Clinical trial NCT02954653
Conditions: Acute Myeloid Leukemia
Keywords: relapsed refractory acute myeloid leukemia AML
Sponsor: Pfizer
Start date: 2016-11-28; Completion date: 2017-12-05
Enrollment: 8 participants; Allocation: NON_RANDOMIZED; Intervention model: 

Brief summary:
Two part, dose escalation and dose expansion study. Open label, multi center, non randomized, multiple dose, safety, pharmacokinetic and pharmacodynamic study of single agent PF-06747143 in sequential dose levels of adult patients with refractory or relapsed AML in order to establish maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) or maximally permitted dose (MPD) following by a 3 arm dose expansion with PF-06747143 in combination with standard of care chemotherapy in adult patients with AML.

Detailed description:
Patients will receive intravenous (IV) PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating doses. The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg. Patients will be monitored for dose limiting toxicity (DLT) in the dose escalation in order to define the MTD. Two of the three arms in the dose expansion will include PF-06747143 in combination with standard of care chemotherapy and will include a safety lead in. The third arm, pending clinical data, will be PF-06747143 as a single agent.

Arms: arm 1: Single agent PF-06747143 dose escalation arm 2: PF-06747143 with standard dose cytarabine and daunorubicin. arm 3: PF-06747143 in combination with Azacitidine or Decitabine. arm 4: PF-06747143 dose expansion as a single agent.
Interventions: intervention 1: PF-06747143 intervention 2: Cytarabine intervention 3: Daunorubicin intervention 4: Azacitidine intervention 5: Decitabine
Intervention descriptions: intervention 1: PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4. intervention 2: 100-200 mg/m2 continuous infusion for 7 days) intervention 3: 60-90 mg/m2 daily for 3 days intervention 4: 75 mg/m2 sub-cutaneous or intravenous for 7 days) intervention 5: 20 mg/m2 continuous intravenous infusion for 5 days in a 4-week schedule

Protocol documents:
Prot_000.pdf: 
PF-06747143
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A PHASE 1 DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, 
PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVENOUS 
PF-06747143, ADMINISTERED AS SINGLE AGENT OR IN COMBINATION WITH 
STANDARD CHEMOTHERAPY IN ADULT PATIENTS WITH ACUTE MYELOID 
LEUKEMIA
Compound:
PF-06747143
Compound Name:
Not applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
125905
European Clinical Trials Database 
(EudraCT) Number:
TBD
Protocol Number:
B7861002
Phase:
1
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Document History  
Document
Version Date
Summary of Changes and Rational
Original protocol
07 March 2016
Not applicable (N/A)
Amendment 1
14 June 2016
Protocol Summary: Background; Protocol: 
Section 3.1. Study Overview; Section 4.1. 
Inclusion Criteria #1 across all populations
The date for the World Health Organization 
(WHO) classification was updated and the 
classification for inclusion was modified from 
Cheson 2003 to WHO 2008.
Rationale: Typographical error and to align the 
diagnosis classification and management of acute 
myeloid leukemia (AML) throughout the protocol.
Protocol Summary: Study Objectives; Protocol: 
Section 2.1. Objectives – Part 1; Section 2.3. 
Objectives – Part 2; Section 3.1. Study 
Overview 
The assessment of anti-leukemia activity was 
modified from Cheson 2003 to Dohner 2010.
Rationale:  To align the diagnosis classification 
and management of AML throughout the protocol.
Protocol Summary: Study Design, Part 2
Attributions to fit and unfit patient populations for 
Part 2 of the study will be based on consensus 
article by Ferrara, et. al. 2013.
Rationale: Based on regulatory body feedback, the 
eligibility criteria were defined for Part 2 fit and 
unfit patient populations.
Protocol Summary: Part 2 Secondary 
Objectives and Endpoints; Protocol: Section 
2.3. Objectives – Part 2; Section 2.4. Endpoints 
– Part 2
The objective and endpoint surrounding drug 
concentration data was modified. 
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Summary of Changes and Rational
Rationale: Language modified to clarify that 
population PK evaluation will likely include PK 
data from both Part 1 and Part 2.
Protocol Summary Inclusion and Exclusion 
Criteria; Protocol: Section 3.1.2. Part 2; 
Section 4. PATIENT SELECTION
Part 1 and Part 2 Cohort 3: eligibility criteria for 
patients with refractory and/or relapsed AML were 
further defined.
Part 2, Cohort 1 and Cohort 2 (fit and unfit), 
Ferrara 2013 was used to define the patient 
population for each cohort per regulatory body 
feedback.  Exclusion criteria specific for the two 
patient populations was included as a separate set 
of criteria.
Rationale: The eligibility criteria for the various 
parts of the study were broken out for clarity and 
consistency across the multiple patient populations 
based on regulatory body feedback. 
Protocol Summary DLT Criteria; Protocol: 
Section 3.1.1.3. DLT Criteria
The language was modified so that all adverse 
events (AEs) meeting the definition of the criteria 
will be considered a DLT unless it can be clearly 
determined that the event is unrelated to 
PF-06747143.
Rationale: in early human trials, the relationship of 
an AE to the drug is not fully known so all AEs 
should be considered relevant to determining dose 
limiting toxicities and reporting unless the event 
can clearly be determined to be unrelated to the 
drug.
Schedule of Activities (SOA) and Protocol: 
Section 7.2. 
In addition to cardiac monitoring, patients in 
Part 2, Cohort 1 will be required to undergo 
pulmonary function tests.
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Rationale: standard requirements for treatment 
with daunorubicin.
Protocol: Section 3.1.1.4. MTD Definition
Maximum tolerated dose (MTD) determination in 
Part 2 was moved to create a new section 
(Section 3.1.2.2.3.). 
Rationale: protocol section consistency.
Protocol Section 5. STUDY TREATMENTS
Reference to the Dosage and Administration 
Instructions (DAI) was removed throughout the 
section. 
Rationale:  Pfizer internal document.  Sites are 
provided an Investigational Product manual with 
details of the internal DAI document. 
Protocol: Section 5.8.4. Anti Diarrheal, Anti 
Emetic Therapy
Text was added that prophylaxis is not permitted 
in Part 1. 
Rationale: not permitted due to need to determine 
dose limiting toxicities in Part 1.
In addition, typographical errors were corrected 
and editorial updates were made.
Amendment 2
06 March 2017
PACL #2 – 27 February 2016:
Protocol Summary: Study Design - Part 1, 
Inclusion Criteria (Part 1 and Part 2/Cohort 3) 
#3; Section 3.1.1.; Section 4.1, Inclusion Criteria 
(Part 1 and Part 2/Cohort 3) #3; Figure 1.
Removed 30% and 30-50% bone marrow blast 
criteria for 0.3 and 1.0 mg/kg dose levels.
Rationale: Initial clinical data indicates total 
peripheral WBC count is a more relevant and 
practical safety measure (see addition of pre-dose 
total peripheral WBC assessment requirement).
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Version Date
Summary of Changes and Rational
Protocol Summary: Inclusion Criteria (Part 1 
and Part 2/cohort 3) #1; Section 4.1, Inclusion 
Criteria (Part 1 and Part 2/cohort 3) #1.
Clarified statement regarding patient’s lack of 
alternative therapeutic options.
Revised relapsed/refractory criteria from two to 
one prior treatment regimens. 
Clarified prior lines of therapy to include standard 
of care and/or chemotherapy.
Added Minimal Residual Disease (MRD) 
inclusion option for study participation. 
Removed age and cytogenetics profile distinctions.
Rationale: Patients with relapsed/refractory disease 
in AML tend to have a poor outcome and 
shortened overall survival. There are very few 
effective therapeutic options available for patients 
with relapsed/refractory AML disease, and often, 
these patients are not eligible to receive re-
induction chemotherapy with intensive regimen 
due to severe toxicities with high rate of treatment 
related morbidity and mortality. In addition, 
patients with MRD in AML have poor outcome 
and shortened overall survival, comparable to 
those patients with relapsed/refractory disease in 
AML.26, 27,28,29  
Protocol Summary: Inclusion Criteria (Part 1 
and Part 2/cohort 3) #1; Section 4.1, Inclusion 
Criteria (Part 1 and Part 2/cohort 3) #1.
Corrected AML blast diagnosis from “and” to “or” 
as per the referenced WHO guideline.
Rational: Corrected statement as per referenced 
WHO guideline.
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Protocol Summary: Study Design - Part 1; SOA 
footnote “k”, “l” and “r”; Table 1 and 2 
footnote “e”; Section 3.1.1.; Section 5.4.1.
Added requirement for pre-dose assessment of 
total peripheral WBC during Cycle 1.
Rationale: Replaces bone marrow blast criteria as a 
more relevant and practical safety measure in 
response to PF-06747143 mediated WBC 
mobilization. 
Protocol Summary: Study Design - Part 1, 
Inclusion Criteria (Part 1 and Part 2) #3 and 
#2; SOA footnote “w”; Section 3.1.1.; 
Section 4.1, Inclusion Criteria (Part 1 and 
Part 2) #3 and #2; Section 5.4.1; Section 5.8.1; 
Section 5.8.2.
Reiterated that hydroxyurea and/or leukapheresis 
can be used during Cycle 1 as needed to control 
total peripheral WBC counts.
Revised statement regarding use of hydroxyurea 
and/or leukapheresis to treat hyperleukocytosis as 
clinically indicated. 
Rationale: The concomitant treatment options were 
originally allowed for in the protocol but sites 
were unaware of the treatment allowance. Hence, 
the option to use these treatments was added to 
additional sections to emphasize these options.
The criteria for using such treatment options was 
also clarified based upon feedback from 
Investigators. 
Protocol Summary: Statistical Method; 
Section 3.1.1., Figure 1; Section 3.1.1.2.; 
Section 9.2.1.; Section 9.3.
Revised minimum sample size of first two PF-
06747143 dosing cohorts, 0.3 and 1.0 mg/kg/wk, 
from 4 to 2-4 patients.
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Rationale: Minimize exposure to potentially sub-
therapeutic dose levels after safety assessment is 
performed. 
Protocol Summary: Exclusion Criteria (Part 1 
and Part 2/Cohort 3) #2; Section 4.2 Exclusion 
Criteria (Part 1 and Part 2/Cohort 3) #2.
Clarify and specify that systemic, but not topical, 
therapy for GVHD is exclusionary.
Rationale: Unlike systemic therapy, topical 
immunosuppressive therapy is localized, and 
should not affect PF-06747143 mediated ADCC 
activity.
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Protocol Summary: Inclusion Criteria (Part 1 
and Part 2) #4 and #2; Section 4.1, Inclusion 
Criteria (Part 1 and Part 2) #4 and #2.
Removed 10,000/uL WBC statement.
Rationale: 10,000/uL WBC did not serve as an 
inclusion criteria requirement, so this was removed 
to prevent misinterpretation.
SOA – Triplicate 12-Lead ECG and footnote j.
Added ECG time point to Day 1 of each Cycle 
after Cycle 2. 
Administrative changes.
Rationale: Additional ECG data to be collected for 
First-in Human study of PF-06747143. 
SOA footnote “k”; Table 1 and 2 footnote “e”; 
Section 7.1.3., Table 7.
SOA footnote “k”; Section 7.1.3., Table 7 
(Hematology).
Added percent blast cell assessment to the 
Hematology lab assessments.
Rationale: Provides critical safety and disease 
burden data. 
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Section 5.5.1.1.
Revised initial sentence structure.
Rationale: Clarified statement to avoid confusion.
Section 5.5.3.1: Body and Table 6.
Clarify that not all DLTs unless noted in Table 6 
require dose modification.
Correct Table 6 to include the DLT of 
hyperleukocytosis and corresponding dose 
modification recommendation.
Rationale: Corrected Table 6 to include 
hematological DLTs. The dose modification text 
of Section 5.5.3.1. was inconsistent with the
corresponding dose modification table (Table 6). 
Update made to body and table to correct 
inconsistency.
Section 7.6.
Clarified definition of disease progression 
according to original referenced guideline (Dohner 
et al.).
Rationale: Minimize disease assessment 
heterogeneity.
All other changes are minor administrative in 
nature.
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................15
LIST OF FIGURES .................................................................................................................15
APPENDICES .........................................................................................................................16
PROTOCOL SUMMARY.......................................................................................................17
1. INTRODUCTION ...............................................................................................................41
1.1. Mechanism of Action/Indication.............................................................................41
1.2. Background and Rationale ......................................................................................41
1.3. PF-06747143 ...........................................................................................................42
1.3.1. Nonclinical Efficacy...................................................................................42
1.3.2. Nonclinical Pharmacokinetics ....................................................................45
1.3.3. Nonclinical Safety ......................................................................................45
1.4. Starting Dose Rationale...........................................................................................47
1.5. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only).....................47
1.5.1. Cytarabine...................................................................................................47
1.5.2. Daunorubicin ..............................................................................................48
1.5.3. Decitabine...................................................................................................48
1.5.4. Azacitidine..................................................................................................48
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................49
2.1. Objectives – Part 1 ..................................................................................................49
2.2. Endpoints – Part 1 ...................................................................................................49
2.3. Objectives – Part 2 ..................................................................................................50
2.4. Endpoints – Part 2 ...................................................................................................51
3. STUDY DESIGN.................................................................................................................53
3.1. Study Overview.......................................................................................................53
3.1.1. Part 1...........................................................................................................53
3.1.1.1. Starting Dose.............................................................................54
3.1.1.2. Criteria for Dose Escalation ......................................................54
3.1.1.3. DLT Definition..........................................................................56
3.1.1.4. MTD Definition.........................................................................57
3.1.1.5. Maximum Permitted Dose Definition.......................................57
3.1.1.6. Recommended Phase 2 Dose (RP2D) Definition......................57
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3.1.2. Part 2...........................................................................................................58
3.1.2.1. Part 2 Combination Cohorts Starting Dose...............................58
3.1.2.2. Part 2/Cohort 1 and 2 ................................................................58
3.1.2.3. Part 2/Cohort 3 – PF-06747143 Single Agent Expansion.........59
3.1.3. Summary.....................................................................................................59
4. PATIENT SELECTION......................................................................................................60
4.1. Inclusion Criteria.....................................................................................................60
4.2. Exclusion Criteria....................................................................................................64
4.3. Lifestyle Guidelines ................................................................................................68
4.3.1. Contraception..............................................................................................68
4.4. Sponsor’s Qualified Medical Personnel..................................................................69
5. STUDY TREATMENTS.....................................................................................................69
5.1. Allocation to Treatment ..........................................................................................70
5.2. Patient Compliance .................................................................................................70
5.3. Investigational Product Supplies.............................................................................70
5.3.1. Dosage Form(s) and Packaging..................................................................71
5.3.1.1. PF-06747143.............................................................................71
5.3.1.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine 
(Part 2 only).......................................................................................71
5.3.2. Preparation and Dispensing........................................................................71
5.3.2.1. PF-06747143.............................................................................71
5.3.2.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine 
(Part 2 only).......................................................................................71
5.4. Administration.........................................................................................................71
5.4.1. PF-06747143...............................................................................................71
5.4.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only)........72
5.5. Recommended Dose Modifications ........................................................................72
5.5.1. Dosing Interruptions...................................................................................73
5.5.1.1. Part 1 .........................................................................................73
5.5.1.2. Part 2 .........................................................................................73
5.5.2. Dose Delays................................................................................................73
5.5.2.1. Part 1 .........................................................................................73
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5.5.2.2. Part 2 .........................................................................................74
5.5.3. Dose Reductions.........................................................................................74
5.5.3.1. Part 1 .........................................................................................74
5.6. Investigational Product Storage ..............................................................................75
5.7. Investigational Product Accountability...................................................................76
5.7.1. Destruction of Investigational Product Supplies ........................................76
5.8. Concomitant Treatment(s).......................................................................................77
5.8.1. Other Anti-leukemia/Anti-cancer or Experimental Drugs .........................77
5.8.2. Supportive Care ..........................................................................................77
5.8.3. Hematopoietic Growth Factors...................................................................77
5.8.4. Anti-Diarrheal, Anti Emetic Therapy.........................................................78
5.8.5. Anti-inflammatory Therapy........................................................................78
5.8.6. Corticosteroids............................................................................................78
5.8.7. Surgery........................................................................................................78
6. STUDY PROCEDURES .....................................................................................................78
6.1. Screening.................................................................................................................78
6.2. Study Period ............................................................................................................78
6.3. Follow-up Visit .......................................................................................................78
6.4. Patient Withdrawal..................................................................................................78
7. ASSESSMENTS..................................................................................................................80
7.1. Safety Assessment...................................................................................................80
7.1.1. Pregnancy Testing ......................................................................................80
7.1.2. Adverse Events...........................................................................................80
7.1.3. Laboratory Safety Assessment ...................................................................80
7.1.4. Vital Signs and Physical Examination........................................................81
7.1.5. (12-Lead) Electrocardiogram......................................................................81
7.2. Cardiac Monitoring and Pulmonary Function Tests (Part 2, Cohort 1)..................82
7.3. Pharmacokinetics Assessments...............................................................................82
7.3.1. Blood for PK analysis of PF-06747143......................................................82
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7.5. Immunogenicity Evaluations...................................................................................84
7.6. Disease Response Assessment ................................................................................85
7.7. Banked Biospecimens .............................................................................................85
7.7.1. Markers of Drug Response.........................................................................85
7.7.2. Additional Research....................................................................................87
8. ADVERSE EVENT REPORTING......................................................................................87
8.1. Adverse Events........................................................................................................87
8.2. Reporting Period .....................................................................................................88
8.3. Definition of an Adverse Event...............................................................................88
8.4. Medication Errors....................................................................................................89
8.5. Abnormal Test Findings..........................................................................................89
8.6. Serious Adverse Events...........................................................................................90
8.6.1. Protocol-Specified Serious Adverse Events...............................................91
8.6.2. Potential Cases of Drug-Induced Liver Injury............................................91
8.7. Hospitalization ........................................................................................................92
8.8. Severity Assessment................................................................................................93
8.9. Causality Assessment..............................................................................................93
8.10. Exposure During Pregnancy..................................................................................94
8.11. Occupational Exposure .........................................................................................95
8.12. Withdrawal Due to Adverse Events (See Also the Section on Patient 
Withdrawal)...............................................................................................................95
8.13. Eliciting Adverse Event Information ....................................................................95
8.14. Reporting Requirements........................................................................................95
8.14.1. Serious Adverse Event Reporting Requirements .....................................96
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8.14.2. Non-Serious Adverse Event Reporting Requirements .............................96
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................96
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................96
9.1. Analysis Sets ...........................................................................................................97
9.2. Statistical Methods and Properties ..........................................................................98
9.2.1. Part 1...........................................................................................................98
9.2.2. Dose Expansion (Part 2).............................................................................99
9.3. Sample Size Determination.....................................................................................99
9.4. Safety Analysis........................................................................................................99
9.4.1. Analysis of Primary Endpoint ..................................................................100
9.4.2. Analysis of Secondary Safety Endpoints..................................................100
9.4.2.1. Adverse Events........................................................................100
9.4.2.2. Laboratory Tests Abnormalities..............................................100
9.4.2.3. Electrocardiogram ...................................................................101
9.5. Efficacy Analysis ..................................................................................................102
9.5.1. Analysis of Overall Response...................................................................103
9.6. Analysis of Pharmacokinetics and 
........................................103
9.6.1. PF-06747143 Pharmacokinetic Analysis..................................................103
9.6.2. Population Pharmacokinetic Analysis or 
Pharmacokinetic/
9.7. Analysis of Other Endpoints .................................................................................105
9.7.1. Immunogenicity........................................................................................105
9.8. Data Safety Monitoring Committee ......................................................................105
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................105
11. DATA HANDLING AND RECORD KEEPING ...........................................................106
11.1. Case Report Forms/Electronic Data Record .......................................................106
11.2. Record Retention.................................................................................................106
12. ETHICS............................................................................................................................107
12.1. Institutional Review Board /Ethics Committee...................................................107
12.2. Ethical Conduct of the Study ..............................................................................107
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12.3. Patient Information and Consent.........................................................................107
12.4. Patient Recruitment.............................................................................................108
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................108
13. DEFINITION OF END OF TRIAL.................................................................................108
13.1. End of Trial in a Member State...........................................................................108
13.2. End of Trial in All Other Participating Countries...............................................108
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................109
15. PUBLICATION OF STUDY RESULTS........................................................................109
15.1. Communication of Results by Pfizer ..................................................................109
15.2. Publications by Investigators ..............................................................................110
16. REFERENCES ................................................................................................................111
LIST OF TABLES
Table 1.
PF-06747143 Pharmacokinetic, Immunogenicity and Biomarker Sampling 
Schedule (Part 1and Part 2: Cohorts S1, S2)........................................................37
Table 2.
PF-06747143 Pharmacokinetic, Immunogenicity and Biomarker Sampling 
Schedule (Part 2: Cohorts E1, E2 and E3)............................................................39
Table 3.
PF-06747143 in vitro Characterization Summary................................................43
Table 4.
PF-06747143 in vivo Pharmacology Summary....................................................44
Table 5.
Possible Dose Levels ............................................................................................55
Table 6.
Dose Modifications for Investigational Product Related Toxicity.......................75
Table 7.
Laboratory Tests ...................................................................................................81
Table 8.
Assay and Sample Source.....................................................................................83
Table 9.
Probability of Escalating Dose .............................................................................99
LIST OF FIGURES
Figure 1.
Part 1 Schema .......................................................................................................54
Figure 2.
Overall Study Schema ..........................................................................................60
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APPENDICES
Appendix 1. Abbreviations....................................................................................................114
Appendix 2. Eastern Cooperative Oncology Group (ECOG) Performance Status ...............118
Appendix 3. Management of Allergic Reactions/Cytokine Release Syndrome or 
Anaphylaxis ........................................................................................................119
Appendix 4. Detailed Dose Escalation/De-Escalation Scheme for mTPI Design.................121
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PROTOCOL SUMMARY
Background
The C-X-C chemokine receptor type 4 (CXCR4) (or CD184) is a G-protein coupled 
chemokine receptor, expressed on the cell surface, and has a 7-transmembrane structure.
CXCR4 plays a role in the cross talking between cancer cells and their microenvironment by 
binding its ligand, chemokine ligand 12 (CXCL12), thereby activating the downstream 
signaling pathways leading to alteration of gene expression, actin polymerization, cell 
skeleton rearrangement, and cell migration and proliferation.
The tumor microenvironment consists of resident non-cancerous cells (stromal fibroblasts, 
endothelial cells, and immune cells), connective tissue and extracellular matrix, altogether 
supporting tumor structure, angiogenesis, and growth.  CXCL12 is physiologically mainly 
expressed by mesenchymal stromal cells in various organs and tissues such as the liver, 
lungs, lymphatic tissues, and bone marrow. High levels of CXCL12 directly stimulate the 
proliferation and invasiveness of CXCR4-expressing cancer cells in an autocrine and 
paracrine manner. Nonclinical mouse models of non-Hodgkin’s lymphoma (NHL), acute 
myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and human multiple 
myeloma (MM)  have shown that CXCR4-positive cancer cells can be recruited to 
CXCL12-rich mesenchymal stroma niches.
Since the CXCL12-CXCR4 interaction is considered crucial for attracting tumor cells to the 
bone marrow niche, CXCR4 inhibitors have been explored as treatment agents in the field of 
leukemia treatment. CXCR4 is overexpressed in 75% of cancers (hematological 
malignancies and solid tumors), and its expression correlates with poor prognosis in various 
cancers.
PF-06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of 
CXCR4.  PF-06747143 has demonstrated robust anti-tumor activity in immune-compromised 
mice engrafted with human cells representing several human hematological malignancies 
including NHL, CLL, MM, and AML with a treatment regimen either as a single agent or in 
combination with standard of care agents.  Based on the nonclinical studies conducted, the 
mechanisms of action of PF-06747143 include: 1) inhibition of CXCR4-CXCL12 signaling, 
thereby inducing cell mobilization from CXCL12-rich niches; 2) direct induction of caspase 
independent cell-death through an antibody (Ab) bivalency-dependent mechanism; and 3) 
induction of cell death through Fc-effector function (antibody-dependent cell-mediated 
cytotoxicity (ADCC)/complement dependent cytotoxicity [CDC]) inherent to the IgG1 
backbone. 
Given the extensive nonclinical anti-tumor activity of PF-06747143 demonstrated in a large 
number of animal models, this Phase 1 clinical trial of PF-06747143 will initially enroll 
patients with acute myeloid leukemia (AML).  
The diagnosis of AML for the B7861002 study will be according to the World Health 
Organization (WHO) classification (2008).  The study will be conducted in two parts, Part 1 
single agent dose escalation and Part 2 PF-06747143 in combination with standard 
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chemotherapy with an option for single agent cohort expansion at the recommended phase 2 
dose (RP2D).  Assessment of anti-leukemia activity of PF-06747143 will be based on
“Diagnosis and management of acute myeloid leukemia in adults: recommendations from an 
international expert panel, on behalf of the European LeukemiaNet” 22.
Study Design
Part 1
This is a dose escalation, open-label, multi-center, single arm, non-randomized, multiple 
dose, safety, pharmacokinetic and pharmacodynamic study of single-agent PF-06747143 in 
sequential dose levels of adult patients with refractory and/or relapsed AML in order to 
establish the maximum tolerated dose (MTD), RP2D and/or maximally permitted dose 
(MPD). 
Patients will receive PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating 
doses.  The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg.  Patients 
enrolled in the first two dose levels (0.3 mg/kg and 1.0 mg/kg) will be required to stay in the 
clinic/hospital overnight (minimum of 24 hours) after receiving the first dose of 
PF-06747143 to monitor for the potential risk of hyperleukocytosis that might be caused by 
the inhibition of the CXCR4 pathway by PF-06747143.  On an individual basis, patients may 
be monitored overnight for the additional doses in Cycle 1 at the treating physician’s 
discretion.
In addition, the use of hydroxyurea and/or leukapheresis is permitted during Cycle 1 
following first dose administration to control total peripheral white blood count (WBC)
counts at the treating physician’s discretion. However, hydroxyurea must be ceased 24 hours 
prior to the first dose of Cycle 1.  Further, total peripheral WBC will be assessed by the
investigator within 12 hours prior to study drug administration during Cycle 1. In the event a 
patient’s total peripheral WBC count is 75,000/uL, the investigator shall consult with and 
obtain the sponsor’s agreement to move forward with the study drug administration.  
For the first three dose levels (ie, 0.3 mg/kg through 3.0 mg/kg), initiation of the first dose of 
PF-06747143 for each patient in the dose level must be at least 72 hours after the first dose of 
the previous patient. Patients enrolled in subsequent dose levels will be treated on an 
outpatient basis with no staggering of patients unless there are safety concerns based on 
findings at the lower doses.  
Once MTD or MPD is identified, additional patients may be enrolled (to a minimum of 9) at 
that dose level to further investigate the anti-leukemia activity, safety, and pharmacokinetic 
(PK) profile of PF-06747143 prior to an expansion cohort with single agent PF-06747143 at 
the MTD/MPD/RP2D.
The total estimated number of patients to be enrolled for the Part 1 dose escalation study will 
be approximately 30-50 patients.  Once the dose of 15 mg/kg in Part 1 is found safe and 
tolerable, the Part 2 combination cohorts will be initiated at 10 mg/kg while the Part 1 single 
agent dose escalation continues to 20 mg/kg for MPD or MTD assessment.  
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Planned Dose Levels for Part 1
Dose 
Level
PF-06747143 Dose (mg/kg)
QW
1
0.3
2
1.0
3
3.0
4
10
5
15
6
20
Part 2
Part 2, dose expansion, is an open-label, multi-center, non-randomized study to assess the 
safety and tolerability and preliminary anti-leukemia activity of PF-06747143 in three 
cohorts (two combination cohorts and one potential cohort of single agent PF-06747143).  
The first cohort will be PF-06747143 in combination with standard dose of intensive 
chemotherapy (ie, cytarabine and daunorubicin; D/C 7+3) in fit, treatment naïve patients with 
AML (Cohort 1).  The second will be PF-06747143 in combination with azacitidine or 
decitabine (based on drug availability and institutional guidance) in treatment naïve unfit 
patients with AML who are not candidates for or decline to receive intensive D/C 7+3 
chemotherapy (Cohort 2).  The third potential cohort is PF-06747143 as a single agent 
(Cohort 3) in patients with refractory and/or relapsed AML and will be opened if data from 
Part 1 warrants. 
Expansion in combination cohorts 1 and 2 (identified as “E1” and “E2”) will not be initiated 
until a safety lead-in (identified by an “S”) group of approximately 3-6 patients is enrolled to 
ensure the combination treatment regimen is safe and tolerable in each patient population.  
The safety lead-in will use a standard 3+3 dose escalation method to evaluate safety profile 
(using the dose limiting toxicity (DLT) criteria described in Section 3.1.1.3) for duration of 
up to 2 cycles.
Attributions to fit or unfit will be based on “Consensus-based definition of unfitness to 
intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of Italian 
SIE, SIES and GITMO group on a new tool for therapy decision making” per Investigator 
judgment.25
Cohort 3 expansion (E3), at the MTD/RP2D, may be initiated in 15-30 refractory and/or 
relapsed AML patients. The initiation of this cohort will require that single agent 
PF-06747143 demonstrates encouraging clinical benefit (eg. significantly improved CR and 
response duration compared to historical data) in the dose escalation Part 1. 
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Objectives and Endpoints
Part 1: Single Agent PF-06747143 Dose Escalation
Primary Objective
Primary Endpoint
To assess safety and tolerability at increasing 
dose levels of PF-06747143 in patients with 
refractory and/or relapsed AML for which no 
standard therapy is available in order to 
estimate the Maximum Tolerated Dose (MTD) 
and select the Recommended Phase 2 Dose 
(RP2D).
Dose Limiting Toxicities (DLTs).
Secondary Objectives
Secondary Endpoints
To evaluate the overall safety profile; 

Adverse Events as characterized by type, frequency, 
severity (as graded by National Cancer Institute 
Common Terminology Criteria for Adverse Events 
(NCI CTCAE) v4.03), 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;
To characterize the single-dose  and multiple-
dose pharmacokinetics (PK) of PF-06747143 
following IV administration;
PK parameters of PF-06747143:  Single Dose (SD) -  Cmax, 
AUClast, and if data permit, AUCinf, Vd, CL, and t1/2.  
Multiple Dose (MD) (assuming steady state is achieved)  -
Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUC), and if data 
permit, CL, Vss, and t1/2.
To evaluate the immunogenicity of PF-
06747143 following repeated administration;
Incidence of anti-drug antibodies (ADA) and neutralizing 
antibodies (Nab) against PF-06747143.
To document any anti-leukemia activity.
Preliminary evidence of anti-leukemia activity including 
objective disease response; as assessed using the
standardized response criteria (Dohner, et. al 2010) including 
objective response rate (ORR), duration of ORR, and relapse
free survival (RFS).
CCI
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Part 2:
PF-06747143: Single Agent and Combination Expansion Cohorts
Primary Objective
Primary Endpoint
To evaluate safety and tolerability and 
preliminary anti-leukemia activity of 
PF-06747143 in combination with standard 
intensive chemotherapy (ie, cytarabine and 
daunorubicin; D/C 7+3) in patients with newly 
diagnosed fit treatment naïve AML patients 
(Cohort 1) or with standard dose of decitabine 
or azacitidine in newly diagnosed unfit 
treatment naïve AML patients (Cohort 2) or 
PF-06747143 as a single agent in patients with 
refractory and/or relapsed AML ((Cohort 3) if 
data warrants).

Adverse Events as characterized by type, frequency, 
severity (as graded by National Cancer Institute 
Common Terminology Criteria for Adverse Events 
(NCI CTCAE) v4.03), 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;

Preliminary evidence of anti-leukemia activity including 
objective disease response; as assessed using the 
standardized response criteria (Dohner, et. al 2010)
including objective response rate (ORR), duration of 
ORR, and relapse free survival (RFS).
Secondary Objectives
Secondary Endpoints
To characterize the single and multiple dose PK 
of PF-06747143 in combination with standard 
intensive cytarabine and daunorubicin 7+3 
therapy in newly diagnosed fit treatment naïve 
AML patients or with standard dose of 
decitabine or azacitidine in newly diagnosed 
unfit treatment naïve AML patients;
PK parameters of PF-06747143: Single Dose (SD) - Cmax, 
Tmax, AUClast, and if data permit, AUCinf, Vd, CL, and t1/2.
Multiple Dose (MD) (assuming steady state is achieved) -
Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUCt), and if data 
permit, CL, Vss, and t1/2;
To collect PF-06747143 drug concentration 
data in patients from the dose expansion cohorts 
for evaluation of population PK.
Peak and trough PF-06747143 concentrations for selected 
doses;
To evaluate the immunogenicity of 
PF-06747143 following repeated 
administration.
Incidence of ADA and Nab against PF-06747143.
CCI
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The overall study scheme is shown below:
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Patient Selection
Patient eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before patients are included in the study. 
Inclusion (Part 1 and Part 2 Cohort 3)
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Patients with AML (primary AML diagnosis is based upon the 2008 WHO classification 
with bone marrow (BM) or peripheral blood (PB) blast counts 20%23) refractory,
relapsed and/or patients that are not candidates to receive standard of care and/or refusing 
the standard care of therapies:

Patient received prior chemotherapy and/or standard of care and have relapsed, 
refractory or Minimal Residual Disease (MRD).26,27,28,29

MRD is defined as patients showing residual blast 10-14 days post-induction 
chemotherapy.
2. Life expectancy at least 12 weeks.
3. Hydroxyurea is allowed prior to Day 1 but must be ceased 24 hours prior to first dose. 
Thereafter, hydroxyurea may be used during Cycle 1 as needed to control total peripheral 
WBC counts (see Section 5.8.1).
4. Age 18 years old.
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2.
6. Patients must have been off previous anti-leukemia therapy for at least 2 weeks or 
5 half-lives, whichever is shorter if the immediate prior regimen included only weekly 
chemotherapy; or 4 weeks from any therapy with therapeutic biologics and from any type 
of investigational therapy prior to the first dose of PF-06747143.
7. Resolved acute effects of any prior therapy to baseline severity or Grade 1 CTCAE 
except for adverse events (AEs) not constituting a safety risk by investigator judgment.
8. At least 4 weeks since radiotherapy prior to the first dose of PF-06747143.  Patients must 
have passed nadir WBC and platelet counts, have full recovery or stabilization of 
absolute neutrophil counts (ANC) and platelet counts, and ANC counts must have 
recovered from prior toxicity.
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9. Adequate renal and hepatic function, including all of the following:

Creatinine clearance 45 mL/min as measured or as calculated using the method 
standard for the institution;

Aspartate aminotransferase (AST) 3 x upper limit of normal (ULN);

Alanine aminotransferase (ALT) 3 x ULN;

Bilirubin 2.0 mg/dL (except patients with Gilbert’s Syndrome who must have total 
bilirubin <3.0 mg/dL).
10. Negative serum/urine pregnancy test (for females of childbearing potential) at screening.
11. Male patients able to father children and female patients of childbearing potential and at 
risk for pregnancy must agree to use 2 highly effective methods of contraception 
throughout the study and for at least 60 days after the last dose of assigned treatment. 
12. Female patients who are not of childbearing potential (ie, meet at least one of the 
following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved post-menopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level within the 
laboratory’s reference range for postmenopausal women.
13. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study.
14. Patients who are willing and able to comply with the study scheduled visits, treatment 
plans, laboratory tests and other procedures. 
Inclusion (Part 2 Cohort 1 and Cohort 2)
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Newly diagnosed, previously untreated, de novo or secondary AML population (AML 
diagnosis is based on the 2008 WHO classification with BM or PB blast counts 20%23):

Cohort 1: Fit to receive intensive remission induction chemotherapy at the time of 
enrolment.  Patients must have NONE of the following to be considered fit:

ECOG of 2 or 3; 
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
Serum creatinine clearance 45 mL/min as measured or as calculated using the 
method standard for the institution;

Severe cardiac disease (eg, left ventricular ejection fraction (LVEF) <45% by 
multigated acquisition scan (MUGA) or echocardiogram (ECHO) at screening.

Cohort 2: Unfit to receive or not considered a candidate for intensive remission 
induction chemotherapy at the time of enrollment based on EITHER: 

75 years of age, OR

<75 years of age with at least 1 of following:

Poor performance status (ECOG) score of 2 or 3; 

Clinically significant heart or lung comorbidities, as reflected by at least 1 of 
following: 

LVEF ≤50%; 

Diffusing capacity of the lungs for carbon monoxide (DLCO) 65% of 
expected; 

Forced expiratory volume in 1 second (FEV1) 65% of expected; 

Chronic stable angina or congestive heart failure controlled with 
medication.

Liver transaminases >3 upper limit of normal (ULN);

Other contraindication(s) to anthracycline therapy (must be documented).

Other comorbidity the investigator judges incompatible with intensive remission 
induction chemotherapy which must be documented and approved by the study 
medical monitor before randomization.
2. Hydroxyurea is allowed prior to Day 1 but must be ceased 24 hours prior to first dose. 
Thereafter, hydroxyurea may be used during Cycle 1 as needed to control total peripheral 
WBC counts (see Section 5.8.1).  
3. Age 18 years old.
4. ECOG performance status: 0 to 3.
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5. Adequate renal and hepatic function, including all of the following:

Creatinine clearance 45 mL/min as measured or as calculated using the method 
standard for the institution;

AST 3 x ULN;

ALT 3 x ULN;

Bilirubin 2.0 mg/dL (except patients with Gilbert’s Syndrome who must have total 
bilirubin <3.0 mg/dL).
6. Negative serum/urine pregnancy test (for females of childbearing potential) at screening.
7. Male patients able to father children and female patients of childbearing potential and at 
risk for pregnancy must agree to use 2 highly effective methods of contraception 
throughout the study and for at least 60 days after the last dose of assigned treatment. 
8. Female patients who are not of childbearing potential (ie, meet at least one of the 
following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved post-menopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level within the 
laboratory’s reference range for postmenopausal women.
9. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study.
10. Patients who are willing and able to comply with the study scheduled visits, treatment 
plans, laboratory tests and other procedures. 
Exclusion Criteria (Part 1 and Part 2 Cohort 3)
Patients with any of the following characteristics/conditions will not be included in Part 1 
and Part 2 Cohort 3 portions of the study: 
1. Patients with acute promyelocytic leukemia (APL), AML with known central nervous 
system (CNS) involvement unless the patient has completed treatment for the CNS 
disease, has recovered from the acute effects of therapy prior to study entry, and is 
neurologically stable.
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2. Chronic graft versus host disease (GVHD) requiring active systemic treatment, active 
GVHD with other than Grade 1 skin involvement, or GVHD requiring systemic 
immunosuppressive treatment.  Patients with GVHD receiving systemic 
immunosuppressive treatment must be able to discontinue the therapy at least 2 weeks 
prior to the first dose of PF-06747143.
3. Patient is known to be refractory to platelet or packed red cell transfusions per 
institutional guidelines. 
4. Patient is within 3 months post allogenic hematopoietic stem cell transplant or within 
30 days post autologous stem cell transplant, and the patient has not recovered from 
transplant-associated toxicities prior to the first dose of PF-06747143. 
5. Known active fungal, bacterial, and/or viral infection requiring systemic therapy within 
3 days prior to the first dose of PF-06747143. 
6. Prior treatment with a compound targeting CXCR4. 
7. Liver cirrhosis Child B or C.
8. Active and clinically significant infection with hepatitis A (HAV), hepatitis B (HBV), 
hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired 
immunodeficiency syndrome (AIDS)-related illness.
9. Participation in other studies involving investigational drug(s) within 4 weeks prior to the 
first dose of PF-06747143 and/or during study.
10. Major surgery within 4 weeks of first dose of PF-06747143.
11. Chronic systemic corticosteroid treatment. Topical applications, inhaled sprays, eye 
drops, local injections of corticosteroids and systemic steroids required for acute medical 
interventions are allowed.
12. Current mental illness requiring psychiatric hospitalization, institutionalization or 
intensive outpatient management, or current cognitive status that produces dependence 
(as confirmed by the specialist) not controlled by the caregiver, or recent (within the past 
year) or active suicidal ideation or behavior.
13. Uncontrolled neoplasia (other than AML).
14. Other severe acute or chronic medical condition 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. 
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15. Patients who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of the 
study.
16. Pregnant females; breastfeeding females; male patients with partners currently pregnant; 
male patients able to father children and female patients of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in this 
protocol for the duration of the study and for at least 60 days after last dose of 
investigational product. 
17. Any of the following in the previous 6 months: myocardial infarction, congenital long QT 
syndrome, Torsades de pointes, arrhythmias (including sustained ventricular 
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior 
hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, 
symptomatic congestive heart failure (CHF New York Heart Association class III or IV), 
cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary 
embolism.  Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or QTc Fridericia
(QTcF) interval >470 msec at screening.
18. Known or suspected hypersensitivity to recombinant human proteins.
Exclusion Criteria (Part 2 Cohort 1 and Cohort 2)
Patients with any of the following characteristics/conditions will not be included in the Part 2 
portions of the study: 
1. Patients with acute promyelocytic leukemia (APL), AML with known central nervous 
system (CNS) involvement unless the patient has completed treatment for the CNS 
disease, has recovered from the acute effects of therapy prior to study entry, and is 
neurologically stable.
2. Patient is known to be refractory to platelet or packed red cell transfusions per 
institutional guidelines. 
3. Known active fungal, bacterial, and/or viral infection requiring systemic therapy within 
3 days prior to the first dose of PF-06747143. 
4. Prior treatment with a compound targeting CXCR4.
5. Prior treatment with hypomethylating agents (eg, decitabine or azacitidine) or 
chemotherapy for antecedent myelodysplastic syndrome (MDS) (Cohort 2).
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6. AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or 
t(15;17) (Cohort 2).
7. Patients who are candidates for allogeneic stem cell transplant at the time of enrollment 
(Cohort 2).
8. Liver cirrhosis Child B or C.
9. Active and clinically significant infection with hepatitis A (HAV), hepatitis B (HBV), 
hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired 
immunodeficiency syndrome (AIDS)-related illness.
10. Participation in other studies involving investigational drug(s) within 4 weeks prior to the 
first dose of PF-06747143 and/or during study.
11. Major surgery within 4 weeks of study entry.
12. Chronic systemic corticosteroid treatment. Topical applications, inhaled sprays, eye 
drops, local injections of corticosteroids and systemic steroids required for acute medical 
interventions are allowed.
13. Uncontrolled neoplasia (other than AML).
14. Current mental illness requiring psychiatric hospitalization, institutionalization or 
intensive outpatient management, or current cognitive status that produces dependence 
(as confirmed by the specialist) not controlled by the caregiver, or recent (within the past 
year) or active suicidal ideation or behavior.
15. Other severe acute or chronic medical condition 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. 
16. Patients who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of the 
study.
17. Pregnant females; breastfeeding females; male patients with partners currently pregnant; 
male patients able to father children and female patients of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in this 
protocol for the duration of the study and for at least 60 days after last dose of 
investigational product. 
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18. Any of the following in the previous 6 months: myocardial infarction, congenital long QT 
syndrome, Torsades de pointes, arrhythmias (including sustained ventricular 
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior 
hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, 
symptomatic congestive heart failure (CHF New York Heart Association class III or IV), 
cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary 
embolism.  Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or QTcF interval 
>470 msec at screening.
19. Known or suspected hypersensitivity to recombinant human proteins.
20. The presence of any one of the following hypersensitivities:

Cohort 1: hypersensitivity to cytarabine (not including drug fever or exanthema) or 
daunorubicin;

Cohort 2: 

Hypersensitivity to decitabine or azacitidine;

Hypersensitivity to mannitol.
DLT Definition
A DLT will be classified according to NCI CTCAE version 4.03 and is defined as any of the 
following adverse events unless the event can clearly be determined to be unrelated to drug
occurring in the first cycle of treatment (within 28 days of first dose or until patient receives 
a second cycle if there are treatment delays).  Data from all cycles of treatment will be 
analyzed for safety, delayed toxicity, and cumulative toxicity.  DLT is defined as:

Hematologic:

Failure to achieve an ANC greater than 1,000/uL and/or a platelet count greater 
than 25,000/uL independent of platelet transfusion by day 42 after the start of 
therapy, with a hypocellular bone marrow (<10% marrow cellularity) and absence 
of persistent leukemia (ie, <5% marrow blasts) measured at the completion of 
Cycle 1 (approximately day 28-32);

If a subject with persisting cytopenias does not exhibit marrow hypoplasia on 
biopsy (or bone marrow aspirate) or demonstrates persisting leukemia, such 
subject will not be considered to have demonstrated a hematological toxicity 
and may continue to receive PF-06747143 at the scheduled time point for 
Cycle 2.

Hyperleukocytosis (WBC 100,000/uL) not managed by hydroxyurea and/or 
leukapheresis and/or resulting in an adverse event.
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
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

Non-hematologic:

Grade 3 toxicities, except for:

Grade 3 nausea or vomiting that resolves to Grade 1 within 72 hours with 
appropriate supportive therapy; 

Grade 3 diarrhea that resolves to Grade 1 within 72 hours with appropriate 
supportive therapy; 

Grade 3 fatigue, asthenia, or other constitutional symptom that resolves to 
Grade 1 within 7 days with appropriate supportive therapy; 

Alopecia of any grade;

Grade 3 infection, fever (including febrile neutropenia), electrolyte 
abnormalities and ALT/AST elevation that returns to Grade 1 or baseline 
within 7 days;

Delay by more than 14 days to receive the next scheduled dose due to a persisting
drug-related AE.
In addition, clinically important or persistent toxicities that are not included in the above 
criteria may be considered a DLT following review by the Investigators and sponsor.  All 
DLTs need to represent a clinically significant shift from baseline.
Grade 3 cytokine release syndrome, infusion reaction, and allergic reaction will not be 
considered as DLTs (as it is unlikely to be dose related), but may be a reason for study 
discontinuation, protocol amendment (eg, pre-infusion treatments, infusion duration) and 
should be reviewed with the sponsor. 
In principle, a patient needs to be on study for at least 28 days to be evaluable for DLT 
observation, and may be replaced if they terminate study participation earlier than 28 days
without experiencing a DLT.  
Statistical Method
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 in dose escalation.  
For all dose levels, patients may be enrolled in cohorts of 2-4 (the target size of each cohort 
will be 3 patients).  Intermediate dose levels to further evaluate the safety and/or PK may be 
evaluated following discussion between sponsor and Investigator.
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to Section 7 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 (QW)
Off Treatment
Time Points and Assessments
Screen§
Cycle 1
(Day 1 to 28)
Cycle 2
(Day 1 to 28)
Cycle 3 and
Subsequent Cycles‡
End of 
Treat.♦
28 Day
F/U◊
60 Day 
F/U◊
Visit Identifier
Within
28 days 
Day
1
Day
2
Day
8
Day
15
Day
22
Day
1
Day
8
Day
15
Day
22
Day
1
Day
8
Day
15
Day
22
Informed Consenta
X
Medical Historyb
X
AML History 
(histology, cytogenetics, karyotype 
and mutation status)c
X
Prior Medications
X
Complete Physical Examination
X
Baseline Signs and Symptoms
Xd
Registration
Xe
Abbreviated Physical Examinationf
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight 
X
Xg
Xg
Xg
Xg
Xg
Xg
X
Vital Signsh (BP/HR)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status 
X
X
X
X
X
X
X
Triplicate 12-lead ECGi
Xj
Xj
Xj
Xj
Xj
Xj
Hematologyk
Xl
Xl
X
Xl
Xl
Xl
Xl
Xl
Xl
X
X
X
Coagulationm
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
X
X
Chemistryn
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
X
X
Urinalysiso
Xl
Xl
Xl
Xl
Xl
Xl
X
X
Pregnancy testp
X
X
X
X
X
X
X
Contraception Checkq
X
X
PF-06747143 Treatmentr
X
X
X
X
X
X
X
X
X
X
X
X
Overnight Stay (Part 1: 0.3 mg/kg 
and 1.0 mg/kg)s
X
Cardiac Monitoring and Pulmonary 
Function Tests (Part 2, Cohort 1)t
X
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Treatment Period (QW)
Off Treatment
Time Points and Assessments
Screen§
Cycle 1
(Day 1 to 28)
Cycle 2
(Day 1 to 28)
Cycle 3 and
Subsequent Cycles‡
End of 
Treat.♦
28 Day
F/U◊
60 Day 
F/U◊
Visit Identifier
Within
28 days 
Day
1
Day
2
Day
8
Day
15
Day
22
Day
1
Day
8
Day
15
Day
22
Day
1
Day
8
Day
15
Day
22
For Part 2, Cohort 1: Cytarabine and 
Daunorubicin
X 
Cytarabine 
Days 1-7; 
Daunorubicin
Days 1-3
Remission; 
Consolidation
No remission; 
Per 
Investigator
Part 2, Cohort 2: Azacitidine or 
Decitabine
X
Azacitidine
Days 1-7
or
Decitabine 
Days 1-5
Azacitidine
Days 1-7
or
Decitabine 
Days 1-5
Azacitidine
Days 1-7
or
Decitabine 
Days 1-5
Disease Assessmentu
X
X
X
X
X
Adverse Event Monitoringv
















Concomitant Medicationsw
















Banked biospecimens (Prep D1) for 
biobankingx
X
X
X
X
Banked biospecimen (Prep B1)x
X
Notes to Table:
The requested assessments and procedures are to be performed unless otherwise specified. 
Tests and procedures should be done on schedule, but occasional changes by 3 days (unless otherwise stated differently) are allowed for holidays, vacations and 
other administrative reasons. 
Sampling schedule for Pharmacokinetic, Immunogenicity and Biomarker sampling is contained in Table 1 and Table 2 below.
§
Screening assessments should be performed within 28 days prior to the first dose. 
‡
To be done each cycle except where noted by footnote or other indication in protocol.
♦
End-of-Treatment (EOT) visit conducted at the visit that the patient is discontinued from the study medication. 
◊ 
28 and 60 days after last dose of PF-06747143.
a.
Informed Consent: Must be obtained prior to any study-specific procedures and can be obtained >28 days prior to first dose of PF-06747143.
b.
Medical History: Including history of prior treatments and any current medical treatments for any condition. 
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c.
AML History: Collected for this study any time after informed consent. This should include details of primary AML diagnosis, biopsy information, and the 
patient’s treatment history (systemic treatment, stem cell transplants, and radiotherapy). For screening, a fresh bone marrow aspirate sample and biopsy 
obtained within 14 days of screening is acceptable for patient eligibility and biomarker assessment.
d.
Baseline Signs & Symptoms: patients will be asked about any signs and symptoms experienced within the 14 days prior to study entry.  Baseline signs and 
symptoms will be recorded on the Baseline Signs and Symptoms (BSS) Adverse Event (AE) case report form (CRF) page.
e.
Registration: To occur within 5 days of first dose of PF-06747143.
f.
Abbreviated PE: A symptom directed exam conducted by a physician, trained physician’s assistant or nurse practitioner, as acceptable according to local 
regulation.
g.
Weight: The patient’s weight from Day 1 of each cycle should be used to calculate the amount of dose of PF-06747143 for all infusions.  If a patient’s 
weight fluctuates by more than 10% in either direction at the beginning of the next cycle, the dose should be recalculated for the infusions of that cycle (in 
cases where individual institution/pharmacy practices require more frequent weight measurements, weight can be obtained on each day of administration, 
and the dose can be adjusted for weight changes of 10%). 
h.
Vitals: Includes blood pressure and heart rate.  Blood pressure should be taken after the patient has been seated quietly for at least 5 minutes.
i.
Triplicate ECG: Three consecutive 12-lead ECGs will be performed approximately 2 minutes apart.
j.
Triplicate 12 lead ECGs should be performed at:

Screening. 

C1D1, C1D15 and Day 1 of each subsequent Cycle: pre-dose (collected within 6 hours prior to dosing) and post-dose (within 1 hour from the end 
of PF-06747143 infusion).

End-of-Treatment.

Additional ECGs may be performed as clinically indicated.  When coinciding with blood sample draws for PK, ECG assessment should preferably 
be performed prior to blood sample collection, such that the blood sample is collected at the nominal time.
k.
Hematology: Hemoglobin (Hgb), platelets, total WBC, percent blast cell, absolute neutrophils, lymphocytes, monocytes, eosinophils and basophils. For 
Cycle 1, 
 noted in Table 1 and Table 2 will also function as the hematology 
safety assessment. 

NOTE: During Cycle 1, the 0 hour (ie, “pre-dose”) peripheral CBC lab must be assessed within 12 hours prior to study drug administration. If the 
patient’s total peripheral WBC count is 75,000/uL, the Investigator shall consult with and obtain the sponsor’s agreement to move forward with 
study drug administration.
l.
Laboratory Assessments: 

Screening labs to be performed within 7 days of randomization/registration. 

Except for the 0 hour CBC, if screening labs are drawn within 7 days prior to C1D1 and are within 10% of eligibility criteria, labs do not need to be 
reviewed prior to Cycle 1 Day 1, but do need to be drawn prior to treatment. However, the 0 hour CBC lab must be drawn within 12 hours and 
reviewed prior to each PF-06747143 infusion during Cycle 1 including C1D1 (see Hematology footnotek).

For subsequent cycles, pre-dose laboratory assessments may also be drawn up to 72 hours in advance of scheduled dosing in order to obtain results 
prior to infusion (if necessary).
m. Coagulation: PTT and International Normalized Ratio (INR) or prothrombin time.
n.
Chemistry: ALT, AST, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, BUN or urea, creatinine, uric acid, 
glucose (non-fasting), albumin, phosphorus or phosphate.
o.
Urinalysis: Protein and blood by dipstick. 
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p.
Pregnancy Test: Patients of childbearing potential must have a negative blood or serum pregnancy test at screening and on C1D1 prior to dosing, on 
Day 1 of all subsequent doses, and at the End-of-Treatment and 60-Day F/U visit.  Additional pregnancy tests may also be undertaken if requested by 
institutional review boards/institutional ethic committees (IRB/IECs) or if required by local regulations.
q.
Contraception Check: The investigator or his or her designee, in consultation with the patient, will confirm that the patient has selected 2 appropriate 
methods of contraception for the individual patient and/or partner from the permitted list of contraception methods and will confirm the patient has been 
instructed in its consistent and correct use.  Assessment should be performed within 7 days of C1D1 and at the 60 Day F/U visit. Refer to Section 4.3.1.
r.
Study Treatment:  PF-06747143 will be infused on Days 1, 8, 15 and 22 of each Cycle beginning in patients enrolled in dose level 1 (0.3 mg/kg).  Please 
refer to the Investigational Product (IP) Manual for more information.  NOTE: Prior to each PF-06747143 infusion during Cycle 1, the patient’s total 
peripheral WBC must be assessed and if 75,000/uL, the Investigator shall consult with and obtain the sponsor’s agreement to move forward with study 
drug administration (see footnote k).
s.
Overnight stay: Patients enrolled in the first two dose levels (0.3 mg/kg and 1.0 mg/kg) will be required to stay in the clinic/hospital overnight (minimum of 
24 hours) after receiving the first dose of PF-06747143 to monitor for the potential risk of hyperleukocytosis.  On an individual basis, patients may be 
monitored overnight for the additional doses in Cycle 1 at the treating physician’s discretion. 
t.
Cardiac Monitoring and Pulmonary Function Testing: Patients in Part 2, Cohort 1 will be required to have:

Cardiac Monitoring:  Screening ECHO/MUGA scan to confirm eligibility. Additional scans will also be performed when the cumulative dose of 
daunorubicin reaches 400 mg/m2, and every 2 cycles thereafter.  Decreases in LVEF will be handled according to institutional guidelines.

Pulmonary Function Testing: Diffusing capacity of the lungs for carbon monoxide (DLCO) and forced expiratory volume ((FEV) measured during 
the first forced breath (FEV1)) will be performed to confirm eligibility.  Additional assessments may be performed as clinically indicated.
u.
Disease Assessment: Disease assessments will be made on the basis of Dohner et al. 2010 (see Section 7.6.).  For screening, a fresh bone marrow aspirate 
sample and biopsy obtained within 14 days of screening is acceptable for patient eligibility and biomarker assessment. Peripheral CBC with WBC
differential, percent blast cell and platelet count as well as bone marrow aspiration and biopsy to assess bone marrow cellularity and percent blasts, are to be 
conducted at completion of Cycle 1, approximately at Day 28, and prior to starting of every other new cycle of treatment (C3, C5, C7, etc.) until 
achievement of a complete response.  Bone marrow aspirates and/or biopsies and peripheral CBC assessments may be obtained at other intervals, if 
clinically indicated.  Responses should be confirmed with repeat blood counts and, as appropriate, bone marrow examinations and other tests.  In patients 
who are discontinued from the study treatment for reasons other than disease progression, every attempt will be made to continue disease assessment until 
disease progression or another treatment is initiated.  
v.
Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) version 4.03.  Patients must be followed for AEs for 60 days after the last study treatment administration or until 
all drug-related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another anti-cancer therapy in the meantime.  
For serious adverse events (SAEs), the active reporting period to Pfizer or its designated representative begins from the time that the patient provides 
informed consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study related procedure and/or receiving 
investigational product, through and including 28 calendar days after the last administration of the investigational product.  SAEs occurring to a patient after 
the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational product are to be reported to the sponsor.
w.
Concomitant Medications: all concomitant medications and Non-Drug Supportive Interventions should be recorded in the CRF. NOTE: Hydroxyurea 
and/or leukapheresis is permitted during Cycle 1 as needed to control total peripheral WBC counts (see Section 5.8.1), however must be ceased.
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x.
Whole Blood (Prep D1) and Plasma (Prep B1) Biospecimens: Unless prohibited by local regulations, or ethics committee decision these samples will be 
banked, in order to provide opportunities to evaluate molecular mechanisms of response and drug action that are manifest in the circulation of cancer 
patients.  Whole blood (D1) samples are collected prior to the first dose, on Day 1 of each cycle from Cycles 1 through 6, and at End-of-Treatment. Plasma 
(Prep B1) biospecimens are collected predose on C1D1 only.
Abbreviations: AML = acute myeloid leukemia; BP = blood pressure; HR = heart rate; ECOG = Eastern Cooperative Oncology Group; ECG = 
electrocardiogram; F/U = follow-up; C = Cycle; D = Day; PK = pharmacokinetics; = ongoing/continuous event; PE = physical exam; ECHO = 
echocardiogram; MUGA = Multigated acquisition scan; AE = adverse event; SAE = serious adverse event.
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Table 1.
PF-06747143 Pharmacokinetic, Immunogenicity and Biomarker Sampling Schedule (Part 1 and Part 2: 
Cohorts S1, S2)
Screen
Cycle 1
Cycle 2
Subsequent 
Cycles
EOT
Visit Day
1
2
3
5
8
15
22
1
2
3
5
8
15
22
1
Hours Post-Dose*
0a
1
4
24
48
96
0a
1
4
0a
1
0a
1
0a
1
24
48
96
0a
0a
0a
0a
Visit Window†
0.5 
hr
8 hrs 8 hrs 24 hrs
0.5 
hr
8 hrs 8 hrs 24 hrs
PK blood sampling
Xb
X
X
X
X
X
Xb
X
X
Xb
X
X
X
X
X
X
X
Xb
Xb
Blood sample for 
ADA/Nabc
X
X
X
Xd
Xd
X
X
X
Abbreviations: EOT = End-of-Treatment; hrs = hours; PK = pharmacokinetic; ADA = anti-PF-06747143 antibodies; 
; Ribonucleic acid = RNA; ADCC = antibody-dependent cell-mediated cytotoxicity; 
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*Collection Time:  Sampling times are related to the start of infusion.
†Sample collection windows: The 1 hr samples should be collected within 1 hr after the end of infusion.  All other sampling should be within the protocol 
specified window in the table above.
a.
0 hour (ie, “pre-dose”) timepoints must be collected within 6 hours prior to start of PF-06747143 infusion, unless otherwise noted. 
b.
A companion blood sample for the determination of PF-06747143 concentration will be collected in conjunction with the ADA sample collection to 
facilitate immunogenicity assessment.
c.
Collection of serum to detect the presence of antibodies to PF-06747143 is to be obtained prior to the start of treatment and according to the schedule above.  
Patients having an unresolved AE that is possibly related to anti-PF-06747143 antibodies at their last assessment will be asked to return to the clinic for 
ADA and drug concentration blood sampling at up to 3 month intervals until the AE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and sponsor.
d.
After Cycle 2, ADA/Nab sample will be collected pre-dose on Day 1 of Cycles 3-6, and pre-dose on Day 1 every 3 cycles thereafter (eg, Cycles 9, 12, 15, 
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Table 2.
PF-06747143 Pharmacokinetic, Immunogenicity and Biomarker Sampling Schedule (Part 2: Cohorts E1, E2 and
E3)
Screen
Cycle 1
Cycle 2
Subsequent 
Cycles
EOT
Visit Day
1
2
3
5
8
15
22
1
2
8
1
Hours Post-Dose*
0a
1
4
24
48
96
0a
1
4
0a
1
0a
1
0a
1
24
0a
0a
Visit Window†
0.5 
hr
8 hrs 8 hrs 24 hrs
0.5 
hr
8 hrs
PK blood sampling
Xb
X
X
Xb
X
Xb
X
X
X
Xb
Xb
Blood sample for 
ADA/Nabc
X
X
X
Xd
Xd
 
Abbreviations: EOT = End-of-Treatment; hrs = hours; PK = pharmacokinetic; ADA = anti-PF-06747143 antibodies; 
; 
 
; Ribonucleic acid = RNA; 
*Collection Time: Sampling times are related to the start of infusion.
†Sample collection windows: The 1 hr samples should be collected within 1 hr after the end of infusion.  All other sampling should be within the protocol 
specified window in the table above.
CCI
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a.
0 hour (ie, “pre-dose”) timepoints must be collected within 6 hours prior to start of PF-06747143 infusion, unless otherwise noted. 
b.
A companion blood sample for the determination of PF-06747143 concentration will be collected in conjunction with the ADA sample collection to 
facilitate immunogenicity assessment.
c.
Collection of serum to detect the presence of antibodies to PF-06747143 is to be obtained prior to the start of treatment and according to the schedule above.  
Patients having an unresolved AE that is possibly related to anti-PF-06747143 antibodies at their last assessment will be asked to return to the clinic for 
ADA and drug concentration blood sampling at up to 3 month intervals until the AE or its sequelae resolve or stabilize at a level acceptable to the 
investigator and sponsor. 
d.
After Cycle 2, ADA/Nab sample will be collected pre-dose on Day 1 of Cycles 3-6, and pre-dose on Day 1 every 3 cycles thereafter (eg, Cycles 9, 12, 15, 
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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist for the 
chemokine CXCR4 and intended to be used for the treatment of adult patients with advanced 
hematological malignancies unresponsive to currently available therapies, and for which no 
standard therapy is available.  This protocol is limited to patients with acute myeloid 
leukemia (AML) who have not obtained remission with induction therapy or who have 
relapsed after achieving remission.
1.2. Background and Rationale
The C-X-C chemokine receptor type 4 (CXCR4) (or CD184) is a G-protein coupled 
chemokine receptor, expressed on the cell surface, and has a 7-transmembrane structure.1,2
CXCR4 plays a role in the cross talking between cancer cells and their microenvironment by 
binding its ligand, chemokine ligand 12 (CXCL12),3,4 thereby activating the downstream 
signaling pathways leading to alteration of gene expression, actin polymerization, cell 
skeleton rearrangement, and cell migration and proliferation.5
The tumor microenvironment consists of resident non-cancerous cells (stromal fibroblasts, 
endothelial cells, and immune cells), connective tissue and extracellular matrix, altogether 
supporting tumor structure, angiogenesis, and growth.6 CXCL12 is physiologically mainly 
expressed by mesenchymal stromal cells in various organs and tissues such as the liver, 
lungs, lymphatic tissues, and bone marrow.7 High levels of CXCL12 directly stimulate the 
proliferation and invasiveness of CXCR4-expressing cancer cells in an autocrine and 
paracrine manner.7 Nonclinical mouse models of non-Hodgkin’s lymphoma (NHL), AML, 
chronic lymphocytic leukemia (CLL), and human multiple myeloma (MM) have shown that 
CXCR4-positive cancer cells can be recruited to CXCL12-rich mesenchymal stroma niches.
Since the CXCL12-CXCR4 interaction is considered crucial for attracting tumor cells to the 
bone marrow niche, CXCR4 inhibitors have been explored as treatment agents in the field of 
leukemia treatment.8,9,10,11,12 CXCR4 is overexpressed in 75% of cancers (hematological 
malignancies and solid tumors), and its expression correlates with poor prognosis in various 
cancers.8,9,10,11,12
PF-06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of 
CXCR4.  PF-06747143 has demonstrated robust anti-tumor activity in immune-compromised 
mice engrafted with human cells representing several human hematological malignancies 
including NHL, CLL, MM, and AML with a treatment regimen either as a single agent or in 
combination with standard of care agents.  Based on the nonclinical studies conducted, the 
mechanisms of action of PF-06747143 include: 1) inhibition of CXCR4-CXCL12 signaling, 
thereby inducing cell mobilization from CXCL12-rich niches; 2) direct induction of 
caspase-independent cell-death through an antibody (Ab) bivalency-dependent mechanism; 
and 3) induction of cell death through Fc-effector function (antibody-dependent 
cell-mediated cytotoxicity (ADCC) /complement dependent cytotoxicity [CDC]) inherent to 
the IgG1 backbone. 
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Given the extensive nonclinical anti-tumor activity of PF-06747143 demonstrated in a large 
number of animal models, clinical trials of PF-06747143 alone or in combination with other 
agents are warranted.
1.3. PF-06747143
1.3.1. Nonclinical Efficacy
The in vitro characterization of PF-06747143 is summarized in Table 3 and described below.  
PF-06747143 is a potent and selective CXCR4 antagonist.  PF-06747143 showed high 
affinity for the human CXCR4 receptor (KD: 0.36 nM).  The antibody showed similar half 
maximal effective concentration (EC50) binding for native human and monkey CXCR4 
(EC50s: 0.27 nM and 0.16 nM, respectively).  In vitro functional testing showed that the 
antibody is a potent antagonist of CXCR4, inhibiting ligand (CXCL12)-induced calcium flux 
with IC50 value of 1.75 nM and stimulating ligand-inhibited cellular cyclic adenosine 
monophosphate (cAMP) production with an EC50 of 9.45 nM.
The ability of the bivalent full-length PF-06747143 antibody, and its Fab (monovalent) and 
F(ab’)2 (bivalent lacking Fc-portion) forms, to induce cell-death was evaluated in NHL 
Ramos cells.  These studies demonstrated that PF-06747143 induces cell-death in a 
bivalency-dependent fashion.  Moreover, the Fc portion of the antibody is not required for 
this activity, demonstrated by the fact that the (Fab’)2 antibody form (bivalent but deprived 
of the Fc effector portion) is capable of inducing cell-death.
The effector function activity of PF-06747143 was evaluated on NHL Ramos cell line, in the 
presence of natural killer (NK) effector cell line (NK92 V158).  The ADCC EC50 was 
0.421 nM.  PF-06747143 showed 20% specific lysis of NHL Daudi cells in the CDC assay 
conducted in the presence of 2.5% donor serum.
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Table 3.
PF-06747143 in vitro Characterization Summary
Assay 
Assay Conditions
Results
Binding Affinity to CXCR4 
(Biacore)
Fab fragment of PF-06747143 binding kinetics 
measured by Biacore using human 
CXCR4-expressing lipoparticles
KD: 0.36 nM
Off-rate (kd): 2.9E-04 (1 /s)
Inhibition of Ligand-induced 
Intracellular Calcium Flux
Functional Potency by measuring Calcium flux 
in T-cell leukemia line (Jurkat) naturally 
expressing CXCR4, in presence of CXCL12 
(ligand) at its EC80.
IC50: 1.75 nM
Stimulation of Ligand-Inhibited 
cAMP
Functional Potency by measuring cAMP 
accumulation in cell line CHO- K1 expressing 
CXCR4 (DiscoveRx), in presence of CXCL12 
(ligand) at its IC80.
EC50: 9.45 nM
Cell-Death
Induced Cell-Death in NHL Ramos cell line, 
measured by Annexin V staining in flow 
cytometry.
32% Cell-Death at 100 nM of Ab
Fc-effector Function Mediated 
Cytotoxicity
ADCC assay: Ramos (NHL) tumor cells at 10:1 
E:T ratio of NK-92(158V) effector cells to tumor 
cells.
CDC assay: Daudi (NHL) tumor cells with 2.5% 
human single donor complement treated with 5 
g/mL (33 nM) of PF-06747143.
ADCC assay EC50: 0.421 nM
CDC assay: 20% specific lysis 
compared to non-binding negative 
control hIgG1 Ab
Ab = Antibody; cAMP = Cyclic adenosine monophosphate; CDC = Complement-dependent cytotoxicity; 
CHO = Chinese hamster ovary; hIgG1 = Human immunoglobulin gamma 1; NHL = Non-Hodgkin’s lymphoma.
PF-06747143 has no cross-reactivity with the murine CXCR4, therefore efficacy and PK/PD
studies were conducted in xenograft models in mice. Human tumor cell lines representing 
diverse hematological tumor types (NHL, AML, CLL and MM) were used to evaluate 
efficacy of PF-06747143 in various tumor models. A summary of PF-06747143 in vivo 
efficacy studies is shown in Table 4 and described below.
PF-06747143 efficacy was first examined in a human NHL xenograft subcut aneous mouse 
model (Ramos NHL cell line) at test doses of 0.1, 1.0, 10 and 30 mg/kg, every 7 days (q7d).  
At doses of 10 mg/kg and 30 mg/kg the antibody produced robust tumor regression that 
persisted for several weeks after dosing was suspended (Day 21).  The non-clinical effective 
concentration (Ceff) resulting in tumor regression (25%) was determined to be 47.3 g/mL in 
this study. 
Treatment with PF-06747143 at 10 mg/kg subcutaneously q7d in a human AML
disseminated xenograft mouse model, in which tumor cells are implanted intravenously and 
spontaneously migrated to bone marrow, produced significant bone marrow and peripheral 
blood tumor burden inhibition, with activity similar to daunorubicin, a component of 
standard of care for AML patients. The non-clinical Ceff resulting in less than 5% of blasts 
in the bone marrow at the end of the study was determined to be 63.5 g/mL. 
Moreover, in the AML MV4-11 model, a single dose of PF-06747143 at 0.3, 1.0, and 
10 mg/kg induced rapid mobilization of tumor cells from bone marrow into peripheral blood 
(3-6 hrs post-dose), followed by a decrease in the number of mobilized cells back to baseline 
at 24 hrs post-dose. This confirmed the ability of PF-06747143 to block homing of 
malignant cells to bone marrow (PD marker) and to induce cell-death in vivo.
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Efficacy of PF-06747143 was also evaluated in the CLL (JVM-13) model and in the MM 
(OPM-2) model at 10 mg/kg, q7d. Single agent treatment led to increased survival and 
decreased bone marrow tumor burden in both models, and it was more efficacious than 
components of standards of care bendamustine (used in CLL) and melphalan (used in MM), 
respectively. 
PF-06747143 showed no anti-tumor effect in a CXCR4-negative TF-1 AML xenograft 
model, indicating that PF-06747143 in vivo efficacy is CXCR4-expression dependent. 
Table 4.
PF-06747143 in vivo Pharmacology Summary
Tumor 
Model
Indication
CXCR4 
Expression
Study 
Name
Compound Tested 
and Dosage
Efficacy Observed
Ramos sc
NHL
Positive
CXCR4-03
2
PF-06747143 
0.1, 1, 10, 30 mg/kg, 
sc q7d
PF-06747143 Tumor 
regression at 30 and 
10 mg/kg.  Dose 
response observed
MV4-11 
Disseminate
d
AML
Positive
CXCR4-03
6
PF-06747143 
0.1, 1, 10 mg/kg sc q7d
Daunorubicin 2 mg/kg, 
Days 1,3 and 5
PF-06747143 
dose-response.  
PF-06747143 10 
mg/kg improved 
survival & reduced PB 
and BM tumor burden.  
Similar to 
daunorubicin
MV4-11 
Disseminate
d
AML
Positive
CXCR4-04
3
PF-06747143  
0.3, 1, 10 mg/kg iv, 
single dose
PF-06737143 induced 
malignant cell 
mobilization at all 
doses tested.  Peak at 
3-6 hrs -back to 
baseline at 24 hrs.
JVM-13 
Disseminate
d
CLL
Positive
CXCR4-03
8
PF-06747143 
10 mg/kg sc q7d
Bendamustine 
30mg/kg, ip, 
QDx2 
PF-06747143 10 
mg/kg reduced tumor 
burden and 
significantly improved 
survival.  Superior to 
bendamustine.
OPM-2 
Disseminate
d
MM
Positive
CXCR4-03
5
PF-06747143 
10 mg/kg s.c q7d 
Melphalan 1 mg/kg, ip, 
2x/week, for 3 weeks
PF-06747143 10 
mg/kg reduced tumor 
burden and 
significantly improved 
survival.  Superior to 
melphalan.
TF-1 
Disseminate
d
AML
Negative
CXCR4-03
4
PF-06747143 
10 mg/kg sc q7d
No activity.
AML = Acute myeloid leukemia; CLL = Chronic lymphocytic leukemia; iv = Intravenously; MM = Multiple 
myeloma; NHL = Non-Hodgkin’s lymphoma; QDx2= two consecutive days on first week of treatment;  q7d 
= Once every 7 days; sc=Subcutaneously.
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In summary, the results from these studies demonstrated binding to the CXCR4 tumor 
antigen with high affinity and specificity.  PF-06747143 treatment inhibited 
CXCL12-induced functional activity in calcium Flux and cAMP assays. PF-06747143 also 
induced bivalency-dependent cell-death and strong effector-function mediated ADCC and 
CDC. PF-06747143 demonstrated single agent anti-tumor activity against a broad spectrum 
of CXCR4 positive xenograft models including NHL, AML, CLL, and MM. PF-06747143 
anti-tumor activity was superior to that of the standards of care components for the treatment 
of CLL and MM diseases. The in vivo activity of PF-06747143 is CXCR4-dependent, with 
no activity observed in a CXCR4-negative model.
1.3.2. Nonclinical Pharmacokinetics
PF-06747143 PK in cynomolgus monkeys has been characterized in 2 studies: Good 
Laboratory Practice (GLP) toxicology study where male and female cynomolgus monkeys 
received 10, 50, and 200 mg/kg PF-06747143 once weekly intravenous (IV) bolus for 
5 doses, and low dose PK study where female cynomolgus monkeys received a single IV 
bolus does at 0.3 mg/kg.  The PK exposure appeared to be linear at doses above 10 mg/kg, 
where a rapid elimination of PF-06747143 was observed at 0.3 mg/kg, suggesting 
target-mediated drug disposition (TMDD).  TMDD model was implemented to fit the 
monkey PK data, and the derived PK parameters were scaled to human based on allometric 
scaling.  PF-06747143 is likely to exhibit TMDD at low doses in patients with high CXCR4 
expression.  When drug concentration and dose above TMDD range, PF-06747143 is 
expected to have a clearance of 3.22 mg/kg/day and a volume of distribution (central 
compartment) of 38.3 mL/kg.  At expected clinically relevant dose ranges (PF-06747143 
3 mg/kg), the apparent terminal elimination half-life is projected to range from 7-16 days. 
1.3.3. Nonclinical Safety
The nonclinical safety profile of PF-06747143 was characterized in a series of nonclinical 
safety studies and included: A Tissue Cross-Reactivity in rat, cynomolgus monkey and 
human tissue panels; 2-week Exploratory Toxicity Study in Monkeys (0, 10, and 
200 mg/kg/week by IV route); and a 1-Month GLP Toxicity Study in Monkeys (0, 10, 50 and 
200 mg/kg by IV route). Additional studies included cytokine release assay and blood 
compatibility assay. Genotoxicity studies were not conducted with PF-06747143 in 
accordance with International Conference on Harmonisation (ICH) S6 (guidance for safety 
testing of biological products)13 and ICH S9 (guidance for nonclinical evaluation of 
anticancer pharmaceuticals).14 Carcinogenicity and Reproductive and Developmental 
Toxicity studies have not been conducted with PF-06747143 at this point. 
PF-06747143 binding EC50s on human and Cynomolgus monkey cells that endogenously 
express the receptor, is 3.02 and 2.59 nM, respectively, indicating similar binding kinetics. 
These results supported the use of Cynomolgus monkeys as a relevant species for toxicology 
studies with PF-06747143.  
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Cynomolgus monkeys were dosed with PF-06747143 once weekly by IV injection at 10 and 
200 mg/kg/dose (2-week Exploratory Study) or at 10, 50 and 200 mg/kg/dose (1-month 
pivotal GLP Study) and findings were similar in both studies.  In the exploratory study, all 
animals survived to scheduled necropsy and the main findings were leukocytosis, 
thrombocytopenia and decreased lymphoid cellularity of lymphoid organs. 
In the pivotal 1-month monkey study, adverse thrombocytopenia (<50,000 L/count) and 
nonadverse leukocytosis (2-5x) were observed at all doses.  Thrombocytopenia and 
leukocytosis did not recover based on the 1-month recovery assessed only in the 
200 mg/kg/week dose group.  This is likely due to significant levels of serum 
PF-06747143 (>10x the Ceff for PF-06747143) in all animals throughout the recovery
phase.  Leukocytes and platelets have high expression of CXCR4 and these findings were 
expected and considered a consequence of the pharmacology of an anti-CXCR4
IgG1 mAb.
PF-06747143 at 50 mg/kg/week was associated with adverse oral lesions that were 
associated with skin lesions, microscopic observations of inflammation, gum necrosis and 
bone lysis coupled with clinical pathology findings of inflammation.  Changes in the oral 
cavity contributing to poor clinical condition resulted in unscheduled euthanasia of 
1/8 animals at 50 mg/kg/week and 2/12 animals at 200 mg/kg/week and were characterized 
by decreased body weight and food consumption, discoloration and/or hemorrhage of the 
gums and/or gingiva, hunched posture, decreased activity, dehydration, and/or decreased skin 
turgor and were likely related to a localized inflammatory response.  The changes observed 
in the oral cavity and skin of animals going into recovery (200 mg/kg group only) fully 
recovered within the 1-month recovery period. 
Other PF-06747143-related changes were considered nonadverse as they were not associated
with any clinical signs, tissue damage, or alterations in clinical pathology parameters.  These 
nonadverse changes consisted of decreased lymphoid cellularity in the spleen, thymus, gut 
associated lymphoid tissue (GALT) and lymph nodes and increased generalized cellularity of 
the liver, adrenal glands, alveolar septa in lungs, spleen, choroid plexus and bone marrow.  
Other nonadverse PF-06747143-related changes in hematology parameters included 
decreases in red cell mass (red blood cell [RBC], hemoglobin [HGB], and hematocrit [HCT])
along with increases in reticulocytes, indicating regeneration.  Extramedullary hematopoiesis 
in the liver and spleen choroid plexus was also observed and correlated with changes in RBC 
mass.  The nonadverse changes described showed partial to full recovery following the 
1-month recovery period assessed in the 200 mg/kg group only.
There were no PF-06747143 related findings in electrocardiogram (heart rate or QTc), ocular 
exams, or cytokines released.  The tissue cross reactivity characterization of PF-06747143
data generally shows similar tissue staining in the human and monkey samples.  The highest 
non-severely toxic dose (HNSTD) was considered to be 10 mg/kg/dose in the pivotal 
monkey study.  Systemic exposure of PF-06747143 at the HNSTD in the pivotal monkey 
study was maximum concentration (Cmax) of 89.3 g/mL and area under the curve to 
168 hours (AUC168) was 5520 g*h/mL.  The safety margin compared to the proposed 
clinical starting dose of 0.3 mg/kg is 14 based on Cmax and 39 based on AUC.  Overall, the 
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nonclinical profile of PF-06747143 has been adequately characterized and was 
consistent with ICH S613 and ICH S9 guidance14 and supports its use in advanced cancer 
patients.
1.4. Starting Dose Rationale
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”.14  The cynomolgus 
monkey was considered to be the most appropriate species for determining the proposed 
starting dose in patients.  The HNSTD in cynomolgus monkey was determined to be 
10 mg/kg administered once weekly.  The proposed starting dose of 0.3 mg/kg given as an 
intravenous infusion once weekly (QW) represents approximately 1/10 of monkey HNSTD 
(based on human equivalent dose normalized to body surface area).  In addition, given the 
projected human PK based on allometric scaling from cynomolgus monkey PK, the projected 
human AUC for PF-06747143 at the proposed starting dose of 0.3 mg/kg is expected to be 
approximately 1/39 of the observed monkey AUC at HNSTD (10 mg/kg).
Prediction of clinical efficacious dose was based on PK/PD modeling of tumor growth 
inhibition in the murine tumor models of Ramos NHL and the disseminated MV4-11 AML.  
Based on the observed biological responses in NHL and AML murine tumor models 
following administration of PF-06747143, the nonclinical Ceff range for PF-06747143 is 
47.3-63.5 g/mL.  Given the predicted human PK based on allometric scaling from 
cynomolgus monkey PK, efficacious clinical doses of 5 mg/kg once every 2 weeks (Q2W) or 
3 mg/kg QW were predicted.
Complete information for this compound may be found in the single reference study 
document (SRSD), which for this study is the investigator’s brochure (IB).
1.5. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only)
1.5.1. Cytarabine
Cytarabine (Ara-C)15 is an antimetabolite analogue of cytidine with a modified sugar moiety 
(arabinose instead of ribose). Cytarabine is converted to the triphosphate form within the cell 
and then competes with cytidine for incorporation into deoxyribonucleic acid (DNA). 
Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, 
DNA replication ceases, specifically during the S phase of the cell cycle. This agent also 
inhibits DNA polymerase, resulting in a decrease in DNA replication and repair.
Standard induction regimens used for patients fit for intensive chemotherapy (usually 
<60 years) are based on cytarabine and daunorubicin and little has changed in the past 
25 years.16  A common therapy is “7+3” for first-line induction therapy, which involves 
7 days of continuous infusion of cytarabine and 3 daily doses of daunorubicin.
The SRSD for Cytarabine is the local package insert.
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1.5.2. Daunorubicin
Daunorubicin17 is an anthracycline antineoplastic antibiotic with therapeutic effects similar to 
those of doxorubicin. Daunorubicin exhibits cytotoxic activity through topoisomerase-
mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and 
protein synthesis.
Standard induction regimens for patients <60 years are based on a backbone of cytarabine 
plus an anthracycline.  Historically, daunorubicin has been the most commonly used 
anthracycline.16
The SRSD for Daunorubicin is the local package insert.
1.5.3. Decitabine
Decitabine18 is a cytidine antimetabolite analogue with potential antineoplastic activity. 
Decitabine incorporates into DNA and inhibits DNA methyltransferase, resulting in 
hypomethylation of DNA and intra-S-phase arrest of DNA replication.
A Phase 3 trial randomly assigned 485 AML patients older than 65 years to receive 
decitabine (n=242) or their preferred choice (n=243) of either supportive care (n=28) or low-
dose cytarabine (n=215).  Although rates of CR + CRp (CR with incomplete platelet 
recovery) were more than double in the decitabine arm (17.8%) compared with the treatment-
choice arm (7.8%) (P =0.001), median OS was not significantly improved for patients 
receiving decitabine (7.7 months) compared with the treatment of choice (5.0 months) (HR 
for death for decitabine, 0.85; 95% CI, .69-1.04; P = 0.11).19  Decitabine is not approved for 
use in patients with AML, but is considered a standard of care in patients not fit to receive 
intensive therapy with cytarabine and daunorubicin.16
The SRSD for Decitabine is the local package insert.
1.5.4. Azacitidine
Azacitidine20 is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity. 
Azacitidine is incorporated into DNA, where it reversibly inhibits DNA methyltransferase, 
thereby blocking DNA methylation. Hypomethylation of DNA by azacitidine may activate 
tumor suppressor genes silenced by hypermethylation, resulting in an antitumor effect. This 
agent is also incorporated into RNA, thereby disrupting normal RNA function and impairing 
tRNA cytosine-5-methyltransferase activity.
Preliminary results from a Phase 3 trial randomly assigned AML patients older than 65 years 
to azacitidine compared with conventional care regimens of best supportive care, low-dose 
cytarabine, and 7+3 AML-type induction chemotherapy and similarly showed a 
nonsignificant difference in median OS for patients receiving azacitidine (10.4 months) 
versus conventional care (6.5 months) (HR for death for azacitidine, 0.84; 95% CI, 
0.69-1.02; (P = 0.08).21 Azacitidine is not approved for use in patients with AML, but is 
considered a standard of care in patients not fit to receive intensive therapy with cytarabine 
and daunorubicin.16
The SRSD for Azacitidine is the local package insert.
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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives – Part 1
Primary Objective

To assess safety and tolerability at increasing dose levels of PF-06747143 in patients 
with refractory and/or relapsed AML for which 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-dose and multiple-dose pharmacokinetics (PK) of 
PF-06747143 following IV administration;

To evaluate the immunogenicity of PF-06747143 following repeated administration;

To document any anti-leukemia activity based on: Diagnosis and management of 
acute myeloid leukemia in adults: recommendations from an international expert 
panel, on behalf of the European LeukemiaNet (Dohner et al. 2010).22
2.2. Endpoints – Part 1
Primary Endpoint

Dose Limiting Toxicities (DLTs).
Secondary Endpoints

Adverse Events as characterized by type, frequency, severity (as graded by National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
v4.03), timing, seriousness, and relationship to study therapy;
CCI
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
Laboratory abnormalities as characterized by type, frequency, severity (as graded by 
NCI CTCAE v.4.03) and timing;

PK parameters of PF-06747143:  Single Dose (SD) -  Cmax, AUClast, and if data 
permit, AUCinf, Vd, CL, and t1/2.  Multiple Dose (MD) (assuming steady state is 
achieved)  - Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUC), and if data permit, CL, 
Vss, and t1/2;

Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) against 
PF-06747143;

Preliminary evidence of anti-leukemia activity including objective disease response; 
as assessed using the standardized response criteria including objective response rate 
(ORR), duration of ORR, and relapse free survival (RFS).22
2.3. Objectives – Part 2
Primary Objective

To evaluate safety and tolerability and preliminary anti-leukemia activity (Dohner, et. 
al 2010)22 of PF-06747143 in combination with standard intensive chemotherapy (ie,
cytarabine and daunorubicin; D/C 7+3) in patients with newly diagnosed fit treatment 
naïve AML patients (Cohort 1) or with standard dose of decitabine or azacitidine in 
newly diagnosed unfit treatment naïve AML patients (Cohort 2) or PF-06747143 as a 
single agent ((Cohort 3) if data warrants).
CCI
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Secondary Objectives

To characterize the single and multiple dose PK of PF-06747143 in combination with 
standard intensive cytarabine and daunorubicin 7+3 therapy in newly diagnosed fit 
treatment naïve AML patients or with standard dose of decitabine or azacitidine in 
newly diagnosed unfit treatment naïve AML patients;

To collect PF-06747143 drug concentration data in patients from the dose expansion 
cohorts for evaluation of population PK;

To evaluate the immunogenicity of PF-06747143 following repeated administration.
2.4. Endpoints – Part 2
Primary Endpoints

Adverse Events as characterized by type, frequency, severity (as graded by National 
Cancer Institute Common Terminology Criteria for Adverse Events (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;
CCI
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
Preliminary evidence of anti-leukemia activity including objective disease response; 
as assessed using the standardized response criteria including objective response rate 
(ORR), duration of ORR, and relapse free survival (RFS).22
Secondary Endpoints

PK parameters of PF-06747143: Single Dose (SD) - Cmax, Tmax, AUClast, and if data 
permit, AUCinf, Vd, CL, and t1/2. Multiple Dose (MD) (assuming steady state is 
achieved) - Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUC), and if data permit, CL, Vss,
and t1/2;

Peak and trough PF-06747143 concentrations for selected doses;

Incidence of ADA and Nab against PF-06747143.
CCI
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3. STUDY DESIGN
3.1. Study Overview
PF-06747143 will initially be developed in patients with acute myeloid leukemia (AML).  
The diagnosis of AML will be according to the World Health Organization (WHO)
classification (2008).23  The study will be conducted in two parts, Part 1 single agent dose 
escalation and Part 2 PF-06747143 in combination with standard chemotherapy with an 
option for single agent cohort expansion at the RP2D.
Assessment of anti-leukemia activity of PF-06747143 will be based on Diagnosis and 
management of acute myeloid leukemia in adults: recommendations from an international 
expert panel, on behalf of the European LeukemiaNet. (Dohner et al, 2010).22
3.1.1. Part 1
Part 1, dose escalation, is an open-label, multi-center, single arm, nonrandomized, multiple 
dose, safety, pharmacokinetic and pharmacodynamic study of single-agent PF-06747143 in 
sequential dose levels of adult patients with refractory and/or relapsed AML in order to 
establish the MTD/RP2D and/or maximally permitted dose (MPD). 
Patients will receive PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating 
doses.  The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg (Figure 1). 
Patients enrolled in the first two dose levels (0.3 mg/kg and 1.0 mg/kg) will be required to 
stay in the clinic/hospital overnight (minimum of 24 hours) after receiving the first dose of 
PF-06747143 to monitor for the potential risk of hyperleukocytosis that might be caused by 
the inhibition of CXCR4 pathway by PF-06747143.  On an individual basis, patients may be 
monitored overnight for the additional doses in Cycle 1 at the treating physician’s discretion.
In addition, the use of hydroxyurea and/or leukapheresis is permitted during Cycle 1 
following first study dose administration to control total peripheral WBC counts at the 
treating physician’s discretion.  However, hydroxyurea must be ceased 24 hours prior to the 
first study dose of Cycle 1.  Further, total peripheral WBC will be assessed by the 
Investigator within 12 hours prior to study drug administration during Cycle 1. In the event a 
patient’s total peripheral WBC count is ≥75,000/uL, the Investigator shall consult with and 
obtain the sponsor’s agreement to move forward with the study drug administration.  
For the first three dose levels (ie, 0.3 mg/kg  through 3.0 mg/kg), initiation of the first dose of 
PF-06747143 for each patient in the dose level must be at least 72 hours after the first dose of 
the previous patient. Patients enrolled in subsequent dose levels will be treated on an 
outpatient basis with no staggering of patients unless there are safety concerns based on 
findings at the lower doses.  
Once MTD or MPD is identified, additional patients may be enrolled at that dose level (to a 
minimum of 9) to further investigate the anti-leukemia activity, safety, and PK profile of 
PF-06747143 prior to an expansion cohort with single agent PF-06747143 at the 
MTD/MPD/RP2D.
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The total estimated number of patients to be enrolled for the Part 1 dose escalation study will 
be approximately 30-50 patients but it is pertinent to recognize that the exact sample size of 
the mTPI design in Part 1 cannot be pre specified in advance because it is a dynamic feature 
of the design.  
Once the dose of 15 mg/kg in Part 1 is found safe and tolerable, the Part 2 combination 
cohorts will be initiated at 10 mg/kg while the Part 1 single agent dose escalation continues 
to 20 mg/kg for MPD or MTD assessment.  
Figure 1.
Part 1 Schema
3.1.1.1. Starting Dose
The starting dose will be 0.3 mg/kg, administered QW in 28 day cycles. 
3.1.1.2. Criteria for Dose Escalation
A modified toxicity probability interval method (mTPI)24 targeting a DLT rate of 25% with 
an equivalence interval (20%-30%) will be utilized in order to estimate MTD in dose 
escalation.  For all dose levels, patients may be enrolled in cohorts of 2-4 (the target size of 
each cohort will be 3 patients).  Intermediate dose levels to further evaluate the safety and/or 
PK may be evaluated following discussion between sponsor and Investigator.
The dose levels planned for Part 1 of the study are shown in Table 5.  Additional dose levels 
may be explored, if appropriate based on emerging safety, PK or PD data.
Intra-patient dose escalation of PF-06747143 or the backbone chemotherapy (in Part 2 
combination cohorts) will not be permitted.
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Table 5.
Possible Dose Levels
Dose 
Level
PF-06747143 Dose (mg/kg)
(QW)
1
0.3
2
1.0
3
3.0
4
10
5
15
6
20
The mTPI method relies upon a statistical probability algorithm, calculated using all patients 
treated in prior and current cohorts at the same dose level to determine where future cohorts 
should be on dose escalation, no change in dose, or dose de-escalation.  The algorithm will 
stop if any of the following criteria is met:

the maximum sample size has been achieved (approximately 50 patients total);

at least 9 patients have been accumulated on a dose that is predicted to be the MTD;
or 

all doses explored appear to be overly toxic and the MTD cannot be determined.
Although dose levels are capped at 20 mg/kg, this mTPI will continue to operate subject to 
the constraints detailed above while allowing for doses higher than specified. 
All clinically relevant adverse events (AEs) and serious adverse events (SAEs) will be 
reviewed by the sponsor and Investigators after each dose level is complete to determine if 
the dose allocation schedule requires modification. 
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.24 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 (Appendix 4).
Patients will continue with study treatment until disease progression (refer to Section 7.6.) 
patient refusal or unacceptable toxicity occurs.  Patients experiencing a DLT may be 
managed with dose modification (after dose interruption) or discontinuation.  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.  Intra-patient dose escalation will not be 
permitted in this study. 
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3.1.1.3. DLT Definition
A DLT will be classified according to NCI CTCAE version 4.03 and is defined as any of the 
following adverse events unless the event can clearly be determined to be unrelated to drug 
occurring in the first cycle of treatment (within 28 days of first dose or until patient receives 
a second cycle if there are treatment delays).  Data from all cycles of treatment will be 
analyzed for safety, delayed toxicity, and cumulative toxicity.  
DLT is defined as:

Hematologic:

Failure to achieve an ANC greater than 1,000/uL and/or a platelet count greater 
than 25,000/uL independent of platelet transfusion by day 42 after the start of 
therapy, with a hypocellular bone marrow (<10% marrow cellularity) and absence 
of persistent leukemia (ie, <5% marrow blasts) measured at the completion of 
Cycle 1 (approximately day 28-32);

If a subject with persisting cytopenias does not exhibit marrow hypoplasia on 
biopsy (or bone marrow aspirate) or demonstrates persisting leukemia, such 
subject will not be considered to have demonstrated a hematological toxicity 
and may continue to receive PF-06747143 at the scheduled time point for 
Cycle 2.

Hyperleukocytosis (WBC 100,000/uL) not managed by hydroxyurea or 
leukapheresis and/or resulting in an adverse event.

Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

Non-hematologic:

Grade 3 toxicities, except for:

Nausea or vomiting that resolves to Grade 1 within 72 hours with 
appropriate supportive therapy; 

Diarrhea that resolves to Grade 1 within 72 hours with appropriate 
supportive therapy; 

Fatigue, asthenia, or other constitutional symptom that resolves to Grade 1 
within 7 days with appropriate supportive therapy; 

Alopecia of any grade;

Infection, fever (including febrile neutropenia), electrolyte abnormalities and 
ALT/AST elevation that returns to Grade 1 or baseline within 7 days;
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
Delay by more than 14 days to receive the next scheduled dose due to a persisting
drug-related AE;

All Grade 4 toxicities.
In addition, clinically important or persistent toxicities that are not included in the above 
criteria may be considered a DLT following review by the Investigators and sponsor.  All 
DLTs need to represent a clinically significant shift from baseline.
Grade 3 cytokine release syndrome, infusion reaction, and allergic reaction will not be 
considered as DLTs (as it is unlikely to be dose related), but may be a reason for study 
discontinuation, protocol amendment (eg, pre-infusion treatments, infusion duration) and 
should be reviewed with the sponsor. 
In principle, a patient needs to be on study for at least 28 days to be evaluable for DLT 
observation, and may be replaced if they terminate study participation earlier than 28 days
without experiencing a DLT.  Patients who are not able to receive at least 80% of the planned 
dose of the PF-06747143 and backbone chemotherapy (in Part 2 combination study) in the 
DLT assessment period are considered not evaluable for DLT and will be replaced. 
However, in some circumstances of a clear drug unrelated event (eg,, traffic accident, clear 
disease progression, or withdrawal of consent) that leads to study termination close to or 
before 28 days, the patient might be deemed evaluable if the Investigators and sponsor agree.  
In addition, patients not evaluable for assessment of DLT, as described in Section 9.1, may
be replaced.
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. Maximum Permitted Dose Definition
The Maximum Permitted Dose (MPD) is 20 mg/kg. 
3.1.1.6. Recommended Phase 2 Dose (RP2D) Definition
The Recommended Phase 2 Dose (RP2D) is the dose chosen for further study based on Part 1
study results.  If the MTD proves to be clinically feasible for long-term administration in a 
reasonable number of patients, then this dose usually becomes the RP2D.  If the MPD is 
determined to be safe, then this becomes the RP2D.  Further experience with the MTD may 
result in a RP2D dose lower than the MTD.
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3.1.2. Part 2
Part 2 dose expansion, is an open-label, multi-center, non-randomized study to assess the 
safety and tolerability and preliminary anti-leukemia activity of PF-06747143 in three 
cohorts (two combination cohorts and one potential cohort of single agent PF-06747143). 
Figure 2.
Part 2 will assess the safety and tolerability and preliminary anti-leukemia activity of PF-
06747143. In Part 2, PF-06747143 will be administered at 10 mg/kg QW (Section 3.1.2.1) 
on 28 day cycles in combination with chemotherapy in two separate cohorts each containing 
up to 30 patients with newly diagnosed AML, including Cohort 1 in fit treatment naïve AML 
patients, in which PF-06747143 will be combined with standard intensive 7+3 chemotherapy 
with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin
(60-90 mg/m2 daily for 3 days), and Cohort 2 in unfit treatment naïve AML patients who are 
considered to not tolerate or decline to receive standard intensive 7+3 treatment, in which 
case PF-06747143 will be combined with standard dose of azacitidine (75 mg/m2
administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by 
continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) based on 
drug availability and institutional guidance.
Attributions to fit or unfit in Part 2 will be based on “Consensus-based definition of unfitness 
to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of Italian 
SIE, SIES and GITMO group on a new tool for therapy decision making”25 per Investigator 
judgment.
An additional single agent PF-06747143 expansion cohort, Cohort 3, at the MTD/RP2D may 
be initiated in Part 2 in 15-30 refractory and/or relapsed AML patients based on single agent 
PF-06747143 clinical benefit in Part 1.
3.1.2.1. Part 2 Combination Cohorts Starting Dose
After the DLT observation period in the first cycle of 15 mg/kg cohort is cleared, the dose of 
10 mg/kg of PF-06747143 will be used to initiate the Part 2 combination studies, which may 
be escalated or de-escalated, depending on emerging data. Additionally, if an MTD in Part 1 
is determined at or below the dose of 15 mg/kg, a lower dose than 10 mg/kg may be 
considered to move into Part 2 dose expansion combination studies.  
3.1.2.2. Part 2/Cohort 1 and 2 
In Part 2, Cohort 1 and 2 expansion cohorts (E1 and E2) will not be initiated until a safety 
lead-in (S) group of  approximately 3-6 patients is enrolled to ensure the combination 
treatment regimen is safe and tolerable in each patient population (ie, fit and unfit AML).  
The safety lead-in will use the standard 3+3 dose escalation method to evaluate safety profile 
(using the DLT criteria described in Section 3.1.1.3) for duration of up to 2 cycles.   
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3.1.2.2.1. Part 2/Cohort 1 - PF-06747143 Combination in Fit Treatment Naïve AML 
Patients
Cohort 1 safety lead-in group (S1) will start with 10 mg/kg dose of PF-06747143 and may be 
escalated to up to 20 mg/kg (the MPD) or de-escalated to below 10 mg/kg based on the pre-
defined DLT criteria (see Section 3.1.1.3) and emerging data.  After completion of the S1 
cohort, PF-06747143 will be administered in combination with intensive therapy
(ie, 7+3 daunorubicin and cytarabine) as induction and continue during consolidation and in 
maintenance for up to a maximum of 6 months (6 cycles) starting from the completion of 
consolidation, until disease progression or relapse, patient refusal or unacceptable toxicity 
occurs (whichever comes first) in newly diagnosed treatment naïve fit AML patients.  The 
expansion cohort (E1) will enroll up to 30 patients. 
3.1.2.2.2. Part 2/Cohort 2 – PF-06747143 Combination in Unfit Treatment Naïve AML 
Patients
Cohort 2 safety lead-in group (S2) will start with 10 mg/kg dose of PF-06747143 and may be 
escalated to up to 20 mg/kg (the MPD) or de-escalated to below 10 mg/kg based on the pre-
defined DLT criteria (see Section 3.1.1.3) and emerging data.   After completion of the S2 
cohort, PF-06747143 will be administered in combination with a hypomethylating drug (ie,
either azacitidine or decitabine, based on institutional guidelines) and may continue for up to 
1 year (~12 cycles) from start of therapy or until disease progression or relapse, patient 
refusal or unacceptable toxicity occurs (whichever comes first) in newly diagnosed treatment 
naïve unfit AML patients).  The expansion cohort (E2) will enroll up to 30 patients.
3.1.2.2.3. MTD Definition
In Part 2, the MTD of the combinations of PF-06747143 and intensive 
daunorubicin/cytarabine or PF-06747143 and decitabine/azacitidine will be determined 
separately within each cohort.
3.1.2.3. Part 2/Cohort 3 – PF-06747143 Single Agent Expansion
An additional single agent PF-06747143 expansion cohort, Cohort 3 (E3), at the MTD/RP2D 
may be initiated in Part 2 in 15-30 refractory and/or relapsed AML patients. The initiation of 
this cohort will require that single agent PF-06747143 demonstrates encouraging clinical 
benefit (eg, significantly improved CR and response duration compared to historical data) in 
the dose escalation Part 1.  Patients in this cohort will be treated until disease progression or 
relapse, patient refusal or unacceptable toxicity occurs (whichever comes first).  
3.1.3. Summary 
Approximately 125-140 patients are expected to be enrolled in this study (approximately 
30-50 patients in Part 1 (actual number of patients enrolled for Part 1 will depend upon 
tolerability of PF-06747143 and the number of dose levels required to identify the MTD) and 
approximately 87-102 patients in Part 2).  The study will be conducted in approximately 
4 sites for Part 1 and approximately 12-15 sites for Part 2.  
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Patients who complete the maximum number of cycles/months on study treatment
(Section 3.1.2.2.1 and Section 3.1.2.2.2), demonstrate clinical benefit with manageable safety 
profile and are willing to continue receiving the assigned treatment may be given the 
opportunity to do so upon agreement between Investigator and sponsor and pending 
investigational product availability.
All patients who completed treatment will have a 60-day post dose follow-up period.
Figure 2.
Overall Study Schema
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 participation in the study is 
considered appropriate.  All relevant medical and non-medical conditions should be taken 
into consideration when deciding whether a particular patient is suitable for this protocol. 
4.1. Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before patients are included in the study.
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Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
Inclusion (Part 1 and Part 2 Cohort 3)
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Patients with AML (primary AML diagnosis is based on the 2008 WHO classification 
with bone marrow (BM) or peripheral blood (PB) blast counts 20%23) refractory,
relapsed and/or patients that are not candidates to receive standard of care and/or refusing 
the standard care of therapies:

Patient received prior chemotherapy and/or standard of care and have relapsed, 
refractory or Minimal Residual Disease (MRD).26,27,28,29

MRD is defined as patients showing residual blast 10-14 days post-induction 
chemotherapy.
2. Life expectancy at least 12 weeks.
3. Hydroxyurea is allowed prior to Day 1 but must be ceased 24 hours prior to first dose. 
Thereafter, hydroxyurea may be used during Cycle 1 as needed to control total peripheral 
WBC counts (see Section 5.8.1.).
4. Age 18 years old.
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2.
6. Patients must have been off previous anti-leukemia therapy for at least 2 weeks or 
5 half-lives, whichever is shorter if the immediate prior regimen included only weekly 
chemotherapy; or 4 weeks from any therapy with therapeutic biologics and from any type 
of investigational therapy prior to the first dose of PF-06747143.
7. Resolved acute effects of any prior therapy to baseline severity or Grade 1 CTCAE 
except for adverse events (AEs) not constituting a safety risk by investigator judgment.
8. At least 4 weeks since radiotherapy prior to the first dose of PF-06747143.  Patients must 
have passed nadir white blood cell (WBC) and platelet counts, have full recovery or 
stabilization of absolute neutrophil counts (ANC) and platelet counts, and ANC counts 
must have recovered from prior toxicity.
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9. Adequate renal and hepatic function, including all of the following:

Creatinine clearance 45 mL/min as measured or as calculated using the method 
standard for the institution;

Aspartate aminotransferase (AST) 3 x upper limit of normal (ULN);

Alanine aminotransferase (ALT) 3 x ULN;

Bilirubin 2.0 mg/dL (except patients with Gilbert’s Syndrome who must have total 
bilirubin <3.0 mg/dL).
10. Negative serum/urine pregnancy test (for females of childbearing potential) at screening.
11. Male patients able to father children and female patients of childbearing potential and at 
risk for pregnancy must agree to use 2 highly effective methods of contraception 
throughout the study and for at least 60 days after the last dose of assigned treatment. 
12. Female patients who are not of childbearing potential (ie, meet at least one of the 
following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved post-menopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level within the 
laboratory’s reference range for postmenopausal women.
13. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study.
14. Patients who are willing and able to comply with the study scheduled visits, treatment 
plans, laboratory tests and other procedures. 
Inclusion (Part 2 Cohort 1 and Cohort 2)
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Newly diagnosed, previously untreated de novo or secondary AML population (AML 
diagnosis is based on the 2008 WHO classification with BM or PB blast counts 20%23):

Cohort 1: Fit to receive intensive remission induction chemotherapy at the time of 
enrolment.  Patients must have NONE of the following criteria to be considered fit:

ECOG 2 or 3;
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
Serum creatinine clearance 45 mL/min as measured or as calculated using the 
method standard for the institution; 

Severe cardiac disease (eg, LVEF <45% by MUGA or ECHO at screening).

Cohort 2: Unfit to receive or not considered a candidate for intensive remission 
induction chemotherapy at the time of enrollment based on EITHER: 

75 years of age, OR

<75 years of age with at least 1 of following:

Poor performance status (ECOG) score of 2 or 3; 

Clinically significant heart or lung comorbidities, as reflected by at least 1 of 
following: 

LVEF ≤50%; 

DLCO ≤65% of expected; 

FEV1 ≤65% of expected; 

Chronic stable angina or congestive heart failure controlled with 
medication.

Liver transaminases >3 ULN;

Other contraindication(s) to anthracycline therapy (must be documented);

Other comorbidity the investigator judges incompatible with intensive 
remission induction chemotherapy which must be documented and approved 
by the study medical monitor before randomization.
2. Hydroxyurea is allowed prior to Day 1 but must be ceased 24 hours prior to first dose. 
Thereafter, hydroxyurea may be used during Cycle 1 as needed to control total peripheral 
WBC counts (see Section 5.8.1.).
3. Age 18 years old.
4. ECOG performance status: 0 to 3.
5. Adequate renal and hepatic function, including all of the following:

Creatinine clearance 45 mL/min as measured or as calculated using the method 
standard for the institution;
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
AST 3 x ULN;

ALT 3 x ULN;

Bilirubin 2.0 mg/dL (except patients with Gilbert’s Syndrome who must have total 
bilirubin <3.0 mg/dL).
6. Negative serum/urine pregnancy test (for females of childbearing potential) at screening.
7. Male patients able to father children and female patients of childbearing potential and at 
risk for pregnancy must agree to use 2 highly effective methods of contraception 
throughout the study and for at least 60 days after the last dose of assigned treatment. 
8. Female patients who are not of childbearing potential (ie, meet at least one of the 
following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved post-menopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level within the 
laboratory’s reference range for postmenopausal women.
9. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study.
10. Patients who are willing and able to comply with the study scheduled visits, treatment 
plans, laboratory tests and other procedures. 
4.2. Exclusion Criteria
Exclusion (Part 1 and Part 2 Cohort 3)
Patients with any of the following characteristics/conditions will not be included in Part 1 
and Part 2 Cohort 3 portions of the study: 
1. Patients with acute promyelocytic leukemia (APL), AML with known central nervous 
system (CNS) involvement unless the patient has completed treatment for the CNS 
disease, has recovered from the acute effects of therapy prior to study entry, and is 
neurologically stable.
2. Chronic graft versus host disease (GVHD) requiring active systemic treatment, active 
GVHD with other than Grade 1 skin involvement, or GVHD requiring systemic 
immunosuppressive treatment.  Patients with GVHD receiving systemic
immunosuppressive treatment must be able to discontinue the therapy at least 2 weeks 
prior to the first dose of PF-06747143.
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3. Patient is known to be refractory to platelet or packed red cell transfusions per 
institutional guidelines. 
4. Patient is within 3 months post allogenic hematopoietic stem cell transplant or within 
30 days post autologous stem cell transplant, and the patient has not recovered from 
transplant-associated toxicities prior to the first dose of PF-06747143. 
5. Known active fungal, bacterial, and/or viral infection requiring systemic therapy within 
3 days prior to the first dose of PF-06747143. 
6. Prior treatment with a compound targeting CXCR4. 
7. Liver cirrhosis Child B or C.
8. Active and clinically significant infection with hepatitis A (HAV), hepatitis B (HBV), 
hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired 
immunodeficiency syndrome (AIDS)-related illness.
9. Participation in other studies involving investigational drug(s) within 4 weeks prior to the 
first dose of PF-06747143 and/or during study.
10. Major surgery within 4 weeks of study entry.
11. Chronic systemic corticosteroid treatment. Topical applications, inhaled sprays, eye 
drops, local injections of corticosteroids and systemic steroids required for acute medical 
interventions are allowed.
12. Current mental illness requiring psychiatric hospitalization, institutionalization or 
intensive outpatient management, or current cognitive status that produces dependence 
(as confirmed by the specialist) not controlled by the caregiver, or recent (within the past 
year) or active suicidal ideation or behavior.
13. Uncontrolled neoplasia (other than AML).
14. Other severe acute or chronic medical condition 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. 
15. Patients who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of the 
study.
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16. Pregnant females; breastfeeding females; male patients with partners currently pregnant; 
male patients able to father children and female patients of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in this 
protocol for the duration of the study and for at least 60 days after last dose of 
investigational product. 
17. Any of the following in the previous 6 months: myocardial infarction, congenital long QT 
syndrome, Torsades de pointes, arrhythmias (including sustained ventricular 
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior 
hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, 
symptomatic congestive heart failure (CHF New York Heart Association class III or IV), 
cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary 
embolism.  Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or QTcF interval 
>470 msec at screening.
18. Known or suspected hypersensitivity to recombinant human proteins.
Exclusion Criteria (Part 2 Cohort 1 and Cohort 2)
Patients with any of the following characteristics/conditions will not be included in the Part 2 
portions of the study: 
1. Patients with acute promyelocytic leukemia (APL), AML with known central nervous 
system (CNS) involvement unless the patient has completed treatment for the CNS 
disease, has recovered from the acute effects of therapy prior to study entry, and is 
neurologically stable.
2. Patient is known to be refractory to platelet or packed red cell transfusions per 
institutional guidelines. 
3. Known active fungal, bacterial, and/or viral infection requiring systemic therapy within
3 days prior to the first dose of PF-06747143. 
4. Prior treatment with a compound targeting CXCR4.
5. Prior treatment with hypomethylating agents (eg, decitabine or azacitidine) or 
chemotherapy for antecedent myelodysplastic syndrome (MDS) (Cohort 2).
6. AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or 
t(15;17) (Cohort 2).
7. Patients who are candidates for allogeneic stem cell transplant at the time of enrollment 
(Cohort 2).
8. Liver cirrhosis Child B or C.
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9. Active and clinically significant infection with hepatitis A (HAV), hepatitis B (HBV), 
hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired 
immunodeficiency syndrome (AIDS)-related illness.
10. Participation in other studies involving investigational drug(s) within 4 weeks prior to the 
first dose of PF-06747143 and/or during study.
11. Major surgery within 4 weeks of study entry.
12. Chronic systemic corticosteroid treatment. Topical applications, inhaled sprays, eye 
drops, local injections of corticosteroids and systemic steroids required for acute medical 
interventions are allowed.
13. Uncontrolled neoplasia (other than AML).
14. Current mental illness requiring psychiatric hospitalization, institutionalization or 
intensive outpatient management, or current cognitive status that produces dependence 
(as confirmed by the specialist) not controlled by the caregiver, or recent (within the past 
year) or active suicidal ideation or behavior.
15. Other severe acute or chronic medical condition 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. 
16. Patients who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of the 
study.
17. Pregnant females; breastfeeding females; male patients with partners currently pregnant; 
male patients able to father children and female patients of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in this 
protocol for the duration of the study and for at least 60 days after last dose of 
investigational product. 
18. Any of the following in the previous 6 months: myocardial infarction, congenital long QT 
syndrome, Torsades de pointes, arrhythmias (including sustained ventricular 
tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior 
hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, 
symptomatic congestive heart failure (CHF New York Heart Association class III or IV), 
cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary 
embolism.  Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or QTcF interval 
>470 msec at screening.
19. Known or suspected hypersensitivity to recombinant human proteins.
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20. The presence of any one of the following hypersensitivities:

Cohort 1: 

Hypersensitivity to cytarabine (not including drug fever or exanthema); or

Daunorubicin;

Cohort 2: 

Hypersensitivity to decitabine or azacitidine;

Hypersensitivity to mannitol.
4.3. Lifestyle Guidelines
4.3.1. Contraception
In this study, male patients who are able to father children and female patients who are of 
childbearing potential will receive PF-06747143, 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 60 days after the last dose.  The investigator or his or 
her designee, in consultation with the patient, will confirm the patient has selected two 
appropriate methods of contraception for the individual patient and his/her partner from the 
list of permitted contraception methods (see below) and will confirm the patient has been 
instructed in their consistent and correct use.  Patients need to affirm that they meet the 
criteria for correct use of at least 2 of the selected methods of contraception.  The investigator 
or his or her designee will discuss with the patient the need to use highly effective 
contraception consistently and correctly according to the Schedule of Activities and 
document such conversation in the patient’s chart.  In addition, the investigator or his or her 
designee will instruct the patient to call immediately if a selected contraception method is 
discontinued or if pregnancy is known or suspected in the patient or the patient’s partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of oral, inserted, injected, implanted or transdermal hormonal 
methods of contraception is allowed provided the patient plans to remain on the same 
treatment throughout the entire study and has been using that hormonal contraceptive 
for an adequate period of time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
or suppository).  For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
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4. Male sterilization with absence of sperm in the post vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive 
procedure (provided that occlusion has been confirmed in accordance with the 
device’s label).
6. Female partner who meets the criteria for non-childbearing potential, defined as:

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or 

Achieved postmenopausal status, defined as follows: 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 women.
All sexually active male patients must agree to prevent potential transfer of and exposure to 
drug through semen to their partners by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for 60 days after the last dose.
4.4. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study materials. 
To facilitate access to appropriately qualified medical personnel on study related medical 
questions or problems, patients are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational compound identifiers, patient study numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
patient’s participation in the study.  The contact number can also be used by investigational 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigational 
site and the study team are not available.  It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational site and the study team 
for advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the patient directly, and if a patient calls that number, he or 
she will be directed back to the investigational site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines investigational product is defined as a pharmaceutical form of an active ingredient 
or placebo being tested or used as a reference in a clinical trial, including a product with a 
marketing authorization when used or assembled (formulated or packaged) in a way different 
from the approved form, or when used for an unapproved indication, or when used to gain 
further information about an approved use.25
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5.1. Allocation to Treatment
Dose level allocation will be performed by the sponsor after patients have given their written 
informed consent and have completed the necessary screening assessments. The site staff 
will fax/e-mail a complete Registration Form to the designated sponsor study team member.  
The sponsor will assign a patient identification number, which will be used on all patient 
specific documentation at the clinical site.
No patient shall receive investigational product until the investigator or designee has received 
the following information in writing from the sponsor:

confirmation of the patient’s enrolment;

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.
For part 2 combination study, attribution to the fit or unfit category will be operated based on 
the patient’s characteristics and eligibility by the Investigator and reviewed by sponsor. 
5.2. Patient Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigational site.
The site will complete required dosage Preparation Record located in the study/pharmacy 
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. 
5.3. Investigational Product Supplies
Upon activation, study centers will receive a supply of PF-06747143 free of charge by Pfizer.  
Re-supplies of PF-06747143 will be made during the course of the study based on need.
Cytarabine, daunorubicin, decitabine and azacitidine are commercially available.  Locally 
obtained commercial supplies of these drugs will be used in accordance with local
regulations and package insert.
The study monitor should be contacted for any issues related to drug supplies.
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5.3.1. Dosage Form(s) and Packaging
5.3.1.1. PF-06747143
PF-06747143 is presented as a sterile solution for intravenous administration.  Each vial 
contains 50 mg/ml in 4 ml (extractable) of aqueous buffered solution in a single use vial.  
The vial is sealed with a coated stopper and an overseal, and is labeled according to local 
regulatory requirements.
5.3.1.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only)
Locally obtained commercial supplies of these drugs will be used in accordance with local
regulations and package insert. Refer to the local package insert or Institutional Guidelines 
for detailed formulation, preparation and dispensing information.
5.3.2. Preparation and Dispensing
Investigational product should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, 
practitioner, pharmacist, or medical assistant) as allowed by local, state, and institutional 
guidance. 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
them and to the environment should undertake the preparation, handling, and safe disposal of 
chemotherapeutic agents.
5.3.2.1. PF-06747143
See the Investigational Product Manual (IP Manual) for instructions on how to prepare the 
investigational product for dispensing and administration.  
5.3.2.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only)
Refer to the local package insert or Institutional Guidelines for detailed formulation, 
preparation and dispensing information.
5.4. Administration
Investigational product is administered in 28 day cycles, and bone marrow evaluations are 
performed at specified times to determine clinical response and duration of investigational 
product administration within the trial.
5.4.1. PF-06747143 
PF-06747143 will be administered intravenously QW in 28 day cycles with adjustment for 
body weight at every cycle. Details for PF-06747143 infusion are provided in the current IP 
Manual.
All patients should be weighed prior to dosing for every cycle (or within 72 hours) to ensure 
they did not experience either a weight loss or gain >10% from the prior weight used to 
calculate the amount of PF-06747143 required for dose preparation. Decision to recalculate
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PF-06747143 dose based on the weight obtained at each cycle can be in accordance with 
institutional practice, however if the patient experienced either a weight loss or gain >10% 
compared to the weight used to calculate the previous dose, the amount of PF-06747143 
required for preparation and administration for the current cycle must be recalculated using 
this most recent weight obtained.
Due to the inhibition of the CXCR4 pathway by PF-06747143, patients enrolled in the first 
two dose levels (0.3 mg/kg and 1.0 mg/kg) will be required to stay in the clinic/hospital 
overnight (minimum of 24 hours) after receiving the first dose of PF-06747143 to monitor 
for a potential risk of hyperleukocytosis.  On an individual basis, patients may be monitored 
overnight for the additional doses in Cycle 1 at the treating physician’s discretion.
In addition, the use of hydroxyurea and/or leukapheresis is permitted during Cycle 1 
following first dose administration to control peripheral WBC counts at the treating 
Investigators discretion.  However, hydroxyurea must be ceased 24 hours prior to the first 
dose of Cycle 1.  Further, total peripheral WBC will be assessed by the Investigator within 
12 hours prior to study drug administration during Cycle 1. In the event a patient’s total 
peripheral WBC is ≥75,000/uL, the Investigator shall consult with and obtain the sponsor’s 
agreement to move forward with the study drug administration.  
For the first three dose levels (ie 0.3 mg/kg through 3.0 mg/kg), initiation of the first dose of 
PF-06747143 for each patient in the dose level must be at least 72 hours after the first dose of 
the previous patient. Patients enrolled in subsequent dose levels will be treated on an 
outpatient basis with no staggering of patients unless there are safety concerns based on 
findings at the lower doses.
5.4.2. Cytarabine, Daunorubicin, Decitabine and Azacitidine (Part 2 only)
Administration of commercially available drugs in Part 2 will follow Institutional Guidelines 
or the package insert. 
5.5. Recommended Dose Modifications
Every effort should be made to administer investigational product on the planned dose and 
schedule.
In the event of significant toxicity dosing may be interrupted, 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 one of 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.
If a treatment interruption or delay results from worsening of hematologic or biochemical 
parameters, the frequency of relevant blood tests should be increased as clinically indicated.
Refer to Section 5.5.3.1 for adverse events requiring dose reduction at the time of treatment 
resumption. 
Dosing interruptions or delays for any reason of more than 14 days should be discussed with 
the sponsor before resumption of therapy.
5.5.1. Dosing Interruptions
5.5.1.1. Part 1
Patients experiencing Grade 2 treatment-related toxicity(ies) that remain intolerable even 
with supportive care or Grade 3 treatment-related toxicityshould have their treatment 
interrupted or delayed.  Appropriate follow-up assessments should be done until adequate 
recovery occurs as assessed by the investigator.  Criteria required before treatment can 
resume are described in Section 5.5.3.
If an adverse event requires 2 consecutive doses to be omitted, then treatment is considered 
interrupted.  The doses omitted for toxicity are not replaced.  The next scheduled dose will 
then be the nominal Cycle Day dose.  If Day 8 and 15 doses are missed, the next dose will be 
Day 22.  If the Day 15 and 22 doses are missed, the next dose will be Day 1 of the next cycle.  
If more than 2 doses are missed, dosing will resume as Day 1 of the next cycle.  If more than 
2 doses are missed, resumption of therapy should be discussed with the sponsor.  
5.5.1.2. Part 2
Guidance related to how to manage dose interruption will be provided in a protocol 
amendment prior to the start of Cohort 1 and 2 in Part 2.
5.5.2. Dose Delays
5.5.2.1. Part 1
If only 1 dose is missed for any reason, the next dose should be given at the next scheduled 
dosing day.  The dose will be considered delayed, and the Day of dosing considered the same 
as the missed dose.  As an example, if the Day 8 dose is missed, the next dose should be 
given on Day 15, but the dose counted as Day 8.
Doses that are given within 3 days of the scheduled day are not considered missed or 
delayed.  The next dose should be given at the next scheduled dosing Day.  As an example, if 
a clinic appointment is rescheduled from Day 8 to Day 5 or Day 11 because of a clinic 
holiday, the next dose should be on the regularly scheduled Day 15.
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Resumption of treatment following treatment delay for treatment-related toxicity may not 
occur until all drug-related toxicity has resolved to baseline or Grade 1 severity (or, at the 
investigator discretion, Grade 2 if not considered a safety risk for the patient).
The need for a dose reduction at the time of treatment resumption should be based on the 
criteria defined in Section 5.5.3, unless expressly agreed otherwise following discussion 
between the investigator and the sponsor.
5.5.2.2. Part 2
Guidance related to how to manage dose delays will be provided in a protocol amendment 
prior to the start of Cohort 1 and 2 in Part 2.
5.5.3. Dose Reductions
5.5.3.1. Part 1
Intra-patient dose escalation for PF-06747143 is not allowed. 
Following dosing interruption or cycle delay due to toxicity, the PF-06747143 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.
Dose reduction of PF-06747143 by 1 and, if needed, 2 dose levels will be allowed depending 
on which dose level the patient was enrolled and the type and severity of toxicity 
encountered.  Dose reduction below the starting dose of 0.3 mg/kg will not be permitted. 
Patients requiring more than 2 dose reductions will be discontinued from the treatment and 
entered into the follow-up phase, unless otherwise agreed between the investigator and the 
sponsor.  All dose modifications/adjustments must be clearly documented in the patient's 
source notes and Case Report Form (CRF).  
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.
Patients experiencing a DLT may resume dosing at the next lower dose level (if applicable) 
once adequate recovery is achieved (see Table 6).  Further, no dose reductions are planned 
for patients experiencing toxicities other than those listed in Table 6.  However, 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.
No dose reduction recommendation is provided for patients experiencing a DLT of prolonged 
myelosuppression as such patients will be withdrawn from study drug treatment even if 
adequate recovery is achieved.  Patients whose hematologic indices improve prior to meeting 
the criteria for prolonged myelosuppression >42 days may resume dosing at the next lower 
dose level or permanently discontinue from treatment at the discretion of the Investigator.
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Recommended dose reductions are described in Table 6.
Table 6.
Dose Modifications for Investigational Product Related Toxicity
Toxicity
Grade 1
Grade 2
Grade 3
Grade 4
Non-hematologic 
Continue at the 
same dose level.
Continue at the 
same dose level. 
Withhold dose 
until toxicity is 
Grade 1, or has 
returned to 
baseline, then 
resume treatment 
at the same dose 
level or reduce 
the dose by 
1 level at the 
discretion of the 
Investigator.
Withhold dose 
until toxicity is 
Grade 1, or has 
returned to 
baseline, then 
reduce the dose 
by 1 level and 
resume 
treatment, or 
discontinue at the 
discretion of the 
Investigator.

*Grade 4 neutropenia 
lasting more than 
5 days; Febrile
neutropenia with any 
duration (ANC <1.0x 
109/L and fever 
38.5C); 

*Grade 4 
thrombocytopenia or 
Grade 3 
thrombocytopenia with 
bleeding, or any 
requirement for 
platelet transfusion
unexplained by 
underlying disease; 

*Grade 4 anemia, 
unexplained by 
underlying disease;

*Treatment delay by 
more than 14 days due 
to a hematologic 
adverse event.

**Grade 3 
Hyperleukocytosis 
(WBC 100,000/uL)

*Hold PF-06747143 until recovery of ANC to 1,000/mm3, platelets 
50,000/mm3 and Hgb 8.0 g/dL or until values/toxicities returns to pre-
treatment levels.

Reduce PF-06747143 by 1 dose level.

If toxicity recurs despite dose reduction, study drug may either be held 
until recovery and continuation at same dose, or undergo further dose 
reduction by another dose level.  

** Hold PF-06747143 until total peripheral WBC 75,000/uL or returns to 
pre-treatment levels. Consult with sponsor prior to resuming PF-06747143.

Following recovery and consultation with the sponsor, PF-06747143 
can be resumed either at the same dose level or reduced by 1 dose 
level.

If toxicity recurs, following resolution and sponsor consultation,
PF-06747143 can be resumed after dose is reduced by 1 level or 
discontinued at the Investigator’s discretion.
5.6. Investigational Product Storage
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
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Investigational product should be stored in its original container and in accordance with the 
label.  See the IP manual for storage conditions of the product once prepared.
Storage conditions stated in the SRSD (IB) will be superseded by the storage conditions 
stated in the labeling. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation 
for excursions should be documented.  The operation of the temperature monitoring device 
and storage unit (for example, refrigerator), as applicable, should be regularly inspected to 
ensure it is maintained in working order. 
Any excursions from the product label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product. It 
will not be considered a protocol deviation if the sponsor approves the use of the 
investigational product after the temperature excursion. Use of the investigational product 
prior to sponsor approval will be considered a protocol deviation. 
Specific details regarding information the site should report for each excursion will be 
provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the product(s) are briefly out of the temperature range described in the labeling are not 
considered excursions.  More specific details will be provided to the sites in the Pharmacy 
Manual.
5.7. Investigational Product Accountability
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.
5.7.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site). If destruction is authorized to take place at the study 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, and all destruction must be adequately documented.
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5.8. Concomitant Treatment(s)
Concomitant treatment considered necessary for the patient’s well-being may be given at 
discretion of the treating physician.
All concomitant treatments, blood products, as well as non-drug interventions received by 
patients from screening until the end of study visit will be recorded on the CRF. 
All concomitant treatments must be approved by the sponsor at study entry. 
5.8.1. Other Anti-leukemia/Anti-cancer or Experimental Drugs
For control of rapidly progressing leukemic disease, hydroxyurea is allowed prior to Day 1 of 
study treatment; however, hydroxyurea is to be ceased 24 hour prior to the first dose.  
However, the use of hydroxyurea and/or leukapheresis is permitted during Cycle 1 to control 
total peripheral WBC counts at the treating physician’s discretion, but other anti-leukemic 
therapies will not be permitted.
No additional anti-cancer/anti-leukemia therapy will be permitted while patients are 
receiving PF-06747143.  Additionally, the concurrent use of herbal supplements for anti-
cancer/anti-leukemia 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.  In 
view of the current lack of data about the interaction of PF-06747143 with radiotherapy, 
PF-06747143 treatment should be interrupted during palliative radiotherapy, stopping 1 week 
before and resuming treatment 1 day after.
5.8.2. Supportive Care 
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.  
Allopurinol/rasburicase may be administered as needed for tumor lysis prophylaxis or 
treatment. As noted above, hydroxyurea and/or leukapheresis is also permitted during 
Cycle 1 to in response to elevated total peripheral WBC counts.
All transfusions provided to the patient during the study must be documented in the source 
documents and corresponding transfusion CRF page.
5.8.3. Hematopoietic Growth Factors
Primary prophylactic use of granulocyte-colony stimulating factors is not permitted during 
Cycle 1, but they may be used to treat treatment emergent neutropenia as indicated by the 
current American Society of Clinical Oncology (ASCO) guidelines.31
Use of erythropoietic growth factors is allowed in Cycle 2 and beyond. 
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5.8.4. Anti-Diarrheal, Anti Emetic Therapy
Primary prophylaxis of diarrhea, nausea and vomiting is not permitted in the first cycle for 
patients enrolled in Part 1.  Primary prophylaxis in subsequent cycles is at the investigator’s 
discretion.  The choice of the prophylactic drug is up to the investigator with sponsor 
approval.
5.8.5. Anti-inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed.
5.8.6. Corticosteroids
Chronic, systemic corticosteroid use for palliative or supportive purposes is not permitted.  
Acute emergency administration, topical applications, inhaled sprays, eye drops, or local 
injections of corticosteroids are allowed.
5.8.7. Surgery
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and PF-06747143 required to minimize the risk 
of impaired wound healing and bleeding has not been determined.  Stopping PF-06747143 is 
recommended at least 1 week prior to surgery.  Postoperatively, the decision to reinitiate 
treatment should be based on a clinical assessment of satisfactory wound healing and 
recovery from surgery.
6. STUDY PROCEDURES 
6.1. Screening
For screening procedures see Schedule of Activities.
6.2. Study Period
For treatment period procedures, see Schedule of Activities.
6.3. Follow-up Visit
For follow-up procedures see Schedule of Activities.
6.4. Patient Withdrawal
Patients may withdraw from treatment at any time at their own request, or they may be 
withdrawn at the discretion of the investigator or sponsor for safety or behavioral reasons, or 
the inability of the patient to comply with the protocol-required schedule of study visits or 
procedures at a given study site. 
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Reasons for withdrawal of study treatment may include:

Objective disease progression;

Global deterioration of health status requiring discontinuation;

Unacceptable toxicity;

Pregnancy;

Significant protocol violation;

Lost to follow-up;

Patient refused further treatment;

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;

Refused 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 that the patient return for a final visit, if applicable, 
and follow-up with the patient regarding any unresolved AEs.
If the patient refuses further visits (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.
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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 that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely fashion.
7.1. Safety Assessment
Safety assessments will include collection of adverse events (AEs), serious adverse events 
(SAEs), vital signs and physical examination, electrocardiogram (12-lead), laboratory 
assessments, including pregnancy tests and verification of concomitant treatments.
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 and assayed in a certified laboratory, will be performed on 
2 occasions prior to starting study treatment-once at the start of screening and once at the 
baseline visit (predose on Cycle 1 Day 1), 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 (predose on Cycle 1 Day 1) 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-Treatment and Follow Up visit, and additionally 
whenever 1 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 treatment and will be 
withdrawn from the study.  Additional pregnancy tests may also be undertaken if requested 
by institutional review board/ethics committee (IRB/ECs) 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
Laboratory assessments will be drawn at the time points described in the Schedule of 
Activities and analyzed at local laboratories.
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Table 7.
Laboratory Tests
Hematology*
Chemistry
Coagulation
Urinalysis
Pregnancy Test
Hemoglobin
ALT
PT or INR
Urine dipstick for 
urine protein: If 
positive collect 24-hr 
and microscopic 
(Reflex Testing)
For female patients 
of childbearing 
potential,  serum or 
urine
Platelets
AST
PTT (or 
aPTT)
WBC
Alk Phos
Absolute Neutrophils
Sodium
Absolute Lymphocytes
Potassium
Absolute Monocytes
Magnesium
Urine dipstick for 
urine blood: If 
positive collect a 
microscopic (Reflex 
Testing)
Absolute Eosinophils
Chloride
Absolute Basophils
Total Calcium
Percent Blast Cells
Total Bilirubin***
BUN or Urea
Creatinine
Uric Acid
Glucose (non-fasted)
Albumin
Phosphorous or 
Phosphate
* For Cycle 1, the CBC with differential and blast cell assessment in perhipheral blood for pharmacodynamics 
biomarker labs will also function as the hematology lab safety assessment.  
*** 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)/INR, and alkaline phosphatase.  
7.1.4. Vital Signs and Physical Examination
Patients will have a physical examination to include weight, vital signs, assessment of ECOG 
performance status and height; height will be measured at screening only.
7.1.5. (12-Lead) Electrocardiogram
Electrocardiogram (ECG): Triplicate 12-lead (with a 10-second rhythm strip) tracing will be 
used for all ECGs.  It is preferable that the machine used has a capacity to calculate the 
standard intervals automatically.  At each time point (see the Schedule of Activities), 
3 consecutive ECGs will be performed at approximately 2 minutes apart to determine the 
mean QTcF interval.  If the mean QTcF is prolonged (501 msec, ie, CTCAE Grade 3), 
then the ECGs should be re-evaluated by a qualified person at the site for confirmation as 
soon as the finding is made, including verification that the machine reading is accurate. 
If manual reading verifies a QTcF of 501 msec, immediate correction for reversible causes 
(including electrolyte abnormalities, hypoxia and concomitant medications for drugs with the 
potential to prolong the QTcF interval) should be performed.  In addition, repeat ECGs 
should be immediately performed hourly for at least 3 hours until the QTcF interval falls 
below 501 msec.  If QTcF interval reverts to less than 501 msec, and in the judgment of the 
investigator(s) and sponsor is determined to be due to cause(s) other than investigational 
product, treatment may be continued with regular ECG monitoring.  If in that timeframe the 
QTcF intervals rise above 501 msec the investigational product will be held until the QTcF 
interval decreases to 501 msec.  Patients will then restart the investigational product at the 
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next lowest dose level.  If the QTcF interval has still not decreased to the acceptable mean on 
treatment upper limit, ie, 501 msec (Fridericia) after 2-weeks, or if at any time a patient has a 
QTcF interval >515 msec or becomes symptomatic, the patient will be removed from the 
study.  Additional triplicate ECGs may be performed as clinically indicated. 
Prior to concluding that an episode of prolongation of the QTcF interval is due to 
investigational product, 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 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). 
7.2. Cardiac Monitoring and Pulmonary Function Tests (Part 2, Cohort 1)
Based on the requirements for treatment with daunorubicin, patients in Part 2, Cohort 1 will 
be required to have a screening ECHO/MUGA scan to confirm eligibility. Additional scans 
will also be performed when the cumulative dose of daunorubicin reaches 400 mg/m2, and 
every 2 cycles thereafter.  Decreases in LVEF will be handled according to institutional 
guidelines.
In addition to cardiac monitoring, pulmonary function tests will also be required at screening.  
Diffusing capacity of the lungs for carbon monoxide (DLCO) and forced expiratory volume 
((FEV) measured during the first forced breath (FEV1)) will be performed to confirm 
eligibility.  Additional assessments may be performed as clinically indicated.
7.3. Pharmacokinetics Assessments
7.3.1. Blood for PK analysis of PF-06747143
Blood samples (3 mL whole blood) to provide serum for the analysis of PF-06747143 
concentrations will be collected as outlined in the Schedule of Activities.  Details regarding 
the collection, processing, storage and shipping of the blood samples will be provided in the 
Laboratory Manual.  PK sampling schedule may be modified based on emerging PK data. 
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from patients experiencing unexpected and/or serious AE’s and the date and time of 
blood sample collection and of last dosing prior to PK collection documented in the CRF.
All efforts will be made to obtain the pharmacokinetic samples at the scheduled nominal time 
relative to dosing and the exact time of the sample collection will always be noted on the 
CRF.  However, samples obtained within the protocol-specified time window will be 
considered protocol compliant.  If a scheduled blood sample collection cannot be completed 
for any reason, the missed sample time may be re-scheduled with agreement of the clinical 
investigator, patient, and sponsor.
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PK samples will be assayed for PF-06747143 using a validated analytical method in 
compliance with Pfizer standard operating procedures. To increase the understanding of the 
PK of PF-06747143, samples may be used for the evaluation of the bioanalytical method as 
well as other internal exploratory purposes. These data will not be included in the clinical 
study report. 
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7.5. Immunogenicity Evaluations
Blood samples (approximately 6 mL) to provide serum for detection of ADA and Nab 
against PF-06747143 will be collected into appropriately labeled tubes at times specified in 
the Schedule of Activities.  Details regarding the collection, processing, storage and shipping 
of the blood samples will be provided in the Laboratory Manual. 
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The ADA samples will be analyzed using a validated analytical method in compliance with 
Pfizer standard operating procedures. The sample analysis will follow a tiered approach of 
screening, confirmation, and titer determination. Samples tested positive for ADA will be 
further analyzed for Nab using a validated assay in compliance with Pfizer standard 
operating procedures.  
For patients with an ongoing AE at the final study visit, ADA/NAb samples may be collected 
during follow-up at approximately 3 month intervals, if the unresolved AE is thought to be 
possibly related to ADA, until the AE or its sequelae resolve or stabilize to a level acceptable 
to the investigator and sponsor.
As part of understanding the immunogenicity of the study medication, samples may be used 
for additional characterization of an observed immunogenicity response and/or evaluation of 
the bioanalytical method.  These data will be used for internal exploratory purposes 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 used within this timeframe, will be destroyed.
7.6. Disease Response Assessment
Disease Response Assessments will be based on Diagnosis and management of acute 
myeloid leukemia in adults: recommendations from an international expert panel, on behalf 
of the European LeukemiaNet.22  
Note: Details of disease assessment for Part 2 will be provided prior to starting the 
combination cohorts.
For screening, a fresh bone marrow aspirate sample and biopsy obtained within 14 days of 
screening is acceptable for patient eligibility and biomarker assessment. 
Complete blood counts with white blood cell differential, blast cell assessment and platelet 
count as well as bone marrow aspiration and biopsy, to assess bone marrow cellularity and 
percent blasts, are to be conducted at completion of Cycle 1, approximately at Day 28, and 
prior to starting of every other new cycle of treatment (C3, C5, C7, etc.) until achievement of 
a complete response.  Bone marrow aspirates and/or biopsies and complete blood counts may 
be obtained at other intervals, if clinically indicated.
For Part 1 of the study and based upon the European LeukemiaNet guidelines22, disease 
progression is defined as Relapse or Treatment Failure – Resistant Disease. In such cases, the 
Investigator should consult with the sponsor regarding PF-06747143 treatment 
discontinuation.
7.7. Banked Biospecimens
7.7.1. Markers of Drug Response  
Studying the 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 deoxyribonucleic acid (DNA), 
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ribonucleic (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. 
To protect patients’ confidentiality, the banked biospecimens and data generated from them 
will be coded with the patient’s study identification (ID) number.  Samples will be kept in a 
facility accessible only by swiping a badge. Data will be stored on password-protected 
computer systems. The key between the code and the patient’s personal identifiers will be 
held at the study site; the researchers using the biospecimens and data generated from them 
will not have access to the key nor any personally identifying information.  Biospecimens 
will be used only for the purposes described here and in the informed consent 
document/patient information sheet; any other uses require additional ethical approval.  
Unless a time limitation is required by local regulations or ethical requirements, 
biospecimens will be stored indefinitely to allow for future research on the topics described 
here, including research conducted during the lengthy drug development process and also 
postmarketing research.  Patients can withdraw their consent for the use of their 
biospecimens at any time by making a request to the investigator, in which case any 
remaining biospecimen will be destroyed; data already generated from the biospecimens will 
continue to be stored to protect the integrity of existing analyses.  It is very unlikely that 
results generated from the biospecimens will have any clinical, diagnostic, or therapeutic 
implications for the individual study participants.  Patients are notified in the informed 
consent document/patient information sheet that their results will not be given to them, unless 
required by local laws or regulations, in which case results will be returned via the 
investigator.  Results will not be provided to family members or other physicians, nor will 
they be recorded in the patient’s medical record.  There is no intention to contact patients 
after completion of the clinical study.
A 4-mL blood biospecimen Prep D1 [K2 edetic acid (ethylenediaminetetraacetic acid)
(EDTA) whole blood collection optimized for DNA analysis] will be collected on Cycle 1 
Day 1 and on Day 1 of every cycle through Cycle 6 (if patient remains on study) and at the 
End-of-Treatment 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. 
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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.
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.
7.7.2. Additional Research
Unless prohibited by local regulations or ethics committee decision, patients will be asked to 
indicate on the consent form whether they will allow the banked biospecimens to also be 
used for the following research:

Investigations of the disease under study in the clinical study, and related conditions;

Biospecimens may be used as controls.  This includes use in case-control studies of 
diseases for which Pfizer is researching drug therapies; use in characterizing the 
natural variation amongst people in genes, RNA, proteins, and metabolites; and use in 
developing new technologies related to pharmacogenomics/biomarkers.  
Patients need not provide additional biospecimens for the uses described in this section; the 
biospecimens specified in the Markers of Drug Response Section will be used.  Patients may 
still participate in the clinical study if they elect not to allow their banked biospecimens to be 
used for the additional purposes described in this section. 
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.
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As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the patient provides informed consent, which is obtained prior to the patient’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product.  SAEs occurring to a patient after the active 
reporting period has ended should be reported to the sponsor if the investigator becomes 
aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to 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 1 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;
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
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.
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 (a 
dose within 10% of the appropriate dose is not considered a medication error). 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
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
Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing 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);

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 the 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.
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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 the section on Serious Adverse Event 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 (× ULN) concurrent with a total bilirubin value ≥2 × ULN with no evidence 
of hemolysis and an alkaline phosphatase value ≤2 × ULN or not available;

For patients with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above:

For patients with preexisting AST or ALT baseline values above the normal range,
AST or ALT value ≥2 times the baseline values and ≥3 × ULN, or ≥8 × ULN
(whichever is smaller);
Concurrent with

For patients with pre-existing values of total bilirubin above the normal range: Total 
bilirubin level increased from baseline by an amount of at least 1 × ULN or if the 
value reaches ≥3 × ULN (whichever is smaller).
The patient should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered. In addition to repeating 
measurements of AST and ALT, laboratory tests should include albumin, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time
(PT)/international normalized ratio (INR), and alkaline phosphatase.  A detailed history, 
including relevant information, such as review of ethanol, acetaminophen, recreational drug,
and supplement consumption, family history, occupational exposure, sexual history, travel 
history, history of contact with a jaundiced person, surgery, blood transfusion, history of liver 
or allergic disease, and work exposure, should be collected. Further testing for acute 
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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);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg,, for 
workup of persistent pre-treatment laboratory abnormality);

Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg., for elective 
cosmetic surgery);
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
Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
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
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 the 
patient’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the SAE reporting requirements if applicable.  
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that the investigational product caused or contributed to an AE; 
generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see the 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.  
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In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
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 an SAE report form and an EDP supplemental
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
patient reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the EDP supplemental form.  This must be done irrespective of whether an
AE has occurred and within 24 hours of awareness of the exposure.  The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form. In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for
the termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless preprocedure 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.
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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 EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the study patient with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the patient was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.11. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an 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 
is maintained in the investigator site file.
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.
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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 time frame 
also applies to additional new information (follow-up) on previously forwarded SAE reports 
as well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg,, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Non-Serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a statistical analysis plan (SAP), which will be maintained by the 
sponsor.  This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
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9.1. Analysis Sets 
Data analysis will be performed on the following analysis populations.
Safety analysis set 
The safety analysis set includes all enrolled patients who receive at least one dose of study 
treatment.
Full analysis set
The full analysis set includes all enrolled patients.
Modified Intent to Treat (mITT) Population
The modified intent to treat (mITT) is the analysis population that will follow the ITT 
principle and include patients 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 disease assessment.  The mITT population may be used for conference presentations 
when the study is still ongoing.
Per protocol analysis set (evaluable for MTD)
The per protocol analysis set includes all enrolled patients who receive at least one dose of 
study treatment at the dose level of MTD and who do not have major treatment deviations 
during first cycle.  Patients with major treatment deviations in Cycle 1 are not evaluable for 
the MTD assessment and may be replaced.  Major deviations include failure to satisfy major 
entry criteria (eg, confirmation of the target disease population; signed informed consent), 
administration of less than 3 out of the 4 doses in Cycle 1 or 80% of the planned Cycle 1 
dose (provided that the reduction is not due to toxicity attributable to PF-06747143) or use of 
other anti-cancer/anti-leukemia treatments during the active treatment and disease follow up 
phases other than as defined/allowed in this protocol.  
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.
The PK concentration population is defined as all patients who receive PF-06747143, have 
no major deviations affecting the PK assessment, and have at least one post-dose 
concentration measurement.
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9.2. Statistical Methods and Properties
9.2.1. Part 1
Part 1 of this study employs a mTPI design to estimate the MTD.  The mTPI design employs 
a Bayesian statistics framework and a simple beta-binomial hierarchical model to compute 
the posterior probability of 3 dosing intervals that reflect the relative difference between the 
toxicity rate of each dose level to the target rate (pT=0.25) with prior a conjugated prior beta 
(1,1).  Decision rules are based on calculating the unit probability mass (UPM) of three 
intervals corresponding to underdosing, proper dosing, and overdosing in terms of dose 
limiting toxicity.  A proper dosing interval is centered at the target toxicity rate(pT ) of 
25% with 5% uncertainty (0.20< pT <0.30).  The underdosing interval is (0, 0.20), and the 
overdosing interval is (0.3, 1).  The three dosing intervals are associated with three different 
dose-escalation decisions.  The underdosing interval corresponds to a dose escalation (E), 
overdosing corresponds to a dose de-escalation, and proper-dosing corresponds to staying at 
the same current dose(S).  Given an interval and a probability distribution, the UPM of that 
interval is defined as the probability of the interval divided by the length of the interval.  The 
mTPI design calculates the UPMs for the three dosing intervals, and the one with the largest 
UPM implies the corresponding dose-finding decision.  That decision provides the dose level 
to be used for future patients.  For example, if the underdosing interval has the largest UPM, 
decision E, to escalate, will be executed, and the next cohort of patients will be treated at the 
next-higher dose level.22
Under the mTPI design, a trial is terminated when either the lowest dose is above the MTD 
or a prespecified maximum sample size 50 is reached. 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.  The decision rules to “dose escalate” E, “no change in dose” (S), “dose 
de-escalate” (D) or “dose de-escalate, unacceptable toxicity” (DU) are also described in 
Appendix 4.
For all dose levels, target size for each cohort will be n= 2 to 4 patients as described in mTPI 
design.24  Intermediate dose levels to further evaluate the safety and/or PK may be evaluated 
following discussion between sponsor and Investigator.
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 MTDF; or

All doses explored appear to be overly toxic and the MTD cannot be determined.
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Due to binomial data variability in small samples, DLT may be observed in a first cohort(s) 
0.3 mg/kg simply by chance even when the true P (DLT at 0.3 mg/kg) is fairly low.  This 
could result in the estimated posterior DLT rate at 0.3 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.  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 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.
Table 9.
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
9.2.2. Dose Expansion (Part 2)
Part 2 of this study is intended to confirm the safety and tolerability of the dose selected in 
Part 1 while assessing the anti-leukemia activity of PF-06747143 in combination with 
standard dose of intensive chemotherapy.  The DLT rate and its 95% confidence interval at 
the selected dose may be estimated.
9.3. Sample Size Determination
Approximately 125-140 patients are expected to be enrolled in this study (approximately 
30-50 patients in Part 1 and 87-102 patients in Part 2). 
The exact sample size of the mTPI design in Part 1 cannot be pre specified in advance 
because it is a dynamic feature of the design.  The maximum sample size after which the 
Part 1 will be stopped and MTD declared is 30-50 patients.  Also, a minimum of 9 patients is 
required to establish the MTD.  The actual sample size of Part 1 will depend on the 
underlying dose toxicity profile and variability in actual data realization. 
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.  For the dose declared as MTD at the end of 
Part 1, this number will be at least 9 patients (to further investigate the anti-leukemia activity, 
safety, and PK profile of PF-06747143).  However, since not every dose listed will be studied 
and variable cohort size is allowed, the actual number of patients treated at each dose will 
vary. 
9.4. 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.
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AEs, ECGs, blood pressure, pulse rate, and safety laboratory data will be reviewed and 
summarized on an ongoing basis during the study to evaluate the safety of patients.  Any 
clinical laboratory, ECG, BP, and PR abnormalities of potential clinical concern will be 
described.  Safety data will be presented in tabular and/or graphical format and summarized 
descriptively, where appropriate.
Medical history and physical exam information collected during the course of the study will 
not be captured for inclusion into the study database, unless otherwise noted.  However, any 
untoward findings identified on physical and/or neurologic exams conducted after the 
administration of the first dose of study medication will be captured as an adverse event, if 
those findings meet the definition of an adverse event.  Data collected at Screening that is 
used for inclusion/exclusion criteria, such as laboratory data, ECGs and vital signs will be 
considered source data, and will not be captured for inclusion into the study database, unless 
otherwise noted.  Demographic data collected at Screening will be included in the study 
database.
9.4.1. Analysis of Primary Endpoint
DLT is the primary endpoint of the dose escalation phase (Part 1) of the study.  The 
occurrence of DLTs observed in the dosing cohorts is used to estimate the MTD as described 
in Section 3.1.1. AEs 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.
9.4.2. Analysis of Secondary Safety Endpoints
9.4.2.1. Adverse Events
AEs will be graded by the investigator according to the CTCAE version 4.03 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 treatment.  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).
9.4.2.2. 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 laboratory assay.  The 
analyses will 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 CTCAE grade definitions, results will be categorized as normal, 
abnormal or not done.
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9.4.2.3. Electrocardiogram
The analysis of ECG results will be based on patients in the safety analysis set with baseline 
and on treatment ECG data.  Baseline will be defined as the predose triplicate ECG on 
Cycle 1 Day 1.
QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie,
Fridericia’s).  Data will be summarized and listed for QT, HR, response rate (RR), PR, QRS, 
QTcF, and by study dose level in Part 1 and cohort in Part 2.  Individual QT` (all evaluated 
corrections) intervals will be listed by study dose level in Part 1 and cohort in Part 2.  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 corrected QT interval and changes from baseline in corrected QT after treatment by 
time point and study dose level in Part 1 and cohort in Part 2.  For each patient and by 
treatment, the maximum change from baseline will be calculated as well as the maximum 
post-baseline interval across time-points.  Categorical analysis will be conducted for the 
maximum change from baseline in corrected QT and the maximum post-baseline QT 
interval. 
ECG measurements (an average of the triplicate 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 
triplicates.  Interval measurements from repeated ECGs will be included in the outlier 
analysis (categorical analysis) as individual values obtained at unscheduled time points.
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval and QRS interval will be summarized by treatment and time.  QT intervals will be 
corrected for heart rate (QTc) using Fridericia’s correction factors (QTcF).
The number (%) of patients with maximum post dose QTcF values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Borderline (msec)
Prolonged (msec)
Absolute Value
450 - <480
480
Absolute Change
30-<60
60
In addition, the number of patients with corrected and uncorrected QT values 500 msec will 
be summarized.
Shift tables will be provided for baseline vs worst on treatment corrected QT (one or more 
correction method will be used) using maximum CTCAE Grade.  Shift tables will also be 
provided for ECG abnormality at baseline (pretreatment) vs. on treatment (yes, no, not done: 
(n, %)).  Patients experiencing clinically relevant morphological ECG changes will be 
summarized (including frequency and percentage).
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The effect of drug concentrations on corrected QT change from baseline will be explored 
graphically.  Additional concentration corrected QT analyses may be performed.  Data may 
be pooled with other study results and/or explored further with PK/PD models.
9.5. Efficacy Analysis 
In this First In Patient study anti-leukemia activity is a secondary objective.  Anti-leukemia
activity will be presented in the form of patient data listings that include, but will not be 
limited to, AML type, starting dose, leukemia assessments, leukemia response at each visit, 
and best overall response.  In addition, progression date, death date, date of first response and 
disease assessment date, and date of last assessment will also be listed.
Cohort 1 and 2:
Clinical assessment will be conducted while the study is ongoing and as these patients are 
receiving SOC, the enrollment can proceed until N=30 and depending on clinical observation 
of safety and activity, enrollment can stop prior to 30 patients.  Posterior probabilities, 
calculated on a sample size of N=20-30, higher than 88% of an ORR 40% in the unfit 
combo group or a 60% of an ORR 70% in the fit cohort will be considered as sufficient 
evidence of activity for proceeding to Phase 2 in the respective indication (see table below).
True ORR
Posterior Probability
(x% that the true ORR y%) 
Posterior Probability
(x% that the true ORR<y%)
10/30=33%
40% (25%)
35% (54%)
15/30=50%
40% (88%)
35% (2.3%)
20/30=66%
70% (30%)
65% (47%)
25/30=83%
70% (93%)
65% (1.8%)
For example, a 50% true ORR (15 out of 30 patients) would predict a posterior probability 
equal to 88% that the true ORR is not inferior to 40% and a posterior probability equal to 
2.3% that the true ORR is inferior to 35%.  Posterior probabilities higher than 88% of an 
ORR 40% in the unfit combo group or a 60% of an ORR 70% in the fit cohort will be 
considered as sufficient evidence of activity for proceeding to Phase 2 in the respective 
indication.  
Cohort 3:
Enrollment of patients in Cohort 3 (single agent PF-06747143) may be discontinued if 
minimal or no anti-tumor activity is observed in the first 15 evaluable patients for that 
cohort. Assuming a non-informative prior (ie, beta[1,1]) if <2 out of 15 patients have tumor 
response, this would predict a posterior probability (Beta-Binomial) equal to 0.90 and 
0.65 that the true response is inferior to 30% and 20% respectively. On the other hand, if 
10 out of 20 patients have tumor response, this would predict a posterior probability equal to 
0.83 that the true response is not inferior to 40% and a posterior probability equal to 
0.03 (3%) that the true response is inferior to 30%. Posterior probabilities may be calculated 
by using informative priors based on the antitumor activity that may be observed during 
Part 1 (eg, 3 out of 6 patients experience tumor response in the dose escalation phase). These 
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posterior probabilities will be assessed for Cohort 3 when at least the first 15 patient are 
enrolled. Posterior Probabilities >0.90 of an ORR<30% (eg, 0,1,2 out of 15) will provide 
evidence of no substantial anti-tumor activity for that indication.  Posterior Probabilities 
>0.90 of an ORR<30% (eg, 0,1,2 out of 15) will provide evidence of no substantial 
anti-tumor activity for that indication. 
9.5.1. Analysis of Overall Response
For patients to be considered evaluable for efficacy they must have received at least one dose 
of study medication and have a baseline disease assessment.  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.
To be assigned a status of PR or CR, changes in leukemia measurements must be confirmed 
by repeat assessments that should be performed no less than 4 weeks after the criteria for 
response are first met.  
9.6. Analysis of Pharmacokinetics and Pharmacodynamics 
9.6.1. PF-06747143 Pharmacokinetic Analysis
PF-06747143 concentrations will be summarized descriptively (n, mean, SD, coefficient of 
variation (CV), median, minimum, maximum, geometric mean and its associated CV) by 
dose level (Part 1), cohort (Part 2: S1, S2), cycle, day and nominal time.  Individual patient 
and median profiles of the concentration-time data will be plotted by dose, cycle and day 
(single dose and steady state) using nominal times.  Individual and median profiles will be 
presented on both linear-linear and log-linear scales.
Serum PF-06747143 concentrations from patients in Part 1 and Cohorts S1 and S2 in Part 2 
will be analysed for PK parameters. Single dose PK parameters estimated will include the 
maximum concentration (Cmax), time to maximum concentration (Tmax), area under the 
concentration versus time curve (AUClast), and, if data permit, area under the concentration 
versus time curve to infinity (AUCinf), apparent volume of distribution (Vd), terminal 
elimination half-life (t1/2), clearance (CL), using non-compartmental analysis.  Multiple dose 
PK parameters estimated will include Cmax, ss, Cmin, ss, AUC, ss, (AUC, ss /AUC), and if data 
permit, CL, t1/2 Vss, and accumulation ratio (Rac) (assuming steady state is achieved).  The PK 
parameters will be summarized descriptively by dose level (Part 1), cohort (Part 2: S1, S2), 
cycle, day and nominal time. For the concentration time data from the Cycle 1, Day 1 and 
Cycle 2, Day 1 dose, dose normalized AUCinf (AUCτ at steady state), and Cmax will be plotted 
against dose (using a logarithmic scale) by dose level for Part 1 and by Cohorts S1 and S2 for 
Part 2.  These plots will include individual patient values and the geometric means for each 
dose.  These plots will be used to help understand the relationship between the PK 
parameters and dose.
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The observed accumulation ratio will be summarized descriptively.  Each will be analyzed 
after natural log transformation using a one-way analysis of variance with a single term for 
dose.  The means and 90% confidence intervals (CIs) obtained from the model will be 
back-transformed to provide means and 90% CIs for the accumulation for each dose.
Trough concentrations will be plotted for each dose using a box-whisker plot by cycle and 
day within cycle in order to assess the attainment of steady state.
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9.7. Analysis of Other Endpoints 
Descriptive statistics will be used to summarize all patient characteristics, treatment 
administration/compliance, and analysis of biomarker endpoints.  Data will also be displayed 
graphically, where appropriate.  Additional details of the analyses are outlined in the SAP. 
9.7.1. Immunogenicity
The development of anti PF-06747143 antibodies will be measured using validated assays.  
Listings and summary tabulations of number of patients and incidence of ADA at baseline
(pretreatment) and post treatment will be generated.
Potential impact of immunogenicity on PK and clinical responses including PD markers, 
safety/tolerability and efficacy of PF-06747143 will be explored, if data is warranted.
9.8. Data Safety Monitoring Committee 
An external Data Safety Monitoring Committee 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 serious adverse events (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 ongoing 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
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
During study conduct and/or after study completion, the study site may be subject to review 
by the institutional review board (IRB)/ethics committee (EC), and/or to quality assurance 
audits performed by Pfizer, or companies working with or on behalf of Pfizer, and/or to 
inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the study site for the inspection and will allow Pfizer or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly 
provide copies of the inspection findings to Pfizer or its agent.  Before response submission 
to the regulatory authorities, the investigator will provide Pfizer or its agents with an 
opportunity to review and comment on responses to any such findings.
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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 are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital's or the physician's patient chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigative site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating patients (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to ICH guidelines, according to local regulations, or 
as specified in the clinical study agreement (CSA), whichever is longer.
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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 /Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996 & 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
12.3. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, patient
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study patients. The study 
site will maintain a confidential list of patients who participated in the study, linking each 
patient’s numerical code to his or her actual identity. In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of patients’ personal data consistent 
with applicable privacy laws.
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The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed and approved by the sponsor, approved by the IRB/EC before use, and available for 
inspection.
The investigator must ensure that each study patient 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 before any study-specific activity is performed, unless a waiver of 
informed consent has been granted by an IRB/EC. The investigator will retain the original of 
each patient's signed consent document.
12.4. Patient Recruitment
Advertisements approved by IRBs/ECs and investigator databases may be used as 
recruitment procedures.  
Pfizer will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study patients before such materials are used.
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately.  
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of trial in a Member State of the European Union (EU) is defined as the time at which it 
is deemed that a sufficient number of 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 patient last visit (LPLV).
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14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06747143 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) prior to their next scheduled treatment day.  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 pediatric 
populations.
Primary completion date is defined as the date that the final patient was examined or received 
an intervention for the purposes of final collection of data for the primary outcome, whether 
the clinical study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts 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
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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 supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product.  
However, to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “Publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before they are 
submitted for publication or otherwise disclosed. If any patent action is required to protect 
intellectual property rights, the investigator agrees to delay the disclosure for a period not to 
exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicentre study, the investigator agrees that the first publication is 
to be a joint publication covering all study sites, and that any subsequent publications by the  
principal investigator will reference that primary publication. However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
study at all participating sites, the investigator is free to publish separately, subject to the 
other requirements of this section.
For all publications relating to the study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study patients, and the CSA will control as to all other 
issues.
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Redjal N, Chan JA, Segal RA, et al. CXCR4 inhibition synergizes with cytotoxic 
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The International Council for Harmonisation (ICH), Work Products, Safety Guidelines: 
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The International Council for Harmonisation (ICH), Work Products, Safety Guidelines: 
S9 Nonclinical Evaluation for Anticancer Pharmaceuticals (Published in the Federal 
Register, 8 March 2010, Vol. 75, No. 44, Docket No. FDA/2009/D/0006, p. 10487). 
http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html. Accessed 
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National Cancer Institute, NCI Drug Dictionary, Cytarabine. 
http://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=39015. Accessed 
February 03, 2016.
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National Comprehensive Cancer Network. 
http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed February 03, 
2016.
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National Cancer Institute, NCI Drug Dictionary, Daunorubicin. 
http://www.cancer.gov/publications/dictionaries/cancer-drug?search=daunorubicin. 
Accessed February 03, 2016. 
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National Cancer Institute, NCI Drug Dictionary, Decitabine. 
http://www.cancer.gov/about-cancer/treatment/drugs/decitabine. Accessed February 03, 
2016.
19.
Kantarjian HM, Thomas XG, Dmoszynska A, et al.: Multicenter, randomized, open-
label, phase III trial of decitabine versus patient choice, with physician advice, of either 
supportive care or low-dose cytarabine for the treatment of older patients with newly 
diagnosed acute myeloid leukemia. J Clin Oncol. 2012 Jul 20; 30(21):2670-7
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National Cancer Institute, NCI Drug Dictionary, Azacitidine. 
http://www.cancer.gov/about-cancer/treatment/drugs/azacitidine. Accessed February 03, 
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Itzykson R, Thépot S, Berthon C, et al.: Azacitidine for the treatment of relapsed and 
refractory AML in older patients. Leuk Res 39 (2): 124-30, 2015.
22.
Döhner H1, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid 
leukemia in adults: recommendations from an international expert panel, on behalf of 
the European LeukemiaNet.  Blood. 2010 Jan 21; 115(3):453-74
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Vardiman JW et al, The 2008 revision of the World Health Organization (WHO) 
classification of myeloid neoplasms and acute leukemia: rationale and important 
changes. Blood. 2009: 114(5):937-951.
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Y Ji, P Liu, Y Li, and BN Bekele. A modified toxicity probability interval method for 
dose-finding trials. Clinical Trials, 7:653 663, 2010.
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25.
Ferrara, et al. Consensus-based definition of unfitness to intensive and non-intensive 
chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on 
a new tool for therapy decision making. Leukemia 2013; 27: 997–999.
26.
Balsat M, Renneville A, Thomas X, et al. Postinduction Minimal Residual Disease Predicts 
Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia 
With NPM1 Mutation: A Study by the Acute Leukemia French Association Group. J Clin 
Oncol. 2017 :35(2):185-93.
27.
Ossenkoppele G, Schuurhuis GJ. MRD in AML: time for redefinition of CR? Blood. 
2013 :121(12):2166-8.
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Ossenkoppele G, Schuurhuis GJ. MRD in AML: does it already guide therapy decision-
making? Hematology Am Soc Hematol Educ Program. 2016 :2016(1):356-65.
29.
Ossenkoppele GJ, Schuurhuis GJ. MRD in AML: it is time to change the definition of 
remission. Best Pract Res Clin Haematol. 2014 :27(3-4):265-71.
30.
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http://www.fda.gov/downloads/Drugs/.../Guidances/ucm073122.pdf. Accessed February 
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Evidence-Based Clinical Practice Guideline. JCO Jul 1, 2006:3187-3205.
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Appendix 1. Abbreviations
Abbreviation
Term
Ab
Antibody
ACRIN
American College of Radiology Imaging Network
ADCC
antibody-dependent cell-mediated cytotoxicity
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
APL
acute promyelocytic leukemia
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AUC
area under the curve
BID
twice daily
BM
bone marrow
BP
blood pressure
BUN
blood urea nitrogen
C
Cycle
C
Concentration
CDC
complement dependent cytotoxicity
CDS
core data sheet
Ceff
effective concentration
CHF
congestive heart failure
CI
confidence interval
CL
clearance
CLL
chronic lymphocytic leukemia
Cmax
maximum concentration
CML
chronic myeloid leukemia
CMML
chronic myelomonocytic leukemia
CNS
central nervous system
CR
complete response
CRF
case report form
CRM
Continuous Reassessment Method
CSA
clinical study agreement
CSF
cerebrospinal fluid
CSR
clinical study report
CT
computed tomography
CTA
clinical trial application
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
CCI
CCI
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Abbreviation
Term
D
day
DLCO
diffusing capacity of the lungs for carbon monoxide
DLI
Donor Lymphocyte Infusion
DLT
dose-limiting toxicity
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DR
Duration of Response
EC
ethics committee
EC50
half maximal effective concentration
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
e.g.
for example
EFS
Event-Free Survival
etc
‘and other things’ or ‘and so forth’
EudraCT
European Clinical Trials Database
FCGR3A
Fcgamma receptor
FDA
Food and Drug Administration (United States)
FDAAA
Food and Drug Administration Amendments Act (United States)
FEV
forced expiratory volume
FEV1
forced expiratory volume in 1 second
FFPE
formalin-fixed paraffin-embedded 
FSH
follicle-stimulating hormone
GALT
gut-associated lymphoid tissue
GCP
Good Clinical Practice
GITMO
Italian Group for Bone Marrow Transplantation
GLP
Good Laboratory Practice
GnRH
gonadotropin-releasing hormone agonist
GVHD
graft versus host disease
HAV
hepatitis A virus
HBV
hepatitis B virus
hCG
human chorionic gonadotropin
HCT
hematocrit
HCV
hepatitis C virus
Hgb
hemoglobin
HIV
human immunodeficiency virus
HNSTD
highest non-severely toxic dose)
HR
heart rate
IB
investigator’s brochure
CCI
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Abbreviation
Term
ICH
International Conference on Harmonisation
ID
identification
i.e.
that is
IgG1
immunoglobulin G1
IND
investigational new drug application
INR
international normalized ratio
IRB
institutional review board
IUD
intrauterine device
IV
intravenous
K2EDTA
dipotassium ethylene diamine tetraacetic acid
LDH
lactate dehydrogenase
LFT
liver function test
LPD
local product document
LSLV
last subject last visit
LVEF
left ventricular ejection fraction
mAb
monoclonal antibody
mITT
modified intent to treat 
mTPI
modified toxicity probability interval
MD
multiple dose
MDS
myelodysplastic syndrome
MedDRA
Medical Dictionary for Regulatory Activities
MFD
maximum feasible dose
MM
multiple myeloma
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
MUGA
multigated acquisition scan
N/A
not applicable
NCI 
National Cancer Institute 
NHL
non-Hodgkin’s lymphoma
OBD
optimal biological dose
OS
overall survival
pT
target probability
PB
peripheral blood
PCD
primary completion date
PD
progressive disease
PET
positron emission tomography
PFS
Progression-Free Survival
PFS
prefilled syringe
B- or T-PLL
prolymphocytic leukemia
PK
pharmacokinetics
CCI
CCI
CCI
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Abbreviation
Term
PR
partial response
PS
performance status
PT
prothrombin time
PTT
partial thromboplastin time
QW
every week
QD
every day
QT
time between the start of the Q wave and the end of the T wave
Q2W
every two weeks (every other week)
R
ratio
RBC
red blood cell
RD
Response/Remission Duration 
RECIST
Response Evaluation Criteria in Solid Tumors
RFS
Relapse-Free Survival
RNA
ribonucleic acid
RP2D
recommended Phase 2 dose
RR
response rate
SAE
serious adverse event
SAP
statistical analysis plan
SC
Subcutaneous
SD
single dose
SIB
suicidal ideation and behavior
SIE
Italian Society of Hematology
SIES
Italian Society of Experimental Hematology
SPEP
serum protein electrophoresis
SPC
Summary of Product Characteristics
SRSD
single reference safety document
T
Time
T1/2
terminal elimination half-life
TBNK
T cell, B cell and natural killer cell
TBR
tumor background ratio
TMDD
target-mediated drug disposition
ULN
upper limit of normal
UPM
unit probability mass
US
United States
USPI
United States Package Insert
UVB
ultraviolet B light
V
volume of distribution
WBC
white blood cell count
WHO
World Health Organization
WM
Waldenstrom's macroglobulinemia
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Appendix 2. Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade
Criterion
0
Fully active, able to carry on all predisease activities without restriction (Karnofsky 90 - 100)
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, for example light housework or office work (Karnofsky 70 - 80)
2
Ambulatory and capable of all self-care but unable to carry out work activities.  Up and about 
more than 50% of waking hours (Karnofsky 50 - 60)
3
Capable of only limited self care, confined to bed or chair 50% or more of waking hours.  
(Karnofsky 30 - 40)
4
Completely disabled, cannot carry on any self-care, totally confined to bed or chair.  
(Karnofsky 10 - 20)
5
Death
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Appendix 3. Management of Allergic Reactions/Cytokine Release Syndrome or 
Anaphylaxis
In the event of allergic/infusion 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
1. Decrease PF-06747143 infusion rate by 50% and monitor for worsening condition.  If the 
reaction worsens, stop the infusion.  Protocol treatment will be discontinued.
NCI-CTCAE Grade 2 allergic reaction or cytokine release syndrome
1. Stop PF-06747143 infusion.
2. Administer bronchodilators, oxygen, acetaminophen, etc. as medically indicated.
3. 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.  
Protocol treatment will be discontinued.
NCI-CTCAE Grade 3 or Grade 4 allergic reaction or cytokine release syndrome or 
anaphylaxis
1. A Grade 3 hypersensitivity reaction consists of symptomatic bronchospasm requiring 
parenteral medications with or without urticaria, allergy-related edema/angioedema, or 
asymptomatic hypotension not requiring treatment.
2. A Grade 4 hypersensitivity reaction (ie, anaphylaxis) is a life-threatening event 
characterized by the same symptoms as in a Grade 3 reaction but also complicated by 
symptomatic hypotension or oxygen saturation of 70% or less.
Treatment of Grade 3 or Grade 4 allergic reaction or cytokine release syndrome or 
anaphylaxis
1. Stop the PF-06747143 infusion immediately and disconnect infusion tubing from the 
patient.
2. Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous 
fluids, vasopressor agents, oxygen, etc. as medically indicated.
3. Telephone sponsor or designated representative to report an SAE and fax SAE 
worksheet.
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For a NCI-CTCAE Grade 3 or 4 hypersensitivity reaction, protocol treatment will be 
discontinued.
Re-treatment following Grade 1 or Grade 2 allergic reactions or cytokine release 
syndrome
1. Once the PF-06747143 infusion rate has been decreased due to an allergic reaction or 
cytokine release syndrome, it will remain decreased for all subsequent infusions.
2. 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-06747143.
3. 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-06747143.
4. 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 4. Detailed Dose Escalation/De-Escalation Scheme for mTPI Design
E=Escalate to the next higher dose
S=Stay at the current dose
D=De-escalate to the next lower dose
DU=The current dose is unacceptably toxic
Probability of target toxicity=0.25
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 to the lower dose

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 DLT -> remain at the same dose

2 DLTs -> de-escalate

3-4 DLTs -> de-escalate and consider current dose as intolerable
Number of Patients
Number of Toxicities
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
With 5 patients treated at current dose level

0 DLT -> escalate

1-2 DLTs -> remain at the same dose

3 DLTs -> de-escalate and consider current dose as intolerable

With 6 patients treated at current dose level

0 DLT -> escalate

1-2 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 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 and consider currentdose as intolerable

With 9 patients treated at current dose level

0-1 DLT -> escalate

2-3 DLTs -> remain at the same dose

4 DLTs -> de-escalate

5-9 DLTs -> de-escalate and consider current dose as intolerable

With 10 patients treated at current dose level

0-1 DLT -> escalate

2-4 DLTs -> remain at the same dose

>5 DLTs -> de-escalate and consider current dose as intolerable

With 11 patients treated at current dose level

0-1 DLT -> escalate

2-4 DLTs -> remain at the same dose

5 DLTs -> de-escalate

6-11 DLTs -> de-escalate and consider current dose as intolerable

With 12 patients treated at current dose level

0-1 DLT -> escalate

2-5 DLTs -> remain at the same dose

6-12 DLTs -> de-escalate and consider current dose as intolerable
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SAP_001.pdf: 
Protocol B7861002 (PF-06747143)
Statistical Analysis Plan
Page 1 of 38
Protocol B7861002
A PHASE 1 DOSE ESCALATION STUDY TO 
EVALUATE THE SAFETY,
PHARMACOKINETICS AND 
PHARMACODYNAMICS OF INTRAVENOUS
PF-06747143, ADMINISTERED AS SINGLE AGENT 
OR IN COMBINATION WITH
STANDARD CHEMOTHERAPY IN ADULT PATIENTS 
WITH ACUTE MYELOID
LEUKEMIA
Statistical Analysis Plan - Revised
(SAP)
Version: 2.0
Author: 
 (Statistics, 
, USA)
Revised: April 26, 2017 – Incorporates changes proposed in Amendment 2, march 6, 2017
PPD
PPD
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Statistical Analysis Plan
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Revised: October 26, 2017 – Added Appendix 3 (Disease Assessment), made minor changes 
in response to issues raised 
Date:     29-August-2016
Revised: May 1, 2017 – Incorporates changes/comments suggested by
. on the 
Apr 26 version.
PPD
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................5
LIST OF FIGURES ...................................................................................................................5
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................6
2. INTRODUCTION .................................................................................................................6
2.1. Study Overview.........................................................................................................6
2.1.1. Part 1.............................................................................................................6
2.1.1.1. Starting Dose...............................................................................7
2.1.1.2. Criteria for Dose Escalation ........................................................7
2.2. Part 2 .........................................................................................................................9
2.2.1. Part 2 Combination Cohorts Starting Dose ..................................................9
2.2.2. Part 2/Cohort 1 and 2....................................................................................9
2.2.2.1. Part 2/Cohort 1 - PF-06747143 Combination in Fit 
Treatment Naïve AML Patients.........................................................10
2.2.2.2. Part 2/Cohort 2 – PF-06747143 Combination in Unfit 
Treatment Naïve AML Patients.........................................................10
2.2.2.3. MTD Definition.........................................................................10
2.2.2.4. Part 2/Cohort 3 – PF-06747143 Single Agent Expansion.........10
2.2.3. Summary.....................................................................................................10
2.3. Study Objectives and Endpoints .............................................................................11
2.3.1. Part 1 Study Objectives ..............................................................................11
2.3.2. Endpoints – Part 1.......................................................................................12
2.3.3. Objectives – Part 2......................................................................................12
2.4. Endpoints – Part 2 ...................................................................................................13
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING................................15
4. HYPOTHESES AND DECISION RULES.........................................................................15
4.1. Statistical Hypotheses .............................................................................................15
4.2. Statistical Decision Rules........................................................................................15
4.2.1. Part 1...........................................................................................................15
4.2.2. Part 2...........................................................................................................16
5. SAMPLE SIZE DETERMINATION ..................................................................................16
6. ANALYSIS SETS ...............................................................................................................16
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6.1. Full Analysis Set .....................................................................................................16
6.2. ‘PER PROTOCOL’ Analysis Set............................................................................16
6.3. Safety Analysis Set..................................................................................................17
6.4. Other Analysis Sets .................................................................................................17
6.4.1. Modified Intent-to-Treat Set.......................................................................17
6.5. Treatment Misallocations........................................................................................17
6.6. Protocol Deviations.................................................................................................17
7. ENDPOINTS AND COVARIATES ...................................................................................18
7.1. Efficacy Endpoint(s) ...............................................................................................18
7.2. Safety Endpoints .....................................................................................................19
7.2.1. DLT Definitions..........................................................................................19
7.2.2. MTD Definition..........................................................................................20
7.2.3. Maximum Permitted Dose Definition ........................................................20
7.2.4. Recommended Phase 2 Dose (RP2D) Definition.......................................20
7.2.5. Vitals Signs.................................................................................................21
7.2.6. Laboratory Data..........................................................................................21
7.2.7. Adverse Events...........................................................................................21
7.2.8. ECG and QTc Interval................................................................................22
7.2.9. Immunogenicity..........................................................................................23
7.3. PK Endpoints...........................................................................................................23
7.4. PD Endpoints...........................................................................................................24
7.5. Covariates................................................................................................................24
8. HANDLING OF MISSING VALUES ................................................................................24
8.1. Missing Dates..........................................................................................................24
8.2. Efficacy Analysis ....................................................................................................24
8.3. Pharmacokinetics ....................................................................................................24
9. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................25
9.1. Statistical Methods ..................................................................................................25
9.2. Statistical Analyses .................................................................................................26
9.2.1. Primary Analysis ........................................................................................26
9.2.2. Secondary Analyses....................................................................................26
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9.2.2.1. Efficacy Analysis ......................................................................26
9.2.2.2. Pharmacokinetics Analyses.......................................................27
9.2.3. Safety Analyses ..........................................................................................29
9.2.4. Standard Analyses ......................................................................................30
10. REFERENCES ..................................................................................................................32
11. APPENDICES ...................................................................................................................33
11.1. APPENDIX 1: CATEGORICAL CLASSES FOR ECG AND VITAL 
SIGNS........................................................................................................................33
11.2. APPENDIX 2: CENSORING DETAILS .............................................................34
11.3. Appendix 3. Detailed Dose Escalation/De-Escalation Scheme for mTPI 
Design........................................................................................................................35
11.4. Disease Assessment...............................................................................................37
LIST OF TABLES
Table 1.
Possible Dose Levels ..............................................................................................8
Table 2.
Overview of Efficacy Analysis.............................................................................27
Table 3.
PK Parameter Summaries.....................................................................................27
Table 4.
Progression Free Survival and Duration of Response..........................................34
Table 5.
Time to Progression..............................................................................................34
LIST OF FIGURES
Figure 1.
Part I schema...........................................................................................................7
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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
Not applicable.
2. INTRODUCTION
This document describes the planned statistical analyses for Protocol B7861002. 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 Overview
PF-06747143 will initially be developed in patients with acute myeloid leukemia (AML).  
The diagnosis of AML will be according to the World Health Organization (WHO) 
classification (Ref (8). The study will be conducted in two parts, Part 1 single agent dose 
escalation and Part 2 PF-06747143 in combination with standard chemotherapy with an 
option for single agent cohort expansion at the RP2D.
Assessment of anti-leukemia activity of PF-06747143 will be based on Diagnosis and 
management of acute myeloid leukemia in adults: recommendations from an international 
expert panel, on behalf of the European LeukemiaNet. (Ref (2).
2.1.1. Part 1
Part 1, dose escalation, is an open-label, multi-center, single arm, non randomized, multiple 
dose, safety, pharmacokinetic and pharmacodynamic study of single-agent PF-06747143 in 
sequential dose levels of adult patients with refractory and/or relapsed AML in order to 
establish MTD/ RP2D or maximally permitted dose (MPD).
Patients will receive PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating 
doses.  The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg. Patients 
enrolled in the first two dose levels (0.3 mg/kg and 1.0 mg/kg) will be required to stay in the 
clinic/hospital overnight (minimum of 24 hours) after receiving the first dose of PF-
06747143 to monitor for the potential risk of hyperleukocytosis that might be caused by the 
inhibition of 
 by PF-06747143.  On an individual basis, patients may be 
monitored overnight for the additional doses in Cycle 1 at the treating physician’s discretion.
In the first three dose levels (ie, starting dose 0.3 mg/kg through 3.0 mg/kg), initiation of the 
first dose of PF-06747143 for each patient in the dose level must be at least 72 hours after the 
first dose of the previous patient. Patients enrolled in subsequent dose levels will be treated 
on an outpatient basis with no staggering of patients unless there are safety concerns based 
on findings at the lower doses.
Once MTD or MPD is identified, additional patients may be enrolled at that dose level (to a 
minimum of 9) to further investigate the anti-leukemia activity, safety, and PK profile of 
PF-06747143 prior to an expansion cohort with single agent PF-06747143 at the
MTD/MPD/RP2D.
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The total estimated number of patients to be enrolled for the Part 1 dose escalation study will 
be approximately 30-50 patients but it is pertinent to recognize that the exact sample size of 
the mTPI design in Part 1 cannot be pre specified in advance because it is a dynamic feature 
of the design.
Once the dose of 15 mg/kg in Part 1 is found safe and tolerable, the Part 2 combination 
cohorts will be initiated at 10 mg/kg while the Part 1 single agent dose escalation continues 
to 20 mg/kg for MPD or MTD assessment.
Figure 1.
Part I schema
2.1.1.1. Starting Dose
The starting dose will be 0.3 mg/kg, administered QW in 28 day cycles.
2.1.1.2. Criteria for Dose Escalation
A modified toxicity probability interval method (mTPI) (Ref (7)) targeting a DLT rate of 
25% with an equivalence interval (20%-30%) will be utilized in order to estimate MTD in 
dose escalation.  For all dose levels, patients may be enrolled in cohorts of 2-4 (the target size 
of each cohort will be 3 patients).  Intermediate dose levels to further evaluate the safety 
and/or PK may be evaluated following discussion between sponsor and Investigator.
The dose levels planned for Part 1 of the study are shown in Table 1 Additional dose levels 
may be explored, if appropriate based on emerging safety, PK or PD data.  Intra-patient dose 
escalation of PF-06747143 or the backbone chemotherapy (in Part 2 combination cohorts) 
will not be permitted.
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Table 1.
Possible Dose Levels
Dose 
Level
PF-06747143 Dose (mg/kg)
(QW)
1
0.3
2
1.0
3
3.0
4
10
5
15
6
20
The mTPI method relies upon a statistical probability algorithm, calculated using all patients 
treated in prior and current cohorts at the same dose level to determine where future cohorts 
should be on dose escalation, no change in dose, or dose de escalation. The algorithm will 
stop if any of the following criteria is met:

the maximum sample size has been achieved (approximately 50 patients total);

at least 9 patients have been accumulated on a dose that is predicted to be the MTD;
or

all doses explored appear to be overly toxic and the MTD cannot be determined.
Although dose levels are capped at 20 mg/kg, this mTPI will continue to operate subject to 
the constraints detailed above while allowing for doses higher than specified.  All clinically 
relevant adverse events (AEs) and serious adverse events (SAEs) will be reviewed by the 
Sponsor and Investigators after each dose level is complete to determine if the dose 
allocation schedule requires modification.
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.(Ref 7) These rules are conceptually similar to those used by the 3+3 design and all 
thedose-escalation decisions for a given trial and can be pre-calculated under the mTPI 
design and presented in a two-way table (Appendix 4).
Patients will continue with study treatment until disease progression, patient refusal or
unacceptable toxicity occurs. Patients experiencing a DLT may be managed with dose 
modification (after dose interruption) or discontinuation. 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. Intra-patient dose escalation will not be permitted in this study.
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2.2. Part 2
Part 2 dose expansion, is an open-label, multi-center, non randomized study to assess the 
safety and tolerability and preliminary anti-leukemia activity of PF-06747143 in three 
cohorts (two combination cohorts and one potential cohort of single agent PF-06747143).
Figure 2.
Part 2 will assess the safety and tolerability and preliminary anti-leukemia activity of 
PF-06747143. In Part 2, PF-06747143 will be administered at 10 mg/kg QW (Section 
3.1.2.1) on 28 day cycles in combination with chemotherapy in two separate cohorts each 
containing up to 30 patients with newly diagnosed AML, including Cohort 1 in fit treatment 
naïve AML patients, in which PF-06747143 will be combined with standard intensive 7+3 
chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and 
daunorubicin (60-90 mg/m2 daily for 3 days), and Cohort 2 in unfit treatment naïve AML 
patients who are considered to not tolerate or decline to receive standard intensive 7+3 
treatment, in which case PF-06747143 will be combined with standard dose of azacitidine 
(75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 
mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week 
schedule) based on drug availability and institutional guidance.
Attributions to fit or unfit in Part 2 will be based on “Consensus-based definition of unfitness 
to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of Italian 
SIE, SIES and GITMO group on a new tool for therapy decision making”25 per Investigator 
judgement.
An additional single agent PF-06747143 expansion cohort, Cohort 3, at the MTD/RP2D may 
be initiated in Part 2 in 15-30 refractory and/or relapsed AML patients based on single agent 
PF-06747143 clinical benefit in Part 1.
2.2.1. Part 2 Combination Cohorts Starting Dose
After the DLT observation period in the first cycle of 15 mg/kg cohort is cleared, the dose of
10 mg/kg of PF-06747143 will be used to initiate the Part 2 combination studies, which may 
be escalated or de-escalated, depending on emerging data. Additionally, if an MTD in Part 1 
is determined at or below the dose of 15 mg/kg, a lower dose than 10 mg/kg may 
beconsidered to move into Part 2 dose expansion combination studies.
2.2.2. Part 2/Cohort 1 and 2
In Part 2, Cohort 1 and 2 expansion cohorts (E) will start with a safety lead-in (S) in 
approximately 3-6 patients to assure the combination treatment regimen is safe and tolerable 
in each patient population (ie, fit and unfit AML). The safety lead-in will use the standard 
3+3 dose escalation method to evaluate safety profile (using the DLT criteria described in 
Section 3.1.1.3) for a duration of up to 2 cycles.
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2.2.2.1. Part 2/Cohort 1 - PF-06747143 Combination in Fit Treatment Naïve AML
Patients
Cohort 1 safety lead-in group (S1) will start with 10 mg/kg dose of PF-06747143 and may be
escalated to up to 20 mg/kg (the MPD) or de-escalated to below 10 mg/kg based on the 
predefined DLT criteria (see Section 3.1.1.3) and emerging data. After completion of the S1 
cohort, PF-06747143 will be administered in combination with intensive therapy (ie, 7+3 
daunorubicin and cytarabine) as induction and continue during consolidation and in 
maintenance for up to a maximum of 6 months (6 cycles) starting from the completion of 
consolidation, until disease progression or relapse, patient refusal or unacceptable toxicity 
occurs (whichever comes first) in newly diagnosed treatment naïve fit AML patients. The 
expansion cohort (E1) will enroll up to 30 patients.
2.2.2.2. Part 2/Cohort 2 – PF-06747143 Combination in Unfit Treatment Naïve AML
Patients
Cohort 2 safety lead-in group (S2) will start with 10 mg/kg dose of PF-06747143 and may be
escalated to up to 20 mg/kg (the MPD) or de-escalated to below 10 mg/kg based on the 
predefined DLT criteria (see Section 3.1.1.3) and emerging data. After completion of the S2 
cohort, PF-06747143 will be administered in combination with a hypomethylating drug (ie, 
either azacitidine or decitabine, based on institutional guidelines) and may continue for up to 
1 year (~12 cycles) from start of therapy or until disease progression or relapse, patient 
refusal or unacceptable toxicity occurs (whichever comes first) in newly diagnosed treatment 
naïve unfit AML patients). The expansion cohort (E2) will enroll up to 30 patients.
2.2.2.3. MTD Definition
In Part 2, the MTD of the combinations of PF-06747143 and intensive 
daunorubicin/cytarabine or PF-06747143 and decitabine/azacitaditine will be determined 
separately within each cohort.
2.2.2.4. Part 2/Cohort 3 – PF-06747143 Single Agent Expansion
An additional single agent PF-06747143 expansion cohort, Cohort 3 (E3), at the MTD/RP2D 
may be initiated in Part 2 in 15-30 refractory and/or relapsed AML patients. The initiation of 
this cohort will require that single agent PF-06747143 demonstrates encouraging clinical
benefit (eg, significantly improved CR and response duration compared to historical data) in 
the dose escalation Part 1. Patients in this cohort will be treated until disease progression or 
relapse, patient refusal or unacceptable toxicity occurs (whichever comes first).
2.2.3. Summary
Approximately 125-140 patients are expected to be enrolled in this study (approximately 
30-50 patients in Part 1 (actual number of patients enrolled for Part 1 will depend upon 
tolerability of PF-06747143 and the number of dose levels required to identify the MTD) and 
approximately 87-102 patients in Part 2). The study will be conducted in approximately 4 
sites for Part 1 and approximately 12-15 sites for Part 2.
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Patients who complete the maximum number of cycles/months on study treatment (Section 
3.1.2.2.1 and Section 3.1.2.2.2), demonstrate clinical benefit with manageable safety profile 
and are willing to continue receiving the assigned treatment may be given the opportunity to 
do so upon agreement between Investigator and sponsor and pending investigational product 
availability.
All patients who completed treatment will have a 60-day post dose follow-up period.
2.3. Study Objectives and Endpoints
2.3.1. Part 1 Study Objectives
Primary Objective

To assess safety and tolerability at increasing dose levels of PF-06747143 in patients
with refractory and/or relapsed AML for which 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-dose and multiple-dose pharmacokinetics (PK) of PF-
06747143 following IV administration;

To evaluate the immunogenicity of PF-06747143 following repeated administration;

To document any anti-leukemia activity based on . Diagnosis and management of
acute myeloid leukemia in adults: recommendations from an international expert
panel, on behalf of the European LeukemiaNet (Ref 2)
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2.3.2. Endpoints – Part 1
Primary Endpoint

Dose Limiting Toxicities (DLTs).
Secondary Endpoints

Adverse Events as characterized by type, frequency, severity (as graded by National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 
v4.03), 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;

PK parameters of PF-06747143: Single Dose (SD) - Cmax, AUClast, and if data 
permit, AUCinf, Vd, CL, and t1/2. Multiple Dose (MD) (assuming steady state is 
achieved) - Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUC, and if data permit, CL, Vss, 
and t1/2;

Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) against 
PF-06747143;

Preliminary evidence of anti-leukemia activity including objective disease response; 
as assessed using the standardized response criteria including objective response rate 
(ORR), duration of ORR, and relapse free survival (RFS).(Ref 2)
2.3.3. Objectives – Part 2
Primary Objective

To evaluate safety and tolerability and preliminary anti-leukemia activity (Dohner, et. 
al 2010)22 of PF-06747143 in combination with standard intensive chemotherapy (ie, 
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cytarabine and daunorubicin; D/C 7+3) in patients with newly diagnosed fit treatment 
naïve AML patients (Cohort 1) or with standard dose of decitabine or azecitidine in 
newly diagnosed unfit treatment naïve AML patients (Cohort 2) or PF-06747143 as a 
single agent ((Cohort 3) if data warrants).
Secondary Objectives

To characterize the single and multiple dose PK of PF-06747143 in combination with 
standard intensive cytarabine and daunorubicin 7+3 therapy in newly diagnosed fit 
treatment naïve AML patients or with standard dose of decitabine or azacitidine in 
newly diagnosed unfit treatment naïve AML patients;

To collect PF-06747143 drug concentration data in patients from the dose expansion 
cohorts for evaluation of population PK;

To evaluate the immunogenicity of PF-06747143 following repeated administration.
2.4. Endpoints – Part 2
Primary Endpoints

Adverse Events as characterized by type, frequency, severity (as graded by National
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 
4.03), timing, seriousness, and relationship to study therapy;
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
Laboratory abnormalities as characterized by type, frequency, severity (as graded by
NCI CTCAE v.4.03) and timing;

Preliminary evidence of anti-leukemia activity including objective disease response;
as assessed using the standardized response criteria including objective response rate
(ORR), duration of ORR, and relapse free survival (RFS).(Ref 2)
Secondary Endpoints

PK parameters of PF-06747143: Single Dose (SD) - Cmax, Tmax, AUClast, and if data 
permit, AUCinf, Vd, CL, and t1/2. Multiple Dose (MD) (assuming steady state is 
achieved) - Cmax, ss, Cmin, ss, AUC, ss, Rac (AUC, ss /AUC), and if data permit, CL, Vss,
and t1/2;

Peak and trough PF-06747143 concentrations for selected doses;

Incidence of ADA and Nab against PF-06747143.
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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.
2. 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
3. All doses explored appear to 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 
975
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Pr( 1
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Rule 2 (dose exclusion), if dose= i is too toxic 
then exclude doses i
4.2.2. Part 2
Part 2 of this study is intended to confirm the safety and tolerability of the dose selected in 
Part 1 while assessing the anti-leukemia activity of PF-06747143 in combination with 
standard dose of intensive chemotherapy. The DLT rate and its 95% confidence interval at
the selected dose may be estimated.  Part 2 data will also be used to determine the safey of 
combining PF-06747143 with standard chemotherapy in addition to justifying the efficacy of 
PF-06747143 monotherapy.
5. SAMPLE SIZE DETERMINATION
Approximately 125-140 patients are expected to be enrolled in this study (approximately 
30-50 patients in Part 1 and 87-102 patients in Part 2).
The exact sample size of the mTPI design in Part 1 cannot be pre specified in advance 
because it is a dynamic feature of the design. The maximum sample size after which the Part 
1 will be stopped and MTD declared is 30-50 patients. Also, a minimum of 9 patients is 
required to establish the MTD. The actual sample size of Part 1 will depend on the 
underlying dose toxicity profile and variability in actual data realization.
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.  For the dose declared as the MTD from Part 
1, a minimum of 9 patients will be observed at this dose to further investigate the anti-
leukemic activity, safety, and PK profile of PF-06747143. However, since not every dose 
listed will be studied and variable cohort size is allowed, the actual number of patients treated 
at each dose will vary.
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.
6.2. ‘PER PROTOCOL’ Analysis Set 
The per protocol analysis set includes all enrolled patients who receive at least one dose of 
study treatment at the dose level of MTD and who do not have major treatment deviations 
during first cycle. Patients with major treatment deviations in Cycle 1 are not evaluable for 
the MTD assessment and may be replaced. Major deviations include failure to satisfy major 
entry criteria (eg, confirmation of the target disease population; signed informed consent), 
administration of less than 3 out of the 4 doses in Cycle 1 or 80% of the planned Cycle 1 
dose (provided that the reduction is not due to toxicity attributable to PF-06747143) or use of 
75
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other anti-cancer/anti-leukemia treatments during the active treatment and disease follow up 
phases other than as defined/allowed in this protocol.
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.  The PK 
concentration population is defined as all patients who receive PF-06747143, have no major 
deviations affecting the PK assessment, and have at least one post-dose concentration 
measurement.
6.3. Safety Analysis Set
The safety analysis set includes all enrolled patients who receive at least one dose of study 
medication.
6.4. Other Analysis Sets
6.4.1. 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 assessment.  The mITT population may be used for interim analysis and conference 
presentations when the study is still ongoing.
6.5. 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.
6.6. Protocol Deviations
All deviations will be listed in the CSR. Major treatment deviations include, but are not 
limited to, less than 80% of the planned Cycle 1 PF-06747143 dose provided the 
reduction/omission is not due to treatment-related toxicity. Subjects with major Cycle 1 
treatment deviations are not evaluable for MTD.
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7. ENDPOINTS AND COVARIATES
7.1. Efficacy Endpoint(s)
Preliminary evidence of anti tumor activity including objective disease response; as assessed 
using the standardized response criteria for the hematologic disease under study including 
objective response rate (ORR), duration of ORR, time to progression (TTP) and progression 
free survival (PFS).
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) – Preliminary evidence of anti-leukemia activity 
including objective disease response will be assessed using the standardized response 
criteria,  as recommended by an international expert panel, on behalf of the European 
LeukemiaNet (Dohner, et. al 2010), including objective response rate (ORR), duration of 
ORR, and relapse free survival (RFS) (section 7.6) All measurable disease must be 
documented at screening and re assesses at each subsequent tumor evaluation.  Overall 
response is the best response recorded from first dose until disease 
progression/recurrence and it must include confirmation.To be assigned a status of PR or 
CR, changes in leukemia measurements must be confirmed by repeat assessments that 
should be performed no less than 4 weeks after the criteria for response are first met.
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 disease progression 
(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.
PFS (days) = [progression/death date – C1D1 + 1].

Overall survival (OS) is defined as the time from initial dose until death from any cause, 
and is measured in the intent-to-treat population.
More details of censoring are provided in Appendix 2.
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7.2. Safety Endpoints
7.2.1. DLT Definitions
A DLT will be classified according to NCI CTCAE version 4.03 and is defined as any of the 
following adverse events unless the event can clearly be determined to be unrelated to drug 
occurring in the first cycle of treatment (within 28 days of first dose or until patient receives 
a second cycle if there are treatment delays). Data from all cycles of treatment will be 
analyzed for safety, delayed toxicity, and cumulative toxicity.
DLT is defined as:

Hematologic:

Failure to achieve an ANC greater than 1,000/ul and/or a platelet count greater
than 25,000/ul independent of platelet transfusion by day ≥42 after the start of
therapy, with a hypocellular bone marrow (<10% marrow cellularity) and 
absence of persistent leukemia (ie, <5% marrow blasts) measured at the 
completion of Cycle 1 (approximately day 28-32);

If a subject with persisting cytopenias does not exhibit marrow 
hypoplasia on biopsy (or bone marrow aspirate) or demonstrates 
persisting leukemia, such subject will not be considered to have 
demonstrated a hematological toxicity and may continue to receive 
PF-06747143 at the scheduled time point for

Hyperleukocytosis (WBC ≥100,000/ul) not managed by hydroxyurea or
leukapheresis and/or resulting in an adverse event.

Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding.

Non-hematologic:

Grade 3 toxicities, except for:

Grade ≥3 nausea or vomiting that resolves to Grade ≤1 within 72 hours 
with appropriate supportive therapy;

Grade ≥3 diarrhea that resolves to Grade ≤1 within 72 hours with 
appropriate supportive therapy;

Grade ≥3 fatigue, asthenia, or other constitutional symptom that 
resolves to Grade ≤1 within 7 days with appropriate supportive 
therapy;

Alopecia of any grade;
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
Grade ≥3 infection, fever (including febrile neutropenia), electrolyte
abnormalities and ALT/AST elevation that returns to Grade ≤1 or 
baseline within 7 days;

Delay by more than 14 days to receive the next scheduled dose due to a persisting
drug-related AE.

All Grade 4 toxicities.
In addition, clinically important or persistent toxicities that are not included in the above 
criteria may be considered a DLT following review by the investigators and sponsor. All 
DLTs need to represent a clinically significant shift from baseline.
Grade ≥3 cytokine release syndrome, infusion reaction, and allergic reaction will not be 
considered as DLTs (as it is unlikely to be dose related), but may be a reason for study 
discontinuation, protocol amendment (eg, pre-infusion treatments, infusion duration) and 
should be reviewed with the sponsor.
In principle, a patient needs to be on study for at least 28 days to be evaluable for DLT 
observation, and may be replaced if they terminate study participation earlier than 28 days 
without experiencing a DLT. Patients who are not able to receive at least 80% of the planned 
dose of the PF-06747143 and backbone chemotherapy (in Part 2 combination study) in the 
DLT assessment period are considered not evaluable for DLT and will be replaced.  
However, in some circumstances of a clear drug unrelated event (eg, traffic accident, clear 
disease progression, or withdrawal of consent) that leads to study termination close to or 
before 28 days, the patient might be deemed evaluable if the Investigators and Sponsor agree.
In addition, patients not evaluable for assessment of DLT, as described in Section 7.2.1, may
be replaced.
7.2.2. 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). 
7.2.3. Maximum Permitted Dose Definition
The Maximum Permitted Dose (MPD) for Part 1 and 2 is 20 mg/kg.
7.2.4. Recommended Phase 2 Dose (RP2D) Definition
The Recommended Phase 2 Dose (RP2D) is the dose chosen for further study based on Part 1 
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.
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7.2.5. Vitals Signs  
Vital signs,  See Schedule of Activities in the protocol for details.
7.2.6. Laboratory Data
The number and percentage of patients who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade observed for each laboratory assay.  The 
analyses will 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 CTCAE grade definitions, results will be categorized as normal,
7.2.7. Adverse Events
AEs will be graded by the investigator according to the CTCAE version 4.03 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 treatment.  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).
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.

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 Adverse Events
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.
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7.2.8. ECG and 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).
In addition, the number of patients with corrected and uncorrected QT values ≥500 msec 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 ≥500 msec, 
but the mean of the triplicates is not ≥500 msec, the data from the subject’s individual tracing 
will be described in a safety section of the study report in order to place the ≥500 msec value 
in appropriate clinical context. However, values from individual tracings within triplicate 
measurements that are ≥500 msec will not be included in the categorical analysis unless the 
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average from those triplicate measurements is also ≥500 msec. Changes from baseline will be 
defined as the change between QTc post dose from Day 0, or the pre-dose values on Day 1.
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.
7.2.9. Immunogenicity
The development of anti PF 06747143 antibodies will be measured using validated assays.  
Listings and summary tabulations of number of patients and incidence of ADA at baseline 
(pretreatment) and post treatment will be generated.
Potential impact of immunogenicity on PK and clinical responses including PD markers, 
safety/tolerability and efficacy of PF 06747143 will be explored, if data is warranted.
7.3. PK Endpoints 
Serum pharmacokinetic parameters including the maximum concentration (Cmax), time to 
maximum concentration (Tmax), and area under the concentration versus time curve 
(AUClast, AUCτ) for PF-06747143 will be estimated using non compartmental analysis.  If 
data permit, area under the concentration versus time curve to infinity (AUCinf), terminal 
elimination half life (t1/2), clearance (CL), apparent volume of distribution (Vss), and 
accumulation ratio (Rac) will be also estimated.  The PK parameters will be summarized 
descriptively by dose, cycle and day.
PF0-06747143 concentrations will be summarized descriptively (n, mean, SD, coefficient of 
variation(CV), median, minimum, maximum, geometric mean and its associated CV) by 
dose, cycle, day and nominal time.  Individual patient and median profiles of the 
concentration time data will be plotted by dose, cycle and day (single dose and steady state) 
using nominal times.  Individual and median profiles will be presented on both linear linear 
and log linear scales.
Dose normalized AUCinf (AUCτ at steady state), and Cmax will be plotted against dose 
(using a logarithmic scale) by cycle and day.  These plots will include individual patient 
values and the geometric means for each dose.  These plots will be used to help understand 
the relationship between the PK parameters and dose.
The observed accumulation ratio will be summarized descriptively.  Each will be analyzed 
after natural log transformation using a one way analysis of variance with a single term for 
dose.  The means and 90% confidence intervals (CIs) obtained from the model will be back 
transformed to provide means and 90% CIs for the accumulation for each dose.
Trough concentrations will be plotted for each dose using a box whisker plot by cycle and 
day within cycle in order to assess the attainment of steady state.
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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 1st of 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 in Section 11.2 Appendix 2.
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 one of the following cases is true:
a.
A concentration has been reported as ND (ie, not done) or NS (ie, no sample),
b. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
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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.  
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 intervals for 
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. 
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Analyses of Continuous Data
Descriptive statistics, such as the 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 efficacy is 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 Set and 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 Response Rate, Progression Free Survival, and Overall 
Survival will 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.
A response rate overall for Part 1 dose escalation and response rates by low, medium, and 
high dose groups may be presented. 
The following table provides an overview of the efficacy analysis.
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Table 2.
Overview of 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 Section 
11.2
Secondary 
Analysis
Progression 
Free Survival 
(PFS)
Per Protocol, 
expansion 
cohorts
Kaplan-
Meier
By malignancy
Censored 
per Section 
11.2
Secondary 
Analysis
Time to 
Progression 
(TTP)
Per Protocol, 
expansion 
cohorts
Kaplan-
Meier
By malignancy
Censored 
per Section 
11.2
Secondary 
Analysis
Duration of 
Response (DR)
Per Prtocol, 
expansion 
cohorts
Kaplan-
Meier
By malignancy
Censored 
per Section 
11.2
Secondary 
Analysis
9.2.2.2. Pharmacokinetics Analyses 
Pharmacokinetic Parameters
To assess the pharmacokinetics of PF-06747143, PK parameters detailed in Section 7.3 will 
be listed and summarized for subjects in the PK analysis set (as defined in Section 9.1 of the 
protocol or Section 6.2 in this document 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: 
Table 3.
PK Parameter Summaries
Parameter
Summary statistics
AUClast, 
AUC∞, 
AUC, Cmax,
CL, Vss, and 
Rac
N, arithmetic mean, median, cv%, standard deviation, minimum, 
maximum, geometric mean
t1/2
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 group and cycle.  
To assess the relationship between the PK parameters and dose, dose normalized AUC∞, 
AUClast, AUC, and Cmax will be plotted against dose (using a logarithmic scale), and will 
include individual subject values and the geometric means for each dose.  Geometric means 
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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-06747143, total antibody and unconjugated payload, PK
concentrations will be listed, summarized and plotted for subjects in the PK analysis set (as 
defined in Section 7.3) Presentations for PF-06747143, total antibody and unconjugated 
payload will include:

a listing of all concentrations sorted by dose, subject ID, day and 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 PK concentration 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.
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.
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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 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, 
serious 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).  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 (Cycle 1 
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,
abnormal high/low or not done.
Other Variables: Immunogenicity
The development of anti PF 06747143 antibodies will be measured using validated assays.  
Listings and summary tabulations of the anti PF 06747143 antibody data at baseline and post 
randomization will be generated.
CCI
CCI
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Potential impact of immunogenicity on PK and clinical responses including 
 
safety/tolerability and efficacy of PF 06747143 will be explored, if data is warranted.
9.2.4. Standard Analyses
Study Conduct and Patient Disposition
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
Baseline characteristics such as demographics, prior medication, medical history, ECOG 
performance status, and primary diagnosis will be tabulated and 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.
Dose modifications may occur in the following ways:

Cycle delay—Day 1 of current cycle starts later than 21 days 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 number of cycles started per subject;

Number (%) of subjects starting a cycle (1, 2, 3…);

Number (%) of subjects 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;
CCI
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
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 1st delay (median, range);

Number of cycles before 1st reduction (median, range);

Number of cycles before 1st interruption (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 
1.
Brookmeyer R, Crowley JJ.  A confidence interval for the median survival time.  
Biometrics 1982; 38:29-41.
2.
Döhner H1, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid 
leukemia in adults: recommendations from an international expert panel, on behalf of 
the European LeukemiaNet.  Blood. 2010 Jan 21; 115(3):453-74
3.
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
4.
ICH E14 - The clinical evaluation of QT/QTc interval prolongation and proarrhythmic 
potential for non-antiarrhythmic drugs.  CHMP/ICH/2/04.
5.
Kaplan EL, Meier P.  Nonparametric estimation from incomplete observations.  J Am 
Stat Assoc 1958; 53:457-481.
6.
NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
http://evs.nci.nih.gov/ftp1/CTCAE/Documentation/CTCAE_Governance_2010-03-
11.pdf
7.
Y Ji, P Liu, Y Li, and BN Bekele. A modified toxicity probability interval method for 
dose-finding trials. Clinical Trials, 7:653 663, 2010.
8.
Vardiman JW et al, The 2008 revision of the World Health Organization (WHO) 
classification of myeloid neoplasms and acute leukemia: rationale and important 
changes. Blood. 2009: 114(5):937-951.
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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: CENSORING DETAILS
Table 4.
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 treatment2 and no 
Progression 
Date of last objective tumor assessment
Censored
Progression Documented on or 
between scheduled tumor assessments 
prior to  treatment discontinuation2
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 discontinuation2
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 5.
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 treatment2 and no 
Progression 
Date of last objective tumor assessment
Censored
Progression Documented on or 
between scheduled tumor assessments 
prior to  treatment discontinuation2
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 discontinuation2
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.
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11.3. Appendix 3. Detailed Dose Escalation/De-Escalation Scheme for mTPI Design
Number of Patients
Number of Toxicities
E=Escalate to the next higher dose
S=Stay at the current dose
D=De-escalate to the next lower dose
DU=The current dose is unacceptably toxic
Probability of target toxicity=0.25
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
o
0 DLT -> escalate
o
1 DLT -> de-escalate to the lower dose
o
2 DLTs -> de-escalate and consider current dose as 
intolerable

With 3 patients treated at current dose level
o
0 DLT -> escalate
o
1 DLT -> remain at the same dose
o
2 DLTs -> de-escalate
o
3 DLTs -> de-escalate and consider current dose as 
intolerable

With 4 patients treated at current dose level
o
0 DLT -> escalate
o
1 DLT -> remain at the same dose
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o
2 DLTs -> de-escalate
o
3-4 DLTs -> de-escalate and consider current dose as
intolerable

With 5 patients treated at current dose level
o
0 DLT -> escalate
o
1-2 DLTs -> remain at the same dose
o
>= 3 DLTs -> de-escalate and consider current dose 
as intolerable

With 6 patients treated at current dose level
o
0 DLT -> escalate
o
1-2 DLTs -> remain at the same dose
o
3 DLTs -> de-escalate
o
4-6 DLTs -> de-escalate and consider current dose as 
intolerable

With 7 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-3 DLTs -> remain at the same dose
o
>= 4 DLTs -> de-escalate and consider current dose 
as intolerable

With 8 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-3 DLTs -> remain at the same dose
o
>= 4 DLTs -> de-escalate and consider currentdose 
as intolerable

With 9 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-3 DLTs -> remain at the same dose
o
4 DLTs -> de-escalate
o
5-9 DLTs -> de-escalate and consider current dose as 
intolerable

With 10 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-4 DLTs -> remain at the same dose
o
>= 5 DLTs -> de-escalate and consider current dose 
as intolerable

With 11 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-4 DLTs -> remain at the same dose
o
5 DLTs -> de-escalate
o
6-11 DLTs -> de-escalate and consider current dose 
as intolerable

With 12 patients treated at current dose level
o
0-1 DLT -> escalate
o
2-5 DLTs -> remain at the same dose
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o
6-12 DLTs -> de-escalate and consider current dose 
as intolerable
11.4. Disease Assessment
The following section describes the CRFcompletion guidelines and the corresponding 
response criteria.
If assessment was done, place 'X' in one box only (unless otherwise specified for that 
selection), to record the disease assessment. Select from the following:
1. Morphologic Complete Remission (CR): This is morphologic leukemia-free state with 
bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary 
disease (EMD); absolute neutrophil count >1000/ul and platelet >100,000/ul; independence 
from red cell transfusions. 
If the CR box is checked, check the box(es) below if patient achieved the following:
a.
Cytogenetic CR (CRc):  Reversion to a normal karyotype at the time of morphologic CR, 
as defined above, in cases with an abnormal karyotype at the time of diagnosis; based on the 
evaluation of 20 metaphase cells from bone marrow.
b. Molecular CR (CRm):  Reversion to a molecular-negative phenotype at the time of 
morphologic CR, as defined above. 
Note: Even if the CRc and/or CRm box(es) are checked, the CR box must still be checked.
OR
2. Morphologic Complete Remission with incomplete blood count recovery (CRi):  All CR 
criteria met except for residual neutropenia (absolute neutrophil count <1000/ul) or 
thrombocytopenia (plateletes <100,000/ul). 
OR
3. Morphologic Leukemia-Free State:  Bone marrow blasts <5%; absence of blasts with 
Auer rods; absence of EMD; no hematologic recovery required.
OR
4. Partial Remission (PR):  Absolute neutrophil count >1000/ul and platelet >100,000/ul; 
bone marrow blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. 
OR
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5. Partial Remission with incomplete blood count recovery (PRI):  residual neutropenia 
(absolute neutrophil count <1000/ul) or thrombocytopenia (plateletes <100,000/ul); bone 
marrow blasts decreased to 5-25% and ≥ 50% decrease from pre-treatment levels. 
OR
6. Treatment Failure (TF): If TF box is checked, one of the options below must be chosen:
a.
TF due to resistant disease:  Failure to achieve CR, CRi, PR or PR; Only includes patients 
surviving ≥7 days following completion of initial course of treatment with evidence of 
persistent leukemia by blood and/or bone marrow examination. Initial course of treatment 
completion is defined as completion of Cycle 1. 
b. TF due to aplasia:  Deaths occurring ≥7 days following completion of initial course of 
treatment while cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 
days of death and without evidence of persistent leukemia. Initial course of treatment 
completion is defined as completion of Cycle 1. 
c.
TF indeterminate cause:  Deaths occurring before completion of therapy, or < 7 days 
following its completion; or deaths occurring ≥7 days following completion of initial course 
of treatment with no blasts in the blood, but no bone marrow examination available. Initial 
course of treatment completion is defined as completion of Cycle 1.
Note: If TF applies, the TF box should always be checked along with one of the three 
options.
OR
7. Relapse: Bone Marrow blast ≥ 5%; or reappearance of blast in the blood; or  development
of EMD
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