Clinical trial NCT03955471
Conditions: Ovarian Neoplasms
Keywords: Open-label Single-arm Efficacy and Safety Platinum-resistant ovarian cancer Niraparib dostarlimab
Sponsor: Tesaro, Inc.
Start date: 2019-10-03; Completion date: 2022-01-12
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.

Detailed description:

Arms: arm 1: Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight \<77 kg or platelet count \<150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months.
Interventions: intervention 1: Niraparib intervention 2: Dostarlimab
Intervention descriptions: intervention 1: Niraparib is a potent, orally active poly (adenosine diphosphate-ribose) polymerase (PARP)-1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors. intervention 2: TSR-042 is a humanized monoclonal antibody that binds with high affinity to programmed cell death-1 (PD-1) resulting in inhibition of binding to programmed cell-death receptor ligands 1 and 2 (PD-L1 and PD-L2).

Protocol documents:
Prot_000.pdf: 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Table 1: 
Document History 
Document 
Date 
Document Number 
Sponsor 
Amendment 3 (Version 4) 
15 December 
2021 
TMF-14140373 
Tesaro, 
Inc., a 
GSK 
Company 
Amendment 2 (Version 3) 
17 November 
2020 
2020N458945_00 
Tesaro* 
Amendment 1 (Version 2) 
18 October 2019 
NA 
Tesaro* 
Original Protocol (Version 1.0) 
04 October 2018 
NA 
Tesaro* 
Abbreviations: GSK=GlaxoSmithKline. 
*Tesaro is a wholly owned  
Amendment 3 (15 December 2021) 
Overall Rationale for the Amendment 
Amendment 03 revises the protocol to reflect the post analysis continuation of treatment 
(PACT) for participants that will continue to receive study treatment following final data 
cut-off (DCO).  
Summary of Changes for the Amendment 
Table 2: 
Summary of Changes for Amendment 03 (15 December 2021) 
Section(s) Affected 
Description of Change 
Brief Rationale 
Headers, cover page, and 
Protocol Amendment 
Summary of Changes 
Headers and cover page were 
updated with new version 
number; headers were updated 
with new document number; 
Protocol Amendment Summary 
of Changes section was updated 
to include rationale for new 
version 
Editorial changes to align 
with the Sponsor’s standard 
protocol template and ways 
of working 
Synopsis  
7.1.3 Continued Treatment 
After Final DCO 
New section added to provide 
clarification on the continuation 
of treatment after the final DCO 
date. 
To provide continued 
treatment options to patients 
still deriving clinical benefit 
from treatment when the final 
DCO date is reached 
7.4.1 Niraparib Dose 
Adjustment  
 
Added new requirement that if a 
patient is diagnosed with 
myelodysplastic syndrome 
(MDS) or acute myeloid 
leukemia (AML), the patient 
Program level update 
 
 


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7.4.2 Dostarlimab Dose 
Adjustment  
 
9.2.3 Supportive Care for 
Adverse Events 
must permanently discontinue 
niraparib. 
Updated dose modifications for 
adrenal insufficiency to include 
endocrine consultation as follow 
up. 
Expanded dose modifications for 
diarrhea / colitis to include 
recurrent Grade 3.  
Expanded dose modifications for 
pneumonitis to include recurrent 
Grade 2. 
“Permanently discontinue” for 
Grade 4 severity was removed 
from adrenal insufficiency, 
hypophysitis, hypothyroidism 
and hyperthyroidism.  
Added dose modifications for 
myocarditis, severe neurological 
events, severe skin reactions, 
hemophagocytic 
lymphohistiocytosis, and other 
immune-related adverse 
events of interest (irAEIs) 
 
 
Clarifications, corrections, 
and program updates, 
including mitigation of 
potentially serious 
complications of immune-
related events. 
 
 
 
Clinical management of these 
endocrinopathies are 
amenable to hormone 
replacement therapies or 
thyroid suppressive therapy 
and the adequacy of 
supplementation monitorable 
symptomatically and with 
laboratory assessments. 
7.6.3 Continued Treatment 
After Final DCO 
New section added to provide 
information on the study 
assessments required for patients 
continuing treatment after the 
final DCO date. 
To provide continued 
treatment options to patients 
still deriving clinical benefit 
from treatment when the final 
DCO date is reached 
10.6.1 Continued Access 
to Study Treatment After 
Final DCO  
New section added to provide 
drug accountability and 
dispensing information for 
patients continuing treatment 
after the final DCO date. 
To provide continued 
treatment options to patients 
still deriving clinical benefit 
from treatment when the final 
DCO date is reached 
7.1.4 Schedule of Safety 
Assessments  
12.3 Safety Monitoring 
For Continuation of 
Treatment After Final 
DCO 
New section added to provide 
information on the safety 
monitoring requirements for 
patients continuing treatment 
after the final DCO date. 
To provide continued 
treatment options to patients 
still deriving clinical benefit 
from treatment when the final 
DCO date is reached 
 


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SPONSOR SIGNATURE PAGE 
 
Declaration of Sponsor or Responsible Medical Officer 
 
Title (3000-02-006): A Phase 2 Open-label, Single-arm Study to Evaluate the Efficacy 
and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients with 
Platinum-Resistant Ovarian Cancer (MOONSTONE) 
 
 
This study protocol was subjected to critical review and has been approved by the 
Sponsor. The information it contains is consistent with the current risk/benefit evaluation 
of the investigational product as well as with the moral, ethical, and scientific principles 
governing clinical research as set out in the Declaration of Helsinki and the guidelines on 
Good Clinical Practice.  
 
 
 
 
  
_________________________________ 
_________________________________ 
Vivek Samnotra, MD 
Date 
Senior Medical Director 
 
 


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


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2. 
SYNOPSIS 
Name of Sponsor/Company: TESARO, Inc., a GlaxoSmithKline Company 
Name of Investigational Product(s): Niraparib and dostarlimab (TSR-042)  
Name of Active Ingredient: Niraparib (niraparib tosylate monohydrate) and dostarlimab 
(TSR-042) (anti-programmed cell death-1 [anti-PD-1] monoclonal antibody, 
immunoglobulin G4) 
Study Number:  3000-02-006/213353 
Title of Study: A Phase 2 Open-label, Single-arm Study to Evaluate the Efficacy and Safety 
of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients with Platinum-
Resistant Ovarian Cancer (MOONSTONE) 
Study center(s): Multi-center 
Principal Investigator: N/A 
Investigators: Multi-center 
Studied period (years):  
Estimated date first patient enrolled: Q1 2019 
Estimated date last patient last visit: Q2 2022 
Phase of development:  
Phase 2 
Hypothesis: 
Treatment with the combination of niraparib and dostarlimab (TSR-042) in patients with 
platinum-resistant ovarian cancer (PROC) without breast cancer susceptibility gene (BRCA) 
mutation who were previously treated with bevacizumab may result in an objective response 
rate (ORR) that is higher than the ORR expected with other available approved therapies for 
this population. This study will evaluate the efficacy of combination therapy by estimating 
the ORR along with the duration of response (DOR) in these patients.   
Objectives:  
Primary: 
The primary objective of this study is to evaluate the efficacy, as measured by confirmed 
ORR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on Investigator 
assessment, of the combination of niraparib and dostarlimab (TSR-042) in:  
• 
patients with PROC without a known BRCA mutation who have been previously 
treated with bevacizumab. 
• 
subset of patients with PROC who have programmed cell death-ligand 1 (PD-L1) 
positive tumors (using a prespecified cut point) without a known BRCA mutation 
who have been previously treated with bevacizumab. 
Secondary: 
Secondary objectives of this study are as follows and will be evaluated in the overall 
population and in the subset of patients with PD-L1 positive tumors: 
• 
To evaluate the overall clinical benefit of the niraparib and dostarlimab (TSR-
042) combination as measured by the following secondary endpoints: 
− 
DOR per RECIST v1.1 based on Investigator assessment 
− 
progression-free survival (PFS) per RECIST v1.1 based on Investigator 


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assessment 
− 
overall survival (OS) 
− 
disease control rate (DCR), defined as the percentage of patients who have 
achieved best overall response (BOR) of confirmed partial response (PR), 
complete response (CR), or stable disease (SD) per RECIST v1.1 based on 
Investigator assessment  
• 
To evaluate the ORR, DOR, PFS, and DCR per RECIST v1.1 based on 
independent review committee assessment 
• 
To evaluate the safety and tolerability of the niraparib and dostarlimab (TSR-
042) combination in patients with PROC as measured by standard safety 
assessments 
Exploratory: 
Exploratory objectives of this study are as follows and will be evaluated in the overall 
population and in the subset of patients with PD-L1 positive tumors: 
• 
To evaluate efficacy of the niraparib and dostarlimab (TSR-042) combination 
among patients with BRCA wild type (BRCAwt) tumors, as measured by 
confirmed ORR, DOR, PFS, OS, and DCR based on Investigator assessment 
using RECIST v1.1 
• 
To evaluate the duration of disease control among patients with BOR of CR, PR, 
or SD based on Investigator assessment and independent review committee 
assessment 
• 
To evaluate health-related quality of life (HRQoL) in patients with PROC treated 
with the combination of niraparib and dostarlimab (TSR-042), as measured by 
the Functional Assessment of Cancer Therapy – Ovarian Symptom Index (FOSI) 
• 
To identify additional potential disease-related or treatment-related biomarkers 
that correlate with responses to the niraparib and dostarlimab (TSR-042) 
combination, including, but not limited to, the measures of homologous 
recombination repair pathway defects and the optimal PD-L1 level for efficacy to 
be used in other dostarlimab ovarian cancer studies. 
Methodology:  
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of the 
combination of niraparib and dostarlimab (TSR-042) in patients with advanced, relapsed, 
high-grade ovarian, fallopian tube, or primary peritoneal cancer without known BRCA 
mutation who have platinum-resistant disease and who have also been previously treated with 
bevacizumab. 
This study will consist of a screening period (Day -28 to Day -1), a treatment period, an 
end-of-treatment period when study treatment is discontinued for any reason, a Safety 
Follow-up Visit occurring 30 ± 7 days after the last dose of study treatment, and recurring 
survival assessments occurring every 90 ± 14 days after the last dose of study treatment. All 
patients will undergo an End of Treatment Visit within 7 days of the decision to discontinue 
treatment for any reason. 
Patients must provide a sufficient tumor tissue sample (formalin fixed paraffin embedded 


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[FFPE] blocks) for BRCA testing and PD-L1 testing at screening. Slides cut from FFPE 
blocks must be approved by the Sponsor Blood samples will be collected at screening for 
central germline BRCA testing. Blood samples will also be collected for exploratory 
biomarker analysis at screening, at Cycle 3 Day 1, at the time of Investigator-assessed PR 
(+ 21 days), at the time of Investigator-assessed CR (+ 21 days), and at the End of Treatment 
Visit.  
All patients will receive treatment with niraparib and dostarlimab (TSR-042) (collectively 
referred to as “study treatment”) beginning on Cycle 1 Day 1 using the regimen detailed 
below. Treatment Cycles 1 to 4 are 3 weeks long and Cycles 5 and later are 6 weeks long. 
Study Regimen 
Niraparib 
Dostarlimab (TSR-042) 
Starting doses are as follows: 
• 
300 mg PO QD continuously in patients 
with screening actual body weight ≥ 77 
kg AND screening platelet count 
≥ 150,000/μL until PD or toxicity  
• 
200 mg PO QD continuously in patients 
with screening actual body weight < 77 
kg OR screening platelet count 
< 150,000/μL until PD or toxicity  
• 
500 mg IV on Day 1 of each 3-week 
cycle (Q3W Cycles 1 to 4), followed by 
1,000 mg IV on Day 1 of each 6-week 
cycle (Q6W Cycle 5 and later) until PD 
or toxicity 
Abbreviations: IV = intravenous; PD = progressive disease; PO = orally; Q3W = every 3 weeks; 
Q6W = every 6 weeks; QD = once daily 
Safety assessments performed will include collection of adverse events (AEs), vital sign 
measurements, symptom-directed physical examinations, and clinical laboratory assessments.  
Radiographic evaluations (ie, computed tomography/magnetic resonance imaging of chest, 
abdomen, and pelvis) to assess the extent of disease will be conducted every 9 weeks 
(63 ± 7 days) for the first year of study treatment, independent of cycle delays or dose 
interruptions, or at any time when progression of disease is suspected. After 1 year of 
radiographic assessments (week 54), imaging will be performed every 12 weeks 
(84 ± 14 days). Per RECIST v.1.1, CR or PR should be confirmed; tumor imaging for 
confirmation of response must be performed at the earliest 28 days after the first indication of 
PR or CR but no later than 35 days after the response. The subsequent tumor imaging after 
the confirmatory scan should be obtained per the original scheduled interval (eg, 9 weeks 
[63 ± 7 days] from a confirmatory scan during the first year of study treatment and every 
12 weeks thereafter). Radiographic evaluations will continue until progressive disease (PD), 
start of alternate anticancer therapy, withdrawal of consent to study participation, becoming 
lost to follow-up, death, or end of the study. If a patient discontinues treatment for a reason 
other than radiographic progression, death, withdrawal of consent, loss to follow-up, or the 
end of the study, radiographic evaluation and cancer antigen 125 (CA-125) testing should 
continue at the specified intervals (ie, every 9 weeks for the first year of study treatment and 
every 12 weeks thereafter until PD). Also, clinically stable patients should not be 
discontinued until progression is confirmed. If a patient discontinues treatment for clinical 
progression and does not meet RECIST criteria for progression, scans and CA-125 testing 
should continue at the specified intervals until progression is confirmed or until the start of 
subsequent anticancer treatment.  


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All AEs (serious and nonserious) will be collected and recorded for each patient from the day 
of signing the informed consent form until 90 days after last study drug administration or 
until alternate anticancer treatment has been initiated, whichever occurs earlier; any 
pregnancies that occur within 180 days post-treatment are to be reported. 
All AESIs must be reported as outlined in Section 12.2.7. All AEs including SAEs 
experienced by a patient, regardless of the suspected causality, will be monitored until the AE 
or SAE has resolved, until any abnormal laboratory values have returned to baseline or 
normalized, until there is a satisfactory explanation for the change(s) observed, until the 
patient is lost to follow-up or withdraws consent, or until the patient has died. 
After the final DCO date, for patients continuing study treatment, all SAEs, AESIs (as 
defined in Section 12.2.7), AEs leading to discontinuation, overdoses, and pregnancies must 
be reported as detailed in Section 12.2.5 to the Sponsor within 24 hours of becoming aware of 
a new event or of new (follow up) information on a previously reported event and signed by 
the Investigator or Sub-Investigator. 
Overall Study Schema 
*Excludes patients who experienced disease progression within 3 months of first-line platinum therapy  
**Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy. 
Treatment with single-agent bevacizumab given as maintenance is not counted as a separate line of 
therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or 
PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of 
therapy. The use of single-agent hormonal therapy given for reasons other than progressive disease 
per RECIST v1.1 (ie, hormonal therapy given for increasing CA-125 levels) is not counted as a 
separate line of therapy. 
Abbreviations: CA-125 = cancer antigen 125; BRCA = breast cancer susceptibility gene; 
ORR = objective response rate; PARPi = poly(adenosine diphosphate-ribose) polymerase inhibitor; 
PD = progressive disease; PD(L)-1 = programmed cell death-1 or programmed cell death-ligand 1. 
Number of patients (planned): It is anticipated that approximately 150 patients will be 
enrolled and dosed. 
Diagnosis and main criteria for inclusion:  
Patients will be eligible for study entry if all of the following criteria are met: 
1. Patient must be female ≥ 18 years of age, able to understand the study procedures, 


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and agree to participate in the study by providing written informed consent. 
2. Patients must have recurrent high-grade serous, endometrioid, or clear cell ovarian, 
fallopian tube, or primary peritoneal cancer.  
3. Patients must be considered resistant to the last administered platinum therapy, ie, the 
time from last administered platinum dose until the initial documented progression 
(as evidenced by radiographic progression per RECIST v.1.1) must be less than 6 
months (183+7 days).  
4. Patients must have completed at least 1 but no more than 3 prior lines of therapy for 
advanced or metastatic ovarian cancer. Neoadjuvant, adjuvant, and the combination 
of both will be considered as one line of therapy. Treatment with single-agent 
bevacizumab given as maintenance is not counted as a separate line of therapy. If a 
therapeutic regimen is modified or changed for a reason other than lack of response 
or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a 
separate line of therapy. The use of single-agent hormonal therapy given for reasons 
other than progressive disease per RECIST v1.1 (ie, hormonal therapy given for 
increasing CA-125 levels) is not counted as a separate line of therapy. 
5. Patients must have been previously treated with platinum-based regimen, taxane 
agent(s), and bevacizumab (bevacizumab could be used as a single agent or in 
combination with another agent, in frontline therapy, as maintenance, or for treatment 
of recurrent disease). 
Note: Bevacizumab refers to bevacizumab and approved biosimilars, for example, 
bevacizumab –awwb (MVASI™), bevacizumab-bvzr (ZIRABEV™), etc. 
6. Patient has measurable disease according to RECIST v.1.1. 
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 
or 1 (see Appendix 3). 
8. Patient has adequate organ function, defined as follows: 
a. Absolute neutrophil count ≥ 1,500/μL, without growth factor support 
(granulocyte colony-stimulating factor or granulocyte-macrophage colony-
stimulating factor administration is not permitted within 2 weeks of screening)  
b. Platelets ≥ 100,000/μL, without platelet transfusion support within 2 weeks of 
screening 
c. Hemoglobin ≥ 9 g/dL, without transfusion or growth factor support (recombinant 
erythropoietin) within 2 weeks of screening 
d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 50 mL/min using Cockcroft-Gault equation  
e. Total bilirubin ≤ 1.5 × ULN, except in patients with Gilbert’s syndrome. Patients 
with Gilbert’s syndrome may enroll if direct bilirubin is ≤ 1.5 × ULN. 
f. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN, unless 
liver metastases are present, in which case they must be ≤ 5 × ULN 
9. Patient meets the following criteria:  
a. Female patient (of childbearing potential) is not breastfeeding, has a negative 
serum pregnancy test within 72 hours prior to taking study treatment, agrees to 
abstain from activities that could result in pregnancy, as outlined in Section 9.2.2, 
from enrollment through 180 days after the last dose of study treatment ; or  


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Note: (a) A urine pregnancy test may be performed if the serum pregnancy result 
is not available before dosing. (b) Women should not breastfeed or store 
breastmilk for use, during treatment, and for 30 days after receiving the final 
dose of study treatment. 
b. Female patient is of nonchildbearing potential, for other than medical reasons, 
defined as any of the following:  
− 
≥ 45 years of age and has not had menses for > 1 year  
− 
Amenorrheic for < 2 years without a hysterectomy and oophorectomy and a 
follicle-stimulating hormone value in the postmenopausal range upon 
screening evaluation  
− 
Has undergone hysterectomy, bilateral oophorectomy, or tubal ligation. 
Documented hysterectomy or oophorectomy must be confirmed with medical 
records of the actual procedure or confirmed by an ultrasound. Tubal ligation 
must be confirmed with medical records of the actual procedure; otherwise, 
the patient must meet the pregnancy test criteria for women of childbearing 
potential in inclusion criterion 9a and must be willing to use highly effective 
contraception throughout the study, starting with the screening visit through 
180 days after the last dose of study therapy.  
Note: Abstinence is acceptable if this is the established and preferred 
contraception method for the patient.  
10. Patient must provide FFPE tumor tissue block(s) with sufficient tumor content (as 
confirmed by the Sponsor’s designated central laboratory) during screening to enable 
BRCA testing and PD-L1 testing.  The use of slides created from paraffin-embedded 
tissue as opposed to FFPE blocks must be approved by the Sponsor. 
11. Patient must agree to complete the HRQoL questionnaire throughout the study. 
Main Criteria for Exclusion: 
Patients will not be eligible for study entry if any of the following criteria are met: 
1. Patients who experienced disease progression within 3 months (12 weeks or 84 days) 
(as evidenced by radiographic progression per RECIST v1.1) of first-line platinum 
therapy.  
2. Patients with known deleterious or suspected deleterious mutation in breast cancer 
susceptibility gene (BRCA) 1 or BRCA2 genes (local testing permitted).    
Note: This will apply to known germline BRCA mutations and known BRCA 
mutations in the tumor. 
3. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or 
anti-programmed death-ligand-2 (anti-PD-L2) agent. 
4. Patient has received prior therapy with a poly(adenosine diphosphate-ribose) 
polymerase (PARP)-1/PARP-2 inhibitor. 
5. Patient has known hypersensitivity to dostarlimab (TSR-042), niraparib, their 
components, or their excipients. 
6. Patient has a known history of myelodysplastic syndrome or acute myeloid leukemia. 


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7. Patient has not recovered (ie, to Grade ≤ 1 or to baseline) from prior chemotherapy 
induced AEs. Note: Patient with Grade ≤ 2 neuropathy or alopecia is an exception to 
this criterion and may qualify for the study.  
8. Patient has a known diagnosis of immunodeficiency or is receiving systemic steroid 
therapy exceeding an equivalent of prednisone 10 mg daily or any other form of 
immunosuppressive therapy within 7 days prior to the first dose of study treatment. 
9. Patient is currently participating in a treatment study or has participated in a study of 
an investigational agent within 4 weeks of the first dose of treatment. 
10. Patient has received prior systemic anticancer therapy including cytotoxic 
chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, or 
biological therapy within 3 weeks of the first dose of study treatment.  
11. Patient has received live vaccine within 14 days of planned start of study therapy. 
12. Patient has symptomatic uncontrolled brain or leptomeningeal metastases. (To be 
considered “controlled,” central nervous system [CNS] disease must have undergone 
treatment [eg, radiation or chemotherapy] at least 1 month prior to study entry. The 
patient must not have any new or progressive signs or symptoms related to the CNS 
disease and must be taking ≤ 10 mg of prednisone or equivalent per day or no 
steroids.) Patients who have untreated brain metastases and who are not symptomatic 
may enroll if the Investigator feels that treatment of these metastases is not indicated. 
A scan to confirm the absence of brain metastases is not required. Patients with spinal 
cord compression may be considered if they have received definitive treatment for 
this and evidence of clinically stable disease for 28 days prior to the first dose of 
study treatment. 
13. Patient had major surgery within 4 weeks of starting the first dose of study treatment 
or patient has not recovered from any effects of any major surgery. 
14. Patient has a known additional malignancy that progressed or required active 
treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, 
squamous cell carcinoma of the skin that has undergone potentially curative therapy, 
or in situ cancer that is considered to be low risk for progression by the Investigator. 
15. Patient is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active, uncontrolled infection. These 
include, but are not limited to, significant cardiovascular disease (eg, significant 
cardiac conduction abnormalities, myocardial infarction, cardiac arrhythmia or 
unstable angina within 6 months prior to enrollment, New York Heart Association 
Grade ≥ 2 congestive heart failure, uncontrolled hypertension, serious cardiac 
arrhythmia requiring medication, Grade ≥ 2 peripheral vascular disease, and history 
of cerebrovascular accident within 6 months prior to enrollment), uncontrolled major 
seizure disorder, unstable spinal cord compression, superior vena cava syndrome, and 
any psychiatric disorder that prohibits obtaining informed consent. 
16. Patient has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the study, might interfere with the 
patient’s participation for the full duration of the study treatment, or is not in the best 


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interest of the patient to participate. 
17. Patient has known active hepatitis B (eg, hepatitis B surface antigen reactive) or 
hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] has been detected). 
18. Patients with known human immunodeficiency virus (HIV) are allowed if they meet 
all of the following criteria:  
a. Cluster of differentiation 4 ≥350/μL and viral load <400 copies/mL 
b. No history of acquired immunodeficiency syndrome-defining opportunistic 
infections within 12 months prior to enrollment  
c. No history of HIV-associated malignancy for the past 5 years 
d. Concurrent antiretroviral therapy as per the most current National Institutes of 
Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and 
Adolescents Living with HIV started >4 weeks prior to study enrollment 
19. Patient is immunocompromised. Patients with splenectomy are allowed.  
20. Patient has an ongoing bowel obstruction, or has other conditions that would lead to 
impaired absorption of oral niraparib. 
21. Patient has active autoimmune disease that has required systemic treatment in the 
past 2 years (ie, with use of disease-modifying agents, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) 
is not considered a form of systemic treatment 
Investigational product, dosage, and mode of administration:  
Niraparib 
The starting dose of niraparib will be 300 mg in patients with a screening actual body weight 
≥ 77 kg AND screening platelet count ≥ 150,000/μL, and 200 mg in patients with a screening 
actual body weight < 77 kg OR screening platelet count < 150,000/μL. Niraparib will be 
administered QD continuously until PD or toxicity.  
Dostarlimab (TSR-042)  
Dostarlimab (TSR-042) will be administered via a 30-minute intravenous (IV) infusion on 
Day 1 every 3 weeks (Q3W) during Cycles 1 through 4 at 500 mg. Beginning at Cycle 5, 
dostarlimab (TSR-042) will be administered via a 30-minute IV infusion on Day 1 of each 
6-week cycle at 1,000 mg until PD or toxicity, for a maximum of 3 years. Continued 
treatment with dostarlimab (TSR-042) beyond 3 years may be considered following 
discussion between the Sponsor and the Investigator. 


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Duration of treatment:  
Treatment in this study will continue until disease progression or toxicity. Patients who 
discontinue one of the treatment agents due to an AE will be able to continue treatment with 
the second agent until disease progression or toxicity. 
Dostarlimab (TSR-042) treatment may continue for up to 3 years or until PD, unacceptable 
toxicity, withdrawal of consent, Investigator’s decision, or death. Continued treatment with 
dostarlimab (TSR-042) beyond 3 years may be considered following discussion between the 
Sponsor and the Investigator. Treatment with niraparib can continue, in the absence of 
disease progression or toxicity, at the discretion of the Principal Investigator. Postprogression 
treatment may be permitted after discussion with the Sponsor’s Medical Monitor if the 
Investigator believes the patient may derive benefit from ongoing treatment.  
Following the final data cut-off (DCO) date, patients may continue to receive study treatment 
per investigator discretion until disease progression or they develop intolerable side-effects, 
or are lost to follow-up, withdraw consent, or pass away. Patients will not be allowed to 
receive study treatment if they become pregnant or demonstrate severe non-compliance with 
the protocol. 
Reference therapy, dosage, and mode of administration:  
Not applicable. 
Criteria for evaluation: 
Efficacy: 
The primary efficacy endpoint is Investigator-assessed confirmed ORR, which is defined as 
the proportion of patients who have achieved confirmed CR or PR. Tumor response will be 
evaluated using RECIST v.1.1. The primary analysis population will be the intent-to-treat 
(ITT) population, consisting of all patients who receive at least 1 complete dose of either 
study drug and who have measurable disease at baseline. Analyses will be performed overall 
(including all patients in the ITT population) and in the subset of patients with PD-L1 
positive tumors. 
Secondary efficacy endpoints include the following and will be analyzed overall (including 
all patients in the ITT population) and in the subset of patients with PD-L1 positive tumors: 
• 
DOR based on Investigator/independent review committee assessment, defined 
as the time from first documentation of response (CR or PR) until the time of first 
documentation of disease progression by RECIST v.1.1 based on 
Investigator/independent review committee assessment or death by any cause in 
the absence of progression by RECIST v.1.1 
• 
PFS based on Investigator/independent review committee assessment, defined as 
the time from the date of the first dose of study treatment to the earlier date of 
assessment of progression by RECIST v.1.1 based on Investigator/independent 
review committee assessment or death by any cause in the absence of progression 
by RECIST v.1.1 
• 
OS, defined as the time from the date of the first dose of study treatment to the 
date of death by any cause 
• 
DCR based on Investigator/independent review committee assessment, defined as 
the percentage of patients who have achieved BOR of CR, PR, or SD per 
RECIST v.1.1 based on the Investigator/independent review committee 
assessment 


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• 
ORR based on independent review committee assessment, defined as the 
percentage of patients who have achieved confirmed CR or PR per RECIST v1.1 
based on the independent review committee assessment 
Safety: 
Safety parameters evaluated during this study will include AEs, vital signs, symptom-directed 
physical examination findings, and clinical laboratory values (including hematology, serum 
or plasma chemistry, coagulation, and thyroid function). 
Exploratory: 
Exploratory endpoints include the following: 
• 
Duration of disease control, defined as the time from the date of the first dose of 
study treatment to the earlier date of assessment of progression by RECIST v.1.1 
based on the Investigator/independent review committee assessment or death by 
any cause in the absence of progression by RECIST v1.1 among patients whose 
BOR is CR, PR or SD. 
• 
The observed change from baseline and time to symptom worsening in the FOSI 
questionnaire. 
• 
Efficacy endpoints will also be evaluated in patients with tumors that are 
BRCAwt.  
• 
Disease-related or treatment-related biomarkers (eg, homologous recombination 
repair pathway deficiency and PD-L1 expression) may be assessed to explore the 
correlations with responses to the combination of niraparib and dostarlimab 
(TSR-042). 
Statistical methods:  
A sample size of approximately 150 patients overall will provide sufficient precision for 
assessment of the primary endpoint of ORR in the overall and PD-L1 positive populations. 
No inferential testing will be performed, and no adjustments will be made for multiplicity. 
Primary analysis will be based on the ORR point estimate and the corresponding 95% exact 
confidence interval (CI).  
With 150 patients overall, if the true ORR is 25%, there is an 87% chance that the lower 
bound of the 95% CI will exceed 15%. 
Assuming the prevalence of PD-L1 positive disease is 50% in this study population, it is 
expected that approximately 75 patients with PD-L1 positive tumors will be enrolled and 
dosed. With 75 patients, if the true ORR is 30%, there is an 84% chance that the lower bound 
of the 95% CI will exceed 15%. 
Analysis Populations: 
The analysis populations will be defined as follows: 
• 
Safety (SAF) Population: All patients who receive any amount of study 
treatment. 
• 
ITT Population: All patients who receive at least 1 complete dose of either study 
drug and who have measurable disease at baseline. Measurable disease at 
baseline is defined by the existence of at least 1 target lesion at baseline tumor 
assessment by RECIST v1.1 criteria. 


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• 
Efficacy-Evaluable (EE) Population: All patients who receive at least 1 complete 
dose of either study drug and who have measurable disease at baseline and do not 
have protocol deviations with the potential to significantly impact the 
interpretation of efficacy results. Patients who withdraw without obtaining a post-
baseline tumor assessment due to withdrawal of consent, loss to follow-up, or 
non-compliance will also be excluded from the EE population. 
Efficacy Analyses: 
All efficacy analyses will be performed using the ITT population, overall (including all 
patients in the ITT population) and in the subset of patients with PD-L1 positive tumors. The 
primary analysis population is the ITT population. Additional supportive analyses may be 
performed using the EE population. 
Primary efficacy analyses of ORR, based on Investigator assessment using RECIST v1.1, will 
be performed on the ITT population. BOR will be summarized by number and percentage. 
The ORR and 2-sided 95% CI, using the exact (Clopper-Pearson) method, will be provided.  
The point estimate and corresponding 2-sided 95% exact CI will be provided for DCR. DCR 
will be evaluated in the ITT and EE populations. Changes from baseline in tumor burden will 
be summarized by time-point. ORR based on independent review will be analyzed using 
similar methodology as described for the primary endpoint. 
DOR, PFS, OS, and the exploratory endpoint of duration of disease control will be 
summarized using Kaplan-Meier analysis, including number and percentage of events, 
number and percentage of censored patients, and 25th, 50th (median), and 75th percentiles of 
times to event.  
Analyses of ORR, DOR, PFS, OS, and DCR based on Investigator assessment using 
RECIST v1.1 will be repeated in the BRCAwt population.  
Descriptive, exploratory subgroup analysis will be performed by baseline characteristics and 
biomarker status.  
Descriptive summary statistics will be used to assess changes from baseline in overall FOSI 
score. Kaplan-Meier methodology will be used to summarize time to symptom worsening as 
assessed by minimally important changes in the overall FOSI score. 
Additional exploratory analyses to explore the correlation of clinical activity with biomarker 
subpopulations and other baseline disease characteristics may be performed.  
An interim futility analysis will be performed on the overall population after the first 40 
patients (regardless of PD-L1 status) have had the opportunity for at least 1 scan 
(approximately 9 weeks of treatment). Eligible patients with a non-evaluable scan will not be 
included. 
Safety Analyses: 
AEs will be coded using the current version of the Medical Dictionary for Regulatory 
Activities (MedDRA) for purposes of summarization. All AEs occurring during the study will 
be included in by-patient data listings and tabulated by MedDRA system organ class and 
preferred term. Safety endpoints for AEs include the following: incidence of treatment-
emergent adverse events (TEAEs), SAEs, AESIs, immune-related AEs, AEs leading to 
discontinuation, and AEs leading to death. Tabulations of TEAEs will also be produced by 
severity and by relationship to study treatment. 
Additional safety summaries will be provided for vital signs, symptom-directed physical 
examination findings, and clinical laboratory tests. 
 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
TITLE PAGE ...................................................................................... 1 
SPONSOR SIGNATURE PAGE .......................................................................... 4 
INVESTIGATOR’S AGREEMENT ..................................................................... 5 
2. 
SYNOPSIS ......................................................................................... 6 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES .......................................................................................... 17 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS... 24 
5. 
INTRODUCTION ............................................................................ 28 
5.1. 
Overview of Ovarian Cancer ............................................................ 28 
5.1.1. 
Biology of Ovarian Cancer ............................................................... 29 
5.1.2. 
Treatment for Platinum Resistant or Refractory Advanced Ovarian 
Cancer ............................................................................................... 29 
5.2. 
Background of Niraparib .................................................................. 30 
5.2.1. 
Clinical Experience ........................................................................... 30 
5.2.2. 
Baseline Body Weight and Platelet Count as Predictors of 
Thrombocytopenia ............................................................................ 31 
5.2.3. 
Clinical Experience of Niraparib Monotherapy in PROC Patients .. 32 
5.3. 
Background of Dostarlimab (TSR-042) ........................................... 33 
5.3.1. 
Nonclinical Development ................................................................. 33 
5.3.2. 
Clinical Development ....................................................................... 34 
5.3.2.1. 
Dostarlimab (TSR-042) Monotherapy .............................................. 34 
5.3.2.2. 
Investigational Therapeutic Combinations with Dostarlimab (TSR-
042) ................................................................................................... 35 
5.4. 
Rationale for Synergy Between Immune Checkpoint Inhibitors and 
PARP Inhibitors ................................................................................ 37 
5.4.1. 
Nonclinical Activity .......................................................................... 37 
5.4.2. 
Clinical Activity in Ovarian Cancer ................................................. 38 
5.5. 
Rationale for Current Study .............................................................. 40 
6. 
STUDY OBJECTIVES .................................................................... 41 
6.1. 
Hypothesis ........................................................................................ 41 
6.2. 
Primary Objective ............................................................................. 41 
6.3. 
Secondary Objectives ....................................................................... 41 


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6.4. 
Exploratory Objectives ..................................................................... 42 
7. 
INVESTIGATIONAL PLAN ........................................................... 43 
7.1. 
Overall Study Design ........................................................................ 43 
7.1.1. 
Schedule of Radiographic Tumor Assessment ................................. 44 
7.1.2. 
Postprogression Therapy .................................................................. 45 
7.1.3. 
Continued Treatment after Final DCO ............................................. 45 
7.1.4. 
Schedule of Safety Assessments ....................................................... 45 
7.2. 
Number of Patients ........................................................................... 46 
7.3. 
Treatment Assignment ...................................................................... 46 
7.4. 
Dose Adjustment .............................................................................. 46 
7.4.1. 
Niraparib ........................................................................................... 46 
7.4.2. 
Dostarlimab (TSR-042) .................................................................... 49 
7.5. 
Criteria for Study Termination ......................................................... 52 
7.6. 
Study Conduct .................................................................................. 52 
7.6.1. 
Schedule of Events ........................................................................... 52 
7.6.2. 
Procedures and Assessments ............................................................ 58 
7.6.3. 
Continued Treatment after Final DCO ............................................. 58 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS .................... 59 
8.1. 
Patient Inclusion Criteria .................................................................. 59 
8.2. 
Patient Exclusion Criteria ................................................................. 60 
8.3. 
Patient Withdrawal Criteria .............................................................. 63 
8.3.1. 
Discontinuation from Treatment ....................................................... 63 
8.3.2. 
Discontinuation from the Study ........................................................ 64 
9. 
TREATMENT OF PATIENTS ........................................................ 65 
9.1. 
Description of Study Drug ................................................................ 65 
9.2. 
Concomitant Medications ................................................................. 65 
9.2.1. 
Prohibited Medications ..................................................................... 65 
9.2.2. 
Contraception .................................................................................... 66 
9.2.3. 
Rescue Medications and Supportive Care Guidelines During 
Treatment with Dostarlimab (TSR-042) ........................................... 67 
9.2.3.1. 
Supportive Care for Adverse Events ................................................ 67 
9.2.3.2. 
Management of Infusion-related Reactions ...................................... 70 
9.2.4. 
Other Study Restrictions ................................................................... 71 


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9.3. 
Treatment Compliance ...................................................................... 71 
9.4. 
Randomization and Blinding ............................................................ 72 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ................. 73 
10.1. 
Study Drug ........................................................................................ 73 
10.1.1. 
Niraparib ........................................................................................... 73 
10.1.2. 
Dostarlimab (TSR-042) .................................................................... 73 
10.2. 
Study Drug Packaging and Labeling ................................................ 73 
10.3. 
Study Drug Storage ........................................................................... 73 
10.4. 
Study Drug Preparation .................................................................... 73 
10.5. 
Administration .................................................................................. 73 
10.5.1. 
Niraparib ........................................................................................... 73 
10.5.2. 
Dostarlimab (TSR-042) .................................................................... 74 
10.6. 
Study Drug Accountability ............................................................... 75 
10.6.1. 
Continued Access to Study Treatment Following Final DCO ......... 75 
10.7. 
Study Drug Handling and Disposal .................................................. 75 
11. 
ASSESSMENT OF EFFICACY ...................................................... 76 
11.1. 
Primary Efficacy Endpoint ............................................................... 76 
11.1.1. 
Evaluation of Tumor Response ........................................................ 76 
11.1.2. 
Timing of Radiographic Evaluations ................................................ 76 
11.2. 
Secondary Efficacy Endpoints .......................................................... 77 
11.2.1. 
Duration of Response ....................................................................... 77 
11.2.2. 
Progression-free Survival ................................................................. 77 
11.2.3. 
Overall Survival ................................................................................ 77 
11.2.4. 
Disease Control Rate ........................................................................ 77 
11.2.5. 
Objective Response Rate Based on Independent Review Committee 
Assessment ....................................................................................... 78 
11.3. 
Exploratory Efficacy Endpoints ....................................................... 78 
11.3.1. 
Duration of Disease Control ............................................................. 78 
11.3.2. 
Functional Assessment of Cancer Therapy – Ovarian Symptom Index
 .......................................................................................................... 78 
11.3.3. 
Efficacy in BRCAwt population ....................................................... 78 
11.3.4. 
Disease-Related or Treatment-Related Biomarkers ......................... 78 
12. 
ASSESSMENT OF SAFETY ........................................................... 79 
12.1. 
Safety Parameters ............................................................................. 79 


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12.1.1. 
Demographic ..................................................................................... 79 
12.1.2. 
Disease History ................................................................................. 79 
12.1.3. 
Medical and Surgical History ........................................................... 80 
12.1.4. 
Previous and Concomitant Medications ........................................... 80 
12.1.5. 
Vital Signs ........................................................................................ 80 
12.1.6. 
Weight and Height ............................................................................ 80 
12.1.7. 
Physical Examination ....................................................................... 80 
12.1.8. 
Electrocardiogram ............................................................................. 80 
12.1.9. 
Laboratory Assessments ................................................................... 81 
12.1.9.1. 
Hematology ....................................................................................... 81 
12.1.9.2. 
Blood Chemistry ............................................................................... 82 
12.1.9.3. 
Urinalysis .......................................................................................... 82 
12.1.9.4. 
Thyroid Panel .................................................................................... 83 
12.1.9.5. 
Hepatitis B and Hepatitis C Testing ................................................. 83 
12.1.9.6. 
Tumor Marker ................................................................................... 83 
12.1.9.7. 
Pregnancy Screen .............................................................................. 83 
12.1.10. 
ECOG Performance Status ............................................................... 83 
12.2. 
Adverse Events and Special Situations ............................................. 84 
12.2.1. 
Definitions ........................................................................................ 84 
12.2.1.1. 
Adverse Event ................................................................................... 84 
12.2.1.2. 
Serious Adverse Event ...................................................................... 84 
12.2.1.3. 
Treatment-Emergent Adverse Event ................................................ 85 
12.2.1.4. 
Adverse Event of Special Interest ..................................................... 85 
12.2.1.5. 
Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure .............................................. 85 
12.2.2. 
Assessment of Adverse Events ......................................................... 86 
12.2.2.1. 
Severity Assessment ......................................................................... 86 
12.2.2.2. 
Relationship to Study Intervention ................................................... 86 
12.2.2.3. 
Expectedness ..................................................................................... 86 
12.2.3. 
Collection and Recording of Adverse Events ................................... 86 
12.2.4. 
Follow-Up of Adverse Events .......................................................... 87 
12.2.5. 
Reporting .......................................................................................... 87 
12.2.6. 
Submission and Distribution of Serious Adverse Event Reports ..... 88 


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12.2.7. 
Adverse Events of Special Interest ................................................... 88 
12.2.8. 
Hypertension, Including Hypertensive Crisis ................................... 88 
12.2.9. 
Posterior Reversible Encephalopathy Syndrome .............................. 89 
12.2.10. 
Allergic Reaction .............................................................................. 89 
12.2.11. 
Pregnancy ......................................................................................... 89 
12.2.12. 
Special Situations .............................................................................. 89 
12.3. 
Safety Monitoring For Continuation of Treatment After Final DCO
 .......................................................................................................... 90 
13. 
STATISTICS .................................................................................... 91 
13.1. 
Sample Size Determination .............................................................. 91 
13.2. 
Analysis Populations ........................................................................ 92 
13.3. 
Patient Disposition ............................................................................ 92 
13.4. 
Demographics, Medical History, Baseline Characteristics, and 
Concomitant Medications ................................................................. 93 
13.5. 
Efficacy Analyses ............................................................................. 93 
13.5.1. 
Primary Efficacy Parameter .............................................................. 93 
13.5.2. 
Secondary Efficacy Parameters ........................................................ 93 
13.5.3. 
Exploratory Analyses ........................................................................ 94 
13.6. 
Safety Analyses ................................................................................ 95 
13.7. 
Biomarker/Interim Futility Analysis ................................................. 95 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS............... 97 
14.1. 
Study Monitoring .............................................................................. 97 
14.2. 
Audits and Inspections ...................................................................... 97 
14.3. 
Institutional Review Board ............................................................... 98 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE ............... 99 
16. 
ETHICS .......................................................................................... 100 
16.1. 
Ethics Review ................................................................................. 100 
16.2. 
Ethical Conduct of the Study .......................................................... 100 
16.3. 
Written Informed Consent .............................................................. 100 
17. 
DATA HANDLING AND RECORDKEEPING ........................... 101 
17.1. 
Inspection of Records ..................................................................... 101 
17.2. 
Retention of Records ...................................................................... 101 
18. 
PUBLICATION POLICY .............................................................. 102 
19. 
LIST OF REFERENCES ................................................................ 103 


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20. 
APPENDICES ................................................................................ 107 
APPENDIX 1. CONTRACEPTION GUIDELINES ...................................... 108 
APPENDIX 2. RESPONSE  EVALUATION CRITERIA IN SOLID TUMORS  
V.1.1 ............................................................................................... 110 
APPENDIX 3. EASTERN COOPERATIVE  ONCOLOGY GROUP  
PERFORMANCE STATUS ........................................................... 112 
APPENDIX 4. WORLD MEDICAL ASSOCIATION DECLARATION OF  
HELSINKI ...................................................................................... 113 
APPENDIX 5. SAMPLE FUNCTIONAL ASSESSMENT OF CANCER 
THERAPY – OVARIAN SYMPTOM INDEX (FOSI) ................. 119 
 
LIST OF TABLES 
Table 1: 
Document History ............................................................................... 2 
Table 2: 
Summary of Changes for Amendment 03 (15 December 2021) ........ 2 
Table 3: 
Abbreviations and Specialist Terms ................................................. 24 
Table 4: 
Tumor Response by Platinum Response and Biomarker Status – 
Efficacy-Evaluable Population (Phase 1 + Phase 2) ......................... 40 
Table 5: 
Treatment Regimens for Patients by Actual Body Weight and 
Platelet Count at Screening ............................................................... 44 
Table 6: 
Recommended Niraparib Dose Modifications for Adverse Reactions
 .......................................................................................................... 47 
Table 7: 
Niraparib Dose Modifications for Non-hematologic Adverse 
Reactions ........................................................................................... 47 
Table 8: 
Niraparib Dose Modifications for Hematologic Adverse Reactions 48 
Table 9: 
Guidelines for Treatment of Immune-related Adverse Events of 
Interest .............................................................................................. 50 
Table 10: Schedule of Events ........................................................................... 53 
Table 11: Investigational Product ..................................................................... 65 
Table 12: Dostarlimab (TSR-042) Infusion Reaction Treatment Guidelines ... 70 
Table 13: Recommended Initial Starting Dose ................................................. 74 
Table 14: Estimates and 95% CIs with 150 Patients ........................................ 91 
Table 15: Estimates and 95% CIs with 75 Evaluable Patients with PD-L1 
Positive Tumors ................................................................................ 92 
Table 16: Censoring Rules Used in DOR and PFS Survival Analysis ............. 94 
Table 17: For Patients with Measurable Disease (ie, Target Disease) ........... 111 


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Table 18: For Patients with Non-Measurable Disease (ie, Non-Target Disease)
 ........................................................................................................ 111 
 
LIST OF FIGURES 
Figure 1: 
Overall Study Schema ...................................................................... 43 
Figure 2: 
Interim Futility Analysis Flowchart.................................................. 96 
 
  


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 3: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
BOR 
best overall response 
BRCA 
breast cancer susceptibility gene 
BRCAmut 
breast cancer susceptibility gene mutated 
BRCAwt 
breast cancer susceptibility gene wild type 
CA-125 
cancer antigen 125 
CNS 
central nervous system 
CBC 
complete blood count 
CI 
confidence interval 
CPS 
complete positive scores 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
disease control rate 
DCO 
data cut-off 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EE 
Efficacy-Evaluable 
EOT 
end of treatment 


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Abbreviation or Specialist Term 
Explanation 
EU 
European Union 
FDA 
Food and Drug Administration 
FFPE 
formalin fixed paraffin embedded 
FOSI 
Functional Assessment of Cancer Therapy – Ovarian 
Symptom Index 
gBRCA 
germline breast cancer susceptibility gene 
gBRCAmut 
germline breast cancer susceptibility gene mutated 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
HRQoL 
health-related quality of life 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IgG4 
immunoglobulin G4 
IL-2 
interleukin-2 
IND 
Investigational New Drug application 
irAE 
immune-related adverse event 
irAEI 
immune-related adverse event of interest 
IRB 
institutional review board 
ITT 
intent-to-treat (population) 
IV 
intravenous 
mAb 
monoclonal antibody 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MID 
minimally important difference 
MRI 
magnetic resonance imaging 
MSI H 
microsatellite instability-high 
mut 
mutant 


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Abbreviation or Specialist Term 
Explanation 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
neg 
negative 
NIH 
National Institutes of Health 
NOAEL 
no observed adverse effect level 
NSAID 
non-steroidal anti-inflammatory drug 
NSCLC 
non-small cell lung cancer 
OC 
ovarian cancer 
ORR 
objective response rate 
OS 
overall survival 
PACT 
post-analysis continuation of treatment 
PARP 
poly (adenosine diphosphate-ribose) polymerase 
PARPi 
PARP inhibitor 
PCA 
primary completion achieved 
PD 
progression of disease 
PD-1 
programmed cell death-1 
PD-L1 
programmed cell death-ligand 1 
PD-L2 
programmed cell death-ligand 2 
PFI 
platinum-free interval 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PLD 
pegylated liposomal doxorubicin 
PO 
orally 
pos 
positive 
PR 
partial response 
PRO 
patient-reported outcome 
PROC 
platinum-resistant ovarian cancer 
Q3W 
every 3 weeks 
Q6W 
every 6 weeks 
QD 
once daily 
RAVE RTSM IRT 
Rave Randomisation and Trial Suppy Management 
Interactive Response Technology 
RECIST 
Response Evaluation Criteria in Solid Tumors 


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Abbreviation or Specialist Term 
Explanation 
RP2D 
recommended phase 2 dose 
SAE 
serious adverse event 
SAF 
safety (population) 
SAP 
statistical analysis plan 
SD 
stable disease 
STING 
stimulator of interferon gene 
T1DM 
type 1 diabetes mellitus 
TEAE 
treatment-emergent adverse event 
TGI 
tumor growth inhibition 
ULN 
upper limit of normal 
unk 
unknown 
US 
United States 
WHO 
World Health Organization 
 


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5. 
INTRODUCTION 
Niraparib is an orally available, potent, and highly selective poly (adenosine diphosphate-
ribose) polymerase (PARP)-1 and PARP-2 inhibitor. Zejula® (niraparib) was approved 
for the maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, 
or primary peritoneal cancer who are in a complete response (CR) or partial response 
(PR) to platinum-based combination chemotherapy by the United States (US) Food and 
Drug Administration (FDA) on 27 March 2017 and received a Marketing Authorization 
in the European Union (EU) on 16 November 2017. 
Niraparib treatment as monotherapy and in combinations is being studied by TESARO 
through a global development plan that involves several ongoing company-sponsored 
clinical studies in ovarian, lung, and breast cancer indications. In addition, TESARO and 
Janssen have a partnership investigating niraparib for use in prostate cancer. 
Dostarlimab (TSR-042) is an anti-programmed cell death-1 (anti PD-1) humanized 
monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)-κ isotype. TESARO 
submitted the original Investigational New Drug application (IND) for dostarlimab (TSR-
042) on 22 December 2015 and obtained the IND approval on 22 January 2016 with 
Study 4010-01-001 titled “A Phase 1 Dose Escalation and Cohort Expansion Study of 
TSR-042, an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors.” 
Dostarlimab (TSR-042) is being studied by TESARO in a global development plan as 
monotherapy in microsatellite instability-high (MSI H) tumors, including endometrial 
cancer, and in combination with other approved and investigational drugs under 
development by TESARO, such as niraparib in other solid tumors, including ovarian 
cancer and non-small cell lung cancer (NSCLC). 
The objective of the proposed study is to evaluate the efficacy and safety of the 
combination of niraparib and dostarlimab (TSR-042) in patients with advanced, relapsed, 
high-grade ovarian, fallopian tube, or primary peritoneal cancer without known breast 
cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and 
who have also been previously treated with bevacizumab. 
5.1. 
Overview of Ovarian Cancer 
Ovarian cancer is the most common cause of gynecologic cancer death in the US, with 
22,240 new cases of ovarian cancer estimated to be diagnosed in 2018.1 Most patients 
with ovarian cancer present with advanced disease at diagnosis. The majority of these 
patients will relapse after initial treatment, which typically includes a combination of 
surgery and platinum-based chemotherapy. It has been long recognized that the most 
robust predictive factor for response to subsequent platinum-based therapy at first relapse 
is the length of response to the first platinum-based chemotherapy.2 Based on the time 
from the administration of last platinum treatment until progression — platinum-free 
interval (PFI), ovarian cancer can be categorized as “platinum-sensitive” (PFI 
> 6 months) or “platinum-resistant” (PFI < 6 months), including “platinum refractory” 
(progression on platinum-based therapy or within 30 days of the last dose). In patients 
with multiple prior lines of treatment, the convention has been to define platinum-
sensitivity status based on the length of response to the last administered platinum, 
regardless of outcomes to subsequent non-platinum treatments. 


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The therapies approved by the FDA for treatment of platinum-resistant disease include 
paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan as single agents, or 
bevacizumab in combination with the above chemotherapeutic agents.3-6 There is no 
standard or well-defined treatment regimen for patients who progress after bevacizumab 
treatment. Single-agent chemotherapy typically has limited efficacy.7-9 Lack of known 
effective therapies in patients with platinum-resistant disease following administration of 
bevacizumab-based therapy remains a high unmet medical need. 
5.1.1. 
Biology of Ovarian Cancer 
In an analysis of approximately 500 high-grade serous ovarian cancer tumors, 
approximately 50% contained homologous recombination defects, which could sensitize 
tumors to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi).10 In 
ovarian cancers, biomarkers used to identify homologous recombination deficiency 
(HRD) tumors include BRCA mutations and homologous recombination deficiency 
assays such as MyChoice® HRD by Myriad Genetics and fLOH by Foundation Medicine.  
The tumor microenvironment can be targeted to improve patient outcomes from ovarian 
cancer. Angiogenesis is essential for both tumor growth and metastases, making it one of 
the hallmarks of cancer and an actionable aberration for drug development. Bevacizumab 
is used in the treatment of newly diagnosed ovarian cancer, platinum-sensitive recurrent 
ovarian cancer, and platinum-resistant ovarian cancer (PROC).11-14 
Immune cells represent a critical component of the tumor microenvironment.15 The 
presence of intratumoral T cells in patients with newly diagnosed ovarian cancer is 
associated with improved progression-free survival (PFS) and overall survival (OS).16 
Programmed cell death-ligand 1 (PD-L1) expression in tumors results in T cell 
inactivation/anergy. Survival outcomes are negatively impacted in tumors with high PD-
L1 expression regardless of tumor stage, histologic type, residual tumor burden, and 
chemotherapy.17 These data suggest a potential role of immune checkpoint inhibitors in 
treatment of ovarian cancers. 
5.1.2. 
Treatment for Platinum Resistant or Refractory Advanced Ovarian 
Cancer 
For patients with platinum-resistant or refractory ovarian cancer, the National 
Comprehensive Cancer Network (NCCN) guidelines recommend nonplatinum-based 
regimens such as docetaxel, oral etoposide, gemcitabine, paclitaxel with or without 
pazopanib, liposomal doxorubicin or topotecan (with or without bevacizumab), and 
paclitaxel/bevacizumab.18 Use of a single chemotherapeutic agent will yield a reported 
objective response rate (ORR) in the range of approximately 5% to 20%, depending on 
the line of therapy, with a median duration of response (DOR) of 4 to 9 months; PFS 
ranges from 3 to 5 months.5,8,9,19,20 The clinical benefit from these agents is even lower 
for patients with platinum-refractory disease. The anti-angiogenesis agent bevacizumab 
has a modest single-agent activity with an ORR of 15% and a median PFS of 4.4 months 
reported for patients with platinum-resistant disease treated with no more than 3 prior 
treatment regimens.21 Chemotherapy with or without bevacizumab was evaluated in 
patients with platinum-resistant disease (excluding patients with platinum-refractory 
disease), who had received 1 to 2 prior lines of therapy in the Phase 3 AURELIA study; 


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the ORR and median PFS were 11.8% and 3.4 months, respectively, for patients 
receiving chemotherapy versus 27.3% and 6.7 months, respectively, for patients receiving 
chemotherapy plus bevacizumab.14 Based on these results, bevacizumab in combination 
with paclitaxel, PLD, or topotecan was approved for the treatment of platinum-resistant 
recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.3 
Currently approved PARPi in the treatment setting are only indicated for patients with a 
BRCA mutation who are ≥ 4th line (olaparib) and ≥ 3rd line (rucaparib).22,23 Efficacy of 
single-agent PARPi in patients with PROC who have BRCA wild type (BRCAwt) tumors 
has a reported ORR of 5%.24-26 Therefore, the unmet need in PROC is highlighted among 
patients without a known BRCA mutation.   
5.2. 
Background of Niraparib 
5.2.1. 
Clinical Experience 
Niraparib is approved in multiple countries worldwide including the US, EU, 
Switzerland, Australia, Canada, and Saudi Arabia. Niraparib was approved by the Food 
and Drug Administration (FDA) on 27 March 2017 (NDA 208447) and received 
European Commission approval on 16 November 2017 as maintenance therapy for 
women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who 
are in CR or PR to platinum-based chemotherapy. Niraparib was approved by the FDA 
on 23 October 2019 for patients with advanced ovarian, fallopian tube, or primary 
peritoneal cancer treated with three or more prior chemotherapy regimens and whose 
cancer is associated with HRD-positive status. Additionally, the FDA approved the 
Myriad myChoice® CDx test (PMA P190014) as a companion diagnostic for 
determination of tumor HRD status to select patients for treatment with niraparib in the 
late line setting. A supplemental NDA (NDA 208447- S017) based on results of the 
PRIMA study, which evaluated the efficacy of niraparib in participants with newly 
diagnosed advanced ovarian cancer after a response to first-line platinum-based 
chemotherapy, is currently under real-time oncology review (RTOR) with the FDA.   
Niraparib has shown an acceptable clinical and pre-clinical safety profile.  
Niraparib was initially approved in the US and EU with a starting dose of 300 mg for all 
patients; the European Summary of Product Characteristics allowed for a 200 mg starting 
dose for a subset of patients (ie, patients with low body weight). In the ENGOT-
OV16/NOVA study, the selection of the 300 mg starting dose of niraparib was based on 
data from the Phase 1 multiple ascending dose study PN001 conducted by Merck & 
Company. No formal Phase 2 dose-ranging studies were conducted. The Phase 1 study 
included both a dose-escalation phase to determine the maximum tolerated dose and an 
expansion arm to further evaluate the selected dose. A total of 104 patients with advanced 
tumors were evaluated in this study, including 60 during dose escalation from 30 mg to 
400 mg; during expansion, a total of 54 patients were treated at the 300-mg dose level. 
The dose-escalation stage determined that the 400-mg dose level exceeded the maximum 
tolerated dose (by traditional dose-limiting toxicity [DLT] evaluations and by using the 
pooled adjacent violators algorithm). No DLTs were observed in the dose-escalation 
stage at the 290- or 300-mg dose level.  


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In the ENGOT-OV16/NOVA study, the most commonly observed nonhematologic 
treatment-emergent adverse events (TEAEs) of any National Cancer Institute (NCI) - 
Common Terminology Criteria for Adverse Events (CTCAE) grade were nausea, fatigue, 
constipation, and vomiting; the majority of the nonhematologic TEAEs were mild to 
moderate in severity. The most commonly observed hematologic TEAEs (any grade) 
were anemia (48.5%), thrombocytopenia (66.2%), and neutropenia (31.4%). The 
incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in 
patients who received niraparib in the ENGOT-OV16/NOVA study was similar to that in 
patients who received placebo (1.4% and 1.1%, respectively). MDS/AML and secondary 
cancers (new malignancies other than MDS or AML) are potential risks of PARPi. Since 
the initial approval of niraparib based on the ENGOT-OV16/NOVA Study, the safety 
profile has been updated to provide cumulative safety; this information can be found in 
the current version of the Investigator’s Brochure. Recommendations for dose 
modification strategies to be used during this study based on the safety profile of 
niraparib are provided in Section 7.4. 
5.2.2. 
Baseline Body Weight and Platelet Count as Predictors of 
Thrombocytopenia 
Additional exploratory analysis of the ENGOT-OV16/NOVA study data identified that 
patients with a baseline body weight < 77 kg or with a baseline platelet count 
< 150,000/μL before the initiation of niraparib treatment have a higher incidence of 
Grade 3 or 4 thrombocytopenia and other adverse events (AEs) during niraparib 
treatment. A dose-response relationship between AEs and dose was also observed for 
most of the commonly reported Grade 3 or 4 events, with the incidence highest at the 
300-mg dose level. The incidence of these Grade 3 or 4 events was lower for patients 
whose doses were reduced to the 200-mg dose level.  
The dose modification approach employed in ENGOT-OV16/NOVA study allowed 
patients to reach their optimal individual dose within the first 3 cycles. Overall, dose 
interruptions for any reason were instituted for 80% of patients on niraparib; 72% of 
patients underwent a dose reduction. Dose reductions tended to occur early and most 
patients reached their individual adjusted dose level by Month 4 of treatment.  
A PFS analysis from the ENGOT-OV16/NOVA study by dose at Month 4 demonstrated 
that, once the patients reach their optimal individualized dose, the efficacy was not 
compromised. Therefore, a lower starting dose will assist in reducing the incidence of 
Grade 3 or 4 thrombocytopenia in these subgroups of patients without a decrement in 
efficacy. Further, despite the intent to deliver a starting dose of 300 mg, the median daily 
dose taken within the first 2 months (where most dose reductions and interruptions 
occurred) was only 207 mg for patients with baseline body weight < 77 kg or baseline 
platelet count < 150,000/μL compared with a median of 295 mg for patients with baseline 
body weight ≥ 77 kg and baseline platelet count ≥ 150,000/μL. Therefore, the efficacy in 
the ENGOT-OV16/NOVA study was achieved with these patients receiving a true 
starting dose consistent with a 200-mg starting dose.  
The safety data from 2 ongoing niraparib studies, QUADRA and TOPACIO, were also 
evaluated for the incidence of thrombocytopenia. In the QUADRA study, the association 
of a decreased incidence of Grade 3 or 4 thrombocytopenia during the first cycle for 


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patients with a baseline body weight ≥ 77 kg and with baseline platelet count 
≥ 150,000/μL was 13.6% compared to those patients with a baseline body weight < 77 kg 
or with a platelet count < 150,000/μL (30.2%).  
As of 4 September 2018, the Phase 2 portion of the ongoing TOPACIO study in patients 
with PROC included 62 patients treated at a starting dose of niraparib of 200 mg QD in 
combination with pembrolizumab 200 mg IV Q3W.28 This study represents the largest 
dataset available with this proactively defined 200-mg niraparib starting dose. The lower 
starting dose in this study led to a lower incidence of Grade 3 or 4 thrombocytopenia 
overall and in patients with the baseline characteristics of body weight < 77 kg or platelet 
counts < 150,000/μL than in studies such as NOVA and QUADRA that utilized the 300-
mg starting dose. 
Overall, the data demonstrate that while AEs appear to be dose dependent, the 
relationship between dose and efficacy is not apparent. In addition, in the NOVA study, 
patients with a baseline body weight < 77 kg or a baseline platelet count < 150,000/μL in 
effect received an average daily dose approximating 200 mg (median = 207 mg) due to 
dose interruption and reduction; the use of a 200-mg niraparib starting dose leads to a 
lower incidence of Grade 3 or 4 thrombocytopenia events without compromising 
efficacy. Therefore, the starting dose of niraparib 200 mg QD is being prospectively 
evaluated in this and other clinical studies in patients with a baseline body weight < 77 kg 
or a baseline platelet count < 150,000/μL.  
5.2.3. 
Clinical Experience of Niraparib Monotherapy in PROC Patients 
TESARO conducted the QUADRA study to assess the activity of single-agent niraparib 
across a broad population of diverse patients in the late line treatment setting. This study 
aimed to enroll patients with the highest unmet need (4th line and later), regardless of 
biomarker status and platinum status, and represents the largest clinical study dataset of 
PARPi administered to patients in a treatment setting that included the BRCAwt 
population.  
QUADRA enrolled 463 patients. The majority of the patients were platinum refractory 
(relapse within 28 days from the last administered platinum, 35%) or platinum resistant 
(relapse 1 to 6 months from the last administered platinum, 33%). The median time from 
last treatment prior to study entry until first niraparib dose was 2 months, suggesting a 
population largely refractory to their last treatment, and 62% of enrolled patients had 
received bevacizumab as part of their prior therapy. Biomarker distribution was 
consistent with previously described prevalence of BRCA mutation (19%) and HRD 
positivity (48%) among patients with high-grade serous ovarian cancer.  
The study met its primary endpoint, demonstrating activity in the primary efficacy 
population of 4th and 5th line HRD-positive patients who were PARPi naïve, and 
considered platinum sensitive to the last platinum therapy (n = 47), with an ORR of 28% 
and median DOR of 9.2 months.  
Among patients with PROC who had received at least 3 prior lines of treatment, 
including platinum-refractory disease, meaningful activity of niraparib and durable 
responses were demonstrated in the subgroup of BRCAmut patients, with ORR of 33% (n 
= 21) in patients who progressed 1 to 6 months after their last platinum and 19% (n = 16) 


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among patients who progressed within 28 days from the last platinum. Outside of the 
biomarker selected patient population, namely among patients with HRD-negative 
platinum-resistant disease, the clinical benefit to patients treated with single-agent 
niraparib was best evidenced by meaningful disease stabilization (as measured by 16-
week clinical benefit rate of 19%) and importantly median OS of 17.1 and 10.3 months 
for patients progressing 1 to 6 months and within 28 days after their last platinum, 
respectively, while the formal Response Evaluation Criteria in Solid Tumors (RECIST) 
ORR remained modest at 3%. Of note, median OS with standard of care chemotherapy, 
regardless of platinum status, is expected to be < 10 months for patients receiving 4th-, 
5th-, or 6th-line therapy.29 
5.3. 
Background of Dostarlimab (TSR-042)  
Dostarlimab (TSR-042) is a humanized mAb of the IgG4-κ isotype that binds with high 
affinity to PD-1, resulting in inhibition of binding to PD-L1 and programmed cell death-
ligand 2 (PD-L2). This antibody was generated based on a proprietary platform that 
utilizes affinity maturation to select highly specific antibodies with desired functional 
characteristics. The functional antagonist activity of dostarlimab (TSR-042) was 
confirmed in a mixed lymphocyte reaction assay, demonstrating enhanced interleukin-2 
(IL-2) production upon addition of dostarlimab (TSR-042).30 Furthermore, dostarlimab 
(TSR-042) has an acceptable safety profile based on toxicology studies in cynomolgus 
monkeys. The nonclinical development with dostarlimab (TSR-042) is discussed in 
Section 5.3.1 and in the dostarlimab (TSR-042) Investigator’s Brochure. 
Dostarlimab (TSR-042) has shown an acceptable clinical and nonclinical safety profile. 
The clinical development with dostarlimab (TSR-042) is discussed in Section 5.3.2 and in 
the dostarlimab (TSR-042) Investigator’s Brochure.  
5.3.1. 
Nonclinical Development 
Dostarlimab (TSR-042) binds with high affinity to human and monkey PD-1. 
Dostarlimab (TSR-042) blocks the binding of soluble ligands to human PD-1 that is 
artificially expressed with a half-maximal inhibitory concentration of approximately 
1 nM. Dostarlimab (TSR-042) enhances T cell activation as measured by the production 
of IL-2 from activated human cluster of differentiation 4+ T cells, with a half-maximal 
effective concentration of approximately 1 nM. Full PD-1 receptor occupancy by 
dostarlimab (TSR-042) in vitro is achieved at concentrations of approximately 1 g/mL. 
Linear pharmacokinetics (PK) was observed for dostarlimab (TSR-042) over the range of 
10 to 100 mg/kg in 18 cynomolgus monkeys. Sex had no effect on exposure. The volume 
of distribution at steady state was low and suggested minimal tissue penetration, which is 
consistent with other therapeutic monoclonal antibodies. Weekly administration resulted 
in approximately a 2- to 3-fold increase in dostarlimab (TSR-042) exposure. 
In a 4-week repeat-dose toxicology study in cynomolgus monkeys, weekly intravenous 
(IV) dostarlimab (TSR-042) at doses of 0, 10, 30, or 100 mg/kg was well tolerated and 
did not result in any study drug-related adverse effects as measured by clinical signs, 
body weight, food consumption, electrocardiography, ophthalmology, safety 
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histopathology. The no observed adverse effect level (NOAEL) was ≥ 100 mg/kg in this 
study. 
In a 13-week repeat-dose toxicology study in cynomolgus monkeys, weekly IV 
dostarlimab (TSR-042) at doses of 0, 10, 30, and 100 mg/kg was well tolerated at 30 and 
100 mg/kg. One male (10 mg/kg/week) was euthanized because of chronic, unresolved 
generalized skin findings associated with swollen and firm inguinal lymph nodes on both 
sides. Microscopic findings noted in the skin of this animal were indicative of an immune 
reaction, which could have been a result of the mechanism of action of dostarlimab 
(TSR-042). Terminal necropsies of the remaining animals showed microscopic findings 
of an immune-mediated nature in the kidney, liver, and heart in animals dosed with 
dostarlimab (TSR-042) at ≥ 10 mg/kg/week. Although these findings are commonly 
observed in cynomolgus monkeys, the severity of these findings was slightly increased in 
dostarlimab (TSR-042)-dosed animals compared to control animals. Considering the 
mechanism of action of dostarlimab (TSR-042), these microscopic findings could be a 
result of the pharmacological effects of dostarlimab (TSR-042). Because of the 
euthanasia of 1 male dosed in the 10-mg/kg dose group, the NOAEL could not be 
determined in this study. 
5.3.2. 
Clinical Development 
In Study 4010-01-001 (GARNET), dostarlimab monotherapy demonstrated clinical 
benefit in participants with recurrent or advanced solid tumours that are DNA mismatch 
repair-deficient (dMMR) or have high microsatellite instability (MSI-H), a phenotype of 
mismatch repair deficiency. As of 08 July 2019, objective response rates (ORRs; blinded 
independent central review using Response Evaluation Criteria in Solid Tumors 
[RECIST] v1.1) of 43.1% and 44.0% were observed in participants with dMMR/MSI-H 
endometrial and nonendometrial cancer. 
5.3.2.1. 
Dostarlimab (TSR-042) Monotherapy 
Dostarlimab is not currently approved in any country. An Original BLA for dostarlimab 
was submitted to the FDA on 19 December 2019 for patients with recurrent or advanced 
dMMR EC who progressed on or following prior treatment with a platinum-containing 
regimen and a Conditional Marketing Authorization Application (CMAA) was submitted 
to the European Medicines Agency (EMA) on 06 March 2020, both of which are 
currently under review. The primary study used for this submission is Study 4010-01-001 
(GARNET).  
Additionally, the clinical benefit of dostarlimab as a single agent or in combination with 
other anticancer agents is being studied in 12 ongoing company-sponsored clinical 
studies in EC, ovarian cancer, nonsmall cell lung cancer (NSCLC), and other solid 
tumors. A summary of all ongoing studies with dostarlimab can be found in the current 
version of the dostarlimab Investigator’s Brochure and a summary is provided in 
Section 5.3.2.2.  
GARNET (Study 4010-01-001) is an ongoing, first-in-human Phase 1 study of 
dostarlimab (TSR-042) that aims to evaluate the safety and tolerability, PK, 
pharmacodynamics, and clinical activity of dostarlimab (TSR-042) in patients with 
recurrent or advanced solid tumors. As of 21 January 2019, a total of 21 patients were 


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dosed in the dose-escalation phase of the study (Part 1). Dose escalation continued to a 
maximally administered dose of 10 mg/kg every 2 weeks and a maximum tolerated dose 
was not identified. No DLTs were observed. In Part 2A of the study, the safety and 
tolerability of dostarlimab (TSR-042) was evaluated at 2 fixed dosing schedules: 500 mg 
every 3 weeks (Q3W) and 1,000 mg every 6 weeks (Q6W). No DLTs were observed in 
Part 2A. The recommended Phase 2 dose (RP2D) regimen was determined to be 500 mg 
Q3W for 4 cycles followed by 1,000 mg Q6W for all cycles thereafter, which is being 
evaluated in expansion cohorts for MSI H and microsatellite stable endometrial cancer, 
NSCLC, and non-endometrial MSI H or polymerase ε-mutated cancer in Part 2B of the 
study.  
Dostarlimab demonstrated an acceptable safety profile, based on safety profile of 
GARNET. Of note, Grade ≥3 TEAEs regardless of causality were reported in 50.3% of 
patients, and events in 13.6% of patients were assessed to be treatment-related. Serious 
TEAEs regardless of causality were reported in 39.4% of patients, and events in 7.8% of 
patients were assessed to be treatment-related. Immune-related adverse events (irAEs) 
(Grade ≥2) regardless of causality were reported in 34.8% of patients; however, immune-
related serious TEAEs were uncommon (5.0% of patients), with treatment-related 
immune-related serious TEAEs reported in 4.1% of patients. TEAEs leading to treatment 
discontinuation regardless of causality were not common and were reported in 9.5% of 
patients, with events in 4.9% of patients assessed to be treatment-related. TEAEs leading 
to death regardless of causality were rare and were reported in 3.1% of patients. None of 
the deaths were due to treatment-related TEAEs. Most of the observed adverse events 
(AEs) were in line with those expected in patients with recurrent or advanced solid 
tumors and were consistent with reported safety profiles of monoclonal antibodies 
blocking the PD-(L)1 interactions ("OPDIVO® (nivolumab) injection, for intravenous use 
prescribing information. Princeton, NJ: Bristol-Myers Squibb; 2016."  ; "KEYTRUDA® 
(pembrolizumab) injection, for intravenous use prescribing information. Whitehouse 
Station, NJ: Merck & Co.; 2017.").  
5.3.2.2. 
Investigational Therapeutic Combinations with Dostarlimab (TSR-042)  
In addition to Study 4010-01-001 of dostarlimab (TSR-042) monotherapy, the following 
additional studies involving dostarlimab (TSR-042) and other therapeutic agents are 
being evaluated.  
Study 4020-01-001 is an open-label, first-in-human Phase 1 study of another mAb, 
TSR-022 (anti-T cell immunoglobulin and mucin domain 3), that is being conducted in 2 
parts in patients with advanced solid tumors. In Part 1C, dostarlimab (TSR-042) is 
administered in combination with TSR-022 to establish the RP2D regimen for this study 
drug combination. In Part 2 of the study, the efficacy of TSR-022 ± dostarlimab (TSR-
042) is evaluated in patients with advanced solid tumors (expansion cohorts for 
melanoma, NSCLC, or colorectal cancer). 
Study 3000-01-002 is a Phase 1b dose-finding study of niraparib, niraparib/bevacizumab, 
carboplatin/paclitaxel, carboplatin-paclitaxel/bevacizumab, carboplatin-paclitaxel/TSR-
022, carboplatin/pemetrexed, carboplatin-pemetrexed/TSR-022, carboplatin/nab-
paclitaxel, or carboplatin-nab-paclitaxel/TSR-022 in combination with dostarlimab (TSR-
042) in patients with advanced or metastatic cancer. The study was initiated on 


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12 October 2017 and is the first to assess dostarlimab (TSR-042) and niraparib 
combination treatment, which have nonoverlapping safety profiles. In Part A of this 
study, the objectives are to evaluate the DLTs of dostarlimab (TSR-042) and niraparib 
combination treatment during the first cycle of treatment, to establish an RP2D of 
niraparib in combination with dostarlimab (TSR-042), and to evaluate the safety and 
tolerability of dostarlimab (TSR-042) and niraparib combination treatment.  
As of 21 January 2019, only Part A of Study 3000-01-002 (dostarlimab [TSR-042] in 
combination with niraparib), Part B (dostarlimab [TSR-042] in combination with 
carboplatin and paclitaxel), Part C (dostarlimab [TSR-042] in combination with niraparib 
and bevacizumab), and Part D (dostarlimab [TSR-042] in combination with carboplatin 
and paclitaxel and bevacizumab) had subjects enrolled. An initial cohort of 16 patients 
was enrolled at niraparib dose level 1 (200 mg), which has been determined to be safe. A 
cohort of 6 patients with baseline weight ≥ 77 kg and baseline platelet count 
≥ 150,000/μL was enrolled at niraparib dose level 2 (300 mg), which has also been 
determined to be safe. Of the 12 evaluable patients treated with niraparib 200 mg orally 
once daily (QD) and dostarlimab (TSR-042) 500 mg, 2 patients experienced a DLT 
(Grade 3 mucosal inflammation, related to niraparib, and Grade 3 exacerbated 
hypertension, related to niraparib). No patients experienced a DLT with niraparib 300 mg 
and dostarlimab (TSR-042) 500 mg. There were no new safety findings at either dose 
level. Thus, the RP2D of the 2-drug combination of dostarlimab (TSR-042) and niraparib 
is dostarlimab (TSR-042) 500 mg IV every 3 weeks and niraparib 200 mg in patients 
with baseline weight < 77 kg or baseline platelet count < 150,000/μL, and niraparib 
300 mg in patients with baseline weight ≥ 77 kg and baseline platelet count 
≥ 150,000/μL. 
Study 4040-01-001 is an open-label, first-in-human Phase 1 study of another mAb, 
TSR-033 (anti-lymphocyte activation gene-3), that is being conducted in 2 parts in 
patients with advanced solid tumors. In Part 1C of the study, dostarlimab (TSR-042) will 
be administered in combination with TSR-033 to establish the RP2D regimen for this 
study drug combination. In Part 2 of the study, the efficacy of TSR-033 with or without 
dostarlimab (TSR-042) will be evaluated in patients with advanced solid tumors 
(expansion cohorts for epithelial ovarian cancer, triple-negative breast cancer, and 
urothelial carcinoma). 
Study 3000-02-001 is an open-label Phase 2 study to evaluate the efficacy and safety of 
single-agent niraparib in patients with locally advanced and metastatic squamous NSCLC 
and of the combination of niraparib and a PD-1 inhibitor (including dostarlimab) in 
patients with locally advanced and metastatic NSCLC (all histologies). 
Study 3000-02-005 is an open-label, Phase 2 study to evaluate the efficacy and safety of 
niraparib novel treatment combinations in patients with advanced, relapsed, high-grade 
ovarian, fallopian tube, or primary peritoneal cancer. All patients receive niraparib in 
combination with dostarlimab (TSR-042) and bevacizumab. 
Please refer to the most current version of the dostarlimab (TSR-042) Investigator’s 
Brochure for updated safety information on these combinations. 
Given the encouraging clinical activity in heavily pretreated patients with diverse tumor 
types and the manageable safety profile of dostarlimab (TSR-042), the benefit-risk profile 


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for dostarlimab (TSR-042) as a treatment for patients with advanced cancers appears 
positive. 
5.4. 
Rationale for Synergy Between Immune Checkpoint Inhibitors 
and PARP Inhibitors 
5.4.1. 
Nonclinical Activity 
It has been demonstrated that PARPi treatment is able to increase lymphocyte infiltration 
and activation in mouse tumor models,31 turning “cold” tumors into “hot” tumors, which 
are more likely to respond to anti-PD-1 therapies. The rationale behind this finding is that 
PARP inhibition leads to accumulation of deoxyribonucleic acid (DNA) damage and 
cytoplasmic DNA, which induces the stimulator of interferon gene (STING)-dependent 
immune response32,33 and results in activation of type I interferon pathway. Multiple 
molecular mechanisms have been reported indicating that intrinsic DNA repair deficiency 
is also able to trigger an innate immune response through the accumulation of cytosolic 
DNA and activation of the STING pathway.34 Type I interferon has been reported to 
activate antitumor immunity through multiple mechanisms, including stimulation of 
innate and adaptive cytotoxic lymphocytes, downregulation of suppressive immune cells 
such as regulatory T-cells and myeloid-derived suppressor cells, and direct inhibition of 
tumor cell proliferation. The type I interferon-mediated activation of immune cells is 
mediated by upregulation of tumor antigen expression; activation of antigen-presenting 
dendritic cells; and stimulation of the release of secondary mediators such as chemokines, 
cytokines, and interleukins.35 Recently, PARPi have been shown to elevate PD-L1 
expression.36 This finding suggests that the immunomodulatory effects of PARPi could 
be muted by the expression of PD-L1. Thus, blocking PD-1 or PD-L1 may enhance the 
ability of niraparib to induce durable responses. 
The efficacy and tolerability of niraparib in combination with anti-PD-1 therapy was 
evaluated in immune-competent nonclinical models, and the combination was well 
tolerated in these studies. The combination was first tested in an HRD ovarian cancer 
mouse model derived from BRCA null genetic background, as PARP inhibition was 
previously shown to increase immune cell infiltration in BRCA-deficient models.31 The 
combination of low-dose niraparib (30 mg/kg QD) and mouse anti-PD-1 antibody 
(10 mg/kg twice every 3 days followed by 3 days of rest) achieved complete tumor 
regression, while niraparib monotherapy induced 64% tumor growth inhibition (TGI) and 
anti-PD-1 antibody monotherapy resulted in 65% TGI. Full dose of niraparib (50 mg/kg, 
QD) also drove the tumor to full regression, but adding anti-PD-1 to full-dose niraparib 
enhanced the anti-tumor activity by accelerating the time to complete regression. When 
the treatments stopped after 29 days of dosing, tumors in the niraparib and anti-PD-1 
combination groups demonstrated no signs of tumor regrowth during the 5-week 
drug-free observation period. Interestingly, no sign of tumor growth was observed when 
the tumor-free mice in the combination groups were re-inoculated with the same tumor 
cells, suggesting the establishment of durable response and immune memory.32,33,37 These 
results suggest that the therapeutic approach of combining niraparib with a PD-1 inhibitor 
such as dostarlimab (TSR-042) may provide additional benefit for patients with HRD 
tumors. 


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The enhanced anti-tumor activity was also observed when combining niraparib with anti 
PD-1 agent in BRCA-proficient tumor models, for example, the breast cancer syngeneic 
transplant MMTV-LPA1-T22 model. Mice treated with either niraparib or anti-PD-1 
monotherapies showed moderate responses of 45% and 30% TGI, respectively. In 
comparison, the combination of the 2 drugs led to a significantly improved anti-tumor 
response of 91% TGI.38 In the lung squamous syngeneic model KLN205, stronger tumor 
growth inhibition was observed for the combination (52.3%) than for niraparib alone 
(36.7%) or anti-PD-1 alone (30.5%).39 In the anti-PD-1 refractory mouse syngeneic skin 
tumor model SA9003, combination of niraparib and anti-PD-1 antibody treatment 
resulted in 51% TGI, while niraparib or anti-PD-1 monotherapies were not effective with 
TGI at 17% and 1%, respectively. These results clearly demonstrated the benefit of 
combination approaches with niraparib and anti-PD-1 antibody in BRCA-proficient 
mouse models. In 5 of 11 immunocompetent BRCA-proficient models, greater than 
additive antitumor responses were observed in 5/11 BRCA-proficient models.32,33 These 
results suggest that the therapeutic approach of combining niraparib with PD-1 inhibitors, 
such as dostarlimab (TSR-042), may provide additional benefit for patients with HR 
proficient tumors.32 
5.4.2. 
Clinical Activity in Ovarian Cancer 
Checkpoint inhibitors, such as PD-1 or PD-L1 inhibitors, have demonstrated modest 
activity in ovarian cancer. Preliminary efficacy rates for single-agent PD-1 or PD-L1 
inhibitors range from 5.9% to 15% in unselected recurrent ovarian cancer patients, in 
clinical studies that include patients with platinum-sensitive disease.40-43 In a small study 
of the safety and antitumor activity of nivolumab in patients with PROC (n = 20), the 
response rate was 15%.40 Two Phase 1b studies of pembrolizumab, a humanized 
monoclonal IgG4-κ PD-1 blocking antibody, and avelumab, a human IgG1 lambda 
monoclonal PD-L1 blocking antibody, demonstrated similar modest response rates of 
11.5% and 10.7%, respectively.44,45 
In the Phase 1b study KEYNOTE-028, 26 patients with ovarian cancer who had PD-L1 
positive tumors had an ORR of 11.5% when treated with pembrolizumab alone, with 1 
CR and 2 PR. Seven other patients achieved SD.46 Pembrolizumab in patients with PD-
L1 positive tumors was further evaluated in KEYNOTE-100, in which 376 patients with 
reoccurring ovarian cancer who had received multiple lines of prior therapy were 
administered pembrolizumab alone. In a confirmation set of patients who received 1 to 3 
prior lines of treatment with a platinum-free interval or treatment-free interval between 3 
and 12 months (n = 188), patients who had complete positive scores (CPS) ≥ 10 for PD-
L1 (indicating a high number of PD-L1 detected) had the highest ORR (10.0%) compared 
with patients who had lower CPS (4.1% for CPS < 1; 5.7% for CPS ≥ 1). In the overall 
population, this trend of highest ORR in patients with the highest PD-L1-expressing 
tumors held true despite differences in the number of prior lines of therapies (1 to 
3 versus 4 to 6) and other various baseline characteristics (eg, age and platinum 
sensitivity).47 
In a Phase 3 study of patients with platinum-resistant or refractory epithelial ovarian 
cancer treated with avelumab, PLD, or avelumab plus PLD,48 median PFS was 
1.9 months (95% CI: 1.8 to 1.9) for avelumab (n = 188), 3.5 months (95% CI: 2.1 to 4.0) 
for PLD (n = 190), and 3.7 months (95% CI: 3.3 to 5.1) for avelumab plus PLD 


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(n = 188). ORR was 3.7% (95% CI: 1.5% to 7.5%) for avelumab, 4.2% (95% CI: 1.8% to 
8.1%) for PLD, and 13.3% (95% CI: 8.8% to 19.0%) for avelumab plus PLD.  
PD-L1 positive tumors were defined as tumors for which the percentage of tumor cells 
expressing membranous PD-L1 was  1% and/or the percentage of tumor area populated 
by PD-L1 positive immune cells was  5%. Median PFS in patients with PD-L1 positive 
tumors was 1.9 months (95% CI: 1.8 to 2.3) for avelumab (n = 100), 3.0 months (95% 
CI: 1.9 to 3.7) for PLD (n = 88), and 3.7 months (95% CI: 2.7 to 6.1) for avelumab plus 
PLD (n = 100), and median PFS in PD-L1 negative patients was 1.9 months (95% CI: 1.8 
to 1.9) for avelumab (n = 70), 3.7 months (95% CI: 2.1 to 5.5) for PLD (n = 77), and 3.6 
months (95% CI: 1.9 to 4.6) for avelumab plus PLD (n = 73).49 
The TOPACIO study was conducted to evaluate the safety and efficacy of combination 
treatment with niraparib and pembrolizumab in patients with advanced triple-negative 
breast cancer or PROC, including patients considered “platinum ineligible” (a previous 
PFI ≥ 6 months but patients were deemed ineligible for subsequent platinum by the 
Investigator). The Phase 1 portion of the study is a dose-escalation evaluation to 
determine the RP2D and schedule of niraparib to be administered in combination with the 
recommended dose of pembrolizumab (n = 14). The Phase 2 portion includes patients 
treated at the RP2D of niraparib 200 mg orally QD on Days 1 to 21, and pembrolizumab 
200 mg IV on Day 1 of each 21-day cycle (n = 108). The primary endpoint of this study 
was Investigator-assessed ORR per RECIST v.1.1. 
In the PROC cohort, a total of 62 patients were enrolled in Phase 1 and Phase 2. The 
median age was 60 years of age. All patients were either Eastern Cooperative Oncology 
Group (ECOG) 0 or 1 at baseline (44 [71%] and 18 [29%], respectively) and 49 patients 
(79%) were BRCAwt. The median number of prior lines of therapy was 3 (range: 1 to 5). 
In this population, all had received prior platinum (100%); 98% had received prior 
paclitaxel, and 63% had received prior bevacizumab. Overall, 48% (30/62) of patients 
were platinum resistant and 27% (17/62) of patients were platinum refractory.28  
No new safety signals were identified for the combination of niraparib and 
pembrolizumab. In the Phase 2 PROC cohort of TOPACIO, incorporating a starting dose 
of 200 mg, the most common Grade ≥ 3 related TEAEs were anemia (21%) and 
thrombocytopenia (9%). 
In the evaluable population (at least 1 on-treatment scan; n = 60), there were 11 patients 
with confirmed responses (3 CRs and 8 PRs) for a confirmed ORR of 18% (90% CI: 11% 
to 29%), with a disease control rate (DCR) of 65% (90% CI: 54% to 75%). Median DOR 
was not reached at the time of the data cutoff (range: 4.2 to  14.5 months). In patients 
with platinum resistant disease, ORR was 21% (6/29), and in patients with platinum 
refractory disease, ORR was 13% (2/16). Patients positive for PD-L1 had an ORR of 
21% (7/33), and patients negative for PD-L1 had an ORR of 10% (2/21). 
The results of clinical activity in patients by platinum response and biomarker status are 
displayed in Table 4. 


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Table 4: 
Tumor Response by Platinum Response and Biomarker Status – 
Efficacy-Evaluable Population (Phase 1 + Phase 2) 
Response All (%) 
Platinum 
Resistant 
(%) 
Platinum 
Refractory 
(%) 
tBRCAmut 
(%)a 
HRDpos 
(%)a 
tBRCAwt 
(%)a 
HRDneg 
(%)a 
ORRb 
11/60 
(18%) 
6/29 (21%) 
2/16 (13%) 
2/11 (18%) 3/21 
(14%) 
9/47 
(19%) 
6/32 
(19%) 
Source: Konstantinopoulos et al 2019.28 
Abbreviations: HRD=homologous recombination deficiency; mut=mutant; neg=negative; ORR=objective 
response rate; pos=positive; tBRCA=tumor breast cancer susceptibility gene; wt=wild type 
a Only patients with known biomarker status were included. 
b Includes only confirmed responses using Response Evaluation Criteria in Solid Tumors, version 1.1. 
Response rates and stable disease rates were similar across the biomarker-defined 
populations as defined by tBRCA mutation and HRD status. Responses observed among 
BRCAwt populations were significantly higher than expected with single-agent PARPi or 
checkpoint inhibitor, suggesting potential combination benefit in this population with 
significant unmet medical need. 
5.5. 
Rationale for Current Study 
Development of more efficacious treatment options for patients with PROC, in particular 
among patients with BRCAwt tumors, remains a high unmet need.  
Nonclinical rationale suggests synergic activity between PARPi and immune checkpoint 
inhibitors. In the Phase 1/2 proof of principle study TOPACIO, results observed in the 
PROC cohort support the synergistic activity of the combination. Activity was not limited 
to biomarker selected populations, and in fact response rates were similar between 
BRCAmut and BRCAwt patient populations. Additionally, the activity of the 
combination in patients previously treated with bevacizumab was not diminished 
compared to patients that were bevacizumab naïve. Based on the nonclinical rationale 
and early clinical data supporting the proof of principle, we propose this study to evaluate 
the efficacy of the combination of niraparib with PD-1 inhibitor dostarlimab (TSR-042) 
in patients without known BRCA mutation who have PROC and who also have been 
previously treated with bevacizumab. 


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6. 
STUDY OBJECTIVES 
6.1. 
Hypothesis  
Treatment with the combination of niraparib and dostarlimab (TSR-042) in patients with 
non-BRCAmut PROC who were previously treated with bevacizumab may result in an 
ORR that is higher than the ORR expected with other available approved therapies for 
this population. This study will evaluate the efficacy of combination therapy by 
estimating the ORR along with the DOR in these patients.   
6.2. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy, as measured by confirmed 
ORR per RECIST v1.1 based on Investigator assessment, of the combination of niraparib 
and dostarlimab (TSR-042) in: 
• patients with PROC without a known BRCA mutation who have been 
previously treated with bevacizumab. 
• subset of patients with PROC who have PD-L1 positive tumors (using a 
prespecified cut point) without a known BRCA mutation who have been 
previously treated with bevacizumab. 
6.3. 
Secondary Objectives 
Secondary objectives of this study are as follows and will be evaluated in the overall 
population and in the subset of patients with PD-L1 positive tumors: 
• To evaluate the overall clinical benefit of the niraparib and dostarlimab (TSR-
042) combination as measured by the following secondary endpoints: 
− DOR per RECIST v1.1 based on Investigator assessment 
− PFS per RECIST v1.1 based on Investigator assessment 
− OS 
− DCR, defined as the percentage of patients who have achieved best overall 
response (BOR) of confirmed PR, CR, or SD per RECIST v1.1 based on 
Investigator assessment  
• To evaluate the ORR, DOR, PFS, and DCR per RECIST v1.1 based on 
independent review committee assessment 
• To evaluate the safety and tolerability of the niraparib and dostarlimab (TSR-
042) combination in patients with PROC as measured by standard safety 
assessments 


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6.4. 
Exploratory Objectives 
Exploratory objectives of this study are as follows and will be evaluated in the overall 
population and in the subset of patients with PD-L1 positive tumors: 
• To evaluate efficacy of the niraparib and dostarlimab (TSR-042) combination 
among patients with BRCAwt tumors, as measured by confirmed ORR, DOR, 
PFS, OS, and DCR based on Investigator assessment using RECIST v1.1 
• To evaluate the duration of disease control among patients with BOR of CR, 
PR, or SD based on Investigator assessment and independent review 
committee assessment  
• To evaluate health-related quality of life (HRQoL) in patients with PROC 
treated with the combination of niraparib and dostarlimab (TSR-042), as 
measured by the Functional Assessment of Cancer Therapy – Ovarian 
Symptom Index (FOSI) 
• To identify additional potential disease-related or treatment-related 
biomarkers that correlate with responses to the niraparib and dostarlimab 
(TSR-042) combination, including, but not limited to, the measures of 
homologous recombination repair pathway defects and the optimal PD-L1 
level for efficacy to be used in other dostarlimab (TSR-042) ovarian cancer 
studies. 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This is an open-label, single-arm, Phase 2 study which will evaluate the efficacy and 
safety of the niraparib and dostarlimab (TSR-042) combination in patients with advanced, 
relapsed, high-grade, ovarian, fallopian tube, or primary peritoneal cancer without known 
BRCA mutation who have platinum-resistant disease and who have also been previously 
treated with bevacizumab.  
A study schema is shown in Figure 1. 
Figure 1: 
Overall Study Schema 
 
*Excludes patients who experienced disease progression within 3 months of first-line platinum therapy.  
**Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy. Treatment 
with single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. If a 
therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as 
allergic reaction, toxicity, or drug availability), this will not be counted as a separate line of therapy. The 
use of single-agent hormonal therapy given for reasons other than progressive disease per RECIST v1.1 
(ie, hormonal therapy given for increasing CA-125 levels) is not counted as a separate line of therapy. 
Abbreviations: CA-125 = cancer antigen 125; BRCA = breast cancer susceptibility gene; ORR = objective 
response rate; PARPi = poly(adenosine diphosphate-ribose) polymerase inhibitor; PD = progression of 
disease; PD(L)-1 = programmed cell death-1 or programmed cell death-ligand 1; RECIST = Response 
Evaluation Criteria in Solid Tumors. 
This study will consist of a screening period (Day -28 to Day -1), a treatment period (Day 
1 to disease progression or toxicity), an end-of-treatment period (occurs when study 
treatment is discontinued for any reason), a Safety Follow-up Visit (30 ± 7 days after the 
last dose of study treatment), and recurring survival assessments (every 90 ± 14 days 
after the last dose of study treatment). All patients will undergo an End of Treatment 
Visit within 7 days of the decision to discontinue treatment for any reason. 
Patients must provide a sufficient tumor tissue sample (formalin fixed paraffin embedded 
[FFPE] blocks) for BRCA testing and PD-L1 testing at screening. Slides cut from FFPE 


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blocks must be approved by the Sponsor. Blood samples will be collected at screening for 
central gBRCA testing. Blood samples will also be collected for exploratory biomarker 
analysis at screening, at Cycle 3 Day 1, at the time of Investigator-assessed PR 
(+ 21 days), at the time of Investigator-assessed CR (+ 21 days), and at the End of 
Treatment Visit. All patients will receive treatment with niraparib and dostarlimab (TSR-
042) (collectively referred to as “study treatment”) beginning on Cycle 1 Day 1, using 
one of the regimens detailed in Table 5, depending on body weight and platelet count at 
screening. Cycles 1 to 4 are 3 weeks long and Cycles 5 and later are 6 weeks long. A 
window of ± 3 days is allowed to start the following cycle to accommodate holidays, 
clinic closing due to inclement weather, or other administrative reasons. 
Niraparib and dostarlimab (TSR-042) will be administered according to the treatment 
regimens displayed in Table 5 below. 
Table 5: 
Treatment Regimens for Patients by Actual Body Weight and Platelet 
Count at Screening 
Baseline Criteria  
Starting Dose 
Body weight ≥ 77 kg AND 
platelet count ≥ 150,000/μL 
Niraparib: 300 mg QD continuously until PD or toxicity 
Dostarlimab (TSR-042): 
Cycles 1 through 4: 500 mg Q3W 
Cycles ≥ 5: 1000 mg Q6W until PD or toxicity 
Body weight < 77 kg OR 
platelet count < 150,000/μL 
Niraparib: 200 mg QD continuously until PD or toxicity 
Dostarlimab (TSR-042): 
Cycles 1 through 4: 500 mg Q3W 
Cycles ≥ 5: 1000 mg Q6W until PD or toxicity 
Abbreviations: PD = progression of disease; Q3W = every 3 weeks; Q6W = every 6 weeks; QD = once 
daily. 
Note: Each cycle is either 3 weeks (21 days) or 6 weeks (42 days), and nominally begins on Day 1.  
Radiographic evaluations (ie, computed tomography [CT]/magnetic resonance imaging 
[MRI] of chest, abdomen, and pelvis) will be used to assess the extent of disease and will 
be conducted every 9 weeks (63 ± 7 days) for the first year of study treatment, 
independent of cycle delays or dose interruptions, or at any time when PD is suspected 
(Appendix 2). After 1 year of radiographic assessments (week 54), patients will undergo 
imaging every 12 weeks (84 ± 14 days).  
7.1.1. 
Schedule of Radiographic Tumor Assessment 
In accordance with the RECIST v.1.1, CR and PR should be confirmed. Tumor imaging 
for confirmation of response must be performed at the earliest 28 days after the first 
indication of PR or CR but no later than 35 days after the first indication of response. The 
subsequent tumor imaging after the confirmatory scan should be obtained per the original 
scheduled interval (eg, 9 weeks [63 ± 7 days] from confirmatory scan during the first year 
of study treatment and every 12 weeks thereafter). Radiographic evaluations will 
continue until any of the following occurs: PD, start of alternate anticancer therapy, 
withdrawal of consent to study participation, becoming lost to follow-up, death, or study 
termination. If a patient discontinues treatment for a reason other than radiographic PD, 


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death, withdrawal of consent, loss to follow-up, or the end of the study, radiographic 
evaluation and CA-125 testing should continue at the specified intervals (ie, every 
9 weeks for the first year of study treatment and every 12 weeks thereafter until PD). 
Also, clinically stable patients should not be discontinued until progression is confirmed. 
If a patient discontinues treatment for clinical progression and does not meet RECIST 
criteria for progression, scans and CA-125 testing should continue at the specified 
intervals until progression is confirmed or until the start of subsequent anticancer 
treatment.  
7.1.2. 
Postprogression Therapy 
Patients with radiographic evidence of PD who are clinically stable may continue 
treatment at the Investigator’s discretion and after discussion with the Sponsor, while 
awaiting confirmatory tumor imaging. Repeat imaging should be performed at ≥ 4 weeks. 
If repeat imaging shows SD, PR, or CR, patients can continue study treatment at the 
Investigator’s discretion. In the event that PD is confirmed, patients still may continue to 
receive study treatment even after confirmed radiographic progression if the patient is 
clinically stable and the Investigator deems that the patient is deriving clinical benefit. 
This allowance to continue treatment despite radiographic progression takes into account 
the observation that some patients may have a transient tumor flare in the first few 
months after the start of immunotherapy, but with subsequent treatment response. 
7.1.3. 
Continued Treatment after Final DCO  
A protocol clarification letter was issued by the sponsor on July 08 2021 regarding a 
decision to not resume study enrollment. Final analysis will be perfomed with data 
collected until August 18 2021 (the date of primary completion achieved [PCA] and final 
data cut-off [DCO]). Following the final DCO date, the data collection for all recruited 
participants who no longer received study treatment was stopped entirely and the clinical 
trial database was closed.  Patients may continue to receive study treatment per 
investigator discretion until disease progression or they develop intolerable side-effects, 
or are lost to follow-up, withdraw consent, or pass away. Patients will not be allowed to 
receive study treatment if they become pregnant or demonstrate severe non-compliance 
with the protocol. Section 7.6.3 describes the study conduct for participants continuing 
treatment following the final DCO date, and Section 12.3 outlines the safety data that will 
be collected for these patients.   
7.1.4. 
Schedule of Safety Assessments 
Safety assessments will include the collection of AEs, vital sign measurements, 
symptom-directed physical examinations, and clinical laboratory assessments 
(Section 12.1). All AEs (serious and nonserious) will be collected and recorded for each 
patient from the day of signing the informed consent form until 90 ± 14 days after the last 
study drug administration or until alternate anticancer treatment has been initiated, 
whichever occurs earlier; any pregnancies that occur within 180 days post-treatment are 
to be reported. All AESIs must be reported as outlined in Section 12.2.7. All AEs 
including SAEs experienced by a patient, regardless of causality, will be monitored until 
one of the following occurs: the AE or SAE has resolved, any abnormal laboratory values 
have returned to baseline or have normalized, there is a satisfactory explanation for the 


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change(s) observed, the patient is lost to follow-up or withdraws consent, or the patient 
has died. The safety assessments required for patients continuing study treatment 
following the final DCO date are described in Section 12.3.  
7.2. 
Number of Patients 
It was planned that approximately 150 patients would be enrolled and dosed.  
7.3. 
Treatment Assignment 
All patients in this single-arm study will receive treatment with niraparib combined with 
dostarlimab (TSR-042). 
7.4. 
Dose Adjustment 
7.4.1. 
Niraparib 
Adverse reactions should be managed with either interruption of treatment, dose 
reduction, or dose discontinuation; the recommended dose modifications for adverse 
reactions should be followed as listed in Table 6, Table 7, and Table 8.50 Niraparib should 
be discontinued for selected AEs that persist beyond 28 days, as noted in the tables. 
For patients whose initial dose is 3 capsules QD, dose reductions to 2 capsules QD 
(200 mg/day) and subsequently to 1 capsule QD (100 mg/day) will be allowed. No 
further dose reduction will be allowed without discussion with the Sponsor’s Medical 
Monitor.  
For patients whose initial dose is 2 capsules QD, dose reduction to 1 capsule QD 
(100 mg/day) will be allowed. No further dose reduction will be allowed without 
discussion with the Sponsor’s Medical Monitor. 
If an AE leading to niraparib dose interruption is clearly attributed to niraparib alone, the 
next treatment cycle can start on time with dostarlimab (TSR-042) administration. 
Niraparib can restart once the AE resolves with an appropriate dose reduction.  
If the attribution of an AE is not clear between dostarlimab (TSR-042) and niraparib 
(examples might include diarrhea and alkaline phosphatase [ALP], AST, or ALT 
elevation), both agents should be withheld, and a discussion with the Sponsor’s Medical 
Monitor is recommended. If the AE has not resolved prior to the scheduled start of a new 
cycle, the new cycle will be delayed until AE resolution. A delay of more than 28 days 
needs to be discussed with the Sponsor’s Medical Monitor. 
If a diagnosis of MDS or AML is confirmed by a hematologist, the patient must 
permanently discontinue niraparib.  
If niraparib is permanently discontinued due to AEs that are clearly attributed to niraparib 
alone, patients may continue treatment with dostarlimab (TSR-042) alone. 


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Table 6: 
Recommended Niraparib Dose Modifications for Adverse Reactions 
Dose level 
Initial Dose: 3 capsules/day 
Initial Dose: 2 capsules/day 
Starting dose 
300 mg QD (three 100-mg 
capsules) 
200 mg QD (two 100-mg 
capsules) 
First dose reduction 
200 mg QD (two 100-mg 
capsules) 
100 mg QDa (one 100-mg 
capsules)  
Second dose reduction 
100 mg QDa (one 100-mg 
capsules) 
N/A 
Abbreviations: N/A = not applicable, QD = once daily. 
a If further dose reduction is required for adverse-event management, discussion with the Sponsor’s 
Medical Monitor is required. 
 
Table 7: 
Niraparib Dose Modifications for Non-hematologic Adverse Reactions 
Non-hematologic NCI-CTCAE ≥ Grade 3 adverse 
reaction where prophylaxis is not considered 
feasible or adverse reaction event persists despite 
treatment 
• Withhold niraparib for a maximum of 28 days 
or until resolution of adverse reaction. 
• For those adverse reactions that do not resolve 
within 28 days, niraparib should be 
discontinued. Otherwise, discussion with the 
Sponsor’s Medical Monitor is required to 
resume niraparib. 
• Resume niraparib at a reduced dose per 
Table 6.  
NCI-CTCAE ≥ Grade 3 treatment-related adverse 
reaction event lasting more than 28 days while the 
patient is administered niraparib 100 mg/day 
Discontinue medication. 
NCI CTCAE Grade ≥2 adverse reaction of PRES 
Discontinue medication. 
Abbreviations: NCI-CTCAE = National Cancer Institute - Common Terminology Criteria for Adverse 
Events. 


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Table 8: 
Niraparib Dose Modifications for Hematologic Adverse Reactions 
Monitor CBC weekly for the first cycle, on Day 1 of Cycles 2 through 4, on Day 1 and Day 22 of 
Cycles 5 and 6, on Day 1 and Day 29 of Cycles 7 through 11, and on Day 1 of each cycle thereafter. 
CBC needs to be performed and results evaluated prior to dosing. If dose interruption or modification is 
required at any point on study because of hematologic toxicity, weekly blood draws for CBC will be 
done until the AE resolves. To ensure safety of the new dose, weekly blood draws for CBC will also be 
required for an additional 4 weeks after the AE has been resolved.  
Platelet count < 100,000/µL First occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥ 100,000/µL. 
• For those adverse reactions that do not resolve within 28 days, 
niraparib should be discontinued. Otherwise, discussion with the 
Sponsor’s Medical Monitor is required to resume niraparib. 
• Resume niraparib at same or reduced dose per Table 6. 
• If nadir platelet count was < 75,000/µL, resume at a reduced dose 
after recovery. 
Second occurrence: 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until platelet counts return to ≥ 100,000/µL. 
• For those adverse reactions that do not resolve within 28 days, 
niraparib should be discontinued. Otherwise, discussion with the 
Sponsor’s Medical Monitor is required to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6. 
• Discontinue niraparib if the platelet count has not returned to 
acceptable levels within 28 days of the dose interruption period, or if 
the patient has already undergone dose reduction to 100 mg QD.a 
Neutrophil < 1,000/µL or  
Hemoglobin < 8 g/dL 
• Withhold niraparib for a maximum of 28 days and monitor blood 
counts weekly until neutrophil counts return to ≥ 1,500/µL or 
hemoglobin returns to ≥ 9 g/dL. 
• For those adverse reactions that do not resolve within 28 days, 
niraparib should be discontinued. Otherwise, discussion with the 
Sponsor’s Medical Monitor is required to resume niraparib. 
• Resume niraparib at a reduced dose per Table 6. 
• Discontinue niraparib if neutrophil or hemoglobin level has not 
returned to acceptable levels within 28 days of the dose interruption 
period or if the patient has already undergone dose reduction to 
100 mg QD.a 
Hematologic adverse 
reaction requiring 
transfusion 
• For patients with platelet count ≤ 10,000/μL, platelet transfusion 
should be considered. If there are other risk factors, such as co 
administration of anticoagulation or antiplatelet drugs, consider 
interrupting these drugs and/or transfusion at a higher platelet count. 
Red blood cell transfusion(s) may be given at the discretion of the 
Investigator. 
• Resume niraparib at a reduced dose. 
Abbreviations: AE = adverse event; AML = acute myeloid leukemia; CBC = complete blood count; 
MDS = myelodysplastic syndrome; QD = once daily. 


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a If MDS/AML is confirmed, discontinue niraparib. 
For clinical situations not covered by this dose modification guidance the Investigator 
must contact the Sponsor’s Medical Monitor. 
The reason for interruption or discontinuation of niraparib should be recorded in the 
electronic Case Report Form (eCRF). 
7.4.2. 
Dostarlimab (TSR-042)  
AEs (both nonserious and serious) associated with dostarlimab (TSR-042) exposure may 
represent an immunologic etiology. These AEs may occur shortly after the first dose or 
several months after the last dose of treatment. 
In general, dostarlimab (TSR-042) must be withheld for drug-related Grade 3 toxicities, 
as well as for certain immune-related adverse events of interest (irAEIs), but may be 
resumed upon recovery to Grade ≤ 1; dostarlimab (TSR-042) will be permanently 
discontinued for any drug-related Grade 4 AE. Dostarlimab (TSR-042) must be 
permanently discontinued for certain irAEIs as described in Table 9. 
The specific immune-related AEs (irAEs) typically observed with anti-PD-1 antibodies 
will be managed according to the guidelines summarized below, and clinical management 
may be supplemented by the recent joint American Society of Clinical Oncology (ASCO) 
and NCCN guidelines for diagnosis and management of irAEs (see Section 9.2.3).51 
If an AE leading to dostarlimab (TSR-042) dose interruption is clearly attributed to 
dostarlimab (TSR-042) alone, the next treatment cycle can start on time with niraparib 
administration. If dostarlimab (TSR-042)-related AE resolves by day 7 of this cycle, 
dostarlimab (TSR-042) can be administered with up to 7 day delay. If AE does not 
resolve by day 7 (or is considered by the Investigator unlikely to resolve within 7 days), 
dostarlimab (TSR-042) should be omitted until the subsequent cycle. If dostarlimab 
(TSR-042)-related AE does not resolve within 28 days, Sponsor’s Medical Monitor 
should be contacted.  
If dostarlimab (TSR-042) interruption is necessary after Cycle 4 (when cycle length 
changes to 6 weeks), Sponsor’s Medical Monitor should be contacted. 
Of note, if the attribution of an AE is not clear between dostarlimab (TSR-042) and 
niraparib (examples might include diarrhea and ALP, AST, or ALT elevation), both 
agents should be withheld and a discussion with the Sponsor’s Medical Monitor is 
recommended. If the AE has not resolved prior to the scheduled start of a new cycle, the 
new cycle will be delayed until AE resolution. A delay of more than 28 days needs to be 
discussed with the Sponsor’s Medical Monitor. 
If dostarlimab (TSR-042) is permanently discontinued due to AEs that are clearly 
attributed to dostarlimab (TSR-042) alone, patients may continue treatment with 
niraparib alone. 
For clinical situations not covered by this dose modification guidance the Investigator 
must contact the Sponsor’s Medical Monitor. 
The reason for interruption or discontinuation of dostarlimab (TSR-042) should be 
recorded in the eCRF. 


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Table 9: 
Guidelines for Treatment of Immune-related Adverse Events of 
Interest 
Toxicity 
Hold Treatment For 
CTCAE Grade 
Restarting Treatment/ discontinuation 
Uveitis 
Symptomatic any grade 
Restart the treatment when toxicity resolves to 
Grade 0. For any recurrent uveitis or uveitis 
resistant to topical steroids, permanently 
discontinue study treatment. 
Diarrhoea/colitis 
2-3 
Restart dosing when toxicity resolves to Grade 0-
1. 
4 or recurrent Grade 3 
Permanently discontinue study treatment. 
AST, ALT, or 
increased bilirubin 
2 
(AST or ALT >3 and 
≤5×ULN or  
total bilirubin >1.5 and 
≤3×ULN) 
Restart dosing when toxicity resolves to Grade 0-
1. 
3-4 
(AST or ALT >5×ULN  
or total bilirubin 
>3×ULN)  
Permanently discontinue study treatment (see 
exception below)a. 
T1DM or 
hyperglycaemia 
3-4 hyperglycaemia or 
T1DM (associated with 
metabolic acidosis or 
ketonuria) 
Restart dosing in appropriately managed, 
clinically and metabolically stable participants. 
Insulin replacement therapy is required. 
Immune-related 
encephalitis  
Any grade 
Permanently discontinue study treatment. 
Hypophysitis 
2-4 
For Grade 2-3, hold until hormonal therapy results 
return to adequate levels by laboratory values and 
restart dosing when toxicity resolves to Grade 0-1. 
For recurrence or worsening of Grade ≥2 
hypophysitis after steroid taper has been 
completed and is on adequate hormone 
replacement therapy, permanently discontinue 
study treatment.  
Adrenal insufficiency 
2-4 
Hold until hormonal therapy results in return to 
adequate levels by laboratory values and restart 
dosing when toxicity resolves to Grade 0-1. For 
recurrent or worsening Grade ≥2 adrenal 
insufficiency while adequate hormonal 
replacement is continuing, permanently 
discontinue study treatment. 
Hypo- and 
hyperthyroidism  
3-4 
Hold until hormonal therapy results in return to 
adequate levels by laboratory values and restart 
dosing when toxicity resolves to Grade 0-1. 
Infusion-related 
reaction 
2b 
Restart dosing when toxicity resolves to Grade 0-
1. 
3-4 
Permanently discontinue study treatment. 


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Toxicity 
Hold Treatment For 
CTCAE Grade 
Restarting Treatment/ discontinuation 
Pneumonitis 
2 
Restart dosing when toxicity resolves to Grade 0-
1. If Grade 2 recurs, permanently discontinue 
study treatment. 
3-4 or recurrent Grade 2 
Permanently discontinue study treatment. 
Severe exfoliative 
dermatologic events 
3 or Suspected DRESS, 
SJS or TEN 
Withhold 
4 or Confirmed DRESS, 
SJS or TEN 
Permanently discontinue study treatment. 
Renal failure or 
nephritis 
2 
Restart dosing when toxicity resolves to Grade 0-
1. 
3-4 
Permanently discontinue study treatment. 
Myositis 
2-3 
Restart dosing when toxicity resolves to Grade 0-
1. 
4 
Permanently discontinue study treatment. 
Myocarditis 
Grade 2, 3 or 4 
Permanently discontinue 
Severe neurologic 
events (myasthenic 
syndrome/myasthenia 
gravis, Guillain Barré 
Syndrome, transverse 
myelitis) 
Grade 2, 3 or 4 
Permanently discontinue 
Hemophagocytic 
lymphohistiocytosis 
Any grade 
Permanently discontinue 
Recurrence of irAEI 
in this table after 
resolution to Grade 
≤1 
3-4 
Permanently discontinue study treatment. 
Other irAEIs 
Based on severity and type 
of reaction (Grade 2 or 3) 
Restart dosing when toxicity resolves to Grade 1 
Grade 4 or recurrent 
Grade 3 
Permanently discontinue 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common 
Terminology Criteria for Adverse Events; DRESS=drug reaction with eosinophilia and systemic 
symptom; irAEI=immune-related adverse event of interest; T1DM=type 1 diabetes mellitus; ULN=upper 
limit of normal. SJS=Stevens Johnson Syndrome; TEN=toxic epidermal necrolysis 
a For participants with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT 
increases by ≥50% relative to baseline and lasts for at least 1 week, then participant should be 
discontinued. 
b Upon resolution within 1 hour of stopping drug infusion, the infusion may be restarted at 50% of the 
original infusion rate (eg, from 100 mL/hr to 50 mL/hr). Otherwise dosing will be held until symptoms 
resolve and the participant should be premedicated for the next scheduled dose; refer to Section 9.2.3.2, 
Infusion-related Reaction Treatment Guidelines, for further management details. 
In addition to the immune-related adverse events listed in Table 9, treatment with 
dostarlimab may be associated with other irAEs, including events which may be less 
commonly associated with PD-(L)1 inhibitors but can similarly result from activation of 


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cellular immune response, e.g. pancreatitis. For these events, the general guidance from 
ASCO/NCCN should be considered. Patients should receive appropriate supportive care 
measures as deemed necessary by the treating Investigator, including but not limited to 
the items outlined below: 
• In general, treatment can continue with close monitoring for Grade 1 
toxicities. 
• Hold treatment for most Grade 2 toxicities and consider resuming when 
symptoms and/or laboratory values revert to Grade 1 or less. Corticosteroids 
(initial dose 0.5 to 1mg/kg/day of prednisone or equivalent) must be 
administered. 
• Hold for Grade 3 toxicities and initiate high-dose corticosteroids (prednisone 
1 to 2 mg/kg/day or methylprednisolone IV 1 to 2 mg/kg/day). Corticosteroids 
should be tapered over the course of at least 4 to 6 weeks. If symptoms do not 
improve within 48 to 72 hours of high-dose corticosteroids, infliximab may be 
offered for some toxicities. 
It is highly recommended that investigators discuss any adverse events with 
the Sponsor prior to using infliximab. 
• When symptoms and/or laboratory values revert to Grade 1 or less, 
rechallenging with immunotherapy may be offered, however caution is 
advised, especially in patients with early-onset immune-mediated events. 
Dose adjustments are not recommended. 
7.5. 
Criteria for Study Termination 
The Sponsor may terminate this study at any time. The Sponsor will notify the 
Investigators when the study is to be placed on hold, completed, or terminated. 
7.6. 
Study Conduct 
Cycles 1 to 4 are 3 weeks long and Cycles 5 and later are 6 weeks long. A window of ± 3 
days is allowed to start the following cycle to accommodate holidays, clinic closing due 
to inclement weather, or other administrative reasons. 
7.6.1. 
Schedule of Events 
Refer to Table 10 for a detailed summary of the events performed during the study. 
 


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Table 10: 
Schedule of Events 
Cycle/Daya 
Screening 
-28 to -1 
C1 
D1 
C2 
D1 
C3 
D1 
C4 
D1 
C5 
D1 
C5 
D22 
C6 
D1 
C6 
D22 
C7 
D1 
C8D1  
and 
Subsequent 
Cycles D1 
EOTb  
Safety 
Follow-up 
Visit 
30 ± 7 days 
post- 
treatment 
Survival 
Assessments 
every 90 
± 14 days) 
Cycle Lengtha  
 
3 weeks / 21 days ± 3 days 
6 weeks / 42 days ± 3 days 
 
 
 
Approximate Week 
 
1 
4 
7 
10 
13 
16 
19 
22 
25 
31 
 
 
 
Procedure 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical, surgical, cancer 
(including genotyping), and 
medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Symptom-directed physical 
examination 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Vital signs (temperature) , 
height, and weightc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs: Blood pressure 
and heart rate (pulse)c 
X 
Xc 
Xc 
Xc 
X 
X 
X 
X 
X 
Xc 
Xc 
X 
X 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Required tumor tissue 
sample (FFPE block)d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBC with differentiale,f 
X 
Xe 
X 
X 
X 
X 
X 
X 
X 
Xe 
Xe 
X 
X 
 
Coagulation 
X 
As clinically indicated 


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Cycle/Daya 
Screening 
-28 to -1 
C1 
D1 
C2 
D1 
C3 
D1 
C4 
D1 
C5 
D1 
C5 
D22 
C6 
D1 
C6 
D22 
C7 
D1 
C8D1  
and 
Subsequent 
Cycles D1 
EOTb  
Safety 
Follow-up 
Visit 
30 ± 7 days 
post- 
treatment 
Survival 
Assessments 
every 90 
± 14 days) 
Cycle Lengtha  
 
3 weeks / 21 days ± 3 days 
6 weeks / 42 days ± 3 days 
 
 
 
Approximate Week 
 
1 
4 
7 
10 
13 
16 
19 
22 
25 
31 
 
 
 
Procedure 
 
Serum/plasma chemistryf,g 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid panelh 
X 
Every 12 weeks (84 ± 7 days) from C1D1 and at EOT 
 
 
Amylase 
X 
Every 12 weeks (84 ± 7 days) and at EOT 
 
 
Serum or urine pregnancy 
testi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
HBV/HCV testj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CA-125 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xk 
CT or MRI for 
RECIST v.1.1 assessmentl 
X 
X (every 9 weeks)l 
Xl 
 
 
Blood sample for central 
gBRCA testingm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sample for 
exploratory biomarkers 
Xm 
 
 
X 
At the time of Investigator assessment of PR (+ 21 days) and at the 
time of Investigator assessment of CR (+ 21 days) 
X 
 
 
HRQoLn 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Oral niraparib 
dispensed/collected 
 
Xo 
Xo 
Xo 
Xo 
Xo  
X 
Xo 
X 
Xo 
Xo 
X 
 
 


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Cycle/Daya 
Screening 
-28 to -1 
C1 
D1 
C2 
D1 
C3 
D1 
C4 
D1 
C5 
D1 
C5 
D22 
C6 
D1 
C6 
D22 
C7 
D1 
C8D1  
and 
Subsequent 
Cycles D1 
EOTb  
Safety 
Follow-up 
Visit 
30 ± 7 days 
post- 
treatment 
Survival 
Assessments 
every 90 
± 14 days) 
Cycle Lengtha  
 
3 weeks / 21 days ± 3 days 
6 weeks / 42 days ± 3 days 
 
 
 
Approximate Week 
 
1 
4 
7 
10 
13 
16 
19 
22 
25 
31 
 
 
 
Procedure 
 
IV dostarlimab (TSR-042) 
administeredp 
 
500mg 
500
mg 
500
mg 
500mg 
1000mg 
 
1000mg 
 
1000mg 
1000mg 
 
 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xq 
Anticancer therapies 
assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Survival assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AML = acute myeloid 
leukemia; AST = aspartate aminotransferase; BRCA = breast cancer susceptibility gene; CA-125 = cancer antigen 125; CBC = complete blood count; CR = 
complete response; CT = computed tomography; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ECI = event of clinical interest; ECOG = Eastern 
Cooperative Oncology Group; EOT = end of treatment; FFPE = formalin fixed paraffin embedded; FOSI = Functional Assessment of Cancer Therapy – Ovarian 
Symptom Index; gBRCA = germline breast cancer susceptibility gene; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HRQoL = health-related quality of life; IV = intravenous; MDS = myelodysplastic syndrome; MRI = magnetic resonance imaging; OC = ovarian cancer; PD = 
progression of disease; PD-L1 = programmed cell death-ligand 1; PR = partial response; Q3W = every 3 weeks; Q6W = every 6 weeks; RECIST = Response 
Evaluation Criteria in Solid Tumors; RNA = ribonucleic acid; SAE = serious adverse event. 
a Treatment cycles are 21 days (± 3 days) for the first 4 cycles (12 weeks); subsequently, treatment cycles are 42 days (± 3 days). 
b All patients will undergo an End of Treatment Visit within 7 days of the decision to discontinue treatment for any reason. If a patient discontinues treatment for 
clinical progression and does not meet RECIST criteria for progression, scans and CA-125 testing should continue at the specified intervals until progression is 
confirmed or until the start of subsequent anticancer treatment. Also, clinically stable patients should not be discontinued until progression is confirmed. 
c Height will be measured only at screening. Weight, temperature, blood pressure, and heart rate (pulse) will be measured at screening, on Day 1 of each treatment 
cycle, and on Day 22 of Cycles 5 and 6. Blood pressure and heart rate (pulse) should also be measured weekly (Day 8 and Day 15) during the first 8 weeks (Cycles 
1 through 3) and on Day 29 ±7 days in Cycles 7 through 11, and entered as an unscheduled visit if abnormal.  
d Patient must provide FFPE tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor’s designated central laboratory) during screening to 
enable BRCA testing and PD-L1 testing. Slides cut from FFPE blocks must be approved by the Sponsor. 


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e Monitor CBC weekly for the first cycle, on Day 1 of Cycles 2 through 4, on Day 1 and Day 22 of Cycles 5 and 6, on Day 1 and Day 29 of Cycles 7 through 11, and 
on Day 1 of each cycle thereafter. CBC needs to be performed and results evaluated prior to dosing. If dose interruption or modification is required at any point on 
study because of hematologic toxicity, weekly blood draws for CBC will be done until the AE resolves. To ensure safety of the new dose, weekly blood draws for 
CBC will also be required for an additional 4 weeks after the AE has been resolved.  
f Clinical laboratory tests may be performed within 36 hours prior to each visit. Serum/plasma chemistry and CBC need to be performed and results evaluated prior 
to dosing. 
g The following serum/plasma chemistry parameters will be measured: sodium, potassium, chloride, calcium, magnesium, glucose, total bilirubin, ALP, AST, ALT, 
total protein, albumin, creatinine, and urea or blood urea nitrogen. 
h Thyroid-stimulating hormone, triiodothyronine or free triiodothyronine, and free thyroxine. 
i For patients of childbearing potential only, a negative serum or urine pregnancy test is required within 72 hours prior to Day 1 of each cycle. If the clinic standard is 
to do a serum or urine pregnancy test more frequently, that is acceptable with the protocol as written. 
j Only if clinically indicated. Testing should be done for HBsAg (or equivalent) and HCV RNA. 
k If a patient discontinues treatment for a reason other than radiographic progression, death, withdrawal of consent, loss to follow-up, or the end of the study, CA-125 
testing should continue every 9 weeks for the first year of study treatment and every 12 weeks thereafter until PD. If a patient discontinues treatment for clinical 
progression and does not meet RECIST criteria for progression, CA-125 testing should continue at the specified intervals until progression is confirmed or until the 
start of subsequent anticancer treatment. Also, clinically stable patients should not be discontinued until progression is confirmed. 
l RECIST v.1.1 tumor assessment via CT or MRI scan of abdomen/pelvis and clinically indicated areas required at screening, every 9 weeks (63 ± 7 days) from 
Cycle 1 Day 1 for the first year (week 54), then every 12 weeks (84 ± 14 days) until disease progression, at which point a final follow up set of imaging is required. 
Per RECIST v.1.1, tumor imaging for confirmation of response must be performed at the earliest 28 days after the first indication of PR or CR but no later than 
35 days after the response. The subsequent tumor imaging after the confirmatory scan should be obtained 9 weeks (63 ± 7 days) from confirmatory scan during the 
first year of study treatment and every 12 weeks thereafter. If a patient discontinues treatment for clinical progression and does not meet RECIST criteria for 
progression, scans should continue at the specified intervals until progression is confirmed or until the start of subsequent anticancer treatment. Also, clinically 
stable patients should not be discontinued until progression is confirmed. 
m The exploratory biomarker samples are to be collected at the same time with blood samples for central gBRCA testing. 
n For HRQoL evaluation, the FOSI assessment will be collected during the treatment period at Cycle 1 Day 1 (prior to dosing and clinical procedures), Cycle 2 Day 
1, and on Day 1 of every cycle thereafter. For patients who discontinue treatment, FOSI assessments should be collected at the EOT Visit, at the Safety Follow-up 
Visit, and at Survival Assessments. 
o On Day 1 of each cycle, niraparib will be administered after completion of the dostarlimab (TSR-042) infusion. 
p IV dostarlimab (TSR-042) will be administered 500 mg Q3W from Cycles 1 through 4. Starting at Cycle 5, administration will change to 1000 mg Q6W. 
Dostarlimab (TSR-042) treatment may continue for up to 3 years or until PD, unacceptable toxicity, withdrawal of consent, Investigator’s decision, or death. 
Continued treatment with dostarlimab (TSR-042) beyond 3 years may be considered following discussion between the Sponsor and the Investigator. Dostarlimab 
(TSR-042) may be administered up to 3 days before or after the scheduled Day 1 of each cycle after Cycle 1 due to administrative reasons. If dostarlimab (TSR-
042) is administered on Day 1 of the cycle, it will be administered after all procedures and assessments have been completed, unless otherwise indicated. If 
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q All AEs (serious and nonserious) are required to be collected and recorded until 90 ± 14 days after last study drug administration or until alternate anticancer 
treatment has been initiated, whichever occurs earlier. All AESIsmust be reported as outlined in Section 12.2.7. Any pregnancies that occur within 180 days post-
treatment discontinuation are to be reported. 
 
 


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7.6.2. 
Procedures and Assessments 
Standard of care tests/procedures, including laboratory assessments, electrocardiogram 
(ECG), physical examination, vital signs, height, and weight, performed before the 
patient signs the Informed Consent Form (ICF) can be used as part of the screening 
assessments as long as the tests/procedures meet the protocol-required timelines. Scans 
performed prior to informed consent as part of routine clinical management are also 
acceptable for use as initial tumor imaging if they are of diagnostic quality and are 
performed within 28 days prior to first dose date. Note that source documents must 
clearly identify the standard of care tests/procedures that are used for screening and the 
results of these tests/procedures must be entered in the eCRF.  
7.6.3. 
Continued Treatment after Final DCO 
Following the final DCO date, patients may continue to receive study treatment as they 
were doing previously, for as long as they and their physician feel that they are gaining 
clinical benefit from and tolerating the study treatment and have not met any study 
discontinuation criterion. The patients will come into the clinic to receive the study 
treatment and follow the same cycle they were on before, and they will continue to be 
monitored according to routine clinical practice as defined by the investigators, but no 
other study assessments will be conducted. The investigators and site staff may conduct 
any safety assessments that they feel the patient requires and follow the local standard of 
care procedures for the patients. The investigators can contact the Medical Monitor at any 
stage to discuss any concerns. 
When the patients withdraw from the study/study treatment or progress, every effort 
should be made to conduct an EOT visit. The only procedure to be performed at the EOT 
visit is the collection of a blood sample for exploratory biomarkers, as described in 
Table 10. No other assessments listed in Table 10 need to be conducted at the EOT visit, 
unless required as part of standard of care.  


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8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
Prior to undergoing any study-specific procedures, all patients will undergo the informed 
consent process, which will be documented by site staff. Results of any BRCA testing 
will not be shared with the patient. 
8.1. 
Patient Inclusion Criteria 
Patients will be eligible for study entry if all of the following criteria are met: 
1. Patient must be female ≥ 18 years of age, able to understand the study procedures, 
and subsequently agreed to participate in the study by providing written informed 
consent. 
2. Patients must have recurrent high-grade serous, endometrioid, or clear cell 
ovarian, fallopian tube, or primary peritoneal cancer.  
3. Patients must be considered resistant to the last administered platinum therapy, ie, 
the time from last administered platinum dose until initial documented 
progression (as evidenced by radiographic progression per RECIST v.1.1) must 
be less than 6 months (183+7 days).  
4. Patients must have completed at least 1 but no more than 3 prior lines of therapy 
for advanced or metastatic ovarian cancer. Neoadjuvant, adjuvant, and the 
combination of both will be considered as one line of therapy. Treatment with 
single-agent bevacizumab given as maintenance is not counted as a separate line 
of therapy. If a therapeutic regimen is modified or changed for a reason other than 
lack of response or PD (such as allergic reaction, toxicity, or drug availability), 
this is not counted as a separate line of therapy. The use of single-agent hormonal 
therapy given for reasons other than progressive disease per RECIST v1.1 (ie, 
hormonal therapy given for increasing cancer antigen 125 [CA-125] levels) is not 
counted as a separate line of therapy. 
5. Patients must have been previously treated with platinum-based regimen, taxane 
agent(s) and bevacizumab (bevacizumab could be used as a single agent or in 
combination with another agent, in frontline therapy, as maintenance, or for 
treatment of recurrent disease). 
Note: Bevacizumab refers to bevacizumab and approved biosimilars, for example, 
bevacizumab-awwb (MVASI™), bevacizumab-bvzr (ZIRABEV™), etc. 
6. Patient has measurable disease according to RECIST v.1.1. 
7. Patient has an ECOG performance status of 0 or 1 (see Appendix 3). 
8. Patient has adequate organ function, defined as follows: 
a. absolute neutrophil count ≥ 1,500/μL, without growth factor support 
(granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage 
colony-stimulating factor administration is not permitted within 2 weeks of 
screening)  
b. platelets ≥ 100,000/μL without platelet transfusion support within 2 weeks of 
screening 


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c. hemoglobin ≥ 9 g/dL without transfusion or growth factor support 
(recombinant erythropoietin) within 2 weeks of screening 
d. serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 50 mL/min using Cockcroft-Gault equation  
e. total bilirubin ≤ 1.5× ULN, except in patients with Gilbert’s syndrome. 
Patients with Gilbert’s syndrome may enroll if direct bilirubin is ≤ 1.5× ULN. 
f. AST and ALT ≤ 2.5× ULN, unless liver metastases are present, in which case 
they must be ≤ 5× ULN 
9. Patient meets the following criteria:  
a. Female patient (of childbearing potential) is not breastfeeding, has a negative 
serum pregnancy test within 72 hours prior to taking study treatment, and 
agrees to abstain from activities that could result in pregnancy, as outlined in 
Section 9.2.2, from enrollment through 180 days after the last dose of study 
treatment; or  
Note: (a) A urine pregnancy test may be performed if the serum pregnancy 
result is not available before dosing. (b) Women should not breastfeed or 
store breastmilk for use, during treatment, and for 30 days after receiving the 
final dose of study treatment. 
b. Female patient is of nonchildbearing potential, for other than medical reasons, 
defined as any of the following:  
− ≥ 45 years of age and has not had menses for > 1 year  
− amenorrheic for < 2 years without a hysterectomy and oophorectomy and 
a follicle-stimulating hormone value in the postmenopausal range upon 
screening evaluation  
− has undergone hysterectomy, bilateral oophorectomy, or tubal ligation. 
Documented hysterectomy or oophorectomy must be confirmed with 
medical records of the actual procedure or confirmed by an ultrasound. 
Tubal ligation must be confirmed with medical records of the actual 
procedure; otherwise, the patient must meet the pregnancy test criteria for 
women of childbearing potential in inclusion criterion 9a and must be 
willing to use highly effective contraception (see Appendix 1) throughout 
the study, starting with the screening visit through 180 days after the last 
dose of study therapy.  
Note: Abstinence is acceptable if this is the established and preferred 
contraception method for the patient.  
10. Patient must provide FFPE tumor tissue block(s) with sufficient tumor content (as 
confirmed by the Sponsor’s designated central laboratory) during screening to 
enable BRCA testing and PD-L1 testing. The use of slides created from paraffin-
embedded tissue as opposed to FFPE blocks must be approved by the Sponsor. 
11. Patient must agree to complete the HRQoL questionnaire throughout the study.   
8.2. 
Patient Exclusion Criteria 
Patients will not be eligible for study entry if any of the following criteria are met: 


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1. Patients who experienced disease progression within 3 months (12 weeks or 84 
days) (as evidenced by radiographic progression per RECIST v1.1) of first-line 
platinum therapy. 
2. Patients with known deleterious or suspected deleterious mutations in BRCA1 or 
BRCA2 genes (local testing permitted). 
Note: This will apply to known germline BRCA mutations and known BRCA 
mutations in the tumor. 
3. Patient has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 
agent. 
4. Patient has received prior therapy with a PARP-1/PARP-2 inhibitor. 
5. Patient has known hypersensitivity to dostarlimab (TSR-042), niraparib, their 
components, or their excipients. 
6. Patient has a known history of myelodysplastic syndrome or acute myeloid 
leukemia. 
7. Patient has not recovered (ie, to Grade ≤ 1 or to baseline) from prior 
chemotherapy induced AEs. Note: Patient with Grade ≤ 2 neuropathy or alopecia 
is an exception to this criterion and may qualify for the study.  
8. Patient has a known diagnosis of immunodeficiency or is receiving systemic 
steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other 
form of immunosuppressive therapy within 7 days prior to the first dose of study 
treatment. 
9. Patient is currently participating in a treatment study or has participated in a study 
of an investigational agent within 4 weeks of the first dose of treatment. 
10. Patient has received prior systemic anticancer therapy including cytotoxic 
chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, 
or biological therapy within 3 weeks of the first dose of study treatment. 
11. Patient has received live vaccine within 14 days of planned start of study therapy. 
12. Patient has symptomatic uncontrolled brain or leptomeningeal metastases. (To be 
considered “controlled,” central nervous system [CNS] disease must have 
undergone treatment [eg, radiation or chemotherapy] at least 1 month prior to 
study entry. The patient must not have any new or progressive signs or symptoms 
related to the CNS disease and must be taking ≤ 10 mg of prednisone or 
equivalent per day or no steroids.) Patients who have untreated brain metastases 
and who are not symptomatic may enroll if the Investigator feels that treatment of 
these metastases is not indicated. A scan to confirm the absence of brain 
metastases is not required. Patients with spinal cord compression may be 
considered if they have received definitive treatment for this and evidence of 
clinically stable disease for 28 days prior to the first dose of study treatment. 
13. Patient had major surgery within 4 weeks of starting the first dose of study 
treatment or patient has not recovered from any effects of any major surgery. 


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14. Patient has a known additional malignancy that progressed or required active 
treatment within the last 2 years. Exceptions include basal cell carcinoma of the 
skin, squamous cell carcinoma of the skin that has undergone potentially curative 
therapy, or in situ cancer that is considered to be low risk for progression by the 
Investigator. 
15. Patient is considered a poor medical risk due to a serious, uncontrolled medical 
disorder, nonmalignant systemic disease, or active, uncontrolled infection. These 
include, but are not limited to, significant cardiovascular disease (eg, significant 
cardiac conduction abnormalities, myocardial infarction, cardiac arrhythmia or 
unstable angina within 6 months prior to enrollment, New York Heart Association 
Grade ≥ 2 congestive heart failure, uncontrolled hypertension, serious cardiac 
arrhythmia requiring medication, Grade ≥ 2 peripheral vascular disease, and 
history of cerebrovascular accident within 6 months prior to enrollment), 
uncontrolled major seizure disorder, unstable spinal cord compression, superior 
vena cava syndrome, and any psychiatric disorder that prohibits obtaining 
informed consent. 
16. Patient has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the study, might interfere with the 
patient’s participation for the full duration of the study treatment, or is not in the 
best interest of the patient to participate. 
17. Patient has known active hepatitis B (eg, hepatitis B surface antigen reactive) or 
hepatitis C (eg, hepatitis C virus ribonucleic acid [qualitative] has been detected).  
18. Patients with known human immunodeficiency virus (HIV) are allowed if they 
meet all of the following criteria:  
a. Cluster of differentiation 4 ≥350/μL and viral load <400 copies/mL 
b. No history of acquired immunodeficiency syndrome-defining opportunistic 
infections within 12 months prior to enrollment  
c. No history of HIV-associated malignancy for the past 5 years 
d. Concurrent antiretroviral therapy as per the most current National Institutes of 
Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and 
Adolescents Living with HIV started >4 weeks prior to study enrollment 
19. Patient is immunocompromised. Patients with splenectomy are allowed. 
20. Patient has an ongoing bowel obstruction or has other conditions that would lead 
to impaired absorption of oral niraparib. 
21. Patient has active autoimmune disease that has required systemic treatment in the 
past 2 years (ie, with use of disease-modifying agents, corticosteroids, or 
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or 
physiologic corticosteroid replacement therapy for adrenal or pituitary 
insufficiency) is not considered a form of systemic treatment. 


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8.3. 
Patient Withdrawal Criteria 
8.3.1. 
Discontinuation from Treatment 
Patients may be discontinued from study treatment at any time. Patients who discontinue 
from study treatment or from the study will not be replaced.  
Specific reasons for discontinuing either treatment include the following, in addition to 
those indicated in Section 7.4: 
• AE 
• Disease progression according to RECIST v.1.1 criteria per Investigator 
assessment 
• Risk to patient, as judged by the Investigator, Sponsor, or both 
• Severe noncompliance with the protocol, as judged by the Investigator, 
Sponsor, or both 
• Patient becomes pregnant 
• Withdrawal of consent 
• Loss to follow-up 
• Death 
For patients who have attained a confirmed CR and have received study treatment for at 
least 2 years, discontinuation of treatment may be considered by the Investigator after 
discussion with the Sponsor’s Medical Monitor. In this instance, patients may be 
permitted to resume treatment only after discussion with the Sponsor’s Medical Monitor 
if the Investigator believes the patient may derive benefit from ongoing treatment. 
Patients with radiographic evidence of PD who are clinically stable may continue 
treatment at the Investigator’s discretion and after discussion with the Sponsor, while 
awaiting confirmatory tumor imaging. Repeat imaging should be performed at ≥ 4 weeks. 
If repeat imaging shows SD, PR, or CR, patients can continue study treatment at the 
Investigator’s discretion. In the event that PD is confirmed, patients still may continue to 
receive study treatment even after confirmed radiographic progression if the patient is 
clinically stable and the Investigator deems that the patient is deriving clinical benefit. 
This allowance to continue treatment despite radiographic progression takes into account 
the observation that some patients may have a transient tumor flare in the first few 
months after the start of immunotherapy, but with subsequent disease response. 
If a patient discontinues treatment for a reason other than radiographic progression, death, 
withdrawal of consent, loss to follow-up, or the end of the study, radiographic evaluation 
and CA-125 testing should continue every 9 weeks for the first year of study treatment 
and every 12 weeks thereafter until PD. Also, clinically stable patients should not be 
discontinued until progression is confirmed. 
If a patient discontinues treatment for clinical progression and does not meet RECIST 
criteria for progression, scans and CA-125 testing should continue at the specified 


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intervals until progression is confirmed or until the start of subsequent anticancer 
treatment.  
Patients who discontinue from all study treatments will continue to receive follow-up 
assessments as part of the study unless they are discontinued from the study. 
8.3.2. 
Discontinuation from the Study 
Specific reasons for discontinuing from the study include the following: 
• withdrawal of consent by the patient, who is at any time free to discontinue 
participation in the study, without prejudice to further treatment 
• loss to follow-up 
• death from any cause 
• Sponsor’s decision to terminate study 
• Investigator’s decision 
If a patient is thought to be lost to follow-up, discontinues study treatment, or 
discontinues the study, attempts should be made to contact the patient to determine the 
reason for discontinuation. For patients who are thought to be lost to follow-up, at least 
3 documented attempts, including 1 attempt via certified mail, should be made to contact 
the patient before the patient is deemed lost to follow-up. 


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9. 
TREATMENT OF PATIENTS 
9.1. 
Description of Study Drug 
The Pharmacy Manual contains descriptions of the packaging of niraparib and 
dostarlimab (TSR-042) and instructions for the preparation and administration of these 
drugs. Table 11 describes the investigational products. 
Table 11: 
Investigational Product 
 
Investigational Product 
Product Name: 
Niraparib 
Dostarlimab (TSR-042) 
Dosage Form: 
Capsule 
Solution for IV infusion 
Unit Dose 
100 mg per capsule 
160 mg, 20 mg/mL, or 
500 mg, 50 mg/mL 
Route of 
Administration 
Oral 
Intravenous 
Physical Description 
Capsules in high-density 
polyethylene bottles 
Solution for IV infusion in single-
use vial 
Abbreviations: IV = intravenous. 
9.2. 
Concomitant Medications 
Any medication the patient takes during the study other than the study treatments, 
including herbal and other nontraditional remedies, is considered a concomitant 
medication. All concomitant medications must be recorded in the eCRF. The following 
information must be recorded in the eCRF for each concomitant medication: generic 
name, route of administration, start date, stop date, dosage, and indication. Any changes 
in the dosage or regimen of a concomitant medication must be recorded in the eCRF. 
At screening, patients will be asked what medications they have taken during the last 30 
days. At each subsequent study visit, patients will be asked what concomitant 
medications they are currently taking or have taken since the previous visit. 
9.2.1. 
Prohibited Medications 
Known prior medications that exclude a patient from participating in the study are 
described in the exclusion criteria (Section 8.2). 
Patients are prohibited from receiving the following therapies during the screening and 
treatment phase of this study: 
• Systemic anticancer or biological therapy 
• Immunotherapy not specified in this protocol 
• Chemotherapy not specified in this protocol 


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• Investigational agents other than niraparib and dostarlimab (TSR-042)  
• Prophylactic cytokines (eg, G-CSF) should not be administered in the first 
cycle of the study but may be administered in subsequent cycles according to 
local guidelines.  
• Systemic glucocorticoids for any purpose other than to manage symptoms of 
suspected irAEs. (Note: Use of inhaled steroids, local injection of steroids, 
topical steroids, and steroid eye drops are allowed.) If medically deemed 
necessary (eg, acute asthma or chronic obstructive pulmonary disease 
exacerbation, prophylaxis for IV contrast if indicated), Investigators are 
allowed to use their judgment to treat patients with systemic steroids. In such 
cases, systemic steroids should be stopped at least 24 hours prior to the next 
dose of dostarlimab (TSR-042). 
An increased risk of infection by the administration of live virus and bacterial vaccines 
has been observed with conventional chemotherapy drugs. Effects with niraparib are 
unknown; therefore, live virus and bacterial vaccines should not be administered to 
patients in the study. Seasonal flu vaccines that do not contain live viruses are allowed. 
Examples of live vaccines include, but are not limited to, the following: measles, mumps, 
rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid (oral) 
vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and 
are allowed. Intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and 
are not allowed. 
No other anticancer therapy is permitted during the course of the study treatment for any 
patient. Palliative radiotherapy (excluding the pelvic region and/or palliative radiotherapy 
encompassing > 20% of the bone marrow within 1 week of the first dose of study 
treatment) is allowed for pre-existing small areas of painful metastases that cannot be 
managed with local or systemic analgesics, as long as no evidence of disease progression 
is present. 
The niraparib safety profile includes risk for thrombocytopenia; therefore, patients should 
be advised to use caution when taking anticoagulants (eg, warfarin) and antiplatelet drugs 
(eg, aspirin). 
Physicians should follow the current versions of the niraparib Investigator’s Brochure 
and the dostarlimab (TSR-042) Investigator’s Brochure for information on the general 
management of the patients receiving these therapies. 
9.2.2. 
Contraception 
Niraparib and dostarlimab (TSR-042) are known to have properties that require patients 
to use contraception. For details on niraparib and dostarlimab (TSR-042), please refer to 
the respective Investigator’s Brochures.  
Based on its mechanism of action, niraparib may cause teratogenicity and/or embryo-fetal 
death when administered to a pregnant woman. 
Patients of childbearing potential may only be enrolled if they have a negative serum 
pregnancy test within 72 hours prior to taking study treatment. Note: A urine pregnancy 
test may be performed if the serum pregnancy result is not available before dosing. 


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Patients must agree to abstain from activities that could result in pregnancy from 
screening through 180 days after the last dose of study treatment, be willing to use a 
highly effective contraception (see Appendix 1), or be of non-childbearing potential, as 
defined in Section 8.1.  
See Appendix 1 for a list of highly effective contraception methods. Patients should be 
informed that taking the study treatment may involve unknown risks to the fetus if 
pregnancy were to occur during the study. To participate in the study, they must adhere to 
the contraception requirements described above. If there is any question that a patient will 
not reliably comply with the requirements for contraception, that patient should not be 
enrolled in the study.  
9.2.3. 
Rescue Medications and Supportive Care Guidelines During Treatment 
with Dostarlimab (TSR-042)  
9.2.3.1. 
Supportive Care for Adverse Events 
During treatment with dostarlimab (TSR-042), patients should receive appropriate 
supportive care measures for AEs as deemed necessary by the treating Investigator, 
including but not limited to the items outlined below. Additional guidance for clinical 
management can be found in the joint ASCO and NCCN guidelines for diagnosis and 
management of irAEs.51 Prophylactic cytokines (eg, G-CSF) should not be administered 
in the first cycle of the study but may be administered in subsequent cycles according to 
current ASCO guidelines.52 Note: It may be necessary to perform additional procedures 
such as bronchoscopy, endoscopy, or skin photography as part of the evaluation of the 
AE. The following sections detail specific guidance by type of AE. 
• Pneumonitis 
− Treat with systemic corticosteroids, oral for Grade 2 (eg, 0.5 to 
1 mg/kg/day of prednisone or equivalent) and IV for Grade 3 or 4 (eg, 1 to 
2 mg/kg/day of prednisone or equivalent). 
− Administer additional anti-inflammatory measures, as needed. 
− Taper corticosteroids when symptoms improve to Grade ≤ 1 over ≥ 4 
weeks. 
− If Grade 2 and no improvement or worsening over 2 weeks, treat as Grade 
3 or 4. 
− Consider prophylactic antibiotics for opportunistic infections in the case of 
prolonged steroid administration. 
• Diarrhea/Colitis 
− Monitor carefully for signs and symptoms of enterocolitis (such as 
diarrhea, abdominal pain, blood or mucus in stool, with or without fever) 
and of bowel perforation (such as peritoneal signs and ileus). 
− All patients who experience diarrhea/colitis should be advised to drink 
liberal quantities of clear fluids. If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be substituted via IV infusion. 


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− For Grade 2 diarrhea/colitis that persists > 3 days, administer oral 
corticosteroids (eg, 0.5 to 1.0 mg/kg/day of prednisone or equivalent). If 
symptoms persist or worsen with steroids, treat as Grade 3 or 4. 
− For Grade 3 or 4 diarrhea/colitis that persists > 3 days, treat with IV 
steroids (eg, 1 to 2 mg/kg/day of prednisone or equivalent) followed by 
high-dose oral steroids. 
− Taper corticosteroids when symptoms improve to Grade ≤ 1 over ≥ 4 
weeks. 
• Type 1 Diabetes Mellitus (T1DM) or Grade 3 or 4 Hyperglycemia 
− For T1DM and for Grade 3 or 4 hyperglycemia associated with metabolic 
acidosis or ketonuria, insulin replacement therapy is required. 
• Hypophysitis 
− Treat with systemic corticosteroids, oral for Grade 2 (eg, 0.5 to 
1 mg/kg/day of prednisone or equivalent) and IV for Grade 3 or 4 (eg, 1 to 
2 mg/kg/day of prednisone or equivalent). 
− Taper corticosteroids when symptoms improve to Grade ≤ 1 over ≥ 4 
weeks. 
− Replacement of appropriate hormones may be required as the steroid dose 
is tapered. 
• Hyperthyroidism or Hypothyroidism 
− Thyroid disorders have been reported with other PD-1 inhibitors occurring 
at any time during treatment. Monitor patients for changes in thyroid 
function (at the start of treatment, periodically during treatment, and as 
indicated based on clinical evaluation) and for clinical signs and 
symptoms of thyroid disorders. 
− Grade 2 HYPERthyroidism: Consider nonselective beta-blockers 
(eg, propranolol) as initial therapy. 
− Grade 3 or 4 HYPERthyroidism: Treat with an initial dose of IV 
corticosteroids followed by oral corticosteroids (eg, 0.5 to 1 mg/kg/day of 
prednisone or equivalent). Taper corticosteroids when symptoms improve 
to Grade ≤ 1 over ≥ 4 weeks. Replacement of appropriate hormones may 
be required as the steroid dose is tapered. 
− Grade 2 to 4 HYPOthyroidism: Thyroid hormone replacement therapy, 
with levothyroxine or liothyronine, is indicated per standard of care. 
• Hepatitis 
− Treat with systemic corticosteroids, oral for Grade 2 (initial dose of 1 to 
2 mg/kg/day of prednisone or equivalent) and IV for Grade 3 or 4 (1 to 
2 mg/kg/day of prednisone or equivalent).  


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− Taper corticosteroids when symptoms improve to Grade ≤ 1 over ≥ 4 
weeks. 
• Renal Failure or Nephritis 
− Treat with systemic corticosteroids, oral for Grade 2 (initial dose of 0.5 to 
1 mg/kg/day of prednisone or equivalent) and IV for Grade 3 or 4 (1 to 
2 mg/kg/day of prednisone or equivalent). 
− Taper corticosteroids when symptoms improve to Grade ≤ 1 over ≥ 4 
weeks. 
• Adrenal Insufficiency: 
− Start treatment with corticosteroids before other hormone replacement 
therapy to avoid adrenal crisis (hydrocortisone slowly titrating doses down 
according to symptoms or prednisone and fludrocortisone titrating up or 
down based on blood pressure, other symptoms, and laboratory results); 
patients with severe symptoms may require additional fluids (eg, saline 
>2 L). 
− Monitor for cortisol level (AM), comprehensive metabolic panel (Na, K, 
CO2, glucose), and renin. 
− Ensure adequate evaluation (eg, endocrine consultation). 
• Severe Exfoliative Dermatologic Events: 
− Suspected: Treat with high potency topical steroids to affected areas. Treat 
with oral prednisone or equivalent at an initial dose of 0.5 to 1 mg/kg/day 
and taper steroid when dermatitis is controlled. Ensure adequate 
evaluation (eg, urgent dermatology consultation) to confirm etiology 
and/or exclude other causes. 
− Confirmed: Administer 1 to 2 mg/kg/day IV methylprednisolone or 
equivalent and taper steroid when dermatitis is controlled. 
• Severe Neurologic Events (Myasthenic Syndrome/Myasthenia Gravis, 
Guillain-Barré Syndrome, Transverse Myelitis) 
− Consider high dose corticosteroids and other therapies as needed. 
− It is highly recommended that Investigators discuss any AEs with the 
Sponsor before using infliximab. 
− Ensure adequate evaluation (eg, neurology consultation). 
− Consider MRI of brain and/or spine depending on symptoms. 
− Consider inpatient management as clinically indicated. 
• Myocarditis 
− Administer high-dose corticosteroids (1 g/day of IV methylprednisolone) 
for 3 to 5 days, followed by oral prednisone taper over 4 to 6 weeks based 
on improvement in cardiac function and biomarkers. 


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Study treatment (niraparib and dostarlimab [TSR-042]) will be administered as detailed 
in Section 10.5. 
Study treatment accountability will be monitored as detailed in Section 10.6.  
9.4. 
Randomization and Blinding 
Not applicable. 


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10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Study Drug 
10.1.1. 
Niraparib 
Niraparib ([3S]-3-[4-{7-(aminocarbonyl)-2H-indazol-2-yl} phenyl] piperidine [tosylate 
monohydrate salt]) is an orally available, potent, highly selective PARP-1 and PARP-2 
inhibitor. The excipients for niraparib are lactose monohydrate and magnesium stearate. 
Niraparib will be supplied as 100-mg capsules. 
10.1.2. 
Dostarlimab (TSR-042)  
Dostarlimab (TSR-042) is a humanized mAb of the IgG4/kappa isotype that binds with 
high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. 
Dostarlimab (TSR-042) for IV infusion will be supplied as a solution of 160 mg (20 
mg/mL) or 500 mg (50 mg/mL) in a single-dose vial. 
10.2. 
Study Drug Packaging and Labeling 
Niraparib 100-mg capsules will be packed in high-density polyethylene bottles with 
child-resistant closures.  
Dostarlimab (TSR-042) will be provided as 8R (20 mg/mL) or 10 mL (50 mg/mL) Type I 
borosilicate clear glass vials, stoppered with a chlorobutyl elastomer stopper laminated 
with fluoropolymer and sealed with an aluminum overseal with a flip-off cap. Expiration 
dates are printed on the product label. 
The label text of the study treatments will comply with Good Manufacturing Practice and 
national legislation to meet the requirements of the participating countries. The study 
treatment will be open-label and non-patient-specific. 
10.3. 
Study Drug Storage 
All study treatment supplies must be stored in accordance with the Pharmacy Manual 
instructions and package labeling. Until dispensed or administered to the patients, the 
study treatment will be stored in a securely locked area, accessible to authorized 
personnel only. 
10.4. 
Study Drug Preparation 
The Pharmacy Manual contains information for specific instructions for the preparation 
of the dostarlimab (TSR-042) infusion and administration of the infusion solution. 
10.5. 
Administration 
10.5.1. 
Niraparib 
Niraparib will be administered orally QD throughout each 21-day or 42-day cycle, in the 
absence of PD, unacceptable toxicity, patient withdrawal, Investigator’s decision to 
withdraw, or death. On Day 1 of each cycle, niraparib will be administered after 
completion of the dostarlimab (TSR-042) infusion.  


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The starting dose of niraparib will be based on the patient’s baseline actual body weight 
or platelet count (Table 13). Patients with a baseline actual body weight of ≥ 77 kg and 
baseline platelet count of ≥ 150,000/µL will take three capsules of 100 mg strength (300 
mg/day) at each dose administration. Patients with a baseline actual body weight of < 77 
kg or baseline platelet count of < 150,000/µL will take two capsules of 100 mg strength 
(200 mg) at each dose administration. Additional dose modifications will not be based 
upon changes in the patient’s actual body weight during study participation.  
For patients whose starting dose is 200 mg/day, the niraparib dose may be escalated on or 
after Cycle 3 Day 1 from 200 mg QD (2 capsules) to 300 mg QD (3 capsules) if the 
laboratory test results are within the specified limits (platelet count ≥ 100,000/μL, 
hemoglobin ≥ 9 g/dL, and neutrophil count ≥ 1,500/μL) during the first 2 cycles of 
treatment. This escalation will occur at the discretion of the Investigator, following 
discussion with the Sponsor’s Medical Monitor or designee.  
Table 13: 
Recommended Initial Starting Dose 
 
Baseline platelets 
≥ 150,000/μL 
Baseline platelets < 150,000/μL 
Baseline weight ≥ 77 
kg 
300 mg (3 × 100 mg capsules) 
QD 
200 mg (2 × 100 mg capsules) 
QD 
Baseline weight < 77 
kg 
200 mg (2 × 100 mg capsules) 
QD 
200 mg (2 × 100 mg capsules) 
QD 
Abbreviation: QD = once daily 
Patients will be instructed to take their niraparib dose QD or as instructed by the 
Investigator. Patients must swallow and not chew all capsules. The consumption of water 
and food is permissible. If a patient vomits or misses a dose of niraparib, a replacement 
dose should not be taken. 
Details on the administration of niraparib can be found in the Pharmacy Manual. 
10.5.2. 
Dostarlimab (TSR-042)  
Dostarlimab (TSR-042) infusion will be administered before the niraparib dose at the 
study site on Day 1 of each 21-day treatment cycle (Q3W) in Cycles 1 through 4 and 
every 6 weeks thereafter, beginning on Cycle 5 Day 1. Dostarlimab (TSR-042) treatment 
may continue for up to 3 years or until PD, unacceptable toxicity, withdrawal of consent, 
Investigator’s decision, or death. Continued treatment with dostarlimab (TSR-042) 
beyond 3 years may be considered following discussion between the Sponsor and the 
Investigator. 
Dostarlimab (TSR-042) may be administered up to 3 days before or after the scheduled 
Day 1 of each cycle after Cycle 1 due to administrative reasons. If dostarlimab (TSR-
042) is administered on Day 1 of the cycle, it will be administered after all procedures 
and assessments have been completed, unless otherwise indicated. If dostarlimab (TSR-
042) is administered earlier or later than Day 1 of the cycle, patients will continue to take 
niraparib as scheduled. 
Dostarlimab (TSR-042) will be administered at a dose of 500 mg IV Q3W in Cycles 1 
through 4 and at a dose of 1,000 mg IV Q6W, starting in Cycle 5, for the rest of the 


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treatment using a 30-minute infusion. Sites should make every effort to target infusion 
timing to be as close to 30 minutes as possible. Given the variability of infusion pumps 
from site to site, infusion durations of 25 to 45 minutes are permitted. 
The Pharmacy Manual contains information for specific instructions for the preparation 
of the dostarlimab (TSR-042) infusion and administration of the infusion solution.  
10.6. 
Study Drug Accountability 
The Investigator or designee is responsible for maintaining accurate dispensing records of 
the study treatments throughout the clinical study. Study drug accountability for niraparib 
should be maintained by each site based on capsules dispensed vs. returned to the clinic 
at each visit and the number of days since the last visit. 
Details of maintaining drug accountability, including information on the accountability 
log, will be provided in the Pharmacy Manual. 
All dispensation and accountability records will be available for Sponsor review. The 
study monitor will assume the responsibility for reconciling the study treatment 
accountability log. The pharmacist will dispense study treatment for each patient 
according to the protocol and Pharmacy Manual, if applicable. 
10.6.1. 
Continued Access to Study Treatment Following Final DCO  
Following the final DCO date, for patients continuing study treatment, the dispensing and 
ordering of study treatment will be done outside of the Rave Randomisation and Trial 
Suppy Management Interactive Response Technology (RAVE RTSM IRT) system. At 
the usual clinic visits, the patients will return used and unused medication, and a thorough 
drug accountability assessment will be performed at the site. Drug dispensing and 
accountability information will be recorded in the patient notes for as long as the patients 
continue to receive study treatment. Details of manual ordering are provided in the 
Pharmacy Manual.  
10.7. 
Study Drug Handling and Disposal 
At the end of study, when all patients have stopped protocol treatment, complete drug 
reconciliation per batch should be available at the site for verification in order to allow 
drug destruction or return procedure. After receiving Sponsor approval in writing, the 
investigational site is responsible for destruction of study drug according to local 
regulations. If a site does not have the capability for onsite destruction, the Sponsor will 
provide a return for destruction service through a third party. Both the unused and 
expired study treatment must be destroyed, upon authorization of the Sponsor, according 
to local regulations and procedures, and a copy of the destruction form must be filed in 
the study binder. 
The medication provided for this study is to be used only as indicated in this protocol and 
only for the patients entered in this study. 


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11. 
ASSESSMENT OF EFFICACY 
11.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is Investigator-assessed confirmed ORR, which is defined 
as the proportion of patients who have achieved confirmed CR or PR. Tumor response 
will be evaluated using RECIST v.1.1 (Appendix 2). The primary analysis population 
will be the intent-to-treat (ITT) population, consisting of all patients who receive at least 
1 complete dose of either study drug and who have measurable disease at baseline. 
Analyses will be performed overall (including all patients in the ITT population) and in 
the subset of patients with PD-L1 positive tumors. 
11.1.1. 
Evaluation of Tumor Response  
The efficacy of the treatment combination will be evaluated by assessment of tumor 
response according to RECIST v.1.1 per the Investigator’s assessment.  
Tumor imaging (chest, abdomen, and pelvis) should be performed by CT with IV 
contrast (preferred, if no contraindication to IV contrast). MRI should only be used if 
clinically appropriate, when CT is contraindicated, or for imaging of the head, but the 
same imaging technique should be used in a patient throughout the study, unless this is 
not feasible. CT scan is the more commonly used modality and is preferred for the 
majority of patients. Positron emission tomography/CT may be used according to 
RECIST v.1.1 guidelines. If the chest or head CT/MRI is clear at screening, repeat 
imaging of these areas is not required in the absence of clinical indication requiring 
follow‐up. Bone scans should be conducted per standard of care. 
When the Investigator reports that the patient has progressed, all imaging and supportive 
clinical data will be submitted for central review, in order to allow evaluation of the 
secondary endpoints of ORR as assessed by independent review. 
11.1.2. 
Timing of Radiographic Evaluations 
All patients will undergo serial radiographic assessments to assess tumor response. Initial 
tumor imaging at screening must be performed within 28 days prior to the date of the first 
dose of study treatment. Scans performed prior to the signing of the ICF as part of routine 
clinical management are acceptable for use as initial tumor imaging if they are of 
diagnostic quality and performed within 28 days prior to the date of first dose.  
Radiographic evaluations to assess extent of disease will be conducted every 9 weeks 
(63 ± 7 days) from Cycle 1 Day 1 for the first year, independent of cycle delays or dose 
interruptions, or at any time when PD is suspected. After 1 year of radiographic 
assessments (week 54), imaging will be performed every 12 weeks (84 ± 14 days).  
Per RECIST v.1.1, CR or PR should be confirmed; tumor imaging for confirmation of 
response must be performed at the earliest 28 days after the first indication of PR or CR 
but no later than 35 days after the response. The subsequent tumor imaging after the 
confirmatory scan should be obtained per original schedule (9 weeks ± 7 days from 
confirmatory scan during the first year of study treatment and every 12 weeks thereafter). 


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Radiographic evaluations will continue until PD, start of alternate anticancer therapy, 
withdrawal of consent to study participation, becoming lost to follow-up, death, or end of 
the study. If a patient discontinues treatment for a reason other than radiographic 
progression, death, withdrawal of consent, loss to follow-up, or the end of the study, 
radiographic evaluation should continue at the specified intervals (ie, every 9 weeks for 
the first year of study treatment and every 12 weeks thereafter until PD). Also, clinically 
stable patients should not be discontinued until progression is confirmed. If a patient 
discontinues treatment for clinical progression and does not meet RECIST criteria for 
progression, scans should continue at the specified intervals until progression is 
confirmed or until the start of subsequent anticancer treatment.  
There is accumulating evidence indicating clinical benefit in a subset of patients treated 
with immunotherapy despite initial evidence of PD.53 Patients with PD may continue 
study treatment at the Investigator’s discretion only after discussion with the Sponsor, 
until the Investigator has determined that the patient is no longer experiencing clinical 
benefit or until study treatment is no longer tolerated by the patient. 
11.2. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints will be analyzed overall (including all patients in the ITT 
population) and in the subset of patients with PD-L1 positive tumors. 
11.2.1. 
Duration of Response  
DOR based on Investigator/independent review committee assessment is defined as the 
time from first documentation of response (CR or PR) until the time of first 
documentation of disease progression by RECIST v.1.1 based on 
Investigator/independent review committee assessment or death by any cause in the 
absence of progression by RECIST v.1.1. 
11.2.2. 
Progression-free Survival  
PFS based on Investigator/independent review committee assessment is defined as the 
time from the date of the first dose of study treatment to the earlier date of assessment of 
progression by RECIST v.1.1 based on Investigator/independent review committee 
assessment or death by any cause in the absence of progression by RECIST v.1.1. 
11.2.3. 
Overall Survival  
OS is defined as the time from the date of the first dose of study treatment to the date of 
death by any cause. Following the End of Treatment Visit, survival status will be 
collected for all patients using acceptable means, including telephone contact. Patients 
without documented death at the time of the final analysis will be censored at the last date 
they were known to be alive. 
11.2.4. 
Disease Control Rate  
DCR based on Investigator/independent review committee assessment is defined as the 
percentage of patients who have achieved best overall response (BOR) of CR, PR, or SD 
per RECIST v.1.1 based on the Investigator/independent review committee assessment. 


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12. 
ASSESSMENT OF SAFETY 
12.1. 
Safety Parameters 
Safety parameters evaluated during this study will include AEs, vital signs, symptom-
directed physical examination findings, and clinical laboratory values (including 
hematology, serum or plasma chemistry, coagulation, and thyroid function).   
All safety parameters will be performed in accordance with the schedule of events 
(Table 10). 
12.1.1. 
Demographic 
Demographic and baseline characteristics consist of those variables that are assessed at 
screening/baseline. Patient demographics consist of age at screening, race, ethnicity, and 
sex. 
12.1.2. 
Disease History 
The following information regarding disease history will be recorded: 
• Date of first diagnosis 
• Tumor type 
• Stage at time of initial diagnosis 
• Histology and grade of disease at diagnosis and most recent biopsy if 
additional biopsy performed 
• Information on first anticancer therapy: 
− Intent (adjuvant, neoadjuvant, curative, and palliative)  
− Date of start of first treatment 
− Agents used in first treatment 
− Date of last dose of first treatment 
• Information on second and subsequent anticancer therapies: 
− Intent (adjuvant, neoadjuvant, curative, and palliative)  
− Dates of start of all subsequent treatments 
− Agents in all subsequent treatments 
− Dates of last dose of all subsequent treatments 
• Best response and reason for treatment discontinuation (including PD and 
toxicities) for each prior anticancer therapy 
• Date of PD for each prior anticancer therapy 
• Genotyping, such as gBRCA or, if known, tBRCA status 


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12.1.3. 
Medical and Surgical History 
Important medical and surgical history, including medication history and history of 
thrombocytopenia, neutropenia, leukopenia, or anemia, will be collected. Details of any 
prior invasive malignancy will be collected. Medical and surgical history will be obtained 
by interviewing the patient or by reviewing the patient’s medical records. 
12.1.4. 
Previous and Concomitant Medications 
Previous and concomitant medications will be documented as described in Section 9.2. 
Medications will be coded using World Health Organization (WHO) Anatomical 
Therapeutic Chemical classification. 
12.1.5. 
Vital Signs 
Vital signs will be measured in all patients and include blood pressure, heart rate (pulse), 
and temperature. Temperature, blood pressure, and heart rate (pulse) will be measured at 
screening, on Day 1 of each treatment cycle, and on Day 22 of Cycles 5 and 6. Blood 
pressure and heart rate (pulse) should also be measured weekly (Day 8 and Day 15) 
during the first 8 weeks (Cycles 1 through 3) and on Day 29 ±7 days in Cycles 7 through 
11, and entered as an unscheduled visit if abnormal. Any abnormal vital signs assessed as 
clinically significant should be recorded as an AE or SAE. If SAE criteria are met or the 
abnormality is an AESI (see Section 12.2.1.4), the event should be recorded and reported 
according to the SAE reporting process (see Section 12.2.6). 
12.1.6. 
Weight and Height 
Weight and height will be measured in accordance with the schedule of events 
(Table 10). 
Height will be measured at screening only. Weight will be measured at screening and at 
every visit. 
12.1.7. 
Physical Examination 
Physical examinations, including height (screening only), weight, and vital signs (blood 
pressure, pulse rate, and temperature), will be performed in accordance with the schedule 
of events (Table 10). 
Any physical examination or vital sign abnormalities assessed as clinically significant 
should be recorded as an AE or SAE. If SAE criteria are met or the abnormality is an 
AESI (see Section 12.2.1.4), the event should be recorded and reported according to the 
SAE reporting process (see Section 12.2.5). 
12.1.8. 
Electrocardiogram 
All patients will undergo ECGs at screening (Table 10). Patients will be supine or in a 
semirecumbent position (about 30 degrees of elevation) and rested for approximately 2 
minutes before ECGs are recorded. 


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12.1.9. 
Laboratory Assessments 
The following laboratory variables will be determined in accordance with the schedule of 
events (Table 10). 
These tests will be performed by the local laboratory at the investigational site. 
Any abnormal laboratory value assessed as clinically significant should be recorded as an 
AE. If SAE criteria are met or the abnormality is an AESI (see Section 12.2.1.4), the 
event should be recorded and reported according to the SAE reporting process (see 
Section 12.2.6). 
Hematologic testing may occur more frequently than is specified in the schedule of 
events, if additional testing is medically indicated per the Investigator’s judgment or if 
the event meets the criteria for study treatment dose adjustment (see Section 7.4). 
Additional tests may be performed at a laboratory facility other than the study site, but 
the test results must be reported to the study site, the study site must keep a copy of test 
results with the patient’s study file, as well as laboratory normal ranges for the facility 
used, and the results must be entered into the eCRF. 
Any suspected case of MDS/AML reported while a patient is receiving treatment or 
followed for post-treatment assessments must be referred for evaluation to a local 
hematologist to perform bone marrow aspirate and biopsy as per local practice. The study 
site must receive a copy of the hematologist’s report of aspirate/biopsy findings, which 
must include a classification according to WHO, and other sample testing reports related 
to MDS/AML. Report data will be entered in the appropriate eCRF pages, and the site 
must keep a copy of all reports with the patient’s study file.  
Any suspected case of secondary cancer (new malignancies other than MDS/AML) 
reported while a patient is receiving treatment or followed for post-treatment assessments 
must be investigated, including obtaining and documenting a histological diagnosis. 
Testing completed as part of standard of care is sufficient as long as the methods are 
deemed acceptable after consultation with the Sponsor’s Medical Monitor. 
12.1.9.1. Hematology 
The following hematologic parameters will be determined in accordance with the 
schedule of events (Table 10): 
• Complete blood count: 
− hemoglobin 
− platelet count 
− white blood cell count 
− differential white blood cell count 
• Coagulation factors: 
− international normalized ratio 
− activated partial thromboplastin time 


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12.1.9.2. Blood Chemistry 
The following blood chemistry parameters will be measured in accordance with the 
schedule of events (Table 10): 
• Serum or plasma chemistry: 
− sodium 
− potassium 
− chloride 
− calcium 
− magnesium 
− glucose  
− total bilirubin 
− ALP 
− AST 
− ALT 
− total protein 
− albumin 
− creatinine 
− urea or blood urea nitrogen 
− amylase  
12.1.9.3. Urinalysis 
The following urinalysis parameters will be measured in accordance with the schedule of 
events (Table 10): 
− specific gravity 
− leukocyte esterase 
− nitrite 
− blood 
− glucose 
− ketones 
− microscopy (if clinically indicated) 


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12.1.9.4. 
Thyroid Panel 
The following thyroid parameters (or equivalent tests) will be measured in accordance 
with the schedule of events (Table 10): 
− thyroid-stimulating hormone 
− triiodothyronine or free triiodothyronine 
− free thyroxine 
12.1.9.5. Hepatitis B and Hepatitis C Testing 
Hepatitis C virus and hepatitis B virus testing will be done at screening if clinically 
indicated. 
12.1.9.6. Tumor Marker 
CA-125 will be obtained at screening and at Day 1 of each cycle. If a patient discontinues 
treatment for a reason other than radiographic progression, death, withdrawal of consent, 
loss to follow-up, or the end of the study, CA-125 testing should continue every 9 weeks 
for the first year of study treatment and every 12 weeks thereafter until PD. If a patient 
discontinues treatment for clinical progression and does not meet RECIST criteria for 
progression, CA-125 testing should continue at the specified intervals until progression is 
confirmed or until the start of subsequent anticancer treatment. 
12.1.9.7. Pregnancy Screen 
Niraparib and dostarlimab (TSR-042) are known to have properties that require the 
patient to use a highly selective contraception measure and may have adverse effects on a 
fetus in utero. For females of childbearing potential, negative serum or urine pregnancy 
test is required within 72 hours prior to Cycle 1 Day 1. Urine pregnancy testing will be 
performed on Day 1 of each subsequent cycle and at the Safety Follow-Up Visit (30 ± 7 
days after the last dose of study treatment) for females of childbearing potential. If the 
clinic standard is to do a serum or urine pregnancy test more frequently, that is acceptable 
with the protocol as written.  
Patients should start using birth control as outlined in Appendix 1 from screening 
throughout the study period up to 180 days after the last dose of study treatment. If there 
is any question that a patient will not reliably comply with the contraception 
requirements, they should not be enrolled in the study, and any patient who becomes 
pregnant should be withdrawn from the study. Any pregnancies that occur within 
180 days post-treatment discontinuation are to be reported as described in 
Section 12.2.11. 
12.1.10. 
ECOG Performance Status 
Performance status will be assessed using the ECOG scale (see Appendix 3) in 
accordance with the schedule of events (Table 10). 


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12.2. 
Adverse Events and Special Situations 
12.2.1. 
Definitions 
12.2.1.1. Adverse Event 
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a medicinal product and that does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including a clinically significant abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment. 
AEs may include the onset of new illness and the exacerbation of pre-existing medical 
conditions. An AE can include an undesirable medical condition occurring at any time 
after the time of treatment assignment, including baseline or washout periods, even if no 
study treatment has been administered. (See Section 12.2.3 for information about AE 
collecting and recording.) 
12.2.1.2. Serious Adverse Event 
Any untoward medical occurrence that, at any dose 
• Results in death;  
• Is life-threatening (ie, an event in which the patient was at risk of death at the time 
of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe);  
• Requires inpatient hospitalization* or prolongation of existing hospitalization;  
• Results in persistent or significant disability/incapacity;  
• Is a congenital anomaly/birth defect; or 
• Is an important medical event** 
*Exception: Preplanned (at time of informed consent) hospitalization for elective 
procedures, for protocol compliance or social reasons, or for observation will not be 
considered criteria for an SAE. The reason for the planned hospitalization should be 
captured in medical history section in the eCRF. Complications experienced during these 
hospitalizations must be reported as AEs (or SAEs, if hospitalization is prolonged due to 
the AE).  
**Medical and scientific judgment should be exercised in determining whether situations 
or events should be considered SAEs: an important medical event may not be 
immediately life threatening or result in death or require hospitalization but may 
jeopardize the patient or require intervention to prevent one of the above outcomes. 
Examples of such events are allergic bronchospasm, blood dyscrasias, or convulsions that 
may require intensive treatment in an emergency room or at home but do not result in 
hospitalization; development of drug dependency or drug abuse; and transmission of 
disease associated with the administration of the study treatment. (See Section 12.2.5 for 
information about SAE reporting.)  


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12.2.1.3. Treatment-Emergent Adverse Event 
Any event that was not present prior to the initiation of study treatment or any event 
already present that worsens in either intensity or frequency following exposure to study 
treatment. 
12.2.1.4. Adverse Event of Special Interest 
Any AE (serious or nonserious) that is of scientific and medical concern specific to the 
study treatment, for which ongoing monitoring and rapid communication by the 
Investigator to the Sponsor is appropriate. The AESIs for this study are MDS, AML, and 
secondary cancers (new malignancies other than MDS or AML). 
12.2.1.5. Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure 
• Abuse: is the persistent or sporadic, intentional excessive use of the study 
treatment, which is accompanied by harmful physical or psychological effects.  
• Misuse: medicinal product is intentionally and inappropriately used not in 
accordance with the authorized/approved product information. 
• Medication error: is any preventable incident that may cause or lead to 
inappropriate study treatment use or patient harm while the study treatment is 
in the control of the health care professionals or patients. Such incident may 
be due to health care professional practice, product labeling, packaging and 
preparation, procedures for administration, and systems, including the 
following: prescribing, order communication, nomenclature, compounding, 
dispensing, distribution, administration, education, monitoring, and use. 
• Overdose: is a deliberate or accidental administration of study treatment to a 
study patient at a dose greater than that which was assigned to that patient per 
the study protocol and under the direction of the Investigator. If an overdose 
occurs, the Investigator and the Sponsor should be notified immediately, and 
the patient should be observed closely for AEs. Associated AEs should be 
treated and monitored by the Investigator. The dosage of study treatment 
administered, any associated AEs, or treatment provided to the patient because 
of the overdose should be documented on the applicable sections within the 
eCRF. An overdose (including an AE or SAE resulting from the overdose, if 
any) will be reported as described in Section 12.2.5. 
• Accidental/Occupational exposure: is the unintentional exposure to a study 
treatment as a result of one’s professional or nonprofessional occupation, or 
accidental exposure to a nonprofessional to whom exposure was not intended 
(ie, study product given to wrong patient).   
Reporting Special Situations: All occurrences of abuse, misuse, medication error, 
overdose, and accidental or occupational exposure with any study treatment must be 
reported on an SAE Report Form [or designated Special Form] to the Sponsor regardless 
of whether or not an AE or SAE has occurred. If the abuse, misuse, medication error, 
overdose, or accidental / occupational exposure is associated with an SAE, an SAE report 


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form must be submitted to the Sponsor within 24 hours of awareness. If there is no AE or 
SAE, the occurrence must be submitted on the designated Special Form (indicate “no AE 
has occurred”) as soon as possible. 
12.2.2. 
Assessment of Adverse Events 
12.2.2.1. Severity Assessment 
All AEs will be assessed by the Investigator for severity* according to CTCAE v4.03: 
14 June 2010; National Institutes of Health (NIH), NCI. The CTCAE severity grades 1 
through 5 provide unique clinical descriptions of severity of each AE. The CTCAE v4.03 
is available on the NCI/NIH website. 
*Please note that there is a distinction between serious and severe AEs: Severity is a 
measure of intensity whereas seriousness is defined by the criteria in Section 12.2.1.2. 
For example, a mild degree of gastrointestinal bleeding requiring an overnight 
hospitalization for monitoring purposes may be considered an SAE but is not necessarily 
severe.  
12.2.2.2. Relationship to Study Intervention 
The Investigator must provide a causality assessment regarding the relationship of the 
event with the study treatment or study procedure for all AEs. One of the following 
categories should be selected based on medical judgment, considering all contributing 
factors: 
• Related: A causal relationship between the medicinal product (or study 
procedures) and AE is a reasonable possibility. For example, the occurrence 
of the AE cannot be explained by other causative factors. The AE, however, 
can be explained by pharmacological effect of the medicinal product such as a 
similar event having been reported previously, alteration of the dose effect, or 
the timing or seriousness of the AE, etc. Positive rechallenge/dechallenge is 
supportive.  
• Not Related: A causal relationship between the medicinal product (or study 
procedures) and AE is not a reasonable possibility: there is no temporal 
relationship between the medicinal product and event, or an alternative 
etiology is more reasonable.  
12.2.2.3. Expectedness 
The Sponsor will be responsible for determining whether an AE is “expected” or 
“unexpected.” An AE will be considered unexpected if the nature, severity, or frequency 
of the event is not consistent with the risk information provided in the Reference Safety 
Information of the effective study treatment Investigator’s Brochure or local approved 
product label. 
12.2.3. 
Collection and Recording of Adverse Events 
AEs may be volunteered spontaneously by the study subject or discovered by the study 
staff during physical examinations or by asking an open, nonleading question such as, 


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“How have you been feeling since your last study visit?” The Investigator will document 
the nature of the AE, date of onset of the AE (and time, if known), date of outcome of the 
AE (and time, if known), severity of the AE, action taken with study treatment as a result 
of the AE, assessment of the seriousness of the AE, and assessment of the causal 
relationship of the AE to study treatment or study procedure. 
AEs, including laboratory abnormalities that are assessed as clinically significant or 
require intervention, should be described using a diagnosis whenever possible, rather than 
individual underlying signs and symptoms. When a clear diagnosis cannot be identified, 
each sign or symptom should be recorded as a separate AE. 
All SAEs will be collected from the signing of the ICF for this study through the Survival 
Follow-up Visit (90 ± 14 days after the last dose of study treatment or until alternate 
anticancer treatment has been initiated, whichever occurs earlier) and recorded in the 
eCRF. SAEs will also be reported on an SAE form as described in Section 12.2.5 of this 
protocol. SAEs considered by the Investigator to be related to study treatment are 
reported throughout the Survival Assessment Period. 
All AEs, regardless of the source of identification (eg, physical examination, laboratory 
assessment, or reported by subject), will be collected and recorded in the eCRF for each 
subject from the day of signed informed consent through the Survival Follow-up Visit 
(90 ± 14 days after the last dose of study treatment or until alternate anticancer treatment 
has been initiated, whichever occurs earlier). 
Concomitant illnesses that existed before entry into the study will not be considered AEs 
unless the illness worsens during the Treatment Period. Pre-existing conditions will be 
recorded as Medical History in the eCRF and on the SAE Report Form. 
Disease progression is an efficacy criterion and is therefore not considered an AE or SAE 
(even if fatal). Disease progression should be reported within the eCRF. If AEs/SAEs 
occur in relation to disease progression that are not consistent with the natural 
progression of the subject’s disease, these AEs/SAEs must be reported per AE/SAE 
reporting requirements described in Section 12.2.5  
12.2.4. 
Follow-Up of Adverse Events 
All AEs experienced by a subject, regardless of the suspected causality, will be 
monitored until the AE or SAE has resolved, until any abnormal laboratory values have 
returned to baseline or normal levels, until stabilized with a satisfactory explanation for 
the changes observed, until the subject is lost to follow-up, or until the subject has died. 
If an Investigator becomes aware of an SAE after the specified follow-up period and 
considers the SAE related to the study treatment, the Investigator should report the SAE 
to the Sponsor according to timelines for reporting SAEs described in Section 12.2.5. 
12.2.5. 
Reporting 
The Investigator must report all SAEs and all follow up information to the Sponsor on an 
SAE Report Form within 24 hours of becoming aware of the initial event or follow-up 
information. SAEs are to be reported per the SAE Form Completion Instructions within 
the Investigator Site File. The Investigator must provide a causality assessment and must 
sign and date all SAE Report Forms. 


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It is the responsibility of the Investigator to review source documentation and describe 
pertinent information on the SAE Report Form. If supporting documentation is requested 
(eg, hospital reports, consultant reports, death certificates, autopsy reports), the 
Investigator should highlight all relevant and pertinent information within such 
documents, ensure that any subject’s personal identifiers (including Medical Record 
number) are removed, and submit the documents with the SAE Form to the Sponsor. The 
Sponsor (or designee) will return a confirmation of receipt for all email reports (if 
received from other than a “no reply” domain) within 1 business day.  
After receipt of the initial report, the Sponsor (or designee) will review the information 
and, if necessary, contact the Investigator to obtain further information. The Investigator 
must promptly respond to queries from the Sponsor. 
12.2.6. 
Submission and Distribution of Serious Adverse Event Reports 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to Investigators, as necessary. 
In addition, the SUSAR will be distributed to the Investigators/investigational sites, 
utilizing a Council for International Organizations of Medical Sciences report form, or 
the MedWatch 3500A form). The Investigator/site will submit a copy of the report to 
their respective Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) per the governing institutional requirements and in compliance with local laws and 
guidelines. 
12.2.7. 
Adverse Events of Special Interest 
AESIs for niraparib are the following:  
• MDS and AML 
• Secondary cancers (new malignancies other than MDS or AML) 
All occurrences of AESIs must be reported. If the AESI is serious, follow the SAE 
reporting outlined in Section 12.2.5. If the AESI is nonserious , it should be reported on 
the designated AESI Form and submitted it to the Sponsor by email or fax within 5 
calendar days of awareness of the event.  
No AESIs have been reported to date for dostarlimab (TSR-042). 
12.2.8. 
Hypertension, Including Hypertensive Crisis 
Hypertension, including hypertensive crisis, has been reported with the use of niraparib. 
Pre-existing hypertension should be adequately controlled before starting niraparib 
treatment. While receiving treatment, hypertension should be medically managed with 
antihypertensive medicinal products with or without niraparib dose adjustment.  
Blood pressure and heart rate should be monitored at least weekly for the first 2 months 
of niraparib treatment in the maintenance setting, then monthly for the first year and 
periodically thereafter during treatment with niraparib. Niraparib should be discontinued 
in case of hypertensive crisis or if medically significant hypertension cannot be 
adequately controlled with antihypertensive therapy. 


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12.2.9. 
Posterior Reversible Encephalopathy Syndrome 
There have been rare reports of niraparib-treated patients developing signs and symptoms 
that are consistent with posterior reversible encephalopathy syndrome (PRES). PRES is a 
rare neurologic disorder that can present with the following signs and symptoms 
including seizures, headache, altered mental status, visual disturbance, or cortical 
blindness, with or without associated hypertension. A diagnosis of PRES requires 
confirmation by brain imaging, preferably magnetic resonance imaging. In patients 
developing PRES, treatment of specific symptoms including control of hypertension is 
recommended, along with discontinuation of niraparib. The safety of reinitiating 
niraparib therapy in patients previously experiencing PRES is not known. 
12.2.10. 
Allergic Reaction 
Niraparib capsules contain tartrazine, which may cause allergic-type reactions. 
12.2.11. 
Pregnancy 
The Investigator must report all pregnancies and the outcomes to the Sponsor. The 
Sponsor has the responsibility to monitor the outcome of all pregnancies reported during 
the clinical study. 
Each pregnancy must be reported by the Investigator to the Sponsor on an Initial 
Pregnancy Report Form within 24 hours of becoming aware of the pregnancy. Pregnancy 
is not an AE and therefore does not need to be reported as an AE in the eCRF unless 
there is a suspicion that the study treatment may have interfered with the effectiveness of 
a contraceptive medication. The Investigator must follow-up all pregnancies, document 
the course and the outcome, and report this information to the Sponsor on a Pregnancy 
Outcome Report Form within 24 hours of becoming aware—even if the subject was 
withdrawn from the study or the study has finished. 
An elective abortion without complications should not be regarded as an AE; however, it 
should be reported as the outcome to the pregnancy on the Pregnancy Outcome Report 
Form. Therapeutic abortions should be reported as a treatment procedure; the reason for 
the therapeutic abortion should be reported on the Pregnancy Outcome Report Form and 
as an AE in the eCRF. Hospitalization for normal delivery of a healthy newborn should 
not be considered an SAE. 
Any SAE that occurs during pregnancy must be recorded on the Pregnancy Outcome 
Report Form, reported as an SAE on the SAE Report Form (eg, maternal serious 
complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, birth defect) and reported to the Sponsor within 24 hours. 
Hospitalization for normal delivery of a healthy newborn should not be considered an 
SAE.  
12.2.12. 
Special Situations 
All occurrences of abuse, misuse, medication error, overdose, and accidental or 
occupational exposure to any study treatment must be reported on a Special Situations 
Report Form to the Sponsor within 5 calendar days of becoming aware of the occurrence, 
regardless of whether it is categorized as an AE. If the occurrence is associated with an 


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13. 
STATISTICS 
Details of the statistical analyses presented below will be provided in the study’s 
statistical analysis plan (SAP). A change to the data analysis methods described in the 
protocol will require a protocol amendment only if it alters a principal feature of the 
protocol. The SAP will be finalized prior to database lock. Any changes to the methods 
described in the plan will be described and justified in the final clinical study report. 
13.1. 
Sample Size Determination 
A sample size of approximately 150 patients overall will provide sufficient precision for 
assessment of the primary endpoint of ORR in the overall and PD-L1 positive 
populations. No inferential testing will be performed, and no adjustments will be made 
for multiplicity. Primary analysis will be based on the ORR point estimate and the 
corresponding 95% exact CI. The PD-L1 positive population will be defined in the SAP 
prior to performance of any PD-L1 assays on patient samples. 
Standard of care treatment options in the BRCAwt population include single-agent 
chemotherapy, such as paclitaxel, doxorubicin, topotecan, and gemcitabine. The 
described ORR with these agents is 10% to 20% in first or second relapse.5,8,9,19,20 
Therefore, a target ORR of 25% (with sufficient precision such that the lower 95% 
confidence bound exceeds 15%) in the described study population (patients with 
BRCAwt PROC previously treated with bevacizumab with 1 to 3 prior lines of therapy) 
with durable response would be considered clinically meaningful. 
Table 14 shows 95% CIs at different observed ORR rates (ranging from 20% to 50%) 
with 150 patients. If the true ORR is 25%, there is an 87% chance that the lower bound of 
the 95% CI will exceed 15%. 
Assuming the prevalence of PD-L1 positive disease is 50% in this study population, it is 
expected that approximately 75 patients with PD-L1 positive tumors will be enrolled and 
dosed. Table 15 shows 95% CIs at different observed ORR rates (ranging from 20% to 
49.3%) for 75 patients with PD-L1 positive tumors. If the true ORR is 30%, there is an 
84% chance that the lower bound of the 95% CI will exceed 15%. 
Table 14: 
Estimates and 95% CIs with 150 Patients 
Sample Size 
Number of 
Responders 
ORR (%) 
Lower 95% 
Confidence Limit 
Upper 95% 
Confidence Limit 
150 
30 
20.0 
13.9 
27.3 
 
32 
21.3 
15.1 
28.8 
 
37 
24.7 
18.0 
32.4 
 
45 
30.0 
22.8 
38.0 
 
52 
34.7 
27.1 
42.9  
 
60 
40.0 
32.1 
48.3 
 
67 
44.7 
36.6 
53.0 
 
75 
50.0 
41.7 
58.3 


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Abbreviations: CI = confidence interval; ORR = objective response rate. 
 
Table 15: 
Estimates and 95% CIs with 75 Evaluable Patients with PD-L1 
Positive Tumors 
Sample Size 
Number of 
Responders 
ORR (%) 
Lower 95% 
Confidence Limit 
Upper 95% 
Confidence Limit 
75 
15 
20.0 
11.7 
30.8 
 
19 
25.3 
16.0 
36.7 
 
23 
30.7 
20.5 
42.4 
 
26 
34.7 
24.0 
46.5 
 
30 
40.0 
28.9 
52.0 
 
34 
45.3 
33.8 
57.3 
 
37 
49.3 
37.6 
61.1 
Abbreviations: CI = confidence interval; ORR = objective response rate; PD-L1 = programmed cell death 
ligand 1. 
13.2. 
Analysis Populations 
Three analysis populations will be defined as follows: 
• Safety (SAF) Population: All patients who receive any amount of study 
treatment. 
• ITT Population: All patients who receive at least 1 complete dose of either 
study drug and who have measurable disease at baseline. Measurable disease 
at baseline is defined by the existence of at least 1 target lesion at baseline 
tumor assessment by RECIST v1.1 criteria. 
• Efficacy-Evaluable (EE) Population: All patients who receive at least 1 
complete dose of either study drug and who have measurable disease at 
baseline and do not have protocol deviations with the potential to significantly 
impact the interpretation of efficacy results. Patients who withdraw without 
obtaining a post-baseline tumor assessment due to withdrawal of consent, loss 
to follow-up, or non-compliance will also be excluded from the EE 
population. 
13.3. 
Patient Disposition 
Patient disposition will be tabulated and will include the number of screened patients 
(who have signed informed consent) and the number of patients in each study population 
for analysis, the number of patients who have discontinued treatment and the reasons for 
treatment discontinuation, and the number of patients who have discontinued study and 
the reasons for study discontinuation. 


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13.4. 
Demographics, Medical History, Baseline Characteristics, and 
Concomitant Medications 
Demographics, baseline characteristics, concomitant medications, and medical history 
information will be summarized using descriptive statistics. 
13.5. 
Efficacy Analyses 
All analyses will include summary statistics, including number and percentage for 
categorical variables and number of patients, mean, standard deviation, median, 
minimum, and maximum for continuous variables. Time-to-event analyses will be 
performed using Kaplan-Meier methods. All efficacy analyses will be performed using 
the ITT population, overall (including all patients in the ITT population) and in the subset 
of patients with PD-L1 positive tumors. The primary analysis population is the ITT 
population. Additional supportive analyses may be performed using the EE population. 
The specific criteria for PD-L1 positive and negative status will be predefined in the SAP 
prior to any PD-L1 samples being analyzed from the study. 
13.5.1. 
Primary Efficacy Parameter 
The primary efficacy endpoint is Investigator-assessed confirmed ORR, which is defined 
as the proportion of patients whose BOR is a confirmed CR or PR. Tumor response will 
be evaluated using RECIST v.1.1 (Appendix 2).  
The primary efficacy analyses will be performed on the ITT population. Patients who 
have no post-baseline evaluable tumor assessments will be considered non-responders. 
BOR will be summarized by number and percentage. The ORR and 2-sided 95% CI, 
using the exact (Clopper-Pearson) method, will be provided. 
13.5.2. 
Secondary Efficacy Parameters 
DOR is defined as the time from first documentation of response (CR or PR) until the 
time of first documentation of disease progression by RECIST v.1.1 based on 
Investigator/independent review committee assessment or death by any cause in the 
absence of progression by RECIST v.1.1. DOR will be evaluated in the subset of patients 
who have achieved a BOR of confirmed CR/PR. 
PFS is defined as the time from the date of the first dose of study treatment to the earliest 
date of assessment of progression by RECIST v.1.1 based on Investigator/independent 
review committee assessment or death by any cause in the absence of progression by 
RECIST v.1.1. PFS will be evaluated in the ITT population. 
Table 16 provides a summary of censoring rules to be used in the DOR and PFS analysis. 


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Table 16: 
Censoring Rules Used in DOR and PFS Survival Analysis 
Situation 
Date of Event or Censoring 
Outcome 
No baseline tumor assessmentsa 
First dose date 
Censored 
No post-baseline tumor assessments 
and no deatha 
First dose date 
Censored 
Start of subsequent anticancer 
therapy without a prior documented 
radiographic progression or death 
Date of last post-baseline 
radiographic tumor assessment prior 
to or on the date of initiation of the 
subsequent anticancer therapy 
Censored 
Free of radiographic progression 
and no subsequent anticancer 
therapy started and no death 
Date of last post-baseline 
radiographic tumor assessment 
Censored 
Documented radiographic 
progression or death after 2 or more 
consecutive missing radiographic 
assessments 
Date of last post-baseline 
radiographic tumor assessment prior 
to the missed radiographic 
assessment 
Censored 
Documented radiographic 
progression or death 
Earliest date of radiographic PD or 
death 
Event 
Abbreviations: DOR = duration of response; PD = progression of disease; PFS = progression-free survival. 
a Not applicable for DOR 
OS is defined as the time from the date of the first dose of study treatment to the date of 
death by any cause. OS will be evaluated in the ITT population. 
DOR, PFS and OS will be presented through use of summary statistics using Kaplan-
Meier methods, to include 25th, 50th (median), and 75th percentiles and associated 
2-sided 95% CIs, number of events and number of censored observations.  
DCR is defined as the percentage of patients who have achieved BOR of confirmed CR, 
PR, or SD per RECIST v.1.1 based on the Investigator/independent review committee 
assessment. Given that the protocol-scheduled tumor assessment interval is every 
9 weeks (63 ± 7 days) for the first year of treatment, the minimum criteria for SD 
duration is that it should be met at least once at least 8 weeks from the date of the first 
dose of study treatment. 
The point-estimate and corresponding 2-sided 95% exact CI will be provided for DCR. 
DCR will be evaluated in the ITT and EE populations. ORR based on independent review 
will be analyzed using similar methodology as described for the primary endpoint. 
In addition, changes from baseline in tumor burden will be summarized by time-point.  
13.5.3. 
Exploratory Analyses 
Descriptive, exploratory subgroup analysis will be performed by baseline characteristics 
and biomarker status. 
Descriptive summary statistics will be used to assess changes from baseline in overall 
FOSI score. Kaplan-Meier methodology will be used to summarize time to symptom 
worsening on the overall FOSI score, defined as the time from treatment assignment to 


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which 
are protected by third party copyright laws and therefore have been excluded.


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The nonbinding rule for futility criteria is ≤5 in 40 responses. The probability of early 
termination is 79% and 43% when the true ORR is 10% and 15%, respectively. 
In the event that the interim analysis demonstrates futility, the protocol may be amended 
as a result to enroll patients with PD-L1 positive tumors only (Figure 2). A cutoff verified 
assay may need to be in place to enroll patients with PD-L1 positive tumors.  
Figure 2: 
Interim Futility Analysis Flowchart 
 
Abbreviations: PD-1 = programmed cell death-1. 


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14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of the 
Sponsor will visit the investigational study site to: 
• Determine the adequacy of the facilities to support the clinical study, including, 
but not limited to, clinical sample collection and management as per the 
laboratory manual. 
• Discuss with the Investigator(s) and other personnel their responsibilities with 
regard to protocol adherence, and the responsibilities of the Sponsor or its 
representatives. This will be documented in a Clinical Study Agreement between 
the Sponsor and the Investigator. 
During the study, a monitor from the Sponsor or representative will have regular contact 
with the investigational site, for the following: 
• Provide information and support to the Investigator(s). 
• Confirm that facilities remain acceptable and that clinical samples are being 
appropriately managed. 
• Confirm that the investigational team is adhering to the protocol, that data are 
being accurately recorded in the CRFs, and that investigational product 
accountability checks are being performed. 
• Perform source data verification. This includes a comparison of the data in the 
case report forms with the patient’s medical records at the hospital or practice, 
and other records relevant to the study. This will require direct access to all 
original records for each patient (eg, clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm 
any SAEs have been forwarded to the Sponsor and those SAEs that met criteria 
for reporting have been forwarded to the IRB. 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
14.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an IEC, or an IRB may 
visit the site to perform audits or inspections, including source data verification. The 
purpose of a Sponsor audit or inspection is to systematically and independently examine 
all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the 
protocol, Good Clinical Practice (GCP) guidelines of the International Council for 
Harmonisation (ICH), and any applicable regulatory requirements. The Investigator 
should contact the Sponsor immediately if contacted by a regulatory agency about an 
inspection. 


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14.3. 
Institutional Review Board 
The Principal Investigator must obtain IRB or IEC approval, as appropriate, for the 
investigation. Initial IRB/IEC approval, and all materials approved by the IRB/IEC for 
this study including the patient consent form and recruitment materials must be 
maintained by the Investigator and made available for inspection. 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor 
may conduct a quality assurance audit. Please see Section 14.2 for more details regarding 
the audit process. 


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16. 
ETHICS 
16.1. 
Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or 
given a favorable opinion in writing by an IRB or IEC as appropriate. The Investigator 
must submit written approval to the Sponsor before he or she can enroll any patient into 
the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment 
to the protocol in accordance with local requirements. In addition, the IRB or IEC must 
approve all advertising used to recruit patients for the study. The protocol must be re-
approved by the IRB or IEC upon receipt of amendments and annually, as local 
regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the 
investigational product. The Sponsor will provide this information to the Principal 
Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to 
the IRB or IEC according to local regulations and guidelines. 
16.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in 
the Declaration of Helsinki (please see Appendix 4) and are consistent with ICH/GCP 
guidelines, applicable regulatory requirements and the Sponsor’s policy on Bioethics. 
16.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and 
adequate oral and written information about the nature, purpose, possible risk and benefit 
of the study. Patients must also be notified that they are free to discontinue from the study 
at any time. The patient should be given the opportunity to ask questions and allowed 
time to consider the information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any 
study procedures. 
The Principal Investigator(s) must maintain the original, signed ICF. A copy of the 
signed ICF must be given to the patient. 


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17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
The Sponsor will be allowed to conduct site visits to the investigation facilities for the 
purpose of monitoring any aspect of the study. The Investigator agrees to allow the 
monitor to inspect the drug storage area, study drug stocks, drug accountability records, 
patient charts and study source documents, and other records relative to study conduct. 
17.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a 
period of 2 years after the last marketing application approval, or if not approved 2 years 
following the discontinuance of the test article for investigation. If it becomes necessary 
for the Sponsor or the Regulatory Authority to review any documentation relating to the 
study, the Investigator must permit access to such records. 


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18. 
PUBLICATION POLICY 
Information regarding publication of study results is contained in the Clinical Trial 
Agreement for this study. 


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Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunological effects of 
conventional chemotherapy and targeted anticancer agents. Cancer Cell. 
2015;28(6):690-714. 
40. 
Hamanishi J, Mandai M, Ikeda T, et al. Safety and Antitumor Activity of Anti-
PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. 
J Clin Oncol. 2015;33(34):4015-4022. 
41. 
Varga A, Piha-Paul SA, Ott PA, et al. Antitumor activity and safety of 
pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: 
Interim results from a phase Ib study. Journal of Clinical Oncology. 
2015;33(15_suppl):5510-5510. 
42. 
Disis ML, Patel MR, Pant S, et al. Avelumab (MSB0010718C; anti-PD-L1) in 
patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor 
phase Ib trial: safety and clinical activity. Journal of Clinical Oncology. 
2016;34(15_suppl):5533-5533. 
43. 
Infante JR, Braiteh F, Emens LA, et al. Safety, clinical activity and biomarkers of 
atezolizumab (atezo) in advanced ovarian cancer (OC). Annals of Oncology. 
2016;27(suppl_6):871P-871P. 
44. 
Varga A OP, Mehnert JM, Berton-Rigaud D, Johnson EA. Antitumor activity and 
safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian 
cancer:  interim results from a phase Ib study. J Clin Oncol. 2015;33. 
45. 
Disis ML, Patel MR, Pant S, et al. Avelumab (MSB0010718C), an anti-PD-L1 
antibody, in patients with previously treated, recurrent or refractory ovarian 
cancer: A phase Ib, open-label expansion trial. J Clin Oncol (Meeting Abstracts). 
2015;33(15_suppl):5509. 
46. 
Varga A, Piha-Paul S, Ott PA, et al. Pembrolizumab in patients with programmed 
death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. 
Gynecol Oncol. 2019;152(2):243-250. 
47. 
Matulonis UA, Shapira-Frommer R, Santin AD, et al. Antitumor activity and 
safety of pembrolizumab in patients with advanced recurrent ovarian cancer: 


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results from the phase II KEYNOTE-100 study. Ann Oncol. 2019;30(7):1080-
1087. 
48. 
Pujade-Lauraine E, Fujiwara K, Dychter SS, Devgan G, Monk BJ. Avelumab 
(anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 
200 Phase III study design. Future Oncol. 2018;14(21):2103-2113. 
49. 
Pujade-Lauraine E, Fujiwara K, Ledermann JA, et al. Avelumab alone or in 
combination with pegylated liposomal doxorubicin vs pegylated liposomal 
doxorubicin alone in platinum-resistant or refractory epithelial ovarian cancer: 
primary and biomarker analysis of the phase 3 JAVELIN Ovarian 200 trial. Paper 
presented at: SGO 50th Annual Meeting on Women’s Cancer; March, 2019. 
50. 
ZEJULA® (niraparib) capsules, for oral use [prescribing information]. Waltham, 
MA: TESARO; 2017. 
51. 
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related 
Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: 
American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 
2018:JCO2017776385. 
52. 
Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations 
for the use of white blood cell growth factors: an evidence-based clinical practice 
guideline. J Clin Oncol. 2006;24(19):3187-3205. 
53. 
Nishino M, Tirumani SH, Ramaiya NH, Hodi FS. Cancer immunotherapy and 
immune-related response assessment: the role of radiologists in the new arena of 
cancer treatment. Eur J Radiol. 2015;84(7):1259-1268. 
54. 
Beaumont J, Yount S, Lalla D, et al. Validation of the Functional Assessment of 
Cancer Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a Phase II Clinical 
Trial of Pertuzumab in Patients with Advanced Ovarian Cancer. Journal of 
Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting 
Edition). 2007;25(18S):16021. 
55. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in 
solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 
2009;45(2):228-247. 
56. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. American journal of clinical oncology. 
1982;5(6):649-655. 
 


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20. 
APPENDICES 


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APPENDIX 1. CONTRACEPTION GUIDELINES 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a to medical cause) 
 
 
Azoospermia is a highly effective contraceptive method provided that the partner is the 
 
 
 
 
sole sexual partner of the woman of childbearing potential and the absence of 
sperm   
 
 
 
has been confirmed. If not, an additional highly effective method of 
contraception   
 
 
 
should be used. Spermatogenesis cycle is approximately 90 
days. 
 
 
Note: documentation of azoospermia for a male participant can come from the site  
 
 
 
 
personnel’s review of the participant’s medical records, medical examination, 
or   
 
 
 
 
medical history interview. 
Highly Effective Methods b That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
• 
Combined (estrogen- and progestogen-containing ) hormonal contraception 
associated with inhibition of ovulationc 
− 
oral 
− 
intravaginal 
− 
transdermal 
− 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
− 
oral 
− 
injectable 
• 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 


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The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates 
differ from those when used consistently and correctly. 
c. 
 Male condoms must be used in addition to hormonal contraception. If locally required, in 
accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable 
contraceptive methods are limited to those which inhibit ovulation as the primary mode of 
action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of 
contraception. Male condom and female condom should not be used together (due to risk of failure from 
friction) 
 
 


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


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Table 17: 
For Patients with Measurable Disease (ie, Target Disease) 
Target 
Lesions 
Non-Target 
Lesions 
New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
> 4 wks. 
Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
> 4 wks. 
Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not evaluated 
No 
PR 
SD 
Non-CR/Non-
PD/not evaluated 
No 
SD 
Documented at least 
once 8 wks. from first 
dose of study 
medication** 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = complete response; PD = progressive disease; PR = partial response; 
RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease.  
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion.55 
** 
Only for non-randomized trials with response as primary endpoint. 
*** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
Note: 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration.” Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
Table 18: 
For Patients with Non-Measurable Disease (ie, Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR = complete response; PD = progressive disease; SD = stable disease. 
*Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly 
used as an endpoint for assessment of efficacy in some trials so to assign this category when no 
lesions can be measured is not advised. 


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


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


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


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


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consent must be sought by an appropriately qualified individual who is 
completely independent of this relationship. 
28. For a potential research patient who is incapable of giving informed consent, the 
physician must seek informed consent from the legally authorized representative. 
These individuals must not be included in a research study that has no likelihood 
of benefit for them unless it is intended to promote the health of the group 
represented by the potential patient, the research cannot instead be performed with 
persons capable of providing informed consent, and the research entails only 
minimal risk and minimal burden. 
29. When a potential research patient who is deemed incapable of giving informed 
consent is able to give assent to decisions about participation in research, the 
physician must seek that assent in addition to the consent of the legally authorized 
representative. The potential patient’s dissent should be respected. 
30. Research involving patients who are physically or mentally incapable of giving 
consent, for example, unconscious patients, may be done only if the physical or 
mental condition that prevents giving informed consent is a necessary 
characteristic of the research group. In such circumstances, the physician must 
seek informed consent from the legally authorized representative. If no such 
representative is available and if the research cannot be delayed, the study may 
proceed without informed consent provided that the specific reasons for involving 
patients with a condition that renders them unable to give informed consent have 
been stated in the research protocol and the study has been approved by a research 
ethics committee. Consent to remain in the research must be obtained as soon as 
possible from the patient or a legally authorized representative. 
31. The physician must fully inform the patient which aspects of their care are related 
to the research. The refusal of a patient to participate in a study or the patient’s 
decision to withdraw from the study must never adversely affect the patient-
physician relationship. 
32. For medical research using identifiable human material or data, such as research 
on material or data contained in biobanks or similar repositories, physicians must 
seek informed consent for its collection, storage, and/or reuse. There may be 
exceptional situations where consent would be impossible or impracticable to 
obtain for such research. In such situations the research may be done only after 
consideration and approval of a research ethics committee. 
Use of Placebo 
33. The benefits, risks, burdens, and effectiveness of a new intervention must be 
tested against those of the best proven intervention(s), except in the following 
circumstances: 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; 
or 
Where for compelling and scientifically sound methodological reasons the use of any 
intervention less effective than the best proven one, the use of placebo, or no intervention 


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is necessary to determine the efficacy or safety of an intervention and the patients who 
receive any intervention less effective than the best proven one, placebo, or no 
intervention will not be subject to additional risks of serious or irreversible harm as a 
result of not receiving the best proven intervention. 
Extreme care must be taken to avoid abuse of this option. 
Post-Trial Provisions 
34. In advance of a clinical trial, sponsors, researchers, and host country governments 
should make provisions for post-trial access for all participants who still need an 
intervention identified as beneficial in the trial. This information must also be 
disclosed to participants during the informed consent process. 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human patients must be registered in a publicly 
accessible database before recruitment of the first patient. 
36. Researchers, authors, sponsors, editors, and publishers all have ethical obligations 
with regard to the publication and dissemination of the results of research. 
Researchers have a duty to make publicly available the results of their research on 
human patients and are accountable for the completeness and accuracy of their 
reports. All parties should adhere to accepted guidelines for ethical reporting. 
Negative and inconclusive, as well as positive results, must be published or 
otherwise made publicly available. Sources of funding, institutional affiliations, 
and conflicts of interest must be declared in the publication. Reports of research 
not in accordance with the principles of this Declaration should not be accepted 
for publication. 
Unproven Interventions in Clinical Practice 
37. In the treatment of an individual patient, where proven interventions do not exist 
or other known interventions have been ineffective, the physician, after seeking 
expert advice, with informed consent from the patient or a legally authorized 
representative, may use an unproven intervention if in the physician’s judgement 
it offers hope of saving life, re-establishing health or alleviating suffering. This 
intervention should subsequently be made the object of research, designed to 
evaluate its safety and efficacy. In all cases, new information must be recorded 
and, where appropriate, made publicly available. 
Source: World Medical Association. World medical association declaration of Helsinki: 
ethical principles for medical research involving human subjects. JAMA. 2013;310(20). 


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SAP_001.pdf: 
 
 
 
 
Statistical Analysis Plan Amendment 2 
 
Study ID: 213353 
 
Official Title of Study: A Phase 2, Open-Label, Single-Arm Study to evaluate the 
efficacy and safety of the combination of Niraparib and Dostarlimab (TRS-042) in 
patients with Platinum-Resistant Ovarian Cancer (MOONSTONE) 
 
Other Identifiers: 3000-02-006 
 
Date of Document: 29-OCT-2020 
 
 


 
Statistical Analysis Plan, Protocol 3000-02-006 
 
Confidential 
 
Page 1 of 50 
 
STATISTICAL ANALYSIS PLAN 
 
 
Protocol Title  
A PHASE 2 OPEN-LABEL, SINGLE-ARM STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF THE 
COMBINATION OF NIRAPARIB AND DOSTARLIMAB 
(TSR-042) IN PATIENTS WITH PLATINUM-RESISTANT 
OVARIAN CANCER (MOONSTONE) 
 
Protocol Number   
3000-02-006 
 
Protocol Version  
Version 2.0: 22 October 2019 (Amendment 1) 
Version 1.0: 04 October 2018 (Original) 
 
Study Drug 
Niraparib, Dostarlimab (TSR-042)  
 
Study Phase 
Phase 2 
 
Methodology  
Open-Label, Single-Arm 
 
Sponsor  
TESARO, Inc. a GSK Company 
1000 Winter Street 
Waltham MA  02451 
Tel: 
 
 
Analysis Plan Version  Version 2.0  
 
Analysis Plan Date  
October 16, 2020 
 
Confidentiality Statement 
All information contained in this document is privileged and confidential to 
TESARO. Any distribution, copying, or disclosure is strictly prohibited without 
prior written approval by TESARO. 
 
 
 
PPD


Statistical Analysis Plan, Protocol 3000-02-006
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SIGNATURE PAGE
Protocol Title:
A PHASE 2 OPEN-LABEL, SINGLE-ARM STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF THE 
COMBINATION OF NIRAPARIB AND DOSTARLIMAB (TSR-
042) IN PATIENTS WITH PLATINUM-RESISTANT OVARIAN 
CANCER (MOONSTONE)
Protocol Number: 3000-02-006
Sponsor:
TESARO, Inc. a GSK Company
1000 Winter Street
Waltham MA 02451
Author:
 MS
Statistics Leader, Development 
Biostatistics, Statistics 
Oncology 
Date
By signing this document, I acknowledge that I have read the document and approve of the 
planned statistical analyses described herein. I agree that the planned statistical analyses 
are appropriate for this study, are in accordance with the study objectives, and are 
consistent with the statistical methodology described in the protocol, clinical development 
plan, and all applicable regulatory guidances and guidelines.
 MD
, 
Clinical Development -
Synthetic Lethality -
Medical
Date
PPD
PPD
PPD
PPD
PPD


 
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Table of Contents 
Table of Contents 
................................................................................................................................ 3 
List of Tables 
.......................................................................................................................................... 5 
Table of Figures 
...................................................................................................................................... 5 
Abbreviations and Definitions 
................................................................................................................ 6 
1 
Statistical Analysis Plan Scope and Revision History 
............................................................ 9 
1.1 Summary of Changes to the Planned Analyses 
................................................................... 9 
2 
Introduction 
............................................................................................................................. 9 
3 
Study Objectives and Endpoints 
........................................................................................... 10 
3.1 Study Objectives 
............................................................................................................... 10 
3.2 Primary Objective 
............................................................................................................. 10 
3.3 Secondary Objectives 
........................................................................................................ 10 
3.4 Exploratory Objectives ..................................................................................................... 11 
4 
Study Methods 
...................................................................................................................... 12 
4.1 General Study Design and Plan ........................................................................................ 12 
4.2 Randomization and Blinding ............................................................................................ 15 
4.3 Study Procedures............................................................................................................... 15 
5 
Sample Size 
........................................................................................................................... 15 
6 
General Considerations 
......................................................................................................... 16 
6.1 Definitions 
......................................................................................................................... 16 
6.2 Analysis Populations 
......................................................................................................... 20 
6.3 Withdrawals, Dropouts, Loss to Follow-up 
...................................................................... 20 
6.4 Covariates and Subgroups 
................................................................................................. 21 
6.5 Missing Data 
..................................................................................................................... 21 
6.6 Visit Windows .................................................................................................................. 22 
6.7 Interim Analyses and Data Monitoring 
............................................................................. 23 
6.8 Multi-Center Studies 
......................................................................................................... 23 
6.9 Multiple Testing 
................................................................................................................ 23 
7 
Summary of Study Data 
........................................................................................................ 23 
7.1 General Considerations 
..................................................................................................... 23 
7.2 Patient Enrollment............................................................................................................. 24 
7.3 Patient Disposition 
............................................................................................................ 24 
7.4 Protocol Deviations 
........................................................................................................... 25 
7.5 Demographic and Baseline Variables 
............................................................................... 25 
7.6 Concurrent Illnesses and Medical Conditions 
................................................................... 27 


 
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7.7 Prior and Concurrent Medications 
.................................................................................... 28 
8 
Efficacy Analyses 
................................................................................................................. 28 
8.1 Primary Efficacy Analysis 
................................................................................................ 30 
8.2 Secondary Efficacy Analyses 
............................................................................................ 32 
8.2.1 
Investigator Assessed Duration of Response 
............................................................ 32 
8.2.2 
Investigator Assessed Progression-Free Survival 
..................................................... 33 
8.2.3 
Overall Survival 
........................................................................................................ 33 
8.2.4 
Investigator Assessed Disease Control Rate 
............................................................. 34 
8.2.5 
Efficacy Endpoints Based on Independent Review Committee Assessment 
............ 34 
8.3 Exploratory Efficacy Analyses ......................................................................................... 34 
Analyses of secondary efficacy endpoints will be performed in the overall population and in the 
subset of patients with PD-L1 positive tumors. 
............................................................................ 34 
8.3.1 
Efficacy in Patients with Documented BRCAwt Tumors 
......................................... 34 
8.3.2 
Duration of Disease Control ..................................................................................... 34 
8.3.3 
Functional Assessment of Cancer Therapy  Ovarian Symptom Index (FOSI) 
....... 35 
8.3.4 
Duration of Survival and PFS Follow-Up 
................................................................. 36 
8.3.5 
Estimation of Optimal Threshold for PDL-1 and Derivation of Combinatorial 
Biomarker Signatures for Identifying Responders and non-Responders 
.................................. 36 
9 
Safety Analyses 
..................................................................................................................... 36 
9.1 Extent of Exposure 
............................................................................................................ 36 
9.2 Adverse Events ................................................................................................................. 38 
9.2.1 
Overview 
................................................................................................................... 38 
9.2.2 
Immune-Related Adverse Events (irAEs) 
................................................................. 40 
9.2.3 
Myelosuppression Events ......................................................................................... 40 
9.2.4 
Adverse Events of Special Interest (AESI) 
............................................................... 41 
9.2.5 
Adverse Events By Treatment Cycle 
........................................................................ 41 
9.3 Clinical Laboratory Evaluations ....................................................................................... 41 
9.4 Vital Signs 
......................................................................................................................... 44 
9.5 Electrocardiogram 
............................................................................................................. 44 
9.6 Physical Examinations and Other Safety Parameters ....................................................... 44 
9.7 COVID-19 
......................................................................................................................... 44 
10 
Computing Environment 
....................................................................................................... 44 
11 
References 
............................................................................................................................. 45 
12 
APPENDIX 
........................................................................................................................... 46 
12.1 APPENDIX 1:  Common Terminology Criteria for Adverse Events (CTCAE) v4.03 .... 46 
12.2 APPENDIX 2:  Myelosuppression Events 
........................................................................ 48 


 
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12.3 APPENDIX 3:  Immune-Related Adverse Events (irAEs) 
............................................... 49 
12.4 APPENDIX 4:  Statistical Output Shells 
.......................................................................... 50 
 
List of Tables 
Table 1  Revision History ................................................................................................................. 9 
Table 2  Primary Objective and Endpoint 
....................................................................................... 10 
Table 3  Secondary Objectives and Endpoints 
................................................................................ 11 
Table 4  Exploratory Objectives and Endpoints.............................................................................. 12 
Table 5  Treatment Regimen 
........................................................................................................... 13 
Table 6: Estimates and 95% CIs with 150 Patients 
......................................................................... 16 
Table 7: Estimates and 95% CIs with 75 Evaluable PD-L1 Patients 
.............................................. 16 
Table 8  Determination of BRCA Status Considering Central gBRCA and tBRCA Results 
......... 18 
Table 9  Determination of HRD Status Considering HRD Score, Central gBRCA and tBRCA 
Results 
19 
Table 10  Classification of Prior Ovarian Cancer Treatment 
............................................................ 26 
Table 11  Overview of Analyses for Efficacy Endpoints Performed in Overall Population and 
Subset of Patients with PD-L1 Positive Tumors 
................................................................................... 29 
Table 12  Time Point Response for Patients with Measurable Disease at Study Entry 
.................... 30 
Table 13  Best Overall Response when Confirmation of CR and PR Required 
............................... 31 
Table 14  Censoring Rules used in the DOR, PFS Analysis and Duration of Disease Control 
........ 32 
Table 15  Exposure Parameters for Niraparib, Dostarlimab and Overall Study Treatment 
.............. 37 
Table 16  Myelosuppression Events ................................................................................................. 41 
 
Table of Figures 
Figure 1: Overall Study Schema 
....................................................................................................... 15 
 
 


 
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Abbreviations and Definitions 
 
Abbreviation 
Definition 
AE 
Adverse event 
AESI 
Adverse event(s) of special interest 
ALP 
Alkaline Phosphatase 
ALT 
Alanine aminotransferase 
AML 
Acute myeloid leukemia 
aPTT 
Activated partial thromboplastin time (aPTT)  
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body mass index 
BOR 
Best overall response 
BRCA 
Breast cancer susceptibility gene 
BRCAmut 
Breast cancer susceptibility gene mutated  
BRCAwt 
Breast cancer susceptibility gene wild type  
CA-125 
Cancer antigen 125 
CBC 
Complete blood count 
CI 
Confidence interval 
CPS 
Combined proportion score 
CR 
Complete response 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
Disease control rate 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EE 
Efficacy-evaluable 
EOT 
End of treatment 
EU 
European Union 
FDA 
(United States) Food and Drug Administration 
FFPE 
Formalin fixed paraffin embedded 
FIGO 
International Federation of Gynecology and Obstetrics 
FOSI 
Functional Assessment of Cancer Therapy  Ovarian Symptom Index 
gBRCA 
Germline breast cancer susceptibility gene 
gBRCAmut 
Germline breast cancer susceptibility gene mutated 
gBRCAwt 
Germline breast cancer susceptibility gene wild type 
GCP 
Good Clinical Practice 
HRD 
Homologous recombination deficiency 
HRQoL 
Health-related quality of life 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug application 
INR 
International normalized ratio 


 
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Abbreviation 
Definition 
irAE 
Immune-related adverse event 
ITT 
Intent-to-treat 
IV 
Intravenous 
KM 
Kaplan-Meier 
LLN 
Lower limit of normal 
MID 
Minimally important difference 
MDS 
Myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MSI H 
Microsatellite instability-high  
mut 
Mutant 
NCI 
National Cancer Institute 
Neg 
Negative 
NSCLC 
non-small cell lung cancer 
OC 
Ovarian cancer 
ORR 
Objective response rate 
OS 
Overall survival 
PARP 
Poly(ADP-ribose) polymerase 
PARPi 
PARP inhibitor 
PD 
Progressive disease (in the context of disease evaluation) or protocol 
deviation 
PD-1 
Programmed cell death-1 
PD-L1 
Programmed cell death-ligand 1 
PFI 
Platinum-free interval 
PFS 
Progression-free survival 
PO 
Orally 
PR 
Partial response 
PROC 
Platinum-resistant ovarian cancer 
PT 
Preferred Term (MedDRA) 
Q1 
First quartile 
Q3 
Third quartile 
Q3W 
Every 3 weeks 
Q6W 
Every 6 weeks 
QD 
Once daily 
RE 
Response-evaluable (population) 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious adverse event 
SAF 
Safety 
SAP 
Statistical analysis plan 
sBRCAmut 
Somatic breast cancer susceptibility gene mutation 
SD 
Stable disease (in the context of disease evaluation) or standard 
deviation (in the context of statistics) 
SDF 
Survival distribution function 
SMQ 
Standard MedDRA Query 
SOC 
System Organ Class (MedDRA) 
tBRCA 
Tumor breast cancer susceptibility gene 
tBRCAmut 
Tumor breast cancer susceptibility gene mutation 


 
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Abbreviation 
Definition 
tBRCAwt 
Tumor breast cancer susceptibility gene wild-type 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
vCPS 
Visually estimated combined positive score 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
wt 
Wild type 
 
 


 
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1 Statistical Analysis Plan Scope and Revision History 
This statistical analysis plan (SAP) is designed to outline the methods to be used in the analyses of 
study data in order to answer the study objectives. Patient populations to be used for analyses, data 
handling rules, statistical methods, and formats for data presentation are identified and provided. The 
statistical analyses and summary tabulations described in this SAP will provide the basis for the 
results sections of the clinical study report (CSR) for this trial. 
This SAP will also outline any differences in the currently planned analyses relative to those 
described in the study protocol. 
The SAP is a living document that will be created during the trial conduct. It will be maintained 
throughout the lifecycle of the trial. Important changes following approval of SAP v1.0 will be 
tracked in this section. Table 1 shows the revision history. 
Table 1  
Revision History 
SAP version 
(date) 
Protocol version 
(date) 
eCRF version  
(date) 
Changes from previous 
version 
1.0 
 
2.0  
(22 October 2019) 
17 March 2020 
Original version 
2.0 
2.0 
(22 October 2019) 
14 April 2020 
Specified cut-point for PD-
L1 assay for determination 
of subgroups (vCPS<5% 
. 
Added details regarding 
PFI calculation 
Removed lists of preferred 
terms for analysis of 
grouped adverse events. 
The lists be maintained in a 
separate document.  
Clarifications to futility 
analysis population 
Described additional 
summaries for COVID-19 
data. 
1.1 Summary of Changes to the Planned Analyses 
No changes are noted to the analyses planned in the protocol.  The statistical analysis plan provides 
additional details to the analyses specified in the protocol. 
2 Introduction 
Niraparib is an orally available, potent, and highly selective poly (adenosine diphosphate-ribose) 
polymerase (PARP)-1 and PARP-2 inhibitor. Zejula® (niraparib) was approved for the maintenance 
treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who 
are in a complete response (CR) or partial response (PR) to platinum based combination 
chemotherapy by the United States (US) Food and Drug Administration (FDA) on 27 March 2017 and 
received a Marketing Authorization in the European Union (EU) on 16 November 2017. 


 
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Niraparib treatment as monotherapy and in combinations is being studied by TESARO through a 
global development plan that involves several ongoing company-sponsored clinical studies in ovarian, 
lung, and breast cancer indications. In addition, TESARO and Janssen have a partnership 
investigating niraparib for use in prostate cancer. 
Dostarlimab (TSR-042) is an anti-programmed death-1 (anti PD-1) humanized monoclonal antibody 
(mAb) of the immunoglobulin G4 (IgG4)-
New Drug application (IND) for dostarlimab (TSR-042) on 22 December 2015 and obtained the IND 
approval on 22 January 2016 with Study 4010-01-
Expansion Study of TSR-042, an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid 
Dostarlimab (TSR-042) is being studied by TESARO in a global development plan as 
monotherapy in microsatellite instability-high (MSI-H) tumors, including endometrial cancer, and in 
combination with other approved and investigational drugs under development by TESARO, such as 
niraparib in other solid tumors, including ovarian cancer and non-small cell lung cancer (NSCLC). 
The objective of the proposed study is to evaluate the efficacy and safety of the combination of 
niraparib and dostarlimab (TSR-042) in patients with advanced, relapsed, high-grade ovarian, 
fallopian tube, or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) 
mutation who have platinum-resistant disease and who have also been previously treated with 
bevacizumab. 
3 Study Objectives and Endpoints 
3.1 Study Objectives 
3.2 Primary Objective 
The primary objective and corresponding endpoint is listed in Table 2. 
Table 2  
Primary Objective and Endpoint 
Primary Objective 
Primary Outcome Variable 
To evaluate the efficacy, as measured by 
confirmed objective response rate (ORR) per 
Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 (Eisenhauer, et al., 2009) based on 
Investigator assessment, of the combination of 
niraparib and dostarlimab (TSR-042) in: 
patients with platinum-resistant ovarian 
cancer (PROC) without a known 
BRCA mutation who have been 
previously treated with bevacizumab 
subset of patients with PROC who have 
PD-L1 positive tumors (
) 
without a known BRCA mutation who 
have been previously treated with 
bevacizumab. 
  
Confirmed ORR, which is defined as the 
proportion of patients achieving confirmed CR 
or PR as assessed by the Investigator per 
RECIST v1.1. 
 
3.3 Secondary Objectives 
The secondary objectives and corresponding endpoints are listed in Table 3. 




 
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Table 4  
Exploratory Objectives and Endpoints 
Exploratory Objectives 
Exploratory Outcome Variables 
Exploratory objectives of this study are as 
follows and will be evaluated in the overall 
population and the subset of patients with PD-
L1 positive tumors: 
 
To evaluate efficacy of the niraparib and 
dostarlimab (TSR-042) combination among 
patients with BRCAwt tumors as measured by 
confirmed ORR, DOR, PFS, OS, and DCR 
based on Investigator assessment using RECIST 
v1.1 
 
Efficacy endpoints (confirmed ORR, DOR, 
PFS, OS and DCR based on Investigator 
assessment using RECIST v1.1) in the BRCAwt 
population  
 
To evaluate the duration of disease control 
among patients with BOR of CR, PR, or SD 
based on Investigator assessment and 
independent review committee assessment   
 
Duration of disease control, defined as the time 
from the date of the first dose of study treatment 
to the earlier date of assessment of progression 
by RECIST v.1.1 or death by any cause in the 
absence of progression by RECIST v1.1 among 
patients whose BOR is CR, PR or SD. 
 
To evaluate health-related quality of life 
(HRQoL) in patients with PROC treated with 
the combination of niraparib and dostarlimab 
(TSR-042), as measured by the Functional 
Assessment of Cancer Therapy  Ovarian 
Symptom Index (FOSI) 
 
The observed change from baseline and time to 
symptom worsening in the FOSI questionnaire.  
 
To identify additional potential disease-related 
or treatment-related biomarkers that correlate 
with responses to the niraparib and dostarlimab 
(TSR-042) combination, including, but not 
limited to, the measures of homologous 
recombination repair pathway defects and the 
optimal PD-L1 level for efficacy to be used in 
other dostarlimab ovarian cancer trials. 
 
Disease related or treatment-related biomarkers 
(eg, DNA repair deficiency, PD L1 expression) 
to explore the correlations with responses to the 
combination of niraparib and dostarlimab. 
 
4 Study Methods 
4.1 General Study Design and Plan 
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of the niraparib and 
dostarlimab (TSR-042) combination in patients with advanced, relapsed, high-grade ovarian, fallopian 
tube, or primary peritoneal cancer without known BRCA mutation who have platinum resistant 
disease and who have also been previously treated with bevacizumab. 
This study will consist of a screening period (Day -28 to Day -1), a treatment period, an end of 
treatment period when study treatment is discontinued for any reason, a Safety Follow-up Visit 
occurring 30 ± 7 days after the last dose of study treatment, and a survival assessment occurring every 
90 ± 14 days after the last dose of study treatment. All patients will undergo an End of Treatment 
Visit within 7 days of the decision to discontinue treatment for any reason. 




 
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should continue at the specified intervals until progression is confirmed or until the start of subsequent 
anticancer treatment. 
All AEs and serious adverse events (SAEs) will be collected and recorded for each patient from the 
day of signing the informed consent form until 90 days after last study drug administration or until 
alternate anticancer treatment has been initiated, whichever occurs earlier; any pregnancies that occur 
within 180 days post-treatment are to be reported. 
Study drug-related SAEs and adverse events of special interest (AESIs) will be collected every 90 ± 
14 days after the last dose of study drug until study closeout, or as otherwise indicated in the protocol. 
AESIs must be reported as soon as the Investigator becomes aware of them. All AEs and SAEs 
experienced by a patient, regardless of the suspected causality, will be monitored until the AE or SAE 
has resolved, until any abnormal laboratory values have returned to baseline or normalized, until there 
is a satisfactory explanation for the change(s) observed, until the patient is lost to follow-up or 
withdraws consent, or until the patient has died. 
A study schema is shown in Figure 1. 
 
 


 
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Figure 1: 
Overall Study Schema 
Abbreviations: CA-125 = cancer antigen 125; BRCA = breast cancer susceptibility gene; ORR = objective 
response rate; PARPi = poly(adenosine diphosphate-ribose) polymerase inhibitor; PD = progression of disease; 
PD(L)-1 = programmed cell death-1 or programmed cell death-ligand 1.RECIST = Response Evaluation 
Criteria in Solid Tumors. 
 
*Excludes patients who experienced disease progression within 3 months of first-line platinum therapy.  
**Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy. Treatment with 
single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. If a therapeutic 
regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, 
toxicity, or drug availability), this will not be counted as a separate line of therapy. The use of single agent 
hormonal therapy given for reasons other than progressive disease per RECIST v1.1 (i.e. hormonal therapy 
given for increasing CA-125 levels) is not counted as a separate line of therapy. 
It is anticipated that approximately 150 patients will be enrolled and dosed. The study will be 
conducted in conformance with Good Clinical Practice (GCP). 
4.2 Randomization and Blinding 
Not applicable as this is a single-arm study. 
4.3 Study Procedures 
The schedule of assessments can be found in Section 7.6.1 of the study protocol. 
5 Sample Size  
A sample size of approximately 150 patients overall will provide sufficient precision for assessment 
of the primary endpoint of ORR in the overall and PD-L1 positive populations. No inferential testing 
will be performed, and no adjustments will be made for multiplicity. Primary analysis will be based 


 
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on the ORR point estimate and the corresponding 95% exact CI. The PD-L1 positive population is 
defined in Section 6.1.3.   
Standard of care treatment options in BRCAwt population include single chemotherapy, such as 
paclitaxel, doxorubicin, topotecan, and gemcitabine. The described ORR with these agents is 10% to 
20% in first or second relapse (Pignata, et al., 2015; Gynecologic Oncology Group, et al., 2006; 
Gordon, et al., 2001; Mutch, et al., 2007; DOXIL®, 1995).  Therefore, a target ORR of 25% (with 
sufficient precision such that the lower 95% confidence bound exceeds 15% in the described study 
population (patients with BRCAwt PROC previously treated with bevacizumab with 1 to 3 prior lines 
of therapy) with durable response would be considered clinically meaningful. 
Table 6 shows 95% CIs at different observed ORR rates (ranging from 20% to 50%) with 
150 patients. If the true ORR is 25%, there is 87% chance that the lower bound of the 95% CI will 
exceed 15%. 
Assuming the prevalence of PD-L1 positive disease is 50% in this study population, it is expected that 
approximately 75 patients with PD-L1 positive tumors will be evaluable. Table 7 shows 95% CIs at 
different observed ORR rates (ranging from 20% to 50%) for 75 patients with PD-L1 positive tumors. 
If the true ORR is 30%, there is 84% chance that the lower bound of the 95% CI will exceed 15%.   
Table 6: 
Estimates and 95% CIs with 150 Patients 
Sample Size 
Number of 
Responders 
ORR (%) 
Lower 95% 
Confidence Limit 
Upper 95% 
Confidence Limit 
150 
30 
20.0 
13.9 
27.3 
 
37 
24.7 
18.0 
32.4 
 
45 
30.0 
22.8 
38.0 
 
52 
34.7 
27.1 
42.9 
 
60 
40.0 
32.1 
48.3 
 
67 
44.7 
36.6 
53.0 
 
75 
50.0 
41.7 
58.3 
Abbreviations: CI = confidence interval; ORR = objective response rate. 
Table 7: 
Estimates and 95% CIs with 75 Evaluable PD-L1 Patients 
Sample Size 
Number of 
Responders 
ORR (%) 
Lower 95% 
Confidence Limit 
Upper 95% 
Confidence Limit 
75 
15 
20.0 
11.7 
30.8 
 
19 
25.3 
16.0 
36.7 
 
23 
30.7 
20.5 
42.4 
 
26 
34.7 
24.0 
46.5 
 
30 
40.0 
28.9 
52.0 
 
34 
45.3 
33.8 
57.3 
 
37 
49.3 
37.6 
61.1 
Abbreviations: CI = confidence interval; ORR = objective response rate; PD-L1 = programmed cell death ligand 
1. 
6 General Considerations 
6.1 Definitions 
6.1.1 Baseline Definitions 


 
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For all analyses, baseline is defined as the most recent measurement prior to the first administration of 
study treatment (considering earlier of niraparib or dostarlimab). If no times are recorded and the 
assessment is performed on the date of the first administration of study treatment, the assessment will 
be considered as the baseline. 
6.1.2 Study Time Periods 
The following study time periods will be defined for analysis: 
Treatment Period: the period of time between the date of first dose of any study medication up to 
and including 90 days after the last dose of study medication or the date of subsequent anticancer 
drug therapy, whichever occurs first.  Safety will generally be reported through the treatment 
period, unless otherwise specified.  The treatment period can be broken down further into the 
active treatment period and the safety follow-up period as defined below. 
Active treatment:  the period of time between the date of first dose and maximum of the 
following dates: 
o date of last dose of dostarlimab + last interval cycle duration (21 days for cycle 1-4 
and 42 days for cycles 5 and beyond),  
o date of last dose of niraparib. 
 
Safety follow-up:  the period of time following active treatment up to and including 90 
days after the last dose of study medication or the date of subsequent anticancer drug 
therapy, whichever occurs first. 
Long term follow-up: the period of time following the treatment period, (after the earlier of 90 
days post last dose of study medication or date of subsequent anticancer drug therapy).  
6.1.3 Biomarker Definitions 
Local germline BRCA results are collected during enrollment when available and will be defined as 
follows:   
Local gBRCA wild type (gBRCAwt): No deleterious or suspected deleterious mutation found 
in BRCA1 or BRCA2 based on local germline BRCA test result. 
Local unknown gBRCA status (gBRCA-unk):  No local gBRCA results available.  
Local tumor BRCA results are collected from sites when available and will be defined as follows:  
Local tBRCA wild type (tBRCAwt): Based on local tumor BRCA test result, no deleterious 
or suspicious deleterious mutation in BRCA1/2 gene  
Local unknown tBRCA status (tBRCA-unk): no local tBRCA results available   
Central germline BRCA status is determined using Myriad BRACAnalysis test on blood samples 
collected at screening and will be defined as follows. 
gBRCA wild type (gBRCAwt): No deleterious or suspected deleterious inherited mutation 
found in BRCA1 or BRCA2 in the blood 


 
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gBRCA mutant (gBRCAmut): Deleterious or suspected deleterious inherited mutation found 
in BRCA1 or BRCA2 in the blood 
Unknown gBRCA status:  No gBRCA results available (e.g. test canceled, incomplete/ 
inconclusive, or data missing for a patient). 
Central tumor BRCA (tBRCA) status is determined using the Myriad HRD test on tumor samples and 
is defined as follows. 
tBRCA mutant (tBRCAmut): At least one deleterious or suspected deleterious mutation found 
in BRCA1 or BRCA2 in the tumor. 
tBRCA wild type (tBRCAwt): No deleterious or suspected deleterious mutation found in 
BRCA1 or BRCA2 in the tumor. 
Unknown tBRCA status:  tBRCA result not available (e.g., test canceled, 
incomplete/inconclusive, or data missing for a patient) 
BRCA status will be determined considering both the central germline BRCA results and central 
tumor BRCA results as shown in Table 8. 
Table 8  
Determination of BRCA Status Considering Central gBRCA and tBRCA Results 
Central gBRCA 
Central tBRCA  
BRCA status taking account 
both central gBRCA and 
tBRCA 
gBRCAwt 
 
tBRCAwt 
BRCAwt 
tBRCAmut 
BRCAmut 
tBRCA unknown 
BRCA unknown 
gBRCAmut 
 
tBRCAwt 
BRCAmut 
tBRCAmut 
BRCAmut 
tBRCA unknown 
BRCAmut 
gBRCA unknown 
 
tBRCAwt 
BRCA unknown 
tBRCAmut 
BRCAmut 
tBRCA unknown 
BRCA unknown 
Note:  local gBRCA status will not be used to determine BRCA status 
 
Homologous recombination deficiency (HRD) is dysregulation in the homologous recombination 
pathway (due to genetic mutations or alterations) leading to cellular genomic instability and an 
inability to efficiently repair damaged DNA. In this study, HRD score is determined using the Myriad 
HRD test on tumor sample collected prior to enrollment.  HRD status will be determined considering 
HRD score and BRCA status, which considers both central gBRCA and tBRCA results as follows and 
per Table 9: 




 
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6.2 Analysis Populations 
The following patient populations will be evaluated and used for presentation and analysis of the data: 
Safety (SAF) population is defined as all patients who have received any amount of study 
treatment. 
Intent-to-Treat (ITT) population is defined as all patients who have received at least 1 
complete dose of either study drug and who have measurable disease (which is defined 
separately under Investigator assessment and Independent Review Committee assessment) at 
baseline. Measurable disease at baseline is defined by the existence of at least 1 target lesion 
at baseline tumor assessment by RECIST v1.1 criteria. 
Efficacy-Evaluable (EE) population is defined as all patients who have received at least 1 
complete dose of either study drug and who have measurable disease (which is defined 
separately under Investigator assessment and Independent Review Committee assessment) at 
baseline and who do not have protocol deviations significantly impacting the interpretation of 
efficacy results.  Patients who are enrolled and dosed who are retrospectively determined to 
have deviations with respect to the following inclusion/exclusion criteria will be excluded 
from the EE population: 
Inclusion Criteria 
o Patients must have recurrent high-grade serous, endometrioid, or clear cell ovarian, 
fallopian tube, or primary peritoneal cancer (Inclusion 2).  
o Patients must be considered resistant to the last administered platinum therapy 
(Inclusion 3). 
o Patients must have completed at least 1 but no more than 3 prior lines of therapy for 
advanced or metastatic ovarian cancer (Inclusion 4).  
o Patients must have been previously treated with platinum-based regimen, taxane 
agent(s), and bevacizumab (Inclusion 5) 
Exclusion Criteria 
o Patients who experienced disease progression within 3 months (as evidenced by 
radiographic progression per RECIST v1.1) of first-line platinum therapy (Exclusion 
1). 
o Patients with known deleterious or suspicious deleterious mutation in breast cancer 
susceptibility gene (BRCA) 1 or BRCA2 genes (Exclusion 2) 
o Patient has received prior therapy with an anti-PD-1, anti-programmed-death-ligand-1 
(anti-PD-L1), or anti-programmed death-ligand-2 (anti-PD-L2) agent (Exclusion 3).  
o Patient has received prior therapy with a poly (adenosine diphosphate-ribose) 
polymerase (PARP)-1/PARP-2 inhibitor (Exclusion 4).  
Patients who withdraw without a post-baseline tumor assessment due to withdrawal of 
consent, loss to follow-up or non-compliance with no evidence of early death or clinical 
progression will also be excluded from the EE population. 
The SAF population is the primary population for the analysis of safety endpoints.  
The ITT population is the primary population for the analysis of efficacy endpoints. The EE 
population will be used in supportive efficacy analyses when applicable.   
6.3 Withdrawals, Dropouts, Loss to Follow-up 
Patients who are withdrawn or discontinue from the study will not be replaced. 


 
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6.4 Covariates and Subgroups 
ORR, as assessed by the Investigator, will be descriptively summarized by subgroup using the ITT 
population.  Subgroups are defined as follows:  
BRCA status (BRCAwt, BRCAmut, BRCA unknown) 
HRD status 
o HRD negative,  
o HRD positive  
BRCAmut 
BRCAwt/BRCA unknown  
o HRD unknown 
PD-L1 status (PD-L1 positive 
), PD-L1 vCPS<5%, PD-L1 unknown) 
70 years,) 
Race (White, non-White) 
Ethnicity (Hispanic/Latino, Not Hispanic/Latino) 
Baseline ECOG (0, 1) 
Previous lines of therapy (1, 2, 3) 
Response to last platinum therapy (refractory, resistant).   
Additional efficacy endpoints (DOR, PFS, DCR and OS), as assessed by the Investigator, will be 
descriptively summarized by biomarker status (BRCA status, HRD status and PD-L1 status) and 
response to last platinum therapy. 
For ORR and DCR, the rate and corresponding 95% CI will be calculated in accordance with the 
methodology described in Section 7.1 for binomial endpoints for each subgroup.  
For DOR, PFS and OS, descriptive analyses will be performed using KM in accordance with the 
methodology described in Section 7.1 for time to event endpoints for each subgroup.  
If applicable, other exploratory subpopulations may be further defined and analyzed. 
6.5 Missing Data 
In general, there will be no substitutions made to accommodate missing data points. Methods for 
handling incomplete FOSI questionnaires will be performed according to the FOSI scoring manual. 
All data recorded on the eCRF will be included in data listings that will accompany the CSR. 
Incomplete dates for disease history and prior anti-cancer therapy (e.g. initial diagnosis date, 
chemotherapy start/end dates) will be imputed as follows:  
If the day is missing, it will be imputed to the 1st day of the month.  
If both day and month are missing, the month and day will be imputed as January 1st.  
If the date is completely missing, no imputation will be performed.  
 
Per inclusion criteria, patients must be considered resistant to the last administered platinum therapy, 
ie, the time from last administered platinum dose until the initial documented progression (as 
evidenced by radiographic progression per RECIST v.1.1) must be less than 6 months.  As platinum-
free interval (PFI) is a critical inclusion criterion, missing dates associated with the last platinum 
therapy should be minimized.  In the case of incomplete dates, the following imputation rules will be 
used for the calculation of PFI: 


 
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Platinum start/end dates will be imputed as above for chemotherapy start/stop dates. 
 
Date of progression for last-administered platinum therapy: 
o If the day is missing, it will be imputed to the 1
st day of the month.  
o If day and month are missing, the start of the next anti-cancer regimen will be used.    
o If the date is completely missing and reason for discontinuation is progressive disease 
by RECIST or clinical criteria, the start of the next anti-cancer regimen will be used. 
o If the date is completely missing and the reason for discontinuation is not progressive 
disease, the PFI will be considered unknown. 
For patients whose last therapy was platinum-based, the start date of the next anti-cancer 
regimen would be the first dose of study treatment received on the MOONSTONE study. 
If the imputed date of the disease progression following the last platinum-based therapy is 
earlier than the end date of the last platinum-based therapy, the imputed date of the 
disease progression will be set equal to the end date of the last platinum-based therapy.  
Imputation of partial dates is used only to estimate PFI; data listings will present the partial date as 
recorded in the eCRF. 
Incomplete dates for adverse event and concomitant medication dates will be imputed as follows: 
Start Date:   
If onl
dose date, use first dose date.  
 is not missing, then impute month and day with 
 
If the year is not the same as the year of first dose, impute 01 for day and 01 for month.  
If the start date is completely missing, it will be set to the first dose date. 
 
Stop Date: 
 
day with 
'31
' (or date of study discontinuation/completion if earlier than 12-31).  
If the stop date is completely missing, it will be set to the date of study 
discontinuation/completion. A stop date will not be applied to ongoing AEs. 
If the imputed stop date is greater than last contact date, then set to last contact date.  
 
Imputation of partial dates is used to determine whether an event is treatment-emergent; or 
classification of medications as prior/concomitant.  In addition, imputed partial dates will be used to 
determine the appropriate cycle for analyses by cycle.  Data listings will present the partial date as 
recorded in the eCRF. 
6.6 Visit Windows 
It is expected that all visits should occur according to the protocol schedule. By-visit summaries and 
analyses will be by nominal visit (all data will be tabulated per the evaluation visit as recorded on the 
eCRF even if the assessment is outside of the visit window for analysis).    
In data listings, the relative day of all assessment dates will be presented. 


 
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6.7 Interim Analyses and Data Monitoring 
An interim futility analysis will be performed after the first 40 patients (regardless of PD-L1 status) 
have had the opportunity for at least 1 scan (approximately 9 weeks after initial dose). Eligible 
patients with a non-evaluable scan will not be included.  In addition, patients who withdraw without a 
post-baseline tumor assessment due to withdrawal of consent, loss to follow-up or non-compliance 
with no evidence of early death or clinical progression will also be excluded from the interim analysis
population. Patients who withdraw due to AE will be included in the interim analysis population . 
Interim futility analysis will be performed considering confirmed and unconfirmed responses that 
have the potential to be confirmed with additional follow-up. Enrollment will continue at the 
discretion of the sponsor while obtaining response data on the first 40 patients.   
 5 responses (complete or partial responses, considering 
both confirmed and unconfirmed) in 40 patients. The probability of early termination is 79% and 43% 
when the true ORR is 10% and 15%, respectively. 
In addition to objective response rate, demographics, baseline characteristics, primary cancer history, 
prior anticancer treatment, baseline biomarker status (as data is available), will be summarized.  ORR 
by subgroups may also be explored. 
If the interim analysis demonstrates futility, the protocol may be amended as a result to enroll patients 
with PD-L1 positive tumors only.   
6.8 Multi-Center Studies 
Data will be pooled across study sites. 
6.9 Multiple Testing 
 There will be no adjustment for multiplicity as there is no formal hypothesis testing planned and the 
efficacy objectives are related only to estimation.   
7 Summary of Study Data 
7.1 General Considerations 
In general, all presentations, unless otherwise noted, will be performed for the overall patient 
population as well as the subset of patients with PD-L1 positive tumors. 
All data listings that contain an assessment date will also contain a relative study day. Pre-treatment 
and on-treatment study days are numbered relative to the day of the first dose of study treatment 
which is designated as Day 1. The preceding day is Day -1, the day before that is Day -2, etc.  
In general, categorical data will be summarized using number of patients (n), frequency and 
percentages, with the denominator for percentages being the number of patients in the analysis set for 
each cohort. Percentages will be rounded to 1 decimal place except for 100%, which will have no 
decimal place. Counts of zero in any category will be presented without percentage. 
Continuous data will be summarized using the number of patients, mean, standard deviation, median, 
first quartile (Q1), third quartile (Q3), minimum, and maximum. In general, the mean, median and 
quartiles (Q1, Q3) will be presented to 1 decimal place greater than the original data; the standard 


 
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deviation will be presented to 2 decimal places greater than the original data; and the minimum and 
maximum will have the same number of decimal places as the original data.  
Two-sided exact 95% confidence intervals (CIs) based on the Clopper-Pearson method (Clopper & 
Pearson, 1934) will be provided to summarize the binomial proportion where applicable.  The 
Clopper-Pearson CI can be carried out using the FREQ procedure in SAS v9.4 or higher by appending 
 
   
Time-to-event analyses will be performed using Kaplan-Meier (KM) methods. Quartile estimates and 
associated 2-sided 95% CIs (Brookmeyer & Crowley, 1982) will be provided. Survival distribution 
function (SDF) estimates from product-limit method along with the corresponding 95% confidence 
using the log-log transformation will be provided at 3-month intervals as data allows. Kaplan-Meier 
plots of the SDF will be presented and will include the number of patients at risk over time. 
Subgroup analyses will be performed using descriptive statistics and are considered exploratory.   
In addition: 
P-values greater than or equal to 0.0001, in general, will be presented to 4 decimal places; 
p-values less than 0.000
0
 
CIs will be presented to 1 decimal place 
Study Day 1 will be considered the first day of study treatment, as the minimum of (first dose 
of niraparib, first dose of dostarlimab) 
Study day will be calculated as follows: 
o Days prior to first dose:  study day=date  first dose date 
o Days on or after first dose:  study day = date  first dose date + 1 
Weeks will be calculated as number of days divided by 7 
Months will be calculated as number of days divided by 30.4375 
Years will be calculated as number of days divided by 365.25 
All tables, figures, and listings will include footers at the bottom of the page reflecting the 
path of the program used to generate the tables, figures, and listings, and date and time of the 
generation of the output. 
Some minor modifications may be necessary to the planned design of tables, figures, and listings to 
accommodate data collected during the actual study conduct. 
7.2 Patient Enrollment 
The number of patients screened (who have signed informed consent) and the number of patients in 
each analysis population will be summarized.   
The number of patients screened and who received at least one dose of study medication by center 
will be provided.   
7.3 Patient Disposition 
Patient disposition will be tabulated and include the following: 
number of patients ongoing study treatment at the time of the data cut 
number who discontinued each treatment and primary reason for withdrawal of each 
treatment 
number of patients on-study at the time of the data cut 


 
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number who discontinued study and the primary reason for withdrawal from study 
In addition, the number of deaths on active treatment, during safety follow-up and during long term 
follow-up, as defined in Section 6.1.2, will be tabulated along with the primary reason for death.   
A by-patient data listing of study completion information including the reasons for treatment 
discontinuation and/or study discontinuation will be presented. 
7.4 Protocol Deviations 
Protocol d
 
A protocol deviation is classified as important if there is the potential to impact the completeness, 
accuracy, and/or reliability of the study data, or 
-being. 
An important protocol deviation is classified as significant if it is confirmed to adversely impact the 
r well-
being. 
All protocol deviations will be identified and finalized prior to database lock. 
The following protocol deviation summaries will be provided: 
Number and percentage of patients with a significant protocol deviation by type of deviation. 
Number and percentage of patients with an important protocol deviation by type of deviation. 
A listing of all protocol deviations. 
7.5 Demographic and Baseline Variables 
Demographics, baseline and disease characteristics will be summarized using descriptive statistics 
using the safety population.  If there is a large difference between the analysis populations, tables may 
also be generated to reflect other analysis populations.  
Demographic, baseline and disease characteristic data for each patient will be provided in data 
listings. 
The demographic and baseline characteristics tables will include the following variables: 
Sex 
Reproductive status (childbearing/non-childbearing potential) 
Race (White, Black, Asian, American Indian/Alaska native, native Hawaiian or other Pacific 
Islander, other, unknown, and not reported).  If more than one race is selected, the patient will 
Multiple Race
 
Ethnicity (Hispanic, non-Hispanic, unknown, and not reported) 
Age at time of screening (years), age as reported on the eCRF, will be used 
Age categories (<65, 65 which will be further sub-categorized as 65 to <70, 70 to < 75 and 
 
Baseline weight (in kilograms, last value prior to first dose; if weight is reported in pounds, 
convert to kilograms by dividing by 2.2) 
Baseline height (in centimeters, last value prior to first dose; if height is reported in inches, 
convert to centimeters by multiplying by 2.54) 


 
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Baseline body mass index (BMI) (kg/m2
baseline [BMI (kg/m
2) = weight (kg) / height (m)
2] 
ECOG performance status at baseline 
Primary cancer history will be summarized, including the following variables 
Primary tumor site (ovarian, primary peritoneal, or fallopian tube) 
Time from first diagnosis to first dose (years), defined as: 
o (date of first dose of study treatment  date of diagnosis + 1)/365.25, where missing 
data is handled per Section 6.5. 
International Federation of Gynecology and Obstetrics (FIGO) stage at time of initial 
diagnosis 
Metastatic Disease (yes/no) 
Histology and grade of disease at diagnosis and most recent biopsy, if additional biopsy 
performed 
Prior ovarian cancer treatment will be summarized by Type, Sub-type as applicable and Preferred 
Term as classified in Table 10 by setting (any setting, neo-adjuvant/adjuvant, maintenance, 
recurrence, other).  Additional treatments may be added as required to accommodate other prior 
cancer treatments that are used in this study. 
Table 10  
Classification of Prior Ovarian Cancer Treatment  
Type 
Sub-type 
Preferred Term (PT) /CRF Term 
Chemotherapy 
Anthracycline 
Doxorubicin,  
Pegylated liposomal doxorubicin hydrochloride 
Platinum  
Cisplatin,  
Carboplatin 
Taxane  
Docetaxel,  
Paclitaxel  
Other 
Cyclophosphamide 
Etoposide 
Gemcitabine 
Pemetrexed 
Topotecan 
Trabectedin 
Hormonal Therapy 
 
Tamoxifen 
Anastrozole 
Letrozole 
Emexestane 
Fulvestrant 
Monoclonal Antibody  
Bevacizumab 
Investigational Drug 
 
Investigational Drug 
Investigational Antineoplastic Drugs 
 
In addition, the following prior ovarian cancer treatment variables will be summarized: 
Any radiotherapy prior to enrollment 
Any surgeries/procedures related to the study indication  
Number of prior lines of therapy, where the following rules will be applied:  


 
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o Neoadjuvant, adjuvant, and the combination of both will be considered as one line of 
therapy.  
o Treatment with single-agent bevacizumab given as maintenance is not counted as a 
separate line of therapy.  
o If a therapeutic regimen is modified or changed for a reason other than lack of 
response or PD (such as allergic reaction, toxicity, or drug availability), this is not 
counted as a separate line of therapy. 
o The use of single agent hormonal therapy given for reasons other than progressive 
disease per RECIST v1.1 (i.e. hormonal therapy given for increasing CA-125 levels) 
is not counted as a separate line of therapy. 
Months between last treatment regimen and first dose of study treatment, defined as: 
o (date of last treatment regimen (end date)  first dose of study treatment + 1)/30.4375, 
where missing data is handled per Section 6.5. 
Number of prior platinum-containing lines of therapy 
Months between last platinum dose and first dose of study treatment, defined as: 
o (date of last platinum regimen (end date)  first dose of study treatment + 1)/30.4375, 
where missing data is handled per Section 6.5. 
PFI (days) after the last platinum-based therapy (summarized as a continuous variable and a 
categorical variable  refractory (
28 days), resistant (PFI >28 days to <190 days, 
unknown)).  PFI is defined as: 
o date of progression on last platinum regimen  date of last platinum regimen (end 
date) + 1, where missing data is handled per Section 6.5. 
For patients who continue on treatment despite progression (i.e. date of last platinum regimen 
is after date of progression), PFI will be set as 0. 
Biomarker status will be summarized, including: 
Local gBRCA status [gBRCAwt, gBRCA unknown] 
Local tBRCA status [tBRCAwt, tBRCA unknown] 
Centralized gBRCA status [gBRCAwt, gBRCAmut, gBRCA unknown]  
Centralized tBRCA status [tBRCAwt, tBRCAmut and tBRCA unknown]   
BRCA status, considering both gBRCA and tBRCA results [BRCAwt, BRCAmut, BRCA 
unknown] 
HRD status [HRD positive, HRD negative, and HRD unknown; HRD positive will be further 
classified as BRCAmut, BRCAwt, BRCA unknown] 
PD-L1 status [PD-L1 positive 
), PD-L1 vCPS<5%, PD-L1 unknown]  
7.6 Concurrent Illnesses and Medical Conditions 
General medical history will be coded using MedDRA v22.0 or later, and the number and percentage 
of patients experiencing at least 1 such diagnosis by MedDRA System Organ Class (SOC) and 
preferred term (PT) will be reported. 
Prior Grade 3 or Grade 4 blood disorders (thrombocytopenia, leukopenia, anemia, or neutropenia) will 
be summarized separately.  


 
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7.7 Prior and Concurrent Medications 
All medications (other than per-protocol study treatments) will be coded using the September 2018 or 
later version of the WHO Drug Dictionary (WHODD). Medication start and stop dates will be 
compared to the date of first dose of study drug to allow medications to be classified as prior or 
concomitant using the following definitions. 
Prior medications: any medications, which started prior to the first dose date of study treatment.
 
Concomitant medications: any medications, being taken on or after the initial study treatment 
dosing date through 90 days after the last dose of study medication or the date of subsequent 
anticancer drug therapy, whichever occurs first.  
Using the definition above, medications can be classified as both prior and concomitant.  For 
example, a patient who starts a medication before first dose and continues during study treatment will 
be considered as having both prior and concomitant medications. Medications starting after the safety 
follow-up period will be listed but will not be classified or summarized. 
Both prior medications and concomitant medications will be summarized by Anatomical Therapeutic 
Chemical (ATC) classification drug class level 3 and WHO preferred name using the number and 
percentage of patients. A patient reporting the same medication more than once will be counted only 
once when calculating the number and percentage of patients who received that medication in a given 
time category (prior or concomitant). The summary of concomitant medications will be ordered by 
descending frequency with respect to drug class and by descending frequency of preferred name in 
total within the drug class. For drugs with the same frequency, sorting will be done alphabetically. 
Summaries will be based on the safety population.   
Prior and concomitant medications will be provided in a by-patient listing sorted by patient ID 
number and administration date in chronological order.  
Anti-cancer systemic therapy, radiotherapy and surgery that occurs post discontinuation of study 
treatment is captured separately from concomitant medication as the existence of such therapies can 
lead to censoring of time to event endpoints. These data will be listed. 
8 Efficacy Analyses 
Table 11 provides a summary of the efficacy endpoints and the respective analysis populations and 
subgroups that will be evaluated.  Further details for each endpoint are provided in the subsequent 
sections.   


 
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Table 11  
Overview of Analyses for Efficacy Endpoints Performed in Overall Population and 
Subset of Patients with PD-L1 Positive Tumors 
Assessor 
Endpoint 
Analysis Method 
Analysis 
Populations 
Descriptive 
Subgroup Analysis  
in ITT Population 
Investigator-
Assessment 
ORR  
Rate and 95% CI; 
 
-ITT 
-EE 
 
All subgroups defined 
in Section 6.4 
DCR 
Rate and 95% CI 
-ITT 
-EE 
 
Biomarker status, 
Response to last 
platinum therapy 
DOR 
Kaplan-Meier 
analysis 
Patients with BOR of 
confirmed CR or PR in: 
-ITT 
-EE 
Biomarker status, 
Response to last 
platinum therapy 
 
PFS 
Kaplan-Meier 
analysis 
-ITT 
-EE 
 
Biomarker status, 
Response to last 
platinum therapy 
Duration of 
Disease 
Control 
Kaplan-Meier 
analysis 
Patients with BOR of 
confirmed CR, PR or SD 
in: 
-ITT 
-EE 
None 
Independent-
Review 
Committee 
(IRC) 
Assessment 
ORR 
Rate and 95% CI; 
 
-IRC ITT 
-IRC EE 
None 
DCR 
Rate and 95% CI 
-IRC ITT 
-IRC EE 
None 
DOR 
Kaplan-Meier 
analysis 
Patients with BOR of 
confirmed CR or PR in: 
-IRC ITT 
-IRC EE 
None 
PFS 
Kaplan-Meier 
analysis 
-IRC ITT 
-IRC EE 
None 
Duration of 
Disease 
Control 
Kaplan-Meier 
analysis 
Patients with BOR of 
confirmed CR, PR or SD 
in: 
-IRC ITT 
-IRC EE 
None 
Not 
Applicable 
 
OS 
Kaplan-Meier 
analysis 
-ITT 
-EE 
 
Biomarker status, 
Response to last 
platinum therapy 
FOSI overall 
score and 
change from 
baseline 
Descriptive summary 
statistics, 
 
-ITT 
None 
FOSI time to 
symptom 
worsening 
Kaplan-Meier 
analysis  
 
-ITT 
None 
Abbreviations:  BOR=best overall response; CI=confidence interval; CR=complete response; DCR=disease 
control rate; DOR=duration of response; EE=efficacy-evaluable; FOSI= Functional Assessment of Cancer 
Therapy  Ovarian Symptom Index (FOSI); IRC=independent review committee; ITT=intent-to-treat. 
ORR=objective response rate; OS=overall survival; PFS=progression-free survival; PR=partial response; 
SD=stable disease; wt=wild-type. 
 


 
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8.1 Primary Efficacy Analysis 
The primary efficacy parameter will be based on the Investigator-assessed confirmed ORR per 
RECIST v1.1. Analyses will be performed in the overall population and in the subset of patients with 
PD-L1 positive tumors. 
At each evaluation, the RECIST v1.1 (Eisenhauer, et al., 2009) criteria in Table 12 will be used to 
eCRF. 
Table 12  
Time Point Response for Patients with Measurable Disease at Study Entry  
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-PD/Not evaluated 
No 
PR 
SD 
Non-CR/Non-PD/Not evaluated 
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = complete response; PD = progressive disease; PR = partial response; SD = 
stable disease. 
 
As confirmed CR/PR is required, the best overall response (BOR) will be determined as shown in 
Table 13 per RECIST v1.1 (Eisenhauer, et al., 2009). 
The protocol scheduled tumor assessment interval is every 9 weeks (63 ± 7 days) for the first year of 
study treatment, and then every 12 weeks (84 ± 7 days) until progression. The minimum criteria for 
SD duration are at least 8 weeks from the date of first dose of study treatment. 


 
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Table 13  
Best Overall Response when Confirmation of CR and PR Required 
Overall 
Response 
First Time 
Point 
Overall 
Response 
Subsequent 
Time Point (at 
least 4 weeks) 
Best Overall Response (BOR) 
CR 
CR 
CR 
CR 
PR 
SD, PD or PR a  
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD provided minimum criteria for SD duration met, otherwise, NE 
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
SD 
SD 
SD provided minimum criteria for SD duration met, otherwise, NE 
SD 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD 
SD 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE 
NE 
NE 
NE 
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response; SD 
= stable disease. 
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR. 
 
Note: The minimum criteria for SD duration are at least 8 weeks from the date of first dose of study treatment. 
 
For each patient, BOR will be determined based on the overall responses at all time points between 
the date of first dose and the date of first documented radiological disease progression, or the date of 
subsequent anti-cancer therapy, whichever occurs first. Radiotherapy to lesions other than target or 
non-target lesions will not be considered subsequent anti-cancer therapy. 
Patients with a BOR of either confirmed CR or PR are considered to have responded to treatment 
-re
 
The ORR and 2-sided 95% confidence interval will be provided, in accordance with the methodology 
described in Section 7.1.  
The primary analysis population will be the ITT population.  Supportive analyses will also be 
performed using the EE population.  Exploratory subgroup analyses will be performed using the ITT 
population as described in Section 6.4. 
Tumor size (sum of longest (non-nodal) dimension and shortest (nodal) axes of all target lesions 
identified at baseline
best percentage change in tumor size as a separate bar, with the bars ordered from the largest increase 




 
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[Earlier of (date of radiological PD or death)  First documentation of response + 1] / 30.4375 
Censoring rules for the analysis of DOR are provided in Table 14. 
A time-to-event analysis of DOR will be performed in accordance with the methodology described in 
Section 7.1 for time to event endpoints.  
The analysis population will be patients in the ITT analysis set with a confirmed CR or PR.  
Supportive analyses will be performed using patients with a confirmed CR or PR in the EE analysis 
population. Exploratory subgroup analyses will be performed using the ITT population as described in 
Section 6.4. 
8.2.2 Investigator Assessed Progression-Free Survival 
PFS (in months) is defined as the time from the date of first dose to the earlier date of radiological PD 
as assessed by the Investigator or death from any cause, calculated as: 
[Earlier of (date of radiological PD or death)  First dose date + 1] / 30.4375 
Censoring rules used in PFS analysis are the same as those used for DOR and are provided in 
Table 14. 
A time-to-event analysis of PFS will be performed in accordance with the methodology described in 
Section 7.1 for time to event endpoints.  
The analysis population will be the ITT population.  Supportive analysis will be performed in the EE 
population.  Exploratory subgroup analyses will be performed using the ITT population as described 
in Section 6.4. 
8.2.3 Overall Survival 
Overall survival (in months) is defined as the time from the date of the first dose to the date of death 
for any cause, calculated as: 
[Date of death  First dose date + 1] / 30.4375 
Patients who are known to be alive will be censored at the last contact date. 
The date of last contact date will be derived using the last complete date among the following data 
sources: 
Patient assessment dates (laboratory blood draws, vital signs, performance status, ECG, tumor 
assessments, ECOG, pregnancy test, physical exams, tumor measurement, or tumor biopsy 
dates)  
Start and end dates of anti-cancer therapies, including anticancer therapy, surgeries or 
radiotherapy, administered after study treatment discontinuation.  
AE start and end dates (non-imputed dates only) 
Concomitant medications, growth factors, transfusions start and end dates (non-imputed dates 
only) 
 
Date of death, collected on the Study Discontinuation CRF form 
Study treatment (niraparib and dostarlimab) start and end dates  


 
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Date of discontinuation on disposition eCRF pages (do not use if reason for discontinuation is 
lost to follow-up).  
Only dates associated with actual examinations of the patient will be used in the derivation. Dates 
associated with a technical operation unrelated to patient status such as the date a blood sample was 
processed will not be used in the derivation.  
A time-to-event analysis of OS will be performed in accordance with the methodology described in 
Section 7.1 for time to event endpoints.  
The analysis population will be the ITT population.  Supportive analysis will be performed in the EE 
population.  Exploratory subgroup analyses will be performed using the ITT population as described 
in Section 6.4. 
8.2.4 Investigator Assessed Disease Control Rate 
Patients who achieved a best overall response rate of confirmed CR, PR, or SD (SD must have met 
the 8-
-
 
The DCR and 2-sided 95% CI will be provided in accordance with the methodology described in 
Section 7.1 for binomial endpoints. 
The analysis population will be the ITT population.  Supportive analyses will also be performed using 
the EE population.  Exploratory subgroup analyses will be performed using the ITT population as 
described in Section 6.4. 
8.2.5 Efficacy Endpoints Based on Independent Review Committee Assessment 
ORR, DOR, PFS, and DCR will be also evaluated using Independent Review Committee assessment.  
The analysis methods will be the same as those described for efficacy parameters as assessed by the 
Investigator in Section 8.1, 8.2.1, 8.2.2 and 8.2.4.  Waterfall plots and swimmer plots as described in 
Section 8.1 will be produced as derived by the Independent Review Committee assessments. 
8.3 Exploratory Efficacy Analyses 
Analyses of secondary efficacy endpoints will be performed in the overall population and in the 
subset of patients with PD-L1 positive tumors. 
8.3.1 Efficacy in Patients with Documented BRCAwt Tumors 
Efficacy endpoints (ORR, DOR, PFS, DCR and OS) as assessed by the Investigator will be assessed 
in patients with documented BRCAwt tumors.  This assessment will be performed as part of the 
subgroup analyses by BRCA status where patients with BRCAwt, BRCAmut and BRCA unknown 
tumors are evaluated, considering both central gBRCA and tBRCA results as described in Table 8.  
The ITT population will be used for analysis. 
8.3.2 Duration of Disease Control 
Duration of disease control is defined as the time from the date of the first dose of study treatment to 
the earlier date of assessment of progression by RECIST v.1.1 or death by any cause in the absence of 
progression by RECIST v1.1 among patients whose BOR is confirmed CR, PR or SD. It is calculated 
as: 
 [Earlier date of radiological PD or death  First dose date) + 1] / 30.4375 


 
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Table 14 provides a summary of the censoring rules used in calculating duration of disease control.   
A time-to-event analysis of duration of disease control will be performed in accordance with the 
methodology described in Section 7.1 for time to event endpoints.  
The analysis population will be ITT patients with SD or confirmed CR or PR.  Supportive analyses 
will be performed using the EE population. 
Duration of disease control will be analyzed using the Investigator assessment of response as well as 
the Independent Review Committee assessment. 
8.3.3 Functional Assessment of Cancer Therapy  Ovarian Symptom Index (FOSI) 
The FOSI is a validated 8 item measure of symptom response to treatment for ovarian cancer based on 
a subset of questions from the Functional Assessment of Cancer Therapy  Ovarian Cancer 
questionnaire (see Protocol Appendix 5). Patients respond to their symptom experience over the past 7 
days using a 5-
 
For items 1 through 6 and item 8, the score used for calculating the total score is the difference 
between the patient
's response and 4. For item 7, the score used for calculating the total score is the 
dividing the result by the number of responses. If 5 or more responses are recorded, the FOSI can be 
scored; otherwise, the FOSI score is recorded as missing. The FOSI score range is  
 
 to 
; a higher score indicates a better Quality of Life (QOL). 
At each time point, the number and percentage of patients who completed the questionnaires will 
summarized in a table, as well as the reasons for non-completion of these measures.  The denominator 
will be based on the number of patients expected to complete the form at the visit.  Expected forms 
will be derived as those who are still on at least one of the components of study treatment at the visit 
where FOSI was to be collected. 
Descriptive summary statistics will be provided for the overall total score and the change from 
baseline by time point using the ITT population with valid FOSI data at each timepoint.  No 
imputation will be performed for missing data.   
Time to symptom worsening will be defined as the time from randomization to the first FOSI 
assessment with a worsening score compared to its baseline score using minimally important 
difference (MID) thresholds (defined as 2-point change) (Beaumont, et al., 2007), which will be 
categorized at each visit as follows:  
Any patient with only improved or stable FOSI scores will be censored at the date of the last 
evaluable FOSI assessment, i.e. FOSI score is not missing. Patients who have no valid baseline FOSI 
assessment or any post-baseline FOSI assessment will be censored at the date of first dose of study 
medication. Kaplan-Meier methodology, in accordance with the methodology described in Section 7.1 
CCI
CCI
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or 
indices, which are protected by third party copyright laws and therefore have been excluded.
PPD
PPD


 
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for time to event endpoints, will be used to summarize time to symptom worsening on the overall 
FOSI score.   
8.3.4 Duration of Survival and PFS Follow-Up 
Duration of survival follow-up, defined as the time from first dose until date of death or date of last 
contact (i.e., date patients were censored for overall survival Section 8.2.3), will be summarized. The 
KM estimate of the median potential survival follow-up, using reverse censoring of survival data (i.e., 
treating death as censored observations, and censored survival observations as events), will also be 
presented (Schemper & Smith, 1996).  Duration of PFS follow-up will be analyzed in a similar 
fashion, defined as the time from first dose until date of progression or death or date of censoring 
(Section 8.2.2). 
8.3.5 Estimation of Optimal Threshold for PDL-1 and Derivation of Combinatorial 
Biomarker Signatures for Identifying Responders and non-Responders  
An ensemble statistical algorithm, called BATTing (Bootstrapping and Aggregating Thresholds from 
Trees), as proposed in (Huang, et al., 2017) and illustrated in (McKeegan, et al., 2015), will be used to 
estimate the optimal threshold (cut-point) value of PDL-1 that would help identify patients that are 
likely to have a tumor response with the combination treatment of Niraparib and Dostarlimab. In 
general, this algorithm selects the optimal cut-point that yields the best differentiation of patient 
subgroups with respect to the clinical endpoints of interest. First a large number (B) of datasets are 
randomly drawn with replacement (bootstrapped) from the original dataset. Then a Tree model with a 
single split on the PDL-1 values is built for each of these B datasets, such that the two terminal nodes 
of the tree will yield the best possible separation of the groups with respect ORR for the patients 
receiving Niraparib-Dostarlimab combination treatment. The threshold value from the split formed by 
each of these B trees is obtained. The median of the B threshold values is the BATTing threshold 
estimate. B=100 will be used in this dataset, per the recommendation in (Huang, et al., 2017) for B to 
be set at 50 or higher for ensuring a stable estimate of the threshold. This procedure is expected to 
yield a more reliable estimate of the PDL-1 threshold because a threshold from just a single Tree built 
on the original dataset or a single Receiver Operating Characteristic (ROC) curve or a single Precision 
Recall Curve tends to be highly unstable and not robust enough to small perturbations in the data and 
outliers, as illustrated clearly in (Huang, et al., 2017).  
9 Safety Analyses 
9.1 Extent of Exposure 
The dosing schedule for niraparib and dostarlimab is provided in Table 5.   
The number and percentage of patients at the starting prescribed dose by cycle will be summarized.   
Exposure parameters as defined in Table 15  will be summarized.  In addition, the number and 
percentage of patients who have a niraparib dose reduction, dose interruption, missed dose, or dose 
escalation beyond the starting dose will be summarized.  Dostarlimab infusion interruption or infusion 
delay will also be summarized.   
For patients treated beyond Investigator-assessed progression (those dispensed with niraparib post-
progression and/or receiving dostarlimab infusion post-progression), the duration of treatment beyond 
progression will be summarized, along with the best overall response observed post-progression as 




 
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9.2 Adverse Events 
9.2.1 Overview
All AEs and serious adverse events (SAEs) will be collected and recorded for each patient from the 
day of signing the informed consent form until 90 days after last study drug administration or until 
alternate anticancer treatment has been initiated, whichever occurs earlier; any pregnancies that occur 
within 180 days post-treatment are to be reported. Study drug-related SAEs and adverse events of 
special interest (AESIs) will be collected every 90 ± 14 days after the last dose of study drug until 
study closeout, or as otherwise indicated in the protocol. Concomitant illnesses that existed before 
entry into the study will not be considered AEs unless the illness worsens during the Treatment 
Period. Pre-existing conditions will be recorded as Medical History in the eCRF.  
Per protocol, treatment-Emergent Adverse Events (TEAEs) are events that were not present prior to 
the initiation of study treatment or events already present that worsen in either intensity or frequency 
following exposure to study treatment.  
For analysis, the following will be considered treatment emergent: 
all AEs and SAEs with an onset on or after the first dose of study treatment throughout 90 
days after the last dose of study treatment (or until the start of alternate anticancer therapy, 
whichever occurs earlier).  
all study drug-related SAEs and AESIs with an onset on or after the first dose of study 
treatment, including new malignancies reported on the survival follow-up form.  
all pregnancies with an onset on or after the first dose of study treatment until 180 days after 
the last dose of study treatment.  
all AEs with completely missing onset and stop dates, or with the onset date missing and a 
stop date later than the first dose date of either study treatment 
Adverse events not considered treatment emergent will be included in the listings, but will not be 
included in the summaries, unless otherwise specified. All analyses of adverse events will be 
performed using the Safety Population. 
Disease progression is an efficacy criterion and is therefore not considered an AE or SAE (even if 
fatal). Disease progression should be reported within the eCRF. If AEs/SAEs occur in relation to 
AEs/SAEs must be reported per AE/SAE reporting requirements. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
v22.0 or later. All AEs will be assessed by the Investigator for severity according to CTCAE v4.03. 
Relationship to each study drug, niraparib and dostarlimab, will be assessed by the Investigator as 
either related or not-related.  Any TEAE for which the relationship to study drug is missing will be 
considered as related. Within the same MedDRA PT, the AE with the highest ranked relationship to 
treatment for each patient will be counted in tabulations by relationship to treatment. Within a 
MedDRA SOC, patients with more than 1 MedDRA PT will be counted only once for the AE that is 
most related to treatment. The imputation for a missing relationship will take place prior to 
determining the most related AE within a SOC or PT for a given patient.   
Overall, patients with the same AE more than once will have that event counted only once within each 
SOC, and once within each PT. When summarized by severity, patients with the same AE more than 


 
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once will have the maximum severity of that event counted within each SOC, and once within each 
PT. When summarized by relationship, the AE will be counted towards each study drug to which a 
related-attribution is given.  For example, if an AE is attributed to both study drugs, it will be counted 
as being related to study treatment, related to niraparib, and related to dostarlimab. 
A high-level overview of AEs will be presented in a summary table.  This table will include the 
numbers and percentages of patients who had: 
Any TEAE 
Any treatment-related TEAE 
o Related to niraparib  
o Related to dostarlimab  
Any TEAE with CTCAE Toxicity Grade >=3 
Any treatment-related TEAE with CTCAE Toxicity Grade >=3 
o Related to niraparib  
o Related to dostarlimab  
Any serious TEAE 
Any treatment-related serious TEAE 
o Related to niraparib  
o Related to dostarlimab  
Any TEAE leading to study drug interruption/reduction/delay 
o TEAE leading to niraparib interruption 
o TEAE leading to niraparib dose reduction 
o TEAE leading to dostarlimab infusion interrupted 
o TEAE leading to dostarlimab infusion delay 
Any TEAE leading to study drug withdrawal 
o TEAE leading to niraparib withdrawal 
o TEAE leading to dostarlimab withdrawal 
Any TEAE with outcome of death 
Any treatment-related TEAE leading to death 
o Related to niraparib 
o Related to dostarlimab 
 
Subgroup analyses of TEAEs will be conducted in the following subgroups: 
 
Race (white, non-white) 
The following lists the AE tables to be displayed; 
the subgroups described above.  Tables summarizing treatment-related adverse events will summarize 
adverse events related to study treatment (either niraparib or dostarlimab), related to niraparib and 
related to dostarlimab. 
Overview of AEs*  
TEAE by SOC and PT*  
TEAE by PT (sorted by frequency)  
Treatment-related TEAE by SOC and PT*   


 
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Treatment-related TEAE by PT (sorted by frequency) 
TEAE by SOC, PT, and maximum grade  
  
Grade 
AEs by PT (sorted by frequency)  
Treatment-
*  
Treatment-
 (sorted by frequency) 
Treatment-emergent SAEs by SOC and PT*  
Treatment-related treatment-emergent SAEs by SOC and PT  
TEAEs with outcome of death by SOC and PT  
Treatment-related TEAEs with outcome of death by SOC and PT  
Non-serious TEAEs by SOC and PT (required by ClinicalTrials.gov)  
TEAEs resulting in study treatment modification by SOC and PT (niraparib dose reduction; 
niraparib dose interruption; dostarlimab infusion interruption; dostarlimab infusion delay)  
TEAEs resulting in study treatment withdrawal by SOC and PT (withdrawal of either study 
treatment; niraparib; dostarlimab)*   
Tables structured as listings will be provided for the following: 
Patients with treatment emergent AEs with Outcome of Death  
Patients with treatment emergent SAEs  
Patients with TEAEs leading to study treatment modification (niraparib dose 
reduction/interruption or dostarlimab infusion interruption or delay)  
Patients with TEAEs leading to study treatment withdrawal (niraparib and/or dostarlimab) 
Patients with treatment emergent immune-related adverse events as described in Section 9.2.2 
Patients with adverse events of Special Interest as described in Section 9.2.4 
Adverse event summaries will be ordered in terms of decreasing frequency for SOC (alphabetically 
for SOCs with the same number of AEs reported), and decreasing frequency for PT within SOC 
(alphabetically for PTs with the same number of AEs reported within a SOC). 
9.2.2 Immune-Related Adverse Events (irAEs) 
irAEs are identified according to a pre-specified search list (Section 12.2, Appendix 3).  The 
incidence of treatment-emergent immune related events will be summarized by Preferred Term 
overall and by maximum CTCAE grade.  Similar summaries will be produced for irAEs related to 
niraparib and dostarlimab.   
9.2.3 Myelosuppression Events 
Myelosuppression events will be grouped for analysis.  Table 16 outlines all the grouped events with 
the criteria of mapping MedDRA PTs for each group using Standardized MedDRA Queries (SMQs) 
and/or select PTs.  The list of terms corresponding to each grouped term is provided in Section 12.2, 
Appendix 2. 
The incidence of myelosuppression events will be summarized by grouped term and Preferred Term 
overall and by maximum CTCAE grade.  Similar summaries will be produced for myelosuppression 
events related to niraparib and dostarlimab.   


 
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Table 16  Myelosuppression Events 
Group Term 
MedDRA Criteria for Selection of Preferred Terms 
Thrombocytopenia events 
Haematopoietic thrombocytopenia SMQ (Broad) 
Anemia events 
Haematopoietic erythropenia SMQ (Broad) 
Leukopenia events 
Haematopoietic leukopenia SMQ (Broad) 
Neutropenia events 
Selected PTs related to neutropenia in the Haematopoietic leukopenia SMQ 
(Broad) 
Pancytopenia events 
Haematopoietic cytopenias SMQ (Broad) 
Abbreviations: MedDRA = medical dictionary for regulatory activities; PT = preferred term; SMQ = Standardized MedDRA 
Query. 
 
9.2.4 Adverse Events of Special Interest (AESI) 
AESIs for this study are the following:  
MDS and AML  
Secondary cancers (new malignancies other than MDS or AML)  
Pneumonitis  
Embryo-fetal toxicity 
AESIs will be identified using the AESI field on the AE eCRF.  The incidence of AESIs will be 
summarized by Preferred Term overall and by maximum CTCAE grade.  Similar summaries will be 
produced for AESIs related to niraparib and dostarlimab.    
9.2.5 Adverse Events By Treatment Cycle 
Incidence and prevalence of adverse events will be summarized by cycles of therapy for all TEAEs 
and TEAEs with CTCAE Toxicity 
.  The number of patients initiating study treatment (i.e., 
dispensed niraparib or started dostarlimab infusion) at the start of the reporting interval will be used as 
the denominator for incidence and prevalence calculations.   
Given the planned cycle duration for Cycles 1-4 is 21 days and Cycle 5 and beyond is 42 days, Cycles 
1-2 and 3-4 will be summarized together to ensure a similar duration.  In addition, adverse events 
  Cycles will be defined by 
the earlier date that niraparib was dispensed or dostarlimab was infused. 
For incidence rates by cycle, the specific AE will be assigned to the relevant time period if the start 
date of the AE occurs within the period. For recurrent events during a reporting interval, the first 
event occurrence is reported. For events that recur in more than 1 reporting interval (event start date is 
in different reporting intervals), the event will be reported in the first applicable reporting interval.  
For prevalence rates by cycle, the specific AE will be assigned to the relevant time period if the AE 
occurs within the period, regardless of the interval in which the event started. Events that are present 
in more than 1 reporting interval will be reported in each applicable reporting interval.  Events 
occurring multiple times within the same interval will be counted only once.  Patients with ongoing 
AEs will be assumed to have the AE until the corresponding last known dosing interval. 
9.3 Clinical Laboratory Evaluations 
established methods.  


 
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For the purposes of summarization in both the tables and listings, all laboratory values will be 
converted to standardized units.  If collected as a percent, differentials of white blood cell (WBC) 
count will be converted to absolute counts, in SI units, for summarization.  Only the numeric part in 
laboratory values that contain non-numeric qualifiers, such as less than (<) a certain value, or greater 
than (>) a certain value, will be considered for analysis. 
Corrected calcium is derived with the following formula: 
Corrected calcium (mmol/L) = (0.02 * (40 (g/L)  albumin (g/L))) + calcium (mmol/L). 
Laboratory data will be summarized both as continuous data and categorically as classified by 
severity grades using CTCAE v.4.03.   
Continuous Summaries 
Absolute values and change from baseline will be summarized by scheduled visit. In addition, the 
largest post-baseline increase and largest post-baseline decrease relative to baseline will be 
summarized (including all post-baseline scheduled and unscheduled visits through the treatment 
period).   
The following tests will be summarized:  
Hematology:  Hemoglobin, WBC count, absolute neutrophil count, eosinophils, basophils, 
lymphocytes, monocytes, platelets 
Chemistry:  Albumin, alanine aminotransferase (ALT), amylase, aspartate aminotransferase 
(AST), alkaline phosphatase (ALP), sodium, urea, blood urea nitrogen, total bilirubin, 
corrected calcium, chloride, creatinine, glucose, magnesium, potassium, total protein  
Coagulation Factors:  International normalized ratio (INR) and activated partial 
thromboplastin time (aPTT)  
Tumor Markers: CA-125 
Analysis by CTCAE Severity Grades 
NCI CTCAE v 4.03 grades will be determined for the following lab parameters: 
Hematology: hemoglobin (anemia), WBC (white blood cell decreased), lymphocytes 
(lymphocytes decreased), neutrophils (neutrophil count decreased), and platelets (platelet 
count decreased) 
Chemistry: albumin (hypoalbuminemia),  ALT (alanine aminotransferase increased), AST 
(aspartate aminotransferase increased), ALP (alkaline phosphatase increased), amylase, total 
bilirubin (blood bilirubin increased), corrected calcium (hypocalcemia, hypercalcemia), 
creatinine (creatinine increased), glucose (hyperglycemia, hypoglycemia), magnesium 
(hypermagnesemia, hypomagnesemia), potassium (hyperkalemia, hypokalemia), and sodium 
(hyponatremia, hypernatremia)  
As fasting glucose is not a requirement of the study protocol, hyperglycemia will only be 
 


 
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The derivation of CTCAE grades will consider only numeric results; clinical assessments will not be 
considered (Section 12.2, Appendix 1). Laboratory measurements that are within their institutional 
limits of normal and are not graded as 1-
is defined as normal. Additionally, if a lab parameter is graded in both directions (e.g. glucose: 
hyperglycemia and hypoglycemia), then low direction toxicity grades at baseline and post baseline 
will be set to 0 when the variables are derived for summarizing high direction toxicity, and vice 
versa.   
A shift summary of baseline to maximum severity on-study treatment (including all post-baseline 
scheduled and unscheduled visits through the treatment period) will be produced for the coded 
hematology and chemistry laboratory parameters above.  Missing values for baseline and on-study 
treatment will be displayed; percentages for each parameter will be based on the total number of 
patients in the safety population. 
Liver function tests 
Summary of liver function tests will include the following categories to assess possible drug induced 
liver toxicity.  The number and percentage of patients with each of the following (including all post-
baseline scheduled and unscheduled visits through the treatment period) will be summarized: 
 
 
 
 
 
 
Concurrent (ALT or 
 
 2×ULN 
ALP < 2×ULN or missing 
Concurrent measurements are those occurring on the same date. 
summarized using frequency and percentage.  
Listings 
A by-patient listing of all laboratory data with laboratory reference ranges, abnormal values 
highlighted, and CTCAE toxicity grading, when available, will be provided for each panel of 
laboratory data (hematology, serum chemistry, urinalysis, coagulation factors, thyroid panel, CA-
125). Screening serology and virology results and urine/serum pregnancy tests will also be listed. 


 
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Separate listings will be created for abnormal laboratory values and laboratory values with CTCAE 
 
9.4 Vital Signs  
Summaries of vital signs parameters (systolic and diastolic blood pressures, heart rate, and 
temperature) and weight will be presented. Observed and change from baseline will also be 
summarized and analyzed by scheduled visit.  In addition, the largest post-baseline increase and 
largest post-baseline decrease relative to baseline will be summarized during the on-study treatment 
period (including all post-baseline scheduled and unscheduled visits through the treatment period).   
Vital sign measurements will be presented for each patient in a data listing. 
9.5 Electrocardiogram 
All patients will undergo a single ECG assessment at the screening visit to verify eligibility into the 
study.  Clinically significant findings will be reported on the Medical History eCRF and presented per 
Section 7.6. 
9.6 Physical Examinations and Other Safety Parameters 
All new clinically significant abnormal findings or clinically significant worsening of the existing 
conditions in physical examinations will be reported on the AE eCRF and presented per Section 9.2. 
The ECOG shift from baseline to highest score during the on-study treatment period (including all 
post-baseline scheduled and unscheduled visits through the treatment period) will be summarized.  
All ECOG assessments will be presented for each patient in a data listing. 
9.7 COVID-19 
A summary of the number and percentage of participants for the following assessments will be 
produced:  Case Diagnosis, COVID-19 Test performed, and Results of the COVID-19 test. Additional 
summaries may be produced, as appropriate. 
10 Computing Environment 
All statistical analyses will be performed using SAS statistical software v9.4 or later, unless otherwise 
noted. Programming will be performed by PRA Health Sciences. Quality control procedures will be 
documented separately in the study-specific quality control plan.  
 


 
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11 References 
Beaumont, J., Yount, S., Lalla, D., Lubeck, D., Derynck, M., & al., e. (2007). Validation of the 
Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Symptom Index (FOSI) in a 
Phase II Clinical Trial of Pertuzumab in Patients with Advanced Ovarian Cancer. Journal of 
Clinical Oncology, 25, 16021-16021. 
Brookmeyer, R., & Crowley, J. (1982). A confidence interval for the median survival time. 
Biometrics, 38, 29-41. 
Clopper, C., & Pearson, E. (1934). The use of confidence or fiducial limits illustrated in the case of 
the binomial. Biometricka, 26, 404-413. 
DOXIL®. (1995). doxorubicin hydrochloride liposome injection) for intravenous use [prescribing 
information]. Bedford, OH: ALZA Corporation. 
Eisenhauer, E., Therasse, P., Bogaerts, J., Schwartz, D., Sargent, D., & Ford, R. (2009). New response 
evaluation criteria in solid tumours; revised RECIST guidline (version 1.1). European 
Journal of Cancer, 45(2), 228-247. 
Gordon, A., JT, F., Guthrie, D., Parkin, D., Gore, M., & Lacave, A. (2001). Recurrent epithelial 
ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus 
topotecan. Journal of Clinical Oncology, 14, 3312-3322. 
Gynecologic Oncology Group, Markman, M., Blessing, J., Rubin, S., Connor, J. H., & Waggoner, S. 
(2006). Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant 
ovarian and primary peritoneal cancers; a Gynecologic Oncology Group study. Gynecol 
Oncol, 101(3), 436-440. 
Huang, X., Sun, Y., Trow, P., Chatterjee, S., Chakravartty, A., Tian, L., & Devanarayan, V. (2017). 
Patient subgroup identification for clinical drug development. Statistics in Medicine, 1414-28. 
Kalbfleisch, J., & Prentice, R. (1980). The Statistical Analysis of Failure Time Data. New York: John 
Wiley & Sons. 
McKeegan, E., Ansell, P., Davis, G., Chan, S., Chandran, R., Gawel, S., . . . Devanarayan, V. (2015). 
Plasma biomarker signature associated with improved survival in advanced non-small cell 
lung cancer patients on linifanib. Lung Cancer, 90(2), 296-301. 
Mutch, D., Orlando, M., Goss, T., Teneriello, M., Gordon, A., & McMeekan, S. (2007). Randomized 
phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with 
platinum-resistant ovarian cancer. Journal of Clinical Oncology, 25(19), 2811-2818. 
Pignata, S., Lorusso, D., Scambia, G., Sambataro, D., Tamberi, S., & Cinieri, S. (2015). Pazopanib 
plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-
refractory advanced ovarian cancer (MITO 11): a randomized open-label, phase 2 trial. 
Lancet Oncology, 16(5), 561-568. 
Schemper, M., & Smith, T. (1996). A Note on Quantifying Follow-up in Studies of Failure Time. 
Controlled Clinical Trials, 17, 343-346. 
 






 
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12.2 APPENDIX 2:  Myelosuppression Events  
The list of MedDRA PTs is provided in a separate document. 
 
 
 
 


 
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12.3 APPENDIX 3:  Immune-Related Adverse Events (irAEs) 
The list of MedDRA PTs is provided in a separate document. 


 
Statistical Analysis Plan, Protocol 3000-02-006 
 
Confidential 
 
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12.4APPENDIX 4:  Statistical Output Shells 
The list of statistical output and corresponding table/figure/listing shells are provided in a separate 
document.