Clinical trial NCT02382796
Conditions: NSCLC
Sponsor: Pfizer
Start date: 2015-07-10; Completion date: 2019-05-30
Enrollment: 7 participants; Allocation: ; Intervention model: 

Brief summary:
The purpose of this study to permit continued access to dacomitinib for patients who participated in other dacomitinib monotherapy treatment protocols in Japan and have the potential to derive clinical benefit without unacceptable toxicity from continued dacomitinib treatment.

Detailed description:
The intention of the study is to allow continued use of dacomitinib in Japan for patients on closed dacomitinib clinical trials and who continue to experience clinical benefit.

Arms: arm 1: 3 dose strengths (45 mg, 30 mg, and 15 mg), continuous oral daily dosing
Interventions: intervention 1: Dacomitinib
Intervention descriptions: intervention 1: Starting at the current dose level in the prior study. Dose reductions and re-escalations are allowed based on tolerability. Patients may continue to be treated with dacomitinib on this protocol as long as there is evidence of clinical benefit in the judgment of the investigator.

Protocol documents:
Prot_000.pdf: 
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CLINICAL PROTOCOL — A7471055
TREATMENT ACCESS PROTOCOL FOR PATIENTS PREVIOUSLY TREATED 
WITH DACOMITINIB ON A CLINICAL TRIAL IN JAPAN
Compound:
PF-00299804
Compound Name:
Dacomitinib
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
N/A
Protocol Number:
A7471055
Phase:
Phase 2
CCI


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Document History
Document
Version Date
Summary of Changes
Original Protocol
28 January 2015
Not Applicable (N/A)


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Abbreviations
Abbreviation
Term
AE
adverse event
ALT
alanine transaminase
AST
aspartate transaminase
ATP
adenosine triphosphate
BUN
blood urea nitrogen
CRF
case report form
CSA
clinical study agreement
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
DAI
dosage and administration instructions
DMC
data monitoring committee
DVT
deep vein thrombosis 
EC
ethics committee
ECG
Electrocardiogram
ECOG
Eastern Cooperative Group
EDP
exposure during pregnancy
EGFR
epidermal growth factor receptor
EDTA
edetic acid (ethylenediaminetetraacetic acid)
GCP
Good Clinical Practice
HDPE
High Density PolyEthylene 
HER
Human Epidermal Growth Factor receptor
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
ID
Identification
IEC
institutional ethics committee
IND
investigational new drug application
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine device
KRAS
Kirsten Rat Sarcoma viral oncogene homolog
LFT
liver function test
LSLV
last subject last visit 
N/A
not applicable
NCIC-CTG
National Cancer Institute of Canada-Clinical Trials Group
NSCLC
non-small cell lung cancer
OS
overall survival
PCD
primary completion date
PFS
progression-free survival
PS
performance status
PT
prothrombin time
RTK
receptor tyrosine kinase


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SAE
serious adverse event
SOP
standard operating procedure
SRSD
single reference safety document
ULN
upper limit of normal
US
United States
WBC
white blood cell


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PROTOCOL SUMMARY
Indication:
This treatment extension study will enroll patients with advanced cancer who are receiving 
single-agent dacomitinib in a prior study in Japan, and have the potential to derive clinical 
benefit without unacceptable toxicity from continued single-agent dacomitinib treatment.
Background and Rationale:
Dacomitinib is an orally available, selective adenosine triphosphate (ATP)-competitive 
irreversible small-molecule inhibitor of Human Epidermal Growth Factor receptor 
(HER, erbB) family receptor tyrosine kinases (RTKs) including the epidermal growth factor 
receptor (EGFR, HER-1), HER-2 receptor (erbB2), and HER-4 (erbB4) receptor and their 
oncogenic variants (ie, EGFR exon 19 deletion, EGFR L858R point mutation, and EGFR 
T790M mutation).
Dacomitinib is being developed globally in locally advanced or metastatic non-small cell 
lung cancer (NSCLC) after at least one prior chemotherapy regimen.  In the course of 
development, Phase 2 and 3 studies are being conducted in several NSCLC treatment
settings.
Complete information for this compound may be found in the Single Reference Safety 
Document (SRSD), which for this study is the Investigator’s Brochure (IB). 
Indications of activity have been seen in a number of dacomitinib clinical trials.  This 
protocol permits continued access to dacomitinib for patients who participated in other 
dacomitinib monotherapy treatment protocols and have the potential to derive clinical benefit 
without unacceptable toxicity from continued dacomitinib treatment.  This treatment access 
protocol is only open to patients in Japan.
Patients will follow a schedule of visits and data collection that permits continued safety 
monitoring.
Objectives:
Primary Objective:

To allow access to dacomitinib for patients who received dacomitinib on a prior study 
in Japan and who have the potential to derive continued clinical benefit from 
single-agent dacomitinib treatment without unacceptable toxicity based upon the 
investigator’s judgment.
Secondary Objective: 

To monitor the specific long-term safety and tolerability of single-agent dacomitinib 
in patients who have already received dacomitinib on a prior study in Japan.


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Endpoints:
Adverse events as assessed by National Cancer Institute Common Terminology Criteria for 
Adverse Events version 4.0 (NCI CTCAE.v4.0). 
Study Design:
This is a multi-center, open-label, treatment extension study open in Japan only. Eligible 
patients include those with advanced cancer who received and tolerated single-agent 
dacomitinib in a prior clinical study and have the potential to derive continued clinical 
benefit based on investigator judgment.  Patients enrolled in this extension study may 
continue to receive dacomitinib starting at the current dose level in the prior study. Dose 
reductions and re-escalations are allowed based on tolerability. Patients may continue to be 
treated with dacomitinib on this protocol as long as there is evidence of clinical benefit in the 
judgment of the investigator.  Adverse events will be graded according to NCI CTCAE v4.0,
and monitored according to the frequency outlined in the Safety Review Plan.
Study Treatment:
Patients will receive continuous daily dosing of dacomitinib at a dose of 45 mg, 30 mg, or 
15 mg.  The starting dose of dacomitinib on this treatment extension study will be the 
patient’s ending dose from the prior study. 
Patients may continue single-agent dacomitinib treatment on this treatment extension study 
as long as there is reasonable evidence of clinical benefit without unacceptable toxicity per 
investigator judgment and with agreement of the Sponsor (see Section 6.1 Patient 
Withdrawal).
Statistical Methods:
Due to the nature of this study, the number of patients to be enrolled is not predetermined.
No statistical methods will be employed to test a specific hypothesis in this study.  Only 
descriptive summaries of safety will be provided, and no inferential analyses are planned.


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SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides details of the protocol visits and procedures.  Refer 
to the Study Procedures and Assessments sections of the protocol for additional information 
on certain specific procedures and assessments required for compliance with the protocol.
The investigator may schedule visits (unplanned visits), in addition to those listed on the 
schedule of activities, in order to conduct evaluations or assessments required to protect the 
well-being of the patient.


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Table 1.
SCHEDULE OF ACTIVITIES
Protocol Activity
Screening
(28 days 
prior to 
study entry)
Cycle 1
Day 1
Cycles 2 and beyond
End of 
Treatment
Follow-up 
Visit9
Every
8 weeks
Every 
6 months
Informed Consent1
X
Patient History 
X
Registration
X
Laboratory
Hematology2
X
X
X
Blood Chemistry3
X
X
X
Urinalysis4
X
Pregnancy test5
X
X
X
Safety/Disease Assessments
Tumor Assessments6
X
AdAdverse Event 
Assessments7
X
X
X
X
X
Concomitant Medication8
X
X
X
X
X
Study Treatment
Dacomitinib
As per dosing regimen in original 
protocol
1.
Informed Consent: All patients must sign an informed consent document prior to any study-related 
procedures that are not considered to be standard of care and prior to receiving study drug.
2.
Hematology: Be performed according to local standard clinical practice.  The interval for laboratory 
assessments should not be longer than every 8 weeks.
3.
Blood Chemistry: Be performed according to local standard clinical practice.  The interval for laboratory 
assessments should not be longer than every 8 weeks.
4.
Urinalysis: Be performed according to local standard clinical practice.
5.
Pregnancy Test: Pregnancy Test (serum or urine) for women of child-bearing potential shall be done at 
screening and before investigational product administration at the baseline visit.  It should be repeated the 
end of study treatment, and additionally whenever one menstrual cycle is missed, or when potential 
pregnancy is otherwise suspected.  Additional pregnancy tests may also be undertaken if requested by 
institutional review boards (IRBs)/ethics committees (ECs), or if required by local regulations.
6.
Tumor Assessments: On-study tumor assessments should be performed according to site standard-of-care 
imaging modality. The interval for monitoring disease status and for progression of disease should not be
longer than every 6 months. 
7.
Adverse Event Assessment: Following the first dose, adverse events (AEs) and serious adverse events 
(SAEs) should be assessed and documented during the study reporting period.  All reported study 
drug-related adverse events must be followed until the event has resolved, returned to baseline, or has been 
deemed irreversible, or until death, whichever occurs first.
8.
Concomitant Medications: Review medications taken by the patient since the last visit to determine 
whether or not treatment with dacomitinib is contraindicated.
9.
Follow-up Visit: At least 28 days, and no more than 35 days, after discontinuation of treatment, patients 
will return to undergo review of concomitant medications and assessment for resolution of any 
treatment-related toxicity.  Patients continuing to experience toxicity at this point following discontinuation 
of treatment will continue to be followed at least every 4 weeks until resolution or determination, in the 
clinical judgment of the investigator, that no further improvement is expected.


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
APPENDICES .........................................................................................................................12
1. INTRODUCTION ...............................................................................................................13
1.1. Mechanism of Action/Indication.............................................................................13
1.2. Clinical Experience with Dacomitinib in Humans..................................................13
1.2.1. Phase 3 Studies ...........................................................................................14
1.3. Background and Rationale ......................................................................................15
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................15
2.1. Objectives................................................................................................................15
2.1.1. Primary Objective.......................................................................................15
2.1.2. Secondary Objective...................................................................................15
2.2. Endpoints.................................................................................................................15
3. STUDY DESIGN.................................................................................................................16
4. PATIENT SELECTION......................................................................................................16
4.1. Inclusion Criteria.....................................................................................................16
4.2. Exclusion Criteria....................................................................................................17
4.3. Registration Criteria ................................................................................................17
4.4. Lifestyle Guidelines ................................................................................................17
4.5. Sponsor’s Qualified Medical Personnel..................................................................18
5. STUDY TREATMENTS.....................................................................................................19
5.1. Allocation to Treatment ..........................................................................................19
5.2. Patient Compliance .................................................................................................19
5.3. Drug Supplies..........................................................................................................19
5.3.1. Dosage Form(s) and Packaging..................................................................19
5.3.2. Preparation and Dispensing........................................................................19
5.4. Administration.........................................................................................................19
5.5. Dose Modification...................................................................................................20
5.6. Adverse Event Management ...................................................................................21
5.7. Drug Storage ...........................................................................................................21
5.8. Drug Accountability................................................................................................22
5.9. Concomitant Treatment(s).......................................................................................22


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5.9.1. CYP2D6 Substrates ....................................................................................22
5.9.2. P-glycoprotein.............................................................................................23
5.9.3. Strong Amines ............................................................................................23
5.10. Supportive Care.....................................................................................................23
6. STUDY PROCEDURES .....................................................................................................23
6.1. Patient Withdrawal..................................................................................................24
7. ASSESSMENTS..................................................................................................................24
7.1. Pregnancy Testing...................................................................................................25
7.2. Baseline Demographics...........................................................................................25
7.3. Patient History.........................................................................................................25
7.4. Laboratories.............................................................................................................25
7.5. Tumor Assessments.................................................................................................25
8. ADVERSE EVENT REPORTING......................................................................................26
8.1. Adverse Events........................................................................................................26
8.2. Reporting Period .....................................................................................................26
8.3. Definition of an Adverse Event...............................................................................26
8.4. Medication Errors....................................................................................................27
8.5. Abnormal Test Findings..........................................................................................28
8.6. Serious Adverse Events...........................................................................................28
8.6.1. Protocol-Specified Serious Adverse Events...............................................29
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................29
8.7. Hospitalization ........................................................................................................30
8.8. Severity Assessment................................................................................................32
8.9. Causality Assessment..............................................................................................32
8.10. Exposure During Pregnancy..................................................................................33
8.11. Occupational Exposure .........................................................................................34
8.12. Withdrawal Due to Adverse Events (Also See Section 6.1).................................34
8.13. Eliciting Adverse Event Information ....................................................................34
8.14. Reporting Requirements........................................................................................34
8.14.1. Serious Adverse Event Reporting Requirements .....................................34
8.14.2. Non-Serious Adverse Event Reporting Requirements .............................35
8.14.3. Sponsor Reporting Requirements to Regulatory Authorities ...................35


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9. DATA ANALYSIS/STATISTICAL METHODS...............................................................35
9.1. Sample Size Determination.....................................................................................35
9.2. Efficacy Analysis ....................................................................................................35
9.3. Analysis of Other Endpoints ...................................................................................36
9.4. Safety Analysis........................................................................................................36
9.5. Data Monitoring Committee ...................................................................................36
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................36
11. DATA HANDLING AND RECORD KEEPING .............................................................36
11.1. Case Report Forms/Electronic Data Record .........................................................36
11.2. Record Retention...................................................................................................37
12. ETHICS..............................................................................................................................38
12.1. Institutional Review Board (IRB)/Ethics Committee (EC)...................................38
12.2. Ethical Conduct of the Study ................................................................................38
12.3. Patient Information and Consent...........................................................................38
12.4. Patient Recruitment...............................................................................................39
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................39
13. DEFINITION OF END OF TRIAL...................................................................................39
13.1. End of Trial ...........................................................................................................39
14. SPONSOR DISCONTINUATION CRITERIA ................................................................39
15. PUBLICATION OF STUDY RESULTS..........................................................................40
15.1. Communication of Results by Pfizer ....................................................................40
15.2. Publications by Investigators ................................................................................41
16. REFERENCES ..................................................................................................................42
17. APPENDICES ...................................................................................................................43


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LIST OF TABLES
Table 1.
SCHEDULE OF ACTIVITIES ..............................................................................8
Table 2.
Doses of Study Drug Administered......................................................................20
APPENDICES
Appendix 1. Adverse Event Management Guidelines.............................................................43
Appendix 2. Guidance on Concomitant Medications involved in CYP2D6 Pathway ............50


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1. INTRODUCTION
1.1. Mechanism of Action/Indication
This treatment extension study will enroll patients with advanced cancer who are receiving 
single-agent dacomitinib in a prior study in Japan, and have the potential to derive continued 
clinical benefit without unacceptable toxicity from single-agent dacomitinib treatment.
Dacomitinib is a potent, orally available, selective adenosine triphosphate (ATP) competitive 
irreversible small molecule inhibitor of Human Epidermal Growth Factor receptor (HER, 
erbB) family receptor tyrosine kinases (RTKs) including the epidermal growth factor 
receptor (EGFR, HER 1), HER 2 receptor (erbB2), and HER 4 (erbB4) receptor and their 
oncogenic variants (ie, EGFR exon 19 deletion, EGFR L858R point mutation, and EGFR 
T790M mutation).
Dacomitinib inhibits the tyrosine kinase activity of the HER family through binding at the 
ATP binding site, which results in covalent modification of a cysteine in the ATP binding 
pocket.  It represents a second generation, irreversible pan-HER inhibitor with superior 
biopharmaceutical and preclinical anti-tumor activity to the first generation, irreversible 
pan-HER inhibitor CI-1033. The development of dacomitinib has focused on addressing the 
potential liabilities of first generation pan-HER inhibitors, which includes limited clinical 
activity possibly due to insufficient drug exposure for adequate target suppression.
Dacomitinib has significantly improved pharmacokinetic properties (greater bioavailability, 
longer half-life, larger volume of distribution, and lower clearance) across all nonclinical 
species tested (rat, dog and monkey).  In preclinical human tumor xenograft models, 
dacomitinib showed greater antitumor effects, better distribution of drug to the tumor, and 
greater and more sustained inhibition of HER activity in the tumor as compared with 
CI-1033.  It exhibited anti-tumor effects in at least four different human xenograft models 
that express and/or overexpresss HER family members.  The unique irreversible and highly 
selective properties of dacomitinib for the HER kinase family, results in sustained 
suppression of receptor tyrosine kinase activity.  The long-lasting inhibition of receptor 
phosphorylation reduces concern over potentially short plasma half-lives.  Furthermore, the 
low nanomolar potency and irreversible binding of the intended targets reduce the need for 
high peak plasma levels, which in turn could minimize target-nonspecific toxicities.
1.2. Clinical Experience with Dacomitinib in Humans
As of 16 May 2014, 2720 patients with advanced cancer have been enrolled and treated in 
15 clinical trials evaluating the safety, efficacy, and pharmacokinetics of dacomitinib. 
Details regarding the dacomitinib clinical studies may be found in the dacomitinib 
Investigator Brochure (IB). 
Ongoing safety monitoring at this stage in the development of dacomitinib included 
evaluation of adverse events in specific populations related to age, race, and hepatic and renal 
impairment.  Although some of these populations were too small for statistical comparison, 
there was no evidence that any specific race group, elderly (65-75) or very elderly (>75) 
patients were at increased risk of more frequent or more severe adverse events. There has 


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not been evidence of hepatic or renal toxicity or an imbalance of other adverse events in 
patients enrolled with normal or abnormal (within protocol inclusion criteria) baseline renal 
or hepatic function. As with any ongoing study, the available data are preliminary in nature 
and are subject to change.
Complete information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the IB.
1.2.1. Phase 3 Studies
Study BR.26 (A7471011) is a randomized, double-blind, placebo-controlled Phase 3 trial in
refractory advanced non-small cell lung cancer (NSCLC) conducted as an 
Investigator-Initiated Research (IIR) study under the auspices of the National Cancer 
Institute of Canada-Clinical Trials Group (NCIC-CTG). Enrollment began in December 
2009. Efficacy and safety were monitored by an independent Data Monitoring Committee 
(DMC), and meeting outcomes shared with NCIC-CTG. Based on these DMC meetings to 
date, the study continued as planned without any recommended protocol changes. 
Enrollment was completed in this study with 720 patients randomized. There were 
716 patients treated in this trial; 477 patients received dacomitinib and 239 patients received 
placebo.  Three patients randomized to dacomitinib and 1 patient randomized to placebo 
were not treated.  Currently, there are 2 patients still receiving active treatment (dacomitinib 
arm). Based on the clinical study report (CSR) data cutoff as of 11 October 2013, the study 
did not demonstrate improved overall survival (OS) versus placebo with statistical 
significance, and the primary objective of the study was not met.
Study A7471009 is a randomized double-blind Phase 3 trial of dacomitinib versus erlotinib
in advanced NSCLC patients following progression after, or intolerance to, at least one (and
no more than two) prior chemotherapies.  Two co-primary populations were explored in this 
study: all patients with advanced NSCLC and NSCLC patients confirmed to be KRAS
(Kirsten rat sarcoma viral oncogene homolog) wild-type. Patients were stratified by 
histology (adenocarcinoma versus non-adenocarcinoma), race (Asian versus non-Asian and 
Indian subcontinent race), ECOG (Eastern Cooperative Oncology Group) performance status 
(PS) (0-1 versus 2), and smoking status (never smoker, defined as 100 cigarettes, cigar or 
pipe lifetime versus ever smoker) at randomization.  Enrollment was completed in this study 
with 878 patients randomized. There were 872 patients treated in this trial; 436 patients 
received dacomitinib, and 436 patients received erlotinib.  Three patients randomized to 
dacomitinib and 3 patients randomized to erlotinib were not treated. Currently, there are 
24 patients still receiving active treatment, and 93 patients are in long-term survival
follow-up. Based on the CSR data cutoff as of 30 September 2013, the study did not
demonstrate statistically improved progression-free survival (PFS) per independent review in 
the co-primary populations, and thus the primary objective was not met.
Study A7471050 is a randomized, open-label, Phase 3 study comparing the efficacy and 
safety of first-line treatment with dacomitinib to treatment with gefitinib in patients with 
Stage IIIB/IV NSCLC conducted in collaboration with SFJ Pharmaceuticals. All patients 
will have tumors that test positive for one EGFR activating mutation (deletion 19 or L858R),
and all tumors will have histology consistent with adenocarcinoma or its pathologically 


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accepted variants. Approximately 440 patients will be randomized (1:1) to one of two 
treatment arms. This study is being conducted in China, Hong Kong, Italy, Japan, Poland,
and Spain.  At the time of the IB cutoff date, there were 130 patients randomized and treated 
in this study (66 patients randomized to dacomitinib and 64 patients randomized to gefitinib).
1.3. Background and Rationale
Dacomitinib is being developed globally in locally advanced or metastatic NSCLC after at 
least one prior chemotherapy regimen.  In the course of development, Phase 2 and 3 studies 
are being conducted in several NSCLC treatment settings: 

After failure of prior chemotherapy and EGFR directed treatment [refractory setting];

After one or two prior systemic therapies [2nd/3rd line]; and 

In selected patients who have had no prior therapy for advanced disease. 
Indications of activity have been seen in a number of dacomitinib clinical trials.  This 
protocol permits continued access to dacomitinib for patients who participated in other 
dacomitinib monotherapy treatment protocols and have the potential to derive clinical benefit
without unacceptable toxicity from continued dacomitinib treatment.  This treatment access 
protocol is only open to patients in Japan.
Patients will follow a schedule of visits and data collection that permits continued safety 
monitoring.
Complete information for this compound may be found in the SRSD.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Primary Objective

To allow access to dacomitinib for patients who received dacomitinib on a prior study 
in Japan and who have the potential to derive continued clinical benefit from 
single-agent dacomitinib treatment without unacceptable toxicity based upon the 
investigator’s judgment.
2.1.2. Secondary Objective

To monitor the specific long-term safety and tolerability of single-agent dacomitinib 
in patients who have already received dacomitinib on a prior study in Japan.
2.2. Endpoints

Adverse events as assessed by NCI Common Terminology Criteria for Adverse 
Events version 4.0 (NCI CTCAE.v4.0). 


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3. STUDY DESIGN
This is a multi-center, open-label, treatment extension study open in Japan only. Eligible 
patients include those with advanced cancer who received and tolerated single-agent 
dacomitinib in a prior clinical study and have the potential to derive continued clinical 
benefit based on investigator judgment.  Patients enrolled in this extension study may 
continue to receive dacomitinib starting at the current dose level in the prior study. Dose 
reductions and re-escalations are allowed based on tolerability. Patients may continue to be 
treated with dacomitinib on this protocol as long as there is evidence of clinical benefit in the 
judgment of the investigator. Adverse events will be graded according to NCI CTCAE v4.0,
and monitored according to the frequency outlined in the Safety Review Plan.
4. PATIENT SELECTION
This study can fulfill its objectives only if appropriate patients are enrolled.  The following 
eligibility criteria are designed to select patients for whom protocol treatment is considered 
appropriate.  All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular patient.
4.1. Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Received dacomitinib on another clinical trial in Japan and judged by the investigator
to be deriving ongoing clinical benefit.
2. No ongoing NCI CTCAE Grade 3 or intolerable Grade 2 adverse events related to 
dacomitinib treatment on the prior study.
3. Evidence of a personally signed and dated informed consent document indicating that 
the patient (or a legally acceptable representative) has been informed of all pertinent 
aspects of the study.
4. Patients who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures.
5. Male and female patients of childbearing potential and at risk for pregnancy must 
agree to continue to use a highly effective method of contraception throughout the 
study and for at least 90 days after the last dose of assigned treatment. 


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4.2. Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Patients who meet one or more study withdrawal criteria on the prior study using 
dacomitinib in Japan.
2. Participation in other studies involving other investigational drug(s) (Phases 1-4) 
when treatment in the current study begins and/or during study participation.
3. Patients who are investigational site staff members directly involved in the conduct of 
the study and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of 
the study.
4. Other severe acute or chronic medical or psychiatric condition [including recent 
(within the past year) or active suicidal ideation or behavior] or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in the judgment of the investigator, would make the patient
inappropriate for entry into this study.
5. Pregnant female patients; breastfeeding female patients; male and female patients of 
childbearing potential who are unwilling or unable to use a highly effective method of 
contraception as outlined in this protocol for the duration of the study and for 90 days 
after the last dose of investigational product.
4.3. Registration Criteria 
The Sponsor must approve the enrollment of each patient.  Patients will be registered into the 
study provided that they have satisfied all patient selection criteria and have withdrawn from
their original dacomitinib clinical study prior to enrollment in this study.
4.4. Lifestyle Guidelines
All male and female patients who, in the opinion of the investigator, are biologically capable 
of having children and are sexually active must agree to use a highly effective method of 
contraception consistently and correctly for the duration of the active treatment period and 
for at least 90 days after the last dose of investigational product.  The investigator or his/her 
designee, in consultation with the patient, will confirm the patient has selected the most 
appropriate method of contraception for the individual patient from the permitted list of 
contraception methods (see below) and instruct the patient in its consistent and correct use.  
Patients need to affirm that they meet at least one of the selected methods of contraception.  
The investigator or his/her designee will discuss with the patient the need to use highly 
effective contraception consistently and correctly according to the schedule of activities and 
document such conversation in the patient’s chart.  In addition, the investigator or his/her 
designee will instruct the patient to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected. 


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Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of oral, inserted, injected, or implanted hormonal methods of 
contraception is allowed provided the patient plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
or suppository). For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Male sterilization with absence of sperm in the postvasectomy ejaculate.
5. Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
Patients should avoid extended unprotected exposure to sunlight (eg, sunbathing) or tanning 
for the duration of the study period.
4.5. Sponsor’s Qualified Medical Personnel
The contact information for the Sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, patients are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, patient study numbers, 
contact information for the investigational site, and contact details for a help desk in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
patient’s participation in the study. The help desk number can also be used by investigational 
staff if they are seeking advice on medical questions or problems; however, it should only be 
used in the event that the established communication pathways between the investigational 
site and the study team are not available. It is, therefore, intended to augment, but not 
replace, the established communication pathways between the investigational site and the 
study team for advice on medical questions or problems that may arise during the study. The 
help desk number is not intended for use by the patient directly, and if a patient calls that 
number, he or she will be directed back to the investigational site.


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5. STUDY TREATMENTS
5.1. Allocation to Treatment
This is an open-label trial.  The starting dose of dacomitinib will be the same as the last dose 
the patient received in the original study. 
Treatment will be administered orally in continuous fashion.  For purposes of scheduling 
visits and assessments, cycles of 4 weeks (28 days) in length will be defined.
5.2. Patient Compliance
There are no compliance criteria that are pre-specified for inclusion in analyses of study 
endpoints.  The patients will bring unused study drug and empty containers to each study 
visit.  The number of tablets will be counted and if more or less than expected, patients will 
be asked to account for missed doses.  The investigator and site study team will also evaluate 
patient compliance with the study regimen.  Potential reasons for non-compliance dosing 
(ie, AEs, lost medication) will be followed up by the study site personnel and strategies to 
improve dosing compliance will be explored.
5.3. Drug Supplies
Pfizer Global Research and Development will supply dacomitinib (PF-00299804) tablets.
5.3.1. Dosage Form(s) and Packaging
Dacomitinib will be provided as tablets for oral administration.  The 45 mg, 30 mg, or 15 mg 
tablets will be supplied in High Density PolyEthylene (HDPE) bottles for oral administration.  
The bottles will be properly labeled according to local regulatory requirements. 
5.3.2. Preparation and Dispensing
Dispensing will be in bottles provided in quantities appropriate for the study visit schedule.  
The patient should be instructed to maintain the product in the bottle provided throughout the 
course of dosing. 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
them and to the environment should undertake the preparation, handling, and safe disposal of 
chemotherapeutic agents.
5.4. Administration
Patients will self-administer dacomitinib at their ending dose schedule from the prior study 
until they experience unacceptable toxicity, tumor progression, or death.  Patients will 
swallow the study medication whole, and will not manipulate or chew the medication prior to 
swallowing.  The tablets will be taken with at least 6 oz. (180 mL) of water on an empty 
stomach (defined as less than 500 calories within 2 hours before or after intake of study 
medication). 


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Patients must be instructed that if they miss a day’s dose, they must not make up missed 
doses on following days, but simply resume the dosing schedule.  Likewise, patients must be 
instructed that if they vomit at any time after taking a dose, they must not “make it up” with 
an extra dose the same day, but resume subsequent dose the next day as prescribed.  Any 
missed or vomited doses must be indicated in the source documents and Case Report Form 
(CRF), just as all administered doses are documented.
5.5. Dose Modification
Dacomitinib will be available at 3 dose strengths, 45 mg, 30 mg, and 15 mg once daily. 
Table 2 outlines dose modifications that will apply to patients order to manage 
treatment-related toxicity that is not controlled by optimal supportive care, or not tolerated 
due to symptomatology or interference with normal daily activities regardless of severity. 
Table 2.
Doses of Study Drug Administered
Dose level
Dacomitinib
Level 0
45 mg
Level -1
30 mg
Level -2
15 mg
Dose reductions may take place whenever toxicity that is not controlled with optimal 
supportive care is noted during the trial. If a patient subsequently tolerates therapy well in 
the judgment of the investigator, resumption of the next higher dose level may be undertaken.
If a patient still cannot tolerate treatment after a dose reduction to the lowest dose of 15 mg, 
treatment will be discontinued.  If a patient is responding to dacomitinib but is requiring a 
dose modification below 15 mg, the investigator must discuss the situation with the 
Sponsor’s Medical Monitor.
For Grade 3, Grade 4, or intolerable Grade 2 toxicity, treatment will be interrupted. Upon 
recovery to Grade 2 or baseline, and per the clinical judgment of the investigator and 
agreement of the patient, the treatment will be resumed:

For treatment interruption due to Grade 3 or intolerable Grade 2 toxicity, treatment 
may be resumed at the same or a lower dose level;

For episodes of Grade 4 toxicity, reduction to the next lowest dose level is mandated.
If the patient fails to recover within 2 weeks of discontinuation, treatment will be 
discontinued unless there is discussion of the clinical circumstance with the Sponsor and 
agreement that the patient may resume treatment after a lapse of greater than 2 weeks.  The
patient will undergo end of treatment evaluations and follow-up visit as per Schedule of 
Activities.


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5.6. Adverse Event Management
Specific guidance which has been developed for the management of common EGFR tyrosine 
kinase inhibitor toxicity at various grades is provided in Appendix 1.  In general (and not as 
substitute for consideration of the more specific guidance in Appendix 1):
For diarrhea, patients should begin therapy with loperamide at first evidence of increased 
frequency of bowel movement with adjustment in dose or prescription of alternative 
medication when necessary.  The potential need for increased oral hydration (including 
electrolyte-containing fluids) should also be evaluated. There is a risk of pre-renal azotemia 
noted from poor fluid intake in the face of diarrhea and/or stomatitis.  Monitor renal function 
tests and consider supplemental IV hydration if necessary. 
For prevention of dry skin, patients should begin a regimen of moisturizers prior (ideal) or 
with start of dosing, and use appropriate measures to prevent excessive sun exposure.
Treatment of acneiform rash may include topical steroids, topical antibiotics, and oral 
antibiotics. 
Mucositis can be treated with antibiotic-free oral rinse; chlorhexidine should be avoided.
Other measures may be utilized per the investigator judgment or emerging data-driven 
guidelines where these are available
5.7. Drug Storage
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including any comparative agents and/or marketed products are 
stored in a secured area with controlled access under recommended storage conditions and in 
accordance with applicable regulatory requirements.
Investigational product should be stored in its original container and in accordance with the 
drug label.  See the Dosage and Administration Instructions (DAI) for storage conditions of 
the product.
Storage conditions stated in the SRSD will be superseded by the storage conditions stated in 
the labeling.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout study.  Even for 
continuous monitoring systems, a log or site procedure which ensures active daily evaluation 
for excursions should be available.  The operation of the temperature monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order. 


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Any excursions from the product label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to labeled storage 
conditions, as soon as possible.  Deviations from the storage requirements, including any 
actions taken, must be documented and reported to the Sponsor. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until the Sponsor provides documentation of permission to use the investigational product.  
Specific details regarding information the site should report for each excursion will be 
provided to the site. 
Site staff will instruct patients on the storage requirements for take home medications 
including how to report temperature excursions. 
The Investigational Product Manual should be referenced for any additional guidance on 
storage conditions and actions to be taken when conditions are outside the specified range.
5.8. Drug Accountability 
The investigator’s site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the drug supplies.  The sponsor or designee will provide guidance on the 
destruction of unused investigational product (eg, at the site).
5.9. Concomitant Treatment(s)
Anticancer therapy with agents other than dacomitinib is not allowed. 
5.9.1. CYP2D6 Substrates 
The use of drugs that are highly dependent on CYP2D6 for metabolism requires 
consideration of both the therapeutic index and the degree of CYP2D6 metabolism.  
Substitution within the therapeutic class is recommended if possible, otherwise the directions 
below should be followed.

Drugs dependent on CYP2D6 metabolism with narrow therapeutic index are 
prohibited: eg, procainamide, pimozide and thioridazine.

Administration of drugs which are highly dependent on CYP2D6 metabolism: dose 
reduction should be based on substrate sensitivity to CYP2D6 metabolism.  As a
guidance, a starting dose reduction of 75% (25% of the dose given without 
co-administration with dacomitinib) and close clinical monitoring is required. 

For drugs that are partly dependent on CYP2D6-mediated metabolism, there is a high 
likelihood of supra-therapeutic exposure in combination with dacomitinib.  No dose 
reduction is required when starting dacomitinib but clinical monitoring is required 
and, based on patient response, dose-reduction may be necessary.


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
Pro-drugs, or drugs with highly active metabolites such as codeine and tramadol 
should be replaced by an alternative within the therapeutic class as conversion to the 
pharmacologically active moiety is CYP2D6 metabolism-dependent and their 
exposure with the co-administration of dacomitinib may be sub-therapeutic.  Opiates 
such as morphine, hydromorphone, oxymorphone and oxycodone can be used as 
substitutes to replace codeine or tramadol for analgesia.
Appendix 2 provides a comprehensive list of CYP2D6 substrates coded according to the 
therapeutic index and the degree of CYP2D6 metabolism.  This is not an all-inclusive list.  If 
there is uncertainty whether a concomitant medication is contraindicated, the Investigator 
should contact the Sponsor study team.
5.9.2. P-glycoprotein
Concurrent administration of drugs which are P-glycoprotein (P-gp) substrates and have a 
narrow therapeutic index should be monitored for exaggerated effect and/or toxicities.
5.9.3. Strong Amines
Lidocaine exposures may significantly increase in the presence of strong amines, such as 
dacomitinib.  Lidocaine may be used systemically but clinical monitoring (including 
telemetry) is recommended.
5.10. Supportive Care
Patients may receive ongoing supportive and palliative care (eg, pain control) as clinically 
indicated throughout the study.
Patients who are receiving bisphosphonates at study entry may continue bisphosphonates 
while on study.  However, the initiation of bisphosphonate therapy after enrollment will be 
considered progression of disease unless otherwise agreed by the investigator in consultation 
with the Sponsor.
6. STUDY PROCEDURES 
Informed Consent: All patients being considered for this study must sign an informed 
consent document prior to any study-related procedures that are not considered to be standard 
of care and prior to receiving study drug.
Registration: The site staff will fax/e-mail a complete Registration Form to the designated 
Sponsor study team member.  The Sponsor will assign a patient identification number, which 
will be used on all CRF pages and other study-related documentation or correspondence 
referencing that patient and fax/e-mail to the site.
Assessments for screening and all other study time points are detailed in the
Table 1 (Schedule of Activities). 


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6.1. Patient Withdrawal
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or Sponsor for safety or behavioral 
reasons, or the inability of the patient to comply with the protocol-required schedule of study 
visits or procedures at a given study site. Reasons for withdrawal include, but are not limited 
to the following:

Progressive disease;

Unacceptable toxicity;

Global deterioration of health-related symptoms;

Study non-compliance;

Pregnancy;

Patient request;

Lost to Follow-Up;

Study termination by Sponsor.
If a patient requires more than 2 consecutive weeks of dosing interruption, a discussion 
should be held with the Sponsor to determine whether or not to withdraw the patient from the 
study.
If a patient does not return for a scheduled visit, every effort should be made to contact the 
patient.  All attempts to contact the patient and information received during contact attempts 
must be documented in the patient’s medical record.  In any circumstance, every effort 
should be made to document patient outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request the patient to return all unused investigational 
product(s), request the patient to return for a final visit, if applicable, and follow up with the 
patient 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 before such 
withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the patient. When a protocol-required test cannot be performed, the 


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investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely fashion.
7.1. Pregnancy Testing
For female patient of childbearing potential, a serum or urine pregnancy test, with sensitivity 
of at least 25 mIU/mL, will be performed at screening, before investigational product 
administration at the baseline visit, and at the end of treatment visit.  A negative pregnancy 
result is required before the patient may receive the investigational product.  Pregnancy tests 
will also be done whenever 1 menstrual cycle is missed during the active treatment period (or 
when potential pregnancy is otherwise suspected), and at the end of the study to confirm the 
patient has not become pregnant during the study. Pregnancy tests may also be repeated as 
per request of institutional review boards (IRBs)/ethics committees (ECs) or if required by 
local regulations. 
In the case of a positive confirmed pregnancy, the patient will be withdrawn from study 
medication and from the study. 
7.2. Baseline Demographics
Demographic data will include date of birth and gender.  The patient’s prior dacomitinib
study number and prior patient ID number will be noted on the CRF.
7.3. Patient History
The patients’ prior history will include their cancer history, medical history and dates of the 
first and most recent dacomitinib administration.
7.4. Laboratories
Laboratory assessments (eg, hematology, blood chemistry, and urinalysis) are to be 
performed according to local standard clinical practice and results should be documented in 
the patient’s clinic chart, but will not need to be reported on the CRF.  The interval for 
laboratory assessments should not be longer than 8 weeks.
7.5. Tumor Assessments
Tumor assessments while the patient is receiving study treatment will be performed
according to each site’s standard-of-care imaging modality and clinical practice.  The results 
should be documented in the patient’s clinic chart but will not need to be reported on the 
CRF. The interval for monitoring disease status and for progression of disease should not be 
longer than 6 months.


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8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a 
serious adverse event (SAE) requiring immediate notification to Pfizer or its designated 
representative.  For all AEs, sufficient information should be obtained by the investigator to 
determine the causality of the AE.  The investigator is required to assess causality.  
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the patient provides informed consent, which is obtained prior to the patient’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product.  SAEs occurring to a patient after the active 
reporting period has ended should be reported to the sponsor if the investigator becomes 
aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the sponsor.
AEs (serious and non-serious) should be recorded on the CRF from the time the patient has 
taken at least 1 dose of study treatment through the last patient visit.
If a patient begins a new anticancer therapy, the AE reporting period for non-serious AEs
ends at the time the new treatment is started.  Death must be reported if it occurs during the 
SAE reporting period after the last dose of investigational product, irrespective of any 
intervening treatment.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation patient administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to: 

Abnormal test findings;


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
Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure;
Worsening of signs and symptoms of the malignancy under study should be reported as AEs 
in the appropriate section of the CRF.  Disease progression assessed by measurement of 
malignant lesions on radiographs or other methods should not be reported as AEs.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong drug, by the wrong patient, at the wrong time, or at the wrong dosage strength.  Such 
medication errors occurring to a study participant are to be captured on the medication error
CRF which is a specific version of the AE page, and on the SAE form when appropriate.  In 
the event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving patient exposure to the investigational product;


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
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating patient.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error should be captured on the medication error version of the 
AE page and, if applicable, any associated AE(s) are captured on an AE CRF page.
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing (outside of protocol-stipulated dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Serious Adverse Events
An SAE is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Progression of the malignancy under study (including signs and symptoms of progression) 
should not be reported as an SAE unless the outcome is fatal within the safety reporting 
period. Hospitalization due to signs and symptoms of disease progression should not be 
reported as an SAE. If the malignancy has a fatal outcome during the study or within the 
safety reporting period, then the event leading to death must be recorded as an AE and as an


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SAE with Common Terminology Criteria (CTC) Grade 5 (see section on Severity 
Assessment).
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other AE outcomes the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.6.1. Protocol-Specified Serious Adverse Events 
Unless the investigator believes that there is a causal relationship between study drug and an 
event specified below, these events should not be reported by the investigator as SAEs as 
described in the Serious Adverse Event Reporting Requirements section on this protocol. 
These events are anticipated to occur commonly in a population with advanced NSCLC.  
However, these events should still be captured as AEs in the CRF.
Protocol-specified events that will not normally be reported in an expedited manner: 

Pulmonary embolism;

Deep vein thrombosis (DVT);

Pneumonia;

Dyspnea;

Respiratory distress or failure.
Should an aggregate analysis indicate that these prespecified events occur more frequently 
than expected based on the expectation of frequency of the event(s) in question in the 
population for comparison, eg, based on epidemiology data, literature, or other data, then this 
will be submitted and reported in accordance with Pfizer’s safety reporting requirements.  
Aggregate analysis of safety data will be performed on a regular basis per internal standard 
operating procedures. 
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate transaminase (AST) and/or alanine transaminase (ALT) levels 
concurrent with abnormal elevations in total bilirubin level that meet the criteria outlined 
below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s Law cases) and should always be considered 
important medical events. 


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The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the patient’s individual baseline values and underlying conditions.  Patients who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Patients with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin value 2 X ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 X ULN or not available;

For patients with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above:

For patients with preexisting AST or ALT baseline values above the normal 
range: AST or ALT values 2 times the baseline values and 3 X ULN, or 
8 X ULN (whichever is smaller).
Concurrent with

For patients with preexisting values of total bilirubin above the normal range: 
Total bilirubin level increased from baseline by an amount of at least 1 X ULN or
if the value reaches 3 X ULN (whichever is smaller).
The patient should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered. 
In addition to repeating measurements of AST and ALT, laboratory tests should include 
albumin, creatinine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl 
transferase, prothrombin time (PT)/ international normalized ratio (INR), and alkaline 
phosphatase.  A detailed history, including relevant information, such as review of ethanol, 
acetaminophen, recreational drug and supplement consumption, family history, occupational 
exposure, sexual history, travel history, history of contact with a jaundiced person, surgery, 
blood transfusion, history of liver or allergic disease, and work exposure, should be collected.  
Further testing for acute hepatitis A, B, or C infection and liver imaging (eg, biliary tract) 
may be warranted.  All cases confirmed on repeat testing as meeting the laboratory criteria 
defined above, with no other cause for liver function test (LFT) abnormalities identified at 
the time, should be considered potential Hy’s Law cases irrespective of availability of all the 
results of the investigations performed to determine etiology of the abnormal LFTs.  Such 
potential Hy’s Law cases should be reported as SAEs.
8.7. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation to an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 


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wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of persistent pre-treatment laboratory abnormality);

Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 


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that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.8. Severity Assessment
GRADE
Clinical Description of Severity
0
No change from normal or reference range (This grade is not included in the 
Version 4.0 CTC document but may be used in certain circumstances.)
1
MILD adverse event
2
MODERATE adverse event
3
SEVERE adverse event
4
LIFE-THREATENING consequences; urgent intervention indicated
5
DEATH RELATED TO adverse event
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the patient's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see section on Reporting Requirements).  If the 
investigator's causality assessment is "unknown but not related to investigational product," 
this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.


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8.10. Exposure During Pregnancy
For investigational products and for marketed products, an exposure during pregnancy occurs 
if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes, or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male patient has been exposed (eg, because of treatment or environmental
exposure) to the investigational product prior to or around the time of conception 
and/or is exposed during his partner’s pregnancy.
If a study patient or study patient’s partner becomes or is found to be pregnant during the 
study patient’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on a SAE Report Form and Exposure During 
Pregnancy (EDP) supplemental form, regardless of whether an SAE has occurred.  In 
addition, the investigator must submit information regarding environmental exposure to a 
Pfizer product in a pregnant woman (eg, a patient reports that she is pregnant and has been 
exposed to a cytotoxic product by inhalation or spillage) using the EDP supplemental form.  
This must be done irrespective of whether an AE has occurred and within 24 hours of 
awareness of the exposure. The information submitted should include the anticipated date of 
delivery (see below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion or until pregnancy termination) and notify Pfizer of the outcome as a follow-up to 
the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;


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
Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to investigational product.
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg, follow-up on preterm infants to identify developmental delays). In the case of paternal 
exposure, the investigator will provide the study patient with the Pregnant Partner Release of 
Information Form to deliver to his partner. The investigator must document in the source 
documents that the patient was given the Pregnant Partner Release of Information Form to 
provide to his partner.
8.11. Occupational Exposure
An occupational exposure occurs when during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an adverse event.
An occupational exposure is reported to safety within 24 hours of Investigator’s awareness, 
using the SAE Report form, regardless of whether there is an associated AE/SAE. Since the 
information does not pertain to a patient enrolled in the study, the information is not reported 
on a CRF, however a copy of the completed SAE Report form is maintained in the study 
master file.
8.12. Withdrawal Due to Adverse Events (Also See Section 6.1)
Withdrawal due to AE should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.
When a patient withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.13. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study patient.  In addition, each study patient will be questioned about AEs.
8.14. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.14.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.


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As noted in the Protocol-Specified Serious Adverse Events section, should an investigator 
judge one of the identified protocol-specified SAE to have a causal relationship with the 
investigational product the investigator must report the event to the sponsor within 24 hours 
of investigator awareness, even if that event is a component of the endpoint.
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This time frame also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of exposure during pregnancy, exposure via 
breastfeeding and occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Non-Serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.14.3. Sponsor Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
9.1. Sample Size Determination
Due to the nature of this study, the number of patients to be enrolled is not predetermined.
9.2. Efficacy Analysis
Efficacy will not be analyzed in this protocol.


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9.3. Analysis of Other Endpoints
Only descriptive summaries of safety will be provided, and no inferential analysis is planned.
Demographic characteristics such as age, gender, and race will be tabulated.  The number of 
patients treated and the number of patients who withdrew from the study, as well as reasons 
for discontinuation, will be summarized.
Study drug administration will be summarized for all patients who received at least one dose 
of study medication. 
9.4. Safety Analysis
The as-treated population will be the primary population for evaluating safety.
The as-treated population will include all patients who receive any study medication and will 
be included in the summaries and listings of safety data.  Overall safety profile and toleration 
of dacomitinib will be characterized by type, frequency, severity (as graded by version 4.0 of 
the NCI CTCAE), timing and relationship of study therapy of adverse events.
9.5. Data Monitoring Committee 
This study will not use a data monitoring committee.
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors 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)/ethics 
committee (EC), 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.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term 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 patient.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 


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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 are true. Any corrections to entries made in the CRFs or 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 hospital's or the physician's patient 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.
11.2. 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 patients (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to International Conference on Harmonisation 
(ICH), according to local regulations, or as specified in the clinical study agreement (CSA), 
whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, 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 an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.


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12. ETHICS
12.1. Institutional Review Board (IRB)/Ethics Committee (EC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. 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 GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
12.3. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data is compiled for transfer to Pfizer and other authorized parties, patient
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study patients. The study 
site will maintain a confidential list of patients who participated in the study linking their 
numerical code to the patient’s actual identity.  In case of data transfer, Pfizer will maintain 
high standards of confidentiality and protection of patient personal data consistent with 
applicable privacy laws.
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB/EC before use, and available for inspection.
The investigator must ensure that each study patient, or his or her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. 


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Whenever consent is obtained from a patient’s legally acceptable representative, the patient’s 
assent (affirmative agreement) must subsequently be obtained when the patient has the 
capacity to provide assent, as determined by the IRB/EC.  If the investigator determines that 
a patient’s decisional capacity is so limited he/she cannot reasonably be consulted, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, then 
the patient’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study patient does not provide his/her own consent, the source documents
must record why the patient did not provide consent (eg, minor, decision impaired adult), 
how the investigator determined that the person signing the consent was the patient’s legally 
acceptable representative, the consent signer’s relationship to the study patient (eg, parent, 
spouse) and that the patient’s assent was obtained, or waived.  If assent is obtained verbally it 
must be documented in the source documents.
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 document.
12.4. Patient Recruitment
Patient recruitment efforts are not required for this study because this study is open to 
patients previously treated on other dacomitinib trials.
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial 
End of Trial is defined as Last Subject Last Visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of dacomitinib at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating patients and 
the hospital pharmacy (if applicable) within a time period set by Pfizer.  As directed by 


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Pfizer, all study materials must be collected and all CRFs completed to the greatest extent 
possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), www.pfizer.com, and/or the 
European Clinical Trials Database (EudraCT), and other public registries in accordance with 
applicable local laws/regulations. 
www.clinicaltrials.gov
Pfizer posts clinical trial Basic Results on www.clinicaltrials.gov for all Pfizer-sponsored 
interventional studies that evaluate the safety and/or efficacy of a Pfizer product.
The timing of the posting depends on whether the Pfizer product is approved for marketing in 
any country at the time the study is completed:

For studies involving products applicable under the US Food and Drug 
Administration Amendments Act of 2007 (FDAAA), ie, Food and Drug 
Administration (FDA)-approved products, Pfizer posts results within 1 year of the 
primary completion date (PCD).  For studies involving products approved in any 
country, but not FDA approved, Pfizer posts results 1 year from LSLV;

For studies involving products that are not yet approved in any country, Pfizer posts 
the results of already-completed studies within 30 days of US regulatory approval, or 
1 year after the first ex-US regulatory approval of the product (if only submitted for 
approval ex-US);

For studies involving products whose drug development is discontinued before 
approval, Pfizer posts the results within 1 year of discontinuation of the program (if 
there are no plans for out licensing, or within 2 years if out licensing plans have not 
completed).
Primary completion date is defined as the date that the final patient was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical study concluded according to the prespecified protocol or was 
terminated.
www.pfizer.com
Pfizer posts clinical trial results on www.pfizer.com for all Pfizer-sponsored interventional 
studies in patients that assess the safety and/or efficacy of an FDA-approved Pfizer product 
with a LSLV on or after 27-Sep-2007 for which Basic Results were posted on 
www.clinicaltrials.gov.


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EudraCT
Pfizer posts clinical trial results on EudraCT in accordance with Commission Guideline 
2012/C 302/03 Guidance on posting and publication of result-related information on clinical 
trials in relation to the implementation of Article 57(2) of Regulation (EC) No 726/2004 and 
Article 41(2) of Regulation (EC) No 1901/2006 for studies with centers in the European 
Economic Area and with LSLV on or after 01-May-2004, regardless of the marketing status 
of the compound.
15.2. Publications by Investigators
Pfizer has no objection to publication by an investigator of any information collected or 
generated by the investigator, whether or not the results are favorable to the investigational 
drug. However, to ensure against inadvertent disclosure of confidential information or 
unprotected inventions, the investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure before it is submitted or otherwise disclosed.
The investigator 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 30 days before they are submitted for publication or otherwise disclosed. If any patent 
action is required to protect intellectual property rights, the investigator agrees to delay the 
disclosure for a period not to exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information (other than the study results themselves) before disclosure.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all centers. However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the study at all 
participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution 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.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.


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16. REFERENCES
NA


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17. APPENDICES
Appendix 1. Adverse Event Management Guidelines 
In all instances, it is recommended that patients be instructed at time of starting drug therapy 
to call the Investigator/Site if no improvement in symptoms has been observed after 24 hours 
of patient taking the recommended/optimal pharmacologic treatment.
Abbreviations:
BSA: Body Surface Area
ADL: Activities of Daily Living 
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications and not bedridden (definitions per NCI CTCAE v4.0).
GABA: Gamma-Aminobutyric Acid
DIARRHEA

Patients should be encouraged to drink 8 to 10 large glasses of clear liquids per day 
while on study in order to maintain adequate hydration;

General dietary measures to limit impact of diarrhea could include:

Stop all lactose-containing products in patients with evidence of lactose 
intolerance;

Eat frequent small meals if experiencing increased frequency of stools;

Consider low-fat regimen enriched with bananas, rice, applesauce, and toast.


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Diarrhea Management Guideline
Grade of Event
Management/Next Dose
Grade 1: increase of <4 stools per day over 
baseline;
Loperamide 4 mg at the first onset of diarrhea and then 2 mg every 
2 hours until the patient is diarrhea-free for at least 12 hours. 
(During the night the patient may take 4mg of loperamide every 
4 hours).
Fluid intake of at least 2 liter (L) should be maintained to avoid 
dehydration: patients are to drink 8-10 large glasses of clear liquids. 
Consideration for maintenance of electrolyte balance would include 
electrolyte-containing drinks, broth, clear juices. 
Study Treatment: should be continued at same dose.
Grade 2: increase of 4-6 stools per day 
over baseline;
Loperamide as above, or consider use of diphenoxylate 
hydrochloride and atropine sulfate formula (eg Lomotil, Diarced, 
Co-Phenotroope) at standard doses.
Fluid intake of at least 2 L should be maintained to avoid 
dehydration. 
Monitor patient closely and consider intravenous hydration. 
Study Treatment: If not improved to Grade <1 within 24 hrs despite 
use of loperamide, hold treatment until Grade 1.  If diarrhea 
of Grade >1 recurs after initial improvement, consider reduction of 
1 dose level. 
Grade 3: increase of 7 stools per day over 
baseline; or incontinence; or limiting self 
care ADL: or hospitalization indicated
Oral therapy with diphenoxylate hydrochloride and atropine sulfate 
formula, or tincture of opium. 
Fluid intake of at least 2 L should be maintained, intravenously if 
necessary. 
Consider use of octreotide (Sandostatin) 100-150 microgram (g)
subcutaneously twice daily with escalation to 500 g three times 
daily.
Consider hospitalization if does not improve to Grade 2 within 
24 hours, or in presence of fever, abdominal pain,etc.
Study Treatment: Hold therapy.  Upon resolution to Grade 1, 
resume therapy with consideration of reduction of one dose level
Grade 4: life-threatening 
Maximal inpatient fluid and nutritional support, antibiotics as 
indicated in judgment of investigator for fever, leucocytosis, marked 
dehydration, etc.
Study Treatment: Hold until Grade 1. Mandatory dose reduction 
of one dose level


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DERMATOLOGIC TOXICITY
Acneiform/ Papulopustular Rash:
Acneiform/ Papulopustular Rash 
Management Guideline
Grade 1:
<10% body surface area (BSA) papules and/or 
pustules (with or without symptoms of pruritis 
or tenderness)
Topical steroids *
And
Topical antibiotic bid (clindamycin 1 - 2%,
erythromycin 1% - 2%, metronidazole 1%)
Grade 2:
10 to 30% BSA papules and/or pustules (with or 
without symptoms of pruritis or tenderness), or 
psychosocial impact, or limited instrumental 
ADL
Oral antibiotic for at least 4 weeks
(doxycycline 100 mg bd, minocycline 
100 mg bd or oxytetracycline 500 mg bd);
Stop topical antibiotic if being used
And
Topical steroids *
Grade 3:
>30% BSA papules and / or pustules (with or 
without symptoms of pruritis or tenderness); or

limiting self-care ADL: or

associated with local superinfection with 
oral antibiotics indicated
Oral antibiotic for 4 weeks 
(doxycycline 100 mg bd, minocycline 
100 mg bd or oxytetracycline 500 mg bd)
If infection suspected (yellow crusts, purulent 
discharge, painful skin/nares):
switch oral antibiotic to broad spectrum/gram 
negative cover for at least 10 days
consider skin swab for bacterial culture, 
And
Topical steroids (continue)*
Consider dermatology consultation
* Moderate/Low strength steroids include: 
Triamcinolone acetonide 0.025% 
Desonide 0.05%
Alclometasone 0.05% cream


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Fluticasone propionate 0.05% 
For patients intolerant or allergic to tetracycline 
antibiotics, use an antibiotic with 
Staphloccoccus coverage (eg, cephalexin, 
sulfamethoxazole/ trimethoprim)
Dry Skin/Xerosis:
Prophylaxis against dry skin would include:

Initiation of skin moisturizing cream or ointment regimen upon establishment of 
eligibility (ie, prior to first dose) (avoid skin lotions, as they may contain alcohol);

Avoidance of excessive exposure to hot water during showering/bathing;

Avoidance of household tasks involving immersion in hot water/ detergent/solvents;

Avoidance of excessive sun exposure/tanning.  Use sunscreen containing zinc oxide 
or titanium dioxide with SPF at least 30:  apply every two hours when exposed to sun.
Xerosis/ Dry Skin Management Guideline
Grade 1:
<10% BSA and no
associated erythema or pruritis
Over-the-counter Moisturizing cream or ointment to 
face bid 
AND
Ammonium lactate 12% (or equivalent) cream to 
body bid
Grade 2:
10 to 30% BSA and associated with erythema or 
pruritis; or
limited instrumental ADL
OTC Moisturizing cream or ointment to face bid; 
AND
Ammonium lactate 12% cream OR salicylic acid 6% 
cream to body bid
Grade 3
>30% BSA and associated with pruritis; or
limiting self-care ADL
OTC Moisturizing cream or ointment to face bid; 
AND
Ammonium lactate 12% cream OR salicylic acid 6% 
cream to body bid 
AND
Topical steroid* to eczematous areas bid
*Moderate/Low strength steroid include:
Triamcinolone acetonide 0.025% (Aristocort A 
cream) 
Desonide 0.05% (DesOwen cream, lotion) 
Alclometasone 0.05% cream (Allocate cream)
Fluticasone propionate 0.05% 


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Paronychia:
Miminization of periungal trauma and superinfection is advised:

Wearing comfortable shoes, 

trimming nails but avoiding aggressive manicuring, 

wearing gloves while cleaning (eg, household, dishes).
Paronychia Management Guideline
Grade 1
Nail fold edema or erythema; or
disruption of the cuticle
Topical Antibiotics and vinegar soaks *
Grade 2
Localized intervention indicated; or oral intervention 
indicated (eg, antibiotic, antifungal, antiviral); or nail 
fold edema or erythema with pain; or associated with 
discharge or nail plate separation; or limiting 
instrumental ADL
Topical antibiotics and vinegar soaks*
Apply silver nitrate weekly
Grade 3
Surgical intervention,  or IV antibiotics indicated; or 
limiting self-care ADL
Topical antibiotics and vinegar soaks*
Apply silver nitrate weekly
Surgical consultation as needed
*Topical antibiotics/ vinegar soaks
Topical antibiotics: Clindamycin 1%, 
erythromycin 1%
Vinegar soaks consist of soaking fingers or toes in 
a 1:1 solution of white vinegar in water for 
15 minutes every day
For a video on how to apply silver nitrate, visit: 
http://www.youtube.com/watch?v=HF5oopqheJY
Pruritis/Itching guidelines:
Prophylaxis against dry skin would include:

Initiation of skin moisturizing regimen prior to first dose. Non-scented emollient skin 
cream should be used;

Avoidance of excessive exposure to hot water during showering/ bathing;

Avoidance of household tasks involving immersion in hot water/ detergent/ solvents;


Dacomitinib
A7471055
Protocol, 28 January 2015
Page 48

Avoidance of excessive sun exposure/ tanning.  Use sunscreen containing zinc oxide 
or titanium dioxide with SPF at least 30:  apply every two hours when sun exposure is 
anticipated.
Pruritis Management Guideline
Grade 1:
Mild or localized; or topical intervention indicated
Topical steroid moderate/low strength (as listed 
above for acneiform rash)
or 
Topical antipruritics (pramoxine 1%, doxepin 
5% cream) applied twice daily
Grade 2
Intense or widespread, intermittent; skin changes from 
scratching (eg, edema, papulation, excoriations, 
lichenification, oozing/crusts); or oral intervention 
indicated; or limiting instrumental ADL
Topical steroid moderate strength
or 
Topical antipruritics (pramoxine 1%, doxepin 
5% cream) applied twice daily
AND
Oral antihistamines 
Grade 3:
Intense or widespread,  constant; or limiting self care 
ADL or sleep; or oral corticosteroid or 
immunosuppressive therapy indicated
Oral antihistamines
AND
GABA agonists (gabapentin or pregabalin) or 
Doxepin 
Antihistamines: diphenhydramine 25-50 mg tid; 
hydroxizine 25 mg tid; fexofenadine 60 mg tid
GABA agonists (adjust if renal impairment) : 
Gabapentin 300 mg every 8 hours or Pregabalin 
50-75 mg every 8 hours
Tricyclics: Doxepin 25-50 mg every 8 hours
MUCOSITIS
Patients who have not had dental checkup within 6 months prior to start of dosing are 
encouraged to do so, especially to identify any persistent issue related to recent 
chemotherapy. Once on treatment, patients are to consult the site health care team prior to 
undertaking any dental or oral surgery procedure to determine if it would be appropriate to 
proceed depending on presence of any ongoing mucosal inflammation/ stomatitis. 
Between scheduled visits, patient self-report of oral mucosal discomfort or of visible changes 
in appearance to oral mucosa is encouraged. Periodic systemic examination of the oral 
cavity is required at scheduled visits and as otherwise indicated by patient self-report 
between visits.
Patients should practice good oral care including a soft-bristle toothbrush replaced frequently 
and use of bland rinses or moisturizers. 


Dacomitinib
A7471055
Protocol, 28 January 2015
Page 49
Regular use of warm water non-medicated saline rinse is recommended if stomatitis 
develops. Frequent sips of water during meals may assist swallowing and therefore maintain 
caloric intake and hydration in patients experiencing oral pain 
Use of chlorhexidine is to be avoided.
Topical anesthetics or systemic analgesics may be used as indicated in judgment of the 
investigator and according to local clinical practices. Topical steroid rinses have been 
reported to be helpful in severe cases (eg, dexamethasone 0.5 mg/5 ml swish and expectorate 
four times daily).
Consultation with nutritionist is to be considered if toxicity may compromise maintenance of 
adequate caloric intake.
Keratoconjunctivitis
Keratoconjunctivtis Guideline
Grade 1
Asymptomatic or mild symptoms; intervention not 
indicated
No intervention or dose modification is mandated
Grade 2:
Symptomatic; topical intervention indicated; or 
limiting instrumental ADL
Preservative free artificial tears, ointments, and /or 
other therapies as clinically indicated, with a 
follow-up examination within 2 weeks to include 
slit-lamp and fundoscopic exam as per the investigator 
judgment. 
Study Treatment: If symptom lasts 2 weeks, 
withhold treatment untilGrade 1 and then reduce one 
dose level.
Grade 3:
Limiting self-care ADL
Preservative free artificial tears, ointments, and/or 
other therapies as clinically indicated, with a 
follow-up examination within 2 weeks to include 
slit-lamp and fundoscopic exam as per the investigator 
judgment. 
Study Treatment: Drug should be withheld until 
recovers toGrade 1 and then reduce one dose level.


Dacomitinib
A7471055
Protocol, 28 January 2015
Page 50
Appendix 2. Guidance on Concomitant Medications involved in CYP2D6 Pathway
For CYP2D6 substrates, drugs for which substitution, dose modification and/or monitoring is 
advised are listed below along with the narrow therapeutic index drugs that are substrate of 
CYP2D6 and its administration is prohibited.  This listing is not an all-inclusive list, and
will be monitored by Sponsor study team for required updates (addition, deletion) but in all 
instances investigators should review potential for drug-drug interaction for concomitant 
medications and take appropriate measures of substitution or dose modification.

For administration of drugs which are highly dependent on CYP2D6 metabolism:

Dose reduction should be based on substrate sensitivity to CYP2D6 metabolism. 
As a guidance a starting dose reduction of 75% (25% of the dose given without 
coadministration with dacomitinib) and close clinical monitoring is required. 

For the drugs that are partly dependent on CYP2D6-mediated metabolism, there is a 
high likelihood of supra-therapeutic exposure in combination with dacomitinib; 
clinical monitoring is required and dose-reduction may be necessary.

Pro-drugs, or drugs with highly active metabolites such as codeine and tramadol 
should be replaced by an alternative within the therapeutic class as conversion to the 
pharmacologically active moiety is CYP2D6 metabolism-dependent and their 
exposure with the co-administration of dacomitinib may be subtherapeutic.  Opiates 
such as morphine, hydromorphone, oxymorphone and oxycodone can be used as 
substitutes to replace codeine or tramadol for analgesia.


Dacomitinib
A7471055
Protocol, 28 January 2015
Page 51
CODE
DRUG
THERAPEUTIC CLASS
CODE
DRUG
THERAPEUTIC CLASS
S
amiflamine
Monoamine Oxidase Inhibitors (MAOIs)
HS
metoprolol
Alpha/Beta Adrenergic Antagonists
HS
amitriptyline
Tricyclics and Tetracyclics
S
mexiletine
Antiarrhythmics
S
aripiprazole
Antipsychotics
S
mianserin
Tricyclics and Tetracyclics
HS
atomoxetine 
Psychostimulants
S
mirtazapine
Tricyclics and Tetracyclics
S
brofaromine
Monoamine Oxidase Inhibitors (MAOIs)
HS
nebivolol
Alpha/Beta Adrenergic Antagonists
S
bufuralol
Alpha/Beta Adrenergic Antagonists
S
nefazodone
Serotonin Modulators
S
carvedilol
Alpha/Beta Adrenergic Antagonists
S
nicergoline
Vasodilators
S
chlorpheniramine
H-1 Receptor Antagonists
S
nortriptyline
Tricyclics and Tetracyclics
S
chlorpromazine
Antipsychotics
S
(S)-ondansetronSerotonin HT3 Receptor Antagonists 
S
citalopram
Serotonin Reuptake Inhibitors (SSRIs)
S
oxycodone
Opioids
S
clomipramine
Tricyclics and Tetracyclics
S
pactimibe
Other Antilipemics
S
clozapine
Antipsychotics
S
paroxetine
Serotonin Reuptake Inhibitors (SSRIs)
PD
codeine
Opioids
S
perhexiline
Vasodilators
S
debrisoquine
Other Antihypertensives
HS
perphenazine
Antipsychotics
HS
desipramine 
Tricyclics and Tetracyclics
S
phenformin
Biguanides
S
dexfenfluramine
Anorexics
P
pimozide
Antipsychotics
HS
dextromethorphan 
Antitussives
HS
prajmaline
Antiarrhythmics
S
dihydrocodeine
Opioids
P
procainamide
Antiarrhythmics
S
donepezil
Anticholinesterase Inhibitors
S
propafenone
Antiarrhythmics
HS
doxepin
Tricyclics and Tetracyclics
S
propranolol
Alpha/Beta Adrenergic Antagonists
S
duloxetine
Ser-Nor Reuptake Inhibitors (SNRIs)
S
ranolazine
Cardiovascular Drugs
S
encainide
Antiarrhythmics
S
repinotan
Serotonin Receptor Agonist
S
fesoterodine
Muscarinic Antagonists
S
risperidone
Antipsychotics
S
flecainide
Antiarrhythmics
S
ritonavir
Protease Inhibitors
S
fluoxetine
Serotonin Reuptake Inhibitors (SSRIs)
S
sabeluzole
CNS Agents
S
fluphenazine
Antipsychotics
S
sparteine
Antiarrhythmics
HS
fluvoxamine
 Serotonin Reuptake Inhibitors (SSRIs)
PD
tamoxifen
Antineoplastic Hormonal
S
gefitinib
Kinase Inhibitors
S
tamsulosin
Alpha/Beta Adrenergic Antagonists
S
haloperidol
Antipsychotics
HS
tetrabenazine
CNS Agents
PD
hydrocodone
Opioids
P
thioridazine
Antipsychotics
S
iloperidone
Antipsychotics
S
timolol
Alpha/Beta Adrenergic Antagonists
S
imipramine
Tricyclics and Tetracyclics
HS
tolterodine
Muscarinic Antagonists
S
lasofoxifene
Estrogen Receptor Modulators
PD
tramadol
Other Analgesics
PD
loratadine
H-1 Receptor Antagonists
HS
traxoprodil
Neuroprotectors
S
maprotiline
Tricyclics and Tetracyclics
S
trazodone
Serotonin Modulators
S
methadone
Opioids
S
trimipramine
Tricyclics and Tetracyclics
S
methamphetamine (MA) 
Recreational Drugs
HS
tropisetron
Serotonin HT3 Receptor Antagonists 
S
3,4-methylenedioxy-MA
Recreational Drugs
S
venlafaxine
Ser-Nor Reuptake Inhibitors (SNRIs)
HS
methoxyphenamine
Beta Adrenoreceptor Agonist
HS
vernakalant
Antiarrhythmics
S
Methylphenidate
Psychostimulants
S
zuclopenthixol
Antipsychotics
S
Metoclopramide
Other Antiemetics
HS
P
PD
S
High likelihood of supratherapeutic exposure in combination with 
dacomitinib; dose-reduction and clinical monitoring IS required, if co-
administration cannot be avoided:  starting dose when 
coadministration with dacomitinib: 25% of original dose 
Narrow therapeutic Index : Prohibited in combination 
with dacomitinib
pro-drug: active ingredient ONLY  or partially upon CYP2D6 metabolism. 
High likelihood of subtherapeutic exposure in combination with 
dacomitinib
High likelihood of supratherapeutic exposure in 
combination with dacomitinib; clinical monitoring is 
required and dose-reduction may be necessary
9/5/2012 v1.0 . Pfizer Inc.

SAP_001.pdf: 
Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 1
PROTOCOL A7471055
TREATMENT ACCESS PROTOCOL FOR PATIENTS PREVIOUSLY TREATED 
WITH DACOMITINIB ON A CLINICAL TRIAL IN JAPAN
STATISTICAL ANALYSIS PLAN (SAP)
Version: 2.0
Author:  
Date:      Jul 2, 2019
PPD


Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 2
TABLE OF CONTENTS
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................3
2. INTRODUCTION .................................................................................................................3
2.1. Study Design .............................................................................................................3
2.2. Study Objectives .......................................................................................................3
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................4
4. HYPOTHESES AND DECISION RULES...........................................................................4
5. ANALYSIS SETS .................................................................................................................4
5.1. Safety Analysis Set....................................................................................................4
6. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ............................4
6.1. Statistical Methods ....................................................................................................4
6.1.1. Analyses of Continuous Data .......................................................................4
6.1.2. Analyses of Categorical/Binary Data ...........................................................4
6.2. Statistical Analyses ...................................................................................................4
6.2.1. Safety Analysis .............................................................................................4
6.2.2. Standard Analysis .........................................................................................5
6.2.2.1. Study Conduct and Patient Disposition.......................................5
6.2.2.2. Baseline Characteristics ..............................................................5
6.2.2.3. Treatment administration/Compliance........................................5


Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 3
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
Summary of Changes
Version
Rationale
Specific Changes
1.0
Not Applicable
Not Applicable
2.0
Blinded Data Review
8.2. Statistical Analyses

Added the analysis plan to pool the data 
from two prior studies.
8.2.1. Safety Analysis

Added the data handling rule of AEs.
8.2.2.3. Treatment
administration/Compliance

Updated the analysis plan for treatment 
exposure.
2. INTRODUCTION
This document describes the planned statistical analyses for protocol A7471055, dated 
Jan 28, 2015.  This analysis plan is meant to supplement the study protocol.  Any deviations 
from this analysis plan will be described in the Clinical Study Report.
Note: in this document any text taken directly from the protocol is italicised. 
2.1. Study Design
This is a multi-center, open label, treatment extension study open in Japan only.  Eligible 
patients include those with advanced cancer who received and tolerated single-agent 
dacomitinib in a prior clinical study and have the potential to derive continued clinical 
benefit based on investigator judgment.  Patients enrolled in this extension study may 
continue to receive dacomitinib starting at the current dose level in the prior study.  Patients 
may continue to be treated with dacomitinib on this protocol as long as there is evidence of 
clinical benefit in the judgment of the investigator.
The patients will be enrolled into this extension study from the two prior studies (A7471009 
and A7471050).
2.2. Study Objectives
Primary Objective:

To allow access to dacomitinib for patients who received dacomitinib on a prior 
study in Japan and who have the potential to derive continued clinical benefit from 
single-agent dacomitinib treatment without unacceptable toxicity based upon the 
investigator’s judgment.


Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 4
Secondary Objective: 

To monitor the specific long-term safety and tolerability of single-agent dacomitinib 
in patients who have already received dacomitinib on a prior study in Japan.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
Formal interim analysis is not planned.  Unblinding is inapplicable to this open label study.
4. HYPOTHESES AND DECISION RULES
No statistical hypotheses and decision rules are defined.
5. ANALYSIS SETS
5.1. Safety Analysis Set
Safety analysis set is the as-treated population which will include all patients who receive 
any study medication.
6. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
6.1. Statistical Methods 
6.1.1. Analyses of Continuous Data
Descriptive statistics, including the mean, standard deviation, median, minimum, and 
maximum values, will be provided for continuous endpoints.
6.1.2. Analyses of Categorical/Binary Data
The number and percentage of patients in each category will be provided for 
categorical/binary variables.
6.2. Statistical Analyses 
Summary tables as described below will be provided and all data collected in this study will 
be presented in listings. In the statistical analyses, the data of patients rolled over from study 
A7471009 and those from study A7471050 will be pooled.
6.2.1. Safety Analysis
AEs will be summarized by the frequency of patients experiencing treatment emergent AEs 
corresponding to system organ class (SOC) and preferred term (PT) according to MedDRA 
terminology.  AEs will be graded by NCI CTCAE v4.0.  AEs will be summarized by 
relatedness to trial treatment.  The percentage of patients with an event will be calculated 
using the number of patients in the safety analysis set as the denominator.
AEs will not be double counted across studies (ie, prior studies and this study).  Counting of 
AEs will be based on start date of AE.  If the start date of an AE is in the prior study, the end 
date of the AE in this study and severity of AE remained the same in both studies or became 
lower, then the AE will be counted in the prior study, not in this study. However, if the same 


Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 5
AE started in the prior study, and get worse in severity in this study, then the AE will be 
counted in both studies. 
Treatment emergent AEs associated with permanent discontinuation, temporary 
discontinuation or dose reduction will also be summarized respectively by MedDRA SOC 
and PT.
A summary of serious adverse events and listing of deaths reported as serious adverse events 
will be provided.
6.2.2. Standard Analysis
Descriptive statistics will be used to summarize study conduct, patient disposition, baseline 
characteristics, and treatment administration/compliance. 
6.2.2.1. Study Conduct and Patient Disposition
The number of patients in safety analysis set including number and percent enrolled, treated,
discontinued for study medication and assessed for AEs.
6.2.2.2. Baseline Characteristics
Demographic characteristics and medical history will be summarized in frequency tables and 
descriptive statistics will be provided for quantitative variables.
6.2.2.3. Treatment administration/Compliance
The following study treatment exposure summaries will be provided.
Extent of Treatment
The extent of treatment will be summarized by initial prescribed daily dose and in total as 
follows:

The number and percent of patients within 26, 52, 78, 104, 156, 208, 260, >260
weeks of treatment.

Duration of study treatment (weeks) summarized with mean, median, minimum, and 
maximum.
Dose Administration and Dose Intensity

Definitions:

A dose reduction is defined as actual dose taken is at least 33% less than the 
prescribed dose taken on any given day for any reason with the exception of a day 
with total dose administered of 0mg, which is not considered a dose reduction.

A dose interruptions/missed dose is defined as a dosing interval of any duration 
with daily dose of 0 mg.


Dacomitinib (PF-00299804)
Protocol A7471055
Statistical Analysis Plan
Page 6

Number (%) of patients with dose reduction/interruption will be summarized by 
initial prescribed daily dose and in total.
Tables will be provided by initial prescribed daily dose whenever applicable for: 

Dose received/Cumulative dose.

Relative dose (ie, percent of actual total dose received relative to intended total dose
initially planned per protocol, where actual total dose = total dose received as 
recorded on CRF; intended total dose = (prescribed daily dose at beginning of the 
study)*(actual dose duration)).
Follow-up Therapy
A listing for follow-up cancer therapy will be provided with subject, regimen, date of last 
dose of study treatment, start date of subsequent cancer regimen, time from last dose of study 
drug to the first subsequent regimen, drugs administered, end date of subsequent cancer 
regimen, duration of the subsequent regimen.