ParpVax2: A Phase II Study Of Maintenance Niraparib Plus Ipilimumab In Patients With Metastatic Pancreatic Cancer Whose Disease Has Not Progressed On Platinum-Based Therapy
Phase: PHASE2
Conditions: Pancreatic Adenocarcinoma Metastatic
Sponsor: Abramson Cancer Center at Penn Medicine

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PARPVAX2: A PHASE II STUDY OF MAINTENANCE NIRAPARIB PLUS 
IPILIMUMAB IN PATIENTS WITH  METASTATIC PANCREATIC 
CANCER WHOSE DISEASE HAS NOT PROGRESSED ON PLATINUM-
BASED THERAPY 
 
Sponsor-Investigator: 
Kim A. Reiss, MD 
University of Pennsylvania, Department of Internal 
Medicine Division of Hematology/Oncology 
Perelman Center for Advanced Medicine  
South Tower, 10th Floor, Room 107  
3400 Civic Center Boulevard  
Philadelphia, PA 19104 
(215) 360-0735 (phone); (215) 662-4646 (fax) 
Email: kim.reissbinder@pennmedicine.upenn.edu 
 
Medical Monitor 
Vivek Narayan 
Statistician: 
Nicholas Seewald, PhD 
Investigational Products: 
Niraparib  
Ipilimumab 
UPCC Number 
19224 
Penn IRB Number 
857488 
IND/ IDE Number: 
Exempt 
ClinicalTrials.gov Number: 
NCT06747845 
Version History 
v.1 11-20-2024 
v.2 01-23-2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
1 
STUDY SUMMARY........................................................................................... 7 
2 
BACKGROUND AND STUDY RATIONALE .................................................. 11 
2.1 
Introduction ................................................................................................................ 11 
2.2 
Background and Relevant Literature .......................................................................... 11 
2.3 
Name and Description of the Investigational Products ............................................... 13 
2.3.1 
Niraparib .................................................................................................................... 13 
2.3.2 
Ipilimumab ................................................................................................................. 13 
2.4 
Niraparib Background and Data ................................................................................. 13 
2.4.1 
Niraparib Pharmacology ............................................................................................ 13 
2.4.2 
Niraparib Pharmacokinetics, Metabolism and Drug-Drug Interaction Potential ........... 14 
Specific Populations: ................................................................................................................. 14 
2.4.3 
Niraparib Toxicology .................................................................................................. 14 
2.4.4 
Niraparib Clinical Studies ........................................................................................... 15 
2.4.1 
Baseline Platelet Count and Weight as Predictors of Thrombocytopenia.................... 16 
2.5 
Ipilimumab ................................................................................................................. 16 
2.5.1 
Clinical Pharmacodynamics ....................................................................................... 16 
2.5.2 
Pharmacokinetics ...................................................................................................... 17 
2.5.3 
Clinical Studies .......................................................................................................... 17 
2.7 
Niraparib Plus Ipilimumab .......................................................................................... 18 
3 
STUDY OBJECTIVES .................................................................................... 19 
3.1 
Primary Objective ...................................................................................................... 19 
3.2 
Secondary Objectives ................................................................................................ 19 
4 
INVESTIGATIONAL PLAN ............................................................................. 19 
4.1 
General Design .......................................................................................................... 19 
4.1.1 
Screening Phase ....................................................................................................... 19 
4.1.2 
Study Intervention Phase ........................................................................................... 20 
4.1.3 
Treatment Discontinuation ......................................................................................... 20 
4.1.4 
Follow Up Phase........................................................................................................ 20 
4.1.5 
Study Schema ........................................................................................................... 21 
4.2 
Study Endpoints ......................................................................................................... 21 
4.2.1 
Primary Study Endpoints ........................................................................................... 21 
4.2.2 
Secondary Study Endpoints ....................................................................................... 21 
5 
STUDY POPULATION AND DURATION OF PARTICIPATION ..................... 22 
5.1 
Inclusion Criteria ........................................................................................................ 22 
5.2 
Exclusion Criteria ....................................................................................................... 23 
5.3 
Patients or Partners of Patients with Reproductive Potential ...................................... 25 
5.4 
Total Number of Subjects and Sites ........................................................................... 26 
5.5 
Vulnerable Populations .............................................................................................. 26 

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6 
STUDY INTERVENTION ................................................................................ 26 
6.1 
Description ................................................................................................................ 26 
6.1.1 
Niraparib .................................................................................................................... 26 
6.1.2 
Ipilimumab ................................................................................................................. 26 
6.1.3 
Rationale for Shorter Infusion Time for Ipilimumab ..................................................... 27 
6.2 
Intervention Regimen ................................................................................................. 27 
6.2.1 
Niraparib + Ipilimumab (Arm A) .................................................................................. 27 
6.2.2 
FOLFIRI (Arm B) ....................................................................................................... 27 
6.2.3 
Starting Dose and Dose Modifications of Protocol-Specified Treatment ..................... 27 
6.2.4 
Dose Modification Criteria and Criteria for Stopping Treatment .................................. 28 
6.2.5.3 Dose Modifications for FOLFIRI ................................................................................. 36 
6.2.5 
Treatment Beyond Progression ................................................................................. 36 
6.3 
Prior and Concomitant Therapies .............................................................................. 37 
6.3.1 
Anticancer or Experimental Therapy .......................................................................... 37 
6.3.2 
Hematopoietic Growth Factors and Blood Products ................................................... 37 
6.3.3 
Bisphosphanates ....................................................................................................... 38 
6.3.4 
Anticoagulants ........................................................................................................... 37 
6.3.5 
Other Concomitant Medications ................................................................................. 38 
6.3.6 
Substrates of P-glycoprotein ...................................................................................... 38 
6.3.7 
Vaccines .................................................................................................................... 38 
6.4 
Warnings and Precautions ......................................................................................... 38 
6.4.1 
Niraparib .................................................................................................................... 38 
6.4.2 
Ipilimumab ................................................................................................................. 40 
6.5 
Receipt ...................................................................................................................... 42 
6.6 
Storage ...................................................................................................................... 42 
6.6.1 
Niraparib .................................................................................................................... 42 
6.6.2 
Ipilimumab ................................................................................................................. 42 
6.7 
Administration and Accountability .............................................................................. 42 
6.8 
Subject Compliance Monitoring ................................................................................. 43 
6.9 
Return or Destruction of Investigational Product ........................................................ 43 
7 
STUDY PROCEDURES .................................................................................. 44 
7.1 
Schedule of Assessments- ARM A (Niraparib + Ipilimumab)...................................... 44 
7.2 
Schedule of Assessments- ARM B (FOLFIRI) ........................................................... 46 
7.3 
Screening Phase ....................................................................................................... 50 
7.4 
Treatment Phase ....................................................................................................... 51 
7.4.1 
Cycle 1, Day 1 (Both Arms Unless Otherwise Specified) ........................................... 51 
7.4.2 
Cycle 1 Day 8 (Both Arms) ........................................................................................ 52 
7.4.3 
Cycle 3 Day 1 (Both Arms .......................................................................................... 52 
7.4.4 
Day 1 of Subsequent Cycles (Both Arms Unless Specified) ....................................... 52 
7.4.6 
Tumor Assessments .................................................................................................. 53 

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7.4.7 
End of Treatment Visit ............................................................................................... 53 
7.5 
30-day Follow-up Visit ................................................................................................ 54 
7.6 
90 Day Follow-up Visit for MDS/AML (Arm A Only) .................................................... 54 
7.7 
Long-term Follow-Up ................................................................................................. 54 
7.8 
Subject Withdrawal .................................................................................................... 54 
7.8.1 
Data Collection and Follow-up for Withdrawn Subjects .............................................. 55 
8 
STUDY EVALUATIONS AND MEASUREMENTS ......................................... 55 
8.1 
Medical Record Review ............................................................................................. 55 
8.2 
Physical Examination ................................................................................................. 55 
8.3 
Body Weight and Height ............................................................................................ 55 
8.4 
Vital Signs ................................................................................................................. 55 
8.5 
ECOG Performance Status ........................................................................................ 55 
8.6 
Clinical Laboratory Evaluations .................................................................................. 56 
8.7 
Efficacy Evaluations ................................................................................................... 56 
8.7.1 
Tumor Assessments .................................................................................................. 56 
8.7.2 
Tumor Markers .......................................................................................................... 56 
8.8 
Correlative Science .................................................................................................... 57 
8.8.1 
Specimen Collection .................................................................................................. 57 
8.8.2 
Minimum Number of Required Biopsies ..................................................................... 57 
8.8.3 
Determining the impact of Immune Health on outcomes on nira/ipi (Wherry Lab) ...... 57 
8.8.4 
Defining the pharmacodynamic response and clinical impact of the immune 
microenvironment in nira/ipi treated tumors (Beatty and Wolpin-Nowak Labs). ...................... 57 
8.8.5 
Investigating the roll of cell proliferation and replication stress status in the response to 
nira/ipi (Wolpin-Nowak Lab). .................................................................................................. 57 
8.8.6 
Studying the impact of tumor transcriptional subtype on outcomes in nira/ipi treated 
tumors (Beatty and Wolpin-Nowak Labs). .............................................................................. 58 
9 
STATISTICAL PLAN ...................................................................................... 58 
9.1 
Primary Endpoints ..................................................................................................... 58 
9.2 
Secondary Endpoints ................................................................................................. 58 
9.3 
Sample Size and Power Determination ...................................................................... 59 
9.3.1 
Statistical Methods ..................................................................................................... 59 
9.3.2 
Baseline Data ............................................................................................................ 59 
9.3.3 
Efficacy Analysis ........................................................................................................ 59 
9.3.4 
Safety Analysis .......................................................................................................... 59 
9.4 
Subject Population(s) for Analysis ............................................................................. 59 
10 
SAFETY AND ADVERSE EVENTS ................................................................ 60 
10.3 
Definitions .................................................................................................................. 60 
10.1.1 Unanticipated Problems Involving Risk to Subjects or others ..................................... 60 
10.1.2 Adverse Event ........................................................................................................... 60 
10.1.3 Serious Adverse Event .............................................................................................. 60 
10.1.4 Adverse Events of Special Interest (AESIs) for Niraparib ........................................... 61 

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10.2 
Recording of Adverse Events .................................................................................... 61 
10.3 
Intensity of Adverse Events........................................................................................ 62 
10.4 
Causal Relationship of Adverse Events to Study Drugs ............................................. 62 
10.5 
Outcome and Action Taken ....................................................................................... 63 
10.6 
Adverse Event Reporting Period ................................................................................ 64 
10.7 
Preexisting Condition ................................................................................................. 64 
10.8 
General Physical Examination Finding ....................................................................... 64 
10.9 
Post-Study Adverse Event ......................................................................................... 64 
10.10 
Abnormal Laboratory Values ..................................................................................... 64 
10.11 
Pregnancy or Drug Exposure ..................................................................................... 65 
10.12 
Hospitalization, Prolonged Hospitalization or Surgery ................................................ 65 
10.13 
Reporting to the UPenn Sponsor ............................................................................... 66 
10.13.1 Adverse Events.......................................................................................................... 66 
10.13.2 Reporting Product Quality Complaints for Niraparib ................................................... 66 
10.14 
Investigator Reporting: Local Reporting Requirements .............................................. 67 
10.15 
Protocol Deviations .................................................................................................... 68 
10.16 
Investigator Reporting to Sponsor of Exceptions and Deviations ............................... 67 
10.17 
Medical Monitor ......................................................................................................... 67 
10.18 
Confidentiality ............................................................................................................ 68 
10.19 
Data Collection and Management .............................................................................. 68 
10.20 
Records Retention ..................................................................................................... 68 
11 
STUDY MONITORING, AUDITING, AND INSPECTING ................................ 68 
11.1 
Study Monitoring Plan ................................................................................................ 68 
11.2 
Auditing and Inspecting.............................................................................................. 69 
12 
ETHICAL CONSIDERATIONS ....................................................................... 69 
13 
STUDY FINANCES ......................................................................................... 69 
13.1 
Funding Source ......................................................................................................... 69 
13.2 
Conflict of Interest ...................................................................................................... 70 
14 
PUBLICATION PLAN ..................................................................................... 70 
15 
REFERENCES ................................................................................................ 71 
16 
APPENDIX ...................................................................................................... 73 
16.1 
Appendix A: ECOG .................................................................................................... 73 
 
 
 
 
 
 
 

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List of Tables 
 
Table 1. 
Median overall survival (mOS), overall response rate (ORR), and 
PFS12 in the Nira/Ipi vs Nira/Nivo arms 
Table 2. 
Recommended Niraparib Dose Reductions for Adverse Reactions 
Table 3. 
Niraparib Dose Modification for Non-hematologic Adverse Reactions 
Table 4. 
Niraparib Dose Modifications for Hematologic Adverse Reactions 
Table 5. 
GI Adverse Event Management Algorithm for Ipilimumab 
Table 6. 
Renal Adverse Event Management Algorithm for Ipilimumab 
Table 7. 
Pulmonary Adverse Event Management Algorithm for Ipilimumab 
Table 8. 
Hepatic Adverse Event Management Algorithm for Ipilimumab 
Table 9. 
Endocrinopathy Management Algorithm for Ipilimumab 
Table 10. 
Skin Adverse Event Management Algorithm for Ipilimumab 
Table 11. 
Neurological Adverse Event Management Algorithm for Ipilimumab 
Table 12. 
Schedule of Assessments – Arm A 
Table 13. 
Schedule of Assessments – Arm B 
Table 14. 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Scale 
Table 15. 
Evaluation of Target Lesions 
Table 16.      Evaluation of Nontarget Lesions 
Table 17. 
Evaluation of Best Overall Response

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1 STUDY SUMMARY 
 
Title 
PARPVAX2: A PHASE II STUDY OF MAINTENANCE NIRAPARIB 
PLUS IPILIMUMAB IN PATIENTS WITH METASTATIC 
PANCREATIC CANCER WHOSE DISEASE HAS NOT 
PROGRESSED ON PLATINUM-BASED THERAPY 
Short Title 
Maintenance Niraparib Plus Ipilimumab in Patients with 
Metastatic Pancreatic Adenocarcinoma Whose Disease Has 
Not Progressed on Platinum-Based Chemotherapy 
 
UPENN IRB 
Number 
857488
 
Protocol Number UPCC 19224 
 
Phase 
Clinical Phase II 
 
Methodology 
Randomized, Two Arm, Non-Comparative, Open Label 
 
Study Duration 
26 months 
Study Centers 
Abramson Cancer Center at University of Pennsylvania and 
Dana Farber Cancer Institute 
 

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Objectives 
Primary: 
• To estimate the progression free survival (PFS) of maintenance 
niraparib/ipilimumab in a population of patients with metastatic 
pancreatic cancer who have not progressed following 4-6 
months of palliative FOLFIRINOX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Number of 
Subjects
 
 
 
 
Secondary: 
• To estimate the overall response rate in the experimental arm 
• To estimate the disease control rate in the experimental arm 
• To estimate the median overall survival in the experimental arm 
• To estimate the PFS, ORR, DCR and OS of a non-comparative 
control arm of patients receiving maintenance chemotherapy 
• To evaluate the safety of niraparib plus ipilimumab in the 
experimental arm 
• To determine biomarkers of response, mechanisms of action 
and immune pharmacodynamics of niraparib/ipilimumab in a 
population of patients with metastatic pancreatic cancer 
 
68 (51 receiving nira/ipi; 17 receiving maintenance FOLFIRI) 
   

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Main 
Inclusion and 
Exclusion 
Criteria 
KEY INCLUSIONS: 
1. Histologically or cytologically confirmed diagnosis of 
metastatic pancreatic adenocarcinoma 
2. Patients must have received first-line FOLFIRINOX 
chemotherapy for metastatic pancreatic cancer and 
have received between four and six months of treatment 
without evidence of disease progression based on the 
investigator’s opinion 
Note: this requires at least stable imaging and a stable 
or decreasing tumor marker as applicable and as 
determined by the investigator. 
3. Measurable disease is not required for study entry 
Note: The study will require that at least 80% of enrolled 
patients (i.e. 55 of all patients) are biopsiable at enrollment. 
The investigators may require measurable/biopsiable 
disease as the study progresses in order to achieve this 
goal. 
4. Adequate organ function 
5. ECOG performance status of 0-1 
 
KEY EXCLUSIONS: 
1. Prior treatment with a PARP inhibitor, ipilimumab, or other 
inhibitors of cytotoxic T-lymphocyte-associated protein (CTLA-
4).  
2. Patients 
who 
have 
demonstrated 
resistance 
to 
FOLFIRINOX are not eligible to participate in this study 
3. Patients who have a known, pathogenic germline or 
somatic variant in BRCA1, BRCA2, PALB2, RAD51C or 
RAD51D are excluded. Patients with MSI-H or MMR 
deficient pancreatic cancer are excluded. 
4. Clinical evidence of uncontrolled malabsorption and/or any 
other gastrointestinal disorder or defect that would, in the 
opinion of the investigator, interfere with the absorption of 
niraparib. 

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5. Received any systemic treatment for pancreatic cancer 
during the 14 days prior to first dose of treatment. 
6. Acute 
infection 
requiring 
intravenous 
antibiotics, 
intravenous antiviral or intravenous antifungal agents 
during the 14 days prior to first dose of study therapy. 
7. Patients will be excluded if they have an active, known or 
suspected autoimmune disease, defined as: patients with a 
history of inflammatory bowel disease are excluded from this 
study, as are patients with a history of symptomatic 
autoimmune disease (e.g. rheumatoid arthritis, systemic 
progressive 
sclerosis 
(scleroderma), 
systemic 
lupus 
erythematosus, autoimmune vasculitis e.g. Wegener’s 
Granulomatosis); 
motor 
neuropathy 
considered 
of 
autoimmune origin (e.g. Guillain-Barre Syndrome). 
NOTE: Patients are permitted to enroll if they have 
vitiligo, type I diabetes mellitus, residual hypothyroidism 
due to autoimmune condition only requiring hormone 
replacement, 
psoriasis 
not 
requiring 
systemic 
treatment, or conditions not expected to recur in the 
absence of an external trigger. 
8. Has a history of interstitial lung disease or active, non-
infectious pneumonitis. 
9. Has received a live vaccine within 4 weeks prior to the first 
dose of trial therapy (Note: seasonal influenza vaccines for 
injection are generally inactivated and are allowed; 
however intranasal influenza vaccines (e.g. Flu-Mist) are 
live attenuated vaccines and are not allowed). 
 
Statistical 
Methodology 
This is a two-arm randomized trial of niraparib/ipilimumab vs. a non-
comparative control arm designed to test, in the niraparib/ipilimumab 
arm, study testing the null hypothesis of median PFS (mPFS) of 5 
months versus the alternative hypothesis of an mPFS 7.5 months.  
Assuming exponential survival, with 51 patients enrolled over 14 
months and with 12 months of additional follow-up, there is 89% 
power for the test and 5% 1-sided type I error rate. With 17 control 
patients, a 90% confidence interval for any binomial parameter 
(toxicity, response, etc.) would be no wider than 43% percentage 
points and the chance of observing one or more rare events (4% true 
probability) is at least 50% and events of true frequency of 9% or 
higher have at least 80% probability of being observed (1 or more 
events out of 17 control patients). 
 
This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 part 
312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures.

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2 BACKGROUND AND STUDY RATIONALE 
2.1 
Introduction 
With the advent of effective multi-agent chemotherapy regimens1,2 for metastatic pancreatic 
cancer (mPC)3, subgroups of patients who show durable responses to treatment are emerging. 
As a result, a growing population with incurable PC now stay on chemotherapy for many months 
and even years. These improvements in outcomes are remarkable for a universally lethal illness. 
However, “perpetual chemotherapy” ultimately fuels therapeutic resistance and drives 
cumulative toxicities that degrade quality of life. In order to mitigate toxicity, chemotherapy is 
commonly dose modified in patients who have durable responses, and there are clinical data to 
support this approach 4,5. However, non-chemotherapy based maintenance strategies (e.g. 
PARP inhibitors and immunotherapy) represent an exciting alternative approach due to their 
favorable toxicity profiles and the possibility of improved outcomes.  Taken together, there is an 
unmet clinical need to identify sustainable, non-chemotherapy based options for patients with 
mPC who achieve durable stability on first-line palliative treatment. 
 
2.2 
Background and Relevant Literature 
Maintenance therapy is known to be effective in BRCA and PALB2 mutant patients. Non-
chemotherapy based maintenance therapy for PC was first tested in patients with pathogenic 
variants in BRCA1, BRCA2, or PALB2: The randomized phase III POLO trial enrolled patients 
with metastatic, platinum-sensitive PC and pathogenic, germline BRCA variants. Chemotherapy 
was discontinued and patients were treated with maintenance olaparib, a poly-ADP ribose 
polymerase (PARP) inhibitor vs placebo. Olaparib significantly increased the median 
progression-free survival (mPFS) compared to placebo6 and the study led to the FDA approval 
of olaparib in this setting. We conducted a smaller, single arm, phase II trial of maintenance 
rucaparib, another PARP inhibitor, in platinum-sensitive patients with advanced PC and 
germline or somatic BRCA or PALB2 variants, which met the primary endpoint (mPFS 13.1 mo)7 
and led to the addition of maintenance rucaparib in the NCCN guidelines for this broader 
population. The positive results of these trials are encouraging and behoove us to explore non-
chemotherapy based maintenance therapy in a larger, phenotypically selected group of patients, 
namely: those who do well with front-line FOLFIRINOX.   
 
In a randomized clinical trial, maintenance niraparib plus ipilimumab (nira/ipi) was effective in 
platinum-sensitive, advanced PC patients. We completed a single-institution, investigator-
initiated phase Ib/II trial of maintenance niraparib, another PARP inhibitor, plus either nivolumab 
or ipilimumab in patients with advanced PC and at least stable disease following ≥4 months of 
platinum-based chemotherapy8. The rationale for combining niraparib with immune checkpoint 
blockade were based on multiple published in vivo models 
demonstrating that (1) PARP inhibitor activity is dependent 
on an active immune system and an intact cGAS-STING 
pathway9, and (2) there is synergy of PARP inhibitors plus 
ICB9,10.  The upregulation of CTLA4 in immunologically 
“warm” PCs (and the absence of PDL1 upregulation in the 
same setting), provided additional rationale for exploring 
ipilimumab in addition 
to nivolumab11. No 
genomic 
alteration 
was required for enrollment on the study. Chemotherapy 
was stopped, and patients were randomized 1:1 to 
niraparib plus nivolumab (nira/nivo) (Arm A) or nira/ipi 
(Arm B). The primary endpoint was PFS, and the primary 
objective was a PFS6 of 60% in each arm. The study 

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enrolled 84 patients (44 Arm A; 40 Arm B). The mPFS of nira/nivo was 1.8 months (PFS6 20.6%) 
and the mPFS of nira/ipi was 8.1 mo (PFS6 59.6%); the trial was therefore positive in the nira/ipi 
arm (Fig 1). Median overall survival (mOS), overall response rate (ORR), and PFS12, were all 
numerically higher in the nira/ipi arm, though the study was not powered to assess these 
endpoints (Table 1). Patient demographics and characteristics were similar between the two 
arms. Additionally, when all patients with known DNA damage repair (DDR) variants were 
removed from the analysis, the results were unchanged. Given that most patients with a 
functional DDR deficiency can be successfully identified on routine panel testing12, the persistent 
efficacy of the nira/ipi arm after removal of all DDR deficient patients suggests that the results 
may not be driven by a DNA repair deficiency in this population. We alternatively hypothesize 
that patients who demonstrated durable responses to chemotherapy may represent an 
immunologically superior population who, in turn, are able to respond more effectively to the 
combination of PARP inhibition and anti-CTLA4. However, the mechanistic basis for response 
to PARP inhibition and anti-CTLA4 remains unknown.  
 
Preliminary analysis of immune determinants of treatment response in patients treated with 
PARP inhibition and immunotherapy. We evaluated 
the immune composition of our study population. 
First, we assessed the initial (at cancer diagnosis) 
and baseline (at study enrollment) neutrophil to 
lymphocyte ratios (NLRs). Literature suggests that 
patients with low NLR are more treatment 
responsive and have improved prognosis compared 
to those with high NLR13. Consistent with this, we 
identified that our patients had low NLRs at cancer 
diagnosis, 
suggesting 
a 
superior immune milieu in this population (Table 2). Next, we 
looked for baseline and on-treatment differences in the peripheral 
blood via evaluation of serially collected peripheral blood 
mononuclear cells (PBMCs). Patients in the nira/nivo arm had 
more baseline T-regulatory cells, while patients in the nira/ipi arm 
had more naïve B cells and proliferating T-cells (Fig 2).  To explore whether these findings might 
have influenced response to therapy, we divided patients into progressors (progression in 
<6mo) and non-progressors (stability for >6mo) and compared the pretreatment levels of naïve 
B-cells, T-regulatory cells, and double negative T-cells in each group. We found no significant 
association with levels of these cell types and response to therapy, suggesting alternative 
determinants of treatment outcomes. Taken together, we have identified an active maintenance 
regimen that is, as of yet, is incompletely mechanistically understood. Therefore, in this proposal 
we aim to: (1) validate nira/ipi as a maintenance option, (2) explore the pharmacodynamics and 
mechanisms of this combination and (3) study biomarkers predictive for response to treatment.   
Our specific aims are: 
• 
Define the activity of maintenance nira/ipi in a population of patients with 
metastatic pancreatic cancer who have not progressed on first line palliative 
FOLFIRINOX after 4-6 months of treatment.  
 
• Determine 
biomarkers 
of 
response, 
mechanisms 
and 
immune 
pharmacodynamics of nira/ipi in a population of patients with metastatic 
pancreatic cancer. 
 

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Clinical 
impact: 
We 
previously 
demonstrated 
the 
efficacy 
of 
maintenance 
niraparib/ipilimumab in a population of patients with advanced pancreatic cancer who had 
not progressed on platinum-based therapy8. We now embark on a second study to validate 
our results and to provide further insights into the mechanisms of action, 
pharmacodynamics and biomarkers that predict success or failure of this combination in 
patients. 
 
2.3 
Name and Description of the Investigational Products 
 
2.3.1 
Niraparib 
Niraparib is an orally available, selective PARP1 and -2 inhibitor. 
The 
chemical 
name 
for 
niraparib 
is 
2-8-2H-indazole 
7- 
carboxamide 
4-
methylbenzenesulfonate hydrate (1:1:1). The empirical molecular formula for niraparib is 
C26H30N4O5S and its molecular weight is 510.61. 
Niraparib tosylate monohydrate drug substance is a white to off-white, non-hygroscopic 
crystalline solid. Niraparib solubility is pH independent below the pKa of 9.95, with an 
aqueous free base solubility of 0.7 mg/mL to 1.1 mg/mL across the physiological pH 
range. 
Niraparib is supplied in HDPE bottles with child resistant closures.  
Niraparib does not contain gluten. 
 
2.3.2 
Ipilimumab 
Ipilimumab (BMS-734016, MDX-010) is a fully human IgG1κ consisting of 4 polypeptide 
chains; 2 identical heavy chains primarily consisting of 447 amino acids each with 2 
identical kappa light chains consisting of 215 amino acids each linked through inter-chain 
disulfide bonds. The physical and chemical properties of ipilimumab drug substance are 
provided in the table below. 
 
BMS Number 
734016 
Molecular 
Weight 
147,991 Daltons 
Appearance 
Clear to slightly opalescent, colorless to pale yellow liquid, may contain particles 
Solution pH 
7.0 
pI 
The isoelectric focusing analysis generates a banding pattern in the pI range 
of 8.5 to 8.8, with the major isoform at an approximate pI of 8.7. 
 
Ipilimumab injection, 200 mg/40 mL (5 mg/mL), is formulated as a clear to slightly 
opalescent, colorless to pale yellow, sterile, nonpyrogenic, single-use, isotonic aqueous 
solution that may contain particles. Ipilimumab injection, 50 mg/10 mL and 200 mg/40 mL, 
is supplied in 10-cc or 50-cc Type I flint glass vials, respectively, stoppered with gray butyl 
stoppers and sealed with aluminum seals. The drug product is formulated at a 
concentration of 5 mg/mL at a pH of 7.0. 
 
2.4 
Niraparib Background and Data 
 
2.4.1 
Niraparib Pharmacology 

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Niraparib is a selective PARP-1 and -2 inhibitor that selectively kills tumor cells in vitro 
and in mouse xenograft models. PARP inhibition leads to irreparable DSBs, use of the 
error-prone DNA repair pathway, resultant genomic instability and ultimately cell-death. 
Additionally, PARP trapping at genetic lesions as a result of the suppression of auto-
parlyation can contribute to cytotoxicity. 
 
2.4.2 
Niraparib Pharmacokinetics, Metabolism and Drug-Drug Interaction 
Potential 
Absorption: Following a single-dose administration of 300 mg niraparib under fasting 
conditions, niraparib was measurable in plasma within 30 minutes and the mean peak 
plasma concentration (Cmax) for niraparib was reached in about 3 hours [804 ng/mL 
(%CV:50.2%)]. Following multiple oral doses of niraparib from 30 mg to 400 mg once 
daily, accumulation of niraparib was approximately 2 fold. The systemic exposures (Cmax 
and AUC) to niraparib increased in a dose proportional manner when the dose of niraparib 
increased from 30 mg to 400 mg. The absolute bioavailability of niraparib is approximately 
73%, indicating minimal first-pass effect. Concomitant administration of a high fat meal 
did not significantly affect the PK of niraparib after administration of 300 mg of niraparib. 
Distribution: Niraparib was moderately protein bound to human plasma (83.0%). The 
apparent Vd/F was 1220 L, indicating extensive tissue distribution of niraparib. In a 
population PK analysis, the Vd/F of niraparib was 1074 L in cancer patients. 
Metabolism: Niraparib is metabolized primarily by Ces to form a major inactive 
metabolite, M1. In a mass balance study, M1 and M10 (the subsequently formed M1 
glucuronides) were the major circulating metabolites. The mean half-life of M1 was 88 
hours. The exposure ratio of M1 to niraparib was approximately 1.3-2.2 fold in plasma. 
Elimination: Following a single oral 300-mg dose of niraparib, the mean terminal half-life 
of niraparib ranged from 48 to 51 hours (approximately 2 days). In a population PK 
analysis, the apparent total clearance of niraparib was 16.2 L/h in cancer patients. 
Niraparib is eliminated primarily through the hepatobiliary and renal routes. Following 
administration of a single oral 300 mg dose of [14C]-niraparib, on average 86.2% (range 
71% to 91%) of the dose was recovered in urine and feces over 21 days. Radioactive 
recovery in the urine accounted for 47.5% (range 33.4% to 60.2%) and the feces for 
38.8% (range 28.3% to 47.0%) of the dose. In pooled samples collected over 6 days, 
36.7% of the dose was recovered in the urine primarily as metabolites and 21.1% of the 
dose was recovered in the feces primarily as unchanged niraparib. 
Specific Populations: 
Geriatric Patients: Population PK analyses indicated that age had no significant impact 
on the PK of niraparib. 
Racial or Ethnic Groups: Population PK analyses indicated that race had no significant 
impact on the PK of niraparib. 
 
2.4.3 
Niraparib Toxicology 
Carcinogenesis: No carcinogenicity studies have been conducted with niraparib. 
Mutagenesis: Niraparib was clastogenic in an in vitro mammalian chromosomal 
aberration assay and in an in vivo rat bone marrow micronucleus assay. This 
clastogenicity is consistent with genomic instability resulting from the primary 
pharmacology of niraparib and indicates potential for genotoxicity in humans. Niraparib 

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was not mutagenic in a bacterial reverse mutation assay (Ames) test. 
Impairment of Fertility: No nonclinical reproductive studies have been conducted with 
niraparib, but a reversible decrease in spermatogenesis was observed in rats and dogs. 
It is not known whether niraparib or its metabolites are excreted in milk. 
Animal Toxicology: In repeat-dose oral toxicity studies, niraparib was administered daily 
for up to 3 months duration in rats and dogs. The major primary target organ for toxicity 
in both species was the bone marrow, with associated changes in peripheral hematology 
parameters. 
Additionally, decreased spermatogenesis was seen in both species. These findings 
occurred at exposures below those seen clinically. All findings showed reversibility within 
4 weeks of cessation of dosing. 
Phototoxicity: Niraparib did not exhibit cutaneous or ocular phototoxicity in a 3-day 
repeat-dose study in pigmented rats. 
 
2.4.4 
Niraparib Clinical Studies 
Kindly refer to the niraparib IB for clinical study updates. 
The safety and efficacy of niraparib as maintenance therapy was studied in a Phase 3 
randomized, double-blind, placebo-controlled trial (NOVA) in patients with platinum-
sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. All 
patients had received at least two prior platinum-containing regimens and were in 
response (complete or partial) to their most recent platinum-based regimen. 
Eligible patients were assigned to one of 2 cohorts based on the results of a germline 
BRCA mutation test. Women who were hereditary germline BRCA mutation carriers were 
assigned to the gBRCAmut cohort (n = 203) and women who did not carry a hereditary 
germline BRCA mutation were assigned to the non-gBRCAmut cohort (n = 350). Within 
each cohort, patients were randomized using a 2:1 allocation of niraparib to placebo. 
Randomization occurred within 8 weeks of the last dose of the most recent platinum-
containing regimen. 
The primary endpoint, PFS, was determined by central independent assessment per 
RECIST (version 1.1) or clinical signs and symptoms and increased CA-125. PFS as 
defined in the NOVA study was measured from the time of randomization (which occurred 
up to 2 months after completion of the most recent chemotherapy regimen) to disease 
progression or death. 
Prior to unblinding of the study, tumors from patients randomized to the non-gBRCAmut 
cohort were tested for the presence of HRD using the Myriad myChoice® HRD test, which 
evaluates three independent biomarkers of tumor genome instability: loss of 
heterozygosity, telomeric allelic imbalance, and large-scale state transitions. Tumors with 
homologous recombination deficiencies and those with somatic BRCA mutations were 
defined as HRDpos. 
PFS was significantly longer for patients who received niraparib compared to those who 
received placebo for all three primary efficacy populations. Within the gBRCAmut cohort, 
the median PFS from time of randomization was 21.0 months with niraparib versus 5.5 
months with placebo. In the overall non-gBRCAmut cohort, the median PFS from time of 
randomization was 9.3 months with niraparib versus 3.9 months with placebo. PFS was 
also significantly longer with niraparib than with placebo in the HRDpos group of the non-
gBRCAmut cohort: 12.9 months versus 3.8 months. 

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2.4.1 
Baseline Platelet Count and Weight as Predictors of Thrombocytopenia 
An analysis was conducted using the data collected in ENGOT-OV16/NOVA and the 
initial phase I study, PN001. This analysis determined that only baseline platelets had an 
impact on platelet nadir; lower baseline platelets (<180 109/L) were associated with an 
increased frequency of thrombocytopenia Grade ≥1 (76%) or Grade ≥ 3 (45%) compared 
to patients with higher baseline platelet counts. Further, an exploratory analysis of clinical 
data versus baseline body weight from ENGOT-OV16/NOVA was conducted. For this 
analysis, the weight categories were based on quartiles with the lowest quartile (patients 
with a body weight less than 58 kg at baseline) compared to the highest quartile (patients 
with a body weight greater than or equal to 77 kg at baseline). While TEAEs occurred in 
most patients regardless of body weight, Grade ≥3 TEAEs, SAEs, and TEAEs leading to 
dose modification or treatment discontinuation occurred more commonly in the weight 
<58 kg cohort than in the ≥77 kg cohort. In the cohort of patients with a body weight <58 
kg, approximately 80% of patients had a dose reduction compared to 59% of patients with 
a weight greater than or equal to 77 kg. Treatment discontinuations were increased in the 
subjects with lower body weight (24%) compared to patients in the highest quartile (10%). 
The potential relationship between body weight and TEAEs was further explored in an 
analysis to evaluate the correlation of grade 3 or 4 thrombocytopenia and baseline body 
weight. The lowest platelet count in the first 30 days was plotted versus baseline body 
weight to determine if low body weight identified a subgroup of patients with higher levels 
of thrombocytopenia during Cycle 1. In the first 30 days of treatment, a baseline body 
weight >77 kg is associated with a lower incidence of grade 3 or 4 thrombocytopenia 
(14%) relative to the group with body weight <58 kg (43%). 
Finally, a classification tree approach was used to refine the best cut-off points for 
predicting the likelihood of a patient developing ≥Grade 3 thrombocytopenia within 30 
days after the first dose of niraparib. The results of the model show that the subgroup of 
patients with a baseline body weight <77 kg or baseline platelet count <150,000 µL had 
a grade ¾ thrombocytopenia rate in the first 30 days of 35.4% compared to 11.5% in the 
group of patients with a body weight >77 kg and a platelet count >150,000 µL. Further, 
the average daily dose was 258 mg through the first two cycles for patients with a body 
weight >77 kg and platelet count >150,000 µL, and was only 206 mg for patients with 
body weight < 77 kg or platelet count <150,000 µL. Thus, the actual delivered dose 
approximated a starting dose of 200 mg despite the intended delivery of a starting dose 
of 300 mg. These observations are to be confirmed in the present study with the inclusion 
of study treatment dosed at 200 mg (2 capsules of niraparib or placebo) in patients whose 
baseline weight is <77 kg or baseline platelet count is <150,000 µL. 
 
2.5 
Ipilimumab 
 
2.5.1 
Clinical Pharmacodynamics 
CTLA-4 is a key regulator of T-cell activity. Ipilimumab is a CTLA-4 immune checkpoint 
inhibitor that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, increasing 
the number of tumor reactive T-effector cells that mobilize to mount a direct T-cell immune 
attack against tumor cells. Preclinical data indicate that CTLA-4 blockade can also reduce 
Treg function, which may lead to an increase in anti-tumor immune response. Ipilimumab 
may selectively deplete Tregs at the tumor site, leading to an increase in the intratumoral 
T- effector/Treg cell ratio which drives tumor response leading to cell death.[21] 
 

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2.5.2 
Pharmacokinetics 
The PPK of ipilimumab was studied in 785 subjects (3200 serum concentrations) with 
advanced melanoma in 4 Phase 2 studies (CA184004, CA184007, CA184008, and 
CA184022), 1 Phase 3 study (CA184024), and 1 Phase 1 study (CA184078). The PPK 
analysis demonstrated that the PK of ipilimumab is linear, the exposures are dose 
proportional across the tested dose range of 0.3 to 10 mg/kg, and the model parameters 
are time-invariant, similar to that determined by non- compartmental analyses. 
Upon repeated dosing of ipilimumab, administered q3w, minimal systemic accumulation 
was observed by an accumulation index of 1.5-fold or less, and ipilimumab steady-state 
concentrations were achieved by the third dose. The ipilimumab CL of 16.8 mL/h from 
PPK analysis is consistent with that determined by non-compartmental PK analysis. The 
terminal T- HALF and Vss of ipilimumab calculated from the model were 15.4 days and 
7.47 L, respectively, which are consistent with that determined by noncompartmental 
analysis. Volume of central compartment (Vc) and peripheral compartment were found 
to be 4.35 and 3.28 L, respectively, suggesting that ipilimumab first distributes into 
plasma volume and, subsequently, into extracellular fluid space. CL of ipilimumab and 
Vc were found to increase with increase in BW. However, there was no significant 
increase in exposure with increase in BW when dosed on a milligram/kilogram basis, 
supporting dosing of ipilimumab based on a weight normalized regimen. The PK of 
ipilimumab is not affected by age, gender, race, and immunogenicity (anti- drug antibody 
[ADA] status); concomitant use of chemotherapy; prior therapy; BW; performance status; 
or tumor type. Other covariates had effects that were either not statistically significant or 
were of minimal clinical relevance. 
 
2.5.3 
Clinical Studies 
Kindly refer to the ipilimumab IB for clinical study updates. 
BMS and Medarex (acquired by BMS in Sep-2009) have co-sponsored an extensive 
clinical development program for ipilimumab, encompassing more than 19,500 subjects 
(total number of subjects enrolled in ipilimumab studies) in several cancer types in 
completed and ongoing studies, including a compassionate use. The focus of the clinical 
program is in melanoma, prostate cancer, and lung cancer, with advanced melanoma 
being the most comprehensively studied indication. Ipilimumab is being investigated both 
as monotherapy and in combination with other modalities such as chemotherapy, 
radiation therapy, and other immunotherapies. 
Phase 3 programs are ongoing in melanoma, prostate cancer, and lung cancer. In 
melanoma, completed Phase 3 studies (MDX010-20 and CA184024) have demonstrated 
a clinically meaningful and statistically significant survival benefit in pretreated advanced 
melanoma and previously untreated advanced melanoma with a manageable safety 
profile, respectively. An ongoing Phase 3 study (CA184029) in melanoma is investigating 
ipilimumab as adjuvant monotherapy for high-risk Stage III melanoma. In addition, a 
Phase 3 study (CA184169) comparing the safety and efficacy of 3 versus 10 mg/kg 
ipilimumab monotherapy in pretreated or treatment-naïve subjects with unresectable or 
metastatic melanoma is ongoing. 
The completed Phase 3 study (CA184043) evaluated ipilimumab in subjects with mCRPC 
who had progressed during or following treatment with docetaxel. Eligible subjects were 
randomized to a single dose of bone-directed RT, followed by either ipilimumab 10 mg/kg 
or placebo (799 randomized: 399 ipilimumab and 400 placebo). This study did not meet 

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its primary endpoint of OS. The HR of 0.85 (95% CI: 0.72, 1.00) for survival favored 
ipilimumab but did not reach statistical significance with a P value of 0.053. Planned 
sensitivity analyses favored ipilimumab, where the greatest benefit appeared to be in 
subgroups defined by good prognostic features and low burden of disease. Additional 
evidence of ipilimumab activity observed in the study included a reduced risk of disease 
progression relative to placebo (HR = 0.70), superior clinical outcomes compared to 
placebo in tumor regression, and declines in PSA. The safety profile in this study was 
consistent with the previously defined AE profile at the same dose. 
A second Phase 3 study (CA184095) evaluated ipilimumab 10 mg/kg versus placebo in 
subjects with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC with 
no visceral metastases. 
Activity was also observed in a large Phase 2 study in lung cancer (NSCLC and SCLC; 
CA184041) in combination with chemotherapy. Two ongoing Phase 3 studies are 
evaluating ipilimumab in combination with chemotherapy in squamous NSCLC 
(CA184104) and SCLC (CA184156). In Study CA184104, the last patient, last visit was 
achieved in June-2015, and database lock occurred on 01-Sep-2015. No final data are 
currently available, but preliminary data indicate that no new safety concerns were 
identified in the course of standard clinical safety monitoring of the study. In Study 
CA184156, preliminary data indicate the primary endpoint of prolonging survival was not 
achieved, but no new safety signals were identified. 
While the types of safety events observed in subjects receiving ipilimumab do not appear 
to change, even in combination with other anti-cancer agents, the proportion of subjects 
experiencing 1 type or another immune related adverse event (irAE) may be impacted by 
the choice of combination partner. Skin and GI irAEs predominate in monotherapy 
studies. In combination with DTIC (melanoma), the incidence of skin and GI irAEs was 
lower than expected, and the incidence of hepatic irAEs was higher. In combination with 
paclitaxel and carboplatin (NSCLC), the incidence of all types of irAEs appeared to be 
numerically lower compared to the incidence observed for ipilimumab monotherapy in the 
Phase 2 program. In a Phase 1 study (CA184161), the concomitant administration of 
vemurafenib and ipilimumab in subjects with BRAF-mutated metastatic melanoma 
resulted in asymptomatic and reversible increases in aspartate aminotransferase (AST) 
and alanine aminotransferase (ALT), exceeding the incidence to be expected when either 
agent is administered as a single agent therapy, leading to discontinuation of this 
treatment. In a Phase 2 study (CA184240), sequential treatment with vemurafenib 
followed by 10 mg/kg ipilimumab in subjects with BRAF-mutated metastatic melanoma 
was tolerable with a manageable safety profile. No significant signals of hepatobiliary 
toxicity were reported. The benefit/risk of this sequence needs to be evaluated further 
based on individual subject characteristics and new treatment options. 
Ipilimumab is also being evaluated in clinical studies conducted independently by the 
Cancer Therapy Evaluation Program of the US NCI, as well as in several additional 
externally- sponsored studies. 
 
 
2.6 
Niraparib Plus Ipilimumab 
Niraparib has previously been studied in our previously reported phase I/II study8. In the 
phase I portion of the study, the combination of niraparib 200mg PO daily plus ipilimumab 
3mg/kg IV Q3 weeks x4 doses was found to be safe. This dosing regimen and schedule 
was the recommended phase II dose. There was no evidence of toxicity overlap between 

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the two agents. Most common grade 3 or worse adverse events were fatigue (14%), 
anemia (11%) and hypertension (9%). There were no treatment-related deaths.  
 
3 STUDY OBJECTIVES 
3.1 
Primary Objective 
• To estimate the progression free survival (PFS) of maintenance 
niraparib/ipilimumab in a population of patients with metastatic pancreatic 
cancer who have not progressed following 4-6 months of palliative 
FOLFIRINOX 
 
 
3.2 
Secondary Objectives 
• To estimate the overall response rate in the experimental arm 
• To estimate the disease control rate in the experimental arm 
• To estimate the median overall survival in the experimental arm 
• To estimate the PFS, ORR, DCR and OS of a non-comparative control 
arm of patients receiving maintenance chemotherapy 
• To determine biomarkers of response, mechanisms of action and immune 
pharmacodynamics of niraparib/ipilimumab in a population of patients with 
metastatic pancreatic cancer 
 
 
4 INVESTIGATIONAL PLAN 
4.1 
General Design 
This is a two arm, open-label randomized study of niraparib plus ipilimumab or 
maintenance FOLFIRI in patients with metastatic pancreatic adenocarcinoma who have 
achieved disease stability on FOLFIRINOX. The control arm is meant to be non-
comparative to the experimental arm and is designed to provide validity to the results. 
Patients will be randomized to either Arm A (niraparib + ipilimumab) or Arm B (FOLFIRI) 
in a 3:1 fashion.  
 
4.1.1 
Screening Phase 
All patients will undergo screening assessments within 28 days prior to the first dose of 
study therapy. AEs that occur after signing of the informed consent form and before 
administration of the first treatment dose will also be collected during this period. 
Screening assessments will include demographics and medical history, family history, 
prior treatments for pancreatic cancer (and other malignancies if applicable), current 
medications and procedures, ECOG performance status, hematology, serum chemistry, 
serum pregnancy for women of childbearing potential, urinalysis, physical examination, 
vital signs, weight and height measurements, adverse events, and radiological 
assessment by CT or magnetic resonance imaging (MRI). For patients who pass the 
screening phase, a mandatory tumor biopsy prior to first dose of treatment will be 

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collected if deemed safe and feasible. Archival tumor tissue samples, if available, will also 
be collected and stored. 
All patients will have blood collected prior to treatment for correlative analyses and 
storage. 
 
4.1.2 
Study Intervention Phase 
During the treatment phase (continuous 21-day cycles (Arm A) or continuous 28-day 
cycles (Arm B), patients will be monitored for safety and efficacy. Assessments during the 
treatment phase will include AEs, ECOG performance status, concomitant medications 
and procedures, physical examination, vital signs and weight measurements, hematology 
and serum chemistry, CA 19-9 measurement, blood samples for research analyses and 
study drug administration and accountability. A mandatory on-treatment tumor biopsy will 
be obtained if considered safe and feasible.  
Patients will be assessed for disease status per RECIST v1.1 after every 3rd cycle of 
treatment (Arm A) or every 2nd cycle of treatment (Arm B). Patients will continue to 
receive treatment until disease progression or other reason for treatment discontinuation. 
Patients will be monitored continuously for safety. 
 
4.1.3 
Treatment Discontinuation 
Upon treatment discontinuation, all patients will return to the clinic for an End of Treatment 
(EOT) visit if they are able to. 
Assessments at this visit will include AEs, ECOG performance status, concomitant 
medications 
and 
procedures, 
physical 
examination, 
vital 
signs 
and 
weight 
measurements, hematology and serum chemistry, CA 19-9 measurement, research 
blood sample for research analyses, disease status assessment and study drug 
accountability. 
 
4.1.4 
Follow Up Phase 
Patients who received ipilimumab (Arm A) will have a 30-day and 90-day follow-up period 
for AEs following the last dose of study treatment. Please refer to the study calendar for 
details. Patients who received standard chemotherapy (Arm B) will have a 30-day follow-
up for AEs following last dose of study treatment.  
CT scans at 30-day follow-up should also be performed for patients who discontinued 
treatment for reason other than disease progression and did not have a radiologic 
assessment at the End of Treatment visit. All patients will be followed for survival every 
six months until death, loss to follow-up, withdrawal of consent or until 5 years have 
passed, whichever occurs first. 
 
 
 
 
 
 
 

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4.1.5 
Study Schema 
 
 
4.1.6 
End of Study 
The trial will be completed when the last subject completes the last study-related phone 
call or visit, discontinues from the trial or is lost to follow-up (i.e. the subject is unable to 
be contacted by the investigator). 
 
4.2 
Study Endpoints 
 
4.2.1 
Primary Study Endpoint 
The primary study endpoint will be progression-free survival (PFS) in the experimental 
arm, defined as the time from randomization to the occurrence of disease progression 
according to RECIST v1.1, as assessed by the investigator, or death from any cause. 
Patients who are alive and progression-free will be censored on the most recent date that 
documents progression-free status (i.e., scan date or clinic visit date).  
 
4.2.2 
Secondary and Exploratory Study Endpoints 
The secondary endpoints include: 
• Evaluation of safety and tolerability of this combination as determined by CTCAE 
v5.0. 
• Disease control, defined as achieving stable disease (SD), partial response (PR), 
or complete response (CR) per RECIST v1.1, in the experimental arm 
• Overall response in the experimental arm (measurable patients only), defined as 
achieving partial or complete response (PR, CR) per RECIST v1.1. 
• Overall survival, defined as time from randomization to death from any cause, in 
the experimental arm 
• Disease control, progression free survival, overall response, and overall survival 
in the control arm 
6
Eligibility
1. Metastatic PDAC
2. No platinum resistance
after 4-6 mo FOLFIRINOX
metastatic disease
3. Prior RT permitted
4. Measurable disease
not required
5. No pathogenic BRCA,
PALB2 or RAD51C/D variant
Maintenance FOLFIRI
Niraparib + Ipilimumab*
51 paƟents
* Experimental Arm: One cycle = 21 days
• Ipilimumab - 3.0 mg/kg IV every 3 weeks x 4 doses (Cycle 1-4)
• Niraparib - 200 mg orally daily D1-D21 of each cycle, continuous
until disease progression or unacceptable toxicity
3:1 randomizaƟon
17 paƟents
Primary Endpoint: PFS
in the experimental
arm

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•  of niraparib and ipilimumab in the experimental arm 
• To determine biomarkers of response, mechanisms of action and immune 
pharmacodynamics of niraparib/ipilimumab in a population of patients with 
metastatic pancreatic cancer 
 
Exploratory endpoints include:  
• Systemic and tumor-specific determinants of response and resistance to 
maintenance therapy with niraparib and ipilimumab 
 
 
5 STUDY POPULATION AND DURATION OF PARTICIPATION 
5.1 
Inclusion Criteria 
Eligible patients must meet the following inclusion criteria: 
• Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma 
with metastatic disease 
• ≥18 years of age. 
• Patients must be able to understand the study procedures and agree to participate 
in the study by providing written informed consent 
• Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX 
or modified FOLFIRINOX for metastatic disease with stable disease or better. 
Patients treated with liposomal irinotecan with oxaliplatin, 5-fluorouracil and 
leucovorin (NALIRIFOX) are also eligible. Patients who were initially treated with 
FOLFIRINOX or NALIRIFOX but stopped oxaliplatin because of toxicity are eligible 
for the trial.  
− Note: This requires at least stable imaging and a stable or decreasing tumor 
marker as applicable and as determined by the investigator. 
• Measurable disease is not a requirement for study entry 
-Note: The study will require that at least 80% of enrolled patients (i.e., 55 of 
all patients) are biopsiable at enrollment. The investigators may require 
measurable/biopsiable disease as the study progresses in order to achieve 
this goal. 
• Participants must be willing to undergo a pre-treatment fresh tumor biopsy (if 
medically feasible).  
• Participants must be willing to undergo an on-treatment tumor biopsy (if medically 
feasible).  
• Female participant has a negative serum pregnancy test within 24 hours prior to 
taking study treatment if of childbearing potential and agrees to abstain from 
activities that could result in pregnancy from screening through 6 months (females) 
or 30 days (males) after the last dose of study treatment, or is of nonchildbearing 
potential (see Section 5.3). 

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• Male patient agrees to use an adequate method of contraception starting with the 
first dose through 90 days after the last dose of study treatment (see Section 5.3). 
• Adequate organ function confirmed by the following laboratory values obtained ≤7 
days prior to the first day of study therapy: 
− Absolute neutrophil count (ANC) ≥1.5 x 109/L 
− Platelets>100 x 109/L 
− Hemoglobin ≥9g/dL 
− Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x 
upper limit of normal (ULN); if liver metastases, then ≤5 x ULN 
− Total bilirubin ≤1.5 x ULN; if liver metastases or metabolic disorder such as 
Gilbert’s syndrome, then ≤2.5 x ULN. 
− Serum creatinine ≤1.5 x ULN or estimated glomerular filtration rate (GFR) ≥45 
mL/min using Cockcroft Gault formula. 
• Eastern Cooperative Oncology (ECOG) performance status of 0 to 1. 
 
5.2 
Exclusion Criteria 
Patients will be excluded from participation if any of the following criteria apply: 
• Prior treatment with a PARP inhibitor, ipilimumab, or other cytotoxic T- 
lymphocyte-associated-4 protein (CTLA-4) inhibitor. 
• Patients who have demonstrated resistance to FOLFIRINOX are not eligible to 
participate in this study. 
• Patients with known pathogenic/likely pathogenic germline or somatic alteration(s) 
in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. 
• Patients with known mismatch repair deficiency or microsatellite instability-high 
cancer. 
• Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal 
disorder or defect that would, in the opinion of the investigator, interfere with the 
absorption of niraparib. 
• Patients with uncontrolled hypertension, defined as systolic BP >140mmHg and/or 
diastolic BP >90mmHg 
• Patients with a prior history of posterior reversible encephalopathy syndrome 
(PRES). 
• Acute infection requiring intravenous antibiotics, intravenous antiviral or 
intravenous antifungal agents during the 14 days prior to first dose of study therapy. 
• Patients will be excluded if they have a history of or active autoimmune disease, 
defined as: patients with a history of inflammatory bowel disease are excluded 
from this study, as are patients with a history of symptomatic autoimmune disease 
(e.g. rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic 
lupus erythematosus, autoimmune vasculitis e.g. Wegener’s Granulomatosis); 

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motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre 
Syndrome). 
NOTE: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, 
residual hypothyroidism due to autoimmune condition only requiring hormone 
replacement, psoriasis not requiring systemic treatment, or conditions not 
expected to recur in the absence of an external trigger. 
• Has a history of interstitial lung disease or active, non-infectious pneumonitis. 
• Has received a live vaccine within 4 weeks prior to the first dose of trial therapy. 
(Note: seasonal influenza vaccines for injection are generally inactivated and are 
allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated 
vaccines and are not allowed). 
• For fertile patient (female able to become pregnant or male able to father a child), 
refusal to use effective contraception during the period of the trial and: 
− Female patients refusing to use effective contraception for 6 months after the 
last dose of study drug. 
− Male patients refusing to use effective contraception for 90 days after the last 
dose of study drug. 
• Received any systemic treatment for pancreatic cancer ≤14 days prior to first dose 
of therapy. Patients must not have had investigational therapy administered ≤ 4 
weeks, or within a time interval less than at least 5 half-lives of the investigational 
agent, whichever is longer, prior to the first scheduled day of dosing in this study. 
• Patients will be excluded if they have a condition requiring systemic treatment with 
either 
corticosteroids 
(>10mg 
daily 
prednisone 
equivalents) 
or 
other 
immunosuppressive medications within 14 days of study drug administration. 
Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisone 
equivalents are permitted in the absence of active autoimmune disease. 
• Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia 
due to prior chemotherapy that persisted > 4 weeks and was related to the most 
recent treatment. 
• Non-study related minor surgical procedure ≤5 days, or major surgical procedure 
≤21 days, prior to the first dose of therapy; in all cases, patients must be sufficiently 
recovered and stable before treatment administration. 
• Active drug or alcohol use or dependence that would interfere with study 
compliance. 
• Presence of any other condition that may increase the risk associated with study 
participation or may interfere with the interpretation of study results, and, in the 
opinion of the investigator, would make the patient inappropriate for entry into the 
study. 
• Patient must not have any known history of myelodysplastic syndrome (MDS) or 
acute myeloid leukemia (AML) 
• Patients must not be simultaneously enrolled in any therapeutic clinical trial. 
• Patients must not have had radiotherapy within 4 weeks of the first dose of study 

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treatment. 
• Patients must not have a known hypersensitivity to the components of niraparib or 
the excipients 
• Patients must not have received a transfusion (platelets or red blood cells) ≤ 4 
weeks of the first dose of study treatment. 
• Patients must not be undergoing treatment for a second active cancer at the time 
of randomization. Exceptions include: (1) local therapies for skin cancers,  (2) 
hormonal therapies for breast or prostate cancer without evidence of active 
disease  Patients may have a history of: (1) adequately treated nonmelanoma skin 
cancers, (2) curatively treated in situ cancer of the cervix, (3) curatively treated 
DCIS, (4) curatively treated stage I, grade 1 endometrial carcinoma, (5) other solid 
tumors and lymphomas (without bone marrow involvement) diagnosed at least five 
years prior to randomization and treated with no evidence of disease recurrence 
• Patients with active hepatitis B or hepatitis C infections, as defined by positive PCR 
testing, may not enroll. 
• Patients with HIV may enroll, but must have an undetectable viral load at the time 
of enrollment and must be receiving a stable regimen of HAART. 
• Patients must not have known, symptomatic brain or leptomeningeal metastases. 
 
5.3 
Patients or Partners of Patients with Reproductive Potential 
Niraparib, ipilimumab, 5-fluourouracil and irinotecan should not be used during pregnancy 
or in women of childbearing potential (WOCBP) not using reliable contraception. 
Women of childbearing potential should not become pregnant while on study treatment 
and may not be pregnant at the beginning of treatment. 
Pregnancy Testing: A pregnancy test (blood or urine based on institutional preferences) 
should be performed on all WOCBP within 3 days prior to enrollment. 
Contraception: Persons of childbearing potential must use effective contraception during 
therapy and for 6 mo (females) or 30 days (males) (nira/ipi) or three months (FOLFIRI) 
after receiving the last dose of study treatment. 
Acceptable methods of birth control include: 
• Two highly effective forms of contraception, defined as contraceptive methods with 
a failure rate of less than 1% per year when used consistently and correctly. 
Patients who have undergone vasectomy or tubal occlusion must also use a male 
condom with spermicide. 
• Permanent sterilization, defined as hysterectomy, bilateral salpingectomy, 
bilateral oophorectomy, or bilateral orchidectomy. 
• Postmenopausal, defined as a female patient or sexual partner >45 years of age 
who has not menstruated for at least 12 consecutive months. 
• Total sexual abstinence. 
 
Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of study treatment and 90 days (Arm A) or 3 
months (Arm B) after the last dose of study treatment. 

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Patients must not breast-feed from the first dose of study drug and for 30 days following 
the final dose of niraparib or 3 months following the final dose of ipilimumab. 
 
5.4 
Total Number of Subjects and Sites 
A total of 68 evaluable subjects will be enrolled between the University of Pennsylvania 
and at the Dana-Farber Cancer Institute. 
 
5.5 
Vulnerable Populations 
Children, pregnant women, fetuses, neonates, or prisoners are not included in this 
research study. 
 
6 STUDY INTERVENTION 
Oral niraparib plus intravenous ipilimumab or maintenance FOLFIRI chemotherapy 
 
6.1 
Description 
 
6.1.1 
Niraparib 
For complete details regarding Niraparib, please refer to the Investigator’s Brochure.  
Niraparib starting dose will be 200mg PO daily. 
Niraparib is an orally available, selective PARP1 and -2 inhibitor. 
The chemical name for niraparib is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7- 
carboxamide 4-methylbenzenesulfonate hydrate (1:1:1). The empirical molecular formula 
for niraparib is C26H30N4O5S and its molecular weight is 510.61. 
Niraparib tosylate monohydrate drug substance is a white to off-white, non-hygroscopic 
crystalline solid. Niraparib solubility is pH independent below the pKa of 9.95, with an 
aqueous free base solubility of 0.7 mg/mL to 1.1 mg/mL across the physiological pH 
range. 
Niraparib is supplied in HDPE bottles with child resistant closures.  
Niraparib does not contain gluten. 
 
6.1.2 
Ipilimumab 
For complete details regarding ipilimumab, please refer to the Investigator’s Brochure and 
FDA approved label. 
 
Ipilimumab dose will be 3mg/kg IV every 3 weeks over a 30-minute period, for a total of 
four doses. Sites should make every effort to target infusion timing to be as close to 30 
minutes as possible. However, given the variability of infusion pumps, a window of -5 
minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5min/+10min). 
Ipilimumab (BMS-734016, MDX-010) is a fully human IgG1κ consisting of 4 polypeptide 
chains; 2 identical heavy chains primarily consisting of 447 amino acids each with 2 
identical kappa light chains consisting of 215 amino acids each linked through inter-chain 
disulfide bonds. The physical and chemical properties of ipilimumab drug substance are 
provided in the table below. 
 

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BMS Number 
734016 
Molecular Weight 
147,991 Daltons 
Appearance 
Clear to slightly opalescent, colorless to pale yellow liquid, 
may contain particles 
Solution pH 
7.0 
pI 
The isoelectric focusing analysis generates a banding 
pattern in the pI range of 8.5 to 8.8, with the major isoform 
at an approximate pI of 8.7. 
 
Ipilimumab injection, 200 mg/40 mL (5 mg/mL), is formulated as a clear to slightly 
opalescent, colorless to pale yellow, sterile, non-pyrogenic, single-use, isotonic aqueous 
solution that may contain particles. Ipilimumab injection, 50 mg/10 mL or 200 mg/40 mL, 
is supplied in 10-cc or 50-cc Type I flint glass vials, respectively, stoppered with gray butyl 
stoppers and sealed with aluminum seals. The drug product is formulated at a 
concentration of 5 mg/mL at a pH of 7.0. 
 
6.1.3 
Rationale for Shorter Infusion Time for Ipilimumab 
Long infusion times place a burden on patients and treatment centers. It is now established 
that ipilimumab can be safely administered using shorter infusion times of 30 minutes’ 
duration. This will limit the burden to patients. Recent data has shown that ipilimumab can 
be safely administered over a 30 minute period with acceptably low incidence of infusion 
related reactions [16]. 
Overall, a change in safety profile is not anticipated with 30-minute infusions of 
ipilimumab. 
 
6.2 
Intervention Regimen 
 
6.2.1 
Niraparib + Ipilimumab (Arm A) 
Niraparib 200mg PO daily on days 1-21 of each 21-day cycle. 
Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only. 
 
6.2.2 
FOLFIRI (Arm B) 
 
5-Fluorouracil, folinic acid, and irinotecan (FOLFIRI) will be administered as per 
standard institutional guidelines. Treatment is given every 14 days and each cycle is 28 
days in length. 
 
6.2.3 
Starting Dose and Dose Modifications of Protocol-Specified Treatment  
 
6.2.4.1 
Niraparib 
The starting dose of niraparib will be 200mg PO daily on days 1-21 of each 21-day cycle. 
Table 2. 
Recommended Niraparib Dose Reductions for Adverse Reactions 
 
Dose Level 
Dose 
Starting Dose 
200mg/day 
First (and only) Dose Reduction 
100mg/day 

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Refer to Section 6.2.5.1 for specific instructions regarding Niraparib dose modifications. 
Patients may not re-escalate once they have been dose reduced. 
 
6.2.4.2 
Ipilimumab 
The starting dose of ipilimumab will be 3mg/kg IV on days 1 of each 21-day cycle, for a 
total of four cycles. 
There are no recommended dose reductions for ipilimumab. Refer to Section 6.2.5.2 for 
specific instructions regarding when to hold and restart therapy for adverse reactions. 
 
6.2.4.3 
FOLFIRI 
Chemotherapy will be given as per standard institutional guidelines. 
 
 
6.2.4 
Dose Modification Criteria and Criteria for Stopping Treatment 
Dose adjustments are for AEs deemed related to the study medications. If, in the opinion 
of the treating Investigator, a toxicity is thought to be unrelated to study medications, no 
dose adjustments for the study medications are necessary. 
For any toxicity leading to discontinuation of Niraparib or Ipilimumab as described below, 
subjects may continue on the other study agent with approval of the PI. 
For any toxicity (regardless of grade) that, despite optimal supportive care, is felt by the 
treating Investigator to present a risk to the patient safety, additional dose reduction, 
treatment delay, or treatment discontinuation is permitted at the discretion of the treating 
Investigator. 
 
6.2.5.1 
Niraparib Dose Modifications 
Table 3. 
Niraparib Dose Modification for Non-hematologic Adverse Reactions 
 
Non-hematologic CTCAE* ≥ Grade 3 treatment- 
related 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. 
Resume niraparib at a reduced dose as per 
Section 6.2.4.1. One dose reduction is permitted. 
CTCAE ≥ Grade 3 treatment-related adverse 
reaction event lasting more than 28 days while 
patient is administered niraparib 100 mg/day 
Discontinue medication. 
*CTCAE = Common Terminology Criteria for Adverse Events 
 
Table 4. 
Niraparib Dose Modifications for Hematologic Adverse Reactions 
 
Test complete blood counts weekly for the first month, monthly for the next 11 months of treatment and 
periodically after this time. Medical and supportive therapy should be optimized for management of toxicities.
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. 
Resume niraparib at same or reduced dose per Section 6.2.4.1. 
If platelet count is <75,000/µL, resume at a reduced dose. 

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Second occurrence: 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
weekly until platelet counts return to ≥100,000/µL. 
Resume niraparib at a reduced dose. 
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. 
Neutrophil <1,000/µL 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
weekly until neutrophil counts return to ≥1,500/µL. 
Resume niraparib at a reduced dose. 
Discontinue niraparib if neutrophil 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. 
Hemoglobin <8 g/dL 
Withhold niraparib for a maximum of 28 days and monitor blood counts 
weekly until hemoglobin returns to ≥9 g/dL. 
Resume niraparib at a reduced dose. 
Discontinue niraparib if hemoglobin 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. 
Hematologic adverse 
reaction requiring 
transfusion or 
hematopoietic growth 
factor support 
For patients with platelet count ≤10,000/μL, platelet transfusion should be
considered. If there are other risk factors such as co-administration of
anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or
transfusion at a higher platelet count. 
Resume niraparib at a reduced dose. 
Confirmed diagnosis of MDS* 
or AML† 
Permanently discontinue niraparib. 
*MDS = myelodysplastic syndrome 
†AML = acute myeloid leukemia 
 
If dose interruption or modification is required at any point on study because of 
hematologic toxicity, weekly blood draws for CBC will be monitored until the AE resolves. 
To ensure safety once drug has been resumed, weekly blood draws for CBC also will be 
required for an additional 4 weeks after the AE has been resolved to the specified levels, 
after which monitoring every 4 weeks may resume. 
Any patient requiring transfusion of platelets or red blood cells (1 or more units) or 
hematopoietic growth factor support must undergo a dose reduction upon recovery if 
study treatment is resumed. 
The patient should undergo further hematologic investigation (1) if frequent transfusions 
are required or (2) if the treatment-related hematologic toxicities have not recovered to 
CTCAE Grade 1 or less after 4 weeks. 
For major surgery while on treatment, up to 28 days of study treatment interruption is 
allowed.  
Once the dose of study treatment has been reduced, any re-escalation must be discussed 
with the medical monitor. 
All dose interruptions and reductions (including any missed doses), and the reasons for 
the reductions/interruptions, are to be recorded. 
 
6.2.5.2 
Ipilimumab Dose Modifications 

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Table 5. 
GI Adverse Event Management Algorithm for Ipilimumab 
 
Grade of Diarrhea/Colitis 
(CTCAE v5) 
Management 
Follow-up 
Grade 1 
Diarrhea: <4 stools/day 
over baseline 
Colitis: asymptomatic 
• 
Continue 
immunotherapy (I-O) 
per protocol 
• Symptomatic treatment 
• Close monitoring for worsening 
of symptoms 
• Educate patient to report 
worsening immediately 
If worsens: 
• Treat as Grade 2 or 3-4 
Grade 2 
Diarrhea: 4-6 stools per day 
over baseline; IV fluids 
indicated 
<24 hrs; not interfering 
with ADL 
Colitis: abdominal pain; blood 
in stool 
• Hold I-O therapy 
• Symptomatic treatment 
If improves to grade 1: 
• Resume I-O therapy per protocol 
If persists > 5-7 days or recur: 
• 0.5-1.0 mg/kg/day 
methylprednisolone or oral 
equivalent 
• When symptoms improve to grade 
1, taper steroids over at least 1 
month, consider prophylactic 
antibiotics for opportunistic 
infections, and resume I- O 
therapy per protocol. 
If worsens or persists > 3-5 days with 
oral steroids: 
• Treat as Grade ¾ 
Grade 3-4 
Diarrhea (G3): ≥7 stools per 
day over baseline; 
incontinence; IV fluids ≥24 
hrs; interfering with ADL 
Colitis (G3): severe 
abdominal pain, medical 
intervention indicated, 
peritoneal signs 
G4: life-threatening, 
perforation 
• Discontinue I-O therapy 
per protocol 
• 1.0 to 2.0 mg/kg/day 
methylprednisolone IV or 
IV equivalent 
• Add prophylactic 
antibiotics for 
opportunistic infections 
• Consider lower endoscopy 
If improves: 
• Continue steroids until grade 1, 
then taper over at least 1 month 
If persists > 3-5 days, or recurs after 
improvement: 
• Add infliximab 5 mg/kg (if 
no contraindication). 
Note: Infliximab should not be 
used in cases of perforation or 
sepsis 
 
Table 6. 
Renal Adverse Event Management Algorithm for Ipilimumab 
 
Grade of Creatinine Elevation 
(CTCAE v5) 
Management 
Follow-Up 

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Grade 1 
Creatinine >ULN and > 
than baseline but ≤1.5x 
baseline 
• Continue I-O therapy 
per protocol 
• Monitor creatinine weekly 
If returns to baseline: 
• Resume routine 
creatinine monitoring 
per protocol 
If worsens: 
• Treat as Grade 2 or 3-4 
Grade 2-3 
Creatinine > 1.5x baseline to 
≤6x ULN 
• Hold I-O therapy 
• Monitor creatinine every 
2-3 days 
• 0.5-1.0 mg/kg/day 
methylprednisolone IV or 
oral equivalent 
• Consider renal biopsy 
with nephrology consult 
If returns to Grade 1: 
Taper steroids over at least 1 
month, consider prophylactic 
antibiotics for opportunistic 
infections, resume I-O therapy 
and routine creatinine 
monitoring per protocol. 
If elevations persist> 7 days or 
worsen: 
• Treat as Grade 4 
Grade 4 
Creatinine >6x 
ULN 
• Discontinue I-O therapy 
per protocol 
• Monitor creatinine daily 
• 1.0-2.0mg/kg/day 
methylprednisolone IV or 
IV equivalent 
• Consult nephrology 
• Consider renal biopsy 
If returns to Grade 1: 
• Taper steroids over at 
least 1 month and add 
prophylactic antibiotics for 
opportunistic infections. 

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Table 7. 
Pulmonary Adverse Event Management Algorithm for Ipilimumab 
 
Grade of Pneumonitis 
(CTCAE v5) 
Management 
Follow-Up 
Grade 1 
Radiographic changes 
only 
• Consider holding I-O therapy 
• Monitor for symptoms every 
2-3 days 
• Consider Pulmonary and 
ID consults 
• Re-image at least every 3 
weeks If worsens: 
• Treat as Grade 2 or 3-4 
Grade 2 
Mild to moderate new 
symptoms 
• Hold I-O therapy 
• Pulmonary and ID consults 
• Monitor symptoms 
daily, consider 
hospitalization 
• 1.0mg/kg/day 
methylprednisolone IV or 
oral equivalent 
• Consider bronchoscopy, 
lung biopsy 
• Re-image every 1-3 
days If improves: 
• When symptoms return to 
near baseline, taper steroids 
over at least 1 month and 
then resume I- O therapy per 
protocol and consider 
prophylactic antibiotics 
If not improving after 2 weeks or 
worsening: 
• Treat as Grade 3-4 
Grade 3-4 
Severe new symptoms; 
New/worsening hypoxia; 
Life- threatening 
• Discontinue I-O therapy 
per protocol 
• Hospitalize 
• Pulmonary and ID consults 
• 2-4mg/kg/day 
methylprednisolone IV or 
IV equivalent 
• Add prophylactic antibiotics 
for opportunistic infections 
• Consider bronchoscopy, 
lung biopsy 
If improves to baseline: 
• Taper steroids over at 
least 6 weeks 
If not improving after 48 hours or 
worsening: 
• Add additional 
immunosuppressi
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Table 8. 
Hepatic Adverse Event Management Algorithm for Ipilimumab 
 
Grade of Liver Test* Elevation 
(CTCAE v5) 
Management 
Follow-Up 
Grade 1 
AST or ALT >ULN – 3x ULN 
and/or T.bili >ULN – 1.5x ULN 
• Continue I-O therapy 
per protocol 
• Continue LFT monitoring 
per protocol 
If worsens: 
• Treat as Grade 2 or Grade 3-4 
Grade 2 
AST or ALT > 3x to ≤5x ULN 
and/or T.bili >1.5 to ≤ 3x ULN 
• Hold I-O therapy 
• Increase frequency of 
monitoring to every 3 days 
If returns to baseline: 
• Resume routine monitoring, 
resume I-O therapy per 
protocol 
If elevation persists >5-7 
days or worsens: 
• 0.5-1mg/kg/day 
methylprednisolone or oral 
equivalent and when LFT 
returns to grade 1 or baseline, 
taper steroids over at least 1 
months, consider prophylactic 
antibiotics for opportunistic 
infections, and resume I-O 
therapy per protocol 
Grade 3-
4 
AST or ALT > 5x ULN or T.bili 
>3x ULN 
• Discontinue I-O therapy** 
• Increase frequency of 
monitoring to every 1-2 days 
• 1.0-2.0mg/kg/day 
methylprednisolone IV or 
IV equivalent*** 
• Add prophylactic antibiotics 
for opportunistic infections 
• Consult gastroenterologist 
If returns to grade 2: 
• Taper steroids over at least 
one month 
If does not improve in >3-5 
days, worsens or rebounds: 
• Add mycophenolate mofetil 
1g BID 
• If no response within an 
additional 3-5 days, 
consider other 
immunosuppressants per 
local guidelines. 
* Exceptions/Notes: 
• If a subject has a baseline AST or ALT that is within normal limits, delay dosing for drug-related 
Grade ≥ 2 toxicity (2 grade shift) 
• If a subject has baseline AST or ALT within the Grade 1 toxicity range, delay dosing for drug-related 
Grade≥ 3 toxicity (2 grade shift) 
• If a subject has baseline AST or ALT within the Grade 2 toxicity range, delay dosing for a two-fold 
drug- related increase in AST or ALT or for AST or ALT values 8x ULN (whichever is lower). 
 
**I-O therapy may be delayed rather than discontinued if AST/ALT ≤8x ULN or T.bili ≤5x ULN 
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Table 9. 
Endocrinopathy Management Algorithm for Ipilimumab 
 
Asymptomatic TSH Elevation 
• Continue I-O therapy per protocol 
• If TSH <0.5x LLN or TSH > 2x ULN, or consistently out of range 
in 2 subsequent measurements: include fT4 at subsequent cycles 
as clinically indicated; consider endocrinology consult 
Symptomatic Endocrinopathy 
• Evaluate endocrine function 
• Consider pituitary scan 
Symptomatic with abnormal 
labs/pituitary scan: 
• Hold I-O therapy 
• 1-2mg/kg/day 
methylprednisolone IV or 
PO equivalent 
• Initiate appropriate 
hormone therapy 
No abnormal lab/pituitary MRI 
scan but symptoms persist: 
• Repeat labs in 1-3 
weeks/MRI in 1 month 
If improves (with or without 
hormone replacement): 
• Taper steroids over at least 1 
month and consider 
prophylactic antibiotics for 
opportunistic infections 
• Resume I-O therapy per 
protocol 
• Patients with adrenal 
insufficiency may need to 
continue steroids with 
mineralocorticoid 
component 
Suspicion of Adrenal Crisis 
(e.g. severe dehydration, 
hypotension, shock out of 
proportion to current illness) 
• Hold or discontinue I-O therapy per protocol 
• Rule out sepsis 
• Stress dose IV steroids with mineralocorticoid activity 
• IV fluids 
• Consult endocrinologist 
• If adrenal crisis ruled out, then treat as above for 
symptomatic endocrinopathy 

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Table 10. 
Skin Adverse Event Management Algorithm for Ipilimumab 
 
Grade of Rash (CTCAE v5) 
Management 
Follow-Up 
Grade 1-2 
Covering ≤30% BSA* 
• Symptomatic therapy (e.g. 
antihistamines, topical 
steroids) 
• Continue I-O therapy 
per protocol 
If persists >1-2 weeks or recurs: 
• Consider skin biopsy 
• Delay I-O therapy per protocol 
• Consider 0.5-1.0mg/kg/day 
methylprednisolone IV or oral 
equivalent. Once improved, 
taper steroids over at least 1 
months, consider prophylactic 
antibiotics for opportunistic 
infections, and resume I-O 
therapy per protocol. 
If worsens: 
• Treat as Grade 3-4 
Grade 3-4 
Covering >30% BSA; 
Life threatening 
consequences 
• Hold or discontinue I-O 
therapy per protocol 
• Consider skin biopsy 
• Dermatology consult 
• 1.0-2.0mg/kg/day IV 
methylprednisolone or 
IV equivalent 
If improves to Grade 1: 
• Taper steroids over at 
least 1 month and add 
prophylactic antibiotics for 
opportunistic infections 
• Resume I-O therapy per 
protocol 
*Refer to NCI CTCAE v5 for term-specific grading criteria 

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Table 11. 
Neurological Adverse Event Management Algorithm for 
Ipilimumab 
 
Grade of Neurological Toxicity 
(CTCAE v5) 
Management 
Follow-Up 
Grade 1 
Asymptomatic or mild 
symptoms; intervention not 
indicated 
• Continue I-O therapy 
per protocol 
• Continue to monitor the 
patient. 
If worsens: 
• Treat as Grade 2 or 3-4 
Grade 2 
Moderate symptoms; 
limiting instrumental ADLs 
• Hold I-O therapy 
• Treat symptoms per 
local guidelines 
• Consider 0.5-
1.0mg/kg/day 
methylprednisolone IV or 
PO equivalent 
If improves to baseline: 
• Resume I-O therapy per 
protocol when improved to 
baseline 
If worsens: 
• Treat as Grade 3-4 
Grade 3-4 
Severe symptoms; limiting 
self- care ADL; Life-
threatening 
• Discontinue I-O therapy 
per protocol 
• Obtain neurology consult 
• Treat symptoms per 
local guidelines 
• 1.0-2.0mg/kg/day IV or IV 
equivalent 
methylprednisolone 
• Add prophylactic antibiotics 
or opportunistic infections 
If improves to Grade 2: 
• Taper steroids over at 
least 1 month 
If worsens of atypical 
presentation: 
• Consider IVIG or other 
immunosuppressive 
therapies per local 
guidelines 
 
 
Hepatic Impairment (Ipilimumab): 
Clearance of ipilimumab in subjects with mild and moderate hepatic impairment was 
similar to that of subjects with normal hepatic function. 
 
6.2.5.3 
Dose Modifications for FOLFIRI 
Dose modifications for FOLFIRI will be performed per standard institutional guidelines at 
the discretion of the treating investigator. 
 
 
6.2.5 
Treatment Beyond Progression 
If the patient has met criteria for radiologic progression by RECIST v1.1, but the patient is 
still receiving benefit from study therapy (e.g., patient has mixed radiologic response or is 
continuing to have symptomatic benefit without decline in performance status) according 
to the Investigator, then continuation of treatment will be considered. In such cases, the 
decision to continue will be made by the Investigator, and must be documented prior to 
continuing treatment with study treatment. Patients will continue to have all protocol-

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required assessments specified in the Schedule of Assessments Table. Treatment must 
be discontinued when the patient is no longer benefiting from therapy, as per the 
Investigator. 
 
6.3 
Prior and Concomitant Therapies 
Patients who have received prior treatment with PARP inhibitors and/or anti-CTLA4 
agents are not eligible to participate in this study. Patients who have demonstrated 
resistance of their pancreatic adenocarcinoma to FOLFIRINOX are not eligible to 
participate in this study. 
During the study, supportive care (e.g., antiemetics; analgesics of pain control) may be 
used at the investigator’s discretion and in accordance with institutional procedures. 
All procedures performed (e.g., thoracentesis, paracentesis etc.) and medications used 
during the study must be documented on the electronic case report form (eCRF). 
 
6.3.1 
Anticancer or Experimental Therapy 
No other concomitant therapies for pancreatic cancer (including chemotherapy, radiation, 
hormonal treatment, antibody or other immunotherapy, gene therapy, vaccine therapy, 
angiogenesis inhibitors, or other experimental drugs) of any kind will be permitted while 
the patient is participating in the study. 
Ongoing therapies for previously treated non-pancreatic cancer (e.g., hormonal treatment 
for prior breast cancer) are permitted. The data on niraparib in combination with cytotoxic 
medicinal products are limited. Therefore, caution should be taken if niraparib is used in 
combination with other cytotoxic medicinal products; review with an oncological 
pharmacist is recommended in these cases. 
Palliative radiotherapy (excluding the pelvic region and/or palliative radiotherapy 
encompassing > 20% of the bone marrow within 4 weeks 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. 
 
6.3.2 
Hematopoietic Growth Factors and Blood Products 
Hematopoietic colony-stimulating factors for treatment of cytopenias should be 
administered according to institutional guidelines. Transfusion thresholds for blood 
product support will be in accordance with institutional guidelines. Prophylactic cytokine 
(Granulocyte Colony-Stimulating Factor [GCSF]) administration may be administered 
according to local guidelines and Section 6.2.5.1. 
 
6.3.3 
Bisphosphonates 
Bisphosphonates are permitted. 
 
6.3.4 
Anticoagulants 
Anticoagulants are permitted. The niraparib safety profile includes risk for 
thrombocytopenia; therefore, patients should be advised to use caution with 
anticoagulation and antiplatelet drugs.

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6.3.5 
Other Concomitant Medications 
Therapies considered necessary for the patient’s well-being may be given at the 
discretion of the investigator. Other concomitant medications, except for analgesics, 
chronic treatments for concomitant medical conditions, or agents required for life-
threatening medical problems, should be avoided. Herbal and complementary therapies 
should not be encouraged because of unknown side effects and potential drug 
interactions. 
 
6.3.6 
Substrates of P-glycoprotein 
Niraparib weakly induces Cytochrome P450 (CYP)1A2 in vitro and is a relatively poor 
substrate for P-glycoprotein (P-gp); therefore, investigators are advised to use caution 
with the substrates for CYP1A2 with a narrow therapeutic range, i.e. theophylline and 
tizanidine. The niraparib safety profile includes risk for thrombocytopenia; therefore, 
patients should be advised to use caution with anticoagulation and antiplatelet drugs. 
 
6.3.7 
Vaccines 
The combination of niraparib with vaccines or immunosuppressant agents has not been 
studied. However, if in the opinion of the investigator, the benefit of a non-live vaccine 
outweighs the risk to the patient, vaccines may be administered. 
 
6.4 
Warnings and Precautions 
 
6.4.1 
Niraparib 
 
6.4.1.1 
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) 
For the OC Pooled Safety Population in the monotherapy studies analysis, MDS/AML 
events were searched using MedDRA preferred terms for Myelodysplastic syndrome and 
Acute myeloid leukemia. In total, 26 niraparib-treated participants (1.9%) were reported 
to have MDS and/or AML as of the data cutoff, and all but one of these events were 
deemed related or likely related to study drug by the investigator. The majority of those 
participants were from the NOVA study (14 participants); 9 participants were in the PRIMA 
study, and 3 participants were in the QUADRA study. Three niraparib-treated participants 
experienced events of both MDS and AML, all related to treatment; in 1 of these 
participants, an event of AML was fatal. 
Seven placebo-treated participants (1.7%) were reported to have MDS and/or AML (MDS, 
5 participants; AML, 2 participants). In the niraparib-treated population, 26 participants 
(1.9%) experienced MDS/AML events (MDS, 17 participants [1.2%]; AML, 12 participants 
[0.9%]). These events were fatal in 9 participants (MDS, 4 participants [0.3%]; AML, 5 
participants [0.4%]). Fatal SAEs of MDS were considered treatment-related in 4 
participants (0.3%) of the niraparib-treated population. Fatal AML events were considered 
treatment-related in 4 participants (0.3%) of the niraparib-treated population. Grade 4 
events of MDS that were considered treatment-related were reported in 6 participants 
(0.4%) in the niraparib-treated population. Grade 4 events of AML that were considered 
treatment-related by the Investigator were reported in 8 participants (0.6%) in the 
niraparib-treated population (includes 1 event of uncoded AML). 
 
6.4.1.2 
Hypertension, including Hypertensive Crisis 

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Hypertension, including hypertensive crisis, has been reported with the use of niraparib. 
Pre- existing hypertension should be adequately controlled before starting niraparib 
treatment. Blood pressure and heart rate should be monitored at least weekly for the first 
2 months, then monthly for the first year and periodically thereafter during treatment with 
niraparib. 
Hypertension should be medically managed with antihypertensive medicinal products as 
well as adjustment of the niraparib dose, if necessary. In the clinical program, blood 
pressure measurements were obtained on Day 1 of each 28-day cycle while the patient 
remained on niraparib. In most cases, hypertension was controlled adequately using 
standard discontinued in case of hypertensive crisis or if medically significant 
hypertension cannot be adequately controlled with antihypertensive therapy. 
 
6.4.1.3 
Posterior Reversible Encephalopathy Syndrome (PRES) 
There have been rare reports (0.09% of clinical trial patients) 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 (MRI). In patients developing PRES, treatment of specific symptoms 
including control of hypertension is recommended, along with discontinuation of niraparib. 
The safety of reinstating niraparib therapy in patients previously experiencing PRES is 
not known. 
 
6.4.1.4 
Embryo-fetal Toxicity 
No embryo-fetal toxicity study has been performed. Based on its mechanism of action, 
niraparib could cause embryonic or fetal harm when administered to a pregnant woman. 
Refer to Section 5.3. 
 
6.4.1.5 
Pregnancy and Contraception 
Refer to Section 5.3. 
 
6.4.1.6 
Overdosage 
An overdose is defined as the accidental or intentional ingestion or infusing of any dose 
of study treatment that exceeds the dose described in the protocol. Overdoses are not 
considered AEs; however, all overdoses should be recorded on a Special Situations 
Report Form or its designated representative, within 24 hours. An overdose should be 
reported even if it does not result in an AE. 
There is no specific treatment in the event of niraparib overdose, and symptoms of 
overdose are not established. In the event of an overdose, physicians should follow 
general supportive measures and should treat symptomatically. 
 
6.4.1.7 
Other Potential Risks of Niraparib 
The following adverse reactions (all CTCAE grades) have been reported in ≥20% of 
patients who received niraparib: anemia, thrombocytopenia, nausea, constipation, 
vomiting, fatigue, platelet count decreased, decreased appetite, headache, and insomnia. 
The median exposure to niraparib in these patients was 250 days. 

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The following adverse reactions and laboratory abnormalities have been identified in ≥10 
to <20% of the 367 patients receiving niraparib: neutropenia, palpitations, asthenia, 
neutrophil count decreased, dizziness, dysgeusia, dyspnea, cough and hypertension. 
The following adverse reactions and laboratory abnormalities have been identified in ≥1 
to <10% of the 367 patients receiving niraparib: tachycardia, dry mouth, mucosal 
inflammation, white blood cell count decreased, aspartate aminotransferase increased, 
alanine aminotransferase increased and photosensitivity reaction. 
 
 
6.4.2 
Ipilimumab 
Blockade of CTLA-4 by ipilimumab leads to T-cell activation, with the potential for clinical 
inflammatory 
AEs 
primarily 
involving 
the 
skin 
(dermatitis/pruritus), 
GI 
tract 
(diarrhea/colitis), liver (hepatitis), endocrine glands (e.g., hypophysitis and adrenal or 
thyroid abnormalities), and other less frequent organs (e.g., uveitis/episcleritis). The 
majority of these inflammatory AEs initially manifested during treatment; however, a 
minority occurred weeks to months after discontinuation of ipilimumab. The majority of 
the inflammatory AEs is reversible with the guidance issued below. In rare cases, these 
inflammatory AEs may be fatal. 
Patients should be assessed for signs and symptoms of enterocolitis, dermatitis, 
neuropathy, and endocrinopathy, and clinical chemistries (including liver function, 
adrenocorticotropic hormone [ACTH] level, and thyroid function tests) should be 
evaluated at baseline and before each dose of ipilimumab. 
During evaluation of a suspected inflammatory AE, all efforts should be made to rule out 
neoplastic, infectious, metabolic, toxin, or other etiologic causes. Serological, 
immunological, imaging, and biopsy with histology (e.g., biopsy-proven lymphocytic) data 
should be used to support the diagnosis of an immune-mediated toxicity or support an 
alternative cause of the AE. 
In general, for severe inflammatory AEs, ipilimumab should be permanently discontinued, 
and systematic high-dose corticosteroid therapy should be initiated. For moderate 
immune-mediated AEs, ipilimumab should be held or delayed, and moderate-dose 
corticosteroids should be considered. 
Based on limited current clinical experience, corticosteroids do not appear to adversely 
affect the anti-tumor response. For example, disease control was maintained in subjects 
with objective responses who received corticosteroid administration for concomitant 
serious inflammatory AEs. 
The management guidelines for general inflammatory GI, liver, skin, endocrine, and 
neurological toxicities are provided in this Protocol in Section 6.2. 
 
6.4.3.1 
Gastrointestinal Toxicities 
The most common site for ipilimumab-induced GI toxicity was the lower GI tract, and the 
most common presentation was mild to severe diarrhea or colitis with occasional bloody 
stools. In some cases, diarrhea began as mild and then worsened. Constipation was 
rarely associated with ipilimumab administration. Delay in corticosteroid treatment may 
be associated with a poor outcome for patients with high-grade diarrhea. 
 
6.4.3.2 
Liver Toxicities 

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Subjects receiving ipilimumab may develop elevations in LFTs in the absence of clinical 
symptoms. Occasionally, patients may present with symptoms, including right upper 
quadrant abdominal pain or unexplained vomiting. Most cases of inflammatory hepatitis 
responded to high-dose corticosteroids (IV route recommended). 
All patients require close medical monitoring of LFTs and immediate intervention to 
prevent serious sequelae. LFTs should be routinely assessed and reviewed prior to 
administration of each dose of ipilimumab. 
 
6.4.3.3 
Endocrine Toxicities 
The most common inflammatory endocrine toxicities occurring in ipilimumab-treated 
subjects are hypophysitis and hypopituitarism. Secondary cortisol deficiency 
(hypoadrenalism), 
hypothyroidism 
or 
thyroiditis, 
and, 
less 
commonly, 
other 
endocrinopathies may occur concomitantly with hypophysitis; however, these may also 
present as the only or as primary endocrinopathy. Most patients with hypopituitarism 
presented with nonspecific complaints such as fatigue, visual field defects, confusion, or 
impotence. Some patients have had headache as the predominant presentation. The 
majority of subjects with hypopituitarism demonstrated enlarged pituitary glands based 
on brain magnetic resonance imaging (MRI). Low ACTH and cortisol were the most 
common biochemical abnormality; abnormal (mostly low) thyroid-stimulating hormone 
(TSH), free thyroxine (fT4), triiodothyronine (T3), testosterone, or prolactin have also 
been reported in some subjects. Symptoms of hypopituitarism and other endocrine 
toxicities were generally controlled with appropriate hormone replacement. 
 
6.4.3.4 
Skin Toxicities 
The most common inflammatory skin toxicities occurring in ipilimumab-treated subjects 
are rash and pruritus, mostly mild to moderate in severity. Two cases of fatal treatment-
related toxic epidermal necrolysis have been reported in clinical trials. Post-marketing 
surveillance identified a fatal toxic epidermal necrolysis event in one subject who received 
ipilimumab after experiencing a severe or life-threatening skin adverse reaction on a prior 
cancer immune- stimulating therapy. Caution should be used when considering the use 
of ipilimumab in patients who have previously experienced a severe or life-threatening 
skin adverse reaction on a prior cancer immune-stimulating therapy (CARES Database 
No. 21333844). 
 
6.4.3.5 
Neurological Toxicities 
Neurological manifestations in subjects treated with ipilimumab may include motor and/or 
sensory neuropathy. Given the difficulty in definitely establishing an inflammatory 
etiology, alternative etiologies (e.g., tumor progression) should be excluded. Fatal 
Guillain-Barre syndrome and cases of myasthenia gravis have been reported in clinical 
trials of ipilimumab. Unexplained motor neuropathy, muscle weakness, or sensory 
neuropathy should be evaluated, and non-inflammatory causes such as disease 
progression, infections, metabolic disorders, and medications should be excluded. 
 
6.4.3.6 
Other Toxicities 
Ocular inflammation, manifested as Grade 2 or 3 episcleritis or uveitis, was associated 
with concomitant diarrhea in a few subjects (< 1%) and occasionally occurred in the 
absence of clinically apparent GI symptoms. 
Other presumed inflammatory events reported include, but were not limited to, the 

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following (individually reported for < 1% of subjects unless noted otherwise): 
arthritis/arthralgias, pneumonitis, pancreatitis, autoimmune (aseptic) meningitis, 
autoimmune nephritis, pure red cell aplasia, non-infective myocarditis, polymyositis, 
eosinophilia, pericarditis, urticaria (2%), large intestinal ulcer, esophagitis, acute 
respiratory distress syndrome, renal failure, infusion reactions, and MG. 
 
6.5 
Receipt 
Niraparib and ipilimumab will be received by the Investigational Drug Pharmacy at each 
clinical site. 
 
6.6 
Storage 
 
6.6.1 
Niraparib 
Niraparib is supplied by GSK in high-density polyethylene (HDPE) bottles with child- 
resistant plastic closures. The study treatment will be open-label and will not be 
participant-specific. Detailed information on the product can be found in the Niraparib 
Storage and Handling Guidelines. 
All study treatment supplies must be stored in accordance with the manufacturer’s 
instructions and package labeling. Until dispensed to the participants, the study treatment 
will be stored in a securely locked area, accessible to authorized personnel only. 
 
6.6.2 
Ipilimumab 
Ipilimumab Injection, 50mg/10mL (5 mg/mL) or 200 mg/40 mL (5 mg/mL), must be stored 
refrigerated (2°C to 8°C) and protected from light. Ipilimumab injection must not be frozen. 
Partially used vials or empty vials of ipilimumab injection should be discarded at the site 
according to appropriate drug disposal procedures. 
Ipilimumab injection may be stored undiluted (5 mg/mL) or following dilution in 0.9% 
Sodium Chloride Injection, or 5% Dextrose Injection in PVC, non-PVC/non-DEHP or glass 
containers for up to 24 hours (at 2°C to 8°C) or room temperature/room light. 
Recommended safety measures for preparation and handling include protective clothing, 
gloves, and safety cabinets. 
 
6.7 
Administration and Accountability 
Niraparib: An adequate quantity of niraparib will be provided to the patient to last until 
the next scheduled visit. Patients will be instructed to record daily doses taken or not 
taken in a provided institutional dosing diary, and will be instructed to bring their niraparib 
tablets, all containers (empty, partially used and/or unopened) and dosing diary to the 
next scheduled visit for reconciliation by site personnel. Food does not significantly affect 
the absorption of niraparib; therefore, niraparib may be taken without regard to meals. If 
a patient vomits or misses a dose of niraparib, an additional dose should not be taken. 
The next dose should be taken at the regularly scheduled time. 
 
Ipilimumab is an injectable drug that will be administered in the clinic by clinical nursing 
staff. 
 

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FOLFIRI is an injectable chemotherapy combination that will be administered in the clinic 
by clinical nursing staff. 
 
6.8 
Subject Compliance Monitoring 
Documentation of dosing will be recorded in a study specific institutional dosing diary. 
Study site personnel will review dosing information with the patient (or legally authorized 
representative) on scheduled clinic visit days, providing instructions regarding dose, dose 
frequency and the number of tablets to be taken for each dose. Patients (or legally 
authorized representative) will be instructed to record dosing information for niraparib 
taken at home in the dosing diary and to bring the dosing diary and all unused tablets with 
them to scheduled clinic visits. A compliance check and tablet count will be performed by 
study personnel during clinic visits. Every effort should be made to ensure patients 
complete the dosing diary and return their study drug containers at the end of each cycle 
of treatment. In the event a patient has unused pills from the prior cycle, these may be 
re-dispensed. The coordinator will keep a record of returned pills and re-dispensed pills. 
It will not be considered a protocol deviation if a participant doesn't return their diary.  The 
study team will utilize the pharmacy drug accountability records to determine compliance 
to the study medication. 
 
6.9 
Return or Destruction of Investigational Product 
Upon completion or termination of the study, all unused and/or partially used 
investigational product will be destroyed on-site in accordance with standard policies for 
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7 STUDY PROCEDURES 
7.1 
Schedule of Assessments- ARM A (Niraparib + Ipilimumab) 
All procedures and assessments are to be completed within ±3 days of the scheduled time point 
Table 12. 
Schedule of Assessments – Arm A 
 
Procedurea 
Day -28 to Day -1 
(unless otherwise 
specified) 
C1D1b 
C1D8 
C2D1 
C3D1 
C4D1 
C5D1 and 
onward 
EOT 
30 Day 
FU 
90 Day 
FU 
LTFU 
Informed Consent 
X 
Randomization 
X 
Demographics/ Medical 
History; Evaluation of 
previously performed 
germline and somatic 
sequencingc 
X 
Physical Exam, Heightd, weight 
X 
X 
 
X 
X 
X 
X 
X 
ECOG PS 
X 
X 
 
X 
X 
X 
X 
X 
Vital Signse 
X 
X 
 
X 
X 
X 
X 
X 
Blood Pressure monitoringw 
X 
 
X 
X 
X 
X 
Adverse Eventsf 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant 
Medications and Procedures 
X 
X 
 
X 
X 
X 
X 
X 
Hematologyg 
Xh 
X 
X 
X 
X 
X 
X 
X 
Serum Chemistryi 
Xh 
X 
 
X 
X 
X 
X 
X 
Lipase 
X 
X 
 
X 
X 
X 
X 
X 
Magnesium 
X 
X 
 
X 
X 
X 
X 
X 
Phosphorus 
X 
X 
 
X 
X 
X 
X 
X 
TSH (Thyroid Function)j 
X 
X 
 
X 
X 
X 
X 
X 
CA 19-9 and/or CEAt 
X 
 
 
X 
X 
X 

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Procedurea 
Day -28 to Day -1 
(unless otherwise 
specified) 
C1D1b 
C1D8 
C2D1 
C3D1 
C4D1 
C5D1 and 
onwardy 
EOT 
30 Day  
FU 
90 Day  
FU 
LTFU 
Serum Pregnancy 
Test (WOCBP only) 
X 
 
 
X 
X 
X 
X 
 
HIV, Hepatitis B and 
C Testing 
X 
 
 
 
 
 
 
 
Disease Assessment/ Tumor 
Scansl 
X 
 
Xm 
Xm 
Xn 
Xo 
Archival Tissue (If availablep) 
X 
Tumor Tissue 
Biopsy (if 
safe/feasible) 
Xq 
 
 
 
Xr 
PBMC/Serum 
X 
Xx 
X 
X 
Xv 
Xv 
Xv 
Whole Blood 
Xv 
X 
X 
X 
Xv 
Xv 
Xv 
Niraparib Dispensation, 
Administration, 
Accountability 
X 
 
X 
X 
X 
X 
 
Ipilimumab Infusion 
X 
 
X 
X 
X 
Survival Status 
Xs 
Follow-Up for MDS/AML 
Xs 
Bone Marrow aspirate and 
biopsy sampleu 
X
u 
ALP = alkaline phosphatase, ALT = alanine transaminase, ANC = absolute neutrophil count, AST = aspartate transaminase, BUN = blood urea 
nitrogen, CR = complete response, CT = computed tomography, hrs = hours, MRI = magnetic resonance imaging, PET = positron emission 
tomography, PK = pharmacokinetics, PR = partial response, SAE = serious adverse event, WBC = white blood cell, WOCBP = women of childbearing 
potential 
a = Treatment cycles are 21 days. Unless otherwise specified, all assessments are to be completed within ±3 days of scheduled time point. Delay 
of treatment schedule up to 10 days, as allowed by the protocol, is permitted at the discretion of the treating Investigator with approval of the PI 
(e.g. toxicity, weather, vacation). 
b = Any procedures required on Day 1 of Cycle 1 may be omitted if completed ≤3 days earlier during the screening period. 
c = Patient’s medical record must include prior treatments received, date of progression, and radiology and/or medical report(s) to support assessment 
of disease progression, and, if applicable, intolerable toxicity to chemotherapy. Previously performed germline and somatic sequencing must be 
evaluated to ensure patient has no pathogenic germline or somatic variant in BRCA1, BRCA2, PALB2, RAD51C or RAD51D. 
d = Height at screening only; not required if previously recorded in the medical record 
e = Vital signs (blood pressure, pulse, and temperature) to be taken pre-dose on clinic visit days. Blood pressure and heart rate should be 
monitored at least weekly for the first 2 months, then monthly for the first year and periodically thereafter during treatment with niraparib. 

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f = AEs are recorded from the time of signing informed consent through 30 days after last dose of niraparib. Ongoing SAEs will be followed to 
resolution or until SAE stabilizes. 
g = Includes hemoglobin, hematocrit, WBC and differential (with ANC) and platelet count. Blood will be analyzed by a local laboratory. Weekly 
CBCs should be performed during the first four weeks of therapy and monthly for one year thereafter. 
h = to be performed ≤7 days prior to the first dose of therapy or prior to dosing on day 1 to confirm eligibility 
i = includes total protein, albumin, creatinine or estimated GFR using Cockgroft Gault formula, BUN, total bilirubin, ALP, ALT, AST, glucose, 
sodium, potassium, chloride, CO2, calcium, phosphorous, magnesium and lipase. Blood will be analyzed by a local laboratory. 
j = If TSH is abnormal, fT4 and T3 will be drawn. The patient will be clinically managed for thyroid abnormalities at the discretion of the investigator. 
l = Disease assessments should be performed at fixed intervals of every 9 weeks (+/- 7 days). Disease assessment to include clinical examination, 
and appropriate imaging techniques, including CT scans of the chest, abdomen and pelvis, with appropriate slice thickness per RECIST; other 
studies (MRI, X-ray, PET, and ultrasound) may be performed if required. Whenever possible, the same method used to detect lesions at baseline 
is to be used to follow the same lesions throughout the clinical study if possible. If a patient has known brain metastases, this disease should be 
evaluated at each required assessment. 
m = Tumor scans to be performed within 7 days prior to start of every 4th cycle or approximately every 9 weeks. Please refer to footnote “y” for 
procedures for stable patients who are stable following 17 cycles of treatment 
n = End of treatment CT scans should be performed if treatment was discontinued for reason other than radiologic disease progression and if previous 
tumor assessment scan was performed ≥8 weeks prior to EOT visit. 
o = If CT scans were not performed at End of Treatment or within 30 days prior to End of Treatment, a CT scan should be performed at the 30-
day follow-up visit. 
p = Archival tumor tissue, if available, will be collected and stored. (Note: This sample is not required to be submitted on Cycle 1, Day 1, 
but should be submitted as soon as possible after a patient begins treatment). 
q = A screening core tumor biopsy will be collected prior to C1D1 if deemed safe and feasible for those patients who pass the screening 
evaluation.  
r = A core tumor biopsy will be performed during treatment at cycle 4 day 1 if deemed safe and feasible +/- 7 days 
s = All patients discontinued from treatment, regardless of reason, should be followed every six months until death, loss to follow-up, withdrawal of 
consent from study, five years, or closure of the study. Follow-up can be performed via telephone, email, EMR review and/or office visit. 
t = Whichever is appropriate for the patient. Patients with a prior history of both markers being elevated will have both drawn serially as per the 
study calendar.  
u = For any patient diagnosed with MDS/AML while on study, a bone marrow aspirate/biopsy must be completed by a local hematologist. A whole 
blood sample will also be collected for cytogenetic analysis (mutations of select myeloid-associated genes). Testing completed as part of standard 
of care is sufficient as long as the methods are acceptable to the PI. The study site must receive a copy of the hematologist's report of aspirate/biopsy 
findings (which must include a classification according to WHO criteria) and other sample testing results related to MDS/AML. 
v = Blood samples for PBMC and whole blood will be collected according to the site lab manual. 
w= blood pressure should be monitored weekly for first 2 months, monthly for first year, and periodically thereafter  
x= PBMC research sample at C1D8 may be collected 
y = Patients on Arm A who are stable (as per the investigator) following 17 full cycles of treatment may go twelve weeks (ie four cycles) between 
clinical assessments and disease assessment imaging. For these patients, four cycles of niraparib may be dispensed at one time. However, all safety 
blood work must still be collected at D1 (+/- 3 days) of each cycle and will be reviewed by the research team. 
 
 
 
7.2 
Schedule of Assessments- ARM B (FOLFIRI) 

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All procedures and assessments are to be completed within ±3 days of the scheduled time point. 
Table 13. 
Schedule of Assessments – Arm B 
 
Procedurea 
Day -28 to Day -1 
(unless otherwise 
specified) 
C1D1b 
C1D8 
D15 of all 
cycles 
D1 of C2 
and 
Beyondy 
C4D1 
EOT 
30 Day  
FU 
LTFU 
Informed Consent 
X 
Randomization 
X 
Demographics/ Medical Historyc 
X 
Physical Exam, Heightd, weight 
X 
X 
 
 
X 
 
X 
ECOG PS 
X 
X 
 
 
X 
 
X 
Vital Signse 
X 
X 
 
X 
X 
 
X 
Adverse Eventsf 
X 
X 
 
X 
X 
 
X 
X 
 
Prior/Concomitant Medications 
and Procedures 
X 
X 
 
 
X 
 
X 
 
Hematologyg 
Xh 
X 
 
X 
X 
 
X 
Serum Chemistryi 
Xh 
X 
 
X 
X 
 
X 

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Procedurea 
Day -28 to Day -1 
(unless otherwise 
specified) 
C1D1b 
C1D8 
D15 of all 
cycles 
D1 of C2 
and 
Beyond 
C4D1 
EOT 
30 Day  
FU 
LTFU 
CA 19-9 and/or CEAt 
 
X 
 
 
X 
 
X 
 
 
Serum Pregnancy 
Test (WOCBP only) 
X 
 
 
 
 
 
 
 
 
HIV, Hepatitis B and 
C Testing 
X 
 
 
 
 
 
 
 
 
Disease Assessment/ Tumor 
Scansl 
X 
 
 
 
Xm 
 
Xn 
Xo 
 
Archival Tissue (If availablep) 
X 
 
 
 
 
 
 
 
 
Tumor Tissue Biopsy 
(if safe/feasible) 
Xq 
 
 
 
 
Xr 
 
 
 
PBMC/Serum 
 
X 
Xv 
 
Xu 
 
Xu 
 
 
Whole Blood 
 
X 
X 
 
X 
X 
X 
 
 
FOLFIRI Infusion 
 
X 
 
X 
X 
 
X 
 
 
Survival Status 
 
 
 
 
 
 
 
 
Xs 
ALP = alkaline phosphatase, ALT = alanine transaminase, ANC = absolute neutrophil count, AST = aspartate transaminase, BUN = blood urea 
nitrogen, CR = complete response, CT = computed tomography, hrs = hours, MRI = magnetic resonance imaging, PET = positron emission 
tomography, PK = pharmacokinetics, PR = partial response, SAE = serious adverse event, WBC = white blood cell, WOCBP = women of childbearing 
potential 
a = Treatment cycles are 28 days. Unless otherwise specified, all assessments are to be completed within ±3 days of scheduled time point. 
Delay of treatment schedule up to 10 days, as allowed by the protocol, is permitted at the discretion of the treating Investigator with approval of 
the PI (e.g. toxicity, weather, vacation). 
b = Any procedures required on Day 1 of Cycle 1 may be omitted if completed ≤3 days earlier during the screening period. 
c = Patient’s medical record must include prior treatments received, date of progression, and radiology and/or medical report(s) to support assessment 
of disease progression, and, if applicable, intolerable toxicity to chemotherapy.  Please collect smoking history as part of medical history 
d = Height at screening only 
e = Vital signs (blood pressure, pulse, and temperature) to be taken pre-dose on clinic visit days.  

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f = AEs are recorded from the time of signing informed consent through 30 days after last dose of 
chemotherapy. Ongoing SAEs will be followed to resolution or until SAE stabilizes. 
g = Includes hemoglobin, hematocrit, WBC and differential (with ANC) and platelet count. Blood will be 
analyzed by a local laboratory.  
h = to be performed ≤7 days prior to the first dose of therapy or prior to dosing on day 1 to confirm eligibility 
i = includes total protein, albumin, creatinine or estimated GFR using Cockgroft Gault formula, BUN, 
total bilirubin, ALP, ALT, AST, glucose, sodium, potassium, chloride, CO2, calcium, phosphorous, 
magnesium and lipase. Blood will be analyzed by a local laboratory. 
j = includes total protein, albumin, creatinine or estimated GFR using Cockgroft Gault formula, 
BUN, total bilirubin, ALP, ALT, AST, glucose, sodium, potassium, chloride, CO2, calcium, 
phosphorous, magnesium and lipase. Blood will be analyzed by a local laboratory. 
l = Disease assessment to include clinical examination, and appropriate imaging techniques, including 
CT scans of the chest, abdomen and pelvis, with appropriate slice thickness per RECIST; other studies 
(MRI, X-ray, PET, and ultrasound) may be performed if required. Whenever possible, the same method 
used to detect lesions at baseline is to be used to follow the same lesions throughout the clinical study. 
If a patient has known brain metastases, this disease should be evaluated at each required assessment. 
m = Tumor scans to be performed within 7 days prior to start of every 2nd cycle (i.e., odd numbered 
cycles starting with C3), or approximately every 8 weeks.  
n = End of treatment CT scans should be performed if treatment was discontinued for reason other than 
radiologic disease progression and if previous tumor assessment scan was performed ≥8 weeks prior to 
EOT visit. 
o = If CT scans were not performed at End of Treatment or within 30 days prior to End of Treatment, 
a CT scan should be performed at the 30-day follow-up visit. 
p = Archival tumor tissue, if available, will be collected and stored. (Note: This sample is not required 
to be submitted on Cycle 1, Day 1, but should be submitted as soon as possible after a patient begins 
treatment). 
q = A screening core tumor biopsy will be collected prior to C1D1 if deemed safe and feasible 
for those patients who pass the screening evaluation.  
r = A core tumor biopsy will be performed at cycle 4 day 1 if deemed safe and feasible +/- 7 
days 
s = All patients discontinued from treatment, regardless of reason, should be followed annually until 
death, loss to follow-up, withdrawal of consent from study, five years, or closure of the study. Follow-up 
can be performed via telephone, email, EMR review and/or office visit. 
t = Whichever is appropriate for the patient. Patients with a prior history of both markers being elevated 
will have both drawn serially as per the study calendar.  
u = Blood samples for PBMC and whole blood will be collected according to the site lab manual. 
v= PBMC research sample at C1D8 may be collected 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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7.3 
Screening Phase 
Following written informed consent, and unless otherwise specified, the following 
assessments will be performed during the 28-day period prior to the first dose of therapy. 
Assessments performed within this window, but prior to patient signing informed consent, 
are acceptable only if confirmed to have been standard of care. 
• Demographic information (birth date, race, gender, etc.), including smoking history 
and status. 
• Evaluation of germline and somatic sequencing results to ensure no pathogenic 
variants in BRCA1, BRCA2, PALB2, RAD51C or RAD51D. 
• Medical/oncology history, including date of cancer diagnosis, prior treatments and 
any surgical procedures 
• Physical examination of body system, height and weight 
• ECOG performance status (16.1 Appendix A) 
• Vital signs (blood pressure, pulse, and temperature) 
• Prior and concomitant medications and any surgical procedure 
• Hematology (hemoglobin, hematocrit, WBC and differential [with ANC], and 
platelet count) ≤7 days prior to first dose of treatment. 
• Serum chemistry (total protein, albumin, creatinine or estimated GFR using 
Cockcroft Gault formula, BUN, total bilirubin, ALP, ALT, AST, glucose, sodium, 
potassium, chloride, CO2, calcium, phosphorous, magnesium and lipase [Arm A 
only]) ≤7 days prior to the first dose of treatment. 
• Serum pregnancy test for women of childbearing potential 
• TSH (Arm A only) 
• CA 19-9 and/or CEA (whichever is appropriate) 
• HIV antibody 
• Hepatitis B and C testing 
• Tumor assessments should consist of clinical examination, appropriate imaging 
techniques including CT scans of the chest, CT or MRI of the abdomen and pelvis, 
with appropriate slice thickness per RECIST; other studies (X-ray, PET, and 
ultrasound) may be performed if required. Whenever possible, the same method 
used to detect lesions at baseline is to be used to follow the same lesions 
throughout the clinical study. If a patient has known brain metastases, this disease 
should be evaluated at each required assessment. 
• FFPE archival tumor tissue sample, if available. Refer to the site Laboratory 
Manual for detailed sample handling instructions. (Note: this sample is not required 
to be submitted on Cycle 1, Day 1, but should be submitted as soon as possible 
after a patient begins treatment) 
• Tumor tissue core biopsy if considered safe and feasible). Tumor tissue will be 
processed locally as formalin-fixed paraffin-embedded (FFPE) tissue. Refer to the 
site Laboratory Manual for detailed sample handling instructions. 
• AE monitoring (after signing informed consent)

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7.4 
Treatment Phase 
The following procedures should be completed before the first dose of study therapy is 
administered, unless otherwise indicated. 
 
7.4.1 
Cycle 1, Day 1 (Both Arms Unless Otherwise Specified) 
• Physical Examination 
• Weight 
• ECOG performance status (16.1 Appendix A) 
• Vital signs 
Arm A only: blood pressure and heart rate should be monitored weekly for first 2 
months, monthly for first year, and periodically thereafter 
• Concomitant medications and procedures 
• Hematology 
Arm A only: Weekly CBCs should be performed during the first four weeks of 
therapy and monthly for one year thereafter. 
• Serum chemistries 
• CA 19-9 and/or CEA measurement 
• TSH and lipase measurements (Arm A Only) 
• Correlative Research Blood samples will be obtained for PBMCs and Whole Blood 
on Cycle 1 Day 1, Cycle 1 Day 8 and every Cycle thereafter 
• Adverse event monitoring 
• The treatment core biopsy will be performed +/- 7 days of cycle 4, if considered 
feasible and safe as by the first reassessment staging scan and evaluation by the 
clinical investigator and the performing department. 
• Study drug accountability  
• Niraparib dispensation (Arm A Only) 
• Ipilimumab (Arm A; Cycles 1-4 only)) or chemotherapy (Arm B) administration 
 
Arm A: Niraparib will be dispensed to the patient in sufficient quantity to last until Day 1 
of the next treatment cycle. Patients will ingest niraparib once daily at about the same 
times every day. Bedtime dosing may mitigate nausea. Food does not affect the 
absorption of niraparib, therefore, niraparib may be taken without regard to meals. If a 
patient vomits or misses a dose of niraparib, an additional dose should not be taken. The 
next dose should be taken at a regularly scheduled time. 
Patients will keep all unused pills and containers (empty, partially used, and/or 
unopened) for accountability at the next visit. In the event of toxicities, re-treatment or 
dose modification will be according to the criteria described the protocol). Patients will 
record dosing information in their dosing diary. 
 

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7.4.2 
Cycle 1 Day 8  
Patients will have blood drawn for PBMCs and for Whole Blood.  These will be collected, 
processed and stored as per the Laboratory Manual.   
 
7.4.3 
Cycle 4 Day 1   
If feasible and considered safe, every patient will undergo treatment-biopsy at C4D1, +/- 
7 days. 
 
7.4.4 
Day 1 of Subsequent Cycles (Both Arms Unless Specified) 
Arm A: Patients will be instructed to refrain from taking their first dose of oral niraparib 
prior to their clinic visits because certain assessments must be performed prior to dosing. 
The following procedures will be completed prior to treatment on Day 1 of Each Cycle. 
• Physical examination 
• Weight 
• ECOG performance status (16.1 Appendix A) 
• Vital signs 
− Arm A Only: blood pressure and heart rate should be monitored monthly for 
first year, and periodically thereafter 
• Concomitant medications and procedures 
• Hematology 
• Serum chemistry including magnesium, phosphate 
• TSH and lipase measurements (Arm A only) 
• CA 19-9 and/or CEA measurement 
• Correlative Research Blood samples will be obtained for PBMCs and Whole Blood 
on Day 1 of each Cycle. 
• Disease/ tumor assessment (using the same methodology as was used at 
screening [e.g., CT scan] whenever possible) prior to the start of every 3 cycles 
(Arm A) or every 2 cycles (Arm B) (within 7 days before is permitted) relative to 
start of treatment on Day 1 of Cycle 1 through to 18 months on study, then every 
16 calendar weeks (within 5 days before is permitted) relative to the start of 
treatment on Day 1 of Cycle 1. Timing of disease/tumor assessments is relative to 
Day 1 of Cycle 1 after enrollment.  
• AE monitoring 
• Study drug accountability (Arm A only) 
• Niraparib dispensation (Arm A only) 
• Ipilimumab administration (Arm A only) 
• Chemotherapy administration (Arm B only) 
Arm A: Niraparib will be dispensed to the patient in sufficient quantity to last until Day 1 
of the next treatment cycle. Patients will ingest niraparib once daily at about the same 
times every day. Bedtime dosing may mitigate nausea. Food does not affect the 

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absorption of niraparib, therefore niraparib may be taken without regard to meals. If a 
patient vomits or misses a dose of niraparib, an additional dose should not be taken. The 
next dose should be taken at a regularly scheduled time. 
Patients will keep all unused niraparib and containers (empty, partially used, and/or 
unopened) for accountability at the next visit. In the event of toxicities, re-treatment or 
dose modification will be according to the criteria described the protocol). Patients will 
record dosing information in their dosing diary. 
7.4.5 
Day 15 of Each Cycle (Arm B Only) 
• Vital signs 
• Adverse Events 
• Hematology 
• Serum Chemistry 
• Chemotherapy Infusion 
 
7.4.6 
Tumor Assessments 
Tumor assessments will be performed after every 9 weeks (+/- 7 days) 3rd cycle for Arm 
A and after every 8 weeks (+/- 7 days) for Arm B. Imaging should be performed prior to 
the first day of the next cycle of therapy. 
 
7.4.7 
End of Treatment Visit 
The following procedures will be performed for all patients as soon as possible after the 
last dose of study therapy: 
• Physical examination 
• Weight 
• ECOG performance status (Appendix A) 
• Vital signs 
• Concomitant medications and procedures 
• Hematology 
• Serum chemistry 
• Magnesium and phosphate  
• TSH measurement and lipase (Arm A only) 
• CA 19-9 and/or CEA measurement 
• Correlative Research Blood samples will be obtained for PBMCs, and Whole 
Blood 
• Tumor assessment scans if patient discontinued therapy for reasons other than 
radiologic disease progression and if previous tumor assessment scan was 
performed ≥8 weeks prior to EOT visit. 
• AE monitoring 

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• Study drug accountability (Arm A only) 
 
7.5 
30-day Follow-up Visit 
The following procedures will be performed for all patients at 30 (±3) days after the last 
dose of study therapy. At least 2 documented attempts will be performed by study team 
to contact the subject. 
• AE monitoring (ongoing SAEs should be followed until resolution or stabilization) 
• If tumor assessment scans were not performed at End of Treatment or within 30 
days prior to End of Treatment, a CT scan should be performed at the 30-day 
follow-up visit. 
 
7.6 
90 Day Follow-up Visit for MDS/AML (Arm A Only) 
Patients who received niraparib (Arm A) will have intermittent monitoring for MDS/AML 
for up to 5 years as described in long-term follow up Section 7.7. Patients on this Arm will 
have an additional follow-up visit at 90 days (±14) days after the last dose of study 
therapy. At least 2 documented attempts will be performed by study team to contact the 
subject. 
• AE monitoring (ongoing SAEs should be followed until resolution or stabilization) 
• MDS and AML are Adverse Events of Special Interest (Section 10.1.4) and should 
be reported to the PI and sponsor. Follow-up for MDS/AML can be performed via 
the telephone. If subject reports a diagnosis of MDS/AML and if feasible at least 2 
documented attempts will be made to obtain appropriate documentation (i.e., 
laboratory and/or pathology reports). 
 
7.7 
Long-term Follow-Up 
All subjects will be followed every 6 months for survival and MDS and/or AML (latter: Arm 
A only) until death, loss to follow-up, withdrawal of consent from study or for 5 years, 
whichever occurs first. 
7.7.1 For Overall survival information and MDS/AML follow-up can be performed 
via telephone, email or, Electronic Medical Record (EMR) review. At least 2 
documented attempts will be performed by study team to contact the subject. 
If attempts to contact are unsuccessful the subject will be considered lost to 
follow up. Death Records and SSDI will still be used for survival purposes. 
 
7.8 
Subject Withdrawal 
Subjects may withdraw from the study at any time without impact to their care. The study 
team must document in the subject record the decision to withdrawal and additional 
details including but not limited to if the subject withdraws consent from the entire study, 
and all research procedures to obtain data about the subject will be discontinued. The 
research study team may obtain follow-up data about the subject from publicly available 
records, e.g.: survival status. If the subject withdraws from the primary intervention and 
agrees to participate study assessments and/or allow for additional data collection 
through medical record review this should be documented in the subject record. 
 

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They may also be discontinued from the study at the discretion of the Investigator for lack 
of adherence to intervention or study procedures or visit schedules or AEs. The 
Investigator or the Sponsor (if applicable) may also withdraw subjects who violate the 
study plan, or to protect the subject for reasons of safety or for administrative reasons. It 
will be documented whether or not each subject completes the clinical study. Subjects 
who withdraw early will have one final visit to collect investigational product and to follow 
up regarding adverse events, if possible.  
 
 
7.8.1 
Data Collection and Follow-up for Withdrawn Subjects 
Subjects who withdraw consent to participate in the study will be seen for one final visit 
to collect the investigational product, if feasible. During this visit or when the subject is 
contacted, they will be asked for permission to have the study team look into their survival 
status via publicly available means. 
 
8 STUDY EVALUATIONS AND MEASUREMENTS 
8.1 
 Medical Record Review 
The following information will be extracted from the medical record of each subject prior 
to the first dose of study therapy. 
• Past medical/oncologic history including date of diagnosis, prior treatments, date 
of progression, and radiology and/or medical report(s) to support assessment of 
disease progression, and, if applicable, intolerable toxicity to chemotherapy. 
• Smoking history 
• Detailed family history of all cancers 
• Any previously performed genetic testing or sequencing results (of tumor tissue, 
circulating tumor DNA and/or germline) should be collected and stored 
 
8.2 
Physical Examination 
Physical examinations will be performed at screening (complete) and at most study visits 
(limited as appropriate). 
 
8.3 
Body Weight and Height 
Height will be measured during the Screening visit only. Weight will be measured per 
institutional guidelines. 
 
8.4 
Vital Signs 
Vital signs will include blood pressure, pulse and body temperature. Vital signs will be 
performed at most study visits. 
 
8.5 
ECOG Performance Status 
ECOG performance status (16.1 Appendix A) will be assessed at Screening, on Day 1 of 
each cycle, and at the End of Treatment visit.   Care will be taken to accurately score 
performance status, especially during screening for study eligibility purposes. Additional 
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patients with significant impairment. 
 
8.6 
Clinical Laboratory Evaluations 
Certified local laboratories will perform study-related clinical laboratory tests according to 
institutional procedures, and the results will be reviewed by the investigator. The panels 
of laboratory tests to be performed are shown below: 
Hematology: Hemoglobin, hematocrit, WBC and differential (with ANC) platelet count at 
Screening, during treatment, and at the End of Treatment visit. Screening hematology 
results must be reviewed by the investigator prior to the start of treatment with study 
treatment. During the treatment phase, results must be evaluated by the investigator and 
acted upon, as appropriate, within 24 hrs. of receipt. 
Clinical Chemistry: Total protein, albumin, creatinine or estimated GFR using the 
Cockcroft Gault formula, BUN or urea, total bilirubin, alkaline phosphatase (ALP), ALT, 
AST, TSH [Arm A only] and lipase [Arm A only], glucose, sodium, potassium, chloride, 
CO2, calcium, and phosphorus at Screening, during treatment, and at the End of 
Treatment visit. 
Tumor Markers: CA 19-9 and/or CEA (whichever is appropriate for the patient) will be 
measured on Day 1 of each cycle and at the End of Treatment visit. 
Serum/Urine Pregnancy: For women of childbearing potential only. Serum pregnancy 
test is to be performed during the screening period. 
Laboratory reports will be reviewed by the investigator or sub-investigator who will then 
comment on out-of-range parameters and assess clinical significance. Clinically 
significant abnormalities and associated panel results, as well as results of any additional 
tests performed as follow-up to the abnormalities, will be documented on the eCRF as an 
AE. Refer to Section 10.4 for guidelines on reporting of abnormal laboratory values as 
AEs. 
 
8.7 
Efficacy Evaluations 
 
8.7.1 
Tumor Assessments 
Tumor assessments will be performed at Screening and within 7 days prior to the start of 
every 3rd cycle (Arm A) or every 2nd cycle (Arm B) and at the End of Treatment visit. If a 
CT scan was not performed at the End of Treatment visit, a CT scan should be performed 
at the 28- day Follow-up visit. Tumor response will be interpreted using RECIST Version 
1.1 (16.2 Appendix B). 
Tumor assessments should consist of clinical examination and appropriate imaging 
techniques (CT scans of the chest, CT or MRI of the abdomen, and pelvis with 
appropriate slice thickness per RECIST); other studies (X-ray, PET, and ultrasound) may 
be performed if required. If a patient has known brain metastases, this disease should be 
evaluated at each required assessment. Whenever possible, the same methods used to 
detect lesions at baseline are to be used to follow the same lesions throughout the clinical 
study. Investigators should perform scans of the anatomical sites that, in their judgment, 
are appropriate to assess based on each patient’s tumor status. 
 
8.7.2 
Tumor Markers 
CA 19-9 and/or CEA (whichever is appropriate for the patient) will be collected on Day 1 
of every cycle and at the End of Treatment visit.   

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NOTE: Please note that a rising tumor marker in the absence of progressive 
disease on imaging is insufficient to determine disease progression.  
 
8.8 
 Correlative Science 
 
8.8.1 Specimen Collection 
Tumor tissue (fresh or if not available, archival) must be available or collected prior to the 
start of treatment. A second treatment biopsy will also be obtained prior to C4D1, if 
considered safe and feasible. Archival tissue will be collected whenever possible. 
Blood draws for whole blood (for cytokine analysis) and peripheral blood mononuclear 
cells (PBMC) and Whole Blood will be collected at baseline and serially during therapy 
as noted above.  
Tumor and blood samples will be processed according to the study Laboratory Manual. 
 
8.8.2 Minimum Number of Required Biopsies 
This protocol will enroll 51 patients in Arm A and 17 patients in Arm B, for a total of 68 
patients. In order to perform the proposed correlative science, we will require that at least 
80% of all patients (i.e. 55 patients total) undergo at least a baseline tissue biopsy.   
 
At halfway through trial enrollment (i.e. once 34 patients have been enrolled), tissue 
acquisition rate will be assessed. Pending these results, the Principal Investigator and 
the Study Team may require that patients enrolled moving forward are required to have 
biopsiable disease as a Study Entry Criteria until the goal of 55 total baseline tissue 
samples is met. 
 
8.8.3 Determining the impact of Immune Health on outcomes on nira/ipi (Wherry 
Lab) 
Whole blood and PBMCs will be processed and stored in the Human Immunology Core 
(HIC) as per the Laboratory Manual.  
 
Assays will be performed with a goal of understanding the circulating immune profile of 
patients who enroll on this study, and the impact that chemoimmunotherapy or 
chemotherapy alone has upon these patients, as can be detected in the peripheral blood.  
The methods will provide a comprehensive and accurate representation of the immune 
system and its dynamics in the setting of nira/ipi exposure, leading to new insights into 
determinants of treatment outcomes. 
 
8.8.4 Defining the pharmacodynamic response and clinical impact of the immune 
microenvironment in nira/ipi treated tumors (Beatty and Wolpin-Nowak 
Labs). 
Tissue samples will be processed and shipped to and/or stored in the Wolpin/Nowak and 
Beatty labs as per the Laboratory manual. The Wolpin laboratory will perform whole 
transcriptome spatial profiling. The Beatty laboratory will perform an evaluation of the 
lymphoid and myeloid cell phenotype, polarization, and spatial orientation in the PC 
microenvironment. 
 
8.8.5 Investigating the role of cell proliferation and replication stress status in the 
response to nira/ipi (Wolpin-Nowak Lab). 

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The Wolpin/Nowak laboratory will use a multiplexed immunofluorescence panel in order 
to assess tissue samples for the status of key proteins and phosphoproteins in the DNA 
damage repair and cell cycle pathways. 
 
8.8.6 Studying the impact of tumor transcriptional subtype on outcomes in nira/ipi 
treated tumors (Beatty and Wolpin-Nowak Labs). 
The Beatty and Wolpin/Nowak laboratories will subtype tumors (i.e. basal, classical) 
using transcriptional subtypes and correlate this with treatment outcomes. 
Additional research: Beyond the assays noted above, and provided that sample 
material is left over, and with approval of the overall PI and sponsor, investigators may 
perform additional research assays on tumor or blood samples collected in this protocol. 
In addition, samples may undergo genomic and transcriptional analysis if there is 
available tissue.  
 
 
9 STATISTICAL PLAN 
This is a two-arm, open-label, randomized study of niraparib/ipilimumab with a non-
comparative control arm of niraparib with maintenance FOLFIRI in patients with 
metastatic pancreatic adenocarcinoma who have achieved stability on FOLFIRINOX. The 
primary aim is to test the null hypothesis of mPFS 5mo versus the alternative hypothesis 
of an mPFS 7.5mo. With 68 patients enrolled over 14 months – 51 given 
niraparib/ipilimumab and 17 in the non-comparative control arm – and with 12 months of 
additional follow-up, there is 89% power for the test assuming exponential survival and 
5% 1-sided type I error rate. With 17 control patients, a 90% confidence interval for any 
binomial parameter (toxicity, response, etc.) would be no wider than 43% percentage 
points and the chance of observing one or more rare events (4% true probability) is at 
least 50% and events of true frequency of 9% or higher have at least 80% probability of 
being observed (1 or more events out of 17 control patients). 
 
9.1 
Primary Endpoint 
Progression-free survival in the experimental arm is the primary endpoint. Progression-
free survival is defined as the time from start of experimental therapy to the occurrence 
of disease progression according to RECIST v1.1, as assessed by the investigator, or 
death from any cause. Patients who are alive and progression-free will be censored on 
the most recent date that documents progression-free status (i.e., scan date or clinic visit 
date). Median PFS and 95% confidence interval will be estimated from the Kaplan-Meier 
curve. 
 
9.2 
Secondary Endpoints 
The secondary endpoints are: 
(1) Overall response rate (ORR) in evaluable patients 
(2) Overall survival (OS) 
(3) PFS in the control arm 
(4) OS in the control arm 
(5) Overall response in evaluable patients within the control arm 
(6) Safety 

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(7) To determine biomarkers of response, mechanisms of action and immune 
pharmacodynamics of niraparib/ipilimumab in a population of patients with 
metastatic pancreatic cancer 
 
 
9.3 
Sample Size and Power Determination 
Sample size was chosen to detect a difference in 5 vs. 7.5 month median PFS in the 
experimental arm with 89% power and 5% 1-sided type-I error, then inflated to account 
for 3:1 randomization between the experimental and non-comparative control arms. 
Sample size was calculated assuming an exponential survival distribution in the 
experimental arm. 
 
9.3.1 
Statistical Methods 
The primary analysis testing the null hypothesis of median PFS (mPFS) of 5 months 
versus mPFS of 7.5 months will be carried out using a Wald test assuming exponential 
survival, following Section 11.1 of Moore (2016). Suitability of the exponential 
distributional assumption will be assessed by plotting the Kaplan-Meier estimate of the 
survival function at each observed death times against the death times; if the assumption 
holds, we expect to see an approximately straight line. If the assumption does not hold, 
we will draw inference using the nonparametric confidence interval around the median 
survival estimate following Brookmeyer and Crowley (1982).  
We will estimate the ORR in each arm as, at the end of the study, the proportion of 
patients who responded to treatment along with exact binomial 95% confidence intervals. 
We will estimate median OS in each arm using the Kaplan-Meier estimate with 95% 
confidence intervals using Greenwood’s formula. 
 
9.3.2 
Baseline Data 
All demographic and baseline characteristics will be summarized for the safety 
population. The following variables will be summarized with frequent tabulations: 
• Time since diagnosis (months) 
• Baseline laboratory parameters: graded based on NCI CTCAE version 5.0 
 
Descriptive statistics may also be used to summarize these variables. 
 
9.3.3 
Efficacy Analysis 
All efficacy evaluations will be conducted using the efficacy population (Section 9.4). If 
the lower bound of the 95% confidence interval for mPFS is > 5 (the null hypothesis value) 
then the study will be declared a success. 
 
9.3.4 
Safety Analysis 
All safety evaluations will be conducted using the safety population (Section 9.4). 
 
9.4 
Subject Population(s) for Analysis 

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The following analysis populations are defined for the study: 
Safety Population: The safety population will consist of all patients who received at least 
one dose of study treatment. 
Efficacy Population: The efficacy population will consist of all patients who received at 
least one dose of study treatment and had a least one post-treatment assessment of 
response by RECIST v.1.1 (16.1 Appendix A). Patients who do not have at least one 
post-treatment assessment of response will be replaced. 
 
10 SAFETY AND ADVERSE EVENTS 
10.3 Definitions 
 
10.1.1 
Unanticipated Problems Involving Risk to Subjects or others 
Any incident, experience, or outcome that meets all of the following criteria: 
• Unexpected in nature, severity, or frequency (i.e. not described in study-related 
documents such as the IRB-approved protocol or consent form, the investigators 
brochure, etc.) 
• Related or possibly related to participation in the research (i.e. possibly related 
means there is a reasonable possibility that the incident experience, or outcome 
may have been caused by the procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm 
(including physical, psychological, economic, or social harm). 
 
10.1.2 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or 
worsens in severity during the course of the study. Intercurrent illnesses or injuries should 
be regarded as adverse events. Abnormal results of diagnostic procedures are 
considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests is considered by the 
investigator to be of clinical significance 
 
 
10.1.3 
Serious Adverse Event 
Any untoward medical occurrence that, at any dose; 
• Results in death; 
• Is life threatening (i.e., an event in which the patient was at risk of death at the time 
of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe); 
• Requires inpatient hospitalization* or prolongation of existing hospitalization; 

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• 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 
documented. Complications experienced during these hospitalizations must be reported 
as SAEs if hospitalization is prolonged due to AE, or if the complication meets other 
serious criteria). 
**Medical and scientific judgment should be exercised in determining whether situations 
or events should be considered serious adverse events: an important medical event may 
not be immediately life-threatening or result in death or require hospitalization but may 
jeopardize the patient or require intervention to prevent one of the above outcomes. 
Examples of such events are allergic bronchospasm, blood dyscrasias, or convulsions 
that may require intensive treatment in an emergency room or at home but do not result 
in hospitalization, development of drug dependency or drug abuse, and transmission of 
disease associated with the administration of the study drug. 
Events of progression of the patient’s underlying cancer as well as events clearly related 
to progression of the patient’s cancer (signs and symptoms of progression) should not be 
reported as a serious adverse event unless the outcome is fatal within the safety reporting 
period. If the event has a fatal outcome within the safety reporting period, then the event 
of Progression of Disease must be recorded as an AE and as a SAE with CTC Grade 5 
(fatal outcome) indicated. 
 
10.1.4 
Adverse Events of Special Interest (AESIs) for Niraparib 
An Adverse Event of Special Interest is defined as any AE (serious or non-serious) that 
is of scientific and medical concern specific to the study treatment. 
Adverse Events of Special Interest (AESI) for niraparib include the following: 
• Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) 
• Secondary cancers (new malignancies [other than MDS or AML]) 
• Embryo-fetal toxicity 
 
AESIs should be reported on SAE Report Forms whether serious or not and reported to 
the Sponsor Investigator in 24 hours. 
 
10.2 Recording of Adverse Events 
At each contact with the patient, the investigator must seek information on adverse events 
by specific questioning and, as appropriate, by examination. Information on all adverse 
events should be recorded immediately in the source document, and also in the 
appropriate adverse event module of the case report form (CRF). All clearly related signs, 
symptoms, and abnormal diagnostic procedures results should recorded in the source 
document, though should be grouped under one diagnosis. All adverse events occurring 

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during the study period must be recorded. The clinical course of each event should be 
followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause. Serious adverse events that are still ongoing 
at the end of the study period must be followed up to determine the final outcome. Any 
serious adverse event that occurs after the study period and is considered to be possibly 
related to the study treatment or study participation should be recorded and reported 
immediately. 
AEs that meet the criteria of serious, related to study intervention, and unexpected for the 
study intervention, qualify for expedited reporting to the Sponsor and regulatory 
authorities. The Site Investigator will assess all SAEs occurring at his/her site and 
evaluate for “unexpectedness” and relationship to study drug. The Site Investigator is 
required to complete a Report for the events identified as serious, study drug related and 
unexpected, using the SAE Form. 
A copy of this report should be kept at the site. 
 
10.3 Intensity of Adverse Events 
The severity of each AE will be graded using the NCI CTCAE, Version 5.0 grading scale.  
For AEs not covered by NCI CTCAE, the severity will be characterized as follows: 
Events not included in the NCI CTCAE will be scored as follows:  
Grade 1: Mild: discomfort present with no disruption of daily activity, no treatment required 
beyond prophylaxis. 
Grade 2: Moderate: discomfort present with some disruption of daily activity, require 
treatment. 
Grade 3: Severe: discomfort that interrupts normal daily activity, not responding to first 
line treatment. 
Grade 4: Life Threatening: discomfort that represents immediate risk of death 
Grade 5: Death related to AE. 
 
10.4 Causal Relationship of Adverse Events to Study Drugs 
All adverse events (AEs) must have their relationship to study therapy and/or interventions 
assessed by the clinician who examines and evaluates the participant based on temporal 
relationship and his/her clinical judgment. The degree of certainty about causality will be 
graded using the categories below. In a clinical trial, the study product must always be 
considered. When assessing causality the investigator should reference the study 
documents such as protocol, informed consent, investigator brochure (s), package insert, 
relevant literature, and take into consideration the disease under study. 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to study intervention 
administration and cannot be explained by concurrent disease or other drugs or chemicals. 
The response to withdrawal of the study therapy (dechallenge) should be clinically 
plausible. The event must be pharmacologically or phenomenologically definitive, with use 
of a satisfactory rechallenge procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence 
of other factors is unlikely. The clinical event, including an abnormal laboratory test result, 

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occurs within a reasonable time after administration of the study therapy, is unlikely to be 
attributed to concurrent disease or other drugs or chemicals, and follows a clinically 
reasonable response on withdrawal (dechallenge). Rechallenge information is not required 
to fulfill this definition. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, 
other factors may have contributed to the event (e.g., the participant’s clinical condition, 
other concomitant events). Although an AE may rate only as “possibly related” soon after 
discovery, it can be flagged as requiring more information and later be upgraded to 
“probably related” or “definitely related,” as appropriate. 
• 
Unrelated – The AE is completely independent of study therapy administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
 
Causality and expectancy of the adverse events will be assessed for the individual drugs 
and the combination. 
 
10.5 Outcome and Action Taken 
The investigator will record the action taken and outcome for each AE according to the 
following criteria: 
Action Taken with Study Drug (note all that apply) 
• None 
• Dose reduced/delayed 
• Study drug temporarily interrupted 
• Study drug permanently discontinued 
• Other (specify) 
 
Outcome 
• Recovered 
• Recovered with sequelae 
• Recovering/ Resolving/ Improving 
• Ongoing 
• Death 
• Lost to follow-up 

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10.6 Adverse Event Reporting Period 
The study period during which AEs must be reported is defined as the period from the 
initiation treatment on trial (i.e. C1D1) through 90 days after patient End of Treatment 
Visit. 
All AEs (including SAEs and AESIs) occurring during the study are to be followed up in 
accordance with good medical and good clinical practice until resolved; judged no longer 
clinically significant; or, if a chronic condition, until fully characterized through 90 days 
(ipilimumab patients) after the last dose of study drug. Any SAEs, AESIs, and treatment 
related Grade 3/4 AEs must be followed until resolution or stabilization, or until lost to 
follow-up. 
 
10.7 Preexisting Condition 
A preexisting condition is one that is present at the start of the study. A preexisting 
condition should be recorded as an AE if the frequency, intensity, or the character of the 
condition worsens during the study period. 
 
10.8 General Physical Examination Finding 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition. At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an AE must also be recorded and documented as an AE. 
 
10.9 Post-Study Adverse Event 
All unresolved AEs should be followed by the investigator until the events are resolved, 
the subject is lost to follow-up, the AE is otherwise explained, or the patient begins 
another anti-cancer therapy. At the last scheduled visit, the investigator should instruct 
each subject to report any subsequent event(s) that the subject, or the subject’s personal 
physician, believes might reasonably be related to participation in this study. The 
investigator should notify the study sponsor if they become aware of any death or AE 
occurring at any time after a subject has discontinued or terminated study participation 
that may reasonably be related to this study. The sponsor should also be notified if the 
investigator should become aware of the development of cancer or of a congenital 
anomaly in a subsequently conceived offspring of a subject that has participated in this 
study. 
 
10.10 Abnormal Laboratory Values 
It is the responsibility of the investigator to assess the clinical significance of all abnormal 
values as defined by the list of reference ranges from the local laboratory. In some cases, 
significant changes in lab values within the normal range will require similar judgment. 
An abnormal laboratory value that is not already associated with an AE is to be recorded 
as an AE only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 
• at the discretion of the investigator should the abnormality be deemed clinically 
significant

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10.11 Pregnancy or Drug Exposure 
If a patient becomes pregnant during the study the investigator is to stop dosing with 
study drug(s) immediately. 
A pregnancy is not considered to be an AE or SAE; however, any pregnancy occurring 
in a study patient during study participation or within 6 months of last dosing, or pregnancy 
occurring in a partner of a study patient during study participation or within 30 days of last 
dosing must be reported to the Penn Sponsor within 1 business day on a SAE Form. 
Elective abortions without complications should not be considered AEs unless they were 
therapeutic abortions, but should be reported to the Sponsor Institution. Hospitalization 
for normal delivery of a healthy newborn should not be considered an SAE. Pregnancy is 
not considered an SAE unless there is an associated serious outcome (e.g., maternal 
serious complications, spontaneous abortions therapeutic abortion, ectopic pregnancy, 
stillbirth, neonatal death, congenital anomaly, and birth defect). 
A pregnancy should be followed through to outcome, whenever possible. Once the 
outcome of the pregnancy is known, an updated SAE form should be completed and 
reported to the UPenn Sponsor Investigator. 
AEs, SAEs, or AESIs that occur during pregnancy will be assessed and processed 
according to the AE or SAE/AESI processes using the appropriate SAE report form. 
 
10.12 Hospitalization, Prolonged Hospitalization or Surgery 
Any AE that results in hospitalization or prolonged hospitalization should be documented 
and reported as an SAE unless specifically instructed otherwise in this protocol. Any 
condition responsible for surgery should be documented as an AE if the condition meets 
the criteria for an AE. 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported 
as an AE in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition. Surgery should not be reported as an outcome 
of an AE if the purpose of the surgery was elective or diagnostic and the outcome was 
uneventful. 
• Hospitalization or prolonged hospitalization required to allow efficacy measurement 
for the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of the 
study, unless it is a worsening or increase in frequency of hospital admissions as 
judged by the clinical investigator. 

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10.13 Reporting to the UPenn Sponsor 
 
10.13.1 
Adverse Events 
The study clinician will immediately report (1 business day) to the sponsor any serious 
adverse events, whether or not considered related to one of the investigational products, 
including those listed in the protocol or investigator brochure and must include an 
assessment of whether there is a reasonable possibility that one of the investigational 
products caused the event. 
The study clinician will immediately report Adverse Events of Special Interest to the 
sponsor. 
Investigators and the protocol sponsor must conform to the AE reporting timelines, 
formats and requirements of the various entities to which they are responsible, but at a 
minimum, those events that must be reported are those that are: 
• Related to study participation, 
• Unexpected, and 
• Serious or involve risks to subjects or others. 
If the AE is considered serious, the investigator should report this event to the sponsor 
within one (1) business day. The IRB should be notified as per institutional guidelines. In 
accordance with institutional and health authority requirements the sponsor investigator 
will make a determination about the necessity to modify the protocol, include additional 
information in the consent form, inform previous participants, temporarily hold enrollment 
of patients, or terminate the study. The study will proceed only if the medical director and 
site IRB all agree on this course of action. 
The investigator or qualified designee will enter the required information regarding the 
SAE into the appropriate module of the eCRF. The event, including the investigator-
determined causality to study drug should be reported via study specific Serious Adverse 
event form.. 
For additional reporting information, please refer to the Manual of Procedures. 
Events significant enough to necessitate modification of study drug dosing will be 
captured on an appropriate eCRF module (“Study Drug Dosing” page). 
New information regarding the SAE shall be reported as it becomes available and in the 
same manner that of the initial SAE. All serious adverse events (SAEs) will be followed 
until satisfactory resolution or until the site investigator deems the event to be chronic or 
the participant is stable. Other supporting documentation of the event may be requested 
by the study sponsor and should be provided as soon as possible. 
 
10.13.2 
Reporting Product Quality Complaints for Niraparib 
Any written, electronic or oral communication that alleges dissatisfaction related to 
manufactured clinical drug product with regards to its manufacturing, testing, labeling, 
packaging, or shipping, must be reported by the investigator or qualified designee to the 
UPenn Sponsor Investigator. The product and packaging components in question, if 
available, must be stored in a secure area under specified storage conditions until it is 
determined whether the product is required to be returned for investigation of the defect. 

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If the product complaint is associated with an SAE, the SAE must be reported separately 
in accordance with the protocol, and the SAE report should mention the product quality 
complaint. 
 
10.14 Investigator Reporting: Local Reporting Requirements 
The investigator will report AEs and SAEs to the IRB/EC of record and other local 
regulatory groups per the local requirements.  
ACC Data Safety Monitoring Committee requires the investigator or their delegated 
study personnel to report: 
• All grade 3 or higher events regardless of attribution or expectedness within 10 
business days of knowledge. 
• All unexpected deaths within two business day of knowledge. 
• All other deaths within 30 days of knowledge. Deaths of subjects greater than 90 
days from the last study treatment/intervention are not reportable unless a longer 
time frame is specified in the protocol.  
Please refer to the Study Manual of Procedures for additional reporting information.  
 
10.15 Protocol Deviations 
Any unintentional action or process that departs from IRB approval and is identified 
retrospectively. The deviation is reportable to the DSMC and the IRB within 10 days from 
the time the event becomes known to the study team only when: one or more participants 
were placed at increased risk of harm, or, the event has the potential to occur again, or 
the event has the potential to qualify as serious or continuing noncompliance. 
If the PI determines that a deviation has any potential to impact participant safety (harm 
and/or risk), or the integrity of data produced from the participant, or some other overall 
impact on the study, the PI will report per the local institutional policy requirements. 
 
 
10.16 Investigator Reporting to Sponsor of Exceptions and Deviations 
If the PI prospectively identifies a one-time, intentional action or process that departs from 
the IRB and CTSRMC approved study protocol (prospective deviation/exception), 
advanced documented IRB and DSMC approval is required. Please refer to the Study 
Manual of Procedures for additional information. The Sponsor Investigator will report to 
collaborators per contract and the FDA according to 21 CFR 312. 
 
10.17 Medical Monitor 
It is the responsibility of the Sponsor Investigator to oversee the safety of the study at 
his/her site. This safety monitoring will include careful assessment and appropriate 
reporting of adverse events. Medical monitoring by an independent clinician, Vivek 
Narayan, MD, Department of Medicine, Division of Hematology-Oncology will include a 
regular assessment of the number and type of serious adverse events on a periodic basis, 
as well as participate in decision-making regarding dose modifications, exemption and 
deviation requests and an ability to stop enrollment or the study for safety concerns.  The 
Medical Monitor will contact the Director of the ACC DOCM and/or DSMC if there are 
concerns that are unable to be addressed by the PI.  

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10.18 Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). 
Those regulations require a signed subject authorization informing the subject of the 
following: 
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI. 
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of 
subject authorization. For subjects that have revoked authorization to collect or use PHI, 
attempts should be made to obtain permission to collect at least vital status (i.e. that the 
subject is alive) at the end of their scheduled study period. 
 
10.19 Data Collection and Management 
This study will use Velos (PennCRMS) as the data management system. The study case 
report form (CRF) is the primary data collection instrument for the study and will be 
electronically created and completed in Velos. CRFs will be provided for each patient. 
Subjects must not be identified by name on any CRFs. Subjects will be identified by their 
patient identification number (PID). All data requested on the CRF must be recorded. All 
missing data must be explained. If a space on the CRF is left blank because the 
procedure was not done or the question was not asked, write “N/D.” If the item is not 
applicable to the individual case, write “N/A.” 
 
10.20 Records Retention 
It is the investigator’s responsibility to retain study essential documents for at least 2 years 
after the last approval of a marketing application in their country and until there are no 
pending or contemplated marketing applications in their country or at least 2 years have 
elapsed since the formal discontinuation of clinical development of the investigational 
product. These documents should be retained for a longer period if required by an 
agreement with the drug manufacturer. In such an instance, it is the responsibility of the 
drug manufacturer to inform the investigator/institution as to when these documents no 
longer need to be retained. 
 
11 STUDY MONITORING, AUDITING, AND INSPECTING 
11.1 Study Monitoring Plan 
It is the responsibility of the Sponsor to oversee the safety of the study. This safety 
monitoring will include careful assessment and appropriate reporting of adverse events 
as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan. This monitoring will include a regular assessment of the number and 
type of serious adverse events. 
 

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11.2 Auditing and Inspecting 
This study will be monitored in accordance with the Abramson Cancer Center’s (ACC) 
Clinical Trials Scientific Review and Monitoring Committee (CTSRMC) Plan, approved by 
NCI during the Core Grant’s most recent review. This plan requires that the investigator 
submit a study-specific plan outlining how data will be reviewed. In addition, the ACC 
Center’s Department of Operations, Compliance and Monitoring (DOCM) will audit this 
study in accordance with their enhanced auditing program as outlined in the Study 
Manual of Procedures. The investigator will allocate adequate time for such monitoring 
activities. The Investigator will also ensure that the monitor or other compliance or quality 
assurance reviewer is given access to all the above noted study-related documents and 
study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), and has adequate 
space to conduct the monitoring visit. 
The investigator will permit study-related monitoring, audits, and inspections by the 
EC/IRB, the Sponsor, government regulatory bodies, and University compliance and 
quality assurance groups of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.). The investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality 
assurance offices. 
This study will be monitored in accordance with the specific plan developed for this 
protocol. 
 
 
12 ETHICAL CONSIDERATIONS 
This study is to be conducted according to US and international standards of Good 
Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures. 
This protocol and any amendments will be submitted to a properly constituted 
independent Institutional Review Board (IRB), in agreement with local legal prescriptions, 
for formal approval of the study conduct. The decision of the IRB concerning the conduct 
of the study will be made in writing to the investigator and a copy of this decision will be 
provided to TESARO/GSK and Bristol-Myer Squibb before commencement of this study. 
All subjects for this study will be provided a consent form describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study. This consent form will be submitted with the protocol for review 
and approval by the IRB and CTSRMC for the study. The formal consent of a subject, 
using the IRB-approved consent form, must be obtained before that subject undergoes 
any study procedure. The consent form must be signed by the subject and the 
investigator-designated research professional obtaining the consent. 
 
13 STUDY FINANCES 
13.1 Funding Source 

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This clinical study and the proposed translational work will be supported by funds 
provided by the Lustgarten Foundation. 
 
13.2 Conflict of Interest 
All University of Pennsylvania Investigators will follow the University of Pennsylvania 
Policy on Conflicts of Interest Related to Research. 
 
14 PUBLICATION PLAN 
Neither the complete nor any part of the results of the study carried out under this 
protocol, nor any of the information provided by the sponsor for the purposes of 
performing the study, will be published or passed on to any third party without the consent 
of the study sponsor. Any investigator involved with this study is obligated to provide the 
sponsor with complete test results and all data derived from the study. 

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15 REFERENCES 
1. 
Conroy, T., et al., FOLFIRINOX versus gemcitabine for metastatic pancreatic 
cancer. N Engl J Med, 2011. 364(19): p. 1817-25. 
2. 
Von Hoff, D.D., et al., Increased survival in pancreatic cancer with nab-paclitaxel 
plus gemcitabine. N Engl J Med, 2013. 369(18): p. 1691-703. 
3. 
Waddell, N., et al., Whole genomes redefine the mutational landscape of 
pancreatic cancer. Nature, 2015. 518(7540): p. 495-501. 
4. 
Holter, S., et al., Germline BRCA Mutations in a Large Clinic-Based Cohort of 
Patients With Pancreatic Adenocarcinoma. J Clin Oncol, 2015. 33(28): p. 3124-9. 
5. 
Goggins, M., et al., Germline BRCA2 gene mutations in patients with apparently 
sporadic pancreatic carcinomas. Cancer Res, 1996. 56(23): p. 5360-4. 
6. 
Carnevale, J. and A. Ashworth, Assessing the Significance of BRCA1 and BRCA2 
Mutations in Pancreatic Cancer. J Clin Oncol, 2015. 33(28): p. 3080-1. 
7. 
Cerami, E., et al., The cBio cancer genomics portal: an open platform for exploring 
multidimensional cancer genomics data. Cancer Discov, 2012. 2(5): p. 401-4. 
8. 
Gao, J., et al., Integrative analysis of complex cancer genomics and clinical profiles 
using the cBioPortal. Sci Signal, 2013. 6(269): p. pl1. 
9. 
Alexandrov, L.B., et al., Signatures of mutational processes in human cancer. 
Nature, 2013. 500(7463): p. 415-21. 
10. 
Kaufman, B., et al., Olaparib monotherapy in patients with advanced cancer and 
a germline BRCA1/2 mutation. J Clin Oncol, 2015. 33(3): p. 244-50. 
11. 
Mateo, J., et al., DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. 
N Engl J Med, 2015. 373(18): p. 1697-708. 
12. 
Choi, Y.E., et al., Platinum and PARP Inhibitor Resistance Due to Overexpression 
of MicroRNA-622 in BRCA1-Mutant Ovarian Cancer. Cell Rep, 2016. 14(3): p. 429-
39. 
13. 
Clark, C.E., G.L. Beatty, and R.H. Vonderheide, Immunosurveillance of pancreatic 
adenocarcinoma: insights from genetically engineered mouse models of cancer. 
Cancer Lett, 2009. 279(1): p. 1-7. 
14. 
Higuchi, T., et al., CTLA-4 Blockade Synergizes Therapeutically with PARP 
Inhibition in BRCA1-Deficient Ovarian Cancer. Cancer Immunol Res, 2015. 
15. 
TESARO Summarizes ZEJULA and TSR-042 Data Presented at the 2017 
ESMOAnnual 
Meeting. 
2017; 
Available 
from: 
http://ir.tesarobio.com/releasedetail.cfm?releaseid=1039856. 
16. 
Momtaz, P., et al., Safety of Infusing Ipilimumab Over 30 Minutes. J Clin Oncol, 
2015. 
33(30): p. 3454-8. 
17. 
Birkbak, N.J., et al., Telomeric allelic imbalance indicates defective DNA repair and 
sensitivity to DNA-damaging agents. Cancer Discov, 2012. 2(4): p. 366-75. 
18. 
Popova, T., et al., Ploidy and large-scale genomic instability consistently identify 
basal- like breast carcinomas with BRCA1/2 inactivation. Cancer Res, 2012. 
72(21): p. 5454-62. 
19. 
Abkevich, V., et al., Patterns of genomic loss of heterozygosity predict homologous 
recombination repair defects in epithelial ovarian cancer. Br J Cancer, 2012. 
107(10): p. 1776-82. 
20. 
Golan, T., et al., Overall survival and clinical characteristics of pancreatic cancer 
in BRCA mutation carriers. Br J Cancer, 2014. 111(6): p. 1132-8. 

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21. 
Heinemann, V., et al., Randomized phase III trial of gemcitabine plus cisplatin 
compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol, 
2006. 24(24): p. 3946-52. 
22. 
National Cancer Institute. Common Terminology Criteria for Adverse Events, 
Version 
4.03. 
14 
June 
2010 
[cited 
19 
November 
2014]; 
Available 
from: 
http://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06- 
14_QuickReference_5x7.pdf. 
23. 
Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 

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16 APPENDIX 
16.1 Appendix A: ECOG 
Table 14. 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Scale 
 
ECOG Performance Status 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature (eg light house work or office work). 
2 
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about 
more than 50% of waking hours. 
3 
Capable only of limited self care; confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry on any self care. Totally confined to bed or chair. 
5 
Dead. 
 
16.2 Appendix B: Response Evaluation Criteria in Solid Tumors Criteria 
The RECIST guidelines (Version 1.1) are described in Eisenhauer (2009)[23] and at 
http://www.eortc.be/Recist/Default.htm. A short summary is given below. 
Measurable Disease: 
Tumor lesions: measurable lesions are defined as those that can be accurately measured 
in at least one dimension (longest diameter to be recorded) with the following: 
• A minimum size of 10 mm by CT scan (CT scan thickness no greater than 5 mm). 
• A minimum size of 10 mm caliper measurement by clinical exam (lesions that 
cannot be accurately measured with calipers should be recorded as 
nonmeasurable). 
• A minimum size of 20 mm by chest X-ray. 
 
All tumor measurements must be recorded n millimeters (or decimal fractions of 
centimeters). 
Malignant lymph nodes: to be considered pathologically enlarged and measurable, a 
lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be not greater than 5 mm). At baseline and in follow-up, only 
the short axis will be measured and followed. 
Nonmeasurable Disease: 
All other lesions (or sites of disease), including small lesions (longest diameter <10 mm 
or pathological lymph nodes with ≥10 to <15 mm short axis), as well as truly 
nonmeasurable lesions, are considered nonmeasurable disease. Lesions considered 
truly nonmeasurable include leptomeningeal disease, ascites, pleural/pericardial 
effusions, inflammatory breast disease, lymphangitic involvement of skin and lung, and 
abdominal masses/abdominal organomegaly identified by physical exam that is not 
measurable by reproducible imaging techniques. 

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

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Table 15. 
Evaluation of Target Lesions 
 
Complete Response 
Disappearance of all target lesions. Any pathological lymph nodes (whether 
target or nontarget) must have reduction in short axis to <10mm 
Partial Response 
At least a 30% decrease in the sum of the LD of target lesions, taking as 
reference the baseline sum LD. 
Stable Disease 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify 
for PD, taking as a reference the smallest sum LD since the treatment started. 
Progressive Disease 
At least a 20% increase in the sum of all the LD of target lesions, taking as 
reference the smallest sum on study (this includes the baseline sum if that is 
the smallest on study). In addition to the relative increase of 20%, the sum 
must also demonstrate an absolute increase of at least 5mm. The 
appearance of one or more new lesions is also considered progression. 
 
Table 16. 
Evaluation of Nontarget Lesions 
 
Complete Response 
Disappearance of all non-target lesions and normalization of tumor marker 
levels. 
Stable Disease/ 
Incomplete Response 
Persistence of one or more non-target lesion(s) or/and maintenance of tumor 
marker level above the normal limits. 
Progressive Disease 
Appearance of one or more lesions and/or unequivocal progression of 
existing non- target lesions. 
 
If tumor markers are initially above the institutional ULN, they must normalize for a patient 
to be considered to be a complete responder. 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment 
until disease progression/recurrence (taking as reference for PD the smallest 
measurements recorded since the treatment started). The patient’s best response 
assignment will depend on the achievement of both measurement and confirmation 
criteria. 
Table 17. 
Evaluation of Best Overall Response 
 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not 
evaluated 
No 
PR 
SD 
Non-PD or not 
evaluated 
No 
SD 
Not Evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
NE = not evaluable 

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Patients with global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be classified as having 
symptomatic deterioration. Every effort should be made to document the objective progression, 
even after discontinuation of treatment. 
In some circumstances, it may be difficult to distinguish residual disease from normal tissue. 
When evaluation of CR depends on this determination, it is recommended that the residual 
lesion be investigated (fine needle aspiration/biopsy) prior to confirming the complete response 
status. 
Confirmatory Measurement/Duration of Response 
Confirmation 
CT scans are required at screening and within 7 days prior to the start of every odd numbered 
cycle (i.e., Cycles 3, 5, 7, etc.). If an initial CR or PR is noted, confirmatory scans must be 
performed >4 weeks later. 
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are met for 
CR or PR (whichever is first recorded) until the first date that recurrent or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded since the 
treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented. 
Duration of Stable Disease 
SD is measured from the start of the treatment until the criteria for progression are met, taking 
as reference the smallest measurements recorded since the treatment started.