A Phase II Study of Niraparib in Combination With EGFR Inhibitor Panitumumab in Patients With Advanced Colorectal Cancer
Phase: PHASE2
Conditions: Advanced Microsatellite Stable Colorectal Carcinoma, Metastatic Microsatellite Stable Colorectal Carcinoma, Microsatellite Stable, RAS Wild Type, Stage IV Colorectal Cancer AJCC v8, MSI-H Colorectal Cancer
Sponsor: Emory University

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A Phase II Study of Niraparib in Combination with EGFR Inhibitor 
Panitumumab in patients with advanced colorectal cancer
Sponsor:
Olatunji Alese, MD
Principal Investigator:
Olatunji Alese, MD
Study Drug Name:
Niraparib, Panitumumab
Clinical Phase: II
Number of Subjects:
26
IND Number:
IND 142710
EudraCT Number:
N/A
Date of Original Protocol:
8 January 2019 
Date of Current Protocol:
27 October 2021
Version: 02
The study will be conducted according to the protocol and in compliance with Good Clinical Practice 
(GCP), with the Declaration of Helsinki, and with other applicable regulatory requirements including 
but not limited to Institutional Review Board/Ethics Committee (IRB/EC) approval.
Confidentiality Statement
All information contained in this document is privileged and confidential. Any distribution, 
copying, or disclosure is strictly prohibited without prior written approval by the Sponsor.

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LIST OF STUDY CONTACTS 
Sponsor
Winship Cancer Institute 
Emory University
1365C Clifton Road NE,
Atlanta, GA 30322
Principal Investigator: 
Olatunji Alese, MD
Winship Cancer Institute 
1365C Clifton Road NE,
Atlanta, GA 30322
Phone: 404 778 1900
Email: oalese@emory.edu
Co- Investigators
Christina Wu, MD
Walid Shaib, MD
Mehmet Akce, MD
Maria Diab, MD
Olumide Gbolahan, MD
Stephen Szabo, MD
Sarah Friend, MD
Neela Natarajan, MD
Co-Principal Investigator: 
Bassel El-Rayes, MD
Winship Cancer Institute 
1365C Clifton Road NE,
Atlanta, GA 30322
Phone: 404 778 1900
Email: bassel.el-rayes@emoryhealthcare.org
Study Coordinators: TBD
Biostatistician: 
Yuan Liu, Ph.D.
Research Associate Professor
Biostatistics Shared Resource at Winship Cancer Institute
Phone: 404-778-1989
Email: YLIU31@emory.edu

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SPONSOR SIGNATURE PAGE
Declaration of Sponsor or Responsible Medical Officer
Title: A Phase II Study of Niraparib in Combination with EGFR Inhibitor 
Panitumumab in patients with advanced colorectal cancer
This study protocol was subjected to critical review and has been approved by the 
Sponsor. The information it contains is consistent with the current risk/benefit 
evaluation of the investigational product as well as with the moral, ethical, and 
scientific principles governing clinical research as set out in the Declaration of 
Helsinki and the guidelines on Good Clinical Practice.
_____________________________________ _____________________
Olatunji Alese, MD
Date
Associate Professor
Winship Cancer Institute of Emory University

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INVESTIGATOR SIGNATURE PAGE
Declaration of the Investigator
Title: A Phase II Study of Niraparib in Combination with EGFR Inhibitor 
Panitumumab in patients with advanced colorectal cancer
I have read this study protocol, including all appendices.  By signing this protocol, 
I agree to conduct the clinical study, following approval by an Independent Ethics 
Committee (IEC)/Institutional Review Board (IRB), in accordance with the study 
protocol, the current International Conference on Harmonization (ICH) Guideline for 
Good Clinical Practice (GCP), and applicable regulatory requirements.  I will ensure 
that all personnel involved in the study under my direction will be informed about the 
contents of this study protocol and will receive all necessary instructions for 
performing the study according to the study protocol.
Investigator
_____________________________________ _____________________
[Name]
Date
[Title]  
[Institution]  

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TABLE OF CONTENTS
Sponsor Signature Page .....................................................................................................4
Investigator Signature Page ...............................................................................................5
List of Abbreviations and Definitions..................................................................................9
1
Introduction .........................................................................................................11
1.1
Study Design...............................................................................................11
1.2
Primary Objective:.......................................................................................11
1.3
Secondary Objectives .................................................................................11
2
Background and significance.................................................................................13
2.1
Background of PARP and Homologous Recombination Deficiency ...........13
2.2
Background of Niraparib .............................................................................14
2.2.1
Nonclinical Experience......................................................................14
2.2.2
Clinical Experience ...........................................................................15
2.3
Rationale for Current Study.........................................................................18
2.3.1
Rationale for Study Population .........................................................18
2.3.2
Clinical Experience with Panitumumab.............................................20
2.3.3
Rationale for Objectives....................................................................23
2.3.4
Rationale for Measures.....................................................................24
3
Participant selection.............................................................................................25
3.1
Inclusion Criteria .........................................................................................25
3.2
Exclusion Criteria ........................................................................................26
4
Treatment Plan.....................................................................................................28
4.1
Method of Treatment Assignment...............................................................28
4.2
Treatment Regimen ....................................................................................28
4.2.1
Niraparib Administration....................................................................28
4.2.2
Panitumumab Administration............................................................28
4.3
Prohibited Therapies...................................................................................29
4.4
Birth Control ................................................................................................29
4.5
Breast Feeding............................................................................................30
4.6
Blood Donation............................................................................................30
4.7
Treatment Discontinuation ..........................................................................30
4.8
Duration of Follow Up..................................................................................30
4.9
Discontinuation from Study .........................................................................30
4.10
Participant Replacement Criteria ................................................................31
5
Dose Modifications...............................................................................................32
5.1
Niraparib......................................................................................................32

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
    Panitumumab. ..................................................................................................35
6
Pharmaceutical Information .................................................................................36
6.1
Niraparib......................................................................................................36
6.1.1
Identity ..............................................................................................36
6.1.2
Potential Risks of Niraparib...............................................................36
6.1.3
Packaging, Labeling and Storage.....................................................36
6.1.4
Drug Accountability...........................................................................36
6.1.5
Disposal and Destruction..................................................................37
6.2
Panitumumab..............................................................................................37
6.2.1
Identity ..............................................................................................37
6.2.2
Potential Risks of Panitumumab.......................................................37
6.2.3
Packaging, Labeling and Storage.....................................................38
6.2.4
Disposal and Destruction..................................................................38
7
Correlative Studies...........................................................................................39-40
7.1
Pharmacokinetics........................................................................................40
8
Schedule of Assessments ......................................................................................41
8.1
Screening....................................................................................................41
8.2
Cycle 1 ........................................................................................................41
8.3
Subsequent Cycles .....................................................................................41
8.4
End of Treatment ........................................................................................42
8.5
Safety Follow-up .........................................................................................42
8.6
Long Term Follow-up ..................................................................................42
8.7
Unscheduled Assessments.........................................................................42
9
STUDY CALENDAR.................................................................................................44
10
Adverse Event Reporting ......................................................................................47
10.0
Definition of Adverse Events.......................................................................47
10.1
Serious Adverse Events (SAEs) .................................................................47
10.2
Adverse Event of Special Interest (AESI) for Niraparib ..............................48
10.3
Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure....................................................................48
10.4
Assessment of Adverse Events ..................................................................49
10.4.1
Severity Assessment ........................................................................49
10.4.2
Relationship to Study Drug ...............................................................49
10.5
Collection and Recording of Adverse Events..............................................50
10.6
Follow-Up of Adverse Events......................................................................50
10.7
Reporting to the Sponsor Institution............................................................51
10.8
Reporting to TESARO/GSK ........................................................................51
10.9
Quarterly AE/SAE Reporting to TESARO/GSK ..........................................51

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10.10 Pregnancy...................................................................................................52
10.11 Suspected Unexpected Serious Adverse Reactions (SUSARs).................52
10.12 Reporting Product Complaints for Niraparib ...............................................53
11
Data reporting ......................................................................................................54
11.0
Data and Safety Monitoring.........................................................................54
12
Statistical Methods......................................................................................56
12.1
Study Design and Endpoints.......................................................................56
12.1.1
Primary Endpoint ..............................................................................56
12.1.2
Secondary Endpoints........................................................................56
12.1.3
Sample size, Accrual Rate and Study Duration................................57
12.1.4
Interim Monitoring Plan.....................................................................57
12.1.5
Analysis of Primary Endpoints ..........................................................57
12.1.6
Analysis of Secondary Endpoints .....................................................57
12.2
Safety Analyses ..........................................................................................58
13
Ethical, Legal, and Administrative Aspects ............................................................60
13.0
Good Clinical Practice.................................................................................60
13.1
Informed Consent........................................................................................60
13.2
Protocol Approval and Amendment ............................................................61
13.3
Investigator Responsibilities........................................................................61
13.4
Subject Confidentiality and Data Protection................................................62
13.5
Access to Source Documents.....................................................................62
13.6
Archival .......................................................................................................63
13.7
Publications.................................................................................................63
14
References............................................................................................................64
Appendix 2 - Performance Status.……………………………………………………………………….………….67
Appendix 2 - Response Criteria……………………………………………………………………………………….68
Appendix 3 - Drug Diary………………………………………………………………………………………………….69

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LIST OF ABBREVIATIONS AND DEFINITIONS
Table 1
List of Abbreviations
Abbreviation
Definition
ADP
adenosine diphosphate 
AE
adverse event
AESI
adverse even of special interest
AML
acute myeloid leukemia
AUC
area under the curve
BER
base excision repair
BRCA
breast cancer gene
CBC
complete blood count 
CL
oral clearance
CRC
Colorectal cancer
CT
computed tomography 
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DLT
dose-limiting toxicity
DNA
deoxyribonucleic acid
DDR
DNA damage repair
DoR
Duration of response
ECOG
Eastern Cooperative Oncology Group
EGFR
Epidermal growth factor receptor
EOT
end of treatment
FE
food effect
gBRCA
germline breast cancer gene
GCSF
Granulocyte-colony stimulating factor
GBM
glioblastoma multiforme 
hCG
human chorionic gonadotropin
HR
homologous recombination
HRD
homologous recombination deficiency 
irAEIs
immune-related adverse events of interest
IUD
intrauterine device
LLN
Lower limit of normal
MDS
myelodysplastic syndrome
MRI
magnetic resonance imaging 
MTD
maximum tolerated dose

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Abbreviation
Definition
NHEJ
non-homologous end joining
ORR
Objective response rate
OS
Overall survival
PARP
poly(ADP-ribose) polymerase
PFS
progression-free survival
P-gp
P-glycoprotein 
PK
Pharmacokinetics
PRO
patient reported outcomes
PS
performance status
QD
once a day
QTc
corrected QT interval 
RAS 
Rat sarcoma gene
SAE
serious adverse event
TEAS
treatment-emergent adverse events
ULN
upper limit of normal
WT
Wild type

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1
INTRODUCTION
1.1
Study Design 
Dose 
level
Niraparib (mg daily)
Panitumumab 
(IV Q2w)
Number of 
patients
Safety 
run-in
300mg (body wt. ≥77kg and platelets ≥150,000 µL) 
OR
200 mg (body wt. <77kg or platelets <150,000 µL)
6mg/kg
6
Additional 20 CRC patients with the same inclusion criteria will be subsequently enrolled 
and treated to determine efficacy. Patients who fail screening will be replaced on the study.
1.2
Primary Objective: 
Evaluate the activity of the combination of Niraparib with EGFR Inhibitor Panitumumab in 
previously treated patients with RAS WT metastatic colorectal cancer.
Hypothesis: The combination of Niraparib and Panitumumab will be safe, tolerable and 
effective in patients with advanced RAS WT colorectal cancer. 
1.3
Secondary Objectives
I.
Define the toxicity profile of the combination of Niraparib and Panitumumab. The 
additional patients enrolled on the expansion cohorts will help confirm the toxicity profile.
II.
Evaluate the activity of the combination of Niraparib and Panitumumab in previously 
treated patients with metastatic colorectal cancer.

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1.4     Endpoints
The primary endpoint of this phase II study will be clinical benefit rate = Complete Response 
+ Partial Response + Stable disease (CR +PR + SD) rate. 
The other secondary end points include:
A. Toxicity profile of the combination of Panitumumab and Niraparib; additional patients 
enrolled on the expansion cohort to confirm the toxicity profile.
B. Efficacy endpoints: Objective response rate, response duration, overall survival and 
progression free survival. This will only be preliminary data since this is a secondary 
objective.
C. Biomarker analysis: Objective of the correlative assays is to try and identify patients 
who respond to the combination. As a standard of care at Emory, patients with stage 
IV CRC receive genomic profiling to evaluate for therapeutic targets. We propose 
analyzing these profiles to identify patients with defects in their DNA repair pathways 
as a potential biomarker for this regimen. Normal skin biopsies from regions that 
contained hair follicles will be obtained in the form of a 4-mm diameter punch biopsy 
(8 mm depth) before treatment and on days 22 of cycle 1. The biopsies will be 
evaluated for: 
1. Four metrics of cytotoxicity - Caspace-3, γ-H2AX, PARP, MAPK, together with 
indicators of EGFR downregulation. 
2. Tumor infiltrating cells using multiplex immunofluorescence panels.

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2
BACKGROUND AND SIGNIFICANCE 
2.1
Background of PARP and Homologous Recombination Deficiency
Poly(ADP-ribose) polymerase (PARP)1 and PARP2 are zinc-finger deoxyribonucleic acid 
(DNA)-binding enzymes that play a crucial role in DNA repair.1 Upon formation of DNA 
breaks, PARP binds at the end of broken DNA strands, a process that activates its 
enzymatic activity.
Activated PARP catalyzes the addition of long polymers of adenosine diphosphate (ADP)-
ribose onto PARP and several other proteins associated with chromatin, including histones 
and various DNA repair proteins.2,3 This results in chromatin relaxation, fast recruitment of 
DNA repair proteins, and efficient repair of DNA breaks. In this manner, PARP plays a key 
role in sensing DNA damage and converting it into intracellular signals that activate the 
base excision repair (BER) and single-strand break repair pathways. Normal cells repair up 
to 10,000 DNA defects daily, and single-strand breaks are the most common form of DNA 
damage. Cells that are unable to repair this burden of DNA damage, such as those with 
defects in the homologous recombination or BER pathways, are at risk for accumulating 
multiple lesions that will ultimately trigger apoptosis. They enter the S phase (DNA 
replication) of the cell cycle with unrepaired single- and double-strand breaks. Pre-existing 
single-strand breaks are converted to double-strand breaks as the replication machinery 
passes. Accumulated double-strand breaks present during S phase are repaired by 
homologous recombination. Homologous recombination is the preferred repair pathway 
because it is associated with a much lower error rate than other forms of repair. Cells that 
are unable to perform DNA repair via homologous recombination (e.g., due to inactivation 
of genes required for homologous recombination, such as breast cancer [BRCA1]- or breast 
cancer 2 [BRCA2]-mutated cells) are at risk for accumulating multiple lesions that will 
ultimately trigger apoptosis. These cells accumulate stalled replication forks during S phase 
and are more likely to use the error-prone nonhomologous end joining (NHEJ) or 
alternative (alt)-NHEJ pathways to repair double-strand breaks in DNA. Accumulation of 
errors in DNA by NHEJ contributes to mutation burden that promotes the development of 
cancer. Over time, the buildup of excessive DNA errors in combination with the inability to 
complete S phase (because of stalled replication forks) contributes to cell death.2,3
Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a 
subset of cancer cells with deficiencies in DNA repair pathways. For example, a tumor 
arising in a patient with a germline BRCA mutation (gBRCAmut) has a defective 
homologous recombination DNA repair pathway and would be increasingly dependent on 
NHEJ, alt-NHEJ, and BER for maintenance of genomic integrity. PARP inhibitors block 
alt-NHEJ and BER, forcing tumors with BRCA deficiencies to use the error-prone NHEJ to 
fix double-strand breaks.1 Non-BRCA deficiencies in homologous recombination DNA 
repair genes could also enhance tumor cell sensitivity to PARP inhibitors.4 The rationale 
for anticancer activity in a subset of non-gBRCAmut tumors is that they share distinctive 
DNA repair defects with gBRCAmut carriers, a phenomenon broadly described as 
“BRCAness.”5 DNA repair defects can be caused by germline or somatic alterations to the 
homologous recombination DNA repair pathway. In a recent analysis of approximately 500 

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high-grade serous ovarian adenocarcinoma tumors, approximately 50% contained 
homologous recombination defects.6 A subset of these tumors had biologically plausible 
molecular alterations that may make them sensitive to PARP inhibition by niraparib. A 
similar analysis of triple-negative breast cancer indicates that 43% to 44% of these patients 
have tumors with homologous recombination defects.7 Homologous recombination is a 
complex pathway, and several genes other than BRCA1 and BRCA2 are required either to 
sense or repair DNA double-strand breaks via the homologous recombination pathway. 
Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies 
in DNA repair proteins other than BRCA1 and BRCA2.1,5,8 
Recent clinical studies have shown PARP inhibitors to be active in breast and ovarian 
cancer. Clinical anticancer activity with PARP inhibitors has been seen in both patients with 
gBRCAmut and without gBRCAmut; however, activity is more robust in patients with the 
germline mutation.1,4,9-15 In summary, treatment with PARP1/2 inhibitors represents a novel 
opportunity to selectively kill a subset of cancer cell types by exploiting their deficiencies in 
DNA repair. Human cancers exhibit genomic instability and an increased mutation rate due 
to underlying defects in DNA repair. These deficiencies render cancer cells more 
dependent on the remaining DNA repair pathways, and targeting these pathways is 
expected to have a much greater impact on the survival of the tumor cells than that of 
normal cells.
2.2
Background of Niraparib
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a 
treatment for patients with tumors that harbor defects in the homologous recombination 
DNA repair pathway or that are driven by PARP-mediated transcription factors.
2.2.1
Nonclinical Experience 
Nonclinical data on niraparib are discussed in detail in the niraparib Investigator’s Brochure 
(IB). Briefly, in nonclinical models, niraparib has been observed to inhibit normal DNA repair 
mechanisms and induce synthetic lethality when administered to cells with homologous 
recombination defects. In a BRCA1-mutant xenograft study, niraparib dosed orally caused 
tumor regression, which was mirrored by a >90% reduction in tumor weight compared with 
control. In a BRCA2-mutant xenograft study, niraparib-dosed mice showed 55% to 60% 
growth inhibition, both by tumor volume and weight.
Niraparib displayed strong antitumor activity in in vivo studies with BRCA1-mutant breast 
cancer (MDA-MB-436), BRCA2-mutant pancreatic cancer (CAPAN-1), and with patient-
derived Ewing sarcoma mice models. Utilizing patient-derived ovarian and breast cancer 
xenograft models, niraparib demonstrated response in both BRCAmut and BRCA wild-type 
tumors.

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2.2.2
Clinical Experience 
Niraparib clinical data are discussed in detail in the niraparib IB. In the Phase 1 clinical 
program, niraparib, as a monotherapy or in combination with chemotherapy, has been 
administered to 144 patients.
Phase 1 Study of Niraparib Monotherapy in Advanced Solid Tumors
Niraparib clinical data are discussed in detail in the niraparib IB. In the Phase 1 clinical 
program, niraparib, as a monotherapy or in combination with chemotherapy, has been 
administered to 144 patients.
Phase 1 Study of Niraparib Monotherapy in Advanced Solid Tumors
Clinical activity data for niraparib administered as monotherapy in patients with ovarian 
cancer are available from 1 early-phase clinical study. In Parts A and B of the Phase 1 
study PN001 (ClinicalTrials.gov identifiers: MK-4827-001 and 2008_501), 100 patients with 
advanced solid tumors who had received a median of 3 prior therapies were enrolled; 49 
patients had ovarian cancer (13 platinum-sensitive, 35 platinum-resistant, and 1 platinum-
refractory).11 An additional 4 patients were enrolled in Part D of the study, which assessed 
pharmacokinetics only.16 
The most common nonhematological TEAEs were nausea, fatigue, anorexia, constipation, 
vomiting, and insomnia. These TEAEs were mainly mild to moderate in severity, self-
limiting, and manageable with standard treatments. Hematological toxicity appeared to be 
dose proportional and most frequently arose in the setting of cumulative doses. Anemia 
was reported in 48 (48%) of 100 patients and was Grade ≥3 in 10 (10%) of 100 patients. 
Thrombocytopenia was less common (35 [35%] of 100 patients) and was Grade ≥3 in 15 
(15%) of 100 patients. Neutropenia was the least commonly reported (24 [24%] of 100 
patients), and was Grade 3 in 4 (4%) of 100 patients at niraparib doses of 300 and 400 mg. 
In all cases, hematological TEAEs were uncomplicated and reversible. Twenty patients 
required dose reductions (usually by 1 dose level) for recurrent anemia or 
thrombocytopenia. Treatment was discontinued due to AEs in 7 patients, including the 4 
patients who had DLTs during the first cycle and 3 patients who had Grade 3 vomiting, 
Grade 2 prolongation of QT interval, and Grade 3 prolongation of QT interval. No treatment-
related deaths occurred.
Of the 49 patients, 22 had confirmed BRCA1 or BRCA2 mutation, of whom 20 were 
radiologically assessable. Eight (40%) of these 20 patients achieved a confirmed partial 
response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) and cancer 
antigen 125 (CA-125) Gynecologic Cancer Intergroup criteria at doses ranging from 80 to 
400 mg per day. Median response duration was 387 days (range: 159 to 518 days). Three 
(33%) of 9 patients with platinum-resistant BRCAmut ovarian cancer had PR by RECIST 
and CA-125 criteria. In patients with platinum-sensitive disease, 5 (50%) of 10 patients 
(95% CI: 19 to 81) with BRCA1 or BRCA2 mutations had RECIST and CA-125 responses.

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Phase 3 Study of Niraparib Monotherapy in Platinum-sensitive, Recurrent Ovarian Cancer
In the randomized, double-blind, Phase 3 NOVA trial (Niraparib Maintenance Therapy in 
Platinum-Sensitive, Recurrent Ovarian Cancer), a total of 553 patients were randomized at 
107 centers worldwide13. Patients were categorized according to the presence or absence 
of a gBRCAmut (gBRCA cohort and non-gBRCA cohort) within their tumors and the type 
of non-gBRCAmut and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) 
or placebo once daily (QD). The primary end point was PFS. The study enrolled 203 
patients in the gBRCAmut cohort and 350 patients in the non-gBRCAmut cohort. Among 
the 350 patients in the non-gBRCAmut cohort, 162 had tumors that were identified as 
homologous recombination deficiency positive (HRDpos), and 134 had tumors that were 
HRD negative (HRDneg). HRD status was not determined for 54 patients.
Demographic and baseline characteristics were well balanced.  Table 1 below shows the 
results for the PFS primary endpoint for each of the 3 primary efficacy populations (ie, 
gBRCAmut cohort, HRDpos cohort, and overall non-gBRCAmut cohort). In addition, 
median PFS in patients with HRDneg tumors was 6.9 months (95% confidence interval [CI]: 
5.6, 9.6) in the niraparib arm, versus 3.8 months (95% CI: 3.7, 5.6) in the placebo arm, with 
a HR of 0.58 (95% CI: 0.361, 0.922) (p = 0.0226).
Table 1: Progression-Free Survival in Ovarian Cancer Patients in NOVA
gBRCAmut Cohort
Non-gBRCAmut Cohort 
(Regardless 
of 
HRD 
Status)
HRDpos 
(Within 
non-gBRCAmut 
Cohort)
Niraparib 
(n = 138)
Placebo 
(n = 65)
Niraparib 
(n = 234)
Placebo 
(n = 116)
Niraparib 
(n = 106)
Placebo 
(n = 56)
Median PFS (95% CI)a
21.0
(12.9, NE)
5.5
(3.8, 7.2)
9.3
(7.2, 11.2)
3.9
(3.7, 5.5)
12.9
(8.1, 15.9)
3.8
(3.5, 5.7)
p-valueb
< 0.0001
< 0.0001
< 0.0001
HR 
(niraparib:placebo) 
(95% CI)c
0.27
(0.173, 0.410)
0.45
(0.338, 0.607)
0.38
(0.243, 0.586)
Source: PR-30-5011-C (NOVA main) CSR
Abbreviation: CI = confidence interval; CSR = clinical study report; gBRCAmut = germline BRCA mutation; 
HR = hazard ratio; HRD = homologous recombination deficiency; HRDpos = homologous recombination 
deficiency positive; NE = not evaluated; PFS = progression-free survival.
a PFS is defined as the time in months from the date of randomization to progression or death.
b Based on stratified log-rank test using randomization stratification factors.
c Based on the stratified Cox proportional hazards model using randomization stratification factors.
The primary data to support the safety of treatment with niraparib are derived from the 
NOVA main study in which a total of 546 patients received study treatment.
All 367 patients who received niraparib and 171 (96%) of 179 patients who received 
placebo experienced at least 1 treatment-emergent adverse event (TEAE). The high rate 
of TEAEs in the placebo group indicates the burden of prior chemotherapy and the patient’s 
underlying ovarian cancer. Review of the data across study cohorts for TEAE incidence 
showed that, in general, the results were similar in the gBRCAmut and non-gBRCAmut 

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cohorts. In the overall safety population, for the niraparib versus placebo treatment arms, 
the incidences of Grade 3 or 4 TEAEs (74% vs. 23%), serious adverse events (SAEs) (30% 
vs. 15%), TEAEs leading to treatment interruption (67% vs. 15%), TEAEs leading to dose 
reduction (69% vs. 5%), and TEAEs leading to treatment discontinuation (15% vs. 2%) 
were higher for niraparib than for placebo. There were no on-treatment deaths reported.
The most commonly observed nonhematologic TEAEs (all grades) observed in niraparib-
treated compared with placebo-treated patients were nausea (74% vs. 35%), fatigue (46% 
vs. 32%), constipation (40% vs. 20%), and vomiting (34% vs. 16%). The majority of the 
nonhematological TEAEs were mild to moderate in severity. The most commonly observed 
hematologic TEAEs (all grades) of niraparib were anemia (49%), thrombocytopenia (46%), 
decreased platelet count (20%), and neutropenia (18%). Although Grade 3 or 4 
hematologic laboratory AEs were common at the initiation of study treatment, no severe 
clinical sequelae were observed, and relatively few patients discontinued study treatment 
due to these AEs. Dose adjustment based on individual tolerability during the first 3 cycles 
substantially reduced the incidence of these AEs beyond Cycle 3, indicating the overall 
effectiveness of the approach to dose modification. These TEAEs can be monitored 
routinely using standard assessments of hematological laboratory parameters, as is routine 
for patients with ovarian cancer receiving anticancer therapies. In the NOVA study, 
niraparib dose adjustment tended to occur early with most patients reaching their individual 
adjusted dose level at the end of Month 3 (ie, Cycle 3) of treatment.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been observed 
in patients receiving treatment with olaparib, a PARP inhibitor; given the common 
mechanism of action, MDS and AML therefore represent a potential risk to patients 
receiving niraparib. In the Phase 3 NOVA study, the incidence of MDS/AML in patients who 
received niraparib (5 of 367; 1.4%) was similar to its incidence in patients who received 
placebo (2 of 179; 1.1%). Guidance on monitoring patients for new AEs of MDS/AML and 
the follow-up of patients with suspected MDS/AML is provided.
Study PR-30-5011-C1 (NOVA corrected QT interval [QTc] substudy; n = 26) is an open-
label evaluation of the effects of niraparib on QTc measurements in patients with 
histologically diagnosed ovarian cancer, fallopian tube cancer, or primary peritoneal 
cancer. There were no reports of clinically significant abnormal electrocardiogram (ECG) 
changes, including QTc interval prolongation, attributed to niraparib. Administration of 
niraparib at the therapeutic dose did not prolong the QT interval. There was no correlation 
between the exposure level (ie, plasma concentration) of niraparib and QTc changes (i.e., 
change in corrected QT interval calculated using Fridericia’s formula [ΔQTcF]). 
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 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 

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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 3/4 
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.
2.3
Rationale for Current Study
2.3.1
Rationale for Study Population
Each year, an estimated 300,000 people are diagnosed with GI cancers, with over 150, 
000 people dying annually17. Almost 135,000 cases of colorectal cancer (CRC) are 
projected to be diagnosed in the US in 2017; with more than 50,000 deaths from the 
disease.  CRC is the second leading causes of cancer death in both sexes the US. 
Therefore, GI cancers are a major area of need for new drug development.
Panitumumab (Vectibix) is a recombinant, human IgG2 kappa monoclonal antibody that 
binds specifically to the human epidermal growth factor receptor (EGFR), and is indicated 
as a single agent for the treatment of metastatic colorectal carcinoma18. The EGFR is a 
transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine 

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kinases, including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in 
normal epithelial tissues, including the skin and hair follicle. EGFR is over-expressed in 
certain human cancers, including colon and rectum cancers. Interaction of EGFR with its 
normal ligands (eg, EGF, transforming growth factor-alpha) leads to phosphorylation and 
activation of a series of intracellular proteins, which in turn regulate transcription of genes 
involved with cellular growth and survival, motility, and proliferation. Signal transduction 
through the EGFR results in activation of the wild-type KRAS protein. However, in cells with 
activating KRAS somatic mutations, the mutant KRAS protein is continuously active and 
appears independent of EGFR regulation.
Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively 
inhibits the binding of ligands for EGFR19. Nonclinical studies show that binding of 
panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and 
activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of 
apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and 
internalization of the EGFR. In vitro assays and in vivo animal studies demonstrate that 
panitumumab inhibits the growth and survival of selected human tumor cell lines expressing 
EGFR.
Safety data are available from 15 clinical trials in which 1467 patients received 
Panitumumab; of these, 1293 received Panitumumab monotherapy and 174 received 
Panitumumab in combination with chemotherapy19-22. Overall Panitumumab is well 
tolerated. Most common adverse reactions (≥ 20%) are skin toxicities (i.e., erythema, 
dermatitis 
acneiform, 
pruritus, 
exfoliation, 
rash, 
and 
fissures), 
paronychia, 
hypomagnesemia, fatigue, abdominal pain, nausea, diarrhea, and constipation. Niraparib 
is an orally active poly(ADP-ribose) polymerase (PARP)–1 and –2 inhibitor. It is well 
tolerated as a single agent and has no overlapping toxicity with Panitumumab.
Colorectal cancer is treated both in the curative and metastatic settings with oxaliplatin-
fluoropyrimidine combinations. The efficacy of these regimens and the sensitivity of CRC 
to the platinum compound have been established in numerous preclinical and clinical 
studies, highlighting the role of such first line chemotherapy combinations in clinical 
practice23-26. Moreover, numerous DNA repair genes have been demonstrated to play 
significant roles in the development and propagation of colorectal cancer in both genetic 
and sporadic cases. Apart from the well described heritable factors with known hereditary 
syndromes such as mismatch repair genes in Lynch syndrome, several lower penetrance 
polymorphisms affect other DNA repair genes. DNA repair pathways, including base 
excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct 
reversal repair (DRR), and double-strand break repair are complex, evolutionarily 
conserved, and critical in carcinogenesis27. A previous study identified 61 polymorphisms 
in 26 different DNA repair genes associated with CRC.
A major consideration in the treatment of different malignancies with PARP inhibition as 
discussed in section 2.1 above is the correlation with platinum sensitivity. Cancer cell 
sensitivity and resistance to both PARP inhibition and platinum have been associated with 

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loss and restoration of HR DNA repair, respectively, indicating similar mechanisms of 
anticancer activity and resistance28,29. Platinum sensitivity in CRC could therefore predict 
for anticancer properties of PARP inhibition when utilized in the setting of synthetic lethality. 
Preliminary data have shown that EGFR inhibition induces synthetic lethality with PARPi in 
head and neck squamous cell carcinomas (HNSCCs) in vitro by attenuating DNA repair 
pathways. Combined EGFR and PARP inhibition resulted in the greatest tumor growth 
delay versus either agent alone in mice bearing head and neck tumor xenografts, correlated 
with persistent γ-H2AX foci indicative of unresolved DNA damage. This susceptibility to 
PARPi induced by EGFR inhibition was associated with deficient NHEJ- and HR-mediated 
DNA repair and subsequent persistence of DNA damage. 
In addition, regulation of homologous recombination repair involving EGFR and BRCA1 
interaction, and alteration of subcellular localization offers a contextual synthetic lethality 
between combined EGFR and PARP inhibitors in triple negative breast cancer. The 
combination therapy induced persistent DNA double strand breaks responsible for 
enhanced cytotoxicity of TNBC to lapatinib and ABT-888, with >3-fold tumor growth delay 
in combination treatment vs. control.
2.3.2 Clinical Experience with Panitumumab
Monotherapy
The safety and efficacy of Panitumumab were studied in Study 1, an open-label, 
multinational, randomized, controlled trial of 463 patients with EGFR-expressing, 
metastatic carcinoma of the colon or rectum (mCRC). Patients were required to have 
progressed on or following treatment with a regimen(s) containing a fluoropyrimidine, 
oxaliplatin, and irinotecan; progression was confirmed by an independent review committee 
(IRC) for 75% of the patients. All patients were required to have EGFR expression defined 
as at least 1+ membrane staining in ≥ 1% of tumor cells by the Dako EGFR pharmDx® test 
kit. Patients were randomized 1:1 to receive panitumumab at a dose of 6 mg/kg given once 
every 2 weeks plus best supportive care (BSC) (n = 231) or BSC alone (n = 232) until 
investigator-determined disease progression. Randomization was stratified based on 
ECOG performance status (0–1 vs 2) and geographic region (western Europe, 
eastern/central Europe, or other). 
Upon investigator-determined disease progression, patients in the BSC-alone arm were 
eligible to receive panitumumab and were followed until disease progression was confirmed 
by the IRC. The analyses of progression-free survival (PFS), objective response, and 
response duration were based on events confirmed by the IRC that was masked to 
treatment assignment.
Based upon IRC determination of disease progression, a statistically significant 
prolongation in PFS was observed in patients receiving Panitumumab compared to those 

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receiving BSC alone. The mean PFS was 96 days in the Panitumumab arm and 60 days 
in the BSC-alone arm. Results are presented in Figure 1 below.
Figure 1. Kaplan-Meier Plot of Progression-Free Survival Time as Determined by the 
IRC
In a series of sensitivity analyses, including one adjusting for potential ascertainment bias, 
i.e., assessment for progressive disease at a nonstudy specified time point, PFS was still 
significantly prolonged among patients receiving panitumumab as compared to patients 
receiving BSC alone.
Of the 232 patients randomized to BSC alone, 75% of patients crossed over to receive 
panitumumab following investigator determination of disease progression; the median time 
to cross over was 8.4 weeks (0.3–26.4 weeks). Partial responses were identified by the 
IRC in 19 patients randomized to panitumumab, for an overall response of 8% (95% CI: 
5.0%, 12.6%). No patient in the control arm had an objective response identified by the 
IRC. The median duration of response was 17 weeks (95% CI: 16 weeks, 25 weeks). There 
was no difference in overall survival between the study arms.
Panitumumab in Combination with Bevacizumab and Chemotherapy
Panitumumab shortened PFS, decreased survival time, and increased toxicity when given 
in combination with bevacizumab and chemotherapy in Study 2, a randomized, open-label, 
multicenter trial in the first-line treatment of metastatic colorectal cancer. Patients (n = 1053) 
were randomized 1:1 to panitumumab at a dose of 6 mg/kg given once every 2 weeks, in 
combination with bevacizumab and an oxaliplatin- or irinotecan-based 5-fluorouracil-
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Randomization was stratified by type of regimen (oxaliplatin- or irinotecan-based); 86% of 
patients received an oxaliplatin-based regimen and 14% received an irinotecan-based 
regimen.
The major study objective was comparison of PFS in the oxaliplatin stratum as determined 
by an independent central review. An interim analysis based on 257 PFS events in the 
oxaliplatin stratum demonstrated shorter PFS in patients receiving Panitumumab, 
bevacizumab, and chemotherapy compared to those receiving bevacizumab and 
chemotherapy alone (median PFS were 8.8 months and 10.5 months; hazard ratio 1.44 
[95% CI: 1.12, 1.85], p-value = 0.0024, Cox model with randomization factors as 
covariates). An unplanned analysis of overall survival after 155 deaths (both strata 
combined), conducted at the time of the interim analysis of PFS, yielded an adjusted hazard 
ratio of 1.55 [95% CI: 1.12, 2.14], comparing patients receiving Panitumumab, 
bevacizumab, and chemotherapy (92 deaths) to those receiving bevacizumab and 
chemotherapy alone (63 deaths)
Lack of Efficacy of Anti-EGFR Monoclonal Antibodies in Patients with mCRC 
Containing KRAS Mutations
Retrospective analyses across seven randomized clinical trials suggest that anti-EGFR-
directed monoclonal antibodies are not effective for the treatment of patients with mCRC 
containing KRAS mutations. In these trials, patients received standard of care (i.e., BSC or 
chemotherapy) and were randomized to receive an anti-EGFR antibody (cetuximab or 
panitumumab) or no additional therapy. In all studies, investigational tests were used to 
detect KRAS mutations in codon 12 or 13. The percentage of study populations for which 
KRAS status was assessed ranged from 23% to 92%.
The data described in Table 2 and in other sections below, except where noted, reflect 
exposure to Panitumumab administered as a single agent at the recommended dose and 
schedule (6 mg/kg every 2 weeks) in 229 patients with mCRC enrolled in Study 1, a 
randomized, controlled trial. The median number of doses was five (range: one to 26 
doses), and 71% of patients received eight or fewer doses. The population had a median 
age of 62 years (range: 27 to 82 years), 63% were male, and 99% were white with < 1% 
black, < 1% Hispanic, and 0% other.
Table 2. Per-Patient Incidence of Adverse Reactions Occurring in ≥ 5% of Patients 
with a Between-Group Difference of ≥ 5% (Study 1)
Patients Treated With Vectibix Plus 
BSC (n = 229)
Best 
Supportive 
Care 
(BSC)  Alone (n = 234) 
Grade
*
Body System 
All Grades (%) 
Grade 3–4 
(%) 
All Grades 
(%) 
Grade 3–4 
(%) 
Body as a Whole 
Fatigue 
26 
4 
15 
3 
General Deterioration 
11 
8 
4 
3 
Digestive 
Abdominal Pain 
25 
7 
17 
5 

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Nausea 
23 
1 
16 
< 1 
Diarrhea 
21 
2 
11 
0 
Constipation 
21 
3 
9 
1 
Vomiting 
19 
2 
12 
1 
Stomatitis 
7 
0 
1 
0 
Mucosal Inflammation 
6 
< 1 
1 
0 
Metabolic/Nutritional 
Hypomagnesemia (Lab) 
38 
4 
2 
0 
Peripheral Edema 
12 
1 
6 
< 1 
Respiratory 
Cough 
14 
< 1 
7 
0 
Skin/Appendages 
All Skin/Integument Toxicity 
90 
16 
9 
0 
Skin 
90 
14 
6 
0 
Erythema 
65 
5 
1 
0 
Dermatitis Acneiform 
57 
7 
1 
0 
Pruritus 
57 
2 
2 
0 
Nail 
29 
2 
0 
0 
Paronychia 
25 
2 
0 
0 
Skin Exfoliation 
25 
2 
0 
0 
Rash 
22 
1 
1 
0 
Skin Fissures 
20 
1 
< 1 
0 
Eye 
15 
< 1 
2 
0 
Acne 
13 
1 
0 
0 
Dry Skin 
10 
0 
0 
0 
Other Nail Disorder 
9 
0 
0 
0 
Hair 
9 
0 
1 
0 
Growth of Eyelashes 
6 
0 
0 
0 
*Version 2.0 of the NCI-CTC was used for grading toxicities. Skin toxicity was 
coded based on a modification of the NCI-CTCAE, version 3.0. 
2.3.3
Rationale for Objectives
APC-induced blockage of base excision repair (BER) pathways have been shown to play 
a significant role in colorectal carcinogenesis, with implications for therapeutic targets. The 
product of the APC gene can modulate base excision repair (BER) pathway through an 
interaction with DNA polymerase β (Pol-β) and flap endonuclease 1 (Fen-1) to mediate 
CRC cell apoptosis. Since PARP inhibitors effectively block BER, PARP inhibition has the 
potential to increase the sensitivity of EGFR inhibition in both MMR-proficient and MMR-
deficient colorectal tumors. Therefore, combining PARP and EGFR inhibition has the 
potential to confer synergistic benefit while also ameliorating a potential resistance 
mechanism to PARP inhibitor therapy. This combination has strong potential to offer a 
superior anticancer efficacy compared to each strategy alone.

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2.3.4
Rationale for Measures
A safety run-in of the approved dose of Panitumumab safely combined with Niraparib will 
be done in the first 6 patients, given that there is no evidence or concerns of additive or 
overlapping toxicities between the two classes of agents being tested. An initial cohort of 6 
RAS WT colorectal cancer (CRC) patients will be enrolled and treated for the safety run-in 
and will be monitored during cycle 1 for toxicities in excess of known side-effect profile of 
both agents. These 6 patients will also be evaluated for efficacy of the combination therapy.  
Additional 20 CRC patients with the same inclusion criteria will be subsequently enrolled 
and treated to determine efficacy. Patients who fail screening will be replaced. We will 
consider the combination of Niraparib and Panitumumab to be ineffective if the true CBR is 
less than 10% (p0). We will also assume that the combination is worthy of further study if 
the true CBR rate is 25% or greater (p1). With an alpha of 0.1 and beta 0.8 (small pilot 
estimate of activity), the sample size will be 26 patients, enrolled and treated on this phase 
II study. Allowance will be made for patients who consent but fail screening for the clinical 
trial. Given our previous enrollment to colorectal cancer trials, we anticipate completion of 
enrollment in 18 months.
In addition, we plan to collect at study entry data on 
a.
Best response to prior therapy with Oxaliplatin (CR, PR, SD for more than 4 months 
OR Progression of Disease; PD) 
b.
Oxaliplatin refractory (progression on Oxaliplatin) OR sensitive (Oxaliplatin stopped 
due to neuropathy) disease. 
We will evaluate the activity (CBR) of the regimen in in each group. This is a secondary 
hypothesis generating aim.

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3
PARTICIPANT SELECTION
3.1
Inclusion Criteria
a. Participant must have advanced, metastatic RAS wildtype colorectal cancer and 
must have received at least one line of palliative systemic therapy. Both 
microsatellite (MSI-H) high and stable (MSS) patients are eligible 
b. Participants may have been intolerant of, progressed on, or failed at least one line 
of systemic chemotherapy in the metastatic setting. Patients who are currently on 
first line Oxaliplatin-containing chemotherapy regimen are allowed on the trial if they 
have remained stable or better (PR or CR) for at least 4 months on that line of 
treatment and are being considered for maintenance therapy as standard of care.
c. Histologic or cytologic diagnosis of colorectal cancer 
d. Participant must have an Eastern Cooperative Oncology Group (ECOG) 
performance status of ≤ 1.
e. Participant must be ≥ 18 years of age
f.
Participant must have adequate organ function, defined as follows:

Absolute neutrophil count ≥ 1,500/µL

Platelets ≥ 100,000/µL

Hemoglobin ≥ 9 g/dL

Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine 
clearance ≥ 30 mL/min using the Cockcroft-Gault equation

Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR 
direct bilirubin ≤ 1 x ULN

Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless 
liver metastases are present, in which case they must be ≤ 5 x ULN 
g. Participant receiving corticosteroids may continue as long as their dose is stable for 
least 4 weeks prior to initiating protocol therapy.
h. Participant must agree to not donate blood during the study or for 90 days after the 
last dose of study treatment.
i.
Female participant has a negative urine or serum pregnancy test within 7 days prior 
to taking study treatment if of childbearing potential and agrees to abstain from 
activities that could result in pregnancy from screening through 180 days after the 
last dose of study treatment or is of nonchildbearing potential. Nonchildbearing 
potential is defined as follows (by other than medical reasons):

≥45 years of age and has not had menses for >1 year

Patients who have been amenorrhoeic for <2 years without history of a 
hysterectomy and oophorectomy must have a follicle stimulating hormone value 
in the postmenopausal range upon screening evaluation

Post-hysterectomy, 
post-bilateral 
oophorectomy, 
or 
post-tubal 
ligation. 
Documented hysterectomy or oophorectomy must be confirmed with medical 

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records of the actual procedure or confirmed by an ultrasound/screening CT/MRI 
scans. Tubal ligation must be confirmed with medical records of the actual 
procedure, otherwise the patient must be willing to use 2 adequate barrier 
methods throughout the study, starting with the screening visit through 180 days 
after the last dose of study treatment. See Section 4.4 for a list of acceptable 
birth control methods. Information must be captured appropriately within the 
site’s source documents. Note: Abstinence is acceptable if this is the established 
and preferred contraception for the patient.
j.
Participant must agree to not breastfeed during the study or for 180 days after the 
last dose of study treatment.
k. Male participant agrees to use an adequate method of contraception (see Section 
4.4 for a list of acceptable birth control methods) starting with the first dose of study 
treatment through 180 days after the last dose of study treatment. Note: Abstinence 
is acceptable if this is the established and preferred contraception for the patient.
l.
Participant must be able to understand the study procedures and agree to participate 
in the study by providing written informed consent
3.2
Exclusion Criteria
a. Participant must not be simultaneously enrolled in any interventional clinical trial
b. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol 
therapy and participant must have recovered from any surgical effects.
c. Participant must not have received investigational therapy ≤ 4 weeks, or within a 
time interval less than at least 5 half-lives of the investigational agent, whichever is 
shorter, prior initiating protocol therapy.
d. Prior therapy with PARP inhibitors or with EGFR inhibitors approved for the 
treatment of colorectal cancer (Cetuximab or Panitumumab)
e. Patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence 
of interstitial pneumonitis or pulmonary fibrosis during screening.
f.
Inability to take oral medications.
g. Participant has had radiation therapy encompassing >20% of the bone marrow 
within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol 
therapy.
h. Participant must not have a known hypersensitivity to components or excipients of 
Niraparib or Panitumumab.
i.
Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 
weeks prior to initiating protocol therapy.
j.
Participant must not have received colony-stimulating factors (e.g., granulocyte 
colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or 
recombinant erythropoietin) within 4 weeks prior initiating protocol therapy. 

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k. Participant 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. 
l.
Participant must not have any known history of myelodysplastic syndrome (MDS) or 
acute myeloid leukemia (AML) 
m. Participant must not have a serious, uncontrolled medical disorder, nonmalignant 
systemic disease, or active, uncontrolled infection. Examples include, but are not 
limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial 
infarction, uncontrolled major seizure disorder, unstable spinal cord compression, 
superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining 
informed consent
n. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
o. Participant must not have had diagnosis, detection, or treatment of another type of 
cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell 
carcinoma of the skin and cervical cancer that has been definitively treated)
p. Participant must not have known active, symptomatic brain or leptomeningeal 
metastases. Subjects with previously treated brain metastases may participate 
provided they are stable (without evidence of progression by imaging (CT/MRI) for 
at least four weeks prior to the first dose of trial treatment and any neurologic 
symptoms have returned to baseline), have no evidence of new or enlarging brain 
metastases, and are not using steroids for at least 7 days prior to trial treatment.  
This exception does not include carcinomatous meningitis which is excluded 
regardless of clinical stability.  

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4
TREATMENT PLAN
4.1
Method of Treatment Assignment
This is a non-randomized, phase II, open-label study.
4.2
Treatment Regimen
A. Panitumumab 6 mg/kg intravenous infusion on Day 1 and 15 of each 28-day cycle 
administered over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg).
B. Niraparib 200mg or 300mg (based on baseline weight and/or serum platelet count – see 
table 2 below) Oral, daily, continuously.
4.2.1
Niraparib Administration
Niraparib will be administered as a flat-fixed, continuous daily dose according to the Table 
2 below. Niraparib should be swallowed whole and not opened, crushed or chewed. Food 
does not significantly affect the absorption of niraparib; therefore, niraparib may be taken 
without regard to meals. Participants should take doses at approximately the same times 
each day.  Bedtime administration may be a potential method for managing nausea.
Vomited doses should not be made up.
If a participant misses a dose (greater than 12 hours from normal dosing time) of niraparib, 
they should skip that dose and take their next dose at its regularly scheduled time.  
If niraparib is dose reduced, participants should be instructed to continue using their current 
supply at their new dose until their supply has been exhausted. 
Participants must be instructed to return unused study drugs to the site at discontinuation 
or completion of treatment. The site personnel must ensure that the appropriate dose of 
each study drug is administered and that the drug accountability is performed and 
documented.
Table 2: Niraparib Dosing 
Baseline Criteria 
Starting Dose 
≥77 kg and ≥150,000 µL
300 mg (3 X 100 mg capsules) daily 
<77 kg or <150,000 µL
200 mg (2 X 100 mg capsules) daily*
* For patients whose starting dose is 2 capsules once daily, escalation to 3 capsules once 
daily is permitted if no treatment interruption or discontinuation was required during the first 
2 cycles of therapy
4.2.2
Panitumumab Administration
Panitumumab is administered at 6 mg/kg intravenous infusion on Day 1 and 15 of each 28-
day cycle, over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg). Pre-medications are 
allowed if the patient has received same for other monoclonal antibodies. Primary skin 

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prophylaxis must be instituted with initiation of therapy, including sunlight protection, skin 
care with hydrophilic cream, and oral antibiotics with doxycycline (100–200 mg/day for ≥8 
weeks) or minocycline (100 mg/day for ≥8 weeks).
4.3
Prohibited Therapies
The following medications are prohibited while receiving protocol therapy:

Systemic anticancer or biological therapy.

Immunotherapy not specified in this protocol.

Chemotherapy not specified in this protocol.

Investigational agents other than niraparib

Radiation therapy encompassing >20% of the bone marrow is prohibited within 
2 weeks prior to Day 1 and during study treatment. Note: Palliative radiation 
therapy to a small field >1 week prior to Day 1 of study treatment may be allowed.

Any surgery that involves tumor lesions. Note: Administration of radiation therapy 
or surgery done that involves tumor lesions will be considered as disease 
progression at the time the procedure is performed.

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. 

Prophylactic cytokines (i.e., granulocyte colony-stimulating factor [GCSF]) 
should not be administered in the first cycle of the study but may be administered 
in subsequent cycles according to current American Society of Clinical Oncology 
(ASCO) guidelines.30 
4.4
Birth Control
Participants of childbearing potential who are sexually active and their partners must agree 
to the use of a highly effective form of contraception throughout their participation beginning 
with time of consent, during the study treatment and for 180 days after last dose of study 
treatment(s):

Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation:

Oral route

Intravaginal route

Transdermal route

Progestogen-only hormonal contraception associated with inhibition of ovulation 

Oral

Injectable

Implantable

Intrauterine device

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
Intrauterine hormone-releasing system

Bilateral tubal occlusion

Vasectomized partner

Sexual abstinence, if the preferred and usual lifestyle of the subject
4.5
Breast Feeding
Participants must not breast-feed while receiving protocol therapy and for 180 days 
following the last dose of protocol therapy
4.6
Blood Donation
Participants must not donate blood during the study or for 90 days after the last dose of 
protocol therapy.
4.7
Treatment Discontinuation 
Participants may continue protocol therapy until one of the following criteria applies:

Disease progression

Serious or life-threatening adverse event

Severe noncompliance with protocol as judged by the Investigator and/or Sponsor

Participant decision to withdraw

Participant becomes pregnant

Participant is diagnosed with MDS or AML (as confirmed by a hematologist)

Investigator, Sponsor, and/or TESARO/GSK becomes aware of conditions or events 
that suggest a possible risk or hazard to participants if the clinical study continues
4.8
Duration of Follow Up
Participants will be followed for 5 years after removal from protocol therapy or until death, 
whichever occurs first.  
4.9
Discontinuation from Study
Participants who discontinue from treatment will continue to be followed for overall survival 
until one of the following criteria apply:

Withdrawal of consent

Loss to follow-up

Death from any cause

Termination of the study

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For participants who are thought to be lost to follow-up, at least 3 documented attempts, 
including 1 via certified mail, should be made to contact the participant before the 
participant is deemed lost to follow-up.
4.10 Participant Replacement Criteria
In the safety run-in cohort, patients who do not complete at least 75% of the intended course 
of chemotherapy due to reasons other than toxicity will be considered as in-evaluable for 
the primary endpoint and will be replaced.

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5
DOSE MODIFICATIONS
5.1
Niraparib
Dose interruption and/or modification of niraparib may be implemented due to 
nonhematologic or hematologic toxicities per the Investigator’s judgement after Cycle 1. 
Treatment must be interrupted for any nonhematologic Common Terminology Criteria for 
Adverse Events (CTCAE) Grade 3 or 4 AE that the Investigator considers to be related to 
administration of niraparib (Table 3). If the nonhematologic toxicity is appropriately resolved 
to baseline or Grade ≤1 within 4 weeks (28 days) of the dose interruption period, the patient 
may restart treatment with niraparib but with a dose level reduction if prophylaxis is not 
considered feasible (see Table 5). If the event recurs at similar or worse grade, treatment 
should be interrupted again and, upon resolution, a further dose reduction must be made 
according to Table 3. 
If the toxicity requiring dose interruption has not resolved completely or to CTCAE Grade 1 
during the maximum 4-week (28-day) dose interruption period, and/or the patient has 
already undergone a dose reduction to a minimum dose of 100 mg QD, the patient must 
permanently discontinue treatment with niraparib.
The dose interruption and modification criteria for niraparib for hematologic parameters will 
be based on blood counts and are outlined in Table 8. If the hematologic toxicity has not 
recovered to the specified levels within 4 weeks (28 days) of the dose interruption period, 
the patient must permanently discontinue treatment with niraparib.
For patients whose initial dose is 3 capsules daily (300 mg/day), dose reductions to 2 
capsules daily (200 mg/day) and subsequently to 1 capsule daily (100 mg/day) will be 
allowed. No further dose reduction will be allowed. 
For patients whose initial dose is 2 capsules (200 mg/day), dose reduction to 1 capsule 
once daily (100 mg/day) will be allowed. No further dose reduction will be allowed.
Both medications should be held at the same time.
Table 3:
Recommended Dose Modifications for Adverse Reactions
A: Niraparib
Dose level
Initial Dose: 3 capsules per day
Initial Dose: 2 capsules per day
Starting dose
3 capsules once daily (300 mg/day) 2 capsules once daily (200 mg/day) 
First 
dose 
reduction
2 capsules once daily (200 mg/day) 1 capsule once daily (100 mg/day)
Second dose 
reduction
1 capsule once daily (100 mg/day)
NA

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Table 4: Niraparib Dose Modifications for Nonhematologic Adverse Reactions
Abnormality
Intervention
Non-hematologic CTCAE ≥ Grade 3 adverse 
reaction where prophylaxis is not considered 
feasible or adverse reaction persists despite 
treatment
Withhold niraparib for a maximum of 28 days or until 
resolution of adverse reaction.
Resume niraparib at a reduced dose. 
CTCAE ≥ Grade 3 treatment-related adverse 
reaction lasting more than 28 days while patient is 
administered niraparib 100 mg/day
Discontinue niraparib.
Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events.
Table 5: Niraparib Dose Modifications for Hematologic Toxicity
Laboratory Abnormality
Intervention
Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and 
periodically after this time.
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 Table 3.
If platelet count is < 75,000/μL, resume niraparib at a reduced dose 
per Table 3.
Platelet count < 100,000/μL
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 per Table 3. 
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 count < 1,000/μL
Withhold niraparib for a maximum of 28 days and monitor blood 
counts until neutrophil counts return to ≥1,500/μL. 
Resume niraparib at a reduced dose per Table3.
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 maximum dose reductions per 
Table 3.
Hemoglobin ≤ 8 g/dL
Withhold niraparib for a maximum of 28 days and monitor blood 
counts until hemoglobin returns to ≥9 g/dL. 
Resume niraparib at a reduced dose per Table 3.
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 maximum dose reductions per Table 3.

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Hematologic 
adverse 
reaction 
requiring transfusion
For patients with platelet count ≤10,000/μL, platelet transfusion 
should be considered. If there are other risk factors such as 
co-administration of anticoagulation or antiplatelet drugs, consider 
interrupting these drugs and/or transfusion at a higher platelet count.
Resume niraparib at a reduced dose per Table 3.  
Confirmed diagnosis of MDS or 
AML
Permanently discontinue niraparib.
Abbreviation: AML = acute myeloid leukemia; MDS = myelodysplastic syndrome; QD = once daily. 
In the case of thrombocytopenia, following the first occurrence, resumption of therapy may 
occur at the same dose or 1 dose level lower when the hematologic toxicity has resolved. 
Subsequent occurrences should trigger dose reduction upon resumption of therapy. If the 
platelet count has not reverted within 28 days of interruption to ≥100,000/μL, then study 
treatment should be discontinued.
If dose interruption and/or modification is required at any point during study treatment 
because of hematologic toxicity, weekly blood draws for complete blood count (CBC) will 
be monitored until the AE resolves to the specified blood count levels. To ensure the safety 
of the new dose, weekly blood draws for CBC will be required for an additional 4 weeks 
after the AE has resolved, after which monitoring every 4 weeks may resume. CBC 
monitoring will continue every 4 weeks (ie, monthly) for the next 11 months of treatment, 
and periodically after this time.
Any patient requiring transfusion of platelets or red blood cells (≥1 unit) must undergo a 
dose reduction upon recovery if study treatment is resumed.
If a diagnosis of MDS/AML is confirmed by a hematologist, the patient must permanently 
discontinue study treatment.
For major surgery while on study treatment, up to 4 weeks (28 days) of study treatment 
interruption is allowed. 
B: Panitumumab
Dose level
Starting dose
6mg/Kg body weight
First dose reduction
4mg/Kg body weight
The recommended dose of Panitumumab is 6 mg/kg, administered as an intravenous 
infusion over 60 minutes, every 14 days. Doses higher than 1000 mg should be 
administered over 90 minutes.

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Appropriate medical resources for the treatment of severe infusion reactions should be 
available during Panitumumab infusions.
Dose Modifications for Infusion Reactions 
Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension,
can occur following Panitumumab administration.
•
Reduce infusion rate by 50% in patients experiencing a mild or moderate (grade 1 or 2) 
infusion reaction for the duration of that infusion.
•
Immediately and permanently discontinue Panitumumab infusion in patients 
experiencing severe (grade 3 or 4) infusion reactions.
Dose Modifications for Dermatologic Toxicity
Primary skin prophylaxis must be instituted with initiation of therapy, including sunlight 
protection, skin care with hydrophilic cream, and oral antibiotics with doxycycline (100–200 
mg/day for ≥8 weeks) or minocycline (100 mg/day for ≥8 weeks).
• Withhold Panitumumab for dermatologic toxicities that are grade 3 or higher or are 
considered intolerable. If toxicity does not improve to ≤ grade 2 within 1 month, permanently 
discontinue Panitumumab.
• If dermatologic toxicity improves to ≤ grade 2, and the patient is symptomatically improved 
after withholding no more than two doses of Panitumumab, treatment may be resumed at 
67% of the original dose.

If toxicities recur, permanently discontinue Panitumumab. 

If toxicities do not recur, subsequent doses of Panitumumab may be increased by 
increments of 25% of the original dose until the recommended dose of 6 mg/kg is 
reached.
Dose Modifications for Other Toxicities

Electrolyte 
Depletion/Monitoring: 
Monitor 
patients 
for 
hypomagnesemia 
and 
hypocalcemia prior to initiating Panitumumab treatment, periodically during 
Panitumumab treatment, and for up to 8 weeks after the completion of treatment. Other 
electrolyte disturbances, including hypokalemia, have also been observed. Replete 
magnesium and other electrolytes as appropriate.

Pulmonary Fibrosis/Interstitial Lung Disease (ILD): In the event of acute onset or 
worsening of pulmonary symptoms, interrupt Panitumumab therapy. Discontinue 
Panitumumab therapy if ILD is confirmed. 

Ocular Toxicities: Monitor for keratitis or ulcerative keratitis. Interrupt or discontinue 
Panitumumab for acute or worsening keratitis. 

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6
PHARMACEUTICAL INFORMATION
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, handling, storage, distribution, and usage of these 
materials in accordance with the protocol and any applicable laws and regulations.
6.1
Niraparib
6.1.1 Identity
Niraparib piperidine [tosylate monohydrate salt]) is an orally available, potent, highly 
selective poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) -1 and -2 inhibitor. 
Niraparib is also known as ZEJULA.
6.1.2 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.
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.
6.1.3 Packaging, Labeling and Storage
Niraparib is supplied by TESARO/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.  
6.1.4 Drug Accountability
The Investigator or designee is responsible for maintaining accurate dispensing records of 
the study treatment throughout the clinical study. The study treatment accountability log 
includes information including a patient identifier, amount and date dispensed, and amount 
and date returned to the pharmacy, if applicable. Product returned to the pharmacy will be 

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stored under the same conditions as products not yet dispensed but will be marked as 
‘returned’ and kept separate from the products not yet dispensed.
All dispensing and accountability records should be stored in accordance to the Sponsor 
institution regulations. The pharmacist will dispense study treatment for each participant 
according to the protocol and storage and handling manual, if applicable.
6.1.5 Disposal and Destruction
Niraparib should be destroyed at the investigational site if permitted by local regulations.
6.2
Panitumumab
Panitumumab (Vectibix) is an epidermal growth factor receptor antagonist indicated as a 
single agent for the treatment of metastatic colorectal carcinoma with disease progression 
on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. 
Approval is based on progression free survival; no data demonstrate an improvement in 
disease-related symptoms or increased survival with Panitumumab. Retrospective subset 
analyses of metastatic colorectal cancer trials have not shown a treatment benefit for 
Panitumumab in patients whose tumors had KRAS mutations in codon 12 or 13. Use of 
Panitumumab is not recommended for the treatment of colorectal cancer with these 
mutations.
6.2.1 Identity 
Panitumumab is supplied as a sterile, colorless, preservative-free in a single-use vial. It is 
a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the 
human epidermal growth factor receptor (EGFR). Panitumumab has an approximate 
molecular weight of 147 kDa. Panitumumab is produced in genetically engineered 
mammalian (Chinese Hamster Ovary) cells.
Panitumumab is a sterile, colorless, pH 5.6 to 6.0 liquid for intravenous (IV) infusion, which 
may contain a small amount of visible translucent-to-white, amorphous, proteinaceous, 
panitumumab particulates. Each single-use 5 mL vial contains 100 mg of panitumumab, 29 
mg sodium chloride, 34 mg sodium acetate, and Water for Injection, USP. Each single-use 
10 mL vial contains 200 mg of panitumumab, 58 mg sodium chloride, 68 mg sodium 
acetate, and Water for Injection, USP. Each single-use 20 mL vial contains 400 mg of 
panitumumab, 117 mg sodium chloride, 136 mg sodium acetate, and Water for Injection, 
USP.
6.2.2 Potential Risks of Panitumumab
Most common adverse reactions (≥ 20%) are skin toxicities (i.e., erythema, dermatitis 
acneiform, pruritus, exfoliation, rash, and fissures), paronychia, hypomagnesemia, fatigue, 
abdominal pain, nausea, diarrhea, and constipation.

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6.2.3 Packaging, Labeling and Storage 
Panitumumab (Vectibix) is provided as one vial per carton.

Each 5 mL single-use vial contains 100 mg of panitumumab in 5 mL (20 mg/mL) 
(NDC 55513-954-01).

Each 10 mL single-use vial contains 200 mg of panitumumab in 10 mL (20 mg/mL) 
(NDC 55513-955-01).

Each 20 mL single-use vial contains 400 mg of panitumumab in 20 mL (20 mg/mL) 
(NDC 55513-956-01).
Store vials in the original carton under refrigeration at 2° to 8°C (36° to 46°F) until time of 
use. Protect from direct sunlight. DO NOT FREEZE. Dispensing
The investigator agrees that study drug(s) will be dispensed by the investigator or sub-
investigator(s) named on the Investigator Agreement or their qualified designees.  The 
investigator, sub-investigators, or qualified designees also agree that the study drug(s) will 
be dispensed only to study subjects who have provided written informed consent and have 
met all entry criteria and in accordance with the instructions provided in the storage and 
handling manual. 
6.2.4 Disposal and Destruction
Since Panitumumab does not contain preservatives, any unused portion remaining in the 
vial must be discarded. The diluted infusion solution of Panitumumab should be used within 
6 hours of preparation if stored at room temperature, or within 24 hours of dilution if stored 
at 2° to 8°C (36° to 46°F). DO NOT FREEZE.

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7
CORRELATIVE STUDIES
Biomarker analysis
Predictive biomarkers will be explored in RAS WT mCRC patients on this phase II study of 
Niraparib in combination with Panitumumab. Skin reactions to EGFRi have previously been 
showed to be surrogate markers for therapeutic efficacy. Skin punch biopsies are easily 
obtained in the clinic (compared to colorectal tumor tissue biopsies) and may be used for 
pharmacodynamic studies and to demonstrate early prediction of response to dual EGFR-
PARP inhibition. Established and tailored statistical methods will be employed to distinguish 
the predictive impact of genetic abnormalities in both diagnostic tumor and research skin 
biopsies. Paired pre- and post-treatment skin biopsy samples will be used to determine 
changes to EGFR+PARP inhibition. Normal skin biopsies from regions that contained hair 
follicles will be obtained in the form of a 4-mm diameter punch biopsy (8 mm depth) before 
treatment and on day 22 of cycle 1. 
Table X-1 Summary of Research Tissue and Blood Specimen Collection
Research 
Sampling
Time point
Comments
Skin Biopsy
Baseline, C1D22
4-mm diameter punch biopsy (8 mm depth) before 
treatment and on days 22 of cycle 1. 
Archival 
Tissue
Screening
Tissue block/at least 10 FFPE slides availability for 
future correlative studies
7. A. Molecular profile of mCRC tumors: 
Because outcomes are improved when novel therapies are applied, all patients who are 
newly diagnosed with mCRC are currently mandated by the professional society guidelines 
to be tested for mutations in KRAS, NRAS, and BRAF V600E, as well as for microsatellite 
instability–high (MSI-H) status or dMMR, HER2 amplifications and rare fusions such as 
NTRK. As standard of care (SOC) at Emory, patients with mCRC receive molecular profiling 
to evaluate for these therapeutic targets. Various commercial genomic platforms (e.g. 
CARIS, FoundationOne CDx™) are used in the clinical care of cancer patients at Emory. 
These next generation sequencing (NGS) based in-vitro diagnostic platforms are used for 
the detection of substitutions, insertion and deletion alterations (indels), and copy number 
alterations (CNAs) in multiple genes and select gene rearrangements. In addition, genomic 
signatures are also detected on these platforms, including MMR/MSI and tumor mutational 
burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor 
tissue specimens. Genes tested include KRAS, NRAS, BRAF, HER2, NTRK, as well as 
DNA repair genes such as MLH1, MSH2, MSH3, PMS2, MSH6, BRCA1, BRCA2, ATM, 
ATR, PALB2, RAD51, BRIP1, PALB2, RAD51B, RAD51C, RAD51D, PARP1, PARP2, 
PARP3. PD-L1 statuses are also determined via immunohistochemistry (IHC) using Dako 
22C3 or Ventana SP142 antibodies. DDR gene deficiencies can lead to dysfunctional DNA 

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repair or chromosome instability, altering features of the somatic genome. To identify the 
association between DDR deficiency and response to the investigational combination 
therapy, a multivariate regression model corrected for clinical variables such as 
demographics and duration of response to frontline platinum chemotherapy will be utilized. 
Tumors of HRD alteration carriers are known to exhibit distinct somatic mutational 
signatures reflecting their specific damages. DDR-associated somatic mutational 
signatures will be identified using the same multivariate regression model.
7. B. Impact of dual EGFR-PARP inhibition on cytotoxic markers and infiltrating 
immune cells in skin biopsies.
Collected pre- and on-treatment skin biopsies will be analyzed for the following biologic 
properties and correlated with clinical outcomes:
1. Four metrics of cytotoxicity – Caspace-3, γ-H2AX, PARP, MAPK, together with indicators 
of EGFR downregulation. 
2. Tumor infiltrating cells using multiplex immunofluorescence panels.
7.1
Pharmacokinetics
N/A

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8
SCHEDULE OF ASSESSMENTS 
8.1
Screening 
At Screening, the following procedures/tests will be performed:

Informed Consent

ECOG Performance Status

Physical Exam

Medical History and Concomitant Medications

Vital Signs: systolic and diastolic blood pressures, weight and temperature

Height 

Pregnancy testing within 7 days prior to initiating protocol therapy

CBC with differentials

Comprehensive metabolic panel

Urinalysis 
8.2
Cycle 1
On Days 1 and 15, the following procedures/tests will be performed: 

Vital signs: systolic and diastolic blood pressures, weight, and temperature

CBC

Comprehensive metabolic panel

Urinalysis

Adverse event monitoring
On Day 8 CBCs will be performed.
On Day 22, Skin biopsy and CBCs will be performed.
8.3
Subsequent Cycles
On Days 1 and 15, the following procedures/tests will be performed: 

Vital signs: systolic and diastolic blood pressures, weight, and temperature

 CBC with differentials

Comprehensive metabolic panel

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
Urine pregnancy test for females of childbearing potential conducted every 3 
cycles for duration of study (ie, Cycle 4, Cycle 7, etc.).

Urinalysis 

Adverse event monitoring
8.4
End of Treatment

Adverse event monitoring
8.5
Safety Follow-up
Follow-up visit should occur at least 30 days from the last administered dose of protocol 
therapy. 

Vital signs: systolic and diastolic blood pressures, weight, and temperature

CBC

Comprehensive metabolic panel

Urine pregnancy test for females of childbearing potential 

Coagulation

Urinalysis

Physical Exam

Adverse event monitoring

Assess for MDS/AML
8.6
Long Term Follow-up

Survival assessment

Follow-up for MDS/AML
8.7
Unscheduled Assessments

SAE monitoring

If at any time after the study is completed, an Investigator becomes aware of 
an SAE that is considered related to the investigational product, the 
Investigator should report the SAE to the Sponsor Institution and 
TESARO/GSK within 24 hours of becoming aware of the SAE

Clinical Laboratory Assessments

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
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, and to ensure safety of the new dose, 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

For any suspected MDS/AML case reported while a participant is receiving 
treatment or being followed for post-treatment assessments, bone marrow 
aspirate and biopsy testing must be completed by a local hematologist.  
Testing completed as part of standard of care is sufficient. The study site must 
receive a copy of the hematologist’s report of aspirate/biopsy findings (which 
must include a classification according to World Health Organization criteria) 
and other sample testing reports related to MDS/AML. The site must keep a 
copy of the report with the participant’s study file. 

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9
STUDY CALENDAR
Screening assessments are to be conducted within 28 days prior to initiating protocol therapy unless otherwise specified.  
Screening assessments occurring within 1 week prior to initiating study treatment do not need to be repeated on Cycle 1 
Day 1 unless otherwise specified.  
Screening laboratory assessments must be done within 8 days prior to initiating protocol therapy.  For women of childbearing 
potential, as defined in the eligibility criteria, a pregnancy test must be completed within 7 days prior to initiating protocol 
therapy.  If a urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.  
Assessments must be performed prior to administration of any study agent. Study assessments and agents should be 
administered within + 3 days of the protocol-specified date, unless otherwise noted.

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Screening
(-28 to -1 days) 
Cycle 1
Cycle 2
Cycle 3+
EOT
Safety
Follow-Up
Long Term
Follow-Up
Study Procedures
D1
D8
D15
D22
D1
D15
D1
D15
At least 30 days 
from last dose
Every 6 months for 2 
years and annually 
thereafterg
Written informed consent
X
Inclusion/Exclusion Criteria
X
Height 
X
Vital signs and weight a
X
X
X
X
X
X
X
X
ECOG Performance Status
X
X
X
X
X
X
X
Medical History b 
X
X
X
X
X
X
X
X
Results of prior genomic profiling 
(including extended RAS analysis)
X
Concurrent Medications
X
X
X
X
X
X
X
Physical Exam
X
X
X
X
X
X
X
X
Adverse Event Monitoring
X
X
X
X
X
Assess for MDS/AML
X
X
X
X
X
X
Pregnancy Testing c
X
Xc
X
PT/INR and aPTT
X
CBC with differential d
X
X
X
X
X
X
X
X
X
X
X
Comprehensive Metabolic Panel e
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
Skin biopsy for correlative studiesf
X
X
Panitumumab Administration
X
X
X
X
X
X
Niraparib dispensed
X
X
X
Pill Diary and pill count
X
X
X
X
X
Bone marrow aspirate and biopsy h
X
Survival assessment h
Xg
Tumor 
Assessment/Imaging 
(CT/MRI)
Xi
Xj
Archival Tissue
X

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Screening
(-28 to -1 days) 
Cycle 1
Cycle 2
Cycle 3+
EOT
Safety
Follow-Up
Long Term
Follow-Up
Study Procedures
D1
D8
D15
D22
D1
D15
D1
D15
At least 30 days 
from last dose
Every 6 months for 2 
years and annually 
thereafterg
Panitumumab: 6 mg/kg intravenous infusion on Days 1 and 15 of each 28-day cycle administered over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg).
Niraparib: 200mg or 300mg (based on baseline weight or serum platelet count) Oral, daily, continuously.
a.
Vital signs to include: systolic and diastolic blood pressures while the patient is in a seated position, weight, and temperature
b.
Medical History should include all prior anticancer therapy
c.
Female subjects of childbearing potential as defined in the eligibility criteria must have a serum or urine beta-hCG pregnancy test within ≤ 7 days 
prior to initiating protocol therapy, every 3 cycles (i.e. C4D1, C7D1) and at End of Treatment
d.
CBC to include absolute neutrophil count, platelets, and hemoglobin.  CBC must be collected on Cycle 1 Day 1.  
e.
Comprehensive metabolic panel to include: serum creatinine, total bilirubin, aspartate aminotransferase and alanine aminotransferase. 
f.
Normal skin biopsies from regions containing hair follicles will be obtained in the form of a 4mm diameter punch biopsy (8 mm depth) before 
treatment and on days 22 of cycle 1. The biopsies will be evaluated for expression of p-Caspace-3, PARP, p-MAPK, Ki-67, and p27 by IHC.
g.
Overall survival to be followed for 5 years following the last dose of Niraparib.
h.
For any patient diagnosed with MDS/AML while on study, a bone marrow aspirate/biopsy must be completed by a local hematologist. Testing 
completed as part of standard of care is sufficient as long as the methods are acceptable to TESARO/GSK. A copy of the hematologist’s report of 
aspirate/biopsy findings including a classification according to WHO criteria and other sample testing results related to MDS/AML will be provided 
to the PI and to TESARO/GSK.
i.
Baseline imaging within 4 weeks of day 1 is mandatory. CT or MRI acceptable
j.
Restaging scans prior to odd treatment cycles

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10 ADVERSE EVENT REPORTING
10.0 Definition of Adverse Events 
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a medicinal product and which does not necessarily have to have a 
causal relationship with this treatment. An AE can therefore be any unfavorable and 
unintended sign (including a clinically significant abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of study treatment, 
whether or not considered related to the study treatment. 
Aes may include the onset of new illness and the exacerbation of pre-existing medical 
conditions. An AE can include an undesirable medical condition occurring at any time 
after the time of randomization and/or treatment assignment, including baseline or 
washout periods, even if no study treatment has been administered.
10.1 Serious Adverse Events (SAEs)
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; 

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. 

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10.2 Adverse Event of Special Interest (AESI) 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, for which 
ongoing monitoring and rapid communication to the Sponsor Institution and to 
TESARO/GSK is required. 
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])

Pneumonitis

Embyro-fetal toxicity
AESIs should be reported on SAE Report Forms whether serious or not, as follows:

MDS and AML along with other secondary cancers should be reported to the 
Sponsor Institution and to TESARO/GSK upon awareness for any patient who 
has received niraparib (regardless of the timeframe since the last dose).  

Pneumonitis should be reported to the Sponsor Institution and to 
TESARO/GSK through 90 days after the last dose of niraparib.

Embryo-fetal toxicity should be reported as outlined in the Pregnancy reporting 
section.
10.3 Special Situations: Abuse, Misuse, Medication Errors, Overdose, and 
Accidental or Occupational Exposure 

Abuse:  is the persistent or sporadic, intentional excessive use of the study 
treatment which is accompanied by harmful physical or psychological effects. 

Misuse: medicinal product is intentionally and inappropriately used not in 
accordance with the authorized/approved product information.

Medication error:  is any preventable incident that may cause or lead to 
inappropriate study treatment use or patient harm while the study treatment is 
in the control of the health care professionals or patients. Such incident may be 
due to health care professional practice, product labeling, packaging and 
preparation, procedures for administration, and systems, including the 
following: prescribing, order communication, nomenclature, compounding, 
dispensing, distribution, administration, education, monitoring, and use.

Overdose:  is a deliberate or accidental administration of study treatment to a 
study patient, at a dose greater than that which was assigned to that patient 
per the study protocol and under the direction of the Investigator.  If an 
overdose with a TESARO/GSK product, the Sponsor Institution and 
TESARO/GSK should be notified immediately, and the patient should be 
observed closely for Aes. Associated Aes should be treated and monitored by 
the Investigator. The dosage of study drug administered, any associated Aes, 

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and/or treatment provided to the patient because of the overdose, should be 
reported. 

Accidental /Occupational exposure:  is the unintentional exposure to a study 
treatment as a result of one’s professional or non-professional occupation, or 
accidental exposure to a non-professional to whom exposure was not intended 
(i.e., study product given to wrong patient). 
Reporting Special Situations:  All occurrences of abuse, misuse, medication error, 
overdose, and accidental or occupational exposure associated with a TESARO/GSK 
product must be reported on a Special Situations Report Form to the Sponsor 
Institution and to TESARO/GSK within 5 business days of awareness regardless of 
whether or not an AE or SAE has occurred. If the abuse, misuse, medication error, 
overdose, or accidental / occupational exposure is associated with an AE, an SAE 
Report Form must also be submitted to the Sponsor Institution and to TESARO/GSK 
within 24 hours of awareness. 
10.4 Assessment of Adverse Events 
Each AE will be assessed by the investigator for severity and for a causal relationship 
with the study treatment as outlined below.
10.4.1
Severity Assessment 
All Aes will be assessed by the Investigator for severity according to Common 
Terminology Criteria for Adverse Events (CTCAE) v4.03: 14 June 2010; National 
Institutes of Health (NIH), National Cancer Institute (NCI). The CTCAE severity grades 
1 through 5 provide unique clinical descriptions of severity of each adverse event. The 
CTCAE v4.03 is available on the NCI/NIH website.
Please note that there is a distinction between serious and severe Aes: Severity is a 
measure of intensity whereas seriousness is defined by the criteria in Section 10.1.  
For example, a mild degree of gastrointestinal bleeding requiring an overnight 
hospitalization for monitoring purposes may be considered an SAE but is not 
necessarily severe. 
10.4.2
Relationship to Study Drug 
The Investigator must provide a causality assessment regarding the relationship of 
the event with the study drug for all Aes.  One of the following categories should be 
selected based on medical judgment, considering all contributing factors:

Related: A causal relationship between the medicinal product and AE is a 
reasonable possibility. For example, the occurrence of the AE cannot be 
explained by other causative factors. The AE, however, can be explained by 
pharmacological effect of the medicinal product such as a similar event having 
been reported previously, alteration of the dose effect, or the timing or 
seriousness of the AE, etc. Positive rechallenge/dechallenge is supportive.

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
Not Related: A causal relationship between the medicinal product AE is not a 
reasonable possibility: there is no temporal relationship between the medicinal 
product and event, or an alternative etiology is more reasonable. 
10.5 Collection and Recording of Adverse Events 
Aes may be volunteered spontaneously by the study patient, or discovered by the 
study staff during physical examinations or by asking an open, nonleading question 
such as, “How have you been feeling since your last study visit?” The Investigator will 
document the nature of AE, date of onset of the AE (and time, if known), date of 
outcome of the AE (and time, if known), severity of the AE, action taken with study 
drug as a result of the AE, assessment of the seriousness of the AE, and assessment 
of the causal relationship of the AE to study drug and/or study procedure.
Aes, including laboratory abnormalities that are assessed as clinically significant or 
require intervention, should be described using a diagnosis whenever possible, rather 
than individual underlying signs and symptoms. When a clear diagnosis cannot be 
identified, each sign or symptom should be recorded as a separate AE.
All SAEs will be collected from the administration of the first dose of study drug and 
must be throughout the study and for at least 30days after the last dose of protocol 
therapy.
SAEs considered by the Investigator to be related to study medication will be reported 
regardless of the timeframe from last dose of protocol therapy.
All Aes will be documented for each patient from the administration of the first dose of 
study drug and must be throughout the study and for at least 30days after the last 
dose of protocol therapy.
Concomitant illnesses that existed before entry into the study are to be documented 
as medical history and will not be considered Aes unless the illness worsens after 
initiating protocol therapy. 
Disease progression is an efficacy criterion and is therefore not considered an AE or 
SAE (even if fatal). Disease progression should be documented but not reported as 
an SAE. If Aes/SAEs occur in relation to disease progression that are not consistent 
with the natural progression of the patient’s disease, these Aes/SAEs must be 
reported per AE/SAE reporting requirements.
10.6 Follow-Up of Adverse Events
All Aes experienced by a patient, regardless of the suspected causality, will be 
monitored until the AE or SAE has resolved, until any abnormal laboratory values have 
returned to baseline or normal levels, until stabilized with a satisfactory explanation 
for the changes observed, until the patient is lost to follow-up, or until the patient has 
died.

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10.7 Reporting to the Sponsor Institution
All SAEs and AESIs must be reported to the Sponsor Institution within 24 hours of 
becoming aware of the initial SAE/AESI or any follow-up information regarding the 
SAE/AESI using the SAE reporting information below.  SAEs/AESIs must be reported 
after study completion if the SAE/AESI is assessed as study-drug related.
MedWatch 3500 Reporting Guidelines:
Note:  MedWatch 3500 forms and other information related to MedWatch reporting 
are available at http://www.fda.gov/medwatch/index.html
A copy of all 15 Day Reports and Annual Progress Reports is submitted as required 
by FDA. Investigators will cross reference this submission according to local 
regulations to the Investigational Compound Number (IND, CSA, etc.) at the time of 
submission.  Additionally, investigators will submit a copy of these reports to 
TESARO/GSK at the time of submission to FDA.
10.8 Reporting to TESARO/GSK
The Sponsor Institution must report all SAEs and all follow up information to 
TESARO/GSK on an SAE Report Form within 24 hours of becoming aware of the 
initial event or follow-up information. 
The Sponsor Institution must provide a causality assessment and must sign and date 
all SAE Report Forms.
If supporting documentation is included in the submission to TESARO/GSK (e.g., 
hospital reports, consultant reports, death certificates, autopsy reports, etc.), please 
redact any patient identifiers (including Medical Record number).
TESARO/GSK SAE, Pregnancy, and AESI Reporting Information
Email: OAX37649@gsk.com
Fax: +44(0) 208754 7822
  On at least an annual basis, the Sponsor Institution will provide a copy of the safety 
reports submitted to applicable Regulatory Authorities or IECs.  Annual reports should 
be provided to TESARO/GSK within 3 business days of submission to the applicable 
regulatory body.
10.9 Quarterly AE/SAE Reporting to TESARO/GSK
On a quarterly basis the Sponsor Institution will provide TESARO/GSK with a line 
listing of all adverse events (serious and non-serious) received during a defined 

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quarter. The line listing will include a subject ID, the AE term, onset date, outcome, 
causality assessment, severity, and study drug dosing information.   
10.10
Pregnancy 
The Sponsor Institution has the responsibility to monitor the outcome of all 
pregnancies reported during the Investigator Sponsored Trial.
The Sponsor Institution must report all pregnancies associated with TESARO/GSK 
product including follow up outcomes to TESARO/GSK within 1 business day of 
awareness. 
Each pregnancy must be reported on an Initial Pregnancy Report Form within 24 
hours of becoming aware of the pregnancy. Pregnancy is not an AE, and therefore 
does not need to be reported as an AE unless there is a suspicion that the study drug 
may have interfered with the effectiveness of a contraceptive medication. 
An elective abortion without complications should not be regarded as an AE, however, 
it should be reported as the outcome to the pregnancy on the Pregnancy Outcome 
Report Form. Therapeutic abortions should be reported as a treatment procedure; the 
reason for the therapeutic abortion should be reported on the Pregnancy Outcome 
Report Form and as an AE. Hospitalization for normal delivery of a healthy newborn 
should not be considered an SAE.
Any SAE that occurs during pregnancy must be recorded on the Pregnancy Outcome 
Report Form, reported as an SAE on the SAE Report Form (e.g., maternal serious 
complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, birth defect) and reported to the Sponsor Institution and 
TESARO/GSK within 24 hours. Hospitalization for normal delivery of a healthy 
newborn should not be considered an SAE. 
10.11
Suspected Unexpected Serious Adverse Reactions (SUSARs) 
Per regulatory requirements, if an event is assessed by the Sponsor as a Serious 
Unexpected Adverse Reaction (SUSAR), it is the responsibility of the Sponsor to 
submit the SUSAR to Regulatory Authorities according to applicable regulations. 
Written IND safety reports will be submitted to the FDA by the IND sponsor, for 
serious, unexpected suspected adverse reactions within 15 calendar days of learning 
of its occurrence. If the event is fatal or is deemed to be life threatening, the report will 
be made within 7 calendar days.  The IND sponsor will also make an assessment of 
whether the event constitutes an unanticipated problem posing risks to subjects or 
others (UP). This assessment will be provided to the Emory University IRB, which, in 
turn will make a final determination.  If the Emory IRB determines an event is a UP it 
will notify the appropriate regulatory agencies and institutional officials.
In addition, the SUSAR will be distributed to the Investigators/sites utilizing a Council 
for International Organizations of Medical Sciences (CIOMS) report form, or the 
MedWatch 3500A form). The Investigator/site will submit a copy of the report to their 
respective Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 

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and TESARO/GSK per the governing institutional requirements and in compliance 
with local laws and guidelines.
10.12
Reporting Product 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 Sponsor Institution or qualified 
designee to GSK within 1 working day of first becoming aware of the possible defect 
to GSK QA at gsk-rd.complaints@gsk.com. 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.  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.

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11 DATA REPORTING
11.0 Data and Safety Monitoring
The Data and Safety Monitoring Committee (DSMC) of the Winship Cancer Institute 
will provide oversight for the conduct of this study.  The DSMC functions independently 
within Winship Cancer Institute to conduct internal monitoring functions to ensure that 
research being conducted by Winship Cancer Institute Investigators produces high-
quality scientific data in a manner consistent with good clinical practice (GCP) and 
appropriate regulations that govern clinical research.    Depending on the risk level of 
the protocol, the DSMC review may occur every 6 months or annually. For studies 
deemed Moderate Risk (such as the current protocol as per Emory standards), initial 
study monitoring will occur within 1 year from the date of the first subject accrued, with 
2 of the first 5 subjects being reviewed.  Subsequent monitoring will occur in routine 
intervals per the Winship Data and Safety Monitoring Plan (DSMP). 
The DSMC will review pertinent aspects of the study to assess subject safety, 
compliance with the protocol, data collection, and risk-benefit ratio. Specifically, the 
Winship Cancer Institute Internal Monitors assigned to the DSMC may verify informed 
consent, eligibility, data entry, accuracy and availability of source documents, 
Aes/SAEs, and essential regulatory documents.  Following the monitoring review, 
monitors will provide a preliminary report of monitoring findings to the PI and other 
pertinent individuals involved in the conduct of the study.  The PI is required to address 
and respond to all the deficiencies noted in the preliminary report.  Prior to the 
completion of the final summary report, monitors will discuss the preliminary report 
responses with the PI and other team members (when appropriate).  A final monitoring 
summary report will then be prepared by the monitor.  Final DSMC review will include 
the final monitoring summary report with corresponding PI response, submitted CAPA 
(when applicable), PI Summary statement, and available aggregate toxicity and safety 
data.  
The DSMC will render a recommendation and rating based on the overall trial conduct.  
The PI is responsible for ensuring that instances of egregious data insufficiencies are 
reported to the IRB.  Continuing Review submissions will include the DSMC 
recommendation letter.  Should any revisions be made to the protocol-specific 
monitoring plan after initial DSMC approval, the PI will be responsible for notifying the 
DSMC of such changes.  The Committee reserves the right to conduct additional 
audits if necessary. 
Decisions regarding moving forward from the safety run-in cohort to the expansion 
phase will be discussed at the GI working group. The PI or designee must obtain 
approval from the DSMC for expansion. A copy of the DSMC approval letter will be 
forwarded to TESARO/GSK. A copy of the de-identified DSMC may be requested by 
TESARO/GSK, but approval of such requests are subject to DSMC internal policies.

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PI and the investigators, the clinical research coordinator and the regulatory affairs 
coordinator will meet to review and discuss study data to ensure subject safety. During 
the meetings, the PI or co-I will review the eligibility criteria for each new patient. In 
addition, during these meeting the group will review all the toxicity (AE/SAE) logs, 
random checks of case report form completion and roadmap for each patient on the 
trial. All study personnel will be trained on the protocol by the PI or co-I. Study 
personnel will sign training log prior to being included on delegation of authority log. 
All AE and SAE will be handled according to Section 10 which provides detailed 
instructions on reporting requirements.

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12 STATISTICAL METHODS
12.1 Study Design and Endpoints 

PFS, defined as the time from the date of the start of study treatment to the 
earlier date of assessment of progression or death by any cause in the absence 
of progression. Progression will be assessed by RECIST v.1.1 criteria using an 
independent review.

ORR, defined as the percentage of patients with CR or PR, as assessed by 
RECIST v.1.1 criteria using an independent review.

DOR, defined as the time from the initial response (CR or PR) until the time of 
first documentation of disease progression, as assessed by RECIST v.1.1 
criteria using an independent review.

DCR, defined as the percentage of patients with CR, PR or SD, as assessed 
by RECIST v.1.1 criteria using an independent review.

OS, defined as measured from the date of randomization (or from the start of 
study treatment if it is a non-randomized study) to the date of death by any 
cause

Safety endpoints include the incidence of treatment-emergent AEs (TEAEs), 
changes in clinical laboratory parameters (hematology, chemistry), vital signs, 
physical examinations, and usage of concomitant medications.
12.1.1 Primary Endpoint
The primary endpoint is clinical benefit rate (CBR) = Complete Response + Partial 
Response + Stable disease (CR +PR + SD) rate. In addition to the 6 patients 
enrolled and treated in the safety run-in cohort, 20 CRC patients with the same 
inclusion criteria will be subsequently enrolled and treated to determine efficacy. 
12.1.2 Secondary Endpoints
A. Toxicity profile of the combination of Panitumumab and Niraparib; additional 
patients enrolled and treated on the expansion cohort to confirm the toxicity 
profile.
B. Efficacy endpoints: Objective response rate, response duration, overall survival 
and progression free survival. This will only be preliminary data since this is a 
secondary objective.
C.Biomarker analysis: The objective of the correlative assays is to identify 
patients who are more likely to respond to the combination. As a standard of 
care at Emory, patients with stage IV CRC receive genomic profiling to 
evaluate for therapeutic targets. We propose analyzing these profiles to 
identify patients with defects in their DNA repair pathways as a potential 

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biomarker for this regimen. Normal skin biopsies from regions that contained 
hair follicles will be obtained in the form of a 4-mm diameter punch biopsy (8 
mm depth) before treatment and on days 22 of cycle 1. The biopsies will be 
evaluated for expression of p-Caspace-3, PARP, p-MAPK, Ki-67, and p27 by 
IHC.
12.1.3 Sample size, Accrual Rate and Study Duration
The sample size of this Phase II study is driven by the primary endpoint of CBR. 
We will consider the combination of Niraparib and Panitumumab to be 
ineffective if the true CBR is less than 10% under the null hypothesis. We will 
also assume that the combination is worthy of further study if the true CBR rate 
is 25% or greater under alternative hypothesis. With an alpha of 0.1 and using 
a one-sided Z test that uses S(P0) to estimate the standard deviation, the 
sample size will be 26 enrolled and treated patients for this study in order to 
achieve at least 80% power to detect the improvement. Patients who fail 
screening will be replaced. Given our previous enrollment to colorectal cancer 
trials, we anticipate completion of enrollment in 18 months.
12.1.4 Interim Monitoring Plan
No interim analysis is planned.
12.1.5 Analysis of Primary Endpoints
The efficacy, as measured by CBR, will be assessed for the total number of 
patients enrolled and treated. The rates of CBR will be presented as a point 
estimate with a 95% exact binomial confidence interval. Assuming 6 patients 
were enrolled and treated in the safety run-in cohort and an additional 20 
patients for the cohort expansion, the 95% exact binomial confidence interval 
for the CBR rate will be within +/- 20%. Chi-square test or Fisher’s exact test will 
be used to compare the efficacy in term of CBR between the different groups 
stratified by dose level or other factors, respectively. Logistics regression model 
will be further employed to test the adjusted effect of dosage on the CBR rate 
after adjusting for other clinical factors and demographic factors.
12.1.6 Analysis of Secondary Endpoints
Objective response rate will be calculated as proportion (Responders/Total 
patients) along with 95% confidence intervals using the Clopper-Pearson 
method. Chi-square test or Fisher’s exact test will be used to compare the 
efficacy in term of response rate between the different groups stratified by dose 
level or other factors, respectively. Logistics regression model will be further 

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employed to test the adjusted effect of dosage on the response rate after 
adjusting for other clinical factors and demographic factors. 
Response duration will be summarized as mean and standard deviation or 
median with range. Two sample t-test or General Linear Model (GLM) will be 
used to compare the response duration between different groups stratified by 
different factors, respectively. 
For progression free survival, progression or death from any cause will be 
defined as the event. Patients will be censored at time of last follow-up. For 
overall survival, death from any cause will be defined as the event. Patients will 
be censored at time of last follow-up. Overall survival (OS) and progression free 
survival (PFS) rates of two patient groups stratified by dose levels or other 
factors will be estimated with the Kaplan-Meier method and compared between 
different groups using the log-rank test, respectively. The PFS and OS of each 
patient group at specific time points, such as 6 months, 1 year, 3 year, and 5 
year, etc. will also be estimated alone with 95% CI. Cox proportional hazards 
models will be further used in the multivariable analyses to assess adjusted 
effect of the treatment regimen on the patients’ OS and PFS after adjusting for 
other factors. Interaction terms between these factors will also be tested for 
statistical significance. The proportional hazards assumption will be evaluated 
graphically and analytically with regression diagnostics. Violations of the 
proportional hazards assumptions will be addressed by use of time-dependent 
covariates or extended Cox regression models. 
For the biomarker study, descriptive statistics will be first used to summarize 
biomarker endpoints, including analyses of tumor biopsies. Biomarker data will 
also be displayed graphically, where appropriate. Depending on whether data 
is normally distributed, t-test or Wilcoxon rank sum test will be used to compare 
each biomarker between any two groups stratified by dosage, response, or other 
factors, respectively. General linear model (GLM) will be used to compare each 
biomarker between multiple dose levels with and without adjusting for other 
factors. Logistics regression model will be further employed to test the adjusted 
effect of biomarker on the response rate after adjusting for dosage as well as 
other factors.
12.2 Safety Analyses
Adverse event terms will be coded using the current version of the Medical Dictionary 
and will be summarized for all treated participants. Incidence of AEs occurring during 
the study will be summarized by system organ class and preferred term. Adverse 
events will also be summarized by causality and grade. Serious adverse events will 
be listed separately. Descriptive summary statistics will be used to summarize 
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for all treated participants. Laboratory parameter changes will be described using shift 
tables, relative to CTCAE. 
Scheduled times of the safety evaluations, rather than actual times, will be used in the 
summaries of safety data. No inferential hypothesis testing will be performed on the 
safety variables. Repeated or unscheduled results will not be included in the 
summaries but will be listed. All the important deviations related to study inclusion or 
exclusion criteria, conduct of the trial, subject management, or subject assessment 
will be described.

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13 ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS
13.0 Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as 
defined by the FDA Guidance and the US Code of Federal Regulations, Title 21, Part 
50 (21CFR50). The study will be conducted in compliance with the protocol. The 
protocol and any amendments and the subject informed consent will receive 
Institutional 
Review 
Board/Independent 
Ethics 
Committee 
(IRB/IEC) 
approval/favorable opinion prior to initiation of the study. All potential serious breaches 
must be reported to the Study Sponsor immediately. A serious breach is a breach of 
the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity 
of the subjects of the study or the scientific value of the study. Personnel involved in 
conducting this study will be qualified by education, training, and experience to 
perform their respective tasks. This study will not use the services of study personnel 
where sanctions have been invoked or where there has been scientific misconduct or 
fraud (e.g., loss of medical licensure, debarment).
13.1 Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which 
they volunteer to participate. In situations where consent cannot be given by subjects, 
their legally acceptable representatives (as per country guidelines) are clearly and 
fully informed about the purpose, potential risks, and other critical issues regarding 
clinical studies in which the subject volunteers to participate. The informed consent 
form (ICF) for this study will adhere to the ethical principles that have their origin in the 
Declaration of Helsinki.
Investigators must:
1. Provide a copy of the consent form(s) and written information about the study in the 
language in which the subject is most proficient prior to clinical study participation. The 
language must be nontechnical and easily understood.
2. Allow time necessary for subject or subject's legally acceptable representative to 
inquire about the details of the study.
3. Obtain an informed consent signed and personally dated by the subject or the 
subject's legally acceptable representative and by the person who conducted the 
informed consent discussion.
4. Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF(s) and 
any other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information.

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5. If informed consent is initially given by a subject’s legally acceptable representative 
or legal guardian, and the subject subsequently becomes capable of making and 
communicating his or her informed consent during the study, consent must 
additionally be obtained from the subject.
6. Revise the informed consent whenever important new information becomes 
available that is relevant to the subject's consent. The investigator, or a person 
designated by the investigator, should fully inform the subject or the subject's legally 
acceptable representative or legal guardian, of all pertinent aspects of the study and 
of any new information relevant to the subject's willingness to continue participation in 
the study. This communication should be documented.
The subject must be informed about the nature of the study to the extent compatible 
with his or her understanding, and he or she should personally sign and date the 
consent form as soon as possible. The explicit wish of a subject who is unable to give 
his or her written consent, but who is capable of forming an opinion and assessing 
information to refuse participation in, or to be withdrawn from, the clinical study at any 
time should be considered by the investigator. The rights, safety, and well-being of the 
study subjects are the most important considerations and should prevail over interests 
of science and society.
13.2 Protocol Approval and Amendment
Before 
study 
initiation, 
the 
investigator 
must 
have 
written 
and 
dated 
approval/favorable opinion from the IRB/IEC for the protocol, consent form, subject 
recruitment materials (e.g., advertisements), and any other written information to be 
provided to subjects. The investigator should also provide the IRB/IEC with a copy of 
the IB or product labeling information to be provided to subjects and any updates. The 
investigator should provide the IRB/IEC with reports, updates and other information 
(e.g., expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
If a deviation or change to a protocol is implemented to eliminate an immediate 
hazard(s) prior to obtaining IRB/IEC approval/favorable opinion, as soon as possible 
the deviation or change will be submitted to:

IRB/IEC for review and approval/favorable opinion

TESARO/GSK

Regulatory Authority(ies), if required by local regulations
13.3 Investigator Responsibilities
By signing the Form FDA 1572, the Investigator agrees to conduct the study according 
to the protocol and the FDA regulations set forth in 21 CFR Parts 50, 54, 56, and 312.
The Investigator must provide TESARO/GSK with the following documents prior to the 
enrollment of any subjects:

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
Copy of the IRB/IEC approval letter for protocol, informed consent, Investigator 
and site

Valid medical license and Signed and dated current curricula vitae of the 
investigator

Copy of approved informed consent document

Copy of the FDA letter and IND receipt and number assignment

Signed Clinical Trial Agreement
Compliance with Trial Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and 
the Food and Drug Administration Amendments Act (FDAAA), the Sponsor of the trial 
is solely responsible for determining whether the trial and its results are subject to the 
requirements 
for 
submission 
to 
the 
Clinical 
Trials 
Data 
Bank, 
http://www.clinicaltrials.gov.  Information posted will allow subjects to identify 
potentially appropriate trials for their disease conditions and pursue participation by 
calling a central contact number for further information on appropriate trial locations 
and trial site contact information.    
13.4 Subject Confidentiality and Data Protection
The confidentiality of records that could identify subjects must be protected, respecting 
the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects' signed ICF and, in the US, the subjects’ signed HIPAA Authorization. The 
consent form(s) must also include a statement that the study Sponsor and regulatory 
authorities have direct access to subject records, and that TESARO/GSK may also 
access records if applicable.
13.5 Access to Source Documents
If source data are created (first entered), modified, maintained, archived, retrieved, or 
transmitted electronically via computerized systems (and/or any other kind of 
electronic devices) as part of regulated clinical trial activities, such systems must be 
compliant with all applicable laws and regulations governing use of electronic records 
and/or electronic signatures. Such systems may include, but are not limited to, 
electronic 
medical/health 
records, 
AE 
tracking/reporting, 
protocol 
required 
assessments, and/or drug accountability records).
When paper records from such systems are used in place of electronic format to 
perform regulated activities, such paper records should be certified copies. A certified 
copy consists of a copy of original information that has been verified, as indicated by 
a dated signature, as an exact copy having all of the same attributes and information 
as the original.

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13.6 Archival
All documentation of adverse events, records of study drug receipt and dispensation, 
and all IRB correspondence will be maintained for at least 2 years after the 
investigation is completed.
13.7 Publications 
The data collected during this study are confidential and proprietary to the study 
sponsor. Any publications or abstracts arising from this study will be discussed with 
TESARO/GSK prior to publication or presentation. Draft publications, including 
abstracts or detailed summaries of any proposed presentations will be submitted to 
TESARO/GSK at the earliest practicable time for review.

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1.
Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in 
tumors from BRCA mutation carriers. N Engl J Med. 2009;361(2):123-134.
2.
De Lorenzo SB, Patel AG, Hurley RM, Kaufmann SH. The Elephant and the 
Blind Men: Making Sense of PARP Inhibitors in Homologous Recombination 
Deficient Tumor Cells. Front Oncol. 2013;3:228.
3.
Jones P, Wilcoxen K, Rowley M, Toniatti C. Niraparib: A Poly(ADP-ribose) 
Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective 
Homologous Recombination. J Med Chem. 2015;58(8):3302-3314.
4.
Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent 
high-grade serous or poorly differentiated ovarian carcinoma or triple-negative 
breast cancer: a phase 2, multicentre, open-label, non-randomised study. 
Lancet Oncol. 2011;12(9):852-861.
5.
Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. 
Nat Rev Cancer. 2004;4(10):814-819.
6.
Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian 
carcinoma. Nature. 2011;474(7353):609-615.
7.
Timms KM, Abkevich V, Hughes E, et al. Association of BRCA1/2 defects with 
genomic scores predictive of DNA damage repair deficiency among breast 
cancer subtypes. Breast Cancer Res. 2014;16(6):475.
8.
Turner NC, Ashworth A. Biomarkers of PARP inhibitor sensitivity. Breast 
Cancer Res Treat. 2011;127(1):283-286.
9.
Kummar S, Ji J, Morgan R, et al. A Phase I study of veliparib in combination 
with metronomic cyclophosphamide in adults with refractory solid tumors and 
lymphomas. Clin Cancer Res. 2012;18(6):1726-1734.
10.
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in 
platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-
1392.
11.
Sandhu SK, Schelman WR, Wilding G, et al. The poly(ADP-ribose) polymerase 
inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with 
sporadic 
cancer: 
a 
Phase 
1 
dose-escalation 
trial. 
Lancet 
Oncol. 
2013;14(9):882-892.
12.
Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor 
olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast 
cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235-244.
13.
Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in 
Platinum-Sensitive, Recurrent Ovarian Cancer. The New England journal of 
medicine. 2016;375(22):2154-2164.
14.
Pujade-Lauraine E, Ledermann JA, Penson RT, et al. Treatment with olaparib 
monotherapy in the maintenance setting significantly improves progression-
free survival in patients with platinum-sensitive relapsed ovarian cancer: 
Results from the phase III SOLO2 study. 48th Annual Meeting for the Society 
of Gynecologic Onocolgy. March 12-15, 2017. National Harbor, Maryland. 
Abstract# LBA-2.

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15.
Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in 
Patients with a Germline BRCA Mutation. N Engl J Med. 2017.
16.
Data on file.
17.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: a cancer journal for 
clinicians. 2018;68(1):7-30.
18.
Wu M, Rivkin A, Pham T. Panitumumab: human monoclonal antibody against 
epidermal growth factor receptors for the treatment of metastatic colorectal 
cancer. Clin Ther. 2008;30(1):14-30.
19.
Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and 
activity of ABX-EGF, a fully human anti-epidermal growth factor receptor 
monoclonal antibody in patients with metastatic renal cell cancer. Journal of 
clinical oncology : official journal of the American Society of Clinical Oncology. 
2004;22(15):3003-3015.
20.
Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of 
panitumumab plus best supportive care compared with best supportive care 
alone in patients with chemotherapy-refractory metastatic colorectal cancer. 
Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. 2007;25(13):1658-1664.
21.
Hecht JR, Patnaik A, Berlin J, et al. Panitumumab monotherapy in patients with 
previously treated metastatic colorectal cancer. Cancer. 2007;110(5):980-988.
22.
Berlin 
J, 
Posey 
J, 
Tchekmedyian 
S, 
et 
al. 
Panitumumab 
with 
irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic 
colorectal cancer. Clin Colorectal Cancer. 2007;6(6):427-432.
23.
Sobrero A, Lonardi S, Rosati G, et al. FOLFOX or CAPOX in Stage II to III 
Colon Cancer: Efficacy Results of the Italian Three or Six Colon Adjuvant Trial. 
Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. 2018;36(15):1478-1485.
24.
Ciardiello F, Normanno N, Martinelli E, et al. Cetuximab continuation after first 
progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized 
phase II trial of FOLFOX plus cetuximab versus FOLFOX. Ann Oncol. 
2016;27(6):1055-1061.
25.
Colucci G, Giuliani F, Garufi C, et al. Cetuximab plus FOLFOX-4 in untreated 
patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia 
Meridionale Multicenter phase II study. Oncology. 2010;79(5-6):415-422.
26.
Rothenberg ML, Cox JV, Butts C, et al. Capecitabine plus oxaliplatin (XELOX) 
versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line 
therapy in metastatic colorectal cancer: a randomized phase III noninferiority 
study. Ann Oncol. 2008;19(10):1720-1726.
27.
Aggarwal N, Donald ND, Malik S, Selvendran SS, McPhail MJ, Monahan KJ. 
The Association of Low-Penetrance Variants in DNA Repair Genes with 
Colorectal Cancer: A Systematic Review and Meta-Analysis. Clin Transl 
Gastroenterol. 2017;8(7):e109.
28.
Edwards SL, Brough R, Lord CJ, et al. Resistance to therapy caused by 
intragenic deletion in BRCA2. Nature. 2008;451(7182):1111-1115.

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29.
Sakai W, Swisher EM, Jacquemont C, et al. Functional restoration of BRCA2 
protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma. 
Cancer Res. 2009;69(16):6381-6386.
30.
Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of 
recommendations for the use of white blood cell growth factors: an evidence-
based clinical practice guideline. J Clin Oncol. 2006;24(19):3187-3205.
31.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria 
in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 
2009;45(2):228-247.

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APPENDIX 1 – PERFORMANCE STATUS
ECOG PS
KARNOFSKY PS
0—Fully active, able to carry on all pre-
disease performance without restriction
100—Normal, no complaints; no 
evidence of disease
90—Able to carry on normal activity; 
minor signs or symptoms of disease
1—Restricted in physically strenuous 
activity but ambulatory and able to carry 
out work of a light or sedentary nature, 
e.g., light house work, office work
80—Normal activity with effort, some 
signs or symptoms of disease
70—Cares for self but unable to carry 
on normal activity or to do active work
2—Ambulatory and capable of all 
selfcare but unable to carry out any 
work activities; up and about more than 
50% of waking hours
60—Requires occasional assistance but 
is able to care for most of personal 
needs
50—Requires considerable assistance 
and frequent medical care
3—Capable of only limited selfcare; 
confined to bed or chair more than 50% 
of waking hours
40—Disabled; requires special care and 
assistance
30—Severely disabled; hospitalization 
is indicated although death not 
imminent
4—Completely disabled; cannot carry 
on any selfcare; totally confined to bed 
or chair
20—Very ill; hospitalization and active 
supportive care necessary
10—Moribund
5—Dead
0—Dead
*Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, ed. Evaluation of 
Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205.
**Zubrod C, et al. Appraisal of methods for the study of chemotherapy in man: Comparative therapeutic trial of nitrogen 
mustard and thiophosphoramide. Journal of Chronic Diseases; 1960:11:7-33.
Available at: http://ecog-acrin.org/resources/ecog-performance-status
 

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APPENDIX 2 – RESPONSE CRITERIA
Response will be assessed by Response Evaluation Criteria in Solid Tumors 
(RECIST) 1.1 Criteria for Evaluating Response in Solid Tumors using an 
independent review.
RECIST version 1.1* will be used in this study for assessment of tumor response 31. 
While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred 
imaging technique in this study.
* As published in the European Journal of Cancer:
E.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. 
Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. 
Dodd, R. Kaplan, D. Lacombe, J. Verweij. New response evaluation criteria in solid 
tumors: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-
47.

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APPENDIX 3 – DRUG DIARY
Protocol
Subject Number
Subject Initials
Visit
WCI 
Cycle
 Patient Diary
Please use this diary to record your daily protocol medication. 
Use the back of the form to make notes about symptoms you experience, and for other medicine 
you have taken, and anything else you think would be of interest.  
Dose of Niraparib ________ mg PO daily
Week 1
                         
Date      
 
Time Taken     
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Week 2
Date      
 
Time Taken     
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Week 3
                 
Date      
 
Time Taken     
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Week 4
                 
Date      
 
Time Taken     
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Please sign at the completion of this cycle and return with pill bottle to the study team.

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Patient’s Signature __________________________ 
Date_________________
Health/Medical Complaints
Please record all health/medical complaints you may have experienced below.
Please describe what you experienced
Date Started
Date Stopped
Other Medications
Record all medications taken during this cycle for example prescriptions and over the counter 
including vitamins.
Name of medication
Why did you take the medication?
Date 
Medication
 Started
Date 
Medication 
Stopped
If you have any questions, please call: 404 778 1900 or ____________________