NON INTERVENTIONAL MULTICENTER STUDY, FOR THE VALIDATION OF MOLECULAR DIAGNOSTIC TECHNOLOGIES IN SUBJECTS WITH NON SMALL CELL LUNG CANCER (NSCLC) PROTOCOL N° X9001083
Conditions: Lung Neoplasms
Sponsor: Pfizer

A non-interventional study of molecular profiling of NSCLC patient samples
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Non-Interventional Multi-Center Study 
for Molecular Diagnostic Technologies 
Validation in NSCLC Patients
Protocol N° X9001083
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TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS ...................................................................................................3
2. RESPONSIBLE PARTIES .......................................................................................................5
3. AMENDMENTS AND UPDATES ......................................................................................10
4. MILESTONES.......................................................................................................................11
5. RATIONALE AND BACKGROUND ................................................................................12
6. RESEARCH QUESTION AND OBJECTIVES ...................................................................14
7. RESEARCH METHODS......................................................................................................15
7.1. Study design ........................................................................................................15
7.1.1. .Inclusion criteria ....................................................................................16
7.1.2. Exclusion criteria.....................................................................................16
7.2. Variables...............................................................................................................16
7.3. Data sources .......................................................................................................17
7.4. Study size ..............................................................................................................17
7.5. Data management...........................................................................................18
7.6. Data analysis .......................................................................................................18
7.7. Quality control ....................................................................................................19
7.8. Record Retention...............................................................................................19
7.9. Other aspects......................................................................................................19
8. PROTECTION OF HUMAN SUBJECTS ...........................................................................20
8.1. Patient Information and Consent..................................................................20
8.2. Patient withdrawal.............................................................................................20
8.3. Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)..........................................................................................................................20
8.4. Ethical Conduct of the Study .........................................................................21
9. PUBLICATION OF STUDY RESULTS.................................................................................21
10. REFERENCES....................................................................................................................22
APPENDIX 1. LIST OF STAND ALONE DOCUMENTS......................................................24
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1
LIST OF ABBREVIATIONS
ABL
Abelson murine leukemia
AE
Adverse Event
ALK
Anaplastic Lymphoma Kinase
ATP
Adenosine Triphosphate
AUC
Area Under the plasma Concentration-time 
curve
BCR
Breakage Cluster Region
cfDNA
cell free DNA
CTCAE
Common Terminology Criteria for Adverse Event 
c-Met
Mesenchymal-epithelial transition factor
CYP
Cytochrome P450
DCR
Disease Control Rate
DR
Duration of Response
EML4
Echinoderm Microtubule-Assosciated Protein-
Linked 3
EORTC QLQ-C30
European Organization for Research and 
Treatment of Cancer Quality of Life 
Questionnaire Core 30
FDA
Food and Drug Administration 
HDFE bottle
High Density Polyethylene Bottle
HGF/R
Hepatocyte Growth Factor/Receptor
INR
International Normalized Ratio 
IRR
Independent Radiology Review
KRAS
Kirstin Rat Sarcoma 
MedDRA
Medical Dictionary for Regulatory Activities
ORR
Objective Response Rate
OS
Overall Survival
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PFS
Progression-Free Survival
PRO
Patient Reported Outcome
QLQ-LC13
Quality of Life Questionnaire Lung Cancer 
module 13
QOL
Quality of Life
QT
Time from the beginning of the QRS complex to 
the end of the T wave in the electrocardiogram
QTc
QT interval, Corrected for heart rate 
RECIST
Response Evaluation Criteria in Solid Tumors 
ROS1
c-ROS oncogene 1, receptor tyrosine kinase
RT-PCR
Reverse Transcription Polymerase Chain 
Reaction
TTR
Time to Tumor Response
VEGF
Vascular Endothelial Growth Factor
VHL
Von Hippel-Lindau
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2
RESPONSIBLE PARTIES
The Precision Medicine Center of Excellence of Pfizer Chile (CEMP in Spanish), based 
in Santiago, Chile will be responsible for the execution of the non-interventional 
protocol.
The mission of the Center (CEMP) is to deliver technical and operational excellence 
in Precision Medicine R&D and molecular diagnostic development in Latin America 
for the benefit of cancer patients all over the world.
The other involved parties will be the hospital Centers that will be providing samples, 
the diagnostics test providers (Vysis ALK Break Apart FISH or Ventana ALK IHC) and
the sequencing providers both in Chile and Brazil.
Their main responsibilities will be the following:
CEMP, through CRO
ICON,
will be responsible for sample collection and 
transportation from hospital centers to the FISH/Ventana ALK test providers, the 
sequencing providers and/or CEMP facilities. Thus, CEMP will receive clinical data 
informed consents, tissue and blood samples coming from hospitals, and data 
results of FISH/Ventana ALK and NGS from research centers.
In Brazil, AC Camargo Cancer Center (ACC), as a FISH/Ventana ALK and NGS
sequencing provider, will perform nucleic acid extraction from both kind of samples 
(tissue and blood). ACC will also perform genomic analysis using a PGM device. 
Biodata (.vcf and .pdf files) coming from the sequencers will be processed and raw 
data will be supported in a Data Center. ACC will be responsible for the storage of 
the remaining tissue and the nucleic acid from blood in Brazil.
In Chile, CEMP Genomic Laboratory and the sequencing center Genoma Mayor will 
perform nucleic acid extraction from both kind of samples (tissue and blood). Also,
they will perform genomic analysis using a PGM device and process the biodata 
coming from the sequencers and will store the raw and processed data 
accordingly. CEMP will be responsible for the storage of the remaining tissue and the 
nucleic acid from blood in Chile.
In both countries, the NGS service providers (ACC, Genoma Mayor and Genomic 
Laboratory at Pfizer) will work as a parallel sequencing facility. 
The reference hospital centers will be responsible for collecting the patient 
identification according to the inclusion criteria, gathering the clinical data and due 
diligence to obtain the inform consent from patients. They will obtain and process 
the tissue and blood samples
according to
guidelines
and perform the 
histopathological analysis. Some of the hospital Centers will perform the 
FISH/Ventana ALK test if technology and expertise is available. If not, samples will be 
sent to the designated FISH/Ventana ALK provider in Brazil or Chile. 
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PPD
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ABSTRACT
Non-Interventional Multi-Center Study for Molecular Diagnostic Technologies 
Validation in NSCLC Patients
To identify patients who can respond to targeted therapies, it is imperative that new 
molecular diagnostics be developed and deployed.  
The research lines planned for the CEMP-Chile are aimed at data generated to 
validate NGS (Next Generation Sequencing) and blood detection for ALK and/or
ROS translocations. These patients may be eligible for ALK and/or ROS inhibitor 
treatment; however treatment and follow-up on care is out-of-scope of this 
protocol.
Study Objectives and Endpoints:
Primary objective
!
To determine concordance between the Vysis ALK Break Apart FISH test or 
the Ventana ALK IHC test and Thermofisher NGS technology.
!
Validation of more sensitive, less invasive and state of the art screening 
platforms for NSCLC.
 
 
 
CCI
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Study Design
This is a non-interventional multi-center diagnostic study to validate novel diagnostic 
technologies, such as Next Generation Sequencing (NGS) from both tissue and 
blood compared to the current gold standard tests.  
As a non-interventional study, patients will not be treated or affected as part of the 
protocol.
This study will determine the correlation between the Vysis ALK Break Apart FISH test 
or the Ventana ALK IHC test of NSCLC tumors and next generation sequencing NGS 
analysis from tissue and blood derived nucleic acids. The study involves the 
collection and analysis of FFPE tumor tissue and blood of NSCLC patients to be 
analyzed with a Thermo Fischer NGS Oncomine fusion panel assay. 
A positive correlation with these novels technologies will mean an efficient, more 
accurate test, which could impact a greater number of cancer patients around 
world.
The endpoint of this Project will be to analyze 30 positive ROS1 and 120 positive ALK 
samples to validate the diagnostic method.
Given an estimated prevalence of ROS1 at 1-2% and ALK at 3-5% for NSCLC, an 
initial set of 1000 patients will be screened. An interim analysis will be performed at 
the first 1000 NSCLC samples to evaluate prevalence rates (tentatively 10 ROS1+ 
and 40 ALK+). 
For the majority of molecular tests, it is expected that at least 50 positive patient 
samples be utilized for validation, and ideally at least 10 positives representing each 
variant being detected1. Given the low prevalence of ROS1 which has 16 unique 
variants and recent analysis demonstrating that in 30 ROS1+ patient samples, there is 
representation of the 3 dominant variants suitable for analytical validation2, it is 
necessary to screen at least 3000 NSCLC samples for identifying positive samples for 
both ROS1 and ALK that should be sufficient for analytical validation of the NGS 
platform. If anticipated prevalence rates at the 3000 sample mark do not align with 
determined prevalence rates at this stage and/or 30 positive ROS1 and 120 positive 
ALK samples are not obtained, an additional 3000 patients will be screened for a 
potential total of 6000 patients. The overall screening will occur at 3 or more sites. 
Patients will only participate in the study for the initial sample collection period.
The study will be completed in approximately 48 months. 
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Study Treatment
None.
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3
AMENDMENTS AND UPDATES
None.
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4
MILESTONES
Milestone
Planned date
Start of data collection 
Initiation of NSCLC FFPE tissue collection  
June 30, 2015
End of data collection
Completion of 6000 FFPE samples, 6000 blood 
samples
June 30, 2019
Interim study report
Data analysis of the first 1000 samples processed by 
NGS will be assessed
October 31, 2016
Interim study report
Data analysis of the first 3000 samples processed by 
NGS, and first 1000 blood samples will be assessed
October 31, 2017
Final study report
Data analysis of the last 6000 samples processed by 
NGS, 3000 blood samples will be assessed
December, 31, 2019
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5
RATIONALE AND BACKGROUND
A. Molecular Diagnostics
Two of the most relevant areas of today’s health care diagnostics are “in vivo” 
imaging and “in vitro” diagnostics.  The first includes such technologies as X-Rays, 
ultrasonic waves, magnetic resonance, or radio-nuclear methods that generate 
images of the body and its organs.  The second areas include tests performed on a 
sample taken from the body (blood, tissue, sputum, urine, etc.)1.
Molecular diagnostics belongs to a subset of in vitro diagnostics.  It describes a 
certain type of diagnostic tests that assess a person’s health literally at a molecular 
level, detecting and measuring specific genetic sequences in deoxyribonucleic 
acid (DNA) or ribonucleic acid (RNA) or the proteins they express.  This allows 
identifying on whether a specific person is predisposed to have a disease, whether 
they actually have a disease, or whether a certain treatment option is likely to be 
effective for a specific disease.
Molecular diagnostics has revolutionized biological and biomedical research 
becoming a growing part of a successful health care system, providing critical 
information that health care providers and patients need to make the right medical 
decisions2. It often provides objective, quantitative measurements that inform every 
stage of care—prevention, detection, diagnosis, treatment, and successful 
management of health conditions.
Personalized medicine, where understanding the underlying molecular mechanisms 
of diseases allows physicians to evolve to an individual more effective therapy is a 
derivative of molecular discovery. 3   The ultimate power of personalized medicine is 
the feasibility to treat smaller groups with therapies tailored to their molecular profile. 
When specific proteins or genetic sequences have a known association with a 
specific health condition or disease, they are often referred to as “biomarkers” 
because they are markers of that condition or disease.4 The detection of Cancer 
biomarkers can be useful in establishing a specific diagnosis and also in establishing 
a specific diagnosis.
World advances in increasing automation are enabling the development of cutting-
edge molecular diagnostics to be performed, better detecting biomarkers and as a 
result stimulating the understanding the mechanism of diseases that will foster the 
discovery of the next breakthrough targeted therapies.5
Therefore the research around new diagnostics technologies that will enhance the 
overall effectiveness of therapies in the treated population is essential to increase 
the proportion of patients with favorable outcomes.
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B. Lung Cancer
Non-small cell lung cancer (NSCLC) is a common cause of cancer mortality 
throughout the world.  In 2007, there were 1.5 million new lung cancer cases 
diagnosed worldwide, including around 733,100 cases in the South American 
Region.6
Approximately 85% of lung cancer is histologically defined as non-small cell and the 
remaining 14% as small cell.  The majority of patients with NSCLC present with 
inoperable locally advanced (Stage IIIB) or metastatic (Stage IV) disease for which 
no curative treatment is yet available.  In newly diagnosed patients with good 
performance status, platinum-based doublet-combination chemotherapies are 
associated with a median overall survival (OS) of 7.4 to 9.9 months. 7, 8, 9, 10, 11, 12  
Therefore, newer agents with novel mechanisms of action are still desperately 
needed for this serious life-threatening disease. 15,16
The rapid and efficient identification of key driver genes in non-small-cell lung
cancer (NSCLC) is becoming increasingly important.17  Clinical screening efforts 
have revealed that the most common mutations in lung cancer specimens involve 
EGFR and KRAS, along with 10 other genes that show a prevalence of mutation in 
5% or less of tumors. The ALK gene is rearranged in around 3%-5% of patients with 
NSCLC and has been the focus of intense basic and clinical research, suggesting 
that the frequency of the gene rearrangement is similar in Asian and Western 
patients.   
ROS1 is a receptor tyrosine kinase of the insulin receptor family. Chromosomal 
rearrangements involving the ROS1 gene were originally described in glioblastomas, 
where ROS1 (chromosome 6q22) is fused to the FIG gene (chromosome 6q22 
immediately adjacent to ROS1), 16 and have been shown to be transforming in 
transgenic mice.17 More recently, ROS1 fusions were identified as potential driver 
mutations in an NSCLC cell line (HCC78; SLC34A2-ROS1) and an NSCLC patient 
sample (CD74-ROS1). 18 These fusions led to constitutive kinase activity and were 
associated with sensitivity in vitro and in vivo to crizotinib. As of December 2013, 16 
different variants have been found.16, 17, 18
The present study is designed to advance the molecular testing methodologies to 
identify ALK+ and ROS1+ NSCLC patients. Advanced next generation sequencing 
screening methodologies will be used to identify NSCLC patients whose tumors 
contain a ROS1 gene inversion or translocation or an ALK translocation. 
A parallel test for ALK+ by either the Abbott ALK FISH test or the Ventana ALK IHC test 
is necessary to validate the NGS test in all samples. A parallel test for ROS1+ by either 
the Kreatech FISH test or the D4D6  ROS1 IHC test may be necessary to validate the 
NGS test in all samples. 
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6
RESEARCH QUESTION AND OBJECTIVES
This investigation intends to validate molecular diagnostics technologies on 
ALK+/ROS1+ NSCLC tumor diagnostic; more accurate and precise methods than 
the existing companion diagnostics (FISH Vysis ALK Break Apart FISH test or the 
Ventana ALK IHC test).
CEMP Genomic Laboratory together with its sequencing providers (ACC in Brazil, 
Genoma Mayor in Chile) will process NGS data from tissue and blood and compare 
it against histopathological and FISH/Ventana ALK results.  With this comparison 
CEMP will be able to determine if NGS technologies are suitable to be considered as 
accurate diagnostic methods.
The main question that will be addressed in this project is the significant global 
demand to develop improved molecular diagnostics for cancer, for both 
translational/clinical applications, as well as companion diagnostics to personalize 
oncology medicines, in order to increase the overall effectiveness of therapies to 
patients which may benefit the most, with significant value add to both payers
(public healthcare and/or healthcare insurance) and drug manufacturers.
Accordingly, next generation molecular diagnostics should leverage scientific 
advancements to become less invasive, require less amount  of patient tissue for 
testing and of greater sensitivity to cancer-specific genetic indicators, whether 
inherited, mutated, or transcribed. 
The primary disease focus of this project is to examine novel technologies for NSCLC 
patient screening for detection of ALK and ROS1 positive patients.
The project will address this technical issue through two research lines:
1) Development of an ALK/ROS fusion specific next generation sequencing
panel;
2) Detection of tumor-derived nucleic acids in the blood of patients diagnosed 
with NSCLC.
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7
RESEARCH METHODS
NGS translocation detection platform
The current study design aims to validate the NGS ALK/RET/ROS detection platform; 
archival or prospective tumor tissue specimens will be collected from previously
diagnosed NSCLC patients enrolled on the study and analyzed for the presence or 
absence of ALK/RET/ROS translocations. 
The data from these assays in combination with the subsequent outcome data 
collected from the clinical sites will be used to define a diagnostics strategy for the 
NGS platform. 
Circulating nucleic acid (CNA) analyses
For the CNA analysis, two blood tubes will be from all patients at baseline and at 
time of progression (if possible). One blood tube will be used for RNA analysis. A 
second blood tube will be used for DNA analysis. Both preparations will be 
processed and stored frozen until extraction and NGS protocols are defined for this 
analysis (2016).
Protocols for FFPE processing and blood collection will be provided (See Appendix 
1).
Additional tests on the tumor tissue and blood samples can be performed. These 
may include other tests for the ALK gene fusion or other lung cancer biomarkers
according to the state-of-art on this area. 
7.1
Study design
This is a non-intervention multi-center study where tissue and blood of NSCLC
patients will be collected. Patients will not be treated as part of this protocol and will 
only participate in the study for the initial samples and clinical parameters collection 
period.
Up to 6000 patients are expected to be screened in the study overall at 3 or more 
sites. 
Samples should include:
1. Archived or tumor tissue as formalin-fixed paraffin-embedded (FFPE) tissue block 
or 10 unstained slides containing serial 5-micron tumor tissue sections. 
2. Blood samples collected in the provided StepCheck tubes. One 8ml tube for 
DNA collection, one 8mL tube for RNA collection. 
The study will evaluate the strength of NGS technology as diagnostics methods for 
ALK+ and or ROS1+ tumors.
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The strength of the study is based on the fact that NGS technology has an
adequate sequencing quality (Q>30) and coverage, which ensures the accuracy 
of results. Given the low prevalence of ALK and ROS rearrangements, it is necessary 
to sample up to 6000 samples to obtain at least 30 ROS1+ for adequate 
concordance against other platforms. This is critical for the diagnostic evaluation 
results, making it eligible as a good diagnostic method. 
Besides this, the clinical data will be correlated to the NGS data. This will provide 
demographics correlations and give information about the incidence of the markers 
in the Chilean and Brazilian people.
The study will be completed in approximately 48 months. 
7.1.1 .Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in
the study:
1. Female or male, 18 years of age or older.  
2. Patients with histologically or cytological proven diagnosis of NSCLC, 
pathologically identified as adenocarcinoma.
3. Patient naïve in lung cancer treatment
4. Signed and dated informed consent document indicating that the 
patient (or legally acceptable representative) has been informed of all 
the pertinent aspects of the study prior to enrollment.
5. Patients must give consent to the research use of their archived or tumor 
FFPE tissue, and if available, 2 blood tubes. 
7.1.2 Exclusion criteria
Patients meeting any of the following criteria will not be included in the study:
1. Prior chemotherapy treatment.
7.2
Variables
The variables that can impact in the project are non-existence of clinical data, of 
properly taken samples, misdiagnosis of adenocarcinoma, insufficient blood
volume, improper sample storage and transportation, insufficient number of slides 
for the RNA extraction, inadequate preparation and handling of FFPE, inadequate 
amounts or bad quality of the RNA derived from FFPE or blood samples, variability in 
FISH/Ventana ALK testing due the operator or the equipment itself.
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7.3
Data sources
The primary data sources for variables relevant to the study objectives will include 
medical records, patient interviews and molecular profiling. 
Data resulting from health or investigator records provided in case report forms will 
be described under the statistical analysis plan.
7.4
Study size
The results regarding the presence or absence of specific gene fusions (ALK and/or 
ROS1) after applying NGS will be confirmed using certified and validated test for 
clinical use, which will allow the specificity of NGS test for the analyzed gene. In all 
participant subjects the presence of gene ALK and ROS1 variation will be analyzed 
which will allow to estimate the sensitivity in the NGS test.
The specificity of the NGS trial will be calculated based on cases with a particular 
gene fusion where a result has been obtained through a certified test. Thus, the 
specificity will be equal to the confirmed cases through certified test divided by the 
total of NGS identified mutated cases number. The sensitivity will be calculated 
dividing the number of cases with a confirmed gene fusion by an ALK and/or ROS1 
certified test by the number of the same cases in which the fusion was identified by 
NGS.
The gene fusion in ROS1 has been selected as the primary variation for the statistical
analysis plan, since is the less frequent variation in lung cancer (COSMIC Sanger 
Database) with a prevalence of 1-2%. The confidence intervals for sensitivity and 
specificity will be calculated according to the efficiency method of the marker 
(efficient score method, Newcombe, 1998, Wilson, 1927). 19, 20
This study expects to analyze a total of 30 tumors with alterations in the ROS1 gene 
and 120 alterations in ALK. Thus, for a precision up to 80% (either specificity or 
sensitivity), will be enough information to stablish a sensitivity and specificity 
estimation of the NGS trial within 0.1 points and 0.05 points (wide of 95% of the 
confidence interval) respectively.
Given an estimated prevalence of ROS1 at 1-2% and ALK at 3-5% for NSCLC, an 
initial set of 1000 patients will be screened. 
An interim analysis will be performed at the first 1000 NSCLC samples to evaluate 
prevalence rates. If anticipated prevalence rates do not align with determined 
prevalence rates at this stage, an additional 2000 patients will be screened for a 
potential total of 3000 patients.
A subsequent interim analysis will be performed at the 3000 NSCLC samples to 
evaluate prevalence rates. If anticipated prevalence rates do not align with 
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determined prevalence rates at this stage, an additional 3000 patients will be 
screened for a potential total of 6000 patients. The overall screening will occur at 3 
or more sites. Patients will only participate in the study for the initial sample collection 
period.
The study will be completed in approximately 48 months. Since it’s a non-
interventional multi-center study involving the collection and analysis of FFPE tumor 
tissue and blood of NSCLC patients, patients will not be treated as part of the 
protocol.
7.5
Data management 
As used in this protocol, the term case report form (CRF) should be understood to 
refer to either a paper form or an electronic data record or both, depending on the 
data collection method used in this study.
A CRF is required and should be completed for each included subject.  The 
completed original CRFs are the sole property of Pfizer and should not be made 
available in any form to third parties, except for authorized representatives of Pfizer 
or appropriate regulatory authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all 
clinical, safety and laboratory data entered on the CRFs and any other data 
collection forms (source documents) and ensuring that they are accurate, 
authentic 
/ 
original, 
attributable, 
complete, 
consistent, 
legible, 
timely 
(contemporaneous), enduring and available when required.  
The CRFs must be signed by the investigator or by an authorized staff member to 
attest that the data contained on the CRFs is true.  Any corrections to entries made 
in the CRFs, source documents must be dated, initialed and explained (if necessary) 
and should not obscure the original entry.” 
In most cases, the source documents are the hospitals or the physician's subject 
chart.  In these cases data collected on the CRFs must match the data in those 
charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In 
these cases, a document should be available at the investigator’s site as well as at 
Pfizer and clearly identify those data that will be recorded in the CRF, and for which 
the CRF will stand as the source document.
7.6
Data analysis 
Detailed methodology for summary and statistical analyses of data collected in this 
study will be documented in a Statistical Analysis Plan (SAP), which will be dated, 
filed and maintained by the sponsor. 
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The SAP may modify the plans outlined in the protocol; any major modifications of 
primary endpoint definitions or their analyses would be reflected in a protocol 
amendment.
7.7
Quality control
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to 
ensure that the protocol and GCPs are being followed.  The monitors may review 
source documents to confirm that the data recorded on CRFs is accurate. 
The investigator and institution will allow Pfizer monitors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.
The study site may be subject to review by the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC), and/or to quality assurance audits 
performed by Pfizer, or companies working with or on behalf of Pfizer, and/or to 
inspection by appropriate regulatory authorities.
It is important that the investigator(s) and their relevant personnel are available 
during the monitoring visits and possible audits or inspections and that sufficient time 
is devoted to the process.
7.8
Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating 
subjects (sufficient information to link records, e.g., CRFs and hospital records), all 
original signed informed consent forms, copies of all CRFs, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (e.g., letters, meeting minutes, telephone calls reports).  
The records should be retained by the investigator according to ICH, local 
regulations, or as specified in the Clinical Study Agreement, whichever is longer.
If the investigator becomes unable for any reason to continue to retain study 
records for the required period (e.g., retirement, relocation), Pfizer should be 
prospectively notified.  The study records must be transferred to a designee 
acceptable to Pfizer, such as another investigator, another institution, or to an 
independent third party arranged by Pfizer.  The investigator must obtain Pfizer’s 
written permission before disposing of any records, even if retention requirements 
have been met.
7.9
Other aspects
Not applicable.
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8
PROTECTION OF HUMAN SUBJECTS
8.1
Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient
names on any sponsor forms, reports, publications, or in any other disclosures, 
except where required by laws.  In case of data transfer, Pfizer will maintain high 
standards of confidentiality and protection of patient personal data.
The informed consent form must be in compliance with local regulatory 
requirements and legal requirements.
The informed consent form used in this study, and any changes made during the 
course of the study, must be prospectively approved by both the IRB/IEC and Pfizer 
before use.
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and 
possible risks associated with participation.  
The investigator, or a person designated by the investigator, will obtain written 
informed consent from each patient
or the patient’s legally acceptable 
representative before any study-specific activity is performed.  The investigator will 
retain the original of each patient's signed consent form and one copy will be given 
to the patient or his/her representative.
8.2
Patient withdrawal
Patients may be withdrawn at any time at the discretion of the investigator or 
sponsor for safety, behavioral, or administrative reasons. In any circumstance, every 
effort should be made to document subject outcome, if possible. The investigator 
should inquire about the reason for withdrawal and follow-up with the subject 
regarding any unresolved adverse events. 
If the patient withdraws from the study, and also withdraws consent for disclosure of 
future information, no further evaluations should be performed, and no additional 
data should be collected. The sponsor may retain and continue to use any data 
collected if no withdrawal of consent is requested.
8.3
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study 
protocol, protocol amendments, and informed consent forms, and other relevant 
documents, (e.g., recruitment advertisements), if applicable, from the IRB/IEC.  
All correspondence with the IRB/IEC should be retained in the Investigator File.  
Copies of IRB/IEC approvals should be forwarded to Pfizer. 
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8.4
Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, 
as well as the general principles set forth in the International Ethical Guidelines for 
Biomedical 
Research Involving Human Subjects 
(Council 
for International 
Organizations of Medical Sciences 2002), Guidelines for Good Clinical Practice 
(International Conference on Harmonization 1996), and the Declaration of Helsinki 
(World Medical Association 2008). 
In addition, the study will be conducted in accordance with the protocol, the 
International Conference on Harmonization guideline on Good Clinical Practice, 
and applicable local regulatory requirements and laws.
9
PUBLICATION OF STUDY RESULTS
Since the objective of Pfizer’s Center of Excellence is to lead the research in 
precision Medicine, publications with Study Researchers will be promoted, whether 
or not the results are favorable to the study.
  
Since the Study is part of a multi-center study, Study Researchers agree that 
publications are to be a joint publications, even after the study is finished.  
To ensure against inadvertent disclosure of Confidential Information or unprotected 
Inventions, Study Researchers will provide Pfizer an opportunity to review any 
proposed joint publication or other type of disclosure before it is submitted or 
otherwise disclosed.
Study Researchers will provide manuscripts, abstracts, or the full text of any other 
intended disclosure (poster presentation, invited speaker or guest lecturer 
presentation, etc.) to Pfizer at least 60 days before they are submitted for 
publication or otherwise disclosed. 
Study Researchers will, on request, remove any previously undisclosed Confidential 
Information (other than the Study results themselves) before disclosure.
For all publications relating to the Study, the Center of Excellence will comply with 
recognized ethical standards concerning publications and authorship, including 
Section II - “Ethical Considerations in the Conduct and Reporting of Research” of the 
Uniform 
Requirements 
for 
Manuscripts 
Submitted 
to 
Biomedical 
Journals, 
http://www.icmje.org/index.html#authorship, 
established 
by 
the 
International 
Committee of Medical Journal Editors.
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APPENDIX 1. LIST OF STAND ALONE DOCUMENTS.
Document reference 
Title
OCP Fusion including DNA/RNA 
extraction
NGS SOP for FFPE processing
Streck cell free RNA BCT
Blood (RNA) tube collection and storage
Streck cell free DNA BCT
Blood (DNA) tube collection and storage
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