Conditions: Neoplasms Triple-Negative Breast Cancer
Keywords: ADC PF-06647263 solid tumors tumors neoplasm metastasis TNBC Triple negative breast cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 60
Healthy volunteers: no

Brief summary:
To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed description:
The clinical study will include 2 parts. Part 1 will estimate the MTD in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the RP2D. Part 2 will include patients with previously treated metastatic triple negative breast cancer (TNBC).

Arms:
arm 1: None

Interventions: intervention 1: PF-06647263 intervention 2: PF-06647263
Intervention descriptions: intervention 1: Part 1- PF-06647263 will be administered intravenously in either a 21 day cycle or weekly in cohorts of 2 or more patients starting at a dose of 0.015 mg/kg. Increases in dose will continue until MTD is determined. intervention 2: Part 2- Patients with triple negative breast cancer will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.

Protocol document:
Prot_000.pdf: 
PF-06647263
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Final Protocol Amendment 5, 17 August 2016
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A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND 
PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH 
ADVANCED SOLID TUMORS
Compound:
PF-06647263
Compound Name:
Not Applicable
US IND Number:
119,331
European Clinical Trial Database 
(EudraCT) Number:
Not Applicable
Protocol Number:
B7521001
Phase:
1


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Document History
Document
Version Date
Summary of Changes and Rationale
Original protocol
01-November-2013
N/A
Amendment 1
13-December-2013
Background: Deleted incorrect name of 
study treatment.  Rationale: 
Administrative Change.
Amendment 2
17-February-2014
Schedule of activities: Revision to the 
PK sample collection timepoints to the 
start of the infusion.  Rationale: 
administrative reasons to remove the “0” 
hour sample nomenclature. 
Schedule of activities, Section 7.3: 
Require one 9 ml sample of whole blood 
per PK collection timepoint.  Rationale: 
revision identified through assay 
development.
Section 3.1.1.3 DLT Definitions: 
Revision to the definition of Dose 
Limiting Toxicity.  Rationale: requested 
by the FDA.
Section 4.1 Inclusion Criteria 2: Revision 
to the inclusion criteria for 
triple-negative breast cancer patients. 
Rationale: requested by the FDA.
Section 5.2.2 Preparation and 
Dispensing: Inclusion of dosing details in 
the protocol. Rationale: requested by the 
FDA. 
Section 5.2.3 Administration: Inclusion 
of pretreatment medications in the case 
of infusion reactions and addition of: 
Appendix 5 Management of Infusion
Related Reactions.  Rationale: requested 
by the FDA. 
Amendment 3
15 July 2015
Section: Background, 
Explanation/Rationale for Change Added 
new arm for investigation of NSCLC 
Section: Study Objectives and Endpoints, 
Explanation/Rationale for Change 


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Section: Study Overview, 
Explanation/Rationale for Change Added 
additional arm (NSCLC) and clarified 
expansion futility and RP2D 
determination.
Section: Schedule of Activities, 
Explanation/Rationale for Change 
Editorials changes to clarify operational 
logistics, 
Section: Pharmacokinetic, ADA and 
Pharmacodynamic sampling schedule 
(for q3w dosing regimen, 
Explanation/Rationale for Change 
Editorials changes to clarify operational 
logistics, 
Section: Pharmacokinetic, ADA, and 
Pharmacodynamic sampling schedule 
(for qw dosing regimen), 
Explanation/Rationale for Change 
Editorials changes to clarify operational 
logistics 
Section: 1.2. Background, 
Explanation/Rationale for Change Added 
NSCLC arm to trial
Section: 1.2.1. EFNA4 expression in 
human cancers, Explanation/Rationale 
for Change Justification for adding 
NSCLC to trial
Section: 1.3.1. Efficacy 
Explanation/Rationale for Change 
Editorial changes.
 
 
Section: 1.6.2. TNBC OVCA and 
NSCLC in dose expansion, 
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Explanation/Rationale for Change Added 
additional NSCLC arm to trial
 
 
 
 
 
Section: 2.1. Objectives, 
Explanation/Rationale for Change 
Exploratory endpoints have been further 
defined.
Section: 2.2. Endpoints, 
Explanation/Rationale for Change 
Exploratory endpoints have been further 
defined.
Section: 3.1. Study overview, 
Explanation/Rationale for Change Added 
additional arm (NSCLC) and clarified 
expansion futility and RP2D 
determination.
Section: 3.1.1.2. Criteria for dose 
escalation/mtd determination, 
Explanation/Rationale for Change 
Editorial clarification for continued 
enrollment of patients deriving clinical 
benefit.
Section: 3.1.1.3. DLT definitions, 
Explanation/Rationale for Change 
Clinical experience update to include 
hyperbilirubinemia in the DLT 
definition.
Section: 3.1.1.5. Recommended phase 
2 dose, Explanation/Rationale for 
Change Clarify investigator notification 
of dose determination for Part 2
Section: 3.1.2. Dose expansion phase 
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part 2, Explanation/Rationale for Change 
Removal of the contingency if the ISH 
assay was not available at the start of part 
2 of the study.
Section: 4.1. Inclusion criteria, 
Explanation/Rationale for Change, 
Inclusion of the third arm for part 
2 (NSCLC) and assay inclusion 
language.
Section: 4.2. Exclusion criteria, 
Explanation/Rationale 
 
 exclusion language added per 
the PF-06647263 clinical experience
Section: 5.2.2. Preparation and 
Dispensing, Explanation/Rationale for 
Change Editorial change
Section: 5.2.3. Administration, 
Explanation/Rationale for Change 
Editorial clarification for continued 
enrollment of patients deriving clinical 
benefit.
Section: 5.2.5. Dose interruptions/delay, 
Explanation/Rationale for Change 
Editorial clarification for continued 
enrollment of patients deriving clinical 
benefit.
Section: 5.2.6. Dose reductions, 
Explanation/Rationale for Change Dose 
reductions clarified for part 2 and 
specific dose reduction for 
hyperbilirubinemia added from current 
clinical experience
Section: 7.1.3. Laboratory safety 
assessment, Explanation/Rationale for 
Change Editorial change to add 
Hyaluronic acid from current clinical 
experience
Section: 7.1.4. Vital signs and physical 
examination, Explanation/Rationale for 
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Change Editorial change
Section: 7.1.5. (12-Lead) ECG, 
Explanation/Rationale for Change 
Editorial change
Section: 7.3.1. Blood for PK analysis of 
pf-06647263, total antibody, and 
unconjugated payload cl-184538, 
Explanation/Rationale for Change 
Editorial change
 
 
 
Section: 8.1. Adverse events, 
Explanation/Rationale for Change 
Editorial change
Section: 8.2. Reporting Period, 
Explanation/Rationale for Change 
 
Section: 8.3. Definition of an adverse 
event, Explanation/Rationale for Change 
Editorial change
Section: 8.4. Medication errors, 
Explanation/Rationale for Change 
Editorial change
Section: 8.6. Serious adverse events, 
Explanation/Rationale for Change 
Editorial change.
Section: 8.6.2. Potential cases of 
drug-induced liver injury, 
Explanation/Rationale for Change 
Editorial change
Section: 8.7. Hospitalization, 
Explanation/Rationale for Change 
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Editorial change
Section: 8.10. Exposure during 
pregnancy, Explanation/Rationale for 
Change Editorial change
Section: 8.11. Occupational exposure, 
Explanation/Rationale for Change 
Editorial change
Section: 8.12. Withdrawal due to adverse 
events (see also the section on patient 
withdrawal), Explanation/Rationale for 
Change Editorial change
Section: 8.14.1. Serious adverse event 
reporting requirement, 
Explanation/Rationale for Change 
Editorial change
Section: 8.14.3. Sponsors reporting 
requirements to regulatory authorities, 
Explanation/Rationale for Change 
Editorial change
Section: 9.3.1. Part 1, 
Explanation/Rationale for Change 
Editorial Change
Section: 9.3.2. Part 2: 
Explanation/Rationale for Change 
Clarification of Part 2 futility and sample 
size
Section: 9.5.2. 
Pharmacokinetic/pharmacodynamic 
analysis, Explanation/Rationale for 
Change Editorial change
Section: 15.1. Communication of results 
by Pfizer, Explanation/Rationale for 
Change Editorial change
Section: Appendix 1 Abbreviations, 
Explanation/Rationale for Change 
Editorial change


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Amendment 4
07 December 2015
Protocol summary: Removal of NSCLC 
from inclusion in Part 2 of this protocol 
and align objectives and endpoints 
accordingly.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 1.2. Background Removal of 
NSCLC from inclusion in Part 2 of this 
protocol.
Section 1.2.1. EFNA4 Expression in 
Human Cancers Removal of NSCLC 
from inclusion in Part 2 of this protocol.
Section 1.6.2. TNBC and OVCA in dose 
expansion Removal of NSCLC from 
inclusion in Part 2 of this protocol.
 
 
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Section 1.8. Clinical Experience Updated 
clinical experience reported.
Section 2.1. Objectives- Removal of 
NSCLC from inclusion in Part 2 of this 
protocol and align objectives and 
endpoints accordingly.
Section 2.2. Endpoints Removal of 
NSCLC from inclusion in Part 2 of this 
protocol and align objectives and 
endpoints accordingly.
Section 3.1. Study overview Removal of 
NSCLC from inclusion in Part 2 of this 
protocol include unselected TNBC in 
Part 2 and align statistics accordingly.
Section 3.1.1.2. Criteria for dose 
escalation/MTD determination Removal 
of NSCLC from inclusion in Part 2 of 
this protocol and align statistics 
accordingly with additional enrollment in 
Part 1
Section 3.1.2. Dose expansion phase 
(part 2) Removal of NSCLC from 
inclusion in Part 2 of this protocol and to 
include unselected TNBC in Part 2 and 
align statistics accordingly.
Section 4.1. Inclusion criteria Removal 
of NSCLC from inclusion in Part 2 of 
this protocol include unselected TNBC in 
Part 2 and align inclusion criteria 
accordingly.
Section 4.2. Exclusion criteria To allow 
for additional prior therapies to be 
included aligning with the current 
standard of care for this patient
population.
Section 5.1. Allocation to treatment
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Clarification of dosing for Part 2.
Section 5.2.6. Dose reduction To prevent 
sub therapeutic dose administration, as 
determined by pharmacokinetics of Part 
1.
Section 5.2.7. Compliance Operational 
clarification
Section 7.1.3. Laboratory safety 
assessment
 
 
Section 7.1.4. Vital signs and physical 
examination Clarification of dosing
weight window.
 
 
Section 9.2. Statistical methods and 
properties Further expansion of the mTPI 
table to accommodate additional 
enrollment in Part 1 for safety data 
collection.
Section 9.3.2. PART 2 Removal of 
NSCLC from inclusion in Part 2 of this 
protocol include unselected TNBC in 
Part 2 and align statistics accordingly.
 
Section 9.5. Analysis of other endpoints 
 
Appendix 1 Abbreviations Updated table 
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to align with current protocol.
Appendix 6 Detailed Dose Escalation/De 
Escalation Scheme for mTPI design
Further expansion of the mTPI table to 
accommodate additional enrollment in 
Part 1 for safety data collection.
Amendment 5
17 August 2016
Protocol Summary: Removal of 
references to ovarian cancer and 
clarification of objective endpoint 
wording.
 
 
Introduction: Removal of ovarian cancer 
to the overview; update to section 1.7-
removal of ovarian cancer for 
EFNA4 expression; section 1.8 – update 
clinical experience to July 27th 2016.
Section 2, 3, 4: Update objective and 
endpoints; removal of ovarian cancer 
throughout the document
 
 
Section 9.3: update to sample size, 
accounting for removal of ovarian cancer 
from the study
Editorial and administrative updates 
throughout the document
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards (IRBs)/ethics committees
(ECs).
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PROTOCOL SUMMARY
Background
Antibody-drug conjugates (ADCs) are compounds comprised of a cytotoxic agent which is 
chemically linked to an antibody that selectively binds to an internalizing tumor-associated 
antigen.1 By delivering the cytotoxic agent to the tumor while minimizing the exposure to 
normal tissues, ADCs have the potential for improving the therapeutic index of cytotoxic 
anti-cancer agents.
PF-06647263 is an anti-EFNA4 ADC for the treatment of patients with cancer.  EFNA4 is a 
novel ADC target that was identified through analysis of the gene expression profiles of 
aggressive tumor cell populations called cancer stem cells (CSCs) or tumor-initiating cells.  
EFNA4 mRNA expression levels have been found to be enriched in some nonclinical models 
of colorectal cancer (CRC) and pancreatic cancer1 Pfizer’s in-house bioinformatics analysis 
suggests that EFNA4 mRNA expression is also elevated in patients with CRC, breast cancer, 
including triple negative breast cancer (TNBC), ovarian cancer (OVCA), non-small cell lung 
cancer (NSCLC), chronic lymphocytic leukemia (CLL) and hepatocellular carcinoma (HCC) 
relative to the corresponding normal tissues.  In non-tumor tissues, EFNA4 is believed to be 
involved in axonal guidance, wound healing, epidermal differentiation, transendothelial
migration of leukocytes, retinal neovascularization, and craniosynostosis.2,3,4
 
TNBC is a heterogeneous disease constituting approximately 15-20% of breast cancers and is 
characterized by the lack of expression of estrogen receptor (ER), progesterone receptor 
(PgR), and the absence of human epidermal growth factor receptor 2 (HER2) overexpression 
and/or amplification.  It occurs more frequently in women less than 50 years old and 
generally behaves more aggressively than other breast cancer subtypes.6 Although TNBC 
patients experience higher rates of pathological complete responses (pCR), when treated with 
neoadjuvant chemotherapy, they experience shorter duration-free survival (DFS) and overall 
survival (OS) relative to patients with non-TNBC.8 The majority of patients receive 
anthracyclines and taxanes in the neoadjuvant or adjuvant settings.  A variety of single 
agent and combination regimens are active in metastatic TNBC, although rapid 
progression is observed in most patients.9 Thus, novel therapeutic options are urgently 
needed.
Study Objectives and Endpoints
Part 1 (Dose escalation) Primary Objective

To assess safety and tolerability at increasing dose levels of 
PF-06647263 administered as an intravenous (IV) infusion every 3 weeks (Q3W) and 
weekly (QW) in patients with advanced solid tumors unresponsive to currently 
available therapies, or for whom no standard therapy is available, in order to estimate 
the Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose 
(RP2D). 
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Secondary Objectives

To evaluate the overall safety profile; 

To characterize the single and multiple dose pharmacokinetics (PK) of PF-06647263, 
total antibody, and unconjugated payload;

To evaluate the immunogenicity of PF-06647263;

To document preliminary evidence of anti-tumor activity based on response rate (RR)
correlating ORR (overall response rate) to EFNA4 expression in archival tumor 
samples
Part 2 (Expansion) Primary Objective

To confirm safety and tolerability and explore preliminary evidence of anti-tumor 
activity of PF-06647263 based on response rate (RR) at the RP2D in previously 
treated metastatic TNBC patients. 
Secondary Objectives

To evaluate the overall safety profile at the RP2D; 

To characterize the single and multiple dose PK of PF-06647263, total antibody, and 
unconjugated payload;

To evaluate the immunogenicity of PF-06647263;

To document preliminary evidence of anti-tumor activity based on progression free 
survival (PFS) and overall survival (OS).
 
 
 
 
 
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Endpoints
Primary Endpoint (Part 1)

First cycle Dose Limiting Toxicities (DLTs) in order to determine the MTD and 
RP2D.
Primary Endpoint (Part 2)

Response rate (RR) as determined by the Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 criteria.
Secondary Endpoints (Parts 1 and 2)

Adverse Events as characterized by type, frequency, severity (as graded by National 
Cancer Institute (NCI) CTCAE v.4.03), timing, seriousness and relationship to study 
therapy;

Laboratory abnormalities as characterized by type, frequency, severity (as graded by 
NCI CTCAE v.4.03) and timing;

Vital Sign abnormalities; 

Systemic PK exposure of PF-06647263, total antibody, and unconjugated payload 

Immunogenicity of PF-06647263; incidence of anti-PF-06647263 antibodies (ADA);

Objective tumor response, as assessed using RECIST version 1.1 by calculating the 
Overall Response Rate (ORR), Clinical Benefit Response Rate (CBRR), Progression 
Free Survival (PFS), and Overall Survival (OS)-stratifying for EFNA4 expression
Part 2 only. 
 
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Study Overview
This is a Phase 1, two part, open label, multi-center, single arm, non-randomized, multiple 
dose, safety, PK and PD study of single agent PF-06647263 in adult patients with advanced 
solid tumors for whom no standard therapy is available. 
The clinical study will include 2 parts.  Part 1 will estimate the MTD in dose escalation 
cohorts in patients with advanced solid tumors for whom no standard therapy is available in 
order to establish the RP2D.  The initial dosing regimen tested in Part 1 will be 
PF-06647263 administered once every 3 weeks (Q3W).  Evaluation of a weekly (QW) 
regimen will be initiated when the first patient treated with the Q3W regimen experiences a 
DLT or Grade 2 thrombocytopenia related to study treatment.  The starting dose of the QW 
regimen will not exceed one-third of the highest Q3W dose evaluated.  Once initiated, the 
2 regimens will be evaluated independently based on the same dose-escalation criteria as 
described below.  The collective safety and efficacy data will be used to identify the regimen 
or regimens to be used in Part 2 of the study.  Part 2 will include patients with previously 
treated metastatic triple negative breast cancer (TNBC). 
It is anticipated that the maximum sample size of approximately 70 patients are expected to 
be enrolled in Part 1 of the study at approximately 3 - 4 sites. The actual number of patients 
enrolled will depend upon tolerability of PF-06647263, and the number of dose levels 
required to identify the MTD in the Q3W and QW dosing regimens. 
The TNBC expansion cohort (Part 2) will enroll approximately 24 response evaluable 
patients.  (defined as having at least one on-study tumor assessment).  Enrollment of TNBC 
patients may be discontinued if no or minimal antitumor activity is observed (eg, no response 
is observed in the first 8 evaluable patients).  Conversely, if a high ORR is observed in 
TNBC patients (See Section 9.3.2), up to 10 additional patients may be enrolled following 
discussion between the Sponsor and Investigators.  In the event DLTs occur in more than 
33% of the patients enrolled in Part 2, enrollment will stop and the MTD dose will be 
reevaluated.  Additional safety information gathered in Part 2 may be used to modify the 
dose recommended for future Phase 2 trials. 
Patients will participate in the study for approximately 6 months in Part 1 and up to 
approximately 18 months in Part 2. This assumes up to 4 weeks of screening, approximately 
4 months of treatment, and a follow-up visit within 4 weeks after the last dose for adverse 
event (AE) and serious adverse event (SAE) collection and, in Part 2 only, long-term 
follow-up for survival every two months for up to 12 months after the last dose.  Treatment 
with study drug will continue until disease progression, patient refusal, unacceptable toxicity 
occurs, or the study is terminated.  Note: Patients deriving clinical benefit from study 
treatment may continue on study at a reduced dose following recovery of the AE to Grade 
0-1 or baseline, only after discussion between the investigator and Sponsor.
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SCHEDULE OF ACTIVITIES 
The Schedule of Activities table provides an overview of the protocol visits and procedures.  Refer to the Assessments section of the 
protocol for detailed information on each assessment 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 wellbeing of the patient.
Treatment Period
Post Treatment
Cycle 1 Only
(Days 1-21)
Cycle 2 and Subsequent Cycles
(Days 1 to 21)
Protocol Activity
Screen/ Baseline1
(28 days)
Day 1
Day 2
Day 4
(1)
Day 8
(1)
Day 15
(2)
Day 1
(2)
Day 8
(±2)
Day 15
(2)
End of 
Treatment25
(+7)
Follow Up26
(+7)
Informed Consent2
X
Tumor History3
X
Medical History4
X
Complete Physical Examination 
including skin examination5
X
X
X
Abbreviated Physical 
Examination including skin 
examination
X
X
X
X
X
X
X
Baseline Signs and Symptoms6
X
Height
X
Weight7
X
X
X
X
Vital signs (BP/PR/Temp)8
X
X
X
X
X
X
X
X
X
ECOG Performance Status9
X
X
X
X
X
(12 lead) ECG10
X
X
X
X
X
X
Laboratory
Hematology11
X
X
X
X
X
X
X
X
X
X
Blood Chemistry12
X
X
X
X
X
X
X
X
Coagulation Panel13
X
X
X
Urinalysis14
X
X
X
X
Pregnancy test15
X
X
X
X
Registration and Treatment 
Registration16
X
Study Treatment (Q3W)17
X
X
Study Treatment (QW)17
X
X
X
X
X
X


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Treatment Period
Post Treatment
Cycle 1 Only
(Days 1-21)
Cycle 2 and Subsequent Cycles
(Days 1 to 21)
Protocol Activity
Screen/ Baseline1
(28 days)
Day 1
Day 2
Day 4
(1)
Day 8
(1)
Day 15
(2)
Day 1
(2)
Day 8
(±2)
Day 15
(2)
End of 
Treatment25
(+7)
Follow Up26
(+7)
Tumor assessments 
CT or MRI scan or equivalent18
X
X (every 
6 weeks, ± 7 
days)
X25
Other samplings 
 
 
Blood Samples for PK20
See Pharmacokinetic, ADA, and Pharmacodynamic Sampling Schedule Table below
Blood Sample for 
Anti-PF-06647263 Antibody21
See Pharmacokinetic, ADA, and Pharmacodynamic Sampling Schedule Table below
Other clinical assessments
Adverse Events23
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medication and non 
drug supportive interventions24
X
X
X
X
X
X
X
X
X
X
X
Unless otherwise specified, laboratory values and assessments should be obtained prior to the PF-06647263 infusion.  If the infusion is held, assessments should 
still be performed.  For subsequent infusions, CBC, blood chemistry, other laboratory tests and brief physical examinations, values/assessments should be 
obtained within 72 hours (ideally within 24 hours) prior to the PF-06647263 infusion and key values should be received and reviewed to ensure appropriate 
values for dosing. 
Footnotes
1.
Screening: To be conducted within 28 days prior to treatment start.
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures and may be > 28 days from first dose.
3.
Tumor History: Will be collected within 28 days prior to treatment start. Includes history of disease under study including details of primary diagnosis and 
treatment history. 
4.
Medical History: Includes history of disease process other than the cancer under study (active or resolved) and concurrent illness.  Includes prior treatments 
and any current medical treatments for any condition.
5.
Physical Exam: Complete physical exam may be performed within 72 hours (ideally within 24 hours) prior to the first dose of PF-06647263. 
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6.
Baseline Signs & Symptoms: On Day 1 prior to the start of study treatment, patients will be asked about any signs and symptoms experienced within the 
past 14 days.  Baseline signs and symptoms will be recorded on the Medical History CRF page.
7.
Weight: Weight may be collected within 7 days prior to the PF-06647263 infusion for dose preparation on Day 1 of each cycle.  The weight measurement 
taken for Day 1 of each cycle should be used to calculate the patient’s dose of study treatment for all doses in that cycle.
8.
Vital signs: Includes blood pressure (BP), and pulse rate (PR) to be recorded in the sitting position after 5 minutes of rest.  On Day 1 of each cycle, vital 
signs should be measured prior to infusion start (- 120 mins pre-dose) and 1 hour (+/- 15 minutes) after the start of the infusion. 
9.
Performance status: per ECOG scale (see Appendix 4).
10. 12 lead ECG: ECGs will be collected during Screening (singlet) and at the End of Treatment visit (triplicate).  Additional ECGs (triplicate) will be collected 
on Day 1 and Day 8 of each cycle both prior to the start of the study treatment infusion, and at 1 hour (within 15 minutes) before the end of the infusion .  If 
the mean QTc is prolonged (value of ≥501 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  Additional 
ECGs should be performed as clinically indicated.  See Section 7 for additional considerations regarding ECG. 
11. Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, absolute neutrophils, lymphocytes, monocytes, eosinophils, and 
basophils.  No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date. 
12. Blood Chemistry: Should include sodium, potassium, chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, calcium, 
magnesium, phosphorus, albumin, total protein, AST/SGOT, ALT/SGPT, alkaline phosphatase, total bilirubin, and lactate dehydrogenase (LDH) No need to 
repeat on C1D1 if baseline assessment performed within 72 hours prior to that date. 
13. Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT). 
14. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  If 2+ protein on urine dipstick, then collect spot urine sample to calculate 
urine protein to creatinine ratio (UPCR).
15. Pregnancy Test (serum or urine): For female patients of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, 
will be performed on two occasions prior to starting study therapy - once at the start of screening and once at the baseline visit, (within 72 hours of the first
investigational product administration).  Pregnancy tests will also be routinely repeated at every cycle during the active treatment period, at the end of study 
therapy 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 IRB/IECs or if required by local regulations.
16. Registration: Patient randomization number and dose level allocation will be provided by Pfizer Inc.
17. Study Treatment: For patients enrolled in the Q3W regimen, PF-06647263 will be administered once every 21 days as an IV infusion over approximately 
60 minutes. For patients enrolled in the QW regimen, PF-06647263 will be administered once a week as an IV infusion over approximately 60 minutes.
18. Tumor Assessments: Tumor assessments will include all known or suspected disease sites and may include chest, abdomen and pelvis CT or MRI scans.  
Brain scans and bone scans will be performed at baseline if disease is suspected and on-study as appropriate to follow disease.  Baseline central nervous 
system (CNS) imaging is not required with the exception of symptomatic patients to rule out CNS metastases.  CT or MRI scans are to be done every 
6 weeks (7 days) from the start of study treatment until disease progression by RECIST (v1.1) or death, or until permanent discontinuation of study 
treatment.  Note: Patients deriving clinical benefit from study treatment may continue on study at a reduced dose following recovery of the AE to Grade 


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0-1 or baseline, only after discussion between the investigator and Sponsor.  The frequency may be reduced to every 12 weeks after 6 months of study 
treatment.  Tumor assessments should be fixed according to the calendar, regardless of treatment delays.  Given the exploratory nature of the study 
confirmation of response (CR/PR) is not required.  Tumor assessments should be repeated at the End of Treatment visit if more than 6 weeks have passed 
since the last evaluation. 
 
20. PK Sampling: Specific timing for collection of pharmacokinetic samples can be found in the Pharmacokinetic, ADA and Pharmacodynamic Sampling 
schedule table below.
21. Anti PF-06647263 Antibodies: Specific timing for collection of anti-PF-06647263 antibody samples can be found in the Pharmacokinetic, ADA, and 
Pharmacodynamic Sampling schedule table below. 
 
 
23. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTC AE version 4.03.  Patients must be 
followed for AEs for 28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 
28 days should the patient commence another anticancer therapy in the meantime.  Serious Adverse Events must be reported from the date the informed 
consent document is signed until 28 days after the last study drug administration or whenever (independently of the elapsed time) there is the suspicion of a 
causal relationship to the study drug.
24. Concomitant Medications and Non Drug Supportive Interventions: All prior/concomitant medications within 28 days (4 weeks) prior to first dose of 
study treatment should be recorded in the CRF including supportive care drugs (eg, anti-emetic treatment and prophylaxis), and the drugs used to treat 
adverse events or chronic diseases, and non drug supportive interventions (eg, transfusions).
25. End of treatment visit: Conducted at the visit that the patient is discontinued from the trial and no longer than 1 week after the patient has been 
discontinued.  Complete tumor assessments if not completed in the last 6 weeks. 
26. Follow up: At least 28 days and no more than 35 days after the discontinuation of treatment visit (end of treatment), patients will return to undergo review of 
concomitant medications, vital signs, ECOG performance status, 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.  Patients in Part 2 will be followed for survival by phone call/email/visit
every 2 months until death or until 12 months from the End of Treatment visit, whichever is earlier.  If a patient is classified as having PD at a post-baseline 
tumor assessment, then confirmation of PD by a second scan in the absence of rapid clinical deterioration is required.  Additionally prior to having PD tumor 
assessments should continue until subsequent therapy or death.
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Pharmacokinetic, ADA, and Pharmacodynamic Sampling Schedule (for Q3W dosing regimen)
Treatment Period
Cycle 1 Only
(Days 1 to 21)
Cycles
2 and 3
Cycle 4
Every Cycle 
Thereafter
EOT 
(+7)
Protocol Activity
Scree
n
(28
days)
Day 1
Day 
2
Day 
4
(1)
Day 
8
(1)
Day 
15
(2)
Day 1
Day 1
Day 
2
Day 
4
(1)
Day 
8
(1)
Day 
15
(2)
Day 1
Pre-d
ose*
1
hr
*
4
hr
*
24
hr*
Pre-dose
*
1
hr
*
Pre-
dose
*
1
hr
*
4
hr
*
24
hr*
Pre-
dose
*
1 hr*
Blood Samples for 
PK1
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for 
Anti-PF-06647263 A
ntibodies 2
X
X
X
X
X
X
 
 
 
 
*Sampling times are related to the start of infusion; 1 hr samples should be collected within the 15 minutes before the infusion ends. All sample time 
windows, except the pre-dose and 1 hr samples, will be ±10% of nominal time. Therefore, a 4 hr sample will have a ± 24 minutes collection window. 
Samples collected on Day 4, 8 and 15 will have a  ±1 or  ±2 day window as indicated in the table.
Footnotes
1.
Blood sample for PK: A 9 ml sample of whole blood will be collected at each timepoint for PK analysis of PF-06647263, total antibody, and unconjugated 
payload CL-184538.
2.
Anti PF-06647263 Antibodies (ADA): Collection of serum to detect the presence of antibodies to PF-06647263 is to be obtained prior to the start of 
treatment.  Patients having an unresolved adverse event that is possibly related to anti-PF-06647263 antibodies at their last assessment will be asked to return 
to the clinic for ADA and drug concentration blood sampling at approximately 3 month intervals until the adverse event or its sequelae resolve or stabilize at 
a level acceptable to the investigator and sponsor.
 
 
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Pharmacokinetic, ADA, and Pharmacodynamic Sampling Schedule (for QW dosing regimen)
Treatment Period
Cycle 1 Only
(Days 1 to 21)
Every Cycle Thereafter
EOT 
(+7)
Protocol 
Activity
Screen
(d28
days)
Day 1
Day 
2
Day 
4
Day 8
Day 
11
Day 15
Day 
18
Day 1
Day 8
Day 15
Pre
-do
se
1
hr
*
4
hr
*
24
hr*
72
hr*
Pre-
dose
1 hr*
72
hr*
Pre-
dose
1 hr*
72
hr*
Pre-dose
1 hr*
Pre-
dose
1 hr*
Pre-d
ose
1 hr*
Blood Samples 
for PK1
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample 
for 
Anti-PF-066472
63 Antibodies 2
X
X
X
X
 
 
 
 
X
* Sampling times are related to the start of infusion; 1 hr samples should be collected within the 15 minutes before the infusion ends. All sample time 
windows, except the pre-dose and 1 hr samples, will be ±10% of nominal time. Therefore, a 4 hr sample will have a ± 24 minutes collection window..
Footnotes
1.
Blood sample for PK: A 9 ml sample of whole blood will be collected at each timepoint for PK analysis of PF-06647263, total antibody, and unconjugated 
payload CL-184538.
2.
Anti PF-06647263 Antibodies: Collection of serum to detect the presence of antibodies to PF-06647263 is to be obtained prior to the start of treatment.  
Patients having an unresolved adverse event that is possibly related to anti-PF-06647263 antibodies at their last assessment will be asked to return to the 
clinic for ADA and drug concentration blood sampling at approximately 3 month intervals until the adverse event or its sequelae resolve or stabilize at a 
level acceptable to the investigator and sponsor.
 
 
 
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................26
LIST OF FIGURES .................................................................................................................26
1. INTRODUCTION ...............................................................................................................28
1.1. Indication.................................................................................................................28
1.2. Background .............................................................................................................28
1.3. PF-06647263 ...........................................................................................................29
1.3.1. Efficacy.......................................................................................................29
1.6. Rationale..................................................................................................................37
1.6.1. Justification for Phase 1 Clinical Starting Dose .........................................37
1.6.2. TNBC in Dose Expansion ..........................................................................38
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................42
2.1. Objectives................................................................................................................42
2.2. Endpoints.................................................................................................................44
3. STUDY DESIGN.................................................................................................................45
3.1. Study Overview.......................................................................................................45
3.1.1. Part 1...........................................................................................................46
3.1.1.1. Starting Dose.............................................................................46
3.1.1.2. Criteria for Dose Escalation/MTD Determination....................46
3.1.1.3. DLT Definitions ........................................................................48
3.1.1.4. MTD Definition.........................................................................49
3.1.1.5. Recommended Phase 2 Dose (RP2D) Definition......................49
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3.1.2. Dose Expansion Phase (Part 2)...................................................................49
4. PATIENT SELECTION......................................................................................................50
4.1. Inclusion Criteria.....................................................................................................50
4.2. Exclusion Criteria....................................................................................................52
4.3. Sponsor Qualified Medical Personnel.....................................................................54
5. STUDY TREATMENTS.....................................................................................................54
5.1. Allocation to Treatment ..........................................................................................54
5.2. Drug Supplies..........................................................................................................55
5.2.1. Formulation and Packaging........................................................................55
5.2.2. Preparation and Dispensing........................................................................55
5.2.3. Administration............................................................................................56
5.2.4. Recommended Dose Modifications............................................................56
5.2.5. Dose Interruptions/Delay............................................................................57
5.2.6. Dose Reductions .........................................................................................57
5.2.7. Compliance.................................................................................................59
5.3. Drug Storage and Drug Accountability...................................................................59
5.4. Concomitant Medication(s).....................................................................................60
5.4.1. Other Anti-tumor/Anti-cancer or Experimental Drugs...............................60
5.4.2. Supportive Care ..........................................................................................61
5.4.3. Hematopoietic Growth Factors...................................................................61
5.4.4. Anti Diarrhea, Anti Emetic Therapy ..........................................................61
5.4.5. Anti-inflammatory Therapy........................................................................61
5.4.6. Corticosteroids............................................................................................61
5.4.7. Surgery........................................................................................................61
6. STUDY PROCEDURES .....................................................................................................62
6.1. Screening.................................................................................................................62
6.2. Study Period ............................................................................................................62
6.3. Follow-up Visit .......................................................................................................62
6.4. Patient Withdrawal..................................................................................................62
7. ASSESSMENTS..................................................................................................................63
7.1. Safety Assessment...................................................................................................64
7.1.1. Pregnancy Testing ......................................................................................64
7.1.2. Adverse Events...........................................................................................64


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7.1.3. Laboratory Safety Assessment ...................................................................64
7.1.4. Vital Signs and Physical Examination........................................................65
7.1.5. (12-Lead) ECG ...........................................................................................66
7.2. Long Term Follow-Up (Part 2 Patients Only) ........................................................66
7.3. Pharmacokinetics Assessments...............................................................................67
7.3.1. Blood for PK analysis of PF-06647263, Total Antibody, and 
Unconjugated Payload CL-184538..................................................................67
7.5. Tumor Response Assessments ................................................................................68
7.7. Immunogenicity Evaluations...................................................................................69
7.8. Banked Biospecimens .............................................................................................70
7.8.1. Markers of Drug Response.........................................................................70
8. ADVERSE EVENT REPORTING......................................................................................71
8.1. Adverse Events........................................................................................................71
8.2. Reporting Period .....................................................................................................71
8.3. Definition of an Adverse Event...............................................................................72
8.4. Medication Errors....................................................................................................73
8.5. Abnormal Test Findings..........................................................................................73
8.6. Serious Adverse Events...........................................................................................73
8.6.1. Protocol-Specified Serious Adverse Events...............................................74
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................74
8.7. Hospitalization ........................................................................................................75
8.8. Severity Assessment................................................................................................76
8.9. Causality Assessment..............................................................................................77
8.10. Exposure During Pregnancy..................................................................................77
8.11. Occupational Exposure .........................................................................................78
8.12. Withdrawal Due to Adverse Events (See also the Section on Patient 
Withdrawal)...............................................................................................................79
8.13. Eliciting Adverse Event Information ....................................................................79
8.14. Reporting Requirements........................................................................................79
8.14.1. Serious Adverse Event Reporting Requirements .....................................79
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8.14.2. Non-Serious Adverse Event Reporting Requirements .............................79
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................80
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................80
9.1. Analysis Sets ...........................................................................................................80
9.2. Statistical Methods and Properties ..........................................................................81
9.3. Sample Size Determination.....................................................................................83
9.3.1. Part 1:..........................................................................................................83
9.3.2. Part 2:..........................................................................................................83
9.4. Efficacy Analysis ....................................................................................................83
9.4.1. Analysis of Overall Response (CR or PR) .................................................84
9.5. Analysis of Other Endpoints ...................................................................................84
9.5.1. Analysis of Pharmacokinetics.....................................................................84
9.5.2. Pharmacokinetic/Pharmacodynamic Analysis............................................84
9.5.3. Immunogenicity..........................................................................................85
9.6. Safety Analysis........................................................................................................85
9.6.1. Analysis of Primary Endpoint ....................................................................85
9.6.2. Analysis of Secondary Safety Endpoints....................................................85
9.6.2.1. Adverse Events..........................................................................85
9.6.2.2. Laboratory Tests Abnormalities................................................85
9.6.3. ECG ............................................................................................................86
9.7. Data Safety Monitoring Committee ........................................................................87
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................87
11. DATA HANDLING AND RECORD KEEPING .............................................................87
11.1. Case Report Forms/Electronic Data Record .........................................................87
11.2. Record Retention...................................................................................................88
12. ETHICS..............................................................................................................................88
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............88
12.2. Ethical Conduct of the Study ................................................................................89
12.3. Patient Information and Consent...........................................................................89
12.4. Patient Recruitment...............................................................................................89
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................89
13. DEFINITION OF END OF TRIAL...................................................................................90


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13.1. End of Trial in a Member State.............................................................................90
13.2. End of Trial in all other Participating Countries...................................................90
14. SPONSOR DISCONTINUATION CRITERIA ................................................................90
15. PUBLICATION OF STUDY RESULTS..........................................................................90
15.1. Communication of Results by Pfizer ....................................................................90
15.2. Publications by Investigators ................................................................................91
16. REFERENCES ..................................................................................................................93
LIST OF TABLES
Table 1.
Mean (± SD) Total Antibody and ADC Pharmacokinetic Parameters in 
Female Nod-scid Mice Following a Single IV Administration of 
PF-06647263 at 1 mg/kg (Study 12ORUE039)....................................................34
Table 2.
ADC, Ab and Free Payload Pharmacokinetic Parameters on Days 1 and 
43 in Cynomolgus Monkeys Following Q3W IV Administration of 
PF-06647263 (Study 12GR141)...........................................................................36
Table 3.
Detection of Anti-Drug Antibodies (ADA) in Select Sample Collected 
During the Cynomolgus Monkey Toxicology Study (12GR141) ........................37
Table 4.
Possible Dose Levels for the Q3W Regimen Based on when Modified 
Fibonacci Scheme is Initiated at 0.06 mg/kg........................................................46
Table 5.
Dose Escalation Scheme.......................................................................................47
LIST OF FIGURES
Figure 1.
Tumor Growth Curves in BR5 TNBC PDX.........................................................30
Figure 2.
Tumor Growth Curves in BR22 TNBC PDX.......................................................30
Figure 3.
Tumor Growth Curves in OV45 Ovarian Cancer PDX........................................31
Figure 4.
Mean (± SD) Total Antibody and ADC Concentration vs Time Profiles in 
Female nu/nu Mice Following a Single IV Administration of 
PF-06647263 at 1 mg/kg (Study 12OREU039)....................................................34
Figure 5.
Mean (± SD) Total Antibody and ADC Concentration vs Time Profiles in 
Female nu/nu Mice Following a Single IV Administration of 
PF-06647263 at 1 mg/kg (Study MASP143)........................................................35
Figure 6.
Mean (± SD) Total Antibody and ADC Concentration vs Time Profiles in 
Female nu/nu Mice Following a Single IV Administration of 
PF-06647263 at 0.027, 0.09, or 0.27 mg/kg.........................................................35
Figure 7.
Expression of EFNA4 in Breast Cancer as Determined by NanoString® ...........39


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APPENDICES
Appendix 1. Abbreviations......................................................................................................94
Appendix 2. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines.......................................................................................................97
Appendix 3. National Cancer Institute (NCI) common Terminology Criteria for 
Adverse Events (CTCAE) ..................................................................................102
Appendix 4. ECOG Performance Status................................................................................103
Appendix 5. Management of Infusion Related Reactions Including Allergic Reactions, 
Cytokine Release Syndrome or Anaphylaxis .....................................................104
Appendix 6. Detailed Dose Escalation/De Escalation Scheme for mTPI design..................106


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1. INTRODUCTION
1.1. Indication
PF-06647263 is intended to be used for the treatment of adult patients with advanced solid 
tumors unresponsive to currently available therapies or for whom no standard therapy is 
available. 
1.2. Background
Antibody-drug conjugates (ADCs) are compounds comprised of a cytotoxic agent which is 
chemically linked to an antibody that selectively binds to an internalizing tumor-associated 
antigen.1 By delivering the cytotoxic agent to the tumor while minimizing the exposure to 
normal tissues, ADCs have the potential for improving the therapeutic index of cytotoxic 
anti-cancer agents. 
PF-06647263 is an anti-EFNA4 ADC for the treatment of patients with cancer.  EFNA4 is a 
novel ADC target that was identified through analysis of the gene expression profiles of 
aggressive tumor cell populations called cancer stem cells (CSCs) or tumor-initiating cells.  
EFNA4 mRNA expression levels have been found to be enriched in some nonclinical models 
of colorectal cancer (CRC) and pancreatic cancer (Clinical Cancer Res. 2015 May 26).  
Pfizer’s in-house bioinformatics analysis suggests that EFNA4 mRNA expression is also 
elevated in patients with CRC, breast cancer, including triple negative breast cancer (TNBC), 
ovarian cancer (OVCA), non-small cell lung cancer (NSCLC), chronic lymphocytic leukemia 
(CLL) and hepatocellular carcinoma (HCC) relative to the corresponding normal tissues.  In 
non-tumor tissues, EFNA4 is believed to be involved in axonal guidance, wound healing, 
epidermal differentiation, transendothelial migration of leukocytes, retinal 
neovascularization, and craniosynostosis.2,3,4
 
 
TNBC is a heterogeneous disease constituting approximately 15-20% of breast cancers and is 
characterized by the lack of expression of estrogen receptor (ER), progesterone receptor 
(PgR), and the absence of human epidermal growth factor receptor 2 (HER2) overexpression 
and/or amplification.  It occurs more frequently in women less than 50 years old and 
generally behaves more aggressively than other breast cancer subtypes.6 Although TNBC 
patients experience higher rates of pathological complete responses (pCR), when treated with 
neoadjuvant chemotherapy, they experience shorter duration-free survival (DFS) and overall 
survival (OS) relative to patients with non-TNBC.8 The majority of patients receive 
anthracyclines and taxanes in the neoadjuvant or adjuvant settings.  A variety of single agent 
and combination regimens are active in metastatic TNBC, although rapid progression is 
observed in most patients.9 Thus, novel therapeutic options are urgently needed.
 
 
 
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1.3. PF-06647263
PF-06647263 comprises the huE22 humanized IgG1 antibody and the 
linker-payload.  Calicheamicin generates double-strand 
deoxyribonucleic acid (DNA) breaks and therefore impacts both rapidly proliferating and 
quiescent or slowly proliferating cells.7,10
1.3.1. Efficacy
Efficacy studies were carried out in immune-compromised mice harboring subcutaneous 
human tumor xenografts.  The panel of tumor models represented a broad range of tumor 
types and included both PDX and cell line xenografts (CLX).  Target expression was 
retrospectively assessed in tumor extracts by qPCR, immunoblot and/or MesoScale 
Discovery (MSD) immunoassay or in formalin-fixed tumors by mRNA ISH. 
PF-06647263 treatment resulted in sustained tumor regressions in tumor models where the 
standard-of-care (SOC) agents dosed at their maximum tolerated dose, were shown to have 
little impact on tumor growth. 
BR5 is a PDX of human TNBC.  In this model, PF-06647263 treatment resulted in sustained 
regressions for more than 80 days in contrast, to doxorubicin or control ADC which had little 
impact on tumor growth (Figure 1).
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Figure 1.
Tumor Growth Curves in BR5 TNBC PDX.
Vehicle
1.5 mg/kg Doxorubicin
0.09 mg/kg PF-06647263
0.27 mg/kg PF-06647263
0.1 mg/kg Control ADC
0.036 mg/kg PF-06647263
The BR22 PDX represented a less sensitive tumor model of TNBC.  In this model 
PF-0667263 delayed tumor growth for ~40 days but did not produce any complete 
regressions.  Dose levels below 0.27 mg/kg had minimal effect.  There was no impact of 
doxorubicin treatment on tumor growth (Figure 2).
Figure 2.
Tumor Growth Curves in BR22 TNBC PDX.
Vehicle
1.5 mg/kg Doxorubicin
0.09 mg/kg PF-06647263
0.27 mg/kg PF-06647263
0.04 mg/kg Control ADC
0.1 mg/kg Control ADC
0.3 mg/kg Control ADC
0.018 mg/kg PF-06647263
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Similar to the observations in TNBC models, PF-06647263 was also active in OVCA PDX 
models.  In the OV45 ovarian cancer PDX, PF-06647263 resulted in sustained regressions 
for more than 75 days in contrast to the control ADC which did not impact tumor growth 
(Figure 3).
Figure 3.
Tumor Growth Curves in OV45 Ovarian Cancer PDX.
10 mg/kg Control mAb
0.09 mg/kg PF-06647263
0.27 mg/kg PF-06647263
0.1 mg/kg Control ADC
0.018 mg/kg PF-06647263
0.036 mg/kg PF-06647263
Several additional efficacy studies were performed in a variety of human tumor models CRC, 
small cell lung cancer (SCLC), NSCLC, mantle cell lymphoma (MCL), and CLL.  In 
general, PF-06647263 strongly inhibited tumor growth in models of TNBC (non-Claudin 
low), OVCA,  and SCLC and outperformed standard-of-care chemotherapy in all cases tested 
(TNBC and SCLC).  In contrast PF-06647263 did not show activity in Claudin low TNBC, 
Her2+ breast cancer,  CLL or MCL in the limited number of models tested.  The Claudin low 
subtype of TNBC comprises ~30% of TNBC patients and is understood to be a generally 
refractory tumor type. 
 
 
 
 
 
 
 
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1.6. Rationale
1.6.1. Justification for Phase 1 Clinical Starting Dose
The selection of the starting dose for the human Phase 1 trial was based on the preclinical 
safety study results following International Conference on Harmonisation (ICH) S9 Guidance 
entitled “Nonclinical Evaluation for Anticancer Pharmaceuticals”.  Cynomolgus monkey was 
considered to be the most appropriate species for determining the proposed starting dose in 
patients.  
 
  The proposed starting dose of 0.015 mg/kg given as an 
intravenous infusion Q3W represents approximately 1/6 of monkey HNSTD (based on 
human equivalent dose normalized to body surface area).  In addition, given the projected 
human PK parameters based on allometric scaling from cynomolgus monkey PK, the 
projected human average concentration (Cavg) for PF-06647263 at the proposed starting 
dose of 0.015 mg/kg is expected to be approximately 1/20th of the observed monkey Cavg at 
HNSTD.
 
 
 
 
 
 
 
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Body weight-based dosing approach (mg/kg) will be applied for the first-in-patient study of 
PF-06647263 with the goal to reduce interindividual variations in PK exposure.  ADCs in the 
clinic have been administered using body-size based approaches (body weight-based, ie,
mg/kg or BSA-based, ie, mg/m2), and these approaches were consistent with the population 
PK of Adcetris, Kadcyla and Inotuzumab Ozogamicin, in which body weight or BSA was 
identified as significant covariates impacting PK exposure.  
 
 
 
 
 
 
 
  
 
 
1.6.2. TNBC in Dose Expansion
The selection of the indication in dose expansion was based on the expression of EFNA4 in 
human TNBC samples.  Furthermore, in human tumor xenograft models, 
PF-06647263 treatment resulted in sustained regressions and was significantly better than the 
standard-of-care tested in these indications.  Collectively, these findings suggest that 
PF-06647263 should be evaluated in patients with these tumors who have few therapeutic 
options and constitute an urgent unmet medical need.
 
 
 
 
 
 
 
 
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Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Total
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
Part 1 (Dose escalation)
Primary Objective
PPD
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
To assess safety and tolerability at increasing dose levels of 
PF-06647263 administered as an intravenous (IV) infusion every 3 weeks (Q3W) and 
weekly (QW)  in patients with advanced solid tumors unresponsive to currently 
available therapies, or for whom no standard therapy is available, in order to estimate 
the Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose 
(RP2D).
Secondary Objectives

To evaluate the overall safety profile;

To characterize the single and multiple dose pharmacokinetics (PK) of PF-06647263, 
total antibody, and unconjugated payload;

To evaluate the immunogenicity of PF-06647263;

To document preliminary evidence of anti-tumor activity based on the response rate 
(RR) correlating ORR to EFNA4 expression in archival tumor samples.
Part 2 (Expansion)
Primary Objective

To confirm safety and tolerability and explore preliminary evidence of anti-tumor 
activity of PF-06647263 based on response rate (RR) at the RP2D in previously 
treated metastatic TNBC patients. 
Secondary Objectives

To evaluate the overall safety profile at the RP2D; 

To characterize the single and multiple dose PK of PF-06647263, total antibody, and 
unconjugated payload;

To evaluate the immunogenicity of PF-06647263;

To document preliminary evidence of anti-tumor activity based on progression free 
survival (PFS) and overall survival (OS).
 
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2.2. Endpoints
Primary Endpoint (Part 1)

First cycle Dose Limiting Toxicities (DLTs) in order to determine the MTD and 
RP2D.
Primary Endpoint (Part 2)

Response rate (RR) as determined by the Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 criteria.
Secondary Endpoints (Parts 1 and 2)

Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), timing, seriousness and relationship to study therapy;

Laboratory abnormalities as characterized by type, frequency, severity (as graded by 
NCI CTCAE v.4.03) and timing;

Vital Sign abnormalities;

Systemic PK exposure of PF-06647263, total antibody, and unconjugated payload;

Immunogenicity of PF-06647263; incidence of anti-PF-06647263 antibodies (ADA);

Objective tumor response, as assessed using RECIST version 1.1 by calculating the 
Overall Response Rate (ORR), Clinical Benefit Response Rate (CBRR), Progression 
Free Survival (PFS), and Overall Survival (OS)-stratifying for EFNA4 expression
Part 2 only. 
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3. STUDY DESIGN
3.1. Study Overview
This is a Phase 1, two part, open label, multi-center, single arm, non-randomized, multiple 
dose, safety, PK and PD study of single agent PF-06647263 in adult patients with advanced 
solid tumors for whom no standard therapy is available. 
The clinical study will include 2 parts.  Part 1 will estimate the MTD in dose escalation 
cohorts in patients with advanced solid tumors for whom no standard therapy is available in 
order to establish the RP2D.  The initial dosing regimen tested in Part 1 will be 
PF-06647263 administered once every 3 weeks (Q3W) consistent with the pre-clinical 
toxicity study. Evaluation of a weekly (QW) regimen will be initiated when the first patient 
treated with the Q3W regimen experiences a DLT or Grade 2 thrombocytopenia related to 
study treatment.  The starting dose of the QW regimen will not exceed one-third of the 
highest Q3W dose evaluated.  Once initiated, the 2 regimens will be evaluated in parallel and
independently based on the same dose-escalation criteria as described below.  The collective 
safety and efficacy data will be used to identify the regimen or regimens to be used in Part 
2 of the study.  Part 2 will include patients with previously treated metastatic triple negative 
breast cancer (TNBC). 
It is anticipated that the maximum sample size of approximately 70 patients are expected to 
be enrolled in Part 1 of the study at approximately 3 - 4 sites. The actual number of patients 
enrolled will depend upon tolerability of PF-06647263, and the number of dose levels 
required to identify the MTD in the Q3W and QW dosing regimens.  The expansion cohort in 
Part 2 will enroll approximately 24 TNBC patients.  These patients will be response 
evaluable (defined as having at least one on-study tumor assessment).  Enrollment of patients 
within this specific expansion cohort may be reassessed in conjunction with the totality of 
clinical information including exposure, expression and others, if no or minimal antitumor 
activity is observed in that indication (eg, no response is observed in the first 8 evaluable 
patients).  One option for the unselected TNBC cohort would be to pause unselected 
enrollment and enroll patients with moderate to high EFNA4 expressing TNBC and reassess 
the activity after the next 8 evaluable patients.  Conversely, if a high ORR is observed in 
TNBC (See Section 9.3.2) the available clinical data would be used to assess the risk/benefit 
of the treatment and up to 10 additional patients may be enrolled following discussion 
between the Sponsor and Investigators. 
In the event DLTs occur in more than 33% of the patients enrolled in Part 2, enrollment will 
stop and the MTD dose will be reevaluated.  Additional safety information gathered in Part 
2 may be used to modify the dose recommended for future Phase 2 trials. 
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Patients will participate in the study for approximately 6 months in Part 1 and up to 
approximately 18 months in Part 2. This assumes up to 4 weeks of screening, approximately 
4 months of treatment, and a follow-up visit within 4 weeks after the last dose for adverse 
event (AE) and serious adverse event (SAE) collection, and in Part 2 only, long term 
follow-up for survival every two months for up to 12 months after the EOT visit.  Treatment 
with study drug will continue until disease progression, patient refusal, unacceptable toxicity 
occurs, or the study is terminated.  Note: Patients deriving clinical benefit from study 
treatment may continue on study at a reduced dose following recovery of the AE to Grade 
0-1 or baseline, only after discussion between the investigator and Sponsor.
The proposed doses, schedule(s) and PK timepoints may be reconsidered and amended 
during the study based on emerging safety and pharmacokinetic data.
3.1.1. Part 1
3.1.1.1. Starting Dose
Successive cohorts of patients will receive doses of PF-06647263 intravenously (IV) on an 
outpatient basis every 21 days starting at a dose level of 0.015 mg/kg.
3.1.1.2. Criteria for Dose Escalation/MTD Determination 
A modified toxicity probability interval method (mTPI) targeting a DLT rate of 25% with an 
equivalence interval (20%-30%) will be utilized in order to estimate MTD. Patients will be 
enrolled in cohorts of 2 to 4, starting with 0.015 mg/kg for the first cohort. Subsequent dose 
levels may include a maximum 100% escalation until either the dose is ≥0.060 mg/kg, a 
patient experiences a DLT or Grade 2 thrombocytopenia considered related to 
PF-06647263 after which, dose escalation in subsequent cohorts will follow a modified 
Fibonacci scheme with maximum dose increases of 67%, 50%, 33%, 33%.  Table 
4 illustrates the possible dose levels when the Modified Fibonacci scheme is initiated at the 
3rd dose level. Intermediate dose levels to further evaluate the safety and/or PK may be 
evaluated following discussion between Sponsor and Investigator. 
Table 4.
Possible Dose Levels for the Q3W Regimen Based on when Modified 
Fibonacci Scheme is Initiated at 0.06 mg/kg
Modified Fibonacci^ scheme starts from 
dose level 3
Dose Level
Dose (mg/kg Q3W)
-1
0.01
1
(Starting dose)
0.015
2
0.030
3
0.060
4
0.100
5
0.150
6
0.200
7
0.267
^ dose increase: 67%, 50%, 33%, 33%, 33%, 33%


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The evaluation of a QW regimen will be initiated when the first patient experiences a DLT or 
Grade 2 thrombocytopenia considered related to PF-06647263 is observed in the Q3W 
regimen.  The starting weekly dose will be ≤33% of the highest cumulative dose that has 
been evaluated.  The same criteria for dose escalation will be applied to the QW dose 
escalation scheme.
The modified toxicity probability interval (mTPI) design uses a Bayesian statistics 
framework and a beta/binomial hierarchical model to tailor dose-escalation and de-escalation 
decisions. These rules are conceptually similar to those used by the 3+3 design and all the 
dose-escalation decisions for a given trial and can be pre-calculated under the mTPI design 
and presented in a two-way table (Table 5).
The decision rules to “dose escalate” (E), “no change in dose” (S), “dose de-escalate” (D) or 
“dose de-escalate, unacceptable toxicity” (U) are described below:
Table 5.
Dose Escalation Scheme
Number of Patients treated at a Dose level
DLT n=2
n=3
n=4
n=5
n=6
n=7
n=8
n=9
n=10
n=11
n=12
n=13 n=14 n=15
0
E
E
E
E
E
E
E
E
E
E
E
E
E
E
1
D
S
S
S
E
E
E
E
E
E
E
E
E
E
2
U
D
D
S
S
S
S
S
S
S
S
E
E
E
3
U
U
D
D
S
S
S
S
S
S
S
S
S
4
U
U
U
D
D
D
D
D
S
S
S
S
5
U
U
U
U
U
D
D
D
D
D
S
6
U
U
U
U
U
U
D
D
D
D
7
U
U
U
U
U
U
U
U
D
In this table, the prior distribution of DLT is set as a beta (0.75,0.65), and the threshold 
probability for early termination and dose exclusion is set to 0.95.  Doses with an incidence 
of DLT >33% (eg, 4 out of 10) will not be declared the MTD but will be allowed by the 
mTPI method. (Appendix 6)
Cohorts of patients could receive doses already tested but a dose that is associated with the 
decision “dose de-escalate, unacceptable toxicity (U)” cannot be revisited and no more 
patients should be treated at this dose or higher doses for the remainder of the trial.
A minimum of 9 patients treated at the MTD is required to establish such dose as the RP2D. 
The maximum sample size is anticipated to be approximately 70 patients but the actual 
sample size will depend on the underlying dose toxicity profile (the variability in actual data 
realization).
Dose escalation will stop under any of the following conditions: 
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2. At least 9 patients have been accumulated at a dose that is predicted to be the
MTD.
3. All doses explored appear to be overly toxic and the MTD cannot be determined.
Dose escalation for other regimens (eg, doses administered weekly) would follow the same 
escalation scheme described above and in Table 5.  All significant AEs and SAEs will be 
reviewed by the sponsor and investigators to determine if the dose allocation schedule 
requires modification.  The cohort steering committee comprised of the Pfizer clinical team 
and the investigators can override the dose escalation increment specified in this protocol if a 
more conservative approach is mandated.
Patients will continue with study treatment until disease progression, patient refusal, or 
unacceptable toxicity occurs.  Note: Patients deriving clinical benefit from study treatment
may continue on study at a reduced dose following recovery of the AE to Grade 0-1 or 
baseline, only after discussion between the investigator and Sponsor.  Patients experiencing a 
DLT may be managed with dose modification or discontinuation.  During dose escalation, 
patients treated in the Q3W regimen who do not complete the DLT evaluation period 
(21 days following the first study treatment administration) for non safety reasons will be 
replaced.  Patients treated in the QW regimen who do not receive all 3 of the scheduled doses 
during the first cycle of treatment due to non safety reasons will be replaced. 
Intra-patient dose escalation will not be permitted in this study.
In general, subsequent dose levels may not be opened until all patients entered at the current 
dose level have been treated and observed for at least one complete cycle and the number of 
DLTs among those patients in their first cycle has been determined.  However, in certain 
situations, such as when sufficient numbers of patients have been evaluated for 1 cycle and 
the outcome in the remaining patients will not change the decision criteria, subsequent dose 
levels may be opened following discussion with the Sponsor. 
3.1.1.3. DLT Definitions
Severity of adverse events will be graded according to NCI CTCAE version 4.03. For the 
purpose of dose escalation, any of the following adverse events which are not considered 
related to disease progression occurring in the first cycle of treatment (Q3W regimen: 
21 days or until the patient receives the 2nd infusion if there are treatment delays, QW 
regimen: 21 days or until the patient receives the 4th infusion if there are treatment delays) 
will be classified as DLTs:

Hematologic:

Grade 4 neutropenia lasting >7 days.

Febrile neutropenia (defined as neutropenia ≥ Grade 3 and a single body 
temperature >38.3°C or a sustained temperature of ≥38°C for more than one 
hour).

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
Any grade thrombocytopenia associated with clinically significant or 
life-threatening bleeding.

Grade 4 thrombocytopenia ≥72 hours or platelets ≤10,000/mm3 regardless of 
duration.

Non-hematologic:

Bilirubin increase ≥2x upper limit of normal (ULN) and not related to disease 
progression or other known cause.

All other Grade 3 toxicities, except those that have not been maximally treated 
(eg, nausea, vomiting, diarrhea).

Delay by more than 2 weeks in receiving the next scheduled cycle due to 
persisting toxicities not attributable to disease progression.  Note: Patients deriving 
clinical benefit from study treatment may continue on study at a reduced dose 
following recovery of the AE to Grade 0-1 or baseline, only after discussion 
between the investigator and Sponsor.
Grade ≥3 cytokine release syndrome, infusion related reaction, allergic reaction, or 
anaphylaxis will not be considered as DLTs but may be a reason for study discontinuation 
and should be reviewed with Pfizer.
3.1.1.4. MTD Definition
The MTD would be any doses with true toxicity probabilities in the Equivalence Interval (EI) 
where the EI is defined as [20%-30%]. 
In practice, the MTD will be the highest dose associated with the occurrence of DLTs ≤33% 
(eg, 3/9 evaluable patients experience a DLT during the first treatment cycle). 
3.1.1.5. Recommended Phase 2 Dose (RP2D) Definition
The Recommended Phase 2 Dose (RP2D) is the dose chosen for further study based on 
Part 1 results and will be communicated to the investigators. If the MTD proves to be 
clinically feasible for long term administration in a reasonable number of patients, such dose 
usually becomes the RP2D. Further experience with the MTD may result in a RP2D dose 
lower than the MTD.
3.1.2. Dose Expansion Phase (Part 2)
Once the MTD or RP2D has been determined, patients with TNBC regardless of 
EFNA4 expression (n=24 response evaluable) will be enrolled in Part 2 of the study. 
 
 
 
If the DLT rate exceeds 33% in the patients treated at the MTD/RP2D (in Part 1 and Part 2), 
enrollment will be interrupted in order to determine whether the MTD/RP2D needs to be 
re-assessed.
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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 non-medical 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 appropriately qualified 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:
(Part 1 only): Histological or cytological diagnosis of solid tumor that is 
advanced/metastatic and resistant to standard therapy or for which no standard 
therapy is available.
(Part 2 only): Histological or cytological diagnosis of the following:
a.
Previously treated metastatic TNBC (n=24 response evaluable).  TNBC as 
characterized by:

≤1% of tumor cell nuclei immunoreactive for ER or PR;
And

HER2 test result as negative per American Society of Clinical 
Oncology/Clinical Association pathologists reccomendations if a single test (or 
both tests) performed show:

IHC (Immunohistochemistry) 1+ as defined by incomplete membrane staining 
that is faint/barely perceptible and within > 10% of the invasive tumor cells, 
or:

IHC 0 as defined by no staining observed or membrane staining that is 
incomplete and is faint/barely perceptible and within ≤ 10% of the invasive 
tumor cells, or:

ISH negative based on: Single-probe average HER2 copy number < 
4.0 signals/cell Dual-probe HER2/CEP17 ratio < 2.0 with an average 
HER2 copy number < 4.0 signals/cell
http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2013.50.9984 accessed 3 December 
2015
Note: Moderate to high EFNA4 expression* may be required after the ongoing 
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*EFNA4 expression analyzed by NanoString ® in Clinical Laboratory Improvement 
Amendments (CLIA) validated laboratory based on the archival sample or fresh biopsy 
sample. (if the archival sample is unavailable) 
(Part 1 only): Patients may have measurable or non-measurable disease.
(Part 2 only): Patients must have at least one measurable lesion as defined by 
RECIST version 1.1. 
Patients must give consent to the collection of archival formalin-fixed 
paraffin-embedded (FFPE) tumor tissue block, if available, for exploratory biomarker 
and EFNA4 expression analysis. 

(Part 2 only): Patients must consent to a pre-treatment biopsy if a recent biopsy is not 
available within 6 months prior to consent and no intervening therapy was 
administered.
Adults age 18 years. 
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
Adequate bone marrow function, including all of the following:
a.
Absolute neutrophil count (ANC) 1,500/mm3 or 1.5 x 109/L;
b. Platelets 100,000/mm3 or 100 x 109/L;
c.
Hemoglobin 9 g/dL.
Adequate renal function, including all of the following:
a.
Serum creatinine 1.5 x upper limit of normal (ULN) or estimated creatinine 
clearance 60 ml/min as calculated using the method standard for the institution;
b. Urinary dipstick <2+ protein.  If 2+ protein on urine dipstick, then urine protein 
to creatinine ratio (UPCR) ratio 0.5 as characterized by spot urine sample.
Adequate liver function, including all of the following:
a.
Total serum bilirubin 1.5 x ULN unless the patient has documented Gilbert 
syndrome.  Note: If organ function abnormalities are considered due to tumor, 
total serum bilirubin must be ≤2 x ULN.;
b. Aspartate and alanine aminotransferase (AST & ALT) 2.5 x ULN; 5.0 x ULN 
if there is liver involvement secondary to tumor; 
c.
Alkaline phosphatase 2.5 x ULN; (5 x ULN in case of bone metastasis). 
Resolved acute effects of any prior therapy to baseline severity or CTCAE 
Grade 1 except for AEs not constituting a safety risk by investigator judgment.


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Negative serum/urine pregnancy test (for females of childbearing potential) at 
screening and within 72 hours of starting treatment.
Male and female patients of childbearing potential must agree to use two (2) highly 
effective methods of contraception throughout the study and for at least 28 days after 
the last dose of assigned treatment.  A patient is of childbearing potential if, in the 
opinion of the investigator, he/she is biologically capable of having children and is 
sexually active. 
Female patients who are not of childbearing potential (ie, meet at least one of the 
following criteria):
a.
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
b. Have medically confirmed ovarian failure or; 
c.
Achieved post-menopausal status, defined as: cessation of regular menses for at 
least 12 consecutive months with no alternative pathological or physiological 
cause; have a serum follicle-stimulating hormone (FSH) level within the 
laboratory’s reference range for postmenopausal females. 
Evidence of a personally signed and dated informed consent document indicating that 
the patient has been informed of all pertinent aspects of the study.
Willingness and ability to comply with the study scheduled visits, treatment plans, 
laboratory tests and other procedures. 
4.2. Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
Patients with known symptomatic brain metastases requiring steroids.  Patients with 
previously diagnosed brain metastases are eligible if they have completed their 
treatment and have recovered from the acute effects of radiation therapy or surgery 
prior to the start of study medication, have discontinued corticosteroid treatment for 
these metastases for at least 4 weeks and are neurologically stable.
Major surgery, radiation therapy (other than palliative radiotherapy to lesions that will 
not be followed for tumor assessment on this study ie, non target lesions) or systemic 
anti-cancer therapy within 4 weeks (6 weeks for mitomycin C or nitrosoureas) or 
hormonal, biological or investigational agents within 2 weeks (or within 5 times the 
half life of the agent) of starting study treatment.  If the immediate prior regimen 
included only weekly chemotherapy, then a 2 week washout period is acceptable.
Previous high dose chemotherapy requiring stem cell rescue or bone marrow 
transplant.
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(Part 2 only): >4 prior systemic chemotherapy-containing regimens.
Significant prior allergic reaction to recombinant human or murine proteins. 
Active and clinically significant bacterial, fungal or viral infection including 
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) 
or acquired immunodeficiency syndrome (AIDS)-related illness.
 
History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
Any of the following in the previous 12 months: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism.
Current active treatment in another interventional therapeutic clinical study. 
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. 
Patients who are investigational site staff members directly involved in the conduct of 
the trial 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 trial.
Pregnant females; breastfeeding females; males and females of childbearing potential 
who are unwilling or unable to use two (2) highly effective methods of contraception 
as outlined in this protocol for the duration of the study and for at least 28 days after 
last dose of investigational product Life Style Guidelines.
In this study, patients of childbearing potential will receive PF-06647263, a compound for 
which the teratogenic risk is currently unknown.  Two (2) methods of highly effective 
contraception must be used throughout the study and continued for at least 28 days after the 
last dose.  The investigator, in consultation with the patient, will select two appropriate 
methods of contraception for the individual patient from the permitted list of contraception 
methods, and instruct the patient in their consistent and correct use.  The investigator, at each 
study visit, will discuss with the patient the need to use highly effective contraception 
consistently and correctly and document such conversation in the patient chart.  In addition, 
the investigator will instruct the patient to call immediately if a selected birth control 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:
Established use of oral, inserted, injected or implanted hormonal methods of 
contraception are allowed provided the patient remains on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness.
Correctly placed copper containing intrauterine device (IUD).
Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
suppository).
Male sterilization with appropriately confirmed absence of sperm in the 
post-vasectomy ejaculate.
Bilateral tubal ligation or bilateral salpingectomy.
4.3. Sponsor Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
trial is documented in the study contact list located in the study manual. 
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 number, 
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 patients 
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 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 they 
will be directed back to the investigational site.
5. STUDY TREATMENTS
5.1. Allocation to Treatment
Eligible patients will be enrolled to receive PF-06647263 in an open-labeled, unblinded 
manner.  In Part 1 patients will be successively assigned to the next available treatment slot 
at a dose level and treatment regimen decided on after the previous cohort’s safety evaluation 
and ongoing observations of earlier enrolled patients.  In Part 2 patients will be dosed at the 
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Dose level allocation will be performed by the Sponsor after patients have given their written 
informed consent and have completed the necessary baseline assessments. The Investigator 
or site staff will complete a Patient Registration Form and send it to the designated Sponsor 
study team member.  The Sponsor will assign a patient identification number, which will be 
used on all Case Report Form (CRF) pages and other trial-related documentation or 
correspondence referencing that patient.  The procedures for enrolling a patient will be 
described in the Study Manual.
No patient shall receive study drug until the Investigator or designee has received the 
following information in writing from the Sponsor:

Confirmation of the patient’s enrollment;

Specification of the dose level for that patient; and

Permission to proceed with dosing the patient.
The Sponsor or designee will notify the other sites of the inclusion of a new patient, and will 
inform study sites about the next possible enrollment date.  The investigator’s knowledge of 
the treatment should not influence the decision to enroll a particular patient or affect the 
order in which patients are enrolled.
5.2. Drug Supplies
PF-06647263 will be supplied for the study by Pfizer.
Study centers will receive a supply of Clinical Trial Material upon activation with 
instructions on how to confirm drug receipt.  Resupplies will be made during the course of 
the study based on need.  The details on drug supply will be provided in the Study Manual.  
The study monitor should be contacted for any issues related to drug supplies. 
5.2.1. Formulation and Packaging
PF-06647263 for injection, 10 mg extractable per vial, is presented as a sterile lyophilized 
product, white to off white cake, packaged in a 10 mL amber glass tubing vial with a 20 mm 
rubber stopper and a 20 mm aluminum overseal. 
 
 
 
 The 
volume of the solution in the vial after reconstitution is 2.34 mL to ensure the extractable 
volume (2 mL) can be withdrawn by syringe.  The vial is designed for single use.
The packages will be properly labeled according to local regulatory requirements.
5.2.2. Preparation and Dispensing
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.  All preparations should take place under aseptic conditions.
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The starting dose level will be 0.015 mg/kg.  The patient’s actual body weight will be used to 
calculate the mg/kg dose and the calculated dose will be rounded off to the first decimal 
point.  Specific preparation and dispensing instructions are provided in the Investigational 
Product (IP) Manual.  Anticipated variance to the instructions in the IP Manual should be 
discussed with the sponsor or designee.
5.2.3. Administration
PF-06647263 will be administered per the IP Manual as an IV infusion over approximately 
60 minutes (± 5 minutes) on an outpatient basis.  Each patient may receive 
PF-06647263 until disease progression, unacceptable toxicity, withdrawal of consent, or 
study termination.  Note: Patients deriving clinical benefit from study treatment may 
continue on study at a reduced dose following recovery of the AE to Grade 0-1 or baseline, 
only after discussion between the investigator and Sponsor.
In the case of infusion related reactions, characterized by fever and chills, and less commonly 
hypotension, the Sponsor should be notified and pretreatment medication should be 
administered prior to subsequent infusions (in the case that the patient is able to continue on 
treatment as per Appendix 5).  The decision to incorporate pre-medication in all patients will
be made following discussions between the Sponsor and Investigators.  Premedication should 
include acetaminophen and diphenhydramine (or other antihistamine) approximately 0.5 to 
2 hours before each PF-06647263 administration.  The pretreatment medications will not be 
supplied by Pfizer. 
Suggested starting doses are 650 to 1000 mg acetaminophen and 50 mg diphenhydramine (or 
equivalent of other antihistamine) IV or oral.  Two (2) additional doses of acetaminophen 
may be administered approximately every 4 hours after the initial pretreatment or as needed. 
The use of an infusion pump is the preferred method of administration to ensure accurate 
delivery of the investigational product, but gravity drips are allowed.  Please refer to the IP 
Manual for infusion rate and duration.
5.2.4. Recommended Dose Modifications
Every effort should be made to administer study treatment on the planned dose and schedule.
In the event of significant toxicity dosing may be delayed and/or reduced as described below.  
In the event of multiple toxicities, dose modification should be based on the worst toxicity 
observed.  Patients are to be instructed to notify Investigators at the first occurrence of any 
adverse symptom.
Dose modifications may occur in three ways:

Within a cycle: dosing interruption until adequate recovery and dose reduction, if 
required, during a given treatment cycle; 

Between cycles: next cycle administration may be delayed due to persisting toxicity 
when a new cycle is due to start;


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
In the next cycle: dose reduction may be required in a subsequent cycle based on 
toxicity experienced in the previous cycle. 
5.2.5. Dose Interruptions/Delay
Patients experiencing Grade 3 or 4 potentially treatment related toxicity or intolerable 
Grade 2 toxicity despite supportive care should have their treatment interrupted/delayed.  
Appropriate follow up assessments should be done until adequate recovery occurs as 
assessed by the Investigator. 
For patients treated in the Q3W regimen, if a treatment interruption continues beyond 
Day 21 of the current cycle, then the day when treatment is restarted will be counted as Day 
1 of the next cycle.  For patients treated in the QW regimen, the day when the patient 
receives the 4th dose will be counted as Day 1 of Cycle 2.  Subsequent cycles will be 21 days 
in length regardless of treatment delays.  A treatment delay or interruption of more than 
14 days due to lack of recovery will result in discontinuation of the patient from treatment
unless there is clinical benefit and discussed with the Sponsor.  A dose of study treatment
may be given only if:

ANC ≥1,000/mm3.

Platelet count ≥75,000/ mm3.

Non-hematologic toxicities have returned to baseline or Grade ≤1 severity or, at the 
investigator discretion, Grade ≤2 if not considered a safety risk for the patient.
If these conditions are not met, treatment must be delayed by 1 week.  If, after a 1-week 
delay, all toxicities have recovered within the limits described above, treatment with 
PF-06647263 can be resumed.  If the patient has not recovered after 1 week of delay, 
treatment may be delayed by 1 more week.  However, initiation of the next cycle can only be 
delayed by a maximum of 2 weeks.  Therefore, if persisting toxicity does not allow 
PF-06647263 treatment resumption within 35 days of Day 1 of the previous cycle (for 
the Q3W dosing regimen), treatment with PF-06647263 will be permanently
discontinued.  A patient may continue on study after discussion with the Sponsor if there is 
documentation of clinical benefit following recovery of the AE to Grade 0-1 or baseline, only 
after discussion between the investigator and Sponsor.
5.2.6. Dose Reductions
Following dose interruption or cycle delay due to toxicity, the PF-06647263 dose may need 
to be reduced when treatment is resumed.
No specific dose adjustments are recommended for Grade 1/2 treatment-related toxicity.  
However, investigators should always manage their patients according to their medical 
judgment based on the particular clinical circumstances.
Patients experiencing recurrent and intolerable Grade 2 toxicity may resume dosing at the 
next lower dose level once recovery to ≤ Grade 1 or baseline is achieved.
Dose reduction of PF-06647263 by 1 and, if needed, 2 dose levels will be allowed depending 
on the type and severity of toxicity encountered.  Patients enrolled in the first cohort should 
be discontinued from the study if more than 1 dose reduction is required.  Patients enrolled in 


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subsequent cohorts should be discontinued from the study if more than 2 dose reductions are 
required, unless otherwise agreed between the Investigator and the Sponsor.  All dose 
modifications/adjustments must be clearly documented in the patient's source notes and
CRF.
In part 2 of the study a similar dose reduction of PF-06647263 by 1 dose level can be made, 
if deemed necessary depending on the type and severity of toxicity observed (see action table 
below).  As 0.015 mg/kg QW is selected as RP2D for dose expansion, 1 level dose reduction 
to 0.01 mg/kg QW will be recommended.  Additional dose reduction or decrease in 
frequency will require discussion and agreement with the sponsor.
For patients experiencing an adverse event related to PF-06647263 that fails to recover to
NCI CTCAE Grade 1 (or within 1 grade of starting values for pre-existing laboratory 
abnormalities) leading to a treatment delay of >2 weeks should be discontinued unless 
discussed with Pfizer.  Patients deriving clinical benefit from study treatment may continue 
on study at a reduced dose following recovery of the AE to Grade 0-1 or baseline, only after 
discussion between the investigator and Sponsor.
Once a dose has been reduced for a given patient, all subsequent cycles should be 
administered at that dose level, unless further dose reduction is required.  Dose re-escalation 
is not allowed.
The following table summarizes the actions following the toxicities observed during the 
study period.
Event
Action
Serum bilirubin ≥2 x ULN or other Grade 3 or 
4 nonhematologic toxicity considered at least 
possibly related to PF-06647263 per investigator 
judgment (including persistent nausea, 
vomiting, diarrhea despite optimal medical 
therapy)
Hold PF-06647263 infusion until recovery to Grade 
0-1, serum bilirubin < 2 xULN or baseline and 
reduce by 1 dose level.
Discontinue PF-06647263 if dose delay is more 
than 2 weeks*.
If toxicity reoccurs despite reduction, patient may 
be dose reduced again by another dose level upon 
recovery to Grade 0-1 or baseline unless the patient 
is in the first dose group, then only 1 dose reduction 
is allowed. 
Prompt palliative measures are strongly encouraged 
(eg, anti-emetics). 
Patients who experience Grade 4 non hematologic 
toxicities despite optimal medical intervention 
should be discontinued from the study*.  
Hematologic toxicity considered at least possibly 
related to PF-06647263 per investigator 
judgment
Grade 4 neutropenia, ie, ANC 500/mm3
(1.0 x 109/L) for more than 7 days. 
Febrile Neutropenia
Febrile neutropenia, ie, fever with a single temp 
>38.3C or sustained temp 38C for more than 
1 hour with ANC <1000/mm3.
Hold PF-06647263 until recovery of ANC to 1.0 x 
109/L (1,000 cells/mm3) 
Reduce PF-06647263 by 1 dose level.
If toxicity reoccurs despite dose reduction, patient 
may either be held until recovery and continuation 
at same dose, or undergo further dose reduction by 
another dose level unless the patient is in the first 
dose group, then only 1 dose reduction is allowed.


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Event
Action
Thrombocytopenia
Grade 4 thrombocytopenia, ie, PLTS 
25,000 mm3 (25.0 x 109/L). 
Or Grade 3 thrombocytopenia with clinically 
significant or life-threatening bleeding.
Hold PF-06647263 until platelets 75,000/mm3.
For platelet counts 10,000 – 25,000/mm3, continue 
monitoring every 3 days until recovery to 
≥25,000/mm3 (Grade 3 or less).  For platelet counts 
≤10,000/mm3 monitor daily until recovery to 
≥25,000/mm3 (Grade 3 or less). 
Reduce PF-06647263 by 1 dose level.
If toxicity reoccurs despite dose reduction, patient 
may either be held until recovery and continuation 
at same dose, or undergo further dose reduction by 
another dose level unless the patient is in the first 
dose group, then only 1 dose reduction is allowed.
Discontinue for life-threatening bleeding.
Other Grade 4 hematologic toxicity despite 
medical therapy considered at least possibly 
related to PF-06647263 and clinically significant 
per investigator’s judgment
Hold PF-06647263 until recovery to Grade 0-1 or 
baseline and reduce PF-06647263 dose by 1 dose 
level.
If toxicity reoccurs despite dose reduction, patient 
may either be held until recovery and continuation 
at same dose, or undergo further dose reduction by 
another dose level unless the patient is in the first 
dose group, then only 1 dose reduction is allowed.
No recovery of toxicities within 2 weeks of 
scheduled PF-06647263 infusion
Discontinue treatment*
*Patients deriving clinical benefit from study treatment may continue on study at a reduced dose following 
recovery of the AE to Grade 0-1 or baseline, only after discussion between the investigator and Sponsor.
5.2.7. Compliance
The site will complete required dosage Preparation Record located in the Study Manual.  The 
use of the Preparation Record is preferred but it does not preclude the use of an existing 
appropriate clinical site documentation system.  The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose.  This may be used in place of the Preparation Record after 
approval from the Pfizer monitor and must be made available to the monitor during their site 
visits. 
At each study visit, the Investigator, or designee, will assess the patient’s compliance with 
the study requirements.  The assessment will include checks of protocol compliance and 
concomitant medication use.
5.3. Drug Storage and Drug Accountability 
The investigator, or an approved representative (eg, pharmacist), will ensure that all 
PF-06647263 is stored in a secure area, under recommended storage conditions and in 
accordance with applicable regulatory requirements.  PF-06647263 should be stored at 2-8C 
(36-46F) and protected from light until ready to use.  PF-06647263 should not be frozen.  
Specific instructions on storage and handling are provided in the IP manual.  To ensure 
adequate records, all PF-06647263 will be accounted for in the case report form and drug 
accountability inventory forms as instructed by Pfizer.  Unless otherwise authorized by 
Pfizer, at the end of the clinical trial all drug supplies unallocated or unused must be returned 


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to Pfizer or its appointed agent (eg, a contract research organization [CRO]).  If Pfizer 
authorizes destruction at the trial site, the investigator must ensure that the materials are 
destroyed in compliance with applicable environmental regulations, institutional policy, and 
any special instructions provided by Pfizer.  Destruction must be adequately documented. 
Storage conditions stated in the SRSD (Investigator Brochure [IB]) may be superseded by the 
label storage. 
Investigators and site staff are reminded to check temperatures daily (ie, manually or by 
using alarm systems to alert of any excursions) and ensure that thermometers are working 
correctly as required for proper storage of investigational products.  These include 
thermometers for both the room storage and refrigerator storage.  Any temperature 
excursions should be reported to the sponsor. 
The investigational product(s) must be stored as indicated.  Deviations from the storage 
requirements, including any actions taken must be documented and reported to the sponsor.  
Once a deviation is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product. 
Under no circumstances should the investigator or other site personnel supply study drug to 
other investigators, patients, or clinics, or allow supplies to be used other than directed by 
this protocol without prior authorization from Pfizer. 
5.4. Concomitant Medication(s)
Concomitant treatment considered necessary for the patient’s well being may be given at 
discretion of the treating physician.
All concomitant medications, blood products, as well as non drug interventions (eg, 
paracentesis) received by patients from screening (within 28 days prior to the first dose of 
study treatment) until the end of study visit will be recorded on the CRF.  This will include 
the name of the procedure or medication, route and duration of treatment.
For patients who are thrombocytopenic, monitor use of nonsteroidal anti-inflammatory drugs 
(NSAIDs) and other platelet-interactive agents. 
Palliative and supportive care for disease related symptoms may be administered at the 
investigator’s discretion and according to any available American Society of Clinical 
Oncology (ASCO) guidelines.11
5.4.1. Other Anti-tumor/Anti-cancer or Experimental Drugs
No additional anti-tumor therapy including chemotherapy, hormonal therapy, radiotherapy, 
or experimental anticancer medications will be permitted while patients are receiving study 
therapy.  Additionally, the concurrent use of herbal supplements for an anti-cancer treatment 
is not permitted. 
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
providing the lesions were known at the time of study entry and the investigator clearly 
indicates that the need for palliative radiotherapy is not indicative of disease progression. 


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Patients currently being treated with a gonadotropin-releasing hormone agonist (GnRH 
agonist) may continue treatment while on clinical trial B7521001 as long as the GnRH 
agonist treatment has been well tolerated for at least three months prior to study entry.
5.4.2. Supportive Care 
Palliative and supportive care for disease related symptoms may be administered at the 
Investigator’s discretion and according to any available ASCO guidelines. 
5.4.3. Hematopoietic Growth Factors
Primary prophylactic use of granulocyte-colony stimulating factors is not permitted during 
the first cycle but they may be used to treat treatment emergent neutropenia as indicated by 
the current ASCO guidelines. 
Erythropoietin may be used at the investigator’s discretion for the supportive treatment of 
anemia. 
5.4.4. Anti Diarrhea, Anti Emetic Therapy
Primary prophylaxis of diarrhea, nausea and vomiting is permitted in this study at the 
investigator’s discretion.  The choice of the prophylactic drug is up to the investigator with 
sponsor approval and assuming the drug is not included in the Concomitant Medication(s)
section, as well as the duration of treatment assuming there is no known or expected 
drug-drug interaction.  If so, it must be approved by the sponsor.
5.4.5. Anti-inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed assuming there is no 
known or expected drug-drug interaction and assuming the drug is not included in the 
Concomitant Medication(s) section. 
5.4.6. Corticosteroids 
Chronic, systemic corticosteroid use (prednisone 12.5 mg/day or dexamethasone 
2 mg/day) for palliative or supportive purpose is not permitted.  Acute emergency 
administration, topical applications, inhaled sprays, eye drops or local injections of 
corticosteroids are allowed.
5.4.7. Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and PF-06647263 required to minimize the risk 
of impaired wound healing and bleeding has not been determined.  Stopping PF-06647263 is 
recommended at least 7 days prior to surgery.  Postoperatively, the decision to reinitiate 
PF-06647263 treatment should be based on a clinical assessment of satisfactory wound 
healing and recovery from surgery.


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6. STUDY PROCEDURES 
6.1. Screening
All patients being considered for the study and eligible for screening must sign an informed 
consent for the study before completing any study-specific procedures.  A patient 
identification number will be assigned.  The investigator (or appropriate delegate at the site) 
will obtain informed consent from each patient in accordance with the procedures described 
in the Schedule of Activities and Assessments section on Patient Information and Informed 
Consent. 
Patients will be screened within 28 days prior to administration of the study treatment to 
confirm that they meet the patient selection criteria for the study. 
The required screening assessments and laboratory tests are summarized in the Schedule of 
Activities and Assessments section.  Following completion of the screening assessments and 
confirmation of eligibility, patients may be enrolled. 
6.2. Study Period
For treatment period procedures, see Schedule of Activities and Assessments section.
6.3. Follow-up Visit
For follow-up procedures see Schedule of Activities and Assessments section.
In the event a patient is unable to return to the clinic for the follow-up visit, telephone contact 
with the patient to assess adverse events and concomitant medications and treatment is 
expected.  If laboratory assessments are needed to follow-up unresolved adverse events, 
retrieval of assessments performed at an institution local to the patient is acceptable. 
Patients enrolled in Part 2 will be followed for survival by phone call/email every 2 months 
until death or until 12 months from the End of Treatment visit
6.4. Patient Withdrawal
The reason for a patient’s discontinuation from treatment will be documented in the end of 
study/withdrawal CRF.  Patients will be followed for at least 28 days after the last dose of 
study drug for adverse events. 
Patients may withdraw from treatment at any time at their own request, they may be 
withdrawn at the discretion of the investigator or sponsor for safety or behavioral reasons, or 
the inability of the subject to comply with the protocol required schedule of study visits or 
procedures at a given study site. 
Reasons for withdrawal of study treatment may include:

Objective disease progression according to RECIST;

Global deterioration of health status requiring discontinuation;

Adverse event;


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
Medication error without associated adverse event;

Significant protocol violation;

Lost to follow-up;

Patient no longer willing to participate in study;

Study terminated by Sponsor;

Death.
Reasons for withdrawal from study follow-up may include:

Completed study follow-up;

Study terminated by Sponsor;

Lost to follow-up;

Patient refusal for further follow-up;

Death.
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 AEs.
If the patient refuses further visits, and the patient withdraws consent for disclosure of future 
information or for further contact, no further study specific 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 
Investigator will document the reason for this and any corrective and preventive actions 
which he/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.


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7.1. Safety Assessment
Safety assessments will include collection of AEs, SAEs, vital signs and physical 
examination, ECG (12 lead), laboratory assessments, including pregnancy tests and 
verification of concurrent medications.
7.1.1. Pregnancy Testing
For female patients of childbearing potential, a serum or urine pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed on two occasions prior to starting study 
therapy - once at the start of screening and once at the baseline visit, immediately before 
investigational product administration.  Following a negative pregnancy result at screening, 
appropriate contraception must be commenced and a further negative pregnancy result will 
then be required at the baseline visit before the patient may receive the investigational 
product.  Pregnancy tests will also be routinely repeated at every cycle during the active 
treatment period, at the end of study therapy and additionally whenever one menstrual cycle 
is missed or when potential pregnancy is otherwise suspected.  In the case of a positive hCG 
test, the patient will be withdrawn from study medication but may remain in the study. 
Additional pregnancy tests may also be undertaken if requested by Institutional Review 
Board (IRB)/ Independent Ethics Committee (IECs) or if required by local regulations.
7.1.2. Adverse Events
Assessment of adverse events will include the type, incidence, severity (graded by the 
National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] 
version 4.03) timing, seriousness, and relatedness.
Adverse events that occur during the study, including baseline signs and symptoms, will be 
recorded on the adverse events CRF page.
7.1.3. Laboratory Safety Assessment
Haematology and blood chemistry will be drawn at the time points described in the Schedule 
of Activities and analyzed at local laboratories.
Investigators may have additional blood tests performed for the purpose of planning 
treatment administration, dose modification, or following AEs. 
Hematology
Chemistry
Urinalysis
Hemoglobin
ALT/SGPT
Creatinine
Urine dipstick for urine protein:
If 2+ protein on urine dipstick, 
then collect spot urine sample to 
calculate urine protein to creatinine 
ratio (UPCR)
Platelets
AST/SGOT
Uric Acid
Urine dipstick for urine blood :
If positive collect a microscopic 
(Reflex Testing)
WBC
Alk Phos
Glucose (non-fasted)
Coagulation tests
Absolute Neutrophils
Sodium
Albumin
PTT
Absolute Lymphocytes
Potassium
Total Protein
PT or INR


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Hematology
Chemistry
Urinalysis
Absolute Monocytes
Magnesium
Phosphorus 
Pregnancy Test
Absolute Eosinophils
Chloride
Total Bilirubin***
For female patients of childbearing 
potential,  serum or urine 
Absolute Basophils
Calcium
LDH
Bicarbonate or 
carbon dioxide
BUN or Urea
*** For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin 
time (PT)/international normalized ratio (INR), alkaline phosphatase, total bile acids and acetaminophen drug 
and/or protein adduct levels. 
If urine dipsticks are not used by the institution, urine samples are acceptable for the urine 
protein and blood results. 
7.1.4. Vital Signs and Physical Examination
Patients will have a physical exam to include weight, vital signs, assessment of ECOG status 
and height as per the schedule of activities; height will be measured at baseline only.
A complete physical examination (PE) will be performed at Screening, Day 1 of Cycle 1, and 
at the End of Treatment visit for each patient and will include an assessment of all body 
systems (including neurological and dermatological examination, genitourinary examination 
is optional), the measurement of body weight, height (measured at screening only), vital 
signs and assessment of ECOG performance status.  Findings of all physical examinations 
should be recorded in the source documents, and any change from baseline considered by the 
investigator to be clinically significant should be recorded as an adverse event in the CRF.
Weight may be collected within 7 days prior to the PF 06647263 infusion for dose 
preparation on Day 1 of each cycle.  The weight measurement taken for Day 1 of each cycle 
should be used to calculate the patient’s dose of study treatment for all doses in that cycle.  
Abbreviated PEs should be performed as appropriate at each visit where complete physical 
exams are not required, and on an as needed basis for assessment of adverse events.  
Abbreviated exams should be targeted to specific symptoms or complaints and be consistent 
with local standard of care and include a dermatological examination. 
Vital signs will include measurements of blood pressure, pulse rate and temperature (oral, 
tympanic or axillary).  Sitting blood pressure (BP) and pulse rate will be measured with the 
patient’s arm supported at the level of the heart and recorded to the nearest mmHg.  The 
same arm (preferably the dominant arm) should preferably be used throughout the trial.  The 
blood pressure cuff, which has been properly sized and calibrated, should be used to measure 
blood pressure.  The use of automated devices for measuring BP and pulse rate is acceptable.  
When the timing of the measurements coincides with a blood collection, blood pressure and 
pulse rate should be obtained prior to the nominal time of the blood collection. 


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7.1.5. (12-Lead) ECG
12-Lead ECG (single at Screening, triplicate for all others) will be collected as per the 
Schedule of Activities and should be performed after the patient has rested quietly for at least 
10 minutes.  ECGs will be compared to the patient’s Screening ECG and any clinically 
significant changes will be recorded as adverse events and evaluated further, as clinically 
warranted. ECG results will not be centrally reviewed. For each triplicate ECG, three 
consecutive ECGs will be performed at approximately 2 minutes apart to determine the mean 
QTc interval.  If the mean QTc is prolonged (value of ≥501 msec, ie, ≥CTC AE Grade 3), the 
ECGs should be re-evaluated by a qualified person at the institution for confirmation, 
including verification that the machine reading is accurate.  If manual reading verifies a QTc 
of ≥501 msec, immediate correction for reversible causes (including electrolyte 
abnormalities, hypoxia and concomitant medications for drugs with the potential to prolong 
the QTc interval) should be performed.  In addition, repeat ECGs should be immediately 
performed hourly for at least 3 hours until the QTc interval falls below 501 msec.  If QTc 
interval reverts to less than 501 msec, and in the judgment of Investigator(s) and Sponsor is 
determined to be due to cause(s) other than study drug, treatment may be continued with 
regular ECG monitoring.  If in that timeframe the QTc intervals rise above 501 msec the 
study drug will be held until the QTc interval decreases to ≤501 msec.  Patients will then 
re-start the study drug at the next lowest dose level.  If the QTc interval has still not 
decreased to <501 msec after 2-weeks, or if at any time a patient has a QTc interval 
>515 msec or becomes symptomatic, the patient will be removed from the study. If a patient 
experiences a Grade 4 QTc prolongation considered related to study treatment, the patient 
will be removed from the study. Additional ECGs should be performed as clinically 
indicated.
Prior to concluding that an episode of prolongation of the QTc interval is due to study drug, 
thorough consideration should be given to potential precipitating factors (eg, change in 
patient clinical condition, effect of concurrent medication, electrolyte disturbance) and 
possible evaluation by specialist.
If the patient experiences a cardiac or neurologic AE (specifically syncope, dizziness, 
seizures, or stroke), an ECG (triplicate) should be obtained at the time of the event. 
When matched with PK sampling, the ECG must be carried out before each PK sample 
drawing, such that the PK sample is collected at the nominal time (ie, the timing of the PK 
collections over rides the timing of the ECG collections). All efforts will be made to 
complete the ECG at the exact nominal time relative to dosing.  However, ECGs obtained 
within the 15-minute window before the end of infusion and within 10% of the subsequent 
nominal times from dosing will be not be captured as a protocol deviation, as long as the 
exact time of the ECG is noted on the source document and data collection tool (eg, CRF). 
7.2. Long Term Follow-Up (Part 2 Patients Only)
Patients who have permanently discontinued treatment with study drug will enter the long 
term follow-up period until death or for 12 months after the End of Treatment visit. 
Long term follow up information will be collected by telephone call, email, or in person 
approximately every 2 months after the End of Treatment visit.  The date of death and cause 
of death, if applicable will be collected.


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7.3. Pharmacokinetics Assessments
7.3.1. Blood for PK analysis of PF-06647263, Total Antibody, and Unconjugated 
Payload CL-184538
One (9 mL whole blood) blood sample for PK analysis will be collected at each timepoint 
into appropriately labeled tubes at times specified in the Schedule of Activities and the Study 
Procedures section of the protocol. 
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from patients experiencing unexpected and/or serious AE, at the time of AE 
occurrence, and the date and time documented in the CRF.
All efforts will be made to obtain the pharmacokinetic samples at the exact nominal time 
relative to dosing.  However, samples obtained within the 15-minute window before the end 
of infusion for the 1-hour post-dose sample and within 10% of the nominal times from 
dosing for the other post-dose samples will be not be captured as a protocol deviation, as 
long as the exact time of the sample collection is noted on the source document and data 
collection tool (eg, CRF).  If a scheduled blood sample collection cannot be completed for 
any reason, the missed sample time may be re-scheduled with agreement of clinical 
investigators, patient and Sponsor.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the study manual.
Samples will be analyzed using validated analytical methods in compliance with Pfizer 
standard operating procedures.  Drug concentrations of PF-06647263, total antibody, and 
unconjugated payload will be measured using validated methods.  Specifically, total antibody 
concentrations will be measured using ELISA method, PF-06647263 concentrations will be 
measured as conjugated payload using a hybrid Liquid Chromatography Tandem Mass 
Spectrometry (LC-MS/MS)method, and unconjugated payload concentrations will be 
measured using an LC-MS/MS method. 
As part of understanding the PK disposition of the study drug, samples from the highest dose 
group will be retained after PK measurements have been completed for possible metabolite 
identification experiments.  These data will be used for internal exploratory purpose and will 
not be included in the clinical report.  Samples collected for this purpose will be retained in 
accordance to local regulations and if not consumed during the course of these experiments, 
will be discarded.
 
 
 
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7.5. Tumor Response Assessments 
Tumor assessments will include all known or suspected disease sites.  Imaging may include 
chest, abdomen and pelvis computed tomography (CT) or magnetic resonance imaging 
(MRI) scans; brain CT or MRI scan for patients with known or suspected brain metastases; 
bone scan and/or bone x-rays for patients with known or suspected bone metastases.
The same imaging technique used to characterize each identified and reported lesion at 
baseline will be employed in the following tumor assessments.
Anti-tumor activity will be assessed through radiological tumor assessments conducted at 
baseline, during treatment as specified in the Schedule of Activities, whenever disease 
progression is suspected (eg, symptomatic deterioration), and at the time of withdrawal from 
treatment (if not done in the previous 6 weeks).
Assessment of response will be made using RECIST version 1.1.  Changes in tumor size will 
be categorized as complete response (CR), partial response (PR), stable disease (SD), or 
progressive disease (PD), the latter incorporating the appearance of new lesions. 
All patients’ files and radiologic images must be available for source verification and for 
potential peer review. 
CT or MRI scan images for patients enrolled into Part 2 may be collected for an independent 
assessment of response.  Details for the collection of the images will be provided in the Study 
Manual. 
 
 
 
 
 
 
 
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7.7. Immunogenicity Evaluations
Assays to assess for anti-drug (anti-PF-06647263) antibodies (ADA) will be performed.  All 
samples that are positive in a screening assay will be further characterized in terms of 
antibody specificity.  Samples tested positive for ADA may also be analyzed for neutraling 
activity in a neutralizing anti-PF-06647263 antibody (Nab) assay.  Patients found to have 
anti-PF-06647263 antibodies at their final study visit and an ongoing AE possibly related to 
ADA will be asked to return to the clinic for ADA assessment at approximately 3 month 
intervals until the adverse event or its sequelae resolve or stabilize at a level acceptable to the 
investigator and sponsor.
Blood samples (5 mL) to provide approximately 2 mL of serum for ADA and Nab analysis 
will be collected into appropriately labeled tubes at times specified in the Schedule of 
Activities and Study Procedures sections of this protocol.
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the study manual.
Samples that are determined to be positive for ADA may be tested for NAb.  Samples for 
ADA and NAb will be analyzed using validated analytical methods in compliance with 
Pfizer standard operating procedures.  Samples may be further tested in order to further 
characterize the immune response to PF-06647263 and/or for evaluation of the bioanalytical 
methods.
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7.8. Banked Biospecimens 
7.8.1. Markers of Drug Response 
Variation in genetic markers and other biomarkers may help to explain some of the 
variability in response seen with some drugs among different individuals.  This is referred to 
as pharmacogenomic/biomarker research.  Comparing the DNA, RNA, protein, and 
metabolite variation patterns of patients who respond well and those who respond poorly to 
treatment may help to better define the most appropriate group of patients in which to target a 
given treatment.  Collecting biospecimens for exploratory pharmacogenomic/biomarker 
analyses and retaining them in the Pfizer BioBank makes it possible to better understand the 
drug’s mechanism of action and to seek explanations for differences in, for example, 
exposure, efficacy, tolerability, or safety not anticipated prior to the beginning of the study.  
Providing these biospecimens is a required study activity for study sites and patients, unless 
prohibited as such by local regulations or ethics committee decision. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A 4 mL blood biospecimen 
 
will be collected at the Baseline visit to be retained for potential 
pharmacogenomic/biomarker analyses related to drug response, unless prohibited by local 
regulations or ethics committee decision.  For example, putative safety biomarkers, drug 
metabolizing enzyme genes, drug transport protein genes, or genes thought to be related to 
the mechanism of drug action may be examined. 
The Banked Biospecimens will be collected from all patients unless prohibited by local 
regulations or ethics committee decision. Detailed collection, processing, storage and 
shipment instructions are provided in the central laboratory manual.
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It is possible that the use of these biospecimens may result in commercially viable products.  
Patients will be advised in the informed consent document/patient information sheet that they 
will not be compensated in this event.
 
 
 
 
 
 
 
 
 
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 an 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 adverse event 
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.  Serious adverse events occurring to a patient 
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after the active reporting period has ended should be reported to the Sponsor if the 
investigator becomes aware of them; at a minimum, all serious adverse events that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product
 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 one dose of investigational product through the patient’s last 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;

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;

Extravasations;

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.
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8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, 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;

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 is captured on the medication error version of the AE page 
and, if applicable, any associated AEs 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
A Serious Adverse Event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);


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
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 SAE with CTCAE 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
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections and will be handled as SAEs in the safety 
database (see Section 8.14.1 SAE Reporting Requirements). 
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (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. 
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 values ≥2 X ULN with no evidence 
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
For patients with preexisting ALT OR AST OR total bilirubin values above the upper 
limit of normal, the following threshold values should be used in the definition 
mentioned above:

For patients with pre-existing AST or ALT baseline values above the normal 
range, AST or ALT ≥2 times the baseline values and ≥3 X ULN, or ≥8 X ULN 
(whichever is smaller).
Concurrent with

For patients with pre-existing values of total bilirubin above the normal range: 
Total bilirubin increased from baseline by an amount of at least one time the 
upper limit of normal or if the value reaches ≥3 times the upper limit of normal 
(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, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time 
(PT)/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 of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
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 an 
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);


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
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 work-up 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;

Pre-planned 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 non-invasive 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 
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 4.03 CTCAE 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


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Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example headache may be severe (interferes significantly with 
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 serious adverse 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 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.
8.10. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:

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).

A male 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 Serious Adverse Event Report Form and 
Exposure in Utero (EIU) Supplemental Form, regardless of whether an SAE has occurred.  In 
addition, the investigator must submit information regarding environmental exposure to a 
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exposed to a cytotoxic product by inhalation or spillage) using the EIU 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 EIU 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 EIU 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 the 
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 baby, 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;

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 the 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 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 AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the 
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 
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8.12. Withdrawal Due to Adverse Events (See also the Section on Patient Withdrawal)
Withdrawal due to AEs 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.  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 timeframe 
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/her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the timeframes 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 
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8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities
Adverse event reporting, including suspected unexpected serious adverse reactions, will be 
carried out in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Additional details of the analyses will be provided in the statistical analysis plan (SAP) and 
the clinical study report (CSR), which will be maintained by Pfizer.  This document may 
modify the plans outlined in the protocol; however, any major modifications of the 
preliminary endpoint definition and/or its analysis will also be reflected in a protocol 
amendment. 
The information may include details of missing and, if applicable, unused and spurious data.  
Deviations from the statistical plan will be reported in the clinical study report.
9.1. Analysis Sets 
Data Analysis will be performed on the following analysis population.
Safety analysis set.

The safety analysis set includes all enrolled patients who receive at least one dose 
of study medication.
Full analysis set.

The full analysis set includes all enrolled patients.
Per protocol analysis set (evaluable for MTD).

The per protocol analysis set includes all enrolled patients who receive at least 
one dose of study medication and who do not have major treatment deviations 
during first cycle. Patients with major treatment deviations during the first cycle 
of treatment are not evaluable for the MTD assessment and will be replaced as 
needed to permit MTD estimation. Major treatment deviations include failure to 
satisfy major entry criteria (eg, confirmation of the target disease; signed 
informed consent) or use of other anticancer treatments during the active 
treatment and disease follow-up phases other than as defined/allowed in this 
protocol.
Modified Intent-to-Treat (mITT) Population.

The modified intent-to-treat (mITT) is the analysis population that will follow the 
ITT principle and include subjects receiving at least 1 dose of study medication
with baseline assessment and at least 1 post baseline assessment, disease 
progression, or death before the first tumor assessment. The mITT population 
may be used for interim analysis and conference presentations when the study is 
still ongoing.


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PK analysis sets.

The PK parameter analysis population is defined as all enrolled patients treated 
who have sufficient information to estimate at least 1 of the PK parameters of 
interest.
 
9.2. Statistical Methods and Properties
This study has been designed to establish the Maximum Tolerated Dose (MTD) defined as 
the dose that yields approximately 25% probability of DLT and considers equivalent doses 
that yield probability of DLT in the interval (Equivalence Interval) 20% to 30%.  The 25% 
target was chosen based on safety considerations and is considered appropriate based on 
simulations and expert input.  Since mTPI algorithms are known to assign more patients 
above the target dose compared to 3+3 designs, the target was chosen below the maximum 
acceptable DLT rate of 33% (in order to protect study patients from exposure to doses with 
DLT rate higher than 30%). For similar reasons the prior distribution of DLT is set as a beta 
(0.75,0.65) (instead of beta (1,1) as suggested in the original mTPI method) and the threshold 
probability for early termination and dose exclusion is set to 0.975 (instead of 0.95 as 
suggested in the original mTPI method).12 Similarly, doses with an incidence of DLT>33% 
(eg, 4 out of 10) cannot be selected as MTD although is allowed by the mTPI method. 
The modified toxicity probability interval (mTPI) design uses a Bayesian statistics 
framework and a beta/binomial hierarchical model to compute the posterior probability of 
three dosing intervals that reflect the relative difference between the toxicity rate of each 
dose level to the target rate (pT = 0.25). If the toxicity rate of the currently used dose level is 
far smaller than pT, the mTPI will recommend escalating the dose level; if it is close to pT, 
the mTPI will recommend continuing at the current dose; if it is far greater than pT, the mTPI 
will recommend de-escalating the dose level. These rules are conceptually similar to those 
used by the 3+3 design, except the decisions of an mTPI design are based on posterior 
probabilities calculated under a coherent probability model. Being a model-based design, 
mTPI automatically and appropriately tailors dose-escalation and de-escalation decisions for 
different trials with different toxicity parameters. More importantly, all the dose-escalation 
decisions for a given trial can be pre-calculated under the mTPI design and presented in a 
two-way table (Table 5).  In this table, the prior distribution of DLT is set as a beta 
(0.75,0.65), and the threshold probability for early termination and dose exclusion is set to 
0.975.  Doses with an incidence of DLT >33% (eg, 4 out of 10) will not be declared the MTD 
but will be allowed by the mTPI method.
The decision rules to “dose escalate” (E), “no change in dose” (S), “dose de-escalate” (D) or 
“dose de-escalate, unacceptable toxicity” (U) are described on Table 5. Cohorts of patients 
could receive doses already tested but a dose that is associated with decision “Dose 
de-escalate, unacceptable toxicity” cannot be revisited and no more patients should be treated 
at this dose or higher doses for the remainder of the trial.
C
C
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Patients will be enrolled in cohorts of 2 to 4, starting with 0.015 mg/kg Q3W in the first
cohort. Evaluation of a weekly (QW) regimen will be initiated when the first patient treated 
with the Q3W regimen experiences a DLT or Grade 2 thrombocytopenia related to study 
treatment.  The starting dose of the QW regimen will not exceed one-third of the highest 
Q3W dose evaluated.  The maximum sample size would be N=70 but actual sample size will 
depend on the underlying dose toxicity profile and variability in actual data realization.  Once 
initiated, the 2 regimens will be evaluated independently based on the same dose-escalation 
criteria as described below.
A minimum of 9 patients treated at the MTD is required to establish such dose as the RP2D. 
The study will continue accruing until one of the three stopping conditions below is 
triggered. 
The algorithm will stop if any of the following criteria is met:
The maximum sample size has been achieved.
MTD has been identified with sufficient accuracy: at least 9 patients have been 
accumulated on a dose that is currently estimated to be the MTD; or
All doses explored appear to be overly toxic and the MTD cannot be determined. 
Due to binomial data variability in small samples, DLTs may be observed in a first cohort(s) 
assigned 0.015 mg/kg simply by chance even when the true Pr (DLT at 0.015 mg/kg) is fairly 
low. This could result in the estimated posterior DLT rate at 0.015 mg/kg (and all higher 
doses) to exceed the targeted 25% very early in the trial, triggering an early stop when very 
few patients (2-4) have been treated. To prevent stopping the trial prematurely in such cases, 
a step-down option with dose of 0.010 mg/kg is added to the dose grid. This dose will be 
explored only if a high DLT rate occurs in the first cohort assigned to 0.015 mg/kg, ie, it will 
not be used as a starting dose and the algorithm will always assign the first cohort of patients 
to 0.015 mg/kg.
The following table shows the probability of escalating to the next dose level for a range of 
underlying true DLT rates.  For example, for a cohort size of n=3 and for a DLT that occurs
in 10% of patients, there is a greater than 90% probability of escalating.  Conversely, for a 
DLT that occurs with a rate of 70%, the probability of escalating is 3%.  It is assumed that 
dose escalation occurs with either 0/3 or 1/6 patients with DLTs.
Probability of Escalating Dose
True underlying DLT rate
10%
20%
30%
40%
50%
60%
70%
80%
90%
Probability of escalating dose 
0.91
0.71
0.49
0.31
0.17
0.08
0.03
0.009
0.001


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9.3. Sample Size Determination
9.3.1. Part 1:
This First In Patient study is divided into 2 parts.  In Part 1, patients will participate in a dose 
escalation phase aimed at estimating the MTD.  The sample size for this component of the 
study will vary depending on the number of DLTs observed.  It is anticipated that the 
maximum sample size of approximately 70 patients are expected to be enrolled in Part 1 of 
the study at 3 - 4 sites.  The actual number of patients enrolled will depend upon tolerability 
of PF-06647263 and the number of dose levels required to identify the MTD in the Q3W and 
QW dosing regimens. Simulations under several toxicity scenarios estimated sample size 
ranging between 15 and 35 patients.
The minimum and maximum sample sizes after which Part 1 can be stopped and MTD 
declared are approximately 9 and approximately 70 patients, respectively.  As for the number 
of patients treated at each dose, it is expected that the typical number will be 2 to 4 patients 
for the doses actually studied. However, since variable cohort size is allowed, the actual 
number of subjects treated at each dose will vary from 2 to 12.  For example, N=12 is 
achieved if 4 additional patients are enrolled in a cohort of n=8. 
Subsequent patients will enter Part 2, an expansion component aimed at evaluating 
PF-06647263 at the MTD. 
9.3.2. Part 2: 
A sample size of n=24 unselected Triple Negative Breast Cancer (TNBC) “response 
evaluable” patients are proposed.  Assuming a noninformative prior for the TNBC patients 
(ie, uniform distribution in the interval 0% to 100%), a 42% response rate (10 out of 24) 
would provide a 92% posterior probability for the Overall Response Rate (ORR) to exceed 
30% in TNBC patients.  Suppose we look at the data after n=10 patients and find 
6 responders in the TNBC group.  It will provide a 91% chance that the ORR >30% at the 
end of the trial if we continue to enroll another 14 TNBC patients to a total of n=24 patients.  
Ongoing assessment of EFNA4 expression and efficacy of the unselected TNBC cohort will 
occur and continually feedback to the status of enrollment.  Depending on the outcome of 
this assessment one option for the unselected TNBC cohort after determining the lack of 
expression and efficacy might be to pause unselected enrollment and enroll patients with 
moderate to high EFNA4 expressing TNBC and reassess the activity after the next 
8 evaluable patients Additionally, the sample size proposed should be sufficient to assess if 
the concordance between EFNA4 positive/negative results in archival and fresh biopsy 
samples is different from perfect concordance (Kappa Cohen’s statistic equal to 1) if the true 
Kappa value is <0.5.
9.4. Efficacy Analysis
In this First In Patient study anti-tumor activity is a secondary objective.
Tumor response will be presented in the form of patient data listings that include, but are not 
limited to, tumor type, starting dose, tumor measurements, tumor response at each visit, and 
best overall response. Objective tumor response rate, progression-free survival, and clinical 
benefit response rate will be summarized and presented (stratifying for EFNA4 expression 
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9.4.1. Analysis of Overall Response (CR or PR)
For patients to be considered evaluable for efficacy they must have received at least one dose 
of study medication and have a baseline tumor assessment. In Part 2, at the MTD, patients 
must also present with measureable disease.
The best overall response is the best response recorded from first dose until disease
progression/recurrence (taking as reference for PD the smallest measurements recorded since 
screening). In general, the patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria. All measurements (or “too 
small to measure”) must be provided for every target lesion to document SD or PR.
The main goal of confirmation of objective response is to avoid an incorrect estimation of the 
response rate observed. In cases where confirmation of response is not feasible, it should be 
made clear when reporting the outcome of such studies that the responses are not confirmed.
Objective Overall Response and Response Rate (RR) includes CR and PR.
Clinical Benefit Response (CBR) is defined as a CR, PR or SD ≥6 cycles.
9.5. Analysis of Other Endpoints
Descriptive statistics will be used to summarize all patient characteristics, treatment 
administration/compliance,
 
Data will also be displayed graphically, where appropriate.  Additional details of the analysis
are outlined in the SAP.
9.5.1. Analysis of Pharmacokinetics
PK parameters will be determined from the respective concentration-time data using standard 
noncompartmental methods.  Actual sample collection times will be used for the parameter 
calculations.  For PF-06647263 and total antibody, PK parameters including the maximum 
plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area 
under the plasma concentration versus time curve (AUCinf, AUCτ), clearance (CL), volume 
of distribution at steady state (Vss), terminal half-life (t1/2), and accumulation ratio (Rac) will 
be calculated.  For unconjugated payload, PK parameters including Cmax, Tmax, AUCinf, 
AUCτ, t1/2, and Rac will be calculated.
Drug concentrations of PF-06647263, total antibody, and unconjugated payload will be 
summarized graphically and with descriptive statistics by dose, cycle, and the nominal PK 
sampling time.  Noncompartmental PK parameters will be summarized descriptively by dose 
and cycle. 
9.5.2. Pharmacokinetic/Pharmacodynamic Analysis
Safety (eg, DLT, platelet count) and efficacy (RR) data from both Part 1 and Part 2 will be 
pooled for the PK/PD analyses which will be conducted to explore the exposure-response 
relationship using appropriate model-based methods to assist MTD estimation. 
 
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9.5.3. Immunogenicity
Listings and summary tabulations of the anti-PF-06647263 antibody and NAb data at 
baseline and post randomization will be generated.  The percentage of subjects with positive 
ADA and NAb will be summarized by dosing cohort.
Potential impact of immunogenicity on PK and clinical responses including PD markers, 
safety/tolerability and efficacy of PF-06647263 will be explored, if warranted.
9.6. Safety Analysis
Summaries and analyses of safety parameters will include all patients in the Safety Analysis 
Set. AEs will be presented with and without regard to causality based on the Investigator’s 
judgment. The frequency of overall toxicity, categorized by toxicity Grades 1 through 5, will 
be described. Additional summaries will be provided for AEs that are observed with higher 
frequency. Adverse events, ECGs, blood pressure, pulse rate, cardiac monitoring, and safety 
laboratory data will be reviewed and summarized on an ongoing basis during the study to 
evaluate the safety of patients. 
Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
9.6.1. Analysis of Primary Endpoint
DLT is the primary endpoint of the dose escalation component of the study. The occurrence 
of DLTs observed in the dosing cohorts is used to estimate the MTD as described in the 
Study Design section. Adverse Events constituting DLTs will be listed per dose level. 
Because the intent is to find a desirable dose that meets the tolerability criteria based on DLT 
rate while demonstrating clinical activity based on response rate, descriptive statistics (n, 
frequency and percentage) will be reported. Corresponding listings of data will be generated.
9.6.2. Analysis of Secondary Safety Endpoints
9.6.2.1. Adverse Events
Adverse Events (AEs) will be graded by the investigator according to the CTCAE version 
1.1 and coded using the Medical Dictionary for Regulatory Activities (MedDRA).  The focus 
of AE summaries will be on Treatment Emergent Adverse Events, those with initial onset or 
increasing in severity after the first dose of study medication. The number and percentage of 
patients who experienced any AE, SAE, treatment related AE, and treatment related SAE 
will be summarized according to worst toxicity grades. The summaries will present AEs 
both on the entire study period and by cycle (Cycle 1 and Cycles beyond 1). 
9.6.2.2. Laboratory Tests Abnormalities
The number and percentage of patients who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade observed for each lab assay.  The analyses will 
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summarize laboratory tests both on the entire study period and by cycle (Cycle 1 and Cycles 
beyond 1). Shift tables will be provided to examine the distribution of laboratory toxicities.
For laboratory tests without CTC grade definitions, results will be categorized as normal, 
abnormal or not done. 
9.6.3. ECG
The analysis of ECG results will be based on Safety Population patients with baseline and 
on-treatment ECG data.
ECG measurements will be used for the statistical analysis and all data presentations. Any 
data obtained from ECGs repeated for safety reasons after the nominal time-points will not 
be averaged along with the preceding values. Interval measurements from repeated ECGs 
will be included in the outlier analysis as individual values obtained at unscheduled time 
points.
QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie, 
Bazett’s, Fridericia’s and possibly a study specific factor). The adequacy of the correction 
method will be assessed graphically (plots of QT and QTc versus RR) and supplementary 
transformations may be considered, as appropriate. Data will be summarized and listed for 
QT, HR, RR, PR, QRS, QTcF and QTcB by treatment and dose. Individual QTc (all 
evaluated corrections) intervals will be listed by compound, time and dose. The most 
appropriate correction factor will be selected and used for the following analyses of central 
tendency and outliers and used for the study conclusions. Descriptive statistics (n, mean, 
median, standard deviation, minimum, and maximum) will be used to summarize the 
absolute QTc value and changes from baseline in QTc after treatment by compound, dose 
and by time point. For each patient and by treatment, the maximum change from baseline 
will be calculated as well as the maximum post-baseline value across time-points. Outlier 
analysis of the QTc data will be conducted and summarized as follows:

The number of patients with maximum change from baseline in QTc (<30, 30-60, and 
≥60 ms);

The number of patients with maximum post-dose (post-baseline) QTc (<450, 
450-<480, 480- <500, and >500 ms).
Shift tables will be provided for baseline vs worst on study QTc (one or more correction 
method will be used) using Maximum CTC AE Grade. As well as tables of ECG 
abnormality at baseline (yes, no, not done: (n, %)). Patients experiencing clinically-relevant 
morphological ECG changes will be summarized (including frequency and percentage).
The effect of drug concentrations on QTc change from baseline will be explored graphically.  
Additional concentration-QTc analyses may be performed.  Data may be pooled with other 
study results and/or explored further with PK/PD models.


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9.7. Data Safety Monitoring Committee
An external Data Safety Monitoring Committee (DMC) will not be established for the study.
For the purpose of this protocol, Pfizer procedures for periodic safety review will be applied 
by an internal safety review team with medical and statistical capabilities to review 
individual and summary data collected in the safety and clinical databases. Procedures 
include:

Surveillance for SAEs according to regulatory guidelines;

Discussions between the Investigators and the Sponsor of AEs and laboratory tests 
alterations seen at each dose level in an on-going manner at regular teleconferences 
and/or meetings to determine the safety profile and risk/benefit ratio and decide if 
further enrollment is appropriate.
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 is 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)/Independent 
Ethics Committee (IEC), and/or to quality assurance audits performed by Pfizer, or 
companies working with or on behalf of Pfizer, and/or to inspection by appropriate 
regulatory authorities.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
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 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic / original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true.  Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
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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, telephone calls reports).  The records should be 
retained by the investigator according to International Conference on Harmonisation (ICH), 
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 to 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.
12. ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with the 
IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
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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 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws.
Patient names, address, birth date and other identifiable data will be replaced by a numerical 
code consisting of a numbering system provided by Pfizer in order to de-identify the trial 
patient.
In case of data transfer, Pfizer will maintain high standards of confidentiality and protection 
of patient personal data.
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements.
The informed consent document(s) used during the informed consent process must be 
reviewed by the sponsor, approved by the IRB/IEC before use, and available for inspection.
The investigator must ensure that each study patient, or his/her legal representative, is fully 
informed about the nature and objectives of the study and possible risks associated with 
participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient or the patient's legal 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
Advertisements approved by ethics committees and investigator databases may be used as 
recruitment procedures. 
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 which might influence the evaluation of the benefits and risks of the 
investigational product, Pfizer should be informed immediately. 


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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 in a Member State 
End of Trial in a Member State of the European Union is defined as the time at which it is 
deemed that sufficient patients have been recruited and completed the study as stated in the 
regulatory application (ie, Clinical Trial Application (CTA)) and ethics application in the 
Member State.  Poor recruitment (recruiting less than the anticipated number in the CTA) by 
a Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State.
13.2. End of Trial in all other Participating Countries 
End of Trial in all other participating countries 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/IEC, drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of PF-06647263 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 reasonable period of time.  As directed by 
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), the European Clinical Trials 
Database (EudraCT), and or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date for 
studies in adult populations or within 6 months of the primary completion date for studies in 
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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 trial concluded according to the pre-specified protocol or was 
terminated.
EudraCT
Pfizer posts European Union EU Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the primary completion date for studies in adult populations or 
within 6 months of the primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer has no objection to publication by Investigator of any information collected or 
generated by Investigator, whether or not the results are favorable to the Investigational 
Drug.  However, to ensure against inadvertent disclosure of Confidential Information or 
unprotected Inventions, Investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure before it is submitted or otherwise disclosed.
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, Investigator agrees to delay the 
disclosure for a period not to exceed an additional 60 days.
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 multi-centre study, 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, Investigator is free to publish separately, subject to the other requirements 
of this Section.
For all publications relating to the study, 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.


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Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.


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16. REFERENCES
1.
Sapra P, Hooper AT, O’Donnell CJ, et al.  Investigational antibody drug conjugates for 
solid tumors.  Expert Opin Invest Drugs 2011; 20:1131-49.
2.
Moss A, Alvares D, Meredith-Middleton J, et al.  Ephrin-A4 inhibits sensory neurite 
outgrowth and is regulated by neonatal skin wounding.  Eur J Neuro 2005; 22:2413-21.
3.
Lin S, Wang B, Getsios S.  Eph/ephrin signaling in epidermal differentiation and 
disease. Sem Cell Dev Biol 2012; 23(1):92-101. 
4.
Du W, Yu W, Huang L, et al.  Ephrin-a4 is involved in retinal neovascularization by 
regulating the VEGF signaling pathway.  Invest Ophthalmol Vis Sci 2012; 
53(4):1990-8.
5.
Hafner C, Schmitz G, Meyer S, et al.  Differential gene expression of Eph receptors and 
ephrins in benign human tissues and cancers.  Clin Chem 2004; 50(3):490-9.
6.
Andre F, and Zielinski CC.  Optimal strategies for the treatment of metastatic 
triple-negative breast cancer with currently approved agents. Ann Oncol 
2012;23;vi46-vi51.
7.
Zein N, Sinha AM, McGahren WJ, Ellestad GA. Calicheamicin gamma 1I: an antitumor 
antibiotic that cleaves double-stranded DNA site specifically.  Science 1988; 
240(4856):1198-1201.  
8.
Liedtke C, Mazouni C, Hess KR, et. al.  Response to neoadjuvant therapy and long-term 
survival in patients with triple-negative breast cancer.  J Clin Oncol 2008; 
26:1275-1281.
9.
Pal SK, Childs BH, and  Pegram M.  Triple negative breast cancer: unmet medical 
needs.  Breast Cancer Res Treat 2011; 125:627-636.
10.
Hinman LM, Hamann PR, Wallace R, et al.  Preparation and characterization of 
monoclonal antibody conjugates of the calicheamicins: a novel and potent family of 
antitumor antibiotics.  Cancer Res 1993; 53(14):3336-42.
11.
Update of Recommendations for the Use of White Blood Cell Growth Factors: An 
Evidence-Based Clinical Practice Guideline. JCO Jul 1, 2006:3187-3205.
12.
Ji Y, Wang SJ; Modified Toxicity Probability Interval Design: A Safer and More 
Reliable Method Than the 3 + 3 Design for Practical Phase I Trials.  Journal of Clinical 
Oncology May 10, 2013 Vol. 31 no 14 1785-1791.


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Appendix 1. Abbreviations
Ab
Antibody
ACD®
Advanced Cell Diagnostics
ARF
Acute renal failure
ADA
Anti drug antibodies
ADC
Antibody-drug conjugate
AE
Adverse event
AIDS
Acquired immunodeficiency syndrome
ALK/ROS
Anaplastic lymphoma kinase and c-ros oncogene
ALT
Alanin aminotransferase
ANC
Absolute neutrophil count
ASCO
American Society of Clinical Oncology
AST
Aspartate aminotransferase
AUC
Area under the concentration-time curve
BP
Blood pressure
BUN
Blood urea nitrogen
CBC
Complete blood count
CBR
Clinical benefit response
CL
Clearance
CLIA
Clinical Laboratory Improvement Amendments
CLL
Chronic lymphocytic leukemia
CLX
Cell line xenografts
Cmax
Maximum concentration
CNS
Central nervous system
CR
Complete response
CRC
Colorectal cancer
CRF
Case report form
CRO
Contract research organziation
CSA
Clinical study agreement
CSC
Cancer stem cells
CSR
Clinical study report
CT
Computed tomopgraphy
CTA
Clinical trial application
CTC
Circultating tumor cells
CTCAE
Common terminology criteria for adverse events
D
Dose de-escalate
DAB
Diaminobenzidine 
DFS
Disease free survival
DLT
Dose limiting toxicity
DMC
Data safety monitoring committee
DMH
Dimethyl hydrazide
DNA
Deoxyribonucleic acid
E
Escalate
ECG
Electrocardiogram
ECOG
Eastern cooperative oncology group
EDTA
Ethylenediaminetetraacetic acid
EI
Equivalence Interval
EIU
Exposure in-utero
EFNA4
Ephrin-A4
ELISA
Enzyme-linked immunosorbent assay
ER
Estrogen receptor


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FDA
US Food and Drug Administration
FDAAA
Food and drug administration amendments act of 2007
FFPE
Formalin-fixed paraffin-embedded
FSH
Follicle stimulating hormone
GCP
Good clinical practices
GGT
Gamma-glutamyl transferase
GI
Gastrointestinal
GLP
Good laboratory practices
GnRH
Gonadotropin-releasing hormone agonist
HBV
Hepatitis B
HCC
Hepatocellular carcinoma
HCV
Hepatitis C
HER2
Hman epidermal growth factor receptor 2
HIV
Human immunodeficiency virus
HNSTD
Highest non-severely toxic dose
IB
Investigator Brochure
ICH
International conference on harmonisation
IEC
Independent ethics committee
IHC
Immunohistochemistry
IND
Investigational New Drug
INR
International normalized ratio
IP
Investigational product
IRB
Institutional review board
ISH
In situ hybridization
IUD
Intrauterine device
IV
Intravenous
LDH
Lactate dehydrogenase
LFT
Liver function test
LSLV
Last subject last visit
MCL
Mantle cell lymphoma
MedRA
Medical dictionary for regulatory activities
mITT
Modified intent-to-treat
Ml
Mililiters
MRI
Magnetic resonance imaging
mRNA
Messenger RNA
MSD
MesoScale Discovery
MTD
Maximum tolerated dose
mTPI
Modified toxicity probability interaval method
NA
Not applicable
Nab
Neutralizing antibody
NCI
National cancer institute
NS
Sample not evaluated
NSAID
Non-steroidal anti-inflammatory drugs
NSCLC
Non-small cell lung cancer
ORR
Overall response rate
OS
Overall survival
OVCA
Ovarian cancer
PCD
Primary completion date
pCR
Pathological complete response
PD
Pharmacodynamic
PD
Progressive disease
PDX
Patient-derived xenograft


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PE
Physical examination
PFS
Progression free survival
PJC
Premature junctional complex
PK
Pharmacokinetics
PR
Pulse Rate
PR
Partial response
PS
Performance status
PT
Prothrombin time
PTT
Partial Thromboplastin Time
PVC
Premature ventricular contraction
qRT-PCR
Quantitative polymerase chain reaction
QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate Fridericia’s
QW
Once weekly
Q3W
Every 3 weeks
Rac
Accumulation ratio
RBC
Red blood cell
RECIST
Response evaluation criteria in solid tumor
RNA
Ribonucleic acid
RP2D
Recommended Phase 2 dose
RR
Response rate
S
No change in dose
SAE
Serious Adverse Event
SAP
Statistical analysis plan
SCLC
Small cell lung cancer
SD
Stable disease
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SOC
Standard of care
SRSD
Single reference study document
STD
Severely toxic dose in 10% of animals
T1/2
Terminal elimination half-life
TLDA
Taqman low density array
Tmax
Maximum concentration
TNBC
Triple negative breast cancer
TSC
Tumor static concentration
U
Dose de-escalate, unacceptable toxicity
ULN
Upper limit of normal
UPCR
Urine protein to creatinine ratio
US
United States
UTI
Urinary tract infection
Vd
Volume of distribution
WBC
White blood cell
WFI
Water for injection
CCI


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Appendix 2. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines
Adapted from E.A. Eisenhauer, et al: New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1). European Journal of Cancer 45 (2009) 228–247. 
CATEGORIZING LESIONS AT BASELINE
Measurable Lesions
Lesions that can be accurately measured in at least one dimension.

Lesions with longest diameter twice the slice thickness and at least 10 mm or greater 
when assessed by CT or MRI (slice thickness 5-8 mm).

Lesions with longest diameter at least 20 mm when assessed by Chest X-ray. 

Superficial lesions with longest diameter 10 mm or greater when assessed by caliper.

Malignant lymph nodes with the short axis 15 mm or greater when assessed by CT.
NOTE: The shortest axis is used as the diameter for malignant lymph nodes, longest 
axis for all other measurable lesions. 
Non-measurable disease
Non-measurable disease includes lesions too small to be considered measurable (including 
nodes with short axis between 10 and 14.9 mm) and truly non-measurable disease such as
pleural or pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, 
lymphangitic involvement of skin or lung, clinical lesions that cannot be accurately measured 
with calipers, abdominal masses identified by physical exam that are not measurable by 
reproducible imaging techniques.

Bone disease: Bone disease is non-measurable with the exception of soft tissue 
components that can be evaluated by CT or MRI and meet the definition of 
measurability at baseline. 

Previous local treatment: A previously irradiated lesion (or lesion patiented to other 
local treatment) is non-measurable unless it has progressed since completion of 
treatment.
Normal sites

Cystic lesions: Simple cysts should not be considered as malignant lesions and should 
not be recorded either as target or non-target disease.  Cystic lesions thought to 
represent cystic metastases can be measurable lesions, if they meet the specific 
definition above.  If non-cystic lesions are also present, these are preferred as target 
lesions.

Normal nodes: Nodes with short axis <10 mm are considered normal and should not 
be recorded or followed either as measurable or non-measurable disease.


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Recording Tumor Assessments 
All sites of disease must be assessed at baseline.  Baseline assessments should be done as 
close as possible prior to study start.  For an adequate baseline assessment, all required scans 
must be done within 28 days prior to treatment and all disease must be documented 
appropriately.  If baseline assessment is inadequate, subsequent statuses generally should be 
indeterminate. 
Note: For the patient population being evaluated in this protocol, the baseline assessment 
may be completed within 6 weeks prior to randomization. 
Target lesions
All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total, 
representative of all involved organs, should be identified as target lesions at baseline.  
Target lesions should be selected on the basis of size (longest lesions) and suitability for 
accurate repeated measurements.  Record the longest diameter for each lesion, except in the 
case of pathological lymph nodes for which the short axis should be recorded.  The sum of 
the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions 
at baseline will be the basis for comparison to assessments performed on study. 

If two target lesions coalesce the measurement of the coalesced mass is used.  If a 
large target lesion splits, the sum of the parts is used.

Measurements for target lesions that become small should continue to be recorded.  If 
a target lesion becomes too small to measure, 0 mm should be recorded if the lesion is 
considered to have disappeared; otherwise a default value of 5 mm should be 
recorded.
NOTE: When nodal lesions decrease to <10 mm (normal), the actual measurement 
should still be recorded.
Non-target disease 
All non-measurable disease is non-target.  All measurable lesions not identified as target 
lesions are also included as non-target disease.  Measurements are not required but rather 
assessments will be expressed as ABSENT, INDETERMINATE, PRESENT/NOT 
INCREASED, INCREASED.  Multiple non-target lesions in one organ may be recorded as a 
single item on the case report form (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple 
liver metastases’).


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OBJECTIVE RESPONSE STATUS AT EACH EVALUATION
Disease sites must be assessed using the same technique as baseline, including consistent 
administration of contrast and timing of scanning.  If a change needs to be made the case 
must be discussed with the radiologist to determine if substitution is possible.  If not, 
subsequent objective statuses are indeterminate. 
Target disease

Complete Response (CR): Complete disappearance of all target lesions with the 
exception of nodal disease.  All target nodes must decrease to normal size (short axis 
<10 mm).  All target lesions must be assessed.

Partial Response (PR): Greater than or equal to 30% decrease under baseline of the 
sum of diameters of all target measurable lesions.  The short diameter is used in the 
sum for target nodes, while the longest diameter is used in the sum for all other target 
lesions.  All target lesions must be assessed. 

Stable: Does not qualify for CR, PR or Progression.  All target lesions must be 
assessed.  Stable can follow PR only in the rare case that the sum increases by less 
than 20% from the nadir, but enough that a previously documented 30% decrease no 
longer holds. 

Objective Progression (PD): 20% increase in the sum of diameters of target 
measurable lesions above the smallest sum observed (over baseline if no decrease in 
the sum is observed during therapy), with a minimum absolute increase of 5 mm. 

Indeterminate.  Progression has not been documented, and 

one or more target measurable lesions have not been assessed; 

or assessment methods used were inconsistent with those used at baseline;

or one or more target lesions cannot be measured accurately (eg, poorly visible 
unless due to being too small to measure);

or one or more target lesions were excised or irradiated and have not reappeared 
or increased. 
Non-target disease

CR: Disappearance of all non-target lesions and normalization of tumor marker 
levels.  All lymph nodes must be ‘normal’ in size (<10 mm short axis).

Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level 
above the normal limits. 


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
PD: Unequivocal progression of pre-existing lesions.  Generally the overall tumor 
burden must increase sufficiently to merit discontinuation of therapy.  In the 
presence of SD or PR in target disease, progression due to unequivocal increase in 
non-target disease should be rare. 

Indeterminate: Progression has not been determined and one or more non-target 
sites were not assessed or assessment methods were inconsistent with those used 
at baseline.
New Lesions 
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example due to its small size, continued assessment will clarify the etiology.  
If repeat assessments confirm the lesion, then progression should be recorded on the date of 
the initial assessment.  A lesion identified in an area not previously scanned will be 
considered a new lesion.
Supplemental Investigations

If CR determination depends on a residual lesion that decreased in size but did not 
disappear completely, it is recommended the residual lesion be investigated with 
biopsy or fine needle aspirate.  If no disease is identified, objective status is CR.

If progression determination depends on a lesion with an increase possibly due to 
necrosis, the lesion may be investigated with biopsy or fine needle aspirate to clarify 
status. 
Subjective progressionPatients requiring discontinuation of treatment without objective 
evidence of disease progression should not be reported as PD on tumor assessment CRFs.  
This should be indicated on the end of treatment CRF as off treatment due to Global 
Deterioration of Health Status.  Every effort should be made to document objective 
progression even after discontinuation of treatment. 


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Table 1. Objective Response Status at Each Evaluation
Target Lesions
Non-target Disease
NewLesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD
No
PR
CR
Indeterminate or Missing
No
PR
PR
Non-CR/Non-PD, 
Indeterminate, or Missing
No
PR
SD
Non-CR/Non-PD, 
Indeterminate, or Missing
No
Stable
Indeterminate or 
Missing
Non-PD
No
Indeterminate
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
If the protocol allows enrollment of patients with only non-target disease, the following table 
will be used:
Table 2. Objective Response Status at Each Evaluation for Patients with Non-Target 
Disease Only
Non-target Disease
New Lesions
Objective status
CR
No
CR
Non-CR/Non-PD
No
Non-CR/Non-PD
Indeterminate
No
Indeterminate
Unequivocal progression
Yes or No
PD
Any
Yes
PD


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Appendix 3. National Cancer Institute (NCI) common Terminology Criteria for 
Adverse Events (CTCAE)
The NCI CTCAE (Version 4.03 date June 14, 2010) has been placed in the Study Manual for 
this protocol.  Alternatively, the NCI CTCAE may be reviewed on-line at the following NCI 
website: http://ctep.cancer.gov/reporting/ctc.html


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Appendix 4. ECOG Performance Status
Grade
ECOG Performance Status
0
Fully active, able to carry on all pre-disease performance without restriction.
1
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light house work, office work.
2
Ambulatory and capable of all self-care but unable to carry out any work 
activities.  Up and about more than 50% of waking hours.
3
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours.
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed 
or chair.
5
Dead.
*As published in Am J Clin Oncol 5:649-655, 1982.


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Appendix 5. Management of Infusion Related Reactions Including Allergic Reactions, 
Cytokine Release Syndrome or Anaphylaxis
In the event of infusion related reactions, Investigators should institute treatment measures 
according to best medical and nursing practice.
The following treatment guidelines should be employed:
If chills and fever occur, the infusion should be interrupted.  Patients may be treated 
symptomatically and the infusion should be restarted at 50% of the original rate.
NCI-CTCAE Grade 1 allergic reaction or cytokine release syndrome

Monitor for worsening condition.  If the reaction worsens, stop the infusion.  Institute 
premedication for subsequent infusions as per Section 5.2.3. 
NCI-CTCAE Grade 2 allergic reaction or cytokine release syndrome

Stop PF-06647263 infusion.

Administer bronchodilators, oxygen, acetaminophen, etc. as medically indicated.

Resume infusion at 50% of previous rate once reaction has decreased to Grade 1 in 
severity.  Monitor closely for any worsening.  If the reaction recurs, stop infusion.  
Institute premedication for subsequent infusions as per Section 5.2.3.
NCI-CTCAE Grade 3 or Grade 4 allergic reaction or cytokine release syndrome or 
anaphylaxis

A Grade 3 anaphylaxis (hypersensitivity reaction) consists of symptomatic 
bronchospasm requiring parenteral medications with or without urticaria, 
allergy-related edema/angioedema, or hypotension.

A Grade 4 anaphylaxis (hypersensitivity reaction) is a life-threatening event requiring 
urgent intervention.
Treatment of Grade 3 or Grade 4 allergic reaction, cytokine release syndrome or 
anaphylaxis

Stop the PF-06647263 infusion immediately and disconnect infusion tubing from the 
patient.

Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous 
fluids, vasopressor agents, oxygen, etc. as medically indicated.

Telephone Sponsor or designated representative to report an SAE as per Section 8.


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
For a NCI-CTCAE Grade 3 or 4 hypersensitivity reaction, study treatment will be 
discontinued.
Re-treatment following Grade 1 or Grade 2 allergic reactions or cytokine release 
syndrome

Once the PF-06647263 infusion rate has been decreased due to an allergic reaction or 
cytokine release syndrome, it will remain decreased for all subsequent infusions.

If the patient has a second reaction at the lower infusion rate, the infusion should be 
stopped and the patient should receive no further PF-06647263.

If the patient experiences a Grade 3 or 4 allergic reaction, cytokine release syndrome, 
or anaphylaxis at any time, the patient should receive no further PF-06647263.

If there are questions concerning whether an observed reaction is consistent with an 
allergic reaction, cytokine release syndrome, or anaphylaxis, the medical monitor 
should be contacted immediately to assist with grading the reaction.

PK, PD and ADA sampling should continue as long as the sampling does not 
interfere with the medical treatment of the patient.


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Appendix 6. Detailed Dose Escalation/De Escalation Scheme for mTPI design
Escalation/De escalation algorithms for total number of patients treated at the current dose 
level (current and previous cohorts)

With 2 patients treated at current dose level
0 DLT > escalate
1 DLT > de-escalate
2 DLTs > de- escalate and consider current dose as intolerable

With 3 patients treated at current dose level
0 DLT > escalate
1 DLT > remain at the same dose
2 DLTs > de escalate 
3 DLTs > de escalate and consider current dose as intolerable

With 4 patients treated at current dose level
0 DLT > escalate
1 DLTs > remain at the same dose
2 DLTs > de-escalate
3-4 DLTs > de-escalate and consider current dose as intolerable

With 5 patients treated at current dose level
0 DLT > escalate
1-2 DLTs > remain at the same dose
3 DLTs > de escalate
4-5 DLTs > de-escalate and consider current dose as intolerable

With 6 patients treated at current dose level
0-1 DLT > escalate
2 DLTs > remain at the same dose
3 DLTs > de escalate 
4-6 DLTs > de-escalate and consider current dose as intolerable

With 7 patients treated at current dose level
0-1 DLT > escalate
2-3 DLTs > remain at the same dose
4 DLTs > de-escalate
5-7 DLTs > de-escalate and consider current dose as intolerable

With 8 patients treated at current dose level
0-1 DLT > escalate
2-3 DLTs > remain at the same dose
4 DLTs > de escalate
5-8 DLTs > de-escalate and consider current dose as intolerable

With 9 patients treated at current dose level
1-0 DLTs > escalate
2-3 DLTs > remain at the same dose
4 DLTs > de-escalate
5-9 DLTs > de-escalate and consider current dose as intolerable


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
With 10 patients treated at current dose level
1-0 DLTs > escalate
2-3 DLTs > remain at the same dose
4-5 DLTs > de-escalate
6-10 DLTs > de-escalate and consider current dose as intolerable

With 11 patients treated at current dose level
1-0 DLTs > escalate
2-3 DLTs > remain at the same dose
4-5 DLTs > de-escalate
6-11 DLTs > de-escalate and consider current dose as intolerable

With 12 patients treated at current dose level
0-1DLTs > escalate
2-4 DLTs > remain at the same dose
5-6 DLTs > de-escalate
>6 DLTs > de-escalate and consider current dose as intolerable

With 13 patients treated at current dose level
0-2 DLTs > escalate
3-4 DLTs > remain at the same dose
5-6 DLTs > de-escalate
>6 DLTs > de-escalate and consider current dose as intolerable

With 14 patients treated at current dose level
0-2 DLTs > escalate
3-4 DLTs > remain at the same dose
5-6 DLTs > de-escalate
>6 DLTs > de-escalate and consider current dose as intolerable

With 15 patients treated at current dose level
1-0 DLTs > escalate
3-5 DLTs > remain at the same dose
6-7 DLTs > de-escalate
>7 DLTs > de-escalate and consider current dose as intolerable

With 16 patients treated at current dose level
0-2 DLTs > escalate
3-5 DLTs > remain at the same dose
6-7 DLTs > de-escalate
>7 DLTs > de-escalate and consider current dose as intolerable

With 17 patients treated at current dose level
0-2 DLTs > escalate
3-5 DLTs > remain at the same dose
6-7 DLTs > de-escalate
>7 DLTs > de-escalate and consider current dose as intolerable

With 18 patients treated at current dose level
0-2 DLTs > escalate
3-6 DLTs > remain at the same dose
7-8 DLTs > de-escalate
>8 DLTs > de-escalate and consider current dose as intolerable


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
With 19 patients treated at current dose level
0-2 DLTs > escalate
3-6 DLTs > remain at the same dose
7-8 DLTs > de-escalate
>8 DLTs > de-escalate and consider current dose as intolerable

With 20 patients treated at current dose level
0-3 DLTs > escalate
4-6 DLTs > remain at the same dose
7-8 DLTs > de-escalate
>8 DLTs > de-escalate and consider current dose as intolerable

With 21 patients treated at current dose level
0-3 DLTs > escalate
4-7 DLTs > remain at the same dose
8-9 DLTs > de-escalate
>9 DLTs > de-escalate and consider current dose as intolerable

With 22 patients treated at current dose level
0-3 DLTs > escalate
4-7 DLTs > remain at the same dose
8-9 DLTs > de-escalate
>9 DLTs > de-escalate and consider current dose as intolerable

With 23 patients treated at current dose level
0-3 DLTs > escalate
4-7 DLTs > remain at the same dose
8-9 DLTs > de-escalate
>9 DLTs > de-escalate and consider current dose as intolerable

With 24 patients treated at current dose level
0-3 DLTs > escalate
4-8 DLTs > remain at the same dose
9-10 DLTs > de-escalate
>10 DLTs > de-escalate and consider current dose as intolerable

With 25 patients treated at current dose level
0-3 DLTs > escalate
4-8 DLTs > remain at the same dose
9-10 DLTs > de-escalate
>10 DLTs > de-escalate and consider current dose as intolerable

With 26 patients treated at current dose level
0-4 DLTs > escalate
5-8 DLTs > remain at the same dose
9-10 DLTs > de-escalate
>10 DLTs > de-escalate and consider current dose as intolerable

With 27 patients treated at current dose level
0-4 DLTs > escalate
5-9 DLTs > remain at the same dose
10-11 DLTs > de-escalate
>11 DLTs > de-escalate and consider current dose as intolerable


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
With 28 patients treated at current dose level
0-4 DLTs > escalate
5-9 DLTs > remain at the same dose
10-11 DLTs > de-escalate
>11 DLTs > de-escalate and consider current dose as intolerable

With 29 patients treated at current dose level
0-4 DLTs > escalate
5-9 DLTs > remain at the same dose
10-11 DLTs > de-escalate
>11 DLTs > de-escalate and consider current dose as intolerable

With 30 patients treated at current dose level
0-4 DLTs > escalate
5-10 DLTs > remain at the same dose
11-12 DLTs > de-escalate
>12 DLTs > de-escalate and consider current dose as intolerable

With 31 patients treated at current dose level
0-5 DLTs > escalate
6-10 DLTs > remain at the same dose
11-12 DLTs > de-escalate
>12 DLTs > de-escalate and consider current dose as intolerable

With 32 patients treated at current dose level
0-5 DLTs > escalate
6-10 DLTs > remain at the same dose
11-12 DLTs > de-escalate
>12 DLTs > de-escalate and consider current dose as intolerable

With 33 patients treated at current dose level
0-5 DLTs > escalate
6-10 DLTs > remain at the same dose
11-12 DLTs > de-escalate
>12 DLTs > de-escalate and consider current dose as intolerable

With 34 patients treated at current dose level
0-5 DLTs > escalate
6-11 DLTs > remain at the same dose
12-13 DLTs > de-escalate
>13 DLTs > de-escalate and consider current dose as intolerable

With 35 patients treated at current dose level
0-5 DLTs > escalate
6-11 DLTs > remain at the same dose
12-13 DLTs > de-escalate
>13 DLTs > de-escalate and consider current dose as intolerable

SAP_001.pdf: 
Protocol B7521001 (PF-06647263) 
Statistical Analysis Plan
Page 1 of 35
 
Protocol B7521001
A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, 
SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 
IN ADULT PATIENTS WITHADVANCED SOLID TUMORS
Statistical Analysis Plan
(SAP)
Version: 1.0
Author:  
(Statistics, BCD, La Jolla, CA, USA)
Date:     11-April-2014
PPD


Protocol B7521001 (PF-06647263) 
Statistical Analysis Plan
Page 2 of 35
 
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
...........................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Design .............................................................................................................5
2.2. MTD Determination (Part 1).....................................................................................5
2.3. Part 2 .........................................................................................................................8
2.4. Study Objectives .......................................................................................................8
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING................................10
4. HYPOTHESES AND DECISION RULES 
.........................................................................10
4.1. Statistical Hypotheses .............................................................................................10
4.2. Statistical Decision Rules........................................................................................10
4.2.1. Part 1...........................................................................................................10
4.2.2. Part 2...........................................................................................................11
5. SAMPLE SIZE DETERMINATION ..................................................................................11
6. ANALYSIS SETS ...............................................................................................................11
6.1. Full Analysis Set .....................................................................................................11
6.2. ‘PER PROTOCOL’ Analysis Set............................................................................12
6.3. Safety Analysis Set..................................................................................................12
6.4. PK Analysis Set.......................................................................................................12
6.4.1. PK Concentration Set .................................................................................12
6.4.2. PK Parameter Set 
........................................................................................12
6.6. Other Analysis Sets 
.................................................................................................12
6.6.1. Modified Intent-to-Treat Set.......................................................................12
6.7. Treatment Misallocations 
........................................................................................13
6.8. Protocol Deviations 
.................................................................................................13
7. ENDPOINTS AND COVARIATES ...................................................................................13
7.1. Efficacy Endpoint(s) ...............................................................................................13
7.2. Safety Endpoints .....................................................................................................14
7.2.1. DLT Definitions..........................................................................................14
CCI


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
Page 3of 35
 
7.2.2. MTD Definition..........................................................................................15
7.2.3. Recommended Phase 2 Dose (RP2D) Definition.......................................15
7.2.4. Vitals Signs.................................................................................................15
7.2.5. Laboratory Data..........................................................................................15
7.2.6. Adverse Events...........................................................................................15
7.2.7. ECG and QTc Interval................................................................................16
7.2.8. Immunogenicity..........................................................................................17
7.3. PK Endpoints...........................................................................................................17
7.4. PD Endpoints...........................................................................................................18
7.5. Covariates................................................................................................................18
8. HANDLING OF MISSING VALUES................................................................................18
8.1. Missing Dates..........................................................................................................18
8.2. Efficacy Analysis....................................................................................................18
8.3. Pharmacokinetics....................................................................................................19
9. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES..........................20
9.1. Statistical Methods..................................................................................................20
9.2. Statistical Analyses.................................................................................................20
9.2.1. Primary Analysis........................................................................................20
9.2.2. Secondary Analyses....................................................................................20
9.2.2.1. Efficacy Analysis......................................................................20
9.2.2.2. Pharmacokinetics Analyses.......................................................21
9.2.3. Safety Analyses..........................................................................................23
9.2.4. Standard Analyses......................................................................................24
9.2.5. Additional Analysis....................................................................................25
10. REFERENCES..................................................................................................................26
11. APPENDICES...................................................................................................................27
11.1. APPENDIX 1: CATEGORICAL CLASSES FOR ECG AND VITAL 
SIGNS........................................................................................................................27
11.2. APPENDIX 2: RECIST 1.1 TUMOR ASSESSMENT CRITERIA.....................28
11.3. APPENDIX 3: CENSORING DETAILS.............................................................35
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LIST OF TABLES
Table1.
Decision Rules........................................................................................................7


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
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1.AMENDMENTS FROM PREVIOUS VERSION(S) 
Not applicable.
2.INTRODUCTION
This document describes the planned statistical analyses for Protocol B7521001. This
analysis plan is meant to supplement the study protocol. In this document, any text taken
directly from the protocol is italicized. Any deviations from this analysis plan will be
described in the Clinical Study Report (CSR).
2.1.Study Design
This is a Phase1, two part, open label, multi-center, single arm, non-randomized, multiple 
dose, safety, pharmacokinetic and pharmacodynamic study of single agent ADC 
(PF-06647263) in sequential cohorts of adult patients with advanced solid tumors for whom 
no standard therapy is available.  Successive cohorts of patients will receive doses of ADC 
(PF-06647263) intravenously on an outpatient basis every 21days starting at a dose of 
0.015mg/kg. 
The proposed doses, schedule(s) and PK timepoints may be reconsidered and amended 
during the study based on the emerging safety and pharmacokinetic data. 
The actual number of patients enrolled will depend upon tolerability of ADC (PF-06647263) 
and the number of dose levels required to identify the MTD. 
Patients will participate in the study for approximately 6months.  This assumes up to 
4weeks of screening, approximately 4months of treatment, and a follow-up visit within 
4weeks after the last dose for adverse event (AE) and serious adverse event (SAE) 
collection.  Treatment with study drug will continue until disease progression, patient refusal, 
unacceptable toxicity occurs, or the study is terminated.
This clinical study will include 2parts.  Part1 will estimate the MTD in dose escalation 
cohorts in patients withadvanced solid tumors for whom no standard therapy is available in 
order to establish the RP2D.  Part2 will include approximately 30patients enrolled at the 
MTD in order to explore benefit from treatment as suggested by preclinical findings and will 
better define the safety profile at the RP2D.  This expansion cohort will include 
approximately 15patients with TNBC and 15 patients with OVCA.  Additional safety 
information gathered in Part2 may be used to modify the dose recommended for future 
Phase2 trials.
2.2.MTD Determination (Part 1)
A modified toxicity probability interval method (mTPI) targeting a DLT rate of 25% with an 
equivalence interval (20%-30%) will be utilized in order to estimate MTD. Patients will be 
enrolled in cohorts of 2 to 4, starting with 0.015mg/kg for the first cohort.Subsequent dose 
levels may include a maximum 100% escalation until either the dose is 0.060mg/kg, a 
patient experiences a DLT or Grade 2 thrombocytopenia considered related to PF-06647263 


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
Page 6of 35
 
after which, dose escalation in subsequent cohorts will follow a modified Fibonacci scheme 
with maximum dose increases of 67%, 50%, 33%, 33%.  Table 1 illustrates the possible dose 
levels when the Modified Fibonacci scheme is initiated at the 3
rddose level.  Intermediate 
dose levels to further evlatuate the safety and/or PK may be evaluated following discussion 
between Sponsor and Investigator. 
Modified 
Fibonacci^ scheme 
starts from dose 
level 3
Modified Fibonacci^ 
scheme starts from 
dose level 2
Modified Fibonacci^ 
scheme starts from 
dose level 1
Dose Level
Dose (mg/kg Q3W)
Dose (mg/kg Q3W)
Dose (mg/kg Q3W)
-1
0.01
0.01
0.01
1
(Starting dose)
0.015
0.015
0.015
2
0.030
0.030
0.025
3
0.060
0.050
0.038
4
0.100
0.075
0.050
5
0.150
0.100
0.067
6
0.200
0.134
0.089
7
0.267
0.178
0.119
8
0.238
0.158
9
0.211
The modified toxicity probability interval (mTPI) design uses a Bayesian decision-theoretic 
framework and a beta/binomial hierarchical model to tailordose-escalation and de-escalation 
decisions. These rules are conceptually similar to those used by the 3+3 design and all the 
dose-escalation decisions for a given trial can be pre-calculated under the mTPI design and 
presented in a two-way table.
The decision rules to “dose escalate” (E), “no change in dose” (S), “dose de-escalate” (D) or 
“dose de-escalate, unacceptable toxicity” (U) are described below:


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
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Table1. Decision Rules
Number
Number of Patients treated at a Dose level
DLT
n=2 n=3 n=4 n=5 n=6 n=7 n=8 n=9 n=10 n=11 n=12
0
E
E
E
E
E
E
E
E
E
E
E
1
D 
S 
S 
S
E
E
E
E
E
E
E
2
U
D
D 
S 
S 
S 
S 
S 
S 
S 
S
3
U
U
D
D 
S 
S 
S 
S 
S 
S
4
U
U
U
D
D
D
D
D 
S
5
U
U
U
U
U
D
D
D
6
U
U
U
U
U
U
D
7
U
U
U
U
U
U
Cohorts of patients could receive doses already tested but a dose that is associated with 
decision “Dose de-escalate, unacceptable toxicity” cannot be revisited and no more patients 
should be treated at this dose or higher doses for the remainder of the trial.
A minimum of 9patients treated at the MTD dose is required to establish such dose as the 
RP2D. The maximum sample size would be N=70 but actual sample size will depend on the 
underlying dose toxicity profile and variability in actual data realization.  The initial dosing 
regimen tested in Part1 will be PF-06647263 administered once every 3weeks (Q3W) 
consistent with the pre-clinical toxicity study.  Evaluation of a weekly (QW) regimen will be 
initiated when the first patient treated with the Q3W regimen experiences a DLT or Grade2 
thrombocytopenia related to study treatment.  The starting dose of the QW regimen will not 
exceed one-third of the highest Q3W dose evaluated.  Once initiated, the 2regimens will be 
evaluated in parallel and independently based on the same dose-escalation criteria as 
described above.
Dose escalation will stop under any of the following conditions: 
1. The maximum sample size has been achieved;
2. At least 9patients have been accumulated at a dose that is predicted to be the MTD;
3. All doses exploredappear to be overly toxic and the MTD cannot be determined.


Protocol B7521001 (PF-06647263) 
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2.3. Part 2
Upon identification of the MTD, approximately 30 patients will be enrolled at the MTD in 
order to explore benefit from treatment as suggested by preclinical findings and will better 
define the safety profile at the RP2D.  This expansion component aims at evaluating ADC 
(PF-06647263) at the MTD in two cancer indications: 
a. Previously treated metastatic TNBC which expresses EFNA-4 (15 patients).
b. Advanced epithelial ovarian cancer, primary peritoneal or fallopian tube cancer 
(OVCA) which expresses EFNA-4 and which has progressed or relapsed during or 
within 6 months post most recent therapy with a platinum agent (15 patients).
2.4. Study Objectives 
Study Objectives and Endpoints
Part 1 (Dose escalation) Primary Objective
• To assess safety and tolerability at increasing dose levels of PF-06647263 
administered as an intravenous (IV) infusion every 3 weeks (Q3W) and weekly (QW) 
in patients with advanced solid tumors unresponsive to currently available therapies, 
or for whom no standard therapy is available, in order to estimate the Maximum 
Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D). 
Secondary Objectives
• To evaluate the overall safety profile; 
• To characterize the single and multiple dose pharmacokinetics (PK) of PF-06647263, 
total antibody, and unconjugated payload;
• To evaluate the immunogenicity of PF-06647263;
• To document preliminary evidence of anti-tumor activity based on response rate 
(RR).
 
 
Part 2 (Expansion) Primary Objective
• To confirm safety and tolerability and explore preliminary evidence of anti-tumor 
activity of PF-06647263 based on response rate (RR) at the RP2D in patients with 
previously treated metastatic TNBC and advanced platinum-resistant OVCA which 
express EFNA4. 
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Protocol B7521001 (PF-06647263) 
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Secondary Objectives
• To evaluate the overall safety profile at the RP2D; 
• To characterize the single and multiple dose PK of PF-06647263, total antibody, and 
unconjugated payload;
• To evaluate the immunogenicity of PF-06647263;
• To document preliminary evidence of anti-tumor activity based on progression free 
survival (PFS) and overall survival (OS).
 
 
Endpoints
Primary Endpoint (Part 1)
• First cycle Dose Limiting Toxicities (DLTs) in order to determine the MTD and 
RP2D.
Primary Endpoint (Part 2)
• Response rate (RR) as determined by the Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 criteria.
Secondary Endpoints (Parts 1 and 2)
• Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), timing, seriousness and relationship to study therapy;
• Laboratory abnormalities as characterized by type, frequency, severity (as graded by 
NCI CTCAE v.4.03) and timing;
• Vital Sign abnormalities; 
• Systemic PK exposure of PF-06647263, total antibody, and unconjugated payload 
will be determined with validated methods.  Standard noncompartmental PK 
parameters will be determined from the respective concentration-time data;
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Protocol B7521001 (PF-06647263) 
Statistical Analysis Plan
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• Immunogenicity of PF-06647263; Human serum ADA (anti-PF-06647263 antibody) 
samples will be analyzed for the presence or absence of anti-PF-06647263 antibodies, 
following a tiered approach using screening, confirmation and titer/quantitation;
• Objective tumor response, as assessed using RECIST version 1.1 by calculating the 
Overall Response Rate (ORR), Clinical Benefit Response Rate (CBRR), Progression 
Free Survival (PFS), and Overall Survival (OS)-Part 2 only. 
 
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING 
No interim analysis or blinding is planned for this study. The final analysis will be 
conducted after the last subject last visit (LSLV).
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
There are no statistical hypotheses. The emphasis of the final analyses will be on estimation 
of key summary statistics.
4.2. Statistical Decision Rules
4.2.1. Part 1
Decision rules are based on calculating unit probability mass (UPM) of three dosing intervals 
corresponding to under, proper, and over dosing in terms of toxicity.  Specifically, the 
underdosing interval is defined as (0; pT-e1), the over-dosing interval (pT+e2), and the 
proper-dosing interval (pT-e1, pT+ e2), where e1 and e2 are small fractions. For a target 
DLT rate of 0.25, the target equivalence interval is (0.20, 0.30).  The three dosing intervals 
are associated with three different dose-escalation decisions (Table 1).  The under-dosing 
interval corresponds to a dose escalation (E), over-dosing corresponds to a dose de-escalation 
(D), and proper-dosing corresponds to remaining at the current dose (S).  Given a dosing 
interval and a probability distribution, the unit probability mass (UPM) is defined as the ratio 
of the probability of the interval to the length of the interval.  Once the safety assessment is 
complete for Cycle 1, the focus will be on allocation of new subjects to the dose most likely 
to be an MTD. 
The study continues accruing until one of the three stopping conditions below is triggered.  
The algorithm will stop if any of the following criteria is met:
1. The maximum sample size has been achieved.
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Protocol B7521001(PF-06647263)
Statistical Analysis Plan
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2. MTD has been identified with sufficient accuracy: at least 9patients have been 
accumulated on a dose thatis currently estimated to be the MTD, or
3. All doses explored appearto be overly toxic and the MTD cannot be determined. 
Specifically the mTPI approach formalizes stopping rules as follow:
Rule 1 (early termination): if the first dose is too toxic 
Rule 2 (dose exclusion), if dose= i is too toxic 
then exclude doses i
4.2.2.Part 2
Part2 of this study is intended to confirm the safety and tolerability of the dose selected in 
Part1 while assessing the antitumor activity of PF-06647263in patients with solid tumors.  
The DLT rate and analyses of concorcance and confidence interval may be estimated.
Analyses may be performed on data from both Part1 and Part2 to explore the relationships 
between PK parameters, safety endpoints, and efficacy endpoints.
5.SAMPLE SIZE DETERMINATION
Similar to the conventional 3+3design, the exact sample size of the mTPI design in Part1 
cannot be pre-specified in advance because it is a dynamic feature of the design.  The 
minimum sample size after which the Part1 can be stopped and MTD declared is9.If two 
dose regimens are evaluated, the maximum sample size would be 70patients. 
As for the numberof subjects treated at each dose, it is expected that the typical number will 
be 2-4subjects for the doses actually studied.  For the dose declared as MTD at the end of 
trial, this number will be at least9. However, since variable cohort size is allowed, the actual 
number of subjects treated at each dose will vary from 2to 12.  For example,N=12 is 
achieved if 4additional patients are enrolled in a cohort of n=8. 
The sample size in Part2 is based on clinical considerations, rather than statistical 
justification.  It will include 30subjects in two cohorts of tumor types of interest (ie,TNBC 
and OVCA) to confirm the safety and tolerability of the recommended dose based on Part1 
and to assess preliminary anti-tumor activity.
6.ANALYSIS SETS
Several analysis sets are defined and will be considered for this study.
6.1.Full Analysis Set
The full analysis set includes all enrolled patients.  This is equivalent to the ITT 
(intent-to-treat) population.
975
.
0
;
)
/
Pr( 1





data
p
p
T
75
9
.
0
;
)
/
Pr(





data
p
p
T
i


Protocol B7521001 (PF-06647263) 
Statistical Analysis Plan
Page 12 of 35
 
6.2. ‘PER PROTOCOL’ Analysis Set 
Part 2: the per protocol (PP) analysis sets includes all enrolled patients (for each indication) 
who receive at least one dose of study medication and who do not have major treatment 
deviations during first cycle. 
Specifically: Patients with major treatment deviations in Cycle 1 are not evaluable for 
the RP2D assessment and therefore will not be included in the PP analisys.  Major 
deviations include failure to satisfy major entry criteria (eg, confirmation of the target 
disease; signed informed consent) or use of other anticancer treatments during the 
active treatment and disease follow-up phases other than as defined/allowed in this 
protocol.  At least one baseline and one post-baseline disease assessment are required 
for the PP analysis.
Modified PP analysis sets may be considered for additional analyses and would include 
patients enrolled either in Part 1 or in Part 2.
6.3. Safety Analysis Set
The safety analysis set includes all enrolled patients who receive at least one dose of study 
medication.
6.4. PK Analysis Set
6.4.1. PK Concentration Set
The PK concentration population is defined as all treated patients who have at least 
1 concentration measured.
6.4.2. PK Parameter Set
The PK parameter analysis population is defined as all enrolled patients treated who have 
sufficient information to estimate at least 1 of the PK parameters of interest.
 
6.6. Other Analysis Sets
6.6.1. Modified Intent-to-Treat Set
The modified intent-to-treat (mITT) is the analysis population that will follow the ITT 
principle and include subjects receiving at least 1 dose of study medication with baseline 
assessment and at least 1 post baseline assessment or disease progression or death before the 
first tumor assessment.  The mITT population may be used for interim analysis and 
conference presentations when the study is still ongoing.
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Protocol B7521001(PF-06647263)
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6.7.Treatment Misallocations 
Subjects who receive the wrong initial dose for whatever reason will be analyzed according 
to the initial dose actually received.  Subjects who receive the wrong dose after the initial 
dose will be analyzed according to the initial dose received.
6.8.Protocol Deviations
All deviations will be listedin the CSR. Major treatment deviations include, but are not 
limited to, less than 80% of the planned Cycle1 PF-06647263dose provided the 
reduction/omission is not due to treatment-related toxicity.  Subjects with major Cycle1 
treatment deviations are not evaluable for MTD.
7.ENDPOINTSAND COVARIATES
7.1.Efficacy Endpoint(s)
Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor 
(RECIST) version 1.1 by calculating the Overall Response Rate (ORR), Progression Free 
Survival (PFS), and Overall Survival (OS).
All efficacy endpoints are secondary in this study, which include objective tumor response, 
progression-free survival (PFS), and overall survival (OS)for each tumor type in the 
expansion cohorts. The above efficacy endpoints are derived based on the disease response 
per investigator evaluation on the CRF pages, which is the primary method of documentation 
of disease. 
Overall Response (OR) –or Response Rate (RR)is defined as complete response (CR) 
or partial response (PR) according to RECIST 1.1 (Appendix 2). Overall response is the 
best response recorded from first dose until diseaseprogression/recurrence.
Progression Free Survival (PFS) -is defined as the time from Cycle 1 Day 1 (C1D1) to 
first documentation of disease progression or to death due to any cause, whichever occurs 
first.  Subjects last known to be 1) alive 2) on treatment or within the post-treatment 
follow-up period and 3) progression-free, are censored at the date of the last disease 
assessment that verified lack of disease progression. Subjects who start new anti-cancer 
treatment prior to the end of post-treatment follow-up period and have adequate baseline 
and on-treatment objective disease assessments without evidence of progressive disease 
are censored at the date of the last objective disease assessment. Subjects with 
inadequate baseline or no on-study disease assessments are censored at C1D1 unless 
death occurred prior to the first planned assessment (in which case the death is an event). 
Subjects with at least one on-study disease assessment who discontinue treatment without 
disease progression and without death within 28 days of discontinuation are censored at 
the date of the last objective disease assessment that verified lack of diseaseprogression 
(if progression or death is within 28 days of discontinuation the progression or death is an 
event). Subjects with documentation of progression or death after an unacceptably long 
interval (>16 weeks) since the previous disease assessment will be censored at the time of 
the previous assessment.


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
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PFS (days) = [progression/death date –C1D1 + 1].
Overall survival(OS) is defined as the time from initial doseuntil death from any cause, 
and is measured in the intent-to-treat population.
More details of censoring are provided in Appendix 3.
7.2.Safety Endpoints
7.2.1.DLT Definitions
Severity of adverse events will be graded according to NCI CTCAE version 4.03.  For the 
purpose of dose escalation, any of the following adverse events which are not considered 
related to disease progression, occurring in the firstcycle of treatment (Q3W regimen: 
21daysor until the patient receives the 2ndinfusion if there are treatment delays, QW 
regimen: 21days or until the patient receives the 4
thinfusion if there are treatment delays) 
will be classified as DLTs:
Hematologic:
Grade 4 neutropenia lasting >7 days.
Febrile neutropenia (defined asneutropenia Grade 3 and a single body 
temperature >38.3°C or a sustained temperature of 38C for more than one 
hour).
Grade 3 neutropenia withinfection.
Any gradethrombocytopenia associated with clinically significant or 
life-threatening bleeding.
Grade 4 thrombocytopenia72hours or platelets 10,000/mm3regardless of 
duration.
Non-hematologic:
Grade 3 toxicities, except those that have not been maximally treated 
(eg,nausea, vomiting, diarrhea).
Delay by more than 2weeks in receiving the next scheduled cycle due to 
persisting toxicities attributable to PF-06647263.
Grade3 cytokine release syndrome, infusion related reaction, allergic reaction, or 
anaphylaxis will not be considered as DLTs but may be a reason for study discontinuation 
and should be reviewed with Pfizer.


Protocol B7521001(PF-06647263)
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7.2.2.MTD Definition
The MTDwould be any doses with true toxicity probabilities in the Equivalence Interval (EI) 
where the EI is defined as [20%-30%]. 
In practice, the MTD will be the highest dose associated with the occurrence of DLTs 33% 
(eg,3/9 evaluable patients experience a DLT during the first treatment cycle). 
7.2.3.Recommended Phase 2 Dose (RP2D) Definition
The Recommended Phase 2 Dose (RP2D) is the dose chosen for further study based on Part1 
results.  If the MTD proves to be clinically feasible for long term administration in a 
reasonable number of patients, such dose usually becomes the RP2D.  Further experience 
with the MTD may result in a RP2D dose lower than the MTD.
7.2.4.VitalsSigns
Vital signs,  See Schedule of Activities in the protocol for details.
7.2.5.Laboratory Data
The laboratory results will be graded according to the NCI CTCAE v4.03severity grade.For 
labs for which an NCI CTCAE v4.03scale does not exist, the frequency of subjectswith 
values below, within, and above the normal ranges will be summarized by dose. Baseline 
evaluations for laboratory data are those collected:
Within 28 days prior to Cycle 1/Day 1.
Closest but prior to Cycle 1/Day 1 if there is more than one baseline evaluation.
7.2.6.Adverse Events
Assessment of adverse events will include the type, incidence, severity (graded by the 
National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE]
version 4.0) timing, seriousness, and relatedness.
All AEs will be coded by system organ class (SOC) and preferred term using Medical 
Dictionary for Regualtory Activities (MedDRA). The severity of all AEs will be gradedby 
the investigator using NCI CTCAE Version4.03wheneverpossible. For other AEs without 
specific CTC definitions, results are identified according to CTCAE “other” categories. 
Adverse events will be assigned to the appropriate cyclebased on Day 1 of each cycle. 
Treatment Emergent Adverse Events
All deaths from start of treatment until 28 days after the final dose.
All treatment related SAEs.
All unrelated SAEs from treatment start until 28 days after final dose of treatment.


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
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All non-fatal AEs occurring after treatment start up until 28 days after final dose of 
treatment or until start of new anti-cancer treatment, whichever is first.
Disease progression is not considered a treatment emergent adverse event unless the 
subject dies of disease prior to 28 days after discontinuation of treatment.
Events that are continuations of baseline abnormalities are considered treatment emergent 
adverse events only if there is an increase in grade over baseline.
Treatment Related AdverseEvents
Treatment Related Adverse Events are treatment emergent adverse events with cause 
categorized by the investigator as related to study treatment.  Events that are continuations of 
baseline abnormalities (signs and symptoms) are not considered treatment emergent, and 
hence are not considered treatment related, unless there is an increase in grade over baseline.
7.2.7.ECGand QTc Interval
The analysis of ECG results will be based on Safety Population patients with baseline and 
on-treatment ECG data. 
ECG measurements will be used for the statistical analysis and all data presentations.  Any 
data obtained from ECGs repeated for safety reasons after the nominal time-points will not 
be averaged along with the preceding values.  Interval measurements from repeated ECGs 
will be included in the outlier analysis as individual values obtained at unscheduled time 
points.
QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie, 
Bazett’s, Fridericia’s and possibly a study specific factor).  The adequacy of the correction 
method will be assessed graphically (plots of QT and QTc versus RR) and supplementary 
transformations may be considered, as appropriate.  Data will be summarized and listed for 
QT, HR, RR, PR, QRS, QTcF and QTcB by treatment and dose.  Individual QTc (all 
evaluated corrections) intervals will be listed by compound, time and dose.  The most 
appropriate correction factor will be selected and used for the following analyses of central 
tendency and outliers and used for the study conclusions.  Descriptive statistics (n, mean, 
median, standard deviation, minimum, and maximum) will be used to summarize the
absolute QTc value and changes from baseline in QTc after treatment by compound, dose 
and by time point.  For each patient and by treatment, the maximum change from baseline 
will be calculated as well as the maximum post-baseline value across time-points.  Outlier 
analysis of the QTc data will be conducted and summarized as follows:
The number of patients with maximum change from baseline in QTc (<30, 30-60, and 
60 ms).
The number of patients with maximum post-dose (post-baseline) QTc (<450, 
450-<480, 480-<500, and >=500 ms).


Protocol B7521001(PF-06647263)
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In addition, the number of patients with corrected and uncorrected QT values 500msec will 
be summarized.
Shift tables will be provided for baseline vs. worst on study QTc (one or more correction 
method will be used) using Maximum CTC AE Grade.  As well as tables of ECG 
abnormality at baseline (yes, no, not done: (n, %)).  Patients experiencing clinically-relevant 
morphological ECG changes will be summarized (including frequency and percentage).
If more than one ECG is collected at a nominal time post dose (for example, triplicate 
ECGs), the mean of the replicate measurements will be used to represent a single observation 
at that time point.  If any of the three individual ECG tracings has a QTc value 500msec, 
but the mean of the triplicates is not 500msec, the data from the subject’s individual tracing 
will be described in a safety section of the study report in order to place the 500msec value 
in appropriate clinical context.  However, values from individual tracings within triplicate 
measurements that are 500msec will not be included in the categorical analysis unless the 
average from those triplicate measurements is also 500msec.  Changes from baseline will 
be defined as the change between QTc post dose from Day0, or the pre-dose values on 
Day1.
The effect of drug concentrations on QTc change from baseline will be explored graphically.  
Additional concentration-QTc analyses may be performed.  Data may be pooled with other 
study results and/or explored further with PK/PD models.
7.2.8.Immunogenicity
Anti-PF-06647263antibody data will becollected at baseline and post randomization
according to the protocol.
7.3.PK Endpoints 
Blood samples for PK analysis of PF-06647263(ADC),total antibody, andunconjugated 
payloadwill be taken according to the Schedule of Activities given in the protocol. 
Pharmacokinetic parameters of PF-06647263(ADC)andtotal antibody:
Cycle 1-C
max, T
max, AUC
last, AUCinf,AUC,t
1/2,CL, and Vssas data permit. 
Cycle 4-C
max, T
max, AUC
last, AUC
, t
1/2, and Racas data permit.
Pharmacokinetic parameters of Payload (unconjugated payload):
Cycle 1-C
max, T
max, AUC
last, AUC
inf,AUC, and t
1/2as data permit. 
Cycle 4-Cmax, T
max, AUC
last, AUC
, t
1/2, and Racas data permit. 
PK parameters will be derived from the concentration-time data as follows:


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Parameter 
Definition 
Method of Determination
AUClast
Area under the concentration-time 
profile from time zero to the time of 
the last quantifiable concentration
Linear/Log trapezoidal method
AUCτ
Area under the concentration-time 
profile from time zero to the time τ, 
the dosing interval
Linear/Log trapezoidal method
AUCinf
Area under the concentration-time 
profile from time zero extrapolated to 
infinite time
AUC(0-t[last])+ (Clast*/kel),
where Clast* is the predicted serum concentration at 
the last quantifiable time point estimated from the 
log-linear regression analysis.
Cmax
Maximum cobserved oncentration 
Observed directly from data
Tmax
Time for Cmax
Observed directly from data as time of first occurrence
T½
Terminal elimination half-life 
Loge(2)/kel,
where kel is the terminal phase rate constant calculated 
by a linear regression of the log-linear 
concentration-time curve.  Only those data points 
judged to describe the terminal log-linear decline will 
be used in the regression.
CL
Clearance
Dose/ AUCinf for cycle 1; Dose/ AUC
τfor cycle 4
Vss
Volume of distribution at steady state
CL×MRT
Rac
Observed accumulation ratio
AUCcycle 4, τ/ AUC
cycle 1, τ
 
 
7.5. Covariates
Not applicable. 
8. HANDLING OF MISSING VALUES
8.1. Missing Dates
In compliance with Pfizer standards, if the day of the month is missing for any date used in a 
calculation, the 1
stof the month will be used to replace the missing date unless the 
calculation results in a negative time duration (eg, date of onset cannot be prior to day one 
date).  In this case, the date resulting in 0 time duration will be used.  Pfizer standards are 
also used if both month and day are missing (Jan 1 unless negative time duration).  This 
excludes the pharmacokinetic, ECG, and pharmacodynamic analyses, which will only use the 
actual date collected or if date not available deem the data missing.
8.2. Efficacy Analysis
Censoring rules for time-to-event endpoints are detailed inSection 11.3 Appendix 3.
CCI


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8.3.Pharmacokinetics
Concentrations below the limit of quantification
In all data presentations (except listings), concentrations below the limit of quantification 
(BLQ) will be set to zero.  (In listings BLQ values will be reported as “<LLQ”, where LLQ 
will be replaced with the value for the lower limit of quantification.).
Deviations, missing concentrations and anomalous values
In summary tables and plots of median profiles, statistics will be calculated with 
concentrations set to missing if oneof the following cases is true:
1. A concentration has been reportedas ND (ie,not done) or NS (ie,no sample),
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
Pharmacokinetic parameters
Actual PK sampling times will be used in the derivation of PK parameters.
If a PK parameter cannot be derived from a subject’s concentration data, the parameter will 
be coded as NC (ie,not calculated).  (Note that NC values will not be generated beyond the 
day that a subject discontinues).
In summary tables, statistics will not be presented for a particular treatment group if more 
than 50% of the data are NC.  For statistical analyses, PK parameters coded as NC will also 
be set to missing.
If an individual subject has a known biased estimate of a PK parameter (due for example to 
an unexpected event such as vomiting before all the drug is absorbed in the body), this will 
be footnoted in summary tables and will not be included in the calculation of summary 
statistics or statistical analyses.
QTc
For the QTc analyses, no values will be imputed for missing data.
Pharmacodynamic parameters
Missing data for the pharmacodynamic parameters will be treated as such and no imputed 
values will be derived.


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9.STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
9.1.Statistical Methods
No formal hypothesis testing will be performed in this exploratory study.
Analyses of Time-to-Event Endpoints 
Time-to-event endpoints will be summarized using the Kaplan-Meier method and displayed 
graphically when appropriate.  Median event times and 2-sided 95%confidence intervalsfor 
each time-to-event endpoint (Brookmeyer and Crowley, 1982) will be provided. 
Analyses of Binary Endpoint
The rates of binary endpoints will be provided along with the corresponding 2-sided 95% 
confidence intervals using an exact method. 
Analyses of Continuous Data
Descriptive statistics, such asthe mean, standard deviation, coefficient of variation, median, 
minimum, and maximum values, will be provided for continuous endpoints. 
9.2.Statistical Analyses
9.2.1.Primary Analysis
Dose Limiting Toxicity (DLT) is the primary endpoint of the dose escalation component of 
the study, which will be summarized by dose level using the Per Protocol Analysis Set for 
patients in the dose escalation portion of the study.  A listing of the DLTs will also be 
provided.
If necessary, a summary and listing of the DLT by malignancy may be provided using the 
Per Protocol Analysis Set for patients in the MTD expansion portion of the study.
9.2.2.Secondary Analyses
9.2.2.1.Efficacy Analysis
In this Phase 1 study efficacyis a secondary objective. Note that the efficacy analysis is to 
be conducted by malignancy for patients in the MTD expansion cohorts who are in the Safety 
Analysis Setand have baseline disease assessment and at least one post-baseline disease 
assessment.  In the event that a large number of patients in the escalation portion of the study 
have the same malignancy, the efficacy analysis may be conducted.
Summary tables of best Overall ResponseRate, Progression Free Survival, and Overall 
Survivalwill be provided overall and by malignancy.  Efficacy listings will be provided that 
include best response, first CR/PR date, last date with CR or PR, most recent date without 
progression, progression date, death date, date of first response and last tumor assessment 
date, etc.


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Aresponse rate overall for Part 1dose escalation and response rates by low, medium, and 
high dosegroupsmay be presented. 
The following table provides an overview of the efficacy analysis.
Endpoint
Analysis Set
Statistical 
Method 
Model/ 
Covariates/ 
Strata
Missing Data Interpretation
Overall 
response
Per Protocol, 
expansion 
cohorts, etc.
Exact CI
By dose range/
malignancy
Censored per 
Section11.3
Secondary 
Analysis
Progression 
Free Survival 
(PFS)
Per Protocol, 
expansion 
cohorts
Kaplan-Meier
By malignancy Censored per 
Section11.3
Secondary 
Analysis
Time to 
Progression 
(TTP)
Per Protocol, 
expansion 
cohorts
Kaplan-Meier
By malignancy Censored per 
Section11.3
Secondary 
Analysis
Duration of 
Response (DR)
Per Prtocol, 
expansion 
cohorts
Kaplan-Meier
By malignancy Censored per 
Section11.3
Secondary 
Analysis
9.2.2.2.Pharmacokinetics Analyses 
Pharmacokinetic Parameters
To assess the pharmacokinetics of PF-06647263(ADC),total antibodyand unconjugated 
payload, the PK parameters detailed in Section 7.3will be listed and summarized for subjects 
in the PK analysis set (as defined in Section 6.4).  Missing values will be handled as detailed 
in Section 8.  Each PK parameter will be summarized by dose and cycle and will include the 
set of summary statistics as specified in the table below: 
Parameter
Summary statistics
AUClast, 
AUC∞, 
AUC, Cmax,
CL, V
ss, and 
Rac
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum, geometric mean
t
1/2
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum
Tmax
N, median, minimum, maximum
There will be 1 summary table presenting all PK parameters.  This will include data from all 
cohorts and will be summarized by dose groupand cycle. 


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To assess the relationship between the PK parameters and dose, dose normalized AUC, 
AUClast, AUC, and C
maxwill be plotted againstdose (using a logarithmic scale), and will 
include individual subject values and the geometric means for each dose.  Geometric means 
will have a different symbol than the individual values.  The values will be dose normalized 
(to a 1 mg/kg dose) by dividing the individual values and raw geometric means by dose.  A 
footnote will be added to the plots to indicate that geometric means are presented are 
presented on the plot. 
Pharmacokinetic Concentrations
To assess the PK profile of PF-06647263(ADC),total antibodyand unconjugated payload, 
PKconcentrations will be listed, summarized and plotted for subjects in the PK analysis set 
(as defined in Section 6.4), where missing and BLQ values will be handled as detailed in 
Section 8.3.
Presentations for PF-06647263(ADC),total antibodyand unconjugated payloadwill
include:
a listing of all concentrations sorted by dose, subject id, dayand nominal time post dose.  
The listing of concentrations will include the actual times.  Deviations from the nominal 
time will be given in a separate listing.
a summary of concentrations by dose, day and nominal time post dose, where the set of 
statistics will include n, mean, median, standard deviation, coefficient of variation (cv) 
and the number of concentrations above the lower limit of quantification.
a plot of mean concentrations against nominal time postdose by dose (based on the 
summary of concentrations by dose and time postdose), preferably with all doses also on 
the same graph.
a plot of median concentrations against nominal time postdose by dose (based on the 
summary of concentrations by dose and time postdose),preferably with all doses also on 
the same graph.
a log-linear plot of mean concentrations against nominal time postdose by dose (on the 
same plot), preferably with all doses also on the same graph.
a log-linear plot of median concentrations against nominal time postdose by dose (on the
same plot), preferably with all doses also on the same graph.
plots (linear and log scale) of individual concentrations against actual time postdose.
The length of time used for the x-axes of these plots will be decided on review of the data, 
and will depend on how long PKconcentration is quantifiable in the matrix.
In addition to the above, a median plot(linear and log scale)of the predose concentrations at 
each cycle against day will be provided for each dose, on the same plot, in order to assess the 
attainment of steady-state.  Individual subject profiles will also be plotted.


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For summary statistics and mean/median plots by sampling time, the nominal PK sampling 
time will be used, for individual subject plots by time, the actual PK sampling time will be 
used.
Population Pharmacokinetic Analysis or PK/PD Modeling
Pharmacokinetic and pharmacodynamic data from this study may be analyzed using 
compartmental or mixed-effect modeling approaches and may also be pooled with other 
study results.  PK/PD modelingmay be attempted to investigate any causal relationship 
between PF-06647263 exposure and biomarkers or significant safety endpoints.  The results 
of these analyses, if performed, may be reported separately.
 
 
 
  
9.2.3.Safety Analyses
Adverse Events
Adverse Events (AEs) will be graded by the investigator according to the CTCAE version 
4.0 and coded using the MedDRA. The focus of AE summaries will be onTreatment 
Emergent Adverse Events, those with initial onset or increasing in severity afterthe first dose 
of study medication. The number and percentage of patients who experiencedany AE, 
serious AE (SAE), treatment related AE, and treatment related SAE will besummarized 
according to worst toxicity grades. The summaries will present AEs both on theentire study 
period and by cycle (Cycle 1 and Cycles beyond 1).  The Safety Analysis Set will be used.
Laboratory Tests Abnormalities
The number and percentage of patients who experienced laboratory test abnormalities will be
summarized according to worst toxicity grade observed for each laboratory test. The
analyses will summarize laboratory tests both in the entire study period and by cycle (Cycle1 
and Cycles beyond 1).Shift tables will be provided to examine the distribution of laboratory 
abnormalities.  The Safety Analysis Set will be used.
For laboratory tests without CTC grade definitions, results will be categorized as normal,
abnormalhigh/lowor not done.
CCI


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Other Variables: Anti-PF-06647263antibody
For anti-PF-06647263antibody, a listing, sorted by subject and study day, of the result of 
anti-PF-06647263antibody screening (positive/negative[<1:negative]), the specificity, and 
titer will be listed.  Summary counts of the patients, who are positive for the antibody, will be 
derived by study treatment and visit for the safety population.  No summary statistics other 
than those cited above, will be generated.
9.2.4.Standard Analyses
Study Conduct and PatientDisposition
An accounting of the study patients will be tabulated.  The subject evaluation groups will be 
listed.  The Full Analysis Set will be used.
Subject discontinuation from treatment and study will be tabulated and listed separately with 
their reason for discontinuation.  The Safety Analysis Set will be used.
Baseline Characteristics
Baselinecharacteristics such as demographics, prior medication, medical history, ECOG 
performance status,and primary diagnosiswill be tabulatedand listed.  For ECOG
performance status a shift table (worst post-baseline vs baseline may be produced).  The 
Safety Analysis Set will be used.
Treatment Administration/Compliance
Listings and tables by dose level will be provided.Cycle length is 21 days. Day 1 of a cycle 
is the first date of dose within that cycle.  The safety analysis set will be used.
Dosemodifications may occur in the following ways:
Cycle delay—Day 1 of current cycle starts later than 21days from Day 1 of the previous 
cycle (only applies to cycle 2 and above); 
Dose reduction—A decrease in the administered total daily dose (non-zero) compared to 
the planned total daily dose upon enrollment.  If in the CRF the prescribed dose unit is 
mg/kg, but the actual dose is in mg the actual dose mg/kg should be calculated 
considering the body weight of the patient at that visit.
Intra-patient dose escalation is not allowed in this study.  The following will be summarized 
by subject for each dose level: 
Number of subjects per dose level 
Median and range of numberof cycles started per subject
Number (%) ofsubjects starting a cycle (1, 2,3…)


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Number (%) ofsubjects with cycle delays
Number (%) of dose interruptions(include both known and unknown dates)
Number (%) of subjects with dose reductions
Number (%) of each reason (AE vs. Other) for cycle delays, dose interruptions and 
dose reductions
Time on treatment (median, range)
The following will be summarized by cycle received for each dose level:
Total number of cycles started
Number of cycles started per subject (median, range)
Number of cycles before 1
stdelay (median, range)
Number of cycles before 1
streduction (median, range)
Number of cycles before 1
stinterruption (median, range)
The following will be summarized for cumulative dose by dose level and cycle: 
Summary statistics (mean, median, standard deviation and range)of cumulative dose 
and percent of starting dose (compared to Day 1 dose of each cycle) 
Listings by subject (ordered by dose level): start date and stop date of each dosing period 
within each cycle (including records with 0mg), administered total daily dose for each 
period, any missed doses with unknown dates (Y/N), number of missed doses with unknown 
dates, reason for any dosing changes.
Listings by subject and each cycle (ordered by dose level): cycle length, total planned dose, 
administered total dose, percentage of planned dose, dose delay (yes/no), dose reduction 
(yes/no), and dose interruption (yes/no). 
Prior, Concomitant, and Further Therapies
Prior, concomitant, and further therapies(drug and non-drug treatments) will be coded by the 
World Health Organization (WHO) medical dictionary.  Listings of prior, concomitant, and 
further therapies will be provided separately.
 
 
 
 


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10.REFERENCES 
Brookmeyer R, Crowley JJ.  A confidence interval for the median survival time.  Biometrics 
1982; 38:29-41.
E.A. Eisenhauer, P. Therasseb, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. 
Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. 
Lacombe, J. Verweij: New response evaluation criteria in solid tumours: Revised RECIST 
guideline (version 1.1). European Journal of Cancer 45 (2009) 228–247
ICH E14 -The clinical evaluation of QT/QTc interval prolongation and proarrhythmic 
potential for non-antiarrhythmic drugs.  CHMP/ICH/2/04.
Kaplan EL, Meier P.  Nonparametric estimation from incomplete observations.  J Am Stat 
Assoc 1958; 53:457-481.
NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
http://evs.nci.nih.gov/ftp1/CTCAE/Documentation/CTCAE_Governance_2010-03-11.pdf


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11.APPENDICES 
11.1.APPENDIX 1: CATEGORICAL CLASSES FOR ECG AND VITAL SIGNS 
Categories for QTcB and QTcF
QTcB/QTcF 
(ms)
max. 450
450< max. 480
480< max.500
max. >500
QTcB/QTcF 
(ms) increase 
from baseline
max. <30
30max. <60
max. 60
Categories for PR and QRS
PR (ms)
max 300
PR (ms) increase 
from baseline
Baseline >200 
and max. 
25% increase
Baseline 200 and 
max. 50% 
increase
QRS (ms)
max 200
QRS (ms) 
increase from 
baseline
Baseline >100 
and max. 
25% increase
Baseline 100 and 
max. 50% 
increase
Categories for Vital Signs
Systolic BP (mm Hg)
min. <90
Systolic BP (mm Hg) 
change from baseline
max. decrease 30
max. increase 30
Diastolic BP (mm Hg)
min. <50
Diastolic BP (mm Hg) 
change from baseline
max. decrease 20
max. increase 20
Supine pulse rate (bpm)
min. <40
max. >120
Measurements that fulfil these criteria are to be listed in the study report.


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11.2.APPENDIX 2: RECIST 1.1 TUMOR ASSESSMENT CRITERIA
Adapted from E.A. Eisenhauer, P. Therasseb, J. Bogaerts, L.H. Schwartz, D. Sargent, R. 
Ford,J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. 
Kaplan, D. Lacombe, J. Verweij: New response evaluation criteria in solid tumours: Revised 
RECIST guideline (version 1.1). European Journal of Cancer 45 (2009) 228–247 
At baseline, individual tumor lesions will be categorized by the investigator as either 
measurable or not,according to the criteria summarized below:
Measurable Lesions
Lesions that can be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
10mm for lesions other than lymph nodes and assessed by CT scan (CT scan slice 
thickness no greater than 5mm)
10mm for lesions assessed clinically by caliper measurement (lesions which cannot 
be accurately measured with calipers should be recorded as non-measurable).
20mm for lesions assessed by chest X-ray.
15mm in short axis for lymph nodes when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm).
Non-measurable Lesions
Non-measurable lesions includesmall lesions (longest diameter <10 mm or pathological 
lymph nodes with a 10 but< 15 mm short axis) as well as truly non-measurable lesions.  
Truly non-measurable lesions include: leptomeningeal disease, ascites, pleural or pericardial 
effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses identified by physical exam andnot measurable by reproducible imaging techniques.
Nodes that have a short axis <10 mm are considered non-pathological and should not be 
recorded or followed. 
Special Considerations Regarding Specific Lesions 
Bone lesions:
Bone scan, PET scan or plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions.
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, 
that can be evaluated by cross sectional imaging techniques such as CT or MRI can be 
considered as measurable lesions if the soft tissue component meets the definition of 
measurability described above.


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Blastic bone lesions are non-measurable. 
Cystic lesions:
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, 
by definition, simple cysts.
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if 
non-cystic lesions are present in the same patient, these are preferred for selection as 
target lesions.
Lesions with prior local treatment:
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion.
Solitary lesions:
If a measurable disease is restricted to a solitary lesion, its neoplastic nature should be 
confirmed by cytology/histology. 
Recording Tumor Measurements
All measurable lesions up to a maximum of 2 lesions per organ and up to 5in totaland
representative of all involved organs should be identified as target lesionsand measured and 
recorded at baseline and at the stipulated intervals during treatment. Target lesions should be 
selected on the basis of their size (lesions with the longest diameters) and their suitability for 
accurate repetitive measurements (either by imaging techniques or clinically). 
The longest diameter will be recorded for each target lesion. The sum of the longest 
diameter of all target lesions will be calculated and recorded as the baseline sum diameter to 
be used as reference to further characterize the objective tumor response of the measurable 
dimension of the disease during treatment. 
One exception to the above described approach is related to pathological lymph nodes.  
Pathological lymph nodes are defined as measurable lesions and may be identified as target 
lesions if the criterion of a short axis of 15 mm by CT scanis met.  Only the short axis of 
these nodes will contribute to the baseline sum.  Nodal size is normally reported as two 
dimensions in the plane in which the image is obtained (for CT scan this is almost always the 
axial plane; for MRI the plane of acquisition may be axial, sagittal or coronal). The smaller 
of these measures is the short axis. 


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A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all 
target lesions will be calculated and reported as the baseline sum diameters.  The baseline 
sum diameters will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease.
All other lesions (or sitesof disease) should be identified as non-target lesionsand should 
also be recorded at baseline. Measurements are not required and these lesions should be 
followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’.In addition, it is 
possible to record multiple non-target lesions involving the same organ as a single item on 
the case record form (eg,‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver 
metastases’).
Definition of Tumor Response 
Target Lesions
Response in target lesions is defined as follows:
Complete Response (CR):disappearance of all target lesions. 
Partial Response (PR): atleast a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters.
Progressive Disease (PD):atleast a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum if 
that is the smallest on study). In addition to the relative increase of 20%, the sum must 
also demonstrate an absolute increase of at least 5 mm. The appearance of one or more 
new lesions is also considered a sign of progression.
Stable Disease(SD):neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum diameters while on study.
When nodal disease is included in the sum of target lesions and the nodes decrease to 
‘normal’ size (<10 mm), they may still have a measurement reported on scans. This 
measurement should be recorded even though the nodes are normal in order not to overstate 
progression should it be based on increase in size of the nodes. As noted earlier, this means 
that patients with CR may not have a total sum of ‘zero’ on the CRF.
Non-Target Lesions
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the time points specified in the protocol. 


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Response in non-target lesions is defined as follows:
Complete Response (CR):Disappearance of all non-target lesions and normalization of 
tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short 
axis).
Non-CR/Non-PD:Persistence of one or more non-target lesion(s) and/or maintenance of 
tumor marker level above the normal limits.
Progressive Disease (PD):Unequivocal progression of existing non-target lesions. 
(Note: the appearance of one or more new lesions is also considered progression).
Cytology, histology 
These techniques can be used to differentiate between PR and CR in rare cases if required by 
protocol (for example, residual lesions in germ cell tumors). When effusions are known to 
be a potential adverse effect of treatment (eg,taxane compounds or angiogenesis inhibitors), 
the cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment can be considered if the measurable tumor has met criteria for response or 
stable disease in order to differentiate between response or stable disease and progressive 
disease.
For patients having effusions or ascites, only cases having cytological proof of malignancy 
should be recorded on the CRF.Effusions that have not been evaluated using cytology or 
were found to be non-malignant should not be recorded on the CRF. 
New Lesions 
The appearance of new malignant lesions indicates PD. New lesion should be unequivocal
(eg,not attributable to differences in imaging technique, or change in imaging modality or 
findings not attributable to tumor). If a new lesion is equivocal, for example due to its small 
size, continued therapy and follow-up assessmentwill clarify the etiology of the disease. If 
repeat scans confirm there is definitely a new lesion, then progression should be declared 
using the date of the initial scan. 
The use of FDG-PET is sometimes reasonable to complement a CT scan assessment of a PD 
(particularly for possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can 
be identified according to the following algorithm: 
Negative FDG-PET at baseline, with a positiveFDG-PETat follow-up 
No FDG-PET at baseline and a positive FDG-PET at follow-up:if the positive 
FDG-PET at follow-up corresponds to anew site of disease confirmed by CT, this is PD.


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If the positive FDG-PET at follow-up is not confirmed asa new site of disease on CT, 
additional follow-up CTscans are needed to determine if there is truly progressionoccurring 
at that site (if so, the date of PD will bethe date of the initial abnormal FDG-PET scan).
If the positive FDG-PET at follow-up corresponds to apre-existing site of disease on CT that 
is not progressingon the basis of the anatomic images, this is not PD.
Determination of Overall Response by the RECIST 1.1 Criteria
When both target and non-target lesions are present,individual assessments will be recorded 
separately.The overall assessment of response will involve all parameters as depicted in 
Table 1.
Table 1: Response Evaluation Criteria in Solid Tumors
Target 
lesions
Non-target 
lesions
New
Lesions
Overall
response
CR
CR
No
CR
CR
Non-CR/no
n-PD
No
PR
CR
Not 
evaluated
No
PR
PR
Non-PD or
not all 
evaluated
No
PR
SD
Non-PD or
not all 
evaluated
No
SD
Not all
evaluated
Non-PD
No
NE
PD
Any
Yes or 
No
PD
Any
PD
Yes or 
No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease,
PD = progressive disease, and NE = inevaluable.


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Best overall response
The best overall response isdefined according to the tumor response along the study. 
Complete or partial responses may be claimed only if the criteria for each are met at a 
following time point as specified in the protocol (generally 4weeks later). In this 
circumstance, the best overall response can be interpreted as in Table 2.
Table 2: Best overall response when confirmation of CR and PR required
Overall 
response 
First time 
point 
Overall 
response 
Subsequent 
time point
BEST overall response
CR 
CR 
CR
CR 
PR 
SD, PD or PRa
CR 
SD
SD provided minimum criteria 
for SD duration met, otherwise, 
PD
CR 
PD
SD provided minimum criteria 
for SD duration met, otherwise, 
PD
CR 
NE 
SD provided minimum criteria 
for SD duration met, otherwise 
NE
PR 
CR 
PR
PR 
PR 
PR
PR 
SD 
SD
PR 
PD
SD provided minimum criteria 
for SD duration met, otherwise, 
PD
PR 
NE
SD provided minimum criteria 
for SD duration met, otherwise 
NE
NE 
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = 
progressive disease, and NE = inevaluable.
aIf a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline,makes the disease PD at that point (since disease must have 
reappeared after CR). Best response would depend on whether minimum durationfor SD was met. 
However, sometimes ‘CR’ may be claimed when subsequent scans suggest small lesions were likely still 
present and in fact thepatient had PR, not CR at the first time point. Under these circumstances, the original 
CR should be changed to PR and the best response is PR.


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
Page 34of 35
 
Patients with a global deterioration of health status requiringdiscontinuation of treatment 
without objective evidenceof disease progression at that time should be reported as
‘symptomatic deterioration’. Every effort should be made todocument objective progression 
even after discontinuationof treatment. Symptomatic deterioration is not a descriptorof an 
objective response: it is a reason for stopping study therapy.  The objective response status of 
such patients is to bedetermined by evaluation of target and non-target lesions.
In some circumstances it may be difficult to distinguishresidual disease from normal tissue. 
When the evaluation of CRdepends upon this determination, it isrecommended that the 
residual lesion be investigated (fineneedle aspirate/biopsy) before assigning a status of 
completeresponse. FDG-PET may be used to upgrade a response to a CRin a manner 
similar to a biopsy in cases where a residualradiographic abnormality is thought to represent 
fibrosis orscarring. The use of FDG-PET in this circumstance should beprospectively 
described in the protocol and supported by diseasespecific medical literature for the 
indication. However, itmust be acknowledged that both approaches may lead tofalse 
positive CR due to limitations of FDG-PETand biopsy resolution/sensitivity.


Protocol B7521001(PF-06647263)
Statistical Analysis Plan
Page 35of 35
 
11.3.APPENDIX 3: CENSORING DETAILS
Table 3:Progression Free Survival and Duration of Response 
Situation
Date of Progression/Censoring1
Outcome
Inadequate baseline assessment 
Start date (C1D1)
Censored
No on-study assessments
Start date (C1D1)
Censored
Alive, on treatment2and no 
Progression 
Date of last objective tumor assessment
Censored
Progression Documented on or 
between scheduled tumor assessments 
prior to treatment discontinuation
2
Date of first objective tumor assessment 
showing objective progression
Progressed (Event)
Treatment discontinuation for 
undocumented progression
Date of last objective tumor assessment 
prior to discontinuation2
Censored
Treatment discontinuation due to 
toxicity or other reason
Date of last objective tumor assessment 
prior to discontinuation2
Censored
Death prior to first planned tumor 
assessment 
Date of death
Death (Event)   
Death without objective progression 
prior to treatment discontinuation
2
Date of death
Death (Event)
                  
Death or progression after 2 or more 
missed tumor assessments
Date of last objective tumor assessment 
prior to the event
Censored
1: For date of censorship, if a tumor assessment takes place over a number of days (eg, superficial lesions one 
day, scans another), the last date is used as the assessment date.
2: or within 28 days of discontinuation of treatment. 
Table 4: Time to Progression
Situation
Date of Progression/Censoring1
Outcome
Inadequate baseline assessment 
Start date (C1D1)
Censored
No on-study assessments
Start date (C1D1)
Censored
Alive, on treatment2and no 
Progression 
Date of last objective tumor assessment
Censored
Progression Documented on or 
between scheduled tumor assessments 
prior to treatment discontinuation
2
Date of first objective tumor assessment 
showing objective progression
Progressed (Event)
Treatment discontinuation for 
undocumented progression
Date of last objective tumor assessment 
prior to discontinuation2
Censored
Treatment discontinuation due to 
toxicity or other reason
Date of last objective tumor assessment 
prior to discontinuation2
Censored
New anticancer treatment <28 days 
after discontinuation of treatment 
without progression
Date of last objective tumor assessment 
prior to new anticancer treatment
Censored
Death prior to first planned tumor 
assessment 
Start date (C1D1)
Censored
Death without objective progression 
prior to treatment discontinuation
2
Date of last objective tumor assessment 
prior to death
Censored
                  
Progression after 2 or more missed 
tumor assessments
Date of last objective tumor assessment 
prior to the event
Censored
1: For censoring date, if a tumor assessment takes place over a number of days (eg, superficial lesions one day, 
scans another), the last date is used as the assessment date.
2: or within 28 days of discontinuation of treatment.