
this study with non-BRCA mutated tumors will be categorized into 1 of 3 HRD groups: 
non-tBRCA LOHhigh (LOH ≥ 16%), non-tBRCA LOHlow (LOH < 16%), or 
non-tBRCA LOHunknown.  
The results from the NGS test will be utilized to stratify patients into one of the above 
subgroups, or the tBRCA subgroup, for randomization, as follows: 
• tBRCA (deleterious BRCA1 or BRCA2 mutation) 
• non-tBRCA LOHhigh (LOH ≥ 16%) 
• non-tBRCA LOHlow (LOH < 16%)  
• non-tBRCA LOHunknown 
 
The complete results of the NGS-based test, which examines exons of 311 genes as well as 
introns of 35 genes, will be provided to all patients who opt to receive this information and 
provide appropriate consent. Tumor tissue results for the BRCA1/2 genes will be provided to 
patients who consent to receive this information upon availability. Results for the remainder 
of the gene panel will be provided to consenting patients upon study treatment 
discontinuation. Results are to be disclosed to consenting patients by the study physician as 
part of an overall clinical discussion. In the event a mutation associated with hereditary 
cancer or other syndrome is detected in tumor tissue, the patient may be referred by the 
investigator for genetic counseling and potential germline testing per institutional guidelines.  
Mutations detected in tumor tissue may be somatic or germline; however, the NGS test will 
not distinguish between the two. A blood sample will therefore be collected for all patients at 
Cycle 1 Day 1 and stored. Prior to final efficacy analysis, genomic DNA may be subjected to 

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exploratory analysis in order to determine whether any mutation identified is of germline or 
somatic origin. This data may be provided to the investigator and/ or consented patient.  
The sponsor will remain blinded to all NGS test results (including all tBRCA results), as well 
as existing BRCA data, with the exception of patients enrolled in the open-label safety 
cohort(s), until the primary efficacy analysis is conducted. 
Enrollment will require sponsor (or designee) review of eligibility, including, but not limited 
to: 
• The details for the front-line platinum-based regimen, including dates administered; 
• Details of primary surgery and biopsies taken prior to neoadjuvant treatment (if 
applicable) 
• Documentation supporting a CR by radiographic response or a PR by RECIST/ CA-125 
GCIG response to most recent platinum-based treatment;  
• Confirmation that sufficient tumor tissue was submitted for HRD stratification for 
randomization 
 
The protocol eligibility worksheet and associated source documents will be saved in the 
eTMF for all patients unless retention of source documents is not allowed per local 
regulations. 
3.1.2 
Enrollment/ Randomization 
Enrollment/ randomization to study treatment must occur within 8 weeks of the first day of 
the last cycle of chemotherapy and is described in more detail in Section 5.4. Study treatment 
must be initiated within 3 days of randomization. 
3.1.3 
Double-blind Treatment Phase 
The Double-blind Treatment Phase will continue in 28-day treatment cycles. The first dose of 
oral study treatment will be administered on Cycle 1 Day 1 and continue BID throughout the 
cycle as monotherapy; IV study drug will begin on Cycle 2 Day 1 (C2D1). Details on study 
drug administration are described in Section 5.5. During the Double-blind Treatment Phase, 
patients will come into the study site for a visit on Day 1 and Day 15 of Cycles 1 and 2, and 
on Day 1 of every cycle thereafter. Study treatment will continue until 24 months after 
initiating oral/IV combination study treatment, disease progression, or unacceptable toxicity, 
whichever happens first. 
During the Double-blind Treatment Phase (continuous 28-day treatment cycles), patients will 
be monitored for safety and efficacy. Assessments will include AEs, physical examination, 
vital signs and weight measurement, central laboratory hematology, serum chemistry, and 
CA-125 measurement, concomitant medications, therapies and procedures, ECOG 
performance status, disease status assessment, ctDNA analysis, study drug administration 
and accountability, and PRO. ECGs and urinalysis will be performed as clinically indicated. 

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Blood samples will also be collected to determine whether any mutation identified is of 
germline or somatic origin and for PPK analyses.  
Patients will be assessed for disease status per RECIST v1.1 every 12 calendar weeks 
(flexibility with scheduling within 1 week prior to planned imaging date is permitted) relative 
to C2D1 (the first scan will be 16 weeks after initiation of oral study treatment) for the first 
3 years and every 24 weeks thereafter until objective radiological disease progression; 
disease status will also be assessed at discontinuation of treatment and as clinically indicated. 
Disease progression will only be determined by RECIST v1.1 (Section 7.5.3.1). Patients with 
a CR at study entry will only be considered to have disease progression if a new lesion is 
identified based on guidelines outlined in RECIST v1.1. Patients who meet GCIG CA-125 
criteria for disease progression should have a radiologic assessment and be assessed by 
RECIST v1.1. If the radiologic assessment does not confirm disease progression, patients 
should continue on treatment and be assessed by RECIST v1.1 per the protocol schedule of 
assessments. Patients experiencing disease progression by RECIST v1.1, as assessed by the 
investigator, will be discontinued from treatment and enter follow-up. If the patient has met 
criteria for radiologic progression by RECIST, but the patient is still receiving benefit from 
the study drug(s) (eg, patient has mixed radiologic response or is continuing to have 
symptomatic benefit), according to the investigator, then continuation of treatment will be 
considered for a maximum cumulative duration of 24 months after initiation of oral/IV 
combination study treatment (see Section 5.13). Patients will continue to have all 
protocol-required assessments specified in the Schedule of Assessments (Table 5). 
PRO assessment will occur on Day 1 of Cycles 1 through 3, Cycle 5, then every 12 weeks 
(aligning with tumor assessment scans) until treatment discontinuation or until the data 
cut-off for the primary endpoint analysis, whichever comes first.  
All CT scans (and other imaging, as appropriate) performed during the treatment period and 
at treatment discontinuation will be collected for BICR. 
Patients will be continuously monitored for safety. An IDMC with multidisciplinary 
representation will evaluate safety in compliance with a prospective charter. 
3.1.4 
End of Treatment 
Upon treatment discontinuation, regardless of reason, patients will have an End-of-Treatment 
Visit. Assessments will include AEs, physical examination, vital signs and weight 
measurements, central laboratory hematology, serum chemistry, and CA-125 measurement, 
12-lead ECG, ctDNA analysis, concomitant medications, therapies and procedures, ECOG 
performance status, disease status assessment (only if 12 weeks or more since last scan), 
study drug accountability, and PRO.  
3.1.5 
Open-label Safety Lead-in 
Prior to the Double-blind Treatment Phase, a small, open-label safety cohort will be enrolled 
to assess the safety of the combination of rucaparib (600 mg BID) and nivolumab (480 mg 
IV on Day 1 of every 28-day cycle, starting with Cycle 2). The eligibility criteria and 
assessments for these patients will be the same as those described for patients enrolled in the 

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Double-blind Treatment Phase of the study. The safety cohort will consist of a minimum of 
6 patients enrolled at sites from North America and/or Europe. A formal safety review will 
occur after the safety cohort has enrolled and patients have been treated with the combination 
for at least 28 days (ie, 1 cycle) and with oral study drug for 2 cycles. The review committee 
will include external experts and sponsor personnel (see Section 9.9). The data will also be 
shared with the Independent Data Monitoring Committee (IDMC; see below and 
Section 8.11). The protocol will be amended as appropriate to incorporate additional patient 
safety monitoring if new safety signals are noted at any review.  
The safety cohort will not be enrolled, and the study will proceed directly to the Double-blind 
Treatment Phase, if, at the time that the first study sites are activated, a minimum of 
6 patients have been enrolled in the ongoing Phase 1/2 study in prostate cancer patients 
(Study CA2099KD [NCT03338790]) with the same rucaparib + nivolumab combination 
regimen, and the safety evaluation of these patients shows no new safety signals.  
Once the evaluation of the safety cohort is complete, the double-blind portion of the study 
can be opened for randomization in all regions with the exception of Japan. Prior to 
randomizing any patients in Japan, a safety cohort of at least 6 patients of Japanese ethnicity 
will be enrolled at investigational sites in Japan. This enrollment is contingent upon 
determination of a monotherapy rucaparib dose that is currently being evaluated in a Phase 1 
dose escalation study (Study CO-338-081) ongoing in Japan. Nivolumab at a dose of 480 mg 
Q4W will be used in this study and is based on equivalence to the approved dose of 3 mg/kg 
Q2W in Japan for numerous indications, including melanoma, lung, and gastric cancers. 
Evaluation of the Japanese safety cohort will proceed in the same manner as the initial safety 
cohort. Once the evaluation of the Japanese cohort is complete, the double-blind portion of 
the study can be opened for randomization in Japan. 
3.1.6 
Post-treatment Follow-up Phase 
All patients will be followed for at least 5 months after the last IV dose of study treatment. 
Safety Follow-up Visit 1 (SFU1) should occur 28 days (± 7 days) after last dose of study 
drug (oral or IV, whichever is later) or can be performed on the date of discontinuation if that 
date is at least 28 days from the last dose. Assessments will include AEs, physical 
examination, vital signs and weight measurements, central laboratory hematology, serum 
chemistry, and CA-125 measurement, ECG, ctDNA analysis (SFU1 only), concomitant 
medications, ECOG performance status, therapies and procedures, study drug accountability, 
and PRO. Safety Follow-up Visit 2 (SFU2) should occur approximately 5 months (± 7 days) 
from the last IV dose of study drug. The same assessments performed at SFU1 will be 
performed at SFU2; however, chemistry and hematology are only necessary if toxicities are 
present. If a patient remains on oral study drug after discontinuation of IV study drug, the 
SFU2 can be performed at the next cycle visit, provided it has been at least 5 months since 
the last IV dose.  
Patients who discontinued treatment for reason other than disease progression or death 
should continue to have tumor scans performed at 12-week intervals relative to C2D1 
(flexibility with scheduling within 1 week prior to planned imaging date is permitted) for the 

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first 3 years and every 24 weeks thereafter until objective radiological disease progression by 
RECIST v1.1 is documented, as assessed by the investigator. 
An optional tumor biopsy will be collected from patients who experience disease 
progression/randomized treatment discontinuation and provide appropriate consent. 
Patients will also be followed long-term for survival, subsequent treatments, and monitoring 
for secondary malignancy every 12 weeks (± 14 days) after SFU1 until death, loss to 
follow-up, withdrawal of consent, or study closure. 
If a patient begins subsequent anticancer therapy, the sponsor will terminate collection of 
SAEs, with the exception of the AESIs of MDS and AML.  
3.2 
Removal of Patients from Therapy or Assessment 
A patient must be discontinued from treatment with study drug if any of the following apply: 
• Consent withdrawal at the patient’s own request or at the request of their legally 
authorized representative. 
• Progression of patient’s underlying disease by RECIST v1.1 as assessed by the 
investigator unless patient is still receiving benefit from the study drug(s) according 
to the investigator, and the patient has provided additional consent. 
• 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. 
 
The sponsor may discontinue the trial early for any of the reasons noted in Section 10.6. 
3.3 
Study Schema 
The study schema is provided in Figure 1. 
 

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Figure 1. 
Study Schema 
 
Abbreviations: BID = twice a day; BRCA = breast cancer gene; CA-125 = cancer antigen-125; ECOG = Eastern Cooperative Oncology Group; 
HRD = homologous recombination deficiency; IDMC = independent data monitoring committee; IV = intravenous; LOH = loss of heterozygosity; 
MRI = magnetic resonance imaging; NGS = next-generation sequencing; PO = oral; PRO = patient reported outcome; Q4W = every 4 weeks; 
tBRCA = tumor tissue alteration in BRCA1 or BRCA2, includes gBRCA and sBRCA. 
RANDOMIZATION 4:4:1:1
stratified by:
HRD status by NGS mutation analysis
 
tBRCA
 
Non-tBRCA LOHhigh
 
Non-tBRCA LOHlow
 
Non-tBRCA LOHunknown
Response to first-line platinum
 
No residual disease
 
Residual disease
SCREENING
 Newly diagnosed, Stage III/IV, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer
 Complete or partial response to first-line platinum doublet
 Completed cytoreductive surgery with sufficient tissue available for analysis
 Excludes any prior treatment for ovarian cancer, including maintenance treatment, other than the first-line platinum regimen
 ECOG performance score     
ARM A
Rucaparib PO 600mg BID +
Nivolumab IV 480mg Q4W
N = 400
ARM B
Rucaparib PO 600mg BID +
Placebo IV
N = 400
ARM C
Placebo PO + 
Nivolumab IV 480mg Q4W
N = 100
ARM D
Placebo PO +
Placebo IV
N = 100
BLINDED TREATMENT PHASE
IV dose administered Day 1 each cycle (starting at Cycle 2); oral dose continuous BID
Disease assessment by RECIST v1.1 every 12 weeks with CT/MRI scans per BICR charter.
PRO on Day 1 of relevant cycle. Safety assessments each visit.  
Continue blinded treatment until 24 months, disease progression, or unacceptable toxicity, whichever happens first. 
POST-TREATMENT PHASE
Treatment discontinuation visit, if applicable. 
Safety follow-up 28 days and 5 months after last dose. 
Disease assessments every 12 weeks for the first 3 years relative to C2D1; every 24 weeks thereafter until disease progression 
per RECIST v1.1
Monitor for survival, subsequent treatment, and secondary malignancy every 12 weeks until death, loss to follow-up, 
withdrawal of consent, or study closure.
Timing of Surgery
 
Primary surgery
 
Interval debulking

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3.4 
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. An unblinding of treatment 
assignment might be performed when the study is still ongoing if recommended by the 
IDMC. However, the study is not anticipated to close until all patients are off treatment and 
sufficient OS follow-up has occurred.  
The sponsor may discontinue the study early for any reason as noted in Section 10.6. 
Upon formal closure of the study, individual patients who are continuing in long-term 
follow-up (LTFU) may transition to have their LTFU and scans, if applicable, captured via 
another mechanism.  
3.5 
Discussion of Study Design 
This is a multicenter, randomized, double-blind, dual placebo-controlled study.  
Sponsor personnel (with the exception of individuals responsible for clinical supply chain 
and drug safety personnel), investigator and clinical site staff (except individuals in the 
pharmacy or authorized designee who are responsible for preparing the IV study drug), and 
patients will all be blinded to all study treatment to avoid bias in the interpretation of the 
efficacy and safety results, with the exception of enrollment to the open-label safety cohorts. 
To avoid bias between treatment arms, patients will be randomized to treatment with active 
treatment arms or placebo with stratification according to HRD classification and best 
response to their first-line platinum regimen.  
Ovarian cancer patients who have a partial or complete response to front-line treatment, 
inclusive of surgery and platinum-based chemotherapy, routinely enter a period of active 
surveillance, with follow-up every 3 months for the first 2 years extending to every 6 months 
for years 2 to 5 and annually subsequently in the absence of relapse or progression. Several 
randomized studies have evaluated whether extending the number of platinum cycles during 
front-line chemotherapy would benefit survival. Eight, 10, and 12 cycles were compared to 
the standard of 5 or 6 cycles, and no improvement in response or prolongation of survival 
was established.75-77 In addition, Copeland et al., showed that weekly paclitaxel given as 
maintenance after platinum-doublet did not have any effect on OS.78 The cumulative toxicity 
and lack of benefit of platinum therapy extended beyond 6 cycles in the first-line setting fails 
to justify additional cycles beyond standard practice. Patients with PR after completion of 
standard first-line treatment who are not suitable for bevacizumab (in regions where it is 
approved in first-line) have the greatest need for improved treatment options. At present there 
are no proven beneficial treatments that delay progression or improve survival in this patient 
subgroup. Therefore, the use of a placebo comparator in the proposed study population is 
justified to objectively test the hypothesis of improved efficacy with the addition of 
nivolumab + rucaparib in combination, as well as each agent alone, as maintenance treatment 
in patients who achieve response to frontline treatment with a platinum regimen. 

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PFS by RECIST will be assessed by the investigator for the primary endpoint (invPFS) and 
by BICR for the secondary endpoint (bicrPFS). 
Ongoing benefit/risk will be assessed regularly by an IDMC that will have access to 
unblinded datasets (see Section 8.11). A Study Steering Committee, consisting of selected 
participating investigators representing Gynecologic Oncology Group (GOG), the European 
Network for Gynecological Oncological Trial groups (ENGOT), and national coordinating 
investigators from other regions, will meet regularly to advise the sponsor regarding 
study-related issues, including safety concerns. 
Monotherapy oral study drug will be administered in Cycle 1 prior to the initiation of the 
combination oral and IV study drug administration in Cycle 2 within this study to explore the 
hypothesis that priming the TMB will enhance activity of the combination. This additionally 
allows for Cycle 1 laboratory values to be assessed prior to initiation the oral/IV study drug 
combination, which ultimately should facilitate more accurate attribution to oral or IV study 
drug so the proper AE management algorithm may be followed. 
The small, open-label safety cohort that will enroll preceding randomization into the 
Double-blind Treatment Phase, was designed to assess the safety of the combination of 
rucaparib (600 mg BID) and nivolumab (480 mg IV on Day 1 every 28-day cycle, starting 
with Cycle 2). Evaluation of the full dose of each agent is recommended as the drugs have 
different mechanisms of action, and the single agent data for rucaparib and nivolumab do not 
have significant overlapping toxicities.  
The safety lead-in provides the opportunity to evaluate the rucaparib + nivolumab 
combination in an open-label manner with a small subset of patients with the same eligibility 
criteria and study assessments as those to be enrolled in the Double-blind Treatment Phase. 
There will be a formal safety review after the open-label safety cohort is enrolled and 
patients have been treated for at least 28 days of combination treatment (ie, 1 cycle) and 
2 cycles of oral study drug; the protocol will be amended as appropriate to incorporate 
additional patient safety monitoring if new safety signals are noted. 
 
 

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4 
STUDY POPULATION SELECTION 
4.1 
Number of Patients and Sites 
In total, approximately 1000 patients will be randomized in the Double-blind Treatment 
Phase at approximately 290 study sites. A maximum of 500 patients with a deleterious 
tBRCA mutation will be enrolled in the Double-blind Treatment Phase. A minimum of 
6 additional patients may be enrolled and treated as part of an open-label safety cohort.  
4.2 
Inclusion Criteria 
All patients enrolling into the study must meet all of the following inclusion criteria: 
1. Have signed an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)-approved informed consent form (ICF) prior to any study-specific evaluation. 
2. Be ≥ 18 years of age at the time the ICF is signed (patients enrolled in South Korea, 
Taiwan, and Japan must be ≥ 20 years of age at the time the ICF is signed).  
a. Patients enrolled in the open-label safety cohort in Japan must be of Japanese 
ethnicity (ie, both parents are native Japanese and were born in Japan) 
3. Have newly diagnosed, histologically confirmed, advanced (FIGO stage III-IV), 
high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. 
4. Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy 
and partial omentectomy, either prior to chemotherapy (primary surgery) or following 
neoadjuvant chemotherapy (interval debulking). 
5. Have received 4 to 8 cycles of first line platinum-doublet treatment per standard clinical 
practice, including a minimum of 4 cycles of platinum/ taxane combination. 
a. A patient with best response of PR must have received at least 6 cycles.  
b. Bevacizumab is allowed during the chemotherapy phase, but not during maintenance 
ie, during therapy directed by this protocol. 
6. Have completed first-line platinum-based chemotherapy and surgery with a response, in 
the opinion of the investigator, defined as no evidence of disease progression 
radiologically or through rising CA-125 (per Gynecologic Cancer Intergroup [GCIG] 
guidelines) at any time during front-line treatment; and: 
a. No evidence of measurable disease by RECIST v1.1 (if complete resection/R0 at 
primary or interval cytoreductive surgery); or 
b. A partial or complete response per RECIST v1.1 (if measurable disease was present 
after surgery and prior to chemotherapy) (Appendix 1); or 
c. A GCIG CA-125 response (if only non-measurable disease was present after surgery 
and prior to chemotherapy) (Appendix 2). 
7. Pre-treatment CA-125 measurements must meet criterion specified below: 
a. If the first value is within upper limit of normal (ULN) the patient is eligible to be 
randomized and a second sample is not required; 

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b. If the first value is greater than ULN a second assessment must be performed at least 
7 days after the first. If the second assessment is ≥ 15% than the first value the patient 
is not eligible. 
8. Patient must be randomized within 8 weeks of the first day of the last cycle of 
chemotherapy. 
9. Have sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue (1 × 4 µm section 
for hematoxylin and eosin [H&E] stain and approximately 8 to 12 × 10 µm sections, or 
equivalent) available for planned analyses. 
a. Submission of a tumor block is preferred; if sections are provided, these must all be 
from the same tumor sample. 
b. Tumor tissue from the cytoreductive surgery is required. 
c. Sample must be received at the central laboratory at least 3 weeks prior to planned 
start of treatment to enable stratification for randomization. 
10. Have adequate organ function confirmed by the following laboratory values obtained 
within 14 days of randomization: 
a. Bone Marrow Function 
ii. 
ANC ≥ 1.5 × 109/L 
iii. 
Platelets ≥ 100 × 109/L  
iv. 
Hemoglobin ≥ 9 g/dL  
b. Hepatic Function 
i. 
AST and ALT ≤ 1.5 × 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 × ULN unless estimated glomerular filtration rate (GFR) 
≥ 30 mL/min using the Cockcroft Gault formula 
11. Have an ECOG performance status of 0 to 1 (Appendix 3).  
 
4.3 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study: 
1. Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential 
(ie, borderline tumors) or mucinous tumors. Mixed mullerian tumors/carcinosarcomas are 
allowed. 
2. Active second malignancy, ie, patient known to have potentially fatal cancer present for 
which she may be (but not necessarily) currently receiving treatment. 

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a. Patients with a history of malignancy that has been completely treated, with no 
evidence of active cancer for 3 years prior to enrollment, or patients with 
surgically-cured low-risk tumors, such as early-stage cervical or endometrial cancer 
are allowed to enroll. 
3. Known central nervous system brain metastases. 
4. Any prior treatment for ovarian cancer, other than the first-line platinum regimen, 
including any maintenance treatment between completion of the platinum regimen and 
initiation of study drug in this study. 
a. Ongoing hormonal treatment for previously treated breast cancer is permitted. 
Hormonal maintenance treatment for ovarian cancer is not allowed. 
5. Has evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of 
myocarditis. 
6. Patients with an active, known or suspected autoimmune disease (eg, autoimmune 
hepatitis). Patients with type I diabetes mellitus, hypothyroidism only requiring hormone 
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring 
systemic treatment, or conditions not expected to recur in the absence of an external 
trigger are permitted to enroll. 
7. Patients with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 
14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent, are permitted in the absence of active 
autoimmune disease. 
8. Drainage of ascites during the final 2 cycles of treatment with the platinum regimen. 
9. Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in 
the opinion of the investigator, interfere with absorption of study treatment. 
10. Known history of a positive test for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be 
performed at all sites where mandated locally. 
11. Any positive test result for hepatitis B and/or known history of hepatitis B infection 
including patients with undetectable hepatitis B virus (HBV) DNA and inactive carriers; 
positive test result for hepatitis C antibody (anti-HCV; except if HCV-RNA negative). 
12. Pregnant, or breast feeding. All study participants must avoid pregnancy achieved 
through assisted reproductive technology for the duration of study treatment and for a 
minimum of 6 months following the last dose of study drug (oral or IV, whichever is 
later). 
13. Received chemotherapy within 14 days prior to first dose of study drug and/or ongoing 
adverse effects from such treatment > National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE, Version [v]5.0) Grade 1, with the 
exception of Grade 2 non-hematologic toxicity such as alopecia, peripheral neuropathy, 
Grade 2 anemia with hemoglobin ≥ 9 g/dL, and related effects of prior chemotherapy that 
are unlikely to be exacerbated by treatment with study drug. 

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14. Non-study related minor surgical procedure (eg placement of a central venous access 
port) ≤ 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. 
15. 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. 
16. Hospitalization for bowel obstruction within 12 weeks prior to enrollment. 
 
4.4 
Patients or Partners of Patients of Reproductive Potential 
Pregnancy is an exclusion criterion. In addition, due to inclusion criteria #4, requiring at least 
a bilateral salpingo-oophorectomy and partial omentectomy, women of child-bearing 
potential will not be randomized in this study.  
All study participants must avoid pregnancy achieved through assisted reproductive 
technology for the duration of study treatment and for a minimum of 6 months following the 
last dose of study drug (oral or IV, whichever is later). 
4.5 
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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5 
STUDY TREATMENT(S) 
5.1 
Description of Treatment(s) and Storage 
For the Double-blind Treatment Phase, eligible patients will be randomized 4:4:1:1 to the 
following arms: Arm A: oral rucaparib + IV nivolumab (n = 400), Arm B: oral 
rucaparib + IV placebo (n = 400), Arm C: oral placebo + IV nivolumab (n = 100) or Arm D: 
placebo (oral and IV) (n = 100).  
For the open-label safety cohort(s), patients will receive open-label oral 
rucaparib + IV nivolumab combination treatment. 
5.1.1 
Investigational Drug Product – Rucaparib or Placebo 
Rucaparib camsylate (also known as CO-338; formerly known as PF-01367338 and 
AG-014447) is an oral formulation. Rucaparib tablets for oral administration will be supplied 
to the study sites by the sponsor. A brief description of rucaparib is provided below in 
Table 2, with details in the Pharmacy Manual. 
Table 2. 
Description of Rucaparib Tablets 
Drug Name: 
Rucaparib 
INN: 
Rucaparib 
Formulation:  
(strengths expressed as 
free base) 
Tablet; film coated; 200 mg (blue, round, debossed with C2), 250 mg 
(white, diamond shape, debossed with C25), 300 mg (yellow, oval, 
debossed with C3)  
How Supplied: 
200 mg, 250 mg, and 300 mg (as free base) strength tablets in 60 count 
bottles. Patients may receive one or more strengths.  
Storage Conditions: 
15–30°C (59–86°F). 
 
Placebo tablets will be identical in appearance to the rucaparib tablets. 
5.1.2 
Investigational Drug Product – Nivolumab or Placebo 
Nivolumab, also referred to as BMS-936558, is a soluble protein consisting of 4 polypeptide 
chains, which include 2 identical heavy chains and 2 identical light chains (molecular weight: 
146 kDa). A brief description of nivolumab is provided below in Table 3, with details in the 
Pharmacy Manual. 
Table 3. 
Description of Nivolumab for Injection 
BMS Number: 
BMS-936558 
INN 
Nivolumab 
Other names: 
Opdivo, BMS-936558, MDX1106, ONO-4538, anti-PD-1 
How Supplied 
10 mg/mL concentrate for solution for infusion as 100 mg/10 mL 
single dose glass vials 
Storage Conditions: 
2–8°C (36–46°F). Protect from light and freezing. 

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Placebo infusion, once prepared for administration, will be identical in appearance to the 
nivolumab (refer to Section 5.2.2). 
5.2 
Packaging and Labeling 
5.2.1 
Rucaparib or Placebo Tablets 
All study drug tablets (rucaparib or placebo) are provided in 60-count bottles and should be 
stored in the provided containers between 15° and 30° C (59 and 86° F). Patients will be 
dispensed one or more strengths depending on their current dose of rucaparib/placebo. The 
number of bottles of each strength dispensed will be sufficient to supply 28-days treatment 
per cycle, including a small overage. 
For the Double-blind Treatment Phase, study drug containers containing rucaparib tablets or 
placebo will be labeled in a blinded way according to national regulations for investigational 
products. Details with respect to packaging and labeling of study drug tablets are described in 
the pharmacy manual. 
5.2.2 
Nivolumab or IV Placebo  
Nivolumab will be supplied by the sponsor as a 10 mg/mL solution.  
The vials and outer carton will be labeled according to national regulations for 
investigational products. 
The solution will be diluted for administration as an infusion in sodium chloride 9 mg/mL 
(0.9%) solution or glucose 50 mg/mL (5%). 
The placebo for nivolumab infusion will be an infusion of sodium chloride 9 mg/mL (0.9%) 
solution or glucose 50 mg/mL (5%). Details regarding placebo infusion may be found in the 
pharmacy manual.  
Both active and placebo infusions will be prepared by an unblinded pharmacist or authorized 
designee in order to maintain the blind to the patients, investigator and other study/site 
personnel during the Double-blind Treatment Phase. Infusions will be labeled in a blinded 
way. 
5.3 
Blinding/Masking of Treatments 
With the exception of the safety lead-in, every attempt will be made to maintain the treatment 
blind throughout the study. 
Active and placebo tablets will be identical in appearance and supplied in identical 
containers. The medication labeling will ensure that no staff member or patient will be able 
to identify whether the tablets are placebo or contain active medication. Patients will take the 
equivalent number of active or placebo tablets according to the treatment assignment and 
scheduled dose. 

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The IV solution (nivolumab or placebo) will be prepared by the unblinded pharmacist or 
authorized designee), as described in the Pharmacy Manual, such that the IV solutions will be 
identical in appearance and supplied in identical IV bags for administration. 
With the exception of the unblinded pharmacist or authorized designee, the investigator, 
study site personnel, clinical research organization (CRO) staff, and sponsor personnel will 
not have access to the randomization scheme during the study except in the case of an 
emergency. 
In the event of a medical emergency, an individual patient’s treatment assignment may be 
unblinded using interactive response technology (IRT). The module to unblind treatment 
assignment is accessible only to specific authorized study personnel. AEs per se are not a 
reason to break the treatment code. Unblinding should only occur for medical emergencies 
that require explicit knowledge of the treatment administered in order to determine the next 
course of action. The IRT vendor operates a 24-hour/365 day helpline as a back-up in the 
rare event the electronic system in unavailable when unblinding is required (refer to IRT 
Manual). 
Only for the safety lead-in will unblinded data be evaluated. Once the Double-blind 
Treatment Phase has commenced, the study will not be unblinded for overall safety 
evaluation. If the blind is broken, the reason and when and how the blind was broken will be 
documented. 
5.4 
Method of Assigning Patients to Treatment Groups 
For the Double-blind Treatment Phase, eligible patients will be randomized 4:4:1:1 to the 
following arms:  
• Arm A: Oral rucaparib + IV nivolumab (n = 400),  
• Arm B: Oral rucaparib + IV placebo (n = 400),  
• Arm C: Oral placebo + IV nivolumab (n = 100), 
• Arm D: Oral placebo + IV placebo (n = 100). 
 
Randomization will occur by a central randomization procedure using an IRT. The following 
will be included as randomization stratification factors at study entry to ensure treatment 
groups are balanced:  
• HRD classification (tBRCA, non-tBRCA LOHhigh, non-tBRCA LOHlow, or 
non-tBRCA LOHunknown) by central laboratory analysis 
• Disease status post-chemotherapy (residual disease vs no residual disease) 
• Timing of surgery (primary surgery vs. interval debulking) 
 

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Prior to randomization in the Double-blind Treatment Phase, an open-label safety cohort will 
be evaluated. A second safety cohort may follow for patients of Japanese ethnicity. Patients 
who provide informed consent and meet all eligibility criteria would be eligible to participate 
in these safety cohorts. 
5.5 
Preparation and Administration of Protocol-specified Treatment 
The investigator or designee will be responsible for distributing oral study drug to all 
patients, and the unblinded pharmacist or authorized designee will be responsible for 
preparing the IV study drug for all patients.  
Study drug (ie, rucaparib/placebo and nivolumab/placebo) will be assigned by the IRT 
according to the patient’s randomization assignment. The IRT will manage all study drug 
supplied by the sponsor. The system should be accessed to record each dispensation of study 
drug, both oral and IV, according to the patient’s randomized treatment. Guidelines for the 
use of the IRT will be provided to study sites.  
Rucaparib and nivolumab will be dispensed by IRT for the open-label safety lead-in portion 
of the study. 
5.5.1 
Rucaparib/Oral Placebo 
Rucaparib 600 mg, or matching placebo, is administered orally BID (as close to 12 hours 
apart as possible, preferably at the same times every day) with at least 8 ounces (240 mL) of 
water starting on Day 1. Study drug (tablets) may be taken with or without food. Tablets 
should be swallowed whole without crushing or chewing. Oral study drug will be provided as 
200, 250, and 300 mg (as free base) dose strength tablets. If a patient vomits after dosing, the 
dose will not be made up; the patient will take their next dose at the regularly scheduled 
interval. 
Each treatment cycle of oral study drug is 28 (± 3) days, and treatment will begin on Day 1 of 
Cycle 1. 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 study drug tablets and all 
containers (empty, partially used, and/or unopened) to the next scheduled visit for 
reconciliation by site personnel.  
5.5.2 
Nivolumab/IV Placebo 
Nivolumab, or matching placebo, is administered IV as a 480 mg via a 30-minute IV infusion 
on Day 1 of every 28-day cycle, starting on Cycle 2. IV study drug infusion should be 
prepared as specified in the Pharmacy Manual. Refer to the current version of the IB and/or 
Pharmacy Manual for complete storage, handling, dispensing, and infusion information. 
5.6 
Dose Modification Criteria 
Doses of oral study drug, and/or IV study drug, may be interrupted or delayed for toxicity 
and other protocol specified criteria. Dose reductions are permitted for oral study drug but 
not for IV study drug. The assessment for delay or discontinuation should be made separately 

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for the oral study drug (rucaparib or placebo) and the IV study drug (nivolumab or placebo); 
however, if toxicity is considered related to all study drugs or if the investigator is unable to 
determine which study drug is the cause of the AE, then all study drugs in the combination 
should be delayed and/or discontinued. Dose delay criteria also apply for the placebo of each 
agent, given the blinded nature of this study. Treatment may be prematurely discontinued due 
to withdrawal of consent, unacceptable toxicity, disease progression, completion of treatment 
cycles, or termination of the study, whichever occurs first. 
An integrated summary of dose modification guidance by CTCAE Grade v5.0 for events 
related to IV and/or oral drug is provided below in Figure 2. In addition to the guidance 
summarized, a dosing delay of ˃ 14 days or ˃ 8 weeks (2 or more consecutive cycles) with 
oral or IV drug, respectively, requires discontinuation except if approved by the study 
medical monitor/designee. More detail is provided in Section 5.6.1 (treatment delay and/or 
interruption), Section 5.6.2 (re-treatment criteria), Section 5.6.3 (dose reduction), and 
Section 5.6.4 (study drug discontinuation). Please also refer to Appendix 8: AE Criteria for 
Delay, Resume and Discontinue of Nivolumab. 

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Figure 2. 
Integrated Dose Modification Guidance for Events Related to IV and/ or Oral Drug by CTCAE Grade 
(CTCAE v5.0)  
 
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AML = acute myeloid leukemia; AST = aspartate aminotransferase; BID = twice a day; 
CTCAE = Common Terminology Criteria for Adverse Events; DRESS = drug reaction with eosinophilia and systemic symptoms; IV = intravenous; 
MDS = myelodysplastic syndrome; SJS = Stevens-Johnson Syndrome; TEN = toxic epidermal necrolysis. 

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5.6.1 
Treatment Delay and/or Interruption 
5.6.1.1 
Rucaparib/Oral Placebo 
Treatment with oral study drug should be held if any of the following are observed: 
• Grade 3 or 4 drug-related hematologic toxicity 
• Grade 3 or 4 drug-related 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 in 
Section 5.6.1.1.1. 
• At the discretion of the investigator, oral study drug may be interrupted or continued if 
new or worsening unexplained pulmonary symptoms suggestive of pneumonitis 
(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 in Section 5.7.2. 
• In addition, and at the discretion of the investigator, the dose of oral study drug may be 
held and/or reduced for Grade 2 toxicity not adequately controlled by concomitant 
medications and/or supportive care. 
 
5.6.1.1.1 
ALT/AST ELEVATIONS 
• Grade 4 ALT/AST elevations: hold oral study drug until values have improved to 
Grade 2 or better, then resume oral study drug with a dose reduction. Monitor liver 
function tests weekly for 3 weeks after oral study drug 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 oral study drug with elevation of ALT/AST up to Grade 3 is 
permitted provided bilirubin is < ULN and alkaline phosphatase is < 3 × ULN.  
- 
If patient has Grade 3 ALT/AST and continues on oral study drug, and levels do not 
decline within 2 weeks or they continue to rise, treatment interruption and 
improvement to ≤ Grade 2 will be required before oral study drug can be resumed, 
either at the current dose or at a reduced dose. 
• ALT or AST > 3 × ULN AND bilirubin > 2 × ULN (suspected DILI).49 
- 
While treatment is interrupted, the patient should be evaluated for the presence of 
confounding factors including malignant disease in the liver, coadministration 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 international normalized ratio (INR) should be implemented as indicated. If 
no alternative cause is identified, oral study drug must be permanently discontinued. 

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- 
Patients should 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. See Section 8.9. 
 
5.6.1.2 
Nivolumab/IV Placebo 
IV study drug administration should be held for the following: 
• Grade 2 non-skin, drug-related AE, with the exception of fatigue and pancreatitis 
• Grade 2 drug-related creatinine (≥ 1.5-3.0 × baseline; > 1.5-3.0 × ULN) or Grade 3 
drug-related creatinine (> 3.0 × baseline; > 3.0-6.0 × ULN) abnormalities 
- 
Baseline is defined as the creatinine value obtained prior to dosing the IV drug on 
C2D1, or first dose of IV drug, whichever is later 
Note: Elevated creatinine is frequently observed with rucaparib monotherapy. 
Rucaparib is a potent inhibitor of MATE1 and MATE2-K transporters, which are 
involved in active secretion of creatinine. Rucaparib-mediated creatinine elevation 
occurs early in treatment (Day 15 of Cycle 1), and is not typically accompanied by 
elevations in urea (blood urea nitrogen [BUN]). Creatinine elevation resolves with 
dose holds of rucaparib and recurs with rechallenge. Rucaparib associated creatinine 
elevation has not been associated with evidence or reports of permanent renal 
impairment. 
• Drug-related AST, ALT, and/or bilirubin abnormalities with the range of AST or ALT > 
3 × and ≤ 5 × ULN or total bilirubin > 1.5 × and ≤ 3 × ULN, regardless of baseline value 
- 
For participants with the above range of AST or ALT elevations with onset during 
dosing of the first cycle of oral study drug, IV study treatment hold is not required if 
AST/ALT elevations begin to resolve before the next scheduled infusion and toxicity 
is considered to be mainly related to oral study treatment. If the patient has an 
existing such elevation, and a subsequent AST/ALT increase of more than 20% is 
observed following infusion of IV study drug, the next IV study drug administration 
will be held and, if further increase is observed, the Hepatic Adverse Event 
Management Algorithm will be followed (see Appendix 7). If AST or ALT or total 
bilirubin elevations are considered mainly related to IV drug, IV drug dosing may 
resume when laboratory values return to baseline. IV drug should be discontinued at 
concurrent AST or ALT > 3 × ULN and total bilirubin > 2 × ULN, regardless of 
baseline value. 
- 
For participants with ALT or AST elevations > 3 × ULN or total bilirubin 
> 1.5 × ULN regardless of baseline value that begin after Cycle 3, the Hepatic 
Adverse Event Management Algorithm will be followed (see Appendix 7). 
Note: Rucaparib may cause transient AST and/or ALT elevations (without increased 
total bilirubin) at Cycle 1, Day 15 that begin to resolve by Day 29, even with 
continued rucaparib dosing.  
• Grade 2 or 3 colitis or diarrhea 

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• Grade 3 pancreatitis with symptoms. Grade 3 increased amylase or lipase without signs 
or symptoms of pancreatitis does not require dose delay 
• Grade 2 rash covering > 30% body surface area or Grade 3 drug-related skin AE. 
Suspected Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or drug 
reaction with eosinophilia and systemic symptoms (DRESS) 
• Endocrinopathies met the following criteria: 
- 
Grade 2 adrenal insufficiency. 
- 
Grade 2 or 3 hyperglycemia requiring initiation or change in daily management. 
- 
Grade 1-3 hypophysitis/hypopituitarism that is symptomatic and also associated with 
corresponding abnormal lab and/or pituitary scan. 
- 
Grade 2 or 3 hyperthyroidism or hypothyroidism. 
• Grade 2 uveitis. 
• Grade 2 neurological (other than Guillain-Barre Syndrome [GBS], myasthenia gravis 
[MG], encephalitis, or myelitis). 
• Any grade of encephalitis or myelitis. After workup for differential diagnosis, 
(ie, infection, tumor-related), if it is not drug related, then dosing may resume when AE 
resolves. 
• Myocarditis with symptoms induced from mild to moderate activity or exertion. 
• Other Grade 3 drug-related AE with first occurrence lasting ≤ 7 days. 
• Grade 3 drug-related laboratory abnormality (not listed above), with the following 
exceptions:  
- 
Grade 3 lymphopenia or Grade 3 increased amylase or lipase without signs or 
symptoms of pancreatitis does not require dose delay.  
- 
Grade 3 thrombocytopenia > 7 days or associated with bleeding requires for dose 
discontinuation. 
- 
AST, ALT, and/or total bilirubin elevations with a range of AST or ALT > 5 × ULN 
or total bilirubin > 3 × ULN, regardless of baseline value, will require dose delay or 
discontinuation. (See Section 5.6.4.2)* 
• Any AE, laboratory abnormality, or intercurrent illness that, in the judgment of the 
investigator, warrants delaying the dose of study medication. 
 
Participants who require dose hold should be re-evaluated weekly or more frequently if 
clinically indicated and resume dosing during the next scheduled dosing window (Cycle X, 
Day 1 ± 3 days) after re-treatment criteria are met (Section 5.6.2).  
Please refer to Appendix 8: AE Criteria for Delay, Resume and Discontinue of Nivolumab. 

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5.6.2 
Retreatment Criteria 
5.6.2.1 
Rucaparib/Oral Placebo 
For patients who meet treatment interruption guidelines in Section 5.6.1, treatment with oral 
study drug should be held until the toxicity improves to ≤ CTCAE Grade 2. Twice a day 
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, treatment should be interrupted, then resumed at a reduced dose following 
improvement of the event to ≤ CTCAE Grade 2. If the patient continues to experience 
toxicity, additional dose reduction steps are permitted (Table 4); however, the investigator 
should consult with the sponsor’s medical monitor before reducing to 300 mg BID. 
If any blood hematology parameters remain clinically abnormal after 4 weeks of dose 
interruption, the patient should be referred to hematologist for further investigations. Bone 
marrow analysis and/or blood cytogenetic analysis should be considered at this stage 
according to standard hematological practice. For management of anemia, please refer to 
Section 5.7.1. 
5.6.2.2 
Nivolumab/IV Placebo 
Participants may resume treatment with IV study drug when the drug-related AE(s) improve 
to Grade ≤ 1 or resolve to baseline value, with the following exceptions: 
• Participants may resume treatment in the presence of Grade 2 fatigue and pancreatitis. 
• Participants who are suspected with SJS, TEN, or DRESS may resume treatment if SJS, 
TEN, or DRESS are ruled out and rash reduces to ≤ 10% body surface area. 
• For participants with elevated AST, ALT, or total bilirubin elevations, dosing may 
resume when laboratory values return to baseline and management with corticosteroids, if 
needed, is complete. 
• Drug-related pulmonary toxicity, diarrhea or colitis must have resolved to baseline before 
treatment is resumed. Participants with persistent Grade 1 pneumonitis after completion 
of a steroid taper over at least 1 month may be eligible for retreatment if discussed with 
and approved by the study medical monitor.  
• Participants with Grade 2 uveitis may resume treatment if uveitis responds to topical 
therapy (eye drops) and after uveitis resolves to Grade ≤ 1 or baseline. If patient requires 
oral steroids for uveitis, then permanently discontinue study drug.  
• For visual complaints, patients should be referred to an ophthalmologist following the 
guidance in Section 7.1.10 of the nivolumab Investigator’s Brochure. 
 
Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment after consultation with the study medical 
monitor.  

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Participants with Grade 2 neurological (other than GBS, MG, encephalitis, or myelitis) may 
resume when AE resolves to baseline 
If the criteria to resume treatment are met, the patient should restart treatment at the next 
scheduled timepoint per protocol. However, if the treatment is withheld past the window 
period of the next scheduled timepoint per protocol to ensure adequate recovery from the 
adverse event or tapering of immunosuppression, the dosing should continue to be withheld 
until the subsequent scheduled timepoint. 
If treatment is withheld > 8 weeks from the last dose (2 or more consecutive IV drug cycles 
missed), the subject must be permanently discontinued from study therapy, except as 
specified in Section 5.6.4.2.  
Please refer to Appendix 8: AE Criteria for Delay, Resume and Discontinue of Nivolumab. 
5.6.3 
Dose Reduction 
There will be no dose modifications permitted for IV study drug. 
5.6.3.1 
Rucaparib/Oral Placebo 
The dose reduction steps for oral study drug are presented in Table 4. 
Dose escalation upon improvement 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 
electronic case report form (eCRF). 
Table 4. 
Oral Study Drug 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. 
 
5.6.4 
Study Drug Discontinuation 
Rucaparib/oral placebo and/or nivolumab/IV placebo should be discontinued according to the 
criteria specified below. The decision to discontinue each agent may be made independently 
of one another. However, if the toxicity is considered related to all study drugs or if the 

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investigator is unable to determine which study drug is the cause of the AE, then both oral 
and IV study drug must be discontinued. 
5.6.4.1 
Rucaparib/Oral Placebo 
Oral study drug should be permanently discontinued for any of the following: 
• If a participant continues to experience drug-related toxicity despite dose reduction steps 
to 200 mg BID or if dosing with oral study drug is interrupted for > 14 consecutive days 
due to toxicity, treatment should be discontinued, with the following exceptions: 
- 
Dosing delay > 14 days may be allowed if approved by the study medical 
monitor/designee. Prior to re-initiating treatment in a participant with a dosing delay 
lasting > 14 days, the study medical monitor/designee must be consulted. Tumor 
assessments should continue as per protocol even if dosing is delayed. 
• Confirmed MDS/AML. 
• Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued oral 
study treatment dosing. 
 
5.6.4.2 
Nivolumab/IV Placebo 
Nivolumab/IV placebo should be permanently discontinued for any of the following: 
• Any Grade of GBS, MG and drug-related encephalitis and myelitis 
• Any Grade 3 non-skin, drug-related AE lasting > 7 days or that recurs with any duration, 
with the following exceptions laboratory abnormalities, drug-related uveitis, pneumonitis, 
myocarditis, bronchospasm, neurologic toxicity, hypersensitivity reactions, infusion 
reactions, and endocrinopathies: 
- 
Grade 3 drug-related uveitis, pneumonitis, myocarditis, bronchospasm, neurologic 
toxicity, hypersensitivity reaction, or infusion reaction of any duration requires 
discontinuation 
- 
Grade 3 drug-related endocrinopathies, adequately controlled with only physiologic 
hormone replacement do not require discontinuation. 
- 
Grade 3 drug-related laboratory abnormalities do not require treatment 
discontinuation except: 
◦ 
Grade 3 drug-related thrombocytopenia >7 days or associated with bleeding 
requires discontinuation 
◦ 
AST, ALT, or total bilirubin elevations with AST or ALT > 5 × ULN or total 
bilirubin > 3 × ULN, regardless of baseline value, requires dose delay or 
discontinuation* 
*In most cases of such AST or ALT elevation, IV study drug will be 
permanently discontinued. For participants with such AST or ALT elevations 
after the start of IV dosing, but on a background of previous elevations on the 

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first cycle of oral study drug, IV study drug hold is required, but discontinuation 
is not required, if AST/ALT elevations begin to resolve before the next 
scheduled infusion, and toxicity is considered to be mainly related to oral study 
treatment, after the investigator discusses the case with the study medical 
monitor. Levels will be monitored every 3 days; if they continue to rise more 
than 20%, the Hepatic Adverse Event Management Algorithm will be followed 
(see Appendix 7). Treatment with IV drug may be resumed if levels return to an 
ALT and ALT < 5 × ULN, and total bilirubin < 3 × ULN. If AST or ALT or total 
bilirubin elevations are considered mainly related to IV drug, and the investigator 
determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, a discussion between the investigator and the Medical Monitor/ 
designee must occur and approval from Medical Monitor prior to resuming 
therapy. IV drug dosing may resume when laboratory values return to baseline. 
• Any Grade 4 drug-related AE or laboratory abnormality (including but not limited to 
creatinine, AST, ALT, or total bilirubin), except for the following events that do not 
require discontinuation: 
- 
Grade 4 neutropenia ≤ 7 days 
- 
Grade 4 lymphopenia  
- 
Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with 
clinical sequelae and are corrected with supplementation/appropriate management 
within 72 hours of their onset 
- 
Grade 4 drug-related endocrinopathy AEs, such as, hyper- or hypothyroidism, or 
glucose intolerance and adrenal insufficiency, that resolve or are adequately 
controlled with physiologic hormone replacement (corticosteroids, thyroid hormones) 
or glucose-controlling agents, respectively, may not require discontinuation after 
mandatory discussion with and approval from the study medical monitor/designee.  
• Grade 3 or 4 hypersensitivity reaction or infusion reaction. Please refer to Section 5.9 on 
Treatment of Related Infusion Reactions 
• Any event that leads to delay in dosing lasting > 8 weeks (2 or more consecutive IV drug 
cycles missed) from the previous dose requires discontinuation, with the following 
exceptions: 
- 
Dosing delays to allow for prolonged steroid tapers to manage drug-related AEs are 
allowed. 
- 
Dosing delays lasting > 8 weeks (2 or more consecutive IV drug cycles missed) from 
the previous dose that occur for non-drug-related reasons may be allowed if approved 
by the study medical monitor/designee. 
Prior to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks (2 or 
more consecutive IV drug cycles missed), the study medical monitor must be consulted. 
Tumor assessments should continue as per protocol even if dosing is delayed. Periodic 
study visits to assess safety and laboratory studies should also continue every 6 weeks or 
more frequently if clinically indicated during such dosing delays. 

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• Any AE, laboratory abnormality, or intercurrent illness that, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued IV study 
drug dosing. 
 
Please refer to Appendix 8: AE Criteria for Delay, Resume and Discontinue of Nivolumab. 
5.7 
Management Algorithms for Oral Study Drug 
5.7.1 
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 8.3 and 8.7 of the protocol for additional information regarding 
classification and reporting of MDS or AML as an AESI. 
5.7.2 
Management of New or Worsening Pulmonary Symptoms Suggestive of 
Pneumonitis 
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 oral study drug may be interrupted or continued per 
investigator discretion. The contribution of IV study drug should also be assessed 
independently. 
Following investigation, if pneumonitis is not confirmed, treatment with oral study drug 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 oral study drug is being considered, please consult the 
study medical monitor. Re-treatment with oral study drug may be resumed at the current or a 
reduced dose, if appropriate.  
Refer to Sections 8.3 and 8.7 of the protocol for additional information regarding 
classification and reporting of pneumonitis (and similar events) as an AESI. 
5.8 
Management Algorithms for Immuno-Oncology Agents 
Immuno-oncology (I-O) agents are associated with AEs that can differ in severity and 
duration than AEs caused by other therapeutic classes. Nivolumab is considered an I-O agent 
in this protocol. Early recognition and management of AEs associated with I-O agents may 

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mitigate severe toxicity. Management Algorithms have been developed to assist investigators 
in assessing and managing the following groups of AEs: 
• Gastrointestinal 
• Renal 
• Pulmonary 
• Hepatic 
• Endocrinopathy 
• Skin 
• Neurological 
• Myocarditis 
 
The above algorithms are found in Appendix 7 of this protocol. 
5.9 
Treatment of Infusion-related Reactions 
Since nivolumab contains only human immunoglobulin protein sequences, they are unlikely 
to be immunogenic and induce infusion or hypersensitivity reactions. However, if such a 
reaction were to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like reactions. All 
Grade 3 or 4 infusion reactions should be reported within 24 hours to the study medical 
monitor and reported as an SAE if it meets the criteria. Infusion reactions should be graded 
according to NCI CTCAE (v5.0) guidelines. 
Treatment recommendations are provided below and may be modified based on local 
treatment standards and guidelines, as appropriate: 
For Grade 1 symptoms: (mild reaction; infusion interruption not indicated; intervention not 
indicated): 
• Remain at bedside and monitor participant until recovery from symptoms. The 
following prophylactic premedications are recommended for future infusions: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 
1000 mg at least 30 minutes before additional IV study drug administrations. 
 
For Grade 2 symptoms: (moderate reaction required therapy or infusion interruption but 
responds promptly to symptomatic treatment (eg, antihistamines, non-steroidal 
anti-inflammatory drugs, narcotics, corticosteroids, bronchodilators, IV fluids); prophylactic 
medications indicated for ≤ 24 hours): 
• Stop the study treatment infusion, begin an IV infusion of normal saline, and treat the 
participant with diphenhydramine 50 mg IV (or equivalent) and/or 

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acetaminophen/paracetamol 325 to 1000 mg; remain at bedside and monitor 
participant until resolution of symptoms. Corticosteroid and/or bronchodilator therapy 
may also be administered as appropriate. If the infusion is interrupted, then restart the 
infusion at 50% of the original infusion rate when symptoms resolve; if no further 
complications ensue after 30 minutes, the rate may be increased to 100% of the 
original infusion rate. Monitor participant closely. If symptoms recur, then no further 
study treatment will be administered at that visit. 
• For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 
1000 mg should be administered at least 30 minutes before IV study drug infusion. If 
necessary, corticosteroids (up to 25 mg of hydrocortisone or equivalent) may be used 
 
For Grade 3 or 4 symptoms: (severe reaction, Grade 3: prolonged [ie, not rapidly 
responsive to symptomatic medication and/or brief interruption of infusion]; recurrence of 
symptoms following initial improvement; hospitalization indicated for other clinical sequelae 
(eg, renal impairment, pulmonary infiltrates). Grade 4: Life-threatening; pressor or 
ventilatory support indicated): 
• Immediately discontinue infusion of study drug. Begin an IV infusion of normal 
saline and treat the participant as follows: Recommend bronchodilators, epinephrine 
0.2 to 1 mg of a 1:1000 solution for subcutaneous administration or 0.1 to 0.25 mg of 
a 1:10,000 solution injected slowly for IV administration, and/or diphenhydramine 
50 mg IV with methylprednisolone 100 mg IV (or equivalent), as needed. Participant 
should be monitored until the investigator is comfortable that the symptoms will not 
recur. Study drug will be permanently discontinued. Investigators should follow their 
institutional guidelines for the treatment of anaphylaxis. Remain at bedside and 
monitor participant until recovery of the symptoms. 
 
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or 
generalized pruritus within 1 week after treatment), symptomatic treatment may be given 
(eg, oral antihistamine or corticosteroids). 
5.10 Interruption of Study Drug for On-study Procedures 
In the case where a patient must undergo a procedure or surgery after the start of dosing 
(eg, ileostomy or colostomy reversal), management of oral and IV drug should proceed as 
follows: 
Oral drug should be held for 3-4 days (5x half-life) prior to planned procedure, and resumed 
once the patient has fully recovered, in the opinion of the investigator. 
IV drug may be continuously administered, at the discretion of the investigator. If possible, 
the procedure should be planned as close to the mid-way point of the cycle as possible 
(Week 2 of a 4-week cycle), and no less than 1 week before or after an IV drug 
administration. If the procedure must occur within 1 week of a scheduled IV drug 

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administration, the investigator should hold IV drug during that cycle, and restart once the 
patient has sufficiently recovered. 
5.11 Treatment Compliance 
5.11.1 
Rucaparib/Oral Placebo Treatment Compliance 
Documentation of dosing will be recorded in a study specific dosing diary provided by the 
sponsor (or designee). Dosing noncompliance is defined as a patient missing > 14 days of 
medication in a 28-day window for 2 consecutive visits for a nonprotocol-specified reason. 
The sponsor may require patients meeting noncompliance criteria to discontinue study 
treatment. 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. 
Additional details regarding study drug dispensation and return can be found in the pharmacy 
manual. 
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. 
5.11.2 
Nivolumab/IV Placebo Treatment Compliance 
Each dose of IV study drug will be prepared by an unblinded pharmacist or authorized 
designee and transferred to a blinded infusion set. The infusion will then be monitored by the 
investigator or study coordinator. Treatment compliance will be monitored by drug 
accountability, and any preparation of infusion deviations (eg, infusion less/greater than 
30 min) will be recorded on the patient’s eCRF.  
5.12 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 site. 
The site is responsible for the return or destruction of study drug supplied by the sponsor. 
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. All study 
drug containers must be accounted for prior to their destruction at the study center, according 
to institutional procedures for disposal of hazardous materials. Unused study drug product 

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and containers should be destroyed on-site if possible. If destruction on site is not possible, 
supply should be returned to the drug depot, following the sponsor’s instructions. 
During the course of the study and at completion of the study, the number of study drug units 
and containers received, dispensed, returned, and destroyed must be recorded and reconciled. 
Additional details regarding study drug accountability can be found in the pharmacy manual.  
5.13 Treatment of Study Drug Beyond Disease Progression 
Patients will receive study drug until confirmed radiologic disease progression as assessed by 
investigator using RECIST Version 1.1 criteria, unacceptable toxicity or inability to tolerate 
further treatment, loss to follow-up, death, or withdrawal of consent.  
If a patient receiving study drug has met criteria for confirmed radiologic disease progression 
by RECIST Version 1.1 criteria, but the patient continues to derive clinical benefit per the 
investigator, then continuation of treatment will be permitted. In such cases, the 
investigator’s decision to continue treatment should be documented in the source documents 
and the patient must provide additional consent prior to continuing treatment with study drug. 
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 study drug will continue to have all protocol-required assessments as 
described in Section 7. 
Continuation of randomized treatment will be considered for a maximum cumulative 
duration of 24 months after initiation of oral/IV combination study treatment. 
 
 

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6 
PRIOR AND CONCOMITANT THERAPY 
Drug-drug interactions between nivolumab and rucaparib are unlikely (see Section 1.1.2.2). 
Patients who have received prior treatment for ovarian cancer, other than the front-line 
platinum regimen, including any treatments in the maintenance setting, are not eligible to 
participate in this study; ongoing hormonal treatment for previously treated breast cancer is 
permitted. Patients who have received prior treatment with a PARP inhibitor including IV or 
oral rucaparib or a PD-1/ PDL-1 targeting agent are not eligible to participate in this study.  
All procedures performed (eg, thoracentesis, etc.) during the study must be documented on 
the eCRF. 
6.1 
Supportive Care 
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.  
Erythropoietin, darbepoetin alfa, and/or hematopoietic colony-stimulating factors for 
treatment of cytopenias should be administered per standard of care and according to 
institutional guidelines. Transfusion thresholds for blood product support will be in 
accordance with institutional guidelines. 
6.2 
Radiotherapy 
Palliative radiotherapy on lesions not considered target lesions for tumor evaluation is 
permitted during the study. Treatment with study drug should be held prior to initiation of 
radiation therapy and until the patient has recovered from any radiation related toxicity. 
6.3 
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 palliative radiotherapy and hormonal treatment. Prior treatment 
with such excluded anticancer therapies must have been completed > 14 days prior to the 
first dose of study drug. 
6.4 
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 on rucaparib taking concomitant medicines that are 
sensitive substrates of CYP1A2, CYP2C9, and/or CYP3A (Appendix 4). Selection of an 
alternative concomitant medication is recommended. 

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Although in vitro rucaparib metabolism is mediated by CYP3A4, results from 
Study CO-338-107 showed that concomitant use of the strong CYP3A4 inducer 
enzalutamide had no clinically significant effect on rucaparib PK. 
6.4.1 
Transporter Inhibitors, Inducers, and Substrates 
Based on the results from Study CO-338-095, rucaparib has no clinically significant effect on 
the PK of oral rosuvastatin, a sensitive BCRP substrate. 
6.5 
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. 
6.6 
Immunosuppressive Agents 
Immunosuppressive agents are prohibited, with the exception of inhaled or topical steroids, 
and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, in the absence of 
active autoimmune disease. Participants are permitted the use of topical, ocular, 
intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic 
absorption). Adrenal replacement steroid doses > 10 mg daily prednisone are permitted. A 
brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) 
or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction 
caused by a contact allergen) is permitted. 
Participants with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 
14 days of treatment assignment are excluded.  
6.7 
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.  

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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.  
6.8 
Imaging Restrictions and Precautions 
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history and renal status), the appropriate imaging modality and 
contrast regimen for each participant. Oral and/or IV contrast should be used whenever 
possible and appropriate, and rectal contrast should only be considered in patients with 
peritoneal disease. Imaging contraindications and contrast risks should be considered in this 
assessment. Participants with renal insufficiency should be assessed as to whether or not they 
should receive contrast and if so, what type and dose of contrast is appropriate. Specific to 
MRI, participants with severe renal insufficiency (ie, estimated GFR < 30 mL/min/1.73 m2) 
are at increased risk of nephrogenic systemic fibrosis. MRI contrast should not be given to 
this participant population. In addition, participants are excluded from MRI if they have 
tattoos, metallic implants, pacemakers, etc. 
The ultimate decision to perform MRI in an individual participant in this study rests with the 
site radiologist, the investigator and the standard set by the local IEC. 
6.9 
General Restrictions 
Photosensitivity has been observed in patients treated with rucaparib. Patients should avoid 
spending time in direct sunlight because they burn more easily during treatment with 
rucaparib. When outdoors, patients should use typical precautions such as applying sunscreen 
(sun protection factor 50 or greater) and/or covering exposed skin with clothing and wearing 
a hat and sunglasses. 
 

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7 
STUDY PROCEDURES AND METHODS 
7.1 
Schedule of Assessments 
Table 5 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. 
Table 6 summarizes the timing of collection of PK and immunogenicity samples.  
Imaging guidelines provided by the BICR vendor should be followed for the collection of 
images and the radiological assessment of disease.  
All serum chemistry, hematology, serology testing, tumor tissues (screening and optional 
sample at the time of disease progression/randomized treatment discontinuation), CA-125, 
PK samples, and all study required blood samples will need to be sent to central laboratories 
for processing. Please refer to study laboratory manuals for detailed collection and shipment 
requirements. 

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Table 5. 
Schedule of Assessments for All Patients 
 
Screening Phase 
Randomizationb 
Treatment Phase 
28-day cycles ± 3 days 
Post-Treatment Follow-up Phase 
 
Cycles 1 & 
2 
Cycles 3+ 
Procedurea 
Pre-Randomization 
Day 
1 
Day 
15 
Day 1 
End of 
Treatment 
Safety 
Follow-up 
(×2)c 
Long-
term 
Follow
-up 
Day -120 
to Day-1 
Day -28 to 
Day -1 
Day -14 to 
Day -1 
Informed Consentd 
X 
 
 
 
 
 
 
 
 
 
Medical/Oncology Historye 
X 
 
 
 
 
 
 
 
 
 
Tumor Tissue Sample (central lab)f 
X 
 
 
 
 
 
 
 
 
 
Physical Examination, Heightg, Weight 
X 
 
 
X 
 
X 
X 
X 
 
Vital Signsh 
X 
 
 
X 
X 
X 
X 
X 
 
12-lead ECGi 
 
X 
 
 
 
 
 
X 
X 
 
Prior/Concomitant 
Medications/Procedures  
X 
 
 
X 
X 
X 
X 
X 
 
Disease/ Tumor assessmentsj 
X 
 
 
 
 
Xk 
Xl  
Xl 
Xl 
Patient-reported outcome (TOI FACT-O, 
EQ-5D-5L)m 
 
X 
 
 
X 
 
X 
X 
X 
 
ECOG Performance Status 
X 
 
 
X 
X 
X 
X 
X 
 
Hematology (central lab)n 
 
X 
 
X 
X 
X 
X 
Xc 
 
Serum Chemistryo including Hep B and 
C testing (central lab, non-fasting) 
 
X 
 
X 
X 
X 
X 
Xc 
 
Urinalysisp 
 
X 
 
 
 
 
CA-125 Measurement (central lab)q 
 
X 
 
X 
 
X 
X 
X 
X 
 

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Table 5. 
Schedule of Assessments for All Patients (cont.) 
 
Screening Phase 
Randomizationb 
Treatment Phase 
Post-Treatment Follow-up Phase 
 
Cycles 1 & 
2 
Cycles 3+ 
Procedurea 
Pre-Randomization 
Day 
1 
Day 
15 
Day 1 
End of 
Treatment 
Safety 
Follow-up 
(×2)c 
Long-
term 
Follow
-up 
Day -120 
to Day-1 
Day -28 to 
Day -1 
Day -14 to 
Day -1 
Randomization to Study Treatment 
 
 
 
Xr 
 
 
 
 
 
 
Blood Sample for g/sBRCA status 
(central lab) 
 
 
 
 
Xs 
 
 
 
 
 
Blood Sample for ctDNA Analysis 
(central lab)t 
 
X 
 
 
X 
 
X 
X 
X 
 
Oral Study Drug Dispensationb 
 
 
 
 
Xb 
 
X 
 
 
 
IV Study Drug Administrationu 
 
 
 
 
Xu 
 
X 
 
 
 
Adverse Eventsv 
(X) 
(X) 
(X) 
 
X 
X 
X 
Xv 
Xv 
Xv 
Blood Sample for PK (central lab) 
Refer to Table 6 for sampling schedule 
Blood Sample for Immunogenicity 
(central lab) 
Refer to Table 6 for sampling schedule 
Post-Treatment Tumor Tissue Biopsy 
(central lab, OPTIONAL; consent 
required) 
 
 
 
 
Xw 
 
Subsequent Treatments, Secondary 
Malignancy Monitoring, and Overall 
Survivalx 
 
 
 
 
 
 
 
X 
X 
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; BICR = blinded independent central radiology review; BUN = blood urea nitrogen; 
CA-125 = cancer antigen-125; CO2/HCO3- = bicarbonate; CR = complete response; CT = computer tomography; ctDNA = circulating tumor deoxyribonucleic acid; 
C2D1 = Cycle 2 Day 1; eCRF = electronic case report form; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EQ-5D-5L = Euro-QoL 5D-5L; 
FACT-O = Functional Assessment of Cancer Therapy – Ovarian; fT3 = free triiodothyronine; fT4 = free thyroxine; QoL= quality of life; Hct = hematocrit; HIV = 
human immunodeficiency virus; Hep B and C = hepatitis B and C; Hgb = hemoglobin; HIV = human immunodeficiency virus; HRD = homologous recombination 

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Table 5. 
Schedule of Assessments for All Patients (cont.) 
deficiency; IRT = interactive response technology; IV = intravenous; gBRCA = germline breast cancer gene; GCIG = Gynecologic Cancer Intergroup; 
GFR = glomerular filtration rate; LDH= lactate dehydrogenase; LOH = loss of heterozygosity; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular 
hemoglobin concentration; MCV = mean corpuscular volume; MDS = myelodysplastic syndrome; MRI = magnetic resonance imaging; PET = positron emission 
tomography; PK = pharmacokinetic; RBC= red blood cell count; RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; 
SFU1 = Safety Follow-up Visit 1; SFU2 = Safety Follow-up Visit 2; T3 = triiodothyronine; T4 = thyroxine; tBRCA = tumor tissue alteration in BRCA1 or BRCA2, 
includes gBRCA and sBRCA; TOI = trial outcome index; TSH= thyroid stimulating hormone; ULN = upper limit of normal; WBC = white blood cell; 
WOCBP = women of child bearing potential. 
a = The study visit window in the treatment phase is ± 3 days, unless noted otherwise for a particular assessment. Study visits should take into account the subject’s 
investigational product supply. Only 1 cycle of oral study drug will be dispensed to the subject on Day 1 of each cycle. 
b = First dose of oral study drug in Cycle 1 should be administered within 3 days of enrollment/randomization. Study treatment continues in 28-day cycles (± 3 days) until 
24 months after initiation of oral/IV combination study treatment, disease progression, or unacceptable toxicity, whichever happens first. 
c = Patients must be followed for at least 5 months after last IV dose of study treatment. Safety Follow-up Visit 1 (SFU1) should occur 28 days (±7) from the last dose of study 
drug (oral or IV, whichever is later) or can be performed on the date of discontinuation if that date is at least 28 days from last dose. Safety Follow-up Visit 2 (SFU2) 
occurs approximately 5 months (± 7) from last IV dose of study drug. Chemistry and hematology are only necessary at SFU2 if toxicities are present. Both follow up visits 
should be conducted in person. If a patient remains on oral study drug after discontinuation of IV study drug, the 5-month Safety Follow-up Visit can be performed at a 
cycle visit, provided it has been at least 5 months since the last IV dose. 
d = Consent may be completed outside the 120-day screening window as consent does not expire. Reconsent is not required if outside the screening window. The screening 
period begins with the first study-specific procedure, performed outside standard of care, and only after consent for study participation has been provided. 
e = Patient’s medical record must include prior treatments received, dates of administration, date of progression and how assessed, and radiology reports. BRCA1/2 mutation 
status and if germline or somatic, if known, will also be recorded on the appropriate eCRF. Medical history should be updated within 3 days of the first dose of study drug. 
f 
= Adequate tumor tissue samples must be provided to enable determination of HRD status for randomization, determination of HRD status prior to final analysis (if required. 
The sample from primary surgery should be provided as well as a core biopsy sample prior to neoadjuvant treatment, if applicable. Submission of a tumor block and tumor 
content ≥ 30% is strongly preferred. Sample must be submitted to the central laboratory at least 3 weeks prior to planned start of treatment in order to enable 
stratification for randomization. 
g = Height at screening only. 
h = Vital signs (blood pressure, pulse, and temperature) to be taken predose on drug administration days, after the patient has been resting for at least 5 min. 
i 
= Heart rate, PR, QRS, QT, QTc, and rhythm. Investigator to review results and assess as normal or abnormal (clinically significant or not clinically significant). ECGs to be 
repeated throughout the study as clinically indicated, at the Treatment Discontinuation Visit, and at both SFUs 1 (28-day post-treatment discontinuation) and 2 (5-month 
post-IV treatment discontinuation). 
j 
= Disease assessments to consist of clinical examination and appropriate imaging techniques per RECIST (CT and/or MRI scans of the chest, abdomen and pelvis, with 
appropriate slice thickness per RECIST). Other complementary studies (X-ray, PET, and ultrasound) may 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. CT/ MRI scans of the chest, abdomen, and pelvis performed to determine the 
extent of disease at baseline should also be performed at each time of disease assessment, even if the scans were negative at baseline. All study-related scans should be 
submitted to the BICR vendor for central read.  

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Table 5. 
Schedule of Assessments for All Patients (cont.) 
k = Tumor scans to be performed every 12 calendar weeks (a 7-day window prior is permitted) relative to Cycle 2 Day 1 (C2D1) for the first 3 years and every 24 weeks 
thereafter until objective radiological disease progression. Disease progression will only be determined by RECIST v1.1. Patients with a CR at study entry will only be 
considered to have disease progression if a new lesion is identified. Patients who meet GCIG CA-125 criteria for disease progression should have a radiologic assessment 
and be assessed by RECIST v1.1. If the radiologic assessment does not confirm disease progression, patients should continue on treatment and continue to be assessed by 
RECIST v1.1 per the protocol schedule of assessments.  
l 
= To be performed every 12 weeks (within 7 days prior is permitted) relative to C2D1 for the first 3 years and every 24 weeks thereafter until investigator-assessed 
radiologic disease progression by RECIST v1.1 or initiating subsequent anticancer treatment for any patient who discontinued from study treatment for reason other than 
disease progression or death. Tumor scans at the End-of-Treatment Visit are only required if it has been 12 weeks or more since the last scan. 
m = The TOI FACT-O and EQ-5D-5L assessments must be completed prior to other scheduled study procedures and dosing (if applicable) at Screening, on Day 1 (Cycle 1 
through 3, and Cycle 5), then every 12 weeks (aligning with CT scans) until treatment discontinuation. In addition, PRO assessments will be performed at the End-of-
Treatment Visit, at the SFU1 (28-day post-treatment discontinuation) and the SFU2 (5-month post-IV treatment discontinuation) for all patients.  
n = 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 
central laboratory. A duplicate sample may be collected and analyzed by the local laboratory for immediate eligibility/treatment decisions. 
o = Includes total protein, albumin, creatinine or estimated GFR using the Cockcroft Gault formula, BUN or urea, total bilirubin, ALP, ALT, AST, total cholesterol, glucose, 
sodium, potassium, magnesium, chloride, CO2/HCO3, calcium, phosphorus, LDH, folic acid (first 6 cycles only), TSH, Free T3, Free T4 at screening; TSH, with reflexive 
fT3 and fT4 if TSH is abnormal on treatment. If pancreatitis is suspected clinically, serum lipase and amylase should be analyzed. Blood will be analyzed by a central 
laboratory. A duplicate sample may be collected and analyzed by the local laboratory for immediate eligibility/treatment decisions. Tests for hepatitis C antibody and 
hepatitis B surface antigen are required at screening. Testing for HIV must also be performed at screening if mandated locally by a given site. 
p = 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.  
q = CA-125 measurement should be performed at screening and on Day 1 of every subsequent cycle, at treatment discontinuation, in follow-up, and as clinically indicated. If a 
patient discontinues treatment for reasons other than disease progression, then a sample should be taken at the same time as radiological imaging.  
r 
= Randomization to study treatment must occur within 8 weeks following a patient’s first day of the last cycle of chemotherapy and oral study treatment must begin within 
3 days of randomization. Randomization will occur by a central randomization procedure using an IRT. Patients will be stratified based on HRD classification (tBRCA, 
non-tBRCA LOHhigh, non-tBRCA LOHlow, and non-tBRCA LOHunknown), disease status (no residual disease vs residual disease), and timing of surgery (primary surgery vs 
interval debulking). 
s = If sample is not collected on Day 1 of Cycle 1, it should be collected as soon as possible thereafter. 
t 
= Screening, Day 1 of Cycle 1 through Cycle 6 and at the same time as radiological imaging thereafter, and at the End of Treatment Visit and Safety Follow-up. If a patient 
discontinues treatment for reasons other than disease progression, then a sample should be taken at the same time as radiological imaging. 
u = First dose of IV study drug occurs C2D1. Study treatment continues on Day 1 every 28-day cycle until 24 months after initiation of oral/IV combination study treatment, 
disease progression, or unacceptable toxicity, whichever happens first. 

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Table 5. 
Schedule of Assessments for All Patients (cont.) 
v = AEs, SAEs, and AESIs that occur after first administration of study drug through to 28 days after last dose of oral or IV study drug, whichever occurs later, and AEs/SAEs 
assessed as related to IV drug that occur up to 5 months after the last IV dose of study drug will be recorded. In addition, AEs that were related to a screening procedure 
will also be recorded. Section 8 includes the details of reporting AEs, SAEs, and AESIs. Ongoing SAEs, AESIs, or treatment-related Grade 3/4 AEs will be followed to 
resolution or stabilization. After the 28-day (oral) or 5-month (IV) windows, only SAEs considered as potentially study-drug related (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 myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) regardless of 
causality, will be recorded. If a patient discontinues from treatment and begins a subsequent anticancer therapy, the sponsor will terminate collection of SAEs, with the 
exception of the AESIs of MDS and AML. 
w = An optional tumor biopsy may be collected from patients at time of disease progression/randomized treatment discontinuation. Additional consent is required. Refer to the 
central Laboratory Manual for detailed sample collection and handling instructions. 
x = All patients discontinued from treatment, regardless of reason, should be followed for subsequent treatments, secondary malignancy, and survival every 12 weeks 
(± 14 days) after SFU1 (28-days after the last dose of study drug) 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 8.7. 
 
 
 

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Table 6. 
Pharmacokinetic and Immunogenicity Sample Collections 
Study Day (Cycle, Day)a 
(1 Cycle = 28 days) 
Time (Event) 
Time (Relative to 
Start of Infusion) 
Pharmacokinetic 
Blood Sample for 
Nivolumab 
Immunogenicity 
Blood Sample 
for Nivolumab 
Pharmacokinetic 
Blood Sample for 
Rucaparibb 
C2D1 
(Predose)c 
00:00 
X 
X 
X 
(EOI)d 
00:30 
X 
 
 
C3D1 
(Predose)c 
00:00 
X 
 
X 
C4D1 
(Predose)c 
00:00 
 
 
X 
C6D1 
(Predose)c 
00:00 
X 
X 
X 
CXD1: Every 4 cycles after C6 D1 (ie, C10D1, C14D1, 
etc.) 
(Predose)c 
00:00 
X 
X 
 
Safety Follow-up Visits 1 & 2 (28 days and 5 months, 
respectively, from the treatment discontinuation during 
the Treatment Phase or at 24 months after initiation of 
oral/IV combination study treatment) 
NA 
NA 
X 
X 
 
Abbreviations: C = cycle; D = day; EOI = end of infusion; IV = intravenous; NA = not applicable; PK = pharmacokinetic; SFU1 = Safety Follow-up Visit 1; 
SFU2 = Safety Follow-up Visit 2.  
a = If a participant discontinues study drug treatment during the sampling period (ie, prior to 24 months after initiation of oral/IV combination study 
treatment), all subsequent CXD1 samples will be inapplicable, but samples will be collected on the 28-day SFU1 and the 5-month SFU2 for nivolumab 
PK and immunogenicity analysis. 
b = PK samples for rucaparib are to be collected approximately 12 hours after the last dose, but prior to the next dose (ie, within 1 hour). If dosing is held for 
toxicity or any other reason, PK sample should still be collected at the end of treatment Cycles 1, 2, 3, and 5. 
c = All predose samples for nivolumab should be taken (preferably within 30 minutes) prior to the start of nivolumab infusion. If it is known that a dose is 
going to be delayed, then the predose sample should be collected just prior to the delayed dose. However, if a predose sample is collected but the dose is 
subsequently delayed, an additional predose sample should not be collected. 
d = EOI-nivo: EOI samples should be collected immediately (preferably within 5 minutes) prior to stopping nivolumab infusion. If the end of infusion 
is delayed, the collection of the EOI samples should be delayed accordingly. Please ensure accurate collection of time/date of sample collection. EOI 
samples may not be collected from the same IV access as drug was administered. 

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7.2 
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. A separate consent form may be used for tissue 
testing. 
Analysis of tumor tissue for a deleterious BRCA1/2 mutation (germline or somatic) will be 
performed using the Foundation Medicine’s NGS test (germline/somatic status will not be 
differentiated as such in the test report). These results 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 mutations other than BRCA1/2 are identified 
by the NGS test, they will also be provided to patients who consent to receive this 
information when they discontinue from treatment. 
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.  
All procedures and assessments are to be completed within ± 3 days of the scheduled time 
unless otherwise stated. 
7.3 
Screening Phase 
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 to be used as a study procedure 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. 
Consent may be completed outside the 120-day screening window as consent does not 
expire. Reconsent is not required if outside the screening window. The screening period 
begins with the first study-specific procedure, performed outside standard of care, and only 
after consent for study participation has been provided. 
7.3.1 
Within 120 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 
ovarian, primary peritoneal, or fallopian tube cancer (and other malignancy, if 
applicable), prior surgeries/treatments received for cancer, dates of treatment 

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administration, best response achieved, 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 × 4 µm section for H&E and approximately 8 to 12 × 10 µm sections 
[unstained], or equivalent) is required for study participation per inclusion criteria #9. In 
addition to this minimum requirement, it is highly desirable to have additional 4 × 4 µm 
sections and 2 × 10 µm sections for other planned analyses. Refer to Section 7.5.7.1 for 
more information and to the central Laboratory Manual for detailed sample handling 
instructions.  
- 
Tumor tissue from the cytoreductive surgery must be provided.  
- 
Tumor tissue from a pre-treatment biopsy should be provided, if available, for 
patients treated with neoadjuvant chemotherapy (a core biopsy is preferred). 
- 
Submission of a tumor block preferred; if sections are provided, these must all be 
from the same tumor sample. 
- 
Tumor content ≥ 30% is strongly preferred for successful genomic scarring/LOH 
analysis. At a minimum, the tumor BRCA status is required. If LOH status is 
unknown in patients without BRCA mutations, enrollment is permitted, but attempts 
will be made to obtain additional tissue to enable an LOH result for final analysis. 
- 
Sample must be submitted to the central laboratory at least 3 weeks prior to planned 
start of treatment in order to enable stratification for randomization. 
 AE monitoring (only record if related to screening procedures). 
 
7.3.2 
Up to 28 days Prior to Randomization 
 PRO collected using the TOI FACT-O, and EQ-5D-5L 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 per RECIST v1.1 (CT scans and/or MRI scans of the 
chest, abdomen, and pelvis with appropriate slice thickness per RECIST v1.1). Other 
complementary studies (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; 
 ECOG performance status (Appendix 3);  
 Blood sample for ctDNA analysis; and 
 AE monitoring (only record if related to screening procedure). 

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 Optional collection of pre-treatment core biopsies from patients who have measurable 
disease and disease that is accessible for biopsy, after chemotherapy is completed and 
prior to initiating study drug as outlined in this protocol. If a biopsy was recently 
performed as standard of care prior to this patient consenting to this study, or after study 
informed consent but outside the 28-day screening window, this may be acceptable with 
advance approval from the sponsor. 
 
7.3.3 
Up to 14 days Prior to Randomization 
 Hematology: includes red blood cell count (RBC) and parameters (hemoglobin, 
hematocrit, MCV, MCH, and mean corpuscular hemoglobin concentration [MCHC]) and 
reticulocyte count, white blood cell count (WBC) and differential (with ANC), and 
platelet count; 
 Serum chemistry: includes 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, magnesium, chloride, bicarbonate (CO2/HCO3-), 
calcium, phosphorus, lactate dehydrogenase (LDH), folic acid, and total cholesterol. 
Also, thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine 
(fT4) at screening; TSH with reflexive fT3 and fT4 if TSH is abnormal on treatment. 
Note: fasting is not required; 
 Serology serum for hepatitis B surface antigen and hepatitis C antibody (screening only). 
Note: testing for HIV must also be performed at screening if mandated locally by a given 
site; 
 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 2);  
 Update medical history; and 
 AE monitoring (only record if related to screening procedure). 
 
7.3.4 
Up to 3 days Prior to First Dose of Study Drug 
 Update medical history; and 
 AE monitoring (only record if related to screening procedure). 
 

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7.4 
Treatment Phase 
7.4.1 
Day 1 of Cycle 1 
The following procedures/assessments will be completed before study drug is administered: 
• PRO using the TOI FACT-O and EQ-5D-5L instruments or other format, as appropriate; 
• Physical examination; 
• Weight; 
• Vital Signs; 
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 3); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• CA-125 measurement; 
• Blood sample for ctDNA analysis; 
• Blood sample for determining germline/somatic BRCA status (Cycle 1 only; if sample is 
not collected on Day 1 of Cycle 1, it should be collected as soon as possible thereafter); 
• Dispensation of oral study drug; 
• AE monitoring. 
 
Oral study drug (rucaparib or oral placebo) will be dispensed to the patient in sufficient 
quantity to last until the next treatment cycle. Patients will ingest oral study drug BID at 
about the same times every day, as close to 12 hours apart as possible. Patients may take 
study drug with or without food (with a regular meal or within 30 minutes after a regular 
meal). Patients will record dosing information in their dosing diary. 
Patients will be instructed to refrain from taking their morning daily dose of study drug at 
home on the day of their clinic visits because certain assessments must be performed prior to 
dosing. 
7.4.2 
Days 15 of Cycle 1 and 2 
The following procedures will be completed: 
• Vital Signs; 
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 3); 
• Hematology; 

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• Serum chemistry (fasting is not required); 
• AE monitoring. 
 
Patients will ingest oral study drug (rucaparib or placebo) BID at about the same times every 
day, at close to 12 hours apart as possible. Patients may take study drug with or without food. 
Patients will record dosing information in their dosing diary. Patients will be instructed to 
refrain from taking their morning daily dose of study drug at home on the day of their clinic 
visits because certain assessments must be performed prior to dosing. 
7.4.3 
Cycle 2 Day 1 
The following procedures/assessments will be completed before study drug is administered: 
• PRO using the TOI FACT-O and EQ-5D-5L instruments or other format, as appropriate; 
• Physical examination; 
• Weight; 
• Vital Signs; 
• Concomitant medications and procedures; 
• ECOG performance status (Appendix 3); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• CA-125 measurement; 
• Blood sample for ctDNA analysis; 
• Blood sample for determining germline/somatic BRCA status (Cycle 1 only; if sample is 
not collected on Day 1 of Cycle 1, it should be collected as soon as possible thereafter); 
• PK samples for nivolumab prior to and after the IV infusion (see Table 6 and 
Section 7.5.6); 
• Immunogenicity sample for nivolumab prior to the IV infusion (see Table 6 and 
Section 7.5.6); 
• Plasma PK sample for rucaparib (prior to first dose taken that day) (see Table 6 and 
Section 7.5.6); 
• Administration of IV study drug; 
• Dispensation of oral study drug; 
• AE monitoring. 
 
Oral study drug (rucaparib or oral placebo) will be dispensed to the patient in sufficient 
quantity to last until the next treatment cycle. Patients will ingest oral study drug BID at 

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about the same times every day, as close to 12 hours apart as possible. Patients may take 
study drug with or without food (with a regular meal or within 30 minutes after a regular 
meal). Patients will record dosing information in their dosing diary. 
Patients will be instructed to refrain from taking their morning daily dose of study drug at 
home on the day of their clinic visits because certain assessments must be performed prior to 
dosing. 
7.4.4 
Day 1 of Cycles 3 and Beyond 
The following procedures will be completed: 
• Physical examination; 
• Weight; 
• Vital signs; 
• Concomitant medications and procedures; 
• Disease assessment/tumor scans every 12 calendar weeks (within 7 days prior is 
permitted) relative to C2D1 for the first 3 years and every 24 weeks thereafter until 
objective radiological disease progression; 
• PRO, using the TOI FACT-O and EQ-5D-5L instruments or other format, as appropriate, 
at Cycle 3, Cycle 5, and then every 12 weeks, to coincide with disease assessment/tumor 
scans (perform before other assessments that day) until treatment discontinuation or until 
the data cut-off for the primary analysis, whichever comes first; 
• ECOG performance status (Appendix 3); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• CA-125 measurement; 
• Blood sample for ctDNA analysis (Day 1 of Cycle 1 through Cycle 6, and at the same 
time as radiological imaging thereafter); 
• PK samples for nivolumab prior to the IV infusion at Cycle 6 and every 4 cycles 
thereafter while IV study drug continues (see Table 6 and Section 7.5.6); 
• Immunogenicity sample for nivolumab prior to the IV infusion at Cycle 6 and every 
4 cycles thereafter while IV study drug continues (see Table 6 and Section 7.5.6); 
• Administration of IV study drug; 
• AE monitoring; 
• Plasma PK samples for rucaparib (prior to the first dose of study drug taken this day; 
Cycle 3 and Cycle 4 only; see Section 7.5.6). 
 

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Oral study drug (rucaparib or placebo) will be dispensed to the patient in sufficient quantity 
to last until the next clinic visit; for Cycles 3 and 4, oral study drug can be resumed after the 
PK sample is collected. Patients may take study drug with or without food. Patient will 
record dosing information in their dosing diary. 
Patients will continue dosing with study drug at home with or without food, taking doses BID 
at about the same times every day. Patients will record dosing information in their dosing 
diary. 
7.4.5 
Post-treatment Follow-up Phase 
7.4.5.1 
End of Treatment 
Upon treatment discontinuation, regardless of the reason, patients will have an 
End-of-Treatment Visit as soon as feasible. The following procedures will be performed: 
• PRO using the TOI FACT-O and EQ-5D-5L instruments or other format, as appropriate; 
• Physical examination; 
• Weight; 
• Vital signs; 
• 12-lead ECG; 
• Concomitant medications and procedures; 
• Tumor scans (using the same methodology as was used at screening and only if it has 
been 12 weeks or more since last scan) if reason for treatment discontinuation was other 
than disease progression based on radiologic assessment; 
• ECOG performance status (Appendix 3); 
• Hematology; 
• Serum chemistry (fasting is not required); 
• CA-125 measurement; 
• Blood sample for ctDNA analysis; 
• AE monitoring; 
• Optional tumor tissue biopsy collection at time of disease progression/randomized 
treatment discontinuation (requires additional consent). Tumor tissue will be processed 
locally as FFPE tissue. Refer to the central Laboratory Manual for detailed sample 
handling instructions. 
 
7.4.5.2 
28-day Safety Follow-up (Safety Follow-up Visit 1 [SFU1]) 
The procedures to be performed for all patients 28 (± 7) days after the last dose of study drug 
(oral or IV, whichever is later) are listed below. 

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• PRO collected using the TOI FACT-O and EQ-5D-5L instruments or other format, as 
appropriate; 
• Physical examination; 
• Weight; 
• Vital signs; 
• 12-lead ECG; 
• ECOG performance status (Appendix 3); 
• Disease assessment for patients who discontinued treatment for reason other than disease 
progression or death. Tumor scans should continue to be performed at 12-week intervals 
(up to 7 days prior permitted) relative to C2D1 for the first 3 years and every 24 weeks 
thereafter until radiologic disease progression by RECIST v1.1, as assessed by the 
investigator, is documented; 
• Blood sample for ctDNA analysis should be collected at the same time as radiological 
imaging; 
• CA-125 measurement should be performed at the same time as radiological imaging; 
• Hematology; 
• Serum chemistry (fasting is not required); 
• PK sample for nivolumab (see Table 6 and Section 7.5.6); 
• Immunogenicity sample for nivolumab (see Table 6 and Section 7.5.6); 
• AE monitoring; 
• Concomitant medications and procedures. 
 
7.4.5.3 
5-month Safety Follow-up (Safety Follow-up Visit 2 [SFU2]) 
The procedures to be performed for all patients 5 calendar months (± 7 days) after the last 
dose of IV study drug are listed below. If a patient remains on oral study drug after 
discontinuation of IV study drug, the 5-month Safety Follow-up Visit can be performed at a 
cycle visit, provided it has been at least 5 months since the last IV dose. 
• PRO collected using the TOI FACT-O and EQ-5D-5L instruments or other format, as 
appropriate; 
• Physical examination; 
• Weight; 
• Vital signs; 
• 12-lead ECG; 
• ECOG performance status (Appendix 3); 

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• Disease assessment for patients who discontinued treatment for reason other than disease 
progression or death. Tumor scans should continue to be performed at 12-week intervals 
(up to 7 days prior permitted) relative to C2D1 for the first 3 years and every 24 weeks 
thereafter until radiologic disease progression by RECIST v1.1, as assessed by the 
investigator, is documented; 
• Blood sample for ctDNA analysis should be collected at the same time as radiological 
imaging; 
• CA-125 measurement should be performed at the same time as radiological imaging; 
• Hematology (only required if toxicities are present); 
• Serum chemistry (fasting is not required) (only required if toxicities are present); 
• PK sample for nivolumab (see Table 6 and Section 7.5.6); 
• Immunogenicity sample for nivolumab (see Table 6 and Section 7.5.6); 
• AE monitoring; 
• Concomitant medications and procedures. 
 
7.4.6 
Long-term Follow-up (LTFU) 
Patients who complete the Safety Follow-up Visit(s) after the last dose of study treatment 
will continue in long-term follow-up as described below. 
• Disease assessment for patients who discontinued treatment for reason other than disease 
progression or death. Tumor scans should continue to be performed at 12-week intervals 
(up to 7 days prior permitted) relative to C2D1 for the first 3 years and every 24 weeks 
thereafter until radiologic disease progression by RECIST v1.1, as assessed by the 
investigator, is documented; 
• CA-125 measurement should be performed at the same time as radiological imaging; 
• Subsequent treatments, secondary malignancy monitoring, and OS information will be 
collected for all patients every 12 weeks (± 14 days) until death, loss to follow-up, 
withdrawal of consent from study, or closure of the study, starting 12 weeks after SFU1. 
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 indicated in Section 8.7; 
• SAEs assessed as potentially related to study drug, and AESIs of MDS and AML 
irrespective of causality, are to be reported as specified in Section 8.7;  
• SAEs unrelated to IV drug do not need to be captured after the 28-day follow-up 
visit/period. Only those related or possibly related to IV drug should be captured until the 
5-month SFU2. 
 

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7.5 
Methods of Data Collection 
7.5.1 
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, 
radiology reports, and BRCA1/2 mutation status and if gBRCA or sBRCA (if known).  
7.5.2 
Prior and Concomitant Medication Assessments 
Medications being used by the patient will be recorded as prior medications during screening 
from Days -28 to -1, and as concomitant medications following receipt of the first dose of 
study drug through the completion of the 28-day Safety Follow-up Visit. Any concomitant 
medication given for AEs related to IV drug up to 5 months after IV treatment 
discontinuation will also be recorded. Medications information will be entered in the 
appropriate eCRF after it is obtained at each study visit. 
Following treatment discontinuation, subsequent anticancer treatments will be collected for 
all patients every 12 or 24 weeks (± 14 days), to coincide with tumor assessments, until 
death, loss to follow-up, withdrawal of consent from study, or closure of the study. With the 
exception of the 28-day and 5-month Safety Follow-up Visits, follow-up can be performed 
via the telephone.  
7.5.3 
Efficacy Evaluations 
7.5.3.1 
Disease/ Tumor Assessments 
Tumor assessment measurements will be performed at screening, at the end of every 
12 weeks of treatment (up to 7 days prior permitted) relative to C2D1 for the first 3 years and 
every 24 weeks thereafter until objective radiological disease progression. If C2D1 visit did 
not occur, the first on-study scan should occur 16 weeks after C1D1. Tumor assessments 
should be performed at the time of treatment discontinuation if the reason for discontinuation 
was other than radiologically confirmed disease progression and it has been ≥ 12 weeks since 
the last assessment. In addition, tumor assessments should be made as clinically indicated. 
Also see Section 6.8. 
Disease assessment will comprise clinical examination and appropriate imaging techniques 
per RECIST v1.1 (CT and/or MRI scans of the chest, abdomen, and pelvis with appropriate 
slice thickness per RECIST). Other complementary studies (X-ray, PET, and ultrasound) 
may be performed if required. If a site can document that the CT performed as part of a 

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PET/CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast) then 
the CT portion of the PET/CT can be used for RECIST measurements. All sites of disease 
should be followed, and the same methods used to detect lesions at baseline are to be used to 
follow the same lesions throughout the clinical study. The same methods used to detect 
lesions at baseline are to be used to follow the same lesions throughout the clinical study. 
CT/MRI scans of the chest, abdomen, and pelvis performed to determine the extent of 
disease at baseline should also be performed at each time of disease assessment, even if the 
scans were negative at baseline. Investigators should perform scans of other anatomical sites 
that, in their judgment, are appropriate to assess based on each patient’s tumor status. 
Imaging guidelines provided by the BICR vendor and should be followed for the collection 
of images and the radiological assessment of disease.  
Tumor response will be interpreted using RECIST v1.1. Disease progression will only be 
determined by RECIST v1.1. Patients with a CR at study entry will only be considered to 
have disease progression if a new lesion is identified. Patients who meet GCIG CA-125 
criteria for disease progression should have a radiologic assessment and be assessed by 
RECIST. If the radiologic assessment does not confirm disease progression, patients should 
continue on treatment and continue to be assessed by RECIST v1.1 per the protocol schedule 
of assessments. 
Patients who discontinued treatment for reason other than disease progression or death 
should continue to have tumor scans performed at 12-week intervals (up to 7 days prior 
permitted) relative to C2D1 for the first 3 years and every 24 weeks thereafter until objective 
radiologic disease progression by RECIST v1.1, as assessed by the investigator, is 
documented, or initiating subsequent anticancer treatment. 
Copies of CT scans (and other imaging, as appropriate) will be collected from all patients for 
BICR. Refer to imaging charter from BICR vendor. 
7.5.3.2 
Tumor Markers 
Blood samples to assess CA-125 will be collected at screening, on Day 1 of Cycle 1, at the 
start of every cycle thereafter, at treatment discontinuation, and as clinically indicated. All 
CA-125 tests will be performed by a central laboratory. 
For patients that are in LTFU and continuing to have disease assessments, CA-125 values 
should be assessed by a local laboratory, if feasible, at the time of radiological imaging. 
7.5.4 
Safety Evaluations 
7.5.4.1 
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. During the screening period, unless 
otherwise required by local regulations, SAEs which are related to protocol-mandated 
assessments will be reported. Once enrolled and study drug is administered, patients will be 
monitored for all AEs/SAEs/AESIs during study participation and until 28 days after the last 
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later. After the 28-day (oral) or 5-month (IV) 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 AESIs of MDS and AML irrespective of 
causality, need to be reported. Any ongoing SAEs, AESIs, or treatment-related Grade 3/4 
AEs will be followed until resolution or stabilization or until loss to follow-up. AEs and 
laboratory abnormalities will be graded according to the NCI CTCAE grading system (v5.0) 
and recorded on the eCRF. 
If a patient begins subsequent anticancer therapy, the sponsor will terminate collection of 
SAEs, with the exception of the AESIs of MDS and AML. 
Complete details for monitoring AEs, including the definition of drug-related AEs, are 
provided in Section 8. 
7.5.4.2 
Clinical Laboratory Investigations 
With the exception of urinalysis samples, all other samples collected will be analyzed by a 
central laboratory; a duplicate sample may be collected and analyzed by the local laboratory 
for immediate eligibility/ treatment decisions. If a patient has a known, clinically significant 
laboratory abnormality and/or associated symptoms that would require AE management or 
interruption of the IV study drug, either central or local laboratory tests should be analyzed 
prior to each administration of an IV drug infusion. The panels of laboratory tests to be 
performed are shown below: 
Hematology: RBC and parameters (hemoglobin, hematocrit, MCV, MCH, and MCHC) and 
reticulocyte count, WBC and differential (with ANC), and platelet count will be assessed for 
all patients at screening, during treatment at each study visit, and at the Treatment 
Discontinuation Visit, 28-day SFU1, and at the 5-month SFU2, if toxicities are present. 
Hematology results must be reviewed by the investigator before the start of study drug and 
ongoing at times testing occurs. Additional and more frequent tests may be performed at the 
investigator’s discretion. 
Clinical Chemistry: total protein, albumin, creatinine or estimated GFR using the 
Cockcroft-Gault formula or institutional standard formula, BUN or urea, total bilirubin, ALP, 
ALT, AST, LDH, glucose, sodium, potassium, magnesium, chloride, bicarbonate 
(CO2,/HCO3-), calcium, phosphorus, TSH, Free triiodothyronine (T3; fT3); Free thyroxine 
(T4, fT4) at screening; TSH with reflexive fT3 and fT4 if TSH is abnormal on treatment, 
folic acid (first 6 cycles only), and total cholesterol will be assessed for all patients at 
screening, during treatment at each study visit, and at the Treatment Discontinuation Visit, 
28-day SFU1, and at the 5-month SFU2, if toxicities are present. Fasting is not required 
before blood sampling. If pancreatitis is suspected clinically, serum lipase and amylase 
should be analyzed. Serum chemistry results must be reviewed by the investigator before the 
start of treatment with study drug and ongoing at times testing occurs. 

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In addition to the clinical chemistry assessments above, serology serum for hepatitis C 
antibody and hepatitis B surface antigen should be performed at screening. Testing for HIV 
must also be performed at screening if mandated locally by a given site. 
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.  
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 8.5 for guidelines on reporting of abnormal laboratory values as AEs. 
7.5.4.3 
Vital Signs 
Vital signs will include blood pressure, pulse, 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. 
7.5.4.4 
12-Lead Electrocardiogram 
For all patients, local 12-lead ECGs will be taken at screening (within 28 days prior to first 
dose of study drug), at End-of-Treatment Visit, and at both SFU1 and SFU2. 
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.  
7.5.4.5 
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, and at the Treatment 
Discontinuation Visit. 
7.5.4.6 
Physical Examinations 
Physical examinations will include an assessment of all the major body systems. Complete 
physical examinations will be performed during screening and at End of Treatment. Physical 
examinations at study visits during the Treatment Phase will be limited as appropriate.  
7.5.4.7 
ECOG Performance Status 
ECOG performance status (Appendix 3) will be assessed during screening, at study visits 
during the Treatment Phase, and at End of Treatment. The ECOG performance status should 

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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. 
7.5.5 
Patient-reported Outcomes 
PRO utilizing the TOI FACT-O and EQ-5D-5L instruments (see Appendix 5 and Appendix 
6) will be assessed at screening, on Day 1 (Cycle 1 through 3, and Cycle 5), then every 
12 weeks (aligning with CT scans) until treatment discontinuation or until the data cut-off for 
the primary analysis, whichever comes first. In addition, PRO assessments will be performed 
at End of Treatment, and at the SFU1 (28-day Safety Follow-up) and the SFU2 (5-month 
Safety Follow-up) for all patients.  
Patients will complete the assessments on an electronic device or other format (ie, paper 
form), as appropriate, before any other scheduled study procedures are performed and dosing 
occurs (if applicable).  
7.5.6 
Pharmacokinetic and Immunogenicity Evaluations 
Samples for nivolumab and rucaparib PK and immunogenicity assessments will be collected 
for all patients, as described in Table 6. For nivolumab, corresponding serum samples 
designated for either PK or immunogenicity assessments may also be used for either of those 
analyses, if required (eg, insufficient sample volume to complete testing). 
7.5.6.1 
Rucaparib Pharmacokinetic Sample Collection 
For all patients, plasma samples are to be collected for trough level PK analysis of oral study 
drug within 1 hour before the morning dose on Day 1 of Cycle 2, 3, 4, and 6. Plasma samples 
are to be collected approximately 12 hours after the last oral dose, but prior to the next oral 
dose (ie, typically within 1 hour prior to dosing). If oral dosing is held for toxicity or any 
other reason, plasma samples for PK should still be collected at the end of treatment 
Cycles 1, 2, 3, and 5. 
A central laboratory will be used for bioanalysis of plasma rucaparib concentration 
measurement. Please refer to the central Laboratory Manual for details on collection and 
processing of blood PK samples. 
7.5.6.2 
Nivolumab Pharmacokinetic Sample Collection 
All time points are relative to the start of IV treatment administration. All on-treatment time 
points are intended to align with days on which IV treatment is administered. If it is known 
that a dose is going to be delayed, then the pre-dose sample should be collected just prior to 
the delayed dose. However, if a pre-dose sample is collected but the IV dose is subsequently 
delayed, then an additional pre-dose sample should not be collected. 
Blood samples should be drawn from a site other than the nivolumab/IV placebo infusion site 
(ie, contralateral arm) on days of infusion. All samples collected pre-dose should be collected 
just prior to the administration from the contralateral arm (ie, the arm not used for the 

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infusion). If the nivolumab/IV placebo infusion was interrupted, the interruption details will 
also be documented on the eCRF. Blood samples will be processed to collect serum and 
stored preferably at -70°C (samples may be stored at -20°C up to 2 months). Further details 
of PK sample collection and processing will be provided to the site in the central Laboratory 
Manual. Serum concentration analyses for nivolumab will be performed by validated 
bioanalytical method(s). 
7.5.6.3 
Nivolumab Immunogenicity Assessments 
Samples for nivolumab immunogenicity assessment will be collected from all patients 
receiving nivolumab/rucaparib, active or placebo, as described in Table 6. 
The serum samples will be analyzed for anti-nivolumab drug antibody (ADA) by validated 
immunoassays. Samples with a positive ADA response may also be analyzed for neutralizing 
ADA response to nivolumab. The immunogenicity (and corresponding drug exposure) data 
from these samples will be reported as part of a participant’s overall immunogenicity 
assessment. Selected serum samples may be analyzed by an exploratory method that measure 
nivolumab or detect ADA for technology exploration purposes; exploratory results will not 
be reported. Further details of immunogenicity sample collection and processing will be 
provided to the site in the central Laboratory Manual.  
7.5.7 
Biomarker Analysis 
7.5.7.1 
Biomarker Analysis – Tumor Tissue 
A sufficient quantity of tumor tissue from the cytoreductive surgery must be provided during 
the screening process and submitted to the central laboratory directly at least 3 weeks 
prior to the planned randomization for determination of HRD status. This tumor tissue is 
required for HRD stratification for randomization and for additional biomarker testing 
described below. If the patient received neoadjuvant chemotherapy, a pre-treatment core 
biopsy should also be provided, if available. 
Sufficient quantity of tumor tissue must be confirmed by central laboratory testing in these 
patients during the study.  
Sufficient archival FFPE tumor tissue (enough for 1 × 4 µm section for H&E and 
approximately 8 to 12 × 10 µm sections [unstained], or equivalent) is required for study 
participation per inclusion criteria #9. In addition to this minimum requirement, it is highly 
desirable to have an additional 4 × 4 µm sections and 2 × 10 µm sections for other planned 
analyses. 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.79 Refer to the central Laboratory 
Manual for details. The tumor tissue sample must be of adequate quality (at least 20% tumor 
content [≥ 30% is strongly preferred] with a minimum of 80% nucleated cellular content), or 
a new sample must be acquired.  

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Optional pre-treatment core biopsies may be taken from patients who have measurable 
disease and disease that is accessible for biopsy, after chemotherapy is completed and prior 
to initiating study drug as outlined in this protocol. 
A tumor tissue biopsy sample from the time of disease progression/randomized treatment 
discontinuation until the start of the next treatment is optional; 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 central Laboratory Manual. 
The tumor specimens will be sequenced using Foundation Medicine’s NGS-based test, which 
examines a panel of cancer-related genes, including BRCA1/2 and other homologous 
recombination pathway genes, and assesses the percentage of genomic LOH. The goal is to 
assess mutations in these genes as molecular markers for predicting response or resistance to 
the combination of rucaparib and nivolumab. The NGS-based test will also enable 
assessment of TMB as a molecular marker for efficacy.  
In addition, immunohistochemistry staining of the tumor specimen will be performed to 
assess protein expression of immune-related markers, such as PD-L1, as a molecular marker 
for efficacy. 
7.5.7.2 
Biomarker Analysis – ctDNA 
Blood samples will be collected during screening, before dosing on Day 1 of Cycles 1 to 6, at 
the time of radiologic imaging, and at treatment discontinuation from all patients entered in 
the study for plasma ctDNA analysis. Sample collection details will be provided in the 
central Laboratory Manual. 
These samples will be used for ctDNA profiling to assess alterations in genes that may be 
associated with response and resistance to the combination of rucaparib and nivolumab. 
7.5.7.3 
Biomarker Analysis - Genomic DNA from Blood 
A blood sample for genomics analysis will be collected at Cycle 1 Day 1 from all patients for 
determination of germline status of mutations identified using NGS testing. Results may be 
provided to patients who consent to receive this information upon availability of this 
information. Sample collection details will be provided in the central Laboratory Manual. 
7.5.7.4 
Additional Research  
The patient will have the option to provide additional consent to allow the sponsor to retain 
residual samples for future unspecified research.  
 
 

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8 
ADVERSE EVENT MANAGEMENT 
8.1 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, instead of the physical examination eCRF, which is reserved for physical signs or 
findings). 
8.2 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 of oral drug or IV study drug, 
whichever occurs later) must be treated as an SAE and reported as such. In addition, any 
event resulting in death that occurs more than 28 days after last dose of oral or IV study 
drug that is considered treatment-related should be reported as an SAE. 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; or 
 Is an 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 

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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. 
 
8.3 
Definition of an Adverse Events 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 8.7 for reporting instructions).  
8.4 
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 study drug or concomitant medication unless associated with an SAE. 
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 AE or SAE; and  
• Events that meet the SAE criteria (as outlined in Section 8.2) and occur after informed 
consent but before the first dose of study drug, which are considered unrelated to 
protocol-mandated screening procedures. 
 
8.5 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 laboratory values within the normal range will require similar 
judgment. 

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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; or 
• at the discretion of the investigator should the abnormality be deemed clinically 
significant. 
 
8.6 Pregnancy or Drug Exposure During Pregnancy 
Pregnancy is an exclusion criterion. In addition, due to inclusion criteria #4, requiring at least 
a bilateral salpingo-oophorectomy and partial omentectomy, women of child-bearing 
potential will not be randomized in this study. 
All study participants must avoid pregnancy achieved through assisted reproductive 
technology, for the duration of study treatment and for a minimum of 6 months following the 
last dose of study drug (oral or IV, whichever is later). 
8.7 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 (serious or non-serious) that occurs 
after first dose of study drug through 28 days after receiving the last dose of oral or IV study 
drug, whichever occurs later, will be recorded on the AE eCRF. Additionally, only AEs that 
are related to IV drug that occur between 28 days and 5 months after the last dose of IV drug 
will be recorded on the AE eCRF. 
After the 28-day reporting window following discontinuation of randomized treatment, only 
SAEs assessed as potentially related to study drug should be reported. 
After the 28-day or 5-month reporting window after discontinuation of randomized 
treatment, 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 SFU1 (28-days after the last dose of rucaparib). After this period, only events 
considered serious and related to study drug should be reported as SAEs (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. 
 
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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 
oral study drug or 5 months after receiving the last dose of IV study drug, whichever is later, 
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. 
8.7.1 
Onset Date of Adverse Events 
The onset date is the date that the event or the signs/symptoms attributed to the event started. 
8.7.2 
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. 
8.7.3 Intensity of Adverse Events 
The severity of each AE will be graded using the NCI CTCAE, v5.0 grading scale.80 
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; or 
• Fatal events are events that lead to the patient’s death. 
 

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8.7.4 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.  
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. 
 
8.7.5 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 
• Other (specify) 
 

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Outcome 
• Recovered 
• Recovered with sequelae 
• Recovering/ Resolving/ Improving 
• Ongoing 
• Death 
• Lost to follow-up 
 
8.8 
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 oral 
study drug or 5 months after the last dose of IV study drug, whichever occurs later. 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 (oral) or 5-month (IV) 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 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, SFU1. 
8.9 Potential Drug-Induced Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities 
should occur prior to the reporting of a potential DILI event. All occurrences of potential 
DILIs, meeting the defined criteria,49 must be reported as SAEs (see Section 8.10 for 
reporting details). 
Potential drug induced liver injury is defined as: 
1. ALT or AST elevation > 3 × 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. 

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8.10 Regulatory Aspects of Serious Adverse Event and Adverse Events 
of Special Interest Reporting 
All SAEs and AESIs, regardless of relationship to study drug, must be reported to the 
sponsor/ SAE designee within 24 hours of knowledge of the event, during the study through 
28 days after receiving the last dose of oral study treatment and 5 months after receiving the 
last dose of IV study treatment, whichever occurs later, according to the procedures below. 
After the 28-day window, only SAEs considered to be potentially treatment-related 
(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 regardless of treatment relationship, should be reported. 
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. The Serious Adverse Event 
(SAE)/Adverse Events of Special Interest (AESI) Report Form must be used for 
reporting SAEs and AESIs. The contact information for reporting of SAEs and AESIs 
can be found on the SAE/ AESI Reporting Form. 
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 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 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. 
8.11 Independent Data Monitoring Committee 
No formal efficacy interim analyses are planned. 
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 women with ovarian cancer and a statistician, all of whom are not otherwise 
involved in the study as investigators. The IDMC responsibilities, authorities, and procedures 
will be documented in the IDMC charter, which will be endorsed and signed by the IDMC 
prior to the first data review meeting. 

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The IDMC will: 
• Review safety and efficacy of rucaparib and nivolumab compared with placebo, as well 
as the rucaparib + nivolumab combination compared to monotherapy to ensure the study 
is beneficial to patients 
• Ensure the study is conducted in a high-quality manner 
• Monitor the size of the HRD subgroups (tBRCA, non-tBRCA LOHhigh, non-tBRCA 
LOHlow, and non-tBRCA LOHunknown) 
 
Results from the open-label safety cohort(s) will be shared with the IDMC. 
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 may 
recommend that the study be stopped for futility 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. 
The IDMC will meet at least semi-annually after sufficient data has been collected. The 
IDMC chairperson may convene 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 documented in a separate committee charter. 
 
 

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9 
PLANNED STATISTICAL METHODS 
9.1 
General Considerations 
All safety analyses will be summarized for all patients who received at least 1 dose of 
protocol-specified treatment.  
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, 50th (median) percentile with the 95% CI will be summarized for each 
randomized treatment group. The stratified hazard ratio from the log-rank test and 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.  
All data will be used to their maximum possible extent but without any imputations for 
missing data. Unless otherwise specified, baseline is defined as the last measurement on or 
prior to the first day of study drug administration.  
All statistical analyses will be conducted with the statistical analysis software (SAS®) 
System, Version 9.4. Further details around the statistical analyses planned in this study will 
be outlined in the Statistical Analysis Plan (SAP).  
9.2 
Determination of Original Sample Size 
9.2.1 
Determination of Sample Size in Original Protocol 
Up to approximately 1000 patients will be randomized in a 4:4:1:1 ratio to receive treatment 
with one of the following 4 arms: 
Arm A: Oral rucaparib + IV nivolumab (n = 400);  
Arm B: Oral rucaparib + IV placebo (n = 400);  
Arm C: Oral placebo + IV nivolumab (n = 100); or  
Arm D: Oral placebo + IV placebo (n = 100). 
 
The randomization is stratified by the following factors: HRD classification (tBRCA, 
non-tBRCA LOHhigh, non-tBRCA LOHlow, and non-tBRCA LOHunknown), disease status (no 
residual disease vs residual disease), and timing of surgery (primary surgery vs. interval 
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Three separate comparisons of the treatment arms will be evaluated independently: 
1. Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib + IV placebo) 
2. Arm A (oral rucaparib + IV nivolumab) vs Arm D (placebo [oral and IV]) 
3. Arm B (oral rucaparib + IV placebo) vs Arm D (placebo [oral and IV]) 
 
The level of statistical significance will be split into 3 so that each of the above comparisons 
will be made independently at a one-sided 0.0083 significance level.  
The median PFS for patients in Arm A (rucaparib + nivolumab) from the total patient 
population (ie, the ITT Population inclusive of both tBRCA and non-tBRCA subgroups) is 
expected to be approximately 24 months while the median PFS for patients in Arm B 
(rucaparib monotherapy) [oral rucaparib + IV placebo]) is expected to be about 17 months.  
The following table provides the sample size and power for comparison 1 of Arm A 
(rucaparib + nivolumab) to Arm B (rucaparib monotherapy) within the HRD and ITT 
sub/populations. The tBRCA and non-tBRCA LOHhigh patients are likely to respond 
similarly to the rucaparib + nivolumab therapy so the ordered step-down procedure will only 
include the HRD and ITT sub/populations. 
Group 
Hazard 
Ratio 
Cumulative 
N (4:4) 
Number of 
Events  
Median PFS 
(months) 
Power 
One-sided 
Alpha 
HRD  
0.67 
540 (270:270) 
400 
25 vs 37  
90% 
0.008 
ITT  
0.725 
800 (400:400) 
600 
17 vs 24 
90% 
0.008 
Abbreviations: HRD = homologous recombination deficiency (tBRCA + non-tBRCA LOHhigh); ITT = intent-
to-treat; PFS = progression free survival. 
 
The following table provides the sample size and power for comparison 3 of Arm B 
(rucaparib monotherapy) to Arm D (placebo) for the tBRCA, HRD and ITT sub/populations. 
The power associated with comparison 2 of Arm A (rucaparib + nivolumab) to Arm D 
(placebo) is assumed to be higher than for comparison 3 of Arm B (rucaparib monotherapy) 
to Arm D (placebo). 
Group 
Hazard 
Ratio 
Cumulative 
N (4:1) 
Number of 
Events  
Median PFS 
(months) 
Power 
One-sided 
Alpha 
tBRCA  
0.50 
170 (135:34) 
120 
18 vs 36 
90% 
0.008 
HRD  
0.60 
340 (270:68) 
230 
15 vs 25  
90% 
0.008 
ITT  
0.65 
500 (400:100) 
340 
12 vs 17 
90% 
0.008 
Abbreviations: HRD = homologous recombination deficiency (tBRCA + non-tBRCA LOHhigh); 
ITT = intent-to-treat; PFS = progression free survival; tBRCA = tumor tissue alteration in BRCA1 or BRCA2, 
includes gBRCA and sBRCA. 
 

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The results of the comparisons of Arm C (nivolumab monotherapy [oral placebo + IV 
nivolumab]) to Arm D (placebo [oral and IV]) will be considered exploratory since these 
comparisons are not included in the multiple testing procedure described above. 
A minimum of 6 patients may be treated in a small, open-label safety cohort with rucaparib 
(600 mg BID) and nivolumab (480 mg IV on Day 1 of every 28-day cycle). A minimum of 
6 patients of Japanese descent may be enrolled into an open-label, safety cohort at 
investigational sites in Japan, contingent upon the recommended rucaparib dose in Japan. 
These 2 safety cohorts will be evaluated individually after each patient receives a minimum 
of one cycle of combination therapy. 
9.2.2 
Changes to Sample Size Assumptions as of Implementation of 
Protocol Amendment 2 
The first patient was randomized in August 2018, and randomization is expected to close the 
third quarter of 2020. Based on the recently established standard of care of PARPi 
monotherapy in the front-line maintenance setting,81,82 the treatment comparison of Arm A 
(oral rucaparib + IV nivolumab) vs Arm D (placebo [oral and IV]) from the original protocol 
will no longer be necessary. Therefore, 2 separate comparisons of the treatment arms will be 
evaluated independently, and at different timepoints based on the maturity of the parts of the 
study, in order to evaluate both rucaparib monotherapy and rucaparib in combination with 
nivolumab: 
• Monotherapy: Arm B (oral rucaparib + IV placebo) vs Arm D (placebo [oral and IV]) 
• Combination: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib + IV 
placebo) 
 
As such, in this amended protocol, the level of statistical significance will be split into two so 
that each of the above comparisons will be made independently at a one-sided 0.0125 
(two-sided 0.025) significance level. The treatment comparison of Arm A (oral 
rucaparib + IV nivolumab) vs Arm D (placebo [oral and IV]) will be performed as an 
exploratory analysis to support contribution of each component in the rucaparib-nivolumab 
combination. 
The 2 treatment comparisons are set up as independent and can thus be unblinded to 
treatment allocations and read out at different time points for this study. The monotherapy 
treatment comparison of Arm B (oral rucaparib + IV placebo) versus Arm D (placebo [oral 
and IV]) is expected to mature earlier than the combination treatment comparison of Arm A 
(oral rucaparib + IV nivolumab) versus Arm B (oral rucaparib + IV placebo). The proposed 
timing of sufficient maturity for the monotherapy treatment comparison is assumed to be at 
as early as 15 months from the last patient randomized, and once approximately 60% of the 
events have occurred.  
Due to the approval of olaparib for BRCA-mutated patients in the frontline maintenance 
setting (SOLO1 study),81 the enrollment of tBRCA is lower than originally anticipated in the 
sample size assumptions in the original protocol. Thus, the monotherapy treatment 

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comparison, comparing Arm B (oral rucaparib + IV placebo) versus Arm D (placebo [oral 
and IV]), will start with the HRD analysis subpopulation, then ITT Population for the 
step-down hierarchical testing and the tBRCA population will be explored as an exploratory 
endpoint. 
The Phase 3 PRIMA study of niraparib also provided information regarding treatment effects 
in a similar population for those patients who are HRD and for the ITT Population.82 Due to 
the above changes to the alpha level and step-down, the adjusted power assumption for the 
monotherapy treatment comparison, comparing Arm B (oral rucaparib + IV placebo) versus 
Arm D (placebo [oral and IV]), is summarized in the table below. 
Monotherapy Treatment Comparison: Arm B (oral rucaparib + IV placebo) vs Arm D (placebo 
[oral and IV]), randomization allocation 4:1 
Protocol 
Version 
Group 
Cumulative 
N (4:1) 
Number of 
Events 
HR 
Median PFS  
Power 
One-
sided 
Alpha 
Original 
Protocol and 
Amendment 
1 
tBRCA 
170 (135:34) 
120 
HR 0.50  
18 vs 36 months 
90% 
0.008 
HRD 
340 (270:68) 
230 
HR 0.60, 
15 vs 25 months 
90% 
0.008 
ITT 
500 (400:100) 
340 
HR 0.65 
12 vs 17 months 
90% 
0.008 
Amendment 
2  
HRD 
205 
(164:41) 
123 
HR 0.4582 
12 vs 26.7 months 
90% 
0.0125 
ITT 
500 (400:100) 
300 
HR 0.6082 
12 vs 20 months 
90% 
0.0125 
Abbreviations: HR = hazard ratio; HRD = homologous recombination deficiency (tBRCA + non-tBRCA 
LOHhigh); ITT = intent-to-treat, IV = intravenous; PFS = progression-free survival. 
The power assumption for the combination treatment comparison is still set at 90% power for 
both HRD and ITT sub/populations as per original protocol, as shown in the table below. 
The following table provides the sample size and power for the clinically relevant 
comparison between Arm A (oral rucaparib + IV nivolumab) and Arm B (oral rucaparib 
+ IV placebo) within the HRD and ITT sub/populations. 
 
 

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Combination Treatment Comparison: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral 
rucaparib + IV placebo), randomization allocation 4:4 
Protocol 
Version 
Group 
Cumulative N 
(4:4) 
Number of 
Events 
HR  
Median PFS 
Power 
One-sided 
Alpha 
Original 
Protocol and 
Amendment 1 
HRD 
540 (270:270) 
400 
HR 0.67 
25 vs 37 months 
90% 
0.008 
ITT 
800 (400:400) 
600 
HR 0.725  
17 vs 24 months  
90% 
0.008 
Amendment 2 
HRD 
380 (190:190) 
285 
HR 0.67  
26.7 vs 39.9 months 
90% 
0. 0125 
ITT 
800 (400:400) 
600 
HR 0.725 
20 vs 28 months 
90% 
0. 0125 
Abbreviations: HR = hazard ratio; HRD = homologous recombination deficiency (tBRCA + non-tBRCA 
LOHhigh); ITT = intent-to-treat, IV = intravenous; PFS = progression-free survival. 
 
9.2.3 
Sample Size Assumptions as of Implementation of Protocol Amendment 3 
The sample size and power assumptions are not changing in Amendment 3. The changes to 
remove the HRD sub-population from the primary and key secondary endpoints for the 
combination treatment comparison will not affect the current sample size design nor power 
of this study, due to the combination treatment comparison already being set at 90% power 
for the ITT Population, as shown in Section 9.2.2 and summarized in the table below. 
Combination Treatment Comparison: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral 
rucaparib + IV placebo), randomization allocation 4:4 
Protocol 
Version 
Group 
Cumulative N 
(4:4) 
Number of 
Events 
HR  
Median PFS 
Power 
One-sided 
Alpha 
Amendment 2 
HRD 
380 (190:190) 
285 
HR 0.67 
26.7 vs 39.9 months 
90% 
0. 0125 
ITT 
800 (400:400) 
600 
HR 0.725 
20 vs 28 months 
90% 
0. 0125 
Amendment 3 
ITT 
800 (400:400) 
600 
HR 0.725  
20 vs 28 months 
90% 
0. 0125 
Abbreviations: HR = hazard ratio; HRD = homologous recombination deficiency (tBRCA + non-tBRCA 
LOHhigh); ITT = intent-to-treat, IV = intravenous; PFS = progression-free survival. 
 

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9.3 
Analysis Populations  
Intent-to-treat (ITT) Population: The ITT Population will consist of all randomized 
patients. This includes all patients randomized into any of the 4 HRD classifications (tBRCA, 
non-tBRCA LOHhigh, non-tBRCA LOHlow, and non-tBRCA LOHunknown). 
HRD Population: The HRD Population will consist of all randomized patients that are either 
tBRCA or non-tBRCA LOHhigh. 
Safety Population: The Safety Population will consist of all patients who received at least 
one dose of protocol-specified treatment. 
9.4 
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. 
9.5 
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 variables will be summarized with frequency tabulations: 
• Time since diagnosis (months): > 12 to 24, > 24 
• Baseline laboratory parameters: graded based on CTCAE 
• Molecularly defined subgroups based on HRD and TMB and other definitions as 
appropriate. 
• Best response to most recent platinum-based regimen (CR [defined as complete 
radiologic response by RECIST v1.1 with normalization of CA-125] or PR [defined as 
partial radiologic response by RECIST v1.1 and/or a GCIG CA-125 response]). All 
responses require that CA-125 be < ULN. 
 
Descriptive statistics may also be used to summarize the continuous variables. 
9.6 
Efficacy Analyses 
9.6.1 
Primary Efficacy Analyses 
The primary efficacy endpoint for the study is investigator-determined PFS (invPFS) by 
RECIST. Investigator-determined PFS is defined as the time from randomization to disease 
progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due 
to any cause, whichever occurs first. Only scans or deaths prior to or on the start of any 
subsequent anticancer treatment will be used in PFS analysis. Any death or progression event 

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occurring within 2 missing expected scan assessments will be included in the analysis. Two 
missed scans or visits is defined as a duration of 26 weeks (12 × 2 + 2) for the first 3 years 
and 50 weeks (24 × 2 + 2) thereafter. Events occurring immediately after 2 consecutive 
missed scans will be censored as below.  
Censoring rule: Any patients who do not experience an event of either disease progression or 
death will be censored on the last on-study tumor assessment prior to start of any subsequent 
anticancer treatment. Any patients with an event of either disease progression or death 
directly following 2 or more missing expected consecutive scans will be censored on the date 
of the last on-study tumor assessment prior to the gap in scan collection. If a patient does not 
have any on-study tumor assessments, then the patient will be censored on the date of 
randomization (ie, Day 1). 
The stratification factors included in the primary analysis of invPFS will be as follows: 
• HRD classification (tBRCA, non-tBRCA LOHhigh, non-tBRCA LOHlow, or non-tBRCA 
LOHunknown) by central laboratory analysis 
• Disease status post-chemotherapy (residual disease vs. no residual disease) 
• Timing of surgery (primary surgery vs. interval debulking) 
 
The primary endpoint is analyzed using stratified Cox proportional hazard model and log-
rank test comparing the treatment groups stratified by the randomization stratification factors, 
ie, HRD classification (tBRCA, non-tBRCA LOHhigh, non-tBRCA LOHlow, and non-tBRCA 
LOHunknown), disease status (no residual disease versus residual disease), and timing of 
surgery (primary surgery vs. interval debulking). The log-rank test will be the official test 
used for evaluating primary endpoint significance in the step-down procedure. 
In addition, a stratified log-rank test of invPFS between the randomized treatment groups, 
together with a graphical presentation of unstratified invPFS distributions, median invPFS 
with 95% CI, and event rates, will be presented as supportive statistics. 
9.6.1.1 
Step-down Procedure to Adjust for Multiplicity 
The primary endpoint of invPFS and key secondary endpoints of OS and ORR will be tested 
among the HRD and ITT sub/populations for the monotherapy comparison and among the 
ITT Population for the combination comparison, using separate ordered step-down multiple 
comparison procedures, as shown in Figure 3. 
That is, for the monotherapy treatment comparison, the invPFS in the HRD subpopulation 
will be tested first at a one-sided 0.0125 significance level. If invPFS in the HRD subgroup is 
statistically significant, then invPFS will be tested in the ITT Population. If both the HRD 
and ITT sub/populations reach statistical significance for the primary endpoint, then the first 
secondary endpoint of OS will be tested at the one-sided 0.0125 significance level in the 
HRD and ITT sub/populations for that treatment comparison and testing will continue to the 
last key secondary endpoint of ORR. Once statistical significance is not achieved for one test, 

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the statistical significance will not be declared for all subsequent analyses in the ordered 
step-down procedure for the monotherapy treatment comparison. 
For the combination treatment comparison, the invPFS in the ITT Population will be tested 
first at a one-sided 0.0125 significance level. If invPFS is statistically significant, then the 
first secondary endpoint of OS will be tested at the one-sided 0.0125 significance level in the 
ITT Population. If OS in the ITT Population is statistically significant, then testing will 
continue to the last key secondary endpoint of ORR. Once statistical significance is not 
achieved, the statistical significance will not be declared for subsequent analyses in the 
ordered step-down procedure for the combination comparison in the ITT Population.  
 
Figure 3. 
ATHENA Statistical Design 
 
 
Abbreviations: HRD = homologous recombination deficiency; invPFS = progression-free survival as assessed 
by investigator; ITT = intent-to-treat; ORR = objective response rate; OS = overall survival. 
 

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9.6.2 
Secondary Efficacy Analysis 
The following secondary efficacy endpoints are included in the step-down procedure as 
outlined in Section 9.6.1.1: 
1. Overall survival 
2. Investigator determined ORR per RECIST  
 
The following secondary efficacy endpoints are stand alone and are not included in the 
step-down procedure (ie, no multiplicity adjustment): 
• PFS according to RECIST as assessed by BICR 
• Investigator determined DOR per RECIST 
 
9.6.2.1 
Progression-free Survival as Assessed by BICR 
Progression-free survival (PFS) as assessed by BICR (bicrPFS) by RECIST 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 anticancer treatment are included. Any death or progression event 
occurring within 2 missing expected scan assessments will be included in the analysis. Two 
missed scans or visits is defined as a duration of 26 weeks (12 × 2 + 2) for the first 3 years 
and 50 weeks (24 × 2 + 2) thereafter. Events occurring immediately after 2 consecutive 
missed scans will be censored as below. 
Censoring rule: Any patients who do not experience an event of either disease progression or 
death will be censored on the last on-study tumor assessment prior to start of any subsequent 
anticancer treatment. Any patients with an event of either disease progression or death 
following 2 or more missing expected consecutive scans will be censored on the date of the 
last on-study tumor assessment prior to the gap in scan collection. If a patient does not have 
any on-study tumor assessments, then the patient will be censored on the date of 
randomization (ie, Day 1). 
9.6.2.2 
Overall Survival 
Overall survival (OS) is defined as the number of days from the date of randomization to the 
date of death (due to any cause). Patients without a known date of death will be censored on 
the date the patient was last known to be alive. 
9.6.2.3 
Investigator determined ORR per RECIST 
Analyses of ORR will be performed in the subgroup of patients with measurable disease at 
baseline and will be summarized with frequencies and percentages. The best ORR will be 
evaluated both as a single time point evaluation and requiring confirmation. 

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9.6.2.4 
Duration of Response 
The duration of response (DOR) as assessed by investigator will be analyzed in the subgroup 
of patients who have a confirmed response by RECIST v1.1. Duration of response is defined 
as the interval from the first documentation of objective response (RECIST v1.1) to the 
earlier of the first documentation of disease progression (per RECIST v1.1) or death from 
any cause. Any patients with an ongoing response will be censored on the date of the last 
post-baseline scan. 
9.7 
Safety Analyses 
All safety analyses will be summarized by randomization treatment group or safety cohort 
and pooled for all patients.  
Safety endpoints are incidence of AEs, clinical laboratory abnormalities, and dose 
modifications. 
Data from all patients who receive at least 1 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. 
9.7.1 
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 v5.0 later. Only treatment-emergent adverse events (TEAEs) will be 
collected: TEAEs are defined as AEs with onset date on or after the date of first dose of study 
drug until 28 days after the last dose of oral study drug or 5 months after the last dose of IV 
study drug, whichever occurs later.  
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 drug; 

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• TEAEs resulting in interruption/delay of study drug; and 
• TEAEs resulting in dose reduction 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 grade will be summarized.  
9.7.2 
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 will be defined as the onset date on or after the date of first dose of study 
drug until 28 days after the last dose of oral study drug or 5 months after the last dose of IV 
study drug, whichever occurs later. 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). 
9.7.3 
Vital Sign Measurements 
The on-treatment period will be defined as the onset date on or after the date of first dose of 
study drug until 28 days after the last dose of oral study drug or 5 months after the last dose 
of IV study drug, whichever occurs later. 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, standard 
deviation [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 and maximum) of the change from baseline to the maximum, 
minimum, and last value during the on-treatment period will also be given.  

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9.8 
Pharmacokinetic Analysis 
9.8.1 
Rucaparib Pharmacokinetic Analysis 
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 may be further analyzed by a PPK approach. The post hoc estimated exposures 
will be used for exposure-response analyses of selected efficacy and safety endpoints if the 
data permit. The PPK and the exposure-response analyses may be presented separately from 
the main clinical study report. 
9.8.2 
Nivolumab Pharmacokinetic Analysis 
The nivolumab concentration versus time data obtained in this study will be combined with 
data from other studies in the clinical development program to develop a PPK model. This 
model will be used to evaluate the effects of intrinsic and extrinsic covariates on the PK of 
nivolumab to determine measures of individual exposure (such as steady-state peak, trough 
and time-averaged concentration). PK drug-drug interaction between nivolumab and other 
component drugs will be studied by a PPK approach. Model-determined exposures will be 
used for exposure response analyses of selected efficacy and safety endpoints if the data 
permit. The PPK analysis will be presented separately from the main clinical study report.  
9.9 
Interim Analysis 
9.9.1 
Open-label Safety Cohort 
A formal safety review will occur after the safety lead-in cohort has enrolled and patients 
have been treated with the combination for at least 28 days. The review committee will 
include external experts and sponsor personnel. The external experts will include, but not be 
limited to, the Coordinating PIs of the study
 
 the Principal 
Investigator(s) who enrolled and treated the respective patients, and key members of the 
Steering Committee. Sponsor reviewers will include the medical monitor, Chief Medical 
Officer, Head of Pharmacovigilance, and the study Biostatistician. The data will also be 
provided to the IDMC. The protocol will be amended as appropriate to incorporate additional 
patient safety monitoring if new safety signals are noted at any review. 
Evaluation of the Japanese safety cohort will proceed in the same manner as the initial safety 
cohort. Once the evaluation of the Japanese cohort is complete, the double-blind portion of 
the study can be opened for randomization in Japan. 
9.9.2 
Double-blind Treatment Phase 
No formal efficacy interim analyses for early stopping are planned. 

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An IDMC will meet regularly to review the efficacy and safety data from this study (see 
Section 8.11). 
 
 

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10 STUDY ADMINISTRATION 
10.1 Regulatory and Ethical Considerations 
This study will be conducted in compliance with the protocol; Good Clinical Practices 
(GCPs), including International Conference on Harmonization (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. The ethical principles underlying European Union Directive 
2001/20/EC and the United States Code of Federal Regulations (CFR), Title 21, Part 50 
(21CFR50) and applicable local requirements.  
10.1.1 
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. 
US-generated data will be handled in accordance with the Health Information Portability and 
Accountability Act (HIPAA). The trial will be registered on www.clinicaltrials.gov, 
EudraCT, and other applicable trial registry systems as appropriate. 
10.1.2 
Institutional Review Board or Independent Ethics Committee Approval 
This protocol and any material to be provided to the patient (such as advertisements, patient 
information sheets, 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 
ICF 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.  
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 ICF, and the 
sponsor is notified.  

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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.  
10.2 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 GCP 
guidelines and the Declaration of Helsinki. 
It is the responsibility of the investigator to obtain signed ICFs from all patients 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.  
10.3 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 screened and 
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.  
The investigator agrees that all information received from the sponsor or designee including, 
but not limited to, the IB, 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 of confidential patient information to any 

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unauthorized party or otherwise into the public domain. The investigator will notify 
pharma& (contact@pharmaand.com) within 24 hours of a security event that impacts or has 
the potential to impact confidentiality, integrity, or availability study data. 
10.4 Study Monitoring 
On behalf of the sponsor, a 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. 
Where applicable, if the sponsor or their representatives are not able to come to the study 
center, patient study data may be reviewed by them remotely, in conformity with the 
applicable institutional guidance and local regulations. The site staff may place relevant 
medical records with personal identifiers removed into a secure computer system for the 
sponsor or their representative to view, allow them to view these records during a video 
conference and/or provide them direct access to patient’s electronic medical records. This 
review would occur in a manner that protects the confidentiality of study patient data. 
Whether a patient’s medical records are reviewed at the study center or remotely, their 
identity and medical records will be kept secure during this process. Remote review of 
patient study data should not be carried out if adequate data protection, including data 
security and protection of personal data even if pseudonymized, is not ensured. Further 
details will be provided in the study training materials. 
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.  
10.5 Case Report Forms and Study Data 
Data collection is the responsibility of the clinical trial 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 

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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 expected adverse reactions data) 
and clinical laboratory data will be entered into Medidata RAVE, a 21 CFR Part 11-
compliant data capture system. The data system 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.  
10.6 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. 
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: 
 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.  
10.7 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. 
10.8 Retention of Study Documents 
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, 

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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, ALCOAC used. Any changes to source data should be 
traceable. 
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 ICFs, 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. 
No data should be destroyed without the agreement of the sponsor. Copies of original 
documents 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. 
10.9 Quality Control and Assurance 
The sponsor will implement and maintain quality control and quality assurance procedures 
with written standard operating procedures to ensure that the study is conducted and data are 
generated, documented, and reported in compliance with the protocol, GCP, and applicable 
regulatory requirements.  
10.9.1 
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 patient having to be withdrawn from the 
study and rendering that subject nonevaluable. 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.  

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10.9.2 
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 via direct access to records, all 
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. 
10.9.3 
Direct Access to Source Data/ Documents for Audits and Inspections 
The investigator 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 investigator will be informed if an audit is to take place and advised as to the 
scope of the audit. Inspections and audits are typically carried out during the clinical and 
reporting phases of this study to ensure that the study is conducted and data are generated, 
documented, and reported in compliance with the protocol, GCP, written standard operating 
procedures (SOPs) and applicable laws, rules, and regulations. 
Representatives of the FDA, EMA, or other regulatory agencies, including IRB/IEC 
representatives may also conduct an audit or inspection of the study. If informed of such an 
activity, the investigator should notify the sponsor immediately. The investigator will ensure 
that the auditors and inspectors have access to the clinical supplies, study site facilities, and 
laboratory, and that all data (including original source documentation) and all study files and 
electronic records are available, if requested. 
10.10 Clinical Study Report 
A clinical study report will be prepared under the responsibility and supervision of the 
sponsor and signed by the sponsor’s Medical & Scientific Director and Quality & Regulatory 
Affairs Director; thereby indicating their agreement with the analyses, results, and 
conclusions of the clinical study report.  
10.11 Publication and Disclosure Policy 
All data generated from this study will be maintained by the sponsor and shared with the lead 
study group, as well as other participating cooperative groups according to the guidelines in 
the Steering Committee Charter and the rules for the respective cooperative groups. All data 

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generated from this study, and all information furnished by the sponsor, the lead study group, 
and other participating study groups shall be held in strict confidence. 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, the lead study group, and 
participating cooperative groups. Written permission to the investigator will be contingent on 
the review of the statistical analysis and manuscripts/abstract by the sponsor and participating 
cooperative groups, and will provide for nondisclosure of the sponsor and cooperative groups 
confidential or proprietary information. In all cases, the parties agree to provide all 
manuscripts or abstracts to all other parties 60 days prior to submission or per specified 
timelines in the Steering Committee Charter. 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.  
10.12 Investigator Oversight 
The investigator has a responsibility for supervising all delegated staff. 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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12 APPENDICES 
Appendix 1 
Response Evaluation Criteria in Solid Tumors Criteria 
A summary of RECIST guidelines (Version 1.1) is provided below. For full details, please 
refer to RECIST guidelines (Version 1.1) described in Eisenhauer (2009)83 and 
http://www.eortc.be/Recist/Default.htm..  
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. 
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. 

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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 diameters of target lesions, taking 
as reference the baseline sum diameters. 
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 diameters of target lesions, taking 
as reference the smallest sum on study (this includes the baseline sum if that 
is the smallest on study). In addition to the relative increase of 20%, the sum 
must also demonstrate an absolute increase of at least 5 mm. (Note: The 
appearance of one or more new lesions is also considered progression.) 
 
Special Notes on the Assessment of Target Lesions 
Lymph Nodes: Lymph nodes identified as target lesions should always have the actual short 
axis measurement recorded (measured in the same anatomical plane as the baseline 
examination), even if the nodes regress to below 10 mm on study. This means that when 
lymph nodes are included as target lesions, the ‘sum’ of lesions may not be zero even if 
complete response criteria are met, since a normal lymph node is defined as having a short 
axis of < 10 mm. 
Target lesions that become too small to measure: While on study, all lesions (nodal and 
non-nodal) recorded at baseline should have their actual measurements recorded at each 
subsequent evaluation, even when very small (eg, 2 mm). However, sometimes lesions or 
lymph nodes that are recorded as target lesions at baseline become so faint on CT scan that 
the radiologist may not feel comfortable assigning an exact measure and may report them as 
being ‘too small to measure’. When this occurs, it is important that a value be recorded on 
the eCRF. If it is the opinion of the radiologist that the lesion has likely disappeared, the 
measurement should be recorded as 0 mm. If the lesion is believed to be present and is faintly 
seen but too small to measure, a default value of 5 mm should be assigned. 
Evaluation of Nontarget Lesions 
Complete Response 
Disappearance of all nontarget lesions and normalization of tumor marker 
level. All lymph nodes must be non-pathological in size (< 10 mm short 
axis) 
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 
Unequivocal progression (see comments below) of existing non-target 
lesions. (Note: the appearance of one or more new lesions is also considered 
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Special Notes on the Assessment of Non-Target Lesions 
The concept of progression of non-target disease requires additional explanation as follows: 
When the patient also has measurable disease: In this setting, to achieve ‘unequivocal 
progression’ on the basis of the non-target disease, there must be an overall level of 
substantial worsening in non-target disease such that, even in presence of SD or PR in target 
disease, the overall tumor burden has increased sufficiently to merit discontinuation of 
therapy (see examples in RECIST1.1).80 A modest ‘increase’ in the size of one or more 
non-target lesions is usually not sufficient to quality for unequivocal progression status. The 
designation of overall progression solely on the basis of change in non-target disease in the 
face of SD or PR of target disease will therefore be extremely rare. 
When the patient has only non-measurable disease: This circumstance arises in some 
Phase 3 studies, such as this study, when it is not a criterion of study entry to have 
measurable disease. The same general concepts apply here as noted above, however, in this 
instance there is no measurable disease assessment to factor into the interpretation of an 
increase in non-measurable disease burden. Because worsening in non-target disease cannot 
be easily quantified (by definition: if all lesions are truly non-measurable) a useful test that 
can be applied when assessing patients for unequivocal progression is to consider if the 
increase in overall disease burden based on the change in non-measurable disease is 
comparable in magnitude to the increase that would be required to declare PD for measurable 
disease: ie, an increase in tumor burden representing an additional 73% increase in ‘volume’ 
(which is equivalent to a 20% increase diameter in a measurable lesion). While it would be 
ideal to have objective criteria to apply to non-measurable disease, the very nature of that 
disease makes it impossible to do so, therefore the increase must be substantial. See further 
examples in Appendix II of the RECIST1.1 publication.80 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some 
‘new’ bone lesions may be simply healing or flare of pre-existing lesions). This is 
particularly important when the patient’s baseline lesions show partial or complete response. 
For example, necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic 
lesion, which it is not.  
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this 
is the patient who has visceral disease at baseline and while on study has a CT or MRI brain 
ordered that reveals metastases. The patient’s brain metastases are considered to be evidence 
of PD even if he/she did not have brain imaging at baseline.  

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If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm 
there is definitely a new lesion, then progression should be declared using the date of the 
initial scan. 
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).  
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 
 
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 
a ‘Non-CR/non-PD’ is preferred over ‘stable disease’ 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 

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lesion be investigated (fine needle aspiration/biopsy) prior to confirming the complete 
response status. 
Duration of Response 
CT scans are required for this study at screening and every 12 calendar weeks (within 7 days 
before is permitted) after initiation of oral/IV combination therapy.  
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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Appendix 2 
Modified Gynecological Cancer Intergroup (GCIG) 
Guidelines for Response or Progression using CA-125 
GCIG CA-125 definitions are available at https://gcigtrials.org/content/ca-125-response-
definition 
 
RESPONSE 
GCIG Guidelines for Response Using CA-12574 (adapted for use in this trial). 
To be evaluable for response by CA-125 requires an elevated baseline value of at least 
2 × ULN and at least 2 additional samples after the start of treatment.  
A response to CA-125 has occurred if there is at least a 50% decrease as the result of the 
treatment. The pre- and post-treatment samples must satisfy the following criteria: 
1. There must be at least 1 sample that is > 2 × ULN prior to initiation of treatment 
2. The second sample (post-treatment) must be ≤ 50% of the pre-treatment sample; 
3. The confirmatory third sample must be ≥ 21 days after the second sample and ≤ 110% of 
the second sample; 
4. Any intervening samples between samples 2 and 3 must be ≤ 110% of the previous 
sample unless considered to be increasing because of tumor lysis. 
 
PROGRESSION 
GCIG Guidelines for Progression Using CA-125: 
For the purposes of evaluating a patient’s eligibility only in the ATHENA study, this 
guidance should be used to determine whether an increase observed in CA-125 levels during 
frontline treatment constitute progression by CA-125. Progressive disease should only be 
determined by RECIST v1.1 assessment for patients during the treatment phase of the study.  
Per GCIG criteria, progression or recurrence based on serum CA-125 levels will be defined 
on the basis of a progressive serial elevation of serum CA-125, according to the following 
criteria: 
A. Patients with elevated CA-125 pre-treatment and normalization of CA-125 must show 
evidence of CA-125 greater than, or equal to, two times the upper normal limit on 
2 occasions at least one week apart, or 
B. Patients with elevated CA-125 pre-treatment, which never normalizes must show 
evidence of CA-125 greater than, or equal to, two times the nadir value on 2 occasions at 
least one week apart or 
C. Patients with CA-125 in the normal range pre-treatment must show evidence of CA-125 
greater than, or equal to, two times the upper normal limit on two occasions at least 
1 week apart. 
 

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Patients are not evaluable by CA-125 if they have received mouse antibodies or if there has 
been medical or surgical interference with their peritoneum or pleura during the previous 
28 days. 
 

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Appendix 3 
ECOG Performance Status Scale 
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. 
 
 
 

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Appendix 4 
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, avanafil, buspirone, conivaptan, darifenacin, darunavir, ebastine, 
everolimus, ibrutinib, lomitapide, lovastatin, midazolam, naloxegol, 
nisoldipine, saquinavir, simvastatin, sirolimus, tacrolimus, 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 202084 
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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Appendix 5 
FACT-O 
Sample forms for the FACT-O is below and background for each questionnaire, respectively, 
is available at: http://www.facit.org/facitorg/questionnaires. 
Patients will complete the IEC/IRB approved version of the assessment on an electronic 
device or other format (ie, paper form), as appropriate.  
FACT-O Sample Questionnaire 
Below is a list of statements that other people with your illness have said are important.  
 
Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
 
PHYSICAL WELL-BEING 
Not at 
all 
A 
little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
GP1 
I have a lack of energy 
 
0 
1 
2 
3 
4 
GP2 
I have nausea  
0 
1 
2 
3 
4 
GP3 
Because of my physical condition, I have 
trouble meeting the needs of my family  
 
0 
 
1 
 
2 
 
3 
 
4 
GP4 
I have pain 
0 
1 
2 
3 
4 
GP5 
I am bothered by side effects of treatment
 
 
0 
1 
2 
3 
4 
GP6 
I feel ill 
 
0 
1 
2 
3 
4 
GP7 
I am forced to spend time in bed  
0 
1 
2 
3 
4 

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Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
 
 
 
 
SOCIAL/FAMILY WELL-BEING 
 
Not at 
all 
A 
little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
GS1 
I feel close to my friends  
0 
1 
2 
3 
4 
GS2 
I get emotional support from my family  
0 
1 
2 
3 
4 
GS3 
I get support from my friends  
0 
1 
2 
3 
4 
GS4 
My family has accepted my illness 
 
0 
1 
2 
3 
4 
GS5 
I am satisfied with family communication 
about my illness  
0 
1 
2 
3 
4 
GS6 
I feel close to my partner (or the person who 
is my main support)  
0 
1 
2 
3 
4 
Q1 
Regardless of your current level of sexual 
activity, please answer the following 
question. If you prefer not to answer it, 
please mark this box           and go to the 
next section. 
 
 
 
 
 
GS7 
I am satisfied with my sex life 
 
0 
1 
2 
3 
4 

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Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
EMOTIONAL WELL-BEING 
Not at 
all 
A 
little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GE1 
I feel sad  
0 
1 
2 
3 
4 
GE2 
I am satisfied with how I am coping with 
my illness  
0 
1 
2 
3 
4 
GE3 
I am losing hope in the fight against my 
illness  
0 
1 
2 
3 
4 
GE4 
I feel nervous  
0 
1 
2 
3 
4 
GE5 
I worry about dying  
0 
1 
2 
3 
4 
GE6 
I worry that my condition will get worse  
0 
1 
2 
3 
4 
 
 
FUNCTIONAL WELL-BEING 
 
Not 
at all 
A 
little 
bit 
Some-
what 
Quite
a bit 
Very 
much 
 
GF1 
I am able to work (include work at home)
 
 
0 
1 
2 
3 
4 
GF2 
My work (include work at home) is 
fulfilling  
0 
1 
2 
3 
4 
GF3 
I am able to enjoy life  
0 
1 
2 
3 
4 
GF4 
I have accepted my illness 
 
0 
1 
2 
3 
4 
GF5 
I am sleeping well  
0 
1 
2 
3 
4 
GF6 
I am enjoying the things I usually do for fun 
0 
1 
2 
3 
4 
GF7 
I am content with the quality of my life 
right now  
0 
1 
2 
3 
4 
 
 
 
 

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Please circle or mark one number per line to indicate your response as it applies to the 
past 7 days. 
 
ADDITIONAL CONCERNS 
 
Not at 
all 
A 
little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
 
 
O1 
I have swelling in my stomach area  
0 
1 
2 
3 
4 
C2 
I am losing weight 
0 
1 
2 
3 
4 
C3 
I have control of my bowels  
0 
1 
2 
3 
4 
O2 
I have been vomiting  
0 
1 
2 
3 
4 
B5 
I am bothered by hair loss 
0 
1 
2 
3 
4 
C6 
I have a good appetite  
0 
1 
2 
3 
4 
C7 
I like the appearance of my body  
0 
1 
2 
3 
4 
BM
T5 
I am able to get around by myself 
0 
1 
2 
3 
4 
B9 
I am able to feel like a woman 
 
0 
1 
2 
3 
4 
O3 
I have cramps in my stomach area 
 
0 
1 
2 
3 
4 
BL4 
I am interested in sex  
0 
1 
2 
3 
4 
BM
T7 
I have concerns about my ability to have 
children 
 
0 
1 
2 
3 
4 
 
 
 
 

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Appendix 6 
Euro-QoL5D-5L 
A sample form for the EQ-5D-5L is below and background for the questionnaire is available 
at http://www.euroqol.org/home.html.  
Patients will complete the IEC/IRB approved version of the assessment on an electronic 
device or other format (ie, paper form), as appropriate. 
Euro-QoL5D-5L (EQ-5D-5L) – English Version for the US 
Under each heading, please check the ONE box that best describes your health TODAY. 
Mobility 
I have no problems walking 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I have slight problems walking  
 
 
 
 
 
 
 
 
 
 
 
 
 
I have moderate problems walking 
 
 
 
 
 
 
 
 
 
 
 
 
I have severe problems walking  
 
 
 
 
 
 
 
 
 
 
 
 
I am unable to walk  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Self-Care 
I have no problems washing or dressing myself  
 
 
 
 
 
 
 
 
I have slight problems washing or dressing myself  
 
 
 
 
 
 
 
I have moderate problems washing or dressing myself 
 
 
 
 
 
 
I have severe 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 doing my usual activities  
 
 
 
 
 
 
 
I have slight problems with doing my usual activities 
 
 
 
 
 
 
 
I have moderate problems with doing my usual activities  
 
 
 
 
 
I have severe problems with doing my usual activities  
 
 
 
 
 
 
I am unable to do my usual activities  
 
 
 
 
 
 
 
 
 
 
 
 

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Pain/Discomfort 
I have no pain or discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I have slight pain or discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
I have moderate pain or discomfort  
 
 
 
 
 
 
 
 
 
 
  
I have severe pain or discomfort  
 
 
 
 
 
 
 
 
 
 
 
 
I have extreme pain or discomfort  
 
 
 
 
 
 
 
 
 
 
 
 
 
Anxiety/Depression 
I am not anxious or depressed 
 
 
 
 
 
 
 
 
 
 
 
 
  
I am slightly anxious or depressed 
 
 
 
 
 
 
 
 
 
 
 
 
I am moderately anxious or depressed  
 
 
 
 
 
 
 
 
 
  
I am severely anxious or depressed  
 
 
 
 
 
 
 
 
 
 
 
I am extremely anxious or depressed  
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 7 
Management Algorithms for Immuno-Oncology Agents 
These general guidelines (28 September 2020; CTCAE v5.0) constitute guidance to the 
Investigator and may be supplemented by discussions with the Medical Monitor representing 
the Sponsor. The guidance applies to all immuno-oncology agents and regimens. 
A general principle is that differential diagnosis should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and 
appropriately treated. 
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The 
oral equivalent of the recommended IV doses may be considered for ambulatory patients 
with low-grade toxicity. The lower bioavailability of oral corticosteroids should be taken into 
account when switching to the equivalent dose of oral corticosteroids. 
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic 
or therapeutic procedure, is recommended. 
The frequency and severity of the related adverse events covered by these algorithms will 
depend on the immuno-oncology agent or regimen being used. 

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GI Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause is identified, treat accordingly and continue I-O therapy.  
Opiates/narcotics may mask symptoms of perforation. Infliximab should not be used in cases of perforation or sepsis. 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
*Discontinue for Grade 4 diarrhea or colitis. For Grade 3 diarrhea or colitis, I-O therapy can be delayed. I-O therapy can be resumed when symptoms improve 
to Grade 1. Please refer to the protocol for dose delay and discontinue criteria for other combinations. 
 

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Renal Adverse Event Management Algorithm – Rucapariba and Nivolumab 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy. 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
a Baseline for creatinine will be considered pre-dose to the first IV infusion. 
 

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Pulmonary Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy.  
Evaluate with imaging and pulmonary consultation. 
  
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
 

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Hepatic Adverse Event Management Algorithm-Rucapariba and Nivolumab 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy.  
Consider imaging for obstruction. 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
^ Please refer to the protocol dose delay and discontinue criteria for specific details. 
* The recommended starting dose for AST or ALT > 20 × ULN or bilirubin > 10 × ULN is 2 mg/kg/day methylprednisolone IV. 
a Rucaparib may cause transient AST and/or ALT elevations (without increased total bilirubin) in Cycle 1. Please see Section 5.6.1.2 and Section 5.6.4.2 for 
details about when a hold or discontinuation of IV drug is not required due to a background of AST and/or ALT elevations that are due to oral drug. 

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Endocrinopathy Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy.  
Consider visual field testing, endocrinology consultation, and imaging. 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 

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Skin Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy. 
 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
* Refer to NCI CTCAE v5 for term-specific grading criteria. 
^ If Steven-Johnson Syndrome (SIS), toxic epidermal necrosis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, withhold I-O 
therapy and refer patient for specialized care for assessment and treatment. If SIS, TEN, or DRESS is diagnosed, permanently discontinue I-O therapy. 

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Neurological Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy. 
 
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
^ Discontinue for any grade myasthenia gravis, Guillain-Barre syndrome, treatment-related myelitis, or encephalitis. 
 

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Myocarditis Adverse Event Management Algorithm 
Rule out non-inflammatory causes. If non-inflammatory cause, treat accordingly and continue I-O therapy. 
  
Patients on IV steroids may be switched to an equivalent dose of oral corticosteroids (eg, prednisone) at start of tapering or earlier, after sustained clinical 
improvement is observed. Lower bioavailability of oral corticosteroids should be taken into account when switching to the equivalent dose of oral 
corticosteroids. 
Prophylactic antibiotics should be considered in the setting on ongoing immunosuppression. 
 
 

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Appendix 8 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab 
Drug-Related Adverse Event 
(AE) per CTCAE V5 
Severity  
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
Gastrointestinal 
Colitis or Diarrhea 
Grade 2  
Delay dose 
Dosing may resume when AE resolves to baseline  
Grade 3  
Nivolumab monotherapy: Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 4  
Permanently discontinue 
  
Renal 
Serum Creatinine Increased 
Grade 2 or 3  
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1  
or baseline value 
Grade 4  
Permanently discontinue 
  
Pulmonary 
Pneumonitis 
Grade 2  
Delay dose 
Dosing may resume after pneumonitis has resolved 
to ≤ Grade 1. 
Grade 3 or 4  
Permanently discontinue 
 
Hepatic 
 
Aspartate aminotransferase 
(AST), alanine 
aminotransferase (ALT), or 
total bilirubin (T.bili) increased 
AST or ALT > 3x and ≤5x 
upper limit of normal (ULN) 
or T.Bili >1.5x and ≤3x ULN, 
regardless of baseline value 
Delay dose 
Dosing may resume when laboratory values return 
to baseline. 
AST or ALT > 5 x ULN or T. 
bili > 3 x ULN, regardless of 
baseline value 
Permanently discontinue  
 
Concurrent AST or ALT > 3 x 
ULN and T.bili > 2 x ULN, 
regardless of baseline value 
Permanently discontinue  
  

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Endocrinopathy 
Adrenal Insufficiency 
Grade 2 adrenal insufficiency 
Delay dose 
Dosing may resume after adequately controlled 
with hormone replacement. 
Grade 3 or 4 adrenal 
insufficiency or adrenal crisis 
Delay dose or permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If adrenal insufficiency resolves or is adequately 
controlled with physiologic hormone replacement, 
participant may not require discontinuation of study 
drug. 
Hyperglycemia 
Hyperglycemia requiring 
initiation or change in daily 
management (Grade 2 or 3) 
Delay dose 
Dosing may resume if hyperglycemia resolves to 
Grade ≤1 or baseline value, or is adequately 
controlled with glucose-controlling agents. 
Grade 4 
Delay dose or permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If hyperglycemia resolves, or is adequately 
controlled with glucose-controlling agents, 
participant may not require discontinuation of study 
drug. 
Hypophysitis/Hypopituitarism  
Symptomatic Grade 1-3 that is 
also associated with 
corresponding abnormal lab 
and/or pituitary scan 
Delay dose  
Dosing may resume if endocrinopathy resolves to 
be asymptomatic, or is adequately controlled with 
only physiologic hormone replacement. 
Grade 4 
Delay dose or permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If endocrinopathy resolves or is adequately 
controlled with physiologic hormone replacement, 
participant may not require discontinuation of study 
drug. 
Hyperthyroidism or  
Hypothyroidism 
Grade 2 or 3 
Delay dose 
Dosing may resume if endocrinopathy resolves to 
be asymptomatic, or is adequately controlled with 
only physiologic hormone replacement or other 
medical management. 
Grade 4 
Delay dose or permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If endocrinopathy resolves or is adequately 
controlled with physiologic hormone replacement 
or other medical management, participant may not 
require discontinuation of study drug. 

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Skin 
Rash 
Grade 2 rash covering >30% 
body surface area or Grade 3 
rash  
Delay dose  
Dosing may resume when rash reduces to ≤10% 
body surface area  
Suspected Stevens-Johnson 
syndrome (SJS), toxic 
epidermal necrolysis (TEN) or 
drug reaction with eosinophilia 
and systemic symptoms 
(DRESS) 
Delay dose 
Dosing may resume if SJS, TEN, or DRESS is 
ruled out and rash reduces to is ≤10% body surface 
area 
Grade 4 rash or confirmed 
SJS,TEN, or DRESS 
Permanently discontinue 
  
Neurological 
Guillain-Barre Syndrome 
(GBS) 
Any Grade 
Permanently discontinue 
 
Myasthenia Gravis (MG) 
Any Grade 
Permanently discontinue 
Encephalitis 
Any Grade encephalitis 
Delay dose  
After workup for differential diagnosis, (i.e. 
infection, tumor-related), if encephalitis is not drug 
related, then dosing may resume when AE resolves  
Any Grade drug-related 
encephalitis  
Permanently discontinue 
  
Myelitis 
Any Grade myelitis 
Delay dose 
After workup for differential diagnosis, (i.e. 
infection, tumor-related), if myelitis is not drug 
related, then dosing may resume when AE resolves  
Any Grade drug-related 
myelitis 
Permanently discontinue 
  
Neurological (other than GBS, 
MG, encephalitis, or myelitis) 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline  
Grade 3 or 4 
Permanently discontinue 
  
Myocarditis 
Myocarditis 
Symptoms induced from mild 
to moderate activity or 
exertion 
Delay dose 
Dosing may resume after myocarditis has resolved 

Rucaparib 
 
pharma& 
Clinical Study Protocol: CO-338-087 Amendment 5 
 
16 June 2023 
Confidential 
Page 173 
 
Severe or life threatening, with 
symptoms at rest or with 
minimal activity or exertion, 
and/or where intervention 
indicated. 
Permanently discontinue 
  
Other Clinical AE 
Pancreatitis:  
 
Amylase or Lipase increased 
Grade 3 with symptoms 
Delay dose 
Note: Grade 3 increased amylase or lipase without 
signs or symptoms of pancreatitis does not require 
dose delay.  
Dosing may resume when patient becomes 
asymptomatic. 
Grade 4 
Permanently discontinue 
  
Uveitis  
Grade 2 uveitis 
Delay dose 
Dosing may resume if uveitis responds to topical 
therapy (eye drops) and after uveitis resolves to 
Grade ≤ 1 or baseline. If patient requires oral 
steroids for uveitis, then permanently discontinue 
study drug.  
Grade 3 or 4 uveitis 
Permanently discontinue 
  
Other Drug-Related AE (not 
listed above) 
Grade 2 non-skin AE, except 
fatigue 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value. 
Grade 3 AE - First occurrence 
lasting ≤ 7 days 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value. 
Grade 3 AE- First occurrence 
lasting > 7 days 
Permanently discontinue 
  
Recurrence of Grade 3 AE of 
any duration 
Permanently discontinue 
  
Grade 4 or Life-threatening 
adverse reaction 
Permanently discontinue 
  
Other Lab abnormalities  
Other Drug-Related lab 
abnormality (not listed above) 
Grade 3 
Delay dose 
Exceptions: 
No delay required for: Grade 3 lymphopenia  
 
Permanent Discontinuation for: Grade 3 
thrombocytopenia > 7 days or associated with 
bleeding.  

Rucaparib 
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Clinical Study Protocol: CO-338-087 Amendment 5 
16 June 2023 
Confidential 
Page 174 
Grade 4 
Permanently discontinue 
Exceptions: The following events do not require 
discontinuation of study drug:  
Grade 4 neutropenia ≤ 7 days
Grade 4 lymphopenia or leukopenia
Grade 4 isolated electrolyte
imbalances/abnormalities that are not associated
with clinical sequelae and are responding to
supplementation/appropriate management within
72 hours of their onset
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other allergic-like 
reactions.) 
Hypersensitivity reaction or 
infusion reaction 
Grade 3 or 4 
Permanently discontinue 
Refer to Section 7.4.4 on Treatment of Related 
Infusion Reactions